Endoscopy in Crohn’s Disease

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Endoscopic Diagnosis of Crohn’s Disease

Endoscopy plays a major role in the diagnosis of Crohn’s disease, especially with colonoscopy and ileoscopy; however, upper gastrointestinal endoscopy, enteroscopy, capsule endoscopy and endoscopic ultrasound (EUS) may help confirm and determine the extent of disease. Direct visualisation of mucosal lesions and the possibility of obtaining histologic specimens make endoscopic procedures the first-line tests in the evaluation of gastrointestinal diseases. However, radiology and magnetic reso- nance imaging (MRI) contribute to the diagnosis when visualising the small bowel [1].

Endoscopic Features of Crohn’s Disease

Morphologic pictures observed during an endoscopic procedure are protean. The earliest endoscopic finding is the aphthous ulcer with a diameter of a few millimeters surrounded by a thin red halo of oede- matous tissue [2], which is found in about 30–40% of patients with Crohn’s colitis. Focal oedema and spo- radic red spots are present in the “preaphthoid phase [3]. These lesions usually are multiple, becoming stellate or linear in shape, with normal intervening mucosa, and can be rounded or long and serpiginous. Cobblestone-like areas are formed when ulcers assume a longitudinal and transverse pattern form- ing a grid. This is due to submucosal oedema, includ- ing nonulcerated mucosa [4]. Sometimes, these lesions differ little from inflammatory polyps or pseudopolyps also often present in Crohn’s colitis [5]. The presence of punched-out ulcers adjacent to inflamed mucosa gives rise after healing to mucosal bridges. Stenosis is often present in areas of severe inflammation, especially in the pyloric sphincter, ileocecal valve and rectosigmoid junction [6]. Length may vary from less than 3 cm to more than 10 cm and a width of less of 5 mm. Fistulae have been reported in more than 8% of patients affected by Crohn’s colitis, often near stenoses [7]. Less common manifesta-

tions are diffuse mucosal irregularities with erythema, oedema, granularity.

Carrying out multiple biopsies in areas both involved and uninvolved by the disease increases diagnostic accuracy of endoscopy and pathology.

The use of large biopsy forceps should be taken in consideration for obtaining a better specimen of the submucosa [8]. Finally, during colonoscopy, it is mandatory that intubation of the terminal ileum is performed in order to take biopsies that may increase the procedure’s sensitivity and specificity [9].

Colonoscopy

Colonoscopy is an important aid in diagnosis and management of patients with inflammatory bowel disease (IBD). This procedure, with multiple biopsies, is indicated when adequate data are not available from clinical, sigmoidoscopic or radiologic studies and there is strong clinical suspicion of IBD. How- ever, colonoscopy carries an increased risk of perforation when the bowel wall is inflamed and presents with ulcers and fistulae. Known or suspected severe inflammation is a relative contraindication to colonoscopy. Toxic megacolon is an absolute contraindication to endoscopy if performed only for diagnostic purpose because of the weakness of the colonic wall, which is paper thin [10]. Endoscopy monitoring to assess response to therapy has been evaluated by a randomised study in which patients were treated with steroids. In one group, steroid tapering was decided on following clinical remission;

in the other group, the decision was based on endoscopic findings. The conclusion was that colonoscopy was not necessary to decide when to taper steroids, as the two groups did equally well [11].

Colonoscopy evaluation of the extent of disease is also part of preoperative assessment in order to decide the extent of resection and define the segments free from disease. The ileocecal area is the

Endoscopy in Crohn’s Disease

Andrea Ederle, Paolo Inturri, Piero Brosolo, Alberto Fantin, Monica Preto

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most frequent site of the disease, accounting for about 70% of cases. Of these, 20–30% involved the colon only, and 40–55% had ileocolic disease [12].

Although considered peculiar of Crohn’s colitis, rectal sparing is found in less than half of patients.

