CA Pancreas

Pancreatic cancer
The right clinical information, right where it's needed
Last updated: Dec 11, 2015
Table of Contents
Summary
Basics
Definition
Epidemiology
Aetiology
Pathophysiology
Classification
Prevention
Primary prevention
Screening
Secondary prevention
Diagnosis
Case history
Step-by-step diagnostic approach
Risk factors
History & examination factors
11
Diagnostic tests
12
Differential diagnosis
14
Diagnostic criteria
15
Treatment
18
Step-by-step treatment approach
18
Treatment details overview
22
Treatment options
23
Emerging
31
Follow up
32
Recommendations
32
Complications
32
Prognosis
33
Guidelines
34
Diagnostic guidelines
34
Treatment guidelines
35
Online resources
37
Evidence scores
38
References
42
Disclaimer
51
Summary
Fourth most common cause of cancer-related death in the US.
Most common presentation is at 65 to 75 years of age with painless obstructive jaundice and weight loss.
Generally presents late with advanced disease.
Surgical resection offers the only hope for cure. Chemotherapy and radiotherapy, as primary treatment modalities,
produce a small but statistically significant benefit. Adjuvant chemotherapy prolongs survival.
Only a minority (5% to 10%) of patients can undergo potentially curative surgery: these patients have a 5-year
survival of up to 22%, which decreases to <2% in the presence of distant metastasis.
Patients with metastatic disease (50% to 55%) have a limited survival of only 3 to 6 months.
Pancreatic cancer
Basics
BASICS
Definition
'Pancreatic cancer' refers to primary pancreatic ductal adenocarcinoma (PDAC), which accounts for >85% of all pancreatic
neoplasms. The course of pancreatic cancer has been shown to follow a linear progression model from pre-invasive
pancreatic intraepithelial neoplastic (PanIN) lesions to invasive ductal adenocarcinoma. Two additional well-defined
precursor lesions are the intraductal papillary mucinous neoplasm (IPMN) and the mucinous cystic neoplasm (MCN).[1]
Epidemiology
Pancreatic cancer is a disease with a dire prognosis. In the UK, the annual incidence is approximately 12 per 100,000. In
2002 there were 7152 new cases diagnosed in the UK, with no gender predilection.[5] In Europe it accounts for 2.6% of
all cancers and is the eighth leading cause of cancer-related mortality. Each year about 65,000 deaths in Europe are due
to this condition.[6] Annual incidence rates in men range from 7.3 to 8.7 per 100,000, and in women from 4.5 to 5.7 per
100,000. Incidence increases with age from 1.5 per 100,000/year in patients between 15 and 44 years of age to 55 per
100,000/year in patients >65 years of age.[6] Pancreatic cancer has a high mortality; >95% of those affected die of their
disease.[6]
In the US, in 2009, an estimated 42,470 new patients were diagnosed with pancreatic cancer (21,050 men and 21,420
women), with 35,240 deaths from it (18,030 men and 17,210 women), which makes it the fourth most common cause
of cancer-related death.[7] The prevalence is similar in men and women.[8] [9] Between 2002 and 2006, the median age
at diagnosis was 72 years and the median age at death was 73 years for cancer of the pancreas. The age-adjusted incidence
rate in this period was 13.1 per 100,000 men and 10.4 per 100,000 women per year.[8] Mortality from pancreatic cancer
varies among countries. In the US, there have been no substantial improvements in survival over the past 30 years. In
cases in which the cancer is still confined within the pancreas (5% to 10% of all cases), the 5-year survival is up to 22.2%;
however, in the presence of local metastases this decreases to 8.7%, and in the presence of distant metastases this
decreases to 1.8%.[8] [9] According to the 1999 to 2005 data, the overall 5-year relative survival rate was 5.5%.[8]
Aetiology
Pancreatic cancer is a disease of older people, with a peak incidence in people 65 to 75 years of age. The only consistently
reported exogenous risk factor for pancreatic cancer is cigarette smoking.[10] It is estimated that 5% to 10% of all
pancreatic cancer cases have an inherited component.[11] Inherited cancer syndromes associated with pancreatic
cancer are hereditary pancreatitis, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, familial breast
cancer syndrome, and hereditary non-polyposis colorectal cancer syndrome.[12] [13] [14]
Pathophysiology
Sixty-five percent of tumours are located within the head of the pancreas, 15% are in the body, 10% are in the tail, and
10% are multi-focal. Characteristically, there is a strong desmoplastic stroma, which can account for >60% of the tumour
mass. Lymph node metastases are common (40% to 75% of tumours <2 cm), as well as perineural and vascular invasion.
Distant metastases are usually found in liver, lung, skin, and brain.[5] Molecular and histopathological analyses have
identified 3 distinct precursor lesions: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm
(IPMN), and mucinous cystic neoplasm (MCN).[15] PanINs are the microscopic precursor lesions (<5 mm), defined as
neoplastic epithelial proliferations in the small pancreatic ducts, and are classified as PanIN-1, PanIN-2, or PanIN-3, based
on their degree of differentiation. The progression from normal epithelium to invasive carcinoma has been proposed to
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Pancreatic cancer
Basics
Classification
Histological classification of invasive ductal adenocarcinoma[2] [3]
Histological features of invasive ductal adenocarcinoma include the following.
Tubular adenocarcinoma (most common form).
Adenosquamous carcinoma.
Colloid (mucinous non-cystic) adenocarcinoma: almost always arises in association with intraductal papillary
mucinous neoplasm (IPMN) and is characterised by well-differentiated neoplastic epithelial cells within large pools
of mucin infiltrating stroma.
Hepatoid carcinoma.
Medullary carcinoma: characterised by poor differentiation with micro-satellite instability, a syncytial growth pattern,
and pushing borders.
Signet ring cell carcinoma.
Undifferentiated carcinoma: highly malignant epithelial neoplasms without a more definite direction of differentiation,
typically non-cohesive, and characterised by loss of E-cadherin expression.
Undifferentiated carcinoma with osteoclast-like giant cells: arises frequently in association with a non-invasive
precursor neoplasm such as mucinous cystic neoplasm (MCN), and is characterised by a mixture of atypical
pleomorphic cells and multi-nucleated giant cells with uniform nuclei.
BASICS
follow a linear progression model, associated with accumulation of genetic alterations. Early genetic alterations include
telomere shortening and mutations in the KRAS2 oncogene (occurring in >90% of early PanIN lesions), followed by
inactivation of the p16/CDKN2A tumour suppressor gene and late alterations including inactivation of the TP53 and
SMAD4 tumour suppressor genes.[16]
Pancreatic cancer
Prevention
Primary prevention
The risk of developing pancreatic cancer can be lowered by continued health education to reduce the use of tobacco.[25]
Screening
High-risk group
There is no routine screening programme; however, high-risk patients should be screened as part of a clinical trial in
specialist centres.[11] Based on initial results it is recommended that screening should be initiated 10 years before the
age at which pancreatic cancer has been first diagnosed in families with syndromes and after 35 years of age in hereditary
pancreatitis, co-ordinated through specialist centres.[45] The Cancer of the Pancreas Screening 2 (CAPS2) project
demonstrated a promising role for endoscopic ultrasound in screening for pancreatic cancer.[46] [47]
PREVENTION
Secondary prevention
Referral to a specialist centre that offers specialist clinical advice, genetic counselling, and genetic testing is recommended
for all patients with an increased inherited risk of developing pancreatic cancer. This includes patients with familial
pancreatic cancer or with other inherited cancer syndromes.
Pancreatic cancer
Diagnosis
Case history
Case history #1
A 70-year-old man who smokes heavily presents with a 6-month history of intermittent abdominal pain and nausea.
He has lost 10 kg of weight in the past 2 months, which he thinks is due to a decreased appetite, and he complains
of pruritus. On physical examination there is icterus in the conjunctival sclerae and epigastric tenderness but no
abdominal mass or lymphadenopathy. Blood tests demonstrate elevated bilirubin and alkaline phosphatase; the rest
of the blood tests are within the normal range.
Case history #2
A 45-year-old woman presents to her physician with vague upper abdominal (epigastric) pain. After treatment with
proton-pump inhibitors, analgesics, and antacids over a period of 3 months, which were ineffective, the patient also
started to experience back pain. This prompted an initial upper gastrointestinal (UGI) endoscopy, which was normal.
Nearly 4 months after initial presentation, an upper abdominal ultrasound reveals a pancreatic mass with liver
metastases.
Other presentations
Because there are no specific symptoms or early warning signs for pancreatic cancer, the clinical diagnosis is difficult
and patients usually present with advanced disease. Pancreatic cancer should be considered in patients 50 years of
age or older with new-onset diabetes mellitus but without a positive family history or other risk factors for diabetes.[4]
An unexplained episode of acute pancreatitis can also be a first presentation of pancreatic cancer. Because patients
with pancreatic cancer have an increased risk of thromboembolic disease, venous thrombosis or migratory
thrombophlebitis (Trousseau's sign) could also be a first presentation of pancreatic cancer.
Step-by-step diagnostic approach
History and physical examination

