Surgery For Gastric Cancer Hoon Noh 1 Ed 2019 PDF

Surgery for
Gastric Cancer
Sung Hoon Noh
Woo Jin Hyung
Editors
123
Sung Hoon Noh • Woo Jin Hyung
Editors
Surgery for Gastric

Cancer
Editors
Sung Hoon Noh Woo Jin Hyung
Department of Surgery Department of Surgery
Yonsei University College of Medicine Yonsei University College of Medicine
Seoul Seoul
South Korea South Korea
ISBN 978-3-662-45582-1 ISBN 978-3-662-45583-8 (eBook)

https://doi.org/10.1007/978-3-662-45583-8
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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

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Contents
Part I History of Gastric Cancer Surgery
1 History of Gastric Cancer Surgery�� 3

Keiichi Maruyama
Part II Staging of Gastric Cancer
2 Staging of Gastric Cancer: Current Revision and Future

Proposal�� 45
Jingyu Deng, Jiping Wang, and Han Liang
Part III Diagnosis of Gastric Cancer
3 Endoscopic Diagnosis: Esophagogastroduodenoscopy

(EGD) and Endoscopic Ultrasound (EUS)�� 59
Sang Kil Lee and Hyunsoo Chung
4 Radiologic Diagnosis (CT, MRI, & PET-CT)�� 67
Nieun Seo, Joon Seok Lim, and Arthur Cho
Part IV Treatment of Gastric Cancer
5 Endoscopic Treatment for Early Gastric Cancer�� 89

Takuji Gotoda
Part V Open Surgery for Gastric Cancer
6 Open Surgery for Gastric Cancer: Distal Subtotal

Gastrectomy with D2 Lymph Node Dissection�� 99
Ji Yeong An, Yoon Young Choi, and Sung Hoon Noh
7 Open Surgery for Gastric Cancer: Total Gastrectomy
with D2 Lymph Node Dissection�� 111
Yoon Young Choi and Sung Hoon Noh
8 Gastrectomy with D3 Lymph Node Dissection�� 117
Mitsuru Sasako
v
vi Contents
9 Open Surgery for Gastric Cancer: Reconstruction�� 127

Joong Ho Lee and Woo Jin Hyung
Part VI Laparoscopic Surgery for Gastric Cancer
10 Laparoscopic Surgery for Gastric Cancer: Distal Subtotal

Gastrectomy with D2 Lymph Node Dissection�� 137
Koichi Suda and Ichiro Uyama
11 Laparoscopic Surgery for Gastric Cancer, Total Gastrectomy
with D2 Lymph Node Dissection�� 153
Yoo Min Kim and Woo Jin Hyung
12 Intracorporeal Reconstruction in Laparoscopic
Gastrectomy�� 159
Hisahiro Hosogi, Yoshiharu Sakai, and Seiichiro Kanaya
Part VII Robotic Surgery for Gastric Cancer
13 Distal Subtotal Gastrectomy with D2 Lymph Node

Dissection�� 171
Kun Yang and Woo Jin Hyung
14 Total Gastrectomy with D2 Lymph Node Dissection�� 183
Hiroshi Okabe
15 Reconstruction Methods After Robotic Distal
or Total Gastrectomy �� 191
Sang-Yong Son and Sang-Uk Han
Part VIII Function-Preserving Surgery
16 Pylorous-Preserving Gastrectomy�� 201

Seung-Young Oh, Hyuk-Jun Lee, and Han-Kwang Yang
17 Surgery for Gastric Cancer: Proximal Gastrectomy�� 207
Young Suk Park and Hyung-Ho Kim
18 Vagus-Preserving Gastrectomy�� 217
Masatoshi Nakagawa and Kazuyuki Kojima
Part IX Sentinel Node Navigation Surgery
19 Sentinel Node Navigation Surgery�� 223

Hiroya Takeuchi and Yuko Kitagawa
Part X Surgery for EG Junction Cancer
20 Surgery for EG Junction Cancer�� 233

Yasuyuki Seto, Hiroharu Yamashita, and Susumu Aikou
Contents vii
Part XI Surgery After Neoadjuvant Chemotherapy
21 Surgery After Neoadjuvant Chemotherapy�� 245

Daniel Reim, Alexander Novotny,
and Christoph Schuhmacher
Part XII Surgery for Remnant Gastric Cancer
22 Surgery for Remnant Gastric Cancer: Open Surgery�� 255

23 Laparoscopic Surgery�� 263
Eishi Nagai and Masafumi Nakamura
Part XIII Peritonectomy and HIPEC
24 Prevention and Treatment of Peritoneal Metastases from

Gastric Cancer �� 277
Mei Li M. Kwong, Chukwuemeka Ihemelandu,
and Paul H. Sugarbaker
Part XIV Palliative Surgery (Including Resection, Bypass and Stent)
25 Palliative Therapy for Gastric Cancer �� 295

K. Ji, P. Yuan, Z. D. Bu, and J. F. Ji
Part XV Postoperative Management and Follow-Up
26 Management of Early Postoperative Complication�� 305

Dong Jin Kim and Wook Kim
27 Management of Late Postoperative Complications�� 315
Masanori Terashima
28 Follow-Up After Gastric Cancer Treatment�� 327
Jimmy BY So and Guowei Kim
Part XVI Neoadjuvant and Adjuvant Treatments for Gastric Cancer
29 Neoadjuvant Treatment for Gastric Cancer�� 343

Sook Ryun Park and Yoon-Koo Kang
30 Adjuvant Treatment for Gastric Cancer�� 353
Do-Youn Oh and Yung-Jue Bang
31 Radiation Therapy for Gastric Cancer�� 359
Do Hoon Lim
32 Novel Agents and the Future Perspectives�� 367
Minkyu Jung and Sun Young Rha
Part I
History of Gastric Cancer Surgery
History of Gastric Cancer Surgery
1
Keiichi Maruyama
We have many dramatic and exciting stories in amusement such as “ether frolics.” An American
the history of surgery [1–4]. I would like to rec- dentist in Boston Horace Wells (1815–1848)
ommend my colleagues to read such interesting (Fig. 1.1a) used nitrous oxide for a painless dental
books, for example, Das Jahrhundert der extraction in 1845 [9]. His business partner and
Chirurgen (The Century of the Surgeon (English fellow dentist William T. G Morton (1819–1868)
edition)) [5] and Das Weltreich der Chirurgen (Fig. 1.1b, e) used dimethyl ether also for dental
(The Triumph of Surgery (English edition)) [6] extractions. He expanded the use for general sur-
written by Jurgen Thorwald. gery. He demonstrated his method for neck tumor
resection to the prominent surgeon John Collins
Warren at the Massachusetts General Hospital on
rogress of Supportive Background
P the 16th of October 1846 (Fig. 1.1e) [10]. The
for Gastric Cancer Surgery next year, a Scottish obstetrician James Young
Simpson (1811–1870) (Fig. 1.1e) of Edinburgh
Progress of the following supportive technolo- used chloroform for general anesthesia [11].
gies was essential in the development of gastric Chloroform anesthesia was rapidly popularized
cancer surgery. after the application for Queen Victoria’s labor in
1853. These developments released patients from
terrible pain and fear during surgery.
Anesthesia
The dawn of surgery was broken by development Aseptic Method

of anesthesia [7, 8]. By the late 1830s, it was
widely known that nitrous oxide and ether pro- A Hungarian obstetrician Ignaz Fulop Semmelweis
duced drunken condition, and they were used for (1818–1865) (Fig. 1.1d) noticed that a clean condi-
tion reduced maternal death. He reported in 1847
that the death rate went dramatically down by
K. Maruyama (*) handwashing and rinsing of medical instruments
Department of Surgical Oncology,
and linens with chlorinated lime solution at the
University of Health and Welfare Sanno Medical Center,
Tokyo, Japan Vienna General Hospital [12]. Semmelweis’s work
was furthered by a Scottish surgeon Joseph Lister
Department of Surgical Oncology, National Cancer
Center Hospital, Tokyo, Japan (1827–1912) (Fig. 1.2a). He used phenol (carbolic
e-mail: keiichi-maruyama@rOl.itscom.net acid) to clean surgical gauze at the Glasgow Royal
© Springer-Verlag GmbH Germany, part of Springer Nature 2019 3

S. H. Noh, W. J. Hyung (eds.), Surgery for Gastric Cancer,
https://doi.org/10.1007/978-3-662-45583-8_1
4 K. Maruyama
a b
c d
Fig. 1.1 (a–f) Historical leaders, pictures of ether anesthe- (d) Ignaz F. Semmelweis: chlorinated lime wash, (e) ether
sia, and Lister’s aseptic method. (a) Horace Wells: nitrous mask for inhalation anesthesia (ether solution was dropped
oxide anesthesia, (b) William T.G. Morton: ether anesthe- on the mask with gauze), (f) Lister’s aseptic method (car-
sia, (c) James Young Simpson: chloroform anesthesia, bolic acid solution was used for washing and spray)
1 History of Gastric Cancer Surgery 5
f Gerhard Domagk (1895–1964) (Fig. 1.3a) and

Josef Klarer (1898–1953) synthesized “sulfon-
amide,” a strong anti-gram-positive cocci sub-
stance, in 1935 [19]. A Scottish Nobel Prize
scientist Alexander Fleming (1881–1955)
(Fig. 1.3b) discovered penicillin at St Mary’s
Hospital, London, in 1928 [20]. He actually
opened a new era in medicine. Penicillin was
purified by Howard Walter Florey (1898–1968)
and Ernst Boris Chain (1906–1979) of the
University of Oxford in 1941 [21]. Penicillin
Fig. 1.1 (continued) showed miraculous effectiveness during the
World War II. Nowadays, we have various anti-
Infirmary of Edinburgh from 1866. And he intro- bacterial agents.
duced phenol vapor to clean his operating room
(Fig. 1.1f) [13]. Ernst von Bergmann (1836–1907)
(Fig. 1.2b), professor of surgery in the University Intravenous Infusion Therapy
of Berlin, and his coworker Curt Schimmelbusch
(1860–1895) developed a heat sterilization method This treatment offered a non-oral route adminis-
for surgical instruments in 1886 (Fig. 1.2g) [14]. tration of fluid, minerals, calories, and drugs to
We have a very romantic history in development of the patient. Using the infusion therapy, the patient
the surgical rubber glove. The world famous sur- can stop drinking and eating after surgery.
geon, William Stewart Halsted (1852–1922) Thomas Latta (1796–1833), a surgeon in Leith,
(Fig.1.2c) of the Johns Hopkins Hospital, USA, Scotland, developed this technology for patients
used strictly Lister’s method using carbolic acid. with cholera in 1832 [22]. Stanley J. Dudrick of
This antiseptic solution produced severe hand skin the University of Pennsylvania, USA, developed
damage of the head nurse of the operation theater, parenteral nutrition in 1968, and this method was
Miss Caroline Hampton. He ordered special thin widely used particularly through the central
skin rubber gloves for her from the Goodyear Tire venous route [23].
and Rubber Company in 1890 [15]. They got mar-
ried in 1890. An Austrian surgeon Antonio Grossich
(1849–1926) (Fig. 1.2d) introduced iodine tincture uture Materials and Surgical
S
for rapid skin sterilization of the surgical field in Instruments
1908 [16]. These aseptic strategies were scientifi-
cally supported by the discovery of “microorgan- In the 1850s, the popular suture materials were
isms.” Louis Pasteur (1822–1895) (Fig. 1.2e) of the linen, cotton, catgut, and silk. They were now
Ecole Nationale Superieure des Beaux-Arts, Paris, completely disappeared except silk. Various syn-
confirmed that the microorganisms caused the fer- thesized absorbable sutures with atraumatic nee-
mentation and putrefaction in 1847 [17]. Robert dle are now in use. Mechanical anastomotic
H. H. Koch (1843–1910) (Fig. 1.2f), a Nobel Prize instruments showed remarkable development.
microbiologist in the University of Berlin, found The first reliable liner stapler was developed by a
the bacteria which caused various infectious dis- Hungarian surgeon Aladar von Petz (1888–1956)
eases in 1878 [18]. These developments reduced of the Trinity Hospital in Györ in 1921 (Fig. 1.3c)
dramatically fatal surgical infections. [24]. The first circular stapler was developed by
Masaru Mine of the Kyoto Prefectural Medical
University, Japan, in 1962 [25]. The improved
Antibacterial Agents models, SPTU and PKS-25 M, were provided by
a Russian company (Fig. 1.3d). An American
The next significant progress appeared on anti- company, the United States Surgical Corporation,
bacterial agents. Bayer chemists (German) bought the license from Russia and supplied the
6 K. Maruyama
a b
c d
e f
Fig. 1.2 (a–g) Historical leaders and Schimmelbusch Grossich: iodine tincture, (e) Louis Pasteur: microorgan-
sterilization apparatus. (a) Joseph Lister: carbolic acid isms, (f) Robert Koch: infectious bacteria, (g)
antiseptic, (b) Ernst von Bergmann: heat sterilization, (c) Schimmelbusch heat sterilization system: for medical
William Stewart Halsted: surgical glove, (d) Antonio instruments
Fig. 1.2 (continued)
Fig. 1.3 (a–e) Historical

a b
leaders and various
mechanical staplers. (a)
Gerhard Domagk: antibiotic
sulfonamide; (b) Alexander
Fleming: antibiotic
penicillin; (c) von Petz
linear stapler; (d) Russian
circular stapler, SPTU; (e)
United States Surgical
Corporation, EEA stapler
c d
e
8 K. Maruyama
improved and disposable devices of TA, GIA, a

and EEA (Fig. 1.3e). Electrocautery was also
improved, and we have now various devices for
different procedures. The other progress was lap-
aroscopic instruments and robot surgery b
machines. Minimally invasive surgery becomes
popular supported by these progress.
Advancement in Pathological
Knowledge
c
Pathology of gastric cancer showed a remarkable
advancement. A German pathologist R. Borrmann
in Bremen published a famous textbook about
gastric cancer in 1926 [26]. He described the
macroscopic-type so-called Borrmann’s classifi-
cation. Detailed and huge follow-up data
informed us the characteristics of the disease.
The data supported the establishment of rational Fig. 1.4 (a–c) Development of gastroendoscope. (a)
Schindler’s prism flexible gastroscope, 1932; (b) Olympus
treatments. gastrocamera, 1950; (c) Hirschowitz gastrofiberscope,
1964
Progress of Diagnostic Methods

nal cancer with stenosis on 9 April 1879 [29].
Preoperative assessment of cancer extension and The procedures lasted two hours and half under a
biological characteristics became significantly 13-cm-long paraumbilical incision. The patient
accurate by endoscopy (Fig. 1.4a, b, c), endo- died on the fifth postoperative day but autopsy
scopic biopsy, double-contrast XP study, CT, was denied. Pe'an did not leave the detailed medi-
ultrasonography, tumor markers, etc. Nowadays cal record, and the cause of death was not clear.
surgeons can make the most appropriate treat- But mismatched blood transfusion or anasto-
ment plan for each individual patient based on motic leakage caused by catgut suture was
these information. speculated.
The Polish surgeon Ludwik Rydygier (1850–
1920) (Fig. 1.5b) carried out the second gastric
Challengers of Gastric Resection resection for a 64-year-old bugle soldier with
pylorus stenosis on 16 November 1880. He was a
Before the introduction of anesthesia and anti- research-oriented surgeon and he left the exact
septic method, a few successful gastric surgeries and detailed record [30, 31]. He made a series of
were reported. Most of them were removal of for- animal experiments on gastric resection and
eign body such as swallowed knife from the reconstruction techniques. He applied Lister’s
stomach [27, 28]. carbolic acid sterilization for hands, instruments,
Three great pioneers performed the memorial and linens by washing and air spraying. He car-
gastric resections for pyloric cancer in the short ried out the surgery at his private clinic with 25
period between 1879 and 1981. Jules-Émile Péan beds in Kulm, Poland. Rydygier performed the
(1830–1898) (Fig. 1.5a) of St Louis Hospital, surgery very carefully taking four hours and half
Paris, performed the first distal gastric resection under an upper midline incision using 60 stitches
(actually a pylorus resection) for a pyloroduode- for gastroduodenal anastomosis (Fig. 1.5c). The
Fig. 1.5 (a–c)
a b
Historical leaders and
Rydygier’s operation.
(a) Jules-Émile
Péan: first gastric
resection, (b) Ludwik
Rydygier: second gastric
resection, (c) pyloric
resection procedure by
Rydygier in 1880 (the
tumor was located close
to the pylorus. It was
resected and a two-layer
gastroduodenal
anastomosis was made
at the lesser curvature
side). (From S. Sokół's
drawing [161])
c
patient had smooth recovery after the surgery but and Winiwarter became a professor of surgery at
suddenly died in the early morning of the first the University of Liege, Belgium. Billroth sent
postoperative day. The cause of death would be his staffs to the Royal Infirmary of Edinburgh and
collapse brought by the preoperative poor condi- King’s College Hospital, London, for introducing
tion. The autopsy revealed no residual tumor and Lister’s aseptic method. On 29 January 1881,
no infection. Anastomotic leakage was denied by Billroth performed distal gastric resection on
water inflation test of the resected material. Therese Heller, a 43-year-old Vienna housewife
The honor of the first successful gastric resec- having eight children.
tion was given to Theodor Billroth (1829–1894) Billroth wrote a letter to Professor
(Fig. 1.6a), professor of surgery at the University L. Wittelshöfer, the publisher of the Wiener
of Vienna and chairman of the Second Surgical Medizinische Wochenschrift (Vienna Medical
Clinic of the Wien Allgemeines Krankenhaus Weekly), by himself informing his historical gas-
(Vienna General Hospital) (Fig. 1.6c). He pre- tric resection [33]. And his operation record was
pared his surgery very carefully. His two staffs, published by his colleague Anton Wölfler (1850–
Carl Gussenbauer (1842–1903) and Alexander 1917) (Fig. 1.6b) [34], and the record was studied
von Winiwarter (1848–1917), made animal in detail by Herbert Ziegler (Fig. 1.6d) [35]. On
experiments on the surgical techniques of gastric the day, his team applied Lister’s aseptic proce-
resection and anastomosis using dogs [32]. They dures except carbolic acid vapor spray method.
also made detailed research on pyloric cancer The surgical instruments; suture material, silk
behavior and possibility of curative resection thread and linens were sterilized with carbolic
using 542 autopsy records. Gussenbauer was the acid solution. They did not use catgut. Before
successor of Billroth at the University of Vienna, starting the operation, her stomach was irrigated
10 K. Maruyama
a c
Fig. 1.6 (a–f) Historical leaders and Billroth’s first suc- Österreichische Galerie Belvedere Palace, Wien; (d) the
cessful gastrectomy. (a) Theodor Billroth: third gastric first distal gastrectomy; (e) resected material of Therese
resection; (b) Anton Wolfler: gastroenterostomy; (c) Heller; (f) autopsy material, the duodenum left side (these
painting depicting Billroth’s operation in 1890 at Wien pathological materials are exhibited at the Josephinum
Allgemeines Krankenhaus by Albert F. Seligmann, Medizinischen Museum Universität Wien)
with 1.5 liters of warm water consuming one side for adjusting the anastomotic size. Thirty-
hour. Under chloroform anesthesia, Billroth three interrupted sutures were applied for gastro-
made an 11-cm-long right transverse incision, duodenal anastomosis not including the mucosal
crossing the midline just over the palpable tumor. layer. He used carbolized silk for ligatures and
A few hazelnut-size swollen lymph nodes were sutures (Fig. 1.6d).
found, and metastasis of medullary carcinoma The patient took smooth recovery from the sur-
was microscopically confirmed on one sample gery. She could drink and eat well from the third
node. Billroth followed the surgical procedures postoperative day. The dressing was changed on
established by dog experiments, and he spent the 6th postoperative day, and there was no sign of
only one hour and 30 minutes for his operation. infection. The patient was discharged from the
The duodenum was divided 1.5 cm distal from hospital on the 22nd postoperative day.
the tumor mass, and the middle part of the stom- The patient died of recurrence on 24 May
ach was divided. The divided stomach stump was 1881, 4 months after the operation. A pathologist
narrowed by 21 stitches at the greater curvature of the Vienna University, Dr. Zemann, made the
12 K. Maruyama
autopsy, and Ziegler made the detailed study [35]. into the new incision of posterior wall of the rem-
We can see the resected specimen and the autopsy nant stomach (Fig. 1.8c) [37]. John M.T. Finney
material in the Josephinum Medical Museum of (1863–1942) (Fig. 1.9a) of the Johns Hopkins
the University of Vienna (Fig. 1.6e, f). Hospital, USA, proposed a gastroduodenostomy
Within 2 months of Billroth’s operation, 21 method with whole gastric stump and lateral wall
similar gastrectomies had been performed, several of the duodenum in 1924 (Fig. 1.8d) [38].
of them in Billroth’s clinic. Survived cases were Various reconstruction methods with gastroje-
only three from them, one by Billroth and the other junostomy were proposed after the first success-
two by his colleagues, Wölfler and Vincenz Czerny ful Billroth I operation (Fig. 1.10). They were
(1842–1916) (Fig. 1.7a) [34]. Czerny was named “Billroth II operation,” with antecolic or
appointed professor at the University of Heidelberg retrocolic and iso- or antiperistaltic anastomosis,
where he founded the German Institute for with or without Braun’s enteroanastomosis, and
Experimental Cancer Research in 1906. A Polish- with partial or whole cut end of the stomach [39].
German surgeon from Danzig, Hans In 1885 Billroth published his Billroth II
Haberkant, reported that the surgical mortality Operation or the antecolic side-to-side gastroje-
rate was 69% (72/109 patients) in Europe in junostomy (Fig. 1.10a) [40, 41]. In 1888 this
1879–1887. The mortality rate was improved to operation was modified by his Austrian staff
43% (42/98 patients) in 1888–1894 [36]. This Anton F. von Eiselsberg (1860–1939) (Fig. 1.9b).
report informed us that gastric resection remained This procedure used retrocolic route with anasto-
as a risky surgery even after the first successful mosis between the stomach stump and side wall
operation. of the jejunum. Furthermore, this procedure was
Theodor Billroth placed the gastroduodenal refined by Franz von Hofmeister (1867–1926)
anastomosis at the lesser curvature side (Fig. 1.8a) (Fig. 1.9c) of the University of Tübingen,
for his first and second patients, but he changed Germany, based on a procedure by Eugen
the anastomotic site at the greater curvature side Alexander Pólya (1876–1944) (Fig. 1.9d) of
(Fig. 1.8b) for the third patient [35]. Emil Semmelweis University, Budapest (Fig. 1.10e)
Theodor Kocher (1841–1917) (Fig. 1.7b), a [42]. It was later refined by Hans Finsterer
Nobel Prize surgeon from the University of Bern, (1877–1955) (Fig. 1.11a) of the University of
Switzerland, reported an unique procedure to Vienna and became known as the “Hofmeister-
prevent anastomotic leakage in 1892. He closed Finsterer gastrectomy” (Fig. 1.10g) [43]. Here
stomach stump and inserted the duodenal stump the stomach cut end of the lesser curvature side is
Fig. 1.7 (a–b)
a b
Historical leaders. (a)
Vincenz Czerny: cancer
surgery, (b) Emil
Theodor
Kocher: reconstruction
Fig. 1.8 (a–d) Various Billroth I a b

type reconstructions. (a) Billroth
T, 1881; (b) Billroth T, 1883; (c)
Kocher E, 1891; (d) Finney JMT,
1924, and von Habere H, 1922
c d
Fig. 1.9 (a–d) Historical leaders of a b

the gastric cancer surgery. (a) John
MT. Finney: reconstruction, (b) Anton
F. von Eiselsberg: Billroth II
operation, (c) Franz von
Hofmeister: Billroth II reconstruction,
(d) Eugen A. Pólya: Billroth II
reconstruction
c d
14 K. Maruyama
closed, and the remaining greater curvature side method was previously performed by Hofmeister.
portion is anastomosed with the jejunum A pupil of Kocher, Ce'sar Roux (1857–1934)
(Fig. 1.10f). This procedure was popularized by (Fig 1.11b) of the University of Lausanne,
Finsterer based on his huge experiences of more Switzerland, described the Roux-en-Y recon-
than 10,000 gastric operations. Heinrich Ch. struction in 1927 (Fig. 1.10h) [47], which can be
Braun (1847–1911) of the University of applied not only for the distal gastric resection
Königsberg, Germany, proposed side-to-side but also for the total gastrectomy.
anastomosis between the afferent and efferent In this period, many Japanese surgeons stayed
jejunal loop for better passage of duodenal juice in Germany, and they introduced the latest surgi-
in 1892 (Fig. 1.10g) [44]. Donald C. Balfour cal technologies. In 1897, 16 years after Billroth’s
(1882–1963) of Mayo Clinic, USA, added Braun success, the first gastric cancer resection was
anastomosis to Po'lya, called Balfour-Pólya oper- done by Jihan Kondo (1866–1944) of Tokyo
ation, in 1917 (Fig. 1.10g) [45, 46]. But several University Hospital [48]. A pupil of Mikulicz,
literatures described that this reconstruction Hayari Miyake (1866–1945) (Fig. 1.11c) of the
Fig. 1.10 (a–h) Various

Billroth II type
a b
reconstructions. (a) Billroth
T, Wölfler A, 1885; (b)
Krönlein RU, 1888; (c)
Mikulicz JR, 1897; (d)
Moynihan B, 1923; (e)
Polya EA, 1911; (f)
Hofmeister-Finsterer, 1895;
(g) Balfour DC, 1917; (h)
Roux C, 1893–1898
c d
Fig. 1.10 (continued) e f
g h
Kyushu University, Japan, reported that 58 Universität Breslau, Germany (now Wroclaw
patients died of postoperative complication from Poland), opened actually the door of scientific
177 patients (33%) treated in 1904–1914 in his oncological surgery in 1898 [50–52]. He
department. He reported that the surgical death described that gastric cancer had four growth
rate was improved to 14.2% (56/395 patients) in directions: (a) local extension, namely, the stom-
1920–1927. The 3-year survival rate was 31.3% ach wall infiltration and adjacent structure inva-
(108/345 patients) in his series [49]. sion, (b) extension through the lymphatic vessels
to the regional nodes, (c) extension through the
blood vessels to the liver, and (d) peritoneal dis-
Powerful Drive for Curability semination. Mikulicz stressed that the cure could
be obtained only when these targets were
Billroth’s Polish-Austrian associate Johann F. removed perfectly. To remove the direct wall
von Mikulicz-Radecki (1850–1905) (Fig. 1.11d) expansion, total gastrectomy was proposed.
of the Schlesischen Friedrich-Wilhelms Combined resection of neighboring organs was
16 K. Maruyama
Fig. 1.11 (a–d)
Historical leaders of the a b
gastric cancer surgery. (a)
Hans Finsterer: Billroth
II operation, (b) C'ésar
Roux: Roux-en-Y
anastomosis, (c) Hayari
Miyake: treatment
results, (d) Jan Mikulicz-
Radecki: surgical
oncology
c d
applied for invasion to the adjacent structures. Total Gastrectomy

Systematic lymph node dissection could remove
the metastatic lymph nodes. However, cure from In 1987, 6 years after Billroth’s gastric resection,
the liver and peritoneal metastases could not be the first successful total gastrectomy for cancer
achieved by surgical treatment. Followings are was performed by a Billroth’s staff, Carl
the progress of these surgical treatments. B. Schlatter (1864–1934) (Fig. 1.13a) of the
University of Zurich, Switzerland [53, 54]. His Kitagawa (1864–1922) of the Nagoya Koseikan
reconstruction method was the Billroth II recon- Hospital [55]. The surgical mortality rate was
struction with antecolic end-to-side esophagoje- significantly high in this period. Various recon-
junostomy without Braun’s anastomosis struction methods were proposed with intention
(Fig. 1.12a). The first total gastrectomy was suc- to prevent leakage of the esophagojejunal anas-
cessfully performed in Japan in 1902 by Otojiro tomosis and regurgitation esophagitis (Fig. 1.12).
Fig. 1.12 (a–h) Various

a b
reconstruction methods
after total gastrectomy.
(a) Schlatter C, 1897;
(b) Schlöffer H, 1917;
(c) Roux C, 1907; (d) Orr
TG, 1943; (e) Graham RR,
1940; (f) Nishi M, 1972;
(g) Siewert-Peiper, 1972;
(h) Hunt CJ, 1952
c d
18 K. Maruyama
Fig. 1.12 (continued) e f
g h
Hermann Schlöffer (1868–1937) (Fig. 1.13b) of [58]. This procedure became the most popular
the University of Prague added Braun’s jejunoje- reconstruction method. Roscoe R. Graham
junostomy to Schlatter’s reconstruction in 1917 (1890–1948) (Fig 1.13d) of the University of
(Fig. 1.12b) [56]. César Roux applied his “Roux- Toronto, Canada, developed a unique anasto-
en-Y anastomosis” for the reconstruction after motic method in 1940, reinforcement of the
total gastrectomy in 1907 (Fig. 1.12c) [57]. esophagojejunostomy using the jejunal stump
Thomas G. Orr (1884–1955) (Fig. 1.13c) of the like a sandwich (Fig. 1.12e) [59, 60]. Mitsumasa
University of Kansas, USA, modified Roux- Nishi (1925–1998) (Fig. 1.13e) of the Cancer
en-Y reconstruction by end-of-esophagus-to- Institute, Tokyo, proposed the so-called double-
side-of-jejunum anastomosis in 1943 (Fig. 1.12c) tract method in 1972 connecting the duodenal
stump to the side of the jejunum in Roux-en-Y place of the resected stomach. Longmire created
reconstruction (Fig. 1.12f) [61]. We have now a single lumen tube from jejunal loop, like a
various reconstructions after total gastrectomy long Braun anastomosis [67]. We have various
(Fig. 1.12) [62–64]. interposition methods (Fig. 1.14) [68] including
Reconstruction by the jejunal segment inter- interposition of the ileocolic segment
position between the esophagus and duodenum (Fig. 1.14d) [69].
(Fig. 1.14a) was developed by Sadanobu Seo By these efforts, the surgical mortality rate
(1886–1946) (Fig. 1.13f) of the Chiba was remarkably improved and total gastrec-
University, Japan, in 1941 [65] and by William tomy became safer. This improvement led to a
Polk Longmire (1913–2003) (Fig. 1.13g) of the new opinion and trend; active application of
UCLA Medical Center, Los Angeles, in 1952 total gastrectomy for obtaining the better cur-
[66]. The other trend was building a reservoir in ability particularly in the USA. Gordon
Fig. 1.13 (a–h)
Carl B. Schlatter: total
gastrectomy, (b) Hermann
Schlöffer:
esophagojejunostomy, (c)
Thomas G. Orr: Roux-
en-Y anastomosis, (d)
Roscoe
R. Graham: anastomosis,
(e) Mitsumasa
Nishi: double-tract
anastomosis, (f) Sadanobu
Seo: jejunal interposition,
(g) William P. Longmire:
jejunal interposition, (h)
Gordon McNeer:
extended radical total
gastrectomy
c d
20 K. Maruyama
e f
g h
McNeer (1905–1967) (Fig. 1.14h) of the indicated in case when the proximal safe mar-
Memorial Sloan Kettering Cancer Center, gin from the cardia cannot be achieved by dis-
New York, reported that aggressive surgery tal gastrectomy.
showed good survival rate in 1948 [70–73].
Frank H. Lahay (1880–1953) (Fig. 1.15a) of
the Lahey Clinic, Boston, reported the indica- Combined Resection
tion and treatment results of total gastrectomy of the Neighboring Organs
in 1944 [74]. This idea was accepted by Mayo
Clinic [75] and many leading institutions in the To remove the cancer invasion to the neighbor-
USA. Some specialists recommended that total ing organs, these organs should be removed sur-
gastrectomy should be applied for any gastric gically. Invasion to the transverse colon and
cancer regardless of location and extension mesocolon and liver is not rare. Resection of
[76, 77]. However the total gastrectomy is now these organs is not difficult and is widely per-
Fig. 1.14 (a–d) Various

reconstruction methods a b
with interposition after
total gastrectomy. (a)
Seo T, 1941, and
Longmire WP, 1952; (b)
Schreiber HJ, 1978; (c)
Henley FA, 1952; (d)
Longmire/Beal, 1952
c d
formed. Combined resection of distal part of the Medical University [82]. This procedure became
pancreas was firstly proposed by Mikulicz in much more aggressive. Gordon McNeer demon-
1898 [50]. This surgical technique system strated the combined resection technique of the
was successively established by Alexander spleen, distal pancreas, and transverse colon
Brunschwig (1901–1969) (Fig. 1.15b) of the with total gastrectomy in 1948 [83]. Also Frank
Memorial Sloan Kettering Cancer Center, Lahay reported extensive combined resection of
New York, in 1948 [78] and Jirou Suzuki (1911– the left lobe of the liver, spleen, distal pancreas,
1968) of Chiba University in 1954 (Fig. 1.16a) and most part of the colon including the terminal
[79]. The surgical mortality rate of total gastrec- ileum in 1944 (Fig. 1.16b) [84]. In 1991
tomy with splenopancreatectomy was dramati- Mitsumasa Nishi proposed the so-called left
cally improved; 1.8% (1/57 patients) in 1955 by upper abdominal exenteration removing the
Tamaki Kajitani (1909–1991) (Fig. 1.15c) of the stomach, spleen, pancreas tail, left adrenal grand,
Cancer Institute Tokyo [80, 81], and 1.8% (2/113 transverse colon, and if necessary diaphragm
patients) in 1956 by Komei Nakayama (1910– and lower esophagus [85, 86]. However com-
2005) (Fig. 1.15d) of the Tokyo Women’s bined resection of the distal pancreas is still
22 K. Maruyama
Fig. 1.15 (a–d)
a b
Historical leaders of the
Frank H. Lahay: radical
total gastrectomy, (b)
Alexander
Brunschwig: distal
pancreatectomy, (c)
Tamaki Kajitani: distal
pancreatectomy, (d)
Komei Nakayama: distal
pancreatectomy
c d
risky, because control of pancreatic juice leakage (Fig. 1.18a) of the University of Berlin in 1895. He
from the resection stump is difficult. It causes developed the so-called Gerota method to visual-
frequent acute pancreatitis, subphrenic abscess, ize the lymphatic network [88]. For demonstrating
anastomotic leakage, and rupture of the ligated lymphatic vessels, he produced a new contrast
artery stump. Furthermore, Brunschwig pointed media: mixed fluid of Prussian blue oil, turpentine,
out the postoperative diabetes mellitus occurred and ether. He injected the fluid into the subserosal
after resection of the tail of the pancreas [87]. layer of the bowel [89]. Using the Gerota method,
Management of resection stump of the pancreas the famous Hungarian surgeon Polya (Fig. 1.9d)
is still an important subject to be improved. demonstrated lymphatic streams from the stomach
using 19 miscarried fetus in 1903 [90]. A French
anatomist Paul Poirier (1853–1907) (Fig. 1.18b)
Lymph Node Dissection of the University of Paris and his coworker Adrien
Charpy (1848–1911) of the University of Toulouse
The scientific study of the lymphatic system and published a textbook of anatomy in 1902 [91]. The
cancer metastasis was started firstly by the book included the detailed atlas of lymphatic
Romanian anatomist Dimitrie Gerota (1867–1939) streams and node stations from the stomach
Fig. 1.17 Lymphatic streams of the stomach (demon-

b strated by Gerota’s method, B. Cunéo and P. Poirier [162])
The next progress was expansion of the

regional node area beyond the upper border of
the pancreas to deeper area. French anatomist
Henri Rouviere (1876–1952) (Fig. 1.18d) of the
University of Paris published an important text-
book in 1932. He described historical achieve-
ments and his own study including the lymphatic
system around the celiac artery and the abdomi-
nal aorta [94]. Japanese anatomist Inoue Y. of the
University of Tokyo made a lymphographic
study by an unique contrast media, India-ink,
using 104 miscarried fetus in 1936 [95].
Along the idea of Mikulicz, big efforts were
paid to develop the effective surgical procedures
Fig. 1.16 Schema of splenopancreatectomy (a) and to remove the metastatic nodes. In 1944 Kajitani
resected material of extended surgery by Lahay FH [84] stressed the low reliability of macroscopic judg-
(b). Lahay removed the whole stomach together with
the abdominal esophagus, left lobe of the liver, distal pan- ment whether a node is metastatic or not. He
creas, spleen, omentum, terminal ileum, cecum, and found 20 false-negative patients (12%) in his 162
ascending/transverse/descending colon series [96]. That means the extent of node dissec-
tion should have enough safe margin based on the
(Fig. 1.17). They used both historical Sappey’s lymphatic stream study. Many leading surgical
mercury injection method [92] and Gerota’s oncologists in Japan (Fig. 1.19a) [61, 80, 82, 97,
method. Anatomist John Kay Jamieson (1873– 98], Korea (Fig. 1.19b, c) [99], Germany
1948) (Fig. 1.18c) and surgeon Joseph Faulkner (Fig. 1.19d, e) [100, 101], the UK (Fig. 1.19f)
Dobson (1874–1934) of the University of Leeds, [102], and the USA (Fig. 1.19g) [103–105]
England, made a detailed study of lymphatic sys- stressed the importance of systematic lymph
tem of the stomach in 1907 [93]. They completed node dissection. They conducted multicenter tri-
the classification of lymphatic streams and regional als in their country for evaluating the systematic
lymph node stations of the stomach. lymphadenectomy. The Japanese Research
24 K. Maruyama
Fig. 1.18 (a–d)
a b
Historical leaders of
the lymphatic system
study on the stomach.
(a) Dimitrie
Gerota: lymphatic
system, (b) Paul
Poirier: lymphatic
system, (c) John Kay
Jamieson: lymphatic
system, (d) Henri
Rouviere: lymphatic
system
c d
Society for Gastric Cancer was established and dure. Japanese nationwide registry of gastric can-
published the Japanese Manual in 1962 [106]. In cer reported that the 5-year survival rate was
the manual, 16 regional lymph node stations 37.5% in 1963–1966, which elevated to 70.l% in
were anatomically defined (Fig. 1.21a) [107]. 2008 [107]. Improvement in survival was remark-
They were classified into N1, N2, N3, and N4 able for Stage II, from 47.7% to 73.1%, and also
categories according to the occupation of main for Stage III, from 26.4% to 44.5%. This improve-
tumor based on the study of Inoue [95]. Complete ment was brought by popularization of the D2
removal of N1 and N2 nodes was called “D2 dis- dissection.
section.” This procedure was strongly recom- For complete node removal around the distal
mended, and it became the gold standard for pancreas and at the splenic hilum, pancreatico-
gastric cancer surgery in Japan and Eastern coun- splenectomy was considered essential
tries. Systematic node dissection could reduce (Fig. 1.16a). However this procedure had a high
the local recurrence and lead to better survival. risk, and it produced various pancreas-related
This is the significant effectiveness of this proce- complications and elevated mortality rate.
Cornelis J. H. van de Velde (Fig. 1.19h) of the attributed to unexperienced surgeons, poorer
Leiden University, Netherlands, organized the patient condition, and particularly unnecessary
Dutch multicenter clinical trial to compare the pancreas resection [109]. To reduce the compli-
D1 and D2 node dissection. He reported miser- cations, “pancreas- preserving total gastrec-
able treatment results on The Lancet in 1995 tomy” (Fig. 1.21b) was proposed by Keiichi
[108]. The mortality rate was 10% for 331 D2 Maruyama (Fig. 1.20a) of the National Cancer
patients and 4% for 380 D1 patients. He con- Center, Tokyo, in 1985 [110]. This procedure
cluded that “D2 dissection should not be used reduced the surgical death rate from 3.1% to
as standard treatment for Western patients.” 1.6% and the surgical complication rate from
Many letters with strong oppositions were sent 39.4% to 19.6% with no dropdown of the sur-
to The Lancet’s editor. They stressed that major vival. Furthermore it reduced the postoperative
reasons of the high mortality rate could be diabetes.
Fig. 1.19 (a–h) Historical

leaders of the gastric a b
cancer surgery. (a)
Dennosuke
Jinnai: lymphadenectomy;
(b) Jin-Pok Kim: Korean
GC Association; (c) Sung
Hoon Noh: KGCA and
IGCA; (d) Henning
Rohde German:
German TNM
Study Group; (e) Jorg
Rudiger Siewert: German
GC Association; (f) Sir
Alfred Cuschieri: British
D2 trial, MRC; (g) Byrl
James Kennedy: US
SEER Program; (h) CJH
van de Velde: Dutch D1/
D2 Trial
c d
26 K. Maruyama
e f
g h
Fig. 1.20 (a–b) a
b
gastric cancer surgery.
(a) Keiichi
Maruyama: pancreas
preservation, (b) Paul
H. Sugarbaker: total
peritonectomy
a b
Fig. 1.21 (a–c) Classification of Japanese manual, pan- (c) Sugarbaker’s procedure of total peritonectomy (left).
creas preservation, and total peritonectomy. (a) Japanese Continuous intraperitoneal perfusion by heated fluid with
classification of the regiona1 lymph nodes of the stomach, anticancer agent (right)
(b) schema of the pancreas-preserving procedure [110],
Surgery for Peritoneal Metastasis peritoneal dissemination in 1910 [111]. This

idea was taken over by a famous oncological sur-
Mikulicz wrote that gastric cancer extension had geon, Hans Finsterer of the University of Vienna,
four directions: direct invasion, lymphatic and he developed the surgical technique [112,
metastasis, vascular metastasis, and peritoneal 113]. A Japanese surgeon Masao Muto (1898–
dissemination [50]. Ernest W. Hey Groves of the 1972) (Fig. 1.22a) of the Tohoku University pub-
Bristol General Hospital, England, described the lished a detailed histological study on cancer
role of the omentum resection for removing the metastasis of the omental bursa in 1958 [114].
28 K. Maruyama
He found histologically confirmed metastases in intention of this procedure was to reduce dumping
78% of 643 resected omentum specimen using syndrome, postgastrectomy gallstone, and diges-
continuous section study. He suggested that the tive function disturbances after distal gastrectomy
metastatic mechanisms were not only by seeding for benign ulcer. His coworker Tsuneo Shiratori
in the peritoneal cavity but also by lymphatic (1922–2012) (Fig 1.22c) of the Nara Medical
and vascular routes. Peritoneal metastasis does University, Japan, expanded the indication for gas-
not occur in the T1 and T2 tumor, and the omen- tric cancer in 1991 [119]. It is now widely applied
tectomy is not indicated for these tumors. for a small-size gastric cancer located at the mid-
However the major role of bursectomy is now dle third of the stomach with no possibility of
considered for accurate lymph node dissection nodal metastasis around the pylorus.
around the pancreas, not for treatment of perito- Additionally nerve preservation was consid-
neal metastasis. ered for early-stage cancer. The most important
Paul H. Sugarbaker (Fig. 1.20b) of the nerve is the cystic branch of the vagal nerve. It
Washington Hospital Center, USA, published a was frequently injured during the lymphadenec-
unique strategy against peritoneal carcinomatosis tomy around the hepatoduodenal ligament. The
in 1995 [115]. He developed a surgical procedure injury caused contraction disturbance of the gall
of total peritonectomy combined with intraperito- bladder and gallstone. Koichi Miwa (Fig. 1.22d)
neal chemo-hyperthermia intended for cytoreduc- of the University of Kanazawa, Japan, recom-
tion (Fig. 1.21c). Yutaka Yonemura of the mended preservation of the pyloric and celiac
University of Kanazawa, Japan, applied this treat- nerves for the pylorus-preserving gastrectomy in
ment for gastric cancer in 1999 [116]. He reported 1996 (Fig. 1.23b) [120, 121].
that this treatment showed better survival benefit Alexander Brunschwig of the Memorial SK
than conventional chemotherapy and chemohy- Cancer Center, New York, pointed out the post-
perthermic peritoneal perfusion. This treatment is operative diabetes mellitus following resection of
now actively studied by Korean specialists [117]. the distal pancreas [78]. For the patients
with direct invasion to the pancreas, resection of
the pancreas is essential. But the pancreas-
New Trends: From Standardized preserving operation can be applied for the
Surgery to Individual Surgery purpose of lymphadenectomy around the pan-
creas and at the splenic hilus [122].
Since 1995 we had a new trend: a shift from
“extended and standardized surgery for radical
treatment” to “reasonable and individual surgery ptimal Extent of Lymph Node
O
considering safety and quality of life (QOL).” Dissection
Background of this shift were (1) remarkable
increase of early-stage cancer, (2) demand for According to the new trends, the extent of node
safe surgery and QOL, (3) progress of technol- dissection should be reasonable and individual-
ogy and instruments, and (4) storage of knowledge ized based on the tumor extension. To get the
and experiences. This new trend produced a large optimal extent area, the following new strategies
variation in surgical treatments. were proposed [122].
Keiichi Maruyama developed a computer sys-
tem, so-called Maruyama’s program, to estimate
Function-Preserving Surgery risk of metastasis at each regional lymph node
station based on detailed database of 3785
Japanese surgeon Tetsuo Maki (1908–2006) patients in 1989 [123]. This program can be
(Fig 1.22b) of the Tohoku University published an applicable even for Western patients showing
interesting surgical procedure, “Pyloruspreserving very high sensitivity, specificity, and accuracy
gastrectomy,” in 1967 (Fig 1.23a) [118]. The [124]. Elfriede Bollschweiler of the Technical
Fig. 1.22 (a–d)
gastric cancer surgery.
(a) Masao
Muto: omentectomy, (b)
Tetsuo Maki: pylorus
preservation, (c) Tsuneo
Shiratori: pylorus
preservation, (d) Koichi
Miwa: nerve
preservation
c d
University of Munich produced the other com- the pancreas head, the para-aortic area, and the
puter system, “artificial neural network,” for pre- mediastinum [127]. The survival benefit of “para-
diction of lymph node metastasis in 1996 [125]. aortic lymphadenectomy” (Fig. 1.26) was not
She reported high reliability in the estimation of high [128–130]. Leading institutions reported
the node metastasis. that 5-year survival of the para-aortic node-
A unique method, “intraoperative lymphogra- positive patients was between 11% and 23% after
phy by India-ink,” was introduced to visualize the para-aortic dissection. Mediastinal node metasta-
lymphatic streams and regional lymph nodes sis was not rare for advanced proximal cancer
(Fig. 1.25) [122]. Toshio Takahashi (Fig. 1.24a) of with esophageal invasion. Most metastases were
the Kyoto Prefectural Medical University and his found in the lower paraesophageal lymph nodes
coworker Akio Hagiwara developed a fine acti- (16.1%) and in the posterior mediastinal lymph
vated carbon particle (190 nanometers in average nodes (3.2%). These nodes can be removed by
diameter) in 1991 [126]. It had a strong affinity for the “transdiaphragmatic approach” proposed by
lymphatic structures and became a useful contrast Henrique Walter Pinotti (1929–2010) (Fig. 1.24b)
media, so colled “India ink.” This staining became of the University of São Paulo, Brazil, in 1983
a useful guide for accurate node removal particu- [131]. Yuji Tachimori of the National Cancer
larly for the para-aortic lymphadenectomy. Center, Tokyo, reported that the 30-day mortality
Lymphadenectomy areas were expanded to of Pinotti’s approach was 0% and the morbidity
the hepatoduodenal ligament, the back surface of was 18% in his series [126, 132]. Next topic was
30 K. Maruyama
a “Sentinel Node Navigation Surgery” [132]. This

idea is now accepted and clinically applied for
breast cancer, melanoma, head and neck tumor,
etc. Yuko Kitagawa (Fig. 1.28a) of the Keio
University, Tokyo, published a detailed clinical
study on this procedure for gastric cancer surgery
in 2002 [133]. He applied a radioactive mm99
Tin colloid as the tracer. He reported high detec-
tion rate, sensitivity, and accuracy, 97%, 94%,
and 99%, respectively, in 210 cT1 and cT2
patients. He found 3.9 hot nodes in average in his
series. Kitagawa stressed that unnecessary lymph
node dissection can be avoidable by the sentinel
node navigation.
According to the instruction stated above,
individual, reasonable, and effective lymph node
b dissection can be applied for each patient.
Minimally Invasive Surgery
Japanese endoscopist Masahiro Tada of the

Yamaguchi University applied endoscopic polyp-
ectomy technique to remove small mucosal can-
cer in 1988 [134]. This idea was improved by
endoscopist team of the National Cancer Center,
Tokyo. They developed “endoscopic mucosal
resection (EMR)” [135] and “endoscopic submu-
cosal dissection (ESD)” (Fig. 1.27) [136].
Intention of the endoscopic resection is to avoid
disadvantages and risk of open gastric resection
and to get quick recovery. This treatment is indi-
cated for early-stage cancer with definitely no
node metastasis, namely, (a) mucosal cancer, (b)
elevated or flat lesion, (c) differentiated adeno-
carcinoma, and (d) less than 3.0 cm in diameter.
They developed a useful device “insulated ball
tip electrosurgical knife (IT-knife)” for peeling
the mucosal and submucosal layer from the mus-
cle layer in 1996 [136, 137]. They reported no
cancer death from their 1783 patients treated in
1989–2003 [138].
The laparoscopic surgery became popular all
over the world, particularly in Japan [139–141],
Korea [142, 143], Taiwan [144, 145], Germany
[146], and Italy [147–149]. The intention is to
Fig. 1.23 (a–b) Pylorus-preserving gastrectomy and nerve get quick recovery, less pain, and cosmetic
branchings of the stomach. (a) Pylorus- and nerve-preserving advantage. The indication was mostly for early-
gastrectomy, (b) nerve branchings (anterior view, back view) stage cancer but now expanded to advanced can-
a b
Fig. 1.24 (a–c) Lymphatic channels from the distal third (a), middle third (b), and proximal third (c). (Demonstrated
by intraoperative subserosal injection of the India ink (fine activated carbon particle solution))
Fig. 1.25 (a–b) a b
Historical leaders.
(a) Toshio
Takahashi: activated
carbon particle,
(b) Henrique Walter
Pinotti:
transdiaphragmatic route
32 K. Maruyama
a b c d
e f g h
i j k l
m n o p
Fig. 1.26 (a–p) Techniques of the para-aortic lymph extended pancreas head mobilization and upper left area
node dissection. Dissection of the lower right (a–f), the (m–p) under mobilization of the spleen and distal
lower left (g–h), and the upper right (i-l) areas under pancreas
cer. Surgical technique, procedures, and (Fig. 1.28b) of the Oita University, Japan, devel-
instruments were remarkably developed in the oped “laparoscopic gastric resection with sys-
last 20 years. And the quality of surgery is now tematic LN dissection” in 1994 [141, 152].
evaluated as the same level of the open surgery. Ichiro Uyama (Fig. 1.28c) of the Fujita Health
Masahiko Ohgami of the Keio University, Tokyo, University, Japan [141, 150, 151], and Cristiano
proposed the “lesion lifting method” or wedge G Hüscher (Fig. 1.28d) of the Azienda G Rummo
resection in 1987 [139]. Seigo Kitano Hospital, Benevento, Italy [147–149], developed
a b
c d
Fig. 1.27 (a–h) Endoscopic submucosal dissection cancer border by electric cautery, (g) mucosal cutting
(ESD). (a): EMR and ESD, (b) insulated ball tip knife completed by IT-knife, (h) pealing up the mucosal and
(IT-knife), (c) cutting the mucosa by IT-knife avoiding submucosal layers, (g) after the ESD exposing the muscu-
perforation, (e) small-size mucosal cancer, (f) marking the lar layer
34 K. Maruyama
e f
g h
various new laparoscopic procedures. Japanese at high-volume centers in the world. The leader
Laparoscopic Surgery Study Group reported the of this field is now Korea. da Vinci robot surgery
treatment results of 1294 patients with distal, system was introduced to Yonsei University,
proximal, and total gastrectomy in 2007. The Seoul, and the Seoul National University in the
postoperative morbidity was 14.8%, the mortal- early period. From these institutions, Woo Jin
ity was 0.0%, and the recurrence was found in Hyung (Fig. 1.28e) and Han-Kwang Yang
only six cases (0.6%). (Fig. 1.28f) published their surgical techniques
We are now introducing “robot surgery sys- and treatment results [151, 152, 153]. Han-
tem” for laparoscopic gastrectomy. Problems of Kwang Yang is now trying the single-port laparo-
this treatment were (a) expensive machine and scopic surgery [154]. Japan and Italy actively
devices and (b) a few institutions and experts. introduced the robot machine and applied it for
Therefore robotic gastrectomy can be done only gastric cancer surgery [155–157].
ational and International Study

N the Deutschsprachiges TNM Ausshuss. Intention
Groups for Gastric Cancer of the manual is to offer “a common language” in
recording their clinical findings and assessing the
The first edition of the UICC TNM classification results of different treatment methods. After
Livre de Poche was published in 1968 [158] with several revisions, the seventh edition is now in
cooperation of the American Joint Committee for use worldwide [159].
Cancer Staging, the Canadian National Specialists of gastric cancer organized their
Committee, the Japanese Joint Committee, and national and international study groups and pub-
Fig. 1.28 (a–g)
a b
gastric cancer surgery
and a robotic surgery
system. (a) Yuko
Kitagawa: sentinel node
navigation, (b) Seigo
Kitano: laparoscopic
gastrectomy, (c) Ichiro
Uyama: laparoscopic/
robotic gastrectomy,
(d) Cristiano G. Hilscher:
laparoscopic gastrectomy,
(e) Woo Jin Hyung:
robotic gastrectomy, (f)
Han-Kwang Yang: single-
port laparoscopic, (g) da
Vinci robotic surgery
system
c d
36 K. Maruyama
e f
lished the manuals to record the findings of this the WHO classification and monographs. The
disease. The most active national study groups are roles were transferred to the International Gastric
listed on Table 1.1. World Health Organization Cancer Association which was established in
nominated the leading institutes as the WHO 1995. The first International Gastric Cancer
Collaborating Center for Gastric Cancer Congress was held in Kyoto in 1995. The con-
(WHO-CC) in 15 countries in 1970. The head gress was held every 2 years in the cities of Asia,
quarter was placed at the National Cancer Center, Europe, and America (Table 1.2). The association
Tokyo. The WHO-CC organized general meet- started to publish their journal Gastric Cancer in
ings, seminars, and training courses and published 1996 [160], and it got now very high citation.
Table 1.1 Active National Gastric Cancer Study Group seems to be minimally invasive surgery and QOL
Japanese Gastric Cancer 1962 6000 Journal for patients with early-stage cancer. However we
Association have still a huge number of patients with advanced
Korean Gastric Cancer 1993 Journal cancer or incurable cancer. I believe the oncologi-
Association
Taiwan Collaborative 1989 500
cal surgeons should pay their effort much more to
Oncology Group cure the advanced cancer.
Chinese Gastric Cancer 1976
Association
Italian Gastric Cancer 2001 References
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Part II
Staging of Gastric Cancer
Staging of Gastric Cancer: Current
Revision and Future Proposal 2
Jingyu Deng, Jiping Wang, and Han Liang
Gastric cancer (GC) is the fourth most com- motherapy and target therapy, and patients’ dis-
mon malignancy and ranks the third as cause of ease characteristics are constantly changing and so
death (990,000 cases, 738,000 deaths) worldwide does the prognosis. Hence, the UICC/AJCC TNM
(ref. [1] WHO). Due to the lack of cost-effective staging system has been revised accordingly every
screening test and the lack of specific symptoms, few years since its induction into clinical prac-
most gastric cancer cases were diagnosed at the tice since 1977. The seventh edition UICC/AJCC
advanced stages. It is very important to appropri- TNM classification for GC was modified after the
ately stage GC patients since it is associated with Buffalo Meeting 2008 as the result of the consen-
the choice of treatment modalities and patients’ sus between the Eastern (Japanese and Korean)
prognosis. The current staging modalities include and Western GC classification. In 2010, the sev-
endoscopy, CT, PET/CT, and laparoscopy. The pri- enth edition (7th ed.) TNM classification for GC,
mary goals of the staging are to evaluate whether comprising of the data from Japan and Korean,
a patient has regional or distant metastasis (M), was published with minor revisions in T stage and
whether the tumor involves local/regional lymph major revisions in N stage compared to the previ-
nodes (N), and whether the depth of tumor invasion ous editions of TNM classification [2].
into the different histology layers between mucosa
and serosa (T). Combining the three components, The seventh edition UICC/AJCC TNM classification
Union for International Control Cancer (UICC)/ for GC
American Joint Committee on Cancer (AJCC) has T1a Tumor invades lamina propria
defined the most commonly used GC staging sys- T1b Tumor invades submucosa
tem, tumor-node-metastasis (TNM) staging sys- T2 Tumor invades muscularis propria
tem [1]. As the improvement in cancer awareness, T3 Tumor invades subserosa
T4a Tumor penetrates serosa without invasion of
methods in cancer screening, advancement in che- adjacent structures
T4b Tumor invades adjacent structures
N1 Metastasis in 1–2 regional lymph nodes
J. Deng · H. Liang (*)
N2 Metastasis in 3–6 regional lymph nodes
Department of Gastroenterology, Tianjin Medical
University Cancer Hospital, City Key Laboratory of N3a Metastasis in 7–15 regional lymph nodes
Tianjin Cancer Center and National Clinical Research N3b Metastasis in more than 15 regional lymph
Center for Cancer, Tianjin, China nodes
M0 No distant metastasis
J. Wang
Hepatobiliary Cancer, Division of Surgery Oncology, M1 Distant metastasis
Brigham and Women’s Hospital, Harvard Medical pM1 Distant metastasis microscopically confirmed
School, Boston, MA, USA

https://doi.org/10.1007/978-3-662-45583-8_2
46 J. Deng et al.
Stage grouping of GC in accordance with the seventh Society for Diseases of the Esophagus (ISDE)
edition UICC/AJCC TNM classification
and has been accepted and used worldwide
Stage 0 Tis N0 M0
before the seventh edition TNM classification
Stage IA T1 N0 M0
Stage IB T2 N0 M0
was published [5].
T1 N1 M0 According to the sixth edition TNM clas-
Stage IIA T3 N0 M0 sification, EGJ carcinoma may classify into
T2 N1 M0 either esophageal cancer or GC on the basis of
T1 N2 M0 the judgment of the physicians. However, many
Stage IIB T4a N0 M0 investigators found that adenocarcinoma of the
T3 N1 M0 proximal stomach was similar, or even identical,
T2 N2 M0 to Barrett’s esophagus-associated distal esopha-
T1 N3 M0
geal adenocarcinoma on the basis of compara-
Stage IIIA T4a N1 M0
ble characteristics in epidemiology [6], clinical
T3 N2 M0
T2 N3 M0 presentations [7], molecular pathobiology [8],
Stage IIIIB T4b N0 or N1 M0 and histopathology [9]. Subsequently, AJCC
T4a N2 M0 adopted the notion that all EGJ cancer should be
T3 N3 M0 required to comply with the rule for esophageal
Stage IIIC T4a N3 M0 adenocarcinoma, which has been published in
T4b N2 or N3 M0 the seventh edition of the cancer staging manual
Stage IV Any T Any N M1 [10]. The seventh edition TNM classification
included the meticulous classification of EGJ
carcinoma. However, an obvious issue of major
concern was the following rule: “A tumor with
evisions on the Current Edition
R the epicenter of within 2 to 5 cm below the EGJ
TNM Classification for Gastric and also extends into the esophagus is classi-
Cancer fied and staged using the esophageal scheme.
Tumors with an epicenter in the stomach greater
xplicit Staging in Esophagogastric
E than 5 cm from the EGJ or those within 5 cm
Junction Carcinoma of the EGJ without extension in the esophagus
are classified and staged using the gastric car-
Carcinoma of the esophagogastric junction (EGJ) cinoma scheme.” In another word, EGJ carci-
is defined by the WHO as “tumors cross the EGJ noma included in the esophageal chapter on the
regardless of where the bulk of the tumors lies” basis of the new TNM staging system according
[3]. The classification carcinoma of EGJ, defined to the anatomical criteria “5 cm rule” proposed
by Siewert and Stein, was approved at the sec- by Siewert was based on an obscure concept of
ond International Gastric Cancer Congress in the tumor epicenter. Some of the gastric fun-
Munich in April 1997 [4]. In accordance with the dus tumor might be considered as esophageal
anatomic cardia, EGJ cancer can be divided into cancer [11]. As the result, the current revision
three subtypes: type I, adenocarcinoma of the did not resolve the well-known controversial
distal esophagus with the tumor center located issue: Should type III tumors be treated as GC
between 1 and 5 cm above the anatomic EGJ; invading the EGJ, considering the origin of
type II, true carcinoma of the cardia with the the tumors? Some literatures have shown that
tumor center within 1 cm above and 2 cm below esophagectomy has not improved the survival
the EGJ; and type III, subcardial carcinoma with rate compared to an extensive gastrectomy for
the tumor center between 2 and 5 cm below type II tumors arising from the same origin as
EGJ. This classification was approved at the con- type III tumors [5]. In fact, more and more clini-
sensus conference of the International Gastric cians think that the optimal treatment modali-
Cancer Association (IGCA) and the International ties should be selected based on the distance
2 Staging of Gastric Cancer: Current Revision and Future Proposal 47
of tumor invasion to the stomach or esophagus of the positive cases among different institu-
rather than the location of the central region of tions. Therefore, the prognosis and treatment of
the tumor [12]. patients with no macroscopic peritoneal metasta-
ses but with peritoneal cytology-positive diseases
remain as controversial issues. Further rigorous
roposal of Positive Cytology
P definition of the methods in detecting peritoneal
as Distant Metastasis washing tumor cell and studies in the staging and
the appropriate comprehensive treatment of this
Peritoneal washing cytology, as a preoperative group of patients are needed.
staging tool, has been gradually adapted into
clinical practice. Leake et al. [13] recently dem-
onstrated that recurrence rates for patients posi- inimum Number of Examined
M
tive for peritoneal cytology ranged from 11.1% Lymph Nodes
to 100%, while those negative for intraperitoneal
free cancer cells (IFCCs) had recurrence rates The recommended minimum number of exam-
of 0–51%. Overall survival was significantly ined (dissected) LNs required for proper staging
decreased for patients with positive peritoneal remains controversial, because this number var-
cytology by using a systematic review of the ies considerably between institutions and coun-
accuracy and utility of peritoneal cytology in tries. Before 1997, all staging systems (UICC,
patients with gastric cancer. Other reports in the AJCC, and Japanese Committee on Cancer) used
literature indicate that a positive peritoneal cytol- for this disease defined N stage by the location
ogy is an independent predictor of poor prognosis of LN metastases relative to the primary tumor (I
following curative surgery, with median survival do not understand this sentence). Subsequently,
of as poor as distant metastasis [14–16]. In addi- many studies revealed that the number of posi-
tion, Yamamoto et al. [17] also validated that GC tive nodes best defined the prognostic influence
with peritoneal cytology (+) had a poor prognosis of metastatic LNs in GC. In 1997, the UICC and
because it is associated with non-curative factors, AJCC redefined the pathologic nodal status based
peritoneal dissemination, and liver or LNs metas- on the number of involved nodes rather than their
tases. Mezhir et al. [16] recommended to abandon location. In an effort to improve staging accuracy,
gastrectomy for patients with positive peritoneal it was recommended that a minimum of 15 lymph
cytology even in the absence of gross peritoneal nodes should be examined to guarantee the accu-
disease due to the poor outcomes. Thus, both the racy of prognostic prediction of N stage, espe-
Japanese Gastric Cancer Association (JGCA) and cially in the definition of N0 [21]. Karpeh et al.
the seventh edition TNM classification classify [22] demonstrated that the overall distribution of
positive peritoneal cytology as stage IV disease patients staged by the fifth edition AJCC classifi-
[18]. Conversely, few authors reported that peri- cation did not change significantly if 15 or more
toneal washing cytology using samples harvested LNs were examined, but median survival for N1,
in the abdominal cavity was not able to predict N2, and N3 by the fifth edition AJCC classifica-
peritoneal recurrence or survival in GC patients tion increased significantly when 15 or more LNs
[19]. Depending on the various methods for per- were examined. It must be emphasized that the
forming a peritoneal washing cytology, there is a extent of LN dissection and the thoroughness of
large discrepancy in the frequency of a positive the pathologist’s examination of the specimen
peritoneal cytology. The rate of positive cases together determine the number of LNs ultimately
was found more than 20% on a routine cytol- retrieved [23]. It is clear that techniques such as
ogy, 35% on immunohistochemistry, and 50% fat clearing can increase the number of nodes
on RT-PCR in cases of a serosa invasion-positive and that an increase in the number of examined
GC [20]. Inevitably, there is a large discrepancy lymph nodes will increase the number of positive
in the positive rates and median survival time nodes, which will alter the stages [24]. Recently,
48 J. Deng et al.
Smith et al. [25] reported that survival would LN. All those evidence indicated two paradox
improve by 7.6% (T1/2N0), 5.7% (T1/2N1), 11% problems that the seventh edition system is fac-
(T3 N0), or 7% (T3 N1) if every 10 extra LNs ing: It is well known that inadequate (<16) exam-
were dissected in the Surveillance, Epidemiology, ined lymph nodes will cause stage migration. On
and End Results database between 1973 and the other hand, most American patients have <16
1999. Furthermore, they demonstrated that a LN examined.
cut-point analysis yielded the greatest survival Bilici et al. [30] recently reported that the
difference at 10 LNs examined but continued to superiority of classification based on the ratio
detect significantly superior survival differences between metastatic and examined nodes to deter-
for cut points at up to 40 LNs, always in favor mine N stage for prediction of overall survival
of more LNs examined [25]. Son et al. [26] ana- of patients with radically resected GC could not
lyzed the survival rates of 10,010 patients who be proved, even in patients with <16 examined
underwent curative gastrectomy from 1987 to LNs. This numeric change seems to arise from
2007 and then showed that patients who had T1 the figure of 16 introduced for N3b in the seventh
tumor classification, N0 LN status, and stage I edition TNM classification more than from the
disease with an insufficient number of examined “numeric controversies” of literature.
LNs (≤15 nodes) after curative gastrectomy had Has the latest UICC TNM stipulated that GC
a significantly worse prognosis than patients who should be staged independent of the number of
had ≥16 examined LNs. In accordance with the examined LNs? As we know, the main reasons
fifth/sixth edition TNM classification, Nio et al. for examination of an insufficient number of LN
[27] analyzed 223 pN0 patients with GC and then s after curative gastrectomy are inaccurate LN
found that patients with pN0 in pT1 stage should dissection or retrieval. Besides, harvesting of a
be required for a minimum of six examined number of nodes “small” to differentiate N sub-
nodes. Jiao et al. [28] reported that the number categories is not a guarantee for enough extent
of examined LNs was the independent predictors of lymphadenectomy. Therefore, it is worthwhile
of overall survival of patients with node-negative to discuss whether the requirement of appropriate
GC, and patients with ≤15 examined LNs were threshold of examined LNs for accurate evalua-
more likely to experience locoregional and peri- tion N stage of GC.
toneal recurrence than those with no less than 16
examined LNs.
Therefore, the latest edition TNM classifica- roposed Lymph Node Ratio
P
tion specifies that “histological examination of to Be Included in the Staging System
a regional lymphadenectomy specimen should
ordinarily include 16 or more LNs” to avoid The ratio between metastatic and dissected (exam-
understaging. However, only 1/3 of the gastric ined) LNs has been proposed as a simple, conve-
cancer patients have more than 15 lymph nodes nient, and reproducible system that can be used
examined (my Annals of Surgery paper). In fact, to better identify the subgroup of gastric, breast,
the new UICC/AJCC system confirmed the fol- pancreatic, and colon cancer patients with simi-
lowing sentence (added in previous editions) as lar prognosis, thus minimizing the stage migra-
regards the pN0 definition: “If the LNs are nega- tion phenomenon that can be observed using the
tive, but the number ordinarily examined is not TNM classification [31–33]. Owing to decrease
met, classify as pN0.” Therefore, this appears to the stage migration, many investigators empha-
mean that the figure of 16 is a recommendation, sized that ratio between metastatic and dissected
but no longer a requirement, for pN0 staging LNs is a convenient, repeatable, and creditable
[11]. At the meantime, Wang et al. [29] clearly variable for accurate prediction of the progno-
showed that for patients who have N0 disease and sis of GC patients, regardless of the number of
<16 LN examined, their survival is the same for dissected LNs and extent of lymphadenectomy
patients who had N1 disease with >15 examined [34, 35]. It is still controversial whether the ratio
between metastatic and dissected LNs is superior tumor does not guarantee recurrence-free long-
to the number of metastatic LNs for predication term survival, but histopathological complete
of the overall survival of GC patients. Wang et al. responders have better prognosis compared to
[29] demonstrated that AJCC staging misclassi- partial responders [47]. Although the percentage
fied 57% of patients and TNrM staging misclassi- of major responder tumors after perioperative
fied only 12% when misclassification was defined chemotherapy is low in GC [48], the pathologi-
as any subgroup in which median survival fell cal assessment may be affected by possible tumor
outside the 95% confidence interval of the GC regression. In the seventh edition TNM classifi-
patient group’s overall median survival. cation, a clinical TNM classification recorded
On the other hand, several authors reported the following the neoadjuvant therapy should be
negative results of the ratio between metastatic identified by the prefix “y,” as “ycTcNcM.”
and dissected LNs for prediction the prognosis Actually, the ypTNM classification is used to
of patients with adequate dissected nodes, espe- reflect the extent variation of tumor after neoad-
cially in the group of patients with 15 or more juvant therapy. In analyzing the results, it can be
dissected nodes [36, 37]. Actually, it is absolutely differentiated between patients treated with pri-
incorrect that the number of the examined nodes mary surgery (cTNM, pTNM) and those treated
can instead be use as an indicator of the extent by surgery following neoadjuvant treatment
of node dissection. In addition, how to accurately (ycTNM, ypTNM) [49].
define the cutoffs of ratio between metastatic and
dissected LNs is unclear else. However, we dem-
onstrated that the ratio between metastatic and roposal of the Next Edition TNM
P
dissected LNs was an important variable which Classification for Gastric Cancer
was capable of the improvement of the survival
discrimination of GC patients with positive LNs mendment Both Extent
A
[37]. Therefore, the clinical values of the ratio and Number of Dissected Lymph
between metastatic and dissected LNs need to be Nodes as the Prerequisites
further discussed in elaborate analysis. for Staging the Lymph Node
Metastasis
refix “y” for TNM Classification After

P As compared with the sixth edition TNM clas-
Neoadjuvantly Treated Tumor sification system involving N stage, the seventh
edition more reliably and accurately categorized
For locally advanced lesion, the standard treat- the number of metastatic LNs for the purpose
ment is perioperative chemotherapy in Europe of predicting the overall survival of patients
[38–42]. So far, R0 resection is aimed for by after curative surgery, regardless of the extent
gastrectomy with standard D2 lymphadenectomy of lymphadenectomy or the number of exam-
[41]. However, even with D2 gastrectomy and ined LNs. However, the only treatment known
adjuvant chemotherapy with S-1, the prognosis of to offer cure for GC is adequate surgery for
tumor is not satisfactory [43]. Neoadjuvant che- potentially exhaustive removal of the primary
motherapy, which is an exception to improve the tumor and the metastatic LNs. It is undoubtedly
radical resection condition, is under heated dis- that the stage migration may be brought out by
cussion about its definite role in improving cure using the seventh edition TNM classification in
rate for GC patients [44, 45]. Authors reported GC patients who have undergone D1 lymphad-
that only about 21% GC patients had complete enectomy or presented with less than 16 exam-
or subtotal tumor regression, which may provide ined LNs, which can result in lower N stage
objective and highly valuable prognostic infor- classifications and falsely higher survival rate.
mation in addition to posttherapeutic lymph node The patients with the extragastric LN metasta-
status [46]. In addition, response of the primary sis had the obviously lower 5-year survival rate
50 J. Deng et al.
than patients with the perigastric LN metastasis GC, even in negative-node patients [60]. Occult
or without any LN metastasis [50]. It is worth tumor cells that comprised micrometastases (MM;
noting that limited lymphadenectomy cannot >0.2 mm and < or = 2.0 mm) and isolated tumor
provide the accurate extent of LN metastasis cells (ITC; < or = 0.2 mm) are the original hema-
owing to the lack of dissection and examination toxylin and eosin-stained sections of all LNs from
of extragastric LNs, which is the key causation patients that are previously considered as tumor-
for the bias of prognosis evaluation. D2 lymph- negative by the local pathologist. The number of
adenectomy and no less than 16 examined/ examined LNs and the percentage of occult tumor
dissected LNs, as the requisite guarantees for cell in positive LNs were identified to be indepen-
adequate quality of the surgery, can provide suf- dent risk factors for locoregional disease recur-
ficient information concerning nodal metastases rence and distant disease recurrence, respectively
to allow the prediction of prognosis using the [58]. Yonemura et al. [61] demonstrated that 5 of
seventh edition of the TNM classification sys- the 37 negative-node patients with isolated tumor
tem involving N staging [51]. cells (pN0(i+)) versus 1 of the 271 negative-node
patients with no evidence of isolated tumor cells
(pN0(i−)) died from recurrence by using immu-
Occult Tumor Cells in Lymph Nodes nohistochemical detection (P = 0.014). Lee et al.
as a Novel Subcategory of N Stage [62] found that LN micrometastases were iden-
tified by cytokeratin immunostaining in 196 GC
Although many researchers demonstrated that patients classified as pN1, consisting of 20 cases
the postoperative prognosis of node-negative with micrometastases (pN1mi(i+)), 34 cases with
GC patients was significantly better than that only micrometastases (pN1mi), and 142 cases
of node-positive GC patients, minority of node- with pN1 with one or more macrometastases
negative GC patients had recurrence and poor (pN1). Although the association between occult
survival [52–54]. Multivariate analysis showed tumor cells and patients’ overall survival is still
that D1 lymphadenectomy, few dissected nodes, controversial, the high recurrence rate for patients
and serosal involvement were the risk factors has been detected by using immunohistochemical
of postoperative recurrence of node-negative method with micrometastases [63].
GC patients [54]. Biffi et al. [55] reported that
more extended LN resection offers protection,
as node- negative GC patients who had ≤15 Extracapsular Lymph Node
nodes removed had significantly worse disease- Involvement in Gastric Cancer
free survival and overall survival at multivariate
analysis than patients in whom >15 nodes were Tumor penetration of the LN capsule in metastatic
removed. In addition, authors also demonstrated LNs is called as extracapsular LN involvement.
that the sufficient number of negative LNs har- For several nongastrointestinal malignancies,
vested might improve the overall survival rate of like breast, prostate, pharynx, larynx, and blad-
GC patients after curative gastrectomy [56, 57]. der cancer, the prognostic value of extracapsular
Occult tumor cells in LN may result in the LN involvement has already been demonstrated
inaccuracy of pathological N category [58]. to be negatively associated with overall and
Latest research revealed that the majority of the disease-free survival of patients [64–70]. Recent
retrieved studies (75%) evaluating the predictive systematic review showed that extracapsular
role of occult tumor cells concluded that its pres- LN involvement was a common phenomenon
ence was associated with a worse prognosis of in patients with gastrointestinal malignancies
GC patients by using the systematic analysis [59]. and could identify a subgroup of patients with
Therefore, increasing the number of examined a significantly worse survival [71]. Tanaka and
LNs during surgery could reduce the chance of colleagues concluded that extracapsular LN
residual malignancy and improve the prognosis of involvement was a significant risk factor for peri-
toneal dissemination and liver metastasis in GC tumors, including GC [80]. More recent studies
patients [72, 73], which was similar to the research released that HER2 is a poor prognostic factor in
results reported by Alakus in 2010 [74]. With the GC patients [81–83], especially those with liver
multivariate analysis, extracapsular LN involve- metastases and/or LN metastasis [84, 85].
ment also was identified to be an independent Yamaguchi et al. [86] proposed that tumor
risk factor influencing the outcome of patients size, given as the maximum diameter of tumor,
with GC [75]. The further study showed that the could provide important information useful for
presence of extracapsular LN involvement could evaluating the potential impact of GC double
affect the survival of GC patients with only sin- time screening programs in terms of the degree
gle LN metastasis [75]. Additionally, Nakamura of improvement in prognosis. Surgeons usually
reported that extracapsular LN involvement was pay more attention to tumor size than depth of
also identified to be useful in combination with tumor invasion because tumor size might have
N stage of the TNM classification, representing a direct impact upon patients’ surgical manage-
a promising indicator to refine the LN metastatic ment and outcome. Researchers demonstrated
category in GC [76]. that there were obvious correlations between
tumor size and other tumor-relative clinicopatho-
logical variables such as LN metastasis, depth of
Other Variables’ Assessment tumor invasion, and type of Lauren classification,
for Enhancement of the Efficiency which might result in the poor prognosis of GC
of Stage of Gastric Cancer patients [87–90].
In view of the impact of occult tumor cells on
Recent researchers showed some variables prognostic evaluation, the negative LNs, identi-
might be potential targets for improvement of fied by the conventionally pathological examina-
the efficiency of the stage of GC, which need to tion, should be reconsidered for the reality of the
be assessed in the future large-scale. Owing to negative results of these LNS. Recently, several
peritoneal dissemination and distal metastases results were reported to demonstrate that the
occurring in the comparatively late stages of dis- number of negative LNs was a potential predictor
ease, accurate diagnosis is critical for successful of prognosis of GC. Deng et al. [91, 92] showed
design of the therapeutic strategy of GC and for the detailed contents of researches of negative
greatly enhancement of the efficacy of medical LNs in gastric cancer as follows: (1) negative
intervention [77]. To date, many potential bio- lymph node count was significantly associated
markers have been elucidated in GC by detecting with the overall survival of patients, which could
serum protein antigens, oncogenic genes, or gene enhance the prognostic prediction accuracy of
families through improving molecular biological the ratio between positive and dissected LNs for
technologies [78]. DNA methylation plays a sig- the GC patients; (2) negative lymph node count
nificant role in the oncogenesis and the progress is a key factor for improvement of the prognosis
of human carcinogenesis. It has been validated of GC patients who underwent the D2 lymphade-
the significant relationship between specific gene nectomy; (3) ratio between negative and positive
methylation and clinicopathological features LNs was identified to be the optimal lymph node
in GC. The ability to detect small amounts of category for evaluation of the overall survival
methylated DNA among tissues allows research- of gastric cancer, rather than N stage or ratio
ers to use DNA methylation as a molecular bio- between positive and dissected LNs.
marker in GC in a variety of samples, including Lastly, a complete harmonization between
serum, plasma, and GC [79]. Gene amplification the TNM classification of stomach tumors pro-
and protein overexpression of human epidermal posed by UICC/AJCC and JGCA would be of
growth factor receptor 2 (HER2) play an impor- great importance. Does the No.14v really need
tant role in the proliferation, apoptosis, adhesion, to be excluded from the local lymph nodes in
angiogenesis, and aggressiveness of many solid advanced GC?
52 J. Deng et al.
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Part III
Diagnosis of Gastric Cancer
Endoscopic Diagnosis:
Esophagogastroduodenoscopy 3
(EGD) and Endoscopic Ultrasound
(EUS)
Sang Kil Lee and Hyunsoo Chung
EGD tric adenoma and in 2.2% of those with gastric

ulcer in the initial examination [6].
EGD is currently the procedure of choice for
the diagnosis of gastric cancer regardless of
stage. Gastric cancer typically presents as a Early Gastric Cancer (EGC)
mass lesion but may present as a non-healing
gastric ulcer or as a diffuse infiltrative form EGC is defined as carcinoma limited to gastric
known as linitis plastica [1]. The standard for mucosa and/or submucosa regardless of lymph
the diagnosis of gastric cancer is endoscopic node status [7]. The Paris endoscopic classifica-
biopsy. Generally, the mass or abnormal mucosa tion of superficial neoplastic lesions is currently
is targeted for biopsy, although in the case of being used for morphologic classification of EGC
a malignant gastric ulcer, at least six to eight [8, 9] (Fig. 3.1). The three types include superfi-
biopsies of the heaped-up edges of the ulcer and cial polypoid (type 0-I), superficial flat/depressed
base should be performed [2]. However, a recent (types 0-IIa-c), and superficial excavated (type
study suggested that three to four biopsy sam- 0-III) lesions.
ples are usually sufficient to diagnose advanced Type 0 lesions are classified in three distinct
gastric cancer in gastric ulcers with 95% sensi- groups:
tivity [3]. EGD has largely replaced upper GI
series as the initial test of choice for the diagno- • Type 0-I, polypoid (Fig. 3.2)
sis of gastric cancer. From the survey in 2006 in • Type 0-I includes two variants: pedunculated
Korea, Koreans prefer endoscopy as a gastric (0-Ip) and sessile (0-Is).
cancer screening method, compared to UGI • Type 0-II, non-polypoid and non-excavated
(67% vs 33%) [4, 5]. If gastric cancer cannot be (Fig. 3.3)
excluded, repeated biopsy should be performed, • Type 0-II includes three variants: slightly ele-
especially in patients aged over 60. A Japanese vated (0-IIa), completely flat (0-IIb), and
study reported that gastric cancer was detected slightly depressed without ulcer (0-IIc).
at repeated EGD in 17.2% of patients with gas- • Type 0-III, non-polypoid with a frank ulcer
(Fig. 3.4)
S. K. Lee (*) · H. Chung The distinction between a depressed (0-IIc)

Internal Medicine, Yonsei University College of and an excavated or ulcerated lesion (0-III) is
Medicine, Seoul, Republic of Korea readily made in the operative specimen. In the
e-mail: SKLEE@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_3
60 S. K. Lee and H. Chung
0-Ip 0-Is
Protruded, pedunculated Protruded, sessile
0-IIa 0-IIb 0-IIc
Superficial, elevated Flat Superficial shallow,

depressed
0-III
Excavated
Fig. 3.1 Schematic depiction of the major variants of type 0 neoplastic lesions of the stomach: polypoid (Ip and Is),
non-polypoid (IIa, IIb, and IIc), and non-polypoid and excavated (III). (From Ref. [8])
top is classified as type 0-IIa + IIc. 0-IIa + IIc

lesions have a poorer prognosis, with a risk of
large invasion in the submucosa than all other
types of lesions.
ips for Early Detection of Gastric

T
Cancer
To detect EGC, there are some important points

on preparation and observation. First of all,
removal of mucus is essential in the detection of
superficial cancers because the surface of gastric
mucosa is covered by thick mucus. This will make
Fig. 3.2 Type 0-I, polypoid cleaning of mucus easier with a small amount of
water mixed with dimethicone. Oral mucolytic
excavated lesion, there is a sharp discontinu- (pronase) and anti-foring agents defoamers can
ity in the epithelial layer, and the muscularis improve the quality of examination by rinsing
mucosae are interrupted. The most commonly away mucus or bubbles. Enough obervation time
observed subtype is 0-IIc. Mixed types associate is important for detection of early gastric cancer
two distinct types of morphology. Superficial as withdrawal time of colonoscopy is important
tumors with two or more components should for polyp detection. Regardless of the appearance
have all components recorded in order of the of the lesion, careful examination of color and
surface area occupied [10]. For instance, a shape, demarcation of rising borders, and surface
depressed lesion with elevated borders or a cen- pattern are important. Elevated lesions can be eas-
tral elevation is classified as type 0-IIc + IIa. An ily detected even for beginners. Differentiating
elevated lesion with a central depression at its neoplastic lesion such as adenocarcinoma and
3 Endoscopic Diagnosis: Esophagogastroduodenoscopy (EGD) and Endoscopic Ultrasound (EUS) 61
a b
Fig. 3.3 Type 0-II, non-polypoid and non-excavated: (a) Ia, (b) IIb, (c) IIc
tubular adenoma, from nonneoplastic lesions

