Small bowel lesions detected with wireless capsule endoscopy in patients with active ulcerative colitis and with post-proctocolectomy

Background: Although rare, duodenal lesions have been reported in association with ulcerative colitis (UC); however, there have been very few reports on small bowel lesions, and many aspects of their pathology and frequency remain unknown. This study determined whether small bowel lesions are present in UC by using wireless capsule endoscopy (WCE). Patients and Methods: WCE was performed on 20 patients with active UC and 10 who had undergone proctocolectomy. Results: Small bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of the 10 post‐proctocolectomy patients. Ulcers that extended over a long segment or whole tertile of the small bowel were observed in five patients, and the disease type was extensive colitis in three of these and pouchitis in the other two. Age at onset was significantly lower in the 20 active UC patients that had small bowel lesions. Conclusion: WCE revealed the presence of ulcers that extended over a long segment or a whole tertile in the small bowel in active extensive colitis and pouchitis. In future, it will be necessary to assess the clinical significance of small bowel lesions in UC in detail.     

Gastroduodenitis associated with ulcerative colitis

Background Ulcerative colitis (UC) is regarded as confined to the colorectum; however, there are several case reports showing upper gastrointestinal involvement. The aim of this study was to examine the prevalence and characteristics of gastroduodenitis associated with UC (GDUC). Methods Esophagogastroduodenoscopy with biopsies was prospectively performed on 250 UC patients (134 men, 116 women; mean age, 42 years; 162 with colectomy, 163 with pancolitis). Criteria for GDUC were created on the basis of endoscopic and histological comparisons with non-UC controls, and the prevalence and characteristics were statistically analyzed. Results GDUC was defined endoscopically as friable mucosa (erosive or ulcerative mucosa with contact or spontaneous bleeding), granular mucosa (multiple white spots almost without a red halo), or, conditionally, multiple aphthae (multiple white spots surrounded by a red halo, clinically excluding other disorders such as Crohn’s disease). The prevalence of GDUC was 19/250 (7.6%). The clinical characteristics included more extensive colitis, lower dose of prednisolone, higher prevalence of pouchitis, and longer postoperative period. In our population, the presence of pancolitis and a lower dose of prednisolone were significant risk factors for developing GDUC in multivariate analysis. Conclusions The high prevalence of GDUC suggests that the gut inflammatory reaction in UC may not be restricted to the large intestine. Administered steroids might conceal GDUC, and more aggressive UC such as active pancolitis may be related to the development of GDUC.     

SURVEILLANCE BY MAGNIFYING ENDOSCOPY IN PATIENTS WITH ULCERATIVE COLITIS

Background: Patients with total or left‐sided ulcerative colitis (UC) for more than 10 years have an increased risk of colon cancer. We studied usefulness of magnifying chromoendoscopy for the surveillance of dysplasia and colitic cancer associated with UC. Methods: From April 2003 through February 2004, 39 patients who had total or left‐sided UC for at least 7 years were prospectively enrolled in an endoscopic surveillance program, including target biopsy. All patients were examined by chromoendoscopy and magnifying endoscopy. Sites showing abnormal mucosal surface patterns or pit patterns suggestive of dysplasia underwent biopsy. Results: Of the 39 patients, 26 had total UC and 13 left‐sided UC. The mean time elapsed since the onset of UC was 16.2 ± 5.9 years. Disease activity at examination was remission in 22 patients, mild in 15, and moderate in two. Dysplasia was diagnosed in two patients (three lesions), dysplastic changes were suspected in two (two lesions), and sporadic adenoma was diagnosed in four (five lesions). On endoscopic examination, dysplasia appeared as flat elevated lesions with types IIIl and IV pit patterns. Resected specimens showed low‐to‐high‐grade dysplasia. The four patients presenting with a type III to IV mucosal pit pattern during remission were evaluated as sporadic adenoma on pathological findings. Conclusions: A combination of chromoendoscopy and magnifying endoscopy is useful for the detection of dysplasia and colitic cancer in patients with UC.     

