Colonic Anastomotic Leak: Risk Factors, Diagnosis, and Treatment

COLLECTIVE REVIEWS

Colonic Anastomotic Leak: Risk Factors, Diagnosis, and Treatment T Peter Kingham MD, H Leon Pachter, MD, FACS Anastomotic dehiscence is one of the most dreaded complications of operations of the large intestine. Breakdown of an anastomosis results in increased morbidity and mortality and adversely affects length of stay, cost, and cancer recurrence. Reported rates of anastomotic dehiscence vary between 1% and 30%, although experienced colorectal surgeons often quote 3% to 6% as an acceptable overall leakage rate(Table 1).1 Despite a paucity of prospective randomized data, intuitively it would appear that emergent operations are at greater risk for anastomotic breakdown than those procedures performed electively. Confounding the issue is that there are differing opinions as to what risk factors have been proved to predict anastomotic dehiscence. The aim of this review is to examine the currently identified risk factors contributing to intestinal anastomotic breakdown and delineate methods of diagnosis and treatment of this universally dreaded complication.

The most detailed definition encompasses a combination of clinical indicators like pain; peritonitis; and biochemical markers, such as fever; tachycardia; radiologic studies showing fluid collections or gas-containing collections; and intraoperative findings.6,7 Risk factors

There are many risk factors that have been attributed to anastomotic leakage (Table 3). In addition, there are studies that have provided evidence supporting the relevance or lack of relevance of most risk factors, adding to the confusion of what are proved risk factors. Risk factors can be categorized as patient-specific, intraoperative, and specific for low rectal anastomosis. Patient-specific risk factors include malnutrition, steroids, tobacco use, leukocytosis, cardiovascular disease, alcohol use, American Society of Anesthesiologists (ASA) score, and diverticulitis. Intraoperative risk factors include low anastomoses, suboptimal anastomotic blood supply, operative time ⬎2 hours, bowel obstruction, perioperative blood transfusion, and intraoperative septic conditions not conducive to primary anastomosis. Risk factors for low rectal anastomosis include gender and obesity.6,8-12 Additional risk factors have been relegated to low colonic anastomoses, thereby stressing the importance of stratifying the location of anastomoses when interpreting the literature.

Definition of anastomotic leak

There is no uniformly accepted definition of an anastomotic leak in the literature (Table 2). In a review of 97 studies from 1993 to 1999, 56 different definitions of what constitutes an anastomotic leak were described.2 In 1991, the United Kingdom Surgical Infection Study Group proposed the definition as a “leak of luminal contents from a surgical join between two hollow viscera.”3 These contents can exit through wounds or drains, or collect at the anastomotic site. Some early studies reporting on anastomotic breakdowns are difficult to interpret because they included extravasation of contrast material on routine postoperative contrast enemas as anastomotic leaks. The majority of contemporary studies do not include radiologic leaks on routine imaging because these are not clinically significant. Although the UK study did set a definition for an anastomotic leak, there have been few references to this study since then. The majority of reports investigating the cause and rate of leaks use variations of clinical signs like peritonitis; feculent wound; or drain discharge, abscess, or fever and radiologic parameters to define an anastomotic leak.4,5

Preoperative patient factors

Obesity has been cited as a risk factor, especially for leftsided colorectal anastomotic leaks. One retrospective review of anterior resections found that when anastomotic leaks occur ⬍5 cm from the anal verge, there was a 33% leak rate in obese patients (defined as 20% heavier than ideal body weight) compared with a 15% leak rate in nonobese patients (p ⫽ 0.03).5 Another retrospective examination of 208 left-sided anastomoses similarly found on multivariate analysis that when emergency resections were required, of ASA class, age, gender, comorbidities, laboratory values, and transfusion requirements, only obesity was a major risk factor for leak.13 Choi and colleagues14 and Vignali and colleagues,15 on the other hand, in prospective studies encompassing nearly 3,500 patients who underwent colorectal resections for malignancy, have not found obesity to be a factor that increased risk of anastomotic leak.14,15 The discrepancy between studies might be related

Disclosure Information: Nothing to Disclose. Received July 23, 2008; Revised October 2, 2008; Accepted October 5, 2008. From the Department of Surgery, NYU Medical Center, New York, NY. Correspondence address: T Peter Kingham, MD, Department of Surgery, NYU Medical Center, 525 1st Ave, New York, NY 10016.

