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PubMed2002

Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND & AIMS: Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial. METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires. RESULTS: Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects. CONCLUSIONS: Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.

Administration, Oral↗
PubMed2004

Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis.

BACKGROUND & AIMS: Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. METHODS: We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). RESULTS: Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). CONCLUSIONS: In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs.

Adolescent↗
PubMed2005

A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models.

BACKGROUND & AIMS: Mice with a disrupted gene for the G-protein alpha inhibitory 2 chain ( Gnai2 -/- ) develop a spontaneous colitis resembling human inflammatory bowel disease. Disease expression differs markedly between inbred strains of mice, indicating genetic control of disease susceptibility. We performed a genome-wide screen to localize the chromosomal regions regulating disease expression. METHODS: A total of 284 F2 mice derived from resistant C57BL/6J Gnai2 -/- mice and susceptible C3H/HeN Gnai2 -/- mice were analyzed in a genome-wide screen for colitis susceptibility and severity. RESULTS: A highly significant locus on chromosome 3 (Gpdc1) contributed to colitis susceptibility and severity (likelihood ratio statistics [LRS] = 32.4; LOD score = 7; P < 1.0 x 10(-5)). The peak linkage of this locus at 62 cM colocalizes exactly with a previously identified locus controlling colitis susceptibility in interleukin-10-deficient mice. In addition, evidence for linkage with a locus on chromosome 1 (Gpdc2 ; LRS = 19.7; LOD = 4.3) was found, and the 2 loci interacted epistatically (combined LRS = 68.2). A third locus (Gpdc3) was found on chromosome 9 and this locus interacted epistatically with a locus on chromosome 7, which by itself did not have an effect on the trait. CONCLUSIONS: The identification of a major locus on chromosome 3 that controls susceptibility to spontaneous colitis in 2 different gene-knockout models indicates that this locus harbors a gene(s) that plays a key role in maintaining mucosal homeostasis. Identification of this gene(s) may contribute to further understanding of the mechanisms underlying human inflammatory bowel disease.

Animals↗
PubMed2005

Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.

BACKGROUND & AIMS: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. METHODS: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. RESULTS: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. CONCLUSIONS: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

Adult↗
PubMed2005

A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts.

BACKGROUND & AIMS: Bone marrow (BM) cells form differentiated adult lineages within nonhematopoietic tissues, with a heightened propensity with increasing regenerative pressure dictated by disease. We have previously shown that BM cells engraft into the gut and contribute substantially to the subepithelial intestinal myofibroblast population in the lamina propria. To investigate the reparative capacity of BM in inflammatory bowel disease (IBD), a well-established model of experimental colitis was used. METHODS: Lethally irradiated female mice were rescued by a BM transplant from male donors. Colitis was induced 6 weeks posttransplantation by injection of trinitrobenzene sulfonic acid (TNBS), and tissues were analyzed 1-14 days later. Donor-derived cells were detected by in situ hybridization using a Y chromosome-specific probe, and their phenotype was determined by immunohistochemistry. RESULTS: TNBS-induced colitis was manifest as patchy lesions that increased in severity between days 1 and 8, and the mucosa gradually regenerated between days 8 and 14. The contribution of BM to intestinal myofibroblasts was significantly increased in regions of colitis compared with noninflamed regions. Furthermore, BM-derived endothelial cells, pericytes, and vascular smooth muscle cells were frequently interspersed throughout blood vessels, suggesting that these cells facilitate angiogenesis in tissue repair, substantiated by a significant increase in the incidence of BM-derived vascular smooth muscle cells in colitic compared with noninflamed regions. Blood vessels formed entirely from BM-derived cells were also seen, suggesting a role for BM in neovasculogenesis. CONCLUSIONS: Our data show that BM contributes to multiple intestinal cell lineages in colitis, with an important function in tissue regeneration and vasculogenesis after injury.

Animals↗
PubMed2006

Therapeutic action of ghrelin in a mouse model of colitis.

BACKGROUND & AIMS: Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. METHODS: We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. RESULTS: Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. CONCLUSIONS: Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Analysis of Variance↗
PubMed2006

Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study.

