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Postoperative Enterocutaneous Fistula: Whento Reoperate and How to SucceedKathryn L. Galie, M.D.1 and Charles B. Whitlow, M.D.2

ABSTRACT

An enterocutaneous fistula (ECF) is a potentially catastrophic postoperativecomplication. Although the morbidity and mortality associated with ECF have decreasedover the past 50 years with modern medical and surgical care, the overall mortality is stillsurprisingly high, up to 39% in recent literature. It seems prudent, then, for every surgeon

to have a thorough grasp of optimal treatment strategies for ECF to minimize theirpatients mortality. Ultimately, the algorithm must begin with prevention. Once an ECF isdiagnosed, the first step is to resuscitate and treat sepsis. The second is to control fistulaoutput. The third step is to optimize the patient medically and nutritionally. The last step isdefinitive restoration of gastrointestinal continuity when necessary. Special mention isgiven in this article to exceptionally refractory fistulas such as those arising in the presenceof inflammatory bowel disease and irradiated bowel. This plan gives a framework for thedifficult task of successfully treating the postoperative ECF with a multidisciplinaryapproach.

KEYWORDS: Enterocutaneous fistula, nutritional support, sepsis, radiation enteritis

Objectives: Upon completion of this article, the reader should be able to summarize the management of postoperative enterocuta-

neous fistulas.

The development of an enterocutaneous fistula(ECF) is a potentially catastrophic postoperative com-plication. Virtually any intra-abdominal procedure canresult in an ECF, with procedures that intentionally orunintentionally damage the bowel wall carrying thegreatest risk.1 Most surgeons have seen previouslyhealthy patients undergoing routine, low-risk operative

procedures have their lives decimated by a postoperativeECF. Although the morbidity and mortality associatedwith ECF have decreased over the past 50 years with theadvent of novel antibiotics, improvements in resuscita-tion, intensive care unit care, nutritional support, woundcare, and new diagnostic and treatment modalities, the

overall mortality is still surprisingly high. Mortality ratesin the recent literature vary from 6.5 to 39%.26

It seems prudent, then, for every surgeon to have athorough grasp of optimal treatment strategies for ECFto minimize their patients mortality. Ultimately, thealgorithm must begin with prevention. Strategies toprevent the formation of ECF are discussed in the

following. Once an ECF is diagnosed, the first step isto resuscitate and treat sepsis. The second is to controlfistula output. The third step is to optimize the patientmedically and nutritionally. The last step, when neces-sary, is definitive restoration of gastrointestinal continu-ity, after extensive preoperative planning.1

1West County Surgical Specialists, Inc., St. Louis, Missouri; 2Depart-ment of Colon and Rectal Surgery, Ochsner Clinic Foundation, NewOrleans, Louisiana.

Address for correspondence and reprint requests: Kathryn L.Galie, M.D., West County Surgical Specialists, Inc., 621 SouthNew Ballas Rd., Ste. 7011B, St. Louis, MO 63141. E-mail: klga-

[email protected] Surgery; Guest Editor, Michael J. Stamos, M.D.Clin Colon Rectal Surg 2006;19:237246. Copyright# 2006 by

Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,NY 10001, USA. Tel: +1(212) 584-4662.DOI 10.1055/s-2006-956446. ISSN 1531-0043.

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DEFINITION

A fistula is defined as an abnormal connection betweentwo epithelealized surfaces. An ECF is defined as anabnormal connection between the gastrointestinal (GI)tract and the skin. Under the strictest definition, thisincludes fistulas from the esophagus, stomach, biliarytree, and pancreas as well as the small bowel, colon, and

anus. More commonly, the term ECF means an abnor-mal connection between the small bowel and skin only.It is this definition we use throughout this discussion.

CLASSIFICATION

Classification of fistulas is by no means standard. Thereare three usual classification systems, and most fistulasbenefit from being described using all of them at once.

The anatomic classification names the fistula using theorgans involved. By convention, the highest pressuresystem is named first, for example, a gastrocutaneous

fistula or an aortoenteric fistula. The anatomic classi-fication may also include a description of the fistulatract, such as complex versus simple, or long versusshort, and a description of the bowel defect, usuallymeasured as greater or less than 1 cm. The physiologicclassification uses output as the defining characteristic.A high-output ECF is defined as one that producesmore than 500 mL/day. A low-output fistula has been

variously defined as producing less than 500 mL/day1,4

by some authors or less than 200 mL/day by others.7 Inthe latter case, there is an additional designation of amoderate-output fistula that secretes 200 to 500 mL/day. The etiologic classification names fistulas by theirassociated disease processes, for example, a diverticularfistula or a neoplastic fistula. These classification sys-tems can be used to estimate the mortality and thechance of spontaneous closure of a fistula.7 Mortality isfive times greater for high-output fistulas than low-output fistulas.5 Table 1 gives examples of fistulacharacteristics that predict the likelihood of the fistulaclosing spontaneously.