© 2009 by the American College of Surgeons Published by Elsevier Inc.

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Table 1. Anastomotic Leak Rates First author

No. of patients

Major leaks (%)

Biondo13 Docherty37 Alves9 Konishi18 Hyman44 Lipska7 Branagan19 Sorenson11 Wong45 Platell16 Karanjia43 Law6 Gastinger48 Rullier5 Vignali15

211 652 707 391 1223 541 1,834 333 1066 1639 219 196 2729 131 284

5.7 4.4 6 2.8 2.7 6.5 3.9 15.9 3.8 2.4 11 10.2 14 19 7.8

<6 cm (%)

97 100 100 100 100

to differences in including low rectal anastomoses. It would seem logical that obesity increases the risks of anastomotic breakdown because of difficulties in properly cleaning off the proximal end, and tension and ischemia caused by a short, thick mesentery. Other factors, such as tobacco and alcohol use, have also been found to be risk factors for anastomotic leaks. One retrospective study examined 333 patients from 1993 to 1996 and found smoking was appreciably associated with anastomotic leak on multivariate analysis. The relationship between the two might be secondary to ischemia caused by smoking-related microvascular disease. Additional studies have also found excessive alcohol use (⬎35 drinks per week) to be an important risk factor for anastomotic leak.11 In this study, large quantities of alcohol consumption might be a surrogate for poor nutritional status. Prospective analysis where the indication for operation was tracked, revealed that diverticular disease was a significant independent predictor of anastomotic leakage (p ⬍ Table 3. Risk Factors for Anastomotic Leak Patient factors Malnutrition, steroids, tobacco and alcohol use, leukocytosis, cardiovascular disease, ASA score, diverticulitis Operative factors Low anastomosis, operative time ⬎2 hours, bowel obstruction, blood supply to anastomosis, perioperative blood transfusion, intraoperative septic conditions Factors associated Male, obesity with leak after low anastomosis ASA, American Society of Anesthesiologists.

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Table 2. Definition of Anastomotic Leak Clinical signs Pain, peritonitis, feculent, or purulent drainage Biochemical markers Fever, tachycardia, leukocytosis Radiological studies Fluid collections Intraoperative findings Gross enteric spillage, anastomotic disruption

0.0001) with a 5.9% leak rate with resections for diverticular disease compared with a 2.4% overall leak rate.16 The almost twofold increase in leak rate seen in patients with diverticular disease might be related to performing a lessthan-adequate resection. If the splenic flexure is not mobilized, and the bowel is not resected from the descending colon to the peritoneal reflection, the subsequent anastomosis can be performed in an area of “muscular hypertrophy.” Placement of sutures either by hand or through a mechanical device through an area of “muscular hypertrophy” can set the stage for an anastomotic breakdown. ASA status

The ASA physical status examination is used by anesthesiologists to classify preoperative physical condition of surgical patients. The scale ranges from 1, signifying a normal, healthy patient, to 5, representing a patient not likely to survive 24 hours. In a multivariate analysis of leaks in 1,417 colon resections above the peritoneal reflection, ASA grade of 3 to 5 and an emergent indication for operation were found to be the only two statistically significant (p ⫽ 0.0001) risk factors for clinical anastomotic leak.14 This finding was bolstered in a case-control study that found ASA score ⬎3 was a substantial risk factor, specifically in left-sided colon anastomotic leaks.10 Comorbid conditions as represented by an ASA score ⬎3, are one method to indicate patients at higher risk for colonic anastomotic leaks. Comorbid conditions, such as diabetes mellitus, hypertension, and cardiac disease all represent conditions that affect ASA status and can cause impaired circulation at the microcirculation required for a healthy anastomosis. Steroid use

Although intuitively it is assumed that impaired healing with steroid use would affect anastomotic leak rates, it is difficult to find an absolute correlation.17 Often, the number of patients who were on steroids in the studied populations was not great enough to show a significant statistical difference in leak rates. For example, one retrospective analysis only had adequate data about 2 of 10 patients treated with steroids in the study, and another retrospective study found a statistically significant correlation between steroid use and colorectal anastomotic leaks on univariate

