Anastomosis Colon

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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 com-plications of operations of the large intestine. Breakdownof an anastomosis results in increased morbidity and mor-tality and adversely affects length of stay, cost, and cancerrecurrence. Reported rates of anastomotic dehiscence varybetween 1% and 30%, although experienced colorectalsurgeons often quote 3% to 6% as an acceptable overallleakage rate(Table 1).1 Despite a paucity of prospectiverandomized data, intuitively it would appear that emergentoperations are at greater risk for anastomotic breakdownthan those procedures performed electively. Confounding

the issue is that there are differing opinions as to what riskfactors have been proved to predict anastomotic dehis-cence. The aim of this review is to examine the currentlyidentified risk factors contributing to intestinal anasto-motic breakdown and delineate methods of diagnosis andtreatment of this universally dreaded complication.

Definition of anastomotic leak

There is no uniformly accepted definition of an anasto-motic leak in the literature (Table 2). In a review of 97studies 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 pro-posed the definition as a leak of luminal contents from asurgical join between two hollow viscera.3 These contentscan exit through wounds or drains, or collect at the anas-tomotic site. Some early studies reporting on anastomoticbreakdowns are difficult to interpret because they includedextravasation of contrast material on routine postoperativecontrast enemas as anastomotic leaks. The majority of con-temporary studies do not include radiologic leaks on rou-tine imaging because these are not clinically significant.Although the UK study did set a definition for an anasto-

motic leak, there have been few references to this studysince then. The majority of reports investigating the causeand rate of leaks use variations of clinical signs like perito-nitis; feculent wound; or drain discharge, abscess, or feverand radiologic parameters to define an anastomotic leak.4,5

The most detailed definition encompasses a combinationof clinical indicators like pain; peritonitis; and biochemicalmarkers, such as fever; tachycardia; radiologic studiesshowing fluid collections or gas-containing collections; andintraoperative findings.6,7

Risk factors

There are many risk factors that have been attributed toanastomotic leakage (Table 3). In addition, there are stud-ies that have provided evidence supporting the relevance orlack of relevance of most risk factors, adding to the confu-sion of what are proved risk factors. Risk factors can becategorized as patient-specific, intraoperative, and specificfor low rectal anastomosis. Patient-specific risk factors in-clude malnutrition, steroids, tobacco use, leukocytosis, car-diovascular disease, alcohol use, American Society of Anes-thesiologists (ASA) score, and diverticulitis. Intraoperativerisk factors include low anastomoses, suboptimal anas-tomotic blood supply, operative time 2 hours, bowelobstruction, perioperative blood transfusion, and intra-operative septic conditions not conducive to primaryanastomosis. Risk factors for low rectal anastomosis in-clude gender and obesity.6,8-12 Additional risk factors havebeen relegated to low colonic anastomoses, thereby stress-ing the importance of stratifying the location of anastomo-ses when interpreting the literature.

Preoperative patient factors

Obesity has been cited as a risk factor, especially for left-sided colorectal anastomotic leaks. One retrospective re-view of anterior resections found that when anastomoticleaks occur 5 cm from the anal verge, there was a 33%leak rate in obese patients (defined as 20% heavier thanideal body weight) compared with a 15% leak rate in nono-bese patients (p 0.03).5 Another retrospective examina-tion of 208 left-sided anastomoses similarly found on mul-tivariate analysis that when emergency resections wererequired, of ASA class, age, gender, comorbidities, labora-tory values, and transfusion requirements, only obesity wasa major risk factor for leak.13 Choi and colleagues14 andVignali and colleagues,15 on the other hand, in prospectivestudies encompassing nearly 3,500 patients who under-went colorectal resections for malignancy, have not foundobesity to be a factor that increased risk of anastomoticleak.14,15 The discrepancy between studies might be related

Disclosure Information: Nothing to Disclose.

ReceivedJuly23, 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.

269 2009 by the American College of Surgeons ISSN 1072-7515/09/$36.00

Published by Elsevier Inc. doi:10.1016/j.jamcollsurg.2008.10.015


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to differences in including low rectal anastomoses. It wouldseem logical that obesity increases the risks of anastomoticbreakdown because of difficulties in properly cleaning offthe proximal end, and tension and ischemia caused by ashort, thick mesentery.

