Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma

AIM: To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999. METHODS AND RESULTS: Data were retrospectively analyzed by chart review. In 95 cases (72 males and 23 females) sufficient data were available for analysis. Twenty five (29%) of 85 patients were HBsAg or anti HBc positive, 21/85 (25%) were anti HCV positive, and 6/85 (7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV positive patients than in the other two groups. Thirty one (34%) of 90 patients had histories of alcohol abuse. In 79/94 (84%) patients, cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/94 (20%). Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%). According to Okuda 28/94 (30%) were grouped to stage I, 53/94 (56%) were grouped to stage II, and 13/94 (14%) were grouped to stage II. Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8 4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival, though patients with an AFP value greater than 100 microg/L did experience shortened survival. Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage II patients. There was longer survival in those Okuda stage II patients who were treated with percutaneous ethanol injection. CONCLUSION: Even in a low incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival.

Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

AIM： Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor （VEGF） via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFItl-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 （Fit-l）, for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS： Murine colorectal carcinoma cells （CT26） were inoculated subcutaneously into Balb/c mice for in vivo studies. Tumor size and survival were determined. 293 cell line was used for propagation of the adenoviral vectors. Human lung cancer line A549 and human umbilical vein endothelial cells were transfected for in vitro experiments.RESULTS： Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 （5×10^9 PFU/animal） was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation, in spite of these antitumoral effects, the survival time was not improved. According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION： In this study we confirmed the value of a systemic administration of AdsFItl-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

Acute hepatitis induced by an Aloe vera preparation: A case report

AIM: Aloe vera, plant extracts of Aloe barbadensis miller,is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described.METHODS: Description of a clinical case.RESULTS: Hepatitis in a 57-year old female could be linked to the ingestion of Aloe barbadensis miller compounds. The patient's hepatitis resolved completely after discontinuing this medication.CONCLUSION: The case emphasizes the importance of considering phytopharmaceutical over-the-counter drugs as causative agents of hepatitis.