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analysis only.7,9 In contrast, a prospective study evaluating 391 consecutive elective colon resections found that longterm preoperative steroid use mandating perioperative steroid coverage was an important risk factor for anastomotic leak when subjected to multivariate analysis.18 A leak rate of 11.8% in was noted in patients with steroid use compared with 2.4% in those without steroids (odds ratio ⫽ 8.7; 95% CI, 1.2⫺45.1; p ⫽ 0.015). Given this prospective study is the strongest clinical study available for interpretation, steroid use should be considered a risk factor for anastomotic leak.

higher rate of leakage in male (5.6%) compared with female patients (2.4%) throughout the colon and rectum. There is, at present, no general consensus about gender as a risk factor for anastomoses above the rectum. Most likely, gender only influences low anastomoses, where the narrower male pelvis makes dissection and anastomoses more challenging. Confirmatory data stems from studies by Biondo and colleagues13 and Choi and colleagues,14 who both found similar rates of anastomotic leaks irrespective of gender in anastomoses performed above the peritoneal reflection.

Radiation

Nutrition

Neoadjuvant radiation therapy is the standard of care for rectal tumors that are classified as either T3 or N1 by endorectal ultrasonography. There are only retrospective studies that have examined the relationship of preoperative radiation and anastomotic leaks. In a review article, Chambers and Mortensen1 found inconclusive data about whether preoperative irradiation leads to higher leak rates. Several retrospective studies found no differences in leak rates between patients with low rectal anastomoses who received radiotherapy and those who did not, regardless of whether or not they also had proximal diversion.5,15 Other reports, such as that by Alves and colleagues,9 showed that previous abdominal or pelvic irradiation was a risk for leak on univariate analysis for anastomotic leak, when they examined 707 patients who underwent colorectal resection. It is unclear from the existing data whether radiation is a risk for anastomotic leak. It is our belief that until substantial data are forthcoming to the contrary, the better part of valor would be to divert low rectal anastomosis in patients treated with neoadjuvant chemoradiation therapy.

Nutritional state is an important factor in contributing to anastomotic leaks. Several studies have shown a correlation between low albumin levels and an increased incidence of anastomotic leaks.10,12 It becomes essential to assess nutritional levels preoperatively and embark on methods to reverse any catabolic state when present. Early postoperative feeding is usually tolerated well after most colorectal resections, and there is no increase in leak rates when early feeding is instituted. Currently, there are no established recommendations as to what level of preoperative malnutrition requires intervention. One case-control study found that malnutrition (serum albumin ⬍35g/L) was a substantial risk factor for anastomotic leak after multivariate analysis, with a 13.2 odds ratio (95% CI, 2.83⫺61.85) in the “leak” and “no leak” group.10 In addition, this study found weight loss of ⬎5 kg was a risk factor for anastomotic leak, with a 27.6 odds ratio (95% CI, 2.83⫺128.74). Their conclusion was that malnutrition, as described by weight loss and low albumin levels, was the strongest risk factor for anastomotic leak. Whether it is hypoalbuminemia or low prealbumin levels, evidence of protein deficiency places a patient at higher risk for anastomotic leaks. Preoperative maximization of nutrition is an important risk-reduction measure, but multiple studies have shown that for the majority of patients, unless severely malnourished, there is no benefit to preoperative parenteral nutrition.20

Gender

Gender is often identified as a risk for colorectal anastomotic leak. In a prospective study of 196 patients with rectal cancer resections, multivariate analysis showed male patients with anastomoses ⬍5 cm from the anal verge had a higher rate of anastomotic leak than did women.6 Similarly, a retrospective analysis of 541 consecutive operations with colonic and rectal anastomoses found an overall leak rate of 11% in men as compared with only 3% in women, which on multivariate analysis was significant (p ⫽ 0.001).7 This difference held throughout their subgroup analyses of patients with cancer, patients with cancer ⬍12 cm from the anal verge, patients requiring an anterior resection, and patients with anastomoses in the pelvis. Some studies have shown higher leak rates in male patients throughout the colon, irrespective of distance from the anal verge. In a prospectively evaluated cohort of male patients, Branagan and Finnis19 noted that there was a substantially

