Chapter 33. Crohn's Disease

Crohn's disease is a chronic inflammatory condition of the gastrointestinal (GI) tract that can give rise to strictures, inflammatory masses, fistulas, abscesses, hemorrhage, and cancer. This disease commonly affects the small bowel, colon, rectum, or anus. Less commonly, it can also involve the stomach, esophagus, and mouth. Often, the disease will simultaneously affect multiple areas of the GI tract.

The cause of Crohn's disease is not known and there is no curative treatment. Current medical and surgical treatment is effective at controlling the disease, but even with optimal treatment recurrences and relapses are frequent. The combined approach of optimal medical treatment with timely and strategic surgical intervention offers the most effective management to patients affected by Crohn's disease. Crohn's disease, however, can be particularly challenging, as it has a myriad of manifestations and potential complications. Additionally, its course and response to therapy can be difficult to predict. To add to the overall complexity, there are many therapeutic options that must be tailored to each individual patient and to each site of involvement to achieve optimal outcomes.

Crohn's disease was fully recognized as a specific pathological entity in 1932 when Crohn et al first identified regional enteritis as a unique clinical entity.1 In retrospect, case descriptions of what appeared to be Crohn's disease date back to at least 1612, when Fabry reported on the death of a boy experiencing severe abdominal pain.2 Autopsy revealed a contracted ulcerated cecum and ileum with complete bowel obstruction. In 1761, Morgagni described a case of an inflamed ileum with perforation and thickened mesentery in a young man with a history of diarrhea and fever.3,4

It is unclear how common Crohn's disease might have been before 1932, as it is likely that cases of this disease occurring in an era of limited abdominal surgery may have been mistaken for other processes such as tumor or intestinal tuberculosis. In 1913, Sir Dalziel of Glasgow, Scotland, reported in the British Medical Journal on 13 patients and provided what is now recognized as a classic clinical and pathologic description of Crohn's disease.5 Although not often cited, Dalziel's description predates the one by Crohn et al, and some have argued that the disease should be known by the eponym “Dalziel-Crohn disease.”

After the report by Crohn et al, increased awareness of the disease led to a marked increase in reported cases in the 1930s through the 1950s. The general public's awareness of the disease increased when, in 1956, one of the most famous figures of the 20th century, President Dwight Eisenhower, was diagnosed with Crohn's disease at the terminal ileum. That same year, President Eisenhower underwent intestinal bypass surgery with the small intestine proximal to the area of disease anastomosed to the transverse colon.6 Following this operation, he remained relatively free of symptoms for the remainder of his life.7

Early in the history of Crohn's disease, optimal surgical management remained disputed. Initially, many thought that the disease was one of both the bowel and the mesentery and, much like malignancies, wide excision with radical dissection of the mesentery was believed to be the best way to provide for the optimal long-term outcome.8 It was also appreciated that diversion of the fecal stream was effective at decreasing active inflammation and ameliorating symptoms. Frequently performed in the 1940s and 1950s, bypass operations are now only rarely undertaken for Crohn's disease.9–11 Additionally, a greater understanding of the clinical course of Crohn's disease has led to more conservative resections, as it is appreciated that wide surgical margins of normal tissue and radical resection of the mesentery are not necessary to avoid early recurrence of disease.

In spite of the increased attention given to Crohn's disease of the ileum, Crohn's colitis was not widely recognized as a form of Crohn's disease until 1960 when Lockhart- Mummery and Morson firmly established the pathologic criteria for distinguishing Crohn's disease from idiopathic ulcerative colitis.12

After the original description of Crohn's disease in 1932, the number of reported cases increased greatly. Today it is estimated that the incidence of Crohn's disease in the United States is approximately four new cases per year for every 100,000 persons. This disease is chronic and patients live for many years with the ailment; thus the prevalence is much higher and is reported to be between 80 and 150 cases per 100,000 persons.13,14 The incidence of Crohn's disease increased rapidly from 1930 to at least the 1980s, but the incidence of new cases now appears to have stabilized.

The United States, Canada, and Europe have the highest incidence of Crohn's disease. It is much less common in Asia, South America, and Japan. Crohn's disease is believed to be uncommon in Africa, but accurate data regarding the incidence of inflammatory bowel disease in this region of the world are lacking. The peak age for contracting Crohn's disease is between 15 and 25 years. As such, Crohn's disease typically affects young adults, yet the disease can occur at almost any age. It should be noted, however, that Crohn's disease is very rare in children younger than 6 years.15

In the United States, the incidence of Crohn's disease is highest among Caucasians, low among blacks, and lowest among Hispanics and Asians. It is three to four times more common among ethnic Jews than non-Jewish whites. It also appears to be slightly more common in women than in men, although a slight male predominance has been reported in some populations.16

Familial clusters of Crohn's disease are not uncommon, with a 6- to 10-fold increase in the risk of this disease in first-degree relatives of those affected by this disease or its sister ailment, ulcerative colitis. Although familial aggregations are common, the distribution within families does not indicate a pattern of simple mendelian inheritance.

The etiology of Crohn's disease is not known. Many possible causes have been the subject of both speculation and investigation.4 Basic science research into the molecular biology of Crohn's disease has begun to give some better insight into the genetics of this condition, but much regarding its ultimate causes remains unclear.

It is known that Crohn's disease is an altered immune response that results in inflammation and destruction of intestinal tissues. It is not clear if this altered immune response is the result of a primary dysfunction in the gut-related immune system or whether an unknown pathological trigger induces an otherwise normal immune system to overreact. Most believe that Crohn's disease occurs in individuals with a genetic predisposition and that development of the disease is dependent on exposure to environmental triggers that start the pathological sequence that ultimately manifests as Crohn's disease.

To date, no specific primary defect in the systemic or mucosal immune system has been identified. Studies of intestinal transport mechanisms have demonstrated an increase in intestinal permeability in both Crohn's disease patients and their symptom-free first-degree relatives.17–21 This has led some to speculate that Crohn's disease is the result of an altered mucosal barrier function that allows abnormal interactions to take place between the multitude of antigenic substrates normally found in the gut lumen and the immunocompetent tissue of the submucosa.

As indicated by the observed familial aggregations and variability of risks among differing ethnic and racial groups, a genetic predisposition is very likely to have a major role in the etiology of Crohn's disease. The distribution of Crohn's disease within family aggregates is complex and defies classification with simple mendelian transmission of disease. Genetic linkage studies have identified susceptibility to Crohn's disease to the CARD15/NOD2 gene mapped to chromosome 16q12.22,23 CARD15 is a gene product related to innate immunity and it is preferentially expressed to Paneth's cells of the ileum.24,25 While the CARD15/NOD2 gene has been linked to susceptibility to Crohn's disease, the known mutations of CARD15 are neither necessary nor sufficient to contract this disease. Hence, it appears that the genetic relationship of CARD15/NOD2 to Crohn's disease is complex and still poorly understood.

The suspicion that infectious agents may play a role, either directly as a primary cause of Crohn's disease or indirectly as a trigger to stimulate a defective immune system, has generated much attention. This hypothesis has always found strength in the identification of noncaseating granulomas as the characteristic histopathologic lesion found in Crohn's specimens and in the isolation of Mycobacterium paratuberculosis from resected Crohn's disease specimens. This finding has been far from consistent, and even sensitive preliminary chain reaction studies have been unable to provide definitive evidence for the presence of M. paratuberculosis–specific DNA in Crohn's disease–affected segments of the bowel. Other infectious agents have been studied and shown not to be causative agents for Crohn's disease. These include measles virus, non-pylori Helicobacter species, Pseudomonas, and Listeria monocytogenes.26 To date, no single infectious agent has been consistently associated with Crohn's disease.

Although diet modification can ameliorate the symptoms of Crohn's disease, no dietary factor has been identified as its cause. Smoking, however, has been associated with the development of Crohn's disease, with smokers having a substantially higher risk for contracting this disease than nonsmokers.27–30 Additionally, smoking is known to exacerbate existing Crohn's disease and can accelerate its recurrence after resection.31,32 The component of cigarette smoke that is responsible for these deleterious effects on the clinical course of Crohn's disease is not known.

Histopathologic examination of Crohn's disease typically demonstrates transmural inflammation characterized by multiple lymphoid aggregates in a thickened submucosa. Lymphoid aggregates may extend beyond the mucosa and can be found within the muscularis propria.33 The presence of well-formed lymphoid aggregates in an edematous fibrotic submucosa is a classic histological feature of the disease. Another sentinel microscopic feature of Crohn's disease is the presence of noncaseating granulomas. Noncaseating granulomas are a valuable diagnostic feature of Crohn's disease, but they are seen in only 50% of resected specimens and are rarely seen on endoscopic biopsies. Additionally, the presence of granulomas does not correlate with disease activity, as areas of active inflammation are no more likely to contain granulomas than areas of quiescent disease.34

The earliest gross manifestations of Crohn's disease are the development of small mucosal ulcerations call aphthous ulcers.33 Aphthous ulcers appear as red spots or focal mucosal depressions and typically occur directly over submucosal lymphoid aggregates. As the inflammation progresses, the aphthous ulcers enlarge and become stellate. The enlarging ulcerations then coalesce to form longitudinal mucosal ulcerations. In Crohn's disease of the small bowel, these linear ulcerations always occur along the mesenteric aspect of the bowel lumen. Further progression leads to a serpiginous network of linear ulcerations that surround islands of edematous mucosa producing the classic “cobblestone” appearance. Mucosal ulcerations may penetrate through the submucosa to form intramural channels that can bore deeply into the bowel wall and create sinuses, abscesses, or fistulas.

The inflammation process progresses to extend through all layers of the bowel wall. The inflammation of Crohn's disease also involves the mesentery and regional lymph nodes such that the mesentery may become massively thickened. With early acute intestinal inflammation, the bowel wall is hyperemic and boggy. As the inflammation becomes chronic, fibrotic scarring develops and the bowel wall becomes thickened and leathery in texture.

The clinical presentation and symptoms of Crohn's disease vary greatly depending on the segment of intestine involved35 and the predominant features of the disease: stricturing, perforating, or inflammatory. In the next few paragraphs the influence of disease pattern and location is described.

Patterns of Disease

Crohn's disease can be categorized into three general manifestations: stricturing disease, perforating disease, and inflammatory disease.36 These three classes do not represent truly distinct forms of the disease; rather they are terms that are used to describe the predominant gross manifestation of the disease.37 It is typical for more than one pattern to occur in the same patient or even the same segment of intestine; even so, one pattern tends to predominate in most cases. It is generally the predominant pattern of disease that determines the clinical presentation and affects the therapeutic options.

Stricturing Pattern

Chronic inflammation of Crohn's disease results in the development of fibrotic scar tissue that constricts the intestinal lumen with cicatricial strictures, often referred to as “fibrostenotic lesions.” Patients with a stricturing pattern of this disease generally develop partial or complete intestinal obstruction, and hence their symptoms are primarily obstructive in nature. Being the result of scar tissue, fibrostenotic strictures are not reversible with medical therapy. Once fibrostenotic areas become symptomatic, significant improvement rarely occurs and surgical intervention is often required.

