42 Surgery for Crohn’s Disease

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42

Surgery for Crohn’s Disease

Scott A. Strong

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Crohn’s disease is a chronic, unremitting, incurable, inflammatory disorder that can affect the entire intestinal tract.

Although the etiology remains uncertain, the distribution and behavior of the disease can be generally characterized.

The presenting symptoms and signs, medical and operative options, and outcome likely depend on the disease genotype and phenotype. Specifically, the surgical procedures typically utilized in the operative management of Crohn’s disease include nonresectional techniques such as internal bypass, fecal diversion, and strictureplasty as well as resectional procedures with or without concomitant anastomoses. The morbidity and risk for disease recurrence varies between the different procedures depending on myriad factors such as preoperative variables, site and behavior of disease, and postoperative influences.

Etiology and Incidence

The cause of Crohn’s disease is unclear but recent investigations continue to provide insight into the etiology and pathogenesis of this inflammatory disorder that can affect any portion of the intestinal tract through a complex interplay between conditioning factors and effector mechanisms. The conditioning factors include genetic influences and triggering events that create a permissive host, whereas the effector mechanisms mediate tissue damage through dysregulation of the intestinal immune and nonimmune functions. Patients afflicted with symptomatic disease are likely genetically sus- ceptible because abnormalities in seven loci on chromosomes 16q, 12, 6p, 14q, 5q, 19, and 1p have been identified in selected populations,¹but there must be other factors at play because these variations have not been replicated in all populations and the proband concordance rate among monozygotic twins is only 50%–60%.^2,3Initiating or triggering events such as environmental factors and microbial agents also probably contribute to disease susceptibility as evidenced by reports that describe the effects of tobacco usage^4–7and fecal flora⁸ on disease activity. In addition, abnormalities in immune

cellular function, nonimmune cell activity, protein expression, and cellular apoptosis hint as to the role of the dysregulated effector mechanisms in the pathogenesis of Crohn’s disease.⁹ The prevalence of Crohn’s disease in the United States is approximately seven cases per 100,000 persons, and the incidence has steadily increased over the past 5 decades.^10,11 Internationally, the prevalence is relatively high in northern Europe, significantly lower in southern Europe and Australia, and the lowest in South America, Asia, and upper Africa. This discrepancy in prevalence is likely multifactorial in nature, but it is recognized that the incidence and prevalence of Crohn’s disease increases as a region becomes more urbanized.

The male-to-female ratio of the disease is 1.1–1.8:1 and the disease has a bimodal age distribution with the first peak occurring between the ages of 15–30 years and the second between 60–80 years; most persons experience the onset of disease symptoms before 30 years of age. The disorder is more common in whites than in blacks, Hispanics, or Asians, and a two- to fourfold increase in the prevalence has been found among the Jewish population in the United States, Europe, and South Africa compared with other ethnic groups.

Disease Classification

The original classification of Crohn’s disease was described nearly three decades ago,¹² but inaccuracies associated with this and subsequent systems led to the most recent refinement, the Vienna Classification.¹³This scheme was generated by a World Congress of Gastroenterology Working Party that prospectively designed a simple phenotypic classification system based on objective and reproducible clinical variables that include age at diagnosis, anatomic location, and disease behavior. The age at diagnosis is stratified into patients < 40 years and those ≥40 years. The anatomic location is classified as terminal ileum, colon, ileocolon, and upper gastrointestinal. Terminal ileal disease is defined as disease limited to the lower third of the small bowel with or without cecal involvement. Colon disease is any colonic involvement between the

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cecum and rectum without small bowel or upper gastrointestinal disease. Ileocolon disease is disease of the terminal ileum with colonic involvement noted between the cecum and rectum. And, upper gastrointestinal disease is defined as any disease location proximal to the terminal ileum regardless of involvement in other areas. The disease behavior is grouped as nonstricturing nonpenetrating (inflammatory), stricturing, and penetrating. Subsequent application of the Vienna Classification to clinical practice has demonstrated that the Crohn’s disease phenotype markedly changes for a given patient over time^14–17 with 15% of patients experiencing a change in anatomic location and 80% of individuals with inflammatory disease ultimately demonstrating a stricturing or penetrating behavior. Moreover, the ability of experts to independently agree on disease phenotype using the Vienna Classification in controlled trials ranges from poor to fair.¹⁸It is unclear whether the varied classification systems fail because of the heterogeneity of the disease or inherent short- comings of the classification schemes. Although these fail- ings limit the utility of the Vienna Classification in clinical trials and disease management, recent advances in determin- ing the genetic linkages associated with Crohn’s disease will likely lead to a revised Crohn’s disease classification system that combines genotype and phenotype characteristics.

Operative Indications

The indications for operative management of Crohn’s disease include acute disease complications, chronic disease complications, and failed medical therapy. The acute complications are toxic colitis with or without associated megacolon, hemorrhage, and perforation, whereas the chronic disease complications include neoplasia, growth retardation, and extraintestinal manifestations. Failed medical therapy can take several forms including unresponsive disease, incom- plete response, medication-related complications, and noncompliance with medication.

