biomedicines

Article
Assessment of Colorectal Anastomosis with Intraoperative
Colonoscopy: Its Role in Reducing Anastomotic Complications
Ri-Na Yoo 1 , Ji-Yeon Mun 1 , Hyeon-Min Cho 1 , Bong-Hyeon Kye 1 and Hyung-Jin Kim 2, *

1 Department of Surgery, St. Vincent’s Hospital, The Catholic University of Korea,

Suwon 16247, Republic of Korea; ninayoo1111@gmail.com (R.-N.Y.); answl89@gmail.com (J.-Y.M.)
2 Department of Surgery, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea,
Seoul 03312, Republic of Korea
* Correspondence: hj@catholic.ac.kr

Abstract: The use of intraoperative colonoscopy (IOC) to evaluate the integrity of newly created
anastomosis has been advocated by some surgeons. However, whether direct visualization of fresh
anastomosis can help reduce anastomotic problems is still unclear. This study investigates the impact
of immediate endoscopic assessment of colorectal anastomosis on anastomotic problems. This is a ret-
rospective study conducted at a single center. Among six hundred forty-nine patients who underwent
stapled anastomosis for left-sided colorectal cancer, the anastomotic complications were compared
between patients who underwent IOC and those who did not. Additionally, patients with subsequent
intervention after the IOC were compared to those without the intervention. Twenty-seven patients
(5.0%) developed anastomotic leakage, and six (1.1%) experienced anastomotic bleeding postopera-
tively. Of the patients with IOC, 70 patients received reinforcement sutures to secure anastomotic
stability. Of 70 patients, 39 patients showed abnormal findings in IOC. Thirty-seven patients (94.9%)
who underwent reinforcement sutures did not develop postoperative anastomotic problems. This
study demonstrates that IOC assessment with reinforcement sutures does not imminently reduce
the rate of anastomotic complications. However, its use may play a role in detecting early technical
failure and preventing postoperative anastomotic complications.

Citation: Yoo, R.-N.; Mun, J.-Y.; Cho, Keywords: colonoscopy; colorectal neoplasms; surgical anastomosis; anastomotic leak
H.-M.; Kye, B.-H.; Kim, H.-J.
Assessment of Colorectal Anastomosis
with Intraoperative Colonoscopy: Its
Role in Reducing Anastomotic 1. Introduction
Complications. Biomedicines 2023, 11,
Anastomotic complications in colorectal cancer surgery are the most feared and dread-
1162. https://doi.org/10.3390/
ful morbidity because of the disastrous impact on postoperative recovery and oncologic
biomedicines11041162
outcome. After left-sided colorectal cancer surgery, the leakage rate ranges from 2.6% to
Academic Editor: Ferenc Sipos 12.3%, of which the overall anastomotic leakage rate is approximately 6% [1,2]. In addition,
Received: 19 March 2023
postoperative bleeding from stapled colorectal anastomosis has been reported to occur in
Revised: 3 April 2023
up to 6.5% of patients [3]. Various risk factors in anastomotic problems, particularly leakage,
Accepted: 11 April 2023
include obesity, male sex, old age, advanced tumor stage, and preoperative chemoradiation,
Published: 12 April 2023 which are often difficult to modify [1]. Nevertheless, some factors are considered modifi-
able, particularly those associated with surgical procedures, such as excessive tension and
poor perfusion on the anastomosis, bleeding in an anastomotic region, and the number of
linear staples used [4].
Copyright: © 2023 by the authors. To minimize anastomotic complications, surgeons have suggested evaluating the
Licensee MDPI, Basel, Switzerland. integrity of anastomosis intraoperatively [5,6]. Different intraoperative techniques are
This article is an open access article available to assess newly constructed anastomosis, such as the intraoperative air leakage
distributed under the terms and test (IALT), intraoperative colonoscopy (IOC), and indocyanine green (ICG) test [7]. IALT is
conditions of the Creative Commons probably the handiest and most popular technique performed by surgeons, requiring little
Attribution (CC BY) license (https://
time and effort [8]. IOC allows the direct visualization of fresh anastomosis and immediate
creativecommons.org/licenses/by/
detection of disruption or bleeding at the anastomotic staple lines. It also directly insufflates
4.0/).

Biomedicines 2023, 11, 1162. https://doi.org/10.3390/biomedicines11041162 https://www.mdpi.com/journal/biomedicines

Biomedicines 2023, 11, 1162 2 of 12

the lumen with enough air pressure, allowing a simultaneous air leak test. In contrast, the
ICG test evaluates the perfusion of the anastomosis by visualizing the fluorescence emitted
by ICG under near-infrared light [9].
Each methodology’s effect on reducing anastomotic complications is inconclusive
and still in the process of building evidence. Therefore, in this study, focusing on the role
of intraoperative colonoscopy, we investigated its impact on lowering the anastomotic
complications of leakage and bleeding.