Evaluation of gastroduodenal mucosal lesions in patients with Crohn's disease and ulcerative colitis

Background: Patients with Crohn's disease (CD) are reported to suffer from upper gastroduodenal lesions with varying frequency, although concurrent Helicobacter pylori infection is reported to be low. Methods: A prospective study was carried out on patients diagnosed with CD or ulcerative colitis (UC) in order to evaluate the degree of upper gastroduodenal tract involvement and the prevalence of Helicobacter pylori infection. Results: Gastroduodenal lesions were found in 18 (78%) of 23 CD patients, the location being the stomach in 18 (78%), the duodenal bulb in 16 (70%) and the descending duodenum in 16 (70%). Bamboo joint‐like lesions were found in four cases (17%) in gastric body and cardia. In contrast, gastroduodenal lesions were found in 10 (53%) of 19 UC patients, the location being the stomach in nine (47%), the duodenal bulb in six (32%), and the descending duodenum in three (16%). The H. pylori‐positive rate in patients with CD and UC was 0%, and 11%, respectively. Conclusion: Minute upper gastroduodenal lesions are much more common in CD than in UC patients, especially in the descending duodenum. Accordingly, upper gastrointestinal endoscopy would seem to be a useful means with which to obtain a definitive diagnosis in all suspected IBD cases.     

Gastric cancer following total proctocolectomy for colon cancer associated with ulcerative colitis

Here we report a case of advanced gastric cancer seen after total proctocolectomy for an early colon cancer associated with ulcerative colitis (UC). A 42-year-old man, diagnosed with UC at the age of 21, had undergone total proctocolectomy at the age of 38 for an early ascending colon cancer. Three years later the patient developed tarry stools and epigastric discomfort. Laboratory data showed anemia together with elevated serum p53 antibody. Gastric endoscopy showed thickening folds around a lesion in the stomach body. The pathological diagnosis was poorly differentiated adenocarcinoma with signet-ring cell carcinoma. Total gastrectomy was performed and the resected specimens showed a diffuse infiltrating tumor (scirrhous gastric carcinoma), 11 × 15 cm in size, with multiple lymph node metastases. Histopathological examination revealed diffuse infiltration of cancer cells throughout the gastric wall and invasion of the serosa. Results of cytology on abdominal lavage were positive for cancer cells. Likewise, immunohistochemical staining showed gastric mucin phenotype cancer cells positive for p53. In conclusion, it is important to bear in mind that patients with UC, especially chronically active pancolitis, potentially bear the risk of upper gastrointestinal complications.     

Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract

Objective. According to epidemiological studies, smoking habit is strongly associated with inflammatory bowel disease. Non-smokers, and especially recent ex-smokers, have an increased risk of ulcerative colitis (UC). Conversely, concerning Crohn's disease, the risk is increased among smokers. Pouchitis is the major long-term complication of restorative proctocolectomy for UC, and seems to be pathogenetically related to this condition. The aims of this study were to test the hypothesis that smoking reduces the risk of pouchitis, and to investigate whether cessation of smoking precedes the onset of the inflammation. Material and methods. All living patients operated on for UC with proctocolectomy and ileal pouch anal anastomosis (IPAA) between November 1982 and November 1996 at Sahlgren's University Hospital were included in the study (n=410). Data concerning smoking habits and pouchitis were obtained from questionnaires and from medical records. The correlation between smoking habits and incidence of pouchitis was statistically evaluated by means of a survival test and a multivariate analysis, i.e. a Poisson model. Results. In all, 327 patients (80%) completed the questionnaires. Ninety-six (29%) of these patients had had at least one episode of pouchitis. Smoking habits during follow-up did not significantly influence the risk of pouchitis (p=0.29). Nor did smoking habits before and at the time of IPAA correlate with the incidence of pouchitis. Women had a decreased risk of pouchitis, compared to men (p=0.014). There was a non-significant tendency for smoking to increase the risk, which was more pronounced in women. Conclusions. Smoking does not decrease the risk of pouchitis following IPAA for UC, and in this respect the pathogenetic model of pouchitis, suggested to be a manifestation of UC, is not supported.     