When the rectum is involved, the disease begins at the rectosigmoid junction or appears with anorectal inflammation. The entire rectum is affected by the disease from 5% to 10%. Lesion progression, from aphthous to serpiginous ulcers, has a discontinuous and asymmetric course, with the inflamed mucosa typically presenting normal “skip areas” [13]. Seg- mental localisation of the disease has a high predictive value [14].

Other endoscopic features found during a colonoscopy include pseudopolyps, erosions and stenosis. A prospective study evaluated the incidence of different lesions found during a colonoscopy. All the patients were affected by Crohn’s disease and underwent the procedure before beginning therapy.

Endoscopy showed the following findings: 93%

superficial erosions, 74% deep erosions, 48% mucosal oedema, 44% erythema, 41% pseudopolyps, 10%

aphthous ulcers, 8% ulcerated stenosis and 2%

nonulcerated stenosis [15].

Pseudopolyps represent regenerative epithelium and may include granulation tissue without prema- lignant potential. They are often multiple and bright, with a fragile surface that bleeds very easily when biopsies are taken. Endoscopic differential diagnosis with adenomas can be difficult, and only biopsy will provide definitive diagnosis [16]. They need to be resected if bleeding or causing obstruction, and polypectomy is performed in the same way as in the general population [17].

Colonoscopy allows direct investigation of strictures. Biopsies are mandatory to rule out stenoses

caused by carcinoma. Malignant lesions are usually eccentric, rigid and may present nodules within the stricture or at its margins [18]. The colonoscope should go beyond the stenosis in order to carry out a thorough inspection, using a pediatric instrument if needed, avoiding the standard colonoscope to act as a dilator [19]. Endoscopic features may also have prognostic value, as reported by Allez and collabora- tors [20]. They found that patients with deep and extensive ulcerations of the colon are at higher risk of penetrating complications and undergoing surgery.

Distribution of severe endoscopic lesions was the following: rectum 13%, sigmoid colon 77%, left colon 62%, transverse colon 51%, right colon 28%.

When disease involves the colon only, the main differential diagnosis is between Crohn’s disease and ulcerative colitis (UC) (Table 1). Usually, the two entities can be differentiated endoscopically, and inflammation distribution can aid diagnosis. Crohn’s colitis is more likely in the presence of skip areas or when the rectum is spared. In UC, the rectum may be spared by local treatment or when the proximal colon is more involved than the rectum during an acute severe attack [21]. Moreover, peculiar to Crohn’s disease is the presence of deep linear ulcerations separated by areas of normal mucosa as well as terminal ileum involvement. Inflamed mucosa extends for more than a few centimeters, and ulcerations are present in this portion of the small intestine. Although the small bowel is not involved by UC, a few centimeters of inflamed mucosa without ulceration may be present in the terminal ileum (backwash ileitis) in 15–20 % of patients with pancolitis.

When extensive inflammation of the colon is present, differential diagnosis between Crohn’s disease and UC may be very difficult. Patients presenting features of both diseases are considered to have indeter-

Table 1.Crohn’s disease and ulcerative colitis: endoscopic differential diagnosis

Crohn’s disease Features Ulcerative colitis

Any portion of gastrointestinal tract Distribution Contiguous involvement of the colon starting from rectum

Often stenotic or ulcerated Ileocecal valve Without ulcerations

Frequent Lesions to terminal ileum Backwash ileitis (15–20%)

Sometimes Lesions proximally to terminal ileum Not present

25–50% Rectal involvement 95–100%

Rare Continuous colitis Yes

Asymmetric inflammation Mucosal involvement Circumferential inflammation

Yes Segmental inflammation No

Yes Skip areas No

Frequent Cobblestones-like areas Rare

Aphthoid/deep Ulcerations Shallow

Frequent Fistulas Rare

Frequent Stenosis Rare

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minate colitis, and at least 10% of patients who present with an IBD is regarded as having indeterminate colitis [22]. Usually, they are treated and monitored as are patients with UC unless signs of Crohn’s disease develop. Other diseases that may resemble Crohn’s disease are functional disorders (e.g. irrita- ble bowel syndrome), immunomediated (e.g. con- nective tissue diseases), drug induced [(e.g. nons- teroidal anti-inflammatory drugs (NSAID)], vascular (e.g. intestinal ischaemia), neoplastic (e.g. carcinoma, lymphoma), infective or diverticular disease.

