Elio Sciarrino

Adriamycin treatment for hepatocellular carcinoma experience with 109 patients

One hundred nine patients with hepatocellular carcinoma were treated with intravenous (IV) Adriamycin (doxorubicin). Cumulative survival rate was 34% at 6 months and 13% at 1 year. Survival was positively related to a good performance status and to alpha‐fetoprotein <50 ng/ml, not influenced by hepatitis B surface antigen (HBsAg) and by presence of clear cells in the tumor. Partial response (alpha‐fetoprotein decrease by <50% of the initial value) was observed in 10 patients and complete response in 1 patient, always within the fourth dose, with a 10% response rate. Twenty of 75 symptomatic patients (27%) achieved improvement in performance and/or pain reduction. Withdrawal of treatment became necessary for side effects in six patients. In conclusion, IV Adriamycin in hepatocellular carcinoma has only limited efficacy. Because of its early activity, treatment can be stopped after three doses if there is no evidence of response.

Asymptomatic hepatocellular carcinoma in Child's A cirrhosis

The present study deals with the natural history of 37 asymptomatic patients with cirrhosis and hepatocellular carcinoma, 25 with 2-9-cm tumors who were not surgically treated (first group) and 12 with tumors smaller than 4 cm who underwent resection (second group). All patients were in Childs A class. Two-year survival (according to life-table analysis by the Kaplan-Meier method) was 50% in the first group and 39% in the second group. This difference was not significant. In the first group no relation was found between survival and initial tumor size or alpha-fetoprotein levels. Ultrasound examinations at 3-mo intervals revealed the following patterns of tumor growth: (a) no significant growth during the follow-up (9 patients); (b) significant growth (tumor size at least doubling) only in the final stage of the disease (11 patients); (c) initial significant growth followed by a period of no increase in size (5 patients). These findings show that in our geographical area (a) 2-yr survival of untreated asymptomatic patients with hepatocellular carcinoma associated with cirrhosis does not differ from that of similar patients undergoing resection and (b) the tumor can exhibit long periods of no growth alternating with periods of exponential growth.

Ultrasonography and alpha-fetoprotein in diagnosis of hepatocellular carcinoma in cirrhosis.

The accuracy of ultrasound (US) and alpha-fetoprotein (AFP) in the diagnosis of hepatocellular carcinoma (HCC) in 363 patients with cirrhosis (C) and a clinical suspicion of HCC was assessed. The ultrasonographic patterns of HCC and their relationship with AFP values were analyzed. Echographic patterns were distributed as follows: 47 patients had sonodense lesions; 30 patients had hypoechoic lesions; 47 had mixed-pattern lesions, and in four patients focal dilated intrahepatic bile ducts were demonstrated. The sensitivity of US was 90%; specificity was 93.3%. Serum AFP level ⩾500 ng/ml (RIA) was the first clue to the diagnosis in 71 patients (48.6%); specificity was 100%. In 28 patients AFP levels became significantly elevated during follow-up after US detection of HCC. No relationship between echo pattern and serum AFP levels was demonstrated. An algorithm for diagnosis of HCC is proposed.

Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer.

One thousand twenty patients consecutively admitted because of a clinical suspicion of pancreatic cancer were investigated to evaluate the accuracy of simple clinical, laboratory, and ultrasonographic data in the diagnosis of pancreatic cancer. Age, weight loss, recent-onset diabetes mellitus, palpable abdominal mass or gallbladder, elevated serum bilirubin or alkaline phosphatase levels, and ultrasonography were significant criteria in discriminating 80 pancreatic cancers from 940 controls. The most sensitive criteria were ultrasonography (83%). weight loss (66%), and bilirubin level of >3 mg/dl(61%); the most specific were ultrasonography (99%), recent-onset diabetes (97%), and a distended palpable gallbladder (94%). Only ultrasonography demonstrated an elevated positive predictive value (86%), while weight loss, elevated bilirubin and alkaline phosphatase, besides ultrasonography had an elevated negative predictive value (95%). These results show that advanced pancreatic cancer may be excluded with simple clinical and laboratory data; ultrasonography can confirm the diagnosis with a high degree of accuracy. We suggest that