Perforating Pattern

Perforating Crohn's disease is characterized by the development of sinus tracts, fistulas, and abscesses. Penetrating sinus tracts develop from deep mucosal ulcerations. These sinus tracts penetrate through the muscularis propria and give rise to abscesses or to fistulas if they penetrate into surrounding structures. The term “perforating” disease can be misleading, as free perforation with spillage of intestinal contents into the abdominal cavity is not a common phenomenon with Crohn's disease. Inflammatory response around the advancing sinus tract typically results in adhesion to surrounding structures. The sinus usually bores through the area of adhesion such that abscess formation or fistulization to other structures occurs much more often than free perforation into the abdominal cavity. Typically, perforating disease is accompanied by a degree of stricture formation, but the fistula or abscess generated by the perforating component of the disease dominates the clinical picture.

Inflammatory Pattern

The inflammatory pattern of Crohn's disease is characterized by mucosal ulceration and bowel wall thickening. The edema that results from inflammation can lead to an adynamic segment of intestine and luminal narrowing. This pattern often gives rise to obstructive symptoms in the small intestine and diarrhea in the colon. Of the three patterns of Crohn's disease, the inflammatory pattern is much more likely to respond to medical therapy.

Location of Disease

Crohn's disease is a panintestinal condition that may affect any area from the mouth to the anus. The most commonly affected location is the terminal ileum, and one-fifth of all patients have more than one intestinal segment affected simultaneously.

Gastroduodenal and Esophageal Crohn's Disease

Crohn's disease of the upper GI tract gives rise to symptoms of nausea, vomiting, dysphagia, or odynophagia.38 Oral Crohn's disease usually manifests with aphthous ulcers in the hard palate that may cause discomfort, especially during mastication and deglutition. Esophageal Crohn's disease is uncommon in both children and adults, but it is believed to be more frequent in children than in adult patients.39 Esophageal involvement with Crohn's disease may be asymptomatic or may give rise to dysphagia or odynophagia. Esophageal Crohn's disease is associated with Crohn's disease elsewhere within the GI tract, as disease isolated to the esophagus is almost never seen. Symptomatic Crohn's disease of the stomach and duodenum is more common than disease of the esophagus, yet both locations are the least frequently involved by Crohn's disease. The symptoms are usually related to the obstructive nature of the disease with delayed gastric emptying, a sense of postprandial gastric fullness, nausea, and vomiting.

Crohn's Disease of the Small Intestine

Abdominal pain is the predominant symptom of small bowel Crohn's disease, as it occurs in 90% of cases.35 Abdominal pain may be the result of obstructive or septic complications. Pain related to partial obstruction is mostly postprandial and crampy in nature; pain from septic complications is typically steady and associated with fevers. Other common symptoms and findings include anorexia and weight loss. Weight loss is usually related to food avoidance, but in severe cases it may be the result of malabsorption. With disease of the small intestine, patients may develop a palpable mass, usually located in the right lower quadrant, related to an abscess or phlegmon in perforating disease or a thickened loop of intestine in obstructive disease. Evidence of fistulization to the skin, urinary bladder, or vagina may also be elicited with an accurate history and physical examination.

Crohn's Colitis

Crohn's involvement of the colon typically results in diarrhea that may or may not be bloody. Acute flares of Crohn's colitis are often associated with fever and abdominal pain that is often exacerbated by bowel movements. Stricturing of the colon with more advanced disease can give rise to colonic obstruction. Like Crohn's disease of the small intestine, Crohn's colitis can give rise to abscess formation and fistulas. Toxic megacolon can occur with Crohn's disease, but this severe complication is rare and less frequently seen than in ulcerative colitis.40

Perineal Crohn's Disease

Crohn's disease frequently affects the anal crypts and gives rise to perianal fistulas, abscesses, and anal strictures. Perineal Crohn's disease is also associated with hypertrophic perianal skin tags, fissures, and perineal scarring. Approximately 40% of patients will develop perineal manifestations of Crohn's disease.41,42 Anal Crohn's disease is almost always associated with Crohn's disease present elsewhere in the GI tract, although perianal disease can be the initial symptomatic manifestation of Crohn's disease.

Extraintestinal Crohn's Disease

In addition to the inflammation of the GI tract, a variety of extraintestinal manifestations can occur in Crohn's disease. These include ocular, dermatological, hepatobiliary, and joint disorders.43,44 Such extraintestinal manifestations occur in a minority of patients, but, when present, they produce symptoms that can be more severe than those of the primary intestinal disease. Ocular manifestations of Crohn's disease include uveitis and episcleritis.45 Cutaneous manifestations of Crohn's disease include erythema nodosum and pyoderma gangrenosum. Joint disorders such as ankylosing spondylitis, sacroiliitis, and seronegative polyarteritis can occur. Patients with Crohn's disease are also at risk for the development of primary sclerosing cholangitis. However, the risk for primary sclerosing cholangitis is much less in Crohn's disease patients than in patients who suffer from ulcerative colitis.

Peripheral polyarteritis, episcleritis, uveitis, and erythema nodosum typically correlate with the activity of intestinal Crohn's disease. These particular extraintestinal manifestations typically regress with complete surgical resection of the affected segment of intestine or with successful medical control of the intestinal inflammation. Pyoderma gangrenosum may also improve with treatment of primary intestinal disease, but available clinical data on this particular issue have not always been consistent. The clinical course of ankylosing spondylitis and primary sclerosing cholangitis tend to be independent of the level of disease activity within the intestine. Ankylosing spondylitis and primary sclerosing cholangitis do not improve with surgical resection of the Crohn's disease–affected bowel.

The onset of Crohn's disease is often insidious and many patients will experience some symptoms for months or even years before the diagnosis is made. The diagnosis of Crohn's disease is typically made by a thorough history and physical examination along with intestinal radiography and endoscopy. There is no specific laboratory test that is diagnostic for Crohn's disease. Advanced imaging studies such as computed tomography (CT) scan or magnetic resonance imaging (MRI) can assess or detect some of the complications and manifestations of Crohn's disease,46 but they are generally not useful in making the initial diagnosis of Crohn's disease.47

History and Physical Examination

The symptoms of Crohn's disease are dependent on the location of the involved segment, the pattern and the severity of disease, and the associated complications. As noted previously, in most cases the onset of disease is gradual with the most common complaints being intermittent abdominal pain, bloating, diarrhea, nausea, vomiting, weight loss, and fever.48 Patients may also have symptoms related to complications of the disease, including abdominal masses, pneumaturia, perianal pain and swelling, or skin rash. In some cases the onset of symptoms can be more sudden, with patients relating a history reminiscent of acute appendicitis. In these cases, pain in the right lower quadrant may have been present only for a few hours or days. However, a brief history of symptoms such as this is atypical.

In patients suspected of having Crohn's disease, a complete physical examination should include a thorough abdominal assessment. In cases of ileal Crohn's disease, tenderness is typically present in the right lower quadrant and occasionally a palpable mass is present. The oral cavity should be examined for the presence of aphthous ulcers. The perianal area should be examined for the presence of fistulas, abscesses, or enlarged skin tags. A digital rectal examination should assess for the presence of anal strictures, fissures, and rectal mucosal ulcerations. The skin in the extremities should be examined for erythema nodosum and pyoderma gangrenosum.

Imaging

Small Bowel Radiography

Upper intestinal contrast studies, either small bowel follow-through or enteroclysis, are the best means for assessing the small bowel for Crohn's disease.49–52 The radiographic abnormalities of small bowel Crohn's disease are often distinctive53 (Fig. 33-1). With early Crohn's disease, mucosal granulations with ulceration and nodularity can be identified. Thickening of the mucosal folds and edema of the bowel wall itself can be demonstrated as the disease progresses. With more advanced disease, cobblestoning becomes radiographically apparent. Small bowel contrast studies can also provide information regarding enlargement of the mesentery, as well as formation of an inflammatory mass or abscess. Such findings are demonstrated by a general mass effect separating and displacing contrast-filled loops of small intestine (see Fig. 33-1; Fig. 33-2). Small bowel contrast studies can demonstrate some of the complications of Crohn's disease, including high-grade strictures and fistulas. It is important to note, however, that small bowel radiography may not identify all such lesions. For instance, many enteric fistulas including ileosigmoid and ileovesical fistulas are not typically demonstrated on contrast radiography.54,55 Thus the absence of radiographic evidence for fistulization does not exclude this possibility. Additionally, small bowel studies may not demonstrate all the areas of disease with significant strictures.56 While small bowel radiographs may underestimate the extent of complicated Crohn's disease, small bowel studies performed by an experienced GI radiologist are very effective as a diagnostic tool for this disease. Besides their diagnostic utility, small bowel radiographs can also help in assessing the extent of the disease by identifying the location and length of involved and uninvolved intestine, and by recognizing whether the disease is continuous or discontinuous with skip lesions separated by areas of normal intestine (Fig. 33-3). Experienced radiologists can also assess areas of luminal narrowing and determine if they are the result of acute inflammatory swelling or are the result of fibrostenotic scar tissue. Such a distinction provides valuable information regarding the value of medical therapy versus early surgical intervention, as inflammatory stenoses are likely to respond to medical therapy while fibrotic strictures are best treated with surgery.

Endoscopy

Upper and lower endoscopies allow for inspection of mucosal disease and provide an opportunity for a biopsy for histologic evaluation. Upper endoscopy is useful in the diagnosis of mucosal lesions of the esophagus, stomach, and duodenum; it also easily identifies strictures and grades their severity. Characteristic colonoscopic features of Crohn's disease include aphthous ulcers, longitudinal ulcerations, skip lesions often with rectal sparing, pseudopolyps, and strictures.53 In many cases the terminal ileum can be entered and evaluated.

Capsule Endoscopy

Capsule endoscopy is a new tool in the diagnosis and evaluation of Crohn's disease.57,58 With this study, a small camera embedded within a capsule-size casing is swallowed and images from the camera are transmitted to a small electronic receiver worn by the patient. Images from the capsule endoscopy can detect subtle mucosal lesions that may not be apparent on small bowel x-rays. Prior to the capsule endoscopy, patients with suspected Crohn's disease should undergo a small bowel contrast study to exclude stricture formation, as the capsule may fail to pass through areas of narrowing and result in intestinal obstruction. The value of capsule endoscopy in the diagnosis of Crohn's disease has been recently evaluated in a prospective study from the Mayo clinic.59 This study compared capsule endoscopy, CT enterography (CTE), ileocolonoscopy, and small bowel follow-through in the diagnosis of small bowel Crohn's disease in a prospective blinded trial and found that the sensitivity of capsule endoscopy was not significantly different from that of the other tests. A meta-analysis of capsule endoscopy studies comparing it to CTE suggested that the prevalence of abnormalities detected on capsule endoscopy was 38% higher than that of CTE.60 However, this value was significantly higher than CTE only for the subgroup of patients with known Crohn's disease. The need for a preliminary small bowel contrast study to detect asymptomatic partial small bowel obstruction before the capsule endoscopy can be safely performed, and the lack of a clear advantage over other imaging studies limits the utility of capsule endoscopy as a first-line test in Crohn's disease and perhaps reserves this study for those cases in which there is a substantial diagnostic uncertainty.

