Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study.

BACKGROUND: Recent mucosal biopsy criteria combined with endoscopy effectively differentiate patients with ulcerative colitis ultimately requiring surgery (UC-S) from those receiving medication alone (UC-M). However, the criteria were inconvenient in practical use because of the need for complicated calculations, and the validity has not been verified in other institutes where the indications for surgery may differ. The aims of this multicenter study were to propose simple criteria in which calculation can be performed by mental arithmetic and to measure their validity. METHODS: Based on the above original criteria, we constructed simple criteria in which coefficients and constant were simplified to integral numbers. The criteria consisted of the diagnostic categories, highest-risk, high-risk, unpredictable, low-risk, and lowest-risk of surgery. The validity of these proposed criteria was evaluated in 121 patients with UC-S and 186 with UC-M from 11 institutes. RESULTS: The categories of high-risk and low-risk had sensitivities exceeding 86.0% and specificities exceeding 95.2%, and the validities were maintained at high levels in most individual institutes. There was little difference in validity between the proposed and original criteria when testing using the same patients. CONCLUSIONS: Despite simplified coefficients and constant, the proposed criteria reliably predicted the eventual clinical outcome of patients with ulcerative colitis and would be helpful in determining the necessity of surgery.

Clinical and colonoscopic investigation of skipped periappendiceal lesions in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is typically a continuous and diffuse inflammation extending proximally from the rectum. However, skipped lesion in the appendiceal region has been reported recently. Although appendectomy has been shown to reduce the risk of UC, the clinical significance of skipped periappendiceal lesion remains unclear. The present study examined the relationship between the continuous distal lesion of UC and the skipped periappendiceal lesion by observing colonoscopic changes in both lesions. METHODS: Among 279 patients with UC who underwent total colonoscopy from January 1994 to December 2000, 54 patients (19.4%) had skipped periappendiceal lesions. Serial colonoscopic examinations were performed in 35 of the 54 patients to determine the activities in the distal UC lesion and skipped periappendiceal lesion during the course of disease. RESULTS: Patients with skipped periappendiceal lesions were younger and had a longer history of UC than those without them, but no differences in sex ratio and treatment modality were observed between the two groups. In 28 of 35 patients (80%), the activity in the distal lesion correlated well with that in the skipped periappendiceal lesion. Both lesions were improved in 17 patients, unchanged in 5 patients and worsened in 6 patients. Linear regression analysis showed a significant correlation between the changes in colonoscopic activity index in the two lesions. CONCLUSION: A close association is found between disease activity in the skipped periappendiceal lesion and that in the distal lesion of UC.

Appendectomy protects against the development of ulcerative colitis and reduces its recurrence: results of a multicenter case-controlled study in Japan.

OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multicenter clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 +/- 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 +/- 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appenectomy group than in the group that did not undergo appendectomies (57. 1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration of disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has a negative association with and perhaps a preventive effect on the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis.

Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic mucosa.

BACKGROUND AND AIMS: Colonic epithelium is involved in the regulation of intestinal function and mucosal immune responses, and its function is altered in inflammatory bowel disease (IBD). However, a comprehensive analysis of the genetic alterations in inflamed colonic epithelium is not available at present. The aim of our study was to detect genes that are preferentially expressed in inflamed colonic epithelia and clarify the biochemical responses of epithelial cells in inflamed colonic mucosa. METHODS: cDNA representation difference analysis was used to identify candidate genes selectively expressed in inflamed colonic epithelia. Selective expression of these genes in the epithelium of inflamed colonic mucosa, including IBD and non-IBD tissues, was examined by real time polymerase chain reaction and in situ hybridisation. The effect of cell confluence and inflammatory mediators on Reg 1alpha gene expression was examined using a colon cancer cell line (HT29). RESULTS: We identified seven candidate genes that were presumed to be upregulated in the inflamed colonic epithelium. Of these, Reg 1alpha and GW112 were the dominant species and expression of these genes was confined to the crypt epithelium. In vitro studies using a colonic epithelial cell line suggested that cell confluence regulates Reg 1alpha gene expression. CONCLUSIONS: Selective expression of Reg 1alpha and GW112 genes in the crypt epithelium of inflamed colonic mucosa suggests the important regulatory functions of these genes.

Bax is downregulated in inflamed colonic mucosa of ulcerative colitis.

