Immunohistologic study of ulcerative colitis with monoclonal antibodies against tumor-associated and/or differentiation antigens

We used monoclonal antibodies (MAbs) (19-9, 55-2, and 73-3) that detect tumor-associated or differentiation antigens, or both, to immunohistochemically study a well-defined group of patients with ulcerative colitis. Monoclonal antibody 19-9 detects the gastrointestinal cancer-associated antigen (sialylated Lewis A). Monoclonal antibody 55-2 detects the Lewis Y antigen and reacts with deep crypt cells in the normal colon. In the normal colon MAb 73-3 reacts with mature superficial columnar cells detecting the protein moiety of a 35,000-dalton glycoprotein. In cases of inactive or mildly active disease, MAbs 19-9, 55-2, and 73-3 had staining patterns similar to normal colon. In 72% and 44% of cases of severely active disease, MAb 19-9 and MAb 73-3, respectively, reacted with epithelial cells at all levels of the crypt, whereas MAb 55-2 reacted only with deep crypt cells. Monoclonal antibodies 19-9, 55-2, and 73-3 reacted with dysplastic epithelium in 70%, 10%, and 60% of cases, respectively. In severely active disease, proliferating epithelial cells "paradoxically" express markers of differentiated epithelium throughout the entire crypt. Similarly, colonic epithelial cells may have the ability to reversibly express tumor-associated antigens. Unfortunately, the MAbs used in this study cannot differentiate dysplasia from reactive epithelium.     

Establishment of monoclonal antibodies against purified mucin from human pancreatic cell line]

Thirty four murine monoclonal antibodies were produced against mucin which was isolated from nude mouse xenografts of the SW1990 pancreatic adenocarcinoma cell line. Twelve of them reacted with formalin-fixed SW1990 cells. The antigenic determinants of these antibodies were composed of carbohydrates and their immunoreactivities were predominant at CsCl fraction #6. The remaining 22 antibodies did not react with formalin-fixed cells, 5 epitope specificities of which antibodies are present in the polypeptide part or the part of linkage between oligosaccharide and polypeptide and the immunoreactivities were predominant at CsCl fraction #5. Immunohistochemical study showed that the incidence of epitope expression of the latter 22 antibodies were higher in pancreatic cancer tissues and lower in normal pancreatic tissues than that of the former 12 antibodies. The incidence of Nd2 (one of the 22 antibodies) expression was highest in pancreatic cancer tissues and lowest in normal tissues. ELISA showed that Nd2 antigen was non-secreting type. In vivo tumor distribution studies showed that Nd2 antibody tended to accumulate in cancer tissues. These results seem to support the clinical availability of Nd2.     

Fifteen-year-old colon cancer patient with a 10-year history of ulcerative colitis

Inflammatory bowel disease (IBD) is regarded as one of the risk factors for colorectal cancer, and early detection of cancer in these patients may be difficult, especially in pediatric patients. Prognosis of pediatric colorectal cancer is known to be poor, because of delayed diagnosis and unfavorable differentiation. We report a case of a pediatric patient with a 10-year history of ulcerative colitis who was diagnosed with sigmoid colon cancer when he was 15 years old. He underwent proctocolectomy with ileal pouch anal anastomosis. Postoperative pathological examination of the tumor revealed adenocarcinoma. The pericolic tissue layer was infiltrated, but metastases were not found in either of the two lymph nodes. Children with a long history of predisposing factors such as IBD need particular attention to the possibility of colorectal cancer. Early diagnosis through regular screening with colonoscopy is one of the most important critical factors for a good prognosis.     

An autopsy case of colon cancer associated ulcerative colitis complicated focal squamous cell carcinoma]

A 28-year-old woman with ascites was admitted to our hospital. We diagnosed peritonitis carcinomatosa caused by colon cancer complicated by ulcerative colitis. We performed peritoneal tap and infusion of mitomycin C, and administered 5-fluorouracil. Her clinical status gradually worsened, and she died 5 months later. At autopsy, the histological examination showed many mucinous adenocarcinoma and signet ring cell carcinoma with dysplasia. There were also some areas of squamous cell carcinoma with squamous metaplasia and dysplasia far from rectum. Squamous cell carcinoma and adenosquamous cell carcinoma of the colon are rare complications of ulcerative colitis. We reported this case as an addition to the literature on the subject.     

