Seminars in Colon and Rectal Surgery 25 (2014) 74–78

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Seminars in Colon and Rectal Surgery

journal homepage: www.elsevier.com/locate/yscrs

Predicting anastomotic leak: Can we?

Jennifer K. Lee, MDa, Nitin Mishra, MDa,b,n
a
Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
b
Atlantic Health System, Edison, NJ

abstract

Anastomotic leaks remain a feared complication in colorectal surgery. A myriad of variables have been
evaluated, but the variability among those studies provides little consensus on absolute risk factors and
clinical application. Nevertheless, identifying these risk factors may assist the surgeon in mitigation of
risk with preoperative optimization, intraoperative decision-making for diversion, and heightened
postoperative vigilance for anastomotic leak. These risk factors can be organized into surgeon-,
patient-, and pathology-related categories.
& 2014 Elsevier Inc. All rights reserved.

Introduction
With prevalence ranging from 0.5% to 21%, anastomotic leaks
remain one of the most serious complications in colorectal
surgery.1,2 Clinically significant leaks can occur in up to 14% of
low anastomoses. Leaks lend themselves to increased morbidity
and mortality, with the latter reported up to 27% in some
studies.3,4 Along with clinical consequences, anastomotic leaks
lead to longer hospital stays, multiple interventions, and overall
increased health care costs when compared to patients without
a leak.
The underlying pathogenesis leading to anastomotic leaks is
not entirely understood but is attributed to several factors affect-
ing the integrity of the anastomosis. These factors are related to
the surgeon, the patient, and the pathology.5–7 Several retrospec-
tive and prospective studies have been performed to identify these
factors. However, interpretation of the data is restricted by the
wide breadth of diseases, patient populations, techniques, and an
assortment of definitions for anastomotic leak among the liter-
ature.8 Anastomotic leak can present both within the immediate
postoperative period and after discharge from the hospital, sug-
gesting a multi-factorial pathogenesis leading to anastomotic
dehiscence.
Provided with predictors of anastomotic leak, the surgeon may
be able to modify preoperative risk factors as well as adjust
perioperative decision-making and increase postoperative vigi-
lance in those with risk factors. Even with optimization of the
patient and improving technique, the rate of anastomotic leak has
n
Correspondence address: 3900 Park Avenue, Edison, NJ 08820. Tel.: þ 1 732
494 6640; fax: þ 1 732 549 8204.
E-mail address: mishranitin@hotmail.com (N. Mishra).
not significantly decreased over time. This reveals that there is
more to the underlining pathology than is understood at this time.
Surgeon-related factors
The essential principles of a successful intestinal anastomosis
include perfect technique joining two healthy ends of bowel
without tension. Adequate blood supply and thus adequate oxygen
delivery sustain the integrity. Various studies have explored the
weight of these factors and practical ways in which they can be
measured in order to determine whether an anastomosis will heal
completely. These factors include blood supply, tension, hypoxia,
resuscitation, blood loss, and operative time. In addition to these
factors, surgical technique, use of mechanical bowel preparation,
experience of the surgeon, and training/certification have also
been considered as potential variables that may affect outcomes.
Blood supply/hypoxia
Oxygen tension measurements of bowel both before resection
and after anastomosis have been evaluated in both animal and
human models.9,10 These studies have demonstrated a large drop
in the oxygen tension after resection, but the effect this drop had
on the viability of the anastomosis was less clear. One study
measured Doppler flow to measure microperfusion to a rectal
stump.11 Flow reduction of 6.2% was evident in those without a
leak compared to 16% in those with a leak (p o 0.001)—a
significant finding supporting the understanding that blood supply
is crucial. There is, however, no practical application of these
measurements. For now, surgeons intraoperatively evaluate via-
bility by mucosa color and bleeding edges. Should there be a lack

http://dx.doi.org/10.1053/j.scrs.2014.04.003
1043-1489/& 2014 Elsevier Inc. All rights reserved.
 J.K. Lee, N. Mishra / Seminars in Colon and Rectal Surgery 25 (2014) 74–78
of bleeding or concern of poor blood supply to either the proximal
or distal end of the intestine, an alternate site of fusion should be
considered.