Computed Tomography

Computed tomography (CT) findings of uncomplicated Crohn's disease are nonspecific, and routine CT is not necessary for the diagnosis of Crohn's disease. CT, however, is very useful in identifying the complications associated with Crohn's disease.61,62 Specifically, CT can readily identify thickened and dilated intestinal loops, inflammatory masses, abscesses, and hydronephrosis resulting from retroperitoneal fibrosis and ureteral narrowing. CT scans are also the most sensitive indicator of an enterovesical fistula as suggested by the presence of air within the urinary bladder. More recently, cross-sectional imaging techniques have assumed an increasing role in the imaging of patients with Crohn's disease. Using ileoscopy and biopsy of the terminal ileum as reference to evaluate the performance characteristics of cross-sectional enterography,63 CTE has been shown to have a higher sensitivity than barium small bowel follow-through.59 These findings have convinced many to use CTE combined with ileocolonoscopy as a first-line test for the diagnosis and staging of Crohn's disease.59 CTE exploits the high spatial resolution and speed of modern CT, using large volumes of neutral oral contrast agents to generate detailed images of the small bowel wall, lumen, and mesentery.64 In addition, CTE has several potential advantages over barium studies in the identification of fistulizing disease. Unlike traditional fistulography, CTE does not suffer from superimposition of bowel loops and displays the mesentery, retroperitoneal, and abdominal wall musculature, typically involved by fistulas. Sinus tracts and abscesses can also be readily characterized by CTE.64 However, recent concerns about radiation-induced cancer arising from medically related CT65 have stimulated a reassessment of the role of CTE in young Crohn's disease patients66 and have encouraged the use of magnetic resonance enterography (MRE). MRE has the advantages of CTE, such as the ability to show the entire small bowel, detect transmural inflammation, grade the severity of inflammation, and detect extracolonic inflammation, but it does not require ionizing radiation. In a recent study, MRE has been shown to have similar sensitivities to CTE for detecting active small bowel inflammation, although image quality across the study cohort was better with CTE.67 Therefore, MRE should be considered an alternative to CTE when radiation exposure is a concern to provide complementary information to ileocolonoscopy in the diagnosis of Crohn's disease.

The differential diagnosis for small bowel Crohn's disease includes irritable bowel syndrome, acute appendicitis, intestinal ischemia, pelvic inflammatory disease, endometriosis, and gynecological malignancies. Other disorders that are within the differential diagnosis include radiation enteritis, Yersinia infections, intestinal injury from nonsteroidal anti-inflammatory agents, intestinal tuberculosis, and small bowel tumors.

Among the most important ailments to consider are small bowel malignancy and intestinal tuberculosis. In patients in whom small bowel malignancy is suspected, resection should be undertaken to make certain the diagnosis. The exclusion of intestinal tuberculosis can be difficult, as the inflammation and stricturing of the terminal ileum can occur in a manner that closely mimics Crohn's disease. The patient should be assessed for exposure to tuberculosis and screened for tuberculosis with a purified protein derivative skin test. Chest radiography should also be considered. Even when the diagnosis of Crohn's disease is certain, patients who coincidentally are found to also have latent tuberculosis should be treated in accordance with American Thoracic Society guidelines prior to the initiation of immunosuppressive therapy for management of their Crohn's disease.68

Intestinal injury from nonsteroidal anti-inflammatory drugs (NSAIDs) can result in focal enteritis with ulceration and stricture formation.69,70 These manifestations can be very difficult to distinguish from Crohn's disease of the small bowel. This rare side effect from the very commonly used NSAIDs often requires resection or biopsy to confirm the diagnosis.

For Crohn's disease of the colon, the differential diagnosis includes ulcerative colitis, infectious colitis, collagenous colitis, ischemic colitis, diverticular disease, Behçet's disease, colonic neoplasm, solitary rectal ulcer syndrome, and NSAID colopathy.

The entity that is most difficult to distinguish from Crohn's colitis is ulcerative colitis. The diagnosis of ulcerative colitis cannot be made with absolute certainty, as it is possible for Crohn's disease of the colon to reproduce all the features of ulcerative colitis. It is only when features appear that are unique to Crohn's disease that the diagnosis of Crohn's disease can be made. Such distinguishing features of Crohn's disease include small bowel involvement, perianal disease, skip lesions, transmural inflammation, fistulas, abscesses, and noncaseating granulomas. After a complete history and physical examination complemented by appropriate radiological, endoscopic, and humoral studies, Crohn's and ulcerative colitis can be distinguished with a high degree of confidence in as many as 85–90% of cases, yet in the remaining 10–15% of cases the differential diagnosis will remain indeterminate. This has major bearing on the surgical options available for such patients.

The goal of medical treatment of Crohn's disease is to provide long-lasting symptomatic relief while avoiding excessive morbidity. Crohn's disease cannot be cured by medical treatment, but it may afford long periods of disease control and avoidance of surgical intervention. Thus it is important that the surgeon have an understanding of the basics of medical therapy for Crohn's disease. Selecting the optimal medical treatment for each individual requires experience and special expertise because of the variable course of the disease, the myriad of different clinical presentations and associated complications, and the desire to optimize medical treatment for each clinical situation.

Corticosteroids

Corticosteroids are the most effective agents for controlling acute exacerbations of Crohn's disease, but their use is limited due to the risk of serious side effects. The majority of patients with active small bowel Crohn's disease will experience clinical remission with a short course of oral prednisone given in a dose between 0.25 and 0.5 mg/kg/d.71 For patients unable to take oral medications, methylprednisolone can be administered in the adult at doses of 40–60 mg given as a daily infusion.72 Common side effects from corticosteroids include diabetes, osteoporosis, cataracts, osteonecrosis, myopathy, psychosis, opportunistic infections, and adrenal suppression. The risks for these side effects are related to both the dose and the duration of steroid therapy.

5-Aminosalicylic Acid

The aminosalicylates as a group of medications include sulfasalazine and 5-aminosalicylic acid (5-ASA) derivatives. The exact mechanism of action for these agents is not clear, but 5-ASA is thought to function through various pathways.73 5-ASA compounds inhibit leukotriene production by inhibition of 5-lipooxygenase activity. 5-ASA also inhibits the production of interleukin-1 and tumor necrosis factor (TNF). 5-ASA compounds are weak inhibitors of cyclooxygenase (COX) activity, and it is unlikely that they act through the inhibition of prostaglandin production. Aminosalicylates are effective in the treatment of mild to moderate Crohn's disease. 5-ASA given in a controlled-release preparation is also effective as maintenance therapy to prevent recurrence after a flare of disease has been effectively managed either medically or surgically.74–77

Aminosalicylates come in a variety of preparations, each designed to deliver the drug in a topical fashion to the affected segments of intestine.78 For instance, Asacol (mesalamine) is 5-ASA contained within a pH-dependent resin designed to release the drug in the terminal ileum and colon where the pH is typically greater than 7.0. Pentasa (mesalamine) is 5-ASA contained within ethylcellulose-coated microgranules designed to slowly release the active compound throughout the entire small bowel and colon. Colazal (balsalazide) is 5-ASA bound to an inert carrier by an AZO bond. This bond is broken by bacterial enzymes found within the colon, releasing the active 5-ASA compound to the colonic mucosa.

It is important to emphasize that mesalamine and its derivatives should not be confused with acetylsalicylic acid (aspirin) and other NSAIDs. Unlike 5-ASA compounds, classic NSAIDs are powerful inhibitors of COX-1 and COX-2. Many clinicians have had concerns that NSAIDs may exacerbate Crohn's disease.79–81 Although the basis of these concerns has been challenged,82–84 it is recommended that patients with Crohn's disease avoid NSAIDs and use alternative medications when appropriate.

Immunomodulators (Azathioprine and 6-Mercaptopurine)

Azathioprine and 6-mercaptopurine (6-MP) are immunosuppressive agents that inhibit cytotoxic T-cell and natural killer cell function. These agents are effective in treating mild to moderate Crohn's disease.72,85 Azathioprine given at 2.0–2.5 mg/kg/d or 6-MP in doses of 1.0–1.5 mg/kg/d will result in a 50–60% response rate in patients with active Crohn's disease.72,86 Both 6-MP and azathioprine are also effective in maintaining remission following surgery or successful medical management.75

Infliximab

Infliximab is a chimeric mouse-human monoclonal antibody to TNF. TNF is a proinflammatory cytokine that is believed to be important in the pathophysiology of Crohn's disease. Infliximab binds to both free and membrane-bound TNF and prevents TNF from binding to its cell surface receptors.73 Clinical trials have demonstrated an 80% response rate with a single dose of infliximab.87,88 It is important to note that the doses and dosing intervals of infliximab must be individualized, but a typical regimen would include 5 mg/kg of infliximab given IV at weeks 0, 2, and 6, with a dose of 5 mg/kg every 8 weeks thereafter. Because infliximab is a potent immunosuppressive agent, concerns have been raised about the risk for poor wound healing and postoperative septic complications. Current available data on the perioperative risks associated with infliximab are somewhat conflicting. Early studies have suggested that preoperative infliximab use does not appear to increase the risk for postoperative complications following abdominal surgery for Crohn's disease.89–91 More recently, however, a study from the Cleveland clinic demonstrated an increased risk for infectious complications and intra-abdominal abscesses in Crohn's disease patients undergoing surgery who received infliximab.92 This study also found that the presence of adverting stoma significantly decreased the risk for septic complications in patients who had been treated with infliximab.

Other Medical Therapies

Other agents that are used with varying success in the treatment of Crohn's disease include methotrexate, metronidazole, cyclosporine, tacrolimus, and thalidomide. With the exception of metronidazole, each one of these agents requires a complete and sophisticated knowledge of appropriate dosing, side effects, and therapeutic efficacy, which is beyond the scope of this chapter. Metronidazole is indicated in the maintenance therapy of chronic perineal septic complications and in the treatment of bacterial overgrowth associated with chronic obstructive disease of the small bowel. Long-term side effects include peripheral paresthesias, which are usually transient if the drug is discontinued as soon as they are experienced.

Similarly to medical treatment, the goal of surgical treatment of Crohn's disease is to provide long-lasting symptomatic relief while avoiding excessive morbidity. Crohn's disease cannot be cured by surgical therapy, and thus surgery, like medical treatment, should be considered palliative. Complete extirpation of disease should not be the primary goal of surgery, as this does not produce cure and is frequently counterproductive. Rather, treatment of complications and palliation of symptoms while avoiding excessive loss of intestine should be the main aims of surgical treatment.

To avoid excessive loss of intestine, nonresectional techniques such as strictureplasty may be required. Additionally, optimal surgical therapy may require leaving behind segments of the intestinal tract affected by mild but asymptomatic disease with resection of only the areas of severe and symptomatic Crohn's disease. The best surgical strategy for each patient with Crohn's disease takes into account the indications for surgical treatment and the natural history of the disease, with its high risk for recurrence and the need for repeated surgeries.

