Influence of hepatitis viruses on clinicopathological profiles and long-term outcome in patients undergoing surgery for hepatocellular carcinoma.

BACKGROUND: The global risk of hepatocellular carcinoma (HCC) is largely due to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years, however, an increased prevalence of non-viral HCC has been noted. The clinical impact of the presence/absence of viral infections in HCC remains controversial. The present study aimed to assess the effect of hepatitis viruses on demographics, clinical and pathological features and long-term outcome in a large cohort of Romanian patients who underwent surgery for HCC. METHODS: The study included 404 patients with HCC who had undergone resection, transplantation or radiofrequency ablation at a single institution between 2001 and 2010. The patients were divided into four groups: 85 patients with hepatitis B virus infection (HBV group), 164 patients with hepatitis C virus infection (HCV group), 39 patients with hepatitis B and C virus co-infection (HBCV group), and 116 patients without viral infection (non-BC group). RESULTS: The patients of both HBV (56.0+/-11.3 years) and HBCV groups (56.0+/-9.9 years) were significantly younger than those of the HCV (61.0+/-8.5 years, P=0.001) and non-BC groups (61.0+/-13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis was significantly lower in the non-BC group (47%) than in any other subsets (72%-90%, P<0.002). Furthermore, the non-BC patients were more advanced according to the Barcelona Clinic Liver Cancer stages than the patients of the HCV or HBCV groups (P<0.020); accordingly, they were more frequently assessed beyond the Milan criteria than any other groups (P=0.001). No significant differences in the disease-free or overall survival rates were observed among these groups. CONCLUSIONS: Patients with non-viral HCC are diagnosed at advanced ages and stages, a situation plausibly due to the poor effectiveness of cancer surveillance in community practice. The presence of viral infections does not appear to impair the long-term prognosis after surgical treatment in patients with HCC; however, there is a trend for worse disease-free survival rates in HBCV patients, though statistical significance was not reached.

Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome.

Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (NRF2, KEAP1, SRXN1, and CES1) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for ß-catenin and NRF2 (P<0.0001). Besides, tumors from patients born in Greater Bucharest carried TP53 mutations more frequently than others (45 vs 10%, P=0.02). Finally, a R249S mutation of TP53, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.

[The value of resection in pancreatic cancer: the analysis of an experience of 180 patients in 10 years]. / Valoarea rezectiei în cancerul pancreatic: analiza unei experiente de 180 de cazuri în 10 ani.

Pancreatic cancer (PC) represents one of the most severe malignant diseases, with an extremely high mortality rate (80% in the first year following diagnosis). The only potentially curative treatment is resection. This report evaluates the last 10-year experience in surgical resection for pancreatic cancer in the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest--Romania), between 01.01.1995-01.05.2004. From a total of 832 patients with pancreatic cancer who were surgically treated, 180 underwent various resections (a resecability rate of 21.6%). There were 120 resections for cancer of the pancreatic head: 61 Whipple procedures, 10 pilorus preserving pancreaticoduodenectomies, 10 pancreaticoduodenectomies associated with complex resection, 17 pancreaticoduodenectomies with resection of the portal vein, 15 pancreaticoduodenectomies with extensive lymphodissection, 2 subtotal pancreatectomies and 5 total pancreatectomies; 60 standard splenopancreatectomies were performed for cancer of the pancreatic tail. The overall morbidity was 34%--61 patients (38 with cancer of the pancreatic head and 23 with pancreatic cancer of the tail), with the prevalent complication represented by pancreatic fistula. The mortality rate was 6.6%--12 patients (9 with cancer of the pancreatic head and 3 with cancer of the tail); there was a continuous decreasing trend from 9.1% between 1994-1999 to 1.6% between 2002-2004. In our Center an increasing preoccupation for pancreatic surgery, along with an improved surgical experience, resulted in a constant raise in the number of patients resected for pancreatic cancer, with a low morbidity and mortality rate.