Tension
Tension on the anastomosis is generally considered to be
unacceptable given the mechanical stress theoretically applied to
the two ends of bowel. Nevertheless, measurements of tension are
poorly studied. A 1986 study compared the tension tolerated by
small bowel to small bowel anastomoses as compared to colonic
anastomosis.12 This showed that the small bowel tolerated tension
better than the colon. It appears that this was directly related to
the laxity of the mesentery and thus the blood supply to the
anastomosis itself. In general, any indication of tension should
prompt further mobilization to lengthen the conduit.
Resuscitation
Restricted fluid strategies have shown to reduce postoperative
complication rates in randomized controlled studies.13–15 The goal
is to maintain baseline weight. In contrast, one study demon-
strated an increase in overall complication rates with restricted
fluid management, thereby making the role of restricted fluid
resuscitation unclear when it comes to the specific effect on
anastomotic leak rates.
Blood loss/OR time
Blood loss and length of operating time have both been shown
to increase rates of overall complications. Leichtle et al.16 meas-
ured several variables among 4340 cases in a prospective study
and found blood loss of greater than 100 mL (p ¼ 0.02, 95% CI: 1.1–
2.4) and 300 mL (p ¼ 0.003, 95% CI: 1.32–3.76) as significant
factors after multivariate regression. Several studies have shown
that substantial intraoperative blood loss and postoperative blood
transfusions (most likely a marker of substantial intraoperative
blood loss) are associated with increased risk for anastomotic
leaks.1,4,17 As such, increased blood loss should be one of several
factors to be considered when assessing the need for diversion in a
patient at a high risk for anastomotic leaks. A prospective study of
391 elective colorectal resections identified a significantly higher
leak rate when the operative procedure was Z 4 h in duration
compared with shorter procedures (5.1 vs. 0.5%).18
The current data is largely difficult to interpret given the
various cutoff values for excessive blood loss and the range of
reported number of transfusions. In addition, the degree of blood
loss and length of operating time are often directly related to the
difficulty of the operation.17,19
Technique
(A) Hand-sewn vs. stapled
Several studies, including a 2012 Cochrane review, show no
significant difference in outcomes, including leak rate,
between hand-sewn and stapled colon anastomoses. There
was also no significant difference found between single- and
double-layer closures.20–22 However, a meta-analysis of six
trials with 955 participants with benign and malignant
disease revealed that hand-sewn ileocolic anastomoses were
associated with a significantly higher rate of anastomotic leaks
compared with stapled ileocolic anastomoses (6.0 vs.
1.4%).23,24
(B) Laparoscopic vs. open
Laparoscopic resection has been shown to have no significant
75
difference in outcomes compared to open resection in benign
and cancer cases.25–27
(C) Level of inferior mesenteric artery (IMA) ligation
The level at which the IMA ligation occurs may play a role in
anastomotic leak rates. A study by Trencheva et al. demon-
strated that high ligation of the inferior mesenteric artery had
3.8 times higher chance of leaking compared to low ligation.
This outcome may be related to the fact that the proximal part
of the anastomosis relies on marginal artery blood flow from
middle colic vessels when high ligation is performed. Without
compromising the needed number of lymph nodes, the study
recommends careful consideration of the level of ligation in
patients with risk factors for poor mesenteric blood flow.28
Nevertheless, a 2012 systematic review of the literature
showed no significant difference in short-term outcomes,
including anastomotic leak, between high and low ligation
among 8666 patients.29
(D) Leak test for anastomoses
After construction of the anastomosis, many will test the
connection with insufflation of air, normal saline, or
povidone-iodine. This is proposed to identify any disruption
that may lend itself to anastomotic leak if missed. This
provides a simple and reproducible method of predicting
anastomotic leak. Most studies supporting air leak tests are
small in size.30 A 2009 retrospective study performed by the
Lahey Clinic investigated 998 left-sided colorectal anastomo-
ses without diversion, 90% of which were stapled. Air leaks
were noted in 7.9% during the air leak test. Of these, 7.7%
clinical leaks were later diagnosed. Comparably, 3.8% of those
with negative air leak tests had clinical leaks, as well as 8.1% of
untested anastomoses (p o 0.03). When comparing repairs
after a positive air leak test, suture repair alone had higher
clinical leak rate compared to recreated anastomoses and