Clinical importance of organ-specific antibodies in ulcerative colitis and Crohn disease]

In 479 patients with chronic inflammatory intestinal diseases and other abdominal diseases autoantibodies against intestinal goblet cells and exocrine pancreas were determined by indirect immunofluorescence. In ulcerative colitis 17% had serum antibodies against intestinal goblet cells, in Crohn's disease 26% against exocrine pancreas. Autoantibody prevalence and level of the titre were dependent on the inflammatory activity of both diseases but independent on the therapy. In Crohn's disease high level of titres of antibodies against exocrine pancreas we found in cases with multiple complications. Antibodies titres against intestinal goblet cells in ulcerative colitis and against exocrine pancreas in Crohn's disease exceeding 1:100 improved the diagnostic decision. Besides clinical states, endoscopic and histological findings a positive result of the antibody investigations had to be considered for final diagnosis.     

Clinical experiences of five cases with ulcerative colitis and recto- or anovaginal fistula]

Clinical aspects, treatment and outcome of five patients with ulcerative colitis recto- or anovaginal fistula and were studied retrospectively. All patients had total colitis (relapse and remission type) and more than a 5 year history of ulcerative colitis. They all had anorectal complications, such as periproctal abscess, stenosis of fistula. Four patients had total colectomy with an ileal pouch anal canal anastomosis for intractability or dysplasia. One was treated conservatively. Complete closure of fistula was obtained in two patients;in one patient rectum was resected below the fistula and in one patient defect of the vaginal posterior wall was reconstructed by using a gluteal fold flap following colectomy. Recto- or anovaginal fistula complicating ulcerative colitis is rare but may occur in the patients with severe rectal inflammation and they can be managed by restorative proctocolectomy with an ileal pouch anal or anal canal anastomosis.     

Detection of blood group A antigen expression in human colon cancer using monoclonal antibodies with different specificities

Blood group antigen expression in human colon cancer was studied by means of two monoclonal antibodies of broad anti-A (HE-14) and anti-type 3 and type 4 chain-based A and H (HE-10) specificity. These antigens were proved to reappear in tumors of the distal colon, the HE-10 antibody reacting more frequently (9 out of 12 samples) than HE-14 (5 out of 12 samples) and frequently with supranuclear staining of the cytoplasm probably in those places of the Golgi apparatus where carbohydrate antigens are synthesized. This staining pattern is characteristic of HE-10 in normal colonic mucosa as well. With HE-14, staining was often absent in less differentiated tumors, while HE-10 did react in such tumors. In this connection, the possible expression of type 3 and type 4 chain H antigens in the tumor tissue is discussed. In some cases, these two antibodies gave different staining patterns in parallel sections from the same tissue sample, primarily at the cellular level. Three out of 12 cases showed blood group antigen expression in the mucosa of the distal colon adjacent to the tumor only when HE-10 antibody was used.     

Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis

Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty-seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow-up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.     

Colectomy with ileoproctostomy for ulcerative colitis: Report of five cases

Summary and Conclusions Twenty-five patients with ulcerative colitis were treated by abdominal colectomy with ileorectal anastomosis. Five additional case reports available since and initial publication in 1964 are presented. Proctocolectomy with permanent ileostomy remains the operation of choice for most patients requiring resectional surgery for ulcerative colitis. For selected patients abdominal colectomy with ileorectal anastomosis is a satisfactory alternative. Such patients should possess an otherwise healthy anorectum with only mild to moderate proctitis. Anal ulcer (chronic fissure-in-ano), fistula-in-ano, and symptomatic hemorrhoidal disease are considered contraindications to this operative procedure.     

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis

Purpose/Aim

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC.

Methods

Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I ² measure of inconsistency. RevMan 5 was utilized for statistical analysis.

Results

Four studies (n?=?281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95?% CI: 0.19?1.48, p?=?0.23) or colon cancer occurrence (OR 0.50; 95?% CI: 0.18?1.43, p?=?0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC.

Conclusion

Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.     

Adalimumab in ulcerative colitis： Two cases of mucosal healing and clinical response at two years

Infliximab （IFX） is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis （UC）. In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.     

Adalimumab in ulcerative colitis: Two cases of mucosal healing and clinical response at two years

Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.