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Colonic lymphoma complicating ulcerative colitis.

Colonic lymphoma is a rare complication of ulcerative colitis. Two cases are described in patients who had had ulcerative colitis for 12 and 22 years respectively. Both patients presented with a recent change in their symptoms, which had become increasingly severe and which had not remitted with customary treatment for ulcerative colitis. Physical and haematological examinations revealed no evidence of generalized lymphoma, though barium enema studies indicated the sites of the lymphomatous lesions superimposed on chronic ulcerative colitis which were confirmed at operation and biopsy.

Colitis, Ulcerative↗

Expression of the Kp43 (CD 94) receptor by natural killer (NK) cells in ulcerative colitis.

BACKGROUND/AIMS: The presence of natural killer cells in the colon mucosa of patients with ulcerative colitis has not been studied, therefore, the study was designed to investigate the densities of cells expressing CD3+, CD4+, CD8+, CD56+ and the new CD94+ in colon mucosa of active and inactive ulcerative colitis patients. METHODOLOGY: Twenty ulcerative colitis patients, 10 with active disease and 10 with inactive disease, and 10 subjects with a histologically normal rectal mucosa were used as patients and controls. Additionally, a subgroup of 6 patients with active proctitis has been studied. Two biopsy specimens from rectal mucosa were taken for all patients and controls. Two biopsy specimens of proximal colon mucosa of the subgroup of 6 patients were also taken. One biopsy was processed for immunohistochemical studies and another for histologic study. RESULTS: The densities of CD3+, CD16+, CD56+ and CD 94+ were significantly increased in active ulcerative colitis patients compared to inactive subjects (P < 0.001). The increase in the CD4+ and CD8+ was not statistically significant. Patients with inactive ulcerative colitis also presented increased numbers of CD3+, CD56+ and CD94+ cells compared to controls (P < 0.001). In the subgroup of proctitis, the densities of cells expressing all the antigens were significantly lower in the normal mucosa compared to the affected colon (P < 0.001). No differences in the number of lamina propria DC1a+ cells between patients and controls were found. CONCLUSIONS: These findings suggest that natural killer cells are increased in active ulcerative colitis subjects and that the affected mucosa of ulcerative colitis patients with inactive disease is in state of "latent" inflammation. On the other hand, the normal looking mucosa from active ulcerative colitis patients does not differ from the mucosa of control subjects. Therefore, it seems that in ulcerative colitis the immunological alterations are limited to the affected mucosa.

Adult↗

Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis.

BACKGROUND: Inflammatory bowel disease (IBD)--and Crohn's disease (CD) and ulcerative colitis (UC) in particular--could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. METHODS: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (P(IBD) and P(CD)) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for P(IBD) and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. RESULTS: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. CONCLUSIONS: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.

Adult↗

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis.

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.

Cholangitis, Sclerosing↗

[Trends in the occurrence (1980-1999) and clinical features of Crohn's disease and ulcerative colitis in a university hospital in southeastern Brazil].

BACKGROUND: Crohn's disease and ulcerative colitis are regarded as uncommon in developing countries, but studies on their occurrence in Brazil are scarce. Aims - To determine the occurrence of Crohn's disease and ulcerative colitis in a Brazilian university hospital throughout a 20-year period, and analyze the demographical, clinical and evolutive features of these cases. METHODS: The frequencies of new cases of Crohn's disease and ulcerative colitis admitted from January 1980 up to December 1999 were calculated and a descriptive analysis of the features of all cases seen from January 1990 up to December 1999 was performed. RESULTS: A total of 257 new cases (126 with Crohn's disease and 131 with ulcerative colitis) was recorded. The frequencies of admissions for both Crohn's disease and ulcerative colitis have increased progressively from 40 up to 61 cases/10.000 new admissions and Crohn's disease gradually became more common than ulcerative colitis. For both diseases, there was predominance of women, age at admission in the range of 30-40 years, Caucasian origin, married state and non-smokers. Digestive symptoms presented were similar to those already described for both diseases and there were no differences between Crohn's disease and ulcerative colitis regarding the frequencies of general complaints and extra-intestinal manifestations (29.5% vs 23.3%), including thromboembolism (5.9% vs 5.4%). Obstruction and/or perforation were seen in up to 59.2% of Crohn's disease cases, whereas 53.7% of all ulcerative colitis cases presented as severe forms. In Crohn's disease cases with obstruction, smoking was significantly more common than in non-complicated cases. In ulcerative colitis cases of increased severity, general complaints, extra-intestinal manifestations and pancolitis were significantly more frequent than in less severe forms. CONCLUSIONS: For the last 20 years, there have been an increased frequency of admission of inflammatory bowel diseases, and Crohn's disease have become more prevalent than ulcerative colitis. Demographical, clinical and evolutive features of these diseases seems to be similar to those already described, but there seems to be a predominance of more severe forms of both diseases.