Toxic Colitis

Toxic colitis is a potentially fatal complication of Crohn’s disease, particularly if accompanied by megacolon. Although several schemes exist to accurately identify toxic colitis, one reasonably simple system uses a definition that includes a disease flare accompanied by two of the following criteria:

hypoalbuminemia (< 3.0 g/dL), leukocytosis (>10.5 × 10⁹ cells/L), tachycardia (> 100 beats/minute), temperature increase (> 38.6°C). Use of this relatively objective definition may aid in the diagnosis and care of these patients whose severe condition can be under-appreciated because of high dosages of steroids, immunomodulators, or biologic agents.

The initial management is directed at reversing physiologic deficits with intravenous hydration, correction of electrolyte imbalances, and blood product transfusions. Free perforation,

increasing colonic dilatation, massive hemorrhage, peritonitis, and septic shock are indications for emergent operation after the patient has been adequately resuscitated. In the absence of these features, medical therapy is initiated with high dosages of intravenous corticosteroids, immunomodulators, and/or biologic agents.¹⁹Broad-spectrum antibiotics directed against intestinal flora are prescribed to minimize the risk of sepsis secondary to transmural inflammation or microperforation.

Anticholinergics, antidiarrheals, and narcotics are avoided because they may worsen already impaired colonic motility or conceal ominous symptoms. Hyperalimentation may be started and the patient is closely observed with serial examinations and abdominal roentgenograms. Any worsening of the clinical course over the ensuing 24–72 hours mandates urgent laparotomy. If the patient improves minimally after 5–7 days of conventional therapy, the medical therapy should be altered or surgery should be advised. Experience with cyclosporine or infliximab in this setting is anecdotal, and should be weighed against operative therapy while understanding that surgery in this setting often relegates the patient to a life-long ileostomy.^20,21

The principal operative options in patients with toxic colitis complicating Crohn’s disease include subtotal colectomy with end ileostomy, total proctocolectomy with end ileostomy, and loop ileostomy with decompressive blowhole colostomy. Of these alternatives, subtotal colectomy with end ileostomy is the most widely practiced procedure. The most difficult aspect of the operation is managing the distal bowel stump. The distal limb may be closed with sutures or staples and then delivered to the anterior abdominal wall where it can lie without tension in the subcutaneous fat of the lower mid- line wound. Dehiscence of the closure during the postoperative period results in a mucous fistula instead of a pelvic abscess as witnessed when the closed stump is left within the peritoneal cavity. If the bowel wall is too friable to hold sutures or staples, a mucous fistula is primarily created.

Rarely, instead of creating the fistula, the rectosigmoid stump must be exteriorized and wrapped in gauze to prevent retrac- tion with a mucous fistula safely fashioned 7–10 days later.

The patient typically improves over the ensuing few days and can be typically discharged within a week of the operation. An ileoproctostomy can be recommended 6 months later in selected persons who demonstrate minimal mucosal inflammation, adequate rectal compliance, absence of significant anoperineal disease, and sufficient sphincter strength.

Otherwise, the diseased rectum is left in place and the patient is counseled about the risk of neoplasia and the need for appropriate surveillance endoscopy.²² In these individuals, proctectomy is usually recommended if disease-related symptoms prove to be too bothersome, neoplasia is identified, surveillance is limited because of stricturing, or laparotomy is warranted for other reasons. Disease-related symptoms are likely to occur in patients with prior anoperineal disease and proctectomy is often required within the first few postoperative years.^21,23

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Proctocolectomy with end ileostomy is rarely performed in the severely ill patient with toxic colitis because of the excessive rates of morbidity and mortality.^24–26 Proctectomy increases the difficulty of the procedure and risks pelvic bleeding as well as autonomic nerve damage. In rare instances of rectal perforation or profuse colorectal hemorrhage, or in the less severely ill patient who would not be a candidate for future ileoproctostomy, proctocolectomy may be a viable option. The surgeon must be cautioned, however, that the macroscopic and microscopic differentiation of ulcerative colitis from Crohn’s proctocolitis is especially difficult in severe colitis, and primary proctocolectomy would nullify the future option of a restorative procedure in a patient with ulcerative colitis.

The need for loop ileostomy combined with decompression blowhole colostomy has virtually disappeared with improved medical recognition and more sophisticated management of toxic colitis. The operation is still useful in extremely ill patients or those in whom colectomy would be especially hazardous (e.g., contained perforation, high-lying splenic flexure, pregnancy). Contraindications to the procedure include colorectal hemorrhage, free perforation, and intraab- dominal abscess. The operation is considered only a tempo- rizing procedure, and a definitive operation is usually performed approximately 6 months later.

Hemorrhage

Crohn’s disease may be responsible for life-threatening lower gastrointestinal hemorrhage and even exsanguination, but fortunately this is an infrequent complication.^27–30 More frequently, entities unrelated to disease involvement, including peptic ulcer disease and gastritis, may precipitate intestinal bleeding. Accordingly, gastric aspiration and possibly esoph- agogastroduodenoscopy are required to exclude sources of hemorrhage indirectly associated with Crohn’s disease. The principal management of disease-related hemorrhage is deter- mined by the severity and persistence of bleeding as well as the risk for recurrence. Localization of the bleeding site is essential regardless of the planned therapy. In a stable patient with colonic disease, endoscopic evaluation is preferred because this approach allows for disease assessment and therapeutic attempts at control of the identified bleeding site.

However, indiscriminate usage of colonoscopy for bleeding colitis should be discouraged because this form of hemorrhage typically accompanies severe colitis, and colectomy with ileostomy is advised in this instance, regardless of the endoscopic findings.