ETIOLOGY, RISK FACTORS

Most (75 to 90%) ECFs are iatrogenic or, to be morespecific, postoperative or postprocedural.1,2,4,7 Approx-imately half of these are thought to be caused byanastomotic leak or dehiscence and about half by in-advertent enterotomy.7The other 10 to 25% of ECFs arespontaneous. These include fistulas from inflammatory

bowel disease, neoplasia, vascular insufficiency such asradiation enteritis or mesenteric ischemia, diverticulitis,appendicitis, pancreatitis, tuberculosis, or other intra-abdominal infections, abscesses, or inflammatory proc-esses such as malakoplakia.8 Penetrating traumaticfistulas are included in the spontaneous category.4

The first step in fighting fistulas is prevention.Understanding the risk factors that predispose a patientto postoperative fistulas can allow surgeons to take stepsto decrease a patients risk and can allow increased

vigilance and earlier diagnosis of fistulas if they do occur.Risk factors for postoperative fistulas include both tech-

nical and patient-related factors. The same technicalprinciples that guide surgeons in reducing postoperativeinfection and anastomotic leak rates are those thatreduce fistula formation. Preoperative skin preparationand perioperative systemic antibiotics reduce the inci-dence of infection and thus ECF. Intraoperatively, thesurgeon should focus on creating a tension-free anasto-mosis and ensuring that the bowel is well perfused.Stapling devices or sutures, or both, should be placedcarefully and accurately to create an intact anastomosis.Surgeons should insist on meticulous hemostasis andavoid leaving hematomas as possible niduses of infection.Performing careful, sharp dissection to avoid unintendedenterotomies and securely repairing any enterotomies orserosal injuries are paramount. Resection and anastomo-sis of defects greater than half of the small bowelcircumference rather than simple oversewing or wedgeresection result in lower fistula rates. Operative timegreater than 2 hours and intraoperative contamination ofthe field have been shown to increase anastomotic leakrates; thus, the surgeon should be efficient and take stepsto reduce contamination. Drains should not be leftimmediately adjacent to anastomoses; they can act asforeign bodies and erode into the anastomosis. If possi-ble, placing omentum between the abdominal wall and

the repair can reduce fistula formation, although wrap-ping the anastomosis in omentum (omentoplasty) hasnot been consistently shown to reduce anastomotic leaks.

The final step is a secure abdominal closure with caretaken to avoid inadvertent small bowel inclusion. Post-operatively, the main focus should be on maximizing thepatients oxygen-carrying capacity by ensuring adequate

volume status and avoiding hypotension, anemia, andhypothermia.1,7,911

When possible, patient-related risk factors forfistula formation should be optimized or treated preop-eratively. Patient factors such as malnutrition, low serum

Table 1 Effect of Fistula Characteristics on Likelihood ofSpontaneous Closure

More Likely to Close Less Likely to Close

Anatomic Jejunal Ileal

Tract 2 cm

Bowel defect 1 cm2

Epithelealized tract

Distal obstruction

Etiologic Appendicitis Neoplastic

Diverticulitis Inflammatory bowel

disease

Postoperative Radiation

Foreign body

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albumin, cardiovascular disease, advanced age, chronicobstructive pulmonary disease, corticosteroid use, priorabdominopelvic radiation therapy, alcohol abuse, smok-ing, two or more systemic diseases, high AmericanSociety of Anesthesiologists status, intra-abdominal ab-scess, peritonitis, and sepsis all increase the risk ofdeveloping a postoperative ECF.11 Medical optimiza-

tion of comorbidities such as diabetes, coronary vasculardisease, and inflammatory bowel disease should beattempted preoperatively. Nutritional status should beoptimized for elective procedures. Smoking and alcoholcessation programs can be initiated preoperatively.Assuring normovolemia, normotension, and adequatehemoglobin prior to the induction of anesthesia opti-mizes tissue perfusion. Intraoperative or postoperativetransfusion of more than two units of packed red bloodcells increases anastomotic leak rate and therefore fistularate.11Taking all of these risk factors into consideration,it is evident that patients undergoing an emergent

surgery have a higher rate of fistula formation; it maybe impossible to alter many of these factors in emergentsituations. Operations performed for adhesions, bowelobstruction, cancer, radiation enteritis, or inflammatorybowel disease have the highest rates of fistula formation.It is in these cases that the meticulous surgical techniquedescribed previously and proper postoperative care arethe mainstays of fistula prevention.

DIAGNOSIS

The definitive diagnosis of an ECF is usually made byvisualizing the drainage of succus from the operativeincision or from a drain site. This usually occurs betweenpostoperative days 5 and 10.1 Alternatively, the fistulamay arise with an overt wound infection; upon openingthe surgical wound, enteric contents are found. Com-monly, in the days preceding the fistulas external pre-sentation, the patient shows a persistent ileus,leukocytosis, abdominal pain, fever, or otherwise unex-plained signs of sepsis. Rarely, a patient may showsudden, severe septic shock with peritonitis, requiringurgent reoperation and the discovery of the fistula.