Upper- and Small-Bowel Endoscopy

Esophagus, stomach and duodenum may be involved by Crohn’s disease [23]. Even in the upper gastrointestinal tract, aphthous ulcer is the most common lesion, but mucosal nodularity and stenosis may be seen [24]. The presence of inflamed mucosa in this portion of the digestive tract is important for differential diagnosis between Crohn’s disease and UC.

Radiologic procedures with barium as small-bowel follow-through or enteroclysis are important for diagnosis of Crohn’s disease localised in the small bowel and for demonstration of strictures and fistulae [25]. However, a study comparing small-bowel barium examination with enteroclysis and ileoscopy showed that the radiology missed 27% of severe inflammatory changes and 50% of mild inflammatory changes [26]. Push enteroscopy allows evaluation of the proximal small bowel whereas intraoperative enteroscopy is used to explore the distal small intestine [27]. The former procedure is useful especially in patients without known Crohn’s disease but who are suspected to have small-bowel involvement. Howev- er, a recent study reported that in patients with known Crohn’s disease, capsule endoscopy has a higher yield in detecting mucosal involvement of the small bowel than does push enteroscopy and enteroclysis [28]. Intraoperative enteroscopy compared with preoperative radiography is able to find more intestinal lesions, especially small ulcers and inflammatory polyps [29].

A new method of carrying out enteroscopy consists of using a double-balloon technique in which a first balloon is placed on the tip of the enteroscope and the second balloon on the tip of the overtube. This technique allows far better insertability and maneuver- ability compared with conventional methods. Prelim- inary experience reported the performance of this procedure on eight patients with abdominal symptoms, three of whom were diagnosed with Crohn’s disease [30]. Enteroscopy with the double-balloon technique was carried out using the oral approach in all patients and additionally with the anal approach in

four patients. In two patients, it was possible to exam- ine the whole small bowel, with a visualised total length of between 180 cm and 500 cm. Recently, Yamamoto reviewed the publications on double-balloon endoscopy, concluding that this method has the potential to be the standard of enteroscopy by replac- ing conventional push and intraoperative enteroscopy for diagnosis by means of bioptic specimens and therapeutic endoscopy of the small bowel [31].

Endoscopic Retrograde Cholangiopancreatography

Primary sclerosing cholangitis is a complication of IBD, present especially in patients affected by UC with an incidence between 1% and 4% and with lower frequency in Crohn’s disease [32]. Patients with IBD and abnormal liver function test need to be evaluated for hepatobiliary complications. Depending on local availability, MR cholangiography or endoscopic retrograde cholangiopancreatography should be performed as the initial diagnostic test in the suspicion of sclerosing cholangitis. The latter procedure is indicated as the procedure of choice when biliary stenosis is suspected or evident.

Endoscopic Ultrasound

EUS is a procedure for imaging the intestinal wall at high resolution. The use of EUS shows findings that distinguish normal colon from IBD as increased wall thickness, lymphadenopathy or enlarged perirectal vessels [33]. In particular, vessel enlargement is more likely associated with patients with acute Crohn’s disease whereas adenopathy is associated with acute UC. Therefore, this procedure could be helpful in dif- ferentiating the two diseases. An alternative to EUS is the high-frequency ultrasound catheter probe. In one study, a 20-MHz radial catheter was used to evaluate the colorectal wall in patients with IBD [34]. Crohn’s disease was associated with thickening of the fourth hypoechoic layer (muscularis propria) or loss of layer structure, and mucosal and submucosal thickening was more likely in ulcerative disease.