Patients with extraintestinal manifestations have a higher risk of developing pouchitis in ulcerative colitis: multivariate analysis

Background: Restorative proctocolectomy and ileal pouch‐anal anastomosis (IPAA) have been the surgical treatments of choice for ulcerative colitis (UC). However, the IPAA is sometimes complicated with pouchitis. Furthermore, the cumulative risk and risk factors for developing pouchitis in patients with UC undergoing IPAA have not been reported in any Asian population. The aim of our study is to clarify the cumulative risk and risk factors for developing pouchitis in Japanese patients with UC undergoing IPAA. Methods: Fifty‐eight patients with UC undergoing IPAA were retrospectively evaluated for the presence of pouchitis, gender, age of onset, history of smoking, presence of extraintestinal manifestations (EIMs) and type of operation. The diagnosis of pouchitis was based on the pouchitis disease activity index. The cumulative risk and risk factors for developing pouchitis were assessed. Results: The cumulative risks for developing pouchitis at 1 and 5 years were 9.0% and 14.4%, respectively. The estimated risks of pouchitis at 5 years was 48.1% in patients with EIMs and 4.6% in those without. Both univariate and multivariate analyses revealed that the presence of EIMs is a significant risk factor (hazard ratio 16.85, 95% confidence interval 3.12–91.00; P?=?0.001). Conclusions: The presence of EIMs is a significant risk factor for the development of pouchitis in Japanese patients with UC undergoing IPAA.     

Does smoking influence the risk of pouchitis following ileal pouch anal anastomosis for ulcerative colitis?

OBJECTIVE: According to epidemiological studies, smoking habit is strongly associated with inflammatory bowel disease. Non-smokers, and especially recent ex-smokers, have an increased risk of ulcerative colitis (UC). Conversely, concerning Crohn's disease, the risk is increased among smokers. Pouchitis is the major long-term complication of restorative proctocolectomy for UC, and seems to be pathogenetically related to this condition. The aims of this study were to test the hypothesis that smoking reduces the risk of pouchitis, and to investigate whether cessation of smoking precedes the onset of the inflammation. MATERIAL AND METHODS: All living patients operated on for UC with proctocolectomy and ileal pouch anal anastomosis (IPAA) between November 1982 and November 1996 at Sahlgren's University Hospital were included in the study (n=410). Data concerning smoking habits and pouchitis were obtained from questionnaires and from medical records. The correlation between smoking habits and incidence of pouchitis was statistically evaluated by means of a survival test and a multivariate analysis, i.e. a Poisson model. RESULTS: In all, 327 patients (80%) completed the questionnaires. Ninety-six (29%) of these patients had had at least one episode of pouchitis. Smoking habits during follow-up did not significantly influence the risk of pouchitis (p=0.29). Nor did smoking habits before and at the time of IPAA correlate with the incidence of pouchitis. Women had a decreased risk of pouchitis, compared to men (p=0.014). There was a non-significant tendency for smoking to increase the risk, which was more pronounced in women. CONCLUSIONS: Smoking does not decrease the risk of pouchitis following IPAA for UC, and in this respect the pathogenetic model of pouchitis, suggested to be a manifestation of UC, is not supported.     

ILEITIS AS A MAIN RECURRENT LESION IN A PATIENT WITH ULCERATIVE COLITIS: REPORT OF A CASE

We report a case of ulcerative colitis complicating ileitis that endoscopically and histologically resembled a colonic lesion. Eight years prior to the time of writing, the patient had undergone proctosigmoidectomy and ileocecal resection because of severe hemorrhagic lesions of ulcerative colitis. A month prior to the time of writing, bleeding from the stoma occurred. Endoscopy revealed erosions on easy‐bleeding mucosa in the ileum but no active inflammatory lesions in colonic mucosa except for small erosions in the descending colon beneath the stoma. Histologic findings of biopsy specimens from the ileal mucosa showed marked inflammation including neutrophile infiltration and crypt abscesses. This is a rare case of ulcerative colitis showing ileitis as a main recurrent lesion, suggesting that careful observation of the small intestine will be required after ileocecal resection in ulcerative colitis patients.     