Indications for Surgery

Failure of Medical Treatment

The failure to respond to medical treatment or the inability to tolerate effective therapy are the most common indications for surgical treatment of Crohn's disease.93 Some patients may respond to the initial medical therapy only to rapidly relapse with tapering of the medical treatment. For example, some patients respond well to steroid therapy but become steroid-dependent as tapering of the steroid dose results in recurrent symptoms. Because of the severe complications that are virtually inevitable with prolonged steroid treatment, surgery is warranted if the patient cannot be weaned from systemic steroids within 3–6 months. The occurrence of complications related to the medical treatment or the progression of disease while on maximal medical treatment represent additional indications for surgical treatment.

Intestinal Obstruction

Partial or complete intestinal obstruction is a common indication for operation for Crohn's disease.94 The clinical presentation of chronic partial small bowel obstruction is much more typical than complete obstruction. Patients with chronic partial small bowel obstruction due to Crohn's disease may experience postprandial cramps, abdominal distension, borborygmi, and weight loss. To avoid symptoms, many patients will restrict their diets to soft foods or even liquids. If partial obstruction from Crohn's disease is primarily due to acute inflammation and bowel wall thickening, initial medical therapy is warranted. If, however, the obstructive symptoms are due to high-grade fibrostenotic lesions, medical treatment will not reverse these lesions and surgery is indicated.

When complete intestinal obstruction occurs, initial conservative treatment with nasogastric decompression and intravenous hydration is warranted.34,95 Intravenous steroids are also administered. This allows for decompression of acutely distended and edematous bowel and, in most cases, for resolution of the complete obstruction. Resolution of the complete obstruction should not lead the physician to attempt treating the patient with continuing medical therapy. Patients with complete obstruction who respond well to initial conservative therapy are at high risk for persistent or recurrent symptoms of obstruction and are best managed with surgery once adequate decompression is achieved. The surgery can be performed under elective and safer conditions after appropriate bowel preparation.

Fistulas

Intestinal fistulas occur in one-third of Crohn's disease patients.54 Intestinal fistulas, however, are the primary indication for surgery in only a minority of patients. Thus the presence of an intestinal fistula is not in and of itself an indication for surgery.96,97 In general, intestinal fistulas are the primary indication for surgical treatment if they connect with the genitourinary tract, or if their drainage is cause for personal embarrassment and discomfort (enterocutaneous and enterovaginal fistulas), or if they create a bypass of such magnitude as to cause intestinal malabsorption.

Fistulas between the ileum and the urinary bladder often result in recurrent urinary tract infections, including pyelonephritis. While it is not mandatory to operate on all cases of enterovesical fistulas, surgery is warranted to avoid deterioration of renal function with recurrent infections or if symptoms persist in spite of appropriate medical therapy.

Enterocutaneous fistulas and enterovaginal fistulas often cause physical discomfort and personal embarrassment. A trial of medical therapy may be elected for enterocutaneous and enterovaginal fistulas, but most such cases will require surgery.98,99

Occasionally, an enteroenteric fistula can result in significant symptoms. Fistulas that result in functional bypass of a major intestinal segment can result in malabsorption or diarrhea. These fistulas need to be addressed surgically.

Abscesses and Inflammatory Masses

Intra-abdominal abscesses and inflammatory masses occur less frequently than fistulas but are more often an indication for operative intervention.100 Small abscesses seen on CT may warrant a trial of treatment with antibiotics, but almost all intra-abdominal abscesses will require drainage. In a vast majority of cases, Crohn's abscesses can be drained percutaneously with CT or ultrasound guidance.101–103 The rare large intraloop abscesses may require open surgical drainage. Often, in such cases the abscess can be completely extirpated with the resection of the diseased segment of intestine.

Crohn's abscesses usually originate from a severely diseased segment of bowel. A Crohn's abscess that has been drained percutaneously is very likely to recur or result in an enterocutaneous fistula, and surgical resection is often advised even after successful drainage.103 Inflammatory masses indicate severe disease and often harbor an unrecognized abscess.100 Thus, inflammatory masses that do not readily respond to antibiotic treatment should be considered for surgical treatment.

Perforation

Free perforation is a rare complication of Crohn's disease occurring in fewer than 1% of cases.104 When this complication occurs, it is an obvious indication for urgent operation. The diagnosis of free perforation is made by detecting a sudden change in the patient's symptoms along with the development of the physical findings of peritonitis or the identification of free intraperitoneal air as demonstrated on plain x-rays or CT scans. The use of immunosuppressants and glucocorticosteroids can blunt many of the physical findings of acute perforation; therefore the index of suspicion for perforation must be higher in immunocompromised patients who complain of worsening symptoms or show early signs of sepsis. Most patients, however, will demonstrate classic signs of peritonitis with rebound, rigidity, guarding, and loss of bowel sounds.

Hemorrhage

Hemorrhage is an uncommon complication from Crohn's disease. Massive GI hemorrhage is rare and occurs more frequently from Crohn's colitis than in small bowel Crohn's disease.105 Hemorrhage from small bowel Crohn's disease tends to be indolent with episodic or chronic bleeding requiring intermittent transfusions, but it rarely requires emergent surgery. Localization of the site of bleeding is accomplished by angiography in the presence of brisk bleeding; otherwise colonoscopy can be attempted preoperatively to localize a source of lower GI hemorrhage. Intraoperative localization can be aided by enteroscopy or colonoscopy.

When severe hemorrhage occurs in Crohn's disease, it is usually due to erosion of a single vessel by a deep ulcer or fissure. Recurrent bleeding in an area of small bowel disease is a common phenomenon, and it has been argued that even after control of hemorrhage from small bowel Crohn's disease with conservative management, elective resection of the areas of Crohn's disease should be undertaken to prevent recurrent bleeding.

Patients with Crohn's disease are also at risk for bleeding from peptic ulcer disease. This is particularly true for patients receiving corticosteroid therapy. For this reason, Crohn's disease patients who develop GI bleeding should undergo an upper endoscopy to rule out gastric or duodenal ulcers.

Cancer or Suspicion of Cancer

The presence of Crohn's disease increases the risk of adenocarcinoma of the colon and small intestine.106 The diagnosis of adenocarcinoma of the small bowel is difficult because symptoms and radiographic findings of small bowel malignancy can be similar to those of the underlying Crohn's disease. Male patients and patients with long-standing disease appear to be at increased risk for small bowel adenocarcinoma.106 Defunctionalized segments of bowel also seem to be at particular risk for malignancy.107 For this reason, bypass surgery should be avoided for Crohn's disease of the small intestine, and defunctionalized rectal stumps should either be restored to their function or excised.

Adenocarcinoma of the small intestine should be suspected in any patient with long-standing disease whose symptoms of obstruction progress after a lengthy quiescent period. Surveillance for colonic malignancies can be undertaken by colonoscopy with random mucosal biopsy. If dysplasia is encountered, resection of the areas of Crohn's disease should be considered.108,109 Areas of stricture formation within the colon should be closely examined and biopsied. Strictures that are too narrow to allow passage of the colonoscope or cannot be adequately assessed colonoscopically should be resected.

Growth Retardation

Growth retardation occurs in a quarter of children affected by Crohn's disease. Although steroid treatment may delay growth in children, the major cause of growth retardation in Crohn's disease patients is the malnutrition associated with active intestinal disease.110,111

Preoperative Preparation and Evaluation

A complete assessment of the GI tract is required prior to surgery. Full delineation of the extent of disease and associated complications is necessary to plan for the optimal surgical strategies.

Assessment of the small intestine can be performed with a small bowel follow-through, an enteroclysis study or a CTE. The colon and rectum are best evaluated by colonoscopy. Barium enema studies can also be used to evaluate for colonic disease, particularly in cases in which strictures do not allow passage of the colonoscope. If the patient has had a previous resection of the ileocecal valve, a contrast enema can be a useful means of evaluating the ileocolonic anastomosis and the preanastomotic segment for recurrent disease. If an abscess, fistula or inflammatory mass is suspected, a CT scan of the abdomen and pelvis with both oral and IV contrast should be obtained. CTE combined with ileocolonoscopy is used by many as a first-line test for the staging of Crohn's disease.59 In patients in whom urgent surgery is required, a full evaluation of the GI tract prior to surgery may not be feasible. In these cases, evaluation of disease must be accomplished intraoperatively, and both the patient and the surgeon must be prepared for a wide variety of surgical possibilities.

As with preparation for any major operation, metabolic derangements must be treated prior to surgery. Fluid and electrolyte abnormalities must be corrected. Patients with profound anemia need to be transfused and coagulopathies must be addressed. Patients with cardiovascular or pulmonary disease should have the condition stabilized and their functional capacity optimized prior to operation. Most patients with Crohn's disease will not require preoperative parenteral nutrition, as most suffer from only a minor degree of malnutrition. There are rare cases, however, in which the nutritional status of the patient has been so severely compromised that they benefit from several weeks of bowel rest, hyperalimentation, and ongoing medical treatment before operation.

The absolute need for mechanical bowel preparation is controversial.112–114 Traditionally mechanical bowel preparations have been an unquestioned standard to lessen the risks of sepsis and to allow for a safe anastomosis. Recently these advantages have been challenged.112,113 Even so, it is common practice for patients undergoing intestinal resection for Crohn's disease to undergo a complete mechanical bowel preparation with either polyethylene glycol or sodium phosphate. Should the patient be unable to tolerate oral preparations, enemas can be utilized. Prophylactic broad-spectrum antibiotics are administered perioperatively,115 and stress dose steroids must be given to patients suspected of hypothalamic-pituitary-adrenal suppression. If feasible, well-contained intra-abdominal abscesses should be drained percutaneously prior to surgery. If an abdominal stoma is contemplated, the optimal site for the stoma location should be marked preoperatively. In patients in whom preoperative CT scan suggests significant inflammation in proximity to the ureters, preoperative ureteral stenting can be helpful.

Some have suggested that, to improve the safety of surgery for Crohn's disease, anti-inflammatory Crohn's medication should be either lowered or discontinued prior to elective surgery. Recent studies, however, have shown that preoperative use of steroids and antimetabolites does not appear to affect the perioperative morbidity, and hence discontinuation of these medications is not likely to result in significant benefit. Methotrexate and infliximab, on the other hand, are two medications that may be worth discontinuing at least 2 weeks and 2–3 months, respectively, prior to surgery. Laboratory studies have shown decreased wound healing with methotrexate,116 and clinical data to evaluate the safety of methotrexate in patients undergoing bowel resection with anastomosis are lacking. A recent study from the Cleveland clinic has demonstrated an increased risk for infectious complications and intra-abdominal abscesses after recent treatment with infliximab.92 If surgical treatment is necessary within 2 months after an infliximab infusion, consideration should be given to postpone reestablishment of the GI continuity or to protecting a newly fashioned anastomosis with a diverting stoma.