Moreover, EUS plays a major role in diagnosis and assessment of Crohn’s anorectal and perineal complications, such as abscesses or fistulae. Barium fistu- lography and computed tomography (CT) of the pelvis have been less sensitive for perianal disease [35] than EUS of the rectum [36]. One study demon- strated that rectal EUS had a diagnostic accuracy of at least 85%, as with examination under anesthesia and pelvic MRI, when evaluating the anatomy of perianal fistulae [37]. When any two tests were combined, the accuracy was 100%.

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Finally, endoscopic-ultrasound-guided fine-needle aspiration may help confirm the diagnosis for suspected abscesses and provide therapeutic procedures [38].

Intestinal Strictures are a Commonly Encountered Problem in Patients with Crohn’s Disease

Management of Strictures

Intestinal strictures are a commonly encountered problem in patients with Crohn’s disease, resulting in bowel obstruction and eventually in repeated bowel resection and short bowel disease. Over one third of patients with Crohn’s disease have a clear stenosing disease phenotype, often in the absence of luminal inflammatory symptoms [39]. At the foundation, as in other organs and tissues, there is transformation and activation of fibroblasts and smooth muscle cells that underlie fibrogenesis in the gut. Endoscopic balloon dilation is the preferred initial therapeutic modality in anastomotic strictures. In fact, endoscopic management with hydrostatic balloon dilation is an effective alternative to surgery in patients with endoscopically accessible lesions shorter than 7–8 cm [40], but careful patient selection is of great impor- tance to ensure favourable long-term results. The presence of inflammation near the stricture should not be considered a contraindication to dilation, and intralesional steroid injection should be considered in these patients.

Among the three clinical patterns of Crohn’s disease (inflammatory, penetrating/fistulising and obstructive/fibrostenotic), the latter is a frequent cause of symptoms and is an indication for surgery in over half of operations for Crohn’s disease. Small- intestinal strictures are found in 21% of patients, duodenale strictures in 5% [41], colonic strictures range from 4% to 9% [42, 43] and anorectal strictures in 7.5% [44]. Strictures may also arise from surgical treatment for Crohn’s disease, with reported rates of 17–81%.

To avoid surgery in patients with symptomatic Crohn’s strictures, various endoscopic techniques have been successfully utilised: balloon dilation with or without corticosteroid injection, Savary dilation, endoscopic needle knife incisions and self-expand- able metal stents, but no randomised clinical trials compare these methods for dilation. However, clinical situations in which to consider endoscopic management of Crohn’s strictures are: endoscopic acces- sibility, multiple previous intestinal resections and short strictures (<8 cm). It is important to consider intralesional steroid injection if significant inflammation is present.

Intestinal balloon dilation is attractive due to the ability to directly apply the radial force achieved during balloon insufflation, in contrast to the shearing force applied during bougienage [45]. Balloon dilation is the most widely reported method for nonsur- gically dilating intestinal strictures in Crohn’s disease [46, 47] resistant to medical therapy, with endoscopic incisions of the stricture or electroincision with or without intralesional steroid injection [48]. The balloon, with a diameter from 18 mm to 25 mm, was inflated for 1–4 min and repeated two to four times per session [49]. Successful dilation was generally defined as allowing the passage of a standard adult colonoscope. One author [50] made four radial incisions into the stricture with a standard papillotome if the colonoscope could not pass the stricture. In this way, dilation sufficient to allow passage of the adult colonoscope was achieved in every patient, with 3%

of complications (minor bleeding and perforation) in a total of 137 dilations, with complete symptom relief achieved in 66% of patients over a mean follow-up of 19 months. It was suggested that the nonresponse group had more aggressive disease. Other authors performed hydrostatic balloon dilation with inflation diameters from 12 mm to 18 mm [51]. Immediate symptomatic relief was noted in 77% of patients, with persistent long-term relief in 44% after a mean follow-up of 25 months. Longer strictures and active inflammation were characteristics that portended poor response. The same authors, in a follow-up study of a larger number of patients undergoing hydrostatic balloon dilation for symptomatic ileocolonic stricture in Crohn’s disease resistant to medical treatment and followed up over a 5-year period, suggested that dilation can be successful in the set- ting of inflammation [52]. Technical success was achieved in 90% of procedures, with best results in ileocolic anastomoses. Overall relief of symptoms was achieved in 62% of patients after mean follow-up of 33.6 months, with 8% of complications and no deaths for a total of 76 dilations. Lack of success was noted in strictures with tight angulation and longer lenght.