A patient who requires ongoing resuscitation to maintain hemodynamic stability or in whom a small bowel source of active bleeding is suspected should undergo emergent mesenteric angiography to localize the source of hemorrhage and arrest ongoing bleeding through selective angiographic infusion of vasopressin or embolization. If the hemorrhage is localized but cannot be controlled by these interventional

modalities, the catheter is left in position and intraoperative angiography is performed to accurately identify the bleeding site and guide a limited bowel resection.³¹ Otherwise, wide resection might be necessary to manage hemorrhage from a small ulcerated area within an extensive segment of affected bowel.

Laparotomy and resection with or without anastomosis are required if the patient’s hemodynamic state cannot be sus- tained, bleeding persists despite 6 units of transfused blood, hemorrhage recurs, or another indication for surgery exists.

Perforation

Free perforation of the small bowel is also unusual and typically occurs at or just proximal to a strictured site.^32,33 The most appropriate treatment is resection of the involved bowel with immediate or delayed anastomosis. A nondiverted anastomosis should be avoided in the setting of delayed treatment, malnutrition, significant comorbidity, or severe sepsis. Resection with proximal ileostomy has an associated mortality rate of 4% compared with 41% with simple suture closure alone.³⁴ Perforation of the colon in patients with Crohn’s disease is also rare and typically requires subtotal colectomy for optimal management because these cases often occur in the setting of severe colitis or steroid usage.³⁵

Neoplasia

Overall, persons with Crohn’s disease are at increased risk for developing cancer compared with the general population. In a population-based study from Canada,³⁶these patients had an increased relative risk of developing carcinoma of the small intestine [17.4; 95% confidence interval (CI), 4.16–72.9] as well as malignancies of the liver and biliary tract (5.22; 95%

CI, 0.96–28.5), and males were at a particular risk for lym- phoma (3.63; 95% CI, 1.53–8.62). Their patients with Crohn’s disease were also at increased risk for the development of colon cancer (2.64; 95% CI, 1.69–4.12) and the risk was similar to that seen in persons with ulcerative colitis (2.75; 95% CI, 1.91–3.97); the risk for rectal carcinoma, however, was similar to that demonstrated by a demographically matched cohort without inflammatory bowel disease.³⁶Other population-based studies have supported the notion that Crohn’s disease of the colon is associated with an increased risk of colorectal cancer,^37–39 whereas reports from some centers^40–42have not noted the same association.

In a series of 22 patients with colorectal carcinoma complicating their Crohn’s disease, 19 (86%) and 9 (41%) had adjacent or distant dysplasia, respectively, supporting a dysplasia-carcinoma sequence in Crohn’s disease.⁴³ When a screening and surveillance program was adopted, dysplasia or cancer was detected in 16% of patients, and the probability of detecting dysplasia or cancer after a negative screening colonoscopy was 22% by the fourth surveillance examination.

Accordingly, despite some controversy, many pundits^44,45

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advocate that the endoscopic screening and surveillance pro- tocols used for patients with ulcerative colitis should also be recommended for individuals with Crohn’s disease of the large bowel. Specifically, a screening endoscopy should be performed 8–10 years after the onset of disease symptoms and four-quadrant random biopsies should be obtained every 10 cm along the length of the large bowel and directed biopsies should be procured from any strictures, lesions, or masses; subsequent surveillance endoscopy with similar biopsies should then be performed every 1–2 years. The finding of multifocal low-grade dysplasia, high-grade dysplasia, or invasive cancer would likely warrant review by a second experienced pathologist and confirmation would prompt a colectomy.

Growth Retardation

Abnormal linear growth secondary to delayed skeletal matu- ration is frequently encountered in children and adolescents with Crohn’s disease. Specifically, more than half of children may have a subnormal height velocity and approximately one-quarter will have short stature.⁴⁶ Fortunately, surgical resection is often accompanied by growth response and associated psychologic benefit.

Extraintestinal Manifestations

Extraintestinal manifestations of Crohn’s disease occur in nearly one-quarter of patients with Crohn’s disease and can involve most organ systems.^47–49Disorders of the skin, mouth, eye, and joints occur frequently with large bowel disease and their activity typically parallels the degree of intestinal inflammation. Operative management of the intestinal disease can provide beneficial control of the extraintestinal manifes- tation. Conversely, abnormalities affecting the hepatic, vascular, hematologic, pulmonary, cardiac, or neurologic systems behave independent of the intestinal disease. Other disorders such as nephrolithiasis and cholelithiasis are disease complications that likely arise from altered intestinal absorption.

Failed Medical Therapy

Antibiotics, probiotics, 5-aminosalicylate compounds, steroids, immunomodulators, and biologic agents all have a potential role in the management of Crohn’s disease depending on the clinical presentation. Each medication within these therapeutic groups possesses appropriate dosing parameters, associated side effects, and an optimal time interval during which beneficial effects should appear. Before initiating treatment with any medication, the patient should be counseled about these features and objective criteria for disease response should be discussed and then sought after an established time interval. If the desired response is not achieved, prohibitive side effects arise, or noncompliance is problematic, the medication has failed and another medication should be trialed. When all appropriate

medical therapy has failed, operative intervention is warranted.

The continuation of ineffective medical management risks the development of further disease complications that may detri- mentally impact surgical outcome.

