Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up <4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ±â€¯197.6 days. RESULTS: Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment. CONCLUSIONS: These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. LAY SUMMARY: Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.

Circulating endothelial cells and risk of progression in patients with hepatocellular cancer receiving sorafenib.

AIM: We investigated the behavior of circulating endothelial cells (CEC) in patients with hepatocellular carcinoma (HCC) receiving sorafenib, and whether CEC levels were associated with time to progression (TTP). MATERIALS & METHODS: CECs in advanced HCC patients receiving sorafenib were counted at baseline and every 4 weeks. RESULTS: Twenty four HCC patients were enrolled in the study. Median TTP was 3.2 months (1-6). Median baseline CEC levels were 67 cells/ml, with an increase of 169.8% after 4 weeks of treatment. Any time CEC levels in patients with a TTP lower than 4 months were higher, but not statistically significant, compared with those in patients with TTP more than 4 months. CONCLUSION: Treatment with sorafenib changed CEC levels in HCC patients.

Pancreatic secondary lesions from renal cell carcinoma.

BACKGROUND: Metastatic lesions to the pancreas are uncommon. The most frequent metastases are from renal cell carcinoma (RCC). We analyzed the clinical features and survival of patients with pancreatic metastasis from renal cell carcinoma. METHODS: We retrospectively reviewed the clinical records of patients with pancreatic metastases from RCC, observed in our department from January 2004 to March 2010. Follow-up continued to September 2013. RESULTS: In the study period 13 patients with a diagnosis of metastasis from RCC were observed in our clinic, and among them 9 pancreatic resections were performed (2 pancreaticoduodenectomy, 1 duodenum-preserving pancreatic head resection, 1 central pancreatectomy, and 5 distal pancreatectomy). Four patients did not undergo a pancreatic resection: two refused surgery, one had an endoscopic biliary stent for jaundice placed and then underwent a surgical biliary bypass, and the fourth patient was too advanced and had only an endoscopic biliary stent. The mean follow-up was 56 months (range 5-115, median 53), with one nonresected patient lost in follow-up after 38 months. Among the other 12 patients, 4 died: two for progression of disease 5 and 20 months respectively after our observation. The mean (±SEM) disease-free survival of seven resected patients with curative intent was 40 ± 11 months (median 34). CONCLUSIONS: Pancreatic metastases from RCC are often asymptomatic. They generally present slow growth and an indolent behavior. Surgery is the treatment of choice in those patients with only pancreatic involvement, achieving long-term survival and disease-free survival.

Laparoscopic microwave ablation in patients with hepatocellular carcinoma: a prospective cohort study.

OBJECTIVES: There are no prospective studies of laparoscopic microwave (MW) ablation in patients with hepatocellular carcinoma (HCC). The aim of this study was to demonstrate the safety and efficacy of laparoscopic MW ablation. METHODS: A prospective study group of consecutive HCC patients considered ineligible for liver resection and/or percutaneous ablation was conducted from December 2009 to December 2010. Short-term (3-month) outcomes included a centralized revision of radiological response, mortality and morbidity. Mid-term (24-month) outcomes included time to recurrence in the study group compared with that in a cohort of consecutive patients treated with laparoscopic radiofrequency (RF) ablation using propensity score analysis. RESULTS: A total of 42 patients were enrolled. Their median age was 64 years; 67% were positive for hepatitis C virus; 33% were of Child-Pugh class B status; the median tumour diameter was 2.5 cm, and 48% of patients had multinodular HCC. In 47 of 50 (94%) nodules treated with MW ablation, a complete radiological response was observed at 3 months. There was no perioperative mortality. The overall morbidity rate was 24%. The 2-year survival rate was 79% and the 2-year recurrence rate was 55%. Using propensity score analysis (in 28 MW ablation patients and 28 RF ablation controls), 2-year recurrence rates were 55% in the MW ablation group and 77% in the control group (P = 0.03). CONCLUSIONS: Laparoscopic MW ablation is a safe and effective therapeutic option for selected HCC patients who are ineligible for liver resection and/or percutaneous ablation.

Laparoscopic ablation of hepatocellular carcinoma in cirrhotic patients unsuitable for liver resection or percutaneous treatment: a cohort study.

The aim of this study was to demonstrate the safety and efficacy of laparoscopic ablation for cirrhotic HCC patients. Between January 2004 and December 2009, laparoscopic ablation was applied prospectively in 169 consecutive HCC patients (median age 62 years, 43% hepatitis C positive) considered ineligible for liver resection and/or percutaneous ablation. There was clinically relevant portal hypertension in 72% of cases. A significant proportion of subjects (50%) had multinodular tumors or nodules larger than 25 mm. The main ablation techniques used were radiofrequency in 103 patients (61%), microwave ablation in 8 (5%), and ethanol injection in 58 (34%). The primary endpoint was 3-year survival. There was no perioperative mortality. The overall morbidity rate was 25%. The median postoperative hospital stay was 3 days (range 1-19 days). Patients survived a median 33 months with a 3-year survival rate of 47%. Cox's multivariate analysis identified patient age, presence of diabetes, albumin ≤37 g/l, and alpha-fetoprotein >400 µg/l as significant preoperative predictors of survival, while the chance to undergo liver transplantation and postoperative ascites were the only independent postoperative predictor of survival. Laparoscopic ablation is a safe and effective therapeutic option for selected HCC patients ineligible for liver resection and/or percutaneous ablation.