Bevacizumab (antiⴚvascular endothelial growth factor monoclonal antibodies)

A new identified risk factor for anastomotic leak is bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor receptor. This drug has been shown in phase III trials, in combination with several other standard chemotherapy regimens, to increase overall survival in patients with colon cancer. The first studies examining bevacizumab reported several patients with bowel perforations.21,22 The mechanism of this perforation is proposed to be arterial microthromboembolic disease leading to bowel ischemia. The same mechanism can cause an anastomotic

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leak, as can inhibition of angiogenesis in the microvascular bed of new anastomoses. There is one report of two patients with anastomotic leaks up to 2 years after operation and treatment with both bevacizumab and radiation, but it is difficult to determine the exact cause of the leaks.23 There is little evidence as to the appropriate interval between the last dose of bevacizumab and elective operation. Because the half-life of the drug is 20 days, and wound-healing complications have been documented up to 56 days after treatment, it is advisable to delay operation for three halflives, or 60 days, after the last treatment.24 Intraoperative factors

There is a category of patients without any preoperative risk factors for anastomotic leak in which this complication develops as a result of intraoperative events. For example, one retrospective review of 1,014 patients noted that in patients where an anastomotic leak occurred after rectal resection, there was a significantly longer mean and median duration of operation (220 minutes versus 186 minutes; p ⬍ 0.05).15 A similar correlation between anastomotic leak rate and duration of operations that lasted ⬎4 hours was found in a prospective examination of 391 colorectal resections.18 These results suggest that a higher leak rate is associated with more difficult resections and anastomoses. Another variable that has been studied is whether or not wrapping an anastomosis with omentum confers a protective effect in mitigating anastomotic leaks. This question was addressed in a prospective, randomized trial of 705 patients who were assigned to anastomotic omental wrap or not. They demonstrated no difference in leak rates (4.9%) between the two groups.25 Additionally, they raised concerns about the potential for devascularized omental pedicles becoming infected, leading to abscess formation and potentially future large bowel obstructions. Because of this data, their conclusion was that omental wraps around colonic anastomoses were not justified. In unreported data, Pachter and Hofstetter, who routinely wrap their anastomosis with omentum, have not experienced either omental infarction or large bowel obstruction in ⬎1,000 colonic anastomosis (unpublished data). Anastomotic ischemia

Tissue ischemia at the site of the anastomosis is frequently cited and implicated as a cause for anastomotic breakdown. To avoid ischemic complications, there have been several attempts to quantify colonic perfusion intraoperatively. One group used laser Doppler scans before and after mobilizing, dividing, and anastomosing the colon to show a 32% reduction in colonic tissue perfusion 2 cm proximal to the anastomotic site and a 51% decrease at the anastomotic site.26 Another study looked at 55 patients and found

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that there was a greater overall reduction in blood flow at the rectal stump when compared with the proximal colon limb.27 When a leak did develop in patients, there was a 16% decrease in blood flow, compared with 6% in patients without a leak (p ⬍ 0.001). Similarly, there was a mean proximal blood flow reduction of 5% in patients without a leak compared with 12.9% in patients with a leak (p ⬍ 0.01). A small change in blood supply to the proximal colon can increase the risk of leak. One manner with which anastomotic blood supply can be increased is by varying the location of mesenteric and vascular ligation. Hall and colleagues28 measured tissue oxygen tension before and after low or high division of the inferior mesenteric artery in 62 elective colorectal resections. He found that after mobilization and vascular ligation, oxygen tension was equal or improved in the transverse and descending colon when they were used for the colorectal anastomoses, but that oxygen tension was diminished in the sigmoid colon. He concluded that location of the vascular ligation had no impact on colonic perfusion, but location of the resection was vital to tissue oxygenation. His hypothesis was that the marginal artery did not provide adequate sigmoid blood flow. In addition to increasing blood supply by using the wellperfused left colon for the proximal limb of the anastomosis, consideration has also been given to increasing anastomotic blood flow by performing side to end anastomoses.1 Theoretically, the blood flow in the proximal pouch of a side to end anastomosis might be more consistent than that of an end colonic anastomosis. Hallbook and colleagues29 performed laser Doppler flow measurements in colorectal anastomoses and found substantially decreased anastomotic blood flow after dissection in end to end anastomoses when compared with side to end anastomoses. This method can be considered in difficult cases, where adequate blood supply to the proximal limb might be in doubt. A simple rule of thumb is to ligate the blood supply to the colon as proximal to the aorta as possible, assuring adequate collateral flow. Proximal lumen of the bowel must always be inspected. If the mucosa is pink then the blood supply is adequate. Relying on merely looking at the serosal surface is fraught with pitfalls, as the serosa might be viable but the mucosa is not. Use of drains