Persistence of high CD40 and CD40L expression after restorative proctocolectomy for ulcerative colitis

AIM:To focus on the role of CD40 and CD40L in their pathogenesis. METHODS:We analyzed by immunohistochemistry the CD40 and CD40L expression in the pouch mucosa of 28 patients who had undergone RPC for UC, in the terminal ileum of 6 patients with UC and 11 healthy subjects. We also examined by flow cytometry the expression of CD40 by B lymphocytes and monocytes in the peripheral blood of 20 pouch patients, 15 UC patients and 11 healthy controls. RESULTS:Ileal pouch mucosa leukocytes presented a significantly higher expression of CD40 and CD40L as compared to controls. This alteration correlated with pouchitis, but was also present in the healthy pouch and in the terminal ileum of UC patients. CD40 expression of peripheral B lymphocytes was significantly higher in patients with UC and pouch, respect to controls. Increased CD40 levels in blood B cells of pouch patients correlated with the presence of spondyloarthropathy, but not with pouchitis, or inflammatory indices. CONCLUSION:High CD40 expression in the ileal pouch mucosa could be implied in the pathogenesis of pouchitis following proctocolectomy for UC, whereas its increased levels on peripheral blood B lymphocytes are associated with the presence of extraintestinal manifestations.     

AUTOFLUORESCENCE IMAGING IS USEFUL TO ASSESS ACTIVITY OF ULCERATIVE COLITIS

The efficacy of autofluorescence imaging (AFI) for assessing ulcerative colitis (UC) activity was reviewed. AFI images of UC lesions could be classified into four categories: green; green with purple spots; purple with green spots; and purple. The strength of purple in AFI images of UC lesions is related to histologic severity, thus this classification is helpful to assess the activity of UC. The autofluorescence of AFI images was also quantified using color analysis software. Active lesions had significantly low autofluorescence/reflex ratio than inactive areas in UC patients. The ratio is inversely proportional to histologic severity. When the cut‐off is 0.9, the accuracy to predict histologic activity by AFI is 92%.     

Outcome after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis

BACKGROUND: During the course of their disease, about 30% of patients with ulcerative colitis (UC) will undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We evaluated the outcome of IPAA in a Belgian referral center. METHODS: Clinical charts were reviewed for pre- and postoperative disease course, functional outcome, and complications in all patients with UC (n = 182) and indeterminate colitis (n = 2) who underwent IPAA in 1990-2004. RESULTS: Follow-up data were available in 173 out of 184 patients (67 female, median age at proctocolectomy 39.0 years). Median functional Oresland score 1 year after IPAA was 3 (range 0-11). Early postoperative complications were seen in 27% of patients. After a median (interquartile range) follow-up of 6.5 (3.4-9.9) years, 35% of patients developed septic and/or obstructive complications. Forty-six percent of patients developed at least 1 episode of pouchitis. Risk factors for pouchitis were the presence of extraintestinal manifestations (odds ratio [OR] 1.92 (1.23-3.01), P = 0.004) and younger age at proctocolectomy (P = 0.004). Chronic pouchitis was present in 33 patients and associated with extraintestinal manifestations (OR 2.93 (1.13-7.62), P = 0.027), backwash ileitis (OR 9.28 (1.71-50.49), P = 0.010), and length of follow-up (P = 0.004). Pouch failure occurred in 5% of patients. CONCLUSIONS: Although proctocolectomy with IPAA surgery has a good functional outcome, postoperative complications, especially pouchitis, remain considerable in patients with UC.     

11 Ileal pouches: adaptation and inflammation

Ileal pouch-anal anastomsis (IPAA) has become the operation of choice following protocolectomy for ulcerative colitis (UC) and familial adenomatous polyposis. Functioning ileal pouch mucosa undergoes histological changes resembling the colon (colonic metaplasia). The possible role of stasis and luminal factors—bile acids, short-chain fatty acids and bacteria—are discussed. It seems likely that colonic metaplasia is an adaptive response to the new luminal environment in IPAA. Inflammation in the ileal reservoir (‘pouchitis’) is the most significant late complication in IPAA. It occurs in 20–30% of patients and is virtually confined to those with prior UC. The clinical picture in pouchitis is highly variable; however, it can be easily categorized into three groups. Nevertheless, in most cases it is likely to represent recurrent UC in the ileal pouch. Current treatments and possible preventative strategies for pouchitis have been outlined.     