2. Materials and Methods

Based on a prospectively collected database constructed from patient records, a retro-
spective review of patients who underwent operative management for colorectal cancer
at our institution between January 2017 and December 2021 was conducted. The local
ethics committee approved this study (IRB #VC22RISI0125). The requirement for informed
consent was waived because of the retrospective design and because the analysis used
anonymous clinical data and involved no additional procedure other than routine practices
in a clinical setting, presenting no risk of harm to the patients.
The database consists of the following parameters: patient demographics, including
age, sex, and body mass index (BMI), American Society of Anesthesiologists (ASA) class,
preoperative condition of colonic obstruction or perforation, neoadjuvant therapy, type
of surgery, operative approach, operation time, location of anastomosis (above or below
the peritoneal reflection level), the height of anastomosis, type of anastomosis (stapled or
hand-sewn), formation of diverting stoma, pathologic TNM stage, anastomotic leakage
or bleeding, and diagnosis timing of anastomotic problem. Anastomotic leakage was
defined and graded according to the definition of the International Study Group of Rectal
Cancer [10].

2.1. Patients
Among 1210 consecutive patients, 1111 underwent primary anastomosis with or
without diverting stoma (Figure 1). The exclusion criteria were patients who underwent
non-sphincter saving surgery, local excision, bypass, or open and closed surgery. Of
1111 patients, 703 identified with left-sided colorectal cancer requiring anterior resection,
low anterior resection, or intersphincteric resection were included in the study. The patients
were categorized into two groups: stapled anastomosis and hand-sewn anastomosis. The
patients with stapled anastomosis were further classified into two groups: those tested with
IOC for the integrity of the anastomosis and those without the test. The primary outcome
measure was the rate of anastomotic complications of bleeding and leakage. The anasto-
motic complication rates in the two subgroups were compared. The clinicopathologic and
operative characteristics were evaluated and compared for the subgroups. Moreover, after
IOC, the anastomotic complication rates were compared between patients who underwent
an additional operative intervention, including transanal or transabdominal reinforcement
sutures, and those who did not. After obtaining approval from the Institutional Review
Board of St. Vincent Hospital at the Catholic University of Korea (VC22RISI0200), we
retrospectively reviewed the patients’ data and clinical information.

2.2. Preoperative Condition and Management

Perioperative management for elective surgery was standardized as a clinical pathway
system for all patients. Patients without signs and symptoms of colonic obstruction were
given preoperative mechanical bowel preparation with 4 L of polyethylene glycol solution
24 h before the surgery. A single dose of second-generation cephalosporin was administered
as a prophylactic antibiotic 30 min before the skin incision.
If colonic obstruction was present preoperatively, colonic decompression was carried
out by colonoscopic insertion of a self-expandable metallic stent (SEMS) or the formation
of a diverting stoma. When the obstruction was successfully relieved within 24 to 48 h,
elective surgery was planned within 7 to 14 days. A diverting stoma was performed when
 Biomedicines 2023, 11, 1162 3 of 12

the tumor was located within the pelvis and palpated on a digital rectal exam; SEMS
was inserted for tumors located intraperitoneally. Emergency surgery was performed if
a patient presented signs and symptoms of peritonitis and unstable hemodynamics with
evidence of free air or impending perforation in a preoperative imaging study. During the
Biomedicines 2023, 11, x FOR PEER REVIEW 3 of 13
operation, an individual surgeon decided whether to perform anastomosis with or without
a diverting stoma.

Figure
Figure1.1.Patients
Patientsflow
flowchart.
chart.Abbreviations:
Abbreviations:AR,
AR,anterior
anteriorresection;
resection;LAR,
LAR,low
lowanterior
anteriorresection;
resection; ISR,
ISR, intersphincteric
intersphincteric resection
resection.