The issue of routine drainage of colonic anastomoses has been a topic of controversy for years. Those championing the use of these drains believe they play a role in evacuating perianastomotic fluid collections, lessening the incidence of abscess formation, at the same time serving as an early warning marker for anastomotic dehiscence. Although theoretically, an undrained fluid collection that becomes in-

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fected can drain through the anastomosis, few cases like these have been documented. Conflicting reports in the literature as to the pros and cons of routine drainage of low pelvic anastomoses exist, but there is no data to support routine use of drains when IP anastomoses are performed. Merad and colleagues performed a controlled, multicenter study encompassing 317 patients that proved intraabdominal drains were not beneficial.30 They randomized patients to either abdominal drainage or no drainage and were unable to find any difference in either group with regard to pelvic abscesses (9% for each group). In this adequately powered study, she concluded that there was no justifiable indication to place a drain in colon resections above the sacral promontory. To the contrary, they believed that it was potentially harmful because one patient had a hematoma related to the drain and another required surgical removal of the drain. A meta-analysis of complications from colorectal resections examined four randomized, controlled trials from 1987 to 1995 that compared the routine use of drains.31 Although the trials were suboptimal in quality, when their results were pooled they found an odds ratio for clinical leak of 1.5, favoring the group without a drain. Yeh and colleagues32 came to a similar conclusion in a prospective study of 978 patients with anterior resections with an overall leak rate of 2.8%, but found a higher rate of leakage when drains were used (odds ratio ⫽ 9.13; 95% CI, 1.16⫺71.76). He also concluded that there was no indication to drain pelvic anastomoses. Conclusions based on nonrandomized studies, such as this in which the surgeon is given preference to place drains in higher-risk anastomoses is inherently biased. Studies such as these are helpful in highlighting that drains do not adequately identify a patient population with early leaks. Yeh noted that only 5% of patients with pelvic leaks had pus or enteric contents in the preexisting drains. The general consensus is that IP anastomoses do not benefit from drainage, although low rectal anastomoses can, allowing for surgeon preference to determine this decision. Mechanical bowel preparation

The fecal load of the colon at the time of anastomosis has been thought to influence anastomotic integrity. Traditionally, on-table lavage was performed during emergency operations on patients with perforations or obstructions. One prospective study determined that bowel decompression and primary anastomosis was safe without intraoperative colonic lavage, so this practice has been abandoned.33 For elective operations, the goal of mechanical bowel preparation is to lower the bacterial load in the colon. One animal model demonstrated higher leak rates in rats when solid feces were present in their colons.34 When canine colonic

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anastomoses were tested in a similar manner, there was no difference in the leak rate between prepared and unprepped colons.35 This suggests that intraluminal stool might have trophic effects on epithelium and the anastomosis. There have been several human studies that have studied the question of the use of colonic bowel preparations. One of the first randomized trials to examine this question included 267 patients who were randomly selected to mechanical bowel prep versus no bowel prep before colonic resection.36 Results revealed a 2% leak rate in the unprepped patients as compared with a 4% leak rate in the prepared patients, but this difference was not significant (p ⫽ 0.28). Several years later, another prospective study enrolled 329 patients and randomized patients to no bowel prep for elective colon operation.37 Similarly, there was no significant difference in anastomotic leak rates between the groups. Although the authors concluded that mechanical bowel preparation was indicated in low rectal resections, given there were only three leaks in total in the study, it is difficult to make a strong conclusion from their study. A third case-controlled study found that mechanical bowel prep did not influence the anastomotic leak rate, and they surmised that with an anastomotic leak there was feculent spillage regardless of the status of the bowel prep.10 The question of whether the presence of solid stool with bacterial collagenases contributes to suture-line breakdown is unanswered in the literature. Given the wide array of results in the literature that has examined the use of a bowel prep, we recommend mechanical preparation to minimize contamination. Anastomotic technique: stapled versus handsewn anastomosis

