Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.

BACKGROUND: Conventional systemic chemotherapy currently available for patients with inoperable hepatocellular carcinoma is ineffective. The purpose of this study was to evaluate the safety and efficacy of eniluracil/5-fluorouracil (5-FU) in the treatment of patients with this highly refractory disease. PATIENTS AND METHODS: This multicenter, open-label study evaluated a 28-day oral regimen of 5-FU (1 mg/m2 twice daily) plus the dihydropyrimidine dehydrogenase inhibitor, eniluracil (10 mg/m2 twice daily), in patients with chemotherapy-naive or anthracycline-refractory inoperable hepatocellular carcinoma. RESULTS: A total of 36 patients enrolled into the study. No patient showed a confirmed partial or complete tumor response, although nine patients (25%) had a best response of stable disease. The median duration of progression-free survival was 9.6 weeks [95% confidence interval (CI) 9.1-10.6 weeks], and the median duration of overall survival was 32.7 weeks (95% CI 17.4-71.6 weeks). Eniluracil/5-FU was well tolerated. Diarrhea, the most frequent treatment-related non-hematological toxicity, occurred in 11 patients (31%). Hematological toxicities were infrequent and usually mild. CONCLUSIONS: Eniluracil/5-FU as a 28-day oral outpatient regimen is well tolerated by patients with inoperable hepatocellular carcinoma, although minimal activity was observed when given as monotherapy at the dose used in this study.

The restricted cellular host range of human herpesvirus 8.

DESIGN: A selection of primary and transformed cell types were evaluated for their susceptibility to infection with human herpesvirus 8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus. METHODS: Sources of HHV-8 included Kaposi's sarcoma lesion punch biopsies that were either cocultured directly with target cells or that were first cocultured with human lymphocytes to derive HHV-8-containing fluids that were inoculated onto target cells. HHV-8 was also obtained from primary effusion lymphoma-derived cell lines. Techniques to detect infection included the PCR, immunofluorescence assays and in situ hybridization. RESULTS: Susceptible cells included human umbilical cord blood mononuclear cells (UCMC), adult CD19 B cells, macrophages and certain endothelial cells of human and animal origin, including some that are transformed with human papilloma virus type 16 E6 and E7 genes. The infection of lymphocytes did not yield established lymphoblastoid cell lines (LCL) and virus infection persisted for only 4-7 days. However, long-term HHV-8 infection of UCMC could be achieved by coinfection with Epstein-Barr virus. HHV-8 could also infect UCMC LCL recently derived by Epstein-Barr virus transformation, but long-established LCL could not be infected with HHV-8. CONCLUSIONS: These data provide further biological evidence in cell culture for the limited cellular host range of HHV-8 to CD19 B cells, macrophages, and certain endothelial cells.

The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer.

PURPOSE: To assess the outcome and tolerance of HIV-positive patients with anal cancer to standard therapy based on their pretreatment CD4 count. METHODS AND MATERIALS: Between 1991 and 1997, 17 HIV-positive patients with anal cancer and documented pretreatment CD4 counts were treated at the University of California, San Francisco or its affiliated hospitals with either concurrent chemotherapy and radiation or radiation alone. The outcome and complications of treatment were correlated with the patients' pretreatment CD4 count. RESULTS: Disease for all 9 patients with pretreatment CD4 counts > or = 200 was controlled with chemoradiation. Although four required a treatment break of 2 weeks because of toxicity, none required hospitalization. Of the 8 patients with pretreatment CD4 counts < 200, 4 experienced decreased counts, intractable diarrhea, or moist desquamation requiring hospitalization. Additionally, 4 of these 8 ultimately required a colostomy either for a therapy-related complication or for salvage. Nevertheless, 6/7 in this group who received concurrent chemotherapy and radiation had their disease controlled, whereas the patient treated with radiation alone failed and required a colostomy for salvage. CONCLUSION: Patients with CD4 > or = 200 had excellent disease control with acceptable morbidity. Patients with CD4 < 200 had markedly increased morbidity; however, disease was ultimately controlled in 7/8 patients.

Advances and future challenges in non-Hodgkin's lymphoma.

The mortality and morbidity burden of Non-Hodgkin's lymphoma (NHL) is increasing within the human immunodeficiency virus- (HIV-) infected population. Recent improvements in HIV management has meant overall reductions in deaths, especially those due to opportunistic infections, and while the outcome of HIV-related NHL may now be somewhat less grim, the incidence remains high and outcome poor. The median survival of those with HIV-related NHL is only approximately 7 months, although those with high CD4 lymphocyte counts seem to do somewhat better. Improved management of the underlying HIV infection, more effective infusional chemotherapy regimens, moderately effective second line regimens, and new investigational approaches all offer promising hope that improvements will soon be seen for the treatment of HIV-related systemic NHL. Immunotherapy, monoclonal antibodies, and adoptive immunotherapy targeting Epstein Barr virus (EBV) all represent novel experimental treatment approaches that are becoming possible based on our increased understanding of the pathogenesis of HIV-related lymphoma. Primary central nervous system lymphoma (PCNSL) in HIV patients has declined in incidence and there now is a rapid, less invasive diagnostic test. The presence of EBV DNA in the cerebral spinal fluid of HIV patients with focal brain lesions strongly suggests a diagnosis of PCNSL. Unfortunately, this disease remains difficult to treat in such an immunocompromised patient population. Further work is needed in order to prevent and effectively manage these diseases.

Intra-abdominal desmoplastic small round-cell tumor: expansion of the pathologic profile.

This report describes an intra-abdominal desmoplastic small round-cell tumor in a 29-year-old man that significantly differed from the classically described appearances of this unique tumor. It showed extensive papillary areas, no necrosis, and very little desmoplasia. The latter was limited, paucicellular, and present in areas separate from the papillary structures. Also, areas of back-to-back, single-cell infiltration, which mimicked lobular breast carcinoma, were present. These epithelial features suggested the diagnosis of adenocarcinoma or peculiar mesothelioma. But, the immunohistochemical features (tumor cells positive for keratin, desmin, and vimentin) were more consistent with an intra-abdominal desmoplastic small round-cell tumor. The diagnosis became clear after application of reverse transcriptase-polymerase chain reaction techniques to formalin-fixed, paraffin-embedded tissue, which showed the presence of a 100-base pair product containing the fusion junction of Ewing's sarcoma-1 exon 7 to Wilms' tumor-1 exon 8. This feature is considered unique to intra-abdominal desmoplastic small round-cell tumors. This case illustrates the less common histologic findings that can be found in intra-abdominal desmoplastic small round-cell tumor. This deviation from the classic histologic findings may be an expression of an uncommon morphologic variant and/or partially produced by the effects of prior chemotherapy. In either event, only by illustrating the various histologic appearances of intra-abdominal desmoplastic small round-cell tumor are the chances increased for the accurate diagnosis of this aggressive neoplasm with a poor prognosis.