BACKGROUND & AIMS: Predictive and protective factors associated with colorectal cancer in chronic ulcerative colitis are not well described. Surveillance colonoscopy and 5-aminosalicylic acid therapy may mitigate cancer risk, but there is debate because these variables have not been evaluated in the same study. The presence of postinflammatory pseudopolyps and use of other anti-inflammatory medications may be important variables that influence risk, but data are sparse. METHODS: Variables associated with colorectal cancer were registered in 188 patients with ulcerative colitis-related cancer and matched controls. Conditional logistic regression, adjusted for age at colitis diagnosis and colitis duration, identified a final set of variables independently associated with colorectal cancer. RESULTS: In the final multiple variable model, the most important factors associated with colorectal cancer were a history of pseudopolyps (OR, 2.5; 95% CI: 1.4-4.6), 1 or 2 surveillance colonoscopies (OR, 0.4; 95% CI: 0.2-0.7), smoking (OR, 0.5; 95% CI: 0.2-0.9) and use of corticosteroids (OR, 0.4; 95% CI: 0.2-0.8), aspirin (OR, 0.3; 95% CI: 0.1-0.8), nonsteroidal anti-inflammatory drugs (OR, 0.1; 95% CI: 0.03-0.5), and 5-aminosalicylic acid agents (OR, 0.4; 95% CI: 0.2-0.9), although the latter was not statistically significant after 5 years. Primary sclerosing cholangitis and immunosuppressive use were not statistically significant. CONCLUSIONS: These results suggest that, in a population matched for extent and duration of chronic ulcerative colitis, surveillance colonoscopy and use of anti-inflammatory medications may reduce the risk of colorectal cancer. A history of postinflammatory pseudopolyps appears to be a predictive factor for cancer.

Adolescent↗
PubMed2006

Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production.

BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.

Animals↗
PubMed1999

Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats?

We investigated the protective role of fish oil (FO-source of n-3 FA) enriched diet (in the first protocol) in 20 rats and FO administration intrarectally (in the second protocol) in 40 rats with trinitrobenzene (TNB) colitis. All colonic specimens were pathologically evaluated, myeloperoxidase enzyme activities were measured, leukotriene B4 (LTB4) and LTC4 levels were determined by radioimmunoassay. In the first protocol 10 rats (group A1) were fed with 8% sunflower and cotton oil enriched diet and (group A2) with 8% FO enriched diet for 6 weeks. At the end of this period, TNB (30 mg in 0.25 ml of 30% ethanol) were intrarectally administered. After 2 weeks, rats were sacrificed. MPO activities (2.47 versus 30.17), LTB4 (34.5 versus 903.3) and LTC4 (77.7 versus 456.0) levels were significantly reduced in group A2 compared with group A1 (P<0.005). There was also a significant difference in pathologic scores (1.55 versus 2.12, P<0.002) between two groups. In the first part of the second protocol, 20 male rats were randomized into two equal groups (B1 and B2) and TNB colitis was induced. After 1 day, 1 ml of saline (group B1) or n-3 FA enemas (group B2) were administered every day for 2 weeks. At the end of this period, rats were sacrificed and evaluated as done for previous groups. Although there was no significant difference between the two groups in comparison with MPO enzyme activities and pathologic scores, the LTB4 (130.1 versus 971.0) and LTC4 (126.0 versus 532.0) levels of FO group were significantly reduced (P<0.005). In the second part of the second protocol, 20 male rats were randomized into two groups. One millilitre of saline (group B3) or FO enemas (group B4) were administered to rats every day for 3 days. At the fourth day, TNB-colitis was induced and after 24 h rats were sacrificed. We could not find any significant difference in MPO activities, pathologic scores, LTB4 and LTC4 levels between groups B3 and B4. In conclusion, FO enriched diet decreased both pathologic damage and tissue LT levels. The second protocol of our study revealed that the long-term FO enemas decreased the LTB4 and LTC4 levels; however, did not have any beneficial effect on the tissue lesions. Short periods of FO enemas did not have a protective role in the occurrence of experimental colitis. The present study showed that FO enemas significantly decreased LT levels. The protective effect of FO (oral and enema) in TNB colitis may open a new insight into the treatment of inflammatory bowel disease.

Animals↗
PubMed1977

[Pregnancy in ulcerative colitis and Crohn's disease (author's transl)].