Operative Considerations

Some fundamental observations that must be considered when operating for Crohn’s disease are as follows:

●Crohn’s disease is incurable

●Intestinal complications are the most common operative indication

●Operative options are influenced by myriad factors

●Asymptomatic disease should be ignored

●Nondiseased bowel can be involved by inflammatory adhesions or internal fistulas

●Mesenteric division can be difficult

●Resection margins should be conservative (2 cm)

Crohn’s disease is a chronic inflammatory disorder that cannot be cured by medical therapy or operative intervention.

Accordingly, treatment focuses on safely alleviating disease symptoms and restoring quality of life while attempting to maintain continuity of the intestinal tract. Of the various operative indications, intestinal complications including stricturing or penetrating disease that are unresponsive to medical therapy constitute the bulk of the indications, and the operative options depend on the multiple variables including patient age, anatomic location, disease behavior, symptoms, prior therapies, nutritional status, comorbid conditions, and associated sepsis. The patient’s symptoms are especially important because the disease encountered at the time of surgery is often unanticipated despite preoperative evaluation.⁵⁰ In these instances, the findings must be compared with the presenting symptoms and signs, and any extensive disease that does not appear to be contributing to symptoms should be typically ignored. Exceptions to this axiom include the management of out-of-circuit bowel and short, uncomplicated small intestine strictures, which should be addressed in most patients.

Nondiseased bowel can be affected through inflammatory adhesions or internal fistulas. With adhesions, every attempt should be made to conserve the nondiseased bowel, although this can be especially difficult when managing enteroparietal or interloop abscesses. Most internal fistulas are best managed by wedge excision and primary closure of the fistula site in the secondarily affected small bowel. However, a short segmental resection with primary anastomosis may be required for fistulas targeting the rectosigmoid region because these often enter the bowel at the mesenteric margin and simple wedge excision may be vulnerable to breakdown of the suture line.

The mesentery of the diseased bowel is usually thickened because of fat deposition and enlarged mesenteric lymph nodes that straddle the ileocolic and sometimes superior

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mesenteric vessels. Attempts at simple division and ligation of the vessels may injure the remaining vascular pedicle lead- ing to a rapidly spreading mesenteric hematoma that risks distal bowel ischemia. Instead, serial overlapping clamps applied to both sides of the intended transection line provide an ample margin or cuff on the mesenteric edge. Heavy, interlocking suture ligatures can then be used to under-run each pedicle caught within the clamps, eliminating concern for a spreading hematoma. Conservative (2 cm), macroscopically normal resection margins are associated with the same rate of operative morbidity and disease recurrence as extensive (12 cm), microscopically normal margins.⁵¹However, the luminal disease margin can be difficult to judge by inspecting the exterior of the bowel. Whereas inspection of the diseased bowel may reveal lymphadenopathy, creeping mesenteric fat, and cork- screwing of the serosal vessels, the nondiseased bowel may appear dilated with muscular hypertrophy and bowel wall edema. The key to discriminating between diseased and nondiseased bowel lies with palpation of the mesenteric margin of the bowel wall. A mesenteric ulcer will obscure the pal- pable transition from the mesentery to the bowel wall because of fat deposition between the terminal branches of the marginal vessels. If the surgeon’s fingers passing from the mesentery onto the bowel can readily identify the edge of the bowel wall, the luminal mucosa will be macroscopically normal.

Operative Options

The surgical procedures performed for intestinal Crohn’s disease can be divided into groups depending on whether resection of an intestinal segment is performed. The nonresectional procedures include internal bypass, fecal diversion, and strictureplasty, whereas the resectional procedures include resected bowel. Patients often undergo multiple procedures at the time of their single operation and these can be a combination of nonresectional as well as resectional procedures.

Internal Bypass

Internal bypass was the procedure of choice in the early days of surgery for Crohn’s disease when mortality rates associated with resection were high because of lack of transfusion tech- nology, antimicrobial medications, adequate anesthetic agents, and nutritional support services. However, with the advent of these modalities and recognition of complications such as recrudescent disease, mucoceles, and malignancy arising in diverted segments, this procedure was largely aban- doned. However, bypass operations are still considered rea- sonable or desirable in specific circumstances. A complicated ileocecal phlegmon with dense attachment to the iliac vessels or retroperitoneum can be aptly managed by an exclusion bypass if the proximal end of the excluded ileal segment is exteriorized as a small mucus fistula and definitive resection is planned to occur in later months. Continuity bypass is

sometimes the preferred method of managing symptomatic gastroduodenal Crohn’s disease that is refractory to medical treatment where resection would entail extensive reconstruc- tion of the upper intestinal tract or pancreaticobiliary system.

Fecal Diversion

Fecal diversion can be permanent or temporary. Many of the stomas created to permanently bypass unresected disease fail to control symptoms secondary to the out-of-circuit bowel, and resection is ultimately warranted. High complex fistulas and deep ulcerations are among the disease characteristics likely to mandate proctectomy with permanent ostomy for persistent disease symptoms despite fecal diversion.⁵² Similarly, temporary diversion intended to heal distal disease or its sequelae is usually unsuccessful unless combined with a secondary procedure such as a rectal mucosal advancement flap that directly addresses the problem.⁵³Even for free perforation of the small bowel, exteriorization of the proximal bowel alone is rarely the procedure of choice.