Surgical Options

Intestinal Resection

Intestinal resection with anastomosis or stoma formation is the most common surgical procedure performed for the treatment of Crohn's disease. Most cases of Crohn's disease require only limited resections that are generally well tolerated and do not place these patients at risk for short bowel syndrome. Cumulative clinical data including randomized studies have indicated that resection of Crohn's disease need only encompass the grossly apparent disease, as wider resections do not improve the outcome after surgery.117–120 Microscopic resection margins that are grossly normal but demonstrate microscopic evidence for Crohn's activity do not result in early recurrence or other complications. Hence, intraoperative frozen section of the resection margins is not necessary.121

The extent of mesenteric dissection does not affect the long-term results either; hence the mesentery can be divided at the most advantageous level. Division of the thickened mesentery of small bowel Crohn's disease can be the most challenging aspect of the procedure. Identification and isolation of individual mesenteric vessels is not feasible with a thickened Crohn's mesentery. Although many approaches to this problem have been described, a common technique is to apply overlapping clamps on either side of the intended line of transection. The mesentery is then divided between the clamps, and the tissue contained within the clamps is suture-ligated (Fig. 33-4). In severe cases, a vascular clamp may be used at the root of the small bowel mesentery to obtain proximal control: mattress sutures may then need to be applied to the cut edge of the mesentery to control bleeding. The use of tissue welding devices such as the LigaSure device (Valleylab, Boulder, CO) can be useful for sealing vessels within the thickened mesentery. Even with these devices, mattress sutures in the mesentery are commonly needed for complete hemostasis. In spite of the difficulty dealing with the thickened and often hyperemic mesentery, resection can be performed with a low risk for postoperative hemorrhage and the risk for postoperative hemoperitoneum requiring reexploration has been reported to be less than 0.5%.93

Anastomosis

There is no overriding consensus regarding the optimal technique for intestinal anastomosis in Crohn's disease.74,122–126 It is well established that recurrent Crohn's disease after resection of terminal ileal disease is most likely to occur at the ileocolonic anastomosis or at the preanastomotic ileum. It has been proposed that large-caliber anastomoses require a longer period to stricture down to a critical diameter that becomes symptomatic. The argument is made that a longer side-to-side anastomosis may be beneficial over an end-to-end or end-to-side anastomosis.125 To date, however, clinical data do not indicate a benefit for one particular intestinal configuration over another.124 Intestinal anastomosis for Crohn's disease cases can be fashioned with a stapling device or may be hand-sutured. When performed under selective conditions, resection with primary anastomosis for Crohn's disease can be performed with a high degree of safety and small bowel anastomotic dehiscence rates can be kept under 1%.93 In the presence of sepsis, severe scarring, malnutrition, or recent use of methotrexate or infliximab, it may be wise to protect the anastomosis with a proximal loop stoma or to forego the anastomosis altogether and bring out an end stoma at the point of resection.

Stoma Formation

Permanent stomas are required for the surgical treatment of Crohn's proctitis and occasionally required for the management of severe, unrelenting perianal disease. Temporary stomas are much more common and typically used as a means of protecting a distal anastomosis or when an anastomosis is not advisable.

If an ileostomy or colostomy is contemplated, selection of the optimal placement of the stoma should be determined preoperatively.127 Proper stoma location is critical to achieve a satisfactory stoma. It is preferable to locate the ileostomy over the left or right rectus abdominis muscle on a flat area away from deep skin folds and bony prominences.128 The surface of the abdomen must be evaluated in both the sitting and standing positions, as this will often demonstrate skin folds and creases not evident in the supine position. Attention must be paid to determining the level of the patient's belt line and every effort is made to place the stoma below it. Once the optimal position of the stoma has been identified, it is marked in a manner that will remain visible at the time of surgery.

Complications related to intestinal stomas are common. They include peristomal hernia, prolapse, and stricture. Peristomal hernia is the most common ostomy-related complication. It can be anticipated that approximately 25% of patients with a permanent stoma will require surgical revision of their ostomy to deal with one or more of these complications.129

Bypass Procedures

Bypass procedures became popular in the 1940s and 1950s once physicians and surgeons realized that aggressive enterectomies did not reduce the incidence of recurrence and were fraught with the development of short gut syndrome. Initially conceived to bypass an area of stricture or obstruction, the use of bypass procedures was eventually extended to Crohn's disease complicated by septic complications. Increased experience with bypass procedures revealed that persistence of disease put patients at risk of persistent sepsis and eventually neoplastic transformation. Because of these complications, bypass procedures were supplanted by limited intestinal resection as the main surgical option in the late 1960s in all intestinal districts except the duodenum, where a simple side-to-side retrocolic gastrojejunostomy adequately relieves the obstructive symptoms. With increased experience and confidence in the performance of strictureplasty, duodenal disease is nowadays more and more commonly handled with strictureplasties.

Strictureplasty

Strictureplasty techniques have gained popularity as a safe and effective means of treating stricturing Crohn's disease of the small intestine without resorting to lengthy resections. Strictureplasties are best used when resection would otherwise result in loss of a lengthy segment of bowel and thus place the patient at risk for short bowel syndrome. This would include cases with long segments of stricturing disease and patients with multiple prior resections. They are also indicated when they offer a simpler alternative to resection, such as in short recurrent disease at a previous ileocolic or enteroenteric anastomosis.

It is generally accepted that the advantage conferred by a strictureplasty over a resection in the preservation of intestinal absorptive capacity is mainly due to the sparing of normal areas in between strictures that would be otherwise sacrificed. Although this is true, there is increased evidence that the acuity of the disease decreases at the site of the strictureplasty and the disease becomes quiescent.130 Whether this correlates with a simultaneous restoration of absorptive function has not yet been established.

The most commonly performed strictureplasty is the Heinecke-Mikulicz strictureplasty.131–133 The Heinecke-Mikulicz is named after the pyloroplasty technique from which this procedure is derived. With the Heinecke-Mikulicz strictureplasty, a longitudinal incision is made along the antimesenteric border of the stricture (Fig. 33-5). This incision should extend for 1–2 cm into the normal elastic bowel on either side of the stricture. Once the enterotomy is made, the area of the stricture should be closely examined. If there is any concern that the stricture may harbor a malignancy, a biopsy with frozen section must be obtained. Complete hemostasis should be obtained with precise application of electrocautery. The longitudinal enterotomy of the Heinecke-Mikulicz strictureplasty is then closed in a transverse fashion. The closure can be accomplished with either single- or double-layered sutures. The Heinecke-Mikulicz stricture technique is appropriate for short-segment strictures of 2–5 cm in length.

The Finney strictureplasty, also named for the pyloroplasty technique from which this approach is derived, can be used for strictures up to 15 cm in length.131 With the Finney strictureplasty technique, the strictured segment is folded onto itself in a U-shape134 (Fig. 33-6). A row of seromuscular sutures is placed between the two arms of the U, and a longitudinal U-shaped enterotomy is then made paralleling the row of sutures. The mucosal surface is examined and biopsies are taken as necessary. Hemostasis is obtained with electrocautery. Full-thickness sutures are then placed beginning at the posterior wall of the apex of the strictureplasty and then continued down to approximate the proximal and distal ends of the enterotomy. This full-thickness suture line is then continued anteriorly to close the strictureplasty. To complete the procedure, a row of seromuscular Lembert sutures is placed anteriorly. In essence, the Finney is a short side-to-side functional anastomosis. A very long Finney strictureplasty may result in a functional bypass with a large lateral diverticulum. This diverticulum, in theory, could be at risk for bacterial overgrowth and the blind loop syndrome. Fortunately, this theoretical concern has not been observed in clinical practice.

The purpose of the strictureplasty is to preserve intestinal length that otherwise would be sacrificed with resection. Those cases with long segments of stricturing disease are the ones in which nonresectional methods should be aggressively pursued. To manage such cases, multiple strictureplasties are typically required. In general, however, repeated Heinecke-Mikulicz or Finney strictureplasties should be separated from each other by at least 5 cm. Otherwise the result can be a bulky and relatively unyielding segment of intestine with considerable tension placed on each suture line.

Patients with long-segment stricturing disease and multiple strictures grouped close together are best managed with a side-to-side isoperistaltic strictureplasty, also called Michelassi strictureplasty.135 With this technique, the segment of stricturing disease is divided at its midpoint. The proximal and distal ends are then drawn onto each other in a side-to-side fashion (Fig. 33-7). Division of some of the mesenteric vascular arcades facilitates the positioning of the two limbs over each other. The proximal and distal loops are then sutured together with a layer of interrupted seromuscular sutures. A longitudinal enterotomy is then made along both of the loops (Fig. 33-8). The intestinal ends are spatulated to provide a smoothly tailored fit to the ultimate closure of the strictureplasty. Again, this is the time to examine the mucosal surface of the intestine to detect potential areas of neoplastic transformation and control bleeding. The outer suture line is reinforced with an interior row of either interrupted or running full-thickness sutures. This inner suture line is continued anteriorly. The anterior closure is then reinforced with an outer layer of interrupted seromuscular sutures to complete the strictureplasty (Fig. 33-9).

Originally described in 1996, this procedure has been utilized with increasing frequency. The isoperistaltic side-to-side strictureplasty is recognized as an effective means of treating extensive small bowel Crohn's disease and provides the best option for those cases that would otherwise require extensive intestinal resection with loss of significant length of small bowel.130,133,136,137

Unlike resection, diseased segments are retained with strictureplasty and suture lines are placed in Crohn's disease–affected tissue. This has been a cause of concern regarding the risk of intestinal suture line dehiscence, long-term recurrences, and risk for malignancy. The ongoing and now substantial clinical experience with these techniques has allayed these concerns.138 In appropriately selected patients, perioperative morbidity from strictureplasty appears to be similar to that of resection and primary anastomosis. Specifically, intestinal suture line dehiscence appears to be uncommon with any of the described strictureplasty techniques.139,140 The most common postoperative complication directly related to strictureplasty is hemorrhage from the strictureplasty site. This has been reported to occur in up to 9% of cases. Fortunately, the GI hemorrhage following strictureplasty is typically minor and can be managed conservatively with transfusions alone. Rarely, more persistent bleeding may require intra-arterial infusion of vasopressin, but the need for reoperation to control hemorrhage after strictureplasty is very rare. It is by now also well established that strictureplasty techniques provide excellent long-term symptomatic relief that is comparable to resections with anastomosis. Although there are no controlled studies directly comparing strictureplasty to resection, multiple reports of the observed symptomatic recurrence rates after strictureplasty compare well with published recurrence rates after resection and anastomosis.133,140,141

Epidemiological studies have shown an increased risk for small bowel adenocarcinoma in Crohn's disease patients.108 This risk is increased in patients with long-standing disease. It is not known if strictureplasty by virtue of its retention of diseased tissue increases this risk. At the time of the writing of this chapter, there have been only two reported cases of an adenocarcinoma developing at a site of previous small bowel strictureplasty, and it is thus believed that the risk of malignancy after strictureplasty is low.142,143

Laparoscopy

Over the past two decades, laparoscopy has been dramatically changing all aspects of GI surgery. Specifically in colon and rectal surgery, laparoscopy has been widely used in benign disease,144,145 including inflammatory bowel disease, and more recently in colon cancer.146 Several single-institution small reports suggest that not only is laparoscopic surgery for Crohn's disease feasible and safe, but also it reduces length of hospitalization and recovery and allows for a smaller wound, with an overall reduction in morbidity.147–160

Most Crohn's disease patients are well suited for laparoscopy. They are usually young, otherwise healthy, and interested in undergoing an operation that involves minimal scarring, because they face the risk of multiple major abdominal operations in their lifetime. On the other hand, Crohn's disease represents a difficult arena even for the experienced open colorectal surgeon. Many of the unique features of Crohn's disease, such as the intense inflammation and thickened mesentery, enteric fistula, inflammatory masses or abscesses, and the multiplicity of areas of intestinal involvement, have deterred many surgeons from even considering a laparoscopic approach.

