David B. Sachar

Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee

Guidelines for clinical practice are aimed to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo controlled studies are preferable, but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aimed to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision analysis. The recommendations of each guideline are therefore considered valid at the time of composition based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at publication to assure continued validity. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), grade B indicates that the evidence would be level 2 or 3, which are cohort studies or case–control studies. Grade C recommendations are based on level 4 studies, meaning case series or poor-quality cohort studies, and grade D recommendations are based on level 5 evidence, meaning expert opinion.

Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study.

To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohns disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohns disease.

Pulmonary manifestations of inflammatory bowel disease

Extraintestinal manifestations of both Crohns disease and ulcerative colitis (UC) have been well described, although pulmonary findings are often overlooked. We summarize the experience of more than 400 cases of pulmonary manifestations of inflammatory bowel disease (IBD). These manifestations will be categorized by disease mechanism into drug-induced disease, anatomic disease, over-lap syndromes, autoimmune disease, physiologic consequences of IBD, pulmonary function test abnormalities, and nonspecific lung disease. We intend to provide the clinician with a practical working update on the spectrum of pulmonary dysfunction associated with IBD.

Outcome of toxic dilatation in ulcerative and Crohn's colitis.

A review of 1,236 patients admitted to The Mount Sinai Hospital with inflammatory bowel disease between 1960 and 1979 yielded 75 cases (6%) with toxic dilatation of the colon. There were 61 cases among 613 patients (10%) with ulcerative colitis (UC), and 14 of 623 (2.3%) with Crohns disease (CD). Fifty-nine of the 75 patients (79%) underwent surgery during their hospitalization with toxic dilatation. Twelve of the 75 patients (16%) died. Both UC and CD groups had similar mean ages at onset of colitis (32 years and 31 years, respectively) and at development of toxic dilatation (37 years); similar durations of overall disease (4.8 and 5.9 years) and of toxic dilatation prior to surgery (11 days and 13 days); and similar anatomic distributions of disease. Both UC and CD also had similar mortality rates (16% and 14%). Mean duration of presenting attack up to onset of toxic megacolon was longer in CD than in UC (62 days versus 31 days) and in unoperated versus operated cases (64 days versus 37 days), but was not significantly different between survivors and mortalities (43 days versus 39 days). Mortality rates were also unaffected by total duration of inflammatory bowel disease, first attack versus relapse (14% versus 18%), or medical versus surgical therapy (13% versus 17%). Factors which affected mortality included age (30% for patients over 40 years old, versus 5% for those younger than 40), sex (21% in women versus 13% in men), and especially the occurrence of colonic perforation (44% for cases with perforation versus only 2% in those without). Of the 12 patients who died, 11 had suffered colonic perforation.(ABSTRACT TRUNCATED AT 250 WORDS)

Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease

Aliment Pharmacol Ther 2011; 34: 497–508

Is perianal Crohn's disease associated with intestinal fistulization?

BACKGROUND:When cases of Crohns disease (CD) are described as “fistulizing,” distinctions are often not drawn between perianal and intestinal fistulization. The question, therefore, remains open as to whether or not there is truly an association between perianal fistulization and intraabdominal intestinal fistulization in CD.AIMS:We have sought to determine the association between perianal and intestinal fistulization by analyzing the cases of CD recorded in databases from six international centers.PATIENTS:Six databases provided information on 5491 cases of CD in the United States, France, Italy, and The Netherlands. Of these cases, 1686 had isolated ileal disease and 1655 had Crohns colitis.METHODS:An association between perianal disease and internal fistulae was sought by calculating relative risks for the chance of internal fistulae among patients with perianal fistulae relative to those without. Statistical significance was calculated by the Mantel-Haenszel procedure, stratifying on the separate centers. All statistical tests and estimates were implemented using SAS for the PC.RESULTS:Among the 1686 cases with isolated ileal disease, the evidence of an association between perianal disease and internal fistulization was not consistent across centers, with relative risks ranging from 0.8 to 2.2. For patients with Crohns colitis (n = 1655), the association was much stronger and more consistent, with an estimated common relative risk of 3.4, 95% confidence interval (2.6–4.6, p < 0.0001).CONCLUSIONS:We have found a statistically significant association between perianal CD and intestinal fistulization, much stronger and more consistent in cases of Crohns colitis than in cases limited to the small bowel.