Adolescent↗

Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody.

BACKGROUND: Microbial agents are a possible cause of ulcerative colitis. We have previously reported evidence of bacteria invading the colonic mucosa of patients with ulcerative colitis. We have isolated bacteria from inflamed colonic mucosa, examined the localization of the species in the mucosa, and assayed for serum antibodies to the bacteria. METHODS: Cohorts of 31 per group were enrolled from patients with active ulcerative colitis, Crohn's disease, ischemic colitis, and colon adenomas. A group of 31 healthy controls were also studied. The presence of bacteria in biopsies of patients with ulcerative colitis was analyzed by both isolation and immunohistochemistry. Sera from patients were tested for bacterial antibodies using both Western blots and enzyme-linked immunosorbent assay (ELISA). RESULTS: Only sera from patients with ulcerative colitis gave specific reactions with Fusobacterium varium in Western blot assays. The detection rate of specific bands was higher for patients with ulcerative colitis (61%) than for subjects with either Crohn's disease (13%) or healthy controls (29%) (P < 0.001 and P = 0.021, respectively). The ELISA showed that the mean optical densities with extracts of F. varium as antigen were significantly higher for ulcerative colitis patients than for subjects with either Crohn's disease or healthy controls (P < 0.001). Immunohistochemical detection of F. varium in colonic mucosa was significantly higher in patients with ulcerative colitis (84%) than for subjects with either Crohn's disease (16%) or other controls (3-13%) (P < 0.001). CONCLUSIONS: Fusobacterium varium bacteria were present in a significant number of patients with active ulcerative colitis, and should be tested in therapeutic trials in order to confirm the causal relationship between F. varium and ulcerative colitis.

Adolescent↗

Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn's disease.

BACKGROUND: Increased expression of CD44v6 on colonic crypt epithelial cells in ulcerative colitis has been suggested as a diagnostic tool to distinguish ulcerative colitis from colonic Crohn's disease. AIMS: To investigate colonic CD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6) in patients with ulcerative colitis and Crohn's disease. METHODS: Colonic biopsy samples were obtained from 16 patients with ulcerative colitis, 13 with ileocolonic Crohn's disease, and 10 undergoing polypectomy. Serum samples were obtained from 15 patients with active ulcerative colitis, 20 with active Crohn's disease, and 20 healthy donors. Colonic CD44v6 expression was evaluated immunohistochemically by monoclonal antibody 2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6 concentrations were measured by ELISA. RESULTS: 2F10 stained colonic epithelium of inflamed ulcerative colitis and Crohn's disease samples in 80% and 40% of cases, respectively, and VFF18 in 95% and 87%, respectively. Both monoclonal antibodies displayed a sensitivity and specificity of 60% and 87% to differentiate ulcerative colitis from colonic Crohn's disease. Serum concentrations of sCD44v6 were lower in patients with ulcerative colitis (median 153 ng/ml; interquartile range (IQR) 122-211) compared with Crohn's disease (219; IQR 180-243) and healthy donors (221; IQR 197-241 (p = 0.002)). Its sensitivity and specificity to discriminate ulcerative colitis from Crohn's disease was 75% and 71%, respectively. CONCLUSION: Colonic CD44v6 and serum sCD44v6 concentrations do not facilitate reliable differential diagnosis between ulcerative colitis and Crohn's disease.

Acute Disease↗

Colonic bicarbonate output as a test of disease activity in ulcerative colitis.

