Wojciech Blonski

A Systematic Review of Factors That Contribute to Hepatosplenic T-Cell Lymphoma in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL. METHODS We collected and analyzed data on the association between HSTCL, and anti-TNF and thiopurine therapies in patients with IBD from published reports and the MedWatch reporting system of the US Food and Drug Administration. RESULTS Of 36 patients with HSTCL, 20 received therapy with infliximab and a thiopurine and 16 received a thiopurine as monotherapy for IBD. Four patients who had been treated with infliximab and a thiopurine also received adalimumab. One of these patients had been given infliximab, adalimumab, and natalizumab. Of 31 patients of known gender, only 2 were female. Twenty-seven of the 30 patients of known age were younger than 35 years old. CONCLUSIONS Most patients with HSTCL who received long-term therapy (at least 2 y) with thiopurines for IBD were men younger than 35 years old. There were no reported cases of HSTCL in patients with IBD who received only anti-TNF therapy. Physicians should consider giving thiopurines and anti-TNF agents to young male patients with IBD only in cases in which a clear benefit is expected, such as in early stage disease in untreated patients or possibly in very severe cases.

Is dysplasia visible during surveillance colonoscopy in patients with ulcerative colitis

Objective. Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. It was widely believed that dysplastic lesions are invisible on colonoscopy and can only be detected by random biopsies, as 95% of dysplastic lesions occur in flat colonic mucosa indistinct from surrounding tissue. The aim of this study was to determine whether dysplasia is visible during routine surveillance colonoscopy by evaluating only patients who had dysplasia without overt carcinoma. Material and methods. The medical records, endoscopy and pathology databases were systematically reviewed between 1997 and 2004 at the University of Pennsylvania Health System. Patients with inflammatory bowel disease and dysplasia were identified and their medical charts reviewed. Results. Of the 113 patients with colonic dysplasia confirmed by pathology at our center, 102 (90%) had UC. Forty-nine of the 102 (48%) patients with UC underwent colonoscopic evaluation prior to dysplasia detection. This group was selected as our study cohort. Overall, 72 macroscopic abnormalities were detected at 49 colonoscopies, including 55 polypoid lesions, 12 areas of ulceration, 3 areas of nodularity, 1 irregular hemicircumferential lesion and 1 area of stricture. Overall, 58 dysplastic sites were detected; 51 were macroscopically visible (87.9%) and 7 were macroscopically invisible (12.1%). Conclusions. Most of the dysplasia in UC is endoscopically visible, but further prospective evaluation of a large number of patients is needed to validate the current observations. Our findings have the potential to modify current recommendations for surveillance biopsies in UC if validated by prospective studies.

High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis.

Objective. The management of high-grade dysplasia (HGD) in polypoid lesions in patients with ulcerative colitis (UC) is not well characterized. The purpose of this study was to characterize the clinical course of patients with HGD in adenoma-like dysplasia-associated lesion or masses (DALMs) in the absence of any synchronous flat dysplasia. We hypothesize that colectomy is not warranted in patients who undergo complete excision of adenoma-like DALMs with HGD in UC. Material and methods. Pathology and clinical databases were systematically searched for the presence of dysplastic lesions in inflammatory bowel disease from 1997 to 2004. Patients with UC who had adenoma-like DALMs were identified, and a subset with HGD lesions was defined as our study cohort. Results. A total of 102 patients with UC were identified. Thirty of them (29%) had adenoma-like DALMs without synchronous flat dysplasia; 9 of these patients (30%) had HGD in these lesions. Thirty-two surveillance colonoscopies were performed in this cohort (mean 3.6 colonoscopies/patient). The patients were followed for a mean of 76.5 months (52–99 months). Three out of 9 patients (33%) had colectomy. None of the patients in this cohort was detected to have carcinoma in surveillance biopsies and/or in the resection specimens. Conclusions. Our data suggest that the presence of HGD in DALMs does not warrant colectomy. Continued close observation is suggested in this patient cohort after complete excision of polyps. Further prospective evaluation of this patient population is merited.

Inflammatory bowel disease therapy: current state-of-the-art.

Purpose of review The aim of this article is to review current evidence-based approaches to treatment of ulcerative colitis and Crohns disease. Recent findings The primary goal of treatment is to induce and to maintain remission in a safe and efficacious fashion. The 5-aminosalicylic acid (5-ASA) agents and oral steroids remain the first-line approach for the treatment of ulcerative colitis and Crohns disease. The ‘step-up’ approach includes the use of immunomodulators [azathioprine (AZA), or 6-mercaptopurine (6-MP)] and newer biologic agents (infliximab, adalimumab, and natalizumab). The ‘step-down’ approach can also be considered individually on the basis of the severity of Crohns disease. Summary Current treatment regimens still involve medications with well known efficacy and safety profiles and progress to more potent treatments such as immunomodulators and biologic agents. Adverse events of potent treatment with biologics and immunomodulators have been recognized. In some cases, aggressive approaches with the use of more potent agents as first-line therapy has been proposed, but they are still not considered a routine approach.