Between 1967 and 1973 15 women with ulcerative colitis had 20 pregnancies. 14 ended with normal deliveries, 4 with spontaneous abortions, and 2 with therapeutic abortions. Fertility was normal. Malformations in the children were not observed. In the case of conception during remission or a latent phase of the disease in general a normal pregnancy is to be expected (12 out of 14). On the other hand conception during an active phase can lead to an unpredictable threat to the life of mother and child. Therapeutic abortion should be seriously considered when ulcerative colitis and pregnancy begin simultaneously. In the same period of time in 15 comparable patients with Crohn's disease (12 with ileo-colitis and 3 with terminal ileitis) who were not taking ovulation inhibitors 4 pregnancies were observed. Fertility is not significantly reduced in terminal ileitis whereas in ileo-colitis it is highly significantly reduced (bilateral tubal irritation). As in ulcerative colitis a normal pregnancy can be expected after conception in an inactive phase (2 out of 4).

Abortion, Spontaneous↗
PubMed2002

[5-Fluorouracil-induced colitis--a review based upon consideration of 6 cases].

BACKGROUND: At increasing use of high-dose 5-fluorouracil-based chemotherapy for metastatic colorectal and gastric cancer complicated drug-induced colitis is observed more frequently. From May 1998 to November 2000 we observed 6 cases of 5-fluorouracil-induced colitis, in which we looked for involvement of small intestine. We report summing up on the 6 cases including both endoscopic and histological findings in both sites of the gut. CASE REPORTS: In 2 men and 4 women (age 49-78 years) with advanced colon (n = 2), gastric (n = 3 ) and gallbladder (n = 1) cancer a palliative weekly high-dose infusional 5-fluorouracil (2,6 g/m(2)/24 h) and folinic acid (500 mg/m(2)/2 h) chemotherapy was performed. Few days after 1-5 chemotherapy courses the patients were admitted to our hospital with abdominal pain and partly severe watery diarrhea (up to 20 times evacuations/per day). The stool cultures were negative and there were no proof both of clostridium difficile and his toxin A and B. In 4 patients colonoscopy showed different grades of colitis up to diffuse erythema and microlesions, 2 patients had no visible lesions. In 4 patients endoscopy of the upper GI-tract showed a severe inflammation (n = 1) and a fibrinopurulent exsudate, severe edema and isolated ulcerations (n = 3) of jejunum after gastrectomy or duodenum with intact stomach. In the histological assessment different grades of 5-FU-induced colitis without (n = 2) or with (n = 4) involvement of the upper small intestine destruction of the superficial mucosa and crypts (epitheliumapoptosis) were found. 5 patients were treated by antibiotics (vancomycin n = 2, metronidazole n = 3), glucocorticoids (n = 5) and Saccaromyces cerevisiae (n = 3). After 8-10 days the patients were complete free of symptoms. One patient died due to the enterocolitis. CONCLUSIONS: The present cases demonstrate that high-dose 5-fluorouracil-based chemotherapy not only induces a colitis but also may involve the upper small intestine tract. Consequently, it represents an increasing and serious adverse event of high-dose chemotherapy. The etiology of the enterocolitis (drug- or bacterial-induced) needs further investigations in order to find a causal therapy and/or prophylaxis.

Aged↗
PubMed2006

Low frequency of colorectal dysplasia in patients with long-standing inflammatory bowel disease colitis: detection by fluorescence endoscopy.

BACKGROUND AND STUDY AIM: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colonic dysplasias. Dysplastic changes in flat mucosa are likely to be missed by conventional colonoscopy. Endoscopic fluorescence imaging, using 5-aminolevulinic acid (5-ALA) as photosensitizer, has evolved as a new technique to differentiate between normal colonic mucosa and dysplasia. We combined this technique with random biopsies to prospectively evaluate the occurrence of dysplasias in patients with long-standing IBD. PATIENTS AND METHODS: 52 colonoscopies were performed in 42 consecutive patients (n = 28 with ulcerative colitis, n = 11 with Crohn's colitis, n = 3 with indeterminate colitis; mean age 43 years, range 21 - 78) with long-standing IBD colitis (median disease duration 14 years, range 3 - 40). All patients were in clinical remission. Patients were examined using both conventional white light and by fluorescence colonoscopy using oral 5-ALA. Four biopsies were taken every 10 cm from mucosa of normal appearance. In addition, macroscopically suspicious and fluorescence-positive areas were biopsied. RESULTS: A total of 688 biopsies of red-fluorescent (n = 20) and nonfluorescent (n = 662) areas of mucosa were taken. Dysplasia was detected histopathologically in only two of the biopsies. These biopsies were taken from two polypoid lesions which were fluorescence-negative. CONCLUSIONS: The rate of colonic dysplasia in patients with long-standing IBD colitis may be lower than previously reported.