(hyperplastic polyp, fundic gland polyp, subepi-
thelial lesions, or intestinal metaplasia), is impor-
tant. If lesion shows red-colored, flat-elevated
appearance with irregular surface patterns and
irregular borders, biopsy should be taken to dif-
ferentiated adenocarcinoma. Tubular adenoma
shows well-demarcated flat-elevated lesions with
regular nodular surface. Subepithelial lesions can
be also seen as elevated lesions, but border of the
lesion is generally smooth because the overly-
ing mucosa is nonneoplastic. When depressed
lesion is detected, it is important to differentiate
erosion and focal atrophy from adenocarcinoma.
Generally, well-differentiated adenocarcinoma is
Fig. 3.4 Type 0-III, non-polypoid with a frank ulcer reddish in color, whereas undifferentiated adeno-
carcinoma is whitish because it destroys vessels layer; the submucosa is represented by an echo-
while growing. genic third layer, the muscularis propria as a
When lesion shows irregular but well- hypoechogenic fourth layer, and the serosa as
demarcated depressions, the risk of adenocar- an echogenic fifth layer.
cinoma is high. Erosion or focal atrophy shows EUS is especially useful in the locoregional
regular, smooth shapes with unclear demarcation. staging for gastric cancer. The therapeutic extent
in 30% of surgical candidates has changed by the
use of EUS in the preoperative stage of gastric
Advanced Gastric Cancer (AGC) cancer, resulting in more limited surgical resec-
tions, especially in stages T1 and T3 [12]. The
T2–4 tumors usually manifest as advanced overall accuracy of EUS in determining T stage
types. The gross appearance of advanced gas- ranges from 71% to 92%. A recent systematic
tric carcinomas can be exophytic, ulcerated, review by analyzing the data on 7747 people
infiltrative, or combined. Based on Borrmann’s from 66 articles published from 1988 through
classification, the gross appearance of advanced 2012, with gastric cancer, who were staged with
gastric carcinomas can be divided into type I endoscopic ultrasonography (EUS), also sup-
(mass) for polypoid tumors, sharply demarcated port the usefulness of EUS for the locoregional
from the surrounding mucosa; type II (ulcer- staging (Fig. 3.6). It showed that sensitivity and
ative) for ulcerated tumors with raised margins specificity of EUS in discriminating T1–T2
surrounded by a thickened gastric wall with (superficial) versus T3–T4 (advanced) gastric
clear margins; type III (infiltrative ulcerative) carcinomas were 0.86 (95% CI 0.81–0.90) and
for ulcerated tumors with raised margins, sur- 0.90 (95% CI 0.87–0.93). For the diagnostic
rounded by a thickened gastric wall; and type IV
(diffuse infiltrative) for tumors without marked
ulceration or raised margins, diffusely infiltrat-
ing growth which is also referred to as linitis
plastica when most of gastric wall is involved by Type 1
infiltrating tumor cells [11] (Fig. 3.5). Tumors Mass
that cannot be classified into any of the above
types can be classified as type V (unclassifi-
able). Particularly, in type IV gastric cancer,
caution should be exercised when taking biopsy
Type 2
and interpreting pathologic reports, because risk
of false-negative result of biopsy specimen can Ulcerative
be higher than any other types. Repeated deep
biopsy at a focused lesion is recommended if
there is no mucosal ulceration or defect in the Type 3
stomach.
Infiltrative
Ulcerative
EUS
EUS plays an important role in the diagnosis Type 4

and staging of gastric cancer. EUS allows the Diffuse
visualization of the five layers of the gastric
Infiltrative
wall. The superficial gastric mucosa is rep-
resented by an echogenic first layer and the Fig. 3.5 Macroscopic type of AGC (Borrmann type): (a)
deeper mucosa by a hypoechogenic second Type 1, (b) Type 2, (c) Type 3, (d) Type 4
a b
c d
capacity to distinguish T1 (early gastric cancer, length of the stomach in some advanced cases.
EGC) versus T2 (muscle-infiltrating) tumors, Overall, EUS accuracy can be considered clini-
the sensitivity and specificity of EUS were 0.85 cally useful to guide physicians in the locore-
(95% CI 0.78–0.91) and 0.90 (95% CI 0.85– gional staging of patients with gastric cancer.
0.93), respectively. In addition, for the capacity However, the results must be taken with caution
to distinguish between T1a (mucosal) versus T1b because between- study heterogeneity was not
(submucosal) cancers, sensitivity and specificity negligible, and thus all the results presented here
were 0.87 (95% CI 0.81–0.92) and 0.75 (95% must be taken with caution. Especially, accuracy
CI 0.62–0.84), respectively [13]. In this system- for EUS T staging can be different according to
atic review, in the nodal staging, sensitivity and the expertise of endoscopists, shape, and size of
specificity were 0.83 (95% CI 0.79–0.87) and the lesion. In addition, overstaging is more com-
0.67 (95% CI 0.61–0.72), respectively. Lower mon than understaging for the lesion with ulcer-
specificity for N staging may lie in the fact that ation because overstaging could be attributed
many small lymph nodes can also harbor metas- to peritumoral fibrosis, ulceration, and inflam-
tases, artifact of ultrasound can interfere full mation. EUS also can identify and sample by
and thorough evaluation of regional lymph node fine-needle aspiration and/or biopsy (FNA/FNB)
station, and the scope cannot introduce the full submucosal or infiltrative lesions, such as gastric
a b
c d
Fig. 3.6 EUS finding of each T stage. (a) T1a, invasion to mucosa; (b) T1b, invasion to submucosa; (c) T2, invasion to
proper muscle; (d) T3, invasion to subserosa; (e) T4, invasion to serosa or adjacent structures
lymphomas, stromal tumors, and linitis plastica 6. Hosokawa O, Watanabe K, Hatorri M, et al. Detection
of gastric cancer by repeat endoscopy within a
that are usually observed as thickened gastric short time after negative examination. Endoscopy.
fold on CT scan or endoscopy. 2001;33:301–5.
7. Saragoni L, Morgagni P, Gardini A, et al. Early gas-
tric cancer: diagnosis, staging, and clinical impact.
Evaluation of 530 patients. New elements for an
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2012;27:36–9. sification, histology and application of molecular
4. Jun JK, Choi KS, Lee HY, et al. Effectiveness of pathology. J Gastrointest Oncol. 2012;3:251–61.
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Radiologic Diagnosis (CT, MRI, &
PET-CT) 4
Nieun Seo, Joon Seok Lim, and Arthur Cho
CT inner mucosa, (2) low-attenuation submucosa, and

(3) slightly higher attenuation outer muscular-
Introduction serosal layers [1]. Gastric cancer appears as thick-
ening of gastric wall with increased enhancement
In patients with gastric cancer, CT has been rou- and destruction of normal layered pattern. On CT,
tinely performed for preoperative evaluation and gastric cancer can manifest as focal wall thicken-
accurate tumor staging. In particular, technical ing with or without ulceration, polypoid mass, or
development in CT such as multidetector-row diffuse infiltrative lesion [2]. Particularly, signet
helical CT (MDCT), three-dimensional (3D) ref- ring cell subtype of gastric cancer usually demon-
ormation, and CT angiography provides dedi- strates scirrhous tumor of the stomach, leading to
cated tumor staging, extraluminal information, the destruction of gastric folds and diffuse thicken-
surgical mapping, and preoperative evaluation of ing of gastric wall (linitis plastica) (Fig. 4.1) [3].
perigastric vascular anatomy. Conventionally, the extent of mural invasion
of gastric cancer on CT has been categorized as
follows (Fig. 4.2) [4]: In T1 and T2 lesions,
Tumor Staging
T Staging
Accurate T staging is the most essential part in
determining proper treatment plans. Although the
gastric wall consists of the five histologic layers
(mucosa, submucosa, muscularis propria, subse-
rosa, and serosa), the normal gastric wall is seen as
a two- or three-layered structure at the contrast-
enhanced CT, that is, (1) prominent enhancing
N. Seo · J. S. Lim (*)

Department of Diagnostic Radiology, Yonsei
University Health System, Seoul, Republic of Korea
Fig. 4.1 Signet ring cell carcinoma in a 53-year-old man
e-mail: jslim1@yuhs.ac
with stomach cancer. Axial CT image shows diffuse thick-
A. Cho ening of gastric wall due to linitis plastica. As a left adre-
Department of Nuclear Medicine, Yonsei University nal mass (arrowhead) did not show interval change during
Health System, Seoul, Republic of Korea follow-up, it is thought to be an adenoma

https://doi.org/10.1007/978-3-662-45583-8_4
68 N. Seo et al.
a d
c f
Fig. 4.2 Stage T1–T4 gastric cancers. (a) Axial CT image tissue in gastric angle. (d) Coronal reformatted image shows
shows a stage T1 cancer (pathological T1b cancer) with focal a stage T4a cancer (arrow), enhancing wall thickening of
nontransmural enhancement in the proximal antrum upper body with gross infiltration of the perigastric fat tissue.
(arrows). (b) Axial CT image shows a stage T2 cancer (e) Coronal reformatted image shows a stage T4b cancer
(arrows), an ulcerofungating lesion at midbody without peri- (arrows), infiltrating the distal transverse colon. (f) Axial CT
gastric extension. (c) Axial CT image shows a stage T3 can- image demonstrates a stage T4b cancer (arrow), an advanced
cer (arrows), with minimal infiltration of the perigastric fat cancer with gross extension to the pancreatic body
invasion is limited to the gastric mural wall, and be seen. In T4b lesions, direct extension of gas-
the outer border is smooth with clear perigastric tric cancer into adjacent organs or structures is
fat. In T3 and T4a lesions, the outer border of visualized on CT.
gastric wall is obscured, and strand-like Recently, the up-to-date MDCT technique
increased attenuation in the perigastric fat could using thin section thickness, optimal contrast
4 Radiologic Diagnosis (CT, MRI, & PET-CT) 69
enhancement, and MPR with 3D imaging provides T3 cancers with subserosal invasion, distinction
the more detailed information for T staging. between the enhancing gastric lesion and the
T1a cancers often show increased enhance- outer layer is nearly impossible, and a smooth
ment of the inner mucosal layer without wall outer margin or a few small linear strandings in
thickening, but they are not generally detected on the perigastic tissue can be detected [6]. T4a can-
2D axial images. T1b cancers more frequently cers have serosal involvement and can show irreg-
appear as well-enhancing mucosal thickening ular or nodular outer margin of gastric wall with a
than T1a cancers do [5]. 3D endoluminal images dense band-like infiltration in perigastric fat [6].
can improve depiction of T1 gastric cancers T4b cancers demonstrate direct invasion of gastric
(Fig. 4.3). In differentiation between T1b and T2 tumor into a contiguous organ or structure and
cancers, T1b cancers show visualized outer low- show obliteration of the fat plane between gastric
attenuation stripe of gastric wall, while T2 can- cancer and contiguous organs. As the indications
cers show destruction of the outer low-attenuation of laparoscopic gastrectomy include T1–3N0M0
stripe but clear outer surface of gastric wall [5]. In disease, differentiation of T1–3 (within subsero-
a b
Fig. 4.3 Multidetector-row CT (MDCT) with three- copy shows an ulcerative lesion with clubbing or radiating
dimensional (3D) imaging of T1b cancer. (a) Axial CT fold at the corresponding site. (c) Endoscopy shows a dis-
image depicts focal enhancement of a nontransmural crete ulcer with abnormal surrounding folds at antrum. A
lesion in proximal antrum (arrows). (b) Virtual gastros- hemoclip was applied to proximal margin of the lesion
70 N. Seo et al.
sal extension) and T4 cancers (beyond subserosal following: (1) lymph node more than 8–10 mm in
extension) is especially important when consider- diameter along the short axis, (2) nearly round
ing whether laparoscopic gastrectomy could be shape (short-to-long axis ratios of more than 0.7),
indicated or not. Adding MPR images to axial CT (3) central necrosis, (4) strong or heterogeneous
images has been reported to improve the diagnos- enhancement, and (5) aggregated three or more
tic performance for distinguishing T3 and T4a perilesional lymph nodes regardless of their size
from T4b gastric cancer and predicting adjacent [3, 14–16]. However, the diagnostic accuracy for
organ invasion [7]. However, differentiation preoperative diagnosis of metastatic lymph nodes
between T3 and T4a cancers on CT imaging is is still unsatisfactory, ranged between 51% and
nearly impossible because the discrimination 76% [1, 17–19]. A meta-analysis by Kwee et al.
between subserosal and serosal layers on visual [9] demonstrated the wide ranges of sensitivity
assessment is impractical due to the limited spa- (62.5–91.9%) and specificity (50.0–87.9%) of
tial resolution of CT. Moreover, individual varia- MDCT for N staging, and these results indicate the
tions in the amount of subserosal adipose tissue lack of worldwide consensus for determining met-
make it more difficult to differentiate between T3 astatic lymph nodes. CT has a major limitation in
and T4a stage cancers [8]. that it cannot detect cancer involvement of normal-
Then, what about diagnostic performance of size lymph nodes (microscopic metastasis) and
CT for T staging in gastric cancers? According to rarely distinguish between reactive hyperplasia
a meta-analysis which was published in 2006, the and metastatic enlargement. Even after the use of
diagnostic accuracy of overall T staging on CT MPR images and 3D imaging in addition to axial
ranged from 77.1% to 88.9% [9]. The sensitivity CT images, accuracy of nodal staging has not sig-
and specificity for evaluating serosal exposure nificantly improved [11, 16].
were 82.8–100% and 80–96.8%, respectively [9]. Although the anatomical nodal location is not
Another meta-analysis which was published in incorporated in the AJCC N staging, it is still
2012 demonstrated that the overall pooled accu- important because the D classification, a descrip-
racy of T staging on CT was 71.5%, and CT scan- tion of the extent of lymphadenectomy, is based
ners with more than four detectors and MPR on the level of lymph node dissection (D1–D4).
images could improve diagnostic accuracy [10]. The D2 dissection is the standard surgical proce-
The detection rate of early gastric cancer (EGC) dure for potentially curable T2–T4 gastric cancers
has been shown in various results from study to and cT1N+ tumors (Figs. 4.4, 4.5 and 4.6) [20].
study. Kim et al. [6] reported that the detection rate
of EGC was 76.3% on 2D images and 92.1% on
3D images, respectively. However, Lee et al. [5]
reported disappointing results that the detection
rate of EGC on 2D and 3D imaging was only 45%
and 59%, respectively. 3D imaging including vir-
tual gastroscopy improves the detection rate of
EGC [11, 12], while combined MPR images and
axial images improve the T staging accuracy, espe-
cially in advanced gastric cancer (AGC) [6].
N Staging
The N stage in the AJCC classification system is
determined according to the number of metastatic
lymph nodes [13]. Positive lymph nodes on CT are Fig. 4.4 Station 3 lymph node metastases in a 54-year-
old man with stomach cancer. Axial CT image demon-
suspected on the basis of size, configuration, and strates several clustered round lymph nodes at lesser
enhancement pattern of lymph nodes. Reported curvature along the branches of the left gastric artery
CT criteria of metastatic lymph nodes include the (arrows)
Therefore, nodal enlargements of Nos. 12–16 on

CT, which are not removed by routine D2 dissec-
tion, may significantly affect the decision of
lymph node dissection extent. In addition, the
regional lymph nodes of Nos. 12–16 (portal, ret-
ropancreatic, mesenteric, para-aortic locations)
are classified as distant nodal group (M1), accord-
ing to the AJCC classification (Figs. 4.7 and 4.8).
Therefore, detailed anatomical descriptions of
lymph node involvement remain an important
part of preoperative nodal staging on CT.
Recently, several researchers have been made
attempts to improve the accuracy of N staging and
to facilitate preoperative sentinel lymph node map-
Fig. 4.5 Station 8 and 11 lymph node metastases in a
61-year-old man with stomach cancer. Axial CT image shows
an enlarged necrotic lymph node in station 8 (arrow) adjacent
to common hepatic artery and an enlarged lymph node in sta-
tion 11 (arrowhead) along proximal splenic artery
Fig. 4.8 Station 14 and 16 lymph node metastases in a

49-year-old man with stomach cancer. Axial CT image
shows station 14 metastases (arrow) along the superior
mesenteric vein (asterisk) and conglomerated station 16
Fig. 4.6 Station 10 lymph node metastasis in a 74-year-old lymph node metastases (arrowheads) along the abdominal
man with stomach cancer. Axial CT image depicts an enlarged aorta
necrotic lymph node in station 10 (arrow) at the splenic hilum
Fig. 4.7 Station 13 lymph node metastasis in a 79-year- Fig. 4.9 Multiple hepatic metastases in a 49-year-old
old woman with stomach cancer. Axial CT image demon- man with stomach cancer. Portal venous phase CT scan
strates a station 13 lymph node metastasis (arrow) on the shows multiple metastatic nodules in both hepatic lobes
posterior aspect of the pancreas head (black arrowheads)
72 N. Seo et al.
ping using CT lymphography. The feasibility of

mapping the sentinel lymph node using ethiodized
oil was reported in porcine stomachs and in patients
with EGC [21]. CT lymphography using fluores-
cent iodized emulsion or nanoscale iodized oil
emulsion could be also a promising tool for senti-
nel lymph node mapping, and it should be more
validated in clinical model [22, 23].
M Staging
The pathway of distant metastases of gastric can-
cer can be categorized into three groups, that is,
hematogenous metastases, lymphatic metastases,
Fig. 4.11 Ovarian metastases in a 40-year-old woman
and peritoneal metastases. Solid organ metastasis with stomach cancer. Axial CT image shows a mixed
is infrequently detected in gastric cancers at the cystic-solid mass in the right ovary (arrows) and a pre-
time of initial diagnosis, but its detection is dominantly solid mass in the left ovary (arrowhead), sug-
gesting ovarian metastases (Krukenberg tumor)
important for proper management. The liver is
the most common organ of hematogenous metas-
tasis, and it is explained by that the stomach is manifest as solid and cystic adnexal masses with
drained by portal vein [24, 25]. As hepatic heterogeneous contrast enhancement, and they
metastases of gastric cancer are usually hypovas- often involve bilateral ovaries (Fig. 4.11) [25]. In
cular, they are commonly detected during the the staging of gastric cancer, metastasis in distant
portal venous phase of CT scan (Fig. 4.9). lymph nodes, such as retropancreatic, mesen-
Hepatic metastases can also appear as target or teric, para-aortic, retroperitoneal, and extra-
rim-enhancing lesions on CT, because metastases abdominal area, is regarded as distant metastasis
have a tendency to outgrow their blood supply, rather than nodal metastasis (Figs. 4.7 and 4.8).
causing central necrosis [26]. Other less affected The presence of peritoneal metastasis implicates
organs of hematogenous metastasis include the that the disease is incurable and the patient has a
lungs, adrenal glands, skeletal system, and ova- poor prognosis. Preoperative imaging diagnosis
ries (Figs. 4.10 and 4.11) [4]. Ovarian metastases of peritoneal metastasis is important, because it
allows the surgeon to preclude an unnecessary
laparotomy. Reported CT findings of peritoneal
carcinomatosis encompass ascites, omental cake,
nodular or infiltrative soft tissue lesions on the
peritoneal surface and bowel wall, irregular pari-
etal peritoneal thickening with enhancement,
intraperitoneal fat haziness, and small bowel wall
thickening or irregularity (Figs. 4.12, 4.13 and
4.14) [27–29]. Ascites is one of the most com-
mon findings of peritoneal metastasis, and the
presence of ascites on CT in AGC patients has
been reported to predict peritoneal metastasis
with 51% sensitivity and 97% specificity [30].
According to the study by Pan et al., the over-
all diagnostic accuracy of MDCT for M staging
Fig. 4.10 Adrenal metastases in a 48-year-old man with
stomach cancer. Coronal reformatted image shows hetero-
in patients with gastric cancer was over 90%
geneous enhancing metastatic masses in both adrenal [31]. However, the diagnostic accuracy of CT for
glands (arrows) diagnosing peritoneal metastasis is disappoint-
Fig. 4.14 Peritoneal metastasis in a 57-year-old woman

with stomach cancer. Axial CT image demonstrates scanty
ascites and minimal peritoneal infiltration (arrow). The
diagnosis of peritoneal metastasis is not definite on
Fig. 4.12 Peritoneal metastasis in a 40-year-old woman CT. The following diagnostic laparoscopy confirmed that
with stomach cancer. Axial CT image demonstrates a large the patients had peritoneal metastasis
volume of ascites and nodular infiltration in the omentum
(arrowheads). CT scan also shows right hydronephrosis
(arrow) due to periureteral metastasis (not shown)
ing. A systemic review including 22 CT studies
reported that the sensitivity of CT for detecting
a peritoneal metastasis was only 33% [32]. With
use of low threshold (at least one finding of peri-
toneal metastasis was equivocally present) as
positive finding, one study reported that sensitiv-
ity and specificity of MDCT for detecting perito-
neal metastasis were 50.9% and 96.2%,
respectively [27]. Therefore, in patients with sus-
picious but not definite findings of peritoneal
metastasis on CT, diagnostic laparoscopy is justi-
fied in the cases of larger tumor volume and
b advanced T stage (Fig. 4.14) [27].
reoperative Evaluation of Perigastric

P
Vascular Anatomy
As laparoscopic gastrectomy is technically
demanding and requires a more comprehensive
understanding of local anatomy than open
gastrectomy, preoperative knowledge of the per-
igastric vascular anatomy may be valuable for
laparoscopic gastrectomy [33]. For safe ligation
Fig. 4.13 Peritoneal metastasis in a 59-year-old man of the arterial origins and veins, and for dissec-
with stomach cancer. (a) Axial CT image shows enhanced
peritoneal thickening (arrowhead), ascites, and omental tion of the lymph nodes under laparoscopic
cake (arrow). Left hydronephrosis is also seen. (b) Axial guidance, 3D CT angiography (CTA) has been
CT image in the same patient shows an infiltrative soft considered to be helpful (Fig. 4.15) [34–36].
tissue mass (arrowheads) at the rectovesical space One study reported that dual-phase (arterial and
74 N. Seo et al.
a b
Fig. 4.15 Preoperative assessment of perigastric vascular celiac axis and the isolated left gastric artery (arrow) from
anatomy on 3D CT imaging. (a) Volume-rendered 3D CT the aorta. (c) Maximum intensity projection image shows
image and (b) maximum intensity projection image show the left gastric vein into the main portal vein (arrow)
the replaced right hepatic artery (arrowhead) from the
venous phase) 3D CTA correctly identified the Differential Diagnosis

celiac trunk, left and right gastric artery, left gas-
tric coronary vein, gastrocolic trunk, right gas- Gastric adenocarcinoma is the most common
troepiploic vein, and accessory right colic vein gastric malignancy, occupying over 95% of
[35]. As 3D CTA shows the stomach, the main malignancy of the stomach, and non-mucinous
arteries, and veins integrated in one image, it subtypes account for most of the gastric cancers.
provides a vascular “road map” for surgical Mucinous subtype of gastric cancers is known to
guidance [36]. Preoperative consideration of have poorer prognosis than non-mucinous sub-
vascular anatomy such as right and left gastric types, and it shows different CT findings from
arteries and the left gastric vein was helpful for non-mucinous subtype. In addition, various
accomplishing a secure lymphadenectomy and other malignant and benign gastric diseases can
for avoiding accidental hemorrhage and isch- potentially mimic gastric cancers. MDCT has a
emic liver damage [36]. primary role in characterizing and differentiating
several gastric conditions because it provides an Lymphoma

excellent evaluation of the gastric lumen, gastric Gastric lymphoma accounts for 1–5% of
wall, adjacent structures, and other distant malignant gastric tumors [45]. Primary gas-
organs. tric lymphomas represent approximately 35%
of gastrointestinal lymphomas and are mainly
Mucinous Adenocarcinoma non-Hodgkin lymphomas of B-cell origin [46].
Mucinous carcinoma is a rare subtype of gastric Lymphoma of mucosa-associated lymphoid tis-
cancers, which is observed in approximately sue (MALT) is a distinct type of extranodal
3–5% of all gastric cancers [37–39]. Mucinous lymphoma, and there is evidence of strong asso-
carcinoma is defined as “an adenocarcinoma in ciation between Helicobacter pylori (H. pylori)
which a substantial amount of extracellular gastritis and the development of MALT lym-
mucin (more than 50% of the tumor) is retained phoma (Fig. 4.17) [47]. MALT has relatively
within tumor” by the World Health Organization indolent clinical course and a better prognosis
classification [40]. As the patients with mucinous than gastric adenocarcinoma, with overall 5-year
carcinoma showed worse overall survival rate survival rates of 50–60% [48]. The typical CT
than that in patients with non-mucinous cancer findings of gastric lymphoma include segmental
[37, 38, 41], it is clinically meaningful to distin- or diffuse marked gastric wall thickening (>1 cm)
guish mucinous from non-mucinous gastric can- with homogeneous and less prominent enhance-
cer on the CT imaging. Mucinous carcinoma ment than gastric cancers (Figs. 4.17 and 4.18)
tends to show segmental or diffuse low- [2, 3]. Transpyloric extension of tumor occurs in
attenuation wall thickening of middle or outer approximately 30% of patients with lymphoma
layer of the stomach with layered pattern of con- [49]. Preservation of the fat plane between the
trast enhancement, while non-mucinous carci- gastric lesion and adjacent organs and bulky ret-
noma shows thickened high-attenuating inner roperitoneal lymphadenopathy below the level of
layer with homogeneous enhancement (Fig. 4.16) the renal hilum more likely indicate lymphoma
[42]. Poorly enhancing thickened gastric wall of than adenocarcinoma [45, 50]. In spite of diffuse
mucinous carcinoma on CT corresponds to the lymphomatous infiltration, distensibility of the
mucin pool in the submucosa or deeper layer stomach is usually preserved without significant
[42]. Some cases with mucinous carcinoma dem- luminal narrowing [3].
onstrated miliary punctate calcification in infil-
trative lesions (Fig. 4.16) [42–44].
Fig. 4.17 Gastric lymphoma in a 56-year-old man.

Coronal reformatted image shows diffuse wall thickening
Fig. 4.16 Mucinous carcinoma in a 57-year-old man with homogeneous enhancement of near entire gastric
with stomach cancer. Axial CT image demonstrates low- wall (arrowheads). The gastric lesion was histologically
attenuation wall thickening (arrows) with punctate calcifi- proved as mucosa-associated lymphoid tissue (MALT)
cations (arrowhead) of the gastric body lymphoma
76 N. Seo et al.
used in the limited clinical situation when patients

are hypersensitive to iodinated CT contrast
agents.
However, recent advances in fast MR imaging
technique using parallel acquisition imaging and
gradient sequence gained attention as a promis-
ing modality. Several studies for evaluating MR
accuracy on T and N staging have been per-
formed. The overall results of the studies suggest
that there is no significant difference in T and N
staging accuracy between MRI and CT [55–58]
Fig. 4.18 Gastric lymphoma in a 36-year-old woman. (Fig. 4.1). The reported MR accuracy for staging
Axial CT image shows marked diffuse circular wall thick- gastric cancer was in the range of 73–88% of
ening with homogeneous enhancement of lower body and
antrum (arrowheads). Bulky lymphadenopathy is also accuracy for T staging and 52–55% of accuracy
noted along lesser curvature of the stomach (arrow) for N staging [9, 57, 59, 60]. The diagnostic cri-
teria of MR imaging for nodal metastasis are
similar to that of CT imaging. Both of them diag-
Helicobacter Gastritis nose the nodal metastasis on the basis of the size
H. pylori infection is prevalent worldwide and and shape of lymph nodes. Therefore, CT and
affects more than 90% of the population in devel- MR imaging has the same issues related with
oping countries and 50% of the population in microscopic metastasis in small-sized lymph
developed countries [51]. H. pylori infection of nodes and enlarged reactive lymph nodes, which
the stomach and duodenum is a well-known result in relatively lower diagnostic accuracy.
cause of active, chronic gastritis. The antrum is Recently, there have been several technical
the most commonly involved site for H. pylori developments in MR imaging. Diffusion-
gastritis. The most common CT features of H. weighted imaging (DWI) has shown substantial
pylori gastritis is prominent circumferential wall promise for diagnosing nodal metastasis in the
thickening of gastric antrum [52]. Thickening of variable oncologic field. DWI derives its contrast
the posterior gastric wall along the greater curva- from differences in the cellular density between
ture was also observed [52]. In cases of acute tissues [61]. As malignant lesions are usually
severe inflammation of H. pylori gastritis, their more cellular or have higher signal intensities
CT findings may simulate those of gastric malig- than benign lesions, DWI has been expected to be
nancy [52, 53]. Findings of absent lymphadenop- a useful method for diagnosing nodal metastasis
athy, preservation of fat planes, and absent (Fig. 4.19). However, the studies on diagnostic
invasion of adjacent organs favor H. pylori gastri- performance of DWI for nodal metastasis are
tis rather than gastric cancer [52]. extremely rare. Joo et al. reported that MRI with
DWI showed a higher accuracy than CT or MRI
without DWI, but there was no statistical signifi-
MR Imaging cant difference [62]. MR imaging with lymph
node-specific contrast agents was attempted for
Despite the intrinsic advantage of magnetic reso- improving the diagnostic accuracy of nodal
nance imaging (MRI) such as better soft tissue metastasis in gastric cancer. Ferumoxtran-10
contrast, multiplanar imaging acquisition, and consists of ultrasmall superparamagnetic iron
the absence of radiation hazard, MRI for the stag- oxide particles which can be obtained by normal
ing of gastric cancer has not been preferred than lymph nodes. Tatsumi et al. reported that
CT because of its higher cost, prolonged scan- ferumoxtran- 10-enhanced MRI showed the
ning time, and motion artifact by respiration, pul- promising diagnostic accuracy of nodal metasta-
sation, and peristalsis [54]. MRI has been mainly sis in gastric cancer patients [63]. However, feru-
a b
c d
Fig. 4.19 A large ulceroinfiltrative mass demonstrates Diffusion-weighted image shows the increased signal
direct pancreatic body invasion on dynamic enhancement intensity at the metastatic lymph nodes (c; arrows). A
T1-weighted axial image (a; arrows). An enlarged meta- small solid hepatic metastasis is also seen in the posterior
static lymph node is seen at the posterior side of the main segment of the right lobe of the liver (d; arrow)
portal vein, which suggests station 12p (b; arrows).
moxtran-10 has not yet been approved by the US (PET/CT) will reveal FDG distribution that
Food and Drug Administration because of rela- reflects glucose usage in the body. FDG in cancer
tively high false positive issue, leading to unnec- imaging is based on the hypothesis initially pro-
essary surgical intervention or avoidance of posed by Warburg, where cancer cells exhibit
surgical treatment [64]. The development of higher rates of glycolysis in the presence of oxy-
second-generation lymph node selective contrast gen [65].
agents is expected for accurate lymph node stag- Due to the increased availability of cyclotrons,
ing of gastric cancer. FDG PET/CT has become more widely used in
the routine workup in certain cancers for staging,
therapy response, and recur evaluation. Recent
PET-CT guidelines have suggested that FDG PET/CT be
used in the diagnostic workup in selected gastric
Introduction cancers. National Comprehensive Cancer
Network (NCCN) staging guidelines have sug-
18Fluoro-deoxy-2-glucose (FDG) is the most gested that PET/CT be included in the staging of
widely used positron emission tomography gastric cancer patients with lesions greater than
(PET) radiotracer in cancer imaging. FDG, a T1 and no evidence of distant metastasis [66].
radiotracer analogue of glucose, is injected into The European Society for Medical Oncology
the body, and imaging acquisition with positron (ESMO) guidelines have also included FDG
emission tomography-computed tomography PET/CT, in that it may improve staging by detec-
78 N. Seo et al.
tion of involved lymph nodes or metastatic dis- cancers. This physiologic stomach uptake can be
ease, but may be uninformative in mucinous reduced by expanding the stomach with fluid,
tumors [67]. which can reduce physiologic stomach uptake,
allowing clearer visualization and delineation of
gastric cancer. Yun et al. have showed in their
iagnosis and TNM Staging with FDG
D study that stomach distention with water results
PET/CT in 90% visualization of gastric cancers [68]. The
imaging protocol consists of having the patient
The anatomical resolution of contrast-enhanced drink water after the routine whole-body scan
CT has been an established protocol in the TNM and then acquiring an additional PET/CT of the
staging evaluation of gastric cancer. FDG PET/ stomach region. Using this method, a recent study
CT has the advantage of evaluating the whole has shown that the normal gastric wall uptake can
body for unsuspected metastasis, as well as non- be significantly reduced from SUVmax of
invasively evaluating the metabolism of the 3.1 ± 0.8 to 1.6 ± 0.6 and helped in the resolution
tumor, which has been shown to be correlated of 36% of indeterminate lesions [69].
with prognosis in many cancers. However, there Another variable that has to be considered
are a few limitations, as FDG PET/CT has insuf- during TNM evaluation of gastric cancers with
ficient spatial resolution (approximately 5–7 mm) FDG PET/CT is the difference in FDG avidity
to fully evaluate local T staging in gastric can- according to histopathology and tumor grade.
cers. Another limitation in evaluating the malig- Tumors of low cellularity, such as signet ring cell
nant infiltration extent in the stomach is the (SRC) type or extracellular mucin adenocarci-
physiologic FDG uptake in the collapsed stom- noma, show lower FDG uptake compared to
ach. The stomach has variable FDG uptake, intestinal-type adenocarcinomas (Fig. 4.20) [70–
which can impede in fully evaluating tumor 72]. Stahl et al. have shown significantly more
extent in the stomach wall and is a reason for tumors of intestinal growth type were detected
lowered sensitivity in detecting incidental gastric (83%) than non-intestinal-type carcinoma (41%)
a c d
Fig. 4.20 Variability of FDG uptake according to histologic subtype. (a, b) PET/CT and CT images of intestinal-type
gastric cancer with intense FDG uptake. (c, d) Mild FDG uptake is seen in the signet ring cell-type gastric cancer
[71]. They suggested that the extracellular or (>3 cm), non-signet ring cell carcinoma type
intracellular mucus deposition, which leads to pathology, and GLUT1 expression were signifi-
lower cellular density, is the likely cause of cant predictors of FDG avidity. Using a PET
decreased FDG uptake in non-intestinal-type car- scoring system using these factors, they have
cinomas. However, SRC has also been shown to shown that FDG avid tumors can be detected
have lower GLUT1 expression (2%) compared to with sensitivity of 85% and specificity of 71%,
other adenocarcinomas such as papillary adeno- which can be useful in selecting which patients
carcinomas (44%), tubular adenocarcinomas that should undergo PET/CT for staging [83].
(32%), or poorly differentiated adenocarcinomas Finally, adjustment of imaging protocols has
(28%) [73]. been shown to be helpful in improving initial
diagnosis. Stomach distention method described
Diagnosis earlier can reduce false positive from 30% to 8%
Multiple studies have evaluated the clinical role [84]. Additional delayed imaging 2 hours after
of FDG PET/CT in gastric cancer. A recent anal- initial PET/CT may also be helpful in differenti-
ysis evaluated studies using National Oncologic ating benign from malignant lesions [85]. Also,
PET Registry and has shown that PET/CT had a knowledge of physiologic uptake is also helpful
37% change in intended treatment, and imaging- to reduce false positive rates. Focal FDG uptake
adjusted impact was 14.5% [74]. The NCCN data in the gastroesophageal junction may be physio-
has also shown that PET/CT has higher accuracy logic in the absence of abnormal findings on
in gastric cancer staging (84%), compared to CT CT. Linear uptake in the GE junction extending
alone (64%) [75]. In the detection and preopera- linearly into the distal esophagus is also likely a
tive staging of gastric cancer, stand-alone PET is benign finding such as gastroesophageal reflux
not an adequate diagnostic procedure, but may be disease [86]. Other known benign lesions that
useful in conjunction with CT [4, 76]. FDG PET/ show increased FDG uptake are mucosal inflam-
CT has better sensitivity for advanced gastric mation, such as superficial gastritis and erosive
cancer (98%) compared to early gastric cancer gastritis [87].
(63%) in detection of gastric cancer [77].
However, previously mentioned biologic factors Lymph Node Staging
affect FDG avidity, which may decrease detec- The limited spatial resolution and variable FDG
tion sensitivity. For example, higher mean stan- uptake according to histopathology limits the
dardized uptake value (SUVmean 7.7) is seen in evaluation of T stage with PET/CT. FDG PET/
intestinal-type gastric adenocarcinoma, com- CT is more clinically useful in the N staging of
pared to mucinous and signet ring cell carcinoma gastric cancers. Overall, FDG PET/CT has low
(SUVmean 4.2) [77], which may account for the sensitivity, but high specificity in detection of LN
lowered sensitivity of 61% for diffuse-type and metastasis, as shown in a recent meta-analysis
77% for intestinal-type gastric cancer [76]. where sensitivity was 54.7% and specificity was
Tumor size has repeatedly been shown to be 92.2% [88]. Especially in N1 disease, PET/CT
an important factor in primary lesion detection shows significantly lower sensitivity compared to
[70, 77–79]. Tumor depth is an important factor conventional CT (PET/CT, 46.4% and 41%; CT,
for visualization of stomach cancer. Mochiki 89.3% and 75%, respectively) [89, 90]. This may
et al. have shown that only 40% were detected in be due to smaller size of perigastric LNs and rela-
T1 tumors, 88% for T2 tumors, 90% for T3 tively intense FDG uptake in the adjacent pri-
tumors, and 100% for T4 tumors [80]. Overall, mary gastric cancer (Fig. 4.21) [89]. However,
specificity for detection rates was reported to be because surgically resectable AGCs undergo at
over 90% [70, 77, 80, 81]. Lesions larger than least D1 dissection during gastrectomy, determi-
3.5 cm and deeper invasion have been reported to nation of D1 LN metastasis may be less clinically
have higher detection rates [82]. In a systematic significant [91]. A previous study by Chen et al.
review by Kaneko et al., larger tumor size has shown that FDG PET/CT has lower sensitiv-
80 N. Seo et al.
a c
b d
Fig. 4.21 FDG avidity of lymph node (LN) metastasis in gastric cancer. (a, b) Minimal FDG uptake is seen in the peri-
gastric LNs. (c, d) Intense FDG uptake in the retroperitoneal LNs
ity than CT in detecting local LN metastasis determining metabolically significant uptake in

(56% vs 78%), but showed higher specificity LN metastasis. Evaluation of FDG intensity in
(92% vs 62%) [77]. Yun et al. have shown a sen- the primary gastric cancer not only helps in
sitivity of 34% for N1/N2 disease and 50% for detecting LN metastasis but is useful in the pre-
N3 disease for FDG PET/CT. In contrast, CT diction of LN metastasis [77, 80, 89, 90, 96, 97].
showed higher sensitivity for detection of N1 dis- The mean SUV in the primary tumor was higher
ease (58%) [92]. Evaluation of accuracy has in group 3 LN metastasis (6.2 ± 0.7) compared to
shown concordant findings, in that accuracy for patients without LN metastasis (3.5 ± 0.3). In
distant LN metastasis was significantly higher for another study, average maximum SUV of pri-
PET than CT (85% vs 62%) [93]. Other studies mary gastric cancer was higher in patients with
have also showed similar findings of low sensi- LN metastasis (7.5–8.7) compared to patients
tivity (31–58.3%) but high specificity (95–97%) without LN metastasis (3.6) [77, 80]. In an exten-
in detection of LN metastasis [92, 94, 95]. sively analyzed study evaluating LN metastasis
Shimada et al. have compiled studies about the according to primary tumor histopathology, Kim
diagnostic ability of FDG PET/CT in detecting et al. have shown that signet ring cell-type pathol-
LN metastasis and have shown consistent find- ogy was associated with lowest sensitivity (15%),
ings of high specificity (89–100%), but low sen- in contrast to other cell types with modest sensi-
sitivity (21–40%), with an overall accuracy tivity (30–71%) [90]. Another recent study
between 46% and 85% [81]. showed that FDG uptake in LN metastasis was
Factors affecting FDG uptake in LN metasta- correlated with higher GLUT-1 expression and
sis are similar to factors influencing FDG uptake Ki-67 index in LN metastases [96].
in the primary lesion. Therefore, evaluation of
initial FDG uptake in the primary lesion is impor- Metastasis
tant not only for staging but also in the subse- FDG PET/CT has been helpful in the evaluation
quent follow-up PET/CT, as knowledge of FDG of metastasis. Due to the high incidence of liver,
avidity of the primary lesion may be helpful in bone, peritoneal, and lung metastasis, determin-
ing patients with metastasis is important to reduce CI: 0.98–1.00) and 0.97 (95% CI: 0.83–1.00) [32].
futile surgeries and improve patient prognosis. They also showed that CT and PET had similar sen-
Because FDG uptake is heavily influenced by the sitivity (0.74 and 0.70, respectively) and specificity
histologic subtype in the primary lesion, it is help- (0.99 and 0.96, respectively), but CT had much
ful to consider predominate dissemination patterns higher diagnostic odds ratio (the ratio of odds of
according to histologic subtype. Diffuse-type gas- positive test results in diseased group relative to
tric cancer more frequently disseminates peritoneal odds of positive results in non-diseased group) of
metastasis and lymph node metastasis and forms 251.1, which is an indicator of test accuracy. In
Krukenberg tumors. In contrast, intestinal type contrast, FDG PET was 56.46 [32]. A potential
frequently involves liver as well as lymph node false positive for peritoneal carcinomatosis is peri-
metastasis [98–100]. The metastasis pattern of toneal tuberculosis, which may show intense FDG
diffuse-type gastric cancer, as well as the relatively uptake (Fig. 4.22).
low cellularity or small size of peritoneal seeding In a review of previous studies evaluating
nodules, is the likely reason why FDG PET/CT diagnostic ability of PET/CT in metastasis evalu-
has been shown to have low sensitivity for carcino- ation, FDG PET/CT shows high specificity of
matosis [101]. However, like LN metastasis, FDG 74–99%, but variable low sensitivity (35–74%),
PET/CT has been shown to have high specificity in with an overall accuracy of 73–96% in detecting
detecting carcinomatosis. In a meta-analysis of 4 distant metastasis [81, 102–105]. A recent study
FDG PET/CT studies and 15 CT studies on perito- evaluating FDG avidity in metastasis is strongly
neal metastasis, Wang et al. showed a pooled sen- influenced by the FDG uptake avidity in the pri-
sitivity of 0.33 (95% CI: 0.16–0.56) and 0.28 (95% mary lesion [106]. The FDG avid tumor group
CI: 0.17–0.44) for CT and PET/CT, respectively. had a 82.1% sensitivity in detecting recurrence,
Pooled specificity for CT and FDG was 0.99 (95% and FDG non-avid group had a 47.4% in detect-
a c
b d
Fig. 4.22 Intense FDG uptake in both carcinomatosis peritoneal carcinomatosis. Intense FDG uptake is seen in
and tuberculosis peritonitis. (a, b) Tuberculosis peritonitis the carcinomatosis
showing intense FDG uptake. (c, d) AGC patient with
82 N. Seo et al.
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Part IV
Treatment of Gastric Cancer
Endoscopic Treatment for Early
Gastric Cancer 5
Takuji Gotoda
Abbreviations mucosal resection (EMR) and endoscopic submu-

cosal dissection (ESD) offer less invasive options to
CI confidence interval patients. These options present important trade-offs
EGC early gastric cancer such as less morbidity but also a higher risk of meta-
EMR endoscopic mucosal resection chronous recurrence. Patients’ preferences and par-
EMRC EMR with cap-fitted panendoscope ticularly fear of recurrence are important elements
method in choosing the optimal therapy.
EMRL EMR using multiband ligation Endoscopic resection to treat cancer is perhaps
ESD endoscopic submucosal dissection the most gratifying endoscopy to perform because
IT knife insulated-tip diathermic knife of its minimally invasive curative potentials. Here,
LNM lymph node metastasis this is a review for endoscopic resection of EGC,
QOL quality of life which is clinically used for the treatment of EGC
in Japan and Korea and is increasingly used glob-
ally [2–6]. Endoscopic resection allows complete
pathological staging of the cancer, which is criti-
Introduction cal for risk stratification of metastatic potential
[7]. Patients who are stratified to have no or lower
In the history of gastric cancer treatment, many of risk for lymph node metastasis (LNM) than the
the cases with gastric cancer discovered in the risk of mortality from surgery are ideal candidates
1970s were in the advanced stage. As represented for endoscopic resection [8]. The optimal staging
by the Appleby operation, extended radical surgery method of early gastrointestinal cancer is to eval-
was globally accepted as a mainstream approach to uate the pathology of an en bloc resected material
gastric cancer, even in the early gastric cancer [9, 10]. In addition to allow pathological staging,
(EGC). With the widespread adoption of nation- en bloc resection with R0 (negative vertical and
wide screening [1] in Japan and South Korea and horizontal margins) is to protect the patient from
the advancement of endoscope technology in the the risk of local recurrence.
1980s, the number of patients diagnosed with early
gastric cancer has increased. Nowadays endoscopic
History of Endoscopic Resection
T. Gotoda (*)
Division of Gastroenterology and Hepatology, The first endoscopic resection of early cancer
Department of Medicine, Nihon University School of was reported in colorectal polypectomy using
Medicine, Tokyo, Japan
high-frequency electric surgical unit [11]. Indeed
https://doi.org/10.1007/978-3-662-45583-8_5
90 T. Gotoda
the first endoscopic polypectomy used to treat wall during the application of cautery and caus-
pedunculated or semipedunculated EGC was first ing perforation. The knife can also be used to dis-
described in Japan in 1974 [12]. sect the submucosa – leading to the name of the
The “strip biopsy” technique, an early technique: endoscopic submucosal dissection
method of endoscopic mucosal resection (EMR) (ESD) technique [23–25]. Subsequent studies
technique, was devised in 1984 as an applica- have proven that ESD, using standard single-
tion of endoscopic snare polypectomy [13]. To channel endoscope, can be used for resection of
obtain the resected material with less tissue large lesions “en bloc,” allowing a precise patho-
damage causing adequate pathological staging, logical staging (Fig. 5.1 a, b, c). Complete en
a technique called ERHSE (endoscopic resec- bloc resection regardless of tumor size, location,
tion with local injection of hypertonic saline and/or submucosal fibrosis can be now possible
epinephrine solution), which is known as a [26]. Other ESD knives and techniques have
model of ESD, was developed by Hirao and col- since been developed and studied in detail
leagues in 1988 [14]. (Fig. 5.2) [27–31]. Very recently, ESD has been
EMR with cap-fitted panendoscope method tried to improve an easier procedure [32, 33].
(EMRC) was developed in 1992 for the resection
of early esophageal cancer and directly applica-
ble for the resection of EGC [15, 16]. The tech- reatment Strategy for Endoscopic
T
nique of EMR using ligation, which subsequently Resection
was extended to EMR using multiband ligation
(EMRL), utilizes band ligation to create a “pseu- Principle
dopolyp” by suctioning the lesion into the band-
ing cap and deploying a band underneath it [17, EGC is defined when the cancer invasion is con-
18]. The EMRC and EMRL techniques have the fined to the mucosa or submucosa (T1 cancer),
advantage of being relatively simple. However, irrespective of the presence of LNM [34].
these techniques cannot be used to remove lesions Because the presence of LNM is a strong predic-
en bloc larger than 2 cm [19, 20]. Piecemeal tor on patients’ prognosis [35, 36], gastrectomy
resections in lesions larger than 2 cm lead to a with lymph node dissection had been the gold
high risk for local cancer recurrence and inade- standard for treatment of EGC in Japan [37].
quate pathological staging [21, 22]. Such an extensive surgery however carries a sig-
Insulated-tip diathermic knife (IT knife) was nificant risk of morbidity and mortality and is
devised in the late 1990s at the National Cancer associated with long-term reduction of patients’
Center Hospital, Japan, in order to resolve prob- quality of life [38].
lems observed from the use of EMR techniques Extensive long-term outcomes data from the
for the resection of EGC. IT knife has a ceramic National Cancer Center Hospital and others in
ball tip, thus preventing it from puncturing the Japan have shown that the 5-year cancer-specific
a b c
Fig. 5.1 (a) A large elevated lesion located on the lesser IT knife-2 or Dual knife with PulseCut slow (40 W), (c)
curvature of the middle gastric body, (b) circumferentially dissecting submucosal layer after additional submucosal
mucosal cutting at the periphery of the marking dots using injection
5 Endoscopic Treatment for Early Gastric Cancer 91
Fig. 5.2 (a) IT knife-2

(KD-611L, Olympus
a b c
Medical Systems), (b)
Hook knife (KD-620LR,
Olympus Medical
Systems), (c) Dual knife
(KD-650L, Olympus
Medical Systems), (d)
Flash knife BT (Fujinon
Optical Co., Ltd.), (e)
Safe knife
(DK2518DV1, Fujinon d e f
Optical Co., Ltd.), (f)
Mucosectom (DP-2518,
PENTAX)
survival rates of EGC limited to the mucosa or larger than 2 cm in diameter en bloc [41, 46]. The
the superficial submucosa were 99% and 96%, empirical indications for EMR were therefore
respectively [39]. In patients with intramucosal [47] (1) papillary or tubular (differentiated) ade-
cancer, the incidence of LNM can be as high as nocarcinoma, (2) less than 2 cm in diameter, (3)
3%. In comparison, the risk increases to as high without ulceration within tumor, and (4) no
as 20% when the cancer involves the deep sub- lymph-vascular involvement.
mucosa [40]. With stratification, subgroups of The subsequent advent of ESD dramatically
patients with EGC and minimal risk of LNM changed the range of lesions indicated for endo-
could be identified [41]. Patients who meet these scopic resection (Table 5.1). With an objective of
very specific endoscopic and pathological criteria expanding the indications, the risks of LNM in
are therefore the most ideal candidates to have early gastric cancer were assessed in 5265 cases
their cancer endoscopically resected. of surgical resection performed at two major
The major advantage of endoscopic resection oncology centers in Tokyo [48]. LNM was
is the ability to provide an accurate pathological observed in 65 of 3016 cases of MGC (2.2%) and
staging without precluding future surgical ther- in 402 of 2249 cases of submucosal invasive car-
apy [42, 43]. After endoscopic resection, patho- cinoma (17.9%). Furthermore, LNM was
logical assessment of the depth of cancer observed in none of the 1230 intramucosal can-
invasion, degree of cancer differentiation, and cers with lesions 30 mm or less in size with or
involvement of lymphatics or vessels allows the without ulceration, with differentiated histology,
prediction of the risk of LNM [44]. The risk of and without lymphatic vessel invasion (95% con-
developing LNM or distant metastasis is then fidence interval (CI): 0–0.3%). In intramucosal
weighted against the risk of surgery [45]. cancer without ulcerated lesions, LNM was
observed in none of the 929 cases with
differentiated histology and without lymphatic
Indication Criteria vessel invasion (95% CI: 0–0.4%). In cases with
undifferentiated histology, analysis of subse-
The traditional criteria for endoscopic resection quently accumulated cases revealed that LNM
of EGC were founded on the technical limitation was observed in none of the 310 cases of intramu-
of traditional EMR for removing gastric lesions cosal cancer, 20 mm or less in size, without either
92 T. Gotoda
Table 5.1 Early gastric cancer with no risk of lymph node metastasis
Incidence (no. with metastasis/total
Criteria number) 95% CI
Intramucosal cancer 0/1230; 0% 0–0.3
Differentiated (well and/or moderately differentiated and/or papillary
adenocarcinoma) type
No lymph-vascular involvement
Irrespective of ulcer findings
Tumor less than 3 cm in size
Differentiated type
Without ulcer findings
Irrespective of tumor size
Undifferentiated (poorly differentiated adenocarcinoma
and/or signet-ring cell carcinoma) type
Without ulcer findings
Minute submucosal penetration (sm1) 0/145; 0% 0–2.5
Differentiated type
Modification by Refs. [41, 47]
lymphatic vessel invasion or ulcerated lesions sis based on the pairing of individual factors such
(95% CI: 0–0.96%) [49]. as of tumor size, depth of submucosal penetra-
The new findings from the study conducted by tion, and lymph-vascular involvement failed to
Choi and colleagues are described below. Their yield a subgroup entirely free of nodal metasta-
retrospective cohort study revealed that LNM was sis. However, the subgroup of 145 lesions with
observed in 0.4% of the cases satisfying the size less than 3 cm, well-differentiated histology,
expanded indications and even 0.3% of cases sat- lack of lymph-vascular involvement, and less
isfying the absolute indications [50]. Their results than 500 μm submucosal penetration was entirely
are sufficient to indicate the importance of inform- free of nodal metastasis (95% CI: 0–2.5%).
ing and helping patients before treatment to under-
stand that, despite endoscopic resection, there is a
low but not negligible risk of recurrence or metas- Pathological Staging
tasis because malignant tumors are treated.
Similarly to intramucosal cancer, there was a Proper pathological assessment of endoscopi-
significant correlation between tumor size larger cally resected specimens is crucial for an accu-
than 30 mm and lymph-vascular involvement rate diagnosis and patient’s stratification for the
with an increased risk of LNM. In addition, those risk of LNM. The Paris classification of
cancers penetrating deeply into the submucosa superficial neoplasia of the gastrointestinal tract
were the most likely to be associated with allows a straightforward endoscopic diagnosis of
regional LNM. The relationship between tumor early lesions including an estimation of tumor
characteristics such as size, depth of submucosal depth and likelihood of risk of LNM [51]. These
invasion, presence of ulceration, differentiation, classifications provide a common terminology in
and lymphatic or vascular permeation is shown. order to speak the same language and compare
For well-differentiated tumors, subgroup analy- results to that reported in the literature.
The importance of meticulous pathological patients treated according to the traditional criteria
staging after endoscopic resection is strongly [60]. The 5-year survival rate was 92% in patients
emphasized. Pathological reports of the resected with traditional criteria group and 93% in the
specimen must include pathological type, tumor expanded criteria group. There was no significant
depth, size, location, and macroscopic appearance. difference in overall survival between both groups.
The presence of ulceration and lymph-vascular The multivariable hazard ratio for the patients of
involvement, if any, and the status of the margin of the expanded criteria group versus those of the tra-
resections should be reported. Without sufficient ditional criteria group was 1.10 (95% CI: 0.67–
specimen, tumor staging cannot be accurately 1.81). Very recently several Korean investigators
assessed, patient’s prognosis cannot be estimated, reported that ESD in the extended indication group
and potential needs for additional therapy, which had similarly acceptable clinical outcomes with a
may be curative, cannot be obtained [52, 53]. relatively high complete resection rate and a low
local recurrence rate [61, 62]. ESD has been now
widely acceptable technique and clinically applied
linical Management After
C in Korea. ESD might be better than EMR in terms
Endoscopic Resection of en bloc resection, complete resection, and long-
term outcome [63].
All patients with curative resection who met the Considering the risk of LNM and predicting
traditional criteria were followed up by annual prognosis, there are several scenarios after patho-
upper gastrointestinal endoscopy in order to detect logical evaluation. It is important to note that a
local recurrence and/or metachronous gastric can- non-curative endoscopic resection because of
cers [54]. Patients with curative resection who met positive lateral margin is completely different to
the expanded criteria were additionally followed a non-curative endoscopic resection that did not
up by alternative abdominal CT and endoscopic fulfill the pathological factors highly associated
ultrasound (EUS) every 6 months for 3 years in with LNM such as deep submucosal invasion or
order to detect lymph node and distant metastases positive lymph-vascular involvement. Non-
and annual upper gastrointestinal endoscopy. curative resection generally requires radical sur-
Especially, in the expanded criteria with sub- gical resection with lymph node dissection as the
mucosal invasion, lesions with minute submuco- standard treatment due to the possibility of LNM
sal invasion – less than 500 μm submucosal for patient’s prognosis (Fig. 5.3 a, b). Additional
invasion of differentiated EGC measuring less surgery following non-curative endoscopic resec-
than 3 cm, without lymphatic-vascular involve- tion improved overall and disease-free survival
ment, no nodal metastasis was found (95% CI: compared with nonsurgical observation even in
0–2.5%). However, this result is based on a retro- elderly patients (>75 years) with non-curative
spective examination of surgical resection cases endoscopic resection for EGC [64].
in which patients suitable for such expanded cri- In cancer treatment, completely curing the ill-
teria were determined to have a low risk of lymph ness is extremely important. However, if the
node metastasis. This means there is a possibility quality of life (QOL) is impaired by procedures
of lymph node metastasis up to the upper limit of that are superior only in terms of reducing mar-
95% CI whenever the lesions fulfill the expanded ginal risks, patients may have difficulties in daily
criteria on the histological assessment [55–57]. life and social rehabilitation after treatment [65].
Long-term outcomes after EMR for small dif- With the risks of surgical procedures and
ferentiated mucosal EGC less than 2 cm in diam- impaired postoperative QOL taken into account,
eter have been reported to be comparable to those there may be situations allowing more expanded
following gastrectomy [58, 59]. Gotoda and col- indications for endoscopic resection, leading to
leagues have reported that patients who underwent approximately 10% of the incidence of metasta-
treatment following the expanded criteria have sis and recurrence or, in other words, death from
similar long-term survival and outcomes as gastric cancer.
94 T. Gotoda
Fig. 5.3 (a) A large a b

elevated lesion located
on the anterior wall of
the angle treated by ESD
as non-curative resection
with deep submucosal
invasion, (b) multiple
liver metastases were
shown 6 months after
ESD
The stomach and small intestine are collec-

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their infiltration to sm1, their small size, and lack of 2015;82(2):308–10.
Part V
Open Surgery for Gastric Cancer
Open Surgery for Gastric Cancer:
Distal Subtotal Gastrectomy 6
with D2 Lymph Node Dissection
Ji Yeong An,$ Yoon Young Choi,$
and Sung Hoon Noh
Introduction than 90% 5-year overall survival, even without

adjuvant chemotherapy or radiotherapy [4]. These
Gastric cancer is a major cancer worldwide but par- statistics highlight the important role of surgeons in
ticularly in East Asia, where two-thirds of the cases the treatment of gastric cancer.
were reported. This area includes Korea, Japan, and
China [1]. Gastrectomy with lymph node dissection
has been a standard treatment for gastric cancer [2]. D2 Lymph Node Dissection
The rationale behind this treatment option is two-
fold. Small tumors should be excised as they will The necessity for radical surgery following diag-
progress to large tumors and invade other organs. nosis of gastric cancer is not under question, but
Second, surgical resection of the primary tumors practitioners were often less sure about the ideal
should effectively reduce the risk of metastatic number of lymph nodes to remove. The stom-
relapse [3]. Outcomes of surgical resection for early ach is supplied with blood mainly from five ves-
stage of gastric cancer are quite good, with a greater sels: the right and left gastric arteries, the right
and left gastroepiploic arteries, and the short
gastric artery. It also has an abundant, com-
$
Ji Yeong An and Yoon Young Choi are contributed equally plex lymphatic network. Consequently, cancer
to this manuscript
can spread in many directions from the stom-
Electronic Supplementary Material The online version ach, and it can be difficult to predict metastases
of this chapter (https://doi.org/10.1007/978-3-662-45583- that may originate from the lymphatic system.
8_6) contains supplementary material, which is available Lymph node dissection has been the subject of
to authorized users. the long debate in the medical community and
J. Y. An
Department of Surgery, Yonsei University Health
System, Yonsei University College of Medicine,
Seoul, Republic of Korea
S. H. Noh (*)
Department of Surgery, Samsung Medical Center, Department of Surgery, Yonsei University Health
Sungkyunkwan University School of Medicine, System, Yonsei University College of Medicine,
Seoul, Republic of Korea Seoul, Republic of Korea
Y. Y. Choi Brain Korea 21 PLUS Project for Medical Science,
Department of Surgery, Yonsei University Health Yonsei University Health System, Yonsei University
System, Yonsei University College of Medicine, College of Medicine, Seoul, Republic of Korea
Seoul, Republic of Korea e-mail: sunghoonn@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_6
100 J. Y. An et al.
was addressed in randomized controlled trials Omentectomy and Bursectomy

[5–8]. The results of these trials have led to the
recommendation by medical professionals in Omentectomy and bursectomy are procedures
both the western and eastern hemispheres that that can be performed during gastric cancer
the D2 lymph nodes be dissected in patients surgery.
with advanced gastric cancer [2, 9, 10]. At pres- The omentum, part of the visceral peritoneum,
ent, distal subtotal gastrectomy and D2 lymph controls the inflammation in the abdominal cavity
node dissection are the recommended basic pro- [12]. Total omentectomy is recommended during
cedure for gastric cancer. surgery for advanced gastric cancer because the
The definition of the D2 lymph nodes has been omentum can act as a gateway for metastasis [2,
modified by Japanese Gastric Cancer Association 13]. It is not a time-consuming procedure in open
[11]. In this chapter, the procedures for D2 lymph surgery (as it would be in laparoscopic surgery.)
node dissection are mainly based on the current It is, in fact, easier to perform total omentectomy
Japanese treatment guidelines [2]. than partial omentectomy in open surgery as it is
easy to access the avascular plane.
Bursectomy, removing the anterior mem-
ncologic Principles for Gastric
O brane of the transverse mesocolon and the
Cancer Surgery capsule of the pancreas, has been widely per-
formed for advanced gastric cancer in Korea
There are fundamental differences between sur- and Japan [14]. The rationale behind this pro-
gery performed in patients with cancer and in cedure is that microscopic cancer cells could
patients with other benign conditions. Protocols exist in the membranes that cover the poste-
based on oncological principles must be fol- rior stomach cavity if the tumor invades the
lowed throughout surgical procedures on cancer serosa layer of the stomach and removing
patients to prevent contamination with, or dis- this membrane may reduce the risk of cancer
semination of, the cancer cells. The fundamental relapse in the peritoneal cavity [15]. The effi-
goal of cancer surgery is complete surgical resec- cacy of bursectomies was assessed in a ran-
tion of tumor, en bloc lymph node dissection, and domized, controlled trial that compared the
careful hemostasis. If this goal is not achieved, long-term outcomes of D2 dissection alone or
cancer cells can be disseminated through bro- with bursectomy. In this study, bursectomies
ken lymphatics and vessels. The extent of gastric were the independent prognostic factors [16].
resection should be decided upon based on the Bursectomies can be performed with minimal
location of tumor in the stomach and the safety complication [17] and can provide an avascu-
resection margin so that microscopic tumors are lar plane in conjunction with omentectomy.
not left in remaining stomach. The “no-touch” Considering all the data, it appears that bur-
technique should be used during the entire pro- sectomies should be recommended during sur-
cedure. The no-touch technique entails wrapping geries for advanced gastric cancer, especially
the primary tumor. This is especially important in for serosa-positive gastric cancer located in
cases of serosa-positive gastric cancer, in which posterior wall of the stomach.
it is of utmost importance to prevent iatrogenic
peritoneal seeding through the surgeon’s hands.
Unnecessary manipulation and dissection should urgical Procedure for Distal
S
be avoided as mitogenic factors for wound heal- Subtotal Gastrectomy with D2
ing could be produced in response to the surgery; Lymph Node Dissection
these could stimulate the proliferation of unde-
tected micrometastatic tumors that remained The specifics for this procedure are identified and
after surgery [3]. explained below.
6 Open Surgery for Gastric Cancer: Distal Subtotal Gastrectomy with D2 Lymph Node Dissection 101
Indication with a belt. Usually, the patient is situated the

right side of the table, and the operator stands
The procedure is indicated when distal stomach on patient’s right.
adenocarcinoma has been diagnosed.
I ncision, Exposure, and Preparation

Contraindication of Main Procedures
The procedure is contraindicated in these circum- Although either upper midline or subcostal inci-
stances: sions are acceptable for distal subtotal gastrec-
tomy, a midline incision extending from the
• When it is not possible to secure the distal resec- xiphoid process to the umbilicus is the most
tion margin due to stomach pylorus invasion common (Fig. 6.1a). An incision below the
• When there are enlarged lymph nodes around umbilicus is not usually necessary; however, the
the head of the pancreas and the right gastroep- original incision can be extended to achieve a
iploic vessels, so that the cancer is unresectable better operative field. After making the skin inci-
sion by knife, the linea alba should be divided,
with careful hemostasis, using an electrocautery
Preoperative preparation device such as Bovie. The open abdominal wall
can be protected with a wound protector device
Routine nasogastric tube insertion pre-/postopera- to reduce the risk of cancer cell and bacterial
tively is not recommended. However, when there contamination. During surgery, applying the
is preoperative gastric outlet obstruction due to wound retractor can provide better operative field
advanced gastric cancer, the gastric contents need (Fig. 6.1b). In cases in which peritoneal metas-
to be removed through a nasogastric tube and gas- tasis is suspected, it is useful to perform stag-
tric lavage before operation to avoid contamina- ing laparoscopy through a potential incision site
tion of the surgical site by the gastric contents. before laparotomy. The surgeon should initially
In addition, if there is an electrolyte imbalance make small midline incisions, sufficient to per-
or malnutrition before operation, it should be mit the insertion of one hand so that the resect-
corrected before the operation is performed. For ability of the stomach can be determined from
early gastric cancer, preoperative endoscopic clip- the pancreas invasion and rectal shelf. The inci-
ping on the proximal part of tumor is useful to sions can be expanded later, during the regular
detect the location of tumor and determine the gastrectomy.
secure resection margin for the operation. Exposure and dissection of the area of the
#4sb lymph node is easier if the spleen is
moved aside. This can be done by lifting the
Anesthesia spleen up gently with the left hand and insert-
ing one or two rolled surgical tapes behind it
General anesthesia via an endotracheal tube is (Fig. 6.2). The tape roll(s) should be counted
used routinely. After endotracheal tube insertion, and removed before closing the abdominal
prophylactic antibiotics should be injected. wall. Sometimes dissecting the spleno-phrenic
or splenorenal ligament is necessary for this
procedure, and care should be taken not to
Position of Patient During Surgery injure the parenchyma of the spleen. If there
are severe adhesions around the spleen from
The patient should be positioned in supine on previous abdominal surgery, it would be better
the flat table with the legs fastened to the table not to perform this procedure.
102 J. Y. An et al.
Fig. 6.1 Incision for

a b
open surgery of gastric
cancer. (a) 15 cm of
incision from xiphoid
process to umbilicus for
open surgery. (b) The
open abdominal wall is
protected by wound
protector device
Fig. 6.2 The process of

lifting the spleen up for
achieving good
operative field for #4sb
lymph node dissection.
The spleen is gently
lifted up, and the rolled
surgical tapes are
inserted behind the
spleen
The dilated stomach and colon hinder surgery, etails of Procedure for D2 Lymph
D
and this problem should be addressed before the Node Dissection
main procedure. Decompression of the dilated
stomach and colon by applying suction with otal Omentectomy and Bursectomy
T
an 18G-needle is one way to accomplish this Total omentectomy and bursectomy are recom-
(Fig. 6.3). The location of the puncture site in mended for advanced gastric cancer, especially
the stomach should not be near the tumor site or when the tumor is located in the posterior wall
the proximal part of the stomach that will remain of stomach (Fig. 6.4a). The first assistant should
after gastrectomy. grasp the transverse colon firmly with both
Fig. 6.3 Decompressing a b
the dilated stomach and
colon can provide good
operative field during
surgery. (a) The dilated
stomach was punctured
by 18G-needle with
suction. (b) The stomach
is decompressed. (c) The
dilated colon was
punctured by
18G-needle with suction.
(d) The colon is c d
decompressed
hands and spread it out so that the anatomy can the duodenum and pancreas. Sufficient exposure
be observed. The omentum should be wrapped of the gastroduodenal ligament is helpful in the
and held gently upward and toward the patient’s subsequent dissection of lymph node #5.
head by the second assistant (Fig. 6.4b). If this
procedure is performed through the appropriate issection of Lymph Nodes #4d
D
anatomical plane, the operation should proceed and #4sb
without bleeding (Fig. 6.4c). The greater omentum should be divided and dis-
sected toward the lower pole of the spleen along
issection of Lymph Node #6
D the region of the anterior taenia of the transverse
This dissection should begin by dividing the colon (Fig. 6.6). As the dissection progresses,
greater omentum and dissecting it to the duo- the left side of the gastrocolic ligament and sple-
denum, head of the pancreas, and pylorus. The nocolic ligament should be dissected. Once the
superior mesenteric vein is located below the gastrosplenic ligament has been dissected, the
inferior border of the pancreas. The adipose tis- left gastroepiploic artery (LGEA) and vein can
sue surrounding this vein should not be dissected be identified and should be ligated in the root.
as it is part of the dissection of lymph node #14v, Sometimes infarction in the lower spleen occurs
not part of a routine D2 lymph node dissection. when the LGEA is ligated in its root; however,
Dissecting the peripancreatic fascia from the this seems to have little clinical consequence.
inferior border of the pancreas to the duodenum Careful dissection from the root of LGEA to its
through the head of the pancreas will expose the branches should permit identification of a branch
right gastroepiploic vein and artery. The ideal artery directed to the lower pole of the spleen.
level for transecting the right gastroepiploic vein Preserving this artery can prevent the infarction
is above the anterior superior pancreaticoduode- of the lower spleen. After ligating the LGEA, adi-
nal vein (Fig. 6.5). The right gastroepiploic vein pose tissue between it and the short gastric artery
should be dissected and ligated, at the level of its should be dissected. For gastric resection, the
root, from the gastroduodenal artery and between terminal branches of the LGEA to the stomach
104 J. Y. An et al.
a b
Fig. 6.4 Illustrations for omento-bursectomy for gastric and toward the patients’ head for omentectomy. (c)
cancer surgery. (a) The anatomy around the stomach with Dissecting anterior leaf of transverse mesocolon for bur-
the plane for bursectomy (red line). (b) First assistant sectomy can be done through avascular anatomical plane.
grasps the transverse colon with both hands and spread it (L liver, S stomach, P pancreas, C colon)
out. Second assistant wraps omentum and holds it upward
in its greater curvature side should be dissected be covered with surgical tape. The liver should
and ligated. This procedure can be performed by be retracted by having the first assistant pulls the
electric devices, clip, or tie ligation, but it also stomach toward the feet and the second assistant
can be performed by an electrocautery device retracts it.
only (see video clip).
Next, a clean surgical tape should be applied issection of Lymph Node #5
D
anterior to the head of the pancreas and posterior and Duodenal Transection
to the stomach. Wrapping the stomach with a sur- The lesser sac should be incised and opened and the
gical towel will prevent the surgeon from touch- visceral peritoneum of hepatoduodenal ligament
ing the tumor during the next step (Fig. 6.7a–c). dissected (Fig. 6.8). If the aberrant left hepatic
Clean surgical tape should next be inserted into artery from the left gastric artery is encountered,
the right subhepatic space, and the liver should it should be incised vertically in the right side of
Rt. gastroepiploic a. v.
Gastroduodenal a.
Post. Sup.
Pancreaticoduodenal a.
Ant. Sup.
pancreaticoduodenal v.
Sup. Mesenteric a. v.
Ant. Inf.
Pancreaticoduodenal a.
Fig. 6.5 Anatomy around infra-pylorus of the stomach and the range for #6 lymph node dissection
Fig. 6.6 Anatomy and

Short gastric a.
anatomical plane for
dissecting left
gastroepiploic vessels
(#4sb) Rt. Gastroepiploic a. Lt. Gastroepiploic a.
the proper hepatic artery and dissected from the of reconstruction. If gastroduodenostomy with
right side to the left. At this point, the surgical a circular staple is intended, a detachable anvil,
tape that had been inserted in the superior bor- 28–29 mm in diameter, should be inserted into
der of the duodenum will be exposed, and the the duodenal stump and a purse-string suture tied
right gastric artery can be identified and ligated over the purse-string tying notch of the anvil.
in the root. The small vessels around the pylorus For other reconstruction, such as loop or Roux-
should be cleared and the duodenum transected. en-Y gastrojejunostomy, the duodenum should
The length of the duodenum to be transected be transected by a linear staple, and the staple
should be determined according the planned type line should be inverted by interrupted seromus-
106 J. Y. An et al.
Fig. 6.7 The procedures

of no-touch technique
for preventing the
spillage of cancer cells
during open surgery. The
stomach is wrapped by
surgical towel to prevent
the surgeon from
touching the tumor
directly
Fig. 6.8 Anatomy
around supra-pylorus of
the stomach and the
range for #5 lymph node
dissection
Proper hepatic a.
Lt. gastric a.
Rt. gastric a. Splenic a.
Gastroduodenal a.
cular sutures. This will require putting the pyloric side of the portal vein should be dissected (lymph
stump of the stomach into the surgical towel that node #12a). The lymph nodes of the pancreas upper
was used earlier to wrap the stomach. The stom- portion should be dissected along the anterior por-
ach should then be lifted up and retracted by the tion of the common hepatic artery (lymph node
second assistant. The liver retraction should be #8a). Because the left gastric vein usually drains
maintained, and counter traction should be main- into the portal vein or the splenic vein, it can be
tained by the first assistant, by gently pushing the identified and ligated during the dissection of these
pancreas toward the feet. areas. Lymph nodes along the celiac axis should
be dissected and the left gastric artery exposed
uprapancreatic Lymph Node
S and ligated at the root after isolation from the sur-
Dissection (#12a, #8a, #7, #11p, and #9) rounding soft tissues, which includes lymph nodes
Figure 6.9 depicts the anatomy of the suprapan- (lymph node #7). It is recommended that the left
creatic lymph nodes. After careful exposure of the gastric artery be ligated twice and its stump suture-
proper hepatic artery and common hepatic artery, ligated to ensure secure ligation. Next, lymph node
the soft tissues and lymph nodes around the left dissection (lymph node #11p) should be performed
Stomach
Lt. Gastric a.
Inferior vena cava
Portal v. Post. Gastric a.
Proper hepatic a.
Splenic a.
Fig. 6.9 Anatomy and the range of supra-pancreatic lymph nodes (#12a, #8a, #7, #9, #11p) for D2 lymph node dissec-
tion of subtotal gastrectomy
through the proximal splenic artery. One assistant be determined by confirming the distance from
should pull down the pancreas from the left of the the tumor as approximately 60–70% of the stom-
ligated left gastric artery, exposing soft tissues on ach is transected. The proximal resection margin
the superior border of the pancreas and along the should be located 2–5 cm from the gastric can-
splenic artery and permitting the #11p lymph node cer. In cases of non-palpable early gastric cancer,
to be dissected. The left border of this node is usu- the clip applied during preoperative endoscopy
ally posterior to the gastric artery, when it exists. is a useful indicator for determining the proxi-
The lymph node dissection (#9) should proceed mal resection line. When it is difficult to decide
cephalad to the esophagogastric junction from the proximal margin that leaves tumor-free tissue, it
ligated left gastric artery. After finalizing suprapan- should be confirmed by cryosection. If the tumor
creatic lymph node dissection, a clean surgical tape is identified in the frozen section, a total gastrec-
should be placed above the area of the dissected tomy needs to be considered.
lymph node #9 and behind the stomach.
issection of Lymph Nodes #1 and #3

D hecking the Status of Lymph Nodes
C
A truncal vagotomy in esophagogastric junction According to Their Anatomical
area should be performed, and the lymph nodes Location
along the lesser curvature of the stomach should
be dissected (Fig. 6.10, video). The lymph nodes The current pathological staging system (pN)
should be dissected to approximately 2–3 cm from the American Joint Cancer Committee/
below the imaginary resection line of the lesser Union Internationale Contre le Cancer (AJCC/
curvature of the stomach. The entire procedure is UICC) is based only on the number of metastatic
summarized in the video clip. lymph nodes. Nonetheless, the anatomical extent
of metastasis in the lymph nodes is still impor-
astric Resection to Achieve a Tumor-
G tant for gastric cancer prognosis [18, 19]. Also,
Free Proximal Margin the location of metastatic lymph nodes relative
After dissection of all lymph nodes around the to the location of the primary tumor in the stom-
stomach, the resection line of the stomach should ach influences the probability and risk of lymph
108 J. Y. An et al.
Vagus n.
Cardic branch
Ascending limb of the left subphrenic a.
of the left gastric a.
Short gastric a.
Fig. 6.10 Anatomy and the range for #1 and #3 lymph node dissection
node metastasis. This information will influence Anatomy, Comprehensive Total Approach, Metic-
the decision on the surgical extent of lymph node ulous Lymph Node Dissection, and Patients’
dissection for gastric cancer. Safety. Surgery is as much an art as a technique,
Dividing lymph nodes according to their ana- and the surgeon’s philosophy is an important com-
tomical location in the specimen and recording their ponent of practice. The surgeon should see the sur-
status is highly recommended. Figure 6.11 depicts gery, first and foremost, as for the patient’s benefit
the location of lymph nodes in the specimen. and have the same concern and regard for the
patient as for a family member. The patient with
gastric cancer has only one chance to be cured by
Discussion surgery. Often this requires innovation and the
adaptation of new technology by the surgeon.
Good surgery for gastric cancer can be summa- However, innovations must always honor accepted
rized in the mnemonic “OPERATIONS”: Onco- oncologic principles and practices and be based on
logic Principles, Good Exposure, Understanding sound scientific rationale.
Fig. 6.11 The locations

of each lymph node
station in D2 level in the
specimen after subtotal
gastrectomy with D2
lymph node dissection
9. Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P,

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Total Gastrectomy with D2 Lymph 7
Node Dissection
Introduction pancreatic tail, in the roots of the short gastric

arteries, and along the left gastroepiploic artery
Total gastrectomy (TG), a total resection of the proximal to its first gastric branch), and #11d
whole stomach including the cardia and pylorus, (distal splenic artery LNs from halfway between
is a surgical procedure to treat gastric cancer its origin and the pancreatic tail end, usually
which is located in proximal stomach and in a from the beginning of posterior gastric artery
case that a satisfactory proximal resection safety from splenic artery, to the end of the pancreatic
margin cannot be guaranteed by distal gastrec- tail) LN groups along with those of distal gas-
tomy. As like distal gastrectomy, the extent of trectomy. TG for gastric cancer is one of chal-
lymph node (LN) dissection of TG for advanced lenging surgical procedure because the extent of
gastric cancer is recommended in D2 level, TG is wider than that of distal gastrectomy, LN
and D2 level for TG additionally includes #2 dissection around spleen hilum is technically
(left paracardial LNs including those along the difficult, and surgical complications such as
esophagocardiac branch of the left subphrenic leak from esophagojejunostomy and pseudoan-
artery), #4sa (left greater curvature LNs along eurysm at splenic artery could be lethal. In addi-
the short gastric arteries), #10 (splenic hilar tion, combined resection versus preservation of
LNs including LNs in splenic artery distal to the adjacent organs such as the pancreas and spleen
for TG has long been in a debate. In this chap-
Electronic Supplementary Material The online version ter, we will discuss about the historical changes
of this chapter (https://doi.org/10.1007/978-3-662-45583- of surgery for TG and technical aspects for
8_7) contains supplementary material, which is available TG with LN dissection. Detailed technique for
to authorized users. reconstruction after open TG will be addressed
Y. Y. Choi in another chapter.
Beginning of TG
S. H. Noh (*)
System, Yonsei University College of Medicine, The first total gastrectomy for cancer was
Seoul, Republic of Korea performed by Carl B. Schlatter from the
Brain Korea 21 PLUS Project for Medical Science, University of Zurich Switzerland who was
Yonsei University Health System, Yonsei University a staff of Billroth in 1897 [1], and the first
College of Medicine, Seoul, Republic of Korea reconstruction type was loop esophagojeju-
e-mail: sunghoonn@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_7
112 Y. Y. Choi and S. H. Noh
nostomy without jejunojejunostomy. After ra of Combined Resection Moved

E
the first case, the reconstruction type had to Organ Preservation for TG
developed, and Cesar Roux suggested “Roux-
en-Y” anastomosis with end-to-end esophago- During the 1900s, combined resection of adjacent
jejunostomy in 1907 [2]. The most popular organs was popular, and TG with distal pancre-
type of reconstruction for TG now is modified atectomy (including splenectomy) was a standard
Roux-en-Y, end-to-side esophagojejunostomy procedure for gastric cancer; consequently mor-
which was firstly reported by Thomas G. Orr bidity and mortality rate were high after TG. The
in 1943 [3]. reason of distal pancreatectomy was for remov-
ing LNs along the upper border of the pancreas
and splenic hilum, and there was a clinical ques-
xtent of Lymph Node Dissection
E tion that dissecting LNs around the pancreas
of TG for Gastric Cancer without pancreatectomy could be feasible and
reduce the complication after TG. Consequently
In the initial efforts to identify lymphatic system a new procedure, pancreas-preserving TG, was
around the stomach was performed based on the proposed by Dr. Keiichi Maruyama in 1979 [14].
visible way by a kind of dye such as Prussian blue His operative outcomes were quite interesting;
or India ink [4, 5]. Accumulated experience and pancreas-preserving TG was related to a less
knowledge about lymphatic system around the postoperative mortality and morbidity (0.3% and
stomach were finally compiled, and the Japanese 19.6% in pancreas- preserving group vs. 0.9%
Research Society for Gastric Cancer reported and 39.4% in pancreas resection group, respec-
Japanese manual that defined 16 regional LN tively) and decreased newly developed diabetes
stations based on their anatomical location in mellitus (0% in pancreas preserving and 37% in
1962 [6]. These regional LN stations were clas- pancreas resection group), with similar progno-
sified into N1, N2, N3, and N4 level, and the sis compared to TG with distal pancreatectomy;
removal of LNs at N1 and N2 level was defined consequently pancreas-preserving TG had settled
as D2 lymph node dissection. Propagation of D2 as a standard procedure for TG.
surgery in Japan led innovative improvement of The next clinical question was the necessity of
prognosis of gastric cancer even in stage II and splenectomy for TG: how about removing LNs
III [7], consequently D2 surgery has become a around the spleen hilum without splenectomy?
standard procedure for gastric cancer surgery. Dr. Sung Hoon Noh presented the technical pos-
Once, there was a controversy in Western coun- sibility and feasibility of spleen-preserving TG
tries whether D2 surgery improves prognosis of with splenic hilar lymph node dissection at the
patients with gastric cancer over D1 surgery or second International Gastric Cancer Congress
not, now D2 surgery is considered as an optimal in 1997 [15, 16]. He reported the outcomes of
extent of LN dissection for gastric cancer in the retrospective results, and spleen-preserving TG
world [8–10]. was related to less blood loss with morbidity, and
D2 LN dissection for total gastrectomy the prognosis was similar that of TG with sple-
includes all LN stations for distal gastrectomy nectomy [17, 18]. A following randomized con-
with additional LNs around the pancreas tail trolled trial which compared splenectomy versus
and the hilum of the spleen [8]. The incidence spleen-preserving TG for proximal gastric cancer
of LN metastasis at the hilum of the spleen has showed similar outcomes: both group had similar
been reported as 9–15% when cancer is located number of retrieved LNs, postoperative morbid-
in upper third of the stomach [11–13]; conse- ity, and prognosis [19]; however this trial did not
quently appropriate dissection in this region calculate statistical power before the study; thus
has been considered as one of the important the outcome could be underpowered. A large-
procedures in total gastrectomy for gastric scale, multi-institutional randomized controlled
cancer. trial was conducted in Japan, and the outcome
7 Open Surgery for Gastric Cancer: Total Gastrectomy with D2 Lymph Node Dissection 113
was reported recently. The results showed that position, incision, exposure, and preparation of
splenectomy was related to a higher morbid- main procedure are same to that of distal gas-
ity (30.3% in splenectomy and 16.7% in spleen trectomy, and they will not be discussed in this
preservation group) and larger blood loss (390.5 chapter. Also, LN dissection for LNs that belong
vs. 315 mL, respectively), but the operation time, to D2 level of distal gastrectomy will be skipped,
hospital mortality (0.4% vs. 0.8%, respectively), and readers would be directed to the chapter that
and prognosis were similar between two groups. dealing with these issues in this book. Readers
Based on those results, the study concluded that can access to the detailed procedure for LN dis-
splenectomy in TG for proximal gastric cancer section of #11d and #10 by open surgery in the
should be avoided because it increases opera- video clip.
tive morbidity without prognostic benefit [20].
However, the real benefit from spleen preserva-
tion is still unanswered question because only Dissection of Lymph Nodes #11d
23% of spleen preservation group underwent
#10 dissection or sampling in this study; con- The borderline of #11p and #11d is posterior
sequently the benefit from spleen preservation gastric vessels, and the area of #11d is from pos-
could be attenuated by the harmful effect of LNs terior gastric vessels to the spleen hilum through
preservation at the spleen hilum. upper border of the pancreas. Through dissect-
On the contrary to a low mortality after TG ing #11p, posterior gastric artery is identified
regardless of splenectomy/pancreatectomy or not and ligated to go through #11d. Operation sur-
in Asian countries, results from United States geon grasps soft tissue on upper border of the
showed TG for gastric cancer is still a challeng- pancreas, and assistant surgeon slightly presses
ing procedure because it is still related to high- the pancreas with stick sponge or hand with sur-
mortality rate [21]. According to the results of gical tape (Fig. 7.1). When soft tissue of upper
American College of Surgeons National Surgical border of the pancreas is divided, splenic artery
Quality Improvement Program database which can be identified. Through the line of pancreas’
were collected between 2005 and 2011, overall upper border, from patients’ right side to left
morbidity and mortality after TG were 36% and side, LNs can be dissected from splenic artery.
4.7%, respectively. Also, splenectomy and pan- In the deeper portion of splenic artery, there is a
createctomy was risk factors of morbidity (odds splenic vein; thus LNs around them can be dis-
ratio was 1.63 and 3.84, respectively), and pan- sected with caution of thermal injury of adjacent
createctomy was related to a high mortality (odds vessels (Fig. 7.2).
ratio: 3.50). In conclusion, routine splenectomy
should be avoided in a purpose of LN dissection
for TG, and dissecting splenic hilar LNs is rec-
ommended if it is technically possible.
urgical Procedure for Total

S
S
Gastrectomy with D2 Lymph Node
Dissection
P
The indication of TG is that cancer is located in
proximal stomach. Sometimes huge tumor or
Borrmann type IV gastric cancer can be indi-
cated when appropriate safety margin cannot be Fig. 7.1 Suprapancratic lymph node dissection between
achieved by distal gastrectomy. Other procedures #11p and #11d. Dot line upper border of pancreas. S stom-
including preoperative preparation, anesthesia, ach, P pancreas
issection of Lymph Nodes #4sa, #10,

D to injure parenchyme of the spleen during this
and #2 procedure. Surgeon’s left hand slightly presses
anterior portion of splenic hilum with surgical
To make good operative field to dissect #10 area, tape, and assistant surgeon makes countertraction
surgeon can insert surgical tapes behind the with stick sponge (Fig. 7.4). Short gastric vessels
spleen for lifting up the spleen to anterior part (there are usually three to five vessels) are identi-
that make surgeon able to access #10 area easily fied and ligated with dissecting LNs around them
(Fig. 7.3). Because rough handling of the spleen (#4sa) (Fig. 7.5). Behind the short gastric vessels,
can lead injury of posterior part of the spleen the main splenic artery and vein can be identi-
and sometimes it is difficult to handle the bleed- fied at splenic hilum. Surgeon grasps soft tissue
ing from spleen, surgeons should be careful not around splenic vessels, and assistant surgeon
makes countertraction with retracting splenic
S SV
SA
Fig. 7.2 Exposed splenic vessels at the upper border of

the pancreas. S stomach, P pancreas, SA splenic artery, Fig. 7.4 Exposed short gastric vessels for #4sa lymph
SV splenic vein node dissection. Arrows: short gastric vessels
Fig. 7.3 The process of

lifting the spleen up for
achieving good
operative field for
splenic hilar (#10) Spleen
The spleen is gently
lifted up, and the rolled
surgical tapes are
inserted behind the
spleen. S spleen
S
S
S
7 Open Surgery for Gastric Cancer: Total Gastrectomy with D2 Lymph Node Dissection 115
3. Orr TG. A modified technique for total gastrectomy.

Arch Surg. 1947;54(3):279–86.
4. D. G. Zur Technik der Lymphagefass-injection, Eine
neue Injectionsmasse fur Lymphagefasse. Polychrome
Injection. Anat Anz. 1896;12:216–23.
5. T. K. Lymph node metastasis of gastric cancer. Jpn J
Surg. 1944:15–6.
6. Cancer JRSfG. Japanese rules for gastric cancer study.
SA 1st ed. (in Japanese). Tokyo/Osaka/Kyoto: Kanehara
& Co LTD; 1962.
7. Cancer JRSfG. Annual report of nationwide reg-
istry of gastric cancer patients (in Japanese).
Tokyo: National Cancer Center Press; 1972–1998.
Fig. 7.5 Exposed short gastric vessel with ligation of it. pp. 1–54.
Arrow: short gastric vessel 8. Japanese Gastric Cancer Association. Japanese gas-
tric cancer treatment guidelines 2014 (ver. 4). Gastric
Cancer. 2017;20(1):1–19.
9. Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das
P, Denlinger C, Fakih MG, Fuchs CS, Gerdes H,
Glasgow RE, Hayman JA, Hofstetter WL, Ilson DH,
Keswani RN, Kleinberg LR, Korn WM, Lockhart
AC, Meredith K, Mulcahy MF, Orringer MB, Posey
JA, Sasson AR, Scott WJ, Strong VE, Varghese TK
Jr, Warren G, Washington MK, Willett C, Wright CD,
McMillian NR, Sundar H, National Comprehensive
SA Cancer Network. Gastric cancer, version 2.2013: fea-
SV tured updates to the NCCN guidelines. J Natl Compr
Cancer Netw. 2013;11(5):531–46.
10. Waddell T, Verheij M, Allum W, Cunningham D,

Cervantes A, Arnold D, European Society for Medical
Oncology, European Society of Surgical Oncology,
Fig. 7.6 Exposed splenic vessel at the hilum of the spleen European Society of Radiotherapy and Oncology.
for #10 lymph node dissection. SA splenic artery; SV Gastric cancer: ESMO-ESSO-ESTRO Clinical
splenic vein Practice Guidelines for diagnosis, treatment and fol-
low-up. Ann Oncol. 2013;24(6):vi57–63.
11. Kosuga T, Ichikawa D, Okamoto K, Komatsu S,

Shiozaki A, Fujiwara H, Otsuji E. Survival benefits
artery and vein (Fig. 7.6). During dissecting this from splenic hilar lymph node dissection by splenec-
area (#10), surgeon should be careful not to make tomy in gastric cancer patients: relative comparison of
thermal injury around splenic artery because it the benefits in subgroups of patients. Gastric Cancer.
sometimes can cause a critical complication, 2011;14(2):172–7.
12. Sasada S, Ninomiya M, Nishizaki M, Harano M,

pseudoaneurysm. When dissecting soft tissue Ojima Y, Matsukawa H, Aoki H, Shiozaki S, Ohno
through splenic vessels to upper pole of spleen S, Takakura N. Frequency of lymph node metasta-
and esophagogastric junction, a branch from left sis to the splenic hilus and effect of splenectomy in
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14. Maruyama K, Sasako M, Kinoshita T, Sano T, Katai

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Dissection 8
Mitsuru Sasako
Table 8.1 Eligibility criteria

Indication
Inclusion criteria Exclusion criteria
Pre-op Pre-op
Prophylactic Nodal Dissection Adenocarcinoma Cancer in gastric stump
75 yrs or younger Borrmann 4 (linitis)
Japan Clinical Oncology Group (JCOG) carried PaO2 > 70 mmHg, Other primary neoplasm
out a phase III study on prophylactic nodal dis- FEV1.0 > 50% History of MI or positive
CCr > 50 ml/min exercise ECG
section of para-aortic lymph nodes (PAN) for Written consent Liver cirrhosis or
potentially curable T3/T4 advanced gastric can- ICG15 > 10%
cer [1]. This study, JCOG9501, is a multi- Intra-op Intra-op
institutional prospective randomized control T2(SS), T3, T4 Macroscopic N4 (frozen
study carried out among 24 Japanese hospitals to Curative resection (R0) section not allowed)
Lavage cytology
evaluate superiority of D2 + PAN dissection (D) negative
over D2 alone. Eligibility criteria are shown in
Table 8.1. The primary end point was overall sur-
vival (OS), and the secondary were recurrent-free major surgical complication such as anastomotic
survival (RFS) and surgery-related complications leak, intra-abdominal abscess, or pancreatic juice
and hospital death. The sample size was pro- leak was the same between two groups, but that
jected as 520 to detect 8% increase of 5-year sur- of total morbidity including minor complication
vival rate for PAND with a one-sided alpha level was significantly higher after D2 + PAND than
of 0.05 and power of 80%. Between July 1995 D2 [2]. Both OS and RFS curves were nearly
and April 2001, 523 patients were randomly completely overlapped, and HR was 1.03 (95%
assigned to D2 alone (263) or D2 plus PAND IC; 0.78–1.37; p = 0.83) (Fig. 8.2) and 1.08 (95%
(260) (Fig. 8.1). All except one underwent allo- CI; 0.83–1.42; p = 0.72) (Fig. 8.3), respectively.
cated nodal dissection and followed without any Sites of initial recurrent did not show any differ-
adjuvant treatment. In terms of patients’ charac- ence between the two groups. In subgroup analy-
teristics and prognostic factors, there was no dif- sis, pathological tumor stage and lymph node
ference between the two groups. Hospital death stage (negative/positive) showed statistically sig-
in both groups was as low as 0.8%. Incidence of nificant interaction, but both of them cannot be
known when performing surgery, and reasonable
M. Sasako (*) explanation could not be given. Although the
Department of Surgery, interaction was not significant, hazard ratio for
Yodogawa Christian Hospital, Osaka, Japan tumors of the upper third of the stomach was
e-mail: msasako@hyo-med.ac.jp

https://doi.org/10.1007/978-3-662-45583-8_8
118 M. Sasako
523 patients randomized
263 assigned D2 gastrectomy 260 assigned D2+PAND gastrectomy
1 patient ineligible because

of other histological type
254 received allocated surgery 257 received allocated surgery

9 protocol violations 3 protocol violations
7 had incomplete dissection 3 had incomplete dissection
1 had D2+PAND gastrectomy
1 had intraoperative frozen biopsy of
the para-aortic nodes
263 included in final analysis 259 included in final analysis
Fig. 8.1 Consort flow chart of the JCOG9501
Fig. 8.2 OS curves of 1

the two arms
D2
D2+PAND
0.75
Proportion surviving
0.5
3-year 5-year
0.25
D2 (263) 76.4% 69.2%
D2 + PAND (259) 76.4% 70.3%

0
0 1 2 3 4 5 6 7 8 9 10 11 12
Years after randomization
*: Survival analysis excluded ineligible patients (n=1).

Stratified log-rank test: P=0.57, HR=1.03 (0.77-1.37)
8 Gastrectomy with D3 Lymph Node Dissection 119
Fig. 8.3 RFS curves of 1

the two arms D2
D2+PAND
0.75
0.5
3-year 5-year
0.25
D2 (263) 67.3% 62.7%
D2 + PAND (259*) 66.8% 62.2%

0
0 1 2 3 4 5 6 7 8 9 10 11
Years after randomization
*: Survival analysis excluded ineligible patients (n=1).
Stratified log-rank test: 1 sided P=0.66, HR=1.06 (0.81-1.39)
0.58, while that of other locations was 1.10. Five- Therapeutic Dissection
year OS of 22 out of 260 (8.5%) patients who had
PAN metastasis was 18.2%, which was almost It has long been known that some patients with
same as our expectation. In summary, PAND PAN metastasis can be cured by dissection of all
should be avoided in patients with potentially nodes including PA area, although the proportion
curable T3/4 tumors without any clinical evi- of cured patients was as low as 10%. The Stomach
dence of PAN metastasis. Cancer Study Group (SCSG) of the JCOG has
In JCOG9501 study, we excluded patients made several clinical studies on gastric cancer
with tumors invading the cardia and esophagus, patients with extended lymph nodal disease, hav-
as we carried out at the same time another study ing either bulky metastatic nodes surrounding the
JCOG9502 for these patients to test the superi- celiac artery or its branches (conglomerate nodes
ority of left thoracoabdominal approach over of 3 cm or larger or two or more nodes of 1.5 cm
transdiaphragmatic approach [3]. In the sub- or larger) or PAN larger than 10 mm. In the first
group analysis of JCOG9501, tumors of the study on this issue, neoadjuvant chemotherapy
upper third of the stomach may have more ben- (NAC) by irinotecan plus cisplatin followed by
efit from PAND than tumors of other middle or D2 + PAND demonstrated 3-year OS of 27%
lower third of the stomach [1]. In JCOG9502, (95% CI, 15–39%), while there were three
the incidence of PAN metastasis was more than treatment-related deaths [4]. In the second study,
double of JCOG9501, 15.2%, and 5-year OS of chemotherapy used for NAC was S-1 plus cispla-
these patients was 18.2%, showing much higher tin. The 3- and 5-year OS of 51 eligible patients
efficacy of PAND for these tumors [3]. were 59% and 53%, respectively [5] (Fig. 8.4).
Prophylactic PAND is not recommended, but The 5-year OS of those with clinical PAN metas-
partial PAND, area limited to the lateral to the tasis without bulky N2 was 57 and that of those
aorta and above the left renal vein, might be with both bulky N2 and PAN metastasis was
considered for patients with Siewert type II or 17%. In these two studies, histologically detected
III tumors. nodal metastasis of PAN among those without
120 M. Sasako
Fig. 8.4 OS curve of JCOG0405 OS curves of all eligible patients

the patients enrolled in including those who did not undergo surgery
the JCOG0405
1.0
0.9 OS at 3ys=58.8% and at 5ys=52.8%
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 1 2 3 4 5 6 7
Years after enrollment
No.at risk 51 44 37 30 27 25 9 0
clinical metastasis in PAN was seen in 30% and IVC

20%, respectively. Thus even for bulky N2 with-
out PAN metastasis, PAND should be carried out
after prompt NAC. Duodenum
Technique Hepatic flexure
1. Extensive Kocher’s maneuver (including

mobilization of the hepatic flexure).
First step of PAND is extensive mobiliza- Fig. 8.5 Mobilization of the hepatic flexure
tion of the duodenum from the retroperito-
neum. In this procedure, the hepatic flexure IVC
of the colon should be mobilized extensively

to get a wide view of the PA area (Fig. 8.5). Pancreas head
We should get in the layer immediately

beneath the duodenum and the pancreas Duodenum
along the retro-pancreatic fascia covering the
entire PAN area (Fig. 8.6). Dissection along Transvers mesocolon
this layer should be continued up to near the
left kidney (Fig. 8.7). The inferior mesen-
teric vein can be seen from behind. Fig. 8.6 Wide mobilization just beneath the retropancre-
2. Division of the membrane on the inferior atic fascia
vena cava (IVC).
The membrane covering the PA area, should be cut at its origin (Fig. 8.9). The ven-
which also covers the vena cava, is divided tral surface of the left renal vein should be
longitudinally on the vena cava from about exposed till the origin of the left adrenal
the position of the inferior mesenteric artery vein. As the whole PA area cannot be dis-
to the level of the left renal vein (Fig. 8.8). sected en bloc in one piece, it should be
Following the exposed surface of the vena divided at the level of the left renal vein. The
cava, the origin of the left renal vein can be tissue ventral to the left renal vein is ligated
easily found. Going caudally, the origin of and divided (Fig. 8.10). As this tissue con-
the right gonadal vein is found, and the vein tains many large lymphatic vessels running
longitudinally, ligation is essential to avoid

lymph ascites (chylo-ascites).
Duodenum
3. Taping of the left renal vein (LRV) and expos-
ing the surface of the aorta.
IVC The left renal vein is taped around
(Fig. 8.11) and pulled ventrally to expose the
ventral surface of the aorta. The aorta is cov-
ered with thick adipose connective tissue,
and it should be divided behind the left renal
vein, as it is the thinnest at that level.
Fig. 8.7 Dissection along the retropancreatic fascia up to
near the left kidney hilum 4. Getting access to the bottom of the para-
aortic tissue right to the aorta.
Dissecting the left lateral side of the IVC
toward the back, we can expose the distal end
Duodenum
L Renal v.
of the right crus and the surface of the psoas
IVC
muscle. Some autonomic nerve structures can
be cut to access these structures. We can recog-
nize the vein connecting with the azygos vein
a few cm below the left renal vein, which can
be divided at its root from the IVC (Fig. 8.12).
The right renal artery can also be recognized.
5. Dissection of the entire adipose connective
Fig. 8.8 Membrane covering the PA tissue is divided on tissue between the IVC and the aorta.
the IVC to expose it After reaching the bottom of the PA tis-
sue, we start to dissect the tissue below the
R Gonadal v.
IVC
L Renal v.
IVC
Fig. 8.9 Ligation and division of the right gonadal vein at

its origin Fig. 8.11 The left renal vein is taped around
L Renal v.
IVC R Renal a.
Lymph vessels
L Renal v. Lumbar v.
communicating with Azygos v.
R Gonadal v. (Stump)
IVC
Fig. 8.10 PA tissue including large lymphatics should be Fig. 8.12 Lumbar vein connecting with Azygous vein
ligated and divided upon the left renal vein should be taken care
122 M. Sasako
right renal artery and go along the surface of 7. Dissection along the left lateral side of the
the psoas muscle caudally and from right to aorta to the posterior border.
left toward the aorta (Fig. 8.12). The preaor- Following the surface of the aorta toward
tic tissue is divided at the level of the left left, the left gonadal artery is exposed, and it
renal vein, and the origin of the left gonadal should be ligated and divided from the aorta
artery is exposed just a few cm below the left (Fig. 8.15). Dissection is now continued
renal vein, and it should be divided at the ori- along the left lateral wall of the aorta until
gin (Fig. 8.13). In this process, the right lum- the left lumbar veins and the anterior verte-
bar arteries can be recognized, and the left bral ligament are seen (Fig. 8.16). During
lumbar veins cross over the psoas muscle this procedure, this layer is followed later-
and anterior vertebral ligament behind the ally on the fascia of the psoas muscle. Care
aorta. should be taken not to injure the sympathetic
6. Defining the caudal border of the nerve chain which is located on the psoas
dissection. muscle.
As we dissect the whole tissue between 8. Separation of the PA tissue from the left
the IVC and the aorta caudally and right to Gerota’s fascia.
left together with preaortic tissue, we can The adipose tissue containing PAN is sep-
recognize the origin of the inferior mesen- arated from that in the Gerota’s fascia, which
teric artery (IMA) after a while. It is the contains the ureter. Division from the left
landmark of the inferior border of the dissec- Gerota’s fascia is performed along the left
tion. Whole dissected tissue between the gonadal vein, which has only a couple of
IVC and the aorta and that of pre-aorta small branches draining from the PA area
should be ligated just below the level of the (Fig. 8.17). Separation from the left Gerota’s
IMA (Fig. 8.14). fascia makes the lateral border of the PA tis-
L Renal v.
IVC Aorta
L Gonadal a. (2)
Aorta
IVC
L Gonadal a.
IMA
Fig. 8.13 Left gonadal artery should be divided at its Fig. 8.15 Sometimes there are two left gonadal arteries
origin
Aorta
IVC
IVC
IMV L Lumbar v. (L3)
IMA
Fig. 8.14 Inferior border the the No.16 B1-int and -pre Fig. 8.16 Dissection along the left wall of the aorta is
PA tissue. It should be divied just below the origin of the continued until the left lumbar vein and anterior vertebral
IMA level ligamant are exposed
L Gonadal v.
Aorta Sympathetic ganglion chain
IMA
Para-aortic tissue
Fig. 8.17 Division along medial side of the left gonadal Fig. 8.19 Dissection should not go behind the left sym-
vein from the tissue encapsulated in the left Gerota’s fascia pathetic ganglion chain, which should be preserved to
avoid orthostatic hypotension after surgery
Aorta
Prevertebral ligament
Aorta
Psoas muscle Sympathetic ganglion chain
IMA L Lumbar v.
IMA
Fig. 8.18 PA tissue lateral to the aorta is divided just Fig. 8.20 View behind the aorta
below the origin of the IMA
sue clear. Once the posterior Gerota’s fascia IVC

Aorta
is exposed, we can easily get into the space L Lumbar a.
behind the posterior Gerota’s fascia of the left

kidney. To prepare the mobilization of the left
L Lumbar v.
kidney, quick and blunt dissection can sepa-
rate the Gerota’s fascia from the fascia of the
psoas and quadratus lumborum muscles.
9. Division of the PA tissue lateral to the aorta
near the IMA. Fig. 8.21 View behind the aorta, slightly cranial to the
Just like the PA tissue between the IVC Fig. 8.20
and the aorta, this part of PA tissue is ligated
and divided at just below the level of the As the whole PA tissue cannot be dis-
IMA (Fig. 8.18). Now the PA tissue is dissected en bloc due to existence of the left
sected from the posterior, inferior, and left renal vessels, the tissue lateral to the aorta is
lateral structures en bloc. divided from the tissue cranial to the left
The left sympathetic ganglion chain can renal vein. Firstly the tissue anterior to the
be recognized and preserved (Fig. 8.19). left renal vein is divided. By this procedure,
Median to the sympathetic ganglion chain the left renal vein is clearly exposed, and the
and posterior to the aorta, left lumbar veins origin of the left adrenal vein can be recog-
and artery can be seen and should be pre- nized. Then the left renal artery, which exists
served (Figs. 8.20 and 8.21). in most cases a few centimeters cranial and
10. Division of the PA tissue ventral to the renal behind the left renal vein, is exposed to avoid
left vein and exposure of the left renal artery. its injury (Fig. 8.22). Then the PA tissue
124 M. Sasako
L Renal v.
Gerota’s fascia
IVC Aorta L Renal a. (L Kidney)
Fig. 8.22 Left renal arteries should be searched carefully Fig. 8.24 The left colonic mesentery lying over the left
along the left side of the aorta. Not commonly but occa- Gerota’s fascia is completely mobilized from it
sionally there are a few of them
L Renal v.
Distal end of L Crus
Aorta Sympathetic ganglion chain
L Lumbar v. L Kidney
IVC
Gerota’s fascia
IMV
Fig. 8.25 Almost final point of the mobilization and

Fig. 8.23 View after dissection of No.16B1(-int, and -lat) dissection
below the left renal artery and dorsal to the

left renal vein is divided from the cranial PA
tissue. Figure 8.23 shows view after dissec-
tion of the 16B1 (para-aortic nodes between
Pancreas tail
the left renal vein and the inferior mesenteric (backside) L Adrenal v.
artery). Gerota’s fascia
(L Kidney)
11. Mobilization of the splenic flexure and expo- L Renal v.
sure of the left Gerota’s fascia.
After mobilizing the splenic flexure of the
colon, the anterior Gerota’s fascia is exposed Fig. 8.26 When the left side colonic mesentery is mobi-
widely until it is completely separated from lized widely together with the pancreas tail and the spleen,
the mesocolon (Figs. 8.24 and 8.25). left renal vein and left adrenal vein are seen from anterior
1 2. Exposure of the left adrenal vein and the
common trunk of hemiazygos and lumbar containing lymph nodes along the left sub-
vein. phrenic vessels and median to the left adre-
When the splenic flexure and the left half nal gland is dissected. The dorsal border is
of the transverse colon are completely the celiac ganglion.
mobilized from the left retroperitoneum, 1 3. Mobilization of the left kidney and dissection
the left kidney and the renal vein can be of the tissue behind the renal vessels.
seen from anterior (Fig. 8.26). The origin of After putting the tapes on the left renal
the left adrenal vein is also recognized. artery and vein, the left kidney is turned up,
Near the origin of the left adrenal vein, the and tissue behind the left renal vessels is dis-
common trunk of lumbar vein and hemiazy- sected carefully from these vessels (Figs. 8.27
gos vein which goes caudally is ligated and and 8.28). The view after complete dissection
divided from the left renal vein. The tissue of the PAN tissue is shown (Fig. 8.29).
References
1. Sasako M, Sano T, Yamamoto S, et al. D2 lymphad-
enectomy alone or with para-aortic nodal dissection
for gastric cancer. N Engl J Med. 2008;359:453–62.
Diaphragm 2. Sano T, Sasako M, Yamamoto S, et al. Gastric cancer
surgery: morbidity and mortality results from a pro-
L Renal a. spective randomized controlled trial comparing D2
and extended para-aortic lymphadenectomy – Japan
Clinical Oncology Group study 9501. J Clin Oncol.
2004;22:2767–73.
3. Sasako M, Sano T, Yamamoto S, et al. Left thora-
Fig. 8.27 Final step of the dissection of A2-lat: tissue coabdominal approach versus abdominal-transhiatal
surrounding the left renal vessels including that behind approach for gastric cancer of the cardia or subcar-
the vessels are completely dissected with the left kidney dia: a randomised controlled trial. Lancet Oncol.
turned up 2006;7:644–51.
4. Yoshikawa T, Sasako M, Yamamoto S, et al. Phase
II study of neoadjuvant chemotherapy and extended
surgery for locally advanced gastric cancer. Br J Surg.
Pancreas tail 2009;96:1015–22.
5. Tsuburaya A, Mizusawa J, Tanaka Y, et al. Neoadjuvant
chemotherapy with S-1 and cisplatin followed by D2
Diaphragm gastrectomy with para-aortic lymph node dissection
L Crus
for gastric cancer with extensive lymph node metasta-
L Renal a. sis. Br J Surg. 2014;101:653–60.
Psoas muscle
Aorta
Fig. 8.28 View after complete dissection with the left

kidney in operator’s left hand
L Gastric a. (Stump)
Pancreas tail L Renal a. L Kidney
L Renal v.
Fig. 8.29 Final view of the entire procedure

Reconstruction 9
Joong Ho Lee and Woo Jin Hyung
Introduction Operative Technique
Restoring gastrointestinal continuity has econstruction After Distal

R
remained an issue since the first successful gas- Gastrectomy
trectomy. Although various reconstruction tech-
niques are possible after gastrectomy, researchers Gastroduodenostomy (Billroth
and clinicians have yet to decide on an optimal I Reconstruction)
or ideal reconstruction method. When choosing Gastroduodenostomy following distal sub-
a reconstruction method, surgeons should seek to total gastrectomy is considered a preferred
maintain, in addition to surgical and oncological reconstruction method, especially in Asia [1].
stability, quality of life by ensuring nutritional Gastroduodenal anastomosis is performed end to
intake after surgery. end between the remnant stomach and the duo-
Possible reconstruction methods after distal denum. Gastroduodenostomy has physiological
gastrectomy include gastroduodenostomy (also advantages by affording duodenal passage pres-
known as Billroth I reconstruction), gastrojeju- ervation, and studies have described enhanced
nostomy (also known as Billroth II reconstruc- nutrient uptake and iron metabolism therewith,
tion) with or without Braun anastomosis, and compared to other reconstruction methods, after
Roux-en-Y fashion gastrojejunostomy. After distal gastrectomy [2, 3]. Anatomical advantages
total gastrectomy, Roux-en-Y reconstruction is (e.g., single anastomosis) theoretically reduce the
the most widely used procedure, although several possibility of complications, such as anastomosis
modifications thereto have been devised. leakage, and allow for easier access to the biliary
system.
Anastomosis can be performed manually or
mechanically with a circular stapling device.
Gastroduodenostomy with a circular stapler has
been performed since the 1970s [4], and various
J. H. Lee modifications thereto have been reported. The
Department of Surgery, National Health Insurance use of a circular stapling device has been found
Service Ilsan Hospital, Goyang, Republic of Korea to significantly shorten operation times, with
W. J. Hyung (*) similar incidences of complications, compared to
Department of Surgery, Yonsei University College of other methods [5, 6].
Medicine, Seoul, Republic of Korea
e-mail: wjhyung@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_9
128 J. H. Lee and W. J. Hyung
Surgical Technique After insertion of the anvil, the proximal cut

To perform a gastroduodenostomy, a purse-string edge of the gastrotomy is grasped, and the body
clamp is applied at the distal resection line of the of the circular stapler is inserted. The central rod
duodenum. A straight clamp is applied just proximal of the circular stapler is then moved to penetrate
to the purse-string clamp. The duodenum is then through the posterior wall or the greater curva-
transected between two clamps (Fig. 9.1a). After a ture of the stomach at the proper place of anasto-
purse-string suture is made at the stump of the duo- mosis (Fig. 9.2b). Afterward, the circular stapler
denum, a detachable anvil from a circular stapler is rotated toward the duodenum 180 degrees to
with a diameter of 28–31 mm is gently inserted into lock the central rod and the anvil (Fig. 9.2c) to
the duodenal stump. Importantly, after the purse- achieve side-to-end anastomosis of the gastro-
string suture is tied over the anvil, the anvil should duodenostomy (Fig. 9.2d).
be grasped with the clamp to prevent its slippage After anastomosis, any bleeding or disruption
down into the duodenal lumen (Fig. 9.1b). in the anastomosis is checked under direct vision
A disposable automatic purse-string device through the opening of the gastrotomy. The donut
can also be used. Performing a Kocher maneu- ring in the anvil should be inspected carefully to
ver at the duodenum may reduce tension on the ensure a complete ring is formed in the tissue.
anastomosis site and readily allows the anvil to Following this procedure, the position of a naso-
be inserted into the duodenum. Before transec- gastric tube can be verified and gastric transec-
tion of the duodenum, the Kocher maneuver can tion performed using linear staplers. The staple
be more easily implemented. line is made about 1–2 cm from the anastomo-
After dividing the duodenum, anastomosis sis line of the gastroduodenostomy (Fig. 9.3a).
can be made before resection of the stomach, or Completed anastomosis of the stapled gastroduo-
gastrectomy can be performed first, followed by denostomy is shown in Fig. 9.3b: the anastomosis
anastomosis. To perform the anastomosis before was performed along the greater curvature of the
gastrectomy, a 3–4-cm gastrotomy in the distal remnant stomach, and note that the anastomosis
part of the stomach is made to insert a circular did not cross the linear stapler lines of the gastric
stapler. The incision must avoid the area around closure.
the tumor and be opened along the greater cur- Anastomosis is easier to perform after retriev-
vature of the stomach, if possible (Fig. 9.2a). ing the tumor specimen during resection of
Through this gastrotomy, a lesion in the stomach the stomach. After duodenal transection and
can be grossly confirmed, and an adequate proxi- completion of lymph node dissection, clamps are
mal resection margin can be determined. applied on the greater curvature of the stomach
a b
Fig. 9.1 Division of the duodenum for performing gastroduodenostomy. (a) A purse-string clamp is applied at the
distal resection line of the duodenum. (b) The duodenum is transected, and the purse-string suture is tied over
9 Open Surgery for Gastric Cancer: Reconstruction 129
a b
c d
Fig. 9.2 Gastroduodenostomy with a circular stapler. (a) stomach. (c) The stomach and stapler are rotated toward
A gastrotomy in the distal part of the stomach is made. (b) the duodenum. (d) The central rod and anvil are locked to
Inserting a circular stapler through the gastrotomy, the perform side-to-end anastomosis
central rod penetrates through the greater curvature of the
a b
Fig. 9.3 Completed gastroduodenostomy with a circular gastroduodenostomy does not cross the linear stapler lines
stapler after distal subtotal gastrectomy. (a) The stomach of the gastric resection
is transected with linear staplers. (b) The staple line of the
along a determined proximal resection line, and remnant stomach (Fig. 9.4c). After approxima-
then the greater curvature side of the stomach is tion of the central rod and the anvil, side-to-end
divided between the clamps (Fig. 9.4a). Gastric anastomosis of the gastroduodenostomy is made
resection is then carried out using a linear sta- by firing the stapler. Then, the entry hole of the
pler, and the specimen is retrieved (Fig. 9.4b). remnant stomach is closed using a linear stapler
For anastomosis, the body of a circular stapler is (Fig. 9.4d). This method provides anastomosis on
inserted at the entry hole in the remnant stom- the posterior wall of the remnant stomach.
ach upon removal of the applied clamp. The cen- In both techniques, the circular and linear
tral rod of the stapler is advanced 1–2 cm away stapler lines do not cross one another, which is
from the resection line to the posterior wall of the thought to lessen the risk of anastomotic leakage
a b
c d
Fig. 9.4 Gastroduodenostomy after resection of the remnant stomach such that the central rod penetrates
stomach. (a) A Payr’s intestinal clamp is applied on the through the posterior wall of the stomach. (d) After finish-
greater curvature side of the stomach. (b) The stomach is ing side-to-end gastroduodenostomy, the entry hole of the
transected with linear staplers, and the tumor specimen is remnant stomach is closed using a linear stapler
retrieved. (c) A circular stapler is inserted through the
[7]. To decrease tension during the gastroduo- Gastrojejunostomy can be performed at the
denostomy, incising the gastrophrenic ligament jejunal loop either behind the transverse colon
in the left edge of the fundus of the stomach (retrocolic) or in front of it (antecolic). While
is helpful, together with performing Kocher’s antecolic anastomosis is preferred because it is
maneuver [8]. technically easier, both show similar long-term
outcomes [9].
astrojejunostomy (Billroth II
G After resection of the stomach, gastrojejunos-
Reconstruction) tomy can be performed in a manner in which the
Gastrojejunostomy provides anastomosis remnant stomach is anastomosed to the antimes-
between the remnant stomach and the proximal enteric side of the jejunum. Hand-sewn anasto-
loop of the jejunum after distal gastrectomy. A moses are classically performed in an end-to-side
gastrojejunostomy is preferred over a gastroduo- fashion at the stump of the remnant stomach. On
denostomy in cases in which only a small amount the other hand, mechanical anastomosis with
of remnant stomach is left because a larger por- a linear stapler is performed side to side in the
tion of the stomach is removed due to a tumor greater curvature of the stomach. As end-to-side
located higher in the stomach. A gastrojejunos- anastomosis allows for a greater range of stom-
tomy is also preferred when a tumor lesion is ach resection than side-to-end anastomosis, end-
close to the pylorus ring of the stomach or when to-
side hand-sewn anastomosis is preferred in
an ulcer is identified at the duodenal bulb. Unlike cases of a tumor located higher in the stomach
gastroduodenostomy reconstruction, gastrojeju- and of a small remnant stomach.
nostomy is always possible without unwarranted
tension after anastomosis. The anastomosis can Surgical Technique
be performed manually or mechanically with a Here, the basic antecolic mechanical gastroje-
linear stapling device. junostomy is described. The side-to-side gas-
trojejunostomy can be performed using linear shown that this reconstruction method yields
staplers. For mechanical anastomosis, the jeju- better long-term outcomes in terms of clinical
nal loop measuring approximately 10–15 cm symptoms and postoperative endoscopic findings
from the ligament of Treitz is brought up to the [10, 11]. For these reasons, many surgeons prefer
stomach in an antecolic position after resec- Roux-en-Y gastrojejunostomy for reconstruction
tion of the stomach. To create an isoperistaltic after distal subtotal gastrectomy.
anastomosis, the afferent loop in the jejunum
is fixed at the proximal part of remnant stom- Surgical Technique
ach, with the efferent loop at the stump. Thus, To begin the Roux-en-Y gastrojejunostomy,
biliopancreatic secretions are emptied to effer- the jejunum, at a length 20–30 cm distal to the
ent loop in direction because it is a dependent ligament of Treitz, is prepared as a Roux limb,
portion. transected using a linear stapler, and brought to
Anastomosis may be performed first after the greater curvature of the remnant stomach
retrieval of the tumor specimen or before resec- via an antecolic route without any tension. A
tion of the stomach. To begin, small holes are cre- gastrostomy is then created at the distal edge
ated at a proper site along the greater curvature of of the greater curvature, and a small incision
the stomach and the antimesenteric border of the is made along the antimesenteric side of the
jejunum. A linear stapler is then placed between jejunum, 6 cm from the stump, for side-to-
the remnant stomach and jejunum, approximated, side anastomosis. The linear stapler is inserted
and then fired to achieve anastomosis (Fig. 9.5a). through enterotomies approximated along the
Following this procedure, gastric transection is edges of the stomach and jejunum, and the pos-
performed using linear staplers (Fig. 9.5b). To terior wall of the stomach and the antimesen-
finish, the common entry hole is closed with a teric side of the jejunum are anastomosed by
single layer of running suture or using a linear firing the stapler. The common enterotomy is
stapler. closed in a single-layer fashion using a run-
ning suture or a linear stapler. Side-to-side
Roux-en-Y Gastrojejunostomy or end-to-side jejunojejunostomy can then be
Being increasingly performed, Roux-en-Y anas- performed at a length along the jejunum of
tomosis after distal gastrectomy seeks to improve approximately 25 cm from the gastrojejunos-
postoperative complications by preventing bile tomy with a hand-sewn technique or stapled
gastritis after vagotomy. Several studies have anastomosis (Fig. 9.6).
a b
Fig. 9.5 Side-to-side gastrojejunostomy with a linear s tapler. (a) A linear stapler is placed between the remnant stomach and
jejunum then achieve anastomosis. (b) The stomach is transected with linear staplers, and the common entry hole is closed
Reconstruction After Total of the digestive tract, these attempts seek to retain
Gastrectomy the nutritional status and to improve the quality of
life of patients after gastrectomy. Notwithstanding,
Roux-en-Y Esophagojejunostomy Roux-en-Y reconstruction is easy to perform and
Roux-en-Y reconstruction is a simple, well-codified the most widely used procedure.
method for achieving anastomosis after total gas-
trectomy. Recently, more complex constructions Surgical Technique
have been described, with the goals of preserving After the whole stomach is removed, a purse-
duodenal passage, creating a reservoir for ingested string suture is applied at the stump of the esoph-
meals, and preventing reflux of biliopancreatic agus as soon as possible to prevent shrinkage of
secretions [12]. In addition to restoring continuity the distal esophagus. An anvil with a diameter of
25–28 mm is carefully inserted into the esoph-
agus. Following anvil placement at the distal
esophagus, the purse-string suture is tied.
To prepare the jejunal loop, an appropriate
Stomach area of the jejunum is transected distal to the liga-
ment of Treitz while identifying the mesenteric
vessel arcade. For esophagojejunostomy, the
25 cm
jejunal loop must be long, mobile, and well vas-
cularized to reach the esophagus without tension.
In general, an esophagojejunostomy is created
in an end-to-side fashion, bringing the jejunal loop
in front of the transverse colon up to the esopha-
Duod
enum gus. A circular stapler is inserted through the tran-
sected end of the jejunum, allowing the central rod
to emerge in the antimesenteric wall at about 5 cm
from the end of the jejunal loop (Fig. 9.7a). After
attaching the anvil to the central rod, the stapler
device is fired, and an end-to-side anastomosis
Fig. 9.6 Completed Roux-en-Y reconstruction after dis-
is completed. The open end of the jejunal loop is
tal subtotal gastrectomy then closed by a linear stapler (Fig. 9.7b).
a b
Fig. 9.7 Esophagojejunostomy with a circular stapler. antimesenteric border of the jejunal loop. (b) The open
(a) The circular stapler is inserted through the transected end of the jejunal loop is closed by a linear stapler
jejunal end such that the central rod penetrates the
Esophagus References
1. Information Committee of Korean Gastric Cancer
A. Korean gastric cancer association nationwide
45 cm
survey on gastric cancer in 2014. J Gastric Cancer.
2016;16(3):131–40. https://doi.org/10.5230/
jgc.2016.16.3.131.
2. Lee JH, Hyung WJ, Kim HI, Kim YM, Son T,
Okumura N, Hu Y, Kim CB, Noh SH. Method of
reconstruction governs iron metabolism after gas-
trectomy for patients with gastric cancer. Ann
Surg. 2013;258(6):964–9. https://doi.org/10.1097/
Duod
enum SLA.0b013e31827eebc1.
3. Kim BJ, O'Connell T. Gastroduodenostomy after
gastric resection for cancer. Am Surg. 1999;65(10):
905–7.
4. Nance FC. New techniques of gastrointestinal
anastomoses with the EEA stapler. Ann Surg.
1979;189(5):587–600.
5. Hori S, Ochiai T, Gunji Y, Hayashi H, Suzuki T. A
prospective randomized trial of hand-sutured ver-
Fig. 9.8 Completed Roux-en-Y reconstruction after total sus mechanically stapled anastomoses for gastro-
gastrectomy duodenostomy after distal gastrectomy. Gastric
Cancer. 2004;7(1):24–30. https://doi.org/10.1007/
s10120-003-0263-2.
After the esophagojejunostomy, a jejunojeju- 6. Takahashi T, Saikawa Y, Yoshida M, Otani Y, Kubota
nostomy is performed to maintain biliopancreatic T, Kumai K, Kitajima M. Mechanical-stapled versus
passage. Anastomosis between the proximal jeju- hand-sutured anastomoses in billroth-I reconstruction
with distal gastrectomy. Surg Today. 2007;37(2):122–
num and the efferent limb is made in an end-to- 6. https://doi.org/10.1007/s00595-006-3361-z.
side fashion at 15–20 cm distal to the ligament 7. An JY, Yoon SH, Pak KH, Heo GU, Oh SJ, Hyung
of Treitz. The length of the jejunal loop between WJ, Noh SH. A novel modification of double sta-
the esophagojejunostomy and jejunojejunostomy pling technique in Billroth I anastomosis. J Surg
Oncol. 2009;100(6):518–9. https://doi.org/10.1002/
should measure 45 cm to prevent regurgitation. jso.21368.
A hand-sewn technique or a stapled anastomosis 8. Kim YN, Aburahmah M, Hyung WJ, Noh SH. A
can be used (Fig. 9.8). simple method for tension-free Billroth I anasto-
mosis after gastrectomy for gastric cancer. Transl
Gastroenterol Hepatol. 2017;2:51. https://doi.
org/10.21037/tgh.2017.05.08.
Summary 9. Umasankar A, Kate V, Ananthakrishnan N, Smile
SR, Jagdish S, Srinivasan K. Anterior or posterior
Gastrointestinal tract reconstruction after gastrec- gastro-jejunostomy with truncal vagotomy for duo-
denal ulcer—are they functionally different? Trop
tomy has evolved with the development of surgical Gastroenterol. 2003;24(4):202–4.
techniques and stapling devices. A lot of effort has 10. Kojima K, Yamada H, Inokuchi M, Kawano T,
been exerted to make anastomosis safe, feasible, and Sugihara K. A comparison of Roux-en-Y and
functionally fit for patients after conventional open Billroth-I reconstruction after laparoscopy-assisted
distal gastrectomy. Ann Surg. 2008;247(6):962–7.
gastrectomy. Surgeons should consider surgical and https://doi.org/10.1097/SLA.0b013e31816d9526.
oncological stability and quality of life by ensuring 11. Inokuchi M, Kojima K, Yamada H, Kato K, Hayashi
nutritional intake after surgery, although optimal or M, Motoyama K, Sugihara K. Long-term out-
ideal reconstruction method is not clearly defined. comes of Roux-en-Y and Billroth-I reconstruction
after laparoscopic distal gastrectomy. Gastric
Cancer. 2013;16(1):67–73. https://doi.org/10.1007/
Disclosures This work was not supported by external or s10120-012-0154-5.
grant funding. None of the authors reports commercial 12. Chin AC, Espat NJ. Total gastrectomy: options for
associations or financial involvement that pose a conflict the restoration of gastrointestinal continuity. Lancet
of interest in connection with the submitted article. Oncol. 2003;4(5):271–6.
Part VI
Laparoscopic Surgery for Gastric Cancer
Laparoscopic Surgery for Gastric
Cancer: Distal Subtotal 10
Dissection
Koichi Suda and Ichiro Uyama
Abbreviations [2]. In terms of prognosis of gastric cancer, the

5-year relative survival was over 60% in Japan,
ASPDA Anterior superior pancreaticoduodenal whereas it was 25% in the Western countries [3].
artery There are two major factors which may cause
ASPDV Anterior superior pancreaticoduodenal such a great difference in long-term outcomes:
vein the early detection of gastric cancer and the
CHA Common hepatic artery extended D2 lymph node dissection [1].
GDA Gastroduodenal artery We introduced laparoscopic assistance into
IPA Infrapyloric artery moderate to advanced gastrointestinal surgery
LGA Left gastric artery in 1995 and developed techniques for laparo-
LGEA Left gastroepiploic artery scopic distal and total gastrectomy with D2 dis-
PHA Proper hepatic artery section for advanced gastric cancer, which were
PV Portal vein published for the first time in the world [1, 4, 5].
RGA Right gastric artery Since then, we have performed more than 1500
RGEA Right gastroepiploic artery laparoscopic gastrectomies. At present, the stan-
RGEV Right gastroepiploic vein dard type of operation for curable gastric cancer
SPA Splenic artery is totally laparoscopic D2 gastrectomy [1].
SPV Splenic vein We herein present the principles and methods
of totally laparoscopic D2 distal gastrectomy.
Introduction Setup
Gastric cancer remains a major public health List of Instruments

problem in the world. Gastric cancer is the fourth
most common cancer and the second leading The operating surgeon basically uses
cause of cancer-related death [1, 2]. The highest THUNDERBEAT (Olympus) and “Mancina”
incidence of gastric cancer is found in East Asia (Olympus) with his/her right and left hands,
respectively. The assistant surgeon uses “Johann”
K. Suda · I. Uyama (*) (Olympus) and “Croce” (Olympus) with his/her
Division of Upper GI, Department of Surgery, Fujita cranial- and caudal-sided hands, respectively
Health University, Toyoake, Aichi, Japan (Fig. 10.1). The 10 mm flexible high-definition
e-mail: iuyama@fujita-hu.ac.jp

https://doi.org/10.1007/978-3-662-45583-8_10
138 K. Suda and I. Uyama
Left-hand type Grasping forceps Johann Grasper Suction and irrigation tube with button electrode
WA64360A (“Mancina”) WA64120A WA51138A + WA51172S
Finger type Maryland Dissection forceps Grasping forceps Johann type Bipolar Grasping forceps
WA64300A (“Natasha”) WA64150A (“Croce”) WA64120C
Fig. 10.1 Forceps and hemostats specialized for advanced laparoscopic surgery
video laparoscope (LTF-S190-10, Olympus) is used for clinical stage IV disease, and radical
is preferably used. All the details are shown in gastrectomy is conducted when downstaging is
Table 10.1. achieved [7, 8].
Distal gastrectomy is used for the tumor local-
ized to M and/or L area. D1+ lymphadenectomy
Patients is conducted for preoperative stage IA disease,
whereas D2 is performed for preoperative stage
The stage of the cancer is classified according IB, II, and III diseases in accordance with the
to the 14th edition of the Japanese Classification fourth edition of the JGCA guidelines [9].
of Gastric Carcinoma [6]. Cancer staging is
performed based on the findings of contrast-
enhanced computed tomography, gastrography, OR Setup
endoscopic study, and endosonography before
the beginning of any treatment and, when appli- Basically, the operating surgeon stands on the
cable, after the completion of chemotherapy. patient’s right side, except for #6 lymph node dis-
The patients with clinical T ≥ 2 cancer over section (Fig. 10.2). When the operating surgeon
5 cm in size and/or a swollen locoregional lymph stands on the patient’s left side, the scrub nurse
node over 1.5 cm in size undergo staging lapa- with the table should move from the caudal to the
roscopy. Clinical stage ≤ IIIC is determined to cranial side of the patient (Fig. 10.2) just to avoid
be resectable. Neoadjuvant chemotherapy (S-1 the cables connecting between the forceps and
80 mg/m2 day 1–21 + CDDP 60 mg/m2 day 8) generators from getting tangled.
is used for those with clinical T ≥ 2 as well as
tumor ≥5.0 cm in size and/or a swollen locore-
gional lymph node ≥1.5 cm in size, unless the Patient’s Position
patients refuse it. Induction chemotherapy (S-1
80 mg/m2 day 1–14 + CDDP 35 mg/m2 day The patient is placed in a supine position with
8, or Docetaxel 30 mg/m2 day 1, 15 + CDDP legs apart, left arm extended, and 15-degree
30 mg/m2 day 1, 15 + S-1 80 mg/m2 day 1–14) head-up tilt.
10 Laparoscopic Surgery for Gastric Cancer: Distal Subtotal Gastrectomy with D2 Lymph Node Dissection 139
Trocar Arrangement (Fig. 10.3) • Note: The distance between CP and RUP

should be longer than eight fingers.
• Camera port (CP): navel or midline below the • Right lower port (RLP): caudally on the
navel median line between CP and RUP
• Right upper port (RUP): one finger caudally • Left upper port (LUP): eight fingers laterally
from the right subcostal line, top of the right sub- to the bottom of the greater curvature of the
phrenic “dome,” affecting the comfortableness stomach, affecting the comfortableness in #6
in grasping the adipose tissue including #11p dissection
Table 10.1 List of instruments used for totally laparoscopic gastrectomy at Fujita Health University
Category Description Product name
Imaging Monitor OEV-261H
NDS SC-WU26-A1511-1
Video system CV-190
Light source CLV-190
Insufflations UHI-4
Scope LTF-S190-10
IMH20
Video recorder
Energy Ultrasonic(THUNDERBEAT) USG400
ESG400, WB50402W foot pedal
TC-E400
TD-TB400 (transducer)
TD-TB400 (transducer)—spare
TB-0545FC
TB-0535FC
MAJ-1871
MAJ-1872
MAJ-1873
MAJ-1876
MAJ-1870
WB50403W (single foot pedal for bipolar)
MAJ-814 (Pcode)
Electrosurgical FORCE TRIAD (Covidien)
HiQ Dissector WA64300A (with A60800A and A60201A) right-hand forceps
WA64370A (with A60800A and A60201A) Fine Maryland
WA64350A (with A60800A and A60201A) Maryland
WA64150A Grasping forceps (Croce)
Grasper WA64360A (with A60800A and A60201A) left-hand forceps
A64120A (with A60800A and A60201A) Johann grasper
Bipolar WA64120C (with WA60800C and WA60101C)
*Bipolar cable: A60003C
Others WA51138A + WA51172L
A60200A (ratchet hand)
*Monopolar cable: A0358 (for FORCE TRIAD)
Storz needle holder (Storz)
WA64710A (Olympus Needle Holder)
(continued)
Table 10.1 (continued)
Category Description Product name
Consumables First trocar COR47 100 mm, balloon-type trocar (Applied Medical)
12 mm × 75 mm (or 100 mm) trocar (Ethicon)
5 mm ONB5STF(Covidien)
Metzenbaum A64810A (with A60800A + A60201A) or CB030
Stapler Tri-Staple, 45/60, Camel and Purple(distributed by Covidien)
egia45avm
egia60avm
egia45amt
egia60amt
Clip Covidien M clip
Covidien M/L clip
Suture 【3-0 Proline, 90 cm, SH-1 (Ethicon) 】or 【3-0, Surgipro II,
90 cm, (Covidien, VP762X)】
【3-0 Monocryl, 90 cm, SH-1 (Ethicon) 】or【3-0,75 cm,
Caprosyn, (Covidien, UC-404)】or【3-0,75 cm, Biosyn
(Covidien, GM324)】
【PDS, SH (for open surgery) (Ethicon)】 or 【3-0, CR, Maxon
(6229–43, Covidien)】
【3-0 Vicryl CR SH-1(Ethicon) 】or【3-0 Polysorb (Covidien,
GLJ-50M)】
Polysorb, 2-0, 75 cm, 27 mm (Covidien, UL-878)
Maxon, 1, CR, 48 mm (Covidien、GMMT540MG)
Others Others Surgical Octopus Retractor L, M, S (Nathanson Hook Liver
Retractors® distributed by Yufu Itonaga Co.)
Dr. Fog Endoscope Anti-Fog Solution, DF-3120 (distributed by AMCO)
EndoClose 173022 (distributed by Covidien)
Endo Universal Stapler 173052 (distributed by Covidien)
Cherry Dissector BTD05 (distributed by Ethicon)
PassSaver MD-49621 (Sumitomo)
First option: Inzii 12/15 mm Retrieval System (Applied Medical)
Second option: EndoCatch II 173049 (distributed by Covidien)
Surgicel NU-KNIT 7.6 cm × 10.2 cm 15732 (Ethicon)
Xylocaine Jelly (AstraZeneca)
Pyoktanin Blue 25 g (KISHIDA)
Storz Duomat (Storz)
Tubes
Y shape connector
These instruments were distributed by the Olympus unless otherwise noted
Scr s
Nur
Anesthetic
Suc
ub
e
Machine
Tab
tion
Ope geon
ht
le
sur
Lig rce tor

Lig
Ins
sou ator
rati
u
so ffla itor
Sco
ht
uffl
ng
su
rce
n
b In Mo
p
ru
Mo
ist
Sc ures
Mo
nit
Pa N Table
or
nito
tient Suction
t n
nt
r
Ass geon
Patie
ta
Sur
Ma thetic
An
sis eon
ista
rator
A urg g
es
chi
tin
S era n
nt
Monit
ne
Op rgeo
Gene
or
Ge su
ne
rat ist
or
op
Sc
Standard setup Setup for #6 dissection
Fig. 10.2 OR setup
LR
3mm
RUP
5mm
Additional port
5mm
RLP LUP
12mm 12mm LR
(or 5mm)
LLP RUP
12mm
LUP
C
12mm RLP
LLP
C
Fig. 10.3 Trocar arrangement in laparoscopic gastrectomy

• LLP: caudally on the median line between CP We termed this layer as the outermost layer of
and LUP the autonomic nerve (Fig. 10.4) [1, 11]. To iden-
• Additional port: cranially on the median line tify this layer throughout the dissection process,
between CP and RUP, suitable for deeply dis- we developed an original surgical theory, “XYZ-
secting suprapancreatic lymph nodes over the axis” theory (Fig. 10.5), consisting of the follow-
pancreas ing three steps—[1] cut the serosal membrane on
the suprapancreatic border, [2] dissect suprapan-
creatic adipose tissue caudocranially toward the
D2 Lymph Node Dissection junction of the three arteries (zero point) to find
the outermost layer, and [3] dissect the target adi-
utermost Layer-Oriented Medial
O pose tissue mediolaterally along the layer spread-
Approach ing on the XZ and YZ axes.
D2 dissection entails removal of the lymph nodes

in the suprapancreatic area in distal gastrec- etails of D2 Dissection in Distal
D
tomy [1]. Dissection of this area is technically Gastrectomy
demanding due to the serious risk of bleeding
and/or pancreatic leakage derived from a major #4d Dissection
vessel or organ injury [1, 10, 12]. To improve the The operating surgeon stands to the right of the
safety, efficacy, and reproducibility of suprapan- patient. The assistant surgeon holds the greater
creatic nodal dissection, we developed our origi- curvature on the “watershed” dividing between
nal methodology called outermost layer-oriented the right and left gastroepiploic arteries (RGEA
medial approach [1, 10, 11]. In this approach, and LGEA) and raise it cranioventrally with
the layer between the autonomic nerve sheaths his/her right hand. Subsequently, the assistant
of the major arteries and the adipose tissue bear- surgeon grasps the greater omentum near the
ing the lymphatic tissue is dissected [1, 10, 11]. transverse colon with his/her left hand. Then, the
The Outermost Layer:

“Vascular Sheath”and “Adipose tissue containing LN”
N
CHA
N
#8a
N
N
LN: Lymph Node N
N: Nerve
LN
N
N N
N #8a
N
N N
N N
N
Appropriate tension generates thin space along the outermost layer

＝Safe and adequate nodal dissection
Fig. 10.4 Outermost layer of the autonomic nerve

Artery
(Z axis) #7 #5
LGA RGA #8a
CHA
#9(L)
#9(R)
SPA GDA
CHA
(3) (3)
Adipose Adipose
tissue tissue RGEA
0 #6
RGEV PHA
(3) (3) #5
GDA
ASPDA RGA
(2) PHA
Artery (1)Suprapancreatic Artery

(X axis) border (Y axis)
Fig. 10.5 XYZ-axis theory
#4sb Dissection
The assistant surgeon holds the posterior aspect
of the upper area of the stomach and determines
the pedicle including the LGEA/LGEV origi-
nating from the pancreatic tail (Fig. 10.7a). By
dividing the bursa along the physiological adhe-
sion line mentioned above, the root of the gastric
branch of LGEA is easily exposed preserving
the omental branch (Fig. 10.7b). Then, the adi-
pose tissue including #4sb is removed out of the
greater curvature from the “watershed” up to the
avascular area between LGEA and short gastric
arteries (SGAs) (Fig. 10.7c).
Fig. 10.6 #4d dissection
#6 Dissection
operating surgeon gently holds the pedicle of the The operating surgeon moves to the left of the
right gastroepiploic artery and vein (RGEA and patient. The transverse colon is mobilized by dis-
RGEV) to create a triangle. The operating sur- secting the fusion fascia, and the pancreatic head
geon starts opening the omental bursa at a thin is widely exposed. The left aspect of the adipose
part of the greater omentum (Fig. 10.6) and tran- tissue including #14v and 6 is dissected along
sects it along the border between the adipose tis- the inferior border of the pancreas (Fig. 10.8a).
sue belonging to the stomach and that belonging Subsequently by dissecting on the edge of the
to the transverse colon referring to the “line” gen- pancreas continuously from the inferior to ante-
erated by physiological adhesion (Fig. 10.7a). rior aspects of the pancreatic neck, RGEA and
Adhesion between the posterior aspect of the the autonomic nerve on the right of RGEA are
stomach and the pancreatic body should also be exposed (Fig. 10.8b). At this site, right gastroep-
detached as much as possible just to recover the iploic vein (RGEV) is running along the nerve,
original anatomy. and the outermost layer of RGEA is widely
a b
LGEA
Stomach
LGEA
Pancreatic tail
#4sb
Fig. 10.7 #4sb dissection: (a) dissection of the physiological adhesion on the left field of the omental bursa, (b) tran-
section of LGEA, (c) dissection of #4sb along the greater curvature of the stomach
exposed by dividing between the vein and nerve Transection of the Duodenum

to facilitate #6v dissection (Fig. 10.8b). The The avascular area between the lesser curvature
prepancreatic fascia is dissected along the ante- side of the duodenal bulb and the adipose tissue
rior superior pancreatoduodenal vein (ASPDV) bearing #5 is opened from the posterior aspect
(Fig. 10.8c). RGEV is transected right above of the stomach (Fig. 10.10a). Then, the duodenal
ASPDV (Fig. 10.8d). Then, the adipose tissue bulb is transected in the posteroanterior direction
bearing #6v is completely removed on the outer- (Fig. 10.10b).
most layer of RGEA and anterior superior pan-
creatoduodenal artery (ASPDA) (Fig. 10.8e). esser Omentum, Top of #1
L
During this process, infrapyloric veins are tran- The operating surgeon moves back to the right
sected at their origins. As a next step, the cra- of the patient. The lesser omentum is dissected
nial aspect of the fat tissue including station #6i along the most cranial hepatic branch of the
and #6a is removed from the greater curvature vagal nerve (“reversed-L shape”) (Fig. 10.11a).
side of the duodenum (“C-loop”) (Fig. 10.9a). The anterior aspect of the subretroperitoneal fas-
Finally, the RGEA and infrapyloric artery (IPA) cia is exposed in front of the right diaphragmatic
are transected (Fig. 10.9b). crus (Fig. 10.11b). The top of the #1 dissection
a b RGEA
Nerve
Pancreatic neck
Inferior aspect of
pancreatic neck RGEV
RGEV
SMV
c d
RGEV
ASPDV
Duodenum
Pancreatic head
e
RGEA
#6v
ASPDA
Pancreas
Fig. 10.8 #6v dissection: (a) exposure of the inferior of RGEA; (c) dissection of the prepancreatic fascia along
aspect of the pancreatic neck; (b) continuous dissection ASPDV; (d) transection of RGEV; (e) #6v dissection
on the edge of the pancreas from inferior to anterior along the outermost layer (arrow) of RGEA and ASPDA
aspects of the pancreatic neck, arrow: the outermost layer
a b
IPA RGEA
Duodenum
#6a,i
Fig. 10.9 #6a and i dissection: (a) dissection of the “C-loop,” (b) transection of RGEA and IPA
a b
Duodenum
Pancreas
Fig. 10.10 Transection of the duodenum: (a) avascular area on the lesser curvature side of the duodenal bulb, (b)
transection of the duodenal bulb
a b
Hepatic branch
Top of #1
Right crus
Subretroperitoneal
fascia
Lesser
omentum
Fig. 10.11 Transection of the lesser omentum: (a) reversed L-shaped dissection of the lesser omentum, (b) the subret-
roperitoneal fascia on the right diaphragmatic crus
is determined confirming the final ascending and the proximal part of the splenic artery (SPA)
branch of the left gastric artery (LGA). (Fig. 10.13b). This dissection is continued along
the outermost layer of the left lateral aspect of
Rolling Up the Stomach the proper hepatic artery (PHA) to the back of the
To facilitate suprapancreatic lymph node dissec- right gastric artery (RGA).
tion, the stomach is rolled up (Fig. 10.12).
#5 Dissection
robing the Outermost Layer of CHA
P The outermost layer along the cranial aspect
and SPA of RGA and the distal part of PHA is exposed
The assistant surgeon retracts the caudal edge (Fig. 10.14a). The origin of RGA was divided by
of the pancreatic body with his/her left hand clips (Fig. 10.14b).
(gauze-holding forceps) and stretches the gas-
tropancreatic fold with his/her right hand. The Medial Approach [1, 11]
operating surgeon stretches the adipose tissue The avascular space of the left gastric artery
containing #8a and #11p carefully and dissects (LGA) is dissected bilaterally along the outer-
it along the stably visualized outermost layer of most layer (Fig. 10.15a, b).
the common hepatic artery (CHA) (Fig. 10.13a)
#12a Dissection
The fat tissue containing #5, 8a, 9(R), and 12a is
lifted ventrally. To create a good surgical field,
the operating surgeon pulls the thick nerve fibers
along the PHA laterodorsally, and the assistant
surgeon pulls the nerve fibers on the cranial side
of the CHA caudodorsally (Fig. 10.16a). Then,
the portal vein (PV) is superficialized, and #12a
lymph nodes are safely dissected along the PV
(Fig. 10.16b).
#9(R) Dissection
The target fat tissue containing #8a, 9(R), and
12a is completely dissected along the outermost
Fig. 10.12 Rolling up the stomach layer of the nerve plexus of the celiac artery, lead-
a RGA b
#7
#8a #8a
CHA
#11p
CHA SPA
Pancreas
Fig. 10.13 Probing the outermost layer: (a) the outermost layer along CHA (arrow), (b) the outermost layer along SPA
(arrow)
a b
RGA
PHA
RGA
PHA
Fig. 10.14 #5 dissection: (a) the outermost layer along the cranial aspect of RGA, (b) transection of RGA
a a b
#7
LGA
#8a
LGA
LGV
#12a #7
SPA
CHA
CHA
Fig. 10.15 Medial approach: (a) the outermost layer along the right aspect of LGA, (b) the outermost layer along the
left aspect of LGA
a b
PHA
#12a
PHA
#12a
PV
CHA
Fig. 10.16 #12a dissection: (a) creation of the good surgical field by pulling the nerves along PHA and CHA, arrow:
outermost layer, (b) safe dissection on #12 along the superficialized PV
ing to sufficient mobilization of the target. Then, aspect of #11p (Fig. 10.19a). The lateral aspect
the lymphatic connection between the target fat of the targeted fat tissue is dissected along the
tissue and #16a2-inter is divided and is dissected outermost layer of SPA (Fig. 10.19b). To obtain
along the right diaphragmatic crus (Fig. 10.17). a good surgical view around the dorsal area of
The left gastric vein (LGV) is transected on the SPA, the assistant surgeon laterodorsally retracts
way (Fig. 10.18a). the thick nerve fibers along the cranial aspect of
SPA (Fig. 10.19b), and the operating surgeon
#7 Dissection pulls the target ventrally. Thus, SPV is superfi-
The origin of LGA is exposed and divided by cialized and the bottom of #11p is dissected on
clips (Fig. 10.18b). the splenic vein (SPV) safely (Fig. 10.19c). #11p
dissection is sometimes more easily conducted
#11p Dissection when it is done right after #4sb dissection.
The massive area of the target fat tissue bearing
suprapancreatic lymph nodes is retracted laterally #9(L) Dissection
to the patient’s left by the assistant surgeon. #11p The fat tissue containing #11p and 9(L) is lifted,
lymph nodes are freed from the subretroperi- and the lymphatic connection between #9(L) and
toneal (Gerota’s) fascia, delineating the dorsal 16a2-lat is divided (Fig. 10.20).
1 and 3 Dissection
#
The adipose tissue bearing #1 and 3 is lifted by
the assistant surgeon’s right hand and the operat-
ing surgeon’s left hand (Fig. 10.21a). The other
LGA hand of the assistant surgeon retracts the poste-
#9R rior aspect of the stomach dorsally (Fig. 10.21a).
LGV
Using this surgical field, #1 and 3 are dissected in
the caudocranial direction (Fig. 10.21b).
Transection of the Stomach
The stomach is transected from the greater to the
lesser curvature on the line between the prefinal
CHA
branch of LGEA and final ascending branch of
Fig. 10.17 #9(R) dissection: division of the lymphatic LGA irrespective of the location of the tumor
connection between #9(R) and #16a2-inter (Fig. 10.22).
a b
LGA
LGV
#17
LGA
SPA
Fig. 10.18 #7 dissection: (a) transection of LGV, (b) transection of LGA

a Esophagus b
#7
Right crus
Subretroperitoneal
fascia #11p
SPA
#7
#11p
SPV
SPA
Fig. 10.19 #11p dissection: (a) mobilization of the dor- most layer of SPA, (c) dissection of the bottom of #11p on
sal aspect of #11p on the subretroperitoneal fascia, (b) the superficialized SPV
dissection of the lateral aspect of #11p along the outer-
#7 Results
#11p
According to our previous publication [8], opera-

tive time, blood loss, and the number of dis-
#9(L) sected lymph nodes were 354 (182–634) min,
34 (0–702) ml, and 40 (0–108), respectively. The
SPV morbidity and the incidence of pancreatic fistula
were 6.7% and 2.5%, respectively. There has
been no conversion to open procedure so far. The
SPA reoperation rate and mortality were both 0.6%.
The duration of postoperative hospital stay was
14 (8–69) days.
Fig. 10.20 #9(L) dissection

a b
#1,3
#1,3
Fig. 10.21 #1 and 3 dissection: (a) surgical field for #1 and 3 dissection, (b) caudocranial dissection of #1 and 3 along
the lesser curvature of the stomach
[7]. Moreover, no significant difference was

observed in terms of long-term outcomes [7].
Thus, at our institute, laparoscopic D2 gastrec-
tomy has been the standard type of operation for
Prefinal both early and advanced gastric cancer.
branch of From the operating surgeon’s point of view,
LGEA to overcome the laparoscopic limited range of
Final
ascending motion enjoying the high quality of laparoscopi-
branch of cally magnified image, we believe mediolateral
LGA
and/or caudocranial dissection must be the most
important. Based on this philosophy, the XYZ-
axis theory was established extending the out-
ermost layer-oriented medial approach [10, 11].
Fig. 10.22 Transection of the stomach Using this theory, the outermost layer could pos-
sibly be detected at any junction of three arter-
Discussion ies, leading to smoother and more reproducible
Laparoscopic gastrectomy has been increas- There is no doubt that #11p and 12a dissec-
ingly performed as a minimally invasive surgical tion is the key to successful D2 distal gastrectomy.
approach that provides significant advantages for From the assistant surgeon’s perspective, skillful
short-term outcomes as opposed to open surgical laterodorsal retraction of the autonomic nerves
procedures for the early gastric cancer patients along SPA, CHA, and PHA allows SPV and PV
[13]. However, laparoscopic gastrectomy for to come up closer to the suprapancreatic border,
advanced gastric cancer remains controversial resulting in pancreas-protective safe D2 dissection.
because of its technical difficulties and lack of
long-term results [1, 7–9, 13]. We have been
demonstrated that use of laparoscopic approach, Conclusions
compared with open approach, not only for early
but also for advanced gastric cancer, extended It has been clearly shown that laparoscopic
operative time, reduced blood loss and did not gastrectomy has considerable short-term ben-
increase morbidity including pancreatic fistula efits over open approach, even though further
investigation would be required to demonstrate 6. Japanese Gastric Cancer Association. Japanese clas-
sification of gastric carcinoma: 3rd English edition.
oncological safety of laparoscopic gastrectomy Gastric Cancer. 2011;14:101–12.
especially for advanced gastric cancer [1, 7, 13]. 7. Shinohara T, Satoh S, Kanaya S, Ishida Y, Taniguchi K,
The principles and methods for totally laparo- Isogaki J, Inaba K, Yanaga K, Uyama I. Laparoscopic
scopic gastrectomy based on our experience versus open D2 gastrectomy for advanced gastric
cancer: a retrospective cohort study. Surg Endosc.
demonstrated in this article may help upper GI 2013;27:286–94.
surgeons overcome technical difficulties in lapa- 8. Suda K, Man-I M, Ishida Y, Kawamura Y, Satoh S,
roscopic D2 gastrectomy. Uyama I. Potential advantages of robotic radical gas-
trectomy for gastric adenocarcinoma in comparison
with conventional laparoscopic approach: a single
Disclosures This work was not supported by any grants
institutional retrospective comparative cohort study.
and fundings. No author has commercial association with
Surg Endosc. 2015;29:673–85.
or financial involvement that might pose a conflict of
9. Japanese Gastric Cancer Association. JGCA gastric
interest in connection with the submitted article.
cancer treatment guidelines 2014 (ver. 4). Tokyo:
Kanehara; 2014.
10. Kanaya S, Haruta S, Kawamura Y, Yoshimura F,

Inaba K, Hiramatsu Y, Ishida Y, Taniguchi K, Isogaki
References J, Uyama I. Video: laparoscopy distinctive technique
for suprapancreatic lymph node dissection: medial
1. Uyama I, Suda K, Satoh S. Laparoscopic surgery for approach for laparoscopic gastric cancer surgery. Surg
advanced gastric cancer: current status and future per- Endosc. 2011;25:3928–9.
spectives. J Gastric Cancer. 2013;13:19–25. 11. Uyama I, Kanaya S, Ishida Y, Inaba K, Suda K, Satoh
2. Crew KD, Neugut AI. Epidemiology of gastric cancer. S. Novel integrated robotic approach for suprapan-
World J Gastroenterol. 2006;12:354–62. creatic D2 nodal dissection for treating gastric can-
3. Dikken JL, van de Velde CJ, Coit DG, Shah MA, cer: technique and initial experience. World J Surg.
Verheij M, Cats A. Treatment of resectable gastric 2012;36:331–7.
cancer. Therap Adv Gastroenterol. 2012;5:49–69. 12. Shinohara T, Kanaya S, Taniguchi K, Fujita T, Yanaga
4. Uyama I, Sugioka A, Fujita J, Komori Y, Matsui H, K, Uyama I. Laparoscopic total gastrectomy with D2
Hasumi A. Laparoscopic total gastrectomy with lymph node dissection for gastric cancer. Arch Surg.
distal pancreatosplenectomy and D2 lymphadenec- 2009;144:1138–42.
tomy for advanced gastric cancer. Gastric Cancer. 13. Nakauchi M, Suda K, Kadoya S, Inaba K, Ishida
1999;2:230–4. Y, Uyama I. Technical aspects and short- and
5. Uyama I, Sugioka A, Matsui H, Fujita J, Komori Y, long-term outcomes of totally laparoscopic total
Hasumi A. Laparoscopic D2 lymph node dissection gastrectomy for advanced gastric cancer: a single-insti-
for advanced gastric cancer located in the middle or tution retrospective study. Surg Endosc. 2016;30(10):
lower third portion of the stomach. Gastric Cancer. 4632–9. https://doi.org/10.1007/s00464-015-4726-4.
2000;3:50–5. Epub 2015 Dec 24.
Laparoscopic Surgery for Gastric
Cancer, Total Gastrectomy with D2 11
Lymph Node Dissection
Yoo Min Kim and Woo Jin Hyung
Introduction hilar lymph node dissection is not recommended

in laparoscopic gastric cancer surgery. Thus,
For advanced gastric cancer located in the upper spleen-preserving hilar lymph node dissection
body of the stomach, total gastrectomy with D2 has not been mostly attempted in laparoscopic
lymph node dissection is recommended [1–4]. surgery procedures [6–8]. However, for the
D2 lymph node dissection for proximal tumors application of the laparoscopic gastrectomy for
requires the retrieval of the soft tissues around cT2 or more advanced lesions especially located
distal portions of the splenic vessels and splenic greater curvature of the upper stomach, lymph
hilum, which contain lymph nodes at stations #10 node dissection of station 10 and station 11d
and #11d [4, 5]. Two options – a total gastrec- should be performed during total gastrectomy for
tomy with splenectomy and a spleen-preserving D2 lymph node dissection [9–12]. Laparoscopic
total gastrectomy – exist for retrieval of lymph total gastrectomy is considered technically more
nodes at station #10. While splenectomy-related difficult than its distal gastrectomy counterpart
postoperative complications, such as subphrenic and, therefore, less widely practiced [13–16].
abscess and postsplenectomy syndrome, are well Herein, we present the principles and detailed
known, complete lymph node dissection of the procedure of totally laparoscopic spleen-
splenic hilum during spleen-preserving total gas- preserving total gastrectomy with D2 lymph
trectomy is a very complex procedure. node dissection.
Currently, most surgeons only offer laparo-
scopic treatment of gastric cancer for early gastric
cancer (cT1); splenectomy or spleen-preserving Setup
Indications for Laparoscopic Total

Electronic Supplementary Material The online version Gastrectomy with D2 Lymph Node
of this chapter (https://doi.org/10.1007/978-3-662-45583-
8_11) contains supplementary material, which is available Dissection
to authorized users.
Y. M. Kim The preoperative diagnosis is made according
Department of Surgery, CHA Bundang Medical Center, to the findings of upper endoscopy with endo-
CHA University, Gyeonggi-do, Republic of Korea scopic ultrasound and abdominopelvic computed
W. J. Hyung (*) tomography. Unless patients have lesions suit-
Department of Surgery, Yonsei University College of able for endoscopic mucosal resection, patients
Medicine, Seoul, Republic of Korea with a preoperative diagnosis of T1 or T2 gas-

https://doi.org/10.1007/978-3-662-45583-8_11
154 Y. M. Kim and W. J. Hyung
tric cancers without evidence of lymph node

metastasis in the extra-perigastric (N2) area by
UICC and JGCA classification are candidates
for laparoscopic surgery. The indication for the
1 3
laparoscopic spleen-preserving splenic hilar
lymph node dissection is gastric cancer in the
upper body of the stomach with a high probabil-
ity of deep submucosa (SM3) or proper muscle
2
invasion without evidence of gross lymph node
Assistant
metastasis along splenic artery or splenic hilar Camera
area through preoperative evaluation.
OR Setup
The surgeon and scopist stand on the patient’s

right side, and an assistant surgeon and scrub
nurse are on the patient’s left side.
Alternatively, the scopist stands between the
patient’s legs if the patient lay on the table with Fig. 11.1 Trocar arrangement in laparoscopic total gas-
trectomy. “1”, red–Right subcostal port (5 mm);
legs apart.
“2”, green–Right lower port (main working, 5–12 mm);
“3”, yellow–Left subcostal port (5 mm); “assistant”,
white–Left lower port (assistant port, 6–12 mm);
Patient’s Position “camera”, blue–camera port (10–12 mm)
Basically, the patient is placed in a supine posi- • Right lower port (main working): 5–12 mm,
tion, both arms extended, and 15-degree reverse laterally from the right subcostal port, mid-
Trendelenburg position, head-up tilt. The arms line between the camera port and the right
(right angle or alongside the body), legs (gathered subcostal port, at the level of the head of the
or apart), and reverse Trendelenburg (10-degree pancreas, to approach the splenic vessels
~ 30-degree tilt) positions are decided with sur- superior to the pancreas with ultrasonic
geon’s preference. shears
• Note: This port can be inserted more medially
in obese patient and laterally in patient with
Port Placement small abdominal cavity for a comfortable
approach to the splenic hilum with laparo-
The camera is first inserted through the infraumbil- scopic instruments.
ical port, after which the other trocars are inserted • Left subcostal port: 5 mm, one finger caudally
under direct vision with laparoscope (Fig. 11.1). from the left subcostal line, on top of the angle
or midportion of the lesser curvature under
• Camera port: 10–12 mm, midline below the laparoscope, inserted slightly caudally com-
umbilicus (Umbilicus or supraumbilicus is to pared to the right subcostal port
the surgeon’s preference.) • Left lower port: 5–12 mm, laterally from the
• Right subcostal port: 5 mm, one finger cau- left subcostal port, midline between the cam-
dally from the right subcostal line, on top of era port and left subcostal port, at the level of
the pylorus, adjusted to the surgeon’s comfort greater curvature, to reach the greater curva-
for grasping and pulling over adipose tissue ture of the stomach for placing the endo-linear
around celiac and splenic vessels stapler
11 Laparoscopic Surgery for Gastric Cancer, Total Gastrectomy with D2 Lymph Node Dissection 155
Liver Retraction 4sb Dissection #4sa Dissection

#
The left gastroepiploic artery and left gastroepi-
After trocar insertion is complete, the liver retrac- ploic vein are divided at the root for removal of
tion is performed because it allows essential for splenic hilar lymph nodes. After division of the
clear visualization of the lesser curvature area left gastroepiploic vessels at their roots, the gas-
and allows the assistant right hand to be free for trosplenic ligament is separated up to the left side
dynamic use. For static retraction, we perform a of the esophageal hiatus by dividing the short
liver suspension method, utilizing a suture and a gastric vessels from the surface of the spleen to
gauze pad as a “sling” [17]. dissect lymph nodes at #4sa around the short gas-
tric vessels and to mobilize the upper part of the
greater curvature of the stomach. For this proce-
etails of D2 Dissection in Total
D dure, the operating table is tilted left side up for
Gastrectomy better exposure of the gastrosplenic ligament and
splenic hilar area using gravity. Because of the
Omentectomy limitation in the number of instruments in laparo-
After establishment of pneumoperitoneum scopic surgery unlike open surgery, traction using
and trocar placement, the operation starts for gravity is important. To better expose the spleen
omentectomy. A partial omentectomy divides and splenic hilar area during division of the gas-
and dissects the greater omentum at 4–5 cm trosplenic ligament, the posterior attachment of
from the greater curvature for the preservation the spleen is not mobilized to keep it suspended
of omentum. A total omentectomy divides the within the splenic fossa against gravity as the dis-
greater omentum from the transverse colon section proceeds.
using ultrasonic shears from the mid-transverse
colon toward the lower pole of the spleen. The 11d and #10 Dissection
#
assistant retracts the omentum toward the head After fully exposing the splenic hilar area for the
with the right hand and pulls downward on the removal of the lymph nodes at #10 and #11d,
teniae coli of the transverse colon with atrau- the tail of the pancreas is retracted caudally with
matic graspers in the left hand. It is important the left hand of the assistant, and the posterior
that no injury is made to the transverse colon wall of the upper stomach is pushed upward with
when dissecting the attachment of the poste- the assistant’s right hand. The splenic vessels
rior greater omentum to the transverse colon are exposed at the junction between the stations
(Fig. 11.2). #11p and #11d lymph nodes, and the dissection
a b
Fig. 11.2 Total omentectomy (a) and isolation of the left gastroepiploic vessels (b)
Fig. 11.3 Splenic vessel exposure at the junction between #11p and #11d
Fig. 11.4 Skeletonization of the splenic vessels from the distal of the posterior gastric vessels to the splenic hilar area
of station #11d lymph nodes starts there from the divided at its origin to enable dissection of the
splenic vessels and then continues to the splenic station 2 lymph nodes.
hilum. By skeletonizing the splenic vessels from
the posterior gastric vessels to the splenic hilar 4d and #6 Dissection and Duodenal
#
area, removal of the #11d and #10 lymph nodes Transection
bearing soft tissues is achieved, and all vessels in After completing the operative procedure of
the splenic hilum are saved with preservation of the left side, the operating table is repositioned
the spleen. For a safe procedure, surgeon should in neutral position. Then, the division of the
take into account the splenic vascular anatomy greater omentum is continued distally toward
preoperatively (Figs. 11.3, 11.4). the pylorus, and the right gastroepiploic vessels
are divided at their roots. Soft tissues attached to
#2 Dissection the duodenum and head of the pancreas are dis-
The retroperitoneal attachment of the posterior sected. The supra-duodenal vessels are ligated
wall of the upper stomach is detached up to the with ultrasonic shears, and the duodenum is tran-
diaphragmatic cruses, and the esophagocar- sected 2 cm distal to the pylorus using an endo-
diac branch of the left inferior phrenic artery is scopic linear stapler.
11 Laparoscopic Surgery for Gastric Cancer, Total Gastrectomy with D2 Lymph Node Dissection 157
uprapancreatic Dissection (#5, #12a,

S To determine the reconstruction method, the
#8, #7, #9, #1, and #11p) patient’s condition, the location of tumor, the
After duodenal transection, the right gastric artery resection margins, and the surgeon’s preference
is exposed and divided at its origin. After dissection are considered. After reconstruction, the cam-
along the gastroduodenal and proper hepatic artery era port site is extended to the lower abdominal
and ligation of right gastric artery, soft tissues at wall about 2–3 cm, and the specimen is retrieved
the medial side of the portal vein are dissected. The through the minilaparotomy site. The minilapa-
pedicle of the left gastric artery and vein is care- rotomy is closed with interrupted 1-0 polydioxa-
fully lifted with the assistant’s right hand, and the none sutures. The trocar sites are closed with 2-0
pancreas is moved downward with gauze in the polydioxanone sutures. The subcutis and cutis
assistant’s left hand. The gastropancreatic ligament are restored with interrupted 3-0 polydioxanone
is divided using ultrasonic shear, and the com- sutures and skin staples.
mon hepatic artery is exposed. The soft tissues at
the anterior part of the common hepatic artery and plenectomy for #10 Dissection
S
right side of the celiac artery are cleared, and theThe complete clearance of splenic hilar lymph
nodes by splenectomy should be considered for
left gastric vein is exposed and divided at its drain-
ing point to the portal vein or splenic vein. The potentially curable T2–T4 tumors with invasion
soft tissues above the upper edge of the pancreas into the greater curvature of the upper stomach or
are completely removed. The left gastric artery into the spleen directly, even though splenectomy
is then exposed and ligated at the root, while the is not routinely performed during total gastrec-
lymph nodes are dissected around the celiac axis tomy for advanced gastric cancer on the upper
area. The stomach is freed from the retroperito- stomach.
neal attachment up to the right diaphragmatic crus. The gastrocolic ligament is first divided up
The dissection is continued from the splenic ves- to the spleen using ultrasonic shears or electro-
cautery. The splenocolic ligament is divided and
sels’ origin toward the pancreatic tail to expose the
proximal half of the splenic artery. lower pole of the spleen is mobilized. The sple-
nophrenic and splenorenal ligament are divided
Distal Esophagus Transection up to the upper pole of the spleen to mobilize the
After the posterior surface of the upper stom- spleen from the retroperitoneum. The splenec-
ach is separated from the retroperitoneum, the tomy and dissection of the station #11d lymph
abdominal esophagus is mobilized by divid- nodes are performed after the mobilization of
ing the phrenoesophageal membrane and vagus the lower stomach with lymph node dissection
nerves. The distal esophagus and the whole and esophageal transection. The upper body of
stomach are fully freed and transected with endo- the stomach is retracted downward and caudally
linear stapler. after distal esophagus transection. The esoph-
agocardiac branch of the left inferior phrenic
Reconstruction and Specimen Retrieval artery is ligated at its origin for lymph node dis-
The stomach is packed within an endo-bag section at station 2. The #11d lymph node dis-
and placed in the right abdominal cavity. After section is performed from the proximal part of
laparoscopic total gastrectomy, bowel continu- splenic vessels to the splenic hilum. The splenic
ity is restored by Roux-en-Y esophagojejunos- artery is skeletonized and ligated just distal to
tomy. There are several reconstruction methods: the bifurcation of the caudal pancreatic artery;
intracorporeally or extracorporeally, creating a the splenic vein is also skeletonized and ligated
side- side esophagojejunostomy with linear distal to the pancreatic tail to avoid pancreatic
to-
stapler or an end-to-side esophagojejunostomy fistula. After skeletonization of splenic vessels,
with circular stapler. A jejunojenostomy is made the splenic artery and vein are ligated with clips
at 45 cm distal to the esophagojejunostomy. or vascular stapler.
Disclosures This work was not supported by external or 9. Aikou T, Shimazu H, Takao T, et al. Significance of
grant funding. None of the authors have commercial asso- lymph nodal metastases in treatment of esophagogas-
ciations or financial involvement that pose a conflict of tric adenocarcinoma. Lymphology. 1992;25:31–6.
interest in connection with the submitted article. 10. Maruyama K, Gunven P, Okabayashi K, et al. Lymph
node metastases of gastric cancer. General pattern in
1931 patients. Ann Surg. 1989;210:596–602.
11. Mönig SP, Collet PH, Baldus SE, Schmackpfeffer
References K, Schröder W, Thiele J, Dienes HP, Hölscher
AH. Splenectomy in proximal gastric cancer: fre-
1. Degiuli M, Sasako M, Ponti A, et al. Randomized clin- quency of lymph node metastasis to the splenic hilus.
ical trial comparing survival after D1 or D2 gastrec- J Surg Oncol. 2001;76(2):89–92.
tomy for gastric cancer. Br J Surg. 2014;101:23–31. 12. Ikeguchi M, Kaibara N. Lymph node metastasis at the
2. Songun I, Putter H, Kranenbarg EM, et al. Surgical splenic hilum in proximal gastric cancer. Am Surg.
treatment of gastric cancer: 15-year follow-up results 2004;70(7):645–8.
of the randomised nationwide Dutch D1D2 trial. 13. Hyung WJ, Lim JS, Song J, Choi SH, Noh

Lancet Oncol. 2010;11:439–49. SH. Laparoscopic spleen-preserving splenic hilar
3. Sasako M, Sano T, Yamamoto S, et al. D2 lymphad- lymph node dissection during total gastrectomy for
enectomy alone or with para-aortic nodal dissection gastric cancer. J Am Coll Surg. 2008;207(2):e6–11.
for gastric cancer. N Engl J Med. 2008;359:453–62. 14.
Shinohara T, Kanaya S, Taniguchi K, et al.
4. Japanese Gastric Cancer Association. Japanese gas- Laparoscopic total gastrectomy with D2 lymph
tric cancer treatment guidelines 2014 (ver. 4). Gastric node dissection for gastric cancer. Arch Surg.
Cancer. 2017;20(1):1–19. 2009;144:1138–42.
5. Japanese Gastric Cancer Association. Japanese clas- 15. Jia-Bin W, Chang-Ming H, Chao-Hui Z, Ping L, Jian-
sification of gastric carcinoma: 3rd English edition. Wei X, Jian-Xian L. Laparoscopic spleen-preserving
Gastric Cancer. 2011;14:101–12. No. 10 lymph node dissection for advanced proximal
6. Katai H, Yoshimura K, Fukagawa T, Sano T, Sasako gastric cancer in left approach: a new operation proce-
M. Risk factors for pancreas-related abscess after total dure. World J Surg Oncol. 2012;10:241.
gastrectomy. Gastric Cancer. 2005;8(3):137–41. 16. Okabe H, Obama K, Kan T, Tanaka E, Itami A, Sakai
7. Yoshino K, Yamada Y, Asanuma F, Aizawa Y. Medial approach for laparoscopic total gastrec-
K. Splenectomy in cancer gastrectomy: recommen- tomy with splenic lymph node dissection. J Am Coll
dation of spleen-preserving for early stages. Int Surg. Surg. 2010;211:e1–6.
1997;82(2):150–4. 17. Woo Y, Hyung WJ, Kim HI, Obama K, Son T, Noh
8. Maruyama K, Sasako M, Kinoshita T, Sano T, Katai SH. Minimizing hepatic trauma with a novel liver
H, Okajima K. Pancreas-preserving total gastrec- retraction method: a simple liver suspension using
tomy for proximal gastric cancer. World J Surg. gauze suture. Surg Endosc. 2011;25(12):3939–45.
1995;19(4):532–6. https://doi.org/10.1007/s00464-011-1788-9.
Intracorporeal Reconstruction
in Laparoscopic Gastrectomy 12
Hisahiro Hosogi, Yoshiharu Sakai,
and Seiichiro Kanaya
Introduction extracorporeal reconstruction decreases the

advantages of the minimally invasive approach,
Since the introduction of laparoscopy-assisted especially in obese patients that need extension
distal gastrectomy (LADG) as a treatment for of the laparotomy to obtain a better view. To
gastric cancer in the 1990s, the number of patients solve these problems, intracorporeal anastomosis
undergoing laparoscopic gastrectomy is rapidly techniques have been developed [5, 6], and a
increasing, particularly in eastern Asia [1, 2]. completely laparoscopic gastrectomy has become
Initially, reconstruction was performed through a widespread not only in laparoscopic distal gas-
minilaparotomy after gastrectomy had been com- trectomy (LDG) but also in laparoscopic total
pleted laparoscopically [3]. Laparoscopy-assisted gastrectomy (LTG) [7–10]. Recent studies of
gastrectomy provides several benefits including gastrectomy with intracorporeal anastomosis
less blood loss, better cosmesis, and earlier have reported acceptable surgical outcomes [7, 8,
recovery when compared with open gastrectomy 11–13]. However, some technical pitfalls need to
[4]. However, the minilaparotomy required for an be understood, and adequate surgical skills
should be acquired to ensure patient safety. In
this chapter, common procedures of intracorpo-
Electronic Supplementary Material The online version real reconstruction in LDG and LTG with endo-
8_12) contains supplementary material, which is available scopic linear staples are introduced, and
to authorized users. reconstruction-related short-term results in our
institution are reported.
H. Hosogi (*)
Department of Surgery, Graduate School of
Medicine, Kyoto University, Kyoto, Japan
Materials and Methods
Department of Surgery, Osaka Red Cross Hospital,
Osaka, Japan
e-mail: hisahoso@kuhp.kyoto-u.ac.jp Patients
Y. Sakai
Department of Surgery, Graduate School of The records of 427 consecutive patients who under-
Medicine, Kyoto University, Kyoto, Japan went LDG or LTG for histologically proven adeno-
e-mail: ysakai@kuhp.kyoto-u.ac.jp carcinoma of the stomach between April 2011 and
S. Kanaya March 2015 were retrieved from a prospective insti-
Department of Surgery, Osaka Red Cross Hospital, tutional database in the Osaka Red Cross Hospital.
Osaka, Japan
LDG was performed for 301 patients and LTG for
e-mail: skanaya@osaka-med.jrc.or.jp

https://doi.org/10.1007/978-3-662-45583-8_12
160 H. Hosogi et al.
126 patients. R
econstruction-related short-term sur- stump were dissected, and a 2 cm length
gical outcomes were retrospectively investigated. from the edge was devascularized in prepara-
Tumor stage was classified according to the seventh tion for stapling. A 45-mm endoscopic linear
edition of TNM classification [14]. Postoperative stapler was applied through the left lower
complications, which occurred within 30 days after trocar, with one fork in each hole. The poste-
the operation, were classified according to the rior wall of the stomach and that of the duo-
Clavien-Dindo classification system [15]. denum was apposed, and the stapler was
fired (Fig. 12.1b). A V-shaped anastomosis
was thus made along the posterior wall. After
Operative Technique checking hemostasis of the staple line, the
common enterotomy was closed temporarily
The detailed procedure was described previously with hernia staplers, and the anastomosis
[6, 8, 16–18]. In all of the following reconstruc- completed with one or two applications of a
tive procedures, the surgeon stood on the right linear stapler (Fig. 12.1c).
side of the patient. Endoscopic linear staplers (b) Gastrojejunostomy in Billroth-II reconstruc-
were used in all the reconstructive procedures. tion (Fig. 12.2 and Video 12.2).
The duodenal stump was reinforced with
Reconstruction in LDG intracorporeal seromuscular suturing with
For reconstruction in LDG, a delta-shaped anas- extracorporeal Roeder’s knots. Enterotomies
tomosis was the first choice when R0 resection were created on the greater curvature of the
was possible, with routine resection of two-thirds remnant stomach and the antimesenteric side
of the stomach [19]. The exception was patients of the jejunum located 25 cm distal to the
with a hiatal hernia. Billroth II or Roux-en-Y ligament of Treitz. A 45-mm endoscopic lin-
reconstruction was performed when the extent of ear stapler was applied through the right
LDG resulted in a small remnant stomach due to lower trocar. We routinely performed
the tumor location or when the duodenal bulb had antecolic antiperistaltic gastrojejunostomy.
to be resected due to tumor invasion. Billroth-II The entry-hole closure with another stapler
reconstruction was selected in elderly patients was not a painstaking task because the enter-
over 75 years of age, and the Roux-en-Y recon- otomy for insertion of the stapler was made
struction was selected in younger patients or in on the afferent loop, and the stoma size of the
those with a hiatal hernia. efferent loop was unaffected by the closure.
Because a Braun anastomosis was not cre-

(a) Delta-shaped anastomosis in Billroth-I ated, some sutures were added between the
reconstruction (Fig. 12.1 and Video 12.1). jejunal wall on the afferent loop and the sta-
After mobilization of the first portion of ple line on the lesser curvature of the rem-
the duodenum, a linear stapler was intro- nant stomach. This was done to help with
duced through the left lower trocar, and the food passage directly into the efferent loop.
duodenal bulb was transected in the ventro- (c) Gastrojejunostomy in Roux-en-Y recon-
dorsal (posterior-to-anterior) direction, not struction (Fig. 12.3 and Video 12.3).
the usual craniocaudal (greater curvature to Both antiperistaltic (functional end-to-
lesser curvature) direction (Fig. 12.1a). The end anastomosis) and isoperistaltic gastroje-
blood supply to the anastomosis was thus junostomies have been reported [7, 9]. We
preserved. After checking if an anastomosis prefer an antecolic, isoperistaltic gastrojeju-
was possible without undue tension, small nostomy. Prior to the gastrojejunostomy, a
enterotomies were created along the greater jejunojejunostomy was made extracorpore-
curvature of the remnant stomach and the ally in the extended umbilical wound (Video
posterior side of the duodenal stump. 12.4). For intracorporeal gastrojejunostomy,
Supraduodenal arteries around the duodenal a small enterotomy in the jejunal limb was
12 Intracorporeal Reconstruction in Laparoscopic Gastrectomy 161
a b
Anterior wall
SDA
DA
G
Posterior wall
Fig. 12.1 Delta-shaped anastomosis in a Billroth-I applied through the left lower trocar. The posterior wall of
reconstruction. (a) View after duodenal transection. Note the stomach and that of the duodenum were put together.
that the duodenum was transected in the ventro-dorsal Traction in the lateral direction by the surgeon and the
(posterior-to-anterior) direction, not the craniocaudal assistant are important (boxed gray arrows). (c) Closing
(greater curvature to lesser curvature) direction. The ante- the common enterotomy with a stapler applied through
rior and posterior walls are shown. SDA, supraduodenal the left lower trocar. The surgeon sets the transection line
artery; GDA, gastroduodenal artery. (b) First stapling in parallel to the axis of the stapler
the delta-shaped anastomosis. A 45-mm stapler was
a b
Fig. 12.2 Gastrojejunostomy in a Billroth-II reconstruc- arrow. (b) Completion of a Billroth-II anastomosis.
tion. (a) Antiperistaltic gastrojejunostomy. A 45-mm sta- Sutures (dashed arrows) between the afferent loop of the
pler was inserted through the right lower trocar. The jejunum and the remnant stomach make orientation into
efferent loop of the jejunum is shown by a boxed gray the efferent loop a straight line (boxed gray arrow)
(a) Functional end-to-end anastomosis (FETE)

in esophagojejunostomy (Fig. 12.4 and
Video 12.5).
This procedure was the first choice as a
reconstruction method in LTG when a suffi-
cient length of the abdominal esophagus was
preserved. After making small enterotomies
on the left side of the esophageal stump and
the antimesenteric side of the jejunal stump,
a 45-mm stapler was applied through the left
lower trocar. To avoid the insertion of the
anvil fork into a submucosal “pseudo-
Fig. 12.3 Gastrojejunostomy in a Roux-en-Y recon- lumen,” a nasogastric tube was used as a
struction. First stapling in an isoperistaltic gastrojejunos- guide (Fig. 12.4a). After confirming the fork
tomy. A 45-mm stapler was applied through the left lower
trocar. Note that the anastomosis was made with the pos- insertion into the “true lumen” and absence
terior wall of the remnant stomach of nasogastric tube involvement, the stapler
was fired. A small stapling “gap” caused by
slippage of the esophageal stump was man-
created on the antimesenteric side 45 mm aged by temporary laparoscopic continuous
from the edge, and the anastomosis was suture closure (Fig. 12.4b), and then another
made on the posterior wall of the remnant linear stapler for closure was applied from
stomach using a 45-mm stapler applied from the right lower trocar. With this procedure,
the left lower trocar. This was done to pre- the jejunal mesentery runs in a straight fash-
vent gastric stasis by avoiding a twist of the ion without any twist (Fig. 12.4c). Petersen’s
jejunal mesentery. During enterotomy clo- defect was always closed with nonabsorb-
sure with a linear stapler, care must be taken able sutures.
not to resect too much of the jejunal wall, (b) Isoperistaltic, side-to-side esophagojeju-

which could potentially cause an anasto- nostomy (overlap method) (Fig. 12.5 and
motic stricture. Petersen’s defect was always Video 12.6).
closed with nonabsorbable sutures to prevent When sufficient length of the abdominal
an internal hernia. esophagus could not be preserved due to
tumor invasion, and the anastomosis had to be
Reconstruction in LTG made in the lower mediastinum, this proce-
The esophagus was transected in the right-to-left dure was selected. When the esophagus could
direction by a linear stapler inserted in the right not be transected with a linear stapler from
lower trocar. Antecolic Roux-en-Y reconstruc- the right lower trocar, opening the left dia-
tion was routinely selected. In some obese phragm widely and using an intrathoracically
patients, reconstruction with a retrocolic route inserted linear stapler through an additional
was selected. The esophagojejunostomy anasto- intercostal trocar were helpful. Two forks of a
mosis was always made on the left side of the linear stapler were inserted into the jejunum
esophagus, as a redo anastomosis can be per- through a small enterotomy made 45-mm
formed by widely opening the left diaphragm if from the edge and another enterotomy on the
necessary. Prior to esophagojejunostomy, a jeju- esophageal stump. An isoperistaltic side-to-
nojejunostomy was made extracorporeally in the side anastomosis was constructed, and then
extended umbilical wound (Video 12.4). the enterotomy was closed using hand-sewn
a b
Fig. 12.4 Functional end-to-end anastomosis in esoph- right lower trocar. A small stapling “gap” caused by the
agojejunostomy (FETE). (a) View during first stapling. A slippage of the esophageal stump can be managed by tem-
45-mm stapler was applied through the left lower trocar. A porary laparoscopic continuous suture. (c) Completion of
nasogastric tube was used as a guide to confirm insertion the anastomosis. The jejunal mesentery runs straight with-
of the anvil fork into the true lumen of the esophagus. (b) out any twist. Petersen’s defect was then closed with non-
Closing the common enterotomy with a stapler from the absorbable sutures
a b
Fig. 12.5 Esophagojejunostomy with overlap method. pulled out through the subcostal trocars while closing. (b)
(a) Completion of the anastomosis in the lower mediasti- Closing the diaphragm with nonabsorbable sutures for
num. Stay sutures on the edges of the enterotomy were prevention of hiatal hernia
interrupted sutures with extracorporeal Table 12.2 Reconstruction-related short-term surgical

outcomes
Roeder’s knots. Because the level of the anas-
tomosis was in the mediastinum, stay sutures LDG LTG
Variables (n = 301) (n = 126)
on the enterotomy were pulled out through
Reconstructive procedures
the subcostal trocars so that the subsequent
Billroth-I 211
enterotomy closure was easier (Fig. 12.5a). Billroth-II 62
After completing the anastomosis, the dia- Roux-en-Y 28 126a
phragm was closed and sutures between the Functional end-to-end 88
jejunal wall and the diaphragm were added to Overlap 35
prevent a hiatal hernia (Fig. 12.5b). Trouble during 1 4
Nonabsorbable sutures were used for this reconstruction 0 0
Conversion, n
procedure. Finally, the antimesenteric side of
Postoperative morbidityb
the jejunal limb was fixed to the duodenal Grade 2 or higher, in 12 (4.0%) 10 (8.0%)
stump to prevent the limb from falling into total, n, (%)
left dorsal subphrenic space and kinking off Grade 2, in total, n (%) 6 (2.0%) 5 (4.0%)
the esophagojejunal anastomosis. Anastomotic leakage 4 (1.3%) 3 (2.4%)
Ileus 2 (0.7%) 2 (1.6%)
Grade 3 or higher, in 6 (2.0%) 5 (4.0%)
total, n (%)
Results
Anastomotic leakage 4 (1.3%) 2 (1.6%)
Ileus 2 (0.7%) 1 (0.8%)
The clinicopathological characteristics of the 427 Anastomotic stenosis 0 (0.0%) 2 (1.6%)
patients are summarized in Table 12.1. The a
A circular stapler was used in one case, and intrathoracic
reconstructive procedures and reconstruction- overlap procedure was performed in two cases
related short-term surgical outcomes are summa- b
According to Clavien-Dindo classification
rized in Table 12.2. Intraoperative problems
during reconstruction were rare but were more
often observed in LTG (4/126, 3%) than in LDG Discussion
(1/301, 0.3%). There were no conversions to
open surgery. The overall reconstruction-related Intracorporeal reconstruction in laparoscopic
morbidity rate was higher in LTG (8.0%) than in gastrectomy was first reported in 1992 in a
LDG (4.0%). Billroth-II gastrojejunostomy with a linear sta-
pler [5]. Because of the technical difficulties of
intracorporeal gastroduodenostomy, Billroth-II
Table 12.1 Clinicopathological characteristics of the gastrojejunostomy was generally preferred over
patients
Billroth-I [20]. Gastroduodenostomy in laparo-
Variables LDG (n = 301) LTG (n = 126) scopic gastrectomy was first introduced in 1994
Age, median 70 (63–77) 70.5 (63–75)
[3], but it was performed extracorporeally with a
(interquartile
range) circular stapler, in a similar fashion to open sur-
Body mass 22.7 (20.8–24.8) 21.8 (20.1–24.0) gery. In 2002, we developed a technique for intra-
index, median corporeal gastroduodenostomy with linear
(interquartile staplers [6], and short-term and long-term out-
range)
comes of 100 consecutive cases were validated
Sex, n, male/ 207/94 84/42
female [8]. There was no conversion to open surgery, and
Clinical stage, n the mean time for the anastomosis was 13 min-
IA/IB 168/43 40/18 utes. Only one minor leak (1%) was observed as
IIA/IIB 25/20 13/19 a postoperative anastomosis-related complica-
IIIA/IIIB/IIIC 19/14/6 16/7/4 tion, and the incidence of dumping syndrome
IV 6 9 was as low as 5% according to the questionnaires
administered at 6 months or more postopera- of the anvil [27]. The handling of a circular sta-
tively. Although some technical pitfalls can pler under a limited laparoscopic view is another
occur, the delta-shaped anastomosis has become obstacle, but it was managed by modifying the
a widely used technique in Japan and Korea as a location of the camera port and the small incision
simple, quick, and safe method for intracorporeal in maintaining an adequate view [10].
gastroduodenostomy [7, 11–13]. Intracorporeal esophagojejunostomy with
With the increasing use of this procedure, the linear staplers is also a common procedure, with
short-term outcomes of intracorporeal gastroduo- the advantages described above. Either the FETE
denostomy with delta-shaped anastomosis were or the isoperistaltic side-to-side anastomosis
compared with those of extracorporeal gastrodu- (overlap method) was selected. Laparoscopic
odenostomy with a circular stapler [11–13, 21]. FETE esophagojejunostomy following total gas-
Some experienced surgeons reported satisfactory trectomy was first reported by Uyama et al. in
surgical outcomes of extracorporeal reconstruc- 1999 [28], with the principle of making the anas-
tion [21], but intracorporeal gastroduodenostomy tomosis with the first staple firing and closing
provided better results with less blood loss and the common enterotomy with the second stapler
faster recovery [11, 12], and further benefits were in an antiperistaltic manner. The anastomosis is
observed in obese patients [13], in whom extra- temporarily closed with sutures or hernia sta-
corporeal anastomosis was difficult in a limited plers before applying the second staple firing.
working space with a concern for excessive trac- This is a simple and quick procedure that does
tion. Considering the limitation of the number of not require hand-sewn suturing to complete the
studies and selection biases, further evidence anastomosis, and the technique is similar to the
with prospective studies is required to confirm delta-shaped anastomosis. The overlap method
the advantage of intracorporeal reconstruction at is another alternative, in cases with a tumor
this moment. invading the esophagus. The first staple firing
In gastrojejunostomy including both makes an isoperistaltic, side-to-side anastomo-
Billroth-II and Roux-en-Y reconstructions, linear sis, and the enterotomy is closed using a hand-
staplers are preferred over circular staplers with sewn technique. Because the anastomosis is
advantages including easy access from a trocar, performed in the mediastinum, ensuring ade-
smooth insertion into the jejunum, anda better quate working space with dissection into the
operative view [9] in the completely laparoscopic mediastinum and adequate preparation of the
procedure. In gastrojejunostomy with a circular esophagus is required for a safe anastomosis,
stapler, transoral placement of the anvil [22] or without which the fork of the stapler cannot be
elimination of the purse-string suture [23] has inserted into the esophagus smoothly and may
been reported. While technically challenging, the result in a long staple gap between the esophagus
rates of reconstruction-related complications, and jejunum. Advanced suturing and knotting
such as anastomotic stenosis, stricture, or Roux skills are mandatory to close the enterotomy in
stasis, were low [7, 9, 22, 23]. this limited space.
The use of LTG remains limited because of Regarding anastomosis-related complications
the technically challenging esophagojejunos- after LTG using either circular or linear staplers,
tomy, but with the experience of intracorporeal the average leak rate was 3.9% with circular sta-
reconstruction in LDG, techniques of intracorpo- plers and 2.8% with linear staplers. The fre-
real esophagojejunostomy have been gradually quency of stricture was 2.2% on average, which
established. In intracorporeal esophagojejunos- was not inferior to the reports on open total gas-
tomy with a circular stapler, insertion of the anvil trectomy [10]. The apparent superiority of any
head into the esophagus was the first obstacle, particular method has not been confirmed. The
managed by hand-sewn purse-string sutures [24, optimal method should therefore be chosen based
25], with the technique of attaching a thread or a on the experience and technical proficiency of
tube with an anvil [26], or by transoral placement each surgical team.
Conclusions gastrectomy for gastric cancer: a report of short-term

outcomes. Surg Endosc. 2011;25:1395–401.
12. Kanaji S, Harada H, Nakayama S, et al. Surgical
With the development of laparoscopic technology outcomes in the newly introduced phase of intra-
and the accumulated experiences for 20 years, corporeal anastomosis following laparoscopic distal
intracorporeal reconstruction has become the gastrectomy is safe and feasible compared with estab-
lished procedures of extracorporeal anastomosis. Surg
standard in laparoscopic gastrectomy. Several dif- Endosc. 2014;28:1250–5.
ferent techniques can be used and can achieve sat- 13. Kim MG, Kawada H, Kim BS, et al. A totally
isfactory outcomes. Understanding the concept laparoscopic distal gastrectomy with gastroduo-
and tips of each procedure is important to com- denostomy (TLDG) for improvement of the early sur-
gical outcomes in high BMI patients. Surg Endosc.
plete the reconstruction safely. 2011;25:1076–82.
14. UICC International Union Against Cancer. TNM clas-
sification of malignant tumours. 7th ed. New York:
Wiley; 2009. p. 73–7.
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Part VII
Robotic Surgery for Gastric Cancer
Distal Subtotal Gastrectomy
with D2 Lymph Node Dissection 13
Kun Yang and Woo Jin Hyung
Introduction long-term survival data of large-scale random-

ized controlled trials.
Since the first laparoscopic distal gastrectomy for Meanwhile, new technology represented by
gastric cancer was first reported in 1994 [1], the robotic surgical systems has been proven useful
minimally invasive surgery has drawn much in allowing surgeons to readily perform proce-
attention worldwide. As the accumulation of the dures regarded as difficult with conventional
data showed the favorable short-term outcomes laparoscopic surgery, enabling complex proce-
and accelerated postoperative recovery without dures to be carried out with a minimally invasive
compromising the oncologic safety [2–4], lapa- approach [5–11]. To overcome the limitation
roscopic distal gastrectomy has been widely associated with laparoscopic surgery, surgical
accepted as an option of minimally invasive treat- robot was adopted as alternative minimally inva-
ments for early cancer. However, the application sive surgery by experienced laparoscopic
of laparoscopic gastrectomy for advanced gastric surgeons.
cancer remains debatable, because of the techni- In this chapter, we demonstrated the current
cal difficulties of D2 lymphadenectomy and status, advantages, indication, and detailed pro-
digestive tract reconstruction, as well as lack of cedures of robotic distal gastrectomy for gastric
cancer.
K. Yang dvantages of Robotic Gastrectomy

A
Department of Gastrointestinal Surgery, West China
Hospital, Sichuan University, Chengdu, Sichuan, China and Clinical Assessment of Its
Application
Laboratory of Gastric Cancer, State Key Laboratory
of Biotherapy, West China Hospital, Sichuan
University, Chengdu, Sichuan, China Overview
W. J. Hyung (*)
Department of Surgery, Yonsei University College of The first case of robotic-assisted gastrectomy
Medicine, Seoul, Republic of Korea was reported in 2003 [5]. With the development
Gastric Cancer Center, Yonsei Cancer Center, Yonsei of a decade, robotic gastrectomy has been proven
University Health System, Seoul, Republic of Korea to be safe and feasible in terms of mortality, mor-
Robot and Minimal Invasive Surgery Center, bidity, conversion rate, postoperative hospital
Severance Hospital, Yonsei University Health stay, and oncological safety when compared with
System, Seoul, Republic of Korea conventional laparoscopic gastrectomy.

https://doi.org/10.1007/978-3-662-45583-8_13
172 K. Yang and W. J. Hyung
Generally, compared with conventional laparo- instruments offer an optimal identification of vas-
scopic surgery, robotic surgery may offer more pre- cular anomalies, such as an aberrant left hepatic
cise lymphadenectomy around vessels by providing artery originating from the left gastric artery, and
various technical advantages, such as three-dimen- allow the aberrant hepatic artery-preserving
sional image, motion scaling, tremor filtering, lymph node dissection. Furthermore, the robotic
coaxial alignment, and articulated endoscopic wrist system facilitates intracorporeal hand-sewn
with seven degrees of freedom, which could mini- sutures in all anastomosis even in deep and nar-
mize blood loss and invasiveness and improve the row spaces, which might promote the shift from
dexterity of surgeons [12]. Furthermore, ergonomic extracorporeal to intracorporeal anastomosis in
design of the robotic console could reduce the dis- robotic surgery [13]. In addition, 3-D views and
comfort and fatigue of surgeons, especially for the articulated instruments of robotic system could
operations with long durations. In addition, the make the control of major bleeding due to vascu-
camera arm and 30° endoscope could lift the lar injury more easily [13]. Meanwhile, robotic
abdominal wall, just like the gasless procedure in distal gastrectomy exhibits a shorter learning
laparoscopic surgery, and expand the space for curve than that for laparoscopic gastrectomy
manipulation and provide excellent visions. [14], which may enable a greater number of sur-
geons to perform D2 lymph node dissection dur-
ing gastrectomy for gastric cancer. Shorter
pecific Advantages in Robotic
S learning curves might also permit experienced
Gastrectomy with D2 surgeons to apply advanced or complicated pro-
Lymphadenectomy cedures more easily for gastric cancer treatment.
With its mechanical superiority, robotic surgical

systems provide 3-D views and ambidextrous linical Assessment of Robotic
C
tremor-filtered bidirectional dissection around Gastrectomy
complex vascular structures, contributing to con-
stantly keeping the right surgical plane, such as Although high-level evidence is still wanting since
the plane between lymph nodes bearing fatty tis- robotic gastrectomy for gastric cancer treatment is
sues and major suprapancreatic vessels (or pan- a relatively novel field, the feasibility, safety, and
creatic parenchyma) in the process of short-term outcomes of robotic gastrectomy have
suprapancreatic lymph node dissection, provid- been reported to be comparable with conventional
ing more thorough and precise dissection, and laparoscopic gastrectomy [15–17].
reducing the possibility of injuries to vessels or The morbidity and mortality rate, as well as
the pancreas [12]. Moreover, the equipment of conversion rate, did not differ significantly
wristed instruments via the robotic arms aids in between laparoscopic gastrectomy and robotic
the approach to and traction of the stomach and gastrectomy [9, 15–17]. Some study even
pancreas, as well as proper and stable exposure of reported that the robotic gastrectomy could
the peripancreatic area, even to the dorsal side of decrease the morbidity significantly, compared
the pancreas where it is difficult for current lapa- with laparoscopic gastrectomy [18]. Several
roscopic instrument and camera system to iden- studies have showed that robotic gastrectomy
tify and reach. Stable retraction of tissues without was associated with reduced intraoperative blood
tremor can reduce potential risk of injury to lym- loss compared with laparoscopic gastrectomy,
phatic tissues and bleeding from dissection plane. which can provide extra potential oncologic ben-
All of these features could make it somewhat efits through decreasing the intraperitoneal free
easier for surgeons to perform D2 lymphadenec- cancer cell dissemination and immunosuppress-
tomy during gastrectomy. Additionally, the 3-D ing caused by perioperative transfusions, espe-
views and the scaled movements of robotic cially for locally advanced cancer [19].
13 Distal Subtotal Gastrectomy with D2 Lymph Node Dissection 173
The postoperative hospital stay after the erative diagnosis of gastric cancer without serosa
robotic gastrectomy was much shorter than that involvement and without evidence of lymph node
of open gastrectomy [15, 16]. No significant dif- metastasis to an extraperigastric area, except
ferences were observed between robotic gastrec- those with lesions suitable for endoscopic treat-
tomy and laparoscopic gastrectomy in terms of ment. Distal gastrectomy is selected when a satis-
time to ambulation, time to start food intake, and factory proximal resection margin can be
postoperative hospital stay [9, 20]. However, obtained. For early gastric cancer patients with-
some studies showed shorter mean postoperative out lymph node involvement (cT1N0M0), lim-
hospital stay in robotic gastrectomy group com- ited lymphadenectomy (D1 or D1+) could be
pared to laparoscopic gastrectomy group [18, performed. The indications for D2 lymph node
21]. Faster recovery allows patients to receive dissection comprise patients with a primary
adjuvant chemotherapy timely. tumor of the deep submucosal layer or deeper
Given the lack of long-term survival data of invasion or patients with suspicious lymph node
robotic gastrectomy, the numbers of harvested metastasis on preoperative diagnostic workup.
lymph nodes and the resection margin are often Patients with serosal involvement in locally
used to evaluate the oncological safety. Some advanced tumors, direct invasion to adjacent
meta-analysis which compared the robotic gas- organs, or suspicion of extraperigastric lymph
trectomy to laparoscopic gastrectomy showed node metastasis are usually excluded from under-
that there was no significant difference in the going minimally invasive surgery. However,
number of retrieved lymph nodes [15–17]. Even robotic gastrectomy for such cancers could be
some authors reported that robotic gastrectomy decided according to the surgeon’s expertise and
can yield more lymph nodes located in the extra- experience but should be performed within the
perigastric area (2nd tier) in D2 lymphadenec- context of clinical trials.
tomy [11, 22], compared with laparoscopic
gastrectomy. For the resection margin, one study
showed that no positive margins were observed
in the robotic group, while some cases in the lap- Operative Procedures [7, 25, 26]
aroscopic group had tumor involvement in the
margin [23]. Operating Room Setup
Regarding the comparisons of long-term sur-
vival between robotic gastrectomy with other The patient cart is positioned at the head of the
approaches, retrospective studies revealed that patient. The vision cart is located caudal to the
long-term survival was similar between laparo- patient. The surgeon’s console is placed where
scopic gastrectomy and robotic gastrectomy [11, the operator could see and check the patient cart
24]. However, because of the lack of randomized and the patient. The assistant should have a posi-
controlled trials demonstrating long-term out- tion at the left side of the patient. And it is useful
comes, advantages of robotic gastrectomy from to have a second monitor on the right side of the
an oncologic view are still to be clarified. table across from the assistant. Sterile back tables
(instruments) are located at the patient’s knee and
at the foot of the bed. The scrub nurse locates at
Indication the lower right side of the table, opposing to the
patient-side assistant. Operating room configura-
Basically, the indications for robotic gastrectomy tion is usually dependent on the room dimension
for gastric cancer are similar to those of the con- as well as the preferences and experience of the
ventional laparoscopic gastrectomy. Candidates surgeons. The operating room setup is shown in
for robotic surgery include patients with a preop- Fig. 13.1a.
a b
Anesthesiologist
Patient-side
assistant
Vision
cart
3 1
2
2-4cm Assistant
Nurse Camera
Monitor
Midline
1-2cm
Surgeon
at console
Fig. 13.1 Operating room setup and placements of trocars (cited from da Vinci Gastrectomy Procedure Guide [25]).
(a) Operating room setup, (b) placements of trocars
atient Positioning and Port

P also be positioned 1 cm above the bowel. Another
Placement 8-mm port for the 2nd robotic arm should be
inserted 2–4 cm above along an imaginary line
Under general anesthesia, the patient’s arms are that intersected the middle of the camera port and
placed alongside the body to prevent injury to the the right subcostal port; this step allows easier
upper extremities by the robotic arms. In order to access to the pancreatic head and duodenum and
prevent the patients from translocation, the achieves a proper angle with the non-wristed
patients should be carefully secured and fixed by ultrasonic shears. The assistant port should be
strap and gel pads across the thigh. After position- placed 1–2 cm below an imaginary line drawn
ing, securing, and preparing the patient in the from the insertion site of the 1st robotic arm to the
supine position, a 12-mm trocar is placed at the umbilical camera port (Fig. 13.1b). Maximizing
midline just below the umbilicus for inserting a the distance between the ports (at least 8 mm,
dual lens laparoscope. After pneumoperitoneum especially between 2nd arm and 3rd arm) for the
of 12-mm Hg is achieved, the table is then placed robotic arms would help to prevent external colli-
in a reverse Trendelenburg position (15°). After sion of the robotic arms. If the patient is thin, the
laparoscopic exploration and checking for the port for the 2nd arm must be placed more cau-
optimal locations of the port sites, four additional dally; the ports for the 1st and 3rd arms can be
ports could be inserted under camera visualiza- positioned more medially for obese patients.
tion: one 12-mm and three 8-mm ports. During the operation, the camera port should be
Specifically, an 8-mm diameter port for the 1st lifted as high as possible to make sufficient use of
arm of the robot is placed 1 cm below the costal the space made by the pneumoperitoneum.
angle, as far lateral as possible, on the patient’s
left side; the port should be at least 1 cm above the
level of the bowel when viewed internally. Docking
Another 8-mm port for the 3rd arm should be
inserted 1 cm below the costal angle, as far lateral The position of the operating table should be
as possible, on the patient’s right side; it should reconfirmed before docking since it’s impossible
to adjust the operating table after docking. Adjust as suspension using Penrose drains [27], the
the camera arm setup joint toward the left side of gauze suspension method [28], and retraction
the patient with only 1st arm and confirm sweet using liver retractor [29] have been described.
spot. The blue arrow should align within the blue Each of the aforementioned methods could be
marker on the second joint or assure an angle less used provided that satisfied operative view is
than 90 degrees between the 1st and 3rd joints on reached. To the authors’ opinion, the gauze sus-
the camera arm. The arm of the patient cart pension method is simple and economic and
should be positioned high enough to provide almost harmless to the liver [28]. Briefly, two
space above the patient’s head. Then, the patient 4 × 4 inch gauze pads threaded by a 2-0 Prolene
cart is rolled up and positioned over the patient’s suture with 70-mm double straight needles are
head. The camera arm, camera arm setup joint, introduced into the intraperitoneal cavity via the
column, camera port, and target anatomy are assistant port. Next, the lesser omentum is
aligned. Once the correct position is reached, the divided up to the right side of the esophageal hia-
patient cart can be locked. Dock the camera arm tus, and the Prolene suture is secured to the pars
firstly and then the other three robotic arms. The condensa with two Hemolocks. The straight nee-
space between the 2nd and 3rd arms, as well as dles are used to pierce the anterior abdominal
the space between the 1st arm and the camera wall directly on both sides of the xiphoid process
arm, should be maximized by spreading these and externally tied to suspend the liver toward the
arms as far apart as possible. Remember to keep abdominal wall by the assistant.
instruments in the center of their range of motion.
eft-Side Dissection and Greater

L
Instrumentations Curvature Mobilization (Lymph Node
#4sb and #4d Dissection)
The instrumentation and settings consist of a
30-degree down endoscope in the camera arm, The greater omentum attaching to the greater
Maryland bipolar forceps in the 1st arm, ultrasonic curvature of the stomach is retracted cranially
shears or the monopolar curved scissors in the 2nd and ventrally by the 3rd arm, while the gravity of
arm, and Cadiere forceps in the 3rd arm, inter- the transverse colon would act as countertraction.
changeably. The 3rd arm is applied at the patient’s Left-side dissection and greater curvature mobili-
right side because the 3rd arm should be at the zation begin by dividing the omentum and enter-
opposite side of the 1st arm for better countertrac- ing the lesser sac from the middle of the greater
tion. Surgeons control the 1st arm by the right curvature, which comprises the fewest number of
hand while 2nd and 3rd arms by the left hand vessels, to the lower pole of the spleen using the
through switching button. The assistant aids the ultrasonic shears. By continuing dissection, the
surgeon to suck, irrigate, and apply stapler or other left gastroepiploic artery and vein can be identi-
additional procedures through the assistant port. fied, ligated using clips via a robotic clip applier,
and divided after giving the branch to the omen-
tum (Fig. 13.2a). Division of adhesions between
Liver Retraction the lower pole of the spleen and greater omentum
can prevent tearing of the splenic capsule. The
Appropriate liver retraction to prepare for the short gastric vessels are usually preserved for a
sufficient operative field is very important, not distal gastrectomy; however, if the tumor is in a
only for maximizing the application of instru- high location, one or two short gastric arteries
ments by liberating the arm used for liver retrac- need to be divided for proper margins and create
tion but also for facilitating dissection, enough space for the resection and anastomosis.
particularly for suprapancreatic lymph node dis- After ligating the left gastroepiploic vessels, all
section. Various methods of liver retraction such of the soft tissue along the greater curvature area
a b
Fig. 13.2 Left-side dissection and greater curvature mobi- tum. (b) The greater curvature is skeletonized to remove
lization. (a) The left gastroepiploic artery and vein can be No. 4sb and No. 4d lymph nodes. LEGA and V, left gastro-
identified and divided after giving the branch to the omen- epiploic artery and vein; Br, branch
should be removed by skeletonizing along the as landmarks to identify the origin of right gas-
greater curvature toward the pylorus to complete troepiploic vein. Soft tissues located on the right
the No. 4sb and No. 4d lymph node dissection for side and left side of the right gastroepiploic vein,
a distal gastrectomy (Fig. 13.2b). as well as the soft tissues anterior to the anterior
superior pancreaticoduodenal vein and Henle’s
trunk, should be dissected together using the
Right-Side Dissection Harmonic shears and the Maryland bipolar for-
and Infrapyloric Area Dissection ceps until the pancreatic parenchyma is exposed.
(Lymph Node #6 and #14v Dissection) Next, the right gastroepiploic vein is clipped and
divided distal to the confluence of the anterior
Right-side dissection and infrapyloric dissection superior pancreaticoduodenal vein (Fig. 13.3a).
are performed by dissecting soft tissue from the In case of No. 6 lymph node metastasis, the No.
middle colic vessels to the surface of the superior 14v lymph nodes should be also removed. Note
mesenteric vessels while exposing the head of the that the venous drainage from the pancreatic head
pancreas and removing lymph node-bearing tis- should be preserved when approaching the right
sues around the right gastroepiploic vessels. side of the right gastroepiploic vein and the
Retract the gastroepiploic pedicle ventrally proper membrane of the pancreas which directly
and appropriately by the 3rd arm. Before per- covers the pancreatic parenchyma should be kept
forming the infrapyloric dissection, the physio- intact to avoid the postoperative pancreatitis. If
logical adhesions between the posterior wall of the middle colonic artery cannot be seen in some
the stomach and pancreas should be fully dis- obese patients, dissect the opposite side first.
sected, and the inferior pancreatic border is Dissection to expose the right gastroepiploic
exposed, which is very helpful to seek and keep artery is continued, and the artery is ligated and
the correct dissected planes. Then, the transverse divided distal to the origin of anterior superior
mesocolon should be detached from the gastro- pancreaticoduodenal artery (Fig. 13.3b). Finally,
epiploic pedicle and the pancreatic head by iden- the infrapyloric artery is identified and divided
tifying the middle colonic artery and following between clips. Thus, the right gastroepiploic ves-
the pulsations to the inferior pancreatic border. sels are dissected en bloc with lymphatic tissue
The physiological adhesions between the trans- (Fig. 13.3c). Sometimes, a ligule of pancreatic
verse colon and the descending part of the duode- parenchyma is extended toward the duodenal
num should also be released at the same time. bulb, or the pancreas is unexpectedly lifted up,
The right colonic vein and the Henle’s trunk that which should be prevented from injuring. And
drains into the superior mesenteric vein are used there are many tiny branches around the root of
a b c
Fig. 13.3 Infrapyloric dissection. (a) The right gastroepi- node dissection. GCT, gastrocolic trunk; RGEV, right gas-
ploic vein is clipped and divided distal to the confluence of troepiploic vein; ASPDV, anterior superior pancreaticodu-
the anterior superior pancreaticoduodenal vein. (b) The odenal vein; MCV, middle colonic vein; ARCV, accessory
right gastroepiploic artery is ligated and divided distal to right colic vein; RGEA, right gastroepiploic artery;
the origin of anterior superior pancreaticoduodenal artery. ASPDA, anterior superior pancreaticoduodenal artery;
(c) View to show the dissection efficacy of No. 6 lymph IPA, infrapyloric artery; GDA, gastroduodenal artery
a b
Fig. 13.4 Supraduodenal dissection and duodenal tran- transection. (b) The duodenum is stapled and divided
section. (a) Supraduodenal vessels are divided by ultra- about 2 cm distal to the pylorus using an endoscopic linear
sonic shears directly, and the duodenum is naked for stapler through the assistant port
right gastroepiploic artery and infrapyloric artery; num. After identification of the proper hepatic artery,
ultrasonic shears benefit to avoid bleeding and a 4-inch by 4-inch gauze is inserted between the
keep a clear surgical field. supraduodenal tissues and pancreas and acts like a
“tent” to facilitate the dissection of the supraduode-
nal area and to avoid unexpected injuries to the pan-
Supraduodenal Dissection creas and major vessels (such as the proper hepatic
and Duodenal Transection artery, gastroduodenal artery, or common hepatic
artery). Supraduodenal vessels are divided by ultra-
The duodenum is mobilized from the pancreas along sonic shears directly, and the duodenum is naked for
the gastroduodenal artery to prepare for the duode- transection (Fig. 13.4a). The duodenum is stapled
nal transection, and the anterior side of the gastro- and divided about 2 cm distal to the pylorus using an
duodenal artery is exposed. The dissection continues endoscopic linear stapler through the assistant port
to the bifurcation of the proper hepatic artery and the (Fig. 13.4b). The staple line of the duodenal stump
gastroduodenal artery. Be sure to coagulate the small could be reinforced by sutures if the Billroth-II or
vessels from the head of the pancreas to the duode- Roux-en-Y anastomosis is considered.
uprapancreatic Area Dissection

S node-bearing tissue and the proper hepatic artery.
(Lymph Node #5, #7, #8a, #9, #11p, Then all the tissues are removed en bloc along the
and #12a Dissection) surgical plane by Harmonic shears until the expo-
sure of anterolateral wall of the portal vein
After transection of the duodenum, the stomach (Fig. 13.5b). After finishing the No. 12a and No.
is retracted to the patient’s left and ventral side to 5 lymph node dissections, retract and tense the
identify the right gastric vessels. In order to have gastropancreatic fold using the Cadiere forceps
an easier dissection of the anterior layer of the ventrally. Lymph nodes bearing soft tissues at the
gastrohepatic ligament, the liver hilum is retracted surface of the common hepatic artery are gently
by the Cadiere forceps of the 3rd robotic arm pulled up by Maryland bipolar forceps, while the
which is padded by a gauze. Dissection continues ultrasonic shears are used to skeletonize the com-
along the proper hepatic artery until the right gas- mon hepatic artery and dissect No. 8a lymph
tric vessels are exposed. The anterolateral surface nodes from right to left. Avoid using active blade
of proper hepatic artery is also exposed. Identify of Harmonic in direct contact with vessels; rotate
and skeletonize the root of the right gastric ves- the Harmonic shears away from vessels while
sels for proper clip application. Divide the right skeletonizing. When dissecting the No. 8a lymph
gastric vessels at roots and dissect the No. 5 nodes cephalad to the common hepatic artery,
lymph node (Fig. 13.5a). When approaching the retract the common hepatic artery dorsally and
medial side of the proper hepatic artery, retraction caudally by grasping the tissues around the artery,
of the liver hilum should be reduced. The tissues which is useful to expose easily and prevent inju-
containing the vagus nerve around the proper ries to major vessels. Complete the dissection of
hepatic artery are grasped by the Cadiere forceps No. 8a and 12a lymph nodes around the proper
and retracted to the right and caudal side, and the and common hepatic artery and portal vein until
soft tissue located anterolateral to the proper the left gastric vein is identified. Clip and divide
hepatic artery which has been dissected before is the left gastric vein at the root. Constantly dissect
countertracted to the left. Thus, a surgical plane in the right plane between the nerve sheaths
could be created between the No. 12a lymph around the major arteries and lymph nodes bear-
a b
Fig. 13.5 Dissection of No. 5 and 12a lymph nodes. (a) Dissection of No. 12a lymph nodes until the exposure of
Identify and skeletonize the root of the right gastric ves- anterolateral wall of the portal vein. CHA, common
sels for proper clip application, and divide the right gastric hepatic artery; GDA, gastroduodenal artery; RGA, right
vessels at roots and dissect the No. 5 lymph nodes. (b) gastric artery; PHA, proper hepatic artery; PV, portal vein
ing fatty tissues, and utilization of the articulation With the 3rd arm padded with gauze to roll
and grasping capabilities of the Cadiere and down the pancreas, compression and retraction
Maryland forceps to create the proper dissection provide the best possible exposure of the soft tis-
angles for the non-wristed Harmonic shears dur- sues containing No. 11p lymph nodes. Also, nat-
ing the process of suprapancreatic lymphadenec- ural traction to the left side can be acquired with
tomy is necessary for a technically safe and compression via the 3rd arm. If compression of
radical lymphadenectomy. the pancreas via the 3rd arm is insufficient, an
Continue the dissection along the common assistant can help. Use the Maryland bipolar to
hepatic artery toward the celiac trunk, and expose create the proper angles and Harmonic shears to
the origin of the splenic artery (Fig. 13.6a). Soft tis- dissect the soft tissues along the superior border
sues around the celiac trunk are dissected and pulled of the pancreas and the splenic artery until the
up to the specimen side. The root of the left gastric origin of posterior gastric artery (if there is not an
artery is skeletonized, clipped, and divided obvious posterior gastric artery, make sure to dis-
(Fig. 13.6b). When skeletonizing the left gastric sect at least 5 cm along the splenic artery)
artery, rotating the camera can reveal the posterior (Fig. 13.6c). If it is not possible to dissect the
side of the left gastric artery in the oblique view, suprapancreatic area with traction via the Cadiere
making the following dissections easier. Also, divi- and Maryland forceps, the use of other endo-
sion of the left gastric artery is important as it allows wristed devices (e.g., hook or monopolar scis-
for greater exposure for the dissection of No. 11p sors) may be helpful. For a complete No. 11p
lymph nodes. The nerve plexus around the celiac lymphadenectomy, the proximal part of the
trunk could be preserved in the cases with prophy- splenic vein should be exposed. Thereafter, the
lactic D2 lymph node dissection. If an aberrant left retroperitoneal attachment of the stomach was
hepatic artery with thick diameter derived from the detached up to the diaphragmatic cruses, com-
left gastric artery exists, or a normal left hepatic pleting the removal of the perigastric lymph
artery originating from the common hepatic artery nodes. Utilization of the Cadiere forceps (3rd
is absent, the aberrant hepatic artery-preserving No. arm) to provide necessary countertraction and the
7 lymph node dissection should be performed, articulated Maryland bipolar forceps to create
which means to skeletonize the trunk of the left gas- proper angles is critical to the dissection of the
tric artery without injuring and dividing and only soft tissues along the superior border of the pan-
divide the gastric branches at their origins. creas and the proximal part of the splenic artery
a b c
Fig. 13.6 Dissection of No. 7, 8a, 9, and 11p lymph splenic artery until the origin of posterior gastric artery,
nodes. (a) Continue the dissection along the common and expose the proximal part of the splenic vein. CHA,
hepatic artery toward the celiac trunk, and expose the ori- common hepatic artery; LGA, left gastric artery; LGV,
gin of the splenic artery. (b) Soft tissues around the celiac left gastric vein; SA, splenic artery; SV, splenic vein;
trunk are dissected, and the root of left gastric artery is GDA, gastroduodenal artery; RGA, right gastric artery;
skeletonized and divided. (c) Dissect the No. 11p lymph PHA, proper hepatic artery; RGEA, right gastroepiploic
nodes along the superior border of the pancreas and the artery
(No. 11p lymph nodes), which facilitate surgeons tion, could be used to restore the digestive conti-
to completely dissect the deep portion of No. 11p nuity [12, 24, 30, 31]. Both intracorporeal and
lymph nodes, one of the most technically com- extracorporeal anastomoses are acceptable.
plex procedures in conventional laparoscopic Either linear or circular staplers or hand-sewn
gastrectomy. sutures could be applied. Each method has its
advantages and disadvantages. Surgeons could
choose the optimal reconstruction method
esser Curvature Dissection
L according to the tumor location, stage, life expec-
(Lymph Node #1 and #3 Dissection) tancy, and surgeon’s preference, as well as their
experience. If the robotic wristed linear stapler
There are two ways to remove No. 1 and 3 lymph which could be applied by robotic arm can be
nodes. Posterior-side approach is known as dis- introduced, the anastomoses would be more com-
section of soft tissues along the lesser curvature fortable and stable.
from the hiatus down to the transection line and Here, we describe our reconstruction proce-
from the posterior to the anterior side of the lesser dures after distal gastrectomy as follows. After
curvature (Fig. 13.7), while anterior-side the resection of the stomach, gastroduodenos-
approach is characterized by keeping the dissec- tomy or gastrojejunostomy is performed intracor-
tion plane from anterior and from transection line poreally, using an endo-linear stapler.
up to the hiatus along the lesser curvature. The Gastroduodenostomy is performed using linear
anterior and the posterior branches of vagal nerve staplers, similar to so-called delta-shaped anasto-
should be divided. mosis. The duodenum should be transected from
the posterior to the anterior wall using an endo-
scopic linear stapler with blue cartilage inserted
astric Resection, Anastomosis,
G through the 12-mm assistant port. After the distal
and Specimen Retrieval subtotal gastrectomy, small holes are created
along the edge of the greater curvature of the
After ensuring the proximal margin, the stomach remnant stomach and the medial edge of the duo-
is transected using endo-linear staplers via the denum. An endoscopic linear stapler is then
assistant port for a distal gastrectomy. The speci- placed between the remnant stomach and duode-
men is bagged intracorporeally and placed aside num (cartridge in the stomach and anvil into the
for later removal. Various methods, such as duodenum), and the posterior wall of the remnant
Billroth-I, Billroth-II, or Roux-en-Y reconstruc- stomach and the posterior wall of the duodenum
a b
Fig. 13.7 Dissection of No. 1 and 3 lymph nodes. rior to the anterior side of the lesser curvature. (a)
Dissection of soft tissues along the lesser curvature from Dissection of No. 1 lymph nodes. (b) Dissection of No. 3
the hiatus down to the transection line and from the poste- lymph nodes
are approximated by the stapler. By firing the sta- Conclusion

pler, a common channel between the stomach and
the duodenum is made. When closing the com- Robotic distal gastrectomy with radical lymphad-
mon entry hole, the previously stapled duodenal enectomy is regarded as safe and feasible pro-
stump is also removed to secure the blood supply vided that the operations are performed by
to the duodenum. For intracorporeal gastrojeju- experienced surgeons, compared with conven-
nostomy, identification of the ligament of Treitz tional laparoscopy. Longer operation time, higher
and creation of an enterotomy in the jejunum costs, and oncologic equivalency to its counter-
15–20 cm from the ligament of Treitz using the parts are still unresolved issues, which need fur-
ultrasonic shears are undertaken. After an enter- ther development and investigation. However,
otomy is created in the remnant stomach with robotic distal gastrectomy for gastric cancer
ultrasonic shears, the endo-wristed grasping would be a promising approach by providing
instrument is used to place endo-linear staplers advantages in an accurate, complete, and delicate
first on the stomach and then on the jejunum. The D2 lymphadenectomy.
stapler is fired after approximation, and the entry
hole is closed with another stapler as well.
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Total Gastrectomy with D2 Lymph
Node Dissection 14
Hiroshi Okabe
Introduction removed in TG with D2 lymph node dissection

[3]. The standard procedure for complete
Robotic surgery is becoming a standard option removal of the #10 lymph nodes has long been a
for prostate cancer surgery, which requires fine combined splenectomy. However, the results of a
anastomotic techniques in deep and physically randomized controlled trial comparing spleen-
limited surgical fields. Radical gastrectomy for preserving surgery and splenectomy (JCOG
gastric cancer also requires precise and compli- 0110) recently revealed that splenectomy
cated procedures; thus, robotic gastrectomy (RG) increases postoperative complications but does
has been employed by some surgeons to provide not improve the survival of patients, at least for
better patient outcomes. Retrospective studies tumors that do not invade the greater curvature
have shown that the advantages include fewer of the stomach [4]. Therefore, spleen-preserving
complications, less blood loss, shorter hospital TG either with or without #10 lymphadenec-
stays, and retrieval of more lymph node. However, tomy is now considered to be a standard surgery
there are few studies showing definite evidence for upper advanced gastric cancer, while sple-
of the superiority of RG in randomized controlled nectomy is still an important option for tumors
trials [1, 2]. Levels of technical difficulty are dif- on the greater curvature.
ferent among several types of surgery for gastric A comparative study of robotic and laparo-
cancer. RG would be expected to show more scopic TG showed the feasibility of robotic TG
advantages in more complicated surgery. Total and retrieved greater numbers of lymph nodes
gastrectomy (TG) with D2 lymph node dissec- along the splenic artery and at the splenic hilum
tion is one of the most technically demanding in the robotic surgery group [5]. However, studies
surgeries. Therefore, advanced upper gastric can- evaluating robotic TG for advanced gastric can-
cer requiring a TG would be a good potential cer, especially with a #10 lymphadenectomy
target of RG. either with/without splenectomy, are still very
The previous Japanese gastric cancer treat- limited [6]. Therefore, surgeons should be aware
ment guidelines ver.3 stated that splenic hilar that robotic TG with D2 lymph node dissection is
lymph nodes (lymph node station #10) should be still in the developmental stage, and its feasibility
and benefits need to be investigated by future
clinical studies. This subchapter will focus on the
H. Okabe (*)
technical aspects of robotic TG with D2 lymph
Department of Gastroenterological Surgery,
New Tokyo Hospital, Matsudo, Japan node dissection and describe the setup of the
e-mail: h-okabe@shin-tokyohospital.or.jp robot, patient positioning, and surgical techniques

https://doi.org/10.1007/978-3-662-45583-8_14
184 H. Okabe
of TG, especially of the lymph node dissection car for fenestrated bipolar forceps. The third arm
around the splenic hilum and the supra-pancre- is used from the left lateral 8-mm trocar for
atic area. Cadiere forceps. Nathanson’s liver retractor is
placed at the epigastric area (Fig. 14.1).
I ndications for Robotic TG with D2

Lymph Node Dissection Surgical Technique
TG with D2 lymph node dissection is generally Splenic Hilar Dissection

indicated for patients with upper advanced gas-
tric cancer. The current Japanese Society of The procedure starts with the division of the
Endoscopic Surgery (JSES) guidelines state that greater omentum. Serosal invasion of the tumor
laparoscopic TG may be considered for clinical requires that the omentum be divided near the
stage IA-IB gastric cancer [7]. However, the evi- transverse colon to perform a total omentectomy.
dence supporting the feasibility of robotic TG is The omentum is freed from the left side of the
currently very weak. Therefore, robotic TG with transverse colon, followed by the division of the
D2 lymph node dissection for advanced cancer is left gastroepiploic vessels. The left gastroepi-
recommended to be performed as prospective ploic artery (LGEA) should be divided at its ori-
clinical studies. Experience in performing lapa- gin in order to remove splenic hilar lymph nodes.
roscopic TG with D2 lymph node dissection is Fat tissue associated with the LGEA is held by
also strongly recommended for surgeons. the Cadiere forceps and retracted to straighten
the vessel. It is important to identify both the
proximal and distal parts of the splenic lower
obot Setup and Patient
R polar artery to determine its origin, because the
Positioning LGEA arises from it in the most common type of
variations. Medial retraction of the LGEA helps
A patient is placed in a modified lithotomy posi- to identify the distal portion of the lower polar
tion with both legs fixed apart using the levita- artery, which is running into the lower pole of the
tors. Upper arms are fixed alongside the body. spleen. Cranial retraction of the LGEA helps to
The first port is inserted through the umbilicus identify the proximal portion of the lower polar
using an open method. Pneumoperitoneum is artery (Fig. 14.2).
established with 8–12 mmHg, and two 8-mm tro-
cars for the robot and two 12-mm trocars are
introduced using video imaging. 8-mm trocars Nathanson’s
are inserted at the lateral sides just below the cos- retractor
tal margins. Twelve-mm trocars are placed
1–2 cm below the central points between the
umbilicus and 8-mm trocars.
The patient cart is then placed above the
patient’s head, and the four robot arms are 3rd arm
2nd arm
docked, while the patient is placed in a 15-degree
reverse Trendelenburg position with the left side Assistant’s
up for better exposure around the splenic hilar port 1st arm
Camera arm
area. The camera arm is connected to the umbili-
cal port. The first arm is connected to an 8-mm
trocar that is inserted through the left lower
12-mm trocar for monopolar scissors. The sec- Fig. 14.1 Trocar placement for robotic total
ond arm is used from the right lateral 8-mm tro- gastrectomy
14 Total Gastrectomy with D2 Lymph Node Dissection 185
a b
LGEA
A LPA
LP
Fig. 14.2 (a) Dissection along the lower polar artery (LPA). (b) Isolation of the left gastroepiploic artery (LGEA)
branching from the LPA
a b
SGA
B
LP
LPB
Fig. 14.3 (a) Dissection along the lower primary branch (LPB). (b) Isolation of the short gastric artery (SGA) branch-
ing from the LPB
The LGEA is divided at its root, and the omen- is important to identify the bifurcation, because
tum and the fat around the LGEA are lifted up there are no short gastric branches in the area
over the stomach for better exposure of the between the upper and lower primary branches of
splenic hilum. The gastrosplenic ligament involv- the splenic artery. However, it should be noted
ing the lowest short gastric artery is grasped by that three primary branches exist in 15–20% of
Cadiere forceps and retracted craniomedially. cases.
Stretching the gastrosplenic ligament with appro- Dissection along the distal splenic artery is
priate tension and dissection along the lower pri- done before dissecting the upper half of the
mary branch of the splenic artery help to identify splenic hilum. The perivascular nerve is preserved
the root of the short gastric artery (SGA; unless it is invaded by metastatic lymph nodes.
Fig. 14.3). Better visualization around the splenic The dissection progresses toward the distal side,
hilum is obtained by further retraction of the gas- and the remaining SGAs are identified. The origin
trosplenic ligament with Cadiere forceps. of each SGA can be easily isolated by retracting
Division of two or three SGAs allows identifying the pedicle of the SGA with Cadiere forceps
the bifurcation of the splenic artery (Fig. 14.4). It (Fig. 14.5). Division of SGAs allows further
186 H. Okabe
a b
B
B
UP
UP
B
LP
Fig. 14.4 (a) Bifurcation of the splenic artery. The pancreas is seen between the upper primary branch (UPB) and LPB.
(b) Dissection of the area between the UPB and LPB
a b SGA
B B
UP UP
Fig. 14.5 (a) Dissection along the upper primary branch (UPB). The perivascular nerve is preserved. (b) Isolation of
the short gastric artery (SGA). The pedicle is stretched to identify its origin
retraction of the gastropancreatic fold, and the crus of the diaphragm. The gastropancreatic fold
fundic portion of the stomach is mobilized by dis- containing the splenic lymph nodes is cleanly
section of Toldt’s fusion fascia. The mobilized dissected from the splenic vessels and the fusion
fundus is flipped over to obtain the better view fascia (Fig. 14.7). The dissection is continued in
around the splenic upper pole. The uppermost the medial direction, and the posterior gastric
SGA is divided to finish the splenic hilar dissec- vessels are identified and divided at the roots.
tion (Fig. 14.6). It should be noted that the upper The splenic artery is then further dissected toward
polar artery is found in about 40% of cases. The the proximal side to mobilize the #11p lymph
uppermost SGA usually branches from the distal nodes.
end of the upper polar artery in those cases. The gastropancreatic fold associated with the
left gastric artery is retracted cranially with
Cadiere forceps. Counter-traction is applied with
issection of the Left Side
D the fenestrated forceps, allowing the common
Gastropancreatic Fold hepatic and splenic arteries to be dissected while
the perivascular nerve is preserved. The coronary
Division of all of the all SGAs is followed by cut- vein is divided, when it is drained to the splenic
ting the gastrophrenic ligament to reach the left vein via the caudal side of the artery. Further
a b
SGA
SPA
Fig. 14.6 (a) Mobilization of the fundus of the stomach by dissecting Toldt’s fusion fascia. SPA, splenic artery. (b) The
uppermost short gastric artery (SGA) at the splenic upper pole
a b
#11p
SPA SPV
Fig. 14.7 (a) Dissection of the left side gastropancreatic splenic lymph nodes (#11p). The splenic vein (SPV) is
fold. Dissection is done along the splenic artery (SPA) and seen at the bottom of the dissection
Toldt’s fusion fascia. (b) Dissection of the proximal
retraction of the gastropancreatic fold helps to left crus of the diaphragm is exposed, and the left
identify the loose perivascular space alongside gastric artery is isolated and divided at its root
the left gastric artery. Dissecting the left space (Fig. 14.8).
allows the #11p lymph nodes to be extracted
from the retroperitoneum, with only the deep
attachment to the pancreas remaining. Precise issection of the Right Side
D
dissection is done to cut this attachment to com- Gastropancreatic Fold
pletely remove the #11p lymph nodes. The
splenic vein or the pancreas can be visualized at The right side omentum is next resected to expose
the bottom after the dissection (Fig. 14.7). The the infrapyloric area. The robot may be undocked
left gastropancreatic fold is dissected, exposing and the patient position reset to the simple head-
the left inferior phrenic artery. The fundic branch up position in cases that underwent total omen-
of the inferior phrenic artery is divided at its root tectomy, in order to obtain better exposure of this
to dissect the left paracardial lymph nodes, and area. The detailed technique of the dissection of
the esophagus is isolated from the left crus. The the infrapyloric area is described in the previous
188 H. Okabe
a b
Fundic branch
LGA
Lt-IPA
Fig. 14.8 (a) Isolation of the fundic branch of the left inferior phrenic artery (Lt-IPA). (b) Isolation of the left gastric
artery (LGA)
subchapter. The dissection of the infrapyloric along the perivascular nerves (Fig. 14.9). The
area is followed by transection of the duodenum #12a lymph nodes are dissected until the portal
with an endoscopic linear stapler, which is vein is exposed. The #9 lymph nodes are dis-
inserted through the left lower 12-mm port after sected until the celiac nerve plexus and the right
removal of the da Vinci port for the first arm. crus of the diaphragm are exposed. The Hem-o-
The pedicle of the right gastric artery is lok® is placed at the bottom of the lymph nodes
grasped with Cadiere forceps and retracted crani- to prevent the chyloleakage.
ally. Applying the appropriate tension allows The dissection of the right side gastropancre-
visualization of the loose dissection space atic fold along the right crus is continued to iso-
between the #8a lymph nodes and the perivascu- late the right side of the esophagus. The lesser
lar nerves of the common hepatic artery. The omentum is divided toward the esophagogastric
space is sharply dissected to mobilize the #8a junction, and the anterior surface of the esopha-
lymph nodes. The direction of the retraction with gus is released. The anterior and posterior vagal
Cadiere forceps is changed medially to approach trunks are divided to completely isolate the
the proper hepatic artery. A sharp dissection is esophagus (Fig. 14.10).
done along the proper hepatic artery to isolate the
right gastric artery. Division of the right gastric
artery at its origin separates the right side gastro- Reconstruction
pancreatic fold including the #8a, #12a, and #9
lymph nodes from the hepatic artery. Advancing The robot is undocked, and the transection of the
the en bloc dissection of these lymph nodes esophagus and Roux-en Y reconstruction are per-
requires the surgeon to control both the main formed laparoscopically. The esophagus is tran-
traction by the Cadiere forceps and the counter- sected using an endoscopic linear stapler, which
traction by the fenestrated forceps. The proper is inserted through the right lower 12-mm port.
hepatic lymph nodes (#12a) are dissected by The umbilical trocar wound is extended, and the
retracting the Cadiere forceps craniomedially, resected stomach is removed through it.
while the counter-traction is applied with the Intracorporeal esophago-jejunal anastomosis is
fenestrated forceps grasping the nerve fibers performed either with a functional end-to-end
alongside the proper hepatic artery. The Cadiere anastomosis or the overlap method. The detailed
forceps is retracted craniolaterally to dissect the technique of the laparoscopic anastomosis is
right side celiac nodes (#9), and counter-traction described in another chapter in this book or in a
is applied by the fenestrated forceps to dissect previous publication [8, 9]. A round-type suction
a PH
A b
PV
CHA
Fig. 14.9 (a) Dissection of the proper hepatic lymph nodes (#9) along the celiac artery. Perivascular nerve is
nodes (#12a) along the portal vein (PV). PHA, proper preserved. CHA, common hepatic artery
hepatic artery. (b) Dissection of the right celiac lymph
a b
Fig. 14.10 (a) Division of the posterior vagal trunk. (b) Complete isolation of the esophagus
drain is inserted from the upper right port and total gastrectomy. Heat injury and direct com-
placed behind the esophago-jejunal anastomosis. pression of the pancreas are potential causes of
The operation is completed by closure of all tro- pancreas-related complications following laparo-
car wounds. scopic surgery [10, 11]. Direct contact between
the dissection device and the pancreas can be
avoided in robotic surgery, thanks to its articu-
Discussion lated shape, minimizing heat injury. In addition,
the dissection around the pancreas can be done
One potential advantage of robot is to make a mostly without compression of the pancreas.
technically difficult procedure, such as splenic Some retrospective studies suggest [5, 6] that
hilar dissection and supra-pancreatic dissection, major pancreas-related complications can be
easier and safer by providing better dexterity. reduced by introduction of the robotic surgery.
Pancreas-related complications, such as pancre- On the other hand, there are still some techni-
atic fistula, peripancreatic abscess, or pancreati- cal issues to be resolved before robotic D2 TG
tis, are common complications following a D2 can be accepted as a “technically feasible” option.
190 H. Okabe
The first is the difficulty of the procedure in obese 2. Kim HI, Han SU, Yang HK, Kim YW, Lee HJ, Ryu
KW, Park JM, An JY, Kim MC, Park S, Song KY, Oh
patients. It is very difficult to understand the vas- SJ, Kong SH, Suh BJ, Yang DH, Ha TK, Kim YN,
cular anatomy around the splenic hilum in obese Hyung WJ. Multicenter prospective comparative
patients during surgery. Careful dissection is nec- study of robotic versus laparoscopic gastrectomy for
essary to identify each vessel, prolonging the gastric adenocarcinoma. Ann Surg. 2016;263:103–9.
3. Japanese Gastric Cancer Association. Japanese gas-
length of the procedure. Preoperative evaluation tric cancer treatment guidelines 2010 (ver. 3). Gastric
of the branching pattern of the splenic vessels Cancer. 2011;14:113–23.
using CT imaging is strongly recommended in 4. Sano T, Sasako M, Mizusawa J, Katayama H, Katai H,
such cases. The second issue is how to obtain a Yoshikawa T. Randomized controlled trial to evaluate
splenectomy in total gastrectomy for proximal gastric
good exposure of the splenic hilum in cases that carcinoma (JCOG0110): final survival analysis. J Clin
require a total omentectomy or those with a large Oncol. 2015;33(abstr):103.
tumor. The exposure is usually obtained by lift- 5. Son T, Lee JH, Kim YM, Kim HI, Noh SH, Hyung
ing up the fundus with the omentum flipped over WJ. Robotic spleen-preserving total gastrectomy for
gastric cancer: comparison with conventional laparo-
the stomach. However, the volume of the omen- scopic procedure. Surg Endosc. 2014;28:2606–15.
tum can be so large that a portion of the organ 6. Suda K, Man-I M, Ishida Y, Kawamura Y, Satoh S,
obscures the view, especially in obese patients. Uyama I. Potential advantages of robotic radical gas-
Exposure of the upper part of the splenic hilum trectomy for gastric adenocarcinoma in comparison
with conventional laparoscopic approach: a single
becomes more difficult in cases with a large institutional retrospective comparative cohort study.
tumor. One technique employed by some sur- Surg Endosc. 2015;29:673–85.
geons is suturing the stomach to the abdominal 7. Uyama I, Okabe H, Kojima K, Satoh S, Shiraishi
wall to prevent its falling down into the operative N, Suda K, Takiguchi S, Nagai E, Fukunaga
T. Gastroenterological surgery: stomach. Asian J
field. The third issue is the reconstruction. Endosc Surg. 2015;8:227–38.
“Robotic” reconstruction generally uses endo- 8. Okabe H, Obama K, Tanaka E, Nomura A, Kawamura
scopic staplers that are operated by the assistant. J, Nagayama S, Itami A, Watanabe G, Kanaya S,
The reconstruction method employed during lap- Sakai Y. Intracorporeal esophagojejunal anasto-
mosis after laparoscopic total gastrectomy for
aroscopic surgery can be used in robotic surgery. patients with gastric cancer. Surg Endosc. 2009;23:
However, this can be problematic when the assis- 2167–71.
tant’s stapler does not move where the surgeon 9. Inaba K, Satoh S, Ishida Y, Taniguchi K, Isogaki J,
intended it to be. A robotic stapler is under devel- Kanaya S, Uyama I. Overlap method: novel intracor-
poreal esophagojejunostomy after laparoscopic total
opment, and further improvement in the future gastrectomy. J Am Coll Surg. 2010;211:e25–9.
will yield the optimal technique. 10. Obama K, Okabe H, Hosogi H, Tanaka E, Itami A,
Sakai Y. Feasibility of laparoscopic gastrectomy with
radical lymph node dissection for gastric cancer:
from a viewpoint of pancreas-related complications.
References Surgery. 2011;149:15–21.
11. Irino T, Hiki N, Ohashi M, Nunobe S, Sano T,

1. Obama K, Sakai Y. Current status of robotic gas- Yamaguchi T. The hit and away technique: optimal
trectomy for gastric cancer. Surg Today. 2015;46: usage of the ultrasonic scalpel in laparoscopic gas-
528–34. trectomy. Surg Endosc. 2015;30:245–50.
Reconstruction Methods After
Robotic Distal or Total 15
Gastrectomy
Sang-Yong Son and Sang-Uk Han
Introduction Jiang et al. reported on the outcomes of robot-

sewn esophagojejunostomy in 65 patients who
Robotic technology has been introduced to gastric underwent totally robotic total gastrectomy [2].
cancer surgery more recently than laparoscopic The mean times for total operation and esoph-
methods. Therefore, most robotic procedures, agojejunostomy were 245 minutes and 45 min-
including radical lymphadenectomy and reconstruc- utes, respectively. One patient was readmitted for
tions, are based on those of laparoscopic surgery. an intestinal obstruction and underwent reopera-
Currently, various reconstruction techniques are tion; however, there were no strictures identified
used in laparoscopic gastrectomy, and these are cur- in any of the patients. Recently, a randomized
rently reproduced by the robotic surgical systems, clinical trial was conducted to evaluate the safety
utilizing the improved dexterity resulting from the and efficacy of full robotic gastrectomy for gas-
internal articulated endoscopic wrist [1–6]. tric cancer with intracorporeal robot-sewn anas-
Robotic systems provide surgeons with the tomosis [7]. A total of 364 patients with gastric
possibility to perform precise sutures, even in cancer were recruited to this study, and 145 open
deep and narrow spaces, and a few studies have gastrectomies and 151 robotic gastrectomies
reported on the feasibility of robot-sewn anasto- were finally analyzed. The operation time was
moses. Hur et al. were amongst the first to report significantly longer in the robotic gastrectomy
on the technical feasibility of robot-sewn anasto- group (242.7 vs. 192 min, p = 0.002), whereas
moses, applied in seven cases of robotic surgery blood loss was less (94 vs. 152 ml, p < 0.001),
for gastric cancer [1]. The median total operation length of postoperative hospital stay was shorter
time was 205 minutes and the median reconstruc- (5.6 vs. 6.7 days, p = 0.021), and restoration of
tion time was 69 minutes, with the various recon- bowel function was earlier (2.6 vs. 3.1 days,
structions consisting of two Roux-en-Y p = 0.028). However, there was no significant dif-
esophagojejunostomies, two Roux-en-Y gastro- ference in complication rate (10.3 vs. 9.3%,
jejunostomies, and three gastroduodenostomies. p = 0.756). The authors concluded that robotic
One patient was readmitted for stasis in the gastrectomy with intracorporeal robot-sewn
remnant stomach, but conservatively recovered. anastomosis is feasible and does not increase
intraoperative or postoperative complication risk.
There is a recent trend for robotic gastrectomy
S.-Y. Son · S.-U. Han (*) reconstructions to move from extracorporeal pro-
Department of Surgery, Ajou University School cedures to intracorporeal procedures, referred to
of Medicine, Suwon, Republic of Korea as “full or totally robotic gastrectomy,” in which
e-mail: hansu@ajou.ac.kr

https://doi.org/10.1007/978-3-662-45583-8_15
192 S.-Y. Son and S.-U. Han
all gastric resection and reconstruction are per- A five-port system is usually used for totally
formed intracorporeally, under direct laparo- robotic gastrectomy. In distal gastrectomy, a sym-
scopic view, without a minilaparotomy. However, metric port placement is recommended; two
the advantages of the “totally robotic procedure” 12 mm trocars are placed on the infraumbilical
have not been firmly identified, even for laparo- area and the left lower abdomen because the first
scopic surgery; its clinical benefits are assumed assistant usually stands or sits on the patient’s left
to be reduced postoperative pain, reduced surgi- side. Three 8 mm trocars are placed on the right
cal site complications, and enhanced postopera- upper and lower abdomens and left upper abdo-
tive recovery [8–11]. men (Fig. 15.1a). By contrast, an asymmetric port
In this chapter, the technical details of intracor- placement is recommended for total gastrectomy
poreal reconstruction methods are discussed, because the target organs such as the esophagus
including their advantages and disadvantages. A and spleen are located left of the midline.
particular focus is paid to the Billroth I anastomosis Especially of note is that the left-side trocars are
after robotic subtotal gastrectomy and Roux-en-Y placed more inferiorly than in distal gastrectomy,
esophagojejunostomy after total gastrectomy. which allows the left-side robotic arm to have suf-
ficient movement for splenic hilar dissection or
esophagojejunostomy reconstruction (Fig. 15.1b).
perative Setting and Preparation
O After gastric resection with radical lymphad-
for Reconstructions enectomy, the specimen is delivered via the
extended umbilical incision. A pneumoperito-
Patients are placed in the reverse Trendelenburg neum of 11–13 mmHg is then re-established,
position to approximately 10–30°, which makes after temporary closure of the umbilical incision
the stomach and colon retract downward due to using towel clips or sutures. After the confirma-
gravity. This preoperative position setting is tion of free resection margins by frozen biopsy
important for performing reconstruction after examination, intracorporeal anastomoses are per-
gastrectomy, as the ability to change the patient’s formed, according to the extent of gastric resec-
position may be limited during the operation. tion and the surgeon’s preference.
8 mm
8 mm 8 mm
8 mm
8 mm 12 mm 8 mm
12 mm
12 mm 12 mm
Extended for specimen delivery Extended for specimen delivery
Fig. 15.1 Port placement for robotic gastrectomy. (a) the patient’s right side. (b) The asymmetric port place-
The symmetric port placement for robotic distal gastrec- ment for robotic total gastrectomy. The left-side trocars
tomy. Two 12 mm trocars are placed on the infraumbilical are placed more inferiorly than in distal gastrectomy
area and the left lower abdomen. The left 12 cm trocar can because the target organs such as the esophagus and
be placed on the right side if the assistant stands or sits on spleen are located left of the midline
15 Reconstruction Methods After Robotic Distal or Total Gastrectomy 193
Intracorporeal Billroth of the duodenum (Fig. 15.2e). After identifying the

I Reconstruction after Robotic stapler line for bleeding, the common entry hole is
Distal Gastrectomy closed by one or two 60 mm lengths of articulated
linear staplers (Fig. 15.2f). In some cases, transient
The delta-shaped gastroduodenostomy was first approximation of the entry hole using three stay
introduced by Kanaya et al. for the intracorporeal sutures may be helpful for the tangential direction
Billroth I anastomosis [12]. The delta-shaped closure of the common entry hole.
anastomosis is a functional end-to-end gastroduo-
denostomy technique performed using only linear
staplers. Compared with extracorporeal Billroth I Intracorporeal Roux-en-Y
methods, it offers technical simplicity, wider Esophagojejunostomy After
lumen anastomosis, and a good surgical field Robotic Total Gastrectomy
(even in obese patients). There has been a general
trend toward the use of delta-shaped gastroduode- Intracorporeal esophagojejunostomy remains the
nostomy during the past decade; however, recent most critical and technically challenging step,
studies on delta-shaped anastomosis showed rela- even in laparoscopic surgery. Various methods for
tively high rates of anastomosis-related complica- laparoscopic total gastrectomy have been intro-
tions and bile reflux [11, 13–22]. Recently, an duced, but no standard protocol has been estab-
alternative method to delta-shaped anastomosis, lished. Intracorporeal reconstruction methods for
so-called linear-shaped gastroduodenostomy, was Roux-en-Y esophagojejunostomy are categorized
introduced by Han et al. [23, 24]. At 6 months into the linear stapler and circular stapler methods,
postoperation, endoscopic findings indicated that according to the type of stapler used for the esoph-
linear-shaped anastomoses showed significantly agojejunostomy. Definitive evidence on the supe-
less food residue, gastritis, and bile reflux than riority of either method is still lacking. A recent
delta-shaped anastomoses. However, there were review suggested that the circular stapler method
no differences in endoscopic findings between the is associated with a significantly higher risk of
two groups at 12 months postoperation. leakage and stenosis of the esophagojejunostomy:
the rates of leakage for the circular and linear sta-
pler methods were 4.7% and 1.1%, respectively
Surgical Techniques for Linear- (p < 0.001), while the rates of stenosis were 8.3%
Shaped Gastroduodenostomy and 1.8%, respectively (p < 0.001). However, this
study was not a systematic review but included 23
After infra- and supra-duodenal dissections, a retrospective and 2 prospective studies [25].
60 mm length of linear stapler is introduced The overlap method is one of the most favored
through the left 12 mm port. The duodenum is linear stapler methods. It was first introduced by
transected in a cranio-caudal direction, without the Inaba et al. in 2010 and has several advantages over
90° rotation that is crucial in the delta-shaped conventional end-to-side anastomosis using a
method (Fig. 15.2a). After completion of lymph- circular stapler [26]. Stapler handling is easier, even
adenectomy and gastric resection, an entry hole is in a narrow space, and stapling can be performed
created on the superior edge of the duodenal stump regardless of the diameter of the esophagus [27, 28].
(Fig. 15.2b). Another entry hole is created on the However, the overlap method that is currently being
greater curvature of the remnant stomach, about used has several technical shortcomings, namely,
60 mm away from the resection line (Fig. 15.2c). difficulties obtaining traction on the esophageal
A 60 mm length of linear stapler is then introduced stump that necessitates the use of an additional stay
through the left 12 mm port, and the cartridge jaw suture, the risk of unintended stapling of the left
is inserted into the stomach (Fig. 15.2d). The lin- crus, and the need for an additional stay suture when
ear stapler is moved toward the duodenal stump, closing the common entry hole. Therefore, a modi-
and the anvil jaw is inserted. The anastomosis is fied technique that overcomes these shortcomings
performed between the greater curvature side of has been introduced, the so-called “modified over-
the remnant stomach and the anterosuperior side lap method using barbed sutures (MOBS)” [29].
a b
Pylorus Entry hole
Duodenum Duodenal
stump
c d
Entry hole Remnant stomach

Resection line of
remnant stomach
Duodenal stump
e f
Stomach
Stomach
Duodenum
Duodenum
Fig. 15.2 Linear-shaped gastroduodenostomy (intracor- jaw of a 60 mm length linear stapler into the stomach. (e)
poreal Billroth I method). (a) View of duodenal transec- First firing in the linear-shaped anastomosis. Note that the
tion. Note that the duodenum is transected in a anastomosis is made between the greater curvature side of
cranio-caudal direction. (b) Creating an entry hole on the the remnant stomach and the anterosuperior side of the
superior edge of the duodenal stump. (c) Creating an entry duodenum. (f) Closure of the common entry hole with an
hole on the remnant stomach. Note that this location is articulated linear stapler. Several stay sutures may be
made on the greater curvature side, at least 6 cm away helpful for tangential direction closure of the com-
from the distal resection line. (d) Inserting the cartilage mon entry hole
Surgical Techniques for the Modified entry hole after firing of the linear stapler. An
Overlap Method Using Barbed entry hole is then made on the esophageal stump
Sutures (MOBS) using ultrasonically activated shears (Fig. 15.3c).
This technique is very useful for the surgeon to
After esophageal mobilization, a 60 mm length readily identify the intraluminal space with a suf-
of stapler is introduced through the left 12 mm ficient opening because cutting the staple line
trocar, and the distal esophagus is transected means that the anterior and posterior walls are cut
transversely (Fig. 15.3a). After checking the free simultaneously. Another entry hole is made on
resection margins, two barbed threads are sutured the anti-mesenteric side of the jejunum, about
on the stapled line of the esophageal stump 15–20 cm away from the Treitz ligament. The
(Fig. 15.3b). The distance between the two cartilage jaw of a 45 mm length of linear stapler
sutures is maintained at about 1 cm because their is then introduced into the jejunum, and the jaws
locations become lateral angles of the common are closed, angled, and ascended toward the axis
of the esophageal stump. Prior to esophagojeju- opened, and the anvil jaw is introduced gently
nostomy, the pre-sutured barbed threads are into the esophagus via the space between the
pulled downward to reduce the tension on the right and left crura (Fig. 15.3d). After firing the
jejunal mesentery. The staple is then slightly stapler and checking the anastomosis, the com-
a b Liver
Liver
Esophagus
Esophagus
Spleen
Pancreas
c d Liver
Liver Esophagus
Esophagus Jejunum
Pancreas
e Liver f
Liver
Esophagus
Esophagojejunostomy
Jejunum
Biliopancreatic limb
Roux limb
Fig. 15.3 Modified overlap method using knotless ultrasonically activated shears. (d) Firing a 45 mm length
barbed sutures for intracorporeal Roux-en-Y esophagoje- of linear stapler for esophagojejunostomy. Note that the
junostomy. (a) View of esophageal transection. Note that pre-sutured barbed threads are pulled downward to reduce
the esophagus is transected transversely. (b) Suture of two the tension on the jejunal mesentery during the anastomo-
barbed threads on the stapled line of the esophageal sis. (e) Closure of the common entry hole by the robot-
stump. Note that the distance between them should be sewn method using the pre-sutured barbed threads. (f)
about 1 cm because their locations become lateral angles Division of the biliopancreatic limb and roux limb using a
of the common entry hole after firing of the linear stapler. 60 mm length of linear stapler. (g) The making of a side-
(c) Creating an entry hole on the esophageal stump using to-side jejunojejunostomy in a caudo-cranial direction
mon entry hole is closed bidirectionally by hand- 2. Jiang ZW, Liu J, Wang G, et al. Esophagojejunostomy
sewing, using the pre-sutured barbed threads reconstruction using a robot-sewing technique during
totally robotic total gastrectomy for gastric cancer.
(Fig. 15.3e). Since the pre-sutured barbed threads Hepato-Gastroenterology. 2015;62:323–6.
are located at lateral angles to the common entry 3. Parisi A, Ricci F, Trastulli S, et al. Robotic total
hole, they function both as a landmark and the gastrectomy with intracorporeal Robot-Sewn anas-
stay sutures during the closure of the common tomosis: a novel approach adopting the double-loop
reconstruction method. Medicine. 2015;94:e1922.
entry hole. After completing the esophagojeju- 4. Yang K, Bang HJ, Almadani ME, et al. Laparoscopic
nostomy, the roux limb and the biliopancreatic proximal gastrectomy with double-tract reconstruc-
limb are separated by dividing the jejunum with a tion by intracorporeal anastomosis with linear sta-
60 mm length of linear staplers (Fig. 15.3f). A plers. J Am Coll Surg. 2016;222:e39–45.
5. Quijano Y, Vicente E, Ielpo B, et al. Full robot-
side-to-side jejunojejunostomy is made with two assisted gastrectomy: surgical technique and prelimi-
60 mm lengths of staplers at the roux limb about nary experience from a single center. J Robot Surg.
45–50 cm away from the esophagojejunostomy 2016;10:297–306.
(Fig. 15.3g). At this moment, the stapler is intro- 6. Kikuchi K, Suda K, Nakauchi M, et al. Delta-shaped
anastomosis in totally robotic Billroth I gastrectomy:
duced in a caudo-cranial direction. The mesen- technical aspects and short-term outcomes. Asian J
teric defect between the roux and biliopancreatic Endosc Surg. 2016;9:250–7.
limbs should be repaired to prevent long-term 7. Wang G, Jiang Z, Zhao J, et al. Assessing the
complications such as internal hernia. safety and efficacy of full robotic gastrectomy with
intracorporeal robot-sewn anastomosis for gastric
cancer: a randomized clinical trial. J Surg Oncol.
2016;113:397–404.
Conclusions 8. Zhang YX, Wu YJ, Lu GW, et al. Systematic review
and meta-analysis of totally laparoscopic versus lapa-
roscopic assisted distal gastrectomy for gastric cancer.
Recent advances in surgical instrumentation and World J Surg Oncol. 2015;13:116.
techniques have allowed surgeons to perform 9. Ikeda O, Sakaguchi Y, Aoki Y, et al. Advantages of
intracorporeal reconstructions after robotic dis- totally laparoscopic distal gastrectomy over laparo-
tal or total gastrectomy; these may reduce post- scopically assisted distal gastrectomy for gastric can-
cer. Surg Endosc. 2009;23:2374–9.
operative pain or complications and enhance 10. Kim MG, Kim KC, Kim BS, et al. A totally lapa-
postoperative recovery. Furthermore, the roscopic distal gastrectomy can be an effective
improved dexterity of robotic surgical systems way of performing laparoscopic gastrectomy in
may allow surgeons to perform precise sutures, obese patients (body mass index≥30). World J Surg.
2011;35:1327–32.
even in deep and narrow spaces, such as in 11. Kim MG, Kawada H, Kim BS, et al. A totally

esophagojejunostomy. However, a meticulous laparoscopic distal gastrectomy with gastroduo-
and careful surgical technique with understand- denostomy (TLDG) for improvement of the early sur-
ing of the concepts of each procedure is impor- gical outcomes in high BMI patients. Surg Endosc.
2011;25:1076–82.
tant for achieving optimal results and preventing 12. Kanaya S, Gomi T, Momoi H, et al. Delta-shaped
anastomosis-related complications after robotic anastomosis in totally laparoscopic Billroth I gastrec-
gastrectomy. tomy: new technique of intraabdominal gastroduode-
nostomy. J Am Coll Surg. 2002;195:284–7.
13. Kanaya S, Kawamura Y, Kawada H, et al. The

delta-shaped anastomosis in laparoscopic distal gas-
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17. Lee HH, Song KY, Lee JS, et al. Delta-shaped anas- scopic total gastrectomy for gastric cancer: literature
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Part VIII
Function-Preserving Surgery
Pylorous-Preserving Gastrectomy
16
Seung-Young Oh, Hyuk-Jun Lee,
and Han-Kwang Yang
Introduction Indication
With the increasing proportion of early gastric For PPG, to preserve pyloric branch of the vagus
cancer (EGC) and the excellent survival out- nerve, lymph node (LN) dissection around
comes after treatment, surgeons are now paying hepatic artery proper and right gastric artery is not
attention to postoperative quality of life (QOL) done. Therefore, an important factor that should
to be as important as survival for these patients be considered before performing a PPG is the
[1, 2]. Function-preserving surgery is a surgical possibility of metastasis to LN station 5 around
approach which meets such trend. Pylorus- right gastric artery, and any case which can have
preserving gastrectomy (PPG) is a good example LN metastasis in this area should not be indicated
of function-preserving surgeries to reduce the for PPG. In a study of the current status of PPG in
surgical extent without compromising oncologic Japan among 144 institutions, dissection of LN
safety. PPG was firstly introduced by Maki et al. station 5 was not performed in 36.8% (53/144)
in 1967 for the treatment of peptic ulcers [3] and and was partially performed in 56.2% (81/144)
then was applied in gastric cancer in Japan and [4]. Our group had reported two important stud-
Korea. EGC located in the middle part of the ies regarding the indication of PPG. Kong et al.
stomach would be indicated, and with preserved analyzed the safety of lymph node station 5 and
pylorus, less postgastrectomy symptom or 6 in PPG using 1802 gastric cancer cohort [5].
sequelae are expected. In this study, if the tumor was located more than
5 cm from the pylorus, the metastasis rate of
station 5 was 0% and 0.9% in T1a and in T1b,
respectively. Similarly, the metastasis rate of
station 6 was 0% and 1.8% in T1a and in T1b.
Also, Yoo et al. reported the median and mean
Maruyama index (MI, sum of the percentage of
Electronic Supplementary Material The online version undissected lymph node station) of PPG as 0 and
8_16) contains supplementary material, which is available 0.8, respectively [6]. Both studies provided the
to authorized users. background data of the oncologic safety of PPG
and concluded PPG is safe for EGC located more
S.-Y. Oh · H.-J. Lee · H.-K. Yang (*) than 5 cm from the pylorus.
Seoul National University College of Medicine, Because the probability of LN metastasis
Seoul, Republic of Korea increases as the depth of the lesion increases, the
e-mail: hkyang@snu.ac.kr

https://doi.org/10.1007/978-3-662-45583-8_16
202 S.-Y. Oh et al.
depth of invasion should also be evaluated [5, 7]. 23.1% of cases (caudal type), or the gastroduode-
For these reasons, PPG should only be consid- nal artery in 12.7% of cases (proximal type) [9].
ered only for patients with a cT1N0M0 gastric During LN dissection of station 6, the right gas-
cancer. According to the Japanese gastric cancer troepiploic artery is ligated at its root in the distal
treatment guidelines, PPG is indicated for the or proximal types. In the caudal-type cases, the
treatment of cT1N0M0 gastric cancers in the right gastroepiploic artery is ligated at a location
middle-third of the stomach, at least 4 cm away distal to the origin of the infra-pyloric artery [4, 5,
from the pylorus [8]. 10, 11]. The hepatic branch of the vagus nerve
that innervates the pylorus usually follows the
course of the supra-pyloric LNs (LN station 5)
Surgical Techniques (Figs. 16.1, 16.2, and should be preserved to maintain the motility
16.3, and 16.4 and Video) of the pylorus. Most surgeons prefer to preserve
the vagus nerve, rather than dissect supra-pyloric
The standard technique for PPG includes the pres- LN during PPG [7, 12–14], although surgeons
ervation of the infra-pyloric vessels and the commonly tried to completely dissect the supra-
hepatic branch of the vagus nerve for the preser- pyloric LNs in the early years of PPG [15].
vation of the pylorus functionally as well as struc- Because an insufficient antral cuff length may
turally [4]. There are three types in accordance lead to postoperative gastric stasis, a representative
with the origin of the infra-pyloric artery, and the complication of PPG, the distance from the lesion
ligation points of the right gastroepiploic artery to the pylorus needs to be carefully considered.
are different according to the anatomical type. When surgeons maintained an antral cuff length of
According to a study by Haruta et al., the infra- 1.5 cm in the initial period of PPG, the incidence
pyloric artery originates from the anterior supe- of postoperative delayed gastric emptying (DGE)
rior pancreaticoduodenal artery in 64.2% of cases was reported to range of 23–40% [12, 16, 17]. The
(distal type), the right gastroepiploic artery in relationship between the length of the antral seg-
a b
Fig. 16.1 (a, b) Preserving infra-pyloric vessels but lymph node around #6 station has been dissected
Fig. 16.2 Dissection of LN #8