diversion (12% vs. 0%). The data from this study favors air leak
testing of all left-sided anastomoses, whether stapled or hand-
sewn.31
(E) Use of drains
A randomized trial found no increase in anastomotic leaks
with drains in patients undergoing elective colonic resection,
while a large observational study found a significant increase
in anastomotic leaks with drains in patients undergoing a low
anterior resection for rectal cancer.32,33 The use of prophylactic
drains in intraperitoneal colonic surgery is not supported by
current data. Prophylactic drainage of the pelvis after complex
pelvic surgery may decrease the development of pelvic col-
lections; however, it is not clear whether drains influence the
rates of anastomotic leak.34
Experience and certification
Another variable closely related to technique among studies
examining anastomotic leak rates is the experience and certifica-
tion of the surgeons performing the surgery. A retrospective study
of 514 surgeons performing 15,427 colectomies between 1994 and
1997 showed improved outcomes with more experience and
volume of cases. While anastomotic leak was not specifically
investigated, the study concluded surgeons without American
Board of Surgery certification had significantly higher complication
rates.35 Although colorectal surgery subspecialty certification did
not significantly affect outcomes in this study, a 1998 study
suggested otherwise. In the setting of rectal cancer and complica-
tions like recurrence,36 Newman et al. reported on 683 patients
involving 52 surgeons, 5 of which were colorectal surgeons who
performed 109 (16%) of the operations. Multivariate analysis
showed that the risk of local failure was increased and disease-
76 J.K. Lee, N. Mishra / Seminars in Colon and Rectal Surgery 25 (2014) 74–78
specific survival was decreased in patients of both noncolorectal
trained surgeons and those of surgeons performing o21 resec-
tions. The authors concluded that in the setting of rectal cancer,
outcomes are with both colorectal surgical subspecialty training
and a higher frequency of rectal cancer surgery. Therefore, the
surgical treatment of rectal cancer patients should be performed
exclusively by colorectal surgeons with more experience.36,37
Mechanical bowel preparation (MBP)
Several meta-analyses, prospective trials, and Cochrane reviews
found no significant difference in overall AL rate for patients with
an MBP compared to those not having a MBP. This conclusion
applied to both low anterior resection and intraperitoneal
anastomosis.38
Use of protective stoma for low anterior resections
Proximal fecal diversion by a protective stoma reduces the
overall risk of a reoperation following a low anterior anastomosis;
however, it is unclear whether it prevents leaks. A meta-analysis of
4 randomized trials including 358 patients undergoing a low
anterior resection for rectal cancer found patients with a protec-
tive stoma had significantly fewer anastomotic leaks compared
with patients who had no protective stoma (9.6% vs. 22.8%). In
addition, patients with a protective stoma had significantly fewer
reoperations for leaks (OR ¼ 0.27, 95% CI: 0.17–0.59).39
Patient-related factors
Various patient-related factors have been studied. Except for a
select few, most risk factors have shown varied results in available
studies. American Society of Anesthesia (ASA) classification and
nutritional status have been consistently found to be a risk factor
for anastomotic leak. Various other reports have suggested age,
obesity, and smoking to be associated with higher rates of
anastomotic leak; however, these studies varied in their cutoff
for age and quantity of smoking and alcohol intake. This hetero-
geneity makes application of this knowledge less clear and gen-
eralizable to all populations.
ASA/CCI
ASA and Charlson Comorbidity Index (CCI) are two scales
measured preoperatively to provide a generalized assessment of
the patient. The ASA score, as measured by the anesthesiologist,
provides an assessment of perioperative adverse events, whereas
the CCI score predicts the 10-year mortality depending on comor-
bidities. For CCI, factors such as congestive heart failure, chronic
pulmonary disease, and diabetes are one point each, whereas
diabetes with end-organ damage and kidney disease are
2 points each.
The ASA score has been shown to have an effect on anastomotic
leak rate. Specifically, an ASA score of 3 or greater is associated
with higher anastomotic leak rate.3,4,40–43 Buchs et al. also iden-
tified an ASA score of 3 or greater to be an increased risk factor in a
study of 811 anastomoses performed (p ¼ 0.004). Overall leak rate
was 3.8%. They identified a 2.5 time increase in anastomotic leak
risk with every unit increase in ASA score. Limitations of the ASA
score include variability among anesthesiologists in subjectively
assigning the class.