Strictureplasty

The incurable and pan-intestinal nature of Crohn’s disease has led to a more conservative operative approach. For patients with multiple strictures of the small bowel, intestinal conser- vation may be maximally achieved by surgically widening the narrowed segment by performing a strictureplasty. This technique was initially described by Katariya et al.⁵⁴for the suc- cessful treatment of tubercular small bowel strictures, and later used in strictures secondary to Crohn’s disease.⁵⁵ The procedure safely relieves obstructive symptoms^56–58with the operated patients demonstrating weight gain accompanied by improved food tolerance as well as discontinuation or reduction of steroid usage.⁵⁹ Moreover, patients undergoing strictureplasty alone are no more likely to require reoperation than those who undergo a concomitant resection,⁶⁰and reoperation rates after first and second operations are also similar.⁶¹ The situations for which strictureplasty is considered are as follows:

●Diffuse involvement of the small bowel with multiple strictures

●Stricture(s) in a patient who has undergone previous major resection(s) of small bowel (>100 cm)

●Rapid recurrence of Crohn’s disease manifested as obstruction

●Stricture in a patient with short bowel syndrome

●Nonphlegmonous fibrotic stricture

The contraindications to strictureplasty are as follows:

●Free or contained perforation of the small bowel

●Phlegmonous inflammation, internal fistula, or external fistula involving the affected site

●Multiple strictures within a short segment

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●Stricture in close proximity to a site chosen for resection

●Hypoalbuminemia (< 2.0 g/dL)

Multiple strictures in a patient with an albumin value < 2.5 g/dL, preoperative weight loss, or advanced age may be regarded by some as a situation in which strictureplasty should be avoided because of concerns of sepsis, but a proximal diverting stoma with multiple strictureplasties should be considered in this instance.⁵⁷Factors that do not seem to be associated with increased operative risk include perforative or phlegmonous disease remote from the strictureplasty site, steroid dosage, synchronous resection, number of strictureplasties, and length of stricture.

The length of the strictured segment dictates the type of strictureplasty technique used. Short (< 10 cm) strictures are best managed by a Heineke-Mikulicz type of strictureplasty, whereas medium length (10–20 cm) strictures can be cor- rected by a Finney-type strictureplasty. Long (> 20 cm) strictures are best managed by a side-to-side isoperistaltic strictureplasty.⁶² Regardless the technique, the bowel is incised along its antimesenteric margin extending 1–2 cm beyond the diseased segment, which is identified by the pres- ence of mesenteric ulceration. Biopsy of any suspicious mucosa is performed to exclude carcinoma^63–65and closure is achieved using an absorbable suture in a one- or two-layer manner. The mesentery at each of the strictureplasty sites is then labeled with metallic clips to allow discrimination between the multiple sites in the unlikely event that postoperative hemorrhage occurs. Selective mesenteric angiography with intraarterial vasopressin infusion will control most bleeding episodes, but the radio-opaque metal clips will help avoid the need to open each of the strictureplasty sites to localize the bleeding site if reoperation is required.⁶⁶

Many centers have used a Finney-type strictureplasty for recurrent terminal ileal disease with the anastomosis created between the terminal ileum and proximal colon.^67–70 Others have extrapolated this experience into patients undergoing their first operation for terminal ileal Crohn’s disease.⁷¹A long ileocolostomy is constructed encompassing the entirety of the diseased bowel. Interestingly, subsequent endoscopic and imaging studies have revealed complete morphologic disease regression.⁷¹

Resection

The basic principles of resection should be followed whether an open or laparoscopic approach is used, and include mobilization of both diseased intestine as well as sufficient nondiseased bowel to facilitate the subsequent creation of a tension-free anastomosis or construction of an ostomy. Extensive mobilization may facilitate operations for terminal ileal disease complicated by fused ileal loops or a phlegmonous mass adherent to matted loops of small bowel, omentum, or retroperitoneal structures. Delivery of the ascending colon and terminal ileum into the wound or to the

anterior abdominal wall enables separation of the involved intestinal loops and permits closer inspection to determine which segments require resection. Enteric fistulas often originate from diseased bowel that communicates with nondiseased intestine. Whereas the primary site usually requires resection, the secondarily affected bowel segments are typically treated by conservative wedge excision and simple closure of the resultant defect. The diseased bowel should be resected with conservative margins and the mesentery divided using the previously described methods.

Removal of enlarged mesenteric lymph nodes is not a goal of resectional surgery because this practice risks vascular injury without reducing the likelihood of recurrent disease.

The specimen should be opened after it has been delivered from the operative field to assure macroscopic disease-free resection margins.

A laparoscopic approach can be used for a variety of resectional procedures and is typically associated with longer procedure times, but shorter lengths of stay and briefer periods of recovery.^72–79 Although disease complicated by fistulas or phlegmons can prove challenging, experienced laparoscopic surgeons have been able to safely complete procedures in these instances without converting to a laparotomy.^80,81

After the diseased bowel has been resected, the surgeon must decide whether to create an end stoma, an anastomosis, or a diverted anastomosis. In general, an end stoma is desirable in patients who are critically ill, demonstrate fecal peritonitis, or have coagulopathy. An anastomosis can be safely created in most other instances assuming a few general principles are respected that include the following:

●Adequate blood supply must be assured

●Tension or torsion are unacceptable

●Luminal size needs to be equivalent

●The mesenteric defect should be closed

A temporary diverting stoma should be considered to protect the anastomosis in instances of incompletely drained sepsis, excessive blood loss during a long operation, or severe hypoalbuminemia (< 2.5 g/dL).

In operations for terminal ileal disease, the neoterminal ileum tends to be the usual site of disease recurrence.

Accordingly, the optimal anastomotic configuration and preferred materials are subject to debate.^82–84Some recent retrospective studies^85–88 and one prospective, randomized trial⁸⁹ suggest that larger side-to-side anastomoses are associated with a reduced risk for disease recurrence. Although many investigators have found no association between the materials used to create the anastomosis and morbidity rates,^86,87at least three studies^85,90,91have reported that a stapled anastomosis is safer than a hand-sewn anastomosis. Regardless, it is important to use a hand-sewn technique when the bowel wall is abnormally thickened because the stapling instruments are not designed to safely construct an anastomosis under these conditions.

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Specific Anatomic Locations

Terminal Ileum

Terminal ileal disease is defined as disease limited to the lower third of the small bowel with or without cecal involvement. Approximately 20% of patients with Crohn’s disease will express this phenotype, and usually present with symptoms suggestive of inflammation or obstruction. In the majority of cases, resection with construction of an ileal-ascending colon anastomosis is feasible and desirable. All nondiseased ascending colon should be preserved to provide the largest possible surface area for water absorption and to avoid a complex fistula involving retroperitoneal structures associated with recurrent disease involving an anastomosis that overlies the second portion of the duodenum. Alternatively, this is the situation in which some centers avoid bowel resection by creating a large Finney-type ileocolostomy.⁷¹

Terminal ileal disease with sparing of the ileocecal valve and cecum is ideally treated with resection and enteroenteros- tomy provided there is sufficient length (5–7 cm) of normal- appearing distal ileum after definitive ileal resection.

Preservation of the ileocecal valve helps to minimize the risk of postoperative diarrhea. In many instances, a hand-sewn anastomosis is preferred because the distal segment may be too short to accommodate a stapled anastomosis.

Colon

Colon disease is any colonic involvement between the cecum and rectum without small bowel or upper gastrointestinal disease. Nearly 40% of patients have this disease distribution, and often complain of inflammatory disease symptoms including abdominal cramping, bloody diarrhea, and urgency.

Persons presenting with segmental disease are best treated with segmental resection to protect against dehydration and electrolyte imbalances associated with loss of the large intestine’s physiologic role. In patients with disease limited to the ascending colon, the transverse colon is divided at the level of the middle colic vessels so that the mesenteric root naturally separates the anastomosis from the retroperitoneum, mini- mizing the risk for recurrent disease complicated by complex fistulas. Alternatively, a more proximal anastomosis may be wrapped with a pedicle of omentum, thereby preventing the anastomosis from lying in direct contact with the retroperitoneum. Disease involving the ascending and transverse colons is treated in a similar manner except an extended right colectomy is recommended because the mesentery of the ileum is more easily approximated to the mesentery of the sigmoid colon than the descending colon. Resection of the additional colonic segment avoids an internal hernia and does not adversely affect the functional outcome. Crohn’s disease of the transverse, descending, and sigmoid colons presents a situation in which segmental resection and colocolic or colorectal anastomosis is most frequently used. Segmental

resection is particularly ideal for older individuals (> 50 years) and patients with colitis who have previously undergone significant small bowel resection (> 30 cm). In both instances, preservation of the ileocecal valve and colonic absorptive surface may protect against diarrhea and dramatically improve the functional outcome. Resection with colo- proctostomy is used for these selected patients with left-sided disease, and a cecorectal anastomosis is constructed if the transverse colon is also involved. In younger patients and those without prior small bowel resection, the diseased segment and uninvolved proximal colon are resected and an ileosigmoid or ileorectal anastomosis is constructed.

Colonic strictureplasty has been described for short strictures and seems to be associated with a morbidity rate, risk for surgical recurrence, and postoperative quality of life comparable to that seen with resection.⁹² However, given the 7%

incidence of malignancy arising in a colonic stricture,⁹³some surgeons argue that resection should be exclusively encour- aged if all of the outcome measures are comparable.

Patients with extensive colonic involvement, relative rectal sparing, and adequate fecal continence without active anoperineal sepsis or compromised rectal compliance are candidates for colectomy with ileoproctostomy. Rectal compliance can be subjectively judged by distending the rectum during proctoscopy or objectively quantified with anorectal physiology testing; patients whose maximum tolerated rectal volume measures <150 mL will do poorly with an ileoproctostomy.⁹⁴ A rare patient presents with pan-colonic disease, significant upper rectal involvement, and sparing of the mid- and distal- rectum. Resection of all disease in this setting leaves an anastomosis only 6–8 cm above the anal verge, and is often associated with impaired function secondary to compromised compliance. Instead, an ileal J-pouch can be configured with 10-cm limbs and joined to the spared mid-rectum after subtotal proctocolectomy. Despite a likely increased disease recurrence compared with that seen with total proctocolectomy and ileostomy, the patient may enjoy several years without a stoma.