16 Pylorous-Preserving Gastrectomy 203
Fig. 16.3 Dissected LN

#8, #7, #1, and #3. In
this case, there was a
replacing left hepatic
artery from left gastric
artery
For anastomosis, both extra- and intracorpo-

real methods can be performed for anastomosis
in LAPPG. For the extracorporeal method, a
hand-sewn anastomosis is usually applied. It gen-
erally requires an about 5 cm upper midline inci-
sion after laparoscopic dissection is finished (just
before resection of the stomach). The distal part
of the stomach is retracted through the incision
and resected first. For the proximal side, after
confirming the proximal margin by palpating a
Fig. 16.4 Gastro-gastroanastomosis hemostatic clip applied preoperatively, lesser
curvature side is resected by 10 cm linear stapler,
ment and the incidence of DGE was investigated and greater curvature side is anastomosed to
by Nakane et al. reporting an incidence rate of antral cuff by continuous interlocking where
DGE of 35% (7/20) among patients with an antral hand-sewn gastro-gastrostomy is performed (or
cuff of 1.5 cm, compared to only 10% (1/10) by interrupted Gambee suture). Intracorporeal
among patients with an antral cuff of 2.5 cm, anastomosis methods using linear staplers have
1 year after PPG [18]. Nunobe et al. reported an recently been introduced. For the intracorporeal
incidence rate of DGE of 6–8% among 90 patients anastomosis, transection of the stomach in the
after PPG in whom vagus innervation and blood sagittal direction (posterior to anterior direction),
flow to the pylorus were preserved with 3 cm of rather than in the transverse direction (greater
antral cuff length [7]. As more studies on the PPG, curvature to lesser curvature direction), can facil-
the length of the antral cuff has tended to be lon- itate the alignment of the linear staplers [20, 21].
ger. Considering a sufficient distal resection mar- After resection of the distal and proximal parts of
gin of >1 cm for EGC, current guidelines indicate the stomach, each arm of a 60 mm linear stapler
that a minimum distance of 4.0 cm should be is inserted into distal and proximal gastric
maintained between the side of the lesion to the remnants through the gastrostomy on the greater
pylorus. However, the optimal length for the antral curvature side corner. The stapler has to be fired
cuff remains to be clarified. between the posterior walls on either side, and
Nowadays, pylorus-preserving gastrectomy then the remaining gastrostomy can be closed
(LAPPG) is commonly performed laparoscopi- using further staplers. [20, 21]
cally because patients who undergo PPG are Robot-assisted pylorus-preserving gastrectomy
diagnosed with EGC. Although the operation (RAPPG) may provide another treatment option
time is longer in LAPPG than in open PPG due to for EGC in the middle-third of the stomach con-
additional setting of laparoscopic surgery, sidering benefits of robotic surgery including a
LAPPG provides several benefits over PPG, such three-dimensional and highly magnified imaging,
as reduced intraoperative blood loss and postop- a steady fixed camera, and an absence of a sur-
erative pain and a faster recovery [7, 15, 19]. geon’s tremors [22]. Han DS et al. reported that
204 S.-Y. Oh et al.
there was no significant difference in complication these studies, however, most patients with metas-
rates between the robot-assisted PPG and laparo- tasis to LN station 5 were ultimately confirmed as
scopic PPG groups. The mean number of exam- having ≥T2 cancer after surgeries, whereas the
ined lymph nodes (33.4 vs. 36.5; P = 0.153) and the metastasis rates to LN station 5 were very low
mean number of lymph nodes at each station were among patients with T1 cancer. Furthermore, Hiki
not different between the two groups. RAPPG can et al. [26] and Nunobe et al. [7] reported supra-
be a safe treatment option for middle-third early pyloric LN metastasis rates of 0.2% and 0.5%,
gastric cancer in terms of surgical complications respectively, among patients with T1 cancer
and oncologic outcomes. However, RAPPG has located in the middle-third of the stomach.
no benefit over LAPPG in this study [23]. In this In terms of long-term outcomes of PPG, Hiki
study, the energy device was ultrasonic device in et al. reported a 5-year survival rate of 98%
RAPPG group; future robotic device such as artic- among patients who underwent PPG for a cT1N0
ulating energy device may improve the result. The gastric cancer without any case of recurrence
benefits of RAPPG over LAPPG from patients’ [27]. Morita et al. reported a 5-year survival rate
perspective remain controversial. of 96.3%, with five cases of recurrence, among
patients who underwent PPG for EGC [28]. Suh
et al. reported a 3-year recurrence-free survival
Oncologic Safety rate of 98.2% for LAPPG for EGC, which is
comparable with the rate for LADG [14].
Preservation of the vessel and nerves to maintain
pyloric function may result in insufficient LN dis-
section at LN stations 5, 6, and 12a. An insufficient Advantages and Pitfalls
LN dissection would compromise the curative
potential of radical gastrectomy in the treatment of Compared to DG, PPG provides several benefits
gastric cancer. According to the Japanese gastric including a lower incidence of dumping syn-
cancer treatment guidelines, D1+ lymphadenec- drome, bile reflux, and gallstone formation, and
tomy should be performed in patients with a better nutritional advantages, which is associated
cT1N0 cancer [8]. LN dissection of station 6 with with a relatively small postoperative change in
infra-pyloric artery preservation is a relatively body weight [11, 14, 29–31]. Our group reported
easy technique, and LN station 12a is considered that PPG had fewer subjective postprandial symp-
to be beyond the D1+ level in patients with toms, less bile reflux than distal g astrectomy [11].
cT1N0M0. However, LN station 5 is considered to Our group also reported that patients who under-
be D1 level. In PPG, dissection of LN station 5 is went LAPPG had a better nutritional status, as
not routinely performed in order to preserve func- compared with those who underwent LADG,
tion of the hepatic branch of the vagus nerve and, including a smaller decrease in serum protein lev-
hence, of pyloric function. This could result in an els, serum albumin levels, and abdominal fat [14].
incomplete D1 LN dissection, which is a concern Gastric stasis is an annoying complication of
regarding the oncologic safety of the procedure. PPG which makes surgeons to hesitate to perform
Sasako et al. used a new index (estimated by PPG despite of many advantages. While the inci-
multiplying the incidence of metastasis and the dence of gastric stasis was as high as 40% during
5-year survival rate of patients having metastasis initial experiences with PPG [32], recent studies
to LN station 5) to evaluate the therapeutic value have reported the incidence of such complications
of LN dissection for gastric cancer, reporting a after PPG of 6.2–10.3% [7, 14, 19, 28, 33, 34].
low index of 0.8 among patients with a cancer in This value is still considered to be high, given that
the middle-third of the stomach [24]. The proba- the rate of these complications after DG is about
bility of metastasis to LN station 5 with an EGC 1.0% [35]. Although the pathophysiologic mecha-
localize to the middle-third of the stomach was nism of gastric stasis after PPG has not yet been
also evaluated. Kodera et al. [25] reported the rate fully defined, anastomotic edema and neurologic
of metastasis rate to LN station 5 to be <5%, and dysfunction, secondary to intraoperative damage,
Kone et al. [5] reported a rate of 4.2%. In both of are known to be contributing factors [13, 32, 33].
16 Pylorous-Preserving Gastrectomy 205
Gastric stasis can be easily diagnosed based on a Table 16.1 Indications and contraindications for
KLASS-04 study
combination of symptoms, such as postprandial
epigastric fullness or indigestion, with diagnosis Indications
confirmed by simple imaging, such as radiogra- 20 ≤ age ≤ 80
Histologically proven gastric adenocarcinoma
phy or an upper gastrointestinal series [36].
Performance status of 0 or 1 on the eastern
Patients who developed gastric stasis after PPG cooperative oncology group (ECOG) scale
may improve via conservative management and 1 ≤ American Society of Anesthesiologists class
radiological interventions, such as balloon dilata- (ASA) ≤ 3
tion or stent insertion [23, 34, 36]. cT1N0M0 (by endoscopic ultrasonography or
computed tomography scan)
Located at the middle-third of the stomach at least
5 cm away from the pylorus and resectable by distal
LASS-04 Study: A Multicenter
K gastrectomy
Prospective Randomized Written informed consent
Controlled Trial Contraindications
Pyloric deformity due to ulcerative disease
Currently, the comparison of the surgical, onco- History of gastric surgery (e.g., gastrojejunostomy or
logical, and patient-reported outcomes between primary closure)
Synchronous early gastric cancer or adenoma in the
LAPPG and LADG for the treatment of the antrum
middle-third of the stomach has only been evalu- Prior treatment with chemotherapy or radiotherapy
ated in a few studies. Most of these studies were against EGC diagnosed this time
retrospective in nature, including data from a lim- Need for combined resection (e.g., cholecystectomy)
ited number of patients at a single center. To sup- History of prior treatment (e.g., surgery,
port the application of LAPPG in clinical chemotherapy, or radiotherapy) against any other
malignancies within the last 5 years (excluding cured
practice, a comparative analysis of the short- and basal cell carcinoma and in situ cervical cancer)
long-term outcomes of prospective randomized Lack of decision-making capacity
data is essential. In order to confirm whether the Pregnant or breast-feeding women
postoperative quality of life and nutritional status Currently involved or participated in another clinical
are better, and whether survival is comparable trial within the last 6 months
between LAPPG and LADG, the KLASS group
has initiated a multicenter RCT (KLASS-04 References
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T. Laparoscopy-assisted pylorus-preserving gastrec- SW, et al. Decreased morbidity of laparoscopic distal
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Surgery for Gastric Cancer:
Proximal Gastrectomy 17
Young Suk Park and Hyung-Ho Kim
Introduction undergoing proximal gastrectomy still remains

low, and its oncologic safety and eligibility crite-
The incidence of gastric adenocarcinoma in the ria remain unclear. New anastomotic methods
upper third of the stomach has steadily increased after proximal gastrectomy may prevent reflux
worldwide, and the incidence of early gastric symptoms, as well as having nutritional benefits
cancer has increased sharply in East Asia. and improving quality of life.
Because the long-term survival of patients with
early-stage cancer is excellent, quality of life
after surgery has become increasingly important. Extent of Resection
This has led to increases in function-preserving and Lymphadenectomy
surgery, such as proximal gastrectomy and
pylorus-preserving gastrectomy. However, con- Japanese gastric cancer treatment guidelines rec-
ventional esophagogastrostomy after proximal ommend proximal gastrectomy for early-stage
gastrectomy has resulted in severe reflux esopha- proximal tumors, if more than half of the distal
gitis and anastomotic stenosis through acid regur- stomach can be preserved [1]. The extent of
gitation. Thus, many surgeons prefer to perform lymph node dissection in patients undergoing
total gastrectomy rather than proximal gastrec- proximal gastrectomy is less than that in patients
tomy for the upper-third gastric cancer. undergoing standard gastrectomy. D1 lymphade-
According to the Japanese gastric cancer treat- nectomy includes lymph node groups 1, 2, 3a,
ment guidelines [1], gastric resection can be 4sa, 4sb, and 7, and D1+ lymphadenectomy adds
modified for clinical T1 N0 tumors, and proximal groups 8a, 9, and 11p (Fig. 17.1). Lymph node
gastrectomy can be utilized to treat proximal groups 3b, 5, and 6, which are included in stan-
tumors. However, the proportion of patients dard gastrectomy such as distal gastrectomy and
total gastrectomy, are excluded in D1 lymphade-
Y. S. Park nectomy of proximal gastrectomy to preserve the
Department of Surgery, Seoul National University vascularity of the remnant distal stomach.
Bundang Hospital, Seoul, Republic of Korea Lymph nodes in group 3a and 3b are anatomi-
H.-H. Kim (*) cally defined as lesser curvature lymph nodes.
Department of Surgery, Seoul National University Group 3a lies along the branches of the left gas-
Bundang Hospital, Seoul, Republic of Korea tric artery, whereas lymph nodes in group 3b are
Department of Surgery, Seoul National University along the second branch and distal part of the
College of Medicine, Seoul, Republic of Korea right gastric artery (Fig. 17.2) [2]. By preserving
e-mail: hhkim@snubh.org

https://doi.org/10.1007/978-3-662-45583-8_17
208 Y. S. Park and H.-H. Kim
Fig. 17.1 The extent of

lymph node dissection
in proximal gastrectomy
4sb
4sa
3a
1 2
7
9
8a 11p
a b
RGA
LN 3a
LN 5
LN 3b LN 5 LN 3b
Fig. 17.2 Lymph node groups on the lesser curvature. (a) Lymph node group 3b and 5. (b) Lymph node group
3a, 3b, and 5
lymph nodes in area 3b and resecting the stomach Reconstruction Methods

along the border between groups 3a and 3b, more and Complications
than half of the stomach can be preserved.
Therefore, the resection margin of the lesser cur- Esophagogastrostomy is a conventional recon-
vature should be at or above the second branch of struction method widely used after proximal gas-
the right gastric artery. trectomy. Although esophagogastrostomy is a
17 Surgery for Gastric Cancer: Proximal Gastrectomy 209
simple, single-site anastomosis technique, it has (2) preservation of the lower esophageal sphincter
been associated with high rates of long-term mor- [4, 5]; (3) preservation of the hepatic and pyloric
bidities, such as reflux esophagitis and anastomo- branches of the vagus nerve with or without
sis stricture. These morbidities may be overcome pyloric drainage procedures, such as pyloromyot-
by the addition of supplementary procedures, omy or pyloroplasty, to prevent delayed remnant
including (1) formation of a narrow (3–4 cm wide) gastric emptying which causes gastroesophageal
gastric tube, with limited storage capacity, and reflux [3–5]; (4) creation of an acute angle at
esophagogastric tube anastomosis (Fig. 17.3) [3]; esophagogastrostomy, forming a new fundus
(Fig. 17.4) [4, 6, 7]; (5) semicircular wrapping of
the abdominal esophagus by the residual stomach,
similar to a Toupet fundoplication (Fig. 17.5) [8];
and (6) a combination of the above procedures.
These procedures were somewhat successful,
reducing the rates of reflux esophagitis and stric-
ture to 18–30% and 0–16%, respectively [3, 8–
10]. Esophagogastrostomies with additional
procedures are simple and easy compared to
Fig. 17.3 Esophagogastric tube anastomosis Fig. 17.4 Esophagogastrostomy with neo-fundus
the anterior wall of the gastric tube. After making

a mucosal window at the bottom of the flap,
3–4 cm below the tip of the gastric tube, the
esophageal and muco-submucosal layers of the
stomach are sutured together. Finally, the com-
pleted esophagogastrostomy is wrapped with the
seromuscular flaps. This double-flap technique
can create a large pseudo-fornix, with the postop-
erative esophagogastrostomy shaped like the
original cardia. Although this reconstruction is
not simple, as well as being technically demand-
ing, a laparoscopic double-flap method has been
described recently [12].
The other alternative to esophagogastrostomy
after proximal gastrectomy is esophagojejunos-
tomy with additional anastomosis. Jejunal
interposition consists of a short, 10–20 cm inter-
posed jejunal limb and two anastomotic sites of
esophagojejunostomy and gastrojejunostomy
(Fig. 17.7). The rates of reflux esophagitis and
esophagojejunal stricture after jejunal interposi-
tion have been reported to be 1.7–5.0% and 6.3%,
respectively [13–15]. Although jejunal interposi-
tion is a powerful anti-reflux reconstruction
method after proximal gastrectomy, the complex-
ity of this procedure can induce internal hernia-
tion through the mesenteric window of the small
intestine, which may result in the loss of a sub-
Fig. 17.5 Esophagogastrostomy with semicircular wrap- stantial proportion of the small intestine due to
ping of the abdominal esophagus necrosis [6, 15].
Another method of esophagojejunostomy
after proximal gastrectomy is double-tract recon-
other anastomotic techniques after proximal gas- struction. This technique consists of three anasto-
trectomy. Therefore, these procedures are not moses: Roux-en Y esophagojejunostomy,
difficult to apply to minimally invasive surgery gastrojejunostomy 15 cm below the esophagoje-
such as laparoscopic or robotic proximal gas- junostomy, and jejunojejunostomy 20 cm below
trectomy. This is another advantage of modified the gastrojejunostomy (Fig. 17.8). Double-tract
esophagogastrostomies. reconstruction therefore adds another anastomo-
In contrast to other modified esophagogastric sis (gastrojejunostomy) to the conventional
reconstruction methods, the double-flap tech- Roux-en Y esophagojejunostomy. Unlike jejunal
nique and valvuloplastic esophagogastrostomy interposition, this method maintains the continu-
are relatively time-consuming. Valvuloplastic ity of the jejunum, making it easier to perform the
esophagogastrostomy prevents gastroesophageal procedure. Furthermore, it has a dual route for
reflux by implanting the esophagus in a submus- food passage, reducing the incidence of delayed
cular tunnel of the remnant stomach, which is remnant gastric emptying. The rates of reflux
expected to act as a one-way valve (Fig. 17.6) esophagitis and anastomosis stricture have been
[11]. The first step in this reconstruction is to cre- reported to be 0–25.0% and 4.7–10.0%, respec-
ate double-door (H-shaped) seromuscular flaps in tively [8, 17, 18]. To date, however, only a few
a b
Fig. 17.6 Valvuloplastic esophagogastrostomy. (a) H-shaped seromuscular double flap. (b) Suturing of the esophagus
and the gastric mucosal window. (c) Esophagogastrostomy covering with the double flap
studies have reported long-term functional Functional Benefits

benefits after double-tract reconstruction, indi-
cating a need for additional studies to prove the The principal reason for choosing proximal rather
functional superiority over other reconstruction than total gastrectomy is the preservation of a par-
methods. tial stomach. Patients are expected to eat suffi-
cient food and maintain their preoperative body

weight after gastrectomy. Maintenance of preop-
erative food intake is more frequent in patients
who underwent proximal than total gastrectomy
[19–21]. Ratios between postoperative 1 year and
preoperative meal intake after proximal gastrec-
tomy and total gastrectomy were found to be
68.3–71.0% and 63.6%, respectively [17, 22].
Consequently, in most studies, body weight main-
tenance was better in patients who underwent
proximal than total gastrectomy [21, 23–25]. In
contrast, one retrospective study reported similar
body weight loss in both sets of patients, but the
rates of long-term complications, such as stenosis
(38.2%) and reflux (29.2%), were very high after
gastric tube reconstruction in patients who under-
went proximal gastrectomy [26]. These findings
indicate that postoperative food intake and weight
maintenance can be associated not only with the
storage function of the remnant stomach but with
late complications, including anastomosis stric-
tures, reflux, and indigestion.
Several studies have used a standard question-
naire to evaluate gastrointestinal symptoms after
Fig. 17.7 Jejunal interposition proximal gastrectomy [3, 21]. Postgastrectomy
symptoms, such as diarrhea, dumping syndrome,
dysphagia, and reflux, are similar between proxi-
mal and total gastrectomy or less frequent follow-
ing proximal gastrectomy [21]. A comparison of
symptoms before and after proximal gastrectomy
also showed no deterioration after surgery [3].
Esophagojejunostomy
The rate of postoperative anemia was lower
after proximal than after total gastrectomy [14,
20, 24, 25]. Anemia may be prevented after proxi-
10-15cm mal gastrectomy due to the secretion of gastric
intrinsic factor from residual gastric mucosa cells.
Retrospective studies showed that serum vitamin
Gastrojejunostomy
B12 was significantly higher after proximal than
after total gastrectomy [16, 25]. Moreover, iron
may be better absorbed by the duodenum during
food passage through the preserved natural gas-
25-30cm
trointestinal tract after proximal gastrectomy, but
this should be clarified in future studies.
Jejunojejunostomy
Oncologic Safety
Major concerns related to the oncologic safety of

proximal gastrectomy for cancers in the upper
Fig. 17.8 Double-tract reconstruction third of the stomach include long-term survival;
metastasis of the supra- and infrapyloric lymph study revealed that endoscopic evaluation of the
nodes, which may not be removed during proxi- remnant stomach may be difficult after jejunal
mal gastrectomy; and recurrent or metachronous interposition or double-tract reconstruction if the
cancer of the remnant stomach. distance between the esophagojejunostomy and
To date, no large-scale prospective random- gastrojejunostomy is longer than 10 cm [13].
ized controlled trials have shown that proximal However, shorter distance between them may lead
gastrectomy achieves oncologic outcomes equiv- to higher chance of gastroesophageal reflux.
alent to those of total gastrectomy. However, sev- Therefore, surgeons have to carefully decide the
eral prospective single-arm studies and distance between the two anastomosis sites when
meta-analyses [27, 28], as well as retrospective performing sphincter- substituting reconstruc-
studies, suggest that long-term survival after tions, considering the postoperative endoscopic
proximal and total gastrectomy is comparable. evaluation of the remnant stomach as well as
Moreover, proximal gastrectomy in most East reflux symptom.
Asian countries is limited to patients with early-
stage gastric cancer. Early gastric cancer of the
upper third of the stomach seldom metastasizes Conclusion
to lymph nodes around the pylorus. Several retro-
spective studies [29, 30] have also reported that Proximal gastrectomy may be a standard proce-
lymph node metastasis along the lower stomach dure for patients with early gastric cancer involv-
(right-sided greater curvature nodes along the ing the upper third of the stomach because of its
right gastroepiploic artery, and supra- and infra- favorable outcomes. However, applicability of
pyloric nodes, corresponding to lymph node proximal gastrectomy to patients with advanced-
groups 4d, 5, and 6, respectively, as defined by stage cancer needs to be carefully debated.
the Japanese Gastric Cancer Association [31]) Although the optimal reconstruction method
was not observed in patients with proximal can- after proximal gastrectomy remains unclear, cur-
cer confined to the muscularis propria. A retro- rent modified anastomotic techniques are suffi-
spective analysis of a large cohort of Japanese cient to make proximal gastrectomy a useful
patients with esophagogastric junctional adeno- function-preserving procedure. To confirm this
carcinoma found that the incidences of metasta- conclusion, a large-scale randomized trial com-
sis to nodal groups 5 and 6 were 1.7% and 0.8%, paring the long-term survival and functional ben-
respectively, even when patients with advanced efits of reconstruction techniques after proximal
tumors were included [32]. This very low inci- gastrectomy is required.
dence of metastasis to lymph nodes along the
lower stomach showed little impact on survival
after proximal gastrectomy. References
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Vagus-Preserving Gastrectomy
18
Masatoshi Nakagawa and Kazuyuki Kojima
Introduction Surgical Anatomy
The radical surgical treatment of gastric cancer There are three main parts of the vagus nerve in
requires resection of a large portion of the stom- gastric surgery: (1) the hepatic branch from the
ach, as well as regional lymphadenectomy. It is anterior vagal trunk, (2) the celiac branch from
well known that gastric resection and reconstruc- the posterior vagal trunk, and (3) the hepatic
tion of the gastrointestinal tract result in a variety nerve plexus (Fig. 18.1).
of functional and physiological disorders such as
dumping syndrome, malabsorption, diarrhea, and
so on. These unpleasant alimentary and/or sys- Hepatic Branch
temic symptoms are collectively referred to as
postgastrectomy syndrome [1]. Vagus nerve pres- The anterior vagal trunk bifurcates into the
ervation, which was first introduced in 1991, is hepatic branch and the anterior gastric branch at
one way to alleviate postgastrectomy syndrome the level of the right cardia. The hepatic branch
[2]. In this chapter, we will describe the surgical consists of a few nerves traversing through the
anatomy, operational procedure, and postopera- compact part of the lesser omentum caudal to the
tive outcomes of vagus-preserving gastrectomy left lobe of the liver, and it joins the hepatic nerve
(VPG). plexus. The anterior gastric branch runs along the
lesser curvature, innervating the anterior wall of
the stomach from the cardia to the gastric body.
Celiac Branch
The posterior vagal trunk runs behind the abdom-

inal esophagus through the gastropancreatic
M. Nakagawa
Department of Gastric Surgery, Tokyo Medical folds, bifurcating into the celiac branch and the
and Dental University, Tokyo, Japan posterior gastric branch. The celiac branch joins
K. Kojima (*) the right and left celiac ganglia. The celiac branch
First Department of Surgery, and the left gastric artery are often fused after
Dokkyo Medical University, Mibu-machi, they are joined together.
Shimotsuga-gun, Japan
e-mail: kojima-k@dokkyomed.ac.jp

https://doi.org/10.1007/978-3-662-45583-8_18
218 M. Nakagawa and K. Kojima
Fig. 18.1 Schema of Anterior vagal trunk

the vagus nerve around
the stomach
Posterior vagal trunk
Celiac branch
Hepatic branch
Celiac plexus
Hepatic plexus
Hepatic Nerve Plexus When the lesser omentum is resected, the

hepatic branch from the anterior vagal trunk,
The hepatic nerve plexus arises from the celiac which runs across the compact part of the lesser
nerve plexus, which consists of the vagus nerve omentum near the liver, should be identified and
from the celiac ganglia and the sympathetic nerve preserved.
from the greater splanchnic nerve. The nerve The posterior vagal trunk and celiac branches
plexus surrounds the common and proper hepatic that run along the posterior wall of the abdominal
arteries, especially dorsal to their cranial circular esophagus and down to the celiac ganglion are
location. identified. With exposure of the diaphragm’s
right crus and the anterolaterodorsal side of the
abdominal esophagus, the posterior vagal trunk is
Operational Procedure isolated and retracted toward the right side with a
vessel loop (Fig. 18.2).
VPG was originally introduced in open surgery After exposure of the common hepatic artery
[2], but recently it has also been performed as a and gastropancreatic folds, the No. 8a lymph
minimally invasive approach, and the magnified nodes, located along the common hepatic artery,
view of laparoscopic and robotic surgery facili- are dissected. In this step, the hepatic nerve
tates identification of the vagus nerve, as well as plexus that runs along the common hepatic artery
a precise procedure. In this section, the laparo- must be preserved. Lymph nodes along the left
scopic procedure will be presented as described gastric artery (No. 7) and celiac artery (No. 9) are
by Kojima et al. in their article [3]. dissected toward the position where the celiac
The surgical procedure begins with port inser- branch of the posterior vagal trunk joins the left
tion and lymph node dissection around the greater gastric artery (Fig. 18.3). The left gastric artery is
omentum and infrapyloric area, followed by duo- divided with double clips after isolation of the
denal resection. celiac branches. The nerves of Latarjet are
18 Vagus-Preserving Gastrectomy 219
Fig. 18.2 Identification and isolation of the posterior Fig. 18.4 Completion of vagus nerve-preserving lymph
vagal trunk. The posterior vagal trunk is isolated with a node dissection
vessel loop
bleeding were seen in the VPG group [4], two

other articles showed comparable perioperative
results, such as blood loss, operative time, mor-
bidity, and postoperative hospital stay, between
VPG and vagus nerve-resection gastrectomy
(VRG) groups [3, 5]. The time to first flatus was
also earlier in the VPG group than in the VRG
group in some reports [5–7].
Two articles investigated the hormonal effects
of vagus nerve preservation. Takiguchi et al. found
that, on postoperative day 7, although plasma fast-
ing ghrelin, which is a brain-gut peptide with
GH-releasing and appetite-inducing properties,
Fig. 18.3 Lymph node dissection around the left gastric decreased significantly in both the VPG and VRG
artery and celiac axis with preservation of the celiac branch groups by about 50% of the baseline values, the
of the vagus nerve. The celiac branch and left gastric artery postprandial reduction of ghrelin was maintained
are joined together at the root of the left gastric artery
only in the VPG group [5]. Kim et al. reported that
a lesser increase of peptide YY [8], acting as a sati-
divided from the celiac branches, along with the ety signal, was observed in the VPG group com-
perigastric lymph nodes. Retraction of the celiac pared to the VRG group. They also concluded that
branches toward the right side facilitates this pro- less body weight loss was observed 1 month after
cedure. The vagus nerve-sparing lymph node dis- surgery in the VPG group, which was related to
section is then completed (Fig. 18.4). After this less increase of peptide YY [9].
procedure, resection of the stomach and recon-
struction are performed.
Long-Term Results
Short-Term Results One article by Kim et al. showed less diarrhea 3

and 12 months after surgery and less appetite loss
As for the perioperative results, although only at 12 months in the VPG group. Yamada et al.
one article by Sakuramoto et al. reported that lon- reported that, at 1-year follow-up, the incidences
ger operative time and greater intraoperative of dumping syndrome and gallstone formation
220 M. Nakagawa and K. Kojima
were significantly lower and significantly more References

residual food was seen on endoscopic examina-
tion in the VPG group than in the VRG group, 1. Carvajal SH, Mulvihill SJ. Postgastrectomy syn-
dromes: dumping and diarrhea. Gastroenterol Clin N
although other clinical symptoms, endoscopic Am. 1994;23(2):261–79. Epub 1994/06/01.
findings, and nutritional status were similar 2. Miwa K, Kinami S, Sato T, Fujimura T, Miyazaki
between the two groups. Uyama et al. also I. Vagus-saving D2 procedure for early gastric carci-
reported a lower incidence of diarrhea and gall- noma. Nihon Geka Gakkai Zasshi. 1996;97(4):286–
90. Epub 1996/04/01.
stone formation in the VPG group with a median 3. Kojima K, Yamada H, Inokuchi M, Kawano T,
follow-up period of 23 months [10]. Sugihara K. Functional evaluation after vagus-nerve-
Two articles showed the data of VPG for up to sparing laparoscopically assisted distal gastrectomy.
5 years. In the article by Inokuchi et al., the inci- Surg Endosc. 2008;22(9):2003–8. Epub 2008/07/03.
4. Sakuramoto S, Kikuchi S, Kuroyama S, Futawatari N,
dence of clinical symptoms such as gastroesoph- Katada N, Kobayashi N, et al. Laparoscopy-assisted
ageal reflux, early dumping syndrome, and distal gastrectomy for early gastric cancer: experi-
chronic diarrhea, endoscopic findings using the ence with 111 consecutive patients. Surg Endosc.
RGB score [11], and nutritional status were simi- 2006;20(1):55–60. Epub 2005/11/12.
5. Takiguchi S, Hiura Y, Takahashi T, Kurokawa Y,
lar between the VPG and VRG groups, but gall- Yamasaki M, Nakajima K, et al. Preservation of the
stone formation was significantly less common in celiac branch of the vagus nerve during laparoscopy-
the VPG group 5 years after surgery [12]. Kim assisted distal gastrectomy: impact on postpran-
et al. compared the oncological outcomes dial changes in ghrelin secretion. World J Surg.
2013;37(9):2172–9. Epub 2013/05/07.
between the two groups, concluding that there 6. Yamada H, Kojima K, Inokuchi M, Kawano T, Sugihara
were no significant differences between the two K. Efficacy of celiac branch preservation in Roux-en-y
groups in cancer recurrence and death over reconstruction after laparoscopy-assisted distal gastrec-
5 years of follow-up [7]. tomy. Surgery. 2011;149(1):22–8. Epub 2010/04/27.
7. Kim SM, Cho J, Kang D, Oh SJ, Kim AR, Sohn TS,
et al. A randomized controlled trial of vagus nerve-
preserving distal gastrectomy versus conventional
distal gastrectomy for postoperative quality of life in
Conclusion early stage gastric cancer patients. Ann Surg. 2016;
263(6):1079–84. Epub 2016/01/05.
Up to now, although there have been few reports 8. Halatchev IG, Ellacott KL, Fan W, Cone RD. Peptide
YY3-36 inhibits food intake in mice through a melanocor-
of the feasibility and efficacy of VPG, and the tin-4 receptor-independent mechanism. Endocrinology.
results have varied article to article, based on the 2004;145(6):2585–90. Epub 2004/03/16.
currently available evidence, it can be concluded 9. Kim HH, Park MI, Lee SH, Hwang HY, Kim SE,
that (1) it is a technically feasible and oncologi- Park SJ, et al. Effects of vagus nerve preserva-
tion and vagotomy on peptide YY and body weight
cally acceptable procedure as long as the appro- after subtotal gastrectomy. World J Gastroenterol.
priate inclusion criteria are applied; and (2) 2012;18(30):4044–50. Epub 2012/08/23.
several positive postoperative outcomes, such as 10. Uyama I, Sakurai Y, Komori Y, Nakamura Y, Syoji
earlier first flatus after surgery, less diarrhea, less M, Tonomura S, et al. Laparoscopic gastrectomy
with preservation of the vagus nerve accompanied by
body weight loss, less appetite loss, less inci- lymph node dissection for early gastric carcinoma. J
dence of early dumping syndrome, and less gall- Am Coll Surg. 2005;200(1):140–5. Epub 2005/01/06.
stone formation, can be achieved by the 11. Nagano H, Ohyama S, Sakamoto Y, Ohta K,

procedure, which improves the patients’ postop- Yamaguchi T, Muto T, et al. The endoscopic evalua-
tion of gastritis, gastric remnant residue, and the inci-
erative quality of life. dence of secondary cancer after pylorus-preserving
In order to further elucidate these issues, and transverse gastrectomies. Gastric Cancer.
more research with larger sample sizes and 2004;7(1):54–9. Epub 2004/03/31.
diverse populations is needed, as well as research 12. Inokuchi M, Sugita H, Otsuki S, Sato Y, Nakagawa
M, Kojima K. Long-term effectiveness of preserved
examining the molecular biological mechanisms celiac branch of vagal nerve after Roux-en-Y recon-
that can explain the efficacy of vagus nerve struction in laparoscopy-assisted distal gastrectomy.
preservation. Dig Surg. 2014;31(4–5):341–6. Epub 2014/12/17.
Part IX
Sentinel Node Navigation Surgery
Sentinel Node Navigation Surgery
19
Hiroya Takeuchi and Yuko Kitagawa
Introduction recovery [5]. However, patients’ quality of life

(QOL) is mainly affected by late-phase compli-
In Japan, early-stage gastric cancer (cT1) is cations including dumping syndrome and body
found in many asymptomatic patients due to weight loss resulting from oral intake disturbance
recent advances in endoscopic diagnosis, and the due to large extent of gastric resection. Therefore,
population with this condition currently reaches both minimal invasiveness for early-phase recov-
in excess of 50% in major institutions [1]. ery by laparoscopic surgery and additional late-
Endoscopic submucosal dissection (ESD) has phase function-preserving gastrectomy should be
already been accepted as the most minimally carefully considered in patients indicated for
invasive procedure for the resection of early gas- these procedures.
tric cancer [1]. Laparoscopic gastrectomy repre- Function-preserving gastrectomy such as par-
sents an important intermediate option between tial gastrectomy, segmental gastrectomy, and
ESD and open surgery for patients with gastric proximal gastrectomy with limited lymph node
cancer [2]. The technique of laparoscopic gas- dissection is known to improve postoperative
trectomy has shifted from partial resection to late-phase function. However, a certain incidence
more radical procedures such as laparoscopy- of skip metastasis in the 2nd or 3rd compartment
assisted distal gastrectomy (LADG) with D2 of regional lymph nodes remains an obstacle to
lymphadenectomy, which is comparable to con- the wider application of these procedures. To
ventional open distal gastrectomy and can be per- overcome these issues, the concept of sentinel
formed in clinical practices [3, 4]. node (SN) mapping may become a novel diag-
Many patients with early gastric cancer are nostic tool for the identification of clinically
currently treated with advanced laparoscopic undetectable lymph node metastasis in early gas-
gastrectomy procedures, such as LADG and tric cancer.
laparoscopy-assisted total gastrectomy (LATG) SNs are defined as the first draining lymph
with standard lymph node dissection in Asian nodes from the primary tumor site [6, 7], and
countries [1–4]. LADG and LATG contribute to they are thought to be the first possible site of
both better esthetics and early postoperative micrometastasis along the route of lymphatic
drainage from the primary lesion (Fig. 19.1). The
pathological status of SNs can theoretically pre-
H. Takeuchi (*) · Y. Kitagawa dict the status of all regional lymph nodes. If SNs
Department of Surgery, Keio University School are recognizable and negative for cancer metasta-
of Medicine, Tokyo, Japan sis, unnecessary radical lymph node dissection
e-mail: htakeuchi@a6.keio.jp; kitagawa@a3.keio.jp

https://doi.org/10.1007/978-3-662-45583-8_19
224 H. Takeuchi and Y. Kitagawa
Tracer injection
Primary tumor Non-SN

Non-SN
Tracer
Biopsy Biopsy
SN SN
Non-SN
SN basin
Non-SN Non-SN
Fig. 19.1 Schema of gastric cancer and sentinel nodes cosally around primary tumor sites before surgery using
(SN). The SN is defined as one or more lymph nodes that endoscopy. Subsequently, the tracers pass through the
first receive lymphatic drainage from primary tumors. For afferent lymphatics, and blue-stained or radioactive nodes
intraoperative lymphatic mapping and SN biopsy, blue are regarded as the SN
dye and/or radioisotope-labeled colloid is injected submu-
could be avoided. SN navigation surgery is aparoscopic SN Mapping

L
defined as a novel, minimally invasive surgery Procedures for Gastric Cancer
based on SN mapping and the SN-targeted diag-
nosis of nodal metastasis. SN navigation surgery A dual-tracer method that utilizes radioactive col-
can prevent unnecessary lymph node dissection, loids and blue or green dyes is currently consid-
thus preventing the associated complications and ered the most reliable method for the stable
improving the patient’s QOL. detection of SNs in patients with early gastric
SN mapping and biopsy were firstly applied to cancer [10, 11]. An accumulation of radioactive
melanoma and breast cancer patients and were colloids facilitates the identification of SNs even
subsequently extended to patients with many in resected specimens by using a handheld gamma
other solid tumors [7–9]. The clinical application probe, and the blue dye is effective for intraopera-
of SN mapping for early gastric cancer has been tive visualization of lymphatic flow, even during
controversial for years. However, single institu- laparoscopic surgery. Technetium-99 m tin col-
tional results, including a recent multicenter trial loid, technetium-99 m sulfur colloid, and techne-
of SN mapping for early gastric cancer, are con- tium-99 m antimony sulfur colloid are
sidered acceptable in terms of the SN detection preferentially used as radioactive tracers. Isosulfan
rate and accuracy of determination of lymph blue and indocyanine green (ICG) are the cur-
node status [10, 11]. On the basis of these results, rently preferred choices as dye tracers.
we are developing a novel, minimally invasive In our institution, patients with clinical T1
function-preserving gastrectomy technique com- tumors, primary lesions less than 4 cm in diame-
bined with SN mapping. ter, and clinical N0 gastric cancer undergo SN
19 Sentinel Node Navigation Surgery 225
mapping and biopsy [10, 11]. In our procedures, has been developed as another promising novel
2.0 ml (150 MBq) of technetium-99 m tin colloid technique for SN mapping [15, 16]. SN could be
solution is injected the day before surgery into clearly visualized by ICG fluorescence imaging
four quadrants of the submucosal layer of the pri- compared to the naked eye. Further studies would
mary tumor site using an endoscopic puncture be needed to evaluate the clinical efficacy of ICG
needle. Endoscopic injections to the submucosal infrared or fluorescence imaging and to compare
layer facilitate accurate tracer injection rather those with radio-guided methods in prospective
than laparoscopic injection from the seromuscu- studies. However these new technologies might
lar site of the gastric wall. Technetium-99 m tin revolutionize the SN mapping procedures in
colloid with relatively large particle size accumu- early gastric cancer.
lates in the SNs after local administration.
The blue or green dyes are injected into four
quadrants of the submucosal layer of the primary esults of SN Mapping
R
site using an endoscopic puncture needle at the in Gastric Cancer
beginning of surgery. Blue lymphatic vessels and
blue-stained nodes can be identified by laparos- To date, more than 100 single institutional stud-
copy within 15 minutes after the injection of the ies have demonstrated acceptable outcomes of
blue or green dyes. Simultaneously, a handheld SN mapping for early gastric cancer in terms of
gamma probe is used to locate the radioactive the SN detection rate (90–100%) and accuracy
SN. Intraoperative gamma probing is feasible in (85–100%) of determination of lymph node sta-
laparoscopic gastrectomy using a special gamma tus; these outcomes are comparable to those of
detector introducible from trocar ports [10, 11]. SN mapping for melanoma and breast cancer
For intraoperative SN sampling, the pick-up [11]. A recent large-scale meta-analysis, which
method is well established for the detection of included 38 relevant SN mapping studies with
melanoma and breast cancer. However, it is rec- 2128 gastric cancer patients, demonstrated that
ommended that the clinical application of intra- the SN detection rate and accuracy of prediction
operative SN sampling for gastric cancer should of lymph node metastasis based on SN status
include sentinel lymphatic basin dissection, were 94% and 92%, respectively [17]. They con-
which is a sort of focused lymph node dissection cluded that the SN concept is technically feasible
involving hot and blue nodes [10, 11]. The gastric for gastric cancer, especially patients with early T
lymphatic basins were considered to be divided stage (T1), with the use of combined tracers and
in the following five directions along the main submucosal injection methods during the SN
arteries: left gastric artery area, right gastric biopsy procedures.
artery area, left gastroepiploic artery area, right Our group in Japan had conducted a multi-
gastroepiploic artery area, and posterior gastric center prospective trial (UMIN ID: 000000476)
artery area [12]. of SN mapping using a dual-tracer method with a
ICG is known to have excitation and fluores- radioactive colloid and blue dye [10]. In the trial,
cence wavelengths in the near-infrared range SN mapping was performed between 2004 and
[13]. Till date, some investigators have used 2008 for 397 patients with early gastric cancer at
infrared ray electronic endoscopy (IREE) to 12 comprehensive hospitals, including our insti-
demonstrate the clinical utility of intraoperative tution. Eligibility criteria were that patients had
ICG infrared imaging as a new tracer for laparo- cT1N0M0 or cT2N0M0 single tumor with diam-
scopic SN mapping [13, 14]. IREE might be a eter of primary lesion less than 4 cm, without any
useful tool to improve visualization of ICG- previous treatments. As results, the SN detection
stained lymphatic vessels and SNs even in the fat rate was 98%, and the accuracy of determination
tissues. More recently, ICG fluorescence imaging of metastatic status was 99% [10]. The results of
that clinical trial are expected to provide us with group has also been conducting the multicenter
perspectives on the future of SN navigation sur- prospective phase III trial to elucidate the
gery for early gastric cancer. oncologic safety including long-term survival of
laparoscopic stomach-preserving surgery with
sentinel lymphatic basin dissection compared to
linical Application of Laparoscopic
C a standard laparoscopic gastrectomy [21].
SN Navigation Surgery in Early A combination of laparoscopic SN biopsy and
Gastric Cancer endoscopic mucosal resection (EMR)/endo-
scopic submucosal dissection (ESD) for early
The distribution of sentinel lymphatic basins and gastric cancer is another attractive option as a
the pathological status of SNs would be useful in novel, whole stomach-preserved, minimally
deciding on the minimized extent of gastric invasive approach. If all SNs are pathologically
resection and in avoiding the universal applica- negative for cancer metastasis, theoretically,
tion of distal or total gastrectomy with D2 dissec- EMR/ESD instead of gastrectomy may be suffi-
tion. Appropriate indications for laparoscopic cient for the curative resection of cT1 gastric can-
surgeries such as partial (wedge) resection, seg- cer beyond the ESD criteria [20, 22]. However,
mental gastrectomy, pylorus-preserving gastrec- further studies are required to verify the safety
tomy, and proximal gastrectomy (LAPG) for and effectiveness of combined treatments involv-
cT1N0 gastric cancer could be individually deter- ing laparoscopic SN biopsy and EMR/ESD.
mined on the basis of SN status (Fig. 19.2) [18– Nowadays, LADG or LAPG is frequently
20]. Earlier recovery after surgery and applied to the patients with early gastric cancer
preservation of QOL in the late phase can be according to the results of pathological assess-
achieved by laparoscopic limited gastrectomy ment of primary tumor resected by EMR/ESD in
with SN navigation. Our study group in Japan has clinical practices. To date, it has not been clari-
currently been conducting the multicenter pro- fied whether the SN mapping is feasible even
spective trial (UMIN ID: 000014401) which will after EMR/ESD. One of the most important
evaluate the function-preserving gastrectomy issues is whether lymphatic flow from the pri-
with SN mapping in terms of long-term survival mary tumor to the original SNs might change
and patients’ QOL as the next step. A Korean after EMR/ESD. In our preliminary study,
Fig. 19.2 Individualized cT1 (<4cm)N0M0 gastric cancer

function-preserving
approaches for cT1N0M0 SN mapping
gastric cancer based on
sentinel node mapping.
ESD, endoscopic Laparoscopic sentinel lymphatic basin dissection
submucosal dissection; Intra-operative pathological (or molecular) diagnosis of SN
EMR, endoscopic
mucosal resection
SN metastasis (-) SN metastasis (+)
Laparoscopic function-preserving gastrectomy Laparoscopic

Wedge resection distal/total gastrectomy
Segmental resection with D2 dissection
Pylorus-preserving gastrectomy
Proximal gastrectomy
Endoscopic resection (ESD/EMR)
h owever, at least the sentinel lymphatic basin is with the risk of lymph node metastasis in the
not markedly affected by previous EMR/ESD clinical trial [23, 24].
[20, 22]. Modified gastrectomy according to SN In brief, after placing mucosal markings, ICG
distribution and metastatic status might be feasi- was injected endoscopically into the submucosa
ble even for the patients who underwent EMR/ around the lesion to examine SNs (Fig. 19.3)
ESD prior to surgery. [24]. The SN basin including hot or stained SNs
was dissected, and an intraoperative pathological
diagnosis confirmed that no metastasis had
Non-exposed Endoscopic Wall- occurred. Subsequently, NEWS was performed
Inversion Surgery Plus SN Mapping for the primary lesion. Serosal markings were
placed laparoscopically, submucosal injection
In current function-preserving surgeries such as was added endoscopically, and circumferential
laparoscopic local resection or segmental gas- seromuscular incision and suturing were per-
trectomy, the approach of gastrectomy is only formed laparoscopically, with the lesion inverted
from the outside of the stomach, in which the toward the inside of the stomach. Finally, the cir-
demarcation line of the tumor cannot be visual- cumferential mucosal incision was performed,
ized at the phase of resection. Therefore, the sur- and the lesion was retrieved perorally (Fig. 19.3).
geons cannot avoid a wider resection of the The NEWS combined with the SN biopsy can
stomach than is desired to prevent a positive sur- minimize not only the area of lymphadenectomy
gical margin. The recent appearance of a new but also the extent of gastric resection as partial gas-
technique, referred to as non-exposed endoscopic trectomy for patients with SN-negative for metasta-
wall-inversion surgery (NEWS), is a technique of sis [22]. Furthermore, NEWS does not need
full-thickness partial resection, which can mini- intentional perforation, which enables us to apply
mize the extent of gastric resection using endo- this technique to cancers without a risk of iatrogenic
scopic and laparoscopic surgery without dissemination. The combination of NEWS with SN
transluminal access mainly designed to treat gas- biopsy is expected to become a promising, ideal
tric cancer. We have been accumulating cases of minimally invasive, function-preserving surgery to
NEWS with SN biopsy for early gastric cancer cure cases of cN0 early gastric cancer.
a NEWS + Sentinel lymphatic

basin dissection
Primary tumor Sentinel node
Sentinel lymphatic basin dissection

Non-exposed endoscopic wall-inversion surgery (NEWS)
Fig. 19.3 Non-exposed endoscopic wall-inversion sur- observation of ICG with normal light. (e) Observation of
gery (NEWS) with SN biopsy and sentinel lymphatic ICG with infrared ray electronic endoscopy. Infrared ray
basin dissection. (a) Schema of the NEWS with sentinel electronic endoscopy can visualize SNs and lymphatics
lymphatic basin dissection. (b) Marking was placed clearly. (f) Resection of sentinel lymphatic basin. (g)
around the primary tumor. (c) Indocyanine green (ICG) Laparoscopic circumferential seromuscular incision. (h)
was endoscopically injected to the gastric submucosal and (i) Laparoscopic seromuscular suturing and
layer surrounding the primary tumor. (d) Laparoscopic inversion of the primary lesion
b c
d e
No. 3a
SN
No. 3a
SN
No. 7 SN
f g
Sentinel lymphatic
basin
h i
g astric cancer: results of a prospective randomized

Conclusion clinical trial. Ann Surg. 2008;248:721–7.
6. Kitagawa Y, Fujii H, Mukai M, Kubota T, Ando N,
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surgical challenge. Although further studies are tomy for breast cancer. Ann Surg. 1994;220:391–401.
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Part X
Surgery for EG Junction Cancer
Surgery for EG Junction Cancer
20
Yasuyuki Seto, Hiroharu Yamashita,
and Susumu Aikou
astric Cancer or Esophageal

G in 7th AJCC TNM classification, both Siewert
Cancer or Else? type II and III tumors had been classified as
esophageal cancer. After some discussions [11–
Should esophagogastric junction (EGJ) cancer be 13], in 8th version, type III was changed to gas-
classified or managed as gastric cancer or esoph- tric cancer classification, while type II still stays
ageal cancer or else? The debate focused on the in esophageal classification [14–15]. There have
issue has still remained [1], though EGJ cancer is been many papers regarding the clinicopatho-
increasing worldwide, in Asia [2–5] as well as logic features of Siewert type II tumors to iden-
western countries [6–8]. Squamous cell carci- tify the pathogenesis and appropriate treatment
noma developed in EGJ region is unanimously strategy. Some papers showed that the character-
treated as esophageal cancer. For EGJ adenocar- istics of Siewert type II were quite similar with
cinoma, Siewert classification has been widely gastric cancers [11, 12]. However, some papers
applied: type I (adenocarcinoma of the distal reported that there were two distinct pathways of
esophagus), tumors with an epicenter located tumorigenesis of EGJ adenocarcinoma, related or
more than 1 cm above the EGJ; type II (true car- unrelated to intestinal metaplasia, gastric atro-
dia cancer), tumors with an epicenter located phy, and gastric acid secretion [16–17]. The etiol-
within 1 cm oral and 2 cm aboral from the EGJ; ogy as well as the treatment strategy has still
and type III (subcardial cancer), tumors with an remained controversy, especially for Siewert type
epicenter located below 2 cm from the EGJ [9, II tumors.
10]. Among Siewert classifications, Siewert type In the EGJ region, the different tissues to be
I and III tumors are usually managed like esopha- potentially cancerous lesion are known to exist:
geal and gastric cancers, respectively. However, esophageal gland, Barrett epithelium, cardiac
gland, fundic glands, etc. Therefore, some
Siewert type II tumors might have different bio-
Electronic Supplementary Material The online version logical features from the esophageal and gastric
8_20) contains supplementary material, which is available cancers and, if so, should be regarded as the inde-
to authorized users. pendent disease. Investigation by cancer genet-
ics, etc. will be undoubtedly needed in the future.
Y. Seto (*) · H. Yamashita · S. Aikou
Department of Gastrointestinal Surgery, Graduate
School of Medicine, University of Tokyo,
Tokyo, Japan
e-mail: seto-tky@umin.ac.jp

https://doi.org/10.1007/978-3-662-45583-8_20
234 Y. Seto et al.
Surgical Procedures worldwide trend toward minimally invasive sur-

gery is observed [20], and it is increasing gaining
There have been various surgical approaches for popularity over open surgery [19]. Intent to per-
EGJ cancers: Ivor Lewis (right thoracic and form the minimally invasive surgery for EGJ can-
abdominal), left thoracoabdominal, transhiatal, cers is, also, absolutely important. Laparoscopic
and abdominal ones. Among them, Ivor Lewis or resection of Siewert type II tumors was reported
transhiatal approaches are mainly applied to to be feasible and oncologically equivalent as
Siewert type II tumor [18]. In the former, esopha- compared to open procedures [26].
gectomy through right thoracotomy with recon-
struction by gastric conduit and intrathoracic
anastomosis is usually performed like esophageal Lymphadenectomy
cancer, while in the latter, extended total gastrec-
tomy is done like gastric cancer. Why are those There have been many papers focusing the
quite different procedures performed to Siewert lymphadenectomy for EGJ cancers, to date.
type II EGJ cancer? Recent paper described that However, the strategy of lymphadenectomy,
the choice of approach has been still based on especially for Siewert type II tumors, has still
surgeon’s discretion [19]. A recent web-based remained controversial. The standard lymph
worldwide questionnaire demonstrated that the node (LN) dissection for type II tumors has not
majority of surgeons favor an extended gastrec- been established, to date. However, most papers
tomy for Siewert type II tumors (66% vs 27%) showed the significance of lymphadenectomy in
[20], while the big data based on 4996 NSQIP/ the pericardial, lesser curvature and at the foot of
SEER patients showed that esophagectomy was the left gastric artery nodes (no.1, 2, 3, 7 LNs)
more frequently performed than gastrectomy [27–29]. Therefore, those LNs should be rou-
(71% vs 29%) in the USA [21]. When the patients tinely dissected in all surgical cases with EGJ
with Siewert type II tumor refer to thoracic sur- cancers, regardless of advanced or early stages.
geons, Ivor Lewis is likely to be indicated. Optimal extent of lymph node dissection in the
Conversely, the abdominal surgeons prefer the mediastinum for Siewert type II tumors has not
transhiatal approach for Siewert type II tumors. been established. However, many papers showed
The potential differences between the east and the survival impact of lymphadenectomy in the
west in EGJ tumor biology were recently pointed lower mediastinum [27–30], while one paper
out, and the optimal surgical approach in western described that mediastinal LN dissection was not
countries was concluded to be Ivor Lewis [22]. essential in early Siewert type II tumors [31].
That is why there have been two quite different And, based on the analysis of recurrence pattern
approaches. and lymph node metastasis, the complete medias-
Several papers compared the short- and long- tinal LN dissection was reported to be not man-
term outcomes between the esophagectomy and datory for type II tumors arising within the
gastrectomy. No significant differences of post- stomach [32]. One paper showed that left renal
operative morbidity and mortality were observed vein nodal involvement (no.16a2; para-aortic
between those procedures [21, 23, 24]. As for the LN) had a similar survival impact with the lower
survival after surgery, two papers showed the bet- mediastinal and celiac axis LNs [29]. Now, multi-
ter results in the esophagectomy than the gastrec- institutional prospective clinical trial to evaluate
tomy groups [21, 23], while no difference the significance of the lower mediastinal and no.
between them was found in one report [24]. The 16a2 LN dissections for Siewert type II tumors is
comparison of long-term quality of life (QOL) ongoing under the collaboration of the Japanese
between the two groups demonstrated the better Gastric Cancer Association (JGCA) and the
QOL after the gastrectomy than the esophagec- Japanese Esophageal Society (JES).
tomy [25]. This should be considered at the deci- LNs along the distal portion of the stomach
sion of surgical procedures. Recently, a strong (no. 4, 5, 6) are located far from EGJ, though
20 Surgery for EG Junction Cancer 235
those LNs are simultaneously dissected when the apparently associated with poor macroscopic rec-
total gastrectomy is performed. Many papers ognition of the anatomical EGJ. In Japan, EGJ can-
reported the poor prognosis and marginal thera- cers are defined as its epicenter within 2 cm
peutic value of the Siewert type II cases with the proximal or distal to the EGJ according to the
nodal involvement in those LNs [27–29, 33]. The Japanese classification system (Nishi’ classifica-
extended abdominal lymphadenectomy was sug- tion), regardless of histological type. Among those
gested to improve survival because the poorer 3177 patients, 2601 cases were proven to be histo-
survival after D1 lymphadenectomy was shown logically adenocarcinoma. The results were sum-
in comparison with D1+/D2 lymphadenectomy marized in the previous paper [35]. The annual
[24]. Consistently, the nodal involvement around number of surgical cases was observed to increase
celiac axis (no. 9) was shown to impact the sur- steadily since 2001, especially for adenocarci-
vival [29, 34]. noma, in Japan. Figures 20.1, 20.2, 20.3, and 20.4
To evaluate the optimal extent of LN dissection show the rates of the dissection (red bar) and LN
during EGJ cancer surgery, the JGCA and the JES metastasis (blue bar) according to each LN stations
conducted a nationwide survey to characterize the of all 2418 adenocarcinoma cases, 1430 early
LN spread pattern of EGJ cancer in a large cohort. cases, 988 advanced cases, and 234 advanced cases
That was a questionnaire-based national retrospec- with its epicenter within esophagus, respectively.
tive study, in which clinical records of 3177 patients The numbers of LN stationed are based on the
underwent R0 resection between 2001 and 2010 at Japanese classification. The cases with neoadju-
the member hospitals of the JGCA and/or the JES vant therapy were excluded from the analysis. No.
were collected. And, the tumors of 40 mm or less in 100–112 and 107–109 LNs are located in the lower
dimension were selected since large tumors were and middle mediastinum, respectively. All figures
0 20 40 60 80 100
No.101
No.104
No.105
No.106r
No.106tb
No.107
No.108
No.109
No.110
No.111
No.112
No.19
No.20
No.1
No.2
No.3
No.4sa
No.4sb
No.4d
No.5
No.6
No.7
No.8a
No.9
No.10
No.11p
No.11d
No.16a1
No.16a2
Fig. 20.1 Rate of dissection (red) and LN metastasis (blue) in all 2418 adenocarcinomas
236 Y. Seto et al.
0 20 40 60 80 100
No.101
No.104
No.105
No.106r
No.106tb
No.107
No.108
No.109
No.110
No.111
No.112
No.19
No.20
No.1
No.2
No.3
No.4sa
No.4sb
No.4d
No.5
No.6
No.7
No.8a
No.9
No.10
No.11p
No.11d
No.16a1
No.16a2
Fig. 20.2 Rate of dissection (red) and LN metastasis (blue) in 1430 early adenocarcinomas
0 20 40 60 80 100
No.101
No.104
No.105
No.106r
No.106tb
No.107
No.108
No.109
No.110
No.111
No.112
No.19
No.20
No.1
No.2
No.3
No.4sa
No.4sb
No.4d
No.5
No.6
No.7
No.8a
No.9
No.10
No.11p
No.11d
No.16a1
No.16a2
Fig. 20.3 Rate of dissection (red) and LN metastasis (blue) in 988 advanced adenocarcinomas
0 20 40 60 80 100
No.101
No.104
No.105
No.106r
No.106tb
No.107
No.108
No.109
No.110
No.111
No.112
No.19
No.20
No.1
No.2
No.3
No.4sa
No.4sb
No.4d
No.5
No.6
No.7
No.8a
No.9
No.10
No.11p
No.11d
No.16a1
No.16a2
Fig. 20.4 Rate of dissection (red) and LN metastasis (blue) in 234 advanced cases with epicenter within esophagus
were shown in the final report of the abovemen-

tioned study (not published but delivered to the par-
ticipating hospitals). The results were quite
consistent with previous reports. Nodes along the
distal portion of the stomach (no. 4, 5, 6) were
much less often metastatic in any stages, though
those were dissected in most cases. And, survival >12cm
analysis failed to show the benefit of those dissec-
tions. Lower mediastinal LN dissection might con-
tribute to improve survival for the EGJ cancer with
esophagus-predominance or esophageal invasion.
Our Surgical Procedure >25cm
When more than half stomach can be preserved,

the proximal gastrectomy (PG) is chosen, because
Fig. 20.5 Shema of remnant stomach
the nutritional status after the PG were shown to
be better than after the total gastrectomy (TG) by
many studies [36–38], and no survival difference think that the TG should be avoided at the utmost.
was observed between those procedures [39]. Usually, the stomach of 12 cm or more along the
Furthermore, as the previous results showed, the lesser curvature and 25 cm or more along the
dissections of no. 4, 5, and 6 LNs are not neces- greater curvature from the pylorus ring is pre-
sary for the radical resection of EGJ cancers. We served (Fig. 20.5).
238 Y. Seto et al.
When the lower mediastinal LN dissection is The length from the esophagojejunostomy to
considered to be beneficial, no. 110, 111, and 112 jejuno-gastrostomy is 8 cm. Some paper recom-
LNs are usually dissected (Video 20.1). Both side mends the 15–25 cm distance between those anas-
pleura are preserved, and the inferior pulmonary tomoses [40], but our data (Fig. 20.7, not
vein is a point of the upper margin of dissection. published) showed that the frequency of reflux
The reconstruction is usually done by jejunal esophagitis was lower after the short than the long
interposition (JI) (Video 20.2). Frozen section JIs. When the lower mediastinal LN dissection is
analysis for the margin is usually submitted to thought to be unnecessary, laparoscopic proximal
confirm no cancer cells in the resection line. The gastrectomy is done followed by esophagogas-
jejuno-gastrostomy is created on the posterior trostomy. That anastomotic site is at the anterior
wall of the remnant stomach by the circular sta- wall with 5 cm distance from the resection line of
pler. That anastomotic site is at 5 cm distance the stomach (Fig. 20.8). And, several stiches
from the resection line of the stomach (Fig. 20.6). between the esophagus and stomach are added to
40
33 %
30
Pseudo-fornix % 20
8cm
14 %
10
5cm
0
~8cm (n=21) 9cm~ (n=9)
Length of jejunal interposition
Fig. 20.7 Frequency of reflux esophagitis according to

length of interposed jejunum
Fig. 20.6 Shema of reconstruction of jejunal interposition
Fig. 20.8 Shema of Pseudo-fornix

esophagogastrostomy
5cm
fix and prevent the reflux. Severe reflux esophagi- ing the rising incidence of this disease. Semin Radiat
Oncol. 2013;23(1):3–9. https://doi.org/10.1016/j.
tis after PG has not been developed in our recent semradonc.2012.09.008.
cases, though higher frequency of reflux esopha- 9. Siewert JR, Hölscher AH, Becker K, Gössner
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TG [41]. classification. Chirurg. 1987;58(1):25–32. Chirurg
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10. Stein HJ, von Rahden BH, Höfler H, Siewert

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Part XI
Surgery After Neoadjuvant Chemotherapy
Surgery After Neoadjuvant
Chemotherapy 21
Daniel Reim, Alexander Novotny,
and Christoph Schuhmacher
Introduction Clinical Trials for Neoadjuvant

Chemotherapy and Their Surgical
Neoadjuvant/perioperative chemotherapy (CT) Outcomes
for locally advanced gastric cancer has become a
routine clinical procedure on the base of recent Neoadjuvant or perioperative CT is an accepted
randomized controlled trials. This chapter and recommended therapeutic approach of GC
describes the European prospective randomized treatment in most European countries [1]. This
controlled trials and focuses on their surgical goes back to the results of the British MAGIC [2]
results. Outcome-related measures are described and the French FNLCC/FFCD trial [3], both of
from a surgical point of view. Numerous aspects which included a rather large number of patients
are discussed, and the influence of surgical out- and were, thus, adequately powered. Both trials
comes on oncologic results is critically reviewed. directly compared surgery with or without neo-
adjuvant or perioperative CT and showed a sig-
nificant benefit for the multimodal approach.
Different theoretical advantages of neoadju-
vant therapy over adjuvant therapy are discussed
for potentially resectable GC [4]. One is the usu-
ally better general health condition of patients in
the neoadjuvant setting. Another advantage is
that downstaging of the tumor may lead to higher
R0 resection rates. Several other benefits like
effects on occult metastasis or single tumor cell
Statement: This review fully has not been published or
submitted before. All authors declare that they partici- dissemination (micrometastasis) at the earliest
pated in the literature review and that they have seen and point in time are also discussed.
approved the final version. None of the authors have any The MAGIC trial is the presently most recog-
conflicts of interest. No funds or grants or company gifts nized landmark study for perioperative CT [2].
have been received, nor has the article been written by a
third party. Between 1994 and 2002 centers in the UK,
Europe and Asia recruited patients with resect-
D. Reim (*) · A. Novotny · C. Schuhmacher (*)
Klinik und Poliklinik für Chirurgie, able GC and adenocarcinomas of the esophago-
TUM School of Medicine, gastric junction (EGJ). Patients were randomized
Munich, Germany to surgery with perioperative CT (n = 250) or sur-
e-mail: Daniel.reim@tum.de; gery only (n = 253). CT consisted of three
christoph.schuhmacher@ecrin.org

https://doi.org/10.1007/978-3-662-45583-8_21
246 D. Reim et al.
p reoperative and three postoperative cycles of i.v. cisplatin. A postoperative CT was recommended
epirubicin, cisplatin, and continuous 5-FU. The in case of a response to the preoperative treat-
fear that preoperative CT jeopardizes the periop- ment or stable disease with positive lymph nodes.
erative outcome was not justified. Although Two hundred twenty-four patients were random-
remarkable and higher than common numbers ized to receive either preoperative CT or primary
presented by Asian authors, there was at least no surgery. The R0 resection rate among the patients
significant difference in postoperative complica- receiving CT was significantly higher compared
tions and 30-day mortality in both treatment arms to the primary surgery arm (84% vs. 73%;
(46% vs. 45% and 5.6% vs. 5.9%). For patients in p = 0.04). OS and DFS were significantly pro-
the CT arm, a downstaging effect could be longed after CT (p = 0.02 and p = 0.003, respec-
observed regarding the ypT and N-categories. OS tively). The 5-year survival rates largely match
as well as progression-free survival (PFS) of those reported for the MAGIC trial (see above)
patients receiving perioperative CT was signifi- with 38% in the CT and 24% in the surgery-only
cantly increased compared to patients treated by arm. [3]
surgery only (p = 0.009 and p < 0.001). The The European Organization for Research and
5-year survival rate was 36% for patients receiv- Treatment of Cancer (EORTC) 40954 Phase III
ing perioperative CT and 23% for patients treated trial investigated the same patient population as
by surgery only [2]. the MAGIC and the FNLCC ACCORD 07 FFCD
Critics of the perioperative treatment pointed 9703 trial, while adenocarcinomas of the distal
out that many patients in the MAGIC trial did not esophagus (AEG I according to the Siewert’s
receive the full number of postoperative CT classification) were excluded [6]. Unfortunately
cycles, because of poor performance status, com- the trial had to be closed early due to poor accrual
plications, or compliance issues in the postopera- after inclusion of 144 patients (n = 72 per treat-
tive period. In fact, only about half (49.5%) of the ment arm), while 360 patients were initially
patients who underwent preoperative treatment planned. The goal of the study was to achieve a
in the study also received the full courses of the surgical quality and higher grade of standardiza-
planned postoperative CT. tion. In contrast to the aforementioned, this trial
Because the importance of the adjuvant com- solely relied on preoperative (neoadjuvant) CT
ponent of the MAGIC regimen is uncertain, this with cisplatin, 5-FU, and folinic acid (PLF proto-
issue was addressed by a retrospective study from col). Resection was performed obeying strict sur-
the UK on a series of 66 patients undergoing peri- gical quality standards, including a D2
operative CT according to the MAGIC protocol. lymphadenectomy. The analysis of the patients
The results of this study showed a considerable included up to then showed a higher R0 resection
prognostic benefit in terms of disease-free sur- rate among the patients treated with neoadjuvant
vival (DFS) for patients receiving neoadjuvant as CT compared to those undergoing primary sur-
well as adjuvant treatment compared to patients gery (81.9% vs. 66.7%; p = 0.036). A significant
who did not undergo postoperative CT, while OS survival benefit could not be shown, but a down-
was not significantly different between the two staging and a tendency toward a prolonged OS
groups. So, administration of the adjuvant part of and DFS for the neoadjuvant treatment arm were
the regimen seemed to postpone tumor recur- observed (p = 0.113 and p = 0.065). Postoperative
rence rather than preventing it [5]. complications and deaths were also more com-
The results of the French FNLCC ACCORD mon among patients treated with neoadjuvant CT
07 FFCD 9703 trial confirmed data in favor of the (27.1% vs. 16.2%; p = 0.09 and 4.3% vs. 1.5%),
establishment of perioperative CT for patients but did not differ significantly. With only 67
with resectable GC and esophageal adenocarci- deaths occurring during the follow-up period, no
noma [3]. The chemotherapeutic regimen con- survival benefit could be shown for the CT arm
sisted of two to three cycles of i.v. 5-FU and (median survival 64.6 mo. vs. 52.5 mo.;
21 Surgery After Neoadjuvant Chemotherapy 247
p = 0.466) (in order to reach a power of 80%, 282 cept is based on the demonstrated beneficial
deaths would have been necessary). The fact that effect of bevacizumab in the treatment of colorec-
patient survival missed significance level in spite tal cancer and promising results in advanced GC
of higher R0 resection rates was attributed to the (AVAGAST trial) [12].
low patient number and the high surgical quality Even though Asia is the traditional stronghold
by the authors [6]. of adjuvant CT, neoadjuvant concepts recently
Ronellenfitsch et al. performed an interesting gained interest for certain indications which are
meta-analysis showing an absolute improvement difficult to cure.
in the survival of 9% at 5 years for patients under- Currently the value of neoadjuvant CT
going perioperative CT [7]. This effect could be in locally advanced, marginally resectable GC
observed starting 18 months after surgery and with poor prognosis, like tumors with paraaortal
was observable for 10 years. The odds of a R0 and/or bulky N2 and N3 nodal disease [13], large
resection in patients treated with perioperative type 3 (≥8 cm) or 4 (linitis plastica) tumors
CT were 1.4 times higher than in untreated (JOCG0210 [14], JCOG0501 [15], JCOG1002
patients. Additionally no increase in postopera- [16]), and T2–T3 N+ or T4 tumors (PRODIGY
tive morbidity and mortality as well as duration trial) [17], is investigated in Eastern Asia.
of hospitalization could be recognized. Also an Despite promising results in the abovemen-
interaction between age and treatment effect was tioned trials, the outcomes appear to be difficult to
considered. In contrast to a recently reported evaluate due to the fact that the beneficial effects
German series, no survival benefit from periop- of perioperative chemotherapy are not directly
erative CT could be shown for elderly patients. attributed to either the neoadjuvant or the adju-
Another remarkable point of a subgroup analysis vant part of the respective chemotherapeutic regi-
was that there seemed to be a higher survival ben- mens. Therefore, careful consideration of the
efit for patients with tumors of the EGJ as com- surgical outcomes within the trials is mandatory.
pared to other sites [7], an observation which was One of the most debated issues regarding surgical
basically confirmed in the patient population of a technique and oncologic outcome is D2 lymphad-
specialized German center [8]. enectomy. Recent data revealed the benefits even
There is also evidence in literature that patients in the criticized Dutch gastric cancer trial [18].
with signet ring cell adenocarcinoma do not ben- The long-term results clearly demonstrated that
efit from perioperative CT. Messager et al. inves- adherence to D2 lymph node dissection resulted
tigated this issue in a multicenter comparative in reduced risk of death in gastric cancer patients.
study including 3010 patients from 19 French Therefore, it is important to review the abovemen-
centers including 1050 patients (34.9%) with sig- tioned trials in the light of surgical procedures.
net cell histology [9]. In a patient cohort from the Despite conceivable differences in ethnicity and
Klinikum rechts der Isar in Munich, Germany biologic properties, survival outcomes between
including 200 patients with diffuse-type histol- Eastern Asian and European patients appear to be
ogy having undergone neoadjuvant CT only, enormous [19]. Whereas 5-year survival rates of
14.5% showed a good histopathologic response around 60%–70% are reported in Japanese gastric
(TRG1 according to Becker) [10]. In comparison cancer trials [20] in the surgery- only arms, a
27.7% of patients with an intestinal type growth 20–30% 5-year survival rate is notable in the
pattern (n = 331) showed a TRG1 in the histo- European trials for those patients undergoing sur-
pathologic workup [unpublished data]. gery only for advanced gastric cancer [2, 3].
An ongoing British trial presently investigates Therefore, surgical procedures appear to be rele-
the safety and efficacy of adding the monoclonal vant regarding the oncologic outcome also in
VEGF antibody bevacizumab to ECX CT admin- patients having been treated by neoadjuvant or
istered perioperatively in patients with resectable perioperative chemotherapy and have to be evalu-
gastric and EGJ adenocarcinomas [11]. This con- ated carefully in order to judge oncologic results.
248 D. Reim et al.
MAGIC EORTC
The MAGIC trial was conducted in 104 centers The EORTC trial was performed in ten experi-
in the UK, the Netherlands, Germany, Singapore, enced centers in Germany, Belgium, Portugal,
New Zealand, and Brazil between 1994 and 2002 the UK, and the Netherlands [6]. In contrast to
[2]. Only 66–69% of the patients received cura- the aforementioned trials, 96% of all patients had
tive resections, whereas 18–28% of all patients laparoscopic staging for pretherapeutic tumor
underwent palliative resection. The D2 dissection classification. 51–54% of the patients revealed
rates ranged from 40% to 43% of the patients, cancers of the GE junction or the proximal third
and 22–27% of the patients underwent esophago- of the stomach. All patients received gastrectomy
gastrectomy for cardia cancer. Seventy-four per- (+/− transhiatal extension), and the D2 dissection
cent of the patients suffered from stomach cancer, rate was 93–96% with a median number of 31–33
whereas all other patients had cancer of the lower dissected lymph nodes. Despite laparoscopic
esophagus or the cardia. The authors state that the staging, 13–16% of the patients revealed meta-
extent of lymphadenectomy was left to the sur- static disease in the final pathologic workup. The
geons’ discretion not making D2 dissection a curative resection rate was 82% in those patients
prerequisite for the surgical procedure. The origi- undergoing neoadjuvant chemotherapy com-
nal paper does not report on preclinical stages but pared to 67% for those patients undergoing sur-
states that one of the inclusion criteria was at gery only. However, this effect did not translate
least stage II. The preoperative workup was not into improved survival rates.
prescribed. Staging laparoscopy was not manda-
tory for the trial, and distant metastases were
ruled out by CT scan. Additionally procedures I mplications of Surgical Outcomes
involving the esophagus were not standardized After Neoadjuvant Chemotherapy
regarding approach, luminal extent of resection,
and lymphadenectomy. Regarding the heterogeneous (European) results
derived from randomized controlled trials inves-
tigating the role of neoadjuvant/perioperative
ACCORD chemotherapy, it has to be stated that surgical
quality reporting is underrepresented in the
The ACCORD trial was conducted in 28 French respective publications. Therefore, interpretation
centers from 1995 to 2003 [3]. Seventy-five per- of the results, especially when it comes to com-
cent of the patients suffered from lower esopha- parisons with Eastern Asian data, has to be con-
geal or gastric cardia cancer, whereas 25% of the ducted carefully. First of all, reporting of
patients had locally advanced gastric cancer. preclinical data is insufficient. The landmark tri-
Forty-nine percent of the patients received esoph- als do not sufficiently report on the staging pro-
agectomies, whereas gastrectomies were per- cess. The EORTC trial may be considered an
formed on 51% of the cases. D2 dissection was exemption, although only clinical T-stage is
recommended for the study cohort, but the paper being reported. There is no information on the
does not report on the success of D2 lymph node clinical N-stage, which may be related to the fact
dissection. However, a median number of 19 dis- that not all centers perform endoscopic ultra-
sected lymph nodes were reported. Preclinical sound. However, this factor could be negligible
stages were not reported in the original paper, due to the fact that endoscopic N-staging did not
and there is no data available if staging laparos- demonstrate to be a reliable method, especially in
copy was performed in order to rule out perito- cT2 cancers. Another point of criticism in the
neal metastasis. Further surgical data is not reported trials is that surgical procedures in the
available from the original publication. MAGIC and ACCORD trials did not adhere to
Eastern Asian standards, either D2 dissection undergo subtotal gastrectomy for cancer. Another
rates are not reported or the number of dissected issue could be the influence of obesity in the
lymph nodes is too low in order to allow for suf- Western world. Another reason for higher com-
ficient surgical quality. The MAGIC trial reported plication rates in Western patient collectives
that only 40% of the patients received D2 dissec- could be the significantly higher BMI compared
tion and the ACCORD trial did not report on D2 to Asians. Kodera et al. published that in Japanese
dissection rates at all. However, adequate lymph patients higher BMIs were significantly related to
node dissection was performed in the EORTC postoperative complications after gastric cancer
trial with a D2 dissection rate of 96% which is surgery [23].
remarkable for European standards. Compared to Comparing the three European landmark stud-
results from Japanese trials, these results appear ies, it appears remarkable that there could be a
to be improvable in future trials. Here D2 dissec- relation between surgical quality and the number
tion rates are 100%, and 5-year survival rate for of participating centers. The lower the number of
the standard treatments for advanced gastric can- trial sites became, the better the outcome in the
cer accounts for over 60%. Nonetheless, D2 dis- surgery-only arm was. Surgery-related morbidity
section cannot be considered as the only culprit was highest in the MAGIC trial where over 100
for these survival differences. The Japanese trial- centers took part, whereas the morbidity rate was
ists rigorously excluded patients from their trials lowest in the EORTC trial with only 10 partici-
when curative resections are not reached. In the pating trial centers. Several analyses in the past
S1 trials, for example, patients were even demonstrated a centralization effect for esopha-
excluded when peritoneal washing cytology was geal and gastric cancer surgery. One study
not done. At least staging laparoscopy was per- reported specifically on gastric cancer which
formed in the EORTC trial to rule out occult peri- demonstrated that 30-day mortality could be
toneal metastasis in contrast to the French and the reduced by over 7% per additional case in sur-
British trial. Another issue could be the frequency geons with an annual volume of at least 14 gas-
of postoperative complications. In the MAGIC trectomies [24]. Another analysis from England
trial, a complication rate of over 40% was reported that increasing hospital volume resulted
reported, whereas postoperative morbidity in lower mortality, especially in the first 30 days
accounted for 20–30% in the ACCORD and after the surgical procedure [25]. Interestingly
EORTC trials. The postoperative complication this effect was also detected in long-term out-
rate in the S1 trial, for example, was below 20% comes leading to the intriguing suspicion that
[20]. Several groups reported that survival of oncologic outcome could possibly be influenced
postoperative complications leads to worsened just by hospital and individual surgeon’s case
long-term outcomes after oncologic surgery [21– volume. This also leads to the conclusion that the
23]. Toner et al. reported that survival of postop- design of future trials should consider these facts
erative complications leads to worsened and include only centers with the respective
long-term outcomes after oncologic surgery [21]. expertise in gastric cancer surgery.
The differences in postoperative complication
rates could also be related to the various distribu-
tions of tumor location within the reported trials. Conclusions
At least half of the patients in all European trials
had GE junction cancer. This stands in stark con- In general, surgery after neoadjuvant chemother-
trast to Eastern Asian patients where GE junction apy should not be different from surgical proce-
cancers rarely occur. This also leads to a higher dures without multimodal treatments especially in
amount of total gastrectomies or even esophagec- advanced gastric cancer patients. The obvious
tomies leading to increased morbidity rates com- advantages of D2 lymphadenectomy and radical
pared to Eastern Asian patients who usually surgery for complete tumor removal have been
250 D. Reim et al.
demonstrated in the past. Especially Eastern those trials could have been avoided by a closer
Asian surgical principles demonstrated their involvement of surgeons when those trials were
effectiveness before and should not be abandoned planned. These surgeons should not only be
for Western patients undergoing treatment for experienced in the performed procedures but also
locally advanced gastric cancers. The European in the development of clinical trials. This is like-
trials on neoadjuvant/perioperative chemotherapy wise a plea to all academic surgeons to involve
produced heterogeneous results regarding onco- themselves more in the conduct and initiation of
logic outcomes. Generally speaking, surgical clinical trials dealing with multimodal treatment
aspects are underrepresented in these multicenter strategies, not leaving this field solely to medical
trials that led to the adoption of neoadjuvant che- oncologists and/or radiooncologists.
motherapy in clinical routine for locally advanced
gastric cancer. These trials are difficult to evaluate
in their efficacy due to the heterogeneous surgical References
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Part XII
Surgery for Remnant Gastric Cancer
Surgery for Remnant Gastric
Cancer: Open Surgery 22
Introduction of effective medical treatment for peptic ulcer

disease, which has led to a decrease in the fre-
Remnant gastric cancer is a type of complicated quency of remnant gastric cancer after surgery
gastric cancer. Although no consensus definition for benign disease. By contrast, nationwide mass
has been established to date, the most popular screening for gastric cancer has increased the
definition of remnant gastric cancer is a cancer in proportion of early gastric cancers detected in
the remaining stomach at least 5 years after gas- Korea and Japan, and treatment strategies for
trectomy, regardless of the reason for the primary gastric cancer have improved, leading to longer
surgery (i.e., whether it was for benign or malig- survival of patients with gastric cancer. Unlike
nant disease). In the 1970s and 1980s, gastrec- gastric cancers in Western countries, which gen-
tomy was frequently performed for complicated erally occur in the upper third of the stomach,
peptic ulcer disease, and most instances of rem- 60–70% of gastric cancers in Korea and Japan
nant gastric cancer were located in the stomach occur in the distal stomach and are usually treated
remaining after surgery for this benign disorder. by distal gastrectomy. Consequently, the inci-
Nowadays, gastrectomy for benign disease has dence of remnant gastric cancer is expected to
become less frequent because of the development increase, especially in East Asia.
Despite the clinical importance of remnant
gastric cancer, the molecular carcinogenesis and
Electronic Supplementary Material The online version
of this chapter (https://doi.org/10.1007/978-3-662-45583- clinical features of this cancer have not been well
8_22) contains supplementary material, which is available characterized; consequently, optimal treatment
to authorized users. strategies for remnant gastric cancer have not
been established. Reasons for the lack of clinical
Y. Y. Choi knowledge about this disease may include its low
Department of Surgery, Yonsei University Health incidence (follow-up after gastrectomy has dem-
Seoul, Republic of Korea onstrated remnant gastric cancer incidence rates
of 1–3% [1–3]) and the use of variable definitions
S. H. Noh (*)
Department of Surgery, Yonsei University Health of remnant gastric cancer in the available studies
System, Yonsei University College of Medicine, (which is especially apparent as we are now in a
Seoul, Republic of Korea transition period, with the incidence after surgery
Brain Korea 21 PLUS Project for Medical Science, for benign disease decreasing and the incidence
Yonsei University Health System, Yonsei University after surgery for cancer increasing).
College of Medicine, Seoul, Republic of Korea
e-mail: sunghoonn@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_22
Because of the paucity of information regard- gastrojejunostomy than after gastroduodenostomy.