Based on the success of using intralesional corti- costeroids in caustic lesions, dilation followed by intralesional steroid injection was performed in Crohn’s strictures [53]. Following hydrostatic dilation, approximately 5 mg betamethasone dipropi- onate diluted into 5–10 ml of normal saline as 0.5- to 1-ml aliquots was injected into the most narrowed area using a standard sclerotherapy needle. Immedi- ate symptom relief was always achieved without complications, and 84% of patients achieved a pro- longed symptom-free period during a follow-up of 6 years after combination dilation/injection without need for surgery. Use and control of a precut papillo-

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tome for luminal incision, followed by injection of triamcinolone, is more difficult than hydrostatic balloon dilation and limited to short strictures although success rate is high [54]. Another study evaluated efficacy and safety of endoscopic balloon dilation with or without intralesional steroid injection for symptomatic upper and lower gastrointestinal Crohn’s disease strictures [55]. Using a mean follow- up of 18.8 months, technical success was achieved in 96.5% of 17 patients. Recurrence rate in the steroid group was 10% and that in the nonsteroid group 31%. Overall, long-term success was achieved in 76.5% of patients, with a complication rate of 10%

with no mortality.

Experience with self-expanding metal stents in Crohn’s disease has been very limited [56], with complete relief of obstructive symptoms after placement despite stent migration some months after insertion.

Similarly, minimal data exist on endoscopic treatment of gastroduodenal strictures in Crohn’s disease.

In one study, a 20-mm balloon was utilised, and symptomatic relief was achieved in every patient, with all responding to repeat dilation [57].

Fistulae Management

Currently, there are no data supporting the role of endoscopy as primary treatment of fistulising Crohn’s disease. Nevertheless, aside from guiding medical and surgical therapy of a fistula, endoscopy may indirectly and directly impact the treatment of fistulising Crohn’s disease [58]. Indirectly, endoscopy may allow for dilation of obstructing strictures that prevent the closure of the fistula. Directly, may treat the fistula via an injection of fibrin-based sealants or anticytokine therapy. A fistula located proximal to an obstructive stricture does not heal due to an increase in luminal pressure. Endoscopic balloon dilation of the stricture would reduce intra- luminal pressure and the amount of bowel contents passing through the fistula, and allow for a better chance of closure. For endoscopic dilation to be successful, the stricture must be accessible, short (<8 cm) and not significantly inflamed, conditions that are often not the present in fistulising Crohn’s disease. Nevertheless, in a patient with a symptomatic fistula that is proximal to a short, noninflam- matory stricture, endoscopic balloon dilation offers an alternative to surgery.

There are case reports of injecting fibrin tissue sealant into a perineal fistula of patients with IBD [59]. Results of an external fistula closure with fibrin sealants are disappointing. Recently, there have been several reports on the endoscopic treatment of a gastrointestinal fistula with various tissue sealants as

fibrin-based, collagen or amino-acid solutions [60, 61].

However, these reports were not related to IBD but to fistulas secondary to other diseases, and endoscopically administered tissue sealants are unlikely to play a role in the treatment of Crohn’s disease fistulas [62]. To date there are no studies that have evaluated the role of endoscopically administered biologic therapy for treatment of Crohn’s fistula, and there is only one published abstract that has evaluated local injection of infliximab into a perianal fistula. As new therapies becomes available, there will be a greater need for therapy administered directly to the mucosa, and therapeutic endoscopy may play a role in the treatment of fistulising Crohn’s disease. One study was performed using EUS to assess and guide combination medical and surgical therapy for patients with Crohn’s perianal fistulas [63]. The presence of fistula healing on EUS was used to guide seton removal and discontinuation of infliximab or antibiotics, demonstrating that EUS may identify a subset of patients who can discontinue infliximab without recurrence of fistula drainage.