Physicians should consider pancreatic cancer in any patient who presents with unexplained upper abdominal pain,
painless obstructive jaundice, weight loss, and back pain. Pancreatic cancer may present as early or advanced disease.
Early disease
In early stages, when there is no obstruction of the biliary tract, the disease presents with non-specific symptoms
such as malaise, abdominal pain, nausea, or weight loss.
Advanced disease
In more advanced disease, tumours in the head of the pancreas often obstruct the common bile duct, presenting
with symptoms of obstructive jaundice such as pale stool, dark urine, and/or pruritus. Tumours in the body and
DIAGNOSIS
Pancreatic cancer most commonly presents late with advanced disease. Symptoms include unexplained upper abdominal
pain, painless obstructive jaundice, weight loss, and, in later stages, back pain. All patients with suspected pancreatic
cancer should be investigated and managed, without delay, in a framework of specialist teams to ensure prompt diagnosis
and early treatment.
Pancreatic cancer
Diagnosis
tail tend to present later and more often with pain, usually epigastric with radiation to the back; jaundice in
these patients is usually caused by hepatic or hilar metastases.
Extensive pancreatic infiltration or obstruction of the major pancreatic ducts will also cause exocrine dysfunction,
resulting in malabsorption and steatorrhoea or an unexplained episode of pancreatitis. Endocrine dysfunction,
resulting in new-onset diabetes presenting with thirst, polyuria, nocturia, and weight loss, is present in 20% to
47% of patients.[26] Pancreatic cancer should be considered in adult patients (50 years of age or older) with
new-onset diabetes but without predisposing features or a positive family history for diabetes mellitus.[4] [25]
[26]
Other signs of advanced disease include weight loss, anorexia, fatigue, an abdominal mass in the epigastrium,
hepatomegaly, a positive Courvoisier's sign (painless palpable gallbladder and jaundice), or signs of disseminated
intravascular coagulation (DIC): petechiae, purpura, bruising.
Because patients with pancreatic cancer have an increased risk of thromboembolic disease, venous thrombosis
or migratory thrombophlebitis (Trousseau's sign) could also be a first presentation of pancreatic cancer.
Laboratory tests
There are no blood tests diagnostic for pancreatic cancer. Laboratory investigations appropriate to perform in the
diagnostic work-up include the following.
Liver function tests (LFTs): abnormal LFTs are associated with the degree of obstructive jaundice but cannot
distinguish biliary obstruction (of any cause) from liver metastases.[25]
DIAGNOSIS
Biomarkers: available biomarkers, such as CA19-9 or CEA, lack the desired sensitivity and specificity for early
detection.[25] [27] CA19-9 has a sensitivity of 70% to 90% and a specificity of 90%. False-positive results are
often obtained in benign obstructive jaundice or chronic pancreatitis. CA19-9 is particularly useful as an aid in
preoperative staging, in identifying recurrence in resected cases, and in assessing the response to treatment
in advanced disease.[5]
Clotting profile and FBC: a derangement of vitamin K-dependent clotting factors will cause a prolonged
prothrombin time (PT). An FBC and clotting profile should be performed before any invasive diagnostic procedure.
Non-invasive imaging
The initial assessment for any patient with a clinical presentation suggestive of pancreatic cancer is a transabdominal
ultrasound. Transabdominal ultrasound may detect tumours >2 cm in size and possibly extrapancreatic spread (mainly
liver metastases) or dilation of the common bile duct, with a reported sensitivity of 80% to 95%; the sensitivity is lower
for early disease, or for tumours in the body or tail of the pancreas.[25] However, a normal abdominal ultrasound does
not exclude pancreatic cancer, because the pancreas may not be adequately assessed by this modality.
All patients with an initial suspicion of pancreatic cancer should undergo assessment by dynamic-phase helical or
spiral CT according to a specific pancreas protocol (i.e., triphasic cross-sectional imaging and thin slices, and in the
specific aspect of venous phase, of intravenous contrast). This has been shown to achieve diagnostic rates of 97%
for pancreatic cancer with accurate prediction of resectability in 80% to 90% of patients.[5] [28]
MRI produces similar results to CT and may be useful in patients who cannot receive intravenous contrast.
Diffusion-weighted (DW) MRI has shown a high specificity (91%) in differentiating pancreatic lesions, and could be
Pancreatic cancer
Diagnosis
considered as a useful test to differentiate malignant from benign pancreatic lesions, especially when used in
combination with fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, which has a sensitivity
of 87% to 90%. However, more studies are needed to establish the precise role of DW-MRI and PET/CT in diagnosing
pancreatic cancer.[29] [30] [31] Magnetic resonance cholangiopancreatography (MRCP) provides detailed information
of the ducts without the risks of invasive endoscopic retrograde cholangiopancreatography (ERCP); MR-angiography
(MRA) demonstrates the vascular anatomy.[5] [25] MRCP is a non-invasive method for the assessment of the biliary
tract, but does not assess the ampulla as clearly as ERCP does.
Invasive imaging
Endoscopic ultrasound (EUS) is highly sensitive in detecting small tumours (as small as 2-3 mm) and the invasion of
major vascular structures (although it is less accurate in imaging the superior mesenteric artery) and in characterising
pancreatic cystic lesions.[32] EUS-guided fine needle aspiration (FNA) for cytology has been shown to be a minimally
invasive and safe procedure, and to have a high accuracy in diagnosing pancreatic cancer, with a sensitivity of 85%
to 91% and a specificity of 94% to 98%.[33] [34] ERCP alone, as a pure imaging technique, has a sensitivity of 70% to
82% and a specificity of 88% to 94%. ERCP has the advantage that it provides an opportunity to sample for cytology
or histology and that a stent can be placed to palliate biliary obstruction when surgery is not elected or must be
delayed.[5] [25]
Laparoscopy, including laparoscopic ultrasound (LUS) and peritoneal washes, can detect occult metastatic lesions
in the liver and peritoneal cavity not identified by other imaging modalities (especially for lesions in the body or tail,
or in patients with a higher risk of disseminated disease: borderline resectable, large primary tumour, high CA19-9).[25]
[35] [36] [37] However, the selection criteria to identify patients in whom staging laparoscopy would have a high
diagnostic accuracy will need to be verified in additional prospective studies.[36] [37]
There is no uniform consensus regarding using additional staging technologies. The selective use of ERCP and/or
MRCP (and occasionally MRA) will accurately define tumour size, infiltration, and the presence of metastatic disease.
EUS is particularly indicated in patients whose CT scans show no lesion or who have questionable vascular or lymph
node involvement. Depending on a centre's expertise, laparoscopic staging may be appropriate in some patients.[25]
[38]
Diagnosis by histology is not required before surgical resection; a non-diagnostic biopsy should not delay appropriate
surgical treatment when clinical suspicion of pancreatic cancer is high.[38] By contrast, in patients with advanced,
unresectable disease selected for palliative therapy, biopsy confirmation is required.[39] All patients should be referred
to a centre with expertise in dealing with pancreatic diseases, without waiting for biopsy.
Guided biopsy or FNA under EUS, or pancreatic ductal brushings, or biopsies at ERCP are preferable to a transperitoneal
approach taken transcutaneously under ultrasound or CT guidance. The two main concerns of transperitoneal
techniques are the risk of a false-negative result and tumour cells spreading along the needle track or within the
peritoneum.[40] Therefore, in patients with potentially resectable disease, transperitoneal techniques should be
avoided; in the case of metastatic disease, percutaneous biopsy from a metastatic site is preferred.[25]
Risk factors
Strong
DIAGNOSIS
Tissue diagnosis
Pancreatic cancer
Diagnosis
smoking
It is estimated that 1 in 4 cases of pancreatic cancer can be attributed to cigarette smoking. Evidence suggests
that people who smoke have a 1.74-fold risk of developing pancreatic cancer.[10] [17] Although the increased risk
is relatively small, cigarette smoking has been firmly linked to pancreatic cancer.[10] 17[B]Evidence
FHx pancreatic cancer

Criteria for familial pancreatic cancer are at least two first-degree relatives with pancreatic cancer, or at least two
second-degree relatives with pancreatic cancer, one of whom had early onset pancreatic cancer (<50 years of age),
without the presence of other inherited cancer syndromes. The risk of pancreatic cancer increases with the number
of relatives affected, suggesting autosomal-dominant inheritance of a rare allele.[18] Although the main gene
responsible has not yet been identified, a germ-line mutation in BRCA2 can be found in up to 20% of families.[14]
other hereditary cancer syndromes

A genetic predisposition to pancreatic cancer may be present in 5% to 10% of patients. In familial pancreatic cancer,
the risk of pancreatic cancer increases with the number of first-degree relatives affected.[13] [14]
Hereditary pancreatitis: mutations in PRSS1 gene and an estimated 35% lifetime risk of pancreatic cancer.
Peutz-Jeghers syndrome: mutations in the STK11/LKB1 gene and an estimated 36% lifetime risk of pancreatic
cancer.
Familial atypical multiple mole melanoma syndrome: mutations in p16 and an estimated 17% lifetime risk of
pancreatic cancer.
Familial breast cancer syndrome: BRCA1 and BRCA2 mutations; the risk of pancreatic cancer is dependent on the
number of relatives affected.
Hereditary non-polyposis colorectal cancer syndrome: mutations in hMLH1 or hMSH2 and an estimated risk of
about 5%.[5]
Weak
DIAGNOSIS
chronic sporadic pancreatitis

The risk of pancreatic cancer in patients with chronic pancreatitis is difficult to assess because there are usually
confounding factors such as smoking, high alcohol intake, or other potential biases. However, relative risks of
pancreatic cancer varying from 2.3% to 18.5% have been reported.[19]
diabetes mellitus
Some evidence suggests that there is a 1% chance of developing pancreatic cancer within 3 years of diagnosis in
people diagnosed with new-onset diabetes mellitus.[4] However, estimates of the magnitude of increased risk of
pancreatic cancer in people with diabetes vary.18[C]Evidence
obesity
A systematic review of prospective studies of the association between BMI, abdominal fatness, and pancreatic
cancer risk in patients with pancreatic adenocarcinoma found that being overweight or obese was associated with
a greater risk of pancreatic cancer.[20] Obesity at older ages, or shortly before cancer diagnosis, was associated
with a reduced overall survival;[21] however, the reported risks vary.19[B]Evidence
dietary factors
High alcohol intake, diets high in meats and fat, and low serum folate levels have all been reported to increase the
risk of pancreatic cancer. However, their exact role is still unclear due to inconsistent results.[22] [23] [24]
10
Pancreatic cancer
Diagnosis
History & examination factors

Key diagnostic factors
presence of risk factors (common)
Key risk factors include tobacco use, family history, and other hereditary cancer syndromes.
jaundice (common)
Suggests biliary obstruction or, very rarely, hepatic or hilar nodal metastases.
non-specific upper abdominal pain or discomfort (common)