Two prospective controlled studies have shown several advantages of the laparoscopic-assisted approach over the conventional approach.147,149 Bemelman and colleagues compared 48 open ileocolic resections with 30 laparoscopic-assisted resections. This study showed similarly low morbidity rates in both groups but a shorter hospital stay and improved cosmetic results in favor of the laparoscopic group.149 Alabaz and associates compared 48 open ileocolic resections with 26 laparoscopic-assisted resections. The patients in the laparoscopic group returned to work more quickly, had better cosmetic results, and were more likely to have improved postoperative quality of life.147 A prospective randomized trial comparing open and laparoscopic-assisted resections in 60 patients undergoing elective ileocecectomy for Crohn's disease not complicated by abscess formation or complex fistula showed a faster postoperative recovery of respiratory function (measured as recovery of 80% of forced respiratory volume and forced vital capacity), shorter abdominal incisions, and longer performance time in the laparoscopic-assisted group. These differences were all statistically significant. With limited follow-up, there was no difference in recurrence rate.154 This paper demonstrated that in experienced hands, morbidity from the laparoscopic approach compares favorably with that of a conventional open approach. Obviously these results need to be confirmed by larger series with longer follow-up.

The indications for laparoscopic surgery for Crohn's disease should not differ from conventional open surgery as described previously. Contraindications to a laparoscopic approach include patients who are critically ill and unable to tolerate the pneumoperitoneum due to hypotension or hypercarbia, patients with extensive intra-abdominal sepsis (abscess, free perforation, or complex fistula), and difficulty in identifying the anatomy (previous surgery, obesity, or adhesions). The same variety of surgical procedures described previously can be performed laparoscopically.

After induction of general anesthesia, the patient is placed on the operating table supine or in the modified lithotomy position. Rectal irrigation with diluted iodine solution is performed, especially in patients with involvement of the rectum and sigmoid colon. An epidural catheter is usually inserted at the time of surgery. The sympathetic blockade achieved with epidural administration of local anesthetics and opioids prevents bowel distension, hence facilitating exploration of the GI tract and handling of the bowel. Depending on the procedure planned, four or five trocars are utilized, with the camera placed at the level of the umbilicus.

Every operation for Crohn's disease, whether open or laparoscopic, should start with a complete examination of the entire GI tract starting from the ligament of Treitz. The patient is placed in the reverse Trendelenburg position and right lateral decubitus with the assistant standing on the patient's left side retracting the transverse colon into the upper quadrants and the surgeon at the right of the patient or in between the patient's legs, tracing the intestine from the ligament of Treitz all the way to the ileocolic pedicle. This maneuver is facilitated by progressively rotating the patient from the reverse Trendelenburg to a full Trendelenburg position and left lateral decubitus. In the presence of skip areas of involvement from Crohn's disease, these are marked intracorporeally with sutures in order to facilitate retrieval of the diseased segments when the specimen is exteriorized.

Laparoscopic-assisted ileocolic resection is the most commonly performed laparoscopic procedure for Crohn's disease. For laparoscopic ileocolectomy, a four-trocar technique is utilized (Fig. 33-10). Trocars of 5 mm can be used exclusively, as a 5-mm, 30-degree camera offers the same resolution as larger ones and the vascular pedicles can be divided intracorporeally with 5-mm instruments. After the bowel has been evaluated in its entirety as previously described, the assistant, standing on the right of the patient or in between the patient's legs, places the ileocolic pedicle under tension with an intestinal grasper placed through the right lower quadrant trocar (Fig. 33-11). The surgeon on the patient's left side dissects and divides it (Fig. 33-12). Once this is accomplished, a medial-to-lateral submesenteric mobilization of the ascending colon all the way to the hepatic flexure is completed (Fig. 33-13). When the submesenteric mobilization is completed, the lateral colonic peritoneal reflection is divided all the way to the hepatic flexure (Fig. 33-14). The terminal ileum is completely mobilized by dividing the peritoneum at the level of the pelvic rim to allow a tension-free anastomosis through a small incision. It is often necessary to completely mobilize the hepatic flexure without dividing the right branch of the ileocolic vessels in order to facilitate exteriorization of the specimen (Fig. 33-15). It is imperative to make sure that the mobilization is adequate before evacuating the pneumoperitoneum and making an incision to avoid a difficult anastomosis through a small incision or the need for a larger incision to exteriorize the specimen. Should this occur, a gel port can be applied through the abdominal incision to allow for creation of the pneumoperitoneum again and further intra-abdominal dissection.

Once the ileum, cecum, and ascending colon are fully mobilized, the instruments are removed. With the pneumoperitoneum still in place, the umbilical port site or the right lower quadrant port site is enlarged. The pneumoperitoneum is evacuated and the specimen is exteriorized. The ileocolonic resection is then completed by dividing the remainder of the mesentery and the bowel extracorporeally. An anastomosis is then constructed in a standard fashion.

Crohn's Disease of the Duodenum

Primary Crohn's disease of the duodenum almost always manifests with stricturing disease that can be managed by strictureplasty or with bypass procedures (Fig. 33-16). Fortunately, resection of the duodenum for Crohn's disease is almost never required.161–163 Perforating Crohn's disease almost never affects the duodenum. When the duodenum is involved with Crohn's fistulas, it is always the result of disease within a distal segment (typically the terminal ileum or neoterminal ileum) that fistulizes into an otherwise normal duodenum.164 Yet, Crohn's disease of the duodenum can offer a particularly challenging problem due to the retroperitoneal location of the organ and its intimate proximity with the pancreas.

Stricturing disease of the duodenum is often focal and many cases can be managed with a strictureplasty.165 In order to safely accomplish a strictureplasty, the duodenum must be fully mobilized with a generous Kocher maneuver. Heinecke-Mikulicz strictureplasties can be safely performed in the first, second, and proximal third portion of the duodenum. Strictures of the last portion of the duodenum are better handled with a Finney strictureplasty constructed by creating an enteroenterostomy between the fourth portion of the duodenum and the first loop of the jejunum.

If the duodenal stricture is lengthy or the tissues around the stricture are too rigid or unyielding, a strictureplasty should not be performed and an intestinal bypass procedure should be undertaken. The most common bypass procedure performed for duodenal Crohn's disease is a simple side-to-side retrocolic gastrojejunostomy.121 This procedure effectively relieves the symptoms of duodenal obstruction related to Crohn's strictures but carries a high risk for stomal ulcerations. To lessen the likelihood of ulcerations forming at the anastomosis, it has been recommended that a vagotomy be performed along with the gastrojejunostomy.121 Because of the concerns of vagotomy-related diarrhea, a highly selective vagotomy is preferred to a truncal vagotomy. If the stricturing Crohn's disease is limited to the third or fourth portions of the duodenum, a Roux-en-Y duodenojejunostomy to the proximal duodenum is preferred to a gastrojejunostomy.164 The Roux-en-Y duodenojejunostomy has the advantage of bypassing strictures and eliminates the concern regarding acid-induced marginal ulceration and the need for vagotomy.

As noted previously, when the duodenum is involved with a Crohn's fistula, it is almost always the case that the diseased segment is located distal in the GI tract and the duodenum itself is otherwise free of active Crohn's disease.164 Most of these duodenal fistulas are small in caliber and asymptomatic, but larger fistulas may shunt the duodenal contents to the distal small bowel such that malabsorption and diarrhea result. In the majority of cases, duodenoenteric fistulas are identified with preoperative small bowel radiography; however, many are discovered only at the time of surgery.166 With complex fistulizing disease involving an inflammatory mass, great care at the time of surgery should be undertaken to limit the size of the duodenal defect resulting from the resection of the fistula. Most duodenal fistulas are located away from the pancreaticoduodenal margin, and thus these fistulas can be managed by resection of the primary Crohn's disease with primary closure of the duodenal defect. Larger fistulas or fistulas that are involved with a large degree of inflammation may result in a sizable duodenal defect. Such large defects may require closure with a Roux-en-Y duodenojejunostomy or with a jejunal serosal patch.166,167 As noted previously, duodenal resections are almost never necessary for Crohn's disease and they should be considered the surgical option of last resort.

Crohn's Disease of the Small Bowel

Complete Intestinal Obstruction

Complete small intestinal obstruction resulting from Crohn's disease only rarely requires urgent surgical intervention, as the vascular supply to the intestinal loop is never compromised and almost all cases of complete or high-grade partial small bowel obstruction from Crohn's disease respond to conservative management. Such patients should be treated with nasogastric decompression, intravenous hydration, and steroid therapy.121 This program allows for resolution of the acute episode of obstruction in a vast majority of cases. Unfortunately, most patients whose Crohn's disease is severe enough to experience an episode of complete or high-grade partial obstruction are at high risk for recurrent episodes and persistent symptoms. For this reason, elective surgery should be considered once the episode of complete obstruction has resolved. The advantage of this approach is that surgery can be performed under safer conditions when the obstruction has resolved, the bowel is not distended or edematous, and an appropriate bowel preparation has been performed. If the obstruction fails to respond to appropriate conservative treatment, surgery is required. In these situations, the surgeon needs to have a high index of suspicion for small bowel cancer as the cause of the obstruction, as obstructions from cancers do not respond to bowel decompression and steroid treatment.

Ileosigmoid Fistulas

Ileosigmoid fistula is a common complication of perforating Crohn's disease of the terminal ileum. Typically, the inflamed terminal ileum adheres to the sigmoid colon that is otherwise normal and free of primary involvement of Crohn's disease. Most ileosigmoid fistulas are small and do not produce any symptoms. Asymptomatic ileosigmoid fistulas do not in and of themselves require operative management. On the other hand, large ileosigmoid fistulas can result in bypass of the intestinal contents from the terminal ileum to the distal colon and thus give rise to debilitating diarrhea (Fig. 33-17). Such symptomatic fistulas often fail to respond to medical therapy and should be managed surgically.

More than half of the ileosigmoid fistulas from Crohn's disease are not recognized prior to surgery.168 For this reason, the surgeon should be prepared to deal with this complication in any case of Crohn's disease that involves the terminal ileum. Ileosigmoid fistulas can be managed by simple division of the fistulous adhesion and resection of the ileal disease. The defect in the sigmoid colon is then débrided and simple closure is undertaken. In this manner, 75% of ileosigmoid fistulas can be managed.55,168 The remainder require resection of the sigmoid colon. Sigmoid colon resection is necessary when primary closure of the fistula is at risk for poor healing. This is the case either when the sigmoid is also involved in Crohn's disease when the fistulous opening is particularly large, or when there is extensive fibrosis extending along the sigmoid colon. Also, fistulous tracts that enter the sigmoid colon in proximity to the mesentery can be difficult to close and often require resection and primary anastomosis.