Ulcerative colitis as a progressive disease: The forgotten evidence

In the management of Crohns disease, earlier aggressive treatment is becoming accepted as a strategy to prevent or retard progression to irreversible bowel damage. It is not yet clear, however, if this same concept should be applied to ulcerative colitis. Hence, we review herein the long-term structural and functional consequences of this latter disease. Disease progression in ulcerative colitis takes six principal forms: proximal extension, stricturing, pseudopolyposis, dysmotility, anorectal dysfunction, and impaired permeability. The precise incidence of these complications and the ability of earlier, more aggressive treatment to prevent them have yet to be determined.

Recurrence patterns after first resection for stricturing or penetrating Crohn's disease.

Background: Crohns disease (CD) usually recurs after resection, but the factors associated with this risk remain obscure. We set out to determine the role of stricturing (Montreal Classification B2) versus penetrating (Classification B3) disease behavior in predicting early (<3 years) versus late (≥3 years) postoperative recurrence. Methods: We identified a cohort of 34 patients seen at The Mount Sinai Hospital who had undergone a first ileocolic resection prior to December 31, 2004, who had been clinically thought to have had stricturing (B2) disease, and for whom we could verify 1) the operative and surgical pathology findings; and 2) the time of onset of symptoms attributable to recurrent CD by endoscopy, radiology, or surgery. Cases were reclassified as either “stricturing” (B2) or “penetrating” (B3) on the basis of operative and surgical pathology reports. Recurrences were classified as either “early” (<3 years) or “late” (≥3 years) depending on the first appearance of postoperative symptoms that were verified endoscopically and histologically, radiologically, or surgically as being attributable to anastomotic recurrence of the CD. Results: Among these 34 patients clinically thought to have had B2 disease, 12 had B2 disease confirmed upon review of surgical and pathology reports and none of them had recurrence within 3 years. Among the 22 patients reclassified as B3 disease, 12 (55%) had early recurrence. This difference was significant at the 0.002 level by the Fisher Exact Test. Conclusions: There is a strong proclivity for early postoperative recurrence of penetrating CD compared to stricturing disease, which may not be evident by behavioral classification on clinical grounds alone. Patients with confirmed uncomplicated stricturing obstruction at their first resection seem unlikely to experience a clinical recurrence within the next 3 years.

Adenocarcinoma following ileal pouch–anal anastomosis for ulcerative colitis: Review of 26 cases

&NA; The occurrence of adenocarcinoma following ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC) is an infrequent and but potentially lethal complication. We have seen 1 such case among 520 IPAAs performed in our group practice between 1978 and February 2008. We have added this case to a review of 25 previously reported cases of adenocarcinoma of the pouch or outflow tract following IPAA for UC. Our conclusions are 1) that post‐IPAA cancer can occur following either mucosectomy or stapled anastomosis; 2) that this malignancy can occur after IPAA performed for UC either with or without neoplasia; and 3) that this complication is seen whether or not the initial cancer or dysplasia had involved the rectum.

Sialosyl-Tn antigen: initial report of a new marker of malignant progression in long-standing ulcerative colitis.

BACKGROUND & AIMSnExpression of the mucin-associated carbohydrate antigen sialosyl-Tn (STn) correlates with malignant transformation in sporadic colonic neoplasms. The aim of this study was to analyze STn antigen expression in patients with long-standing ulcerative colitis (UC).nnnMETHODSnSTn antigen was assessed by immunohistochemistry in archival tissues. Study A was a retrospective chronological case-control study. Serial surveillance colonoscopic biopsy specimens without inflammation or dysplasia were analyzed in 7 patients who developed colon cancer and in 8 controls who did not develop colon cancer. Study B analyzed the anatomic distribution of STn expression in 17 cancer-bearing (case) and 6 cancer-free (control) colectomy specimens from patients with UC. In some colectomy specimens, STn was compared with aneuploidy, which was determined by flow cytometry.nnnRESULTSnIn study A, among the 7 patients with UC who developed cancer, 6 patients (86%) expressed STn in at least one prior nondysplastic surveillance biopsy specimen from the same site. Only 3 of 8 control patients (38%) expressed STn. In study B, STn was expressed in 40 of 82 specimens (49%) from cancer-bearing colons but only 8 of 62 specimens (13%) from cancer-free colons. STn was expressed in most aneuploid areas but was also found in diploid, nondysplastic mucosa.nnnCONCLUSIONSnSTn antigen seems to be a promising marker of cancer risk in patients with UC.