ing treatment options for remnant gastric cancer Chronic inflammation due to bile reflux is one of
per se, clinical practice has generally been based the putative mechanisms responsible for the devel-
on knowledge about primary gastric cancer, espe- opment of remnant gastric cancer, whereas the eti-
cially in terms of staging of the disease [4], extent ology of other remnant gastric cancers may be
of surgical resection, and chemotherapy regi- similar to that of primary gastric cancer.
mens. The available knowledge about remnant
gastric cancer, derived from retrospective studies
at large-volume hospitals and multiple centers, ymph Node Metastases
L
suggests that the prognosis of this cancer is com- in Remnant Gastric Cancer
parable to that of primary gastric cancer.
However, this does not mean that the treatment of Lymphatic flow around the remnant stomach is
remnant gastric cancer does not need to be distin- changed because of the altered anatomy caused
guished from that of primary gastric cancer by the previous surgery; lymphatic drainage of
because the lymphatic structure and molecular the remnant stomach after gastroduodenostomy
carcinogenesis of the two types of cancer could is different from that after gastrojejunostomy. In
differ [5]. addition, lymphatic drainage is also affected by
Detailed discussions of the molecular mecha- the reason for the initial surgery because a more
nisms of, and perioperative chemotherapy and extended lymph node dissection would have been
radiotherapy for, remnant gastric cancer are performed for malignant disease, whereas a more
beyond the scope of the current section. In this limited or no lymph node dissection would have
chapter, we introduce the clinicopathologic char- been performed for benign disease. Therefore,
acteristics of remnant gastric cancer and the the surgical approach should be distinguished
expected patterns of lymphatic metastases according to the type of reconstruction and rea-
according to the type of previous reconstruction. son for the initial surgery.
In addition, we briefly introduce the possibility of After gastroduodenostomy, cancer in the rem-
endoscopic treatment and minimally invasive nant stomach can spread to the hepatoduodenal
surgery (laparoscopic or robotic surgery) for ligament, superior mesenteric vein, splenic ves-
remnant gastric cancer. Finally, the issues sur- sels, and short gastric vessels (Fig. 22.1). After
rounding, and the detailed procedures of, gastrec- gastrojejunostomy, the lymphatic flow is similar
tomy and lymph node dissection for remnant to that observed gastroduodenostomy, so the can-
gastrectomy will be addressed and related to cer can spread through the splenic and short gas-
treatment outcomes of remnant gastric cancer. tric vessels. However, lymphatic flow differs after
gastrojejunostomy in that metastases can also
spread to the mesentery of the jejunum through
Clinicopathologic Characteristics the anastomosis site (Fig. 22.2). Of course, when
of Remnant Gastric Cancer the right gastroepiploic, right gastric, and left gas-
tric vessels are retained after the previous surgery
Remnant gastric cancer has an incidence of 1–3% (mainly after surgery for benign disease), cancer
and is much more common in males than females in the remnant stomach can spread through the
(the male/female ratio is 3–5:1). The time interval lymphatics around these remaining vessels as
between primary gastrectomy and the diagnosis of well. Thus, although there is no definition of D2
remnant gastric cancer depends on the reason for for remnant stomach cancer, all D2 lymph nodes
the initial surgery: the interval is generally shorter for primary gastric cancer should be removed.
after surgery for malignant disease (approximately Furthermore, because lymphatics around the
10 years) than after gastrectomy for benign dis- splenic vessels are the main lymphatic flow of the
ease (approximately 30 years). In addition, rem- remnant stomach, lymph node dissection in this
nant gastric cancer is more frequent after area should be performed meticulously. Routine
22 Surgery for Remnant Gastric Cancer: Open Surgery 257
plete removal of lymph nodes is a prerequisite for

spleen-preserving completion total gastrectomy
for remnant gastric cancer.
Minimally Invasive Treatment

for Remnant Gastric Cancer
Endoscopic Treatment
Endoscopic resection of gastric cancer, such as

by endoscopic mucosal resection and endoscopic
submucosal dissection, has become widely used
to treat primary gastric cancer in the very early
stages. The absence of lymph node metastases is
a prerequisite for endoscopic resection of gastric
cancer because the procedure only involves
removal of the primary cancer, without any
lymph node dissection. Selection of which
Fig. 22.1 The lymphatic flows of remnant stomach after patients can be candidates for this treatment was
gastroduodenostomy. The cancer can spread to hepatodu- based on a large-scale review of pathologic
odenal ligament, superior mesenteric vessels, splenic ves-
sels, and short gastric vessels results from surgical specimens. Gotoda et al.
reviewed the pathologic results of 5265 patients
who underwent gastrectomy with lymph node
dissection for early gastric cancer and developed
a stratification system regarding the risk of lymph
node metastasis [6]. Based on these results,
patients with a very low risk of lymph node
metastases have been treated with endoscopic
resection. It is not yet clear whether endoscopic
resection is feasible or efficacious for remnant
gastric cancer, however, because of the limited
number of cases of this type of tumor. In addi-
tion, endoscopic resection would be technically
challenging because of the narrow space and
fibrotic changes around the stapled anastomosis
site. Despite these difficulties, recent studies have
shown that endoscopic resection for remnant gas-
Fig. 22.2 The lymphatic flows of remnant stomach after tric cancer is feasible [7–12], and it has been sug-
gastrojejunostomy. The cancer can spread not only
through vessels around stomach but also through the mes- gested that the same indications for endoscopic
entery of the jejunum resection of primary gastric cancer might be
applied to remnant gastric cancer as well [13].
Considering the high degree of difficulty per-
splenectomy for lymph node dissection around forming completion total gastrectomy for rem-
the splenic vessels is not recommended, which is nant gastric cancer because of fibrosis, adhesions,
similar to the situation for primary gastric cancer and changed anatomy, endoscopic resection
in the upper third of the stomach; however, com- could be a reasonable treatment option for
remnant gastric cancer with a very low risk of reason for previous surgery was cancer, lymph
lymph node metastases, especially in patients nodes around the celiac axis would have been
with severe comorbidities. dissected, which in turn produces more adhesions
and fibrosis in the supra-pancreatic area.
Consequently, surgeons should be very careful to
Laparoscopic and Robotic Surgery avoid injuring major vessels, such as the common
hepatic artery, portal vein, splenic artery and
Surgery for remnant gastric cancer is technically vein, and even the aorta and inferior vena cava.
challenging because of fibrosis, adhesions, and Dissecting the lymph nodes from the patient’s
altered anatomy caused by previous surgery. left to right side rather than right to left side may
Thus, minimally invasive surgery (such as lapa- help identify the appropriate anatomical plane
roscopic or robotic surgery) for remnant gastric because the anatomy of the left side (around the
cancer is difficult to perform, and substantial sur- splenic hilum) may not be affected by the previ-
gical skills and experience, as well as a compre- ous surgery. The right gastroepiploic and right
hensive understanding of the anatomy, are gastric vessels would usually have been ligated
required to perform this procedure. Some sur- during the prior surgery, but the left gastroepi-
geons with advanced laparoscopic skills have ploic and left gastric vessels would rarely have
attempted this seemingly impossible surgery and been ligated when the reason for previous gas-
reported it to be feasible and possible to perform trectomy was benign disease. Although the right
safely, with morbidity and mortality rates compa- gastroepiploic and right gastric vessels would
rable to those of open surgery [14–18]. When sur- have already been ligated by the previous sur-
geons try to perform completion total gastrectomy gery, careful lymph node dissection around #5
by laparoscopic or robotic methods, there should and #6 would be required if the previous surgery
be no hesitation to convert to open surgery if a was for benign disease. Lymph nodes around the
problem arises. Detailed results and surgical superior mesenteric vein (#14v) are not included
techniques for minimally invasive surgery of in the current D2 lymph node dissection for pri-
remnant gastric cancer are addressed in another mary gastric cancer, but if this node remains and
chapter. the tumor in the remnant stomach is located near
the gastroduodenostomy site, dissecting #14v
would be helpful for accurate staging and prog-
pen Surgery for Remnant
O nosis determination.
Gastric Cancer After careful dissection between the abdomi-
nal wall and intestines, the anatomy around rem-
Difficulties with performing completion total nant stomach should be identified through
gastrectomy for remnant gastric cancer arise adhesiolysis. When the greater omentum remains,
from two distinct characteristics of remnant gas- total omentectomy is performed in the same
tric cancer: (1) the presence of adhesions and manner as during primary gastric cancer surgery.
fibrosis caused by the previous surgery and (2) Usually adhesions exist between the liver and the
changes in the lymphatic drainage. It is generally ventral side of the stomach, and gentle dissection
agreed that there will be more adhesions and of the plane between the liver surface and gastric
fibrosis when the previous surgery was for cancer wall is required. When the tumor is located on the
rather than for benign disease. There will be anterior side of the stomach, the surgeon should
adhesions around the remnant stomach extending be careful not to injure the gastric wall during the
to the wound, other peritoneal surfaces, small dissection.
bowel, colon, and liver, but the most critical When the previous surgery involved a gastro-
region for completion total gastrectomy will be duodenostomy, the duodenum is transected by
the supra-pancreatic area. Especially when the stapling, after fully identifying the borders of the
duodenum, stomach, and pancreas. Sometimes gastric cancer, but relatively fewer adhesions are
the gastroduodenostomy was performed by sta- located here because this area will not have been
pling during the previous surgery and is close to affected by the previous gastrectomy, regardless
the head of the pancreas; if so, resecting the duo- of the reason for the surgery. When the left gas-
denum by stapling will be difficult. In this situa- troepiploic vessels were not previously dissected,
tion, the duodenum can be transected by a scalpel dissecting #4Sb and ligating the short gastric ves-
and the opening repaired by hand suturing sels (#4Sa) can expose the hilum of the spleen. If
(recently, delta anastomosis for laparoscopic gas- it is technically difficult to dissect the lymph
troduodenostomy has become popular [19], and nodes at the splenic hilum, splenectomy must be
it would be difficult to secure enough space for considered. However, routine splenectomy for
duodenectomy with stapling after this type of completion total gastrectomy is not recom-
anastomosis because the previous staple line may mended, which is similar to the situation with
extend into the deep part of the duodenum). total gastrectomy for primary gastric cancer.
Previous gastrojejunostomy would have Note that spleen-preserving completion total gas-
been performed via an antecolic or retrocolic trectomy is not the same as lymph nodes-around-
route. When the previous anastomosis was the-splenic-hilum-preserving gastrectomy.
anterior to the transverse colon, if the cancer Figures 22.3 and 22.4 depict the extent of
does not invade the transverse colon, adhesions resection of the remnant stomach for remnant
between the stomach, jejunum, and transverse gastric cancer according to the type of previous
colon should be carefully dissected, and both anastomosis. The attached video clip summarizes
the afferent and efferent jejunum should be the procedure of open completion total gastrec-
divided and transected. Because remnant gas- tomy for remnant gastric cancer. This 71-year-
tric cancer can spread through the mesentery of old female patient underwent gastrectomy with
the jejunum (Fig. 22.2), the lymph nodes around gastrojejunostomy (loop, antecolic) for peptic
this mesentery should be removed as appropri- ulcer disease 35 years previously. The order of
ate. When the previous gastrojejunostomy was dissection can be changed according to the sur-
performed by the retrocolic route, the mesoco- geon’s preferences.
lon should be carefully divided without damag-
ing the vessels supplying the transverse colon.
If the cancer invades the transverse colon or
vessels of the transverse colon, segmental
resection of the transverse colon should be
considered.
After resection of the duodenum following gas-
troduodenostomy or resection of both the afferent
and efferent jejunum (and sometimes the trans-
verse colon as well) following gastrojejunostomy,
the remnant stomach is lifted upward and retracted
by a second assistant. There will be fibrotic adhe-
sions in the supra-pancreatic area if the reason for
previous surgery was cancer. Adhesions in the
supra-pancreatic area are divided, and any lymph
nodes at #12a, #8a, #7, #11p, or #9 remaining
from the previous surgery are dissected in the
same manner as for primary gastric cancer.
Splenic hilar lymph node dissection is one of Fig. 22.3 The extent of resection of remnant stomach
the most important parts of surgery for remnant after gastroduodenostomy for remnant gastric cancer
studies were significantly heterogeneous [5]. In

subgroup analyses, the prognosis of remnant
gastric cancer was similar in the early stages
(stage I/II according to the current TNM staging
system for primary gastric cancer) but poorer in
the advanced stages (stage III/IV), compared to
the prognosis after primary gastric cancer in the
upper third of the stomach. These findings can-
not be considered conclusive, and the reason for
these results is not yet clear. However, they
emphasize the importance of early detection of
remnant gastric cancer.
Fig. 22.4 The extent of resection of remnant stomach

after gastrojejunostomy for remnant gastric cancer Discussion
Remnant gastric cancers that we encounter clini-

reatment Outcomes of Remnant
T cally are mixtures of cancers that are similar to
Gastric Cancer primary gastric cancers, tumors caused by
chronic inflammation secondary to bile reflux,
Short-term outcomes of completion total gas- and other cancers caused by mechanisms that are
trectomy for remnant gastric cancer have been not yet well understood. These varying etiologies
reported by several studies. Postoperative mor- of remnant gastric cancer lead to heterogeneous
bidity rates have varied from 20% to 40%, and clinical responses to standard treatments, which
postoperative mortality rates have ranged from are generally based on our current knowledge
0% to 12.5% [20–24]. Of note, most of these regarding primary gastric cancer. In addition,
studies were conducted in East Asia, including remnant gastric cancer in recent years primarily
Korea, Japan, and China. The mortality was rela- involves cancer in the remnant stomach after dis-
tively high in a study from the West [24]; how- tal gastrectomy. Recently, function-preserving
ever, this report was too old (published in 1986) gastrectomy (e.g., proximal gastrectomy) has
to allow one to conclude that there is difference become popular to improve the quality of life of
in mortality after completion total gastrectomy patients with early-stage gastric cancer, and sur-
between the East and West. Overall, the morbid- vivors who have undergone this type of surgery
ity and mortality rates after completion total gas- are becoming more common. If we consider that
trectomy for remnant gastric cancer seem to be two-thirds of gastric cancers in Korea and Japan
generally similar to those reported after gastrec- occur in the lower third of the stomach, remnant
tomy for primary gastric cancer. Few studies gastric cancer after proximal gastrectomy for
have directly compared short-term outcomes gastric cancer will likely increase in frequency, as
after remnant gastric cancer surgery to those the lower third of the stomach remains after this
after primary gastric cancer surgery; in these surgery; consequently, the landscape of remnant
reports, outcomes were similar after both types gastric cancer will change again. However,
of surgery [21, 25]. whether this type of remnant gastric cancer would
Whether the prognosis of remnant gastric or would not be similar to primary gastric cancer
cancer is poorer than that of primary gastric can- is another unclear issue.
cer in the upper third of the stomach is contro- Even amidst the aforementioned complexity,
versial [3, 26–34]. A recent systematic review it is clear that radical surgery for remnant gastric
that conducted pooled analyses examining this cancer is the only treatment strategy available to
issue found that the outcomes among previous provide a true cure. Nevertheless, radical surgery
for remnant gastric cancer is technically difficult for cancers of the remnant stomach after distal gas-
trectomy. Gastrointest Endosc. 2008;67(2):359–63.
and challenging because of adhesions and fibro- https://doi.org/10.1016/j.gie.2007.10.021. Epub
sis due to the previous surgery and because of 2008/01/30. PubMed PMID: 18226704
alterations in the anatomy, including changes in 9. Hirasaki S, Kanzaki H, Matsubara M, Fujita K,
the lymphatic drainage. Therefore, surgeons Matsumura S, Suzuki S. Treatment of gastric remnant
cancer post distal gastrectomy by endoscopic submu-
should refine their surgical skills and experience cosal dissection using an insulation-tipped diathermic
to conquer the present and upcoming complex knife. World J Gastroenterol. 2008;14(16):2550–5.
disease, remnant gastric cancer. In addition, it Epub 2008/04/30. PubMed PMID: 18442204;
cannot be overemphasized that following onco- PubMed Central PMCID: PMCPMC2708368
10. Nonaka S, Oda I, Makazu M, Haruyama S, Abe S,
logic principles for cancer surgery is important Suzuki H, et al. Endoscopic submucosal dissection
for all operations involving remnant gastric for early gastric cancer in the remnant stomach after
cancer. gastrectomy. Gastrointest Endosc. 2013;78(1):63–72.
https://doi.org/10.1016/j.gie.2013.02.006. Epub
2013/04/10PubMed PMID: 23566640
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K. Surgical treatment of carcinoma of the gastric 23233273
Laparoscopic Surgery
23
Eishi Nagai and Masafumi Nakamura
Introduction Laparoscopic gastrectomy is now a widely

accepted treatment of primary early gastric
Recently, a declining incidence and mortal- cancer, because of its less invasive nature and
ity rate of gastric cancer has been observed in shorter recovery time [9, 10]. And laparoscopic
western countries, as well as Asian countries gastrectomy has gradually gained acceptance
[1]. However, gastric cancer is still considered for the treatment of advanced gastric cancer
as the third most common cause of cancer death [11]. On the other hand, laparoscopic total gas-
worldwide [2]. Despite the development of che- trectomy (LTG) for remnant gastric cancer is
motherapy, surgical resection still remains the still not a standard surgical treatment, because
only potentially curative treatment. Among the of the presence of severe adhesions of adja-
surgical procedures for gastric cancer (e.g., total cent organs and displacement of anatomical
gastrectomy, distal gastrectomy, and proximal structures due to initial surgery. There are very
gastrectomy), distal gastrectomy is the most few reports indicating the feasibility of laparo-
common procedure, which risks the occurrence scopic surgery for remnant gastric cancer, and
of a synchronous and/or metachronous gastric the number of cases reported was very small.
lesion. The clinical entity of remnant gastric The benefit of laparoscopic surgery for RGC is
cancer (RGC) was initially reported in 1922 still controversial; thus the indication for lapa-
[3]. According to the 2011 Japanese classifica- roscopic surgery should be based on surgeon or
tion of gastric cancer [4], RGC is defined as all institutional experience.
carcinomas arising in the remnant stomach fol-
lowing a gastrectomy, irrespective of the histol-
ogy of the primary lesion. The incidence of RGC Indications
has been reported as 2–3% in patients who have
undergone an initial gastrectomy [5–7] and was LTG is our procedure of choice for all cases of
reported to account for 1.8% of all gastric can- resectable remnant gastric cancer. We do not
cers in a large series [8]. hesitate to convert to an open procedure when
we cannot achieve good operative exposure due
to large tumor size or when we encounter unex-
E. Nagai (*) · M. Nakamura pected complications such as injury to major
Department of Surgery and Oncology, Graduate blood vessels or adjacent organs.
School of Medical Sciences, Kyushu University,
Fukuoka, Japan
e-mail: eishi@surg1.med.kyushu-u.ac.jp

https://doi.org/10.1007/978-3-662-45583-8_23
264 E. Nagai and M. Nakamura
Preoperative Evaluation sia, five trocars are inserted into the abdomen
with the patient in supine position with legs
Preoperative clinical factors, including clinical clas- slightly apart. The patient is then placed in
sification of tumor depth (cT), nodal involvement reverse Trendelenburg position as the operation
(cN), and distant metastasis (cM), are evaluated by commences. The primary surgeon stands on
upper gastrointestinal contrast studies, esophago- the patient’s right, the assistant on the patient’s
gastroduodenoscopy, endoscopic ultrasonography, left, and the camera operator stands between the
abdominal ultrasonography, and computed tomog- patient’s legs.
raphy (CT), consistent with the TNM staging sys-
tem. Three-dimensional CT is especially useful
to check for the presence of vascular anatomical Trocar Placement
variations in patients with RGC (Fig. 23.1a–c).
First, a 12-mm trocar is inserted at the umbilical
area using the open technique. If severe adhesions
perating Room Setup and Patient
O are expected, the left lateral abdomen would be
Position another option for entry of the first 12-mm trocar
in order to avoid injury. A 5-mm trocar is then
Our preference is to use a high-definition video inserted at the left hypochondriac region, and/
system with two monitors for use by the primary or a 12-mm trocar is inserted at the right lateral
and assistant surgeon. Under general anesthe- abdominal in an area without adhesions. These
a b Spleen
Remnant stomach
LGA
SpA
LGA
CHA
SMA CHA
LGV
c Pancreas
Spleen
GEA
GEV
Remnant stomach
PV
Pancreas
Fig. 23.1 Three-dimensional computed tomography (3D pancreatic area (b) and splenic hilum (c), the relation
CT). 3D CT demonstrates the LGA (left gastric artery), between artery and vein is also clearly seen (b). (LGV, left
SpA (splenic artery), CHA (common hepatic artery), and gastric vein; GEA, gastroepiploic artery; GEV, gastroepi-
SMA (superior mesenteric artery) clearly (a). In supra- ploic vein)
23 Laparoscopic Surgery 265
a b
2
4
3
5
1
Port Instrument
1: Hasson camera
2: 5mm left hand (operator)
3: 12mm right hand (operator)
4: 5mm right hand (assistant operator)
5: 12mm left hand (assistant operator)
6: Nathanson liver retractor
Fig. 23.2 Trocar positions in LTG for RGC (a) and schematic diagram of the trocar positions (b)
two or three trocars are then used for adhesioly- patients with initial surgery for gastric cancer. In
sis due to initial surgery. Subsequent trocars are our series, Billroth I reconstruction is associated
then inserted until there are five trocars in total with malignant initial disease. Here, we present
sequentially (Fig. 23.2), as shown in the figure. two types of surgical technique of laparoscopic
Liver retractor is inserted at the epigastric region gastrectomy for RGC: Billroth I reconstruction
(Fig. 23.2a, b). with malignant initial disease and Billroth II with
benign initial disease.
Surgical Procedures
atients Who Previously Underwent
P
The choice of surgical procedure is influenced by Billroth I Reconstruction
the type of reconstruction (Billroth I vs. Billroth
II) as well as disease entity (malignant vs. benign) After doing adhesiolysis between the abdominal
of the initial surgery. The lymphatic pathway wall and the intestines (Fig. 23.3), the greater
along the left gastric artery and left gastroepi- omentum is dissected along the gastrocolic liga-
ploic artery is preserved in patients with initial ment, avoiding injury of transverse colon and
surgery for benign disease. Lymph node dissec- mesocolon (Fig. 23.4a). The root of the first
tion at the supra-pancreatic area and along the short gastric artery is then exposed, clipped, and
left gastroepiploic artery is necessary for these cut (Fig. 23.4b). Short gastric arteries are subse-
patients. On the other hand, severe adhesions quently cut at their roots. Adhesions between the
at the supra-pancreatic area are expected in the posterior wall of the stomach and the pancreas
a b
Liver
Transverse colon
Spleen
Fig. 23.3 The transverse colon (a) is adherent to the previous surgical scar and the upper abdominal wall. Omentum
(b) is adherent to the dorsal surface of the liver
a b
First short gastric srtery
Transeverse colon
c d
Liver Stomach
Pancreas
Stomach
Fig. 23.4 The greater omentum is dissected along the transverse colon (a). The first short gastric artery is identified
(b). Adhesiolysis is performed around the gastric wall (c, d)
are then dissected (Fig. 23.4c, d). Because of the lymphadenectomy (Fig. 23.5c). When the adhesions
presence of severe adhesions between the infe- between the inferior surface of the left lateral seg-
rior surface of the left lateral segment of the liver ment of the liver and the remnant stomach are very
and the ventral surface of the remnant stomach, severe, the hepatic capsule is removed to avoid injury
this area is dissected carefully to avoid gastric to the gastric wall (Fig. 23.5d). The connective tis-
wall injury. After separating the gastric wall and sues along the common hepatic artery, celiac trunk,
duodenal wall from the pancreatic parenchyma, and splenic artery are then dissected, avoiding injury
the gastroduodenal anastomosis is completely of these vessels. If the root of the left gastric vessel
exposed (Fig. 23.5a). The duodenum is then was left intact during the initial surgery, meticulous
divided at just the aboral side of the anastomosis dissection is necessary to avoid inadvertent injury
with the use of a linear stapler (Fig. 23.5b). (Fig. 23.6a, b). After lymph node dissection along
The gastric remnant is retracted upwards to obtain the surface of the diaphragmatic crus, the esophagus
adequate operative view for gastric mobilization and is exposed (Fig. 23.6c) and is divided at a sufficient
a b
Duodenum
Liver
Pancreas
Duodenum
c d Liver
Liver
Stomach
Stomach
Fig. 23.5 The gastroduodenal anastomotic site is exposed resection of the hepatic capsule is performed to avoid injury
(a), and the duodenum is divided using a linear stapler (b). to the gastric wall (d)
The gastric remnant is retracted upwards (c). The combined
a b Stomach
CHA
Pancreas
Pancreas
c d
Esophagus
Stomach
Fig. 23.6 Meticulous dissection is necessary to avoid inadvertent injury (a, b). The esophagus is exposed entirely (c)
and divided using a liner stapler (d)
distance from the tumor (Fig. 23.6d). Finally, the cal incision, which is enlarged to approximately
lymphadenectomy of stations #2 and 4Sa is com- 3 cm. As described elsewhere [12], Roux-en-Y
pletely carried out. The resected specimen is placed reconstruction is performed using an isoperistal-
in a plastic bag and removed through the umbili- tic 40-cm Roux limb, divided at 30 cm from the
duodenojejunal junction. The Roux limb is pulled atients Who Previously Underwent
P
up via an antecolic route. Esophagojejunal anasto- Billroth II Reconstruction
mosis is performed using a linear stapler (Fig. 23.7).
Side-to-side jejunojejunostomy is performed at In our experience, previous Billroth II (B-II) recon-
40 cm from the esophagojejunostomy using a linear struction is usually via the retrocolic route. The gas-
stapler. The jejunojejunostomy and Petersen’s mes- trojejunal anastomosis is clearly identified behind
enteric defect are closed with continuous sutures. the mesocolon (Fig. 23.8). Caution must be exer-
a b
Jejunum
Esophagus
Jejunum
Fig. 23.7 Esophagojejunal anastomosis is performed using a liner stapler (a, b). The entry hole is closed by interrupted
sutures (c)
a b
Transeverse colon
Jejunum
Jejunum Pancreas
c d
Remnant stomach
Anastomosis
Remnant stomach
Jejunum
Jejunum
Anastomosis
Fig. 23.8 The gastrojejunal anastomosis is identified behind the mesocolon (a) and exposed (b–d)
cised so as not to cause injury in this area. The affer- its root. Subsequently, the gastrosplenic ligament is
ent and efferent limbs are sequentially divided at an dissected near the splenic hilum. The lymph nodes
appropriate distance from the gastrojejunal anasto- along the common hepatic artery, celiac trunk, and
mosis using a linear stapler (Fig. 23.9a). After dis- splenic artery are also dissected (Fig. 23.10b). After
section of adhesions between the abdominal wall dissection of the lesser omentum adjacent to the left
and the intestines (Fig. 23.9b), the stumps of the lateral segment of the liver, the esophagus is exposed
jejunum are pulled up to the oral side of the meso- and divided on the oral side of the esophagogastric
colon. The gastric remnant is retracted upwards to junction (Fig. 23.11a). In general, lymphadenectomy
get a good operative view for lymphadenectomy is performed according to the concept of D2 nodal
(Fig. 23.9c, d). The left gastric vessel is usually pre- dissection for primary gastric cancer (Fig. 23.11b,
served during initial surgery but is divided at its root c). If there is tumor invasion into the jejunal wall,
for lymphadenectomy of station #9 (Fig. 23.10a). the mesenteric lymph nodes close to the anastomo-
The greater omentum is dissected along the sis are also dissected. After removal of the resected
transverse colon for lymphadenectomy of station specimen, Roux-en-Y reconstruction is performed
#4Sb, and the left gastroepiploic artery is ligated at as described in the previous section (Fig 23.11d).
a b
Liver
Efferent limb
c d
Efferent limb
Stomach
Pancreas
Fig. 23.9 The afferent and efferent limbs are sequentially divided using a linear stapler (a). After adhesiolysis between
the intestines and the abdominal wall (b), the jejunum are pulled cephalad (c, d)
a b
Jejunum
LGA SpA
Fig. 23.10 Left gastric artery is identified and divided at its origin (a). Lymph node dissection is performed along the
splenic artery (b)
a b
Esophagus
Stump of LGA
CHA
CeA
c d
Esophagus
Spleen
Jejunum
SpV
SpA
Fig. 23.11 The esophagus is exposed and divided (a). mosis is performed using linear stapler (d). (SpV, splenic
The final view of completion of lymphadenectomy at the vein; CeA, celiac artery)
supra-pancreatic area (b, c). The esophagojejunal anasto-
Our Clinical Experience was 29.4 ± 16.9 years. The mean time from the
initial surgery to the second operation was signifi-
We have performed laparoscopic total remnant cantly longer in patients with initial benign dis-
gastrectomies for RGC on a total 14 patients ease (Group B) than patients with carcinoma at
from July 2005 to December 2013. In 2007, we initial surgery (Group C) (41.1 ± 10.0 years vs.
expanded our indication for laparoscopic gastrec- 13.7 ± 10.3 years; p = 0.00057) (Table 23.1). The
tomy to include advanced gastric cancer. Thus, mean operation time of the second operation in all
all patients were subsequent cases of LTG for 14 patients was 377.6 ± 85.4 min (380.0 ± 43.5 min
RGC after December 2006, except for one case in Group C and 375.9 ± 106.4 min in Group B;
performed in 2005. These patients underwent p = 0.9353). The mean estimated blood loss in
potentially curative surgery with appropriate all 14 patients was 121.9 ± 218 g (42.2 ± 29.5 g
lymphadenectomy. in Group C and 181.8 ± 271 g in Group B;
The said 14 patients comprised of 12 males p = 0.2194). The mean number of lymph nodes
and 2 females. The mean patient age was harvested in all 14 patients was 23.7 ± 11.2
67.1 ± 6.9 years. Initial gastrectomy was for gas- (14.8 ± 9.3 in Group C and 29.3 ± 8.3 in Group
tric cancer in six patients and peptic ulcer disease B; p = 0.0213) (Table 23.2). There were no con-
in eight. The initial surgery was laparoscopic in versions to open surgery and no mortalities; how-
3 patients and open in 11. As for reconstruction ever, there was one case of postoperative bleeding
during initial surgery, there were six Billroth I which necessitated reoperation.
(B-I) gastroduodenostomies, seven B-II gastro- The final pathologic stages are as follows: IA
jejunostomies, and one esophagogastrostomy. in ten patients (71.4%), IIA in three (21.4%), and
The mean interval between the initial surgery and IIIC in one (7.1%). The mean times to postopera-
completion total gastrectomy in all 14 patients tive liquid and food intake were 3.3 ± 3.1 days and
Table 23.1 Clinicopathologic characteristics of the 14 Table 23.3 Postoperative course of the 14 patients
patients who underwent gastrectomy from July 2005 to
Morbidities (Clavien-Dindo classification [13], III or
December 2013
more)
Number of patients 14 Anastomotic leakage None
Age (years) 67.1 ± 6.9 Pancreatic leakage None
Male/female 12/2 Postoperative hemorrhage 1 case
Body mass index (kg/m2) 20.9 ± 3.0 Total 1 case
Tumor size (cm) 3.6 ± 2.6 Mortalities None
Interval (years) 29.4 ± 16.6 Final pathologic stage
Type of initial gastrectomy IA/IIA/IIIC 10/3/1
Distal gastrectomy 13 Mean time to water intake (days) 3.4 ± 3.6
Proximal gastrectomy 1 Mean time to food intake (days) 5.1 ± 3.4
Etiology of initial gastrectomy Mean postoperative length of hospital 12.4 ± 5.1
Cancer 6 stay (days)
Peptic ulcer 8 Median follow-up period (months) 54.7
Type of reconstruction after initial gastrectomy (28.1 ~ 85.2)
B-I 6 One patient died of disease
B-II 7 Two patients died of diseases other than gastric
Esophagogastrostomy 1 cancer (malignant lymphoma, alcoholic liver
Preoperative comorbidities dysfunction)
Liver cirrhosis 1 Eleven patients still alive and without recurrence
Diabetes mellitus 2
Hypertension 2
Arrhythmia 2 Discussion
(Warfarin, low-dose aspirin)
Interstitial pneumonia 1
Despite developments of chemotherapy for gas-
Hyperthyroidism 1
Ischemic heart disease 1
tric cancer, the mainstay of treatment for RGC
Total 10 is still surgical resection, as with primary gastric
Synchronous malignancies cancer [14]. Surgical treatment is more difficult
Malignant lymphoma 1 in patients with RGC than in patients with pri-
mary gastric cancer, and laparoscopic surgery
for RGC requires more advanced skills. RGC
Table 23.2 Perioperative findings of the 14 patients is very rare and accounts for only 2–3% of gas-
Mean operative time (min) 377.6 ± 68.4 tric remnants [5–7]. This is why there are only
Mean blood loss (g) 121.9 ± 62.0 few reports describing LTG for RGC [15–23].
Mean number of retrieved lymph nodes 23.7 ± 11.2 Moreover, almost all literature include only a
Synchronous operations small number of cases and only deal with issues
Cholecystectomy 2
of technical feasibility and short-term outcomes.
There are two issues or potential problems that
5.1 ± 3.3 days, respectively. The mean length of must be addressed in order to successfully perform
postoperative hospital stay was 12.4 ± 5.1 days. total gastrectomy for RGC; one is gastric mobiliza-
The median follow-up time was 54.7 months tion and lymphadenectomy under severe adhesions
(range 28.1–85.2 months). Eleven out of the 14 and fortuitous anatomical variations, and another is
patients were still alive without relapse at the reconstruction. The difficulties of gastric mobiliza-
time of writing of this paper. Two patients died of tion and lymphadenectomy of a second operation
other diseases, and one died of metastatic disease are dependent on whether or not lymphadenec-
to the brain and multiple nodal metastases around tomy was performed during the first operation and
the aorta (Table 23.3). whether B-I or B-II reconstruction was performed
at the time. After B-I reconstruction at initial sur- age, nor conversion to open surgery, if we follow
gery, there are usually severe adhesions around the these precautions.
gastroduodenal anastomotic site and between the As for reconstruction, we prefer totally laparo-
dorsal surface of the left lateral segment of the liver scopic esophagojejunostomy using linear stapler,
and the anterior surface of the remnant gastric wall. termed “Inverted T anastomosis,” as described
If lymphadenectomy was performed for gastric previously [12]. In this series, we successfully
cancer during initial surgery, severe adhesions are performed Roux-en-Y reconstruction using liner
usually recognized at the operative site, especially stapler.
at the supra-pancreatic area.
In our series, five out of six patients with B-I
reconstruction underwent initial gastrectomy Short-Term Outcome
for malignancy, and all seven patients with B-II
reconstruction underwent initial gastrectomy for Although the number of patients is limited, there
peptic ulcer disease. Patients with B-I recon- have been several reports of the technical feasibil-
struction, therefore, mostly underwent lymph- ity of laparoscopic or laparoscopic-assisted total
adenectomy of the supra- and infra-pyloric and gastrectomy for RGC from high-volume centers
supra-pancreatic nodes, resulting in severe adhe- [16, 17, 20, 22]. Laparoscopic remnant total gas-
sion formation in those areas. trectomy is reported to be less invasive than open
There are some important technical points for surgery and with favorable short-term outcomes,
adhesiolysis: such as minimal operative blood loss [17, 20],
faster recovery of bowel movement [16, 17], and
1. Gastroduodenal anastomotic site short hospital stay [16, 17]. On the other hand,
Adhesiolysis should be performed care- some authors emphasize that immediate conver-
fully along the pancreatic surface to avoid sion to an open procedure should be considered if
injury to the pancreatic parenchyma and duo- intraoperative complications occur [20].
denal wall.
2. Supra-pancreatic area
After isolation of the common hepatic Long-Term Outcome
artery near the origin of the gastroduodenal
artery, dissection should be continued along The 5-year survival rate of LTG for RGC was
the common hepatic artery to the left gastric reported to be comparable with open completion
artery and splenic artery. total gastrectomy for RGC [16, 17]. However, the
3. Dorsal surface of the left lateral segment of number of patients enrolled was relatively small,
the liver and follow-up period was not enough to make
Dissection should be performed carefully a conclusion about survival rate. Further data
in this area to avoid injury to the gastric wall. collection and analysis of patients with RGC is
The hepatic capsule may be removed if neces- necessary.
sary, to avoid injury to the gastric wall.
4. Gastrojejunal anastomotic site
The jejunal and gastric walls are severely Conclusion
adherent to the mesocolon in patients with
B-II reconstruction, and it is important to LTG is considered to be technically acceptable
avoid injury to the colonic vessels during for the treatment of RGC with favorable short-
adhesiolysis. term outcomes; however, it is a very technically
complicated procedure even for surgeons skilled
It may be possible to successfully perform in laparoscopy. The indication for laparoscopic
LTG for RGC without perioperative massive surgery for RGC should be determined by the
bleeding, pancreatic leakage, anastomotic leak- surgeon’s and institution’s experience. Surgeons
should not hesitate to convert to an open proce- 12.

Nagai E, Ohuchida K, Nakata K, Miyasaka
Y, Maeyama R, Toma H, Shimizu S, Tanaka
dure when unexpected intraoperative complica- M. Feasibility and safety of intracorporeal esoph-
tions occur. agojejunostomy after laparoscopic total gastrectomy:
inverted T-shaped anastomosis using linear staplers.
Conflicts of Interest The authors declare no conflicts of Surgery. 2013;153:732–8.
interest. 13. Dindo D, Demartines N, Clavien PA. Classification of
surgical complications: a new proposal with evalua-
tion in a cohort of 6336 patients and results of a sur-
vey. Ann Surg. 2004;240:205–13.
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Part XIII
Peritonectomy and HIPEC
Prevention and Treatment
of Peritoneal Metastases 24
from Gastric Cancer
Mei Li M. Kwong, Chukwuemeka Ihemelandu,
and Paul H. Sugarbaker
Introduction ses, peritoneal mesothelioma, and a limited extent

of peritoneal metastases from colorectal carcino-
Gastric cancer is a common and deadly disease. It matosis [9–11]. Gastric cancer with peritoneal
is the fourth most commonly diagnosed cancer in metastases is aggressive, and current treatment
the world with a 5-year survival rate of 25% [1, 2]. efficacy remains controversial. The following is
In follow-up, almost half of gastric cancer patients an attempt to summarize the role and efficacy of
will develop peritoneal spread which results in a NACS, NIPS, CRS, and HIPEC and/or EPIC as a
less than 5% 5-year survival rate [3–5]. Peritoneal treatment for peritoneal metastases of gastric can-
metastases are a common finding in primary gas- cer (Fig. 24.1).
tric cancer found in 5–20% of patients undergoing
gastrectomy [6]. The peritoneum is also the most
common location of first recurrence observed in Perioperative Intraperitoneal
about half of the patients [7]. Standard of care for Chemotherapy as an Adjuvant
treatment of primary or recurrence of gastric can- Treatment
cer involves surgery, intravenous chemotherapy,
and radiotherapy. However, specific treatments Local and intra-abdominal tumors are usually
for peritoneal metastases such as neoadjuvant sys- the most common and only sites of first recur-
temic chemotherapy (NAC), neoadjuvant intra- rence in gastric cancer after curative resection
peritoneal and systemic chemotherapy (NIPS), [12–14]. This is true regardless of whether they
cytoreductive surgery (CRS), and perioperative underwent neoadjuvant chemotherapy or postop-
chemotherapy which may include hyperthermic erative adjuvant treatment compared to surgical
intraperitoneal chemotherapy (HIPEC) and/or resection alone [15]. The peritoneal surfaces and
early postoperative intraperitoneal chemotherapy liver remain the major sites of recurrence. Less
(EPIC) are currently being explored [8]. CRS and localized recurrence is observed when extended
HIPEC and/or EPIC are already considered stan- lymphadenectomy as compared to limited sur-
dard of care for appendiceal peritoneal metasta- gery is used [16–18].
Although confined to the abdomen, peritoneal
seeding has deadly consequences [19–22]. Sources
M. L. M. Kwong · C. Ihemelandu
P. H. Sugarbaker (*) of recurrence after curative resection are (1) spon-
Center for Gastrointestinal Malignancies, taneous dissemination from the primary tumor and
Program in Peritoneal Surface Oncology, Medstar (2) traumatic dissemination of cancer cells during
Washington Hospital Center, Washington, DC, USA the surgical procedure. If the serosal surface is
e-mail: paul.sugarbaker@medstar.net

https://doi.org/10.1007/978-3-662-45583-8_24
278 M. L. M. Kwong et al.
Suspected gastric cancer
Initial workup
EGD
CT
± EUS
EARLY ADVANCED METASTATIC

Clinical stage T1/T2, N0, M0 Clinical stage T3/T4, N1-3, M0 Tany,Nany,M1
Standard gastrectomy
with/without standard Diagnostic Metastasis other
adjuvant therapy Laparoscopy than peritoneum
No peritoneal disease Limited peritoneal disease

Established peritoneal
and negative (PCI <10) or positive
disease (PCI >10)
peritoneal washing peritoneal washing
Gastrectomy Gastrectomy Neoadjuvant

with adjuvant/ with systemic
prophylactic cytoreduction chemotherapy or
HIPEC and HIPEC NIPS
No progression or
evidence of response Progression
Gastrectomy
with Palliative care
cytoreduction
and HIPEC
Fig. 24.1 An algorithm for treatment of gastric cancer with and without peritoneal metastases
24 Prevention and Treatment of Peritoneal Metastases from Gastric Cancer 279
Tumor cell entrapment hypothesis

- resected gastric cancer -
Serosal invasion Lymphatic invasion Venous invasion

+ + +
Surgical trauma Lymphatic transection Hemorrhage
Free intraperitoneal tumor emboli
* Fibrin entrapment
Inflammatory cell infiltration
Growth factor stimulation
Cancer implant
* Occurs at resection site, on abraided bowel surface, and beneath abdominal incision.
Fig. 24.2 The tumor cell entrapment hypothesis suggests three mechanisms for microscopic residual cancer cells in
patients having an R-0 gastrectomy. (From Sethna et al. with permission [24])
involved with tumor, then spontaneous dissemina- for wound healing, may also promote tumor pro-
tion is more common, and patients are frequently gression. The tumor cell entrapment hypothesis
found to have viable intraperitoneal cancer cells explains part of the pathogenesis of local and intra-
(positive cytology) [19, 21–23]. Tumor cells can abdominal recurrence and theoretically shows how
also seed the intra-abdominal cavity during surgery adjuvant perioperative intraperitoneal chemother-
according to the tumor cell entrapment hypothesis apy can be beneficial.
(Fig. 24.2) [24]. During surgery there is disrup-
tion of lymphatics, close margins of resection, and
tumor-contaminated blood spillage. Iatrogenically Rationale of Perioperative Timing
disseminated tumor cells adhere spontaneously of Intraperitoneal Chemotherapy
within minutes, and vascularization is facilitated
by fibrin entrapment and the wound healing pro- Intraperitoneal chemotherapy should be adminis-
cess. Cytokines, such as growth factors important tered perioperatively in order to access the tumor
cells prior to entrapment within fibrin and con- to be used in the meta-analysis [27]. There was
version into cancer progression within adhesive a survival benefit associated with HIPEC (haz-
scar tissue. If chemotherapy is given after the ard ration [HR] = 0.060; 95% CI = 0.43–0.83;
formation of adhesive scars, then it will have p = 0.002) or HIPEC with EPIC (HR = 0.45;
uneven distribution and lack of uniform cytotox- 95% CI = 0.29–0.68; p = 0.0002). There was a
icity for viable cancer cells. Kinetics of residual marginal effect with normothermic intraoperative
tumor cells change within 24 h of resection, and intraperitoneal chemotherapy (NIPEC) but no
therefore a delay in local-regional treatments will significant improvement in survival with EPIC
decrease the cytotoxic effectiveness [24]. alone or delayed postoperative intraperitoneal
chemotherapy (Fig. 24.3) [27].
Although there may be a survival benefit,
Perioperative Chemotherapy intraperitoneal chemotherapy can increase mor-
with D2 Gastrectomy bidities. Even the most experienced peritoneal
surface oncology centers that remove all macro-
Perioperative intraoperative chemotherapy can limit scopic disease and then administer intraperito-
progression of peritoneal dissemination after cura- neal chemotherapy have a higher morbidity and
tive surgery; however, it cannot treat residual dis- cost [29–31]. Yan et al. discussed an association
ease at systemic sites or metastases within lymph of improved overall survival with HIPEC with
nodes. Therefore, a complete D2 lymphadenec- or without EPIC after resection of advanced
tomy is essential. Simple diffusion of chemotherapy gastric primary cancer; however, with EPIC
only penetrates to 1 or 2 mm [25]. Local-regional there was an associated greater risk for intra-
chemotherapy is not effective in lymph nodes. Also, abdominal abscess (RR = 2.37; 95% CI = 1.32–
macroscopic peritoneal nodules larger than 1 or 4.26; p = 0.003) and neutropenia (RR = 4.33;
2 mm have ineffective drug delivery, and visible 95% CI = 1.49–12.61; p = 0.007) [27]. Yu et al.
nodules should be removed prior to treatment. also saw an increased risk of intra-abdominal
abscess with the use of intraperitoneal chemo-
therapy, especially in the early postoperative
iterature Regarding Perioperative
L setting, compared to the control patients [32].
Intraperitoneal Chemotherapy Theoretically, intraperitoneal chemotherapy
for Advanced T-Stage Primary Gastric should have less systemic toxicity as compared
Cancer to systemic chemotherapy. However, the meta-
analysis demonstrated a significantly higher risk
There have been randomized and non-randomized of neutropenia in the intraperitoneal chemother-
trials regarding perioperative intraperitoneal apy arm [27].
chemotherapy as compared to surgery alone for Most of the trials studied by Yan were com-
resectable primary gastric cancer with and without pleted in Asia, and it is unknown if they can be
peritoneal spread. Sugarbaker, Yu, and Yonemura compared with gastric cancer in Western coun-
published a meta-analysis in 2003 of articles pub- tries. It is possible that perioperative chemo-
lished in English [7]. Xu et al. published a similar therapy may be better in Western patients with
study in 2004 [26]. Yan et al. published a summary more advanced disease and less lymph nodes dis-
of randomized control trials concerning adjuvant sected. Data does suggest a role of HIPEC with
intraperitoneal chemotherapy for resectable gas- or without EPIC to improve overall survival for
tric cancer in 2007 [27]. Feingold et al. published advanced primary gastric cancer with advanced
the most recent summary of non-randomized and T-stage and no peritoneal metastases. A prospec-
randomized studies in English of CRS and HIPEC tive multi- institutional randomized controlled
and/or EPIC in gastric cancer [28]. trial (GASTRICHIP) with well-defined eligibil-
Yan et al. selected 10 of 13 randomized con- ity criteria, interventions, and end points is cur-
trolled trials that were judged to be of fair quality rently in progress in France [33].
Companson: 01 Adjuvant lntraperitoneal chemotherapy versus control

Outcome: 02 Local-regional recurrence
Study I.P. chemo Control RR (random) Weight RR (random)
or sub-category n/N n/N 95% CI % 95% CI Year
01 Hyperthermic intraoperative i.p. chemo

Yonemura 6/48 7/47 100.00 0.84 (0.30, 2.31) 2001
Subtotal (95% Cl) 48 47 100.00 0.84 (0.30, 2.31)
Total events: 6 (I.P. chemo), 7 (Control)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
02 Normothermic intraoperative i.p. chemo
Yonemura 9/44 7/47 27.69 1.37 (0.56, 3.37) 2001
Miyashiro 19/135 23/133 55.34 0.81 (0.47, 1.42) 2005
6/46 4/45 16.97 1.47 (0.44, 4.86) 1998
Rosen 225 225 100.00 1.00 (0.64, 1.55)
Subtotal (95% Cl)
2 2
Test for heterogeneity: Chi = 1.40, df = 2 (P = 0.50), l = 0%
03 Early postoperative i.p. chemo 100.00 0.51 (0.31, 0.84) 2001
Yu 19/125 37/125 100.00 0.51 (0.31, 0.84)
Subtotal (95% Cl) 125 125
Test for heterogeneity: not applicable
0.1 0.2 0.5 1 2 5 10

Favours i.p. chemo Favours control
Fig. 24.3 Forest plot of the relative risk (RR) of the fidence interval (CI). On each line, the numbers of events,
local-regional recurrence with adjuvant intraperitoneal expressed as a fraction of the total number randomized,
(IP) chemotherapy versus controls for advanced gastric are shown for both treatment groups. For each subgroup
cancer. The studies were analyzed according to the regi- the sum of the statistics, along with the summary RR, is
mens of intraperitoneal chemotherapy used. The estimate represented by the middle of the solid diamonds. (From
of the RR of each individual trial corresponds to the mid- Yan et al. with permission [27])
dle of the squares, and horizontal line gives the 95% con-
astric Cancer with Peritoneal

G 31, 36–40]. Glehen et al. studied 159 patients with
Metastases a median follow-up of 20.4 months. There was
a median overall survival of 9.2 months, but the
In the past, gastric cancer with peritoneal dissemina- 5-year survival rate was 13% [30]. Although CRS
tion was thought to be uniformly lethal. Prospective and HIPEC is less effective for gastric cancer than
studies had a median survival of less than 6 months results from other peritoneal surface malignan-
[34]. Although response rates to systemic chemo- cies, CRS and HIPEC results in an improvement
therapy regimens have improved, there has not been for gastric cancer versus surgery alone. Gastric
a corresponding improvement in survival rates [35]. cancer patient with peritoneal metastases treated
There may be some increased effectiveness with with CRS and HIPEC were the only patients that
palliative gastric cancer resections in patients with reported a 5-year survival [37, 38, 41].
peritoneal metastases; however there are no long- These studies may underestimate the poten-
term improvements in survival. tial of CRS with HIPEC, as there was no
strict patient selection criteria utilized. The
extent of peritoneal metastases as measured by
RS and HIPEC as an Effective
C Sugarbaker’s peritoneal cancer index (PCI) sig-
Strategy nificantly influences survival and is correlated
with the completeness of cytoreduction [42].
There is potential for long-term survival for patients Cytoreductive surgery must reduce the residual
with gastric cancer and peritoneal metastases as a disease to a minimum for intraperitoneal chemo-
result of cytoreductive surgery and HIPEC. There therapy to be effective (due to minimal chemo-
are single-institution data and phase II studies that therapy penetration). Glehen et al. demonstrated
support use of this strategy (Table 24.1) [20, 29– a 5-year survival of 23% with median survival
Table 24.1 Reports of patients with gastric peritoneal metastases treated by cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy
Anticancer agent used Median survival 1-year 3-year 5-year
Reference Year N during HIPEC (months) survival (%) survival (%) survival (%)
Fujimoto et al. [20] 1997 48 MMC 16 54 41 31
Hirose et al. [36] 1999 17 MMC-cisplatin- 11 44 – –
etoposide
Rossi et al. [37] 2003 13 MMC-cisplatin 15 – – –
Glehen et al. [38] 2004 49 MMC 10.3 48 – 16
CC-0 or CC-1 25 21.3 74.8 29.4
Hall et al. [31] 2004 34 MMC – – – –
CC-0 11.2 45
Yonemura et al. [29] 2005 107 MMC-cisplatin- 11.5 – – 6.5
CC-0 47 etoposide 15.5 – – 27
Scaringi et al. [39] 2008 32 MMC-cisplatin 6.6 – – –
CC-0 8 15
Glehen et al. [30] 2010 159 Various 9.2 43 18 13
CC-0 85 15 61 30 23
Adapted from Glehen et al. with permission [40]
CC-0 complete macroscopic cytoreduction; CC-1 residual tumor nodules <5 mm; MMC mitomycin C; N number of
patients
Fig. 24.4 Overall survival 1.0

of 159 patients treated by Completeness of cytoreduction
cytoreductive surgery and 0.9
hyperthermic 0.8
0.mm
intraperitoneal
<2.5 mm
chemotherapy according to 0.7
Survival probability
completeness of ≥2.5 mm
cytoreductive surgery. 0.6
(From Glehen et al. with
0.5
permission [30])
0.4
0.3
0.2
0.1
0.0
0 1 2 3 4 5
Years
of 15 months in patients after a complete mac- have morbidity and therefore should not be used
roscopic resection (Fig. 24.4) [30]. Yonemura for patients with bulky residual disease, although
et al. d emonstrated a similar 27% 5-year sur- palliative use for ascites may always be consid-
vival rate and 15.5 months median survival [29]. ered [43, 44].
Hall et al. reported a 11.2-month overall survival Unfortunately, even if completely cytore-
after CRS and HIPEC with mitomycin C; how- duced, HIPEC is less useful for patients with
ever there was no patient alive after 2 years who high burden of peritoneal metastatic disease.
had residual disease at CRS [31]. CRS with a Glehen et al. showed that one of the strongest
minimum residual disease burden is essential for prognostic factors was extent of carcinomatosis
effective HIPEC. HIPEC used with macroscopic [30]. When the PCI was greater than 12, despite a
disease does not improve survival. HIPEC can complete cytoreduction, there were no survivors
Fig. 24.5 Overall survival 1.0

of 159 patients treated by Peritoneal cancer index
complete cytoreductive 0.9
surgery according to extent 0-6
0.8
of peritoneal metastases
assessed by the peritoneal 7-12
0.7
cancer index. (From
Survival probability
13-19
Glehen et al. with 0.6
permission [30]) >19
0.5
0.4
0.3
0.2
0.1
0.0
0 1 2 3 4 5
Years
greater than 3 years (Fig. 24.5) [30]. Fujimoto Table 24.2 Selection of gastric cancer patients with peri-
et al. reported 40–50% 5-year survival for lim- toneal metastases for gastrectomy, peritonectomy, and
ited peritoneal metastases but only an 18% 1-year perioperative chemotherapy
survival for patients with extensive peritoneal Clinical features
metastases [20]. Cytoreduction with HIPEC in Young age (<65 years) Lymph nodes,
negative or limited
gastric cancer patients with a PCI score greater extent
than 12 may be contraindicated. Low operative risk (no other No liver metastases
Yang et al. have provided the first and only diseases)
phase III study regarding CRS and HIPEC in Patient symptoms present Peritoneal cancer
gastric cancer presenting with peritoneal metas- index <12
tases. They used cisplatin (120 mg) and mito- Pain Obstruction Expect complete
Bleeding Ascites clearing of the
mycin C (30 mg) in 6000 ml of normal saline Perforation primary cancer
at 43C for 60–90 min. Median follow-up was Adapted from Glehen et al. with permission [40]
32 months, and 97.1% (33 of 34) of patients
after CRS died, but 85.3% (29 of 34) of CRS
and HIPEC patients died. Median survival was ole of Laparoscopy for Patient
R
6.5 months (95% CI 4.8–8.2 months) after CRS Selection
and 11 months (95% CI; 10.0–11.9 months) in
CRS and HIPEC group (p = 0.046) [43]. There Laparoscopy has three important roles in the
was similar morbidity between the groups. The management of gastric cancer. First, laparos-
independent predictors in a multivariate analy- copy may select and exclude patients with intra-
sis for improved survival were synchronous abdominal metastases who would not benefit
peritoneal metastases, CC 0–1 cytoreduction, from an aggressive and complex procedure that
more than six cycles of systemic chemotherapy, is unlikely to improve their survival. If a pri-
and no adverse events. Glehen et al. suggested mary gastric cancer patient is found to perito-
that HIPEC should be reserved for patients with neal metastases or would otherwise not be able
limited peritoneal carcinomatosis [30]. Also, to be completely cytoreduced, HIPEC would not
the prognostic factors analyzed by Yang et al. be warranted, and the morbidity of laparotomy
suggest that it should be restricted to a limited could be avoided [45, 46]. Laparoscopy is use-
patient population (Table 24.2) [43]. ful to show that patients have clinically absent
peritoneal metastases. Recent randomized trials Patients Treated

suggest that neoadjuvant chemotherapy should
be used for gastric cancer patients free of perito- In this phase II study, Yonemura and cowork-
neal disease [47]. ers treated patients with peritoneal metastases
Second, laparoscopy performed in primary identified by laparoscopy, laparotomy biopsy,
gastric cancer patients can select those patients or cytology from ascites. To qualify for NIPS,
with a low volume (P1 or PCI < 10) of perito- patients must have (1) proven peritoneal seeding
neal metastases for CRS with gastrectomy and by histology or cytology; (2) no hematogenous or
HIPEC. In these patients with minimal disease remote lymph node metastases; (3) be less than
who can undergo complete cytoreduction, a or equal to 65 years; (4) have an Eastern Clinical
5-year survival of 25% is expected. Oncology Group score of 2 or less; (5) adequate
A third use of laparoscopy is serial exams in bone marrow, liver, cardiac, and renal function;
patients with a greater extent of peritoneal metas- and (6) no other severe medical comorbidities or
tases. If the peritoneal metastases respond on synchronous malignancies.
repeated laparoscopic examination, CRS with Qualifying patients had a peritoneal port sys-
gastrectomy and HIPEC is considered a treatment tem (Bard Port, C.R. Bard Inc., USA) inserted
option. The use of laparoscopy with NIPS (neo- into the abdominal cavity under local anesthe-
adjuvant intraperitoneal and systemic chemother- sia with the tip placed within the cul-de-sac of
apy) will be described in the following sections. Douglas.
Neoadjuvant Intraperitoneal Chemotherapy Regimen

and Systemic Chemotherapy (NIPS)
Prior to administration of chemotherapy, 500 ml
If patients have peritoneal dissemination, the of saline was instilled into the peritoneal cavity,
effects of systemic chemotherapy are disappoint- and fluid was removed for cytology. Docetaxel
ing. Preusser et al. demonstrated that an aggres- 40 mg and carboplatin 150 mg were used for intra-
sive systemic chemotherapy regimen can have a peritoneal chemotherapy in addition to 1000 ml
50% response rate in advanced gastric cancer; of saline over 30 min. Methotrexate 100 mg/m2
however this response is less robust in patients and 5-fluorouracil 600 mg/m2 in 100 ml of saline
with peritoneal metastases [48]. Ajani et al. gave over 15 min were administered intravenously the
neoadjuvant chemotherapy, and the failure of same day. This regimen was administered weekly
the regimen was most common with peritoneal for two cycles. After the second cycle, peritoneal
metastases [49]. Systemic chemotherapy alone wash cytology was again performed. If cytology
for primary gastric cancer with peritoneal metas- was positive, neoadjuvant chemotherapy was
tases is not satisfactory. continued for two more cycles. Peritoneal cytol-
Neoadjuvant chemotherapy for gastric cancer ogy testing is repeating after the fourth cycle, and
can be modified to address peritoneal seeding by the process is continued as long as cytology is
combining systemic and intraperitoneal chemo- positive.
therapy. Chemotherapy may gain access to small If cytology became negative, upper endoscopy,
peritoneal cancer nodules via the systemic cir- repeat laparoscopy, and CT scan were performed.
culation and by diffusion from a chemotherapy If tumors showed no demonstrable change, then
solution within the peritoneal cavity. Yonemura two more cycles were administered. The number
and coworkers proposed a prospective phase II of NIPS chemotherapy cycles was controlled by
study to identify the efficacy and assess toxici- the effect on the primary cancer and peritoneal
ties in patients with gastric cancer with peritoneal cytology. Complete cytoreduction was required
metastases [50]. The following summarizes this for prolonged survival in prior studies that exam-
study. ined peritoneal metastases. Therefore, the goal of
the NIPS regimen was complete or near complete If peritoneal metastases on small bowel surfaces
response of metastases on small bowel surfaces were eliminated by NIPS, there was a possibility
[36, 51–53]. that gastrectomy and parietal peritonectomy could
The Japanese General Rules for Gastric achieve a complete cytoreduction. Sugarbaker and
Cancer Study was used to determine the perito- Yonemura reported the use of peritonectomy for
neal stage as (P1) peritoneal metastases in the peritoneal metastases to cytoreduce the peritoneal
upper abdomen above the transverse colon, (P2) surface and facilitate total resection of the primary
several countable metastases in the peritoneal gastric cancer [55, 56]. Peritonectomies required
cavity, and (P3) numerous metastases in the peri- for gastric cancer have been described [7]. The epi-
toneal cavity [54]. Distribution and size of perigastric peritonectomy includes any prior midline
toneal metastases were recorded at laparoscopy abdominal scar with the preperitoneal epigastric
and at surgery. Tumor location, size, and number fat pad, xiphoid process, and round and falciform
were evaluated before and after NIPS to deter- ligaments (Fig. 24.6). The anterolateral perito-
mine effects of neoadjuvant chemotherapy. nectomy removes the greater omentum with the
anterior layer of peritoneum from the transverse
mesocolon, peritoneum of the right paracolic gut-
urgery for Gastric Cancer
S ter along the appendix, and the peritoneum in the
with Peritoneal Metastases After right subhepatic space. Sometimes the peritoneum
Neoadjuvant Intraperitoneal of the left paracolic gutter must also be removed
and Systemic Chemotherapy (NIPS) (Fig. 24.7). The subphrenic peritonectomy takes
the peritoneal surfaces from the medial half of
Gastrectomy and peritonectomy were performed if the right and left hemidiaphragm as well as the
peritoneal wash cytology became negative or there left triangular ligament (Fig. 24.8). The omental
was a partial response to neoadjuvant chemother- bursa peritonectomy starts with cholecystectomy
apy. Patients with progressive disease or who con- and then removes the peritoneal covering of the
tinue to have positive cytology despite 4–6 cycles porta hepatis, hepatoduodenal ligament, and floor
of NIPS were not candidates for surgery. of the omental bursa including the peritoneum
Xyphoid process
Falciform ligament
Round ligament
New incision
Scar from old incision
Extent of peritonectomy
Fig. 24.6 Epigastric peritonectomy

overlying the pancreas (Fig. 24.9). If tumor was esults After Neoadjuvant
R
within the cul-de-sac, a pelvic peritonectomy was Intraperitoneal and Systemic
also performed, and electroevaporative surgery Chemotherapy (NIPS)
strips the peritoneum from the pouch of Douglas
(Fig. 24.10). Sometimes, the pelvic peritonec- Table 24.3 shows the clinical characteristics of the
tomy will necessitate removal of the rectosigmoid 194 patients. Average age was 51.5 years. One hun-
colon. Visceral resections and parietal peritonecto- dred four patients had primary gastric cancer, and
mies were performed to completely remove gross 90 patients had recurrent peritoneal metastases.
disease. Peritoneal fluid cytology was positive in 137 patients
Any complications related to chemotherapy and negative in 57 patients prior to NIPS. There was
and peritonectomy were prospectively collected complete resolution of peritoneal metastases after
and verified retrospectively. NIPS chemotherapy in 24.3% of patients. After
induction treatment, 152 patients underwent surgery.
Operative interventions, such as total gastrec-
Greater omentum
tomy (n = 94), subtotal gastrectomy (n = 17), and
small bowel resection (n = 44), are displayed in
Table 24.3. Left and right subdiaphragmatic peri-
Pancreas
tonectomy and pelvic peritonectomy were com-
pleted in 44, 31, and 61 patients, respectively.
Complete cytoreduction was achieved in 103
(67.7%) of patients.
Figure 24.11 demonstrates overall sur-
vival of the 194 patients. Median survival
was 15.8 months for the 152 patients who had
Left paracolic
sulcus received surgical intervention versus 7.5 months
for patients who did not have an opera-
tion. Median survival of the 194 patients was
14.4 months. One-year survival was 54% for
all patients. There was a significant survival dif-
ference (p = 0.03) between patients who under-
went operative intervention versus those who
Fig. 24.7 Anterolateral peritonectomy did not. There was a higher median survival of
Fig. 24.8 Subphrenic Attachment of

peritonectomy falciform ligament Attachment of liver
segments 1 and 2
Esophageal hiatus
Attachment of spleen
Fig. 24.9 Omental
Hepatogastric
bursa peritonectomy
ligament
Duodenum
Omental bursa
Gall bladder
Pancreas
Fig. 24.10 Pelvic
peritonectomy
Line of transection
of peritoneum
Cul de sac
of Douglas
18 months for patients who received a complete pression and diarrhea. Bone marrow suppression
cytoreduction. There was no difference between occurred after three courses in three patients,
primary and recurrent disease after cytoreduc- after five courses in three patients, and after six
tion with a median survival of 17.6 months ver- courses in four patients. Less common adverse
sus 14.1 months, respectively (p = 0.39). events were port site infection (n = 2) and renal
failure (n = 1). After cytoreduction with perito-
nectomy, 18 patients (14%) developed compli-
dverse Events from Neoadjuvant
A cations. Two patients had pneumonia and one
Intraperitoneal and Systemic patient developed renal failure. Six patients had
Chemotherapy (NIPS) an anastomotic leak, and two patients had an
and Cytoreductive Surgery abdominal abscess. The overall operative mor-
tality rate was 1.5% (2 of 133 patients). These
The most common chemotherapy-related grade patients died of multiple organ failure from sep-
3 or 4 adverse events were bone marrow sup- sis from abdominal abscess [40].
Table 24.3 Clinicopathological characteristics of 194 linical Data Supporting Complete

C
gastric cancer patients with peritoneal carcinomatosis
Cytoreduction as the Goal
Variables No. of patients in Management of Gastric Cancer
Age, years (range) 51.5 ± 12.6
Patients with Peritoneal Seeding
Male/female ratio 89/105
Histological diagnosis
Well/intermediately differentiated 7 Complete cytoreduction is crucial in the surgical
adenocarcinoma treatment for carcinomatosis from appendiceal
Poorly/undifferentiated 187 and colon cancer. Five-year survival for complete
adenocarcinoma cytoreduction was 54% versus 15% for incom-
Organ resections
plete cytoreduction as reported by Culliford
Right diaphragmatic copula 31
Left diaphragmatic copula 44
et al. [57]. Glehen et al. also reported a median
Total gastrectomy 94 survival difference of 32 months and 8.4 months
Subtotal gastrectomy 17 for patients with macroscopic complete resection
Pelvic peritoneum 61 versus incomplete cytoreduction, respectively
Colectomy 68 [58]. This has shown that complete cytoreduction
Small bowel resection 44 had better survival rates in gastric cancer [59,
Cytology before BIPS
60]. There is a difference in biological aggres-
Negative 57
Positive 137
siveness between colon and gastric cancers;
Cytology after BIPS however, macroscopic complete cytoreduction is
Negative 152 necessary for long-term survival with peritoneal
Positive 42 metastatic disease in these diseases. If there is P3
Pathological response to BIPS dissemination, complete cytoreduction should
Grade 0 63 not be attempted. NIPS was shown to diminish
Grade 1 38
disease on intestinal surface and facilitate com-
Grade 2 24
plete cytoreduction.
Grade 3 27
From Canbay et al. with permission [60]
alliative Benefits to All Patients

P
with Cancerous Ascites
Survival (%)
100
There was improvement in symptoms for the
80
78 patients who had ascites [40]. These benefits
occurred in patients with primary gastric can-
cer and also in patients with recurrent disease.
60
Cunliffe et al. hypothesized that peritoneal metas-
tases are nourished via ascites as well as blood
40
supply. Therefore, peritoneal implants should be
treated via a combined intraperitoneal and intra-
20
venous approach [61]. Intravenous chemotherapy
has minimal effects on peritoneal metastases, and
0 2 4 6 8 10 intraperitoneal chemotherapy alone has a less
Time than 30% effect on ascites [31, 32, 48, 49]. The
Fig. 24.11 Overall survival in 194 gastric cancer patients bidirectional chemotherapy (intraperitoneal and
with peritoneal carcinomatosis. (From Canbay et al. with intravenous) has a response rate of 57% with
permission [60]) 100% resolution of ascites [40].
hemotherapy Agents Selected

C 8. Glehen O, Mohamed F, Gilly FN. Peritoneal carcino-
matosis from digestive tract cancer: new management
for Neoadjuvant Intraperitoneal by cytoreductive surgery and intraperitoneal chemo-
and Systemic Chemotherapy (NIPS) hyperthermia. Lancet Oncol. 2004;5(4):219–28.
9. Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal
Different chemotherapy regimens have been used carcinomatosis treated with surgery and perioperative
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for NIPS such as docetaxel, cisplatin, and pacli- of 523 patients from a multicentric French study. J Clin
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Part XIV
Palliative Surgery (Including Resection,
Bypass and Stent)
Palliative Therapy for Gastric
Cancer 25
K. Ji, P. Yuan, Z. D. Bu, and J. F. Ji
The past decades have witnessed the constant pain, improve their quality of life, and prolong
decrease in the morbidity and mortality of gas- survival by alleviating symptoms. The palliative
tric cancer; however, as the fifth most common care for advanced gastric carcinoma can be either
malignant tumor, gastric cancer is still the third local therapy or systemic therapy. Cytotoxic
most common cause of cancer death [1]. There chemotherapy has been applied as the preferred
were about one million new cases and 723,000 systemic treatment in patients with metastatic
deaths from gastric cancer in 2012, among which gastric cancer; however, it often cannot alleviate
Chinese patients accounted for about 50% [1]. the local symptoms (e.g., nausea, pain, gastro-
Due to its insidious onset and the lack of speci- intestinal obstruction, and bleeding) in patients
ficity of signs and symptoms, over 80% of gastric with locally advanced tumors or with distant
cancer cases are in an advanced stage for being metastasis. For these patients, multidisciplinary
diagnosed. The 5-year survival rate is low. Even management using local treatments including
in patients who have received radical resection, endoscopy, surgery, and radiotherapy should be
the risk of distal metastasis or local recurrence used. In this chapter, we will describe the pallia-
can still be high [1]. The vast majority of patients tive care in patients with locally advanced unre-
with gastric cancer still need palliative care after sectable gastric cancer or those with metastatic
the disease progresses to a certain stage. For gastric cancer.
patients with unresectable or advanced gastric
cancer, palliative care should be provided as early
as possible. The principles of palliative treat- Local Palliative Care
ment for advanced gastric cancer are to relieve
Local palliative care is a therapeutic option for
K. Ji · Z. D. Bu · J. F. Ji (*) controlling the progression of local symptoms
Department of Gastrointestinal Surgery, such as obstruction, pain, nausea, and bleeding.
Key Laboratory of Carcinogenesis and Translational It includes palliative surgery, surgical bypass,
Research (Ministry of Education), Peking University endoscopic techniques, and palliative radiother-
Cancer Hospital, Beijing Cancer Hospital
and Institute, Beijing, China apy. Improving the overall prognosis of patients
e-mail: jijiafu@hsc.pku.edu.cn should be the major principle during the select-
P. Yuan ing of any local palliative care protocol; that is,
Department of Endoscopy, Key Laboratory of effort should be made to lower the morbidity and
Carcinogenesis and Translational Research (Ministry mortality of patients with advanced gastric can-
of Education), Peking University Cancer Hospital,
cer and avoid long hospital stay.
Beijing Cancer Hospital and Institute, Beijing, China

https://doi.org/10.1007/978-3-662-45583-8_25
296 K. Ji et al.
Palliative Gastrectomy was not significantly different between patients

who had undergone palliative gastrectomy and
Palliative gastrectomy is feasible for advanced those had not, although they also mentioned that
gastric cancer patients who had received systemic there might be sample selection bias. Compared
treatment. The benefits of palliative gastrectomy with patients who had only received bypass
include alleviating symptoms including obstruc- surgery or those without surgical intervention,
tion, bleeding, pain, and nausea. Retrospective patients who had undergone surgical resection
studies have suggested surgery may be associ- might have lower disease burden, better physical
ated with a survival benefit [2–5]. Meanwhile, status, and better prognosis [6].
some literature also has questioned the benefits In a phase III clinical randomized controlled
of palliative resection for patients with advanced trial (REGATTA) jointly initiated by Fujitanni K
gastric cancer (Fig. 25.1) [6, 7]. In a retrospective and Yang HK, the authors investigated the supe-
study, Schmidt B. et al. found that the survival riority of gastrectomy followed by chemotherapy
a 1.0 b 1.0
No gastrectomy (n=35)
Gastrectomy (n=162) No chemotherapy (n=44)
0.8 0.8
Chemotherapy (n=153)
Cumulative survival
Cumulative survival
0.6 0.6
0.4 0.4
P = 0.003 P < 0.001
0.2 0.2
0.0 0.0
0 10 20 30 40 50 0 10 20 30 40 50
c Survival time (months) Survival time (months)
1.0
No gastrectomy or chemotherapy (n=13)
Gastrectomy alone (n=30)
0.8 Chemotherapy alone (n=23)
Gastrectomy combined with
chemotherapy (n=131)
Cumulative survival
0.6
0.4 P < 0.001
0.2
0.0
0 10 20 30 40 50
Survival time (months)
Fig. 25.1 Survival curves of patients grouped with dif- therapy (MST 13.2 vs. 4.3 months, P < 0.001). (c) The
ferent treatments. (a) Overall survival between patients comparison between patients with non-curative gastrec-
undergoing non-curative gastrectomy and those without tomy combined with postoperative chemotherapy and the
(12.4 vs. 7.1 months, P = 0.003). (b) Overall survival other treatment groups (P < 0.001). MST median survival
between patients with and without postoperative chemo- time [5]
25 Palliative Therapy for Gastric Cancer 297
versus chemotherapy alone with respect to overall mean surgery time (116 vs. 116 min) (P = 0.99);
survival in patients with advanced gastric cancer however, the blood loss (23 vs. 142 ml; P = 0.19)
with a single non-curable factor [8]. A single non- was less, and the length of stay (8 vs. 14 days;
curable factor was defined as hepatic metastasis P = 0.14) was shorter in the laparoscopic group,
(H1), peritoneal metastasis (P1) without massive although the difference was not statistically
ascites or intestinal obstruction, or para- aortic significant due to the small sample size [10].
lymph node metastasis above the celiac axis or According to the currently available evidences,
below the inferior mesenteric artery (lymph node gastrojejunal anastomosis may be an alternate
N016a1/b2 of maximum diameter ≥1 cm), or both treatment for patients who cannot be treated by
[8]. Patients were randomized into two groups: in minimally invasive approaches (e.g., palliative
the surgery group, patients underwent gastrec- radiotherapy and endoscopic techniques [such
tomy (D1) followed by palliative chemotherapy, as ablation, stenting, or J-tube placement] with/
without receiving D2 lymphadenectomy or mul- without chemotherapy).
tivisceral resection; in the chemotherapy alone
group, only palliative chemotherapy was applied.
The overall survival analysis showed that there Endoscopic Stent Placement
was no significant survival benefit in patients who
had received palliative gastrectomy. The 2-year Malignant intestinal obstruction is a common
survival (25.7% vs. 31.4%, HR 1.08, 95% CI complication in patients with advanced gastric
0.74–1.58, P = 0.66) and median overall survival cancer. Its main symptoms include pain, nausea,
(mOS) (14.3 months vs. 16.6 months, HR 1.09, vomiting, abdominal distention, and decreased
95% CI 0.78–1.52, P = 0.70) were even worse in oral intake, which can lead to dehydration
the surgery group, although the difference was and malnutrition and thus seriously affect the
not statistically significant [8]. In addition, the patients’ quality of life. Compared to traditional
incidences of several chemotherapy-associated gastroduodenal anastomosis, the self-expandable
adverse events (leucopenia, anorexia, nausea, and metal stents (SEMS) have become a routine clin-
hyponatremia) significantly increased in patients ical technique and can be used in patients with
assigned to surgery group; thus, gastrectomy can- inoperable malignant intestinal obstruction due
not be justified for treatment of patients with these to advanced gastric cancer or other accompany-
tumors [8]. ing medical conditions; in particular, it can be
used as a palliative treatment for elderly patients
[11]. The indications of SEMS for advanced
Gastrojejunal Anastomosis gastric cancer include the following: (a) unable
to eat; (b) with poor nutritional status; (c) inop-
Gastrojejunal anastomosis (e.g., surgical bypass) erable; and (d) with surgical risk or refuse to
is suitable for patients with unresectable advanced take a surgery. In our center, the gastric outlet
gastric cancer accompanied by malignant gastric obstruction scoring system (GOOSS) was used
outlet obstruction. Palliative gastrojejunostomy for assessing the oral intake. In 13 advanced gas-
can improve food intake in these patients [9]. tric cancer patients and 1 patient with duodenal
Minimally invasive laparoscopic gastrojejunal cancer accompanied by pyloric obstruction who
anastomosis is a feasible procedure for the pal- had undergone the placement of uncovered self-
liative treatment of malignant gastric outlet expandable metal stents (Niti-STM Taewoong
obstruction. In a small-scale retrospective study Medical, Korea) in our center in 2016 (Figs. 25.2
compared the surgical outcomes of laparoscopic and 25.3 and Table 25.1), GOOSS scoring
(n = 10) and open (n = 10) gastrojejunostomies in results (Table 25.2) showed that the oral intake
patients with gastric outlet obstruction secondary was significantly improved after stent place-
to advanced malignancies. It was found that there ment (Fig. 25.4). The median time to reconstruc-
was no significant difference between groups in tion after stent placement was 186 days, during
298 K. Ji et al.
Fig. 25.2 Endoscopic view of SEMS at the site of sinuses ventriculi
Fig. 25.3 Endoscopic view of SEMS at the site of esophagogastric junction
which three patients suffered from complications for malignant gastric outlet obstruction, is safe
and one patient with duodenal cancer died from and effective and can maintain the patency of the
bleeding 3 days after stent placement at pylo- gastrointestinal tract within a certain time, it still
rus (Tables 25.3 and 25.4). Notably, all patients has certain limitations. For malignant obstruction
suffered from pain and discomfort after stent caused by other reasons, endoscope placement of
placement and thus needed the oral administra- a gastrojejunal feeding tube can also be applied
tion of pain medications. Although our study has in patients who are unable to undergo endoscopic
shown that SEMS, as a non-surgical treatment placement of SEMS.
Table 25.1 Patient characteristics Table 25.3 Results

Characteristics No. % Technical success, no./total no. (%) 14/14(100%)
Patients 14 Clinical success, no./total no. (%) 13/14(92.86%)
Sex (M/F) 14 (100/0) Mean procedure time, minutes 68.79 ± 10.47
Mean ± SD age, years 68.79 ± 10.47 Improvement in mean GOOSS score 0.36 → 2.21*
(range) (pre → post)
Causative disease Median stent patency, days 186
Esophagogastric junction 6 42.88 GOOSS gastric outlet obstruction scoring system
carcinoma *P < 0.001
Recurrences of at the 1 7.14
anastomotic site after
operation for gastric
carcinoma
Table 25.4 Stent malfunction and complications
Gastric antrum carcinoma 2 14.28
with pyloric obstruction Stent malfunction No./Total No. %
Recurrences of remnant 1 7.14 Occlusion 0/14 0
gastric cancer Migration 0/14 0
Gastric antrum carcinoma 2 14.28 Other complications
Duodenal carcinoma with 1 7.14 Stent fracture 0/14 0
pyloric obstruction Insufficient stent expansion 0/14 0
Gastric carcinoma with 1 7.14 Breeding 1/14 7.14
abdominal metastases Stent obstruction 2/14 14.28
M male, F female, SD standard deviation Cholangitis 0/14 0
Pancreatitis 0/14 0
Perforation 0/14 0
Table 25.2 Patient scores
Death 1/14 7.14
Before SEMS After SEMS Cause
placement placement
Breeding 1/14 7.14
GOOSS score No. % No. %
3 0 0 4 28.5
2 0 0 9 64.3
1 5 35.7 1 7.2
0 9 64.3 0 0
Fig. 25.4 A statistically P<0.001 2.21

significant improvement 3
demonstrates in the
comparison between the 2.5
mean value of GOOSS
before SEMS placement
2
and after SEMS placement
1.5
0.36
1
0.5
0
GOOSS before SEMS placement GOOSS after SEMS placement
–0.5
300 K. Ji et al.
Palliative Radiotherapy to laser photocoagulation, argon plasma coagula-

tion has increasingly been applied.
As a noninvasive treatment, palliative radio-
therapy can reduce tumor burden and help to
control the common clinical symptoms (e.g., Conclusions and Recommendations
pain, dysphagia, and malignant obstruction) in
patients with locally advanced gastric cancer or 1. Palliative treatment is recommended after the
in those with distant metastasis and thus improve gastric cancer has progressed to a certain
the patients’ quality of life [12–14]. Tey J. et al. stage.
retrospectively analyzed the outcomes of 115 2. For local symptoms (e.g., nausea, obstruction,
gastric cancer patients who had received three- pain, and bleeding caused by locally advanced
dimensional (3D) conformal radiation therapy. or locally recurrent primary tumors) that are
Dose fractionation regimen ranged from 8-Gy not responsive to systemic therapy (e.g.,
single fraction to 40 Gy in 16 fractions. Of 115 chemotherapy), endoscopic techniques and

patients with median age of 77 years, 78 (67.8%) palliative radiotherapy are recommended for
patients had metastatic disease at the time of multidisciplinary management.
treatment. Index symptoms included gastric 3. According to the REGATTA study initiated
bleeding (89.6%), obstruction (14.3%), and pain by Fujitanni K and Yang HK, palliative gas-
(9.2%). Response rates for bleeding, obstruc- trectomy is recommended for some advanced
tion, and pain were 80.6%, 52.9%, and 45.5, gastric cancer patients who have received sys-
respectively. Median survival was significantly temic therapy.
longer in patients who responded to radiotherapy 4. In advanced gastric cancer patients with

compared with patients who did not (113.5 vs obstructive symptoms, endoscopic stent
47 days, P < 0.001). There was no significant dif- placement is recommended, whereas pallia-
ference in response rates between low (≤39 Gy) tive surgery should not be used.
and high (>39 Gy) biologically effective dose 5. Compared with endoscopic techniques, palli-
(BED) regimens [14]. No controlled study has ative radiotherapy has relatively extended effi-
directly compared the effectiveness of pallia- cacy in controlling bleeding and obstruction.
tive radiotherapy and endoscopic techniques in Research has shown that a BED of 40 Gy in
alleviating symptoms. However, compared with fractions is preferred for controlling bleeding
endoscopic techniques or palliative gastrectomy, and alleviating obstruction.
palliative radiotherapy has relatively extended 6. Endoscopic laser therapy may be an alterna-
efficacy. Research has shown that a BED of tive treatment option for alleviating dysphagia
40 Gy in fractions is preferred for controlling due to obstruction.
bleeding, and this dose is also recommended for
alleviating obstruction [15].
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Part XV
Postoperative Management and Follow-Up
Management of Early
Postoperative Complication 26
Dong Jin Kim and Wook Kim
Incidence tive studies would be informative and reliable data

(Table 26.1). Kitano et al. reported morbidity of
Incidence of early complication following gas- laparoscopic distal gastrectomy from multicenter
trectomy is different depending on time period, retrospective study as 12.9%. The Korean multi-
nations, and institutions. Dutch and MRC trial center randomized controlled trial (KLASS-01)
showed 43–46% morbidity and 10–13% mortality showed 18.9% and 13.7% of morbidity in open
rate following distal gastrectomy with D2 lymph and laparoscopic distal gastrectomy, respectively.
node dissection [1, 2]. Additionally, as previously
reported in literatures, morbidity and mortality
rates were ranged 18.0–46.0% and 0.8–13.0%, isk Factors Related with Early
R
respectively [1–6]. Past data are originated from Complication Following Gastrectomy
retrospective studies or randomized controlled tri-
als (RCTs) which do not performed strict surgical Various conditions were evaluated as risk factors
quality control. Moreover, laparoscopic surgery is in the development of postoperative complications.
one of the mainstreams nowadays. For these rea- Elucidating the risk factors of complication is the
sons, evaluation for complication from well-con- first step to prevent complications. Those risk factors
trolled RCTs comparing open and laparoscopic are divided into patient- and operation-related factor.
gastrectomy and large-scale multicenter retrospec- In the patients’ side, the number of comor-
bidity is the most important risk factor in the
D. J. Kim development of complications. In KLASS retro-
Division of Gastrointestinal Surgery, spective study, comorbidity was a predictive risk
Department of Surgery, Eunpyeong St. Mary’s Hospital,
College of Medicine, The Catholic University of Korea,
factor for local complication and systemic com-
Seoul, Republic of Korea plication in multivariate analysis [12]. Except for
W. Kim (*)
comorbidity, age, sex, and nutritional status are
Division of Gastrointestinal Surgery, also included [13–19].
Department of Surgery, Eunpyeong St. Mary’s Hospital, In the operation-related side, the extent of
College of Medicine, The Catholic University of Korea, lymph node dissection, extent of gastric resection,
type of reconstruction, operation time, estimated
Division of Gastrointestinal Surgery, Department of blood loss, presence of combined resection, and
Surgery, Yeouido St. Mary’s Hospital, College of
Medicine, The Catholic University of Korea,
experience of surgeon are included. However,
Seoul, Republic of Korea those risk factors are suggested differently
e-mail: kimwook@catholic.ac.kr depending on various literatures [14, 17, 18].

https://doi.org/10.1007/978-3-662-45583-8_26
306 D. J. Kim and W. Kim
Table 26.1 Recent morbidity and mortality rate from randomized controlled trial and multicenter retrospective
studies
Open Laparoscopy
Study Resection Indication n Morbidity Mortality Morbidity Mortality
2005 Huscher et al. [7] DG EGC, AGC 59 27.6% 6.7% 23.3% 3.3%
2007 Kitano et al. [8] All EGC 1185 12.9% 0%
2014 Kim et al. [9] All EGC, AGC 2976 15.1% 0.3% 12.5% 0.5%
2016 Hu et al. [10] DG AGC 1056 12.9% 0% 15.2% 0.4%
2016 KLASS-01 M&M [11] DG EGC 1416 18.9% 0.3% 13.7% 0.6%
DG: Distal gastrectomy, EGC: Early gastric cancer, AGC: Advanced gastric cacer
Fig. 26.1 Computed tomography revealed localized hematoma and extravasation of contrast media near infra-
pancreatic area
Early Postoperative Complications bleeding can be developed after 1–2 weeks due

to vessel erosion by anastomosis leakage or intra-
Bleeding (Intra-abdominal, abdominal abscess and pseudoaneurysm rupture
Intraluminal) formed by vessel injury due to energy devices.
Postoperative bleeding is not common. The inci- Intra-abdominal bleeding can be diagnosed
dence is 0.6–3.3% and occurred mostly until easily by bloody drainage if patient still has
24 h after operation [8, 11, 20–24]. Postoperative drain. If there is no drainage catheter placed, vital
bleeding can be divided into intra-abdomi- sign or postoperative hemoglobin change should
nal (extraluminal) bleeding and intraluminal be closely focused. Computed tomography (CT)
bleeding. can be helpful for evaluating degree and origin
of bleeding with the findings such as hemoperi-
1. Intra-abdominal (Extraluminal) Bleeding toneum, localized hematoma, or extravasation of
contrast dye (Fig. 26.1). According to KLASS-01
Early postgastrectomy intra-abdominal bleed- study from Korea, the most vulnerable site was
ing is originated from imperfectly ligated vessel, the peripancreatic head area which is no. 6 lymph
lymph node dissection area, omentectomy site, node dissection area [11].
staple line, splenic hilum, divided jejunal mes- Optimal timing to perform intervention or
entery, and trocar insertion site in case of lapa- reoperation is controversial and dependent on
roscopic surgery. Sometimes delayed massive surgeon’s preference. If patient’s vital sign is
26 Management of Early Postoperative Complication 307
unstable, reoperation should be immediately per- erative day. Delayed intraluminal bleeding can be
formed. Although the patient’s vital sign is within found to be originated from marginal ulceration
normal range, reoperation or angiographic inter- near gastrojejunostomy. Diagnosis can be made
vention is strongly recommend when bleeding is by evident hematemesis or bloody drainage from
continuous or extravasation of contrast media is Levine tube. The chance of intraluminal bleeding
definite by CT. increases when number of anastomosis increased
Angiographic intervention can be a unique tool and anastomosis included remnant stomach that
for bleeding control and avoiding additional reoper- has more tendency to make intraluminal bleeding
ation. However, decision-making for angiographic due to fluent blood flow. For this reason, during
intervention is crucial, because not all intra-abdom- the operation, it is crucial to check anastomosis
inal bleeding cases are applicable. Bleedings from line formed either by linear staple or hand sewing
pseudoaneurysm near splenic artery or visible ves- method. In the case of delayed intraluminal bleed-
sel confirmed by CT are optimal for angiographic ing, it occurred 1–2 weeks later after operation;
hemostasis. On the other hand, venous bleeding marginal ulcer bleeding, erosive gastritis, and
or bleeding from minor branch such as omental anastomosis disruptions are possible factors. In
vessel, trocar site, raw surface of lymph node dis- case of massive hematemesis, there can be a pos-
section, or staple line oozing is not applicable for sibility of aneurysmal rupture into luminal side.
angiographic bleeding control. Although minor bleeding is usually self-
Regarding the reoperation, laparoscopic limiting, when continuous bleeding is evident,
approach can be initially considered. Unless endoscopic approach should be firstly attempted.
bleeding is not too severe to obscure laparoscopic There are several endoscopic tools to stop intra-
view, we can efficiently find bleeding focus with luminal bleeding such as endoscopic metal clip,
magnified view through laparoscopy. Because heater probe coagulation, and epinephrine injec-
most reoperation is performed within 48 h after tion. Among them, metal clip is most reliable
gastrectomy, adhesion is not that severe. than other modalities (Fig. 26.2).
2. Intraluminal Bleeding Anastomosis Leakage

Anastomosis leakage means intraluminal con-
Bleeding from anastomosis site mostly devel- tents escape from intraluminal space to intra-
oped in the early period, within the first postop- abdominal cavity or out of the skin. Although
a b
Fig. 26.2 (a) Endoscopic finding shows intraluminal bleeding from artificial lesser curvature staple line. (b) Endoscopic
hemoclip successfully controlled intraluminal bleeding
anastomosis leakage rate is decreasing, thanks gastroduodenostomy, or gastrojejunostomy site.