Unexplained, non-specific upper abdominal pain or discomfort is usually one of the first symptoms and may be
overlooked by patients and physicians. Persistent back pain is associated with retroperitoneal metastases.
weight loss and anorexia (common)

Other signs of advanced disease include weight loss and anorexia. Rapid weight loss is usually associated with
unresectability.
Other diagnostic factors

age: 65 to 75 years (common)
Pancreatic cancer is a disease of older people, with a peak incidence in people 65 to 75 years of age.[9]
steatorrhoea (uncommon)
Extensive pancreatic infiltration or obstruction of the major pancreatic ducts will also cause exocrine dysfunction,
resulting in malabsorption and steatorrhoea.
thirst, polyuria, nocturia, and weight loss (uncommon)
nausea, vomiting, anorexia, and mid-epigastric pain (uncommon)

Pancreatic cancer should be excluded in patients with an unexplained episode of acute pancreatitis characterised
by nausea, vomiting, anorexia, and mid-epigastric pain.[25]
hepatomegaly (uncommon)
Sign of advanced disease with hepatic metastases.
epigastric abdominal mass (uncommon)

Sign of advanced disease.
positive Courvoisier's sign (uncommon)

Sign of advanced disease (indicated by painless palpable gallbladder and jaundice).
petechiae, purpura, bruising (uncommon)
11
DIAGNOSIS
Endocrine dysfunction, resulting in new-onset diabetes presenting with thirst, polyuria, nocturia, and weight loss,
is present in 20% to 47% of patients.[26]
Pancreatic cancer should be considered in adult patients (50 years of age or older) with new-onset diabetes but
without predisposing features or a positive FHx for diabetes mellitus.[4] [25] [26]
Diagnosis
Pancreatic cancer
Signs of disseminated intravascular coagulation (DIC) in advanced disease.
Trousseau's sign (uncommon)

Because patients with pancreatic cancer have an increased risk of thromboembolic disease, venous thrombosis
or migratory thrombophlebitis (Trousseau's sign) could also be a first presentation of pancreatic cancer.
Diagnostic tests
1st test to order
Test
Result
abdominal ultrasound
pancreatic mass, dilated bile

Ultrasound of the pancreas, bile duct, and liver is recommended, without delay, ducts, liver metastases
in a clinical presentation suggestive of pancreatic cancer.[25] There is a high
sensitivity for tumours in the head of the pancreas (80% to 95%); sensitivity is
lower for early disease, or for tumours in the body or tail of the pancreas.[5]
[25] A normal ultrasound does not exclude pancreatic cancer, and where
suspicion is present an axial scan (CT or MRI) is recommended.
liver function tests (LFTs)

Demonstrates the degree of obstructive jaundice, but cannot distinguish
between any cause of obstructive jaundice or liver metastases.
bilirubin, alkaline phosphatase,

and gamma-GT elevated in
obstructive jaundice;
aminotransferases (ALT)
normal or slightly elevated
DIAGNOSIS
Other tests to consider

Test
Result
prothrombin time (PT)
prolonged
A derangement of vitamin K-dependent clotting factors will cause a prolonged

PT. An FBC and clotting profile should be performed before any invasive
diagnostic procedure.
FBC
platelets decreased in DIC;

An FBC and clotting profile should be performed before any invasive diagnostic anaemia in GI bleeding
procedure.
CA19-9 biomarker
elevated
Sensitivity of 70% to 90% and a specificity of 90%. False-positive results are

often obtained in benign obstructive jaundice or chronic pancreatitis.
Particularly useful as an aid in preoperative staging, in identifying recurrence
in resected cases, and in assessing the response to treatment in advanced
disease.[5]
pancreatic protocol CT
may demonstrate a mass in the

pancreas and the extent of local
All patients with suspected disease on ultrasound should undergo
pancreas-specific CT. This has been shown to achieve 97% diagnostic rates of or distant spread
pancreatic cancer with accurate prediction of resectability in 80% to 90% of
patients.[25]
12
Diagnosis
Pancreatic cancer
Test
Result
endoscopic retrograde cholangiopancreatography (ERCP)
ampullary tumour may be seen;

In patients for whom the CT scan is equivocal, ERCP is a useful diagnostic tool. all other pancreatic tumours
are only detectable if there is
Samples can be taken for cytology or histology, and symptomatic biliary
pancreatic duct involvement
obstruction can be alleviated by placement of a stent.[25] ERCP alone, as a
pure imaging technique, has a sensitivity of 70% to 82% and a specificity of
88% to 94%.
magnetic resonance cholangiopancreatography (MRCP)
can show detailed information

Non-invasive method for assessment of the biliary tract; does not assess the of duct involvement
ampulla as clearly as ERCP. Has a role in patients who cannot receive contrast
for CT or if ERCP is not technically feasible.[25]
endoscopic ultrasound (EUS)

Should be considered if there is no mass on CT but a clinical suspicion of
pancreatic cancer. Highly sensitive in detecting small tumours and the
involvement of major vascular structures (but less accurate in imaging the
superior mesenteric artery), and in characterising pancreatic cystic lesions.[32]
Can be used for FNA.[33] [34]
small tumours in the pancreas

can be detected, as well as the
involvement of certain veins:
for example, portal vein
staging laparoscopy (with laparoscopic ultrasound)
can identify peritoneal,

capsular, or serosal
Particularly useful in patients with borderline resectable lesions or poor
prognostic factors such as markedly elevated CA19-9, large primary tumour, involvement, or small hepatic
metastases not seen on CT
or tumour in the body or tail of the pancreas.[37]
biopsy
13
DIAGNOSIS
may confirm pancreatic ductal

Diagnosis by histology is not required before surgical resection; a non-diagnostic adenocarcinoma
biopsy should not delay appropriate surgical treatment when clinical suspicion
of pancreatic cancer is high.[38] By contrast, in patients with advanced,
unresectable disease selected for palliative therapy, biopsy confirmation is
required.
All patients should be referred to a centre with expertise in dealing with
pancreatic diseases, without waiting for biopsy.
Guided biopsy or FNA under EUS, or pancreatic ductal brushings, or biopsies
at ERCP, are preferable to a transperitoneal approach taken transcutaneously
under ultrasound or CT guidance. The two main concerns of transperitoneal
techniques are the risk of a false-negative result and tumour cells spreading
along the needle track or within the peritoneum.[40] Therefore, in patients
with potentially resectable disease, transperitoneal techniques should be
avoided. In the case of metastatic disease, percutaneous biopsy from a
metastatic site is preferred.[25]
Diagnosis
Pancreatic cancer
Differential diagnosis
Condition
Differentiating signs /
symptoms
Differentiating tests
Because typical symptoms of

chronic pancreatitis are also seen
in pancreatic cancer,
distinguishing between these two
diseases can be difficult. Patients
may present with pain radiating
to the back, malabsorption,
malnutrition, and pancreatic
endocrine insufficiency. There
may be a past history of repeated
admission for acute pancreatitis
or alcohol abuse.
A few histological features are

diagnostic for pancreatic cancer,
which can differentiate between
pancreatic cancer and chronic
pancreatitis.[41]
Bile duct stones
Obstructive jaundice may be

painful due to calculous disease.
Patients may be younger.
Stones can be demonstrated on

abdominal ultrasound, both in the
gallbladder and in the bile duct.
However, stones may also be seen
in patients with pancreatic cancer.
ERCP will clarify the situation by
ruling out stricture (seen in
pancreatic cancer) and confirming
bile duct stones, which can be
cleared at the time of
intervention.
Ampullary carcinoma
Patients may present with

iron-deficiency anaemia before
presenting with obstructive
jaundice. Jaundice may be of a
waxing and waning nature due to
sloughing of ampullary cancer,
resulting in transient resolution
of the jaundice.
Upper gastrointestinal (UGI)

endoscopy will confirm the
presence of ampullary lesion, and
biopsy at the time of procedure
will verify presence of dysplasia or
cancer. A side-viewing endoscope
gives a better view of ampullary
lesions than the traditional
front-viewing endoscope.
Cholangiocarcinoma
Mid- and low bile-duct cancers are

indistinguishable on presentation
from pancreatic cancer. Both
present with painless obstructive
jaundice.
Cross-sectional imaging such as

CT scan or MRI may reveal
absence of pancreatic mass and
perhaps thickening of bile duct
suggestive of
cholangiocarcinomas.
DIAGNOSIS
Chronic pancreatitis
14
Diagnosis
Pancreatic cancer
Condition
Differentiating signs /
symptoms
Autoimmune pancreatitis
Almost no distinguishing features

between pancreatic cancer and
autoimmune pancreatitis.
In contrast to pancreatic cancer,
autoimmune pancreatitis is at
least twice as common in men as
it is in women. And, rarely,
patients with autoimmune
pancreatitis present with
symptoms related to
extrapancreatic organ
involvement (renal, pulmonary,
hepatic, gastroduodenal, or
involvement of the hypophysis
have been reported).[42]
Differentiating tests
A uniformly enlarged pancreas

without duct dilation on axial
scanning may prompt serum IgG4
levels or pancreatic biopsy (which
may be diagnostic), but this
should be managed at a
pancreatic centre.
Diagnostic criteria
American Joint Committee on Cancer (AJCC) TNM staging[43]
TNM (tumour, node, metastasis) definitions:
Primary tumour (T)
Tx: primary tumour cannot be assessed
T0: no evidence of primary tumour
Tis: carcinoma in situ
DIAGNOSIS
T1: tumour limited to the pancreas and <2 cm

T2: tumour limited to the pancreas and >2 cm
T3: the cancer has extended beyond the pancreas but does not involve the coeliac axis or superior mesenteric
artery
T4: the cancer has extended beyond the pancreas and involves the coeliac axis or the superior mesenteric artery
(unresectable primary tumour)
Regional lymph nodes (N)
Nx: regional lymph nodes cannot be assessed
N0: no lymph node involvement
N1: regional lymph node involvement
Distant metastasis (M)
15
Pancreatic cancer
Diagnosis
Mx: distant metastasis cannot be assessed

