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.

Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis.

BACKGROUND: The arginine-degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI-SS PEG 20,000 mw reduces HCV viral titers through nitric oxide (NO)-dependent effects. METHODS: The effects of ADI-SS PEG 20,000 mw (dose, 160 IU/m2; three cycles of four once-weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were evaluated using archived plasma from patients with HCC and HCV and in vitro cell model measurements of HCV replication. RESULTS: ADI-SS PEG 20,000 mw selectively inhibited HCV replication in vitro (IC50 = 0.027 IU/mL). Fifteen HCC/HCV patients completed treatment. The HCV titers were reduced by up to 99% in five out of 10 (50%) HCV-serotype 1b patients (P = 0.0093). These patients also experienced significant improvements in liver function (P = 0.0091). There were concomitant reductions of plasma arginine and serum NO levels. The HCV titer was not reduced in HCV-type 2c patients. CONCLUSION: Reduction of extracellular arginine by ADI-SS PEG 20,000 mw in HCC patients reduces HCV viral titers and improves liver function, possibly through suppression of NO.

Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Radiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA. METHODS: All patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival. RESULTS: A total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39-86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively. CONCLUSIONS: Treatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered.