Anastomotic Leakage After Laparoscopic Colectomy: Who Will Require Emergency Fecal Diversion?

Abstract

Background:

To identify predictive factors for reoperation because of anastomotic leakage (AL) after colectomy.

Methods:

Between 2007 and 2016, all patients who developed AL following right or left colectomy in an expert center were included. Patients who were treated surgically (all including fecal diversion) were compared with those who were managed conservatively.

Results:

Overall, 81 (6.5%) patients developed AL, of which 32 (39%) were managed nonoperatively and 49 (61%) required reoperation. On average, AL was diagnosed on postoperative day 4 (3–8) and mortality reached 4.9% (n = 4). Reoperation included anastomosis resection in 31 (67%) patients of which 26 (100%) had right colectomy and 5 (25%) left colectomy. Reoperation for AL was associated with increased intensive care management (P = .026) and deep abdominal collection (P = .002). T stage >2 and right-sided colectomy were the only independent risk factors associated with the need for reoperation for AL. Stoma reversal was performed in 42 (98%) patients after a median of 4 months.

Conclusions:

AL after colectomy is more likely to require reoperation with fecal diversion after right-sided colectomy and T > 2 colorectal cancer.

Introduction

Considered as the main curative treatment in several conditions (including colorectal cancer, inflammatory bowel disease, and complicated diverticular disease), colorectal surgery has evolved during last decades, mainly with the exponential use of laparoscopic approach¹ and enhanced recovery after surgery programs (ERAS).² These technical refinements have improved patient comfort and drastically decreased length of hospital stay.³ With day-case laparoscopic colectomy as the next step, this could lead to potentially underestimate the severity of complications. Anastomotic leakage (AL), which remains the most feared postoperative complication, is associated with increased morbimortality^4–9 (especially in case of delayed management) and an increased rate of reoperation with fecal diversion.^10–12 Some authors have therefore classified AL according to the required treatment,^13,14 Grade C AL requiring reoperation. AL risk factors have thus been identified, including level of anastomosis,^15–19 male gender,²⁰ malnutrition,²¹ malignancy,²² and increased operative time.^17,18,23

In patients with well-tolerated sepsis, nonoperative management of AL (including antibiotics ± radiologic percutaneous drainage)^10–14 should be preferred to reoperation with fecal diversion (diverting stoma with or without resection of the anastomosis) to avoid complications related to fecal diversion, including dehydration and failed reversal.²⁴ Reoperation with fecal diversion is compelled by clinical assessment and when necessary, considered as a life-saving procedure.

Currently, success of nonoperative management is mostly unpredictable, leading in worst cases to delayed management of AL requiring fecal diversion and so, dramatic increase of morbimortality. The main objective of the present study was to determine predictive factors of Grade C AL, patients requiring secondary fecal diversion after laparoscopic colectomy.

Materials and Methods

Patients' selection

From January 2007 to December 2016, all consecutive patients who underwent laparoscopic right and left colectomy at our institution were identified from a prospectively collected database. Among them, all patients who developed postoperative AL were analyzed. AL was defined as 1/an extravasation of water-soluble contrast medium at the site of anastomosis or 2/an abscess surrounding the anastomosis without extravasation of contrast medium or 3/fecal peritonitis revealed by abdominal drainage (when used) or 4/fecal peritonitis with obvious signs of an anastomotic leak (such as fecal collection) during surgical reoperation. Patients who underwent colectomy in an emergency setting, had an atypical colectomy or rectal resection with infraperitoneal anastomosis or colectomy with intraoperative fecal diversion were excluded. This study was approved by the local Institutional Review Board.

Surgical procedures

As previously reported,^25,26 surgical technique for colectomy was standardized for all patients (including in benign condition), associating complete mesocolic excision, central vascular ligation, laparoscopic approach, without abdominal drainage. In brief, laparoscopic right colectomy was completed from the bottom up and ileocolonic anastomosis was performed extracorporeally (side-to-side or end-to-end hand-sewn simple layer suture)²⁵ or intracorporeally (side-to-side stapling).²⁷ During laparoscopic left colectomy, inferior mesenteric vessels (vein and artery) with systematic splenic flexure mobilization, and horizontal division of the rectum below the rectosigmoid junction were achieved; a side-to-end intracorporeal anastomosis was completed mechanically after the specimen retrieval.

Postoperative outcomes and management of AL

Postoperatively, patients were evaluated daily by a physician. Nasogastric tube and abdominal drain were avoided; opioid use was restricted; patients resumed early oral intake and ambulation according to ERAS principles. C-reactive protein (CRP) levels were measured on postoperative day (POD) 4. Increased CRP level (>130 mg/L), unexplained fever, suspicious abdominal examination or septic hemodynamic profile during the postoperative course led to perform water-soluble contrast computed tomography (CT) scan to detect AL.

In case of sepsis with signs of shock or generalized peritonitis associated with AL at CT-scan, emergency reoperation was performed. Reoperation consisted in abdominal lavage, drainage of the anastomosis with a drain mostly positioned behind the anastomosis, and fecal diversion; the preferred fecal diversion was a diverting ileostomy, except when major anastomosis dehiscence was observed (>50% of circumference), which usually led to anastomosis resection and end-stoma placement (Hartmann's procedure or ileocolostomy).

In case of AL with well-tolerated sepsis (no signs of shock), a nonoperative management, including intravenous (IV) antibiotics ± percutaneous drainage for 48–72 hours was performed. First line IV antibiotics included Tazobactam+Piperacillin, followed by oral antibiotic regimen for 7 days in case of patient improvement. Percutaneous drainage was proposed in case of accessible, larger than 3 cm-diameter perianastomotic collection; percutaneous drain was removed after decreased clinical and biological septic signs and a control CT scan reporting a collapsed collection. In the absence of significant decrease of inflammatory syndrome (CRP and leucocytes) after 48–72 hours of conservative treatment or in case of clinical deterioration, reoperation was also proposed (as described above).

Statistical analyses

Since the aim of the study was to identify predictive factors for reoperation with fecal diversion, two groups of AL patients were compared based on the success or failure of nonoperative management (failure leading to reoperation).

Patient characteristics and postoperative outcomes were analyzed and compared between both groups. Categorical variables were compared using the χ² test or Fischer's exact test when appropriate, and expressed as numbers (percentage), while continuous variables were compared using the Mann–Whitney test, and expressed as median (range). Preoperative and intraoperative variables achieving statistical significance at the 0 · 1 level in univariable analysis, as well as relevant variables were considered for multivariable analysis. A backward variable procedure was used to identify independent predictive factors of conservative treatment failure. A P value of .05 was considered statistically significant and odds ratios with 95% confidence intervals were calculated. All statistical analyses were performed with PASW (SPSS) 18.0 (SPSS, Inc., Chicago, IL).

Results

Patients' characteristics

During the study period, 1242 patients underwent an elective laparoscopic right or left colectomy. AL was diagnosed in 81 (6.5%) patients with 35 (43.2%) successfully managed nonoperatively and 46 (56.8%) requiring reoperation with fecal diversion. Patient characteristics are detailed in Table 1. On average, AL was diagnosed on POD 4, ranging from 3 to 8 days. Overall, patients with AL were mainly male (63%), smokers (21%), with a median age of 67 years (range: 26–92 years) and a median body mass index of 25.4 kg/m² (range: 17.1–54.9). Surgical procedure was performed for malignancy in 44 (54.3%) patients. Right and left colectomies were reported in 32 (39.5%) and 45 (60.5%) patients, respectively. For patients suffering from colorectal cancer, tumor-node-metastasis (TNM) staging was detailed in Table 1 and 14 (31.8%) patients had N+ status. Five (11.4%) patients had synchronous metastases, including 4 (9.1%) with liver metastasis. Patient management is summarized in Figure 1.

FIG. 1.

Summarized patients' management.

Table 1.

Demographic Characteristics

	Successful nonoperative management (n = 35)	Surgical management (n = 46)	P
Age, median (range)	67 (27–87)	69 (26–92)	.183
Gender (male), n (%)	20 (57.1)	31 (67.4)	.343
BMI, median (range), kg/m²	25.5 (18.7–37.5)	24.7 (17.2–54.9)	.919
Smoker, n (%)	7 (21.9)	10 (22.2)	.971
Elevated blood pressure, n (%)	13 (37.1)	18 (40.0)	.795
Diabetes mellitus, n (%)	3 (8.6)	5 (10.9)	1.000
Cardiac comorbidity, n (%)	8 (22.9)	8 (17.4)	.540
Pulmonary comorbidity, n (%)	1 (2.9)	4 (8.7)	.383
Renal comorbidity, n (%)	1 (2.9)	1 (2.2)	1.000
Cancer, n (%)	17 (48.6)	27 (58.7)	.365
T stage
1	5	1	.018
2	3	2
3	5	20
4	4	4

Bold values indicate statistical significance (p < 0.05).

BMI, body mass index.

Successful nonoperative management

Among the 35 (43.2%) patients successfully treated nonoperatively, 5 (14.3%) underwent percutaneous drainage (2 following right colectomy and 3 following left colectomy). Two (5.7%) patients presented with deep abdominal collection before any treatment. Median hospital stay reached 14 days (range: 5–55 days). One postoperative death was reported in a patient who developed massive pulmonary embolism at POD 5 in a 67-year-old patient.

Failure of nonoperative management and fecal diversion

Reoperation with fecal diversion was required for 46 (56.8%) patients with AL. Among them, 16 (34.8%) patients had deep abdominal collection before any treatment, including 5 patients who had percutaneous drainage (after right colectomy n = 3 and left colectomy n = 2). Reoperation with fecal diversion was performed after a median delay of 6 days (range: 4–14 days) following colectomy. During reoperation, isolated AL, AL with local abscess, AL with purulent peritonitis and AL with fecal peritonitis were found in 16 (34.8%), 5 (10.9%), 20 (21.7%), 5 (10.9%) patients, respectively. Anastomosis resection was performed in 31 (67.4%) patients, including all 26 (100%) patients who had right colectomy and 5 (25%) patients who had left colectomy. Overall, 3 (8.6%) patients died. Fecal peritonitis was found at reoperation in 2 patients who died at POD 10 and 23, respectively. One patient died of multiple organ failure at POD 70 due to AL without peritonitis at reoperation.

In the 46 patients who underwent reoperation with fecal diversion, median hospital stay was 25 (range: 8–179) days and was significantly higher compared with successful conservative management group (P = .003). Out of 43 surviving patients, 42 (97.7%) underwent stoma reversal after a median time of 4 (range: 1–10) months following colectomy. Among patients who underwent stoma reversal, 2 (5.4%) presented with AL recurrence. One required Hartmann's procedure and the other died after multiorgan failure due to septic shock (leading to 2.7% mortality rate after stoma reversal). Otherwise, an overall morbidity rate of 43.2% was reported, including 68.8% of minor postoperative complications (Clavien–Dindo I-II).

Risk factors of nonoperative management failure

Univariate analysis (Tables 1 and 2) showed statistical difference between both groups for right colectomy (P < .001), intensive care unit management (P = .026), deep abdominal collection (P = .002), and T stage >2 (P = .018); there was no difference in terms of demographics and comorbidities. In multivariate analysis (Table 3) right-sided colectomy (P = .007) and colorectal cancer with T stage >2 (P = .044) were found to be independent predictive factors of reoperation with fecal diversion in case of AL after colectomy.

Table 2.

Postoperative Events After Colectomy

	Successful nonoperative management (n = 35)	Surgical management (n = 46)	P
Intensive care unit requirement, n (%)	3 (8.6)	14 (30.4)	.026
Postoperative mortality, n (%)	1 (2.9)	3 (6.5)	.216
Evisceration, n (%)	1 (2.9)	8 (17.4)	.070
Deep abdominal collection, n (%)	2 (5.7)	16 (34.8)	.002
Percutaneous drainage, n (%)	5 (14.3)	5 (10.9)	.739
Sepsis, n (%)	5 (14.3)	14 (30.4)	.089
Median hospital stay, (range), (days)	14 (5–55)	25 (8–179)	.003

Bold values indicate statistical significance (p < 0.05).

Table 3.

Multivariate Analysis: Predictive Factors of Reoperation with Fecal Diversion in Patients Presenting Anastomotic Leakage After Laparoscopic Colectomy

	Successful nonoperative management	Surgical management	P	OR	95% CI	P
Right-sided colectomy	29 (82.9%)	26 (43.5%)	<.001	8.387	1.778–37.559	.007
T ≥ 3	9 (52.9%)	24 (88.9%)	.012	6.078	1.047–35.294	.044

Bold values indicate statistical significance (p < 0.05).

CI, confidence interval; OR, odds ratio.

Discussion

In colorectal surgery, interest for AL might be seen as obsessive and so, disregarded. Indeed, there are several definitions for AL after colectomy^{10–14,23,28,29} and discrepancy between surgeons from different countries has been reported.^14,28 Some criteria are considered as clear signs of leakage (such as extravasation of contrast medium after rectal enema on a CT scan^28,29 and fecal leakage observed in drains/from the wound²⁹) leading some authors to classify AL according to required treatment.^13,14 In these classifications, AL requiring reoperation (Grade C in both classifications), considered as the most severe ones, are consensually recognized by all surgeons. AL is associated with poor short-term outcomes with reported postoperative mortality rates reaching 6% to 39%^4–9; in current report, mortality rates after successful and failed conservative management reached 2.9% and 6.5%, respectively (P = .216). These poor outcomes are seemingly related to delayed treatment: late reoperation results in increased mortality as patient presents with severe sepsis. Therefore, early detection of AL and reoperation with fecal diversion (when required) should improve outcomes^6–9,30,31 and could potentially help to preserve the anastomosis after left colectomy (25% of Hartmann's procedure in our series).

Comparing patients with AL requiring fecal diversion to patients with AL successfully treated nonoperatively through univariate analysis, showed intensive care management, deep abdominal collection, length of hospital stay, right-sided resection, and T > 2 TNM staging to be associated with reoperation. Because intensive care management, deep abdominal collection, and length of hospital stay were not considered as predictive variables but rather as consequences of AL (and intuitively increased in patient presenting with AL), they were not included in multivariate analysis. The only two independent predictive factors for reoperation were right-sided colonic resection and T status >2.

Current analysis confirmed that AL after right-sided resection was associated with reoperation, as recently suggested by Voron et al.¹⁵ Results from this study focusing on colorectal cancer,¹⁵ showed that nonoperative management was successful in right-sided resection and left-sided resection in 31.8% and 64.3%, respectively, compared with 18.9% and 59.2% in our series, respectively. Also, mortality rate associated with AL has been shown to be higher in case of ileocolic anastomosis compared with colorectal anastomosis³²; in the current analysis, mortality was multiplied by 100 in patients requiring reoperation due to AL compared with patients who did not present with AL (0.07% versus 6.5%). To explain this major increase, several hypotheses may be drawn. First, the liquid content in ileum is more likely to spread in the peritoneal cavity (compared with feces from the colon), leading to generalized peritonitis more than localized collection. Second, vascularization of transverse colon is difficult to intraoperatively assess, leading to uncertain blood supply for ileocolic anastomosis, whereas rectum is vascularized by hypogastric vessels. Finally, when performed extracorporeally, ileotransverse anastomosis compels to exteriorize the transverse colon from the abdominal cavity, potentially leading to nonanatomical position while completing the anastomosis, microtraumatisms, and more fragile anastomosis.^27,33

Regarding T status, the current study suggested that colectomy performed because of larger tumor is associated with severe AL. When final pathology is very rarely available during early postoperative course, indication is known (benign or benign) and size of the lesion may also be anticipated. Tumor size^16,23 and advanced TNM staging¹⁶ have been previously associated with increased rate of AL,^16,23 potentially because of poor general condition in patients with advanced TNM staging¹⁶; in the current study, malnutrition was not investigated because of the retrospective design. Also, larger tumors are more difficult to handle, especially with laparoscopic approach, leading to more technically challenging procedures. In patients suffering from colorectal cancer, AL has been associated with worsened long-term outcomes: recurrence was more frequent,^15,34 including distant metastasis^35,36 and overall survival was inferior.¹⁵ In our series, we observed 3 (6.8%) patients with recurrence (distant metastases). These outcomes probably result from delayed adjuvant chemotherapy due to poor general condition and complications (such as intra-abdominal collection); and as larger tumors (requiring adjuvant chemotherapy) are associated with severe AL and reoperation, AL in these patients is understandably worsened.

Naturally, this study yields several limitations. First of all, it has been recorded retrospectively (despite a prospective inclusion). The length of the study—a decade—may have led to minor heterogeneity in management. In the same way, when operative protocol was uniform, 6 surgeons were involved. Also, this study is not a comparison of AL treatment but an attempt to predict patient who will ultimately require reoperation because AL. Despite its retrospective design, this report enabled to identify predictive factors of reoperation with fecal diversion because of consistent and standardized postoperative policy after colectomy during the study period: all patients were screened for AL after colectomy (including CT scan in case of clinical signs or increased inflammatory markers) and patients presenting with AL as well as hemodynamics instability or ineffective conservative treatment (antibiotics +/− percutaneous drainage) underwent reoperation. Also, rectal resections were excluded to homogenize the studied population, as management is distinct.

In conclusion, half of AL require reoperation with fecal diversion, and should be seen as severe AL because of increased mortality. Finally, AL after colectomy is more likely to require reoperation with fecal diversion after right-sided colectomy and in patient presenting with T > 2 colorectal cancer.

Ethics Approval

This article does not contain any studies with human participants performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Author Contributions

Conception of the work: A.Z.L.B., D.F.; Acquisition, analysis, interpretation of data: A.Z.L.B., N.T., C.D., A.L., J.M.F., B.G., and D.F.; Drafting the work or revising it critically for important intellectual content: A.Z.L.B., N.T., T.G., C.T., and D.F.; Final Approval: A.Z.L.B., N.T., C.D., T.G., A.L., J.M.F., C.T., B.G., and D.F.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

References

Freischlag

, Adam

, Turner

, Watson

, Ezekian

, Schroder

, et al. With widespread adoption of MIS colectomy for colon cancer, does hospital type matter?. Surg Endosc, 2019; 33:159–168.

Aarts

, Rotstein

, Pearsall

, Victor

, Okrainec

, McKenzie

, et al. Postoperative ERAS interventions have the greatest impact on optimal recovery: Experience with implementation of ERAS across multiple hospitals. Ann Surg, 2018; 267:992–997.

Balvardi

, Pecorelli

, Castelino

, Niculiseanu

, Liberman

, Charlebois

, et al. Measuring in-hospital recovery after colorectal surgery within a well-established enhanced recovery pathway: A comparison between hospital length of stay and time to readiness for discharge. Dis Colon Rectum, 2018; 61:854–860.

Gessler

, Eriksson

, Angenete

. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis, 2017; 32:549–556.

Gessler

, Bock

, Pommergaard

, Burcharth

, Rosenberg

, Angenete

. Risk factors for anastomotic dehiscence in colon cancer surgery-a population-based registry study. Int J Color Dis, 2016; 31:895–902.

Longo

, Northover

Reoperative Colon and Rectal Surgery. London, UK: Martin Dunitz, Taylor and Francis Group, 2003.

Rullier

, Laurent

, Garrelon

, Michel

, Saric

, Parneix

. Risk factors for anastomotic leakage after resection of rectal cancer. Br J Surg, 1998; 85:355–358.

Enker

, Merchant

, Cohen

, Lanouette

, Swallow

, Guillem

, et al. Safety and efficacy of low anterior resection for rectal cancer: 681 consecutive cases from a specialty service. Ann Surg, 1999; 230:544–552.

Macarthur

, Nixon

, Aitken

. Avoidable deaths still occur after large bowel surgery. Scottish Audit of Surgical Mortality, Royal College of Surgeons of Edinburgh. Br J Surg, 1998; 85:80–83.

10.

Murrell

, Stamos

. Reoperation for anastomotic Failure. Clin Colon Rectal Surg, 2006; 19:213–216.

11.

Thomas

, Margolin

. Management of colorectal anastomotic leak. Clin Colon Rectal Surg, 2016; 29:138–144.

12.

Rickert

, Willeke

, Kienle

, Post

. Management and outcome of anastomotic leakage after colonic surgery. Colorectal Dis, 2010; 12:e216–e223.

13.

Rahbari

, Weitz

, Hohenberger

, Heald

, Moran

, Ulrich

, et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: A proposal by the International Study Group of Rectal Cancer. Surgery, 2010; 147:339–351.

14.

Chadi

, Fingerhut

, Berho

, DeMeester

, Fleshman

, Hyman

, et al. Emerging trends in the etiology, prevention, and treatment of gastrointestinal anastomotic leakage. J Gastrointest Surg, 2016; 20:2035–2051.

15.

Voron

, Bruzzi

, Ragot

, Zinzindohoue

, Chevallier

, Douard

, et al. Anastomotic location predicts anastomotic leakage after elective colonic resection for cancer. J Gastrointest Surg, 2019; 23:339–347.

16.

Zhu

, Feng

, Lu

, Wang

, Hu

, Li

, et al. Laparoscopic low anterior resection for rectal carcinoma: Complications and management in 132 consecutive patients. World J Gastroenterol, 2010; 16:4605–4610.

17.

Choi

, Hwang

, Ko

, Jang

, Shin

, Lee

, et al. Risk factors for anastomotic leakage after laparoscopic rectal resection. J Korean Soc Coloproctol, 2010; 26:265–273.

18.

Huh

, Kim

. Anastomotic leakage after laparoscopic resection of rectal cancer: The impact of fibrin glue. Am J Surg, 2010; 199:435–441.

19.

Park

, Choi

, Kim

, Lee

, et al. Multicenter analysis of risk factors for anastomotic leakage after laparoscopic rectal cancer excision: The Korean laparoscopic colorectal surgery study group. Ann Surg, 2013; 257:665–671.

20.

Shinji

, Ueda

, Yamada

, Koizumi

, Yokoyama

, Takahashi

, et al. Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage after laparoscopic anterior resection in patients with rectal cancer. BMC Gastroenterol, 2018; 18:117.

21.

Shimura

, Toiyama

, Hiro

, Imaoka

, Fujikawa

, Kobayashi

, et al. Monitoring perioperative serum albumin can identify anastomotic leakage in colorectal cancer patients with curative intent. Asian J Surg, 2018; 41:30–38.

22.

Kirchhoff

, Dincler

, Buchmann

. A multivariate analysis of potential risk factors for intra- and postoperative complications in 1316 elective laparoscopic colorectal procedures. Ann Surg, 2008; 248:259–265.

23.

Kawada

, Hasegawa

, Hida

, Hirai

, Okoshi

, Nomura

, et al. Risk factors for anastomotic leakage after laparoscopic low anterior resection with DST anastomosis. Surg Endosc, 2014; 28:2988–2995.

24.

Åkesson

, Syk

, Lindmark

, Buchwald

. Morbidity related to defunctioning loop ileostomy in low anterior resection. Int J Colorectal Dis, 2012; 27:1619–1623.

25.

Levard

, Denet

, Gayet

. Laparoscopic right colectomy from top to bottom. J Visc Surg, 2012; 149:e34–e37.

26.

Zarzavadjian Le Bian

, Denet

, Tabchouri

, Levard

, Besson

, Perniceni

, et al. The effect of metabolic syndrome on postoperative outcomes following laparoscopic colectomy. Tech Coloproctol, 2018; 22:215–221.

27.

Zarzavadjian Le Bian

, Cesaretti

, Smadja

, Costi

. Total laparoscopic right colectomy: The duodenal window first approach. Surg Oncol, 2016; 25:117–118.

28.

van Rooijen

, Jongen

, Wu

, Ji

, Slooter

, Roumen

, et al. Definition of colorectal anastomotic leakage: A consensus survey among Dutch and Chinese colorectal surgeons. World J Gastroenterol, 2017; 23:6172–6180.

29.

Adams

, Papagrigoriadis

. Little consensus in either definition or diagnosis of a lower gastro-intestinal anastomotic leak amongst colorectal surgeons. Int J Colorectal Dis, 2013; 28:967–971.

30.

Golub

, Goulb

, Cantu

, Stein

. A multivariate analysis of factors contributing to leakage of intestinal anastomosis. J Am Coll Surg, 1997; 184:364–372.

31.

Karanjia

, Corder

, Holdsworth

, Heald

. Risk of peritonitis and fatal septicemia and the need to defunction the low anastomosis. Br J Surg, 1991; 78:196–198.

32.

Bakker

, Snijders

, Grossmann

, Karsten

, Havenga

, Wiggers

. High mortality rates after non-elective colon cancer resection: Results of a national audit. Colorectal Dis, 2016; 18:612–621.

33.

Shapiro

, Keler

, Segev

, Sarna

, Hatib

, Hazzan

. Laparoscopic right hemicolectomy with intracorporeal anastomosis: Short- and long-term benefits in comparison with extracorporeal anastomosis. Surg Endosc, 2016; 30:3823–3829.

34.

Kim

, Kim

. The impact of anastomotic leakage on oncologic outcomes and the receipt and timing of adjuvant chemotherapy after colorectal cancer surgery. Int J Surg, 2015; 22:3–9.

35.

Krarup

, Nordholm-Carstensen

, Jorgensen

, Harling

. Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: A nationwide cohort study. Ann Surg, 2014; 259:930–938.

36.

Nordholm-Carstensen

, Rolff

, Krarup

. Differential impact of anastomotic leak in patients with stage IV colonic or rectal cancer: A nationwide cohort study. Dis Colon Rectum, 2017; 60:497–507.