Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma: a prospective feasibility analysis.

BACKGROUND: Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with HCC and CP class B. PATIENTS AND METHODS: A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. [Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19-21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.] RESULTS: Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar. CONCLUSION: Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.

Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

Ultrasound-assisted percutaneous liver biopsy: superiority of the Tru-Cut over the Menghini needle for diagnosis of cirrhosis.

A total of 1192 consecutive patients with diffuse liver disease were randomized to have percutaneous liver biopsy specimens taken with the Menghini or the Tru-Cut needle, to compare tissue yield, safety, and accuracy of the two needles for diagnosing cirrhosis. The sites of puncture were determined by prebiopsy ultrasound scans. Adequate samples were obtained from 94% with the Tru-Cut needle and from 79.2% with the Menghini needle (p less than 0.001). Accuracy in diagnosing cirrhosis was 89.5% for the Tru-Cut needle and 65.5% for the Menghini needle (p less than 0.05). Complication rates were very low and similar for both needles. Under these conditions, the Tru-Cut needle is superior to the Menghini needle for diagnosing cirrhosis.

Determination of CA 19-9 antigen in serum and pancreatic juice for differential diagnosis of pancreatic adenocarcinoma from chronic pancreatitis.

Serum CA 19-9 levels were measured in 63 patients with ductal pancreatic adenocarcinoma and in 49 patients with chronic pancreatitis. Concentrations were abnormally high (greater than 40 U/ml) in 57 (90%) patients with cancer and only in 5 (10%) patients with chronic pancreatitis. All patients with falsely normal serum values had poorly differentiated carcinomas. Median CA 19-9 concentrations were progressively higher in patients with more advanced cancer. Fifteen of 16 (93%) patients with localized cancer has abnormal serum levels but only 5 (31%) of them had values greater than 120 U/ml, which was the highest score observed in patients with chronic pancreatitis. Pure pancreatic juice was obtained endoscopically from 23 patients with pancreatic cancer and from 20 with chronic pancreatitis. CA 19-9 concentrations in pancreatic juice were significantly higher in patients with cancer than in non-neoplastic patients. All 11 patients with resectable cancer investigated had a ratio of CA 19-9 to secretory protein concentration in pancreatic juice above the range of patients with chronic pancreatitis. We conclude that serum CA 19-9 determination is highly sensitive and specific for the differential diagnosis of pancreatic cancer versus chronic pancreatitis. However, moderately increased values (less than 120 U/ml), as seen in patients with localized pancreatic adenocarcinoma, are not conclusive for malignancy. The measurement of CA 19-9 to total protein ratio in pure pancreatic juice is proposed as an adjunctive, accurate diagnostic marker for early stages of pancreatic adenocarcinoma.

Observation of thoracic duct morphology in portal hypertension by endoscopic ultrasound.

BACKGROUND: Thoracic duct dilation has been demonstrated in portal hypertension and hepatic cirrhosis by lymphangiography and laparotomy and at autopsy. It is thought to be secondary to increased hepatic lymph flow and has been described in the absence of ascites or esophageal varices. The aim of the present study was to observe thoracic duct morphology by endoscopic ultrasound in various subsets of patients with portal hypertension and hepatic cirrhosis and also to validate existing radiologic/surgical data. METHODS: The thoracic duct of 33 patients with cirrhosis and portal hypertension was studied by endoscopic ultrasound. Patients were divided into four groups: 1, patients with ascites and esophageal varices; 2, esophageal varices without ascites; 3, without esophageal varices or ascites; 4, extrahepatic portal hypertension due to pancreatic malignancy. The thoracic duct diameter was also measured in 14 control subjects (group 5). RESULTS: When the thoracic duct diameter for the five groups was compared with analysis of variance, significance was p < 0.0001; by pairwise comparison, group 1 differed from the other four groups (p < 0.05). Thoracic duct dilation (5.61 mm) was seen in group 1 patients, whereas no dilation was present in groups 2 through 4. Additionally, thoracic duct diameter in 33 portal hypertensive and/or cirrhotic patients was significantly different from that in the 14 control subjects (p = 0. 003). CONCLUSION: The thoracic duct can be reliably identified by EUS in patients with hepatic cirrhosis and portal hypertension. Dilation of the duct is seen only in patients with hepatic cirrhosis, ascites, and esophageal varices. No thoracic duct dilation is present in extrahepatic portal hypertension. Contrary to existing radiologic/surgical data, thoracic duct dilation is not seen in all patients with hepatic cirrhosis and portal hypertension signifying advanced disease. A dilated thoracic duct by endoscopic ultrasound should be considered yet another sign of portal hypertension.