No available test objectively measures impairment of function of the inflamed colonic mucosa in ulcerative colitis. To study function we assessed rectal bicarbonate output by rectal dialysis in the presence of water and bacterial fatty acid (n-butyrate) in 21 controls, 18 patients with acute ulcerative colitis, 12 patients with ulcerative colitis in remission, and 12 patients with other forms of colitis. In acute ulcerative colitis, compared with controls, bicarbonate output and pH was reduced (p less than 0.001); stimulated bicarbonate output with bacterial fatty acid (incremental bicarbonate output) was reduced by 80% in acute ulcerative colitis (p less than 0.01). Results indicate that bicarbonate output is a useful and selective test of mucosal function in acute ulcerative colitis. A diminished incremental bicarbonate output with n-butyrate supports the view of inadequate oxidation of bacterial fatty acids in vivo by the mucosa in ulcerative colitis. Whether the test will prove to be an index of prognosis or will aid choice between medical or surgical therapy requires further study.

Acute Disease↗

Survival and causes of death in Italian patients with ulcerative colitis. A GISC nationwide study.

BACKGROUND: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease. AIM: To evaluate overall and cause-specific mortality rate in a large group of Italian patients with ulcerative colitis. METHODS: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated. RESULTS: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0). CONCLUSIONS: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system.

Adult↗

Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are specific to ulcerative colitis pouches, they may play a role in the pathogenesis of pouchitis.

Adenomatous Polyposis Coli↗

Successful treatment of ulcerative colitis with leukocytapheresis using non-woven polyester filter.

Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Although the pathogenesis of ulcerative colitis is not fully elucidated, cell-mediated immunity plays an important role in disease pathogenesis. Leukocytapheresis is a newly emerging therapy to eliminate activated leukocyte from systemic circulation. We have studied the effects of leukocytapheresis on patients with ulcerative colitis who had failed to respond to conventional therapy. A total of 51 patients with ulcerative colitis were treated with apheresis using a non-woven polyester fiber filter (Finecell, Asahi Medical Co.,Tokyo, Japan) originally developed as a microcoagulation elimination filter for massive transfusion. Of the 51 patients, 33 (64.7%) achieved clinical remission manifested by clinical activity and colonoscopic findings without any adverse effects. This result suggested that leukocytapheresis using Finecell might serve as an alternative therapy for ulcerative colitis as other leukocytapheresis using centrifugation or column.

Adolescent↗

Rectal cell proliferation and colon cancer risk in ulcerative colitis.

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.

Adenoma↗

Addition of leukocytapheresis to steroid therapy: is it beneficial in recurrence of moderate-to-severe ulcerative colitis?

PURPOSE: In Japan, leukocytapheresis has become an accepted therapy for ulcerative colitis. The purpose of this retrospective study was to determine the efficacy of additional leukocytapheresis in patients with moderate-to-severe recurrence of ulcerative colitis. METHODS: From 1998 to 2002, 35 patients with moderate-to-severe recurrence of ulcerative colitis were treated by intravenous prednisolone only or prednisolone plus leukocytapheresis once per week. Previous clinical features of ulcerative colitis, activity index at four weeks, and subsequent course were compared between patients with leukocytapheresis and those without. RESULTS: Sixteen patients were treated with prednisolone only (prednisolone group), and 19 patients were treated with prednisolone plus leukocytapheresis (leukocytapheresis group). Previous prednisolone dose (13.6 +/- 10.4 g vs. 7.9 +/- 9.8 g; P < 0.05) was higher in the leukocytapheresis group than the prednisolone group. Clinical response rate at four weeks was not different between the two groups (leukocytapheresis group, 68.4 percent vs. prednisolone group, 75 percent). However, ulcerative colitis activity index at four weeks was significantly higher in the leukocytapheresis group than the prednisolone group (180.5 +/- 44.2 vs. 142.5 +/- 45.3; P < 0.05). During the subsequent clinical course, 15 of 35 patients required proctocolectomy (leukocytapheresis group, 11 patients vs. prednisolone group, 4 patients). Proctocolectomy rate was significantly different when patients were divided by previous prednisolone dose (P = 0.0029) and ulcerative colitis activity index at four weeks (P = 0.002), but it was not different according to the application of leukocytapheresis. Cox proportional hazards model revealed previous prednisolone dose to be the only independent risk factor for proctocolectomy. CONCLUSIONS: Addition of leukocytapheresis to prednisolone therapy does not seem beneficial in ulcerative colitis patients with moderate-to-severe recurrence.

Adult↗

Risk factors and indications for colectomy in ulcerative colitis patients are different according to patient's clinical background.

PURPOSE: Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy. METHODS: The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively. RESULTS: Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001). CONCLUSIONS: In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Adrenal Cortex Hormones↗