2.2. Preoperative
Patients with Condition
cancerand Management
located within 15 cm from the anal verge, defined as rectal cancer,
were subject to preoperative chemoradiotherapy
Perioperative management for elective surgery (CRT)wasifstandardized
the disease showed clinicalpath-
as a clinical stage
(c) T3 or positive metastatic mesorectal node in imaging workups.
way system for all patients. Patients without signs and symptoms of colonic obstruction Either short- or long-
course CRT was given if indicated, depending on the patient’s
were given preoperative mechanical bowel preparation with 4 L of polyethylene glycol preference and eligibility.
The eligibility
solution criteria
24 h before theinclude
surgery.(1)Ahistologically
single dose of confirmed cancer; (2) cephalosporin
second-generation distal tumor margin was
located within 8 cm from the anal verge; (3) cT3-4N0-2
administered as a prophylactic antibiotic 30 min before the skin incision. classification determined by MRI
and/or endorectal
If colonic ultrasonography;
obstruction (4) no evidence colonic
was present preoperatively, of distant metastasis; (5)
decompression wasKarnofsky
carried
performance score greater
out by colonoscopic insertion than
of 70;
a and (6) adequate
self-expandable bone
metallic marrow,
stent liver,
(SEMS) and
or renal
the functions
formation
of(leukocyte
a diverting count
stoma. × 109the
>4.0When /L, obstruction
hemoglobin was levelsuccessfully
> 10 g/dL, platelet
relievedcountwithin> 100
24 to 109h,
× 48 /L,
serum bilirubin level <1.5 mg/dL, serum transaminase level < 2.5
elective surgery was planned within 7 to 14 days. A diverting stoma was performed when times the normal upper
limit, and serum creatinine level < 1.5 mg/dL) [11]. The long-course treatment consists of
the tumor was located within the pelvis and palpated on a digital rectal exam; SEMS was
two cycles of intravenous 5-fluorouracil (5-FU) with a dose of 400 mg/m2 before radiother-
inserted for tumors located intraperitoneally. Emergency2 surgery was performed if a pa-
apy and intravenous leucovorin with a dose of 20 mg/m before each dose of 5-FU on days
tient presented signs and symptoms of peritonitis and unstable hemodynamics with evi-
1–5 and 29–33 delivered concurrently with radiation of 45–50 Gy in 25–28 fractions to the
dence of free air or impending perforation in a preoperative imaging study. During the
pelvis. In the short-course treatment, capecitabine at a dose of 825 mg/m2 twice daily from
operation, an individual surgeon decided whether to perform anastomosis with or with-
days 1–12 was delivered concurrently with radiation of 33 Gy in 10 fractions for two weeks.
out a diverting stoma.
Total mesorectal excision (TME) was performed 6 to 8 weeks after preoperative CRT.
Patients with cancer located within 15 cm from the anal verge, defined as rectal can-
cer, were subject toProcedures
2.3. Intraoperative preoperative chemoradiotherapy (CRT) if the disease showed clinical
stage (c) T3 or positive metastatic mesorectal node in imaging workups. Either short- or
Three colorectal surgeons performed standardized surgical procedures for left-sided
long-course CRT was given if indicated, depending on the patient’s preference and eligi-
colorectal cancer, including high ligation of the inferior mesenteric artery (IMA) and splenic
bility. The eligibility criteria include (1) histologically confirmed cancer; (2) distal tumor
flexure mobilization. After resecting the specimens, intracorporeal end-to-end anastomosis
margin locatedbywithin
was created 8 cm from
the double the anal
stapling verge;If(3)
method. cT3-4N0-2
a tumor classification
involved the distal determined
rectum or
by MRI and/or endorectal ultrasonography; (4) no evidence of
anal canal, a transanal approach for intersphincteric resection was performed. An end- distant metastasis; (5)
Karnofsky performance score greater than 70; and (6) adequate
to-end anastomosis was created by the hand-sewn method. For the stapled anastomosis,bone marrow, liver, and
renal functionsof(leukocyte
the integrity count >4.0
the anastomosis was× double-checked—first,
109/L, hemoglobin levelwith > 10 an
g/dL,
air platelet
leak testcount
using> a
100 × 10
50 cc
9 /L, serum
enema bilirubin
syringe. level <1.5
Then, upon mg/dL, serum
the availability of a transaminase
colonoscopy, alevel < 2.5colonoscope
flexible times the
normal upper limit, and serum creatinine level < 1.5 mg/dL) [11]. The long-course treat-
ment consists of two cycles of intravenous 5-fluorouracil (5-FU) with a dose of 400 mg/m2
before radiotherapy and intravenous leucovorin with a dose of 20 mg/m2 before each dose
of 5-FU on days 1–5 and 29–33 delivered concurrently with radiation of 45–50 Gy in 25–
28 fractions to the pelvis. In the short-course treatment, capecitabine at a dose of 825
Biomedicines 2023, 11, 1162 4 of 12

was inserted through the anus and advanced to the stapler line. The anastomotic line
and the proximal and distal limbs were evaluated for disruption, bleeding, and mucosal
discoloration. During the air leak test and IOC assessment, the pelvis was filled with
warm saline for the air bubbles from the anastomotic defect. The proximal limb above the
anastomosis was clamped for air trapping in the colon. Loop ileostomy was constructed if
(1) preoperative CRT was given, (2) complete total mesorectal excision was performed, or
(3) the operator made a judgment call about the necessity of protecting the anastomosis.

2.4. Statistical Analysis

All statistical analyses were performed using IBM SPSS Statistics ver. 26.0 (IBM
Corp., Armonk, NY, USA). Univariate analysis was performed using Fisher’s exact test
or Pearson’s test for categorical variables and Student’s t-test for continuous variables. In
addition, logistic regression analysis was carried out for multivariate analysis to evaluate
the independent risk factors for anastomotic complications. p values less than 0.05 were
considered statistically significant.

3. Results
Of 703 patients undergoing radical resection for left-sided colorectal cancer, 44 patients
(6.3%) experienced anastomotic complications—38 (5.4%) with leakage and 6 (0.9%) with
bleeding, as shown in Table 1. Anastomotic leakage mainly occurred in patients with low
anterior resection (LAR) or intersphincteric resection (ISR). On the other hand, anastomotic
bleeding occurred only in the patients undergoing anterior resection. An amount of 11.1%
of patients with hand-sewn anastomosis experienced anastomotic leakage, while 5% of
patients with stapled anastomosis experienced leakage. Anastomotic bleeding occurred
at an overall rate of 0.9%, all in the stapled anastomosis. In those patients with stapled
anastomosis, the bleeding occurred more frequently when the anastomosis was above
10 cm from the anal verge. On the contrary, the leakage was observed at the highest rate as
the anastomosis was below 5 cm.