The role of CCI is also variable among studies. Trencheva et al.28
identified the CCI score of 3 or higher to be a risk factor to
anastomotic leak. In contrast, Tan et al.44 reviewed 505 colorectal
resections and found that while the ASA score of 3 or greater was
an independent risk factor for anastomotic leak (ASA III: p ¼
0.049, ASA IV: p ¼ 0.012), a higher CCI scores did not increase the
risk of anastomotic leak (p 4 0.05). In this study, individual
components of each index were evaluated showing significance in
those with congestive heart failure (p o 0.001) and metastatic
disease (p ¼ 0.019). The study did not identify a significant risk
factor with comorbidities such as IBD or intraoperative factors
such as blood loss.
Nutrition/albumin
Nutrition is one of the few risk factors that has been consis-
tently identified as a risk factor for anastomotic leak. In particular,
a weight loss of 4 10% from preoperative weight and an albumin
of less than 3.0–3.5 have been associated with higher rates
of anastomotic leak.17,41,43,45 Patients with greater than 10%
weight loss or albumin less than 3.5 may benefit from preoperative
nutritional optimization. Enteral approach is preferred to paren-
teral but either one may be used. The usual recommended
duration of preoperative nutritional supplementation is 7
days.17,45
Gender
Various studies have shown male gender to be a risk factor for
anastomotic leak, including several studies noting higher risk in
males in the setting of low rectal cancers.28,46,47 In contrast, this
increased risk of anastomotic leak in males was not seen in
intraperitoneal anastomotic leak.42 This may imply that the
increased incidence of anastomotic leak in low rectal cancer cases
may be due to the challenges faced with the narrower male bony
pelvis.
BMI
Numerous studies have shown increased rates of anastomotic
leak with increasing BMI for left colon and rectal resections.48,49
BMI appears to play less of a role in right colectomies.48,49 Buchs
et al.3 identified a BMI of 4 25 to be an increased risk factor
(p ¼ 0.04).
Smoking/alcohol
Smoking and alcohol have been considered a possible risk
factor for anastomotic leak. Studies evaluating alcohol use as a
risk factor are difficult to interpret as limitations of patient reports
and cutoff amounts of alcohol use are varied.50,51
In summary, the rate of anastomotic leak is likely related to a
number of patient-related factors; however, the individual impact
these factors have is extremely difficult to distinguish. Even so, the
presence of these factors should be considered preoperatively and
intraoperatively when taking into consideration the need for fecal
diversion as well as heighten the surgeon's awareness for peri-
operative complications.
Pathology-related factors
Emergent cases
The priority of an emergent case is typically patient salvage,
and for this reason, an anastomosis is often avoided. Nevertheless,
in the absence of shock or sepsis, an anastomosis may still be
considered. Several studies support this approach, although the
majority the study results are skewed as there is a propensity to
avoid anastomosis on left-sided resections and less hesitancy with
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right-sided resections. In a study focusing on left-sided intra-
peritoneal anastomoses performed after on-table lavage, an emer-
gency operation (p ¼ 0.03; odds ratio ¼ 4.6; 95% confidence
interval ¼ 1.9–9.8) was found to be an independent risk factor
associated with anastomotic leak. This finding was also supported
in subsequent study.42,49
Steroids/IBD/chemotherapy
Steroid use is common in the inflammatory bowel disease (IBD)
patient, and various studies exist confirming the negative effects of
steroids on general healing by decreasing activation and infiltra-
tion of inflammatory cells.4,40,41 Many patients with IBD will
require operations. Unfortunately, there is a lack of data regarding
the timing and safety of stopping steroids. The effect of steroids on
anastomotic leak as a specific complication is not as well defined.
Slieker et al.52 found long-term (p ¼ 0.02, 95% CI: 1.24–14.76) and
perioperative corticosteroids (p ¼ 0.001, 95% CI: 3.32–100.15) to
be independent risk factors for anastomotic leak in a prospective
study of 259 left-sided anastomoses.