M0: no distant metastasis
M1: distant metastasis present
Stage grouping
Stage 0: Tis, N0, M0
Stage IA: T1, N0, M0
Stage IB: T2, N0, M0
Stage IIA: T3, N0, M0
Stage IIB: T1, N1, M0; T2, N1, M0; T3, N1, M0
Stage III: T4, any N; M0
Stage IV: any T, any N, M1
American Joint Committee on Cancer (AJCC) histological grading[43]

Gx: grade cannot be assessed
G1: well differentiated
G2: moderately differentiated
DIAGNOSIS
G3: poorly differentiated

G4: undifferentiated
Clinical stages
Resectable disease: there are no universally accepted criteria for resection, and decisions about resectability should be
made by a multidisciplinary team. Based on clinical experience, resectable pancreatic cancer can be defined as a tumour
without evidence of involvement of the superior mesenteric artery (SMA) or coeliac axis, a patent superior mesenteric-portal
venous confluence, and no evidence of distant metastases.[38] [44]
Borderline resectable disease: criteria for borderline resectable tumours include superior mesenteric vein (SMV) or portal
impingement, <180 tumour abutment on SMA, abutment or encasement of hepatic artery (if reconstructible), SMV
occlusion of a short segment and reconstructible, or, in tumours in the tail of the pancreas, SMA or coeliac encasement
<180.[38] [44]
Locally advanced unresectable disease: tumours involving nearby structures to an extent that renders them unresectable
despite the absence of evidence of metastatic disease. Metastases to a regional lymph node beyond the field of resection
are considered unresectable.[38] [44]
Metastatic disease: evidence of distant metastasis (to liver, lung, or bone).[43] [44]
Extent of resection
16
Pancreatic cancer
Diagnosis
R1: microscopic disease left behind after surgical removal (the surgeon does not know at the time of the operation but
is informed by the pathologist).
R2: macroscopic disease left behind after surgical removal (the surgeon is aware at the end of the operation that a part
of the tumour was left behind, and this is confirmed by the pathologist).
DIAGNOSIS
17
Pancreatic cancer
Treatment
Step-by-step treatment approach

All patients with suspected pancreatic cancer should be investigated and managed, without delay, in a framework of
specialist teams to ensure prompt diagnosis and early treatment. Treatment is based on the extent of the disease, and
the only potentially curative treatment is operative resection. Alternative treatments, for more extensive disease, include
palliative surgery to relieve symptoms and endoscopic or percutaneous biliary stenting to relieve jaundice.[25]
Chemotherapy and radiotherapy may be used as palliative treatment as well as in the adjuvant setting with surgery.[25]
Decisions about management and resectability should be made by a multidisciplinary team. Owing to the poor prognosis,
clinical trials are appropriate alternatives for treatment of patients with any stage of disease and should be considered
before selecting palliative approaches.
Resectable disease (stages I and II)

All patients with resectable pancreatic cancer, about 15% to 20%, should be referred to a high-volume specialist
centre for surgical resection to increase resection rates and decrease hospital morbidity and mortality.[25] [48] [49]
Resectable disease is defined as a tumour without evidence of involvement of the superior mesenteric artery (SMA)
or coeliac axis, a patent superior mesenteric-portal venous confluence, and no evidence of distant metastases.
However, approaches to patients with locoregional disease involvement differ between institutions. Criteria for
borderline resectable tumours include superior mesenteric vein (SMV) or portal impingement, <180 tumour abutment
on SMA, abutment or encasement of hepatic artery (if reconstructible), SMV occlusion of a short segment and
reconstructible, or, in tumours in the tail of the pancreas, SMA or coeliac encasement <180.[38] [44]
Surgical management
TREATMENT
Surgical resection is the preferred treatment in patients with resectable disease.2[B]Evidence 3[C]Evidence
The type and extent of the surgery depend on location and site of the tumour. The most widely used procedures
are the proximal pancreaticoduodenectomy with antrectomy (Kausch-Whipple procedure) or the
pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire procedure) for tumours in the head of the
pancreas. Pylorus-preserving pancreaticoduodenectomy may lead to similar quality of life and survival compared
with Kausch-Whipple pancreaticoduodenectomy.[50] [51] 4[B]Evidence 5[B]Evidence Surgery with extended
lymphadenectomy and/or partial excision of the nerve plexus around the superior mesenteric artery and coeliac
axis is associated with increases in adverse effects compared with standard resection, without conferring any
survival benefit.[52] [53] 16[C]Evidence Extended resections, including the portal vein or total pancreatectomy,
may be required in some cases in specialist centres but do not increase survival when carried out routinely.[25]
Left pancreatectomy (with splenectomy) is appropriate for localised tumours in the body or tail of the pancreas
(rare).[54] A systematic review comparing open versus laparoscopic distal pancreatectomy suggests that the
laparoscopic approach may be safe in selected cancer patients. However, further evaluation of oncological
outcome is required before this will become a more widely used procedure.[55]
Significant evidence of benefit has not been demonstrated from routine stenting of jaundiced patients before
resection; there is no improvement in surgical outcome, and it may increase the risk of infective
complications.[25] [56] However, patients with symptoms of cholangitis (or whose definitive surgery is delayed
by >10 days due to logistical reasons) may require an internal biliary stent. If a stent is placed before surgery, a
plastic stent should be placed endoscopically.[25] A temporary stent is also recommended in patients undergoing
neoadjuvant induction therapy before surgery in the setting of a clinical trial.
Neoadjuvant therapy
18
Pancreatic cancer
Treatment
Neoadjuvant therapy (treatment given prior to surgery to reduce the size or extent of the tumour, in order to
enhance chances of successful surgical removal of all tumour tissue) remains under investigation in pancreatic
cancer; to date, no large randomised controlled trials have been reported. Although no significant improvement
in survival has been shown,[25] neoadjuvant radiotherapy alone or in combination with chemotherapy
(gemcitabine or fluorouracil or oxaliplatin or cisplatin) may result in better locoregional control.[25] [57] [58]
[59] 5-fluorouracil-based neoadjuvant chemoradiotherapy may be considered in patients with borderline
resectable disease; however, in patients with resectable disease, it has been shown to result in similar survival
compared with patients who had surgery without neoadjuvant treatment and, therefore, it is only recommended
in the setting of a clinical trial.[25] [57] [58] [60] Prospective randomised controlled trials testing different
neoadjuvant regimes, such as gemcitabine-based chemotherapy or chemoradiotherapy, are ongoing.
Adjuvant therapy
Adjuvant therapy is treatment given after surgery to minimise the risk of relapse due to occult disease.
Completely resected: no definite standard has been established. Adjuvant fluorouracil- or gemcitabine-based
chemotherapy increases median and 5-year survival in people with completely resected pancreatic cancer,
compared with surgery alone.[61] [62] 10[B]Evidence 23[C]Evidence Based on consensus, when chemotherapy
alone is the choice of adjuvant chemotherapy, gemcitabine is preferred over fluorouracil or capecitabine.[38]
However, the results of one large prospective randomised controlled trial of bolus fluorouracil and folinic acid
versus gemcitabine (ESPAC-3) did not reveal a significant difference in survival between adjuvant fluorouracil
and gemcitabine.[63] Folinic acid enhances the effect of 5-fluorouracil, and is therefore commonly administered
with fluorouracil. Both agents inhibit thymidylate synthase, the enzyme required for the synthesis of the
nucleotide thymidine.
Incompletely resected: adjuvant chemoradiotherapy remains controversial.11[C]Evidence Data from ESPAC-1
and meta-analysis[64] [65] 9[B]Evidence suggest that chemoradiotherapy seems to prolong survival only in
incompletely excised (R1 or R2 resection) cancers. When the choice of treatment is chemoradiotherapy,
fluorouracil-based chemoradiotherapy with additional systemic gemcitabine is recommended.[66] [67] [68]
Adjuvant chemotherapy or chemoradiotherapy should only be considered in patients who have adequately
recovered from surgery; treatment should ideally be initiated within 4 to 8 weeks of surgery.[38] Adjuvant
chemoradiotherapy should not be given to patients who also received neoadjuvant radiotherapy or
chemoradiotherapy.
Locally advanced unresectable disease (stage III)
Palliative surgery or endoscopic stent insertion

19
TREATMENT
Two studies compared pancreatic resection with systemic palliative treatment in patients with locally advanced
disease.[69] Although the quality of evidence is low with a high risk of bias, carefully selected patients may benefit
from surgical resection when sufficient expertise is available and patients are willing to accept the potentially increased
morbidity associated with surgery.[69] However, routine practice for patients presenting with locally advanced
pancreatic cancer (about 30%) is palliative treatment with endoscopic stent insertion into the bile duct, and sometimes
bypass surgery if endoscopic stenting fails or if patients are found to be unresectable at the time of operation (but
deemed resectable on preoperative imaging), followed by chemotherapy or chemoradiotherapy. Locally advanced
unresectable disease includes tumours involving nearby structures to an extent that renders them unresectable
despite the absence of evidence of metastatic disease. Metastasis to a regional lymph node beyond the field of
resection is considered unresectable.[38]
Pancreatic cancer
Treatment
Endoscopic palliation is preferred over surgical approaches. However, patients failing trial dissection (attempt
to remove locally advanced cancer) may benefit from surgical bypass of bile duct and gastric outlet obstruction
(termed 'double bypass'), in which the biliary bypass should be constructed with the bile duct in preference to
the gallbladder,[70] or from prophylactic gastroenterostomy.[71]
Endoscopic stent placement is preferable to transhepatic plastic stent placement.[25] The choice between
plastic or self-expanding metal stent depends on clinical factors and local availability and expertise. The life of
a plastic stent is about 3 months; therefore, metal stents are recommended for patients with good performance
status and a favourable prognosis.[70] [72] 13[A]Evidence Covered metal stents generally have a longer patency
compared with uncovered metal stents (approximately 7 months versus 5 months), and are increasingly used.[73]
Chemotherapy or chemoradiotherapy
After relief of biliary obstruction and sometimes, if required, of gastric obstruction, chemotherapy with
gemcitabine or fluorouracil (or capecitabine) or chemoradiotherapy is given to control the tumour.
Two treatment options with similar outcome are gemcitabine-based chemotherapy or chemoradiotherapy with
fluorouracil; these have both been shown to increase overall survival and quality of life in patients with locally
advanced unresectable disease, compared with best supportive care or radiotherapy alone.[74] [75] Patients
with good performance status appear to benefit from monotherapy with gemcitabine or gemcitabine-based
chemotherapy, with either a platinum analogue (oxaliplatin or cisplatin), a fluoropyrimidine (fluorouracil or
capecitabine), or erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor).[76] [77] [78] [79] [80] [81] [82] [83]
[84] 12[B]Evidence Based on the strong evidence of the effects of the FOLFIRINOX regimen (oxaliplatin,
irinotecan, fluorouracil, and folinic acid) in the metastatic setting,[85] combination therapy with oxaliplatin,
fluorouracil, and folinic acid can be considered as an appropriate alternative to gemcitabine-based combination
therapy.[38] Folinic acid enhances the effect of fluorouracil and is therefore commonly administered with this
drug. Both agents inhibit thymidylate synthase, the enzyme required for the synthesis of the nucleotide
thymidine. Fluorouracil-based chemotherapy has been shown to reduce mortality rates at 1 year in people with
non-resectable pancreatic cancer.20[A]Evidence
Due to the nature of the disease and poor survival statistics, trials investigating second-line treatment options
are limited, but patients who received first-line gemcitabine chemotherapy alone and continue to have a good
performance status may benefit from second-line combination therapy of oxaliplatin, fluorouracil, and folinic
acid.[86]
Metastatic disease: stage IV