Ileovesical Fistula

Ileovesical fistulas occur in approximately 5% of Crohn's disease patients.93 Hematuria and fecaluria are virtually diagnostic of ileovesical fistula, but these symptoms are absent in one-third of cases.169 Small bowel x-rays, cystograms, and cystoscopy often do not detect the fistula. Air within the bladder, as noted on CT scan, is often the best indirect evidence for the presence of an enterovesical fistula. An ileovesical fistula is an indicator of complex fistulizing disease, as most ileovesical fistulas occur along with other enteric fistulas. For example, as many as 60% of patients with an ileovesical fistula will also have an ileosigmoid fistula.55

The necessity for surgery for ileovesical fistula is controversial. Many patients with ileovesical fistulas can be managed medically for extended periods of time without significant complications. Healing rates with medical treatment are not clearly defined, but they are probably low and most patients with ileovesical fistulas will ultimately come to surgery. Surgery is indicated when recurring urinary infections occur, particularly pyelonephritis, with concomitant potential for worsening of renal function.

Surgical treatment of ileovesical fistulas requires resection of the ileal disease with closure of the bladder defect. Most ileovesical fistulas involve the dome of the bladder, and thus débridement and primary closure can be accomplished without risk of injury to the trigone. Decompression of the bladder with an indwelling Foley catheter should be continued postoperatively until the bladder is confidently healed without leaks. A cystogram taken on postoperative day 5 is a convenient means for confirming the seal of the bladder repair and the safety of removing the Foley catheter.

Enterovaginal and Enterocutaneous Fistulas

These are rare fistulas caused by perforating small bowel disease draining through the vaginal stump in a female who has previously undergone a hysterectomy or through the abdominal wall, usually at the site of a previous scar. These fistulas often require surgical intervention because they cause physical discomfort and personal embarrassment. Surgical treatment requires resection of the small bowel disease. The vaginal cuff does not need to be closed; the chronic infection along the abdominal wall fistulous tract requires debridement and wide drainage to allow healing by secondary intention.

Abscess

Intra-abdominal abscesses that result from Crohn's disease tend to follow an indolent course with modest fever, abdominal pain, and leukocytosis. Rapidly progressive and overwhelming sepsis is not typical for the clinical course of Crohn's disease–related abscesses. In fact, in up to one-third of intra-abdominal Crohn's abscesses preoperative clinical signs of localized infection are absent and the abscesses are discovered only at the time of operation. When an abscess is suspected or an abdominal mass is palpated, a CT scan should be obtained, as 50% of tender intra-abdominal masses will harbor an abscess collection within.100 The CT scan can detect most chronic abscesses and can also delineate the size and location of the abscess as well as the relationship of the abscess to critical structures such as the ureters, duodenum, and the inferior vena cava (Fig. 33-18).

Most abscesses with Crohn's disease are in fact very small collections that are contained within the area of diseased intestine and its mesentery. In the case of small intraloop or intramesenteric abscesses, resection of the defective segment and its mesentery often extirpates the abscess such that drains are not necessary and primary anastomosis can be performed without risk.

Large abscesses related to Crohn's disease are best managed with CT-guided percutaneous drainage.102 Percutaneous drainage is often very effective at controlling the sepsis and healing the abscess cavity.101 With percutaneous drainage of a Crohn's disease abscess, an enterocutaneous fistula often occurs as the abscess typically connects to a deeply penetrating sinus emanating from a segment of Crohn's disease–affected intestine. Percutaneous drainage then completes the fistulous tract from the intestine through the sinus to the abscess cavity and out the drain. Such a fistula may spontaneously close or it may persist, and the intestine may continue to be a source of sepsis. With successful drainage of the abscess, the sepsis often clears well enough that it can be tempting to try to manage the disease without subsequent surgery. Published clinical data on the optimal approach to such patients are unfortunately lacking. Even so, in the absence of Crohn's symptoms, initial nonoperative management after successful percutaneous drainage can be undertaken in carefully selected patients.103 On the other hand, if drainage through the fistula continues, surgical resection of the affected segment of intestine becomes necessary.

Perforation

Free perforation is a surprisingly uncommon phenomenon because the chronic progressive inflammation of Crohn's disease normally leads to adhesions with adjacent structures. Most perforations from Crohn's disease occur in the ileum and are usually proximal to a stenotic lesion.104,121 The diagnosis of free perforation is made by detecting a sudden change in the patient's symptoms along with the development of the physical findings of peritonitis or the identification of free intraperitoneal air as demonstrated on plain x-rays or CT scans. Free perforation is an absolute indication for emergent laparotomy with resection of the diseased segment and exteriorization of the proximal bowel as an end ileostomy. The distal bowel end can be exteriorized as a mucous fistula or closed as a defunctionalized pouch, depending on the degree of peritoneal contamination. Creation of a primary anastomosis even with a proximal protecting loop ileostomy carries a high risk of anastomotic breakdown and should be avoided. Primary closure of the perforation should never be attempted, as sutures will not be able to approximate the edges of the perforated, edematous, and diseased bowel in a satisfactory and tension-free way and the presence of a distal intestinal stenosis or partial obstruction will cause an increase in the intraluminal pressure at the level of the local repair with subsequent dehiscence.

Hemorrhage

Hemorrhage from small bowel Crohn's disease is managed by resection of the diseased portion of intestine. For patients with multiple skip areas of Crohn's disease, small bowel angiography may be attempted to localize the exact site of bleeding.105 Localization with angiography may be unsuccessful if the bleeding is episodic or insufficiently brisk to be identified with angiography. In patients in whom small bowel hemorrhage stops spontaneously, the risk for rebleeding is high. Thus elective resection of active Crohn's disease after the first episode of hemorrhage should be considered.

Crohn's Disease of the Colon

The optimal management of Crohn's disease of the colon is dependent on the distribution and the location of the disease (Fig. 33-19).

Cecal Disease

Colonic disease limited to the cecum is almost always associated with terminal ileal disease. The terminal ileitis is the predominant component of the ileocecal disease. Terminal ileal disease with extension into the cecum behaves much like disease limited to the terminal ileum. For this pattern of disease, surgical resection should encompass the margins of gross disease with an anastomosis between the neoterminal ileum and the proximal ascending colon. Recurrence of disease at the anastomosis or at the preanastomotic ileum is common, but the risk for recurrent disease within the distal colon or the rectum is low. This pattern of disease does not imply a predisposition to more extensive colonic disease.

Right-Sided Colitis

Disease involving the entire right colon can occur alone but more typically occurs along with disease of the terminal ileum. Extensive involvement of the right colon as a form of ileocolonic disease is less common than the ileocecal pattern. Surgical treatment involves a standard right hemicolectomy to encompass the gross limits of the disease. An anastomosis between the ileum and the transverse colon is then fashioned. With a standard right hemicolectomy, the anastomosis may rest in proximity to the duodenum. Recurrent disease at the preanastomotic ileum may thus secondarily involve the duodenum. This phenomenon can place the patient at risk for substantial morbidity should inflammatory encasement of the duodenum or fistulization into the duodenum occur. For this reason it is advantageous to protect the duodenum by interposing omentum between the duodenum and the ileocolonic anastomosis.

Extensive Colitis with Rectal Sparing

Extensive colitis with sparing of the rectum occurs in approximately 20% of individuals suffering from Crohn's colitis. In such cases, the rectum should be closely examined endoscopically, and, should the rectum be truly free of disease, a total abdominal colectomy with ileorectal anastomosis can be performed when fecal continence is adequate and the patient does not have extensive perineal septic complications. This procedure often results in good long-term function and enables many patients to avoid an ileostomy. Older patients or patients who have undergone an extensive small bowel resection may experience frequent and loose stools to the point that incontinence may develop after an ileorectal anastomosis. Additionally, recurrent disease within the rectum can result in significant deterioration of bowel function requiring further medical or even surgical intervention. Up to 50% of patients who undergo an ileorectal anastomosis for colonic Crohn's disease will ultimately require a proctectomy with permanent ileostomy because of poor bowel function with incontinence or recurrence of disease in the rectum.170

Proctocolitis

Surgical management of extensive involvement of the colon and rectum requires total proctocolectomy with permanent ileostomy in almost all cases. In most instances, a total proctocolectomy can be performed in a single step. The presence of severe perianal disease, however, may require that the procedure be performed in two stages. At the first stage, the intra-abdominal colon and majority of the rectum are removed and a short rectal stump is created at the level of the levator muscles. At the same time, perineal abscesses are drained and fistulas are laid open. This first step removes the diseased colon and rectum without creating a perineal wound that may be difficult to heal in the presence of active perineal sepsis. Once the perineal sepsis is cleared and the perineum is healed, the short anorectal stump can be removed through a perineal approach. At the second stage, primary closure of the perineum can be accomplished without the high risk of persistent perineal wounds.

Restorative procedures such as an ileal pouch–anal anastomosis or continent ileostomy have traditionally not been offered to patients who have Crohn's colitis because of the recurrent nature of the disease. Even so, some of these procedures have been performed in patients whose diagnosis of Crohn's disease was not known or suspected at the time of surgery. Various reports indicate that recurrence of Crohn's disease within the pouch is common and removal of the pouch is often necessary. On the other hand, those patients who do not suffer from recurrent disease generally do well and typically experience good pouch function.

While it is commonly accepted that restorative proctocolectomy with J-pouch ileoanal anastomosis should not be undertaken for Crohn's colitis, there is a specific pattern of Crohn's disease that appears to be at low risk for problems with recurrence after an ileoanal anastomosis.171,172 In cases in whom Crohn's disease is limited to the colon and rectum without any history of small bowel involvement and without any perineal manifestations, the risk for pouch failure after ileoanal anastomosis appears to be low and such patients can be considered for the ileoanal procedure. This particular pattern of Crohn's disease, however, is rare, as most patients with Crohn's proctocolitis will have some degree of small bowel involvement or perineal manifestations and thus would not be considered candidates for the ileoanal procedure.

Proctitis

Crohn's inflammation limited to the rectum is unusual. Surgical management of Crohn's proctitis mandates proctectomy with permanent stoma. The need for resection of the normal proximal colon is controversial. Abdominoperineal resection with end sigmoid colostomy has been associated in some reports with a high risk for stomal complications and recurrent disease in the proximal intestine when compared to total proctocolectomy with end ileostomy. For these reasons, total proctocolectomy with ileostomy has been recommended for Crohn's disease limited to the rectum and distal colon. This more extensive resection may be of greater value in younger patients who have no history of small bowel Crohn's disease, as it appears that colorectal Crohn's disease without small bowel involvement is unlikely to result in recurrence within the small bowel once a proctocolectomy is performed.40 If the patient has undergone a prior resection for small bowel Crohn's disease, they may be at risk for high output from the ileostomy and therefore may benefit from the preservation of colonic absorptive capacity. Preservation of the colonic absorptive capacity may be beneficial also in the elderly patient. Thus these patients may be better managed with a proctectomy and end sigmoid colostomy.