to improved surgical skills and development of In addition, oral contrast CT can provide a defini-
surgical instruments, it is still a dreadful compli- tive diagnosis of leakage by detecting the accu-
cation that can result in sepsis and even mortality. mulation of extraluminal contrast [36].
The incidence of anastomotic leakage follow- Although management for anastomosis leak-
ing distal gastrectomy and total gastrectomy is age is somewhat different according to leak-
0.7–2.6% and 2.3–10.4%, respectively [11, 25– age site, the main principle for enterocutaneous
31]. It induces bacterial and digestive enzyme fistula management is similar. If leakage site is
dissemination that results in localized abscess, small and well-controlled by drainage catheter,
generalized peritonitis, sepsis, pulmonary infec- almost leakage can be managed with conservative
tion, mediastinitis, and even death. It is usually method. When we perform conservative manage-
developed within 10 days postoperatively [32– ment, it is important to perform sterile saline
35]. Typical symptom can be different according irrigation through drainage catheter to wash out
to the site of anastomosis leakage. However, gen- dirty materials in abscess cavity and evoke rapid
eralized or localized peritoneal irritation sign can growth of granulation tissue. If the leakage site is
abruptly develop, and some patients show agita- large or poorly controlled, interventional percuta-
tion or dyspnea. There can be signs of fever more neous Foley catheter enterostomy or reoperation
than 38 °C, leukocytosis, and elevation of CRP is considered.
level. When drainage catheter was remained, When leakage event was developed with-
nature of drainage contents can be changed to out surgical drainage catheter, sono-guided or
turbid or bile-contained color. However, drain CT-guided percutaneous catheter insertion at the
never guarantees early detection of anastomosis target fluid collection area should be performed.
leakage. If percutaneous drainage is impossible due to the
When anastomosis leakage is suspected, location of fluid collection area, irrigation and
abdominal enhance CT should be checked. We drainage catheter insertion should be performed
can find small or large amount of dirty fluid collec- by surgical approach.
tion with or without extraluminal air (Fig. 26.3). Advanced technique for leakage control:
When CT finding is equivocal, hypaque swallow-
ing test can be helpful for esophagojejunostomy, –– Duodenal stump leakage
• Regarding the management for duodenal
stump leakage, recently introduced percu-
taneous Foley duodenostomy insertion
through perforation site by Seldinger tech-
nique is usefully performed.
After duodenal stump leakage occurs,
percutaneous drainage is performed for
fluid collections near duodenal stump.
Several days later, abscess cavity is
decreasing, and internal tract with duode-
nal stump can be found with tubography
via pigtail catheter. Then, the guide wire
can be introduced into luminal side of duo-
denal stump, and Foley catheter can be
introduced along the guide wire. Ballooning
and gentle traction of Foley catheter can
Fig. 26.3 Computed tomography performed on postop-
erative 7 days following distal gastrectomy, and Billroth II
obscure leakage site and evoke rapid heal-
anastomosis revealed air-containing fluid collection con- ing of abscess cavity (Fig. 26.4). It can
sistent with duodenal stump leakage reduce the frequency of wound dressing,
a b c d
Fig. 26.4 Fluoroscopic findings and illustration of Foley Foley catheter through the guide wire. (d) The confirma-
catheter insertion into the site of leakage. (a) Leakage tion of placement of the Foley catheter by tubogram.
confirmation. (b) The introduction of guide wire through (Reprint from J Korean Surg Soc. 2010;78:165–70)
the guide catheter. (c) The insertion and ballooning of the
skin irritation, and related pain. mediastinitis. This type of leakage is diffi-
Additionally, within a few days after the cult to perform radiologic intervention due
procedure, diet can be started. Then ambu- to target area surrounded by the chest wall,
latory care can be done if there was no diaphragm, or spleen. Endoscopic stent
complaint of fever or abdominal pain. After insertion is unique method for the
controlled fistula is formed, Foley catheter management of esophagojejunostomy [25,
can be removed within 1–2 weeks at outpa- 38, 39]. Esophageal stenting is to limit the
tient office [37]. sepsis from continued leak and to allow
–– Esophagojejunostomy leakage early resumption of enteral feeding
• Esophagojejunostomy leakage is one of the (Fig. 26.5). After placement of esophageal
most troublesome early postoperative com- stent, stent migration, stent perforation,
plications after total gastrectomy. It can and stent-related bleeding should be thor-
frequently induce lung complication or oughly monitored. While the stent is kept
a b
Fig. 26.5 (a) Endoscopic finding shows defect of esophagojejunostomy site. (b) Endoscopic covered stent is placed at
the esophagojejunostomy site
in proper position, drainage catheter should form operation. According to small-sized case
be placed beside leakage point to maximize series, omental adhesion to staple line following
the effect of esophageal stent. Duration of intracorporeal Billroth II anastomosis was the
stent placement is variable from 1 week to cause of afferent loop syndrome [40]. In those
8 weeks between studies [39]. Because situations, Braun anastomosis can be applied. In
reestimation of leakage site can be exactly case of internal herniation, reduction of herniated
performed after stent removal, timing of small bowel and mesenteric defect repair should
stent removal should be decided by each be done.
patient’s condition. However, stent place-
ment no more than 8 weeks is recom- ancreatic Abscess and Fistula
P
mended due to tissue ingrowth into metal D2 lymph node dissection is currently regarded
portion that may interfere smooth stent as a safe and effective procedure. However, D2
removal. extended lymph node dissection can cause pan-
creatic fistula that can result in abscess, sepsis,
Obstruction and critical bleeding from the pseudoaneurysm.
Intestinal obstruction as an early postopera- The definition of pancreatic fistula is not uni-
tive complication following gastrectomy is not fied, but the criteria of the International Study
common. However, there are several types of Group on Pancreatic Fistula (ISGPF) are gener-
intestinal obstruction which are highly specific ally followed [41]. By the definition, output via
for gastric cancer surgery. For example, except an operatively placed drain of any measurable
Billroth I gastroduodenostomy, there remain pos- volume of drain fluid on or after postoperative
sibilities of internal herniation or obstruction of day 3 with an amylase content more than three
afferent limb after total gastrectomy or distal gas- times higher than the upper normal serum value.
trectomy with Roux-en-Y or Billroth II anasto- However, not only with drain amylase level,
mosis. To reduce those complications, mesenteric clinical signs or CT findings such as peripancre-
repair should be thoroughly performed. Definite atic fluid collection or pancreatic fistula-related
management for intestinal obstruction is to per- peripancreatic abscess are also regarded as pan-
creatic fistula [42–44]. Since the definition may If there is no definite obstructive lesion and
include many asymptomatic patients, ISGPF also delay of gastric emptying is caused by anastomo-
suggested grading system for pancreatic fistula sis edema or functional problem, gastric clear-
from grade A to C. Grade A is called transient fis- ing with Levine tube drainage or gastric lavage
tula without clinical impact. Grade B requires a and conservative care would be the first choice.
change in management or adjustment in the clini- After that, liquid form meal can be applied.
cal pathway such as NPO, total parenteral nutri- Anastomosis edema can be applied with balloon
tion (TPN), drain repositioning, or somatostatin dilatation, if symptom improvement is delayed.
analog use. Grade C refers a major change in
clinical management or deviation from the nor- Miscellaneous
mal clinical pathway. 1. Acute Pancreatitis
Management for pancreatic fistula starts with
efficient drainage of leaked pancreatic juice. During the gastric cancer surgery, the pan-
When closed suction drain is remained, and creas is frequently manipulated for proper supra-
placed proper position for drainage of pancre- pancreatic lymph node dissection. In addition,
atic leakage, keep the drain and saline irrigation some patients with history of chronic alcohol
is most optimal treatment. When drain is located consumption have quite hard pancreas and
different position from the peripancreatic fluid fibrotic change around the pancreas. This can
collection, repositioning or percutaneous drain make lymph node dissection difficult and also
insertion should be attempted. evoke pancreatitis after operation. Great caution
If pancreatic leakage is prolonged, NPO, is always needed when manipulating pancreas.
TPN, or somatostatin analog injection can help
to reduce secretion of pancreatic juice. 2. Acute Cholecystitis
elayed Gastric Emptying

D Although cholelithiasis would not be devel-
Gastric surgery may potentiate or induce delayed oped within the early postoperative period, rarely
gastric emptying and result in chronic gastropa- sludge can evoke acute cholecystitis when NPO
resis. The reported incidence of delayed gastric period is prolonged in specific patients. When the
emptying after gastrectomy has been reported degree of cholecystitis is mild without fever, anti-
ranging from 5 to 30% [45]. Generally, incidence biotics can be optimal management. However, if
of delayed gastric emptying is increasing in order pain is severe and cholecystitis-induced fever
of gastrojejunostomy, gastroduodenostomy, and developed, percutaneous cholecystostomy is
Roux-en-Y gastrojejunostomy following dis- firstly recommended. This can be removed after
tal gastrectomy. However, those risk factors for 4–6 weeks later.
delayed gastric emptying are different between
studies. 3. Chylous Ascites
When patient suffers from postprandial epi-
gastric discomfort, nausea, vomiting, or left-side Chylous ascites is defined as the leakage of
shoulder pain, delayed gastric emptying can be milky triglyceride-rich lymphatic fluid from lym-
suspected. Diagnosis for delayed gastric emptying phatic system to the peritoneal cavity, which can
is made by the finding of gastric distension and be encountered after various abdominal oncologic
food stasis in simple abdomen X-ray or delayed surgeries [46]. The management includes cessa-
contrast passage with Gastrografin swallowing tion of oral feeding, TPN, somatostatin analog
test. The most important point for differential administration, clamping and/or removal of the
diagnosis for delayed gastric emptying is mechan- drainage, diuretics, and diet therapy with medium
ical obstruction. Endoscopic evaluation should be chain triglyceride. The fistula closure time was
performed to confirm the patency of food passage. reported ranging from 1 to 7 weekdays [47].
Conclusion 8. Kitano S, Shiraishi N, Uyama I, Sugihara K, Tanigawa

N. A multicenter study on oncologic outcome of lapa-
roscopic gastrectomy for early cancer in Japan. Ann
Recent advancement of diagnostic and interven- Surg. 2007;245(1):68–72.
tional modalities shifted paradigm of complica- 9. Kim HH, Han SU, Kim MC, Hyung WJ, Kim W, Lee
tion management. Reoperation is not the first HJ, et al. Long-term results of laparoscopic gastrec-
tomy for gastric cancer: a large-scale case-control and
choice anymore, and nonoperative managements case-matched Korean multicenter study. J Clin Oncol.
improved not only results of perioperative sur- 2014;32(7):627–33.
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example, interventional Foley duodenostomy Morbidity and mortality of laparoscopic versus
open D2 distal gastrectomy for advanced gastric
insertion was novel technique to improve the cancer: a randomized controlled trial. J Clin Oncol.
patient’s recovery from illness during periopera- 2016;34(12):1350–7.
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management for complications is crucial for care SW, et al. Decreased morbidity of laparoscopic distal
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Management of Late
Postoperative Complications 27
Masanori Terashima
Introduction Table 27.1 Postgastrectomy syndrome

Functional disorders
Following surgery for gastric cancer, gastrectomy Early dumping syndrome
and dissection of the vagus nerve surrounding the Late dumping syndrome
stomach can lead to postgastrectomy syndrome Small gastric remnant syndrome
(PGS) as a late postoperative complication [1]. Diarrhea
Constipation
Although PGS occurs in most patients who have
Roux stasis
undergone gastrectomy, the condition is said to
Delayed gastric emptying
be severe in 5–10% of cases. The main conditions Digestion disorder
in PGS, as listed in Table 27.1, can reduce oral Anemia
intake, lower body weight due to decreased mus- Bone disorder
cle mass, and increase mental stress, which in turn Lactose intolerance
can reduce the quality of life (QOL). During the Steatorrhea
follow-up observation of patients who have under- Organic disorders
gone gastrectomy, the state of PGS should be fully Reflux gastritis
ascertained and treated appropriately. This chapter Reflux esophagitis
Stomal ulcer
explains the underlying pathophysiology of the
Anastomotic stenosis
principal types of PGS and their management.
Cholecystitis, cholecystolithiasis
Afferent loop syndrome
Ileus
Functional Disorders Internal hernia
Early Dumping Syndrome

and the release of vasomotor substances (brady-
Early dumping syndrome occurs when hyper- kinin, serotonin, histamine, and catecholamine)
osmolar food enters the small intestine rapidly, [2]. The syndrome occurs in 25–40% of patients
causing a shift in the intravascular water content after gastrectomy. It is more common following
in the gut, which leads to circulatory collapse, total gastrectomy than distal gastrectomy and
often occurs following reconstruction by Billroth
M. Terashima (*) I (B-I) in distal gastrectomy. However, it is rare
Division of Gastric Surgery, Shizuoka Cancer Center, with Roux-en-Y (RY) reconstruction and pyloris-
Nagaizumi, Japan preserving gastrectomy (PPG) [3, 4].
e-mail: m.terashima@scchr.jp

https://doi.org/10.1007/978-3-662-45583-8_27
316 M. Terashima
Symptoms of early dumping syndrome occur Treatment is administered essentially as per

within 30 min of eating and include general and early dumping syndrome, and because the syn-
abdominal symptoms. General symptoms include drome is more likely to occur in individuals
drowsiness, general malaise, cold sweats, palpi- who eat quickly, such individuals are advised to
tations, dizziness, shortness of breath, headache, eat more slowly. In particular, sufferers should
and flushing as well as feeling feverish, heavy- refrain from an excessive intake of carbohy-
headed, and faint. Abdominal symptoms include drates. Furthermore, they are advised to eat sug-
bloating, gurgling, abdominal pain, diarrhea, and ary foods when it appears that hypoglycemia
nausea. will occur. Effective pharmacotherapy includes
Diagnosis is determined by the presence of α-glucosidase inhibitors [8].
two general symptoms or one general symptom
with one abdominal symptom among those noted
above. In cases where diagnosis is difficult, a Delayed Gastric Emptying
provocation test is performed by loading with
50% oral glucose [5]. Delayed gastric emptying (DGE) is often experi-
Diet therapy is essential while treating early enced after gastrectomy. Kubo et al. observed the
dumping syndrome. It is advised that patients eat gastric remnant by endoscopy following distal
small meals frequently, avoid a high-carbohydrate gastrectomy. They found food residues in 22% of
diet, and reduce their water intake during meals. cases and reported that it was more common with
With respect to medication, antiserotonin agents, B-I reconstruction than with RY, with a higher
antihistamine agents, anticholinergic agents, rate after PPG [9]. The relationship between the
antibradykinin agents, local anesthetic agents, presence of such food residues and weight loss
and antianxiety agents are used for the treatment with complaints is unclear; it is thought that a
of general symptoms. It has been reported that small amount of residue would not pose a major
octreotide, a somatostatin analog, is sometimes problem.
effective [6]; however, long-term efficacy has not However, DGE after PPG is often a problem,
been demonstrated [7]. with food regurgitation and a sense of abdominal
bloating observed after meals. An effective way
to prevent DGE after PPG involves preserving
Late Dumping Syndrome 2 cm or more of the pyloric cuff and preserving
the pyloric branch of the vagal nerve, the right
Late dumping syndrome is associated with gastric artery, and the infrapyloric artery [10].
decreased gastric retention capacity and occurs Furthermore, in some instances, despite the
because of the rapid entry of carbohydrates into absence of any organic abnormality, reduced
the upper jejunum. The rapid absorption of car- tonicity of the wall of the gastric remnant can
bohydrate from the intestines leads to temporary result in enlargement of the gastric remnant (gas-
hyperglycemia, which causes excessive secretion tric atony), and excretory disorders are observed.
of insulin, and leads to reactive hypoglycemia. It is thought that the condition readily occurs
Symptoms appear 2–3 h after eating and include in patients with diabetes, hypothyroidism, and
a sense of hunger, cold sweats, lethargy, palpita- dysautonomia.
tions, weakness, dizziness, hand tremors, rapid As treatment, sufferers are advised to reduce
breathing, headache, and fainting. The syndrome the amount of food intake per meal, split meals,
is more common after total gastrectomy than dis- take time to eat, chew well, consume the proper
tal gastrectomy and is more common with B-I amount of fluids with meals, maintain good
than RY reconstruction in distal gastrectomy [3]. dental hygiene, and eat meals low in dietary
Diagnosis is relatively easy based on symp- fiber. Oral nutritional supplements (ONS) are
toms. Symptoms improving with sugar intake used in combination with these steps to main-
make the diagnosis more definite. tain caloric intake. For medication, drugs that
27 Management of Late Postoperative Complications 317
improve gastrointestinal motility are adminis- function-controlling drugs, digestive enzyme

tered. In the event that there is no improvement preparations, and gastrointestinal motility inhibi-
with conservative therapy, surgical treatment is tors are prescribed. It has recently been reported
considered [11]. that preserving the celiac branch of the vagal
nerve reduces the incidence of diarrhea [14, 15].
Roux Stasis Syndrome

Constipation
Approximately 30% of patients who undergo
reconstruction by RY after gastrectomy develop Constipation is caused by attenuated gastro-
a sense of abdominal bloating, abdominal pain, colonic reflex, reduced food intake, low intake
nausea, vomiting, and loss of appetite. It is of fat and fiber, as well as reduced abdominal
thought that these symptoms are due to abnormal pressure due to a decrease in muscle mass. It
Roux limb movement (hypoperistalsis, retroperi- has been reported that patients with stool abnor-
stalsis, and abnormal contractions) [5]. The syn- malities exhibit a disturbance in their intestinal
drome often develops early after surgery but is bacterial flora and changes in the intra-intestinal
also observed after long periods. The syndrome environment [16]. Sufficient water intake, with
easily develops in patients with a long Roux consumption of adequate dietary fiber and fat,
limb [12]. It also tends to occur when the gastric is recommended. Lifestyle improvements, such
remnant is large. Treatment is administered via as exercising regularly, also effectively improve
agents that improve gastrointestinal motility, but constipation. In the event that these interven-
if this treatment is ineffective, surgical treatment tions result in no improvement, agents that
is considered. When the gastric remnant is too improve laxatives and gastrointestinal motility
large, gastrectomy is performed to reduce its size. are administered.
When the Roux limb is too long, it is shortened.
The methods considered effective for preventing
the syndrome include making the gastric remnant Digestion and Absorption Disorders
small at the time of the initial surgery; making the
Roux limb short (approximately 30 cm); and, for Various digestive, absorption, and metabolic
the retrocolic pathway, fixing the mesocolon to changes occur after gastrectomy. Among these,
the gastric remnant [13]. digestion and absorption disorders are caused
by a loss of gastric retention capacity, changes
in the normal pathway, changes in the secretion
Diarrhea of gastrointestinal hormones, and asynchrony
as a result of gastrectomy and reconstruction. It
Diarrhea is caused by the rapid entry of food into has recently been reported that ghrelin, which is
the small intestine, acceleration of bowel peri- produced by the stomach, has a major effect on
stalsis, changes in the intestinal bacterial flora, appetite and fat metabolism.
exocrine pancreatic insufficiency, and postci- Such a loss of appetite, along with reduced
bal pancreaticobiliary asynchrony. Loose stool, digestive and absorptive capacities, causes con-
watery stool, and increased stool frequency are siderable weight loss after gastrectomy. The rate
observed. Eating quickly and consuming a high- of continued weight loss at 3–6 months following
fat diet, cold drinks, milk, and alcohol can cause surgery is higher in total gastrectomy than in par-
diarrhea; therefore, sufferers are given advice tial gastrectomy [17]. Particular caution should
about what and how they should eat. They are be exercised in slim, elderly patients who have
also advised not to allow the abdomen to become undergone total gastrectomy. In total gastrectomy
cool. When such dietary counseling does not patients, weight loss is greatly affected by loss
result in symptom improvement, intestinal- of appetite due to the reduced levels of ghrelin.
318 M. Terashima
Postoperative weight loss can have major social milk can be consumed instead or a lactase prepa-
effects, such as reduced QOL and delayed return ration can be administered. Symptoms are con-
to work. It has also been reported that patients sidered less likely with fermented milk drinks
who lost a large amount of weight postopera- than with raw milk.
tively had inferior completion rates for postop-
erative adjuvant chemotherapy. Therefore, the
prevention of weight loss soon after surgery is Fatty Stool
an important issue. Furthermore, sarcopenia has
recently been noted, with reports that more than Fatty stool occurs as a result of reduced secre-
25% of patients exhibited a loss of more than tion of digestive enzymes, impaired small intes-
10% of their pre-surgery skeletal muscle mass tinal absorption through the mucosal epithelium,
following total gastrectomy [18]. and poor mixture of food and digestive juices
It has been reported that in patients who have (postcibal asynchrony). White stools that float
undergone total gastrectomy, ghrelin administration in water and give off a unique bad smell are due
effectively improves appetite, increases food intake, to impaired digestion and absorption of fat and
and reduces weight loss; thus, its clinical applica- are therefore associated with weight loss and
tion in the future is much anticipated [19, 20]. deficiency of fat-soluble vitamins (vitamins A,
D, E, and K). Fatty stool is more common with
total gastrectomy than partial gastrectomy. Friess
Lactose Intolerance et al. [22] reported that trypsin and chymotryp-
sin secretion is reduced by 91% following total
Changes in intestinal bacterial flora can lead gastrectomy. In patients who undergo concur-
to low lactase activity in the small intestinal rent resection of the pancreatic body and tail, the
mucosa, and a relative deficiency in lactase absolute amount of secretion in the pancreatic
may be caused by rapid entry of lactose into the duct is reduced; therefore, such patients are prone
small intestine due to impaired gastric reten- to fatty stool. For treatment, patients who have
tion capacity. Insufficient lactase levels indicate been consuming an excessive amount of fat are
that lactose cannot be broken down into glucose advised to limit the amount of fat that they con-
and galactose, causing osmotic diarrhea and fer- sume and to eat slowly. If there is no subsequent
mentation in the intestines, which consequently improvement, digestive enzyme preparations are
results in abdominal bloating, nausea, gurgling, administered [23]. In the event that fat-soluble
and abdominal pain. Lactase activity is lower vitamin deficiency is suspected, a fat-soluble
among Asian individuals than among Westerns vitamin preparation is administered.
[21]. Furthermore, because lactase activity is
highest in the upper jejunum, lactose intolerance
appears to be high in cases that have undergone Anemia
RY reconstruction, indicating that food does not
pass into the upper jejunum. Because diarrhea Following gastrectomy, microcytic anemia
can occur simply by drinking cold drinks, when caused by iron-deficiency and macrocytic anemia
these symptoms appear even with warm milk, caused by vitamin B12 deficiency both occur.
lactose intolerance is likely. Iron intake from the diet is oxidized by gas-
For a definite diagnosis, a lactose tolerance tric acid from Fe3+ to Fe2+ and absorbed through
test, a quick lactose test, and a lactose breath test the duodenum and upper jejunum. Following
are performed. gastrectomy, there is a lack of gastric acid, tran-
Symptoms will improve after restricting the sit through the jejunum is rapid, and the upper
intake of milk and dairy products. If the patient jejunum may be bypassed because of reconstruc-
wants to continue drinking milk, lactose-free tion. As a result, this causes iron malabsorption.
Lee et al. reported that iron deficiency occurs in Metabolic Bone Disease
69% of patients after surgery for gastric cancer,
and iron-deficiency anemia is observed in 31%. Insufficient calcium intake, calcium malabsorp-
According to the surgical procedure, anemia was tion (due to reduced gastric acid, rapid passage
more common after total gastrectomy than distal through the upper jejunum, and lactose intoler-
gastrectomy, and with distal gastrectomy, anemia ance), and vitamin D malabsorption (fat mal-
was more common with RY than B-I reconstruc- absorption) following gastrectomy can lead to
tion [24]. a loss of bone mineral content, increased bone
Symptoms generally present as per general absorption, and reduced bone density. Symptoms
anemia, and in the event of severe iron deficiency, include lower back pain, pain in the four limbs,
glossitis, cheilosis, and nail deformity can occur. and leg cramps. In severe cases, lumbar compres-
Blood tests show microcytic anemia, low sion fractures and femoral neck fractures can
serum iron, low serum ferritin, increased total occur. It is more common after total gastrectomy
iron-binding capacity, and increased unsaturated than after distal gastrectomy, and after distal
iron-binding capacity. gastrectomy, it is more common with Billroth
First-line treatment is the administration of II (B-II) and RY reconstruction than B-I. Dual-
oral iron tablets. If possible, a ferric oxide formu- energy X-ray absorptiometry (DEXA) is useful
lation is chosen. In the event that oral treatment is for diagnosis. Blood tests show low serum levels
difficult, intravenous treatment is administered; of calcium, phosphorus, and 25(OH)D, with high
however, caution should be exercised with this to levels of 1,25(OH)2D and parathyroid hormone
avoid an overdose. (PTH).
Vitamin B12 binds to the Castle’s intrinsic fac- Patients are advised to eat foods rich in cal-
tor secreted in gastric parietal cells and is absorbed cium, vitamin D, and vitamin K as a treatment
through the ileum terminal. After total gastrec- method. As pharmacotherapy, bisphosphonate
tomy, deficiency of the castle intrinsic factor preparations are recommended [26].
causes vitamin B12 malabsorption. Vitamin B12
deficiency develops in 100% of total gastrectomy
cases and 16% of distal gastrectomy cases [25]. Organic Disorders
Because vitamin B12 is stockpiled in the body, it
takes 3–5 years to be completely consumed. When Reflux Esophagitis
vitamin B12 reserves are depleted, megaloblastic
anemia develops. When blood tests show a low Reflux esophagitis is caused by the reflux preven-
red cell count, with a high mean corpuscular vol- tion mechanism of the cardiac orifice, increased
ume (MCV) and mean corpuscular hemoglobin internal pressure of the gastric remnant, and
(MCH), it indicates low serum levels of vitamin excretory disorder of the gastric remnant asso-
B12. If vitamin B12 deficiency becomes severe, it ciated with gastrectomy, which in turn causes
can cause peripheral neuropathy, tongue pain, and acidic gastric juices in the gastric remnant and
hypogeusia. Administration of fluoropyrimidine alkaline duodenal fluid to flow into the esopha-
anticancer agents can also cause megaloblastic gus. Conjugated bile acid and pepsin in the pres-
anemia, but the underlying mechanism of this dif- ence of gastric acid and unconjugated bile acid
fers to that of vitamin B12 deficiency. and trypsin in the absence of gastric acid have
Administering parenteral vitamin B12 prepa- a harmful effect on the esophageal mucous
rations has been recommended as treatment; membrane.
however, it has been reported that similar out- Symptoms include heartburn, post sternal
comes can be achieved with oral preparations. pain, difficulty in swallowing, epigastric pain,
Thus, oral vitamin B12 preparations are also and a burning sensation. When attempting to go
administered. to sleep, some patients complain of gastric acid
320 M. Terashima
Table 27.2 The Los Angeles classification of distance should be at least 40 cm. Furthermore,
esophagitis
as reflux easily occurs when passage through the
Grade A One (or more) mucosal break no longer distal jejunum is impaired, due care should be
than 5 mm that does not extend between
the tops of two mucosal folds
exercised to avoid intestinal torsion and bending.
Grade B One (or more) mucosal break more than In PPG, it has been reported that reflux esopha-
5 mm long that does not extend between gitis is less common compared with B-I; how-
the tops of two mucosal folds ever, reflux occurs when the oral gastric remnant
Grade C One (or more) mucosal break that is is small, when delayed emptying of the stomach
continuous between the tops of two or
more mucosal folds but which involves
contents is observed, and with hiatal hernia. In
less than 75% of the circumference the event of concern about these factors, RY
Grade D One (or more) mucosal break which reconstruction should be performed as distal
involves at least 75% of the esophageal gastrectomy. In proximal gastrectomy, there is
circumference a high rate of reflux with esophagogastrostomy.
Citation from [27] When the gastric remnant is small and when
performing esophagogastrostomy, some kind of
rising up into the throat and their pillow being additional reflux prevention measures should be
soiled by yellow digestive juices. Reflux at night considered such as jejunal interposition as well
can also cause concurrent aspiration pneumonitis. as double tracts method. Recently, it has been
Diagnosis is determined on the basis of clini- reported that reconstruction with the double flap
cal findings and upper gastrointestinal endos- method can prevent reflux [33].
copy. Findings by endoscopy include redness of Dietary guidance is crucial in treatment and
the esophageal mucosa, inflammation, ulceration, should include advising patients to reduce the
hemorrhage, and edema, the severity of which is volume of each meal, to chew well, and to avoid
determined using the Los Angeles Classification stimulants, carbonated drinks, and high-fat foods.
(Table 27.2) [27]. In many instances, endoscopic Patients should also be advised to not lie down
findings and subjective symptoms do not corre- soon after meals, to eat at least 2 h before bed-
spond. To accurately diagnose reflux, 24-h pH time, and to sleep in Fowler’s position. If there is
monitoring is useful. no improvement with this guidance or in severe
In relation to the surgical procedure, follow- cases, medication should be considered, with the
ing distal gastrectomy, reflux is common when administration of agents that improve gastroin-
the gastric remnant is small after B-I and B-II testinal motility and mucosa protective agents.
reconstruction, whereas the condition is rare Depending on the type of digestive juice that
with RY reconstruction [28–31]. It has been refluxes, protease inhibitors, proton pump inhibi-
reported that short-segment Barrett’s esophagus tors, and H2-blockers are selected. When conser-
(SSBE) occurs in approximately 25% of patients vative treatment yields no improvement and the
who undergo B-II reconstruction [32]. It has patient’s daily life is greatly affected or in cases
been found that the incidence of reflux esopha- when aspiration pneumonitis repeatedly occurs,
gitis is high after proximal gastrectomy with surgery should be considered. In the event of
esophagogastric anastomosis. Caution should B-I and B-II reconstruction, improvements can
be exercised with B-I and B-II reconstruction to be achieved by performing repeat reconstruction
avoid making the gastric remnant small, to main- using the RY method.
tain an appropriate His angle, and to prevent
hiatal hernia from occurring. When the gastric
remnant appears small, in patients with a hiatal Anastomotic Ulcers
hernia, it is preferable to select RY reconstruc-
tion. Following total gastrectomy, reflux tends With RY and B-II reconstruction, when the
to occur when the distance from the esophago- extent of gastric resection is small and vagotomy
jejunal anastomosis to the Y limb is short. The is insufficient, the secretion of gastric juices from
the gastric remnant can cause ulcers on the jeju- Cholecystolithiasis and Cholecystitis
nal side of the anastomosis. Anastomotic ulcers
can also arise from impairment of the anasto- Cholecystolithiasis and cholecystitis follow-
motic blood flow, as a foreign body reaction to the ing gastrectomy are caused by cholecystasis
sutures or staples, and in response to drugs such because of reduced secretion of cholecystoki-
as steroids and nonsteroidal anti-inflammatory nin (CCK) after eating as a result of rapid gas-
drugs (NSAIDs) [34]. tric emptying and by cholestasis resulting from
The condition presents with epigastric dis- dyskinesia of the Oddi muscle in response to
comfort, epigastric pain, heart burn, nausea, CCK. Hyposecretion of gastric juices and the
vomiting, hematemesis, and bloody stools. fact that food cannot pass through the duodenum
Anastomotic ulcers can be confirmed by endos- causes an increase in the bacterial flora in the
copy. Pharmacotherapy is the preferred treatment, duodenum, and biliary infection causes deposi-
with the administration of PPIs, H2-blockers, and tion of calcium bilirubinate, which promotes the
gastric mucosa protecting agents. In the event formation of stones. Cholecystolithiasis and cho-
of pharmacotherapy- refractory ulcers, surgical lecystitis are also caused by a decrease in gall-
treatment is considered, such as vagotomy and bladder contraction as a result of sectioning of the
additional resection of the gastric remnant. hepatic branch of the vagal nerve and dissection
around the hepatoduodenal ligament associated
with lymph node dissection. The gall stones that
Anastomotic Stenosis follow gastrectomy are most often black stones
or calcium bilirubinate stones. The incidence of
In total gastrectomy and proximal gastrectomy, cholecystolithiasis is reported to be 10–47% and
anastomotic stenosis often occurs when a circular more common in total gastrectomy than in distal
anastomosis device is used for esophagojejunal gastrectomy [36]. Cholecystolithiasis following
or esophagogastric anastomosis [35]. Although distal gastrectomy is considered common with
rare, anastomotic stenosis can also occur when RY and B-II reconstructions, but rare with B-I
a circular anastomosis device is used for distal and PPG reconstructions [28]. Generally, most
gastrectomy. Furthermore, anastomotic stenosis cases are asymptomatic and are often detected
tends to occur during the healing process when by chance through routine follow-up computed
anastomotic leakage occurs after surgery. It gen- tomography (CT) or ultrasound examinations. If
erally occurs 1–3 months after surgery. Many asymptomatic, patients may undergo follow-up
patients with stenosis at the lower end of the observations without treatment, but the condition
esophagus complain of difficulty in swallowing. can also be resolved sometimes by the adminis-
In the initial stage after onset, patients may expe- tration of choleretics. In the event of concurrent
rience difficulty with the intake of solid matter cholecystitis, antibacterial therapy is adminis-
and repeated saliva-like vomiting. Furthermore, tered, and percutaneous drainage or emergency
if the stenosis is severe, ingested matter may surgery is performed. For symptomatic cases,
be frequently vomited. Diagnosis is determined cholecystectomy is considered.
based on the observation of anastomotic steno- The safety of preventive cholecystectomy has
sis by endoscopy. Instances of membranous ste- been confirmed by a randomized controlled trial
nosis are often alleviated by endoscopic balloon [37]; however, the efficacy of the procedure has
dilatation. In general, the condition is cured after not been clarified.
the 2nd or 3rd dilatation, but anastomotic steno-
sis occurring after leakage is often refractory.
Surgical treatment is considered if no improve- Afferent Loop Syndrome
ment is observed after ten or more endoscopic
treatments, when the interval between treatments The condition encompassing afferent loop ste-
is short. nosis and obstruction as a result of torsion,
322 M. Terashima
bending, adhesion, internal hernia, and peri- intestines and ascites are observed, strangula-
toneal dissemination following B-II and RY tion is highly suspected.
reconstruction is referred to as afferent loop In mild cases, symptoms can be alleviated
syndrome. It causes pooling of duodenal juices, through fasting and fluid replacement only, but
including bile and pancreatic juices in the affer- if intestinal dilatation is severe or in the event of
ent loop, leading to complaints of postprandial repeated vomiting, an ileus tube is placed to drain
abdominal and back pain, with large amounts the contents of the intestines and reduce the pres-
of bilious vomiting observed. In the event of sure. If symptoms are not alleviated with conser-
complete obstruction, duodenal distention and vative treatment or in the event of recurrent ileus,
circulatory insufficiency cause gastrointestinal surgery is considered. When strangulation is sus-
perforation, peritonitis, and shock, requiring pected, emergency surgery is required. The stran-
emergency surgery [38]. gulation is removed immediately and blood flow
Diagnosis is easily determined on the basis of is restored, after which any necrotic intestine is
characteristic symptoms and if afferent loop dila- resected and reconstructed.
tation is observed on CT examination. Treatment
for mild cases includes follow-up observations
with dietary guidance and pharmacotherapy. Internal Hernia
However in the event of repeated onset, if pos-
sible, endoscopic dilatation of the site of stenosis With the popularization of laparoscopic surgery,
is attempted. If endoscopic treatment is not pos- its use has increased rapidly in recent years.
sible, strategies such as repeat surgery with anas- Internal hernia refers to the condition in which
tomosis of the Y limb, changing reconstruction the viscera penetrate the mesentery, the hiatus of
from B-II to RY, and additional Braun anastomo- the greater omentum, and the fossa, within the
sis are considered. abdominal cavity. The common sites of internal
hernia following gastrectomy include the small
intestinal mesenteric space produced with RY
Ileus reconstruction and Petersen’s defect (Fig. 27.1).
The incidence ranges from 0.1% to 2%, and the
Mechanical ileus often occurs late after surgery condition is more common with laparoscopic
and is classified into simple ileus and strangu- surgery than with open surgery. There is no
lated ileus. Causes include adhesions, bend- difference in incidence related to total gastrec-
ing, inflammation, tumor, hernia (mentioned tomy or distal gastrectomy. The risk factors for
below), intussusception, and volvulus. The internal hernia include laparoscopic surgery and
condition presents with abdominal pain, vom- weight loss following surgery [39]. The condi-
iting, and fever. On palpation, epigastric dis- tion presents with various symptoms, including
tention, with pressure pain, is often observed. abdominal pain, vomiting, and abdominal dis-
In the event of perforation, signs of peritoneal comfort, and strangulated hernia can develop
irritation and muscle guarding are observed. On suddenly during follow-up observation after
chest X-ray imaging, intestinal dilatation, with diagnosis of an unidentified complaint. In par-
the formation of air–fluid levels and gas in the ticular, hernias that develop in Petersen’s defect
small intestine, can be observed. Identification can cause extensive strangulation of the small
of the site of stenosis, assessment of the under- intestine, and due care should be exercised to
lying condition, and verification of the presence prevent postoperative short bowel syndrome.
or absence of strangulation can be performed Abdominal contrast-enhanced CT is useful for
by abdominal contrast-enhanced CT. In the diagnosis, which is determined upon the obser-
event that there is no contrast medium in the vation of a whirl sign, aggregate formation in
Evaluation of Postoperative QOL
To objectively evaluate a patient’s condition

following gastric resection, evaluation of
QOL according to patient-reported outcomes
as an objective tool is extremely important.
The methods of assessing QOL include global
scales [such as the Sickness Impact Profile
(SIP), Short-Form 36 (SF-36), and World
Health Organization Quality of Life-26 (WHO/
QOL26)], which evaluate the overall level of
health and how it affects daily life and social
life [40–42], and disease-specific scales [such
as the Gastrointestinal Symptom Rating Scale
(GSRS) and the European Organization for
Research and Treatment of Cancer Quality of
Life Questionnaire-C30 (EORTC QLQ-C 30)],
which evaluate the level of health and how it
affects daily life according to specific disease
symptoms [43, 44]. Other tools include pref-
erence scales [such as the EuroQol-5D (EQ-
5D) and the Health Utilities Index (HUI)] to
determine the utility value in terms of health
Fig. 27.1 Anatomic mapping of internal hernias. economics [45, 46]. The evaluation of QOL
Although the figure is for total gastrectomy followed by
retrocolic Roux-en-Y reconstruction, it serves to show the
following gastrectomy is generally performed
anatomic locations of internal hernias. (Reproduction combining a global scale and a disease-spe-
from [39] with permission) cific scale, with reports to date describing the
use of the SF-36 combined with the GSRS and
the EORTC-C30 combined with the European
the invaginated bowel loop, and abnormal mes- Organisation for Research and Treatment of
enteric vascular extension. Cancer Quality of Life Questionnaire-Stomach
Surgery is the only treatment option and (EORTC-STO22). However, these evaluation
includes laparotomy or laparoscopy to reposi- methods are not specific to conditions follow-
tion the intussusception and to close the hernia ing gastrectomy; therefore, it cannot be stated
orifice. When necrosis of the small intestine has that they always accurately reflect patients’
occurred because of strangulation, resection and conditions after gastrectomy. A QOL assess-
reconstruction, if possible, of the small intestine ment tool specific to patients’ conditions fol-
are required. lowing gastrectomy has been recently reported
To prevent internal hernia when performing in Japan. The Japanese Postgastrectomy
gastrectomy, closure of the mesenteric space Syndrome Working Party (JPGSWP) devel-
is considered effective, and the mesentery and oped a questionnaire consisting of 45 items
Petersen’s defect should be closed using non- in addition to 22 items uniquely devised by
absorbable sutures while performing surgery. surgeons, along with the SF-8 (8 items) and
However, as complete closure of Petersen’s the GSRS (15 items) [47] (Fig. 27.2). This
defect is difficult, it should be kept to the lower questionnaire was used to survey the QOL of
end of the transverse colon. 2368 patients who have undergone surgery for
324 M. Terashima
45 items of PGSAS Main outcome measures
Conventional 15 items Esophageal reflux SS

(GSRS) (intensity) Abdominal pain SS
MeaI-related distress SS Total symptom
Indigestion SS score
Original 8 items Diarrhea SS
Symptoms (intensity) Constipation SS
Dumping SS
2 items
(type & number
of dumping Sx)
Ingested amount of food per meal
Amount of meals
5 items
Necessity for additional food
Living status Quality of mealls

Quality of ingestion SS Consolidation
3 items
Selection
Social activity
1 item Ability for working Subscale
Dissatisfaction
Dissatisfaction for daily life SS
3 items
QOL
Conventional Physical component summary (PCS)
8 items
(SF-8) Mental component summary (MCS)
Change in body weight (%)
Fig. 27.2 The process of consolidation and selection to constitute main outcome measures of PGSAS45. (Reproduction
from [47] with permission)
gastric cancer as a multicenter collaborative 2. Ukleja A. Dumping syndrome: pathophysiology and
treatment. Nutr Clin Pract. 2005;20(5):517–25.
clinical trial. The results of the trial have been
3. Mine S, Sano T, Tsutsumi K, Murakami Y, Ehara K,
published as numerous articles; thus, the tool Saka M, Hara K, Fukagawa T, Udagawa H, Katai
has drawn attention as a means to objectively H. Large-scale investigation into dumping syndrome
evaluate QOL following gastrectomy [4, 15, after gastrectomy for gastric cancer. J Am Coll Surg.
2010;211(5):628–36. https://doi.org/10.1016/j.
17, 31]. In the future, the tool is expected to
jamcollsurg.2010.07.003.
be utilized as a means of evaluating QOL in a 4. Tanizawa Y, Tanabe K, Kawahira H, Fujita J,
prospective trial. Takiguchi N, Takahashi M, Ito Y, Mitsumori N,
Namikawa T, Oshio A, Nakada K, Japan postgastrec-
tomy syndrome working P. Specific features of dump-
Acknowledgment This work is supported in part by the ing syndrome after various types of gastrectomy as
Practical Research for Innovative Cancer Control assessed by a newly developed integrated question-
(#15ck0106043h0002) from Japan Agency for Medical naire, the PGSAS-45. Dig Surg. 2015;33(2):94–103.
Research and Development, AMED. https://doi.org/10.1159/000442217.
5. van der Kleij FG, Vecht J, Lamers CB, Masclee
AA. Diagnostic value of dumping provocation in
patients after gastric surgery. Scand J Gastroenterol.
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Follow-Up After Gastric Cancer
Treatment 28
Jimmy BY So and Guowei Kim
Introduction tice of follow-up after gastrectomy is weak [11],

with only retrospective studies and no RCTs to
The follow-up of patients who have undergone date. Despite this, many units actively investigate
surgical resection for gastric cancer is controver- patients in order to detect recurrences at an earlier
sial. Despite the fact that many clinicians perform and asymptomatic stage, in the hope that this will
postoperative follow-up or surveillance for these lead to improved outcomes. The lack of strong evi-
patients, there appears to be no clear consensus on dence for this begets some to question the use of
the utility or mode of surveillance in these patients. scarce resources in intensive follow-up [12].
This can partly be explained by a number of fac- There are four main reasons for follow-up:
tors (low rate of resectability, poor patient tolerance
for treatment, frequent postoperative morbidity 1. Post-surgical: To detect problems associated
and mortality after operation and an overall dis- with the operation
mal prognosis) [1–3] which have led to pessimism 2. Oncological: To detect and manage recurrent
when faced with recurrent gastric cancer [2]. disease
In colorectal cancer, national and interna- 3. Pastoral: To provide psychological and emo-
tional bodies such as the American Society of tional support
Clinical Oncology (ASCO), the Association of 4. Research: To collect outcome data
Coloproctology of Great Britain and Ireland and
the European Society of Medical Oncology have In this chapter, we shall delve into the lit-
issued guidelines on the follow-up of colorectal erature on recurrence patterns of gastric cancer,
cancer [4–7]. These guidelines are based on multi- predictive scoring for recurrence, metachronous
ple randomized controlled trials (RCTs) and meta- gastric cancer (gastric stump cancer), surveil-
analyses [8–10], some of which have demonstrated lance modalities, the impact of follow-up on
improved survival in patients undergoing intensive survival outcomes, the current guidelines and
follow-up. In contrast, the evidence for the prac- recommendations and what the future holds.
J. B. So (*) · G. Kim
Division of Surgical Oncology, National University
Cancer Institute of Singapore (NCIS), National
ecurrence Patterns of Gastric
R
University Health System, Singapore, Singapore Cancer
Department of Surgery, National University of
Singapore, Singapore, Singapore The recurrence rate of gastric cancer after resec-
e-mail: jimmyso@nus.edu.sg tion with curative intent is about 21–55% [2, 3,

https://doi.org/10.1007/978-3-662-45583-8_28
328 J. B. So and G.-W. Kim
13–20]. While this figure is discouraging, resection. Peritoneal recurrence is defined as cancer
tion for early gastric cancer can give recurrence recurrence in the abdominal cavity because
rates as low as 1.5–5.1% [2, 21–23]. In order to of intraperitoneal distribution. Hematogenous
rationalize follow-up for gastric cancer, an under- recurrence has been defined as any metastatic
standing of when, where and in whom recurrence lesion detected within distant organs [1, 2, 25].
occurs is needed. However, there are some variations in the defi-
nitions of type of recurrences in the literature,
especially with regard to recurrences in the dis-
Timing of Recurrence tant lymph nodes as well as peritoneal disease
in the tumour bed (locoregional versus perito-
The timing of recurrence in gastric cancer, like neal). These differences in semantics can pos-
in many gastrointestinal cancers, usually occurs sibly lead to differences in recurrence patterns
in the first 2 years after resection with curative among studies [14].
intent. Most studies report that 66.5–92% of Recurrences can occur at a single site or at
recurrences occur within 2 years [3, 13, 14, 16, multiple sites (locoregional/peritoneal, locore-
18, 20, 22] and the risk of recurrence seems to gional/hematogenous, peritoneal/hematog-
plateau after 2–3 years [2, 15, 24]. This suggests enous, locoregional/peritoneal/hematogenous).
that efforts should be concentrated on the first Recurrences occur at only one site in 50.2–83.7%
2 years after gastrectomy as this would be when of patients [2, 13–16, 22]. Conversely, at the time
most recurrences occur. of recurrence, 16.3–49.9% of patients will have
However, there seems to be a large variation of metastases in more than one site, which suggests
the timing of recurrences for specific subgroups that some effort should be made to actively look
of patients. In a study from Korea, 43.5%, 67.1% for other metastases in patients diagnosed with
and 85.6% of recurrences occurred within 2, 3 recurrence. This may translate to a change in
and 5 years, respectively, in patients who under- management strategy depending on the sites of
went curative resection for early gastric cancer recurrences.
[21]. This suggests that the follow-up of these Taking into account patients who have single
patients should necessarily be longer and differ- and multiple sites of recurrences, locoregional
ent from patients who undergo curative gastrec- recurrences occur in 11.2–63.3% of patients.
tomy for advanced gastric cancer. Peritoneal recurrences occur in 29–58% and hema-
Patients who have undergone partial gastrec- togenous recurrences occur in 13–51% of patients
tomy may develop metachronous gastric cancer of who suffer from recurrence [2, 3, 13–17]. The
the remnant gastric stump (stump cancer/remnant large variation in location of recurrences reflects
gastric cancer). This subgroup should be viewed the heterogeneity of gastric cancer with regard to
and managed as a separate entity from recurrence tumour biology, primary treatment as well as the
and is covered in more detail subsequently in this mode and timing of recurrence detection. Some
chapter (Surveillance Modalities, Endoscopy, studies have shown that the pattern of recurrence
Endoscopy After Partial Gastrectomy). depended on the timing of recurrence. Patients
with early recurrence (within 1 year) were more
likely to have hematogenous recurrence compared
Location of Recurrence with patients who had late recurrences, who were
more likely to have a locoregional recurrence [1,
Recurrence patterns of gastric cancer can be 15], though this finding was not seen consistently
classified into three broad groups: locoregional, in other studies [3, 26]. Patients with locoregional
peritoneal and hematogenous. Locoregional recurrence may have a longer median survival
recurrence is defined as cancer recurrence at the compared with patients who had hematogenous
resection margin, within the lymph nodes or in or peritoneal disease [17]. As locoregional recur-
the operation bed within the region of the resec- rence is seen more frequently in late recurrences,
28 Follow-Up After Gastric Cancer Treatment 329
survival after recurrence is also better in patients extent of lymphadenectomy, tumour location and
who suffer late recurrence as compared to early advanced age as independent predictors of recur-
recurrence [1, 3]. rence and was able to predict recurrences with
Recurrent gastric cancer is rarely amenable to a sensitivity of 83.5% and specificity of 81.1%
oncologic resection. Most studies report that less with an overall accuracy of 82.2%. This score has
than 20% of patients with recurrence received since been externally validated [19, 35], though it
surgery, of which complete resection of recur- is important to note that this score has only been
rence was possible in only a quarter of them [2, validated for Western populations.
27–29]. Of these recurrences, the most common
indications for resection were local recurrence in
the gastric stump. Other less common indications Surveillance Modalities
for resection were isolated small liver metastasis
and localized peritoneal metastasis [28]. Imaging
For recurrent disease not amenable to surgery,
chemotherapy has become the standard of care The ideal imaging modality must be able to detect
and is offered in the hope of improving survival various patterns of recurrence, namely locore-
and quality of life despite conflicting evidence gional, peritoneal and distant/hematogenous dis-
[12]. However, there is no evidence that initiating ease. Furthermore, the imaging used should have
chemotherapy at an earlier stage improves out- high specificity and sensitivity with low false-
comes [30, 31]. positive rates and low cost. Unfortunately, the
ability of imaging to detect recurrence is poor for
gastric cancer. While the use of imaging for the
Predictive Scoring for Recurrence detection of local recurrences and hepatic metas-
tasis can be fraught with inaccuracies [36], all
Many studies have tried to identify factors to pre- imaging are poor at detecting peritoneal disease,
dict recurrence after curative gastrectomy. Some which accounts for around 29–58% of recur-
factors that are associated with increased risk of rences. Barium enema has been used in the diag-
recurrence are [2, 15, 18, 21]: nosis of peritoneal carcinomatosis in colorectal
cancer [37], and this imaging has been used in
1 . Large tumour size (>3–4 cm) Japanese institutions to confirm the presence of
2.
Depth of tumour invasion (serosal peritoneal disease when clinically suspected [12].
involvement) Imaging in the search for asymptomatic recur-
3. Tumour subtype (poorly differentiated, dif-
rence is fraught with difficulties, missing many
fuse, signet ring, lymphovascular invasion, recurrences and producing a number of false-
perineural invasion) positive results. Changes in the anatomical struc-
4. Proximal or diffuse tumour location ture after gastric surgery can make it difficult to
5. Lymph node metastasis (high lymph node
diagnose recurrence accurately as well. Imaging
ratio) is perhaps more useful when a clinical recurrence
is suspected, such as in the face of rising tumour
While there are predictive scores and nomo- markers [12]. Overall, the ability to detect asymp-
grams in the literature with regard to prognosti- tomatic recurrences despite intensive follow-up
cating patients (disease-free survival and overall is poor, with the proportion of such recurrence
survival) after gastrectomy with curative intent detected varying from only 22% to 45% [30, 31].
[32–34], the Italian Research Group for Gastric
Cancer (GIRCG) has developed a score predic- Computed Tomography
tive of gastric cancer recurrence based on vari- Computed tomography is an essential tool for pre-
ables commonly used in clinical practice [18]. operative staging and follow-up of gastric cancer
This score utilizes nodal status, depth of invasion, [25]. Currently, CT is used most frequently and is
regarded as the most reliable method for assess- patterns of recurrence, such as local recurrence
ing cancer recurrence, with a reported accuracy involving the stomach remnant, regional lymph
of 60–70% [38]. Recurrences have been shown nodes, peritoneal dissemination, liver metastases
using CT imaging in 55–81.1% of patients with and remote metastases. PET is an advantageous
recurrence [21, 39]. imaging tool because it enables the evaluation of
Although CT is the primary tool for inves- the entire body at once, although PET has limita-
tigation of suspected recurrence because of its tions with a significant false-negative rate in early
widespread availability and relatively low cost, it cancer, signet-ring cell tumours and poorly dif-
often cannot help differentiate treatment-induced ferentiated histotypes. PET is useful when con-
morphologic changes from tumour recurrence ventional imaging is equivocal, as it can confirm
[40]. In addition, CT shows a low positive pre- the presence of true recurrence [46].
dictive value (60–70%) for peritoneal or distant 18F-fluorodeoxyglucose positron emission
lymph node metastasis [41, 42]. The ability of tomography/computed tomography (18F-FDG-
CT to primarily diagnose recurrence in the rem- PET/CT) scans represent a superior postoperative
nant stomach is also likely poor when extrapolat- surveillance modality for the diagnosis of recur-
ing its use in diagnosing primary gastric cancer, rent GC compared with other imaging modalities
and there is a direct trade-off between sensitivity as previously mentioned. An integrated PET/CT
and specificity. When the criterion for diagnosis scan provides fusion images, combining func-
was a gastric wall thickness of 2 cm or more in tional and anatomic imaging together. It may also
one study, sensitivity and specificity were only be helpful in optimizing the treatment strategy
50% and 88%, respectively. By reducing the cri- and may play an important role in individualized
terion to 1 cm, sensitivity increased to 100%, but treatment in the future. In one study, FDG-PET/
specificity dropped to only 36% [43]. Hence, its CT had a high impact on patients’ management
use is mainly limited to detecting hepatic and, to or care. Further diagnostic or treatment plans
a lesser extent, locoregional recurrences. were changed in 52.9% of patients. Suspected
recurrent lesions were accurately confirmed by
agnetic Resonance Imaging
M FDG-PET/CT in some patients; thereafter, they
and Endoscopic Ultrasound were treated with previously unplanned surgery
Magnetic resonance imaging has the obvious or recurrent chemotherapy. Abnormal diagnostic
benefit of having no exposure to ionizing radia- CT scans in another group of patients revealed
tion. It has high diagnostic accuracy in the evalu- lesions with physiological or inflammatory
ation of T staging of primary gastric cancer of uptake of FDG leading to cancellation of previ-
74% though N staging with MRI was only 47% ously planned diagnostic procedures and chemo-
accurate [44]. MRI and endoscopic ultrasound therapy [47].
(EUS) are both employed for GC staging, but 18F-FDG-PET/CT reportedly has very good
EUS is recognized to be the first-choice imag- sensitivity (89.7%) and specificity (85.7%) in
ing modality in locoregional staging compared detecting distant and local recurrences during
with MRI and CT and could affect the therapeu- postoperative follow-up. Positive 1 8F-FDG-PET/
tic management of these patients [45]. However, CT findings may lead to an early change in the
there is little data in support of the use of EUS or management of patients after radical gastrec-
MRI in the follow-up of patients after curative tomy, directing them towards rescue surgery or
resection for gastric cancer. chemoradiotherapy and therefore improving their
overall survival [48]. Despite this, PET/CT was
Positron Emission Tomography/ not as sensitive as contrast CT for detecting peri-
Computed Tomography toneal disease. Furthermore, the addition of PET/
In the detection of recurrence during follow-up CT on contrast CT did not increase diagnostic
after curative resection, positron emission tomog- accuracy in detection of recurrence in some stud-
raphy (PET) is often useful for detecting different ies [49].
Laparoscopy When considering endoscopy as part of routine

surveillance for patients who have undergone
Laparoscopy can provide more accurate informa- gastrectomy with curative intent, the evidence is
tion than that provided by conventional imaging even more scarce. One of the difficulties in jus-
methods [50]. Laparoscopy has been suggested to tifying routine endoscopic surveillance is due to
be a potential method for detecting minimal peri- the relatively low rates of true local recurrence,
toneal metastasis or recurrence because it not only with endoscopy being unable to detect regional,
allows visualization of the entire abdominal cav- peritoneal and hematogenous recurrences.
ity but can also provide a means to obtain tissue
and peritoneal fluid for pathologic confirmation. ndoscopy After Partial Gastrectomy
E
Although staging laparoscopy has primarily been The entity of remnant gastric cancer should also
conducted to avoid unnecessary laparotomy, for be considered here. Patients who have undergone
potentially curative surgery, it can also be used forinitial gastrectomy for early gastric cancer have
the detection of early-stage peritoneal recurrence cumulative prevalence rates of remnant gastric
in post-surgical patients with equivocal radiologic cancer of 2.4% at 5 years and 6.1% at 10 years
findings to clarify the diagnosis of recurrence. [57] with another study giving a 4% cumulative
A recent study [51] evaluated the feasibility and risk at 20 years post initial gastrectomy [58]. Other
accuracy of second-look laparoscopy for patients studies report incidences of remnant gastric can-
with gastric cancer at high risk of peritoneal recur-cer of 3.2–10% [59, 60]. Despite this, follow-up
rence after completion of 6 months of systemic endoscopy is still commonly performed and rec-
adjuvant chemotherapy. In this study, second-look ommended [57, 61]. The main reason for this is
laparoscopy was a safe and effective approach for because tumour recurrence in the remnant stom-
early reassessment of peritoneal disease for the ach after partial gastrectomy can be treated by an
selection of patients who needed further systemic additional total gastrectomy, and this may occa-
chemotherapy. In addition, a minimally invasive sionally result in long-term survival [29]. Patients
approach with laparoscopy may be an alternative with partial gastrectomy are usually identified
to the complicated second-look laparotomy [25]. as a high-risk gastric cancer group. The interval
Despite this, its role is still limited due to the rela-
between the preceding examination and diagnosis
tive invasiveness of laparoscopy as compared to was 22.5 months in patients with early gastric rem-
the other surveillance modalities. nant cancer, while it was 67.4 months in patients
with advanced cancer. It can therefore be postu-
lated that periodic surveillance endoscopies could
Endoscopy be performed at intervals of 2–3 years in order to
detect patients with early-stage disease [57]. The
Endoscopy, which is commonly used in clinical development of remnant gastric cancer after distal
practice, is a promising screening method for gastrectomy for gastric cancer usually occurs after
gastric cancer. Although gastric cancer screen- a mean interval of 8.3 years and is more frequently
ing has been actively performed in South Korea found away from the anastomosis and on the lesser
and Japan [52–54], endoscopic screening has curve [62–65], which lend further weight to the
been carried out as a national programme only in concept of long-term endoscopic surveillance in
Korea. It has been shown to reduce mortality by this group of patients. The caveat for this being
57% [54] with detection rates of gastric cancer that thus far, there is still no good quality prospec-
about 2.7–4.6 times higher than barium studies tive evidence that this approach would improve
or photofluorography [55]. In spite of this, cost- overall survival as well as be cost-effective.
effectiveness of endoscopy for a mass national
screening programme is still not conclusively Endoscopy After Total Gastrectomy
proven, though targeted screening for high-risk The role of follow-up endoscopy for patients
populations has shown positive results [56]. with gastric cancer who have undergone total
gastrectomy is even smaller, as there is no rem- 9.5%, 13.1% and 22.7%, respectively, suggesting
nant gastric mucosa. Moreover, unresectable dis- that endoscopic surveillance should probably be
tant recurrence is more common than locoregional performed beyond the previously recommended
recurrence after total gastrectomy [2]. One study 5 years [71].
from Korea reported that follow-up endoscopy With no established guidelines at present, it
may be useful in detecting early postoperative ste- would be prudent to consider initial early endos-
nosis as well as tumour recurrence in patients who copy within 6 months of endoscopic curative
had total gastrectomy for advanced gastric cancer resection, followed by yearly endoscopy for a
[66], though admitting that this did not translate to period of at least 10 years, if not indefinitely.
improved survival outcomes. Meanwhile, it would
be prudent to adopt a ‘scope when symptomatic’
approach to patients who have undergone total Tumour Markers
gastrectomy for gastric cancer.
Increased preoperative serum levels of carcino-
ndoscopy After Endoscopic Resection
E embryonic antigen (CEA), CA 19–9 and CA
The increase in detection rate of early gastric 72–4 are predictors of poor prognosis [72–76].
cancer together with the expanded indications CEA, one of the most commonly used serum
for endoscopic resection has resulted in many tumour markers in gastric cancer patients, is a
patients in high-prevalence countries undergo- glycoprotein with a molecular weight of 180
ing endoscopic resection for early gastric can- kD. Although CEA is of limited use in screening
cer. With appropriate patient selection, curative tests due to its low sensitivity and specificity in
resection rates in the literature for endoscopic early cancer, it is able to detect recurrence early
mucosal resection (EMR) and endoscopic sub- in colorectal cancer [77, 78] and is performed
mucosal dissection (ESD) are 61% and 74–95%, routinely postoperatively in many centres dur-
respectively [67]. This group of patients who ing follow-up. The serum level of CA 19–9,
have undergone curative endoscopic resection of an incomplete glycolipid antigen of the Lewis
early gastric cancer represent a distinctly differ- blood group, can be increased in benign con-
ent subgroup in whom post resection endoscopic ditions such as cholecystitis, obstructive jaun-
surveillance may play a larger role. Compared dice, cholangitis, cholelithiasis, liver cirrhosis
to gastrectomy, endoscopic treatment leaves the and acute pancreatitis and is also increased in
high-risk native stomach in place. As such, meta- colorectal, liver, ovarian, bile duct and gastric
chronous cancer can develop in 5–14% of patients cancer. CA 72–4 is a high molecular weight
who have undergone curative endoscopic resec- tumour-associated glycoprotein of 220–400 kD
tion for early gastric cancer [68–70]. The need that is recognized by the monoclonal antibody
for early endoscopic surveillance after endo- B72.3. CA 72–4 is known to be expressed in
scopic resection may be justified, as about 1.7% breast, colorectal, pancreatic, endometrial, lung
of patients who underwent ESD had synchronous and gastric cancer [79, 80].
gastric cancers which were missed by the initial Despite the prognostic value that these tumour
pre-resection endoscopic evaluation [69], lead- markers provide, the most important prognostic
ing to some centres recommending endoscopic factors of gastric cancer remain the depth of inva-
surveillance within 6 months after endoscopic sion and lymph node metastasis [81, 82], which
resection. Subsequent yearly endoscopies are has led to the shift in the use of CEA, CA 19–9
also recommended as the incidence rate of meta- and CA 72–4 in early detection of recurrence as
chronous cancers is around 3% [68, 69]. Another they have been reported to be elevated in patients
recent study reported 5-year, 7-year and 10-year with recurrence [83, 84]. Preoperative positivity
cumulative incidence functions of metachro- of CEA, CA 19–9 and CA72–4 was found to be
nous gastric cancer on surveillance endoscopy of 20.2–28.3%, 25–52% and 42.9–59%, respec-
tively [85–87], with sensitivity for recurrences of Follow-Up and Survival

44–65.8%, 55–56% and 51%, respectively [84,
88]. Sensitivities were significantly improved There is no high-level evidence supporting a rou-
when more than one tumour marker was used – tine follow-up schedule for curatively resected
85% when either/both CEA/CA 19–9 was ele- gastric cancer patients. All data are retrospective
vated post-surgery and 87% if one of CEA, CA and observational, thus preventing any definitive
19–9 and CA 72–4 was elevated post-surgery. conclusion [90].
When looking at early versus advanced gas- Most studies focused on the possible survival
tric cancer, the sensitivity of CEA, CA 19–9 and benefit of early detection of recurrence by inten-
CA 72–4 in early gastric cancer was 40.0, 5.6 and sive postoperative surveillance. Some studies
2.8%, respectively, and the specificity was 99.3, indicate that an intense postoperative follow-up
99.0 and 98.9%, respectively. In advanced gastric protocol was successful in identifying asymp-
cancer, the sensitivity of CEA, CA 19–9 and CA tomatic recurrences earlier than symptomatic
72–4 was 100.0, 68.2 and 51.3%, respectively, recurrences. Nevertheless, they could not achieve
and the specificity was 79.4, 80.0 and 81.3%, any evident advantage in overall survival [31, 91].
respectively. These data showed that the sensitiv- A study from Memorial Sloan-Kettering Cancer
ity and specificity of these tumour markers for Centre [92] showed that follow-up did not detect
recurrence in advanced gastric cancer were high asymptomatic recurrences earlier than symptom-
enough to be useful tests in the surveillance of atic recurrences in patients with gastric cancer
gastric cancer patients, although CA 19–9 and who underwent a curative gastrectomy. In this
CA 72–4 are less useful in the surveillance of report, patients with asymptomatic recurrences
early gastric cancer patients because of their low showed better post-recurrence and disease-
sensitivity and high false-positive rate (60%, specific survival than those with symptomatic
94.4% and 97.2% for CEA, CA 19–9 and CA recurrences. Similarly in a study from Korea
72–4, respectively) [89]. [38], median overall survival and post-recurrence
When looking at lead time, CEA was able to survival were worse for patients with a symp-
detect recurrence at a mean of 3.1 months ear- tomatic recurrence than for those with an asymp-
lier when comparing with imaging. The lead time tomatic recurrence. Furthermore, asymptomatic
for CA 19–9 was 2.2 months [84]. This lead time patients had more benefit from re-resection and
advantage was also seen in another study where post-recurrence chemotherapy; at multivariate
the average time between CEA, CA 19–9 and survival analysis, the presence of symptoms was
CA 72–4 positivity and recurrence was 4, 5 and the only independent factor of poor survival, sug-
4 months, respectively [88]. gesting a more biologically aggressive disease
Despite the apparent advantages in earlier in symptomatic patients. Another study from
recurrence detection, tumour markers have a Turkey [92] of 173 patients with recurrent gastric
number of disadvantages. Firstly, the use of cancer also found that symptomatic recurrence
tumour markers is mainly confined to patients is an important prognostic factor for post-recur-
with advanced gastric cancer. Secondly, the grim rence survival and that the presence of symptoms
prognosis and lack of good treatment options may be considered a marker of biologic tumour
for recurrent gastric cancer limit the usefulness aggressiveness, which is an important determi-
of detecting recurrences earlier, though this nant of survival at the time of recurrence diagno-
may change with new therapeutic strategies and sis during follow-up for gastric cancer.
agents. Thirdly, the high false-positive rates could A systematic review enrolling a total of 810
significantly increase patient anxiety, and com- patients did not find any evidence suggesting
bined with the lack of good therapeutic options, that postoperative surveillance has any overall
one would question the need to detect recurrences survival benefit; it also stressed that no studies
while the patient is still asymptomatic. addressed quality of life issues. Lead-time bias,
in which the observed prolonged survival is due 2. In the advanced disease setting, identification
to earlier detection of recurrence, rather than to of patients for second-line chemotherapy and
an effect on disease outcome, was mentioned as clinical trials requires regular follow-up to
a major limitation in these studies which showed detect symptoms of disease progression
significantly higher post-recurrence survival in before significant clinical deterioration.
the asymptomatic patients [11]. 3. If relapse/disease progression is suspected,

then a clinical history, physical examination
and directed blood tests should be carried out.
Other Primary Cancers Radiological investigations should be carried
out in patients who are candidates for further
One of the potential benefits of follow-up for chemo- or radiotherapy.
patients would be the possibility of detect-
ing extra-gastric cancers early. 2.6–11.2% of Guidelines from the Association of Upper
patients who have undergone curative resection Gastrointestinal Surgeons of Great Britain and
for early gastric cancer were found on follow- Ireland, the British Society of Gastroenterology
up to have other synchronous or metachronous and the British Association of Surgical Oncology
extra-gastric tumours (lung, colorectal, hepa- (2011) [95] as well as national guidelines from
tocellular carcinoma, head and neck, urologic, the Scottish Intercollegiate Guidelines Network
biliary, breast and hematologic malignancies) (SIGN) (2006) [96] and Korea [97] do not recom-
[21, 58]. mend any specific follow-up schedule.
The Charter Scaligero Consensus Conference
held in 2013 during the 10th International Gastric
Clinical Guidelines Cancer Congress (IGCC) of the International
and Recommendations Gastric Cancer Association recently published in
2016 the following six consensus statements [98]:
The National Comprehensive Cancer Network
Guidelines (2015) [93] recommend a follow-up 1. Routine follow-up should be offered to all
schedule involving a complete history and physi- patients.
cal examination every 3–6 months for 1–2 years, 2. Follow-up should be offered by members of
every 6–12 months for 3–5 years and annually the multidisciplinary team who performed the
thereafter. Complete blood count, chemistry initial diagnosis, staging and treatment,
profile, imaging studies or endoscopy are rec- including the gastroenterologist, the surgeon,
ommended only if clinically indicated, and mon- the medical and radiation oncologists and the
itoring and treatment for vitamin B12 and iron general practitioner.
deficiency should also be performed. 3. Follow-up of patients following curative treat-
The European Society for Medical Oncology ment of gastric cancer should be tailored to
(ESMO), the European Society of Surgical the individual patient, to the stage of their dis-
Oncology (ESSO) and the European Society ease and to the treatment options available in
of Radiotherapy and Oncology (ESTRO) clini- the event that recurrence is detected.
cal practice guidelines (2013) [94] which were 4. Physical examination rarely detects asymp-
endorsed by the Japanese Society of Medical tomatic recurrence of gastric cancer. A follow-
Oncology (JSMO) do not make any recommen- up
programme intended to detect
dations on follow-up schedule, instead suggest- asymptomatic recurrence should be based on
ing that: cross-sectional imaging. There is no evidence
that intensive cross-sectional imaging surveil-
1. Regular follow-up may allow investigation
lance of gastric patients is associated with
and treatment of symptoms, psychological improved long-term survival. However, as a
support and early detection of recurrence. matter of clinical care following curative
treatment of gastric cancer, it is reasonable to nurses) from the UK, 68% of time is spent on
prescribe periodic imaging at a frequency clinical matters, of which 48% is physical care
consistent with recurrence risk. The incre- and 32% psychological care. Not surprisingly,
mental value of screening for elevated levels 33% of the nurses’ time is given to telephone
of biochemical markers in addition to cross- advice and 34% spent in an outpatient setting.
sectional imaging remains undefined. The remaining time is spent on administration
5. Upper gastrointestinal tract endoscopy may (24%), research (2%) and education (3%) [101].
be used to detect local recurrence or meta- CNSs use ‘brokering’ skills, provide ‘clini-
chronous primary gastric cancer in patients cal rescue work’, advise on symptom control
who have undergone a subtotal gastrectomy. and support and negotiate care pathways, all of
True local recurrence is uncommon, but if which are intended to prevent adverse events,
present it may be considered for resection particularly readmission [101, 102]. The impact
with curative intent, especially in patients who of psychological care and tailored information
initially presented with early-stage disease. given in a supportive environment improves the
The cost-benefit ratio of endoscopic surveil- patients’ experience and health-related quality of
lance of the anastomosis and/or gastric rem- life [103].
nant remains undefined. The multidisciplinary team is central to patient
6. Routine screening for asymptomatic recur-
care, with CNSs having an integral role: consult-
rence of gastric cancer may be discontinued ing with medical, surgical and allied healthcare
after 5 years, as recurrence beyond that time is professionals in order to provide a coordinated
very rare. approach to care and enhancing quality of care
and patients’ well-being. Nurses also have access
to important information, particularly acting as
The Future the patient’s advocate, that may influence clinical
decisions, and it is therefore essential that MDTs
Nurse-Led Follow-Up listen to their views [104].
The importance of nurses in the follow-up of

patients after resection of gastric cancer can- ovel Prognostic and Therapeutic
N
not be underestimated, and this has been recog- Modalities
nized in recent guidelines [95]. New strategies
for patient follow-up are currently undergoing Presently, there is little a clinician can offer a
evaluation, including patient-led self-referral and patient with recurrent gastric cancer except pal-
services led by clinical nurse specialists (CNS). liative chemotherapy. Soon, biomedical research
The strategy of nurse follow-up after esophagec- will hopefully provide better prognostic and
tomy in the Netherlands has been shown to be therapeutic tools for metastatic cancer patients
both cost-effective and provides equal if not bet- and/or relapsing patients. One example would be
ter patient experience [99]. the development of nanostring-based multigene
CNS provision for UGI cancer particularly at assay to predict recurrence after surgery [105].
cancer units is still not well developed. The role Survivin-expressing circulating tumour
of the nurse includes clinical education, psycho- cells were recently shown to be an independent
logical support, research and consultation. The predictor for recurrence [106] and could be a
extent of the CNS role is difficult to measure good clinical biomarker for prognostication
because of the multifaceted nature of the work, [107]. Molecular approaches using real-time
complexity of the patient pathway and the more reverse transcription-polymerase chain reac-
specific requirement to respond to individual tion (RT-PCR) have made it possible to increase
patient needs [100, 101]. In a study of the work the sensitivity of detecting micrometastasis in
patterns of 463 CNSs (including gastrointestinal the peritoneal cavity, suggesting that multiplex
RT-PCR assay for CEA and CK-20 was highly evidence-based guidelines, follow-up of patients
sensitive for detection and might be useful for after treatment for gastric cancer must necessar-
prediction of peritoneal dissemination [108, 109]. ily be individualised and tailored to each patient’s
The vascular endothelial growth factor specific needs.
(VEGF) family is considered to be a major
inducer of angiogenesis and lymphangiogen-
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Part XVI
Neoadjuvant and Adjuvant Treatments for
Gastric Cancer
Neoadjuvant Treatment for Gastric
Cancer 29
Sook Ryun Park and Yoon-Koo Kang
Rationale of Neoadjuvant contrast, in East Asian countries such as Korea

Treatment and Japan, where relatively high curative resec-
tion rates are achieved and local tumor control
Although advances in surgical treatment have is adequate with standard D2 lymphadenectomy,
improved survival outcomes in patients with adjuvant chemotherapy is the main strategy
localized gastric cancer, the high recurrence adopted for curatively resected gastric cancer.
rates even after curative resection require a Neoadjuvant treatment for gastric cancer has
multimodal approach. In recent decades, sig- several potential advantages: (1) Preoperative
nificant progress has been made in the area of therapy could downsize or downstage tumors,
multidisciplinary treatments for gastric cancer. thus enhancing curative resectability; (2) neoad-
Of note, these multimodality multidisciplinary juvant systemic chemotherapy could reduce the
approaches have developed differently accord- incidence of systemic metastasis by eradicating
ing to geographical regions, which are differently undetectable micrometastasis at an early point
affected by disease incidences, clinicopathologi- in the disease course; (3) preoperative treat-
cal features, surgical techniques, and treatment ment could be administered with a higher likeli-
outcomes (e.g., curative resection rate, relapse hood of treatment completion than postoperative
patterns, and survival outcomes). Three different treatment because presurgical patients are more
multimodal approaches have been based on the likely to tolerate treatments due to good perfor-
timing of treatment relative to surgery: preop- mance, whereas postoperative therapy may be
erative (neoadjuvant), postoperative (adjuvant), not given in a timely manner and with adequate
and perioperative (neoadjuvant plus adjuvant) dose-intensity because of surgical complications;
treatment. The neoadjuvant approach has mainly and (4) treatment responses to neoadjuvant ther-
been pursued in Western countries where locally apy can be assessed clinically or pathologically,
advanced disease and gastroesophageal junction which could allow an early evaluation of thera-
(GEJ) or proximal gastric cancers are common, peutic effectiveness and prognostic information.
curative resection rates are relatively low, and
surgical outcomes remain suboptimal [1–4]. In
Neoadjuvant Chemotherapy
S. R. Park · Y.-K. Kang (*)
Department of Oncology, Asan Medical Center, Neoadjuvant chemotherapeutic strategies have
University of Ulsan College of Medicine, been investigated in the context of preop-
Seoul, Republic of Korea erative therapy alone or perioperative therapy
e-mail: ykkang@amc.seoul.kr

https://doi.org/10.1007/978-3-662-45583-8_29
344 S. R. Park and Y.-K. Kang
comprising combined pre- and postoperative in terms of OS (hazard ratio [HR], 0.84; 95%
chemotherapy. Two prospective randomized tri- confidence interval [CI], 0.52–1.35; P = 0.466)
als comparing neoadjuvant chemotherapy plus or progression-free survival (PFS) (HR, 0.76;
surgery with surgery alone were conducted in 95% CI, 0.49–1.16; P = 0.20). Only 62.5% of
patients with resectable gastric or GEJ can- patients assigned to the chemotherapy arm com-
cer [5, 6]. Unfortunately, these two trials were pleted the planned two treatment cycles, and
likely underpowered because of small sample most patients (>92% in both arms) underwent
sizes. A randomized study conducted by the extensive D2 lymphadenectomy, which might
Dutch Gastric Cancer Group compared four have diluted the contributions of neoadjuvant
cycles of neoadjuvant chemotherapy (5-fluoro- chemotherapy to the treatment outcomes.
uracil, leucovorin, doxorubicin, and methotrex- The randomized phase III study conducted by
ate [FAMTX] in a 4-week cycle) with surgery the Swiss Group for Clinical Cancer Research
alone in patients with resectable gastric can- (SAKK 43/99) compared neoadjuvant vs. adju-
cer (except T1) with the intent to demonstrate vant docetaxel/cisplatin/fluorouracil (TCF) in
improved curative resectability with neoad- patients with cT3–T4 anyN M0 or anyT cN1–
juvant chemotherapy [5]. However, this study N3 M0 gastric carcinomas that were staged
was terminated early after 59 patients were using endoscopic ultrasonography, computed
randomized because of slow accrual and poor tomography, bone scans, and laparoscopy [7,
interim results. Notably, 44% of patients in 8]. Four cycles of chemotherapy were admin-
the neoadjuvant arm were unable to complete istered in a 3-week cycle either before or after
all four cycles because of disease progression gastrectomy. This study was also prematurely
(26%) or chemotherapy toxicity (18%). The terminated because of slow accrual, and only 69
results demonstrated that neoadjuvant chemo- patients were randomized. Ninety percent of the
therapy did not increase the curative resection patients underwent D2 or greater lymphadenec-
rate (67% in the neoadjuvant arm vs. 66% in tomy, and the incidences of surgical morbidity
the surgery alone arm) or 5-year overall sur- (28.5% for neoadjuvant therapy vs. 25.7% for
vival (OS) rate (21% vs. 34%, respectively; adjuvant therapy; P = 0.86) and mortality (0%
P = 0.17). Another randomized study, European vs. 5.7%, respectively) were similar between the
Organisation for Research and Treatment of groups. The neoadjuvant chemotherapy group
Cancer (EORTC) 40954, compared two cycles exhibited better treatment compliance (median
of neoadjuvant chemotherapy (biweekly cispla- number of cycles, four vs. three, P < 0.01; four-
tin, weekly folinic acid, and infusional fluoro- cycle completion rate, 76% vs. 38%), com-
uracil in a 7-week cycle) with surgery alone in pared with the adjuvant chemotherapy group.
patients with locally advanced (stages III and Although neoadjuvant chemotherapy resulted
IV[cM0]) adenocarcinoma of the stomach and in pathologic complete responses (pCRs; 12%)
GEJ [6]. Although this trial was also termi- and partial responses (53%), it neither increased
nated prematurely for poor accrual after 114 the curative R0 resection rate (85% for neoadju-
patients were randomized, the neoadjuvant che- vant therapy vs. 91% for adjuvant therapy) nor
motherapy arm had a higher R0 curative resec- decreased the pathologic stage (stage I/II, 9%
tion rate (81.9% vs. 66.7%; P = 0.036) and for both groups). Furthermore, there were no
lower lymph node metastases rate (61.4% vs. differences in event-free survival (EFS) (5-year
76.5%; P = 0.018) than did the surgery alone EFS, 44.1% for neoadjuvant therapy vs. 43.5%
arm. However, neoadjuvant chemotherapy was for adjuvant therapy; HR, 0.79; 95% CI, 0.43–
associated with a higher postoperative compli- 1.45; P = 0.5) or OS (5-year OS; 47% vs. 46%,
cation rate (27.1% vs. 16.2%; P = 0.09) than respectively; P = 0.5) between the treatment
surgery alone and failed to demonstrate benefits groups.
29 Neoadjuvant Treatment for Gastric Cancer 345
Perioperative Chemotherapy Another French phase III randomized study

conducted by the Fédération Nationale des
Two randomized phase III trials were conducted in Centres de Lutte Contre le Cancer (FNCLCC)/
Western countries to evaluate the impact of peri- Fédération Francophone de Cancérologie
operative chemotherapy before and after surgery Digestive (FFCD) (FNCLCC/FFCD 9703) con-
for resectable gastric, GEJ, or esophageal adeno- firmed the survival benefits of perioperative
carcinoma [9, 10]. The United Kingdom Medical chemotherapy in patients with resectable gastric
Research Council Adjuvant Gastric Infusional cancer [10]. A total of 224 patients with adeno-
Chemotherapy (MAGIC) trial was the first large- carcinoma of the stomach (25%), GEJ (64%),
scale randomized controlled study to demonstrate or distal esophagus (11%) were randomized to
survival benefits of perioperative chemotherapy in receive surgery plus perioperative chemotherapy
gastric or GEJ cancer [9]. A total of 503 patients (cisplatin plus 5-fluorouracil [CF] in a 4-week
with adenocarcinoma of the stomach (74% of cycle comprising 2 or 3 preoperative cycles and
patients), GEJ (15%), or distal esophagus (11%) 3 or 4 postoperative cycles for a total of 6 cycles)
were randomized to receive surgery plus periop- or surgery alone. The patient inclusion criterion
erative chemotherapy (three cycles each of epiru- was a disease suitable for curative resection as
bicin/cisplatin/continuously infused 5-fluorouracil evaluated by endoscopy, barium meal study,
[ECF] in a 3-week cycle before and after surgery) abdominal and thoracic computed tomogra-
or surgery alone. Patients were required to have phy, and optional endoscopic ultrasonography.
resectable stage II or higher disease as determined Surgery was performed in 96.5% of patients in
by computed tomography, chest radiography, the chemotherapy group and 99% in the surgery-
ultrasonography, or laparoscopy. Surgery was per- alone group. Similar to the MAGIC trial, sig-
formed in 91.6% of patients in the chemotherapy nificant improvements in disease-free survival
group and 96.4% of patients in the surgery-alone (DFS) (5-year DFS, 34% vs. 19%; HR, 0.65;
group. Although the curative resection rate did 95% CI, 0.48–0.89; P = 0.003) and OS (5-year
not differ between the treatment groups (69.3% in OS, 38% vs. 24%; HR, 0.69; 95% CI, 0.50–0.95;
the chemotherapy group vs. 66.4% in the surgery P = 0.02) were observed in the perioperative che-
group), the perioperative chemotherapy group motherapy group, compared to the surgery-alone
exhibited a significant improvement in PFS (HR, group. Furthermore, the perioperative chemo-
0.66; 95% CI, 0.53–0.81; P < 0.001) and OS (HR, therapy group had a significantly higher cura-
0.75; 95% CI, 0.60–0.93; 5-year OS 36.3% vs. tive resection rate (87% vs. 74%; P = 0.04) and
23.0%; P = 0.009). The perioperative chemother- a trend toward a reduced lymph node metastasis
apy group also had lower rates of local recurrence rate according to surgical pathology (N+, 67%
(14.4% vs. 20.6%) and distant metastases (24.4% vs. 80%; P = 0.054) than did the surgery alone
vs. 36.8%) than did the surgery alone group. In group; however, the pathologic T-stage distri-
addition, the perioperative chemotherapy group bution did not significantly differ between the
had a significantly smaller resected tumor size groups (T0–T2, 42% in the chemotherapy group
(the median maximum diameter, 3 cm vs. 5 cm, vs. 32% in the surgery alone group; P = 0.17).
P < 0.001) and lower pathologic stage (T1/T2, Distant metastasis occurred less frequently in the
51.7% vs. 36.8%, P = 0.002; N0/N1, 84.4% vs. chemotherapy group than in the surgery-alone
70.5%, P = 0.01). Of note, the incidence of postop- group (43% vs. 56%), although the locoregional
erative complications (45.7% in the chemotherapy recurrence rates were similar (25% vs. 26%). The
group and 45.3% in the surgery group), mortality incidences of postoperative morbidity (25.7% in
rate within 30 days (5.6% and 5.9%, respectively), the chemotherapy group vs. 19.1% in the surgery
and median hospital stay (13 days in both groups) group; P = 0.24) and 30-day mortality (4.6% vs.
were similar in the two groups. 4.5%, respectively; P = 0.76) were also similar.
Based on the survival benefits demonstrated contrasted to the low rates of locoregional recur-
in the MAGIC and FNCLCC/FFCD 9703 trials, rence (<10%) in Korea and Japan, where D2
perioperative chemotherapy was established as a lymphadenectomy is routinely performed [15,
standard treatment for resectable gastric cancer in 16]. Another surgical issue involved the rate of
Western countries. The National Comprehensive curative resection in patients considered to have
Cancer Network guidelines recommend periop- potentially resectable gastric cancer during pre-
erative chemotherapy plus surgery in patients operative staging. Although this rate was reported
with clinically T2 or higher, potentially resect- to be approximately 90% in Eastern series [17,
able gastric cancer, although postoperative 18], only 66.4% and 74% of patients who under-
chemotherapy or chemoradiation is also recom- went surgery alone in the MAGIC and FNCLCC/
mended if patients underwent R0 resection with- FFCD 9703 trials, respectively, were able to
out preoperative therapy (version 3. 2015, http:// undergo curative resection [9, 10]. Besides dif-
www.nccn.org/professionals/physician_gls/pdf/ ferences in surgical techniques, this discrepancy
gastric.pdf). According to the American College is likely associated with the higher proportion of
of Surgeons National Cancer Database, the use advanced stage cases at presentation in Western
of neoadjuvant chemotherapy increased over countries, as the curative resection rate decreased
time in the United States, from 25.9% in 2003 to significantly as the clinical T stage (T1, 99.6%;
46.3% in 2012 [11]. A survey of curative treat- T2, 96.1%; T3, 75.3%; T4, 46.3%; P < 0.001) and
ment provided for 4668 resectable esophagogas- N stage (N0, 96.1%; N1–N2, 82.1%; P < 0.001)
tric cancer cases in 5 European countries during increased, according to the sixth edition of the
the period of 2011–2012 revealed neoadjuvant American Joint Committee on Cancer (AJCC)
chemotherapy administration rates that ranged staging system [17]. In addition, the 5-year OS
from 22% to 51% [12]. rates following surgery alone in both the MAGIC
However, despite the proven survival benefits (23.0%) and FNCLCC/FFCD 9703 studies (24%)
of perioperative chemotherapy, this approach was were much lower than those reported for Eastern
not accepted as a standard therapy in East Asian studies (61.1–69%), despite considering the dif-
countries such as Korea and Japan because of ferent clinical setting; specifically potentially
criticisms regarding the MAGIC and FNCLCC/ resectable disease was evaluated in the MAGIC
FFCD 9703 trials. First, an issue of surgical and FNCLCC/FFCD 9703 studies, whereas cura-
quality, particularly the extent of lymphadenec- tively resected disease was evaluated in Eastern
tomy, was raised. After a long period of debate, studies [9, 10, 15, 16]. Although the MAGIC and
D2 lymphadenectomy was established as the FNCLCC/FFCD 9703 trials both included pre-
standard surgical procedure in both Eastern and and postoperative chemotherapy, postoperative
Western countries based on its survival benefit therapy was poorly administered, in contrast to
relative to limited dissection, when applied in preoperative therapy. Among patients assigned
experienced centers [13, 14]. Although both the to the chemotherapy group, preoperative che-
MAGIC and FNCLCC/FFCD 9703 trials recom- motherapy was completed as planned in 86.0%
mended D2 lymphadenectomy as the protocol (MAGIC) and 86.7% of patients (FNCLCC/
treatment, this procedure was performed only FFCD 9703), whereas postoperative chemo-
in 41.4% of patients who underwent surgery therapy was initiated in only 54.8% (MAGIC)
in the MAGIC study and 61.9% of gastric can- and 47.8% of patients (FNCLCC/FFCD 9703),
cer patients in the FNCLCC/FFCD 9703 study resulting in a poor six-cycle perioperative chemo-
[9, 10]. This limited D2 lymphadenectomy rate therapy completion rate (approximately 40%) in
might have partly contributed to the relatively both trials [9, 10]. Moreover, both studies faced
high rates of locoregional recurrence with sur- the challenge of disease heterogeneity, as the
gery alone in these trials (20.6% in the MAGIC cases comprised gastric, GEJ, and distal esopha-
and 26% in the FNCLCC/FFCD 9703), which geal adenocarcinoma. The trials were originally
designed to recruit only gastric adenocarci- tive therapy (89% and 88% of patients, respec-
noma (MAGIC) or distal esophagus/GEJ cancer tively) and three cycles of postoperative therapy
(FNCLCC/FFCD 9703) but were extended to (73% and 77% of patients, respectively). The
include tumors of the distal esophagus/GEJ and addition of bevacizumab to the perioperative che-
stomach, respectively, because of issues related motherapy regimen did not improve OS (median,
to timely recruitment. Lastly, both trials encoun- 33.97 months with ECX vs. 34.46 with ECX-
tered challenges regarding pretreatment clinical B; HR, 1.067; P = 0.4784), DFS (HR, 1.006;
staging. The inaccuracy of preoperative staging P = 0.9425), or PFS (HR, 1.026; P = 0.7683).
before neoadjuvant therapy, a consequence of There were also no differences in the R0 resec-
the lack of sufficiently r eliable staging methods, tion (75% with ECX vs. 76% with ECX-B), clini-
may lead to unnecessary preoperative treatment cal response (42% vs. 40%, respectively), and
in patients with clinically overestimated tumors. pCR rates (8% vs. 10%, respectively). Although
In addition, the clinical stage, which might reflect the addition of bevacizumab did not increase the
the tumor burden and prognosis, was not strati- toxicity attributed to chemotherapy (grade ≥3
fied at the time of randomization [17]. toxicity, 47% with ECX vs. 50% with ECX-B
Recent clinical trials have explored approaches during preoperative chemotherapy and 49% vs.
toward improving perioperative chemotherapy 54%, respectively, during postoperative chemo-
for resectable gastric cancer. A German random- therapy), preoperative bevacizumab adminis-
ized phase II/III study (AIO-sto-0210 FLOT4) is tration was associated with an increased risk of
currently comparing a perioperative triplet regi- postoperative anastomotic leak (9% with ECX
men comprising fluorouracil, leucovorin, oxali- vs. 18% with ECX-B), particularly in patients
platin, and docetaxel (FLOT; four cycles each in who underwent esophagogastrectomy (9% vs.
a 2-week cycle both pre- and postsurgery) with 23%, respectively).
perioperative ECF (or capecitabine [X] instead of In East Asia, an approach involving the addi-
fluorouracil; three cycles each in a 3-week cycle tion of preoperative chemotherapy to adjuvant
pre- and postsurgery) for cT2–T4 anyN M0 or chemotherapy in the setting of D2 surgery was
anyT N + M0 resectable gastric or GEJ adeno- evaluated in a randomized study of 107 locally
carcinoma (NCT01216644). Phase II of this advanced gastric cancer patients with decreased
study, which included 127 patients with gastric mobility on upper gastrointestinal series and/
cancer (47.9%) and 138 patients with GEJ cancer or pancreas invasion on computed tomography
(52.1%) and designated pCR rate as the primary scans who were randomized to receive two or
endpoint, demonstrated a significantly higher three cycles of neoadjuvant chemotherapy (cis-
pCR rate in the FLOT arm than in the ECF(X) platin, etoposide, and 5-fluorouracil [PEF] in
arm (15.6% vs. 5.8%; P = 0.015) [19]. a 3-week cycle; CS arm) or upfront surgery (S
A randomized phase II/III United Kingdom arm). In both arms, adjuvant chemotherapy with
Medical Research Council MAGIC-B/ST03 three to six cycles of PEF was administered
study compared perioperative epirubicin, cispla- according to the postoperative stage (three cycles
tin, and capecitabine (ECX, each three cycles, for curatively resected cases and six cycles for
pre- and postsurgery) with or without bevaci- not curatively resected cases) [21]. Although
zumab (B), a monoclonal antibody that targets the CS arm had a higher curative resection rate
vascular endothelial growth factor A, in 1063 (81% vs. 61%; P = 0.03) and greater pathologic
patients with resectable stage Ib–IV(M0) adeno- downstaging (CS arm vs. S arm; stages 0 and 4
carcinoma of the lower esophagus (14%), GEJ vs. 0; IA, 1 vs. 0; IB, 3 vs. 0; II, 6 vs. 9; IIIA, 14
(51%), or stomach (36%) [20]. All six periop- vs. 10; IIIB, 9 vs. 12; IV, 10 vs. 23; P = 0.035)
erative chemotherapy cycles were completed by than did the S arm, there was no significant dif-
40% of patients in the ECX arm and 37% in the ference in OS between the two arms (median,
ECX-B arm, including three cycles of preopera- 33 months vs. 32 months; P = 0.42). These results
contrasted with the survival benefits obtained resectable cT2–T3/N+ or T4/anyN gastric or GEJ
from perioperative chemotherapy vs. surgery adenocarcinoma are randomized to receive pre-
alone in the MAGIC and FNCLCC/FFCD 9703 operative docetaxel/oxaliplatin/S-1 followed by
trials. However, considering the small sample D2 surgery and postoperative S-1 or surgery fol-
size and inclusion of only locally advanced cases lowed by postoperative S-1 [22, 23]. In addition,
in the East Asian study, the effect of neoadjuvant ongoing Chinese phase III studies are comparing
chemotherapy on resectable gastric cancer in perioperative chemotherapy vs. adjuvant chemo-
the setting of D2 surgery followed by standard therapy using various chemotherapy regimens or
adjuvant chemotherapy remains to be eluci- different chemotherapy regimens in a periopera-
dated. Large-scale phase III trials are currently tive setting (Table 29.1).
in progress to clarify this issue. In the Korean Although the MAGIC-B/ST03 study failed
PRODIGY study (NCT01515748), patients with to demonstrate a benefit of bevacizumab, active
Table 29.1 Representative ongoing randomized phase III studies of neoadjuvant or perioperative chemo(radio)therapy
in resectable localized gastric cancer
ClinicalTrials.gov
identifier (study Primary
name) Country Stage Treatment No. endpoint
Chemotherapy
NCT01216644 Germany cT2–T4 or N+ M0 Perioperative FLOT 714 OS
Resectable gastric
or GEJ
adenocarcinoma
Perioperative ECF(X)
NCT01364376 China Locally advanced Perioperative SOX 583 OS
(FOCUS) gastric cancer with
invasion or
penetration of
serosa
Perioperative FOLFOX
NCT01515748 Korea cT2–T3/N + M0, Preoperative DOS → D2 surgery → 530 PFS
(PRODIGY) T4/anyN M0, postoperative S-1
resectable gastric or
GEJ
adenocarcinoma
D2 surgery → postoperative S-1
NCT01516944 China Resectable cT3–T4/ Perioperative SOX 729 DFS
NxM0 gastric or
GEJ
adenocarcinoma
Perioperative XELOX
Postoperative SOX
NCT01534546 China Potentially Preoperative SOX → D2 surgery → 1059 DFS
resectable postoperative SOX five cycles then
T4N + M0 S-1 three cycles
D2 surgery → postoperative SOX
eight cycles
D2 surgery → postoperative XELOX
eight cycles
NCT01583361 China Stage II/III gastric Preoperative SOX → D2 surgery → 772 DFS
(RESONANCE) or GEJ postoperative SOX
adenocarcinoma
Table 29.1 (continued)
ClinicalTrials.gov
identifier (study Primary
name) Country Stage Treatment No. endpoint
D2 surgery → postoperative SOX
NCT02512380 China cT3–T4 anyN M0 Preoperative DOS → surgery → 380 OS
resectable gastric postoperative SOX
cancer or GEJ
adenocarcinoma
Preoperative SOX → surgery →
postoperative SOX
NCT02555358 China Stage III resectable Preoperative DOX → surgery → 300 pCR
gastric cancer postoperative XELOX
Preoperative XELOX → surgery →
postoperative XELOX
Surgery → postoperative XELOX
NCT02581462 Germany cT2 anyN M0 or Perioperative FLOT + trastuzumab + 404 PFS
(PETRARCA) anyT N + M0, pertuzumab
HER2+ gastric or
GEJ
adenocarcinoma
Perioperative FLOT
Chemoradiotherapy
NCT00407186 Netherlands Stage Ib–IV(M0) Preoperative ECX → D1+ surgery → 788 OS
(CRITICS) resectable gastric postoperative CRT (45 Gy, XP)
cancer
Perioperative ECX
NCT01924819 Australia/ Stage IB (T1 N1)– Preoperative CRT (induction ECF(X), 752 OS
(TOPGEAR) New IIIC (T3–T4 and/or 45 Gy, 5-FU) → D1+ surgery →
Zealand N+) resectable postoperative ECF(X)
gastric or GEJ
cancer
Perioperative ECF(X)
NCT01815853 China cT4 anyN M0 Preoperative CRT (45 Gy, 620 OS
localized gastric XELOX) + surgery + postoperative
cancer XELOX
Preoperative
XELOX + surgery + postoperative
XELOX
NCT02193594 China cT3–T4NxM0 Preoperative CCRT (50 Gy, 214 OS
SOX) + D2 surgery + postoperative
SOX
D2 surgery + postoperative SOX
GEJ gastroesophageal junction, FLOT fluorouracil/leucovorin/oxaliplatin/docetaxel, OS overall survival, ECF epirubi-
cin/cisplatin/fluorouracil, X capecitabine, SOX S-1/oxaliplatin, FOLFOX fluorouracil/leucovorin/oxaliplatin, DOS
docetaxel/oxaliplatin/S-1, PFS progression-free survival, DFS disease-free survival, XELOX capecitabine/oxaliplatin,
DOX docetaxel/oxaliplatin/capecitabine, pCR pathologic complete response, ECX epirubicin/cisplatin/capecitabine, XP
capecitabine/cisplatin, 5-FU 5-fluorouracil
investigation of molecular targeted agents aims tested as perioperative treatments in an EORTC/