Risk of colorectal cancer in ulcerative colitis in India

BACKGROUND: The risk for colorectal cancer (CRC) in ulcerative colitis (UC) in India is not known. METHOD: Retrospective cohort from a tertiary level hospital in South India. Analysis of archived records of all patients with UC who underwent colonoscopy and segmental biopsies over the last 25 years. Incidence densities and risk of developing high grade dysplasia or CRC was calculated and chi-squared test was performed for risk factors of interest. RESULTS: Complete records were available for 532 patients, 336 (63.2%) male. The mean (+/- SEM) duration of illness was 6.04 +/- 0.29 years. In total, 234 patients (44%) had pancolitis, 121 (22.7%) had left-sided colitis and 177 (33.3%) had proctitis or proctosigmoiditis. Overall, five (0.94%) patients developed carcinoma and one (0.19%) patient had high grade dysplasia. The incidence density and risk of developing either CRC or high grade dysplasia was zero in the first 10 years of disease. In those with disease duration of 10-20 years, incidence density was 2.34 per 1000 person years' duration (PYD) for all patients with colitis and 4.5 per 1000 PYD for patients with pancolitis alone. This corresponded to risks of 2.3% and 4.4%, respectively. For those with disease duration longer than 20 years, incidence density was 2.73 per 1000 PYD for all patients and 4.9 per 1000 PYD for patients with pancolitis. This corresponded to risks of 5.8% and 10.2%, respectively. Duration of disease beyond 10 years and extent of colitis were the only risk factors significantly associated with CRC. CONCLUSIONS: The risk of developing CRC is Indian patients with UC is lower than that reported from the West. Strategies for cancer surveillance in Indian patients with UC need to be tailored accordingly.     

Immune thrombocytopenic purpura in patients with ulcerative colitis

Extraintestinal manifestations of ulcerative colitis (UC) are well known, but immunologically mediated hematological diseases are relatively rare. We describe two cases of immune thrombocytopenic purpura (ITP) associated with preexisting UC. Our patients had typical symptoms of UC, and endoscopy showed pancolitis. During treatment with 5-aminosalicylic acid and steroids, severe thrombocytopenia was noted. ITP was diagnosed based on a normal to high number of megakaryocytes in the bone marrow, positive autoantibody to platelet membrane antigen, and absence of splenomegaly. Medical treatment, including increased dosage of steroids, failed to control UC and ITP in both patients. In the first patient, the platelet count recovered after colectomy, while the second patient died of a cerebral hemorrhage. We stress that a diagnosis of ITP should be considered for thrombocytopenia in patients with UC, especially those showing extensive and significant colonic inflammation, and that colectomy of UC might resolve resistant ITP.     

Patients with extraintestinal manifestations have a higher risk of developing pouchitis in ulcerative colitis: multivariate analysis

BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) have been the surgical treatments of choice for ulcerative colitis (UC). However, the IPAA is sometimes complicated with pouchitis. Furthermore, the cumulative risk and risk factors for developing pouchitis in patients with UC undergoing IPAA have not been reported in any Asian population. The aim of our study is to clarify the cumulative risk and risk factors for developing pouchitis in Japanese patients with UC undergoing IPAA. METHODS: Fifty-eight patients with UC undergoing IPAA were retrospectively evaluated for the presence of pouchitis, gender, age of onset, history of smoking, presence of extraintestinal manifestations (EIMs) and type of operation. The diagnosis of pouchitis was based on the pouchitis disease activity index. The cumulative risk and risk factors for developing pouchitis were assessed. RESULTS: The cumulative risks for developing pouchitis at 1 and 5 years were 9.0% and 14.4%, respectively. The estimated risks of pouchitis at 5 years was 48.1% in patients with EIMs and 4.6% in those without. Both univariate and multivariate analyses revealed that the presence of EIMs is a significant risk factor (hazard ratio 16.85, 95% confidence interval 3.12-91.00; P=0.001). CONCLUSIONS: The presence of EIMs is a significant risk factor for the development of pouchitis in Japanese patients with UC undergoing IPAA.     

