Gallstones in inflammatory bowel disease

Chronic disease of the terminal ileum is associated with a high prevalence of gallstones. To decide whether the ileal location of the disease is responsible for this finding, we determined the prevalence of gallstones in 189 patients with all types of inflammatory bowel disease. The prevalence of gallstones in patients with disease involving the terminal ileum (regional enteritis and granulomatous ileocolitis) was 28.2% compared to a prevalcolon (ulcerative colitis and granulomatous colitis),P<.001. The prevalence of gallstones in a hospital comparison population, age and sex matched to the regional enteritis-granulomatous ileocolitis group, was 11.7%,P<.01. In patients with disease of the ileum, the presence of gallstones was correlated with the length of ileum involved (P<.001), ileal resection (P<.02), and duration of disease (P<.001). The data suggest that the ileal location of the disease is of major importance.     

Crohn's disease

One theory of the pathogenesis of Crohn's disease is that rather than being caused by a unique environmental agent, it is the result of an abnormal immune response in the gastrointestinal tract. Recent studies indicate that Crohn's disease in its early stages is frequently associated with the presence of circulating antigen-non-specific suppressor T cells. Such T cells are also found in experimental inflammation caused by Chlamydia organisms in the gastrointestinal tract of nonhuman primates. Taken together, these data suggest that the suppressor T cells are markers of an underlying and persistent, antigen-specific immune response to an as yet unidentified antigen or set of antigens. We postulate that this underlying antigen-specific response is the result of a primary immunoregulatory abnormality involving an imbalance between the effects of antigen-specific helper and suppressor T cells which recognize a common antigen or antigens present in the mucosal environment.     

Fibrogenesis in Crohn's disease

INTRODUCTION: Over one-third of patients with Crohn's disease (CD) will develop an intestinal stricture and the great majority of these will require at least one surgical procedure. While the pathogenesis of inflammation in CD has been extensively investigated, knowledge of stricture pathogenesis remains limited. The aim of this review is to discuss the current understanding of fibrogenesis in CD and to outline potential directions in research and therapeutics. METHODS: The electronic literature (January 1966 to May 2006) on CD-associated fibrosis was reviewed. Further references were obtained by cross-referencing from key articles. RESULTS: CD-associated fibrosis results from chronic transmural inflammation and a complex interplay among intestinal mesenchymal cells, cytokines, and local inflammatory cells. The fibroblast is the key cell type mediating stricture formation. The cytoarchitecure of the bowel wall is altered with disruption of the muscularis mucosa, thickening of the muscularis propria, and deposition of collagen throughout. The cytokine TGF-beta appears critical in this process, acting to increase growth factor and extracellular matrix (ECM) production and dysregulate ECM turnover. Potential therapeutic interventions are likely to concentrate on modulating down-stream targets of TGF-beta. CONCLUSIONS: Greater understanding of the biology of fibrostenosis is likely to yield significant advances in our ability to care for patients with stricturing CD. Potential dividends of this approach include identification of novel therapeutic targets and biomarkers useful for prognostication and therapeutic monitoring.     

Malignancy in Crohn's disease

The incidence of cancer in Crohn's disease has been evaluated in 473 patients admitted to Rigshospitalet during the period 1 April 1964 to 1 January 1983. The patients' condition at the end of the survey, their survival, and the number and location of cancers were registered. During the survey period 23 cancers (4.9%) were found. Five were intestinal (1.1%) and were split evenly among the two sexes, whereas among 18 patients with extraintestinal cancers there was only 1 man. There was no increased risk of developing cancer inside the gastrointestinal tract compared with a background population matched for age, sex, and calendar time. Extraintestinal cancer in women was, however, significantly in excess.     

Diet in Crohn's disease

The consumption of sugar and sugar-containing foods in 32 patients with recently diagnosed Crohn's disease was significantly greater than in matched controls; the assessment was made by a questionnaire and depended upon patients recalling their eating habits. In a further study of 16 patients with Crohn's disease, all food eaten over 5 days was weighed and recorded, and no significant difference was found in the consumption of carbohydrate, protein, fats, or sugars, although the consumption of added sugars in patients was greater than controls. Patients who participated in both studies significantly reduced their intake of added sugar, and this was not found to correlate with either total intake of monosaccharides and disaccharides or the total carbohydrate consumption. The increased consumption of added sugar in patients with Crohn's disease does not appear to be related to other dietary abnormalities and may simply reflect a deficiency in perception of sweet taste in patients with this condition.     