Other factors, such as tobacco and alcohol use, have alsobeen found to be risk factors for anastomotic leaks. Oneretrospective study examined 333 patients from 1993 to1996 and found smoking was appreciably associated withanastomotic leak on multivariate analysis. The relationshipbetween the two might be secondary to ischemia caused by

smoking-related microvascular disease. Additional studieshave also found excessive alcohol use (35 drinks perweek) to be an important risk factor for anastomotic leak.11

In this study, large quantities of alcohol consumptionmight be a surrogate for poor nutritional status. Prospec-tive analysis where the indication for operation wastracked, revealed that diverticular disease was a significantindependent predictor of anastomotic leakage (p

0.0001) with a 5.9% leak rate with resections for divertic-ular disease compared with a 2.4% overall leak rate.16 Thealmost twofold increase in leak rate seen in patients withdiverticular disease might be related to performing a less-than-adequate resection. If the splenic flexure is not mobi-lized, and the bowel is not resected from the descendingcolon to the peritoneal reflection, the subsequent anasto-mosis can be performed in an area of muscular hypertro-phy. Placement of sutures either by hand or through a

mechanical device through an area of muscular hypertro-phy can set the stage for an anastomotic breakdown.

ASA status

The ASA physical status examination is used by anesthesi-ologists to classify preoperative physical condition of sur-gical patients. The scale ranges from 1, signifying a normal,healthy patient, to 5, representing a patient not likely tosurvive 24 hours. In a multivariate analysis of leaks in 1,417colon resections above the peritoneal reflection, ASA gradeof 3 to 5 and an emergent indication for operation werefound to be the only two statistically significant (p

0.0001) risk factors for clinical anastomotic leak.14 Thisfinding was bolstered in a case-control study that foundASA score 3 was a substantial risk factor, specifically inleft-sided colon anastomotic leaks.10 Comorbid conditionsas represented by an ASA score 3, are one method toindicate patients at higher risk for colonic anastomoticleaks. Comorbid conditions, such as diabetes mellitus, hy-pertension, and cardiac disease all represent conditions thataffect ASA status and can cause impaired circulation at themicrocirculation required for a healthy anastomosis.

Steroid use

Although intuitively it is assumed that impaired healingwith steroid use would affect anastomotic leak rates, it isdifficult to find an absolute correlation.17 Often, the num-ber of patients who were on steroids in the studied popu-lations was not great enough to show a significant statisticaldifference in leak rates. For example, one retrospectiveanalysis only had adequate data about 2 of 10 patientstreated with steroids in the study, and another retrospectivestudy found a statistically significant correlation betweensteroid use and colorectal anastomotic leaks on univariate

Table 1. Anastomotic Leak Rates

First author No. of patients Major leaks (%)


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analysis only.7,9 In contrast, a prospective study evaluating391 consecutive elective colon resections found that long-term preoperative steroid use mandating perioperative ste-roid coverage was an important risk factor for anastomoticleak when subjected to multivariate analysis.18A leak rate of11.8% in was noted in patients with steroid use comparedwith 2.4% in those without steroids (odds ratio 8.7;95% CI, 1.245.1; p 0.015). Given this prospectivestudy is the strongest clinical study available for interpreta-tion, steroid use should be considered a risk factor for anas-tomotic leak.

Radiation

Neoadjuvant radiation therapy is the standard of care forrectal tumors that are classified as either T3 or N1 by en-dorectal ultrasonography. There are only retrospectivestudies that have examined the relationship of preoperativeradiation and anastomotic leaks. In a review article, Cham-bers and Mortensen1 found inconclusive data aboutwhether preoperative irradiation leads to higher leak rates.Several retrospective studies found no differences in leakrates between patients with low rectal anastomoses whoreceived radiotherapy and those who did not, regardless ofwhether or not they also had proximal diversion.5,15 Otherreports, such as that by Alves and colleagues,9 showed thatprevious abdominal or pelvic irradiation was a risk for leakon univariate analysis for anastomotic leak, when they ex-amined 707 patients who underwent colorectal resection.It is unclear from the existing data whether radiation is arisk for anastomotic leak. It is our belief that until substan-tial data are forthcoming to the contrary, the better part ofvalor would be to divert low rectal anastomosis in patientstreated with neoadjuvant chemoradiation therapy.