STABILIZATIONPrimary treatment is resuscitation. Attention shouldfirst be paid to restoring intravascular volume withcrystalloid solutions. Patients are in general hypovole-mic because of bowel losses from the fistula as well asintra-abdominal third spacing related to inflammationinduced by succus in the peritoneal cavity. Correctionof electrolytes with intravenous replacement should beimmediately initiated. Anemia should be corrected

with transfusion if needed. Septic patients are at riskfor capillary leak secondary to systemic inflammatoryresponse syndrome and progression to multiple organ

dysfunction syndrome; thus, these patients should beclosely monitored, with adequate venous access and acentral venous pressure monitor or pulmonary arterycatheter if necessary.

TREATMENT OF SEPSIS

Untreated sepsis is the primary cause of mortality inECF. The control of any septic foci should begin whenthe patient is sufficiently stable to undergo diagnosticand therapeutic intervention. Computed tomography(CT) is the best test for elucidation of intraperitonealabscesses, which can then be drained. In a stabilizedpatient, these collections are preferentially drained per-cutaneously by an experienced interventional radiologyteam. Alternately, the abscess can be drained through thefistula tract with a sump drain, with the tip of the drainplaced near the enteric opening. Again, this should bedone by an experienced interventional radiology team

under fluoroscopic guidance with fistulography.12

Whiledraining the abscess collection, cultures should be sent. Ifthe patient is septic, broad-spectrum antibiotics shouldbe started with the intent to narrow antibiotic coverageas culture results permit. A patient with an ECF withoutfevers, tachycardia, or signs of local infection such ascellulitis does not need antibiotics.

A patient with severe sepsis unresponsive toresuscitation or with an abscess unable to be percuta-neously drained may need an urgent return to theoperating room for washout of the abdominal cavityand control of the fistula. In this case, the best manage-ment is often a diverting proximal stoma.13 In mostpatients who are hemodynamically stable after resusci-tation, the optimal treatment is to delay a return trip tothe operating room and control sepsis through anti-biotics, drainage, and supportive care. The postsurgicalabdomen 1 week after laparotomy is an inhospitablearena where dense adhesions and friable, edematousbowel make reoperation difficult and increase the chanceof further complications. Avoidance of reoperation atthis time, when possible, is imperative.

SKIN PROTECTION

Protection of the skin around the fistula is a vital earlystep. The fistula effluent can be acidic or alkaline,depending on its origin, but at high volume or withstasis on the skin excoriation can occur within 3 hours.Once the skin is raw, painful, and weeping, stomaappliances and other output control methods are muchmore difficult to use. Enzymes in the succus can digestthe abdominal wall and result in a large wound with afistula at its center. In cases where the fistula is discov-ered upon opening a midline wound for presumed

wound infection, the fistula is already situated in a large,open abdominal wound. This can greatly complicate

POSTOPERATIVE ENTEROCUTANEOUS FISTULA/GALIE, WHITLOW 239

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management of the fistula effluent. Thus, it is importantto control effluent early in the course of the fistula and toprevent skin damage when possible. It is also importantto involve an experienced enterostomal therapy team tomanage the fistula output.

To protect the skin, an ostomy appliance may beattached to the skin, with a custom fit for the exterior

opening of the fistula. The ostomy nurse can contributevarious pastes and powders to compensate for moist skinand uneven fistula edges. Rapidly draining wounds mayrequire a sump tube through the appliance to controloutput further. Fistulas in large wounds may benefitfrom sump drains and a large Eakin stoma appliance toprotect the tissue around the fistula.14

A newer approach is the application of a negative-pressure dressing, such as the vacuum-assisted closuredevice (VAC, KCI International, San Antonio, TX.) Inthe late 1990s the VAC system was thought to promoteor at least potentiate fistulas and was not used for this

indication; however, there has been a resurgence ofinterest and use in this device for fistulas. The VACsystem can be tailored in many ways to divert fistulaeffluent. As described by Goverman et al,15 the VACalso treats the wound bed around the fistula withnegative-pressure dressing, resulting in increased gran-ulation tissue and wound contracture. The device alsofunctions as a bolster to grafted skin around the fistula

while diverting the enteral contents from the graft.15

Other studies have shown that the VAC does notprevent spontaneous fistula closure.16,17 The concept ofnegative-pressure dressing is not limited to the VAC; asimple drain with an occlusive balloon inserted into afistula tract and set to negative pressure has been shownto be effective in controlling effluent and allows sponta-neous closure as well.18

NUTRITION

After sepsis, other significant causes of mortality fromECF include fluid and electrolyte disturbances andmalnutrition.4 These are managed with nutritional sup-port. The introduction of total parenteral nutrition(TPN) by Dudrick et al in 1968 revolutionized thetreatment of patients with ECFs. Fistulas may result in

massive daily fluid and electrolyte losses. Commoncomplications of high-output fistulas can include dehy-dration, hyponatremia, and hypokalemia as well asmetabolic acidosis. Rehydration and electrolyte replace-ment are performed intravenously during the stabiliza-tion phase but, once replete, can often be taken orally.Nutritional supplementation should begin as soon as thepatients volume and electrolyte status is stabilized.4

Malnutrition in ECF is due mainly to GI losses,hypercatabolic state secondary to sepsis, and inadequatecaloric intake. Malnourished patients show weight lossand hypoproteinemia; hypoproteinemia is independently

associated with a higher mortality in ECF.4 The initialevaluation of a patients nutritional status is customarilydone with a baseline laboratory evaluation includingtransferrin, albumin, and prealbumin but can include ametabolic cart analysis and multiple-frequency bioelec-trical impedance analysis.19 The Harris-Benedict equa-tion multiplied by a stress factor for sepsis can be

calculated to approximate the patients caloric needs.Patients with ECF generally require from 25 to 32kcal/kg/day and 1.0 to 2.5 g/kg/day of protein, depend-ing on the fistula output.4,9 Continuing evaluation of thepatients nutritional status is necessary and facilitates fineadjustments of the nutritional supplementation.

The route of nutritional supplementation shouldbe enteral when possible. Enteral nutrition is associated

with fewer complications than TPN, such as line in-fections and central venous thrombosis.4,20 Enteral feed-ing also improves gut absorptive function and maydecrease bacterial translocation,21 and it may improve

the immunologic and hormonal function of the intestineand increase hepatic protein synthesis. When givenenterally, as little as 20% of caloric needs are beneficial.9

Eating per os is the preferred form of enteral nutrition,but some patients may need nasogastric, nasojejunal,gastrostomy, or enterostomy feedings to maintain caloricintake. Patients with proximal jejunal fistulas may bene-fit from fistuloclysis or feeding the distal limb of a fistula.

This requires adequate distal bowel for absorption andlack of distal obstruction. A feeding catheter withballoon tip is placed into the distal limb of intestineunder fluoroscopic guidance and used to infuse enteralfeeding solution. Benefits of this approach include ad-equate nutrition, decreased use of TPN in patients withproximal fistulas, decreased cost, and improvement inbowel quality distal to the fistula, making subsequentdefinitive surgery easier.22 Fistuloclysis catheters shouldbe tightly secured; they have been drawn completely intothe distal small bowel by peristalsis in two patients, oneof whom required reoperation for obstruction.23

Not all patients are candidates for enteral nutri-tion. TPN-dependent patients are those who cannotobtain enteral access, who have fistulas with outputstoo high to replace enterally, or who cannot tolerateenteral feedings because of nausea, abdominal disten-

tion, or pain. Patients with inadequate length of smallbowel to allow absorption of needed calories and nu-trients are also TPN dependent. Most patients arestarted on enteral and parenteral nutrition simultane-ously, and TPN is weaned as enteral feedings areincreased to goal.

Patients who are dependent on TPN usually needto supplement their vitamins and trace minerals as well.ECF patients should receive twice the recommendeddaily allowance for trace minerals and vitamins and up to10 times the recommended daily allowance for vitaminC, selenium, and zinc.4


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TPN is best administered with the assistance of amultidisciplinary team. These teams usually consist ofphysicians, pharmacists, nurses, nutritionists, infusiontherapists, social workers, and home health providersas necessary. The team approach reduces line-associatedcomplications such as infection, air embolism, venousthromboembolism, line placement complications, and

electrolyte and fluid imbalances and can also reducecost.2,20 Home administration of TPN is ideal forpatients who require long-term TPN and has beenshown to be safe and effective. It assists patients intolerating their period of nutritional optimization lon-ger, during which time a proportion of fistulas closespontaneously with medical management, decreasing theneed for definitive surgery.20

REDUCTION IN FISTULA OUTPUT

Reduction in fistula output alone would seem intuitively

to increase the rate of spontaneous closure of a fistula, asless volume traversing the fistula should allow easierclosure. However, the association of decreased fistulaoutput with increased rate of spontaneous closure hasnot been proved. Reduction of fistula output, however,does allow patients to maintain their volume, electrolytestatus, and nutrition more easily and decreases theamount of effluent on the skin, making fistula care easier.Several strategies for reducing fistula output have beenstudied.

Bowel rest with TPN decreases fistula outputbut, as discussed earlier, does not outweigh the bene-fits of enteral feeding. Acid suppression with H2blockers or proton pump inhibitors can decrease fistulaoutput as well as reduce gastric acidity, prevent stressulceration, and reduce electrolyte losses, although ithas not been shown to increase the rate of fistulaclosure.4,9,24

Somatostatin is a tetradecapeptide foundthroughout the body that inhibits multiple GI hor-mones, such as secretin, gastrin, glucagon, vasoactiveintestinal peptide, cholecystokinin, and insulin. It de-creases GI tract output by decreasing pancreatic, gastric,enteric, and biliary secretions and also decreases motilityof the intestine.4,9 Somatostatin has an extremely short

half-life of 2 to 3 minutes and is degraded by digestiveenzymes; thus, it must be administered by continuousintravenous (IV) infusion. Complications of somatosta-tin infusion include frequent hyperglycemia and reboundhypersecretion of insulin, glucagon, and growth hor-mone on cessation of use.4

Octreotide is a synthetic analog of somatostatinthat has a longer half-life and thus more convenientdosing. It lasts 1.5 to 2 hours after either IV or subcuta-neous injection. Complications of hyperglycemia andrebound effects are decreased compared with somatos-tatin; however, both somatostatin and octreotide cause

an increased incidence of gallbladder sludge and chol-elithiasis as well as pain at the site of administration. 4,9,25

Somatostatin and octreotide have both beenstudied in randomized, controlled trials to determinethe effect of these drugs on fistula output, fistula closurerate, and time to fistula closure. The only randomized,controlled trial using somatostatin that addressed fistula

output showed a significant decrease in output comparedwith placebo; however, pancreatic fistulas were includedin the study.26 Randomized, controlled trials usingoctreotide have not consistently shown a decrease infistula output.24 No study has shown an increased rate offistula closure with use of either somatostatin or octreo-tide.27 In several studies, somatostatin has been shown toreduce the time to fistula closure, although pancreaticfistulas were not considered separately in the series withthe largest number of patients.2427 Results of trialsusing octreotide with time to closure as an endpointhave been divergent and inconclusive.3,24,27 It should be

noted that neither somatostatin nor octreotide can beexpected to assist in the closure of a fistula kept open bymechanical means, such as distal obstruction. Thus,treatment with either should only follow adequate de-lineation of fistula and bowel anatomy.28 Although theevidence is stronger for the use of somatostatin, currentliterature shows no clear improvement in outcome withthe use of either octreotide or somatostatin for ECF.Although outcome may not be improved, managementof the fistula effluent, fluid and electrolyte management,and skin protection may be easier with somatostatin oroctreotide treatment if, in a particular patient, it resultsin reduction in fistula output.28 At this time, not enoughdata exist to support using either somatostatin or octreo-tide in the routine treatment of ECFs.

ELUCIDATION OF THE FISTULA ANATOMY

Fistulas that have not spontaneously closed despitecontrol of sepsis, skin protection, medical management,and nutritional support need further evaluation. Com-plicating factors such as foreign bodies in or near thefistula tract, radiation enteritis or inflammatory boweldisease in the associated bowel, untreated infection,epithelialization of the tract or mucocutaneous continu-

ity, neoplasm in the fistula tract, and distal obstructioncan prevent spontaneous closure. At this point, a fullevaluation of the fistula tract and bowel must be per-formed.

If there is doubt about the existence of a fistula,the initial test often recommended is oral administra-tion of methylene blue.4 This is inexpensive and rela-tively risk free and may be performed in the diagnosticphase of fistula management. If the fistula effluent takeson a blue color, the existence of a fistula is confirmed, asis its origin from a portion of the bowel in continuity

with the rest of the digestive tract rather than from a


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defunctionalized limb, such as a Roux limb. Oralcharcoal has also been used in this manner.

As previously discussed, early CT is the study ofchoice in patients with signs of sepsis, as it maydelineate areas of undrained abscess. Repeating theCT as needed after percutaneous drainage to ensurecomplete drainage is recommended.12 These scans,

when performed with oral contrast material, may alsodemonstrate the fistula tract and provide anatomicinformation about the orientation and length of thetract and its feeding bowel.

The gold standard for examining a fistula is afistulogram performed with water-soluble contrast ma-terial. This should be performed later in the manage-ment of the fistula, after stabilization and treatment ofsepsis. A fistulogram can show the configuration of thetract, the source of the fistula, and any abscess cavitythat communicates with the fistula. It can show under-lying disease of the bowel at the origin of the fistula

such as inflammatory bowel disease. Distal bowel ob-struction, such as a stricture, can be diagnosed. Lastly,the fistulogram allows an estimate of the size of thebowel defect at the origin of the fistula.9This informa-tion is combined to assess the chance of spontaneousclosure of the fistula with supportive care. Upper GIseries and Gastrografin enemas may also be useful inthe evaluation of the fistula and its anatomic relation tothe bowel as well as of the bowel quality and presence orabscess of distal obstruction.

Ultrasonography can demonstrate involvedbowel, abscess cavities, and areas of possible stenosisbut does not adequately evaluate the fistula tract. Ultra-sonography supplemented with hydrogen peroxide fis-tulography has been shown to be at least as accurate asbarium enema and static x-ray fistulography in charac-terizing the fistula tract and involved bowel and aseffective as CT scan in identifying undrained abscess.29

This study is particularly operator and interpreter de-pendent.

Endoscopy can be used in the accumulation ofdata regarding the characteristics of a fistula and sur-rounding bowel. Therapeutic endoscopic maneuvers canalso be attempted which may assist in fistula closure.Uncommonly, the first presenting sign of Crohns dis-

ease may be an ECF. In this case, endoscopy can be usedto make a new diagnosis in patients with inflammatorybowel disease who present in this manner. Endoscopycan also be used to evaluate for neoplasm associated withthe origin of the tract or distally. Strictures can beidentified and treated endoscopically with dilation.30

Further endoscopic treatments are discussed subse-quently. Fistuloscopy (endoscopic evaluation of the fis-tula tract through the external fistula opening) can beused for identification and removal of foreign bodies,debridement of the tract, diagnosis and biopsy of neo-plasm in the tract, and treatment in selected cases.31

NONSURGICAL FISTULA CLOSURE

Several methods of nonsurgical fistula closure have beenattempted but none has been proved in a randomized,prospective trial.

The injection of fibrin glue into the fistula tracthas been described in many case reports. In someinstances, the fistula is located endoscopically and its

internal opening injected with fibrin glue, a mixture ofbovine thrombin and human fibrinogen.32 In othercases, the fibrin glue is injected from the external open-ing, with or without guidance by fistuloscopy.31 Manyfistulas require multiple applications. Results have beenencouraging, although most fistulas described in theseseries are internal, pancreatic, biliary, gastric, esophageal,rectal, or colonic. In general, the fistulas treated success-fully with this method have been low output, short,uncomplicated, and uninfected, without evidence ofneoplasia or inflammatory bowel disease.30 A largerandomized, controlled trial is needed to determine the

true efficacy of this intervention.Because of the bovine proteins in fibrin glue, thereis a risk of allergic reaction and, theoretically, of prioncontamination.33 As recombinant human thrombin be-comes available, this risk should decline. Fistuloscopycan lead to air embolism through increased pressure inthe fistula tract. It can also lead to sepsis if the tractconnects to an undiagnosed abscess cavity or the tract isinfected.30 As an alternative to surgery, fibrin glueapplication is safer and much less invasive and maysave selected patients the mortality associated withoperative intervention.

Other injectable treatments include histoacrylglue, which is not derived from animal products andthus has no risk of transmitting infection or causingallergic reactions related to bovine protein. Histoacrylglue also has the benefit of resisting enzymatic break-down by fistula effluent as it is not a protein; thus, it maybe more suited to high-output fistulas. Dalton and

Woods reported a case of a recurrent, high-outputduodenocutaneous fistula treated successfully with oneapplication of histoacryl glue after failure of standardconservative therapy.33 As with fibrin glue, a random-ized, controlled trial is needed to evaluate this technique.

Porcine small intestinal submucosa (Oasis, Cook

Biotech, West Lafayette, IN) is a naturally derived,extracellular matrix material that acts as a scaffold forhost tissue ingrowth. It has been used most commonlyin the treatment of abdominal wall defects but has beenrecently used to treat perianal fistulas and, less com-monly, in small bowel fistulas.34,35 Schultz et al re-ported treating two patients with ECF resistant toconservative therapy by inserting a tightly rolled pieceof small intestinal submucosa into the external fistulaopening. The first patients fistula closed immediately,and the second patients fistula closed after removal andreapplication of the product the next day. The risk of


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application of this product is minimal; infectious risk islow as the product is acellular and sterilized. Again, arandomized, controlled trial is needed to evaluate thistechnique in ECFs.

TIMING

The best time to abandon conservative managementalone and attempt nonoperative fistula closure or defin-itive surgical closure has not been proved definitively inthe literature. In the absence of complicating factors suchas foreign bodies in or near the fistula tract, radiationenteritis or inflammatory bowel disease in the associatedbowel, untreated infection, epithelialization of the tractor mucocutaneous continuity, neoplasm in the fistulatract, and distal obstruction, up to 74% of ECFs healspontaneously with maximum conservative therapy.4,6,14

Of these spontaneously closing ECFs, 91% close by 4weeks and the remaining 9% close by 12 weeks.1,4,9

Characteristics of fistulas that decrease their likelihoodof closing spontaneously were discussed earlier in thesection on classification of fistulas. If, after appropriateeradication of sepsis and medical management, 6 weekshas passed and the fistula has not closed or shownmarked decrease in output, planning for definitive sur-gical closure should begin.

Surgical intervention should be delayed until in-tra-abdominal and systemic conditions are optimal. Theabdomen after laparotomy complicated by ECF andsepsis shows a dense fibroadhesive reaction from10 days to 6 weeks or longer. There is no definitive

way to tell when this dense reaction has subsided, butthere are indications on careful clinical examination. Theabdomen should be soft and nontender and the prior scarshould be pliable. The abdominal wall should have healedas much as possible around the fistula and be free ofinflammation.1 Fistulas with mucocutaneous continuityshould begin to prolapse when the intra-abdominaladhesions have softened and a neoperitoneum has devel-oped.14,36 Until these clinical signs occur, the abdomenshould be considered hostile. During this time of adhe-sion remodeling the bowel is edematous, hyperemic, andfriable. Division of adhesions can cause significant bloodloss from continuous oozing of cut surfaces. Operating

too early can result in further enterotomies, recurrentfistulas, and may even necessitate the excision of largeamounts of small bowel, resulting in short gut syndrome.

Systemically, the patient must be optimized med-ically and nutritionally prior to elective fistula repair. Allabscesses should be drained and any infections ad-equately treated. The patient should have adequateserum albumin and normal serum electrolytes. Anycomorbidities such as hypertension and diabetes shouldbe well controlled, and patients should stop smoking.

In general, the longer the patient and surgicalteam can wait to undertake the elective operation, the

easier and safer it will be and the lower the fistularecurrence rate. These preoperative requirements maytake up to 6 months to fulfill, and it is not unreasonableto wait that long to progress to definitive surgicalintervention.14 Recommendations vary but usually spec-ify waiting 3 to 6 months or longer after the originaloperation.9,10,14,36 In determining when to reoperate to

close an ECF, there is no substitute for good clinicaljudgment and patience.