Although there are no reports of stricture dilation in Crohn’s disease patients with ileal or colonic stomas, the same principles as with ileocolonic or colonic strictures apply [51]. Endoscopic management of these strictures may be more desirable in many of these patients who have already undergone multiple bowel resections. Radiologic contrast imaging and endoscopy will provide information on whether the stricture is amenable to hydrostatic balloon dilation. The procedure may be repeated with progressively larger-diameter balloons until a satis- factory result is obtained, such as being able to pass a standard colonoscope through the stricture. Con- traindications to dilation include coagulopathy and strictures associated with large and deep ulcerations.

Capsule Endoscopy in Crohn’s Disease

Video capsule endoscopy (VCE) is a new, noninva- sive imaging technique for the complete small bowel.

The video capsule is a small device with a diameter of 11 mm and a length of 26 mm, which can be swal- lowed. It contains six light-emitting diodes, a lens, a colour camera chip and two batteries. The video capsule obtains two images per second. Video images are transmitted by means of radiotelemetry to the sensor array attached to the body with a belt. Images from a period of time as long as 8 h are stored in a portable recorder.

There are no standard preparations before the examination: certain operators prescribe only a liq- uid diet after lunch on the day preceding the capsule endoscopy and a fast for 8 h before the procedure.

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Others recommend more complex preparation with various combinations of laxatives [sennoside, poly- ethylene glycol (PEG) solution]. After swallowing the capsule endoscope with 100–200 ml of water contain- ing 100 mg of simethicone, the patient could drink 2 h later and eat 4 h later. In patients who have undergone gastric surgery or those with gastropare- sis, the video capsule could be inserted endoscopically in the small intestine. Stomach passage takes an average of 34 min, and passes through the small intestine in about 4 h. Complete visualisation of the small bowel up to the caecum is achieved in 80% of patients. Most operators recommend a plain abdominal X-ray be performed 7–14 days after the examination if the capsule examination does not show images of the colon and the patient does not see the capsule passage in the stool. The capsule is designed to be used once, and after it is passed with the stool, it is not reusable [64]. On completion of the examination, the recorded images are downloaded and converted into a movie by connecting the recorder to a work- station. Data are reviewed by an operator in about 1 h with dedicated software.

The main contraindication is the presence of small-bowel stenosis that may lead to capsule reten- tion and obstruction (see below). Other contraindi- cations are a patient with difficulty swallowing, preg- nancy or the presence of implanted medical devices such pacemakers. Capsule endoscopy is very useful in the management of patients with suspected small- bowel disease.

The diagnosis of Crohn’s disease is difficult. Cur- rent radiologic and endoscopic studies are limited in the diagnosis of early small-bowel mucosal disease in patients with this disease. VCE detects early lesions in the small bowel of patients with Crohn’s disease and is effective in diagnosing patients with suspected Crohn’s disease undetected by small-bowel series and enteroclysis [65, 66] and in some cases of Crohn’s disease with intestinal strictures missed by enteroclysis. Enteroclysis in patients with Crohn’s disease has a diagnostic yield of 37% while capsule endoscopy has a yield of 70%. This is not surprising since enteroclysis will not easily detect flat or mucosal abnormalities [67]. VCE is also superior to CT enteroclysis [5] in patients with known or suspected Crohn’s disease, especially in the detection of significantly more inflammatory lesions in the proximal and middle part of the small bowel. VCE probably is less effective than radiology at detecting fistulae, and this might be a reason for sometimes choosing radi- ological investigations in preference to VCE [68].