to improve perioperative therapies for gastric Korean Cancer Study Group (KCSG) random-
cancer. The monoclonal antibodies, trastuzumab ized phase II study of stage Ib–III resectable
and pertuzumab, which inhibit human epider- HER2-positive gastric or GEJ adenocarcinoma
mal growth factor receptor 2 (HER2), are being (INNOVATION; NCT02205047). In that study,
patients are randomized to receive perioperative and colleagues reported the results of two cycles
chemotherapy (three cycles each of cisplatin plus of induction chemotherapy (infusion fluoroura-
capecitabine or 5-fluorouracil in a 3-week cycle cil, bolus leucovorin, and cisplatin in a 4-week
pre- and postsurgery) vs. perioperative chemo- cycle) plus preoperative chemoradiation (45 Gy
therapy plus trastuzumab vs. perioperative che- of radiation with continuous fluorouracil over
motherapy plus trastuzumab with pertuzumab. 5 weeks) in 33 patients with resectable cT2–
The major pathologic response rate (<10% vital T3 anyN M0 or T1N1M0 gastric cancer [25].
tumor cells) has been defined as the primary end- In that study, 85% of patients underwent sur-
point. In addition, a German phase II/III study is gery, with an R0 resection rate of 70% and pCR
planning to enroll patients with HER2+ gastric rate of 30%. The median OS was 33.7 months,
or GEJ adenocarcinoma (cT2 anyN M0 or anyT and patients achieving a pathologic response
N+ M0) who are randomized to receive periop- had a significantly longer median survival
erative FLOT plus trastuzumab with pertuzumab than did those without a pathologic response
or perioperative FLOT alone (PETRARCA; (63.9 months vs. 12.6 months; P = 0.03). Two
NCT02581462). treatment-related deaths occurred during che-
motherapy and within 30 days of surgery. In the
RTOG 9904 study, patients with resectable cT2–
Neoadjuvant Chemoradiotherapy T3 anyN M0 or T1N1M0 gastric or GEJ adeno-
carcinoma received up to two cycles of induction
Neoadjuvant chemoradiation has not been as well chemotherapy (cisplatin plus continuous infu-
studied or as frequently adopted for gastric cancer sion fluorouracil in a 4-week cycle) followed by
treatment as for esophageal and GEJ cancer treat- chemoradiotherapy (45 Gy of radiation with con-
ment. A German phase III study (Preoperative tinuous infusion fluorouracil plus weekly pacli-
Chemotherapy or Radiochemotherapy in taxel for 5 weeks) [26]. Among the 43 assessable
Esophagogastric Adenocarcinoma Trial, POET) patients, 39 (91%) received 2 cycles of induc-
compared neoadjuvant chemoradiotherapy with tion chemotherapy and all underwent concurrent
chemotherapy in patients with cT3–T4NxM0 chemoradiotherapy. Thirty-six patients (83%)
adenocarcinoma of the GEJ [24]. A total of 119 underwent surgery; R0 resection was achieved
eligible patients (Siewert’s classification type I: in 63% and pCR in 26%. Although the median
55%, type II/III: 45%) were randomly assigned OS of all 43 patients was 23.2 months, the 1-year
to induction chemotherapy (two cycles of cis- OS rate was better among patients who achieved
platin/leucovorin/fluorouracil in a 6-week cycle) pCR (82%) than among those with less than a
followed by either concurrent chemoradiother- pCR (69%). Although toxicities were considered
apy (30 Gy of radiation with cisplatin/etoposide acceptable, with a grade 4 event incidence of
over 3 weeks) and surgery or chemotherapy only 21%, performing radiotherapy and surgery with-
(2.5 cycles of cisplatin/leucovorin/fluorouracil in out unacceptable variations was possible in only
a 6-week cycle) followed by surgery. Although 35% of patients.
the study suggested a trend toward improved sur- The feasibilities of pre- and postoperative
vival with chemoradiation compared to that with chemoradiotherapy were compared in two paral-
chemotherapy (3-year OS, 47.4% vs. 27.7%; HR, lel phase II studies of resectable gastric cancer
0.67, 95% CI, 0.41–1.07; P = 0.07), along with (FFCD 0308) [27]. Chemoradiotherapy com-
a higher pCR rate (15.6% vs. 2.0%; P = 0.03) prised four cycles of 5-fluorouracil/leucovorin/
or ypN0 rate (64.4% vs. 36.7%; P = 0.01) and irinotecan, followed by concurrent continuous
similar R0 resection rate (71.5% vs. 69.5%), the fluorouracil infusion and radiotherapy over a
power was inadequate because of low accrual. 5-week period (50 Gy in the preoperative study,
In gastric cancer, single-arm phase II studies 45 Gy in the postoperative study). Although
have yielded encouraging R0 resection and pCR patients in the preoperative chemoradiotherapy
rates with preoperative chemoradiotherapy. Ajani study had a higher rate of therapeutic sequence
completion than did those in the postoperative Conclusions

chemoradiotherapy study (73.8% [31/42] vs.
42.9% [9/21]), the primary endpoint of an 88% Recent decades have seen substantial advances
completion rate was not achieved. in the treatment of localized gastric cancer. A
Currently, an international randomized phase multidisciplinary approach has been established
II/III EORTC study (Trial of Preoperative as the standard of care for resectable gastric can-
Therapy for Gastric and Esophagogastric Junction cer, although this has developed to include dif-
Adenocarcinoma, TOPGEAR; NCT01924819) ferent strategies among geographical regions.
is comparing preoperative chemoradiotherapy Although neoadjuvant treatment was adopted
and preoperative chemotherapy, in combination early in Western countries, it remains under
with postoperative chemotherapy for resectable investigation in the setting of extensive D2 sur-
gastric cancer. In this trial, patients with stage gery in East Asian countries. Ongoing clinical
IB (T1 N1)–IIIC (T3–T4 and/or N+) resectable trials to evaluate the best chemotherapy and/or
gastric or GEJ cancer are randomized to receive radiotherapy regimen or sequence and the use
preoperative chemoradiotherapy (two cycles of of or molecular targeted agents will help us to
ECF(X) followed by 45 Gy of radiation given further refine neoadjuvant treatment in the con-
concurrently with fluorouracil) plus postopera- text of a multidisciplinary strategy for localized
tive chemotherapy (three cycles of ECF(X)) or gastric cancer.
perioperative chemotherapy (three cycles of
ECF(X) pre- and postsurgery). The interim anal-
ysis of phase II of this study indicated that preop- References
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Adjuvant Treatment for Gastric
Cancer 30
Do-Youn Oh and Yung-Jue Bang
Surgical technique is the most important factor This chapter will cover the role of adjuvant
for patients’ long-term outcome. There has been chemotherapy compared with surgery alone in
a long debate about the extent of lymph node especially D2-resected gastric cancer.
dissection between Asian surgeons and Western
surgeons. Japanese and Korean surgeons believe
that wider lymph node dissection, e.g., D2 dis- Meta-analysis of Adjuvant
section, is necessary for the better outcome. On Chemotherapy in Gastric Cancer
the other hand, Western surgeons insisted that
there is no evidence for the benefit of D2 dissec- Before the availability of phase III clinical trials
tion over less lymph node dissection, e.g., D1 demonstrating the role of adjuvant chemother-
dissection, based on the negative results of two apy after curative resection of gastric cancer, the
European studies. MRC ST01 trial compared D1 beneficial effect of adjuvant chemotherapy was
surgery and D2 surgery in the 1990s and found supported by several meta-analyses (Table 30.1)
the 5-year overall survival rate was similar (35%, [7–12]. These studies, in general, showed a
33%, respectively). The postoperative morbid- small benefit by adding adjuvant chemotherapy.
ity (28% vs 46%) and mortality (6.5% vs 13%) Janunger et al.’s meta-analysis showed the benefit
were higher with D2 surgery [1, 2]. Dutch D1D2 of adjuvant chemotherapy in 3972 gastric can-
study compared the outcomes of D1 surgery with cer patients retrieved from 21 clinical trials (HR,
D2 surgery and reported that the 5-year over- 0.84; 95% confidence interval, 0.74–0.96) [10].
all survival rate was not different, that is, 34%, When Western and Asian studies were analyzed
33%, respectively [3]. However, 15-year follow- separately, they found no survival benefit in the
up data demonstrated the gastric cancer-related Western groups (HR, 0.96; 95% confidence inter-
death rate was lower in patients with D2 dissec- val, 0.83–1.12). These meta-analyses have several
tion than those with D1 dissection (37% vs 48%) limitations. The surgical technique was different
[4]. At present, D2 resection is recommended for among the retrieved trials even in one meta-anal-
advanced gastric cancer, including the USA and ysis. The patient population was also diverse in
Europe [5, 6]. terms of stage, etc., and the used adjuvant treat-
ments were various. Therefore, to conclude the
D.-Y. Oh · Y.-J. Bang (*) role of adjuvant treatment after surgery in gastric
Department of Internal Medicine, Seoul National cancer is difficult without the result of random-
University College of Medicine, ized controlled studies enrolling homogeneous
Seoul, Republic of Korea population and applying same surgical technique.
e-mail: bangyj@snu.ac.kr

https://doi.org/10.1007/978-3-662-45583-8_30
354 D.-Y. Oh and Y.-J. Bang
Table 30.1 Meta-analysis for adjuvant treatment in gastric cancer

Meta-analysis Number of clinical trials Number of patients HR (95% CI)
Herman et al. [7] 11 2096 0.88 (0.78–1.08)
Earle et al. [8] 13 1990 0.80 (0.66–0.97)
Mari et al. [9] 20 3658 0.82 (0.75–0.89)
Janunger et al. [10] 21 3972 0.84 (0.74–0.96)
Panzini et al. [11] 17 3118 0.72 (0.62–0.84)
GASTRIC [12] 17 3838 0.82 (0.76–0.90)
The Global Advanced/Adjuvant Stomach gastric cancer (stage II 44.8%, stage IIIA 38.6%,
Tumor Research International Collaboration stage IIIB 16.5%). The used adjuvant chemother-
(GASTRIC) group conducted a meta-analysis apy was S-1 (tegafur, gimeracil, and oteracil, 80
from individual data of 3838 patients from 17 to 120 mg per day) with 4 weeks/2 weeks on/off
randomized clinical trials which were closed to schedule for 12 months. After 5 years of follow-
patient recruitment before 2004 (9 from Europe, up, the overall survival rate at 5 years was higher
4 from the USA, and 4 from Asia) [12]. With a in the S-1 arm (71.7%, 95% confidence interval,
median follow-up exceeding 7 years, overall, a 67.8–75.7%)) than that of the surgery-alone arm
significant long-term survival benefit was found (61.1%, 95% confidence interval, 56.8–65.3%)
for adjuvant chemotherapy, corresponding to an (HR, 0.669; 95% confidence interval, 0.540–
overall 18% reduction of death risk with adju- 0.828) [14].
vant chemotherapy (HR, 0.82; 95% confidence The 5-year relapse-free survival rate was
interval, 0.76–0.90). The estimated median 65.4% (95% confidence interval, 61.2–69.5%) in
overall survival was 4.9 years (95% confidence the S-1 arm and 53.1% (95% confidence inter-
interval, 4.4–5.5) in surgery alone group and val, 48.7–57.4%) in the surgery-alone arm. The
7.8 years (95% confidence interval, 6.5–8.7) HR for relapse in the S-1 group compared with
in adjuvant chemotherapy group. The absolute that in the surgery-alone arm was 0.653 (95%
benefits of overall survival rate at 5 years and confidence interval, 0.537–0.793). However,
10 years were 5.8% and 7.4%, respectively. in subgroup analysis of ACTS-GC, the benefit
Regarding different regions, the hazard ratio of adjuvant S-1 was compromised in stage IIIB
was 0.83 in Europe (95% confidence interval, (HR, 0.855; 95% confidence interval, 0.510–
0.74–0.94), 0.88 in the USA (95% confidence 1.431) and stage IV (HR, 0.784; 95% confidence
interval, 0.75–1.04), and 0.70 in Asia (95% con- interval, 0.422–1.458) based on the UICC sixth
fidence interval, 0.56–0.88). There was no sig- staging system.
nificant heterogeneity for overall survival across Common sites of first relapse were the peri-
clinical trials globally; there were no time trends toneum, hematogenous sites, and lymph nodes.
in the treatment effect according to the year of Rates of metastasis and relapse were consistently
last inclusion (P = 0.82). lower in the S-1 group than in the surgery-alone
arm for all sites. In particular, the rates of recur-
rence in lymph nodes and of peritoneal relapse
ACTS-GC Trial were lower in the S-1 arm.
In S-1 arm, treatment was continued for
The ACTS-GC trial investigated the benefit of at least 3 months in 452 patients (87.4%), at
S-1 adjuvant chemotherapy compared to surgery least 6 months in 403 patients (77.9%), at least
alone in stage II or III Japanese gastric cancer 9 months in 366 patients (70.8%), and 12 months
patients after D2 surgery [13]. The primary end- in 340 patients (65.8%). Except for anorexia
point was overall survival, and the secondary end- (incidence, 6%), grade 3 or 4 adverse events
points were relapse-free survival and safety. This occurred in less than 5% of the patients in the
study enrolled 1059 patients with stage II or III S-1 group.
30 Adjuvant Treatment for Gastric Cancer 355
CLASSIC Trial interruptions, and 369 had cycle delays, and

163 patients needed oxaliplatin dose reductions.
The CLASSIC trial investigated the ben- The median relative dose intensity was 85% for
efit of combination chemotherapy of XELOX capecitabine and 98% for oxaliplatin. The most
(capecitabine and oxaliplatin) compared to sur- commonly reported adverse events at any grade
gery alone in stage II or III gastric cancer patients in the XELOX arm were nausea, neutropenia,
after D2 surgery [15]. The trial was conducted in decreased appetite, peripheral neuropathy, diar-
37 centers in South Korea, China, and Taiwan. rhea, and vomiting. The most common grade
Only patients with Karnofsky performance status 3 or 4 adverse events in the XELOX arm were
of 70% or more were enrolled and randomized neutropenia, thrombocytopenia, nausea, and
to surgery alone or XELOX chemotherapy in a vomiting. Grade 3 or 4 peripheral neuropathy, a
1:1 ratio within 6 weeks of D2 gastrectomy. The cumulative toxic effect associated with oxalipla-
XELOX regimen was composed of capecitabine tin, occurred in 12 (2%) patients. After median
2000 mg/m2/day for 14 days and oxaliplatin 62.4-month follow-up, disease-free survival was
130 mg/m2 on day 1, which was repeated every significantly better in the XELOX arm than in the
3 weeks for 6 months. The primary endpoint was surgery-alone arm, and the HR was 0.58 (95%
3-year disease-free survival, and secondary end- confidence interval, 0.47–0.72; p < 0.0001) [16].
points were overall survival and safety. Between Estimated 5-year disease-free survival was 68%
2006 and 2009, 1035 patients were randomly (95% confidence interval, 63–73) for the adju-
assigned (515 patients in surgery-alone arm, 520 vant XELOX arm versus 53% (47–58) for the
patients in XELOX arm). Stage distribution was surgery-alone arm, and estimated 3-year disease-
stage II 50%, IIIA 37%, and IIIB 13%. Examined free survival was 75% (71–79) versus 60% (56–
lymph nodes was 43.6 surgery-alone arm and 65). Overall survival was significantly better in
45.0 in XELOX arm. Node-negative (N0) patients the adjuvant XELOX arm than in surgery-alone
were only 10%, and 60% of patients had N1, and arm in the intention-to-treat population (HR 0.66,
30% of patients had N2 disease. After 34 months 95% confidence interval, 0.51–0.85; p = 0.0015).
of follow-up, the 3-year disease-free survival was The estimated 5-year overall survival was 78%
74% (95% confidence interval, 69–79) in the (95% confidence interval, 74–82) and 69% (95%
XELOX arm and 59% (95% confidence interval, confidence interval, 64–73) in XELOX arm and
53–64) in the surgery-alone arm (HR, 0.56; 95% surgery-alone arm, respectively.
confidence interval, 0.44–0.72; P < 0.0001). In
the XELOX arm, 96 patients (18%) developed
recurrences compared with 155 patients (30%) in SAMIT Trial
the surgery-alone arm. The sites of gastric can-
cer recurrence were the peritoneum (47 in the Japanese investigator randomly assigned 1495
XELOX arm vs 56 in the surgery-alone arm), gastric cancer patients with T4a or T4b after D2
locoregional sites (21 vs 44), and distant sites (49 surgery into 4 arms (374 UFT alone, 374 S-1, 374
vs 78). The benefits by XELOX were observed paclitaxel and then UFT, 373 paclitaxel and then
across all stages; the HRs for disease-free sur- S-1) [17]. 85% of patients had node-positive dis-
vival were 0.55 (95% confidence interval, 0.36– ease. Stage was based on Japanese Classification
0.84), 0.57 (95% confidence interval, 0.39–0.82), of Gastric Carcinoma, and stage IA or IB was
and 0.57 (95% confidence interval, 0.35–0.95) in 5%, II 22%, IIIA 35%, IIIB 25%, and IV 11%.
stage II, IIIA, and IIIB, respectively. In N1 and Patients received UFT only (267 mg/m2 per
N2 patients, 3-year disease-free survival was sig- day) and S-1 only (80 mg/m2 per day) for 14 days,
nificantly improved with XELOX, but not in N0 with a 7-day rest period or three courses of inter-
patients. 346 patients (67%) assigned to XELOX mittent weekly paclitaxel (80 mg/m2) followed
arm received eight cycles as planned. 167 patients by either UFT or S-1. Treatment duration was
had capecitabine dose reductions, 147 had cycle 48 weeks in monotherapy arms and 49 weeks
356 D.-Y. Oh and Y.-J. Bang
in sequential chemotherapy arms. The primary References

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follow-up, protocol treatment was completed by 1. Cuschieri A, Fayers P, Fielding J, et al. Postoperative
morbidity and mortality after D1 and D2 resections
215 (60%) patients in the UFT arm, 224 (62%) for gastric cancer: preliminary results of the MRC
in the S-1 arm, 242 (68%) in the paclitaxel and randomised controlled surgical trial. The Surgical
then UFT arm, and 250 (70%) in the paclitaxel Cooperative Group. Lancet. 1996;347:995–9.
and then S-1 arm. The primary endpoint, 3-year 2. Cuschieri A, Weeden S, Fielding J, et al. Patient sur-
vival after D1 and D2 resections for gastric cancer:
disease-free survival for monotherapy was 54.0% long-term results of the MRC randomized surgi-
(95% CI, 50.2–57.6), and that of sequential treat- cal trial. Surgical co-operative group. Br J Cancer.
ment was 57.2% (53.4–60.8; [HR] 0.92; 95% 1999;79:1522–30.
CI, 0.80–1.07; p = 0.273). A 3-year disease- 3. Bonenkamp JJ, Hermans J, Sasako M, et al. Extended
lymph-node dissection for gastric cancer. N Engl J
free survival for the UFT arm was 53.0% (95% Med. 1999;340:908–14.
CI, 49.2–56.6), and that of the S-1 group was 4. Songun I, Putter H, Kranenbarg EM, et al. Surgical
58.2% (54.4–61.8; HR, 0.81; 95% CI, 0.70–0.93; treatment of gastric cancer: 15 year follow-up results
p = 0.0048; p for non-inferiority = 0.151). The of the randomised nationwide Dutch D1D2 trial.
Lancet Oncol. 2010;11:439–49.
result of SAMIT trial was that sequential treat- 5. Waddell T, Verheij M, Allum W, et al. Gastric cancer:
ment did not improve disease-free survival, and ESMO-ESSO-ESTRO clinical practice guidelines
UFT was not non-inferior to S-1 (and S-1 was for diagnosis, treatment and follow-up. Ann Oncol.
superior to UFT); therefore, S-1 monotherapy 2013;(Suppl 6):vi57–63.
6. NCCN Clinical Practice Guidelines in Oncology.
should remain the standard treatment for locally Gastric Cancer. Version 3.2016.
advanced gastric cancer in Japan. 7. Hermans J, Bonenkamp JJ, Boon MC, et al. Adjuvant
The most common grade 3–4 hematologi- therapy after curative resection for gastric cancer:
cal adverse event was neutropenia (41 [11%] of meta analysis of randomized trials. J Clin Oncol.
1993;11:1441–7.
359 patients in the UFT arm, 48 [13%] of 363 in 8. Earle CC, Maroun JA. Adjuvant chemotherapy after
the S-1 arm, 46 [13%] of 355 in the paclitaxel curative resection for gastric cancer in non-Asian
and then UFT arm, and 83 [23%] of 356 in the patients: revisiting a meta-analysis of randomised tri-
paclitaxel and then S-1 arm). The most common als. Eur J Cancer. 1999;35:1059–64.
9. Mari E, Floriani I, Tinazzi A, et al. Efficacy of adju-
grade 3–4 non-hematological adverse event was vant chemotherapy after curative resection for gastric
anorexia (21 [6%], 24 [7%], 7 [2%], and 18 [5%], cancer: a meta-analysis of published randomised tri-
respectively). als: a study of the GISCAD (Gruppo Italiano per lo
Studio dei Carcinomi dell’Apparato Digerente). Ann
Oncol. 2000;11:837–43.
10. Janunger KG, Hafström L, Glimelius B. Chemotherapy
in gastric cancer: a review and updated meta-analysis.
Concluding Remarks Eur J Surg. 2002;168:597–608.
11. Panzini I, Gianni L, Fattori PP, et al. Adjuvant che-
The surgical technique is of utmost importance to motherapy in gastric cancer: a meta-analysis of
cure patients of advanced gastric cancer. At pres- randomized trials and a comparison with previous
meta-analyses. Tumori. 2002;88:21–7.
ent, D2 resection is recommended as standard of 12.
GASTRIC (Global Advanced/Adjuvant Stomach
care worldwide. Two randomized phase III trials Tumor Research International Collaboration)
and meta-analyses have demonstrated the benefit Group, Paoletti X, Oba K, et al. Benefit of adjuvant
of adjuvant chemotherapy resulting in higher cure chemotherapy for resectable gastric cancer: a meta-
analysis. JAMA. 2010;303:1729–37.
rate. Adjuvant chemotherapy with S-1 for 1 year 13. Sakuramoto S, Sasako M, Yamaguchi T, et al.

or XELOX for 6 months is regarded the standard Adjuvant chemotherapy for gastric cancer with S-1,
of care, especially after D2 resection. For patients an oral fluoropyrimidine. N Engl J Med. 2007;357:
with stage II disease, two regimens produced sim- 1810–20.
14. Sasako M, Sakuramoto S, Katai H, et al. Five-year
ilar benefits; however, for patients with stage III outcomes of a randomized phase III trial compar-
disease, XELOX seems to be preferred. ing adjuvant chemotherapy with S-1 versus surgery
30 Adjuvant Treatment for Gastric Cancer 357
alone in stage II or III gastric cancer. J Clin Oncol. open-label, randomised phase 3 trial. Lancet Oncol.
2011;29:4387–93. 2014;15(12):1389–96.
15. Bang YJ, Kim YW, Yang HK, et al. Adjuvant
17. Tsuburaya A, Yoshida K, Kobayashi M, et al.

capecitabine and oxaliplatin for gastric cancer after D2 Sequential paclitaxel followed by tegafur and uracil
gastrectomy (CLASSIC): a phase 3 open-label, ran- (UFT) or S-1 versus UFT or S-1 monotherapy as adju-
domised controlled trial. Lancet. 2012;379:315–21. vant chemotherapy for T4a/b gastric cancer (SAMIT):
16. Noh SH, Park SR, Yang HK, et al. Adjuvant
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capecitabine plus oxaliplatin for gastric cancer after Oncol. 2014;15(8):886–93.
D2 gastrectomy (CLASSIC): 5-year follow-up of an
Radiation Therapy for Gastric
Cancer 31
Do Hoon Lim
After the introduction of the Gastrointestinal Radiation and GI Tract

Cancer Intergroup Trial (INT 0116) [1], the larg-
est phase III trial comparing surgery alone versus Radiation treats patients with cancer by using
postoperative chemoradiotherapy (CRT) in gas- X-ray, which is generated from the machine
tric cancer, radiation therapy (RT) has attracted named linear accelerator. The mechanisms of
increasing attention as a treatment modality for X-ray for killing cancer cells are either direct
patients with gastric cancer. Before INT 0116, effect of destroying cancer cell membrane or
RT has not been frequently considered as a induction of apoptosis from chromosomal aber-
modality for gastric cancer with several rea- ration through DNA double strands break.
sons. First, the radiation effect has been known However, radiation cannot differentiate cancer
to be inferior in adenocarcinoma compared with cells from normal cells, and it causes the vari-
squamous cell carcinoma or undifferentiated car- ous types of radiation complications. Because
cinoma. Second, the gastrointestinal (GI) com- GI tract is one of the radiosensitive organs, the
plications of RT have been exaggerated. Third, high dose of radiation to the abdomen for gastric
the gastric cancer can be considered as a systemic cancer should be applied with caution. The radia-
disease rather than localized disease because the tion tolerance doses of GI tract are lower than
main patterns of failure are peritoneal seeding or the curative doses for gross tumor; therefore, the
liver metastasis after radical resection. However, roles of RT for gastric cancer patients are neo-
with the several clinical studies showing the adjuvant or adjuvant modality to intensify surgi-
additional effect of preoperative or postoperative cal effect and palliative modality to increase the
RT and the development of radiation techniques quality of life of patients through pain relief or
such as three-dimensional conformal radiother- cancer bleeding control.
apy or intensity-modulated radiotherapy (IMRT) To increase the radiation effect, some chemo-
decreasing radiation- induced bowel complica- therapeutic agents are combined with RT, and
tions, the application of RT to patients with gas- those agents are called as radiosensitizer. The most
tric cancer is now gradually increasing. commonly used radiosensitizer is 5-fluorouracil
(5-FU), and the concurrent CRT can be applied
for adjuvant or palliative purpose. If the patient is
D. H. Lim (*) hard to tolerate the concurrent CRT, RT alone can
Department of Radiation Oncology, Samsung be applied without chemotherapy.
Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Republic of Korea
e-mail: dh8lim@skku.edu

https://doi.org/10.1007/978-3-662-45583-8_31
360 D. H. Lim
Preoperative Neoadjuvant ostoperative Adjuvant Radiation

P
Radiation Therapy Therapy
Neoadjuvant RT increases the complete resec- The postoperative adjuvant RT, chemotherapy, and
tion rates of gastric cancer through tumor combined CRT have been investigated worldwide
downstaging effect and decreases the pos- to prevent recurrences in patients with resected
sibility of distant metastasis with concurrent gastric adenocarcinoma. However, there has been
chemotherapy. Theoretically, neoadjuvant RT a controversy of the application of RT in adjuvant
has many advantages compared with postop- setting until now. In the Western countries, peri-
erative adjuvant RT, but the clinical studies of operative chemotherapy (MAGIC trial) [6] and
neoadjuvant RT in gastric cancer have been postoperative CRT (INT 0116) [1] are generally
limitedly performed, and most of the studies recommended; however, in the Eastern countries,
were performed to patients with esophageal adjuvant chemotherapy (ACTS-GC and CLASSIC
cancer or gastroesophageal junction cancer. trials) without RT is considered as standard adju-
According to randomized phase III trial of the vant modality after D2 gastrectomy [7, 8].
Chemoradiotherapy for Oesophageal Cancer The relatively underestimated role of adjuvant
Followed by Surgery Study (CROSS), neoad- RT in the Eastern countries mainly comes from
juvant CRT in potentially curable esophageal the undoubted role of surgery with extended
or gastroesophageal cancer showed overall sur- LN dissection, the higher risk of distant metas-
vival (OS) benefit compared with surgery alone tasis than that of locoregional recurrence after
(median OS 49.4 months vs. 24.0 months) [2]. D2 gastrectomy, and the exaggerated concern
And the OS advantage of neoadjuvant CRT was of radiation- induced complications. However,
repeated by another randomized phase III trial high rates of locoregional recurrences have been
[3], though the study was early closed due to reported even after radical resection [9–18],
poor accrual. and the benefit of adjuvant RT was reaffirmed
In the phase III randomized trial, comparing in several meta-analyses [19–21]. Furthermore,
surgery alone versus preoperative RT and sur- the recent prospective randomized controlled
gery for 370 patients with gastric cardia cancer, trials in Korea and China [22–24] have demon-
Zhang et al. [4] reported improved 5-year sur- strated the benefit of adjuvant RT combined with
vival rates, which were 20.3% in surgery alone chemotherapy in D2-dissected gastric cancer
group and 30.1% in preoperative RT followed patients.
by surgery group (p < 0.01). The incidences To justify postoperative adjuvant RT in gas-
of local recurrence and intra- or extra-abdom- tric cancer patients, some critical issues should
inal lymph node (LN) metastasis in the preop- be answered: the patterns of failure after surgi-
erative RT group were obviously lower than cal resection, the evidence of adjuvant RT effi-
those of surgery alone group: 38.6% vs. 51.7% cacy in randomized clinical trials, the incidence
(p < 0.025) and 38.6% vs. 54.6% (p < 0.005). of radiation-induced complications, and a subset
Ajani et al. [5] reported that the three-step strat- of patients who would benefit from adjuvant RT
egy of preoperative induction chemotherapy after radical resection.
followed by CRT resulted in 30% of pathologic
complete response that resulted in durable sur-
vival time. atterns of Failure After Surgical
P
Though the clinical trials about neoadjuvant Resection
RT focusing gastric cancer only are scarce, the
neoadjuvant approach is worthy of further inves- Several retrospective studies have analyzed the
tigation to find out which patients with clinical patterns of failure after curative resection in
stage and tumor location will be beneficial from gastric cancer, and they might be divided into
RT as a neoadjuvant modality. three groups: autopsy, reoperation, and clini-
31 Radiation Therapy for Gastric Cancer 361
Table 31.1 Patterns of failure after surgical resection

Autopsy Reoperation Clinical FU
Locoregional 80–93% 69% 19–45%
Gastric bed 52–68% 55% 21%
Anastomosis/stump 54–60% 27% 6–25%
Abdominal/stab wound – 5% –
Lymph nodes 52% 43% 8–13%
Peritoneal seeding 30–50% 42% 23–44%
Distant metastasis 49% 23% 35–52%
FU follow-up
cal follow-up groups (Table 31.1). The autopsy However, when analyzed according to actual
data showed the end result of surgery [9–11], treatment received, the difference was not sig-
and reoperation data focused to the patients with nificant because of small patient numbers. The
potentially high risk for recurrences [12, 13]. The British Stomach Cancer Group [27] compared
clinical follow-up data [14–18] showed recur- surgery alone, adjuvant RT, and adjuvant chemo-
rences which could be detected with clinical therapy. The result was that there was no survival
examination and imaging studies during follow- advantage for those with RT or chemotherapy
up period. As expected, high locoregional recur- compared to those with surgery alone but the
rences were shown in autopsy and reoperation locoregional failure rate was lowest in patient
groups compared with clinical follow-up group. with adjuvant RT group.
However, even in clinical follow-up group, the Overall, it is difficult to make any conclusion
locoregional recurrence was up to 45% of patients from these earlier randomized trials because
with surgical resection. When the extended LN of the heterogeneous cohort, small numbers of
dissection was performed, locoregional recur- patients, different surgical extent, and subopti-
rence developed also in many patients, and the mal radiation dose. Therefore, the well-designed
percentage of locoregional recurrence without INT 0116 trial was very attractive, and it dem-
liver metastasis or peritoneal seeding was as high onstrated a definite survival benefit with CRT
as 20% [17, 18]. group compared with surgery alone group in
initial report and updated report of a more than
10-year median follow-up [1, 28]. They showed
arlier Prospective Randomized Trials
E a consistent and strong benefit of adjuvant CRT
Including INT 0116 in overall and relapse-free survival, and the
decrease of locoregional failure from adjuvant
Three prospective randomized studies were CRT may account for the reduction in overall
performed before the introduction of INT 0116 relapse. Although INT 0116 trial had some limi-
trial. Dent et al. [25] randomly assigned 142 tations such as inappropriate surgical extent and
patients, and the result was no difference in no adjuvant chemotherapy alone arm, it was a
survival between concurrent CRT and control pivotal clinical event resulting to pay attention
group. However, patients with M1 disease were to adjuvant RT in resected gastric cancer, and
included, and the radiation dose was only 20 Gy several randomized trials were initiated after
that was inappropriate dose for adjuvant set- the report of INT 0116. From the results of INT
ting. Moertel et al. [26] randomly assigned 62 0116 trial, the adjuvant CRT demonstrated sur-
patients with poor prognosis gastric carcinoma vival benefit to the patients with suboptimally
to receive concurrent CRT or surgery alone. The resected gastric cancer. However, it needs to be
5-year survival rate for patients randomized to answered whether adjuvant CRT provides simi-
adjuvant concurrent CRT was 23% and for those lar benefit shown in INT 0116 trial if D2 gastrec-
randomized to no treatment, 4% (p < 0.05). tomy is done.
362 D. H. Lim
Postoperative Chemoradiotherapy decreased the regional LN recurrences, and there

in Patients with D2 Gastrectomy was no difference in distant metastasis between
two cohorts. On the contrary, Dikken et al. [36]
Although there was a controversy over the ben- retrospectively compared patients between D1
efit of gastrectomy with D2 LN dissection in the and D2 LN dissection from the Dutch Gastric
Western randomized studies [29, 30], several Cancer Group Trial. Their conclusion was that
studies [31–34] reported that extended (D2) LN the addition of postoperative CRT had a major
dissection leads to better results than limited (D0 impact on local recurrence in patients with D1
or D1) LN dissection in locoregional recurrence surgery but there was no additional effect of adju-
or OS. And D2 gastrectomy has been the most vant CRT in patients with D2 surgery.
widely accepted and recommended as a standard Because of the heterogeneous results as
surgical procedure for resectable gastric cancer. well as limitations originated from retrospec-
However, randomized trials in patient cohort tive study design, phase III randomized trials
with D2 gastrectomy are uncommon, and lately, should be needed to justify postoperative adju-
several randomized studies were published. vant RT after D2 gastrectomy. Until now, three
ACTS-GC and CLASSIC trials [7, 8] com- randomized trials were published, and two trials
pared adjuvant chemotherapy after D2 gastrec- (CRITICS and ARTIST II) are ongoing to elu-
tomy with surgery alone. They showed improved cidate the role of adjuvant RT in patients with
3-year OS and disease-free survival (DFS). Based D2 gastrectomy. The Adjuvant Chemoradiation
on these results, adjuvant chemotherapy not CRT Therapy in Stomach Cancer (ARTIST) trial
is recommended in D2-resected gastric cancer was the first and largest prospective random-
patients in the current NCCN guideline. ized study to address the role of CRT as adju-
Then, is there any room for adjuvant RT or vant treatment in D2 gastrectomy patients [22].
CRT in patients with extended LN dissection? Totally, 458 patients were randomly assigned to
Table 31.2 shows several gastric cancer studies adjuvant chemotherapy or CRT group, and the
which were performed to patients with D2 gas- conclusion was that the addition of RT to chemo-
trectomy. According to the observational study by therapy did not significantly reduce recurrences.
Kim et al. [35], there was an advantage in OS in This negative result may have been influenced
patients with postoperative CRT (INT-0116 treat- by the large proportion of patients (60%) with
ment scheme) compared with those who under- early stage (stage IB and II). However, in the
went surgery alone. Adjuvant CRT significantly subset analysis, the adjuvant CRT significantly
Table 31.2 Gastric cancer studies performed to patients with D2 gastrectomy

Treatment
Study Stage Group Patient number RT/CTx Survival p
1. Retrospective studies
Kim et al. II~IVA Control 446 – MS 62.6 mos 0.02
CCRT 544 45 Gy / FL 95.3 mos
Dikken et al. – Control 325 – 2-yr LRR 13% 0.84
CCRT 25 45 Gy / FL, XP 12%
2. Prospective randomized studies
ARTIST IB~IVA CTx 228 XP 3-yr DFS 74.2% 0.0862
CCRT 230 45 Gy / XP 78.2%
NCC, SK III~IV CTx 175 FL 5-yr DFS 50% >0.05
Zhu et al. IB~IVA CCRT 205 45 Gy / FL 61% 0.122
CTx FL MS 48 mos
CCRT 45 Gy / FL 58 mos
Adapted from Ref. [45], with permission
RT radiotherapy, CTx chemotherapy, CCRT concurrent chemoradiotherapy, FL fluorouracil, leucovorin, MS median
survival, XP capecitabine, cisplatin, LRR local recurrence rate, DFS disease-free survival
improved the 3-year DFS in node-positive patients in chemotherapy arm and 5 in CRT arm,
patients. After 7 years of median follow-up, p < 0.001), and LRRFS was significantly differ-
the effect of the addition of RT on DFS and OS ent between study arms (p = 0.03), especially in
differed by Lauren classification (p = 0.04 for patients with LN metastasis (p = 0.009). Based
DFS, p = 0.03 for OS) and LN ratio (p < 0.01 for on the results of ARTIST trial, the ARTIST II
DFS, p < 0.01 for OS). Subgroup analyses also trial evaluating adjuvant chemotherapy and CRT
showed that CRT significantly improved DFS in patients with node-positive, D2-resected GC
in patients with node-positive disease and with is under way.
intestinal-type gastric cancer [37]. The National
Cancer Center in South Korea conducted a
phase III trial using INT 0116 treatment scheme Radiation Targets in D2-Dissected
in patients with stage III and IV gastric cancer Gastric Cancer
[23], but this study was early closed due to poor
patient accrual. Although 5-year DFS was not The main role of postoperative adjuvant RT is to
significantly improved in CRT group, the 5-year decrease locoregional recurrences. However, the
locoregional recurrence-free survival (LRRFS) RT target volume has varied between the adjuvant
was significantly improved, and in stage III RT trials. In the INT 0116 trial, the recommenda-
patients, DFS was also improved. Zhu et al. [24] tion of RT field includes tumor bed (preoperative
recently reported on a similar trial conducted tumor volume) and 2 cm beyond the proximal
in Chinese population and resulted a signifi- and distal resection margins and regional LNs
cant difference in DFS not only in patients with (perigastric, celiac, local para- aortic, splenic,
positive nodes but in the whole population. In hepatoduodenal, and pancreaticoduodenal LNs)
the meta-analysis of 895 patients from these [1]. In ARTIST trial, RT field for tumor bed and
three randomized trials, there was no apparent regional nodes was modified according to T stage
survival benefit with the addition of RT to che- and primary tumor location [22].
motherapy, but LRRFS and DFS in CRT group From the results of randomized trials of
were significantly improved [38]. Eastern countries comparing adjuvant CRT with
The ChemoRadiotherapy after Induction che- adjuvant chemotherapy alone after D2 gastrec-
moTherapy In Cancer of the Stomach (CRITICS) tomy, CRT group showed the improvement of
trial is currently randomizing patients after neo- DFS or LRRFS [22–24]. Even after D2 LN dis-
adjuvant chemotherapy followed by D2 lymph- section, radiation decreased regional recurrence
adenectomy. They randomly assigned either especially in Group 3 LN areas [40] (Fig. 31.1).
three additional courses of chemotherapy or This result is supported by the study which inves-
CRT to compare the efficacy of the MAGIC trial tigated patterns of nodal recurrence after D2
regimen, which showed the survival benefit of a dissection for 382 patients with stage III (N3)
perioperative approach combined with intensive disease [41]. In this retrospective study, the most
chemotherapy, with that of INT 0116 trial. The prevalent nodal recurrence was in the nodal basin
results of CRITIC trial will demonstrate whether outside the D2 dissection field.
the combination of preoperative chemotherapy Unlike the regional recurrence, the inci-
and postoperative CRT will improve the clini- dence of local recurrence (tumor bed, remnant
cal outcome of the current European standard stomach, anastomosis sites) was not different
of perioperative chemotherapy [39]. To find out between chemotherapy alone and CRT arms, and
which subgroups might benefit from adjuvant the incidence was relatively low. In a retrospec-
RT in patients with D2 gastrectomy, the recur- tive trial, the exclusion of remnant stomach from
rence patterns in ARTIST trial were reanalyzed the radiation field had no effect on failure rates
after minimum follow-up of 5 years [40]. The or survival, and the patients treated excluding
regional LN recurrence was the most impor- remnant stomach experienced a low GI compli-
tant difference between the two groups (23 cation rate [42].
364 D. H. Lim
Chemo alone CRT
Porta hepatis
Celiac
Portocaval
Peripancreatic
Para-aortic
Aortocaval
Retrocaval
Fig. 31.1 Patterns of regional recurrence in ARTIST lymph nodes outside the D2 dissection field. (Modified
trial. Regional recurrence in chemotherapy alone group illustration originally published in Yu et al. 2015.
was significantly higher than that in chemoradiotherapy Published with kind permission of © ScienceDirect 2016.
group. The most nodal recurrences developed in Group 3 All Rights Reserved)
Treatment-Related Complication treated cohort, and there was no statistically sig-

in Clinical Trials nificant difference between CRT and chemother-
apy alone groups [40].
The concern of radiation-induced GI complica-
tions has been one of the obstacles for the appli-
cation of RT in adjuvant setting. However, there Palliative Radiation Therapy
was no increase in treatment-related toxicity in
CRT group compared with chemotherapy alone In patients with locally advanced unresect-
group in three randomized trials from Eastern able gastric cancers, the quality of life of the
countries [22–24]. Especially in ARTIST trial, patients is not so satisfied due to various symp-
the treatment compliance was even higher in toms such as tumor bleeding, gastric outlet
CRT group. This could be explained by the modi- obstruction, and abdominal or back pain. For
fication of RT target volume and the application palliation of such symptoms, RT could be a
of modern RT techniques. The late GI compli- good candidate. According to Tey et al. [43],
cations such as paralytic ileus or anastomosis the response rates of palliative RT were 54%
site stricture were developed in less than 2% of for tumor bleeding, 25% for obstruction, and
25% for pain. And Lee et al. [44] reported that 9. McNeer G, Vandenberg H, Donn FY, Bowden L. A
critical evaluation of subtotal gastrectomy for the cure
RT may be an effective treatment for gastric of cancer of the stomach. Ann Surg. 1951;134:2–7.
cancer bleeding when other modalities are not 10. Thomson FB, Robins RE. Local recurrence follow-
feasible and 91% of the patients experienced ing subtotal resection for gastric carcinoma. Surg
symptomatic palliation with an elevated hemo- Gynecol Obstet. 1952;95:341–4.
11.
Wisbeck WM, Becher EM, Russell
globin level and a decreased number of trans- AH. Adenocarcinoma of the stomach: autopsy obser-
fusions after RT. vations with therapeutic implications for the radiation
oncologist. Radiother Oncol. 1986;7:13–8.
12. Wangensteen OH, Lewis FJ, Arhelger SW, Muller
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Novel Agents and the Future
Perspectives 32
Minkyu Jung and Sun Young Rha
Introduction demand for new therapies to improve treatment

and survival. In this present review, we summa-
Gastric cancer is an important health problem rized current evidence of clinical efficacy of
worldwide, with high incidence and a poor prog- novel agents including targeted agents and
nosis [1]. Surgical resection is the only curative immune checkpoint inhibitors (ICI), especially
treatment strategy for localized gastric cancer, focus on phase III trials.
used in combination with adjuvant chemotherapy
[2, 3]. However, recurrence is common, and in
Western countries gastric cancer is often diag- pidermal Growth Factor Receptor
E
nosed at a more advanced stage than in Japan and (EGFR)/Human Epidermal Receptor
Korea, where screening is widespread [4]. For (HER) Inhibitors
advanced or metastatic gastric cancer patients,
chemotherapy is the primary treatment. There is The EGFR pathway has been recognized as play-
no globally accepted standard first-line regimen ing a key role in tumorigenesis, influencing cell
in advanced gastric cancer, double regimen (fluo- proliferation, migration, differentiation, survival,
rouracil and platinum) and triple regimen (fluoro- and transformation in cancer cells [11]. The
uracil, platinum plus docetaxel or epirubicin) are EGFR family has four members: HER1 (also
most commonly used [5–9]. Although several known as EGFR), HER2, HER3, and HER4 [12].
clinical trials have sought to improve survival EGFR overexpression is reported in 27–55% of
among patients with gastric cancer, median over- gastric cancers and has been associated with poor
all survival with metastatic disease is limited to survival [13–15]. Therefore, drugs targeting the
about 1 year [10]. Therefore, there is an urgent EGFR could be therapeutic agents for gastric
cancer.
M. Jung
Division of Medical Oncology, Yonsei Cancer Center, nti-EGFR Monoclonal Antibody
A
Yonsei University College of Medicine,
Seoul, Republic of Korea (mAbs)
S. Y. Rha (*)
Division of Medical Oncology, Department of Panitumumab
Internal Medicine, Yonsei Cancer Center, Yonsei Panitumumab is a fully human monoclonal anti-
University College of Medicine, body against EGFR that has shown survival ben-
Seoul, Republic of Korea efits in advanced colorectal cancer [16]. In the
e-mail: rha7655@yuhs.ac

https://doi.org/10.1007/978-3-662-45583-8_32
368 M. Jung and S. Y. Rha
REAL3 phase III trial [17], 553 patients with pre- advanced gastric cancer patients. The
viously untreated advanced gastric or esophago- Trastuzumab for Gastric Cancer (ToGA) phase
gastric junction (EGJ) cancer were randomly III trial enrolled 594 gastric cancer patients with
assigned to EOC (epirubicin, oxaliplatin, and HER2 overexpression and compared standard
capecitabine) plus panitumumab or EOC alone. chemotherapy (six courses of cisplatin plus either
Contrary to expectations, median overall survival infusional 5-fluorouracil or capecitabine) with
(OS) was significantly shorter in the EOC plus and without trastuzumab [21]. All tumors were
panitumumab than in the EOC group (8.8 vs. screened for HER2 status by both immunohisto-
11.3 months, hazard ratio (HR) = 1.37, 95% con- chemistry (IHC) and fluorescent in situ hybrid-
fidence interval (CI) 1.07–1.76, p = 0.013). In ization (FISH), and patients were eligible if their
addition, rates of grade 3–4 diarrhea (48% vs. tumor was positive by either IHC (i.e., showing
11%), rash (11% vs. 1%), mucositis (5% vs. 3+ expression) or FISH (i.e., showing a HER2/
none), and hypomagnesemia (13% vs. none) CEP17 ratio of 2 or greater). The objective
were increased in the panitumumab group. response rate (ORR) was significantly increased
Adding panitumumab to EOC chemotherapy in the trastuzumab arm (47% vs. 35%,
decreased OS and cannot be recommend as first- p = 0.0017). With a median follow-up of
line chemotherapy in the treatment of advanced 18.6 months (interquartile range (IQR)
esophagogastric adenocarcinoma. 11–25 months), median OS and PFS were signifi-
cantly longer with trastuzumab than with chemo-
Cetuximab therapy alone (OS, 13.8 vs. 11.1 months,
Cetuximab is a monoclonal IgG antibody target- HR = 0.74, 95% CI 0.60–0.94, p = 0.0046; PFS,
ing EGFR, used for the treatment of metastatic 6.7 vs. 5.5 months, HR = 0.71, 95% CI 0.59–
colorectal cancers, non-small cell lung cancer, 0.85, p = 0.0002). Overall, grade 3 or 4 adverse
and head and neck cancers [18–20]. In the events did not differ between the two groups
EXPAND phase III study, 904 patients previ- (68% vs. 68%). A pre-planned exploratory analy-
ously untreated for advanced unresectable or sis incorporating HER2 status suggested that
metastatic adenocarcinoma of the stomach or trastuzumab was most effective in prolonging
EGJ were randomly assigned to XP (capecitabine survival in the subgroup of patients with IHC
plus cisplatin), with or without cetuximab. The scores of 2+ or 3+ that were also FISH-positive.
median progression-free survival (PFS) and OS Compared with those assigned to chemotherapy
did not differ between the two groups (PFS, 4.4 alone, OS for this group was 16.0 months vs.
vs. 5.6 months, HR = 1.09, 95% CI 0.92–1.29, 11.8 months (HR = 0.65, 95% CI 0.51–0.83).
p = 0.32; OS, 9.4 vs. 10.7 months, HR = 1.00, Base on the ToGA trial, trastuzumab in combina-
95% CI 0.87–1.17, p = 0.95). Adverse events of tion with fluorouracil and cisplatin is recom-
grade 3–4 were more common in the cetuximab mended for use as a first-line therapy in gastric or
group, including diarrhea, hypokalemia, hypo- EGJ adenocarcinoma patients with HER2
magnesemia, rash, and hand-foot syndrome. overexpression.
Therefore, the addition of cetuximab to XP che-
motherapy did not increase survival in the first- T rastuzumab Emtansine (T-DM1)
line treatment of advanced gastric cancer. T-DM1 is composed of trastuzumab conju-
gated with the cytotoxic agent DM1 (a deriva-
tive of maytansine). T-DM1 binds to the
Anti-HER2 mAbs extracellular domain of HER2 and is internal-
ized into the tumor cell, where the emtansine is
Trastuzumab released [22]. The efficacy of T-DM1 was dem-
Trastuzumab, a monoclonal antibody against onstrated in patients with HER2-positive meta-
human HER2 (also known as ERBB2), was the static breast cancer patient progressed on
first molecular-targeted agent approved for use in trastuzumab [23].
32 Novel Agents and the Future Perspectives 369
In the phase III GATSBY trial [24], 416 patients were randomly assigned to paclitaxel plus lapa-
with previously treated advanced gastric or EGJ tinib or paclitaxel alone. The addition of lapatinib
cancers that were HER2 positive (IHC 3+ or IHC to paclitaxel did not significantly improve OS
2+/FISH-positive) were randomly assigned to (11.0 vs. 8.9 months, p = 0.1044) or PFS (5.4 vs.
T-DM1 or paclitaxel. The OS and PFS were not 4.4 months, HR = 0.85, p = 0.2441). However, a
different between the two groups (median OS, 7.9 significant benefit of lapatinib was seen in
vs. 8.6 months, HR = 1.15, 95% CI 0.87–1.51, patients with 3+ IHC scores for HER2 (PFS, 5.4
p = 0.86; median PFS 2.7 vs. 2.9 months, vs. 4.2 months, HR = 0.54, p = 0.0101; OS, 14.0
HR = 1.13, 95% CI 0.89–1.43, p = 0.31). The rate vs. 7.6 months, HR = 0.59, p = 0.0176). The inci-
of grade 3–4 adverse events was lower in the dence of adverse events leading to permanent
T-DM-1 group (59.8% vs. 70.3%). discontinuation was higher in the lapatinib group
than with paclitaxel alone (16% vs. 9%).
Pertuzumab In the phase III LOGiC trial [30], 545 patients
Pertuzumab is a humanized monoclonal antibody with HER2-positive advanced gastroesophageal
that binds to the extracellular dimerization adenocarcinoma were randomly assigned to a
domain of HER2 and prevents heterodimeriza- combination of lapatinib and capecitabine/oxali-
tion of HER2 and HER3 [25]. Addition of pertu- platin or capecitabine/oxaliplatin alone as a first-
zumab to trastuzumab plus docetaxel improved line treatment. The addition of lapatinib did not
survival in patients with HER2-positive breast significantly improve OS (12.2 vs. 10.5 months,
cancer [26]. The success of dual HER2-targeted HR = 0.91, 95% CI 0.73–1.12, p = 0.3492) over
therapy in breast cancer was applied in gastric capecitabine/oxaliplatin chemotherapy alone.
cancer with HER2-positive gastric cancer. However, PFS was significantly longer (6.0 vs.
In phase III JACOB trial [27], 780 patients with 5.4 months, HR = 0.82, p = 0.0381), and ORR
HER2-positive metastatic gastric or EGJ cancer was higher in the lapatinib group (53% vs. 39%,
were assigned to receive either pertuzumab plus p = 0.0031). No correlation was found between
trastuzumab and chemotherapy or trastuzumab intensity of staining for HER2 by IHC and out-
and chemotherapy. The OS was not significantly come. However, in a subgroup analysis, Asian
different between treatment groups (median OS, patients (OS, 16.5 vs. 10.9 months, HR 0.68,
17.5 vs. 14.2 months, HR = 0·84, 95% CI 0.71– 95% CI 0.48–0.96, p = 0.026) and those under
1.00, p =0·057). However, PFS was significantly age 60 (OS, 12.9 vs. 9 months, HR 0.69, 95% CI
longer (8.5 vs. 7.0 months, HR = 0.73, 95% CI 0.51–0.94, p = 0.0141) seemed to benefit from
0.62–0.86, p = 0.0001), and ORR was higher in lapatinib. Adverse events were increased in the
pertuzumab group (56.7% vs. 48.3%, p = 0.026). lapatinib group, especially diarrhea (Grade ≥ 3,
12% vs. 3%).
Based on the TyTan and LOGiC trials, the
ER2 Tyrosine Kinase Inhibitors
H addition of lapatinib to chemotherapy in patients
(TKIs) with HER2-positive gastric cancer as a first- or
second-line treatment cannot be recommended.
Lapatinib
Lapatinib is an oral small molecule inhibitor of
both EGFR and HER2. A benefit from the addi- Angiogenesis Inhibitors
tion of lapatinib to capecitabine vs. capecitabine
alone was demonstrated in patients with previ- nti-vascular Endothelial Growth
A
ously treated advanced breast cancer with HER2 Factor (VEGF) mAbs
overexpression [28].
In the phase III TyTAN trial [29], 261 patients Angiogenesis is strongly linked to metastasis and
with previously treated advanced or metastatic progression in cancer. VEGF is a key regulatory
gastric cancer that was HER2-positive by FISH molecule in angiogenesis, and several VEGF-
targeting agents have been developed, including In the phase III REGARD trial [34], 355
antibodies against VEGF or its receptor VEGFR patients with previously treated advanced or met-
and TKIs of VEGFR [31]. astatic gastric or EGJ adenocarcinoma were
assigned (2:1) to receive ramucirumab or pla-
Bevacizumab cebo. Those treated with ramucirumab had lon-
Bevacizumab is a humanized monoclonal anti- ger PFS (2.1 vs. 1.3 months, HR = 0.483, 95% CI
body against VEGF-A. Bevacizumab was 0.376–0.620, p < 0.001) and OS (5.2 vs.
approved for use, with chemotherapy, in the 3.8 months, HR = 0.78, 95% CI 0.60–0.998,
treatment of metastatic colorectal cancer, non- p = 0.047) compared with those treated with pla-
squamous non-small cell lung cancer, glioblas- cebo. Although the ORR was not different (8%
toma, renal cell carcinoma, cervical cancer, and vs. 3%, p = 0.76), the overall disease control rate
ovarian cancer. (objective response plus stable disease) was sig-
In the AVAGAST phase III trial [32], 774 nificantly higher in the ramucirumab group than
patients with previously untreated advanced in the placebo group (49% vs. 23%, p < 0.0001).
gastric or EGJ cancer were randomly While the rate of hypertension was higher with
assigned to bevacizumab plus chemotherapy ramucirumab than with placebo (16% versus
(capecitabine and cisplatin) or chemotherapy 8%), ramucirumab was not associated with
alone. Although addition of bevacizumab to increased bleeding, venous thromboembolism,
chemotherapy had significant improvement in perforation, fistula formation, or proteinuria.
PFS (6.7 vs. 5.3 months; HR = 0.80; 95% CI In the phase III RAINBOW trial [35], 665
0.68–0.93; p = 0.0037 and ORR (46.0% vs. patients who had disease progression after first-
37.4%; p = 0.0315), OS did not different betwen line fluorouracil and cisplatin were randomly
two (12.1 vs. 10.1 months, HR = 0.87, 95% CI assigned to weekly paclitaxel plus ramucirumab
0.73–1.03, p = 0.1002). In a subgroup analy- or placebo. Both median OS and PFS were sig-
sis, patients from the Americas (largely Latin nificantly longer in the paclitaxel plus ramuci-
America) showed a survival benefit with bevaci- rumab group, compared with paclitaxel alone
zumab (11.5 vs. 6.8 months, HR = 0.63, 95% CI (OS, 9.6 vs. 7.4 months, HR = 0.807, 95% CI
0.43–0.94), whereas Asians appeared to have no 0.678–0.962, p = 0.017; PFS 4.4 vs. 2.9 months,
benefit (13.9 vs. 12.1 months, HR = 0.97; 95% HR = 0.635, 95% CI 0.536–0.752, p < 0.001).
CI 0.75–1.25), and European patients had inter- The ORR was higher in the ramucirumab group
mediate results (11.1 vs. 8.6 months, HR = 0.85, (28% vs. 16%, p = 0.001). Grade 3 or worse neu-
95% CI 0.63–1.14). In addition, a biomarker tropenia was more common with ramucirumab
study from the AVAGAST trial reported that (41% vs. 19%), but rates of febrile neutropenia
baseline plasma VEGF-A levels and tumor neu- were low and similar between groups (3% vs.
ropilin-1 expression were potential predictors 2%). Rates of grade 3–4 hypertension were 14%
of bevacizumab efficacy. However, both bio- vs. 2%.
markers were demonstrated only in non-Asian Based on the REGARD and RAINBOW tri-
patients [33]. als, ramucirumab monotherapy and the combina-
tion of paclitaxel plus ramucirumab were
amucirumab
R approved for treatment in patients with advanced
Ramucirumab, a fully humanized monoclonal or metastatic gastric or EGJ cancer with progres-
antibody against vascular endothelial growth sion after prior fluorouracil and cisplatin
factor receptor 2 (VEGFR-2), has shown a sur- treatment.
vival benefit when used as monotherapy and in In addition, RAINFALL study was designed
combination with paclitaxel, in patients with to assess whether the addition of ramucirumab to
previously treated gastric or EGJ adenocarci- first-line chemotherapy improves outcome in
noma [34, 35]. patients with HER2-negative advanced gastric or
EGJ adenocarcinoma [36]. In the phase III Other Targeted Agents

RAINFALL trial, 645 patients with previously
untreated, metastatic, HER2 negative gastric or Mammalian Target of Rapamycin
EGJ cancer were randomly assigned to ramuci- (mTOR) Inhibitors
rumab plus chemotherapy (cisplatin plus
capecitabine or 5-fluorouracil) or chemotherapy Everolimus is an oral inhibitor of mTOR that
alone. Its primary endpoint of investigator- has demonstrated antitumor activity against
assessed PFS was significantly longer in ramuci- many types of cancer [41]. Such effects were
rumab group than chemotherapy alone group (5.7 seen in a preclinical gastric cancer model [42]
vs. 5.4 months, HR = 0.753, 95% CI 0.607–0.935, and in a phase II trial of everolimus in 53 gas-
p = 0.016). However, central independent review tric cancer patients, where it showed favorable
of the radiological images did not confirm the efficacy (median PFS 2.7 months, 95% CI
investigator-assessed difference in PFS 1.6–3.0; median OS 10.1 months, 95% CI

(HR = 0.961, 95% CI 0.768–1.203, p = 0.74), and 6.5–12.1) [43].
there was no difference in OS between groups In the GRANITE-1 phase III study, 656
(11.2 vs. 10.7 months, HR = 0.962, 95% CI 9.5– patients with progression after first- or second-
11.9). Therefore, the addition of ramucirumab to line therapy were randomly assigned (2:1) to
chemotherapy is not recommended as first-line everolimus or placebo. Everolimus did not sig-
treatment for patients with HER2-negative nificantly improve OS (5.4 vs. 4.3 months,
advanced gastric or EGJ adenocarcinoma. HR = 0.90; 95% CI 0.75–1.08, p = 0.124), a pri-
mary endpoint of this study, although PFS was
significantly prolonged in the everolimus group
VEGFR TKI (1.7 vs. 1.4 months, HR = 0.66; 95% CI 0.56–
0.78, p < 0.001) [44].
Apatinib
Apatinib is an inhibitor of the VEGFR-2 tyrosine
kinase, targeting the intracellular ATP-binding Mesenchymal-Epithelial Transition
site of the receptor. Apatinib showed antitumor Factor (MET) Inhibitors
activity in both in vitro and in vivo models [37].
On the basis of preclinical studies, phase I and MET is a known oncogene, regulating cell
phase II clinical trials were conducted, and apa- growth and survival in cancer cells [45]. High
tinib significantly improved PFS compared with expression of c-MET is correlated with poor
placebo in Chinese gastric cancer patients [38, survival in various types of cancer [46], and
39]. Finally, a randomized, phase III trial of third- c-MET may be activated by multiple mecha-
line treatment for gastric cancer was conducted, nisms, such as stimulation by its ligand, hepa-
and OS was significantly improved in the apa- tocyte growth factor (HGF), gene amplification
tinib group compared to the placebo group (6.5 or mutation, and cross talk from other
vs. 4.7 months. HR = 0.71, 95% CI 0.54–0.94, receptors [47].
p < 0.016). In addition, apatinib showed signifi-
cantly longer PFS (2.6 vs. 1.8 months, HR = 0.44, Rilotumumab
95% CI 0.33–0.61, p < 0.0001) and better ORR Rilotumumab is a fully humanized monoclonal
(2.8% vs. 0%) than the placebo group. Apatinib antibody against HGF that prevents its binding to
was well tolerated, with grade 3–4 adverse events the MET receptor. Addition of rilotumumab to
occurring in no more than 2% of patients; these chemotherapy was tested as first-line treatment
included hypertension, hand-foot syndrome, pro- of MET-positive gastric or EGJ cancers in two
teinuria, fatigue, anorexia, and elevated amino- phase III clinical trials, RILOMET-1 and
transferase levels [40]. RILOMET-2.
In RILOMET-1 phase III trial [48], 609 oly ADP-Ribose Polymerase (PARP)
P
patients with previously untreated tumors that Inhibitor
were MET-positive by IHC were randomly
assigned to rilotumumab and ECX (epirubicin, Olaparib
cisplatin, and capecitabine) or to ECX alone. Olaparib, an oral PARP inhibitor, is a key acti-
This study was stopped due to increased deaths. vator of the DNA damage response [50].
Rilotumumab showed significantly worse OS Olaparib has demonstrated clinical benefits in
(9.6 vs. 11.5 months, HR = 1.37, 95% CI 1.06– ovarian cancer patients with BRCA mutations
1.78, p = 0.016), unimproved PFS (5.7 vs. [51]. In a gastric cancer cell line, low ataxia tel-
5.7 months, HR = 1.30, 95% CI 1.05–1.62, angiectasia mutated (ATM) levels were associ-
p = 0.016), and lower ORR (30% vs. 39.2%, ated with olaparib sensitivity [52]. ATM has an
p = 0.027). Most common adverse events were essential role in maintaining genome stability
increased with rilotumumab, including periph- against DNA damage [53]. Olaparib plus pacli-
eral edema, hypoalbuminemia, deep vein throm- taxel showed better OS compared to paclitaxel
bosis, and hypocalcemia. In addition, the monotherapy as second-line therapy in a ran-
RILOMET-2 study, a randomized, phase III study domized phase II study [54]. In particular,
of adding rilotumumab to CX (cisplatin and olaparib showed better efficacy in patients with
capecitabine) as a first-line therapy for untreated low ATM by IHC (HR = 0.35; 95% CI 0.17–
MET-positive gastric or EGJ cancer, was recently 0.71; P = 0.003).
terminated after a pre-planned data monitoring In GOLD phase III study [55], 525 Asian
committee safety review. patients that had progressed from first-line che-
Accordingly, the addition of rilotumumab to motherapy were randomly assigned to olaparib
chemotherapy in patients with MET2-positive plus paclitaxel or placebo plus paclitaxel. Unlike
gastric cancer as a first line cannot be phase II study, OS did not differ between two
recommended. groups in the overall population (8.8 vs.
6.9 months, HR = 0.79, 95% CI 0.63–1.00,
Onartuzumab p = 0.026) or the ATM-negative population (12.0
Onartuzumab is a humanized monoclonal anti- vs. 10.0 months, HR = 0.73, 95% CI 0.40–1.34,
body directed against MET. In the METGastric p = 0.25). In addition, PFS and ORR were not
phase III trial [49], 562 patients with previously differ between two groups (PFS, 3.3 vs.
untreated gastric and EGJ cancers that were 3.2 months, HR = 0.84, 95% CI 0.67–1.04,
HER2-negative and MET-positive (1+/2+/3+) by p = 0,065; ORR, 24% vs. 16%, p = 0.055).
IHC were randomly assigned to onartuzumab
plus mFOLFOX6 or mFOLFOX6 alone.
Enrollment was stopped early due to negative Immunotherapy
results from a phase II trial assessing mFOLFOX6
plus onartuzumab. Median OS was not different Recently, immunogenic checkpoint blockade has
between the two groups (11.0 vs. 11.3 months, emerged as a cancer treatment, targeting compo-
HR = 0.82, p = 0.244). In the subgroup with MET nents of T-cell regulatory mechanisms, including
2+/3+, onartuzumab showed a marginal survival cytotoxic T lymphocyte antigen-4 (CTLA-4), the
benefit (11.0 vs. 9.7 months, HR = 0.64, programed cell death protein (PD-1), or its ligand
p = 0.062). In addition, exploratory subgroup (PD-L1) [56, 57]. Monoclonal antibodies to
analyses showed improved OS for the onartu- CTLA-4, PD-1, and PD-L1 have proved effec-
zumab group in non-Asian patients and in tive, especially in metastatic melanoma, and are
patients with no prior gastrectomy, regardless of currently being investigated in stomach cancer
MET status. [58, 59].
PD-1 Inhibitor zumab might be more marked in patients with a

better performance status, higher levels of PD-L1
Nivolumab expression, and tumor with microsatellite insta-
Nivolumab is an anti-PD-1 monoclonal antibody bility (MSI)-high. Grade 3–5 treatment-related
and was investigated for use in gastric cancer adverse events occurred in 14% of patients
cohort in the checkmate-032, a phase I/II trial treated with pembrolizumab and 35% of patients
that used nivolumab as either monotherapy or in treated with paclitaxel.
combined with ipilimumab in patients with
refractory solid tumors [60]. In the gastric cohort
treated with nivolumab monotherapy demon- PD-L1 Inhibitor
strated ORR of 12% and a median OS of
6.8 months. Avelumab is a human anti-PD-L1 monoclonal
In phase III ATTRACTION-2 trial [61], 493 antibody and has demonstrated treatment effi-
Asian patients with progressed to standard ther- cacy in various cancer including advanced uro-
apy randomly assigned (2:1) nivolumab or pla- thelial carcinoma [64]. In JAVELIN Gastric 300
cebo regardless of PD-L1 expression. OS was trial, 371 patients who received two prior lines
significantly improved in the nivolumab group were randomized to avelumab or physician’s
compared to the placebo group (5.26 vs. choice of chemotherapy (paclitaxel or irinote-
4.14 months. HR = 0.63, 95% CI 0.51–0.78, can). The primary endpoint of OS was not differ-
p < 0.001). Twelve months OS rates prolonged in ent between two groups (4.6 vs. 5.0 months,
nivolumab group than placebo group (26.2% vs. HR = 1.1, 95% CI 0.9–1.4, p = 0.81). Subgroup
10.9%). G3 or 4 treatment-related adverse events analyses of OS according to PD-L1 expression
occurred in 10% of patients treated with showed no difference favoring either treatment
nivolumab and 4% of patients treated with group. Grade 3–5 treatment-related adverse
placebo. events occurred in 9.2% of patients in the ave-
Base on ATTRACTION-2 trial, nivolumab lumab group and 31.6% of patients in the chemo-
should be considered as therapeutic option in therapy group.
Asian gastric cancer patients progressed from
standard therapy.
Conclusions
Pembrolizumab
Pembrolizumab is an anti-PD-1 monoclonal anti- Many phase III clinical trials of various targeted
body and was investigated in gastric cohort of agents for gastric cancer have failed (Table 32.1).
phase 1b KEYNOTE-012 study [62]. In this However, trastuzumab is the first targeted drug to
study, 39 patients with PD-L1 positive were have shown a survival benefit in gastric and EGJ
enrolled, and the ORR was 22%, and the 6-month cancer when added to first-line chemotherapy.
OS rate was 69%. Ramucirumab has shown efficacy as a monother-
In phase III KENOTE-061 study [63], 395 apy or in combination with paclitaxel as a second
patients were assigned to pembrolizumab or line. Apatinib and nivolumab monotherapy dem-
paclitaxel as a second-line therapy. onstrated their efficacy in the salvage-line set-
Pembrolizumab did not significantly prolong OS ting. Future studies should be designed to identify
compared with paclitaxel (9.1 vs. 8.3 months, robust predictive biomarkers for efficacy and to
HR = 0.82, 95% CI 0.66–1.03, one-sided include more comprehensive background infor-
p = 0.042). However, pembrolizumab demon- mation, addressing tumor heterogeneity and bio-
strated clinically meaningful 12-month survival logical resistance mechanisms specific to each
of about 40%. The treatment effect of pembroli- target.
Table 32.1 Completed randomized phase III trials with targeted agents and immune checkpoint inhibitors in gastric cancer
374
Line of Patients RR PFS OS Primary

Trials therapy Regimen no. (%) (months) (months) P-valueb endpoint Conclusion
REAL3 1st Panitumumab + EOX 278 46 6 8.8a 0.013 OS No benefit in PFS. OS was
EOX 275 42 7.4 11.3 significantly inferior
EXPAND 1st Cetuximab + XP 339 30 4.4 9.4 0.32 OS No significant benefit to PFS
XP 334 29 5.9 10.7 or OS
ToGA 1st Trastuzumab + XP/FP 167 47a 6.7a 13.5a 0.0048 OS Significant prolongation in both
XP 182 35 5.5 11.1 PFS and OS
LOGIC 1st Lapatinib + XELOX 273 53a 6a 12.2 0.35 OS Significant prolongation in PFS
XELOX 272 40 5.4 10.5 but not its primary endpoint of OS
JACOB 1st Pertuzumab + 388 56.7 8.5 17.5 0.057 OS A trend toward therapeutic
Trastuzumab + XP activity of PFS, but not its
Trastuzumab + XP 392 48.3 7.0 14.2 primary endpoint of OS
AVAGAST 1st Bevacizumab + XP 387 46a 6.7a 12.1 0.1002 OS Significant prolongation in PFS
XP 387 37 5.3 10.1 but not its primary endpoint of OS
RAINFALL 1st Ramucirumab + XP/FP 326 41.1 5.7a 11.2 0.676 PFSc Significant improvement in
XP/FP 319 36.4 5.4 10.7 investigator assessed PFS, but no
XP 334 29 5.9 10.7 benefit in central independent
reviewed PFS or OS
RILOMET-1 1st Rilotumumab + ECX 304 30a 5.7a 9.6a 0.016 OS No significant benefits to PFS and
ECX 305 39.2 5.7 11.5 OS were significantly inferior
METGastric 1st Onartuzumab + 280 46 6.7 11 0.244 OS No benefit to PFS or OS
mFOLFOX
mFOLFOX 282 41 6.8 11.3
GATSBY 2nd T-MD1 228 20.6 2.7 7.9 0.86 OS No significant prolongation in
Docetaxel or paclitaxel 117 19.6 2.9 8.6 PFS or OS
REGARD 2nd Ramucirumab 238 8 2.1a 5.2a <0.001 OS Significant prolongation in both
Placebo 117 3 1.3 3.8 PFS and OS
RAINBOW 2nd Ramucirumab + 327 28a 4.4a 9.6a 0.017 OS Significant prolongation in both
paclitaxel PFS and OS
Paclitaxel 329 16 2.9 7.4
GOLD 2nd Olaparib + paclitaxel 263 24 3.7 8.8 0.026d OS No significant benefit to PFS or
Placebo + paclitaxel 262 16 3.2 6.9 OS
GRANITE-1 2nd and Everolimus 439 4 1.7a 5.4 0.124 OS Significant prolongation in PFS
3rd Placebo 217 2 1.4 4.3 but not its primary endpoint of OS
M. Jung and S. Y. Rha
KEYNOTE-061 2nd Pembrolizumab 196 16 1.5 9.1 0.042e OS, PFS No significant prolongation in
Paclitaxel 199 14 4.1 8.3 PFS or OS
Apatinib 3rd and Apatinb 180 2.8 2.6a 6.5a 0.016 OS Significant prolongation in both
above Placebo 90 0 1.8 4.7 PFS and OS
ATTRACTION-02 3rd and Nivolumab 330 11.2 1.6a 5.3a <0.001 OS Significant prolongation in both
above Placebo 163 0 1.5 4.1 PFS and OS
JAVELIN 3rd Avelumab 185 2.2 1.4 4.6 0.81 OS No significant prolongation in
Gastric 300 Paclitaxel or irinotecan 186 4.3 2.7 5.0 PFS or OS
XP capecitabine+cisplatin, FP 5-fluorouracil+cisplatin, EOX epirubicin+oxaliplatin+capecitabine, XELOX capecitabine+oxaliplatin, ECX epirubicine+cisplatin+capecitabine,
mFOLFOX modified FOLFOX (5-FU + oxaliplatin), RR response rate, PFS progression-free survival, OS overall survival
a
Statistically significant
b
p value for overall survival
c
Investigator assessed
d
a significant difference was defined as p < 0.025 based on Hochberg procedure
e
one-side p value
32 Novel Agents and the Future Perspectives
375
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Surgery for

Surgery for Gastric

ISBN 978-3-662-45582-1 ISBN 978-3-662-45583-8 (eBook)

Library of Congress Control Number: 2018968148

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Part I History of Gastric Cancer Surgery

1 History of Gastric Cancer Surgery������������������������������������������������ 3

Part II Staging of Gastric Cancer

2 Staging of Gastric Cancer: Current Revision and Future

Part III Diagnosis of Gastric Cancer

3 Endoscopic Diagnosis: Esophagogastroduodenoscopy

Part IV Treatment of Gastric Cancer

5 Endoscopic Treatment for Early Gastric Cancer�������������������������� 89

Part V Open Surgery for Gastric Cancer

6 Open Surgery for Gastric Cancer: Distal Subtotal

9 Open Surgery for Gastric Cancer: Reconstruction���������������������� 127

Part VI Laparoscopic Surgery for Gastric Cancer

10 Laparoscopic Surgery for Gastric Cancer: Distal Subtotal

Part VII Robotic Surgery for Gastric Cancer

13 Distal Subtotal Gastrectomy with D2 Lymph Node

Part VIII Function-Preserving Surgery

16 Pylorous-Preserving Gastrectomy�������������������������������������������������� 201

Part IX Sentinel Node Navigation Surgery

19 Sentinel Node Navigation Surgery�������������������������������������������������� 223

Part X Surgery for EG Junction Cancer

20 Surgery for EG Junction Cancer���������������������������������������������������� 233

Part XI Surgery After Neoadjuvant Chemotherapy

21 Surgery After Neoadjuvant Chemotherapy���������������������������������� 245

Part XII Surgery for Remnant Gastric Cancer

22 Surgery for Remnant Gastric Cancer: Open Surgery����������������� 255

Part XIII Peritonectomy and HIPEC

24 Prevention and Treatment of Peritoneal Metastases from

Part XIV Palliative Surgery (Including Resection, Bypass and Stent)

25 Palliative Therapy for Gastric Cancer ������������������������������������������ 295

Part XV Postoperative Management and Follow-Up

26 Management of Early Postoperative Complication���������������������� 305

Part XVI Neoadjuvant and Adjuvant Treatments for Gastric Cancer

29 Neoadjuvant Treatment for Gastric Cancer���������������������������������� 343

The dawn of surgery was broken by development Aseptic Method

© Springer-Verlag GmbH Germany, part of Springer Nature 2019 3

f Gerhard Domagk (1895–1964) (Fig. 1.3a) and

Fig. 1.3 (a–e) Historical

improved and disposable devices of TA, GIA, a

Progress of Diagnostic Methods

Fig. 1.8 (a–d) Various Billroth I a b

Fig. 1.9 (a–d) Historical leaders of a b

Fig. 1.10 (a–h) Various

applied for invasion to the adjacent structures. Total Gastrectomy

Fig. 1.12 (a–h) Various

Fig. 1.14 (a–d) Various

Fig. 1.17 Lymphatic streams of the stomach (demon-

The next progress was expansion of the

Fig. 1.19 (a–h) Historical

Surgery for Peritoneal Metastasis peritoneal dissemination in 1910 [111]. This

a “Sentinel Node Navigation Surgery” [132]. This

Minimally Invasive Surgery

Japanese endoscopist Masahiro Tada of the

 ational and International Study

56. Schlöffer H. Resektion des Ganzen Magens (in

Part I History of Gastric Cancer Surgery

1 History of Gastric Cancer Surgery�� 3

Part II Staging of Gastric Cancer

2 Staging of Gastric Cancer: Current Revision and Future

Part III Diagnosis of Gastric Cancer

3 Endoscopic Diagnosis: Esophagogastroduodenoscopy

Part IV Treatment of Gastric Cancer

5 Endoscopic Treatment for Early Gastric Cancer�� 89

Part V Open Surgery for Gastric Cancer

6 Open Surgery for Gastric Cancer: Distal Subtotal

9 Open Surgery for Gastric Cancer: Reconstruction�� 127

Part VI Laparoscopic Surgery for Gastric Cancer

10 Laparoscopic Surgery for Gastric Cancer: Distal Subtotal

Part VII Robotic Surgery for Gastric Cancer

13 Distal Subtotal Gastrectomy with D2 Lymph Node

Part VIII Function-Preserving Surgery

16 Pylorous-Preserving Gastrectomy�� 201

Part IX Sentinel Node Navigation Surgery

19 Sentinel Node Navigation Surgery�� 223

Part X Surgery for EG Junction Cancer

20 Surgery for EG Junction Cancer�� 233

Part XI Surgery After Neoadjuvant Chemotherapy

21 Surgery After Neoadjuvant Chemotherapy�� 245

Part XII Surgery for Remnant Gastric Cancer

22 Surgery for Remnant Gastric Cancer: Open Surgery�� 255

Part XIII Peritonectomy and HIPEC

24 Prevention and Treatment of Peritoneal Metastases from

Part XIV Palliative Surgery (Including Resection, Bypass and Stent)

25 Palliative Therapy for Gastric Cancer �� 295

Part XV Postoperative Management and Follow-Up

26 Management of Early Postoperative Complication�� 305

Part XVI Neoadjuvant and Adjuvant Treatments for Gastric Cancer

29 Neoadjuvant Treatment for Gastric Cancer�� 343

The dawn of surgery was broken by development Aseptic Method

Progress of Diagnostic Methods

applied for invasion to the adjacent structures. Total Gastrectomy

Surgery for Peritoneal Metastasis peritoneal dissemination in 1910 [111]. This

Minimally Invasive Surgery

ational and International Study

refix “y” for TNM Classification After

EGD tric adenoma and in 2.2% of those with gastric

ips for Early Detection of Gastric

CT inner mucosa, (2) low-attenuation submucosa, and

reoperative Evaluation of Perigastric

venous phase) 3D CTA correctly identified the Differential Diagnosis

several gastric conditions because it provides an Lymphoma

Introduction than 90% 5-year overall survival, even without

was addressed in randomized controlled trials Omentectomy and Bursectomy

Indication with a belt. Usually, the patient is situated the

I ncision, Exposure, and Preparation

issection of Lymph Nodes #1 and #3

Introduction pancreatic tail, in the roots of the short gastric

nostomy without jejuno- jejunostomy. After ra of Combined Resection Moved

urgical Procedure for Total

issection of Lymph Nodes #4sa, #10,