The main objective for patients with metastatic disease (50% to 55%) is palliation. These patients have a limited
survival (3-6 months) that is dependent on tumour burden and performance status at presentation.[48] [87] Metastatic
disease is characterised by evidence of distant metastasis to the liver, lung, or bone.[43] [44]
TREATMENT
Palliative surgery or endoscopic stent insertion

Endoscopic palliation is preferred over surgical approaches. However, patients failing trial dissection (attempt
to remove locally advanced cancer) may benefit from surgical bypass of bile duct and gastric outlet obstruction
(termed 'double bypass'), in which the biliary bypass should be constructed with the bile duct in preference to
the gallbladder,[70] or from prophylactic gastroenterostomy.[71]
20
Pancreatic cancer
Treatment
Endoscopic stent placement is preferable to transhepatic plastic stent placement.[25] The choice between
plastic or self-expanding metal stent depends on clinical factors and on local availability and expertise. The life
of a plastic stent is about 3 months; therefore, metal stents are recommended for patients with good performance
status and a favourable prognosis.[70] 13[A]Evidence Covered metal stents generally have a longer patency
compared with uncovered metal stents (approximately 7 months versus 5 months), and are increasingly used.[73]
Chemotherapy
Monotherapy with gemcitabine given weekly, 3 out of every 4 weeks, remains the palliative treatment of choice
for patients with poor performance status.[88] 14[A]Evidence 21[C]Evidence Since the initial trial that confirmed
superiority of gemcitabine in 1997,[88] many studies have investigated different combination regimens or the
addition of targeted therapies.[77] [78] [79] [80] [81] [82] [83] [84] Patients with good performance status may
benefit from combination therapy of gemcitabine and either a platinum analogue (oxaliplatin or cisplatin), a
fluoropyrimidine (fluorouracil or capecitabine), erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor), or a
combination of oxaliplatin with fluorouracil and folinic acid.[38] [77] [78] [79] [80] [81] [82] [83] [84] Despite
the lack of a clear benefit in overall survival in clinical trials,[89] [90] [91] these combination regimens are still
used in clinical practice because subsets of patients respond very well (and there is no biomarker to select these
patients). Combination chemotherapy of fluorouracil plus gemcitabine has been shown to be no more effective
at 1 year than gemcitabine monotherapy at reducing mortality rates or time to progression in people with
non-resectable pancreatic cancer. However, 2 new treatment options are available for patients with metastatic
pancreatic cancer and good performance status: the combination of oxaliplatin, irinotecan, fluorouracil, and
folinic acid (FOLFIRINOX);[85] or nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with
gemcitabine.[92] Both regimens improved survival compared with gemcitabine alone (median overall survival
was 11.1 months in the FOLFIRINOX group versus 6.8 months with gemcitabine;[85] and 8.5 months in the
nab-paclitaxel/gemcitabine group versus 6.7 months with gemcitabine[92]). Folinic acid enhances the effect
of fluorouracil and is therefore commonly administered with this drug. Both agents inhibit thymidylate synthase,
the enzyme required for the synthesis of the nucleotide thymidine. There is insufficient evidence to recommend
chemoradiotherapy over chemotherapy alone in people with metastatic pancreatic cancer.
Due to the nature of the disease and poor survival statistics, trials investigating second-line treatment options
are limited, but patients who received first-line gemcitabine chemotherapy alone and continue to have a good
performance status may benefit from second-line combination therapy of oxaliplatin, fluorouracil, and folinic
acid.[86]
Supportive therapies
All patients with pancreatic cancer should have access to palliative medicine specialists.[25]
In all patients with pancreatic cancer, pancreatic enzyme supplements should be used to maintain weight and increase
quality of life, together with attention to dietary intake and additional nutritional supplements.[5] [25]
21
TREATMENT
Pancreatic pain (abdominal and back pain) can be a troublesome symptom to control in locally advanced non-resectable
disease and metastatic disease. Pain control should be commenced along 'the analgesic ladder', but opioids are often
required to control the pain. Dosing has to be titrated according to individual requirements and symptom relief versus
adverse effect balances. Additional options include using appropriate long-acting opioid analgesics, percutaneous
(or endoscopic ultrasound-guided) coeliac block, or splanchnicectomy.[93] [94] [95] [96]
Treatment
Pancreatic cancer
Treatment details overview

Consult your local pharmaceutical database for comprehensive drug information including contraindications, drug
interactions, and alternative dosing. ( see Disclaimer )
Acute
( summary )
Patient group
resectable (stages I and II)
completely resected
incompletely resected
locally advanced unresectable (stage III)
Treatment
1st
surgical resection
plus
pancreatic enzyme replacement
adjunct
preoperative biliary stenting
adjunct
neoadjuvant radiotherapy or chemoradiotherapy
plus
adjunct
adjuvant chemotherapy
adjuvant chemoradiotherapy
1st
endoscopic stent insertion or palliative surgery
plus
chemotherapy or chemoradiotherapy
plus
pain management + pancreatic enzyme

replacement
1st
plus
chemotherapy
plus

replacement
TREATMENT
metastatic (stage IV)
Tx line
22
Treatment
Pancreatic cancer
Treatment options
Acute
Patient group
resectable (stages I and II)
Tx line
1st
Treatment
surgical resection
Surgical resection is the preferred treatment in
patients with resectable disease.2[B]Evidence
3[C]Evidence
The nature and extent of the surgery depends on the
location and site of the tumour.
The most widely used procedures are the proximal
pancreaticoduodenectomy with antrectomy
(Kausch-Whipple procedure) or the pylorus-preserving
pancreaticoduodenectomy (Traverso-Longmire
procedure) for tumours in the head of the pancreas.
Pylorus-preserving pancreaticoduodenectomy may
lead to similar quality of life and survival compared with
Kausch-Whipple pancreaticoduodenectomy.[50] [87]
4[B]Evidence 5[B]Evidence
Extended lymphadenectomy is associated with
increases in adverse effects compared with standard
lymphadenectomy, without conferring any survival
benefit.[52]
plus
pancreatic enzyme replacement

In all patients with pancreatic cancer, pancreatic
enzyme supplements should be used to maintain
weight and increase quality of life, together with
attention to dietary intake and additional nutritional
supplements.[5] [25]
Primary options
pancrelipase: 500-2500 lipase units/kg/meal,
titrate dose according to response, maximum
10,000 lipase units/kg/day
adjunct
preoperative biliary stenting

Significant evidence of benefit has not been
demonstrated from routine stenting of jaundiced
patients before resection; there is no improvement in
surgical outcome, and it may increase the risk of
infective complications.[25] [56]
23
TREATMENT
However, patients with symptoms of cholangitis (or

whose definitive surgery is delayed by >10 days due to
logistical reasons) may require an internal biliary stent.
If a stent is placed before surgery, a plastic stent should
be placed endoscopically.[25]
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
A temporary stent is also recommended in patients
undergoing neoadjuvant induction therapy before
surgery, in the setting of a clinical trial.
adjunct
neoadjuvant radiotherapy or chemoradiotherapy

Neoadjuvant therapy remains under investigation in
pancreatic cancer; to date no large randomised
controlled trials have been reported.
Although no significant improvement in survival has
been shown,[25] neoadjuvant radiotherapy alone or
in combination with chemotherapy may result in better
locoregional control.[25] [57] [58] [59]
Neoadjuvant chemoradiotherapy may be considered
in patients with borderline resectable disease; however,
in patients with resectable disease, it has been shown
to result in similar survival compared with patients who
had surgery without neoadjuvant treatment and,
therefore, it is only recommended in the setting of a
clinical trial.[25] [57] [58] [60]
See local specialist protocol for dosing guidelines.
Primary options
radiation
OR
radiation
--AND- gemcitabine
-or fluorouracil
-or oxaliplatin
-or cisplatin
completely resected
plus
adjuvant chemotherapy
No definite standard has been established.
TREATMENT
Adjuvant fluorouracil- or gemcitabine-based

chemotherapy increases median and 5-year survival
in people with completely resected pancreatic cancer,
compared with surgery alone.[61] 10[B]Evidence
Based on consensus, when chemotherapy alone is
the choice of adjuvant chemotherapy, gemcitabine is
preferred over fluorouracil or capecitabine.[38]
However, the results of one large prospective
randomised controlled trial of bolus fluorouracil and
folinic acid versus gemcitabine (ESPAC-3) did not reveal
24
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
a significant difference in survival between adjuvant
fluorouracil and gemcitabine.[63]
Primary options
gemcitabine
OR
fluorouracil
-and folinic acid
OR
capecitabine
incompletely resected
adjunct
adjuvant chemoradiotherapy
Adjuvant chemoradiotherapy remains
controversial.11[C]Evidence
Data from ESPAC-2 and meta-analysis[64]
9[B]Evidence suggest that chemoradiotherapy seems
to prolong survival only in incompletely excised (R1 or
R2 resection) cancers.
When choice of treatment is chemoradiotherapy,
fluorouracil-based chemoradiotherapy with additional
systemic gemcitabine is recommended.[66] [67] [68]
Adjuvant chemoradiotherapy should not be given to
patients who have also received neoadjuvant
chemoradiotherapy.
Primary options
fluorouracil
-and folinic acid
-and gemcitabine
-and radiation
1st