Mycobacteriophage in Crohn's disease

Numerous similarities between Crohn's disease and sarcoidosis are being reported. Because of previous findings of culturable mycobacteriophage in the serum of many patients with sarcoidosis, mycobacteriophages were sought in serum of patients with Crohn's disease. No difference was found in the frequency of positive cultures between patients with Crohn's disease and normal control subjects.     

Corticosteroids in Crohn's disease

Crohn's disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohn's disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohn's disease. The controlled trials of the National Cooperative Crohn's Disease Study and the European Cooperative Crohn's Disease Study established that corticosteroids were effective for the induction of remission in Crohn's disease for the duration of the studies (6-17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohn's disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohn's disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohn's disease.     

Cancer in Crohn's disease

There has been a multitude of case reports, case series, hospital-based, and population-based studies that link CD to various types of cancers. When each of these studies is scrutinized, however, there is only enough evidence to support a link between colorectal adenocarcinoma, SBA, and squamous and adenocarcinomas that are associated with perianal fistulizing disease. All of the studies of large bowel adenocarcinoma or SBA follow patients in an era during which there were far fewer effective medicines to treat CD and surgery was more commonplace. The only surveillance study of patients who had extensive, long-duration Crohn's colitis showed a 22% risk for developing neoplasia (low-grade, high-grade, or cancer) after four surveillance examinations. Overall results from this study and the multitude of the other studies show that the risk for cancer in Crohn's colitis is equal to that in UC given equal extent and duration of disease. Patients who have Crohn's colitis that affects at least one third of the colon and with at least 8 years of disease should undergo screening and surveillance, just as in UC. Although the absolute risk for SBA in CD is low (2.2% at 25 years in one study), we should not rule out screening and surveying for this complication that is associated with significant morbidity and mortality in patients who have long-standing, extensive, small bowel disease. The risk for lymphoma and leukemia in CD is low, but immunomodulators and biologics may increase this risk. The evidence that links carcinoid tumors to CD is weak, and population-based studies need to be done. The study of cancers that are associated with CD is an evolving field that surely will change given that immunomodulators and biologics are being used with greater frequency.     

Fistula-in-ano in Crohn's disease

The outcome of aggressive surgical treatment of 64 symptomatic anal fistulas in 55 patients with Crohn's disease has been studied. Forty-one fistulas, in 33 patients, were treated by conventional fistulotomy (17 subcutaneous, 19 intersphincteric, 5 low transsphincteric fistulas). Thirty wounds (73 percent) healed within 3 months and eight more wounds (93 percent) healed within 6 months. Three wounds did not heal within 12–18 months. Two of these patients subsequently required proctocolectomy. Wound healing was not influenced by the presence of rectal Crohn's disease or granulomatous inflammation in the tract. No change in continence was experienced by 26 of the 33 patients who underwent fistulotomy. Three patients required proctocolectomy and the remaining four patients experienced minor degrees of incontinence postoperatively. Sixteen high transsphincteric, five suprasphincteric, and one extrasphincteric fistula in 22 patients were treated by laying open external tracts and placing a noncutting seton through the sphincter, which was left in place for prolonged periods to maintain drainage. During follow-up (6 months to 10 years, median 2.5 years), three fistulas healed and seven remained quiescent. Nine patients required further treatment by a new seton and three patients required proctocolectomy. Eight of the 22 patients who had a seton inserted had no change in continence, and six patients in this group developed minor changes in continence, mostly related to diarrhea associated with intestinal disease. Anal fistulas in Crohn's disease, which involve minimal sphincter muscle, can be successfully treated by fistulotomy. High fistulas should be treated with seton drainage to limit recurrent suppuration and preserve sphincter function.Read at the 89^th meeting of the American Society of Colon and Rectal Surgeons, St Louis, Missouri April 29–May 4 1990.