In order for an anastomosis to heal properly, three critical factors must be present: no tension, adequate blood supply, and an inverted anastomosis. In an era that has seen an explosion in technological devices that aid in bowel resection and creation of mechanical anastomosis, the question arises whether leak rates are comparable with the traditional handsewn anastomosis. There is strong evidence that rates are equal from a multicenter, randomized, prospective trial comparing handsewn to stapled anastomosis in elective and emergent colorectal operations.38 Of 652 randomized patients studied, there was no significant difference (p ⫽ 0.93) in the clinical leak rate (4.4%) between sutured and stapled anastomoses. There was a difference in radiologic leak rates. Fourteen percent of patients with a sutured colorectal anastomosis had a radiologic leak, as compared with only 5% of patients with stapled anastomoses. The importance of subclinical leaks such as these has yet to be defined. Similar results were found in a prospective study that enrolled 1,417 patients with colon resections above the peritoneal reflection and found that there was no dif-

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ference in leak rates between stapled and handsewn anastomoses.14 A Cochrane analysis was performed to answer the question of whether leak rates were lower with stapled low (⬍6 cm from the anal verge) anastomoses. The conclusion was that there was not a statistically significant difference even with low anastomoses.39 Laparoscopic versus open

When laparoscopic operation was extended to colorectal resections, two major questions were raised: Will this approach result in an adequate cancer operation; and what effect, if any, will this method have on the anastomotic leak rate? Fifty-two articles in the literature comparing laparoscopic and open colorectal resections were reviewed by Chapman. Based on the cumulative number of patients studied, there were no differences in the anastomotic leak rate between the two groups.40 Subsequent trials about the number of lymph nodes sampled, extent of resection, and survival, likewise could not attribute any negative factors to the laparoscopic approach.40,41 Additionally, the Clinical Outcomes of Surgical Therapy Study Group found no difference in leak rates when they randomized 872 patients at 48 institutions to open and laparoscopic colon resections for cancer.42 The safety of laparoscopic colorectal resections was confirmed in a prospective, multicenter study group.43 Of 948 anastomoses examined there were 46 (4.8%) leaks. Sixty-eight percent of the leaks were managed nonoperatively, although 32% required reoperation. The highest leak rate (12.7%), as expected, was noted in those patients undergoing anterior resections, compared with a 7% rate with left hemicolectomies. The authors also noted that there was a higher leakage rate when the anastomosis was ⬍10 cm from the anal verge.

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variate analysis, there was a 4.56 odds ratio (95% CI, 1.64⫺12.71) of anastomotic leak for these low resections. There are also studies that have examined whether ileorectal or colorectal anastomoses have higher leak rates. There are retrospective studies that have shown higher leak rates with both type of anastomosis when the two are compared.45 One possible reason for ileorectal leak is that the caliber of the ileum can be too small in some patients to fit some anvils, but otherwise there is no data to support one anastomosis over the other. Role of proximal diversion

There are well-defined indications for proximal diversion to abate the consequences of an anastomotic leak in highrisk patients, such as low anastomoses in male patients.6 In instances where these indications are lacking, there appears to be a paucity of statistically significant data to support the concept that proximal diversion abates the incidence of leaks compared with those patients not diverted.46 One study that did find a difference randomized 234 patients to proximal diverting stoma or not with low anterior resections.47 They found a symptomatic leak rate of 19% (45 of 234 patients), but it was 10.3% for patients with a proximal stoma compared with 28% in patients without diversion (p ⬍ 0.001). These findings were refuted by two randomized trials that found no difference in leak rates when proximal diversion was routinely used.48,49 It should be recognized that proximal diversion does not prevent leaks, but merely lessens the dreaded sequelae should a clinical leak occur, even in higher-risk patients.7,18,50,51 One reason why there is concern in performing unnecessary stomas is that stomas are not without inherent complications of their own, such as necrosis, retraction, prolapse, and disuse stricture of a distal anastomosis.1,51,52