Hepatocellular carcinoma in Italy: report of a clinical trial with intravenous doxorubicin.

Sixty-six patients with hepatocellular carcinoma (HCC) in various stages of hepatic involvement were studied prospectively. Of these, 50 (75%) had associated cirrhosis and 19 (28%) had serum hepatitis B surface antigen (HBsAg). Six (9%) patients were eligible for tumor resection, 34 were selected for doxorubicin chemotherapy (60 mg/m2, i.v., given every 3 weeks, up to a maximum dose of 550 mg/m2), and 26 were followed up without treatment. Untreated patients survived 1-18 months (median 1) after diagnosis. Surgically treated patients survived 1-14 months (median 4.5). In the doxorubicin group, six patients died soon after the first course of treatment, leaving 28 patients to be evaluated. Seven (24.5%) responded to therapy, surviving 2-26 months (median 8.0). Twenty-one (75.5%) did not respond to chemotherapy and had a median survival of 3.5 months (range: 2-12). Initial performance status and the degree of hepatic impairment were found to be covariates of prognostic significance. The type and severity of drug-related side-effects appeared to be comparable to those reported by others. In accordance with previous reports, our patients with HCC often had non-resectable tumors or responded poorly to chemotherapy. The association between this tumor and cirrhosis might partially account for treatment failure.

Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma.

A sensitive radioimmunoassay was used to detect antibodies to hepatitis C virus (HCV) in patients with hepatocellular carcinoma and chronic hepatitis. HCV antibodies (anti-HCV) were detected in 86 of 132 patients with hepatocellular carcinoma with no relation to the presence or absence of hepatitis B surface antigen (HBsAg). The prevalence of anti-HCV was also high in patients with diseases thought to predispose to hepatocellular carcinoma, such as non-A, non-B chronic hepatitis and cirrhosis (74%). In HBsAg-negative patients with hepatocellular carcinoma the prevalence of anti-HCV was lower than that in patients with non-A, non-B chronic hepatitis (16% vs 55%); the prevalence of serum antibodies to hepatitis B core antigen (anti-HBc), a marker of hepatitis B virus infection, was 70% and 28%, respectively. In HBsAg-negative patients with hepatocellular carcinoma, anti-HCV and anti-HBc occurred together nearly three times as often as in patients with chronic hepatitis (54% vs 19%). These data indicate that, in Italy, HCV is an important factor associated with hepatocellular carcinoma and non-A, non-B chronic hepatitis.

Hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma.

Hepatitis C virus (HCV) is the major etiologic agent of parenterally transmitted non-A, non-B hepatitis. To determine whether there is a relationship between this virus agent and hepatocellular carcinoma (HCC), the sera of patients with HCC and chronic hepatitis were assessed using a sensitive immunoassay for HCV antibody. Anti-HCV was detected in 65% of 132 patients with HCC, without any relationship with the presence of the hepatitis B surface antigen (HBsAg). The prevalence (74%) of anti-HCV was high, as expected in patients with putative non-A, non-B cirrhosis also. The prevalence of anti-HCV was less in patients with HBsAg-positive cirrhosis (28%) and in patients with disease not related to viral hepatitis and healthy controls (8%). These data suggest, but do not prove, that HCV is an important factor associated with HCC.