The use of immunomodulators and anti-TNF alpha therapy
appears to be safe in the treatment of IBD, and stopping their use is
acceptable preoperatively. In the setting of infliximab use in UC,
Mor et al. found that infliximab increased the occurrence of
J-pouch leaks and pelvic sepsis, although other studies have
questioned that association. It is worth noting that the majority
of patients who leaked while on Remicade were also noted to be
taking concomitant steroids suggesting that the patients who
leaked were more likely to represent a more severely ill group
than those who were more likely to leak due to Remicade.53
In regards to Crohn's disease, several factors have been identi-
fied including histologically involved margins, intraabdominal
abscess, presence of fistulas, and malnutrition.17,54 Involvement
of the microscopic margin has been shown to be statistically
significant for anastomotic leak risk.17,55,56 This finding provides
an added concern in the setting of a patient population in which
bowel length preservation is essential.
Chemotherapeutic agents may also contribute to the risk for
anastomotic leak. In particular, bevacizumab (Avastins, Roche,
Basel, Switzerland) has been shown to increased the risk of
anastomotic leak if used before and after surgery. Anastomotic
leaks have been reported at various times in the postoperative
period ranging from the immediate postoperative day up to 40
months postoperatively. These findings support delaying surgery
at least 6 weeks after the last dose and resuming treatment almost
a month after surgery.57
Radiation
The effect of radiation on the bowel and its oxygen supply is
also a confounding factor that surgeons should be wary of when
determining bowel viability. The point of transaction should not
only depend on adequate blood supply but also on extent of
radiation changes. The current data is open to debate with several
retrospective studies reporting positive, negative, and inconclusive
association between neoadjuvant radiation and risk of anastomotic
leak.6,58–63
Location of pathology
Distance from the anal verge is widely understood to be an
independent risk factor for anastomotic leak. High anastomotic
leak rates have been consistently reported with resections below
the peritoneal reflection.1,3,28,42 Comparing ileocolic and coloco-
lonic anastomotic leak, relative risk for anastomotic leak is higher
with colorectal anastomoses (RR ¼ 11.06; 95% CI: 3.32–36.85).50
77
Other factors such as technical difficulty, blood supply, and
increased tension may be causal in the elevated risk of low
anastomoses for anastomotic leak, but there is a lack of evidence
to support exactly why.64
Metastatic disease/concomitant liver resection
With improved medical treatment of metastatic colorectal
cancer, patients who were once considered unresectable at the
time of diagnosis may prove otherwise after several months of
systemic chemotherapy. In fact, 5-year survival rates have been
shown to improve with resection of synchronous liver metastases,
although the strategy for approaching these resections is still
controversial.65 Concomitant resection of stage IV disease may
increase the incidence and effect of anastomotic leak.66,67 Naka-
jima et al. studied 86 patients who underwent simultaneous
resection of the primary colon tumor and hepatic tumor. Post-
operative morbidity was 64%, and anastomotic leak 21%. Of the
anastomotic leak group, 6 patients required reoperation. Patients
in the group who did not have a synchronous liver resection had
an anastomotic leak rate of 7.1%. Operating time greater than 8 h
was a significant factor for anastomotic leak on multivariate
analysis (p o 0.01; 95% CI: 2.09–20.9). Other variables such as
extent of resection and total time of the Pringle maneuver were
not predictive factors for anastomotic leak in this study. They
concluded that stage resections should be considered in cases
when the surgical stress may be expected.67
Conclusion
Anastomotic leaks remain a devastating complication despite
evolution of anastomotic techniques and preoperative modifica-
tion of identified risk factors for postoperative complications.
Despite a wide range of literature describing various possible
contributing factors, there remain a variety of conclusions. Some
variables, such as those related to pathology, cannot be modified.
Other factors continue to be investigated including microbiological
variables that may contribute to the pathogenesis of anastomotic
leak.
What is clear from these studies is the complexity of factors
that contribute to the success of an anastomosis. While most
studies focus on a few risk factors, there remains a complex
interaction among the patient-, surgeon-, and pathology-related
factors. The key remains in identifying these factors in order for
surgeons to modify their approach to the individual patient in
order to mitigate outcomes and to anticipate postoperative com-
plications in those deemed to have a high risk for anastomotic
leak.
References
1. Boccola MA, Buettner PG, Rozen WM, et al. Risk factors and outcomes for
anastomotic leakage in colorectal surgery: a single-institution analysis of 1576
patients. World J Surg. 2010;35(1):186–195.
2. Nasirkhan MU, Abir F, Longo W, et al. Anastomotic disruption after large bowel
resection. World J Gastroenterol. 2006;12(16):2497–2504.