Endoscopic palliation is preferred over surgical
approaches.
However, patients failing trial dissection (attempt to
remove locally advanced cancer) may benefit from
25
TREATMENT
locally advanced unresectable (stage III)
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
surgical bypass of evident or anticipated bile duct and
gastric outlet obstruction, termed 'double bypass', in
which the biliary bypass should be constructed with
the bile duct in preference to the gallbladder,[70] or
from prophylactic gastroenterostomy.[71]
Endoscopic stent placement is preferable to
transhepatic plastic stent placement.[25]
The choice between plastic or self-expanding metal
stent depends on clinical factors, local availability, and
expertise.
The life of a plastic stent is about 3 months; therefore,
metal stents are recommended for patients with good
performance status and a favourable prognosis.[70]
13[A]Evidence
plus
chemotherapy or chemoradiotherapy
Two treatment options with similar outcome are
gemcitabine-based chemotherapy or
chemoradiotherapy with fluorouracil; these have both
been shown to increase overall survival and quality of
life in patients with locally advanced unresectable
disease, compared with best supportive care or
radiotherapy alone.[74] [75] 12[B]Evidence
Patients with good performance status appear to
benefit from monotherapy with gemcitabine or
gemcitabine-based chemotherapy, with either a
platinum analogue (oxaliplatin or cisplatin), a
fluoropyrimidine (fluorouracil or capecitabine), or
erlotinib (an oral HER1/EGFR tyrosine kinase
inhibitor).[76] [77] [78] [79] [80] [81] [82] [83] [84]
Based on the strong evidence of the effects of the
FOLFIRINOX regimen (oxaliplatin, irinotecan,
fluorouracil, and folinic acid) in the metastatic
setting,[85] combination therapy with oxaliplatin,
fluorouracil, and folinic acid can be considered as an
appropriate alternative to gemcitabine-based
combination therapy.[38] Folinic acid enhances the
effect of fluorouracil and is therefore commonly
administered with this drug. Both agents inhibit
thymidylate synthase, the enzyme required for the
synthesis of the nucleotide thymidine.
TREATMENT
Fluorouracil-based chemotherapy has been shown

to reduce mortality rates at 1 year in people with
Primary options
gemcitabine
26
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
OR
gemcitabine
--AND- oxaliplatin
-or cisplatin
-or capecitabine
-or erlotinib
OR
gemcitabine
-and fluorouracil
-and folinic acid
OR
fluorouracil
-and folinic acid
-and radiation
OR
oxaliplatin
-and fluorouracil
-and folinic acid
plus

replacement
Pancreatic pain (abdominal and back pain) can be a
troublesome symptom to control.
Pain control should be commenced along 'the
analgesic ladder', but opioids are often required to
control the pain.
Local pain-management protocols should be
consulted for suggested analgesics. Dosing has to be
titrated according to individual requirements and
symptom relief versus adverse effect balances.
TREATMENT
Additional options include using appropriate

long-acting opioid analgesics, percutaneous (or
endoscopic ultrasound-guided) coeliac block, or
splanchnicectomy.[94] [95] [96]
27
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
Pancreatic enzyme supplements should be used to
maintain weight and increase quality of life, together
with attention to dietary intake and additional
nutritional supplements.[5]
Primary options
metastatic (stage IV)
1st

Endoscopic palliation is preferred over surgical
approaches.
However, patients failing trial dissection (attempt to
remove locally advanced cancer) may benefit from
surgical bypass of evident or anticipated bile duct and
gastric outlet obstruction, termed 'double bypass', in
which the biliary bypass should be constructed with
the bile duct in preference to the gallbladder,[70] or
from prophylactic gastroenterostomy.[71]
Endoscopic stent placement is preferable to
transhepatic plastic stent placement.[25]
The choice between plastic or self-expanding metal
stent depends on clinical factors, local availability, and
expertise.
The life of a plastic stent is about 3 months; therefore,
metal stents are recommended for patients with good
performance status and a favourable prognosis.[70]
13[A]Evidence
plus
chemotherapy
Monotherapy with gemcitabine given weekly, 3 out
of every 4 weeks, remains the palliative treatment of
choice for patients with poor performance status.[88]
14[A]Evidence 21[C]Evidence
TREATMENT
Patients with good performance status may benefit

from combination therapy with oxaliplatin, irinotecan,
fluorouracil, and folinic acid (FOLFIRINOX),[85] or from
nanoparticle albumin-bound paclitaxel (nab-paclitaxel)
in combination with gemcitabine.[92]
Other frequently used combination regimens include:
gemcitabine with a platinum analogue (oxaliplatin or
cisplatin); gemcitabine with a fluoropyrimidine
(fluorouracil or capecitabine); gemcitabine with
erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor);
or a combination of oxaliplatin with fluorouracil and
28
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
folinic acid.[38] [77] [78] [79] [80] [81] [82] [83]
[84]Despite the lack of a clear benefit in overall survival
in clinical trials,[89] [90] [91] these combination
regimens are still used in clinical practice because
subsets of patients respond very well (and there is no
biomarker to select these patients).
Combination chemotherapy of fluorouracil plus
gemcitabine has been shown to be no more effective
at 1 year than gemcitabine monotherapy at reducing
mortality rates or time to progression in people with
Folinic acid enhances the effect of fluorouracil and
is therefore commonly administered with this drug.
Both agents inhibit thymidylate synthase, the enzyme
required for the synthesis of the nucleotide thymidine.
There is insufficient evidence to recommend
chemoradiotherapy over chemotherapy alone in
people with metastatic pancreatic cancer.
Primary options
gemcitabine
OR
gemcitabine
--AND- oxaliplatin
-or cisplatin
-or capecitabine
-or erlotinib
OR
gemcitabine
-and paclitaxel nanoparticle albumin-bound
OR
TREATMENT
gemcitabine
-and fluorouracil
-and folinic acid
OR
oxaliplatin
29
Treatment
Pancreatic cancer
Acute
Patient group
Tx line
Treatment
-and irinotecan
-and fluorouracil
-and folinic acid
OR
oxaliplatin
-and fluorouracil
-and folinic acid
plus

replacement
Pancreatic pain (abdominal and back pain) can be a
troublesome symptom to control.
Pain control should be commenced along 'the
analgesic ladder', but opioids are often required to
control the pain.
Local pain-management protocols should be
consulted for suggested analgesics. Dosing has to be
titrated according to individual requirements and
symptom relief versus adverse effect balances.
Additional options include using appropriate
long-acting opioid analgesics, percutaneous (or
endoscopic ultrasound-guided) coeliac block, or
splanchnicectomy.[94] [95] [96]
Pancreatic enzyme supplements should be used to
maintain weight and increase quality of life, together
with attention to dietary intake and additional
nutritional supplements.[5]
Primary options
TREATMENT