Hepatosplenic T-Cell Lymphoma in Inflammatory Bowel Disease: A Possible Thiopurine-Induced Chromosomal Abnormality

Hepatosplenic T-Cell Lymphoma in Inflammatory Bowel Disease: A Possible Thiopurine-Induced Chromosomal Abnormality

Clinical pharmacology of 5-ASA compounds in inflammatory bowel disease.

Mesalamine has been the first-line of therapy in patients with inflammatory bowel disease (IBD) since the 1960s. This article serves as a review of the different 5-aminosalicylic acid compounds, release formulations, use and dosing in the treatment of IBD, in particular ulcerative colitis.

What is the optimal therapy for Crohn’s disease: step-up or top-down?

Crohn’s disease (CD) is an idiopathic chronic inflammatory disorder of the digestive tract, which is incurable. Present therapeutic guidelines follow a sequential step-up approach that focuses on treating acute disease or ‘inducing clinical remission’ and subsequently aims to ‘maintain clinical response’. In view of the chronic relapsing–remitting disabling disease course, new treatment approaches have been sought with the ultimate end point of disease course modification and mucosal healing. A recent preliminary study from D’Haens et al. has provided evidence suggesting that reversing the treatment paradigm from a ‘step-up’ to a ‘top-down’ approach may positively alter the natural course of this illness. Their findings indicate that early use of biologic therapy, in combination with immunomodulators, resulted in remission occuring more rapidly than the conventional ‘step-up’ treatment, with a longer time period to relapse, a decreased need for treatment with corticosteroids, a faster reduction in clinical symptoms, rapid decline in biochemical inflammatory markers (C-reactive protein) and improved endoscopic mucosal healing. These results, supported by previous studies on infliximab use, may hold a promising outcome of fewer stricturing complications, hospitalizations and surgeries for patients with CD. However, we need to better define the timing and candidates for the ‘top-down’ approach as we are still uncertain about the safety data and the long-term benefits if biologic agents are given as routine maintenance treatment, since most of the trials in CD have been short term, and approximately 30% of patients might have been overtreated. Future clinical trials will be crucial in answering these questions.

A Case of Cronkhite-Canada Syndrome with Taste Disturbance as a Leading Complaint

Cronkhite-Canada syndrome was first described in 1955. The clinical features of this rare syndrome of unknown etiology include nonhereditary gastrointestinal polyposis together with diarrhea, nail dystrophy, alopecia, and hyperpigmentation of the skin. This syndrome has been divided into five clinical types based on initial symptoms. We describe a case of Cronkhite-Canada syndrome presenting with taste disturbance as the major symptom, present a comprehensive review of the literature concerning this rare syndrome, and suggest therapeutic treatment options.

Clinical Predictors of Aggressive/Disabling Disease: Ulcerative Colitis and Crohn Disease

Many clinical factors predict the aggressive course of CD. Younger age at initial diagnosis, the presence of perianal lesions, ileal involvement, smoking, and the need for therapy with corticosteroids are the major predictors of disabling disease or change of behavior to a more aggressive disease. On the other hand, treatment with azathioprine and biologic agents and colonic localization of disease are the major factors that are predictive of less aggressive CD course. The problem we face with determining the factors that increase the risk of disabling disease is that there is no standardized and consistent definition of disabling or aggressive disease. Only two studies analyzed predictors using the same definition of aggressive disease. Only Beaugerie and colleagues developed the score predictive of disabling disease based on three independent factors associated with disabling course that were present at the time of initial diagnosis of CD (requirement of corticosteroids, age less than 40 years, and presence of perianal disease). This score ranged from 0 to 3 points based on the presence of given parameters. The positive predictive value was 0.91 and 0.93 in patients having two or three risk factors, 0.61 for no factors present, and 0.67 for one factor present. In order to determine factors predictive of disabling CD there is a need to establish consistent definition of disabling disease with subsequent future studies on large group of patients to validate such definition and determine factors that may predict the aggressive course.

Treatment of ulcerative colitis.

Purpose of review Ulcerative colitis is a chronic inflammatory disease of the colon of unknown cause that is characterized by alternating intervals of active and inactive disease in 80–90% of patients. The primary goal of treatment is to induce and maintain remission using therapy tailored to the individual patient. The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents. Recent findings Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis. In a recent study, infliximab was found to have comparable efficacy to cyclosporine in treatment of acute severe refractory to corticosteroids ulcerative colitis. Summary Anti-TNF therapy should be initiated in patients with acute severe refractory to corticosteroids ulcerative colitis and in patients with moderate-to-severe ulcerative colitis who are not responsive to conventional treatment with aminosalicylates, corticosteroids and immune modulators. Alternatives to infliximab are ADA and golimumab. Future research is needed to further assess the long-term efficacy and safety of ADA and golimumab in ulcerative colitis.