SURGICAL TECHNIQUES

Reoperation for ECF is technically challenging and timeconsuming. The case should be booked for the entire dayto resist the urge to rush through the likely tediousdissection. The abdomen should be reopened away fromany areas of possible contamination. If an old laparotomyincision will be used, the surgeon should enter theabdomen above or below the surgical scar to reduce the

chance of encountering dense adhesions to the midlineand creating an enterotomy. Once inside the abdominalcavity, gentle traction and sharp dissection should beused to divide adhesions. Many surgeons advocate ad-hesiolysis with a knife blade.1,9 Patient, meticulousdissection is crucial. Any serosal injuries should berepaired with Lembert sutures and enterotomies securelyclosed transversely in two layers. The bowel should beseparated from the abdominal wall and fully freed ofadhesions from the ligament of Treitz to the cecum.

This facilitates examination of the entire bowel, resec-tion of the area containing the fistula, and reconstructionof the bowel without tension; rules out distal pathology;and releases any bands of adhesion that may compromisepostoperative bowel function and put the anastomosis atrisk. Simply freeing the bowel near the fistula enough forresection and reanastomosis is not adequate.1,9,14

When the fistula has been identified, the methodleast likely to result in recurrent fistula is resection andprimary anastomosis of the area of bowel involved in thefistula. This should be performed in an area of bowel freeof edema and friability, such that the anastomosis ispositioned outside of any abscess cavity and away fromthe prior fistula site. Oversewing the fistula defect andperforming a wedge resection of the involved bowel are

associated with higher incidence of recurrence (32.7%)than resection and reanastomosis (18.4%.)10 Diversionof the loop of bowel containing the fistula by exclusion ofthat segment of bowel without excision can be per-formed in the case of palliative operations for unresect-able malignancy.37 In nonneoplastic circumstances,diversion in this fashion should be reserved as a lastresort, as it rarely results in fistula closure.28

After resection and anastomosis, the entirebowel should be run to identify any further serosal orfull-thickness injuries. These should be repaired asdescribed earlier. The abdomen should be copiously


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irrigated and any bleeding controlled. The omentum, ifavailable, should be placed between the bowel and themidline wound. Seprafilm can be used under the mid-line wound to decrease adhesion formation but shouldnot be placed directly over the anastomosis. The ab-dominal wall should be closed securely. In the case of alarge abdominal wall defect, consultation with a plastic

and reconstructive surgeon can facilitate abdominalwall closure with separation of components or a my-ocutaneous flap.9

Postoperatively, maintenance of the patients oxy-gen-carrying capacity by assuring adequate volume statusand avoiding hypotension, anemia, and hypothermiaallows the new anastomosis to heal correctly. Avoidinginfection and breakdown of the midline wound alsohelps prevent recurrent fistulas. Nutritional supportshould be continued.

Recurrence of ECF is a disheartening complica-tion, which occurred in 21% of cases in one large series.10

The treatment of recurrent ECF is identical to that of aninitial ECF. The fistula closure rate was not influencedby a previous attempt at operative fistula closure in thepreviously mentioned study or by the number of priorintra-abdominal surgeries. This supports the view that

with persistence, even recurrent fistulas close.

UNDERLYING DISEASE

The presence of Crohns disease, cancer, or radiationenteritis in the segment of bowel related to the ECF is apoor prognostic factor. Fistulas associated with theseunderlying diseases deserve special mention and case-by-case consideration in their management.

Crohns disease is an immune-mediated diseaseof unknown cause that primarily affects the GI tract.An inflammatory process in the intestine causes micro-perforations and can lead to fistulas in one out of threecases. Most ECFs in Crohns disease are spontaneous,arising from the site of a flare of the disease, or occurafter percutaneous drainage of a spontaneous abscess.Unlike that with common postoperative ECFs, theassociated bowel in this case is abnormal (affected

with Crohns.) This results in a lower incidence ofspontaneous closure with conservative treatment. If

fistulas do close spontaneously, they are more likely toreopen.38 Postoperative ECFs in patients with Crohnsdisease usually arise from bowel uninvolved withCrohns (or an anastomosis would not have beenfashioned there) and act like common postoperativeECFs in non-Crohns patients.