Table 1. Rate of anastomotic complications for left-sided colorectal cancer.

No Complication Leakage Bleeding

Total n = 703 p-Value
(n = 659, 93.7%) (n = 38, 5.4%) (n = 6, 0.9%)
AR (n = 351) 342 (97.4%) 3 (0.9%) 6 (1.7%)
LAR (n = 298) 269 (90.3%) 29 (9.7%) 0 (0%) <0.001
ISR (n = 54) 48 (88.9%) 6 (11.1%) 0 (0%)
Handsewn (n = 54) 48 (88.9%) 6 (11.1%) 0 (0%)
Anastomosis type 0.160
Stapled (n = 649) 611 (94.1%) 32 (5.0%) 6 (0.9%)
Stapled anastomosis (n = 649) No problem (n = 611) Leakage (n = 32) Bleeding (n = 6) p-value
>10 cm 239 (97.2%) 2 (0.8%) 5 (2.0%)
Height of the
anastomosis from >5~10 cm 116 (93.5%) 7 (5.6%) 1 (0.8%) <0.001
the anal verge ≤5 cm 153 (89.5%) 18 (10.5%) 0 (0%)
AR, anterior resection; LAR, low anterior resection; ISR, intersphincteric resection.

When the patients with anastomotic problems in stapled anastomosis were compared
to those without these problems, a higher anastomotic complication rate was noticed in the
male sex, in patients treated with neoadjuvant chemoradiotherapy and in patients with
diverting stoma formation, as shown in Table 2. Additionally, lower anastomosis in the
pelvis showed a higher rate of anastomotic complications. In the multivariate analysis,
the male sex, neoadjuvant therapy, diverting stoma formation, and anastomosis located
within 5 cm from the anal verge appeared to be significant risk factors for anastomotic
complications.
Biomedicines 2023, 11, 1162 5 of 12

Table 2. Univariate and multivariate analysis comparing patients with and without anastomotic
complications in stapled anastomosis.

Univariate Analysis Multivariate Analysis

No Leakage or 95%
Stapled Anastomosis Odds
Complications Bleeding p-Value Confidence p-Value
(n = 649) Ratio
(n = 611) (n = 38) Interval
Patient characteristics
Age (Mean ± SD) 64.75 ± 11.52 63.05 ± 9.86 0.129 0.98 0.944–1.018 0.308
<65 316 (51.7%) 21 (55.3%)
0.739
≥65 295 (48.3%) 17 (44.7%)
Male 377 (61.7%) 33 (86.8%) 10.02 2.29–43.96 0.002
Sex 0.002
Female 234 (38.3%) 5 (13.2%) 1
BMI (Mean ± SD, kg/m2 ) 24.47 ± 3.44 24.30 ± 3.29 0.742
I/II 557 (91.2%) 36 (94.7%)
ASA 0.763
III/IV 54 (8.8%) 2 (5.3%)
Preoperative disease status

Colonic perforation No 603 (94.1%) 38 (5.9%)

before surgery 1.0
Yes 8 (100%) 0 (0.0%)

Colonic obstruction No 524 (94.2%) 32 (5.8%)

before surgery 0.811
Yes 87 (93.5%) 6 (6.5%)
No 571 (93.5%) 35 (92.1%)
Colonic obstruction
requiring preoperative Diversion 7 (1.1%) 1 (2.6%) 0.723
decompression
Metallic Stent 33 (5.4%) 2 (5.3%)
Yes 123 (20.1%) 19 (13.4%) 4.26 1.08–19.88 0.039
Neoadjuvant therapy <0.001
No 488 (79.9%) 19 (3.7%) 1
None 488 (79.9%) 19 (50.0%)
CTx + RTx 107 (17.5%) 17 (44.7%)
Cytotoxic
2 (0.3%) 0 (0%)
CTx only
Neoadjuvant therapy-yes <0.001
Cytotoxic CTx
12 (2%) 2 (5.3%)
+ target agent
Cytotoxic CTx
+ target agent 2 (0.3%) 0 (0%)
+ RTx
Operation characteristics
No 606 (94.2%) 37 (5.8%)
Emergency surgery 0.305
Yes 5 (83.3%) 1 (16.7%)
Open 64 (97.0%) 2 (5.3%)
Surgical approach Minimally 0.413
547 (89.5%) 36 (6.2%)
invasive
Operation time (Mean ± SD, min) 217.26 ± 75.12 252.08 ± 81.72 0.192 1.00 0.995–1.007 0.672
No 103 (16.9%) 5 (13.2%)
IOC 0.659
Yes 508 (83.1%) 33 (86.8%)

Additional intraoperative No 532 (87.1%) 35 (92.1%)

0.459
intervention Yes 79 (12.9%) 3 (7.9%)

Formation of No 406 (66.4%) 15 (39.5%) 1

diverting stoma 0.001
Yes 205 (33.6%) 23 (60.5%) 7.88 1.306–47.57 0.024
Pathologic characteristics
Biomedicines 2023, 11, 1162 6 of 12

Table 2. Cont.

