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Gupta N.K.,Gastrointestinal Unit | Masia R.,Massachusetts General Hospital
American Journal of Surgical Pathology | Year: 2013

Cord colitis syndrome (CCS) is a recently described diarrheal illness of uncertain pathogenesis that affects recipients of umbilical cord blood transplant and is associated with negative cultures. CCS exhibits a peculiar histopathologic appearance, as it commonly manifests as granulomatous inflammation involving the upper and lower gastrointestinal tract, with features of chronicity in the colon. Importantly, the treatment for CCS differs from that for acute graft-versus-host disease, which is commonly in the clinical differential diagnosis: CCS responds to antibiotic treatment, whereas acute graft-versus-host disease responds to immunosuppression. We describe here the case of a 36-year-old woman with a history of acute myeloid leukemia who developed refractory diarrhea after cord blood transplant. Endoscopic biopsies of the stomach and colon revealed granulomatous inflammation, consisting of scattered ill-defined aggregates of epithelioid histiocytes, with associated mild neutrophilic inflammation and mildly increased epithelial cell apoptosis. In the colon, the granulomatous inflammation was associated with surface epithelial injury (including surface erosions) and contained occasional multinucleated epithelioid giant cells. Paneth cell metaplasia was present in the distal colon, but crypt architecture was preserved, and there was no basal lymphoplasmacytosis. Special stains and immunohistochemical stains for infectious organisms were negative. A diagnosis of CCS was made, and the patient promptly responded to treatment with ciprofloxacin and metronidazole. We present this case to raise awareness among pathologists of this newly described entity, in order to facilitate its timely diagnosis and treatment. © 2013 Lippincott Williams and Wilkins. Source


Shimoyama S.,Gastrointestinal Unit
Hepato-Gastroenterology | Year: 2011

Background/Aims: Statin is the most promising agent in the improvement of blood lipid profiles, and a substantial risk reduction of subsequent cardiovascular events leads to a rapid increase in current prescription rates. However, statin use or a lower total cholesterol has been associated with an increased cancer risk, although some deny such an association. Whether a positive statincancer association exists or not remains a matter of debate because such a causal association, if any, may offset anticipated cardioprotective benefits from statins. So far, no statin-cancer association in gastric cancer has been systematically highlighted in the literature. Methodology: Original studies concerning the effect of statins on gastric cancer incidence were searched in PubMed Central published between 1993 and 2008. A manual search was additionally performed though reference lists in the retrieved manuscripts. Pooled gastric or upper gastrointestinal cancer risk ratio (RR) with 95% confidence interval (CI) was independently calculated by random effects model, provided by the Cochrane Library software Review Manager 5. Results: Six publications were considered finally eligible, three were for gastric cancer risk and three were for upper gastrointestinal cancer risk. Statin use proved no significant increase (RR; 1.37, 95% CI; 0.57-3.25) in gastric cancer risk, nor was there any evidence of increased risk (RR; 1.20, 95% CI; 0.94-1.53) even in upper gastrointestinal cancer. Conclusions: These results suggest that statins had no short-term effect on gastric or upper gastrointestinal cancer incidence. Further investigation of long-term associations between statin use and gastric cancer is warranted. © H.G.E. Update Medical Publishing S.A. Source