Treatment of spontaneous or postdrainage ECFsin Crohns follows the same algorithm as for non-Crohns fistulas, with the addition of medical manage-ment for the treatment of Crohns disease. Steroids and5-aminosalicylic acid (5-ASA) have not been shown toeffect healing of Crohns ECF. 6-Mercaptopurine has

been used with some success, but response is slow andcomplications of neutropenia and pancreatitis limit itsuse. Cyclosporine has also been used, but the dosenecessary for response is high and associated withfrequent complications. Relapse occurred with switchingto oral cyclosporine.38

The most promising medical treatment for ECF

in Crohns is infliximab. Infliximab is an immunoglo-bulin G1 murine-human chimeric monoclonal anti-body to tumor necrosis factor a. It has been shown toeffectively treat moderate to severe Crohns disease and

was noticed to cause closure of enterocutaneous fistulasin this population. Present et al developed a multi-center, randomized, placebo-controlled study to assessthe effect of infliximab on fistulas. This study showed asignificant reduction in draining fistulas and a signifi-cant higher and faster rate of complete response in thepatients in the infliximab groups compared with pla-cebo.39 A high proportion of the patients had perianal

fistulas, which responded better to infliximab thanileocutaneous fistulas.The ACCENT II study was a multicenter, dou-

ble-blind, randomized, placebo-controlled trial to eval-uate infliximab maintenance therapy on fistulas inCrohns disease.40 This study found that respondersafter induction therapy showed a significantly longertime until the loss of response, which was defined asthe reduction of at least 50% of the draining fistulas, anda higher rate of fistula closure as compared with placeboafter 1 year maintenance therapy with infliximab. Therate of adverse events, especially infection, is high.Because of the immune modulation of infliximab, thereis a concern for infliximab-induced cancer and a risk ofdevelopment of antinuclear antibodies, which may ariseas an overt lupus-like syndrome. This also has not beendefinitively proved in the ACCENT II trial. This trialalso had a high percentage of perianal fistulas as com-pared with abdominal fistulas; thus, its results may not beas meaningful for abdominal ECF in Crohns.

In a retrospective chart review, Poritz et altreated 26 patients with varying fistula types with aninduction dose of infliximab and then followed theirsurgical course to evaluate the impact of infliximabtreatment on the need for surgery.41 They found that

more than half of these patients still required surgicalintervention but that the timing, indications, and diffi-culty were altered. More patients underwent operationsfor stricture than for fistula excision; this may attest toscarring from rapid fistula healing with infliximab.Intraoperatively, they also found less inflammationaround the fistula tract and technically easier proce-dures in the patients treated with infliximab. As withthe Present and ACCENT II trials, patients withperianal disease responded better to infliximab. Poritzet al found that no patients with ECF had completeclosure with induction doses of infliximab.41


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Infliximab has also been used efficaciously as atreatment for non-Crohns disease ECF in three cases.42

The authors postulated that infliximab decreased thepersistent inflammation that was causing these ECF tofail to close spontaneously despite maximal conservativetreatment. Infliximab in Crohns ECF and non-CrohnsECF patients certainly deserves further investigation.

Current literature regarding infliximabs role in closingCrohns fistulas is promising.

ECFs associated with neoplasm are also resistantto spontaneous closure and may be resistant to operativeclosure. The presence of a malignancy increases themortality associated with ECF. Among patients withpostoperative ECF, 48% had prior radiation therapy and48% had prior chemotherapy, which suggests that thesefactors increase the risk of postoperative ECF in patients

with cancer. Chamberlain et al found that the presenceof an ECF may delay or prevent the pursuit of adjuvanttreatments for cure or palliation in 63% of cases.43

Radiation damage to the bowel may cause com-plications weeks to years after the insult. The longestreported interval between radiation treatment and fistuladevelopment is 27 years.44 Late injury usually occursfrom progressive vasculitis, collagen deposition, andfibrosis. This causes tissue hypoxia, which can result inulceration, necrosis, and perforation, ultimately leadingto fistulization. ECFs associated with radiation enteritisare resistant to spontaneous closure and frequentlyrequire operative closure. The technique recommendedat operation is variable. When possible, resection andreanastomosis is the preferred treatment, although theanastomosis must be made from healthy bowel.45 If thiscannot be accomplished because of the risk of short gutsyndrome, a proximal defunctionalizing stoma should beconsidered in healthy bowel proximal to the fistularesection.10 Using healthy bowel to bypass the fistulain situ obviates the need to dissect radiation-damagedbowel, although the anastomotic dehiscence rate at thebypass can equal that of a resection.46 Fistulas caused byradiation enteritis are often kept open by a distal stric-ture; in this case, stricturoplasty is the treatment ofchoice. Consulting with a plastic or reconstructive sur-geon for a muscle or myocutaneous flap to buttress thefistula repair may decrease leak and improve healing by

moving healthy tissue into the area.47 Unfortunately,recurrence of fistulas from radiation is high.

CONCLUSION

An ECF is a devastating postoperative complication.Prevention cannot be stressed enough and is much moreeffective than the best treatments available for ECF.Once an ECF is diagnosed, the best outcomes comefrom early implementation of a treatment algorithm.

The first priority is to resuscitate and to treat any sepsis;the second is to protect the skin. The third step is to

optimize the patient medically and nutritionally, whichmay allow spontaneous fistula closure. The last step isdefinitive operative treatment when necessary. The keyto successful operative intervention is patiencefirst,patience in delaying the definitive operation until con-ditions are optimal, and second, performing a patientand technically precise procedure. Lastly, persistence is

needed in the case of recurrent fistulas. With earlyimplementation of a management plan, the patience todelay operative intervention until most likely to succeed,and persistence, nearly all fistulas close.

DISCLOSURE

The authors have no conflicts to disclose relative to thisarticle.

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