Univariate Analysis Multivariate Analysis

No Leakage or 95%
Stapled Anastomosis Odds
Complications Bleeding p-Value Confidence p-Value
(n = 649) Ratio
(n = 611) (n = 38) Interval
p or yp CR
135 (22.1%) 5 (13.2%)
or T1

Pathologic T stage p or yp T2 93 (15.2%) 11 (28.9%) 0.101

p or yp T3 285 (46.6%) 18 (47.4%)
p or yp T4 98 (16.0%) 4 (10.5%)

Circumferential margin Negative 594 (97.2%) 37 (97.4%)

1.0
status Positive 17 (2.8%) 1 (2.6%)
Stage 0 or I 195 (31.9%) 15 (39.5%)
Stage II 162 (26.5%) 11 (28.9%)
Pathologic TNM stage 0.239
Stage III 204 (33.4%) 7 (18.4%)
Stage IV 50 (8.2%) 5 (13.2%)
Height of the anastomosis
9.46 ± 5.48 6.21 ± 4.0 0.005 0.88 0.72–1.07 0.165
(Mean ± SD, cm)
>10 cm 297 (48.6%) 7 (18.4%) 1
Height of the
anastomosis from the >5~10 cm 135 (22.1%) 8 (21.1%) <0.001 2.92 0.968–8.792 0.057
anal verge
≤5 cm 179 (29.3%) 23 (60.5%) 6.77 1.56–29.31 0.011
SD, standard deviation; BMI, body mass index; ASA, American Society of Anesthesiologists; CTx, Chemotherapy;
RTx, Radiotherapy; IOC, Intraoperative colonoscopy; CR, Complete response.

In the patients with stapled anastomosis, the newly created anastomosis was assessed
with IOC in 541 patients (83.4%). As shown in Table 3, the anastomotic leakage rates were
similar in the patients with the IOC assessment compared to those without it. However,
all anastomotic bleeding cases occurred in patients with IOC assessment. Furthermore,
patients with IOC assessment experienced anastomotic complications not only within
30 days but also after 30 days. After the IOC assessment, seventy patients (12.9%) received
the additional intraoperative intervention of reinforcement sutures due to anastomotic
instability. As shown in Table 4, two patients with additional intraoperative intervention
developed leakage within 30 days of the operation, but none had bleeding or leakage after
30 days. On the other hand, of the patients without additional intervention, 31 patients
experienced anastomotic complications: 5.3% experienced leakage, and 1.3% experienced
bleeding. The anastomotic complications occurred mainly within postoperative day 30;
however, four patients developed leakage after postoperative day 30.

Table 3. Comparison of anastomotic complication rates based on the intraoperative colonoscopic

evaluation.

IOC (−) IOC (+)

Stapled Anastomosis (n = 649) p-Value
(n = 108, 16.6%) (n = 541, 83.4%)
None 103 (95.4%) 508 (93.9%)
Anastomotic
Leakage 5 (4.6%) 27 (5.0%) 0.537
complications
Bleeding 0 (0%) 6 (1.1%)
None 103 (95.4%) 508 (93.9%)
Anastomotic
Within 30 days 5 (4.6%) 29 (5.4%) 0.634
complications
After 30 days 0 (0%) 4 (0.7%)
IOC, intraoperative colonoscopy.
Biomedicines 2023, 11, 1162 7 of 12

Table 4. Comparison of anastomotic complication rates based on the additional intraoperative

intervention.

Additional Intraoperative Additional Intraoperative

IOC (+) (n= 541) Intervention (−) Intervention (+) p Value
(n = 471, 87.1%) (n = 70, 12.9%)
None 440 (93.4%) 68 (97.1%)
Anastomotic complications Leakage 25 (5.3%) 2 (2.9%) 0.437
Bleeding 6 (1.3%) 0 (0%)
None 440 (93.4%) 68 (97.1%)
Anastomotic complications Within 30 days 27 (5.7%) 2 (2.9%) 0.444
After 30 days 4 (0.8%) 0 (0%)
IOC, intraoperative colonoscopy.

Table 5 details the abnormalities observed during the IOC assessment and the un-
derlying reasons for additional intraoperative intervention. The most common cause was
bleeding or hematoma formation in the stapler line (53.9%). The others include mucosal
edema of the proximal limb and stapler line disruption with or without air leakage. The
two patients who developed leakage after the reinforcement sutures showed abnormal
findings in the IOC assessment—one with proximal bowel limb edema and bleeding and
the other with air leakage. Both patients required reoperation within 14 days of the index
surgery—one underwent Hartmann’s procedure due to the proximal limb ischemia, and
the other underwent resection of the proximal limb and recreation of the anastomosis due
to anastomotic failure.