Proctectomy for Crohn's disease does not require a wide excision of perirectal tissue. To avoid injury to pelvic sympathetic and parasympathetic nerves, the dissection should be undertaken close to the rectal wall. This is sometimes challenging in the presence of severe rectal mesenteric inflammatory reaction. In the absence of significant perianal disease, the perineal dissection is best carried out along the plane between the internal and external sphincters.173 This intersphincteric dissection allows for a perineal closure that is associated with fewer complications and better healing than wider dissections that encompass the entire sphincter mechanism. In some patients, fistula from the perianal Crohn's disease can traverse the intersphincteric plane and a wider dissection is required in order to encompass the diseased tissue. In the presence of significant perianal disease, a staged approach, as described previously, can be utilized as an option. Occasionally, however, because of extensive rectal disease, closure of the rectal stump may be technically challenging or not feasible, forcing the surgeon to proceed with a proctectomy in the face of perianal sepsis. These dissections may need to be carried out widely and extensive loss of perianal skin and subcutaneous tissue may occur. The resultant defects are often too large for primary closure, and closure may require advanced tissue transfer techniques such as gluteal flaps, gracilis flaps, or myocutaneous rectus abdominis pedicle flaps. These closures may have to be staged as well in the presence of perineal sepsis. Large open perineal wounds may be managed temporarily or definitively with the assistance of the vacuum-assisted closure device. This device allows for rapid contracture of the wound and facilitates healing.

Segmental Colitis

The optimal management of segmental colitis is dependent primarily on the location of the disease and secondarily on the presence and severity of concurrent perineal complications, the degree of fecal continence, and the natural history of the disease in the residual colon. Segmental involvement of the right colon should be managed by simple right hemicolectomy with ileotransverse anastomosis. For segmental disease involving the transverse colon, an extended right hemicolectomy is generally preferred to a segmental transverse colectomy. Such an approach may have a lower risk of recurrence compared to a segmental resection of the transverse colon. Additionally, the extended right hemicolectomy avoids a colocolonic anastomosis that is associated with a higher risk for anastomotic dehiscences and strictures.

For disease in the descending or sigmoid colon, the appropriate surgery is more controversial. Presence and severity of concurrent perineal complications, the degree of fecal continence, and the natural history of the disease in the residual colon all play a role in deciding on the approach for each individual patient. Studies have indicated that segmental colonic resection with colocolonic anastomosis or even colonic strictureplasty can be performed with overall good results.174,175 However, such a strategy may be at risk for early disease recurrence within the colon.40 Even if the risk for recurrence is higher with segmental resection, the benefits of preserving the absorptive capacity in appropriately selected cases may outweigh the higher risk of recurrence.

Perianal Disease

The perianal manifestations of Crohn's disease include abscesses, fistulas, fissures, anal stenosis, and hypertrophic skin tags.176,177 Perianal Crohn's disease originates from inflammation within the anal crypts. This inflammation gives rise to sepsis and to fistulization (Fig. 33-20). Perianal Crohn's disease is common and occurs in one-third of the patients who suffer from intestinal Crohn's disease.42 Perianal Crohn's disease is usually associated with active or quiescent disease elsewhere within the GI tract. It is controversial as to whether the activity of perianal Crohn's disease parallels that of the intestinal disease. There is also controversy over whether medical or surgical control of the intestinal disease can ameliorate the perianal manifestations. Unlike idiopathic perianal abscesses and fistula-in-ano that occur in patients without Crohn's disease, perianal Crohn's disease tends to be recurrent, complex, and sometimes progressive.

Surgical incision and drainage are required to manage perianal abscesses (Fig. 33-21). Attempts at treating purulent collections with antibiotics alone are invariably unsuccessful. With surgical drainage of the abscess, the incision should be placed close to the anal margin. The cavity may be packed with ribbon gauze or drained with a 10–16F mushroom catheter. If a fistula tract can be identified at the time of drainage of the suppuration, a loose seton may be placed to ensure adequate drainage.

Uncomplicated submucosal or intersphincteric fistulas are best treated with an initial trial of either metronidazole or ciprofloxacin. These antibiotics are moderately effective in promoting healing of Crohn's fistulas and are associated with a low risk of complication.178,179 If a low-lying submucosal or intersphincteric fistula fails to heal with antibiotic treatment, a surgical fistulotomy can be performed. These low-lying fistulas typically heal well after fistulotomy and the risk of incontinence is low.

Surgical fistulotomies and cutting setons should not be used for suprasphincteric fistulas and should also be avoided for most transsphincteric fistulas. For complex fistulas, the risk for surgical complications is higher and more aggressive medical therapy is warranted before surgery is recommended. Medical treatment for extensive Crohn's fistulas includes the use of 6-MP, azathioprine, and cyclosporine. Probably the most effective agent at promoting healing of perianal fistulas related to Crohn's disease is infliximab. With infliximab treatment, healing of complex perianal fistulas is seen in 60% of cases.180,181 Recurrence of the fistula after infliximab is discontinued, however, may be high. Additionally, persistent stasis or sepsis within the fistula tract can impede effective healing with medical treatment. To provide for adequate drainage throughout the fistula tract, many patients may benefit from placement of setons. The use of setons with infliximab therapy can improve the overall effectiveness of infliximab.182 Typically the seton is placed prior to the initiation of infliximab therapy and then it is removed after the second or third dose.

Fibrin glue has been used for the treatment of Crohn's disease–related fistulas, but reported experience is limited. Success rates with this approach are low, but, given the low risk of complications, an attempt at fibrin glue may be worthwhile in selected cases.183,184

Closure of the internal opening of the fistula with a rectal advancement flap can be considered in cases of Crohn's disease.185 With this approach, an incision is made at the dentate line, and a flap of mucosa and muscularis is undermined and advanced down over the internal opening of the fistula. The advancement flap is then sutured into position with absorbable sutures. Rectal advancement flaps for Crohn's disease have a low risk for anal incontinence but are associated with a high failure rate. Rectal advancement flaps are not appropriate in patients in whom the rectal mucosa is involved with Crohn's disease. In severe cases of perianal disease that do not respond to aggressive medical and surgical therapy, fecal diversion with a stoma may be necessary. Diversion of the fecal stream typically results in significant relief of local inflammation and can assist in the healing of perianal fistulas. Proctectomy is indicated when perianal disease is unrelenting or when damage to the sphincters results in debilitating incontinence.

Recurrent Disease

Crohn's disease carries a high risk for recurrence after surgery. The actual incidence of recurrent disease depends on the defining parameters of recurrence. For example, histological evidence for recurrence can be seen in many patients within days of surgical resection.186 Endoscopic evidence for recurrent Crohn's disease can be seen in over 80% of patients within 3 years.187 Most cases of histological or endoscopically detected recurrences, however, do not go on to produce symptoms of Crohn's disease. For this reason, histological or endoscopic evidence of recurrent disease may be used as an end point in investigative studies but are not typically used as a guide for clinical management.188

The development of symptoms related to recurrent Crohn's disease activity is the most commonly applied definition of disease recurrence, as it is the recurrence of symptoms that has the most relevance to the patient. The onset of symptoms of recurrent Crohn's disease is often insidious and the severity of symptoms varies greatly. To create a reproducible standard for recurrence of Crohn's disease symptoms, the Crohn's Disease Activity Index (CDAI) can be applied as a means of measuring recurrent disease.189,190 A CDAI of greater than 150 is generally accepted as defining clinical recurrence. Once symptoms suggestive of recurrent disease occur, it is still necessary to carry out radiological and endoscopic tests to confirm that the symptoms are in fact related to Crohn's disease.

The clearest end point as a definition of recurrence is the need for reoperation. Dates of surgery are readily documented even in a retrospective fashion. While reoperation is the most precise definition of recurrence, even this standard does not allow for accurate and reproducible comparisons between series as some centers may submit patients to surgery earlier than other centers.

Reported crude and cumulative recurrence rates vary greatly. Symptomatic or clinical recurrence occurs in about 60% of patients at 5 years, and recurrences increase with time such that at 20 years clinical recurrence can occur in between 75 and 95% of cases.35,191,192 Reports of surgical recurrence rates range from 10 to 30% at 5 years, 20 to 45% at 10 years, and 50 to 70% at 20 years.70,94,191–195 Some interesting observations regarding the pattern of recurrent disease have been made. Recurrent Crohn's disease is most likely to occur in proximity to the location of the previously resected intestinal segment, typically at the anastomosis and preanastomotic bowel.94 This is particularly true for terminal ileal disease. Additionally, the length of small bowel involved with recurrent disease parallels the length of disease originally resected.196,197 Short-segment disease tends to recur over a short segment of the preanastomotic bowel, and lengthy disease typically is followed by lengthy recurrence. Also, to a lesser degree of concordance, stenotic disease tends to recur as stenotic disease and perforating disease tends to recur as perforating disease.197

While many factors that may influence the risk of recurrence have been studied, the cumulative literature has validated very few as true risk factors. The data are conflicting for most of the proposed predictors of recurrent Crohn's disease. Much of the clinical data examining potential risk factors are confounded by poorly defined end points and improper study design. There is, however, general consensus that cigarette smoking has a significant effect on the clinical course of Crohn's disease.30 Smoking not only exacerbates existing Crohn's disease but also has been identified as a risk factor for the development of Crohn's.27,28,30 What is so striking about the effect of cigarettes on Crohn's disease is that smoking has the opposite effect on what is thought to be a very similar disease, ulcerative colitis.29 While smoking exacerbates Crohn's disease, it seems to lessen the activity of ulcerative colitis.

The mechanism by which smoking results in exacerbation of Crohn's disease is not known. Smoking is an independent risk factor for endoscopic, symptomatic, and surgical recurrence.31,32 The risk from smoking appeared to be dose-related with heavy smokers being at higher risk. This effect is reversible, as smokers who quit smoking prior to surgery can lower their risk of recurrence to a level similar to that of nonsmokers. Because of the harmful effects on the clinical course of Crohn's disease combined with the many other clearly established health hazards caused by cigarette smoking, all patients with Crohn's disease should be strongly counseled to quit smoking.

There is concern that NSAIDs may exacerbate the activity of both ulcerative colitis and Crohn's disease.70,80 Although there are no studies that have examined the specific issue of NSAIDs and the risks for postoperative recurrence of Crohn's disease, the currently available data certainly warrant some caution and patients with Crohn's disease should be advised to avoid NSAIDs.

The risk for recurrent disease can be lessened with postoperative maintenance therapy. The most common agents used for postoperative suppression of disease are controlled-release 5-ASA (Pentasa) and 6-MP.75–77 Maintenance with 5-ASA is associated with few side effects, but up to 16 pills have to be taken daily. 6-MP is less expensive and is taken on a once-daily basis. Additionally, 6-MP may be more effective in diminishing the risk of recurrence.75 6-MP, however, is associated with potential bone marrow suppression, so that patients on 6-MP maintenance must be followed with periodic blood cell counts. The effect of these agents on the natural course of Crohn's disease is not dramatic, and many patients will go on to develop recurrence while on maintenance therapy. The largest benefit demonstrated with 6-MP in a multicenter trial showed a decrease of symptomatic recurrence from 77% with placebo to 50% with 6-MP.75 The option for maintenance therapy should be considered for Crohn's disease patients, but the decision for such therapy must be individualized for each patient.