Patients with proctocolitis that warrants operative treatment usually require a total proctocolectomy with creation of an end ileostomy, especially those persons with colitis whose proctitis, sphincter dysfunction, or anoperineal sepsis is too severe for rectal preservation and ileoproctostomy. If proctectomy is required, the entirety of the rectum should be excised in a single or staged procedure because of the significant risk of cancer developing in the defunctioned rectal stump despite surveillance proctoscopy.⁹⁵An unhealed perineal wound that persists 6–12 months after endoanal proctectomy should be evaluated to exclude concomitant pyoderma gangrenosum, perineal sinus, enteroperineal fistula, and malignancy. A simple shallow wound will usually respond to repeated wound debridements and diligent wound care with vacuum-assisted closure system and split-thickness skin grafts providing additional benefit. Wounds complicated by a perineal sinus or enteroperineal fistula require more extensive procedures that often include omental, muscle, or myocutaneous flaps.^96–98

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One center has chosen to offer patients with Crohn’s disease isolated to the colon and rectum a total proctocolectomy with ileal pouch–anal anastomosis.⁹⁹They have reported that the rates of Crohn’s disease–related complications and pouch excision are 35% and 10%, respectively, after 10 years of follow-up. However, other reports suggest that 12%–29% and 45%–52% of patients with Crohn’s disease subsequently require pouch excision 5 and 10 years after restorative proctocolectomy, respectively.^100–103 Consequently, a restorative proctocolectomy is usually avoided in the setting of recognized Crohn’s disease, and is typically performed only as part of a controlled trial.

Ileocolon

Ileocolon disease is disease of the terminal ileum with colonic involvement noted distal to the cecum and proximal to the rectum. This disease phenotype occurs as often as terminal ileal disease, and the operative approach to these patients is similar to that already outlined for individuals with terminal ileal or colon disease. Specifically, the surgeon must conserve as much of the nondiseased colon as possible and avoid large mesenteric defects. This often requires the construction of two anastomoses, which does not seem to significantly increase operative morbidity.

Upper Gastrointestinal

Upper gastrointestinal disease is defined as any disease location proximal to the terminal ileum regardless of involvement in other areas, and represents the phenotype that is often the most difficult to manage because of its predilection for extensive disease and predominantly stricturing or penetrating behavior.

Small bowel disease proximal to the terminal ileum is often typified by several stenotic segments separated from one another by noninvolved bowel. These diseased segments range in length and can measure > 50 cm. The prognosis for Crohn’s disease diffusely involving the small bowel is significantly worse than that of localized disease.¹⁰⁴The operative options in a symptomatic patient with diffuse jejunoileitis include internal intestinal bypass, strictureplasty, and resection. Intestinal bypass is reproved by most clinicians because of concerns about bacterial overgrowth and malignant degen- eration. Resection risks immediate or future short bowel syndrome and is not generally recommended. An operation that consists of multiple strictureplasties is the procedure of choice using the previously discussed techniques to safely conserve small bowel and relieve symptoms secondary to luminal stenosis. The involved segments can be ignored only in the rare instance in which the diseased intestine appears to be inflamed without evidence of stricture or penetration.

Gastroduodenal Crohn’s disease is relatively rare, and the most common presenting complaints are upper abdominal pain and symptoms of duodenal obstruction. Endoscopy will

demonstrate macroscopic abnormalities in the majority of patients with the antrum most frequently involved.¹⁰⁵Isolated gastric disease is exceedingly rare and any reports of success- ful treatment are purely anecdotal.¹⁰⁶ For duodenal disease, medical therapy is the mainstay of treatment for inflammatory and penetrating disease, whereas strictures present a different challenge.¹⁰⁷Ulcer-like lesions are nonspecific, rarely cause stenosis, spontaneously regress, and are usually associated with other diseased sites. Contrarily, stenotic duodenal segments are typically unifocal and often respond poorly to medical management. Endoscopic balloon dilatation has been safely used to treat short duodenal strictures, and the procedure seems to be well tolerated while providing marked symptom relief.^108,109In the past, the operative management of duodenal strictures was restricted to gastrojejunostomy with or without concomitant vagotomy.^110,111Protagonists of truncal vagotomy cited the high risk for marginal ulceration whereas antagonists raised concerns about postoperative diarrhea. Recently, success with duodenal strictureplasty has been reported by several centers, and the technique seems to be the procedure of choice if the affected bowel is sufficiently supple and devoid of associated sepsis.^112–115

Anoperineum

Crohn’s disease will affect the anus or perineum in as many as 61%–80% of patients, and typically occurs with or following the onset of disease in other anatomic locations.¹¹⁶ Involvement of this area can manifest itself as a fissure, skin tag or hemorrhoid, cavitating ulcer, abscess or fistula, anovaginal fistula, anorectal stricture, or carcinoma. These comprise the basis of the accurately descriptive and compre- hensive Cardiff classification of anal Crohn’s disease,¹¹⁷ which has not been widely accepted by clinicians because it is perceived to be of minimal clinical relevance.^118,119 Whereas this classification system is solely based on the anatomic and pathologic features, scoring systems of disease activity have been proposed to complement this scheme.