Difference in location of leaks

Multiple studies have identified distance from the anal verge to be a substantial risk factor contributing to anastomotic breakdown, but few are prospective studies. In a prospectively obtained database of 1,834 patients with colorectal resections, a substantially higher leak rate in patients with rectal or rectosigmoid resections (6.7%) compared with colonic anastomoses (2.6%) was reported.19 There are several retrospective studies that have found similar results. One examination of 219 low anterior resections found an 11% major leak rate with peritonitis.44 All major leaks, and 13 of 14 radiologic leaks, occurred in anastomoses that were ⬍6 cm from the anal verge. These results were confirmed in other retrospective studies that showed leak rates of 7% above the peritoneal reflection compared with 18% ⬍5 cm from the anal verge.5 Lipska and colleagues7 found a higher rate of leak with cancers that were ⬍12 cm from the anal verge in their retrospective study. On multi-

Intraoperative testing of the integrity of the anastomosis

There are several methods to test the integrity of an anastomosis at the time of operation. Often, after completion of the anastomosis, the pelvis is filled with saline and the proximal bowel is manually occluded. Air is then insufflated through the rectum, and if air bubbles are noted, an incomplete anastomosis is present. If no air bubbles are present, it has been the authors’ preference to distend the rectum with Betadine-tinged saline and look for extravasation. The rationale behind this maneuver is that we have seen several instances where the “air test” has been negative, but the “Betadine test” has been positive. In either case, repair of the anastomotic defect should be attempted and the anastomosis then retested. If the repair is complete there is no need, in our opinion, to divert the patient. If, on the other hand, air bubbles or Betadine leakage is still

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noted, proximal diversion is mandatory. There is one prospective randomized study that examined whether intraoperative anastomotic testing with air reduced the incidence of leak.52 Twenty-five percent of patients in the air-leak group had a positive intraoperative test and an anastomosis that was repaired. Postoperative leaks occurred in 4% of the test group compared with 14% of the no-test group (p ⬍ 0.043). Timing of leaks

Anastomotic leaks are detected anywhere from 3 to 45 days postoperatively.44,45 There appears to be two peaks when the diagnosis is made. When leaks occur clinically, the median postoperative day of diagnosis is 7 days; when made radiographically the median postoperative day of leakage is 16. In addition, and quite concerning, is that 42% of the patients were diagnosed after they had already been discharged from the hospital and required readmission for abdominal symptoms. Equally concerning is that in an additional 12%, diagnosis was made ⬎30 days after their operation. This study raises a concern and a recommendation. The concern is that with quicker discharges from the hospital, usually within 5 days, leaks will occur outside of a hospital setting. Patients must be educated as to what signs to look for and that any notable change should mandate a call to their surgeon. In addition, close followup must be carried out during the first 40 days after operation, as late leaks can occur anywhere during this time frame.9,47 This is relevant to overall outcomes, because there is increased morbidity when there is a delay in treating anastomotic leaks. Management of anastomotic leaks in an era of expanding technology

Patients with anastomotic leaks most often require volume resuscitation and should all be started on broad spectrum antibiotics. Once an anastomotic leak has been recognized, management should be individualized to accommodate patient’s needs. Available strategies include observation and bowel rest, percutaneous drainage, colonic stenting, and surgical revision, diversion, or drainage. With a small degree of contamination, right-sided colonic leaks can often be reanastomosed and drained. With more extensive contamination, resection with ileostomy and mucous fistula or creation of a Hartman’s pouch should be used. Management of left-colon leaks depends on the level of the anastomosis. Intraperitoneal leaks should be resected with the ends brought out as ostomies, if possible. Extremely low anastomotic leaks should be extensively drained with proximal complete diversion with either an ileostomy or colostomy.4,8 Newer approaches use endostents and transanal endoscopic vacuum devices.53,54 The latter device is placed

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through the lumen of the colon into the abscess cavity to decompress the cavity and help generate granulation tissue. This approach is hampered by the need for the sponge system to be changed every 48 to 72 hours and by the excessively long duration of treatment (mean of 34 days with 11 endoscopic sessions per patient). Leakage and cancer recurrence