30
Pancreatic cancer
Treatment
Emerging
Clinical trials
Many clinical trials are ongoing for all stages of disease. [National Cancer Institute: clinical trials] Although albumin-bound
paclitaxel with gemcitabine[92] and the FOLFIRINOX combination[85] improve survival for patients with metastatic
pancreatic cancer, the improvements are modest and the prognosis for patients with pancreatic cancer remains poor.
Research has significantly increased our understanding of the molecular nature of pancreatic cancer: specific agents
designed to target specific pathways or the dense desmoplastic stroma are of great interest and an important focus of
clinical trials. Although initial results in clinical trials in unselected patients were disappointing with respect to survival,
development of targeted therapies and various combination regimens (of both targeted therapies and cytotoxics),
combined with better patient selection, continues to be a high priority.[97] [98] [99] [100] [101] [102] [103] [104] [105]
TREATMENT
31
Follow up
Pancreatic cancer
FOLLOW UP
Recommendations
Monitoring
Data regarding the role of monitoring patients with resectable pancreatic cancer are limited. Based on consensus,
the National Comprehensive Cancer Network (NCCN) panel recommends symptom assessment by history and physical
examination, every 3 to 6 months for 2 years after resection. No uniform consensus exists in the role and frequency
of CA19-9 determinations (suggested to indicate overall survival in patients with resectable disease) and follow-up
CT scans.[38] [116]
Patients with advanced metastatic disease treated with chemotherapy should be closely followed for toxicity at each
cycle of chemotherapy, and assessed for response to chemotherapy every 2 months. These patients may have abrupt
changes in clinical status due to rapid tumour progression with increased risk of complications. Given that there is
no possibility of cure, a follow-up schedule should be discussed with the patient and designed to avoid emotional
stress and economic burden for the patient.
Patient instructions
Patients should be encouraged to follow established guidelines for good health, such as maintaining a healthy weight,
not smoking, eating a balanced diet, and having recommended cancer-screening tests. If indicated, patients with
locally advanced or metastatic pancreatic cancer should receive formal assessment by a palliative medicine service.
Many avenues for support exist within the local community and beyond: for example, The American Cancer Society
has information on many local support groups, and social workers, counsellors, psychiatrists, [American Cancer
Society: support programs and services] or clergy can be helpful in providing information.
Complications
Complications
surgical complications: pancreatic leaks and fistula
Timeframe
Likelihood
short term
medium
The mortality associated with pancreaticoduodenectomy is <5% in high-volume specialist centres. However, morbidity
ranges from 30% to 60%. Given that one of the major complications and causes of death after pancreaticoduodenectomy
is leakage from the residual pancreatic stump, both pharmacological and technical attempts have been tried to prevent
pancreatic stump-related complications. The only treatments shown to be effective in preventing complications
(pancreatic leak and intra-abdominal collections) are somatostatin and its analogues, particularly octreotide.[108]
[109] 6[C]Evidence Pancreatic duct occlusion does not assist in preventing complications associated with pancreatic
leak when added to anastomosis and is not recommended due to reported increase in pancreatic fistula and pancreatic
endocrine and exocrine insufficiency.[108] 7[C]Evidence Although some studies suggest that pancreaticogastrostomy
reduces post-operative pancreatic fistula compared with pancreaticojejunostomy,[110] [111] the evidence is weak,
with studies reporting conflicting results and a high risk of bias.[108] [112] Dual-loop (Roux-en-Y) reconstruction with
isolation of the pancreaticojejunostomy from biliary drainage significantly prolonged operating times, without reducing
post-operative complications, and is thus not superior to conventional single-loop reconstruction.[113] There is no
evidence that using fibrin glue is effective for preventing pancreatic leak.[108] [112] 8[C]Evidence
surgical complications: early delayed gastric emptying
short term
medium
Early delayed gastric emptying is usually associated with intra-abdominal sepsis; the treatment should be directed
towards treating the cause. Prokinetic agents such as erythromycin may help. Evidence suggests that placement of
gastro-enteric anastomosis either ante-colic or retro-colic makes no difference.[114] Furthermore, a Billroth type II
reconstruction may reduce early delayed gastric emptying over Roux-en-Y reconstruction.[115]
duodenal obstruction
32
long term
low
Follow up
Pancreatic cancer
Complications
Timeframe
Likelihood
cholangitis
variable
medium
Patients present with fever, jaundice, right upper quadrant (RUQ) pain, and, in severe cases, sepsis or mental confusion.
Cholangitis has significant potential for mortality and morbidity, with reported mortality rates from 13% to 88%.
Antibiotics are required for the treatment of cholangitis, where the choice of antibiotic treatment depends on the
organism found and its antibiotic sensitivity. Many patients respond to antibiotic therapy; patients who do not respond
require emergency biliary drainage.
deep vein thrombosis and pulmonary embolism
variable
medium
Patients with pancreatic cancer have an increased risk of developing venous thromboembolic disease: incidence rates
range from 17% to 57%. Long-term use of low molecular weight heparins is preferred over warfarin in both primary
and secondary prevention of venous thromboembolic disease.[107]
bleeding
variable
low
If a pancreatic tumour ulcerates into the duodenum and bleeds, therapeutic options include super-selective embolisation
of bleeding vessels or covered metal stent.
Prognosis
Resectable disease (stage I, II)
At the time of diagnosis, 15% to 20% of patients have resectable disease. However, even in patients who have undergone
radical pancreatic resection, median survival ranges from 15 to 19 months, with a 5-year survival rate of about 20%. The
strongest prognostic indicators for long-term patient survival include negative resection margins, tumour DNA content,
tumour size, and absence of lymph node metastases.[48]
Unresectable locally advanced disease (stage III)

About 30% of patients present with locally advanced pancreatic cancer. Although chemotherapy with or without
radiotherapy may give a modest improvement in survival and palliation, it rarely controls the cancer. Within months of
completion of treatment, patients frequently have evidence of local tumour progression or new metastatic disease.[48]
These patients most probably harboured sub-clinical metastatic disease and should be considered for treatment with
novel agents. The prognostic impact of molecular factors, such as K-Ras, epidermal growth factor receptor, PTEN, or AKT,
and detection of circulating tumour cells is under evaluation.[74]
Metastatic disease (stage IV)

Patients with metastatic disease (50% to 55%) have a limited survival of only 3 to 6 months. Survival is dependent on
tumour burden and performance status at presentation.[48]
33
FOLLOW UP
About 5% of patients develop duodenal obstruction secondary to pancreatic carcinoma. Patients usually present with
abdominal pain, vomiting, absolute constipation, and varying degrees of abdominal distension. Treatment of duodenal
obstruction can be operatively with a gastrojejunostomy or by endoscopic stenting.[106]
Guidelines
Pancreatic cancer
Diagnostic guidelines
Europe
Pancreatic adenocarcinoma: ESMOESDO clinical practice guidelines for diagnosis, treatment
and follow-up
Published by: European Society for Medical Oncology; European Society of DigestiveLast published: 2012
Oncology
Summary: Provides diagnostic, therapeutic, and surveillance recommendations.
GUIDELINES
Guidelines for the management of patients with pancreatic cancer periampullary and
ampullary carcinomas
Published by: Pancreatic Section of the British Society of Gastroenterology;
Last published: 2005
Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal
Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest
Group for Gastro-Intestinal Radiology
Summary: Comprehensively reviews the diagnostic tests available for the diagnosis of pancreatic cancer and
summarises these in brief statements of recommendation, with level of evidence, for the investigation, staging, and
tissue diagnosis of pancreatic cancer.
North America
NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma
Published by: National Comprehensive Cancer Network
Summary: This guideline provides a comprehensive overview of the diagnostic approach for this cancer.
The role of ERCP in benign diseases of the biliary tract

Published by: American Society for Gastrointestinal Endoscopy
Summary: Provides guidance in the use of GI endoscopy in the diagnosis of benign pancreatic disease and in
differentiating chronic pancreatitis from pancreatic adenocarcinoma.
Guidelines for diagnostic laparoscopy

Published by: Society of American Gastrointestinal and Endoscopic Surgeons
Summary: These diagnostic laparoscopy guidelines are a series of systematically developed statements to assist
surgeons (and patients) decisions about the appropriate use of diagnostic laparoscopy (DL) in specific clinical
circumstances. The statements included in this guideline are the product of a systematic review of published work on
the topic, and the recommendations are explicitly linked to the supporting evidence. The strengths and weaknesses
of the available evidence are described, and expert opinion sought where the evidence is lacking.
34
Pancreatic cancer
Guidelines
North America
Cystic neoplasms of the pancreas
Published by: Society for Surgery of the Alimentary Tract
Summary: Provides guidance on the diagnosis and treatment of cystic pancreatic tumours including mucinous
adenocarcinoma.
ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal
cancer
Published by: American Society of Clinical Oncology
Treatment guidelines
Europe
Pancreatic adenocarcinoma: ESMOESDO clinical practice guidelines for diagnosis, treatment
and follow-up
Published by: European Society for Medical Oncology; European Society of DigestiveLast published: 2012
Oncology
Summary: Provides diagnostic, therapeutic, and surveillance recommendations.
Control of pain in adults with cancer

Published by: Scottish Intercollegiate Guidelines Network
Summary: Provides evidence-based recommendations for the management of pain in adult patients who have cancer.
Guidelines for the management of patients with pancreatic cancer periampullary and
ampullary carcinomas
Published by: Pancreatic Section of the British Society of Gastroenterology;
Pancreatic Society of Great Britain and Ireland; Association of Upper Gastrointestinal
Surgeons of Great Britain and Ireland; Royal College of Pathologists; Special Interest
Group for Gastro-Intestinal Radiology
Summary: Reviews current treatment options for pancreatic cancer and summarises these in brief statements of
recommendation, with level of evidence, for interventions and management of patients with pancreatic cancer.
35
GUIDELINES
Summary: Provides recommendations for the use of tumour markers in tumour diagnosis and surveillance, including
CA 19-9 in pancreatic cancer. CA 19-9 is not recommended for use as a screening test for pancreatic cancer. Use of
CA 19-9 testing alone is not recommended to determine either the operability of or the surgical results in pancreatic
cancer. CA 19-9 measurements alone cannot provide definitive evidence of disease recurrence without confirmation
with imaging studies, clinical findings, and/or biopsy. Present data are insufficient to recommend the routine use of
serum CA 19-9 alone for monitoring response to treatment. However, CA 19-9 may be measured at the start of
treatment for locally advanced metastatic disease and every 1 to 3 months during active treatment. If there is an
elevation in such serial CA 19-9 determinations, this may indicate disease progression, and confirmation with other
studies should be sought.
Guidelines
Pancreatic cancer
Europe
The use of gemcitabine for the treatment of pancreatic cancer
Published by: National Institute for Health and Care Excellence
Summary: Provides guidance for the use of gemcitabine for patients with advanced or metastatic adenocarcinoma
of the pancreas.
North America
NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma
Published by: National Comprehensive Cancer Network
GUIDELINES
Summary: This guideline provides a comprehensive overview of the management of this cancer.
The treatment of locally advanced pancreatic cancer

Published by: Cancer Care Ontario
Summary: Provides a good, systemic overview of treatment of unresectable, locally advanced pancreatic cancer with
a clear summary of randomised controlled trials to date.
Cystic neoplasms of the pancreas

Published by: Society for Surgery of the Alimentary Tract
Summary: Provides guidance on the diagnosis and treatment of cystic pancreatic tumours including mucinous
adenocarcinoma.
36
Pancreatic cancer
Online resources
Online resources
1.
National Cancer Institute: clinical trials (external link)
2.
American Cancer Society: support programs and services (external link)
ONLINE RESOURCES
37
Pancreatic cancer
Evidence scores
Evidence scores
1.
Decreased pancreatic cancer risk: there is medium-quality evidence that the risk of developing pancreatic cancer
can be lowered by continued health education to reduce the use of tobacco.
Evidence level B: Randomized controlled trials (RCTs) of <200 participants, methodologically flawed RCTs of >200
participants, methodologically flawed systematic reviews (SRs) or good quality observational (cohort) studies.
2.
Mortality in resectable disease: there is medium-quality evidence that pancreaticoduodenectomy (primarily

