Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients.

BACKGROUND: Immunosuppressed transplant recipients are at increased risk of developing several forms of malignancy. The aim of this study is to report the clinical presentation, treatment, and outcome of four liver transplant recipients with Helicobacter pylori-associated gastric mucosae-associated lymphoid tissue (MALT) lymphoma. METHODS: The medical records of four liver transplant recipients with gastric MALT lymphoma were reviewed. In situ hybridization for Epstein-Barr-encoded ribonucleic acid was performed on formalin-fixed tissues. RESULTS: All four subjects presented with abdominal symptoms at a mean of 6.1 years posttransplant. Ulcerative lesions biopsied at endoscopy demonstrated early-stage gastric MALT lymphoma with associated Helicobacter pylori gastritis. In situ hybridization revealed no evidence of Epstein-Barr virus infection in examined tissues. Antibiotic eradication of Helicobacter pylori lead to disease remission in three subjects with a mean follow-up of 21 months, and one subject failed to respond to antibiotics and radiation therapy and died from metastatic gastric adenocarcinoma. CONCLUSIONS: Early-stage, low-grade gastric MALT lymphoma that was associated with Helicobacter pylori gastritis responded to antibiotic therapy with a sustained clinical remission in three of four treated subjects. If other studies confirm a higher than expected incidence of gastric MALT lymphoma in immunosuppressed transplant recipients with Helicobacter pylori infection, screening and treating Helicobacter pylori infection in selected transplant patients may prove beneficial.

Acute liver failure due to hepatic involvement by hematologic malignancy.

Infiltration of the liver by secondary malignancies is a rare cause of acute liver failure. Acute liver failure caused by malignant infiltration is associated with almost 100% mortality and is typically diagnosed postmortem. Richter's transformation is a well-recognized complication of chronic lymphocytic leukemia. This transformation is the progression of chronic lymphocytic leukemia to a high-grade lymphoma. We describe the case of a 64-year-old man with a history of chronic lymphocytic leukemia who presented with acute liver failure. Liver biopsy revealed hepatic infiltration by a high-grade lymphoma. The patient responded to chemotherapy with normalization of hepatic function and remained disease-free after eight months. This case represents the first report of Richter's transformation presenting as acute liver failure. It also represents the fourth reported case of a patient with acute liver failure secondary to involvement by a hematopoietic malignancy that was successfully recognized and treated.

Management of hepatitis C patients by primary care physicians in the USA: results of a national survey.

Hepatitis C is a major health problem worldwide, yet very little research has been performed to assess the knowledge base and practice patterns of primary care physicians (PCPs) regarding hepatitis C. The aim of this study is to determine the knowledge base and practice patterns of a nationwide cohort of PCPs. A survey was developed to assess the knowledge of PCPs regarding risk factors for hepatitis C, management of hepatitis C patients and attitude regarding testing for hepatitis C. The survey was mailed to 4000 PCPs in the USA. A total of 1412 (39%) PCPs completed the survey. The vast majority, > 90%, of PCPs correctly identified the most common risk factors for hepatitis C. However, only 59% indicated they ask all patients about hepatitis C risk factors, 70% reported they test all patients with hepatitis C risk factors and 78% test all patients with elevated liver enzymes for hepatitis C. Most (72%) PCPs would refer an HCV-positive patient with elevated aminotransferase but only 28% would refer an HCV-positive patient with normal aminotransferase to a specialist. One-fourth of the PCPs did not know what treatment to recommend for hepatitis C patients. Our data suggest that hepatitis C patients may be underdiagnosed and under-referred. Specific educational initiatives and practice guidelines for PCPs are needed to optimize the recognition of patients at risk for hepatitis C and to ensure appropriate testing and referral.

Current practice patterns of primary care physicians in the management of patients with hepatitis C.

Approximately 4 million Americans are infected with the hepatitis C virus (HCV). Most patients with hepatitis C have no symptoms until cirrhosis is established. Thus, initial diagnosis and management of hepatitis C rely on primary care physicians identifying and screening high-risk individuals. We administered a survey to 1,233 primary care physicians in a health maintenance organization (HMO) in April 1997 to assess their knowledge of the risk factors for HCV infection and approach to the management of 2 hypothetical HCV antibody-positive patients, 1 with elevated and the other with normal alanine transaminase (ALT). Four hundred four (33%) physicians returned the survey. Ninety percent of respondents correctly identified the risk factors for HCV infection, but 20% still considered blood transfusion in 1994 as a significant risk factor for HCV infection. Sixty-two percent of respondents would refer HCV antibody-positive patients with abnormal transaminase levels, but 33% would follow these patients themselves, even though none of the respondents had treated any hepatitis C patient on their own. Forty-three percent of respondents overestimated, while 29% did not know the efficacy of interferon treatment. Sixty-five percent of respondents would retest patients for HCV antibody, regardless of risk factors and transaminase levels. We found that most primary care physicians correctly identified the significant risk factors for HCV infection and appropriately managed the 2 hypothetical patients, but there was considerable confusion about the use of HCV tests and the effectiveness of treatment. Educational programs for primary care physicians are needed to implement hepatitis C screening and to initiate further evaluation and management of those who test positive.

Transforming growth factor beta as a potential tumor progression factor among hyperdiploid glioblastoma cultures: evidence for the role of platelet-derived growth factor.

Among early-passage, near-diploid gliomas in vitro, transforming growth factor type beta (TGF beta) has been previously shown to be an autocrine growth inhibitor. In contrast, hyperdiploid (> or = 57 chromosomes/metaphase) glioblastoma multiforme (HD-GM) cultures were autocrinely stimulated by the TGF beta. The mechanism of this 'conversion' from autocrine inhibitor to mitogen is not understood; previous studies have suggested that platelet-derived growth factor (PDGF) might be modulated by TGF beta. The similar expression of TGF beta types 1-3, PDGF-AA; -BB, as well as the PDGF receptor alpha and beta subunits (a/beta PDGFR) between biopsies of the HD-GM and near-diploid, TGF beta-inhibited glioblastomas (GM) by immunohistochemistry did not explain the discrepancy in their regulatory responses. Flow cytometry demonstrated that TGF beta's mitogenic effect was selective for the aneuploid subpopulations of two of three selected HD-GM cultures, while the diploid cells were inhibited. Among the HD-GM, TGF beta 1 induced the RNA of PDGF-A, c-sis and TGF beta 1. The amount of PDGF-AA secreted following TGF beta treatment was sufficient to stimulate the proliferation of a HD-GM culture. Antibodies against PDGF-AA, -BB, -AB, alpha PDGFR and/or beta PDGFR subunits effectively neutralized TGF beta's induction of DNA synthesis among the HD-GM cell lines, indicating that PDGF served as the principal mediator of TGF beta's growth stimulatory effect. By comparison, TGF beta induced only the RNA of PDGF-A and TGF beta 1 among the near-diploid GM, c-sis was not expressed at all. However, the amount of PDGF-A which was secreted in response to TGF beta 1 was insufficient to prevent TGF beta's arrest of the near-diploid cultures in G1 phase. Thus, the emergence of hyperdiploidy was associated with qualitative and quantitative differences in TGF beta's modulation of PDGF-A and c-sis, which provided a mechanism by which the aneuploid glioma cells might achieve 'clonal dominance'. We hypothesize that TGF beta may serve as an autocrine promoter of GM progression by providing a selective advantage to the hyperdiploid subpopulation through the loss of a tumor suppressor gene which mediates TGF beta's inhibitory effect.