Table 5. IOC findings of intraoperative anastomotic complications and postoperative anasto-

motic complications.

Additional Intraoperative Abnormal Finding (−) Abnormal Finding (+)

Intervention (+) in IOC in IOC
(n = 70) (n = 31, 44.3%) (n = 39, 55.7%)
Mucosal edema 5 (12.8%)

Intraoperative anastomotic Stapler disruption 8 (20.5%)

complications Bleeding or hematoma 21 (53.9%)
Air leakage 5 (12.8%)
None 31 (100%) 37 (94.9%)
Postoperative anastomotic
Leakage 0 (0%) 2 (5.1%)
complications
Bleeding 0 (0%) 0 (0%)
None 31 (100%) 37 (94.9%)
Postoperative anastomotic
Within 30 days 0 (0%) 2 (5.1%)
complications
After 30 days 0 (0%) 0 (0%)
IOC, intraoperative colonoscopy.

Table 6 shows the clinical, surgical, and pathological characteristics of patients who
were more likely to have undergone additional intraoperative intervention. Patients with
colonic obstruction were more likely to undergo additional intervention. Patients who
underwent emergency, open surgery, or surgery requiring a long operation time underwent
additional intervention. Additionally, a higher proportion of the patients who underwent
anterior resection received additional intervention than those who underwent low anterior
resection. Patients with an advanced tumor stage were more likely to receive the additional
reinforcement suture in the anastomosis.
Biomedicines 2023, 11, 1162 8 of 12

Table 6. Univariate analysis comparing patients with and without additional intraoperative interven-
tion after IOC evaluation.

Additional Additional
Intraoperative Intraoperative
Patients with IOC (n = 541) p Value
Intervention (−) Intervention (+)
(n = 471) (n= 70)
Patient characteristics
Age (Mean ± SD) 64.75 ± 10.89 64.32 ± 13.54 0.765
<65 247 (87.0%) 37 (13%)
1.0
≥65 224 (87.4%) 33 (12.8%)
Male 292 (86.1%) 47 (13.9%)
Sex 0.430
Female 179 (88.6%) 23 (11.4%)
BMI (Mean ± SD, kg/m2 ) 24.54 ± 3.30 23.92 ± 3.61 0.150
I/II 434 (87.1%) 64 (12.9%)
ASA 0.813
III/IV 37 (86.0%) 6 (14.0%)
Preoperative disease status
Colonic perforation before No 467 (87.1%) 69 (12.9%)
0.501
surgery Yes 4 (80.0%) 1 (20.0%)
Colonic obstruction before No 421 (89.6%) 49 (10.4%)
<0.001
surgery Yes 50 (70.4%) 21 (29.6%)
No 452 (89.2%) 56 (11.0%)
Colonic obstruction requiring
Diversion 5 (71.4%) 2 (28.6%) <0.001
preoperative decompression
Metallic Stent 14 (53.8%) 12 (46.2%)
No 110 (92.4%) 9 (7.6%)
Neoadjuvant therapy 0.062
Yes 361 (85.5%) 61 (14.5%)
Operation characteristics
No 470 (87.4%) 68 (12.6%)
Emergency surgery 0.045
Yes 1 (33.3%) 2 (66.7%)
Open 22 (47.8%) 24 (52.2%)
Surgical approach <0.001
Minimally
449 (90.7%) 46 (9.3%)
invasive
Operation time (Mean ± SD, min) 212.29 ± 68.45 235.52 ± 100.26 0.014
AR 240 (81.9%) 53 (18.1%)
Surgery type <0.001
LAR 232 (93.5%) 16 (6.5%)
No 301 (85.0%) 53 (15.0%)
Formation of diverting stoma 0.059
Yes 170 (91.4%) 17 (9.1%)
Anastomotic complications No 440 (86.6%) 68 (13.4%)
0.292
(bleeding and leakage) Yes 31 (93.9%) 2 (6.1%)
Pathologic characteristics
p or yp CR or T1 111 (94.1%) 7 (5.9%)
p or yp T2 78 (90.7%) 8 (9.3%)
Pathologic T stage <0.001
p or yp T3 225 (87.9%) 31 (12.1%)
p or yp T4 57 (70.4%) 24 (29.6%)
Negative 461 (87.1%) 68 (12.9%)
Circumferential margin status 0.660
Positive 10 (2.1%) 2 (16.7%)
Stage 0 or I 167 (93.3%) 12 (6.7%)
Stage II 124 (82.7%) 26 (17.3%)
Pathologic TNM stage 0.009
Stage III 147 (86.5%) 23 (13.5%)
Stage IV 33 (78.6%) 9 (21.4%)
Anastomosis Level
Height of the anastomosis
9.05 ± 5.47 11.12 ± 4.91 0.012
(Mean ± SD, cm)
>10 cm 206 (43.7%) 40 (57.1%)
Height of the anastomosis from
>5~10 cm 107 (22.7%) 17 (24.3%) 0.033
the anal verge
≤5 cm 158 (33.5%) 13 (18.6%)
SD, Standard deviation; BMI, body mass index; ASA, American Society of Anesthesiologists; IOC, intraoperative
colonoscopy.
Biomedicines 2023, 11, 1162 9 of 12