Kausch-Whipple or pylorus-preserving pancreaticoduodenectomy) is more effective than chemoradiotherapy at
increasing survival rates in people with resectable pancreatic cancer.
More info from BMJ Clinical Evidence
3.
Quality of life in resectable disease: there is poor-quality evidence that pancreaticoduodenectomy (primarily
Kausch-Whipple or pylorus-preserving pancreaticoduodenectomy) may be no more effective than
chemoradiotherapy at improving quality of life in people with resectable pancreatic cancer.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized controlled
trials (RCTs) of <200 participants.
4.
Mortality in resectable disease: there is medium-quality evidence that pylorus-preserving pancreaticoduodenectomy

is no more effective than Kausch-Whipple pancreaticoduodenectomy at increasing survival rates in people with
resectable pancreatic cancer.
5.
Quality of life in resectable disease: there is medium-quality evidence that pylorus-preserving

pancreaticoduodenectomy may be no more effective than Kausch-Whipple pancreaticoduodenectomy at improving
quality of life in people with resectable pancreatic cancer.
EVIDENCE SCORES
6.
38
Complications after pancreatic surgery: there is poor-quality evidence that somatostatin and its analogues may be
more effective than placebo/control at reducing overall pancreas-related complications (leaks, fistula, abscess,
and intra-abdominal collection) after pancreatic surgery, but may be no more effective after
pancreaticoduodenectomy.
Pancreatic cancer
Evidence scores
7.
Preventing pancreatic leak: there is poor-quality evidence that adding temporary duct occlusion of the main
pancreatic duct to enteric anastomosis may be no more effective than anastomosis alone at decreasing
intra-abdominal collections, but it is not known whether duct occlusion may be more effective at decreasing
pancreatic fistulas. Adding temporary duct occlusion of the main pancreatic duct to enteric anastomosis may
increase endocrine and exocrine insufficiency at 3 months to 1 year compared with anastomosis alone.
8.
Symptom severity: there is poor-quality evidence that fibrin glue may be no more effective than no glue at preventing
pancreatic leak in people who have undergone pancreatic surgery for neoplasms or inflammatory disease.
9.
Survival in people with pancreatic cancer with positive resection margins: there is medium-quality evidence that
chemotherapy is an effective adjuvant treatment in pancreatic cancer, but not chemoradiotherapy. The trials
demonstrated an increase in 2- and 5-year survival rates in patients with pancreatic cancer with positive resection
margins who received chemotherapy, compared with patients who did not.
10.
Survival in people with completely resected pancreatic cancer treated with post-operative gemcitabine: there is
medium-quality evidence that post-operative gemcitabine chemotherapy significantly delayed the development
of recurrent disease after complete resection of pancreatic cancer, compared with observation alone.
11.
Mortality in resected pancreatic cancer: there is poor-quality evidence that adjuvant chemoradiotherapy is no more
effective than surgery alone at decreasing mortality rates in people with resected pancreatic adenocarcinoma.
Survival in locally advanced unresectable disease: there is medium-quality evidence that chemoradiotherapy
increases overall survival in patients with locally advanced unresectable pancreatic cancer compared with supportive
care or exclusive radiotherapy, but is more toxic. Chemoradiotherapy is not superior to chemotherapy in terms of
39
EVIDENCE SCORES
12.
Pancreatic cancer
Evidence scores
survival; fluorouracil is the reference chemotherapy in association with radiotherapy. Two options are available for
treatment: gemcitabine-based chemotherapy and chemoradiotherapy .
13.
Symptomatic relief in patients with obstructive jaundice due to unresectable pancreatic cancer: there is good-quality
evidence that endoscopic metal stents are the intervention of choice in patients with malignant distal obstructive
jaundice due to pancreatic cancer.
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200 participants.
14.
Survival and clinical benefit with gemcitabine: there is good-quality evidence that gemcitabine is more effective
than fluorouracil in palliative treatment of advanced symptomatic pancreatic cancer. The study also demonstrated
an increase in the survival rate at 12 months for gemcitabine-treated patients compared with those treated with
fluorouracil.
15.
Survival in advanced pancreatic cancer: there is good-quality evidence that combination therapy with erlotinib and
gemcitabine significantly improves survival in patients with advanced pancreatic cancer. The trial showed that
1-year survival was greater with erlotinib plus gemcitabine compared with placebo.
16.
Complications in people receiving pancreaticoduodenectomy: there is poor-quality evidence that extended (radical)
lymphadenectomy may increase post-operative complications, wound infections, transfusion requirements, rates
of delayed gastric emptying, and operating time in people receiving pancreaticoduodenectomy, compared with
standard lymphadenectomy.
EVIDENCE SCORES
17.
Risk of developing pancreatic cancer in people who smoke: there is medium-quality evidence from a meta-analysis
of 82 studies published between 1950 and 2007 that found current smokers have a 1.74-fold (95% CI 1.61 to 1.87)
increased risk of developing pancreatic cancer.
18.
Risk of developing pancreatic cancer in patients with new-onset diabetes mellitus: there is poor-quality evidence
from one population-based cohort study of >2000 people suggesting that there was a 1% chance of developing
pancreatic cancer within 3 years of diagnosis in people diagnosed with new-onset diabetes mellitus. However, this
study does suggest that the value of using new-onset diabetes as an indicator of early pancreatic cancer needs to
be evaluated further.
40
Pancreatic cancer
Evidence scores
19.
Risk of developing pancreatic cancer in overweight or obese patients: there is medium-quality evidence that being
overweight or obese is associated with a greater risk of pancreatic cancer, independent of diabetes status, and with
a younger age of disease onset. Obesity at older ages, or shortly before cancer diagnosis, was associated with a
reduced overall survival.
20.
Mortality in non-resectable cancer: there is good-quality evidence that fluorouracil-based chemotherapy reduces
mortality rates at 1 year in people with non-resectable pancreatic cancer, compared with supportive care.
21.
Mortality rates in non-resectable cancer: there is poor-quality evidence that gemcitabine monotherapy seems as
effective at 1 year as fluorouracil monotherapy at reducing mortality rates in people with non-resectable pancreatic
cancer.
22.
Reduction in mortality rates in non-resectable cancer: there is good-quality evidence that fluorouracil plus
gemcitabine combination chemotherapy is no more effective at 1 year than gemcitabine monotherapy at reducing
mortality rates or time to progression in people with non-resectable pancreatic cancer.
23.
Mortality and relapse rates in people with resected pancreatic cancer: there is poor-quality evidence that
fluorouracil-based adjuvant chemotherapy may increase survival rates in people with resected pancreatic
adenocarcinoma, compared with surgery alone. Furthermore, adjuvant chemotherapy may reduce relapse rates
in people with resected pancreatic cancer, compared with surgery alone.
EVIDENCE SCORES
41
Pancreatic cancer
References
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51
Contributors:
// Authors:
Fieke E.M. Froeling, MD, MRCP, PhD
NIHR Academic Clinical Lecturer
Specialist Registrar Medical Oncology, Imperial College London, London, UK
DISCLOSURES: FEMF is an author of a reference cited in this monograph.
Hemant M. Kocher, MBBS, MS, MD, FRCS
Professor of Liver and Pancreas Surgery
Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, London, UK
DISCLOSURES: HMK is an author of a number of references cited in this monograph. HMK has received a grant from Celgene to
conduct an Investigator Initiated trial and received meeting organisation grants from Celgene and AbbVie.
// Peer Reviewers:
Ross Carter, FRCS
Consultant Pancreatic Surgeon
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
DISCLOSURES: Not disclosed.
Nikhil I. Khushalani, MD
Assistant Professor of Oncology
Roswell Park Cancer Institute, Buffalo, NY
DISCLOSURES: NIK has received funding for the conduction of clinical trials and associated translational studies from Merck,
Pfizer, and Astra-Zeneca. NIK has a grant from the NCCN (from research support by Roche).

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Pancreatic cancer

The right clinical information, right where it's needed

Last updated: Dec 11, 2015

Step-by-step diagnostic approach

History & examination factors

Step-by-step treatment approach

Treatment details overview

Fourth most common cause of cancer-related death in the US.

Step-by-step diagnostic approach

History and physical examination

FHx pancreatic cancer

other hereditary cancer syndromes

chronic sporadic pancreatitis

History & examination factors

non-specific upper abdominal pain or discomfort (common)

weight loss and anorexia (common)

Other diagnostic factors

thirst, polyuria, nocturia, and weight loss (uncommon)

nausea, vomiting, anorexia, and mid-epigastric pain (uncommon)

epigastric abdominal mass (uncommon)

positive Courvoisier's sign (uncommon)

petechiae, purpura, bruising (uncommon)

Trousseau's sign (uncommon)

pancreatic mass, dilated bile

liver function tests (LFTs)

bilirubin, alkaline phosphatase,

Other tests to consider

prothrombin time (PT)

A derangement of vitamin K-dependent clotting factors will cause a prolonged

platelets decreased in DIC;

Sensitivity of 70% to 90% and a specificity of 90%. False-positive results are

may demonstrate a mass in the

endoscopic retrograde cholangiopancreatography (ERCP)

ampullary tumour may be seen;

magnetic resonance cholangiopancreatography (MRCP)

can show detailed information

endoscopic ultrasound (EUS)

small tumours in the pancreas

staging laparoscopy (with laparoscopic ultrasound)

can identify peritoneal,

may confirm pancreatic ductal

Because typical symptoms of

A few histological features are

Bile duct stones

Obstructive jaundice may be

Stones can be demonstrated on

Patients may present with

Upper gastrointestinal (UGI)

Mid- and low bile-duct cancers are

Cross-sectional imaging such as

Almost no distinguishing features

A uniformly enlarged pancreas

T1: tumour limited to the pancreas and <2 cm

Mx: distant metastasis cannot be assessed

American Joint Committee on Cancer (AJCC) histological grading[43]

G3: poorly differentiated

Step-by-step treatment approach

Resectable disease (stages I and II)

Locally advanced unresectable disease (stage III)

Palliative surgery or endoscopic stent insertion