Administration, Oral↗
PubMed1998

Acute colitis following colonoscopy.

Colitis following colonoscopy is an acute, self-limited condition characterized by tenesmus and bloody diarrhea appearing within 48 hours of colonoscopy or sigmoidoscopy. Glutaraldehyde used for disinfection of the endoscopes is considered to be the main etiological agent. Three cases of severe acute self-limited colitis are described in this report. All three were observed within one week, and showed the typical anamnestic, clinical, endoscopic, histological, and radiological features of glutaraldehyde-induced colitis. The main characteristics in these cases were the time relationship with colonoscopy and the severity of the clinical presentation, with symptoms of systemic reaction and intense and diffuse edema of the colonic mucosa. The clinical and morphological features may mimic those of colonic ischemia. All three patients recovered completely within a few days, one spontaneously and two after treatment with steroids, antibiotics, and mesalazine. Acute colitis following colonoscopy should be regarded as one of the complications related to colonoscopy, and it should be taken into account in the differential diagnosis of acute colitis.

Acute Disease↗
PubMed1995

The role of colonoscopy in the differential diagnosis of acute, severe hemorrhagic colitis.

BACKGROUND AND STUDY AIMS: This study assesses the diagnostic value of colonoscopy performed at an early stage of a first attack of acute, severe hemorrhagic colitis. PATIENTS AND METHODS: One hundred fourteen consecutive patients were prospectively studied. The colonoscopic diagnosis was compared with the final diagnosis of the colitis, which was based on clinical, microbiological, endoscopic, and histological criteria during the acute illness, but also on the results of a thirty-month follow-up of the patients aiming to confirm whether the colitis was relapsing or nonrelapsing in nature. RESULTS: The colonoscopic diagnosis was ulcerative colitis (UC) in 40, Crohn's disease in four, and infective colitis (IC) in 70 patients. The endoscopic diagnosis was finally confirmed in all 40 UC patients and in 68 of 70 (97.1%) IC patients. Two patients with an initial endoscopic and histological diagnosis of IC presented with typical attacks of UC 28 and 30 months later, respectively. Prominent endoscopic appearances in IC were mucosal edema, erythematous areas, hemorrhagic spots, bleeding, microaphthoid ulcers, and luminal exudate. Although rectal sparing was occasionally seen, endoscopic lesions were continuous and severe in the distal colon, but were patchily and unevenly distributed in other parts of the colon in IC. In UC, prominent colonoscopic findings were bleeding, mucosal friability, granularity, and ulceration; lesions were continuously distributed in the involved area. CONCLUSIONS: Colonoscopy is a useful procedure in the differential diagnosis of severe bloody diarrhea of unknown cause.

Acute Disease↗
PubMed1989

Treatment of diversion colitis with short-chain-fatty acid irrigation.

A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohn's, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients.

Colitis↗
PubMed1990

Ulcerative colitis and colorectal cancer. A population-based study.

BACKGROUND: The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies. METHODS: To provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis, we studied a population-based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984. RESULTS: Ninety-two cases of colorectal cancer occurred in 91 patients. As compared with the expected incidence, the incidence of colorectal cancer in the cohort was increased (standardized incidence ratio [ratio of observed to expected cases] = 5.7; 95 percent confidence interval, 4.6 to 7.0). Less extensive disease at diagnosis was associated with a lower risk; for patients with ulcerative proctitis, the standardized incidence ratio was 1.7 (95 percent confidence interval, 0.8 to 3.2); for those with left-sided colitis, 2.8 (95 percent confidence interval, 1.6 to 4.4); and for those with pancolitis (extensive colitis, or inflammation of the entire colon), 14.8 (95 percent confidence interval, 11.4 to 18.9). Age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer. For each increase in age group at diagnosis (less than 15 years, 15 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and greater than or equal to 60 years), the relative risk of colorectal cancer, adjusted for the extent of disease at diagnosis, decreased by about half (adjusted standardized incidence ratio = 0.51; 95 percent confidence interval, 0.46 to 0.56). The absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age. CONCLUSIONS: Close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis, especially those who are less than 15 years of age at diagnosis.

Adolescent↗
PubMed1994

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗
PubMed2005

Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Adult↗