There have been many studies that have examined the relationship of anastomotic leak with local cancer recurrence for colorectal resections. There is some evidence to support the theory that there are tumor cells present in the colonic lumen after resection that can implant and grow in the remaining colorectal segment.55,56 Docherty and colleagues38 showed a statistically significant increase in mortality in patients in their prospective, randomized trial comparing patients with a leak after large bowel resection to those with no leak. The cancer-specific mortality was 53% in the leak population compared with 31% in the no-leak population, and leak was a prognostic factor for recurrence and mortality. Other authors looked at 1,722 patients in their prospectively obtained database who underwent colorectal resections for cancer from 1971 to 1999.57 Their leak rate was 5.1% overall. Five-year survival was 44% in patients with an anastomotic leak compared with 64% in patients without a leak. After regression analysis, anastomotic leakage had an independent negative association with overall survival and cancer-specific survival (hazard ratio ⫽ 1.8; 95% CI, 1.2⫺2.6). Similarly, McArdle and colleagues58 retrospectively studied 2,235 patients who had colorectal resections between 1991 and 1994. Excluding postoperative deaths, 5-year cancerspecific survival rate was significantly lower in patients with a leak (50%) compared with those without a leak (68%; p ⬍ 0.001). They demonstrated that anastomotic leak is independently associated with worse longterm outcomes. There are several explanations that can explain these findings. There might be a selection bias not recognized in the prospective trials, or intraluminal tumor cells that are normally inconsequential after a colon resection implant after a leak. A third option is these patients might have decreased immune function from morbidity associated with a leak. New methods for preventing anastomotic leaks

One area of current intense investigation is preventing anastomotic dehiscence. There have been several animal and human studies done with different types of buttressing material to strengthen anastomoses. Some devices such as the SBS tube (absorbable) and the Coloshield (permanent) are intraluminal tubes that are meant to aid in suturing and protecting an intracorporeal anastomosis. Currently, no studies have shown a clear benefit to these adjuncts and

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complications, such as erosion of the tube through the colon and obstruction were reported.59 After application in lung resections, there have been several investigations into using fibrin glue to seal off gastric anastomoses, but no large studies have been reported for colonic anastomoses.60 Van der Ham and colleagues61 found no change in collagen concentration or anastomotic strength when colon anastomoses were sealed with fibrin in rats. A third strategy to prevent anastomotic leaks from staple lines is to buttress the staple line with bovine pericardial strips. This has led to development of various types of nonabsorbable, semiabsorbable, and absorbable material to buttress staple lines.60 Although Yo and colleagues59 advocate absorbable staple-line reinforcement in their review of staple-line buttressing, there is little evidence to support its widespread use currently. In conclusion, sequelae of colon and rectal anastomotic leaks are substantial. Mortality rates range from 0% to 32%.14,18 Proved patient-specific risk factors include alcohol and tobacco use, patients with diverticular disease, ASA score ⬎3, steroid use, and weight loss and malnutrition. Intraoperative factors that can affect the leakage rate include the duration of the surgical procedure, adequate blood supply to prevent ischemia, and intraoperative testing of left-sided anastomoses. Laparoscopic colon resections have been proved to have a similar leak rate when compared with open colon resections. Similarly, stapled and handsewn anastomoses also have equal complication rates. Proximal diversion of high-risk anastomoses does not alter the anastomotic leak rate, but it does decrease the sequelae of a leak. There is not enough definitive data to prove whether wrapping the omentum around an anastomosis, leaving drains around low rectal anastomoses, or using preoperative bowel preparations have a substantial effect on leak rates. The two proved risks associated with low rectal anastomoses include male patients and obesity. One important observation about anastomotic leaks when the literature is viewed in total is that it is common for leaks to occur in a bimodal distribution, with the second group of patients leaking after they have been discharged from the hospital. It is vital that the operating surgeon continues to investigate for a leak, when clinically relevant, even 1 month after operation. Diagnosing leaks relies on the clinical picture and radiographic findings. Treatment of a colonic anastomotic leak must then be individualized to the location and sequelae of the leak. Treatments range from nonoperative percutaneous drainage to surgical revision or resection of the anastomosis. Although there is ongoing research into new technological methods to prevent anastomotic leaks, no currently available methods have been widely accepted. The basic principles of ad-

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equate blood supply, no tension, and inverted mucosa still apply.

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