Durable remission induced by rituximab-containing chemotherapy in a patient with primary refractory Burkitt's lymphoma

We describe a 65-year-old man diagnosed with Burkitt's lymphoma arising from the intestine. The tumor cells had a mature B-cell immunophenotype and rearrangement of the c-myc gene. The patient was treated with intensive multiagent chemotherapy. After four courses of chemotherapy, an ileus developed due to a residual abdominal disease. We administered rituximab in combination with the same chemotherapy regimen. A dramatic clinical improvement was observed and abnormal uptake by 18F-fluorodeoxyglucose positron emission tomography disappeared. The patient experienced complete remission for 1 year. This encouraging result indicates that rituximab might be an important treatment choice in management of Burkitt's lymphoma.     

Survival After Curative Resection for Mucinous Adenocarcinoma of the Colorectum

PURPOSE: Previous reports have suggested that mucinous colorectal adenocarcinomas are more advanced at diagnosis and have a poorer prognosis than nonmucinous colorectal adenocarcinomas. The purpose of this study was to clarify whether the mucin-producing histologic type of carcinoma is associated with a worse prognosis than nonmucinous, differentiated colorectal adenocarcinoma for patients who undergo curative surgery. METHODS: Using a database of 2,678 surgical patients with colorectal cancers operated on at Aichi Cancer Center between 1965 and 1994, we investigated 97 cases of mucinous adenocarcinoma and 2,197 cases of nonmucinous adenocarcinoma. We also evaluated the outcomes of patients who underwent surgery with curative intent. To determine whether the mucinous adenocarcinoma itself was an independent prognostic factor in the curative resected patients, a multivariate analysis was performed. RESULTS: The mucinous adenocarcinoma patients were found to be younger (P = 0.0003), have more lymph node involvement (48.5 vs. 40.3 percent; P = 0.0564), more peritoneal dissemination (19.6 vs. 5.6 percent; P < 0.0001), greater frequency of advanced stage disease (P = 0.0006), a lower rate of curative resection (76.3 vs. 84.4 percent; P = 0.0450), and lower overall 5-year survival rates (41 vs. 62.4 percent; P = 0.0002) than nonmucinous adenocarcinoma patients. In the subjects who underwent curative resection, the 5-year survival rate for those with mucinous adenocarcinoma was significantly worse than for those with nonmucinous adenocarcinoma (54 vs. 73.3 percent; P = 0.0020). Multivariate analysis using the Cox proportional hazards model showed that the clinically significant predictive factors were stage at diagnosis, mucinous histology, tumor location, gender and age. The mucinous histologic type itself was an independent factor for poor prognosis for patients who underwent curative surgery. CONCLUSIONS: In patients with colorectal carcinomas who underwent surgery with curative intent and who had colorectal carcinomas of the mucinous histologic type, there was significant correlation with prognosis as measured by overall survival rate after adjustment had been made for major confounders.     

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus

Background: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. Methods: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. Results: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV (P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV (P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. Conclusions: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations. Received: April 18, 2002 / Accepted: October 25, 2002 Reprint requests to: S. Kakumu     

Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats

Previously, we reported that the inhibition of Rho-kinase by a microinjection of Y-27632 or the transfection of dominant-negative Rho-kinase into cells of the nucleus tractus solitarii (NTS) reduces blood pressure, heart rate, and sympathetic nerve activity. In the present study, we examined the effects of another Rho-kinase inhibitor, hydroxyfasudil, on blood pressure and heart rate in anesthetized rats. The results were compared between normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The microinjection of hydroxyfasudil was performed unilaterally or bilaterally into the NTS of WKY rats and SHR. A unilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in SHR but not in WKY rats. A bilateral microinjection of hydroxyfasudil elicited depressor and bradycardic responses in both SHR and WKY rats. However, the magnitude of the decrease in these variables was greater in SHR than in WKY rats. The expression levels of RhoA in the membrane fraction and phosphorylated ERM family (ezrin, radixin, and moesin) in the NTS were greater in SHR than in WKY rats. These results suggest that the microinjection of hydroxyfasudil into the NTS causes cardiovascular responses similar to those caused by Y-27632 and that these responses are probably mediated by the inhibition of Rho-kinase.     

Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice

We have recently demonstrated that endogenous erythropoietin (Epo)/Epo receptor (EpoR) system plays an important protective role in hypoxia-induced pulmonary hypertension. However, it remains to be examined whether vascular EpoR system contributes to angiogenesis in response to ischemia. We examined angiogenesis in EpoR(-/-)-rescued mice that lack EpoR in most organs including cardiovascular system except erythroid-lineage cells. Two weeks after femoral artery ligation, blood flow recovery, activation of VEGF/VEGF receptor system, and mobilization of endothelial progenitor cells were all impaired in EpoR(-/-)-rescued mice as compared with wild-type (WT) mice. Bone marrow (BM) transplantation with WT-BM cells in EpoR(-/-)-rescued mice partially but significantly improved blood flow recovery after hindlimb ischemia. The extent of VEGF upregulation and the number of BM-derived cells in ischemic tissue were significantly less in EpoR(-/-)-rescued mice compared with WT mice even after BM reconstitution with WT-BM cells. Similarly, the recovery of blood flow was significantly impaired in recipient EpoR(-/-)-rescued mice that had been transplanted with WT-BM or EpoR(-/-)-rescued-BM as compared with recipient WT mice. Furthermore, the Matrigel implantation assay and aortic ring assay showed that microvessel growth in vitro was significantly reduced in EpoR(-/-)-rescued mice as compared with WT mice. These results indicate that vascular EpoR system also plays an important role in angiogenesis in response to hindlimb ischemia through upregulation of VEGF/VEGF receptor system, both directly by enhancing neovascularization and indirectly by recruiting endothelial progenitor cells and BM-derived proangiogenic cells.