Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma.

PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

Efficacy of a haemostatic matrix for the management of bleeding in patients undergoing liver resection: results from 237 cases.

BACKGROUND: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intraoperative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours. METHODS: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded. RESULTS: 105 women (age 61 +/- 9 years) and 132 men (age 61 +/- 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 +/- 1 min; this was significantly increased in patients with coagulopathy versus noncoagulopathic patients (4 +/- 1 vs. 2 +/- 1 min, p < 0.001). CONCLUSIONS: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intraoperative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.

An assessment of hepatitis C virus infection among health-care workers of the National Cancer Institute of Naples, Southern Italy.

BACKGROUND: As many people with chronic hepatitis C virus (HCV) infection are asymptomatic, HCV infection could spread easily among the health-care workers of the National Cancer Institute of Naples (especially before the identification of HCV and in the absence of good, effective preventative measures, e.g. sterile syringe use, gloves, protective glasses). METHODS: In order to determine whether there is a transmission risk for HCV infection from patient to health-care worker, we carried out a cross-sectional study of a cohort of National Cancer Institute health-care workers in Naples, Southern Italy. RESULTS: The chi2-test was not significant; we did not find any significant risk for HCV in the 'other untrained staff' group [odds ratio (OR) 2.2; 95% confidence interval (CI) 0.4-10.9] or in the health-care workers group (OR 1.6; 95% CI 0.4-7.0). In the health-care worker subgroups, doctors were the reference category because of the low prevalence of HCV in this subgroup (3.3%). A non-significant association was found in the professional nurses group (OR 2.7; 95% CI 0.8-8.8), as well as in the categories of technicians and biologists. CONCLUSIONS: No excessive risk was found among the health-care workers as a whole or among the different categories of personnel, confirming that health-care employees have benefited sufficiently from preventative measures.