3. Buchs NC, Gervaz P, Secic M, et al. Incidence, consequences, and risk factors for
anastomotic dehiscence after colorectal surgery: a prospective monocentric
study. Int J Colorectal Dis. 2008;23(3):265–270.
4. Alves A, Panis Y, Trancart D, et al. Factors associated with clinically significant
anastomotic leakage after large bowel resection: multivariate analysis of 707
patients. World J Surg. 2002;26(4):499–502.
5. Tagart RE. Colorectal anastomosis: factors influencing success. J R Soc Med.
1981;74(2):111–118.
6. Kingham TP, Pachter HL. Colonic anastomotic leak: risk factors, diagnosis and
treatment. J Am Coll Surg. 2009;208(2):269–278.
7. Davis B, Rivadeneira DE. Complications of colorectal anastomoses: leaks,
strictures, and bleeding. Surg Clin North Am. 2013;93(1):61–87.
78 J.K. Lee, N. Mishra / Seminars in Colon and Rectal Surgery 25 (2014) 74–78
8. Bruce J, Kukowski ZH, Al-Khairy G, et al. Systematic review of the definition and
measurement of anastomotic leak after gastrointestinal surgery. Br J Surg.
2001;88(9):1157–1168.
9. Myers C, Mutafyan G, Petersen R, et al. Real-time probe measurement of tissue
oxygenation during gastrointestinal stapling: mucosal ischemia occurs and is
not influenced by staple height. Surg Endosc. 2009;23(10):2345–2350.
10. Sheridan WG, Lowndes RH, Young HL. Tissue oxygen tension as a predictor of
colonic anastomotic healing. Dis Colon Rectum. 1987;30(11):867–871.
11. Vignali A, Gianotti L, Braga M, et al. Altered microperfusion at the rectal stump
is predictive for rectal anastomotic leak. Dis Colon Rectum. 2000;43(1):76–82.
12. Shikata J, Shida T. Effects of tension on local blood flow in experimental
intestinal anastomoses. J Surg Res. 1986;40(2):105–111.
13. Rahbari NN, Zimmermann JB, Schmidt T, et al. Meta-analysis of standard,
restrictive and supplemental fluid administration in colorectal surgery. Br J
Surg. 2009;96(4):331–341.
14. Brandstrup B, Tonnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid
restriction on postoperative complications: comparison of two perioperative
fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg.
2003;23(5):641–648.
15. Abraham-Nordling M, Hjern F, Pollack J, et al. Randomized clinical trial of fluid
restriction in colorectal surgery. Br J Surg. 2012;99(2):186–191.
16. Leichtle SW, Mouawad NJ, Welch KB, et al. Risk factors for anastomotic leakage
after colectomy. Dis Colon Rectum. 2012;55(5):569–575.
17. Telem DA, Chin EH, Nguyen SQ, et al. Risk factors for anastomotic leak following
colorectal surgery: a case-control study. Arch Surg. 2010;145(4):371–376.
18. Konishi T, Watanabe T, Kishimoto J, et al. Risk factors for anastomotic leakage
after surgery for colorectal cancer: results of prospective surveillance. J Am Coll
Surg. 2006;202(3):439–444.
19. Manilich E, Vogel JD, Kiran RP, et al. Key factors associated with postoperative
complications in patients undergoing colorectal surgery. Dis Colon Rectum.
2013;56(1):64–71.
20. Neutzling CB, Lustosa SA, Proenca IM, et al. Stapled versus hand-sewn methods
for colorectal anastomosis surgery. Cochrane Database Syst Rev. 2012
[CD003144].
21. Burch JM, Franciose RJ, Moore EE, et al. Single-layer continuous versus two-
layer interrupted intestinal anastomosis: a prospective randomized trial. Ann
Surg. 2000;231(6):832–837.
22. Sarin S, Lightwood RG. Continuous single-layer gastrointestinal anastomosis: a
prospective audit. Br J Surg. 1989;76(5):493–495.
23. Choy PY, Bissett IP, Docherty JG, et al. Stapled versus handsewn methods for
ileocolic anastomoses. Cochrane Database Syst Rev. 2007 [CD004320].
24. Choy PY, Bissett IP, Docherty JG, et al. Stapled versus handsewn methods for
ileocolic anastomoses. Cochrane Database Syst Rev. 2011 [CD004320].