There is concern that a capsule might become stuck or impacted against a stricture. In fact, capsule impaction does occur approximately in the 2–5 % of cases. Most capsule impactions are asymptomatic

and rarely produce obstructive symptoms. A “patency” capsule has been developed to detect possible strictures noninvasively and more accurately than enteroclysis. This device has the same dimensions as the VCE but has a dissolving body. Use of the patency capsule may be of value to rule out the possibility of intestinal strictures in patients with Crohn’s disease and suspected small-bowel obstruction although the patency capsule can also cause transient obstruction.

The major difficulty of VCE is the definition of a gold standard for diagnosis. Crohn’s disease pro- duces mucosal inflammation and ulceration of various intensities in different bowel areas. The earliest lesion in Crohn’s disease displays tiny mucosal foci of chronic inflammation and, more recently, a focal loss of villi [69]. Another early lesion is aphthoid ulceration. The finding of one or two aphthous ulcers or erosion in patients during capsule endoscopy is common, and it is likely that many of these do not have Crohn’s disease [70].

It must be remembered that all ulceration is not indicative of Crohn’s disease. Clinically relevant points to keep in mind are the difficulty in differenti- ating ulcers of Crohn’s disease from those of NSAID use and the high prevalence of NSAID-induced ulcers in 71% of NSAID users [71]. Hence, it is critical to evaluate the history of NSAID use in every patient undergoing VCE. In the absence of NSAID use, diagnosis of Crohn’s disease was purposed by certain authors on the presence of multiple aphthous or ero- sive lesions (>10) that were either continuous or seg- mentally distributed [72]. Infections must be exclud- ed by duodenal biopsy, stool microbiology or serolo- gy.

It is known from older studies that the small bowel is affected in Crohn’s disease in about one third of cases [73, 74]. Newer studies based on VCE show that the small bowel could be involved in approximately 60% of patients with Crohn’s disease. This might be kept in mind in case of lack of response in patients treated with drugs released into the terminal ileum or colon [66, 68].

Diagnostic costs for Crohn’s disease can be very high. This is probably due to the low diagnostic yield of certain diagnostic procedures. VCE has a higher average diagnostic yield than comparative procedures due to imaging clarity and the ability to visu- alise the entire small bowel [75–77]. Literature review found the average diagnostic yield of small-bowel follow-through (SBFT) and colonoscopy of Crohn’s disease to be 53% whereas VCE had a diagnostic yield of 69%. Recent economic analysis comparing VCE with traditional diagnostic procedures demonstrates that employing VCE as a first-line diagnostic procedure appears to be less costly than current common

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procedures for diagnosing suspected Crohn’s disease in the small bowel [77].

Risk of Cancer and Endoscopic Surveillance

The first description of a cancer of the colon compli- cating “regional enteritis” was described in 1948 [79].

After this, published works abounded with reports of colorectal cancer in series of patients with Crohn’s disease [80]. In a recent population-based study [81], Bernstein et al. determined the incidence of cancer by linking records from the IBD and non-IBD cohort with the Comprehensive Cancer Care Manitoba Reg- istry. IBD patients were matched 1:10 to randomly selected members of the population without IBD based on year, age gender and postal area of resi- dence. There was an increased risk of colon carcinoma for both Crohn’s disease patients [2.64: 95% con- fidence interval (95% CI), 1.69–4.12) and UC patients (2.75; 95% CI, 1.91–3.97]. There was an increased IRR of rectal carcinoma only among patients with UC (1.90; 95% CI, 1.05–3.43) and an increased IRR of carcinoma of the small intestine only in Crohn’s disease patients (17.4; 95% CI, 4.16–72.9). An increased IRR of extraintestinal tumours was observed only for the liver and biliary tract in both Crohn’s disease patients (5.22; 95% CI, 1.05–14.9) and UC patients (3,96; 95% CI, 1.05–14.9). Gillen et al. [82] concluded that when cases of ulcerative and Crohn’s colitis of similar anatomic extent are followed for similar durations, the two diseases may ultimately prove to have similar increases in risk for colorectal cancer [83]. In fact, they compared the cancer risk in two hospital-referred but identically selected cohorts of patients with extensive UC and equally extensive Crohn’s disease of the colon. As in the classic 1973 paper by Weedon et al. [84], the overall risk of colorectal cancer was increased nearly 20-fold over the general population. Moreover, both relative risks and absolute 20-year cumulative incidences of cancer were virtually identical in the ulcerative and Crohn’s colitis cohorts. This study, therefore, conclusively establishes the previously reported [85–87] but still underappreciated similarity between cancer risks in these two diseases.