4. Discussion
For the early diagnosis and intervention of anastomotic complications, the use of
IOC to assess the integrity of anastomosis has been employed by surgeons worldwide.
However, the effectiveness of IOC in reducing anastomotic complications has been contro-
versial and still lacks sufficient evidence. In a systematic review of different intraoperative
assessment techniques, Hirst et al. reported that the IOC assessment might provide poten-
tial advantages in detecting anatomical abnormalities; however, the impact on reducing
anastomotic leakage failed to reach clinical significance [12]. The more recent meta-analysis
by Kryzauskas et al., including 12 primary studies, suggested that IOC could reduce the
anastomotic leakage rate following lower gastrointestinal tract resection [6]. However, the
authors doubted the efficacy of IOC based on the controversial results of the two studies.
Because those two studies included a small number of patients, the impact of the pooled
analysis on the study result was only minor. In addition, only two randomized controlled
trials (RCTs) are available in the literature. Beard et al. and Ivanov et al. demonstrated that
the IOC could effectively lower the anastomotic leakage rate [13,14]. However, concerns
about the small sample size and the outdated data on surgical technology and techniques
hinder a firm conclusion.
Nevertheless, in this study, including a relatively homogenous cohort with a larger
sample size than in other studies, the anastomotic leakage rate was similar in either group
of patients with or without IOC—5% vs. 4.7%. Postoperative anastomotic bleeding is a
noticeable complication that occurred after the IOC assessment. Six patients who showed
no abnormalities during the IOC assessment developed anastomotic bleeding within
postoperative Day 2, and they were all managed by endoscopic clipping successfully
without developing further complications. Consistent with these results, Shibuya et al. and
Shamiyeh et al. reported that postoperative anastomotic bleeding and leakage occurred in
patients who did not show any abnormal findings during IOC assessment [15,16]. Caused
by submucosal edema and ischemia during the first 24 to 48 h, local inflammation and
tissue necrosis of anastomosis can induce postoperative anastomotic bleeding in the process
of wound healing [17]. Such evidence suggests that the IOC assessment does not readily
predict anastomotic complications.
However, most patients who showed abnormalities in the IOC assessment could avoid
anastomotic complications after the additional intervention of reinforcement sutures. In
this study, 94.9% of patients with unstable anastomosis detected intraoperatively could
avoid postoperative anastomotic complications. Air leakage detected intraoperatively
in four out of five patients could be successfully managed by immediate intervention.
Other anastomotic problems, particularly bleeding, could be treated, resulting in no further
postoperative bleeding. Several other studies also demonstrated that technical anastomosis
failure was readily detected in IOC and managed [13–15]. These results suggest that the
routine use of IOC can help reduce anastomotic complications caused by possible technical
errors, such as mucosal edema, bleeding, staple line disruption, and air leakage, in the IOC
assessment indicating prompt intervention and management.
On the other hand, even if the additional intervention of reinforcement suture was
performed due to abnormal findings detected in IOC, anastomotic leakage in some patients
was not controlled. Li et al. reported two patients with postoperative leakage after the
IOC testing showing no defect and a negative air leakage test [18]. Additionally, Lanthaler
et al. reported a similar observation of patients developing postoperative leakage that
was not detected in intraoperative testing [19]. The authors suggested that the causes of
postoperative anastomotic insufficiency could be inadequate anastomosis blood supply
or too much tension. Consistent with the previous reports, two patients in this study
required reoperation for anastomotic leakage due to proximal limb ischemia. Both pa-
tients eventually required reoperation—one with resection of the proximal limb and end
ileostomy and the other with the re-creation of the anastomosis with a temporary stoma.
Since high ligation of the IMA was performed in these patients, the insufficient blood
supply to the proximal colonic limb might have progressed and aggravated ischemia. In
Biomedicines 2023, 11, 1162 10 of 12