Clinical significance of microsatellite instability in the inflamed mucosa for the prediction of colonic neoplasms in patients with ulcerative colitis

BACKGROUND AND AIM: Although molecular mechanisms underlying ulcerative colitis (UC)-associated neoplasms have been studied for years, understanding of these mechanisms remains incomplete and no good predictable marker for development of colonic neoplasms in patients with UC has been established. The aim of this study was to assess if microsatellite instability (MSI) contributes to the development of colonic neoplasms in patients with UC. METHODS: We have examined MSI in chronic inflamed and neoplastic colonic mucosa of UC patients. We have also obtained serial biopsied colonic tissues retrospectively 2-12 years before the final diagnosis from patients with high level MSI (MSI-H+) UC-associated neoplasms, and analyzed MSI using them at different periods. RESULTS: Eight of 12 UC-associated colon cancers (67%), four of six UC-associated high grade dysplasias (67%), and two of six UC-associated low grade dysplasias (33%) revealed MSI-H+ phenotypes. In contrast, 15 of 59 lesions (25%) in inflamed UC mucosa without colonic neoplasm revealed MSI-H +. Interestingly, all four patients with MSI-H+ phenotypes at the final diagnosis of UC-associated colon cancer or dysplasia had already had MSI-H+ at the stage of chronic colitis, 2-12 years before the final diagnosis. CONCLUSION: These results support the notion that MSI contributes to the carcinogenesis of UC-associated neoplasms, and indicate that this analysis in inflamed colonic mucosa at surveillance colonoscopy is useful for identifying UC patients who have high risk for neoplastic progression.     

Long-term Clinical Outcome and Anemia after Restorative Proctocolectomy for Ulcerative Colitis

Background: The purpose of this study was to evaluate long-term outcome and hematologic data after restorative proctocolectomy (RPC) and mucosectomy with hand-sewn J-pouch-anal anastomosis for ulcerative colitis (UC). Methods: Forty-eight (75%) out of 64 consecutive patients operated on during the period 1985-1990 participated in a long-term follow-up in 1998. Study visits involved an interview according to a 23-item functional questionnaire, pouch endoscopy and blood samples. Pre- and postoperative data on these patients were reviewed at our own database covering all operations performed for UC at our institute. Results: Functional disturbances were common and unchanged during long-term follow-up. Minor incontinence occurred in 37.5% and outlet difficulties in 10.5% of patients. Bowel obstruction occurred in 16.7% and usually needed operative treatment. Twenty-four (50.0%) patients had had at least one episode of pouchitis and chronic or severe pouchitis occurred in 18 (37.5%) cases. Males seem to have chronic pouchitis more often. Ten (20.8%) patients had anemia during follow-up. Recurrent bleeding from the pelvic pouch and chronic pouchitis exposed to the anemia. Conclusions: Minor morbidity is common after RPC. Pouchitis occurred in half of our patients during long-term follow-up. There may be a risk of anemia with chronic pouchitis and bleeding from the pelvic pouch mucosa.     

Arthritis related to ileal pouchitis following total proctocolectomy for ulcerative colitis

OBJECTIVE: To draw attention to arthritis that developed in patients who underwent total proctocolectomy with ileal pouch construction for ulcerative colitis (UC). METHODS: The course of 4 patients who developed arthritis for the first time after ileal-anal pouch anastomosis is described. In addition, the relationship to the chronic inflammation of the pouch-pouchitis-is discussed. RESULTS: The clinical manifestations were very similar to seronegative arthritis affecting mainly the joints of the lower extremities. It was accompanied by enthesopathy (2 patients) and by sacroiliitis (2 patients). All had active pouchitis. The abnormal laboratory test results were nonspecific, indicating chronic inflammation. All 4 patients tested negative for human leukocyte antigen (HLA) B27, and none had other concomitant extraintestinal manifestations. Steroids rapidly improved both the arthritis and pouchitis; however, disease-modifying antirheumatic drugs were required to maintain remission with minimal daily steroids. Flares of the arthritis were always associated with active pouchitis, but the opposite was not necessarily true. CONCLUSIONS: Arthritis related to ileal pouchitis after total colectomy for UC has many similarities to the arthritis associated with inflammatory bowel disease and should be added to the list of enteropathic arthropathies.     

Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis

INTRODUCTIONPouchitis after total colectomy with ileal pouch anal anastomosis can sometimes occur in patients with ulcerative colitis (UC). Despite intensive studies the cause of pouchitis remains unknown, but many contributing factors, such as faecal sta…