BACKGROUND AND AIMS: One form of epithelial cell injury in inflamed colonic mucosa in ulcerative colitis (UC) is reported to involve apoptosis of these cells. Bcl-2 family proteins Bax and Bcl-2 are the major regulators of apoptosis. The aim of this study was to elucidate the involvement of the Bax/Bcl-2 system in induction of apoptosis of the inflamed colonic epithelium in UC. METHODS: Colonic epithelium was isolated from colonic biopsy specimens. Expression of CD95, Bax, Bcl-xL, and Bcl-2 proteins was determined by western blotting. Bax gene expression was assessed by both reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern hybridisation and a real time PCR assay. RESULTS: Equal levels of expression of CD95, Bcl-xL, and Bcl-2 proteins were noted in normal and UC colonic epithelia. Equal levels of expression of Bax protein and mRNA were noted in epithelia of normal colon and inactive UC. Levels of expression of Bax protein and mRNA were markedly reduced in inflamed UC colonic epithelium. CONCLUSIONS: Our study showed for the first time downregulation of Bax in inflamed colonic epithelium of UC. The Bax/Bcl-2 system did not seem to be involved in induction of apoptosis of epithelial cells in the inflamed colonic mucosa of UC.

[Cardio vascular disease associated with ulcerative colitis].

Although cardiovascular complications such as Aortic syndrome (Takayasu's aortitis), Pericarditis and Myopericarditis might not be common, these complications should be noted as one of the fatal manifestation of IBD. It can be the sole or one of the several extraintestinal manifestation of either ulcerative colitis or Crohn's disease. Because of the therapeutic implications, we reviewed the literature documenting cardiovascular complication associated with ulcerative colitis. The comparatively high prevalence of Takayasu's aortitis with ulcerative colitis in Japanese patients may be explained by a immune genetic influence. HLA-B52 and DR2, were highly expressed in the patient with both disease. Myopericarditis and Pleuropericarditis associated with IBD were divided into two groups by pathogenesis, 1) drug (5-ASA)-induced disease, and 2) autoimmune disease. The cardiovascular symptom may occur while the patient's gastrointestinal disease is quiescent.

[Vitamin K deficiency syndrome caused by antituberculous agents].

Vitamin K deficiency caused by antituberculous agents was examined in clinical patients and in experimental rats. When antituberculous agents given to the patients who had only total elental diet because of small intestinal dysfunction, a marked increase in plasma PIVKA-II and a decrease in thrombo-test value were observed. These changes were quickly normalized by administration of vitamin K, despite of succeeding or stopping of antituberculous agents. In rat experiments, effects of four agents (ethambutol, isoniazid, paraaminosalicylate, and rifampicin) on prothrombin time were studied. Among these agents, only rifampicin prolonged prothrombin time. This prolongation depended on drug doses and duration of administration. In addition to this hypoprothrombinemia, an increase in plasma PIVKA-II was also observed, and these changes were normalized within 24 hours of vitamin K administration. These data suggest that rifampicin inhibits vitamin K epoxide reductase interfering re-use of vitamin K and caused vitamin K deficiency in patients with total elental diet.

Colonoscopic diagnosis of dysplasia and early cancer in longstanding colitis.

Five colitic cancers were detected among 40 patients with longstanding total colitis. The colitic cancers did not show the common polypoid or ulcerated appearance in the early stage, often being flat or plaque-like. It was not easy to detect these lesions endoscopically, and it was often impossible to do so radiologically. The flat or plaque-like early cancers were often surrounded by granular and/or red mucosa. We believed that the colonoscopic detection of this colitic cancer and dysplasia was difficult because: (1) the morphology of the lesions was difficult to determine, (2) the background mucosa was not normal. When the lesions were small, it was more difficult to detect them on the colitic mucosa than on the normal mucosa. The contrast between the lesion and the background mucosa was not clear in the latter condition. In surveillance colonoscopy (using a TV colonoscope) for longstanding ulcerative colitis, careful scrutiny throughout the large intestine is required to detect colitic cancers and dysplasia at an early state.

Localized colitis cystica profunda of the sigmoid colon.

Localized colitis cystica profunda (CCP) is a rare condition found in the rectum. Localized CCP of 70-year-old man was found in the sigmoid colon, it was accompanied by a cancer in the ascending colon and an adenomatous polyp with focal malignancy in the sigmoid colon. Colonoscopically, the tumor appeared like a submucosal tumor.

Polypectomy of a large juvenile polyp in the ascending colon.

A large juvenile polyp in the ascending colon of a 5-year-old boy was successfully polypectomized . The boy often had rectal bleeding, and anemia was known. Transection was necessary to prevent bleeding and anemia.