These include the Perianal Crohn’s Disease Activity Index¹²⁰ and a newer system intended to evaluate and predict the outcome of operative management.¹²¹

The evaluation of anoperineal Crohn’s disease should include a regional examination as well as investigations to determine the extent and activity of disease located elsewhere through varied imaging and endoscopic studies. The regional examination may be significantly enhanced by assessment with fistulography,^122,123 endoanal ultrasonography,^124–126 magnetic resonance imaging,^127–130 or examination under anesthesia. Comparative reports suggest that these modalities are associated with comparable accuracy,^131,132 and overall accuracy might be best enhanced by combining the results of any two modalities.¹³¹

The first priority of therapy is to drain any associated sepsis through the insertion of drainage catheters with or without placement of noncutting setons. The second priority focuses

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on stabilizing the infectious component using antibiotic therapy such as metronidazole or ciprofloxacin. In addition, attempts at medical management of the disease process are initiated with immunomodulators and biologic agents;

5-aminosalicylic acid compounds and steroids provide little benefit. The third priority is optimization of quality of life through continued medical therapy or operative intervention used individually or in combination. Asymptomatic fissures, skin tags, or hemorrhoids are best ignored because surgical treatment may escalate the disease to a point in which proctectomy is eventually required.^52,133,134Cavitating ulcers may dramatically improve with operative debridement and intrale- sional steroid injection in combination with appropriately aggressive medical therapy.

Medical management typically includes antibiotics, immunomodulators, and biologic agents used individually or in combination. Metronidazole (20 mg/kg/day) prescribed for 6–8 weeks is associated with a 50%–56% healing rate, but nearly half of patients will experience disease exacerbation and paresthesias with dosage reduction.^135,136 Azathioprine (2–3 mg/kg/day) or 6-mercaptopurine (1.5 mg/kg/day) used alone heals 54% of fistulas compared with a 21% healing rate with placebo.¹³⁷Three doses of infliximab (5 mg/kg) delivered at 0, 2, and 6 weeks can promote fistula closure in 55%

of the patients, as compared with 13% of the patients treated with placebo, and the median length of time during which the fistula remains closed is 3 months.¹³⁸However, ciprofloxacin (1000 mg/day) in combination with infliximab tends to be more effective than infliximab alone,^132,139and re-treatment with infliximab every 8 weeks is more effective than placebo in maintaining fistula closure.^140,141 Lastly, concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes because of a reduction in the frequency of human anti- chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies.

The operative management of a perineal abscess or anoperineal fistula is predicated upon the patient’s baseline continence, complexity of the fistula, amount of sphincter encompassed by the fistula, and severity of rectal involvement. In a review of 21 retrospective studies that focused on fistulotomy for a low-lying fistula, the postoperative incontinence rates ranged from 0% to 50%, and 6% to 60% ultimately required a stoma.¹⁴²The initial healing rates in these studies ranged from 8% to 100%, with rates of 80%–100% in 13 of 21 studies, 60%–79% in five of 13 studies, and < 60%

in three of 21 studies. The clinical scenario best suited for fistulotomy is the continent patient with a simple, low-lying, posterior fistula without associated rectal disease.

Fistulotomy for an anterior fistula in this setting, especially in a woman, may risk incontinence. If fistulotomy is likely to cause a disturbance in fecal continence in a patient with minimal rectal inflammation, a rectal mucosal advancement flap is recommended. The healing rates with this procedure range

from 50% to 80% in series containing at least 20 patients,^143–145and a history of non-colon Crohn’s disease is a predictor of failure.¹⁴⁴ Alternatively, a chronic indwelling noncutting seton can be used in this setting. These setons are more ideally suited for chronic drainage of a fistula complicated by rectal inflammation, with proctectomy required in 0%–33% of patients reported in series composed of at least 20 patients.^146–150Fibrin sealant has also been used in these situations to obliterate the fistula tract, but success has been limited.^151–153In some patients, the severity of rectal inflammation or extent of perineal sepsis mandates endoanal proctectomy and permanent fecal diversion.^116,142

Anovaginal fistulas are more difficult to manage than anoperineal fistulas because they often originate from an anal ulcer and traverse a short distance through sometimes attenu- ated muscle. Fistulas that are not associated with an anal canal ulcer are usually managed with a rectal mucosal advancement flap if the rectal mucosa is noninflamed,^145,154or an anocuta- neous flap if the rectum is moderately diseased.¹⁵⁵For women with an anovaginal fistula and anal canal ulceration or severe proctitis, proctectomy is often required.

Many clinicians are beginning to use medical therapy in combination with operative treatment. They are reporting that an examination under anesthesia before infliximab treatment accelerates healing¹⁵⁶and infliximab treatment followed by definitive surgery has a beneficial additive effect in a multi- step treatment regimen for the management of complex anal fistulas arising in patients with active proctitis.¹⁵⁷

Strictures, which are typically situated at the top of the anorectal ring, should be ignored if asymptomatic or gently dilated if associated with complaints suggestive of outlet obstruction.^158,159 In selected patients with nondiseased rec- tums, a rectal sleeve advancement may be attempted.¹⁶⁰Both squamous cell carcinoma and adenocarcinoma can compli- cate preexisting anoperineal Crohn’s disease and persons with chronic involvement may require examinations under anesthesia with both directed and random biopsies of chronically indurated areas to exclude the possibility of malignant degen- eration.^95,161–164 If a cancer is identified, the lymph node drainage basin should be closely examined and an oncologic resection planned with or without perioperative adjuvant therapy depending on the histology and stage of the tumor.

Special Circumstances

Enteroparietal Abscess

An enteroparietal abscess is likely best treated by initial external drainage using a computed tomography (CT)-guided catheter if the cavity is accessible or, otherwise, by surgical drainage. Conversely, some surgeons suggest that the abscess is best managed by laparotomy, resection, and occasional anastomosis.¹⁶⁵ Antagonists of this approach cite their concerns about short bowel syndrome after laparotomy because