addition, a retrospective review of the patient who underwent resection of the proximal
limb and end ileostomy revealed that the patient had suffered from a cerebrovascular
accident. Thus, pre-existing vascular insufficiency probably affected mesenteric artery
ischemia; consequently, the patient ended up with resection of the remnant colon and end
ileostomy. Inadvertent compromise of vascular arcades might have been caused by ligation
of the left colic artery, resulting in nonocclusive ischemia [20–22]. Identifying the mucosal
discoloration and the proximal limb ischemia might be challenging on IOC testing during
the operation. Reinforcement suture intervention is undoubtedly inadequate to secure
anastomosis and correct the insufficient blood flow. Nonetheless, ICG testing may be an
excellent additional method to assess the actual perfusion of the new anastomosis and
assess vascular compromise [7].
The etiology of anastomotic complications, particularly leakage, is multifactorial,
in which the risk factors are mainly categorized into three different aspects—patient-,
tumor-, and surgical procedure-related. Patient- and tumor-related factors are often difficult
to change or non-modifiable. However, preventive measures, such as splenic flexure
mobilization for tension-free anastomosis or a temporary stoma formation, can be adopted
in surgical procedures to decrease the rate and the associated morbidity of anastomotic
complications [2,23]. In this study, patients with LAR were indicated for temporary stoma if
neoadjuvant chemoradiotherapy was given, the anastomosis level within 8 cm from the anal
verge, or unstable anastomosis with abnormality found in the IOC assessment. In addition
to the splenic flexure mobilization and diverting stoma formation, the IOC assessment was
performed routinely to reduce the anastomotic complication rates in our institute. As a
result, postoperative anastomotic complications could be prevented with prompt treatment
in 94.9% of patients with technical errors detected in IOC. Although not all complications
are detected and predictable, the routine use of IOC may be valuable for evaluating technical
failures that are immediately treatable. Reflecting that the anastomosis located below 5 cm
from the anal verge poses a significant risk of leakage, patients with low anastomosis
would require IOC testing and the subsequent intervention of reinforcement suture as a
preventive measure. Further evaluation of possible technical errors not identified in the
present study may help expand the indications of intraoperative intervention, particularly
for patients with multiple risk factors.
Despite full splenic flexure mobilization and diverting stoma formation, anastomotic
leakage occurred after postoperative Day 30 in four patients who did not show abnormal-
ities in the IOC assessment. Three patients developed minor leakage symptoms on the
postoperative Days 5 to 7 and were managed conservatively. One patient did not show any
signs or symptoms of pelvic sepsis. However, they developed major signs and symptoms
of anastomotic leakage at least 8 to 12 weeks after the closure of diverting stoma. All were
male patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal
cancer. Consistent with our multivariate analysis of risk factors for leakage in the stapled
anastomosis, all three components are considered significant risk factors for anastomotic
leakage [2,24,25]. Regardless of various preventive measures, including preoperative me-
chanical bowel preparation, splenic flexure mobilization, formation of diverting stoma,
and IOC assessment, anastomotic leakage was unavoidable in those patients. This finding
suggests that along with ischemia, other factors, such as gut microbiota or remnant tumor
cells, may influence the intestinal anastomosis healing process [26,27]. Further investigation
on the role of gut microbiota in intestinal wound healing is necessary, which may help
identify other modifiable factors related to anastomotic leakage.
This study has some limitations. First, it was a retrospective study conducted at
a single institution. Nevertheless, this study included a relatively homogenous, large
cohort of colorectal cancer patients evaluated with IOC for newly created anastomosis. In
addition, the database was prospectively collected without many missing data. Second,
there could be inter-surgeon variability in the interpretation of endoscopic findings, which
might influence the study outcome. However, the perioperative management and surgical
procedures were all standardized, and all three colorectal surgeons strictly adhered to
Biomedicines 2023, 11, 1162 11 of 12

the standard protocol. In addition, they are all board-certified in colorectal surgery and
colonoscopy; thus, endoscopic findings and descriptions may not differ much among them.

5. Conclusions
The IOC assessment has the core value of confirming anastomosis integrity by directly
visualizing newly created anastomosis. Indeed, the routine use of IOC may benefit patients
with unstable anastomosis detected in IOC, allowing immediate intervention. Quick as-
sessment with IOC may reduce technical error, aiding in securing anastomosis of patients
with multiple risk factors. However, IOC testing is limited in predicting anastomotic insuf-
ficiency caused by progressive ischemia or other causes interfering with wound healing.
Further investigation on combining other testing methods evaluating vascularity and per-
fusion, such as ICG, with IOC testing is necessary. Perhaps applying both tests may help
further reduce the anastomotic complication to achieve optimal and secure anastomosis.

Author Contributions: Conceptualization, B.-H.K. and H.-J.K.; methodology, R.-N.Y., J.-Y.M., B.-H.K.
and H.-J.K.; software, J.-Y.M.; validation, R.-N.Y., J.-Y.M. and H.-J.K.; formal analysis, R.-N.Y. and
H.-J.K.; investigation, R.-N.Y., B.-H.K. and H.-J.K.; resources, H.-M.C. and H.-J.K.; data curation,
H.-J.K.; writing—original draft, R.-N.Y. and H.-J.K.; writing—review and editing, R.-N.Y., J.-Y.M.,
B.-H.K. and H.-J.K.; visualization, H.-J.K.; supervision, B.-H.K. and H.-J.K.; project administration,
H.-J.K. All the authors reviewed the manuscript. All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Institutional Review Board of St. Vincent’s Hospital (VC22RISI0125)
for studies involving humans.
Informed Consent Statement: Patient consent was waived due to a retrospective study.
Data Availability Statement: MDPI Research Data Policies at https://www.mdpi.com/ethics
(accesed on 19 March 2023).
Acknowledgments: We thank all participating patients and people who set up the cancer databases.
Conflicts of Interest: The authors declare no conflict of interest.

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