25. Clinical Outcomes of Surgical Therapy Study Group. A comparison of lapa-
roscopically assisted and open colectomy for colon cancer. N Engl J Med.
2004;350(20):2050–2059.
26. Guillou PJ, Quirke P, Thorpe H, et al. Short-term endpoints of conventional
versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC
CLASICC trial): a multicentre, randomised controlled trial. Lancet. 2005;365
(9472):1718–1726.
27. Tjandra JJ, Chan MK. Systematic review on the short-term outcome of laparo-
scopic resection for colon and rectosigmoid cancer. Colorectal Dis. 2006;8(5):
375–388.
28. Trencheva K, Morrissey KP, Wells M, et al. Identifying important predictors for
anastomotic leak after colon and rectal resection: a prospective study on 616
patients. Ann Surg. 2013;257(1):108–113.
29. Cirocchi R, Trastulli S, Farinella E, et al. High tie versus low tie of the inferior
mesenteric artery in colorectal cancer: a RCT is needed. Surg Oncol. 2012;21(3):
e111–e123.
30. Beard JD, Nicholson ML, Sayers RD, et al. Intraoperative air testing of colorectal
anastomoses: a prospective, randomized trial. Br J Surg. 1990;77(10):1095–1097.
31. Ricciardi R, Roberts PL, Marcello PW, et al. Anastomotic leak testing after
colorectal resection. Arch Surg. 2009;144(5):407–411.
32. Merad F, Yahchouchi E, Hay JM, et al. Prophylactic abdominal drainage after
elective colonic resection and suprapromontory anastomosis: a multicenter
study controlled by randomization. French Associations for Surgical Research.
Arch Surg. 1998;133(3):309–314.
33. Yeh CY, Changchien CR, Wang JY, et al. Pelvic drainage and other risk factors for
leakage after elective anterior resection in rectal cancer patients: a prospective
study of 978 patients. Ann Surg. 2005;241(1):9–13.
34. Puleo FJ, Mishra N, Hall JF. Use of intra-abdominal drains. Clin Colon Rectal Surg.
2013;26(3):174–177.
35. Prystowsky JB, Bordage G, Feinglass JM. Patient outcomes for segmental colon
resection according to surgeon's training, certification, and experience. Surgery.
2002;132(4):663–670.
36. Porter GA, Soskolne CL, Yakimets WW, et al. Surgeon-related factors and
outcome in rectal cancer. Ann Surg. 1998;227(2):157–167.
37. Nugent E, Neary P. Rectal cancer surgery: volume-outcome analysis. Int J
Colorectal Dis. 2010;25(12):1389–1396.
38. Güenaga KF, Matos D, Wille-Jørgensen P. Mechanical bowel preparation for
elective colorectal surgery. Cochrane Database Syst Rev. 2011 [CD001544].
39. Huser N, Michalski CW, Erkan M, et al. Systematic review and meta-analysis of
the role of defunctioning stoma in low rectal cancer surgery. Ann Surg.
2008;248(1):52–60.
40. Golub R, Golub RW, Cantu RJr, et al. A multivariate analysis of factors
contributing to leakage of intestinal anastomoses. J Am Coll Surg. 1997;184(4):
364–372.
41. Suding P, Jensen E, Abramson MA, et al. Definitive risk factors for anastomotic
leaks in elective open colorectal resection. Arch Surg. 2008;143(9):907–911.
42. Choi HK, Law WL, Ho JW. Leakage after resection and intraperitoneal anasto-
mosis for colorectal malignancy: analysis of risk factors. Dis Colon Rectum.
2006;49(11):1719–1725.
43. Makela JT, Kiviniemi H, Laitinen S. Risk factors for anastomotic leakage after
left-sided colorectal resection with rectal anastomosis. Dis Colon Rectum.
2003;46(5):653–660.
44. Tan WP, Talbott VA, Leong QQ, et al. American Society of Anesthesiologists class
and Charlson's comorbidity index as predictors of postoperative colorectal
anastomotic leak: a single-institution experience. J Surg Res. 2013;184(1):
115–119.
45. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group.
Perioperative total parenteral nutrition in surgical patients. N Engl J Med.
1991;325(8):525–532.