Gender

Gender is often identified as a risk for colorectal anasto-motic leak. In a prospective study of 196 patients withrectal cancer resections, multivariate analysis showed malepatients with anastomoses5 cm from the anal verge hada higher rate of anastomotic leak than did women.6 Simi-larly, a retrospective analysis of 541 consecutive operationswith colonic and rectal anastomoses found an overall leakrate 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 subgroupanalyses of patients with cancer, patients with cancer 12cm from the anal verge, patients requiring an anterior re-section, and patients with anastomoses in the pelvis. Somestudies have shown higher leak rates in male patientsthroughout the colon, irrespective of distance from the analverge. In a prospectively evaluated cohort of male patients,Branagan and Finnis19 noted that there was a substantially

higher rate of leakage in male (5.6%) compared with fe-male patients (2.4%) throughout the colon and rectum.There is, at present, no general consensus about gender as arisk factor for anastomoses above the rectum. Most likely,gender only influences low anastomoses, where the nar-rower male pelvis makes dissection and anastomoses morechallenging. Confirmatory data stems from studies byBiondo and colleagues13 and Choi and colleagues,14 whoboth found similar rates of anastomotic leaks irrespective ofgender in anastomoses performed above the peritonealreflection.

Nutrition

Nutritional state is an important factor in contributing toanastomotic leaks. Several studies have shown a correlationbetween low albumin levels and an increased incidence ofanastomotic leaks.10,12 It becomes essential to assess nutri-tional levels preoperatively and embark on methods to re-verse any catabolic state when present. Early postoperativefeeding is usually tolerated well after most colorectal resec-tions, and there is no increase in leak rates when earlyfeeding is instituted. Currently, there are no establishedrecommendations as to what level of preoperative malnu-trition requires intervention. One case-control study foundthat malnutrition (serum albumin35g/L) was a substan-tial risk factor for anastomotic leak after multivariate anal-ysis, with a 13.2 odds ratio (95% CI, 2.8361.85) in theleak and no leak group.10 In addition, this study foundweight loss of5 kg was a risk factor for anastomotic leak,with a 27.6 odds ratio (95% CI, 2.83128.74). Theirconclusion was that malnutrition, as described by weightloss and low albumin levels, was the strongest risk factor foranastomotic leak. Whether it is hypoalbuminemia or lowprealbumin levels, evidence of protein deficiency places apatient at higher risk for anastomotic leaks. Preoperativemaximization of nutrition is an important risk-reductionmeasure, but multiple studies have shown that for the ma-jority of patients, unless severely malnourished, there is nobenefit to preoperative parenteral nutrition.20

Bevacizumab (antivascular endothelial growth

factor monoclonal antibodies)

A new identified risk factor for anastomotic leak is bevaci-zumab, a monoclonal antibody targeting the vascular en-dothelial growth factor receptor. This drug has been shownin phase III trials, in combination with several other stan-dard chemotherapy regimens, to increase overall survival inpatients with colon cancer. The first studies examining be-vacizumab reported several patients with bowel perfora-tions.21,22The mechanism of this perforation is proposed tobe arterial microthromboembolic disease leading to bowelischemia. The same mechanism can cause an anastomotic

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leak, as can inhibition of angiogenesis in the microvascularbed of new anastomoses.There is one report of twopatientswith anastomotic leaks up to 2 years after operation andtreatment with both bevacizumab and radiation, but it isdifficult to determine the exact cause of the leaks.23 There islittle evidence as to the appropriate interval between thelast dose of bevacizumab and elective operation. Becausethe half-life of the drug is 20 days, and wound-healingcomplications have been documented up to 56 days aftertreatment, it is advisable to delay operation for three half-lives, or 60 days, after the last treatment.24

Intraoperative factors

There is a category of patients without any preoperativerisk factors for anastomotic leak in which this complicationdevelops as a result of intraoperative events. For example,one retrospective review of 1,014 patients noted that inpatients where an anastomotic leak occurred after rectalresection, there was a significantly longer mean and medianduration of operation (220 minutes versus 186 minutes;p 0.05).15 A similar correlation between anastomoticleak rate and duration of operations that lasted 4 hourswas found in a prospective examination of 391 colorectalresections.18 These results suggest that a higher leak rate isassociated with more difficult resections and anastomoses.Another variable that has been studied is whether or notwrapping an anastomosis with omentum confers a protec-tive effect in mitigating anastomotic leaks. This questionwas addressed in a prospective, randomized trial of 705patients who were assigned to anastomotic omental wrapor not. They demonstrated no difference in leak rates(4.9%) between the two groups.25Additionally, they raisedconcerns about the potential for devascularized omentalpedicles becoming infected, leading to abscess formationand potentially future large bowel obstructions. Because ofthis data, their conclusion was that omental wraps aroundcolonic anastomoses were not justified. In unreported data,Pachter and Hofstetter, who routinely wrap their anasto-mosis with omentum, have not experienced either omentalinfarction or large bowel obstruction in 1,000 colonicanastomosis (unpublished data).

Anastomotic ischemia

Tissue ischemia at the site of the anastomosis is frequentlycited and implicated as a cause for anastomotic breakdown.To avoid ischemic complications, there have been severalattempts to quantify colonic perfusion intraoperatively.One group used laser Doppler scans before and after mo-bilizing, dividing, and anastomosing the colon to show a32% reduction in colonic tissue perfusion 2 cm proximalto the anastomotic site and a 51% decrease at the anasto-motic site.26Another study looked at 55 patients and found

that there was a greater overall reduction in blood flow atthe rectal stump when compared with the proximal colonlimb.27 When a leak did develop in patients, there was a16% decrease in blood flow, compared with 6% in patientswithout a leak (p 0.001). Similarly, there was a meanproximal blood flow reduction of 5% in patients without aleak compared with 12.9% in patients with a leak (p 0.01). A small change in blood supply to the proximalcolon can increase the risk of leak. One manner with whichanastomotic blood supply can be increased is by varying thelocation of mesenteric and vascular ligation. Hall and col-leagues28 measured tissue oxygen tension before and afterlow or high division of the inferior mesenteric artery in 62elective colorectal resections. He found that after mobiliza-tion and vascular ligation, oxygen tension was equal orimproved in the transverse and descending colon whenthey were used for the colorectal anastomoses, but thatoxygen tension was diminished in the sigmoid colon. Heconcluded that location of the vascular ligation had noimpact on colonic perfusion, but location of the resectionwas vital to tissue oxygenation. His hypothesis was that themarginal artery did not provide adequate sigmoid bloodflow.

In addition to increasing blood supply by using the well-perfused left colon for the proximal limb of the anastomo-sis, consideration has also been given to increasing anasto-motic blood flow by performing side to end anastomoses.1

Theoretically, the blood flow in the proximal pouch of aside to end anastomosis might be more consistent than thatof an end colonic anastomosis. Hallbook and colleagues29

performed laser Doppler flow measurements in colorectalanastomoses and found substantially decreased anasto-motic blood flow after dissection in end to end anastomo-ses when compared with side to end anastomoses. Thismethod can be considered in difficult cases, where ade-quate blood supply to the proximal limb might be indoubt. A simple rule of thumb is to ligate the blood supplyto the colon as proximal to the aorta as possible, assuringadequate collateral flow. Proximal lumen of the bowel mustalways be inspected. If the mucosa is pink then the bloodsupply is adequate. Relying on merely looking at the serosalsurface is fraught with pitfalls, as the serosa might be viablebut the mucosa is not.