Purpose: Molecular targeting approaches have been an intensive focus of treatment strategies against advanced gastric and colorectal cancers. Recent clinical trials have demonstrated promising survival prolongation of targeted human epidermal growth factor receptors; however, patients harboring mutations in the K-Ras gene (human homolog of the Kirsten rat sarcoma-2 virus oncogene) do not derive benefit from the anti-epidermal growth factor receptor antibodies. K-Ras mutations cause a stimuli-independent activation of a large cohort of downstream effectors that permit cells to acquire a sustained growth. The perpetuated growth activation manifests resistance to molecular targeting therapies. Methods: Literature review has been made to explore the possibilities that, given that K-Ras or downstream effector proteins require farnesyl or geranylgeranyl moiety for their activity (e.g., prenylation), statins are logical candidates to overcome the limitations of or to potentiate the effect of molecular targeting therapies as statins suppress the mevalonate pathway leading to depletion of an end product of mevalonate such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are used as substrates by their respective transferase enzyme for protein prenylation, and ultimately impair functions of K-Ras and downstream effector proteins. Results: In the last few years, statins have gained interest in therapeutic value for anticancer treatments extending beyond their lipid-lowering effects as single agents or in combined use with other chemotherapeutic agents. This review provides insights into possible anticancer mechanisms of statins and introduces current achievements or ongoing studies of statins in the field of cancer treatment in single or combined uses. This review also offers information to help establish optimal treatment schedules of statins that overcome current limitations of molecular targeting therapies. Conclusions: It is expected that therapeutic scope of statins will expand considerably in the future as anticancer agents in addition to their proven benefits of hyperlipidemia. © 2011 Springer-Verlag. Source


Wedlake L.,Royal Marsden NHS Foundation Trust | Wedlake L.,Kings College London | Slack N.,Kings College London | Andreyev H.J.N.,Gastrointestinal Unit | Whelan K.,Kings College London
Inflammatory Bowel Diseases | Year: 2014

Background: Dietary fiber may favorably influence fermentation, gastrointestinal inflammation, and disease progression in Crohn's disease, ulcerative colitis (UC), and pouchitis and offer an attractive therapeutic addition to pharmacological treatment. This systematic review appraised data from randomized controlled trials of fiber in the management of inflammatory bowel disease. Methods: The review followed Cochrane and PRISMA recommendations. Seven electronic databases were searched along with hand searching and contacting experts. Inclusion criteria were randomized controlled trials of the effects of fiber on clinical endpoints (primarily disease activity for treatment or maintenance) or physiological outcomes in patients with inflammatory bowel disease. Results: In total, 23 randomized controlled trials fulfilled the inclusion criteria (UC, 10; Crohn's disease, 12; and pouchitis, 1) recruiting 1296 patients. In UC, 3/10 studies reported fiber supplementation to benefit disease outcomes. In Crohn's disease, 0/12 studies and in pouchitis 1/1 study reported a benefit on disease activity. Despite this, a number of studies reported favorable intragroup effects on physiological outcomes including fecal butyrate, fecal calprotectin, inflammatory cytokines, microbiota, and gastrointestinal symptom indices. Meta-analysis was not possible. Conclusions: There is limited weak evidence for the efficacy of fiber in improving disease outcomes in UC and pouchitis. The potential antiinflammatory role of fiber is intriguing and merits further investigation in adequately powered clinical trials. Excluding overt gastrointestinal obstruction, there was no evidence that fiber intake should be restricted in patients with inflammatory bowel disease. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc. Source


Ciuffreda D.,Gastrointestinal Unit | Kim A.Y.,Harvard University
Current Opinion in HIV and AIDS | Year: 2011

Purpose of review: The goal of this study is to review key recent findings related to the immunopathogenesis of hepatitis C virus (HCV) infection, especially in regards to T lymphocytes. It aims to complement other reviews in this issue on the roles of host genetics (IL-28B), acute HCV infection (when disease outcome is determined) and other factors that may influence fibrosis progression (microbial translocation). The main focus is on specific immunity and T cells in the context of success and failure to control viral infection. Recent findings: This review focuses on two areas of intense interest in the recent literature: the relationship between the human leukocyte antigen (HLA), class I-restricted T-cell responses and the evolution of the virus and the role of inhibitory markers on T cells in the immunopathogenesis of HCV. When appropriate, we compare findings from studies of HIV-specific immunity. Summary: From examining the virus and the mutational changes associated with T-cell responses and from analyzing the markers on T cells, there have been numerous advances in the understanding of immune evasion mechanisms employed by HCV. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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