46. Law WI, Chu KW, Ho JW, et al. Risk factors for anastomotic leakage after low
anterior resection with total mesorectal excision. Am J Surg. 2000;179(9):
92–96.
47. Lipska MA, Bissett IP, Parry BR, et al. Anastomotic leakage after lower gastro-
intestinal anastomosis: men are at higher risk. Aust N Z J Surg. 2006;76(7):
579–585.
48. Gendall KA, Raniga S, Kennedy R, et al. The impact of obesity on outcome after
major colorectal surgery. Dis Colon Rectum. 2007;50(12):2223–2237.
49. Biondo S, Pares D, Kreisler E, et al. Anastomotic dehiscence after resection and
primary anastomosis in left-sided colonic emergencies. Dis Colon Rectum.
2005;48(12):2272–2280.
50. Sorensen LT, Jorgensen T, Kirkeby LT, et al. Smoking and alcohol abuse are
major risk factors for anastomotic leakage in colorectal surgery. Br J Surg.
1999;86(7):927–931.
51. Richards CH, Campbell V, Ho C, et al. Smoking is a major risk factor for
anastomotic leak in patients undergoing low anterior resection. Colorectal Dis.
2012;14(5):628–633.
52. Slieker JC, Komen N, Mannaerts GH, et al. Long-term and perioperative
corticosteroids in anastomotic leakage. Arch Surg. 2012;147(5):447–452.
53. Mor IJ, Vogel JD, de Luz Moreira A, et al. Infliximab in ulcerative colitis is
associated with an increased risk of postoperative complications after restor-
ative proctocolectomy. Dis Colon Rectum. 2008;51(8):1202–1207.
54. Yamamoto T, Allan RN, Keighley MR. Risk factors for intra-abdominal sepsis
after surgery in Crohn's disease. Dis Colon Rectum. 2000;43(8):1141–1145.
55. Heuman R, Boeryd B, Bolin T, et al. The influence of disease at the margin of
resection on the outcome of Crohn's disease. Br J Surg. 1983;70(9):519–521.
56. Pennington L, Hamilton SR, Bayless TM, et al. Surgical management of Crohn's
disease: influence of disease at margin of resection. Ann Surg. 1980;192(3):
311–318.
57. Deshaies I, Malka D, Soria JC, et al. Antiangiogenic agents and late anastomotic
complications. J Surg Oncol. 2010;101(2):180–183.
58. Enker WE, Merchant N, Cohen AM, et al. Safety and efficacy of low anterior
resection for rectal cancer. Ann Surg. 1999;230(4):552–554.
59. Rullier E, Laurent C, Garrelon JL, et al. Risk factors for anastomotic leakage after
resection of rectal cancer. Br J Surg. 1998;85(3):355–358.
60. Matthiessen P, Hallbook O, Andersson M, et al. Risk factors for anastomotic
leakage after anterior resection of the rectum. Colorectal Dis. 2004;6
(6):462–469.
61. Chambers WM, Mortensen NJ. Postoperative leakage and abscess formation
after colorectal surgery. Best Pract Res Clin Gastroenterol. 2004;18(5):865–880.
62. Vignali A, Fazio VW, Lavery IC, et al. Factors associated with the occurrence of
leaks in stapled rectal anastomoses: a review of 1014 patients. J Am Coll Surg.
1997;185(2):105–113.
63. Alves A, Panis Y, Mathieu P, et al. Postoperative mortality and morbidity in
French patients undergoing colorectal surgery: results of a prospective multi-
center study. Arch Surg. 2005;140(3):278–283.
64. Shogan BD, Carlisle EM, Alverdy JC, et al. Do we really know why colorectal
anastomoses leak? J Gastrointest Surg. 2013;17(9):1698–1707.
65. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical
indications in the treatment of liver metastases from colorectal cancer: long-
term results. Ann Surg. 2000;231(4):487–499.
66. Boccola MA, Lin J, Rozen WM, et al. Reducing anastomotic leakage in oncologic
colorectal surgery: an evidence-based review. Anticancer Res. 2010;30(2):
601–607.
67. Nakajima K, Takahashi S, Saito N, et al. Predictive factors for anastomotic
leakage after simultaneous resection of synchronous colorectal liver metastasis.
J Gastrointest Surg. 2012;16(4):821–827.