Friedman et al. [88] in 2001 concluded that colonoscopy surveillance should be strongly considered in chronic extensive Crohn’s colitis. In fact, they reported on 259 patients with chronic Crohn’s colitis who underwent screening and subsequent surveillance colonoscopy and biopsy since 1980. Biopsies were performed at 10-cm intervals and from strictures and polypoid masses. A total of 663 examinations were performed on 259 patients. Median interval between examinations was 24 months. The

screening and surveillance programme detected dysplasia or cancer in 16%. A finding of definite dysplasia or cancer was associated with age >45 years and increased symptoms. By life table analysis, the prob- ability of detecting dysplasia or cancer after a nega- tive screening colonoscopy was 22% by the fourth surveillance examination. It is interesting from a clinical point of view that the pediatric colonoscope helped increase the yield of neoplasia by 19%.

Despite this report, Mpofu et al. [89] concluded a review indicating that there is no clear evidence that surveillance colonoscopy prolongs survival in patients with IBD with extensive colitis.

There is evidence that cancers tend to be detected at an earlier stage in patients who are undergoing surveillance, and these patients have a correspondingly better prognosis but lead-time bias could contribute substantially to this apparent benefit. There is indirect evidence that surveillance is likely to be effective at reducing the risk of death from IBD-associated colorectal cancer and indirect evidence that it is accept- ably cost effective. Therefore, the follow-up of colonic Crohn’s disease must be similar to the follow-up of ulcerative colitis. Itzkowitz et al. suggested [90], await- ing more data about Crohn’s and colorectal cancer, that it seems prudent to follow a UC-based surveillance strategy for patients with at least 8 years of Crohn’s colitis involving at least one third of the colon. The suggested surveillance strategy is reported in Fig. 1 with the performance reported in Table 2 indicated by these authors. Information on family history of colorectal cancer may be a simple way to identify individuals with extensive colonic Crohn’s disease at more and more elevated risk of developing colorectal cancer [91], especially with a first-degree diagnosed with colorectal cancer before 50 years of age.

Cases of colorectal cancer in Crohn’s disease are in reality few, less than in UC, because many patients with extensive Crohn’s colitis have early surgical resection, eliminating the risk of cancer [82]. An increased number of small intestinal carcinoma in patients affected by Crohn’s disease has been reported although the strength of this association (age, length of disease, characteristics and distribution) still has to be elucidated. Relative risk is estimated between six and 50 times by different authors, but small intestinal cancer is very rare, and this relative risk does not justify endoscopic surveillance. Long- standing disease, previous intestinal exclusion surgery and enterocutaneous or other types of fistulae should probably be considered for the development of cancer [92] for eventual clinical suspicion but not for scheduled endoscopic surveillance. Small intestinal cancer in Crohn’s disease usually arises in distal ileum [93], and therefore it seems reasonable to attempt to extend surveillance colonoscopy to this

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bowel tract, dilating and biopsying stenosis, if possible.

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Table 2.Suggested performance of surveillance colonoscopy

– Obtain four biopsy specimens of flat mucosa every 10 cm (consider sampling every 5 cm in the rectosigmoid) – Place each quadruplicate set in a separate specimen jar (as opposed to pooling biopsy specimens from several

colonic segments)

– Sample suspicious lesions or polyps

– Make sure to biopsy flat mucosa around the base of any suspicious polyp and submit specimen in a separate container – Consider suppressing symptoms of active inflammation with medical therapy prior to surveillance colonoscopy – In Crohn’s colitis, strictures may require using a thinner calibre colonoscope

– Consider brush cytology or barium enema to evaluate impassible strictures

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