Use of drains

The issue of routine drainage of colonic anastomoses hasbeen a topic of controversy for years. Those championingthe use of these drains believe they play a role in evacuatingperianastomotic fluid collections, lessening the incidenceof abscess formation, at the same time serving as an earlywarning marker for anastomotic dehiscence. Although the-oretically, an undrained fluid collection that becomes in-

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fected can drain through the anastomosis, few cases likethese have been documented. Conflicting reports in theliterature as to the pros and cons of routine drainage of lowpelvic anastomoses exist, but there is no data to supportroutine use of drains when IP anastomoses are performed.Merad and colleagues performed a controlled, multicenterstudy encompassing 317 patients that proved intraabdomi-nal drains were not beneficial.30 They randomized patientsto either abdominal drainage or no drainage and were un-able to find any difference in either group with regard topelvic abscesses (9% for each group). In this adequatelypowered study, she concluded that there was no justifiableindication to place a drain in colon resections above thesacral promontory. To the contrary, they believed that itwas potentially harmful because one patient had a hema-toma related to the drain and another required surgicalremoval of the drain.

A meta-analysis of complications from colorectal resec-tions examined four randomized, controlled trials from1987 to 1995 that compared the routine use of drains.31

Although the trials were suboptimal in quality, when theirresults were pooled they found an odds ratio for clinicalleak of 1.5, favoring the group without a drain. Yeh andcolleagues32 came to a similar conclusion in a prospectivestudy of 978 patients with anterior resections with an over-all leak rate of 2.8%, but found a higher rate of leakagewhen drains were used (odds ratio 9.13; 95% CI,1.1671.76). He also concluded that there was no indica-tion to drain pelvic anastomoses. Conclusions based onnonrandomized studies, such as this in which the surgeonis given preference to place drains in higher-risk anastomo-ses is inherently biased. Studies such as these are helpful inhighlighting that drains do not adequately identify a pa-tient population with earlyleaks.Yeh noted that only 5% ofpatients with pelvic leaks had pus or enteric contents in thepreexisting drains. The general consensus is that IP anasto-moses do not benefit from drainage, although low rectalanastomoses can, allowing for surgeon preference to deter-mine this decision.

Mechanical bowel preparation

The fecal load of the colon at the time of anastomosis hasbeen thought to influence anastomotic integrity. Tradition-ally, on-table lavage was performed during emergency op-erations on patients with perforations or obstructions. Oneprospective study determined that bowel decompressionand primary anastomosis was safe without intraoperativecolonic lavage, so this practice has been abandoned.33 Forelective operations, the goal of mechanical bowel prepara-tion is to lower the bacterial load in the colon. One animalmodel demonstrated higher leak rates in rats when solidfeces were present in their colons.34 When canine colonic

anastomoses were tested in a similar manner, there was nodifference in the leak rate between prepared and unpreppedcolons.35 This suggests that intraluminal stool might havetrophic effects on epithelium and the anastomosis. Therehave been several human studies that have studied the ques-tion of the use of colonic bowel preparations. One of thefirst randomized trials to examine this question included267 patients who were randomly selected to mechanicalbowel prep versus no bowel prep before colonic resection.36

Results revealed a 2% leak rate in the unprepped patients ascompared with a 4% leak rate in the prepared patients, butthis difference was not significant (p 0.28). Several yearslater, another prospective study enrolled 329 patients andrandomized patients to no bowel prep for elective colonoperation.37 Similarly, there was no significant difference inanastomotic leak rates between the groups. Although theauthors concluded that mechanical bowel preparation wasindicated in low rectal resections, given there were onlythree leaks in total in the study, it is difficult to make astrong conclusion from their study. A third case-controlledstudy found that mechanical bowel prep did not influencethe anastomotic leak rate, and they surmised that with ananastomotic leak there was feculent spillage regardless ofthe status of the bowel prep.10 The question of whether thepresence of solid stool with bacterial collagenases contrib-utes to suture-line breakdown is unanswered in the litera-ture. Given the wide array of results in the literature thathas examined the use of a bowel prep, we recommendmechanical preparation to minimize contamination.

Anastomotic technique: stapled versus

handsewn anastomosis

In order for an anastomosis to heal properly, three criticalfactors must be present: no tension, adequate blood supply,and an inverted anastomosis. In an era that has seen anexplosion in technological devices that aid in bowel resec-tion and creation of mechanical anastomosis, the questionarises whether leak rates are comparable with the tradi-tional handsewn anastomosis. There is strong evidence thatrates are equal from a multicenter, randomized, prospectivetrial comparing handsewn to stapled anastomosis in elec-tive and emergent colorectal operations.38 Of 652 random-ized patients studied, there was no significant difference (p 0.93) in the clinical leak rate (4.4%) between suturedand stapled anastomoses. There was a difference in radio-logic leak rates. Fourteen percent of patients with a suturedcolorectal anastomosis had a radiologic leak, as comparedwith only 5% of patients with stapled anastomoses. Theimportance of subclinical leaks such as these has yet to bedefined. Similar results were found in a prospective studythat enrolled 1,417 patients with colon resections abovethe peritoneal reflection and found that there was no dif-



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ference in leak rates between stapled and handsewn anas-tomoses.14 A Cochrane analysis was performed to answerthe question of whether leak rates were lower with stapledlow (6 cm from the anal verge) anastomoses. The con-clusion was that there was not a statistically significantdifference even with low anastomoses.39

Laparoscopic versus open

When laparoscopic operation was extended to colorectalresections, two major questions were raised: Will this ap-proach result in an adequate cancer operation; and whateffect, if any, will this method have on the anastomotic leakrate? Fifty-two articles in the literature comparing laparo-scopic and open colorectal resections were reviewed byChapman. Based on the cumulative number of patientsstudied, there were no differences in the anastomotic leakrate between the two groups.40 Subsequent trials about thenumber of lymph nodes sampled, extent of resection, andsurvival, likewise could not attribute any negative factors tothe laparoscopic approach.40,41 Additionally, the ClinicalOutcomes of Surgical Therapy Study Group found no dif-ference in leak rates when they randomized 872 patients at48 institutions to open and laparoscopic colon resectionsfor cancer.42 The safety of laparoscopic colorectal resectionswas 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 nonopera-tively, although 32% required reoperation. The highestleak rate (12.7%), as expected, was noted in those patientsundergoing anterior resections, compared with a 7% ratewith left hemicolectomies. The authors also noted thatthere was a higher leakage rate when the anastomosis was10 cm from the anal verge.

Difference in location of leaks

Multiple studies have identified distance from the analverge to be a substantial risk factor contributing to anasto-motic breakdown, but few are prospective studies. In aprospectively obtained database of 1,834 patients withcolorectal resections, a substantially higher leak rate in pa-tients with rectal or rectosigmoid resections (6.7%) com-pared with colonic anastomoses (2.6%) was reported.19

There are several retrospective studies that have found sim-ilar results. One examination of 219 low anterior resectionsfound an 11% major leak rate with peritonitis.44All majorleaks, and 13 of 14 radiologic leaks, occurred in anastomo-ses that were6 cm from the anal verge.These results wereconfirmed in other retrospective studies that showed leakrates of 7% above the peritoneal reflection compared with18% 5 cm from the anal verge.5 Lipska and colleagues7

found a higher rate of leak with cancers that were 12 cmfrom the anal verge in their retrospective study. On multi-

variate analysis, there was a 4.56 odds ratio (95% CI,1.6412.71) of anastomotic leak for these low resections.There are also studies that have examined whether ileorec-tal or colorectal anastomoses have higher leak rates. Thereare retrospective studies that have shown higher leak rateswith both type of anastomosis when the two are com-pared.45 One possible reason for ileorectal leak is that thecaliber of the ileum can be too small in some patients to fitsome anvils, but otherwise there is no data to support oneanastomosis over the other.

Role of proximal diversion

There are well-defined indications for proximal diversionto abate the consequences of an anastomotic leak in high-risk patients, such as low anastomoses in male patients.6 Ininstances where these indications are lacking, there appearsto be a paucity of statistically significant data to support theconcept that proximal diversion abates the incidence ofleaks compared with those patients not diverted.46 Onestudy that did find a difference randomized 234 patients toproximal diverting stoma or not with low anterior resec-tions.47 They found a symptomatic leak rate of 19% (45 of234 patients), but it was 10.3% for patients with a proxi-mal stoma compared with 28% in patients without diver-sion (p 0.001). These findings were refuted by two ran-domized trials that found no difference in leak rates whenproximal diversion was routinely used.48,49 It should berecognized that proximal diversion does not prevent leaks,but merely lessens the dreaded sequelae should a clinicalleak occur, even in higher-risk patients.7,18,50,51 One reasonwhy there is concern in performing unnecessary stomas isthat stomas are not without inherent complications of theirown, such as necrosis, retraction, prolapse, and disuse stric-ture of a distal anastomosis.1,51,52

Intraoperative testing of the integrity of

the anastomosis

There are several methods to test the integrity of an anas-tomosis at the time of operation. Often, after completionof the anastomosis, the pelvis is filled with saline and theproximal bowel is manually occluded. Air is then insuf-flated through the rectum, and if air bubbles are noted, anincomplete anastomosis is present. If no air bubbles arepresent, it has been the authors preference to distend therectum with Betadine-tinged saline and look for extravasa-tion. The rationale behind this maneuver is that we haveseen 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 andthe anastomosis then retested. If the repair is completethere is no need, in our opinion, to divert the patient. If, onthe other hand, air bubbles or Betadine leakage is still



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noted, proximal diversion is mandatory. There is one pro-spective randomized study that examined whether intraop-erative anastomotic testing with air reduced the incidenceof leak.52 Twenty-five percent of patients in the air-leakgroup had a positive intraoperative test and an anastomosisthat was repaired. Postoperative leaks occurred in 4% of thetest group compared with 14% of the no-test group (p 0.043).

Timing of leaks

Anastomotic leaks are detected anywhere from 3 to 45 dayspostoperatively.44,45 There appears to be two peaks whenthe diagnosis is made. When leaks occur clinically, the me-dian postoperative day of diagnosis is 7 days; when maderadiographically the median postoperative day of leakage is16. In addition, and quite concerning, is that 42% of thepatients were diagnosed after they had already been dis-charged from the hospital and required readmission forabdominal symptoms. Equally concerning is that in anadditional 12%, diagnosis was made30 days after theiroperation. This study raises a concern and a recommenda-tion. The concern is that with quicker discharges from thehospital, usually within 5 days, leaks will occur outside of ahospital setting. Patients must be educated as to what signsto look for and that any notable change should mandate acall to their surgeon. In addition, close followup must becarried out during the first 40 days after operation, as lateleaks can occur anywhere during this time frame.9,47 This isrelevant to overall outcomes, because there is increasedmorbidity when there is a delay in treating anastomoticleaks.

Management of anastomotic leaks in an era of

expanding technology

Patients with anastomotic leaks most often require volumeresuscitation and should all be started on broad spectrumantibiotics. Once an anastomotic leak has been recognized,management should be individualized to accommodate pa-tients needs. Available strategies include observation andbowel rest, percutaneous drainage, colonic stenting, andsurgical revision, diversion, or drainage. With a small de-gree of contamination, right-sided colonic leaks can oftenbe reanastomosed and drained. With more extensive con-tamination, resection with ileostomy and mucous fistula orcreation of a Hartmans pouch should be used. Manage-ment of left-colon leaks depends on the level of the anas-tomosis. Intraperitoneal leaks should be resected with theends brought out as ostomies, if possible. Extremely lowanastomotic leaks should be extensively drained with prox-imal complete diversion with either an ileostomy or colos-tomy.4,8 Newer approaches use endostents and transanalendoscopic vacuum devices.53,54 The latter device is placed

through the lumen of the colon into the abscess cavity todecompress the cavity and help generate granulation tissue.This approach is hampered by the need for the spongesystem to be changed every 48 to 72 hours and by theexcessively long duration of treatment (mean of 34 dayswith 11 endoscopic sessions per patient).

Leakage and cancer recurrence

There have been many studies that have examined the re-lationship of anastomotic leak with local cancer recurrencefor colorectal resections. There is some evidence to supportthe theory that there are tumor cells present in the coloniclumen after resection that can implant and grow in theremaining colorectal segment.55,56 Docherty and col-leagues38 showed a statistically significant increase in mor-tality in patients in their prospective, randomized trialcomparing patients with a leak after large bowel resectionto those with no leak. The cancer-specific mortality was53% in the leak population compared with 31% in theno-leak population, and leak was a prognostic factor forrecurrence and mortality. Other authors looked at 1,722patients in their prospectively obtained database who un-derwent colorectal resections for cancer from 1971 to1999.57 Their leak rate was 5.1% overall. Five-year survivalwas 44% in patients with an anastomotic leak comparedwith 64% in patients without a leak. After regression anal-ysis, anastomotic leakage had an independent negativeassociation with overall survival and cancer-specific sur-vival (hazard ratio 1.8; 95% CI, 1.22.6). Similarly,McArdle and colleagues58 retrospectively studied 2,235 pa-tients who had colorectal resections between 1991 and1994. Excluding postoperative deaths, 5-year cancer-specific survival rate was significantly lower in patients witha leak (50%) compared with those without a leak (68%;p 0.001). They demonstrated that anastomotic leak isindependently associated with worse longterm outcomes.There are several explanations that can explain these find-ings. There might be a selection bias not recognized in theprospective trials, or intraluminal tumor cells that are nor-mally inconsequential after a colon resection implant aftera leak. A third option is these patients might have decreasedimmune function from morbidity associated with a leak.

New methods for preventing anastomotic leaks

One area of current intense investigation is preventinganastomotic dehiscence. There have been several animaland human studies done with different types of buttressingmaterial to strengthen anastomoses. Some devices such asthe SBS tube (absorbable) and the Coloshield (permanent)are intraluminal tubes that are meant to aid in suturing andprotecting an intracorporeal anastomosis. Currently, nostudies have shown a clear benefit to these adjuncts and



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complications, such as erosion of the tube through thecolon and obstruction were reported.59After application inlung resections, there have been several investigations intousing fibrin glue to seal off gastric anastomoses, but nolarge studies have been reported for colonic anastomoses.60

Van der Ham and colleagues

61

found no change in collagenconcentration or anastomotic strength when colon anasto-moses were sealed with fibrin in rats. A third strategy toprevent anastomotic leaks from staple lines is to buttressthe staple line with bovine pericardial strips. This has led todevelopment of various types of nonabsorbable, semi-absorbable, and absorbable material to buttress staplelines.60 Although Yo and colleagues59 advocate absorbablestaple-line reinforcement in their review of staple-line but-tressing, there is little evidence to support its widespreaduse currently.

In conclusion, sequelae of colon and rectal anastomotic

leaks are substantial. Mortality rates range from 0% to32%.14,18 Proved patient-specific risk factors include alco-hol and tobacco use, patients with diverticular disease, ASAscore 3, steroid use, and weight loss and malnutrition.Intraoperative factors that can affect the leakage rate in-clude the duration of the surgical procedure, adequateblood supply to prevent ischemia, and intraoperative test-ing of left-sided anastomoses. Laparoscopic colon resec-tions have been proved to have a similar leak rate whencompared with open colon resections. Similarly, stapledand handsewn anastomoses also have equal complicationrates. Proximal diversion of high-risk anastomoses does not

alter the anastomotic leak rate, but it does decrease thesequelae of a leak. There is not enough definitive data toprove whether wrapping the omentum around an anasto-mosis, leaving drains around low rectal anastomoses, orusing preoperative bowel preparations have a substantialeffect on leak rates. The two proved risks associated withlow rectal anastomoses include male patients and obesity.

One important observation about anastomotic leakswhen the literature is viewed in total is that it is commonfor leaks to occur in a bimodal distribution, with the sec-ond group of patients leaking after they have been dis-charged from the hospital. It is vital that the operating

surgeon continues to investigate for a leak, when clinicallyrelevant, even 1 month after operation. Diagnosing leaksrelies on the clinical picture and radiographic findings.Treatment of a colonic anastomotic leak must then be in-dividualized to the location and sequelae of the leak. Treat-ments range from nonoperative percutaneous drainage tosurgical revision or resection of the anastomosis. Althoughthere is ongoing research into new technological methodsto prevent anastomotic leaks, no currently available meth-ods have been widely accepted. The basic principles of ad-

equate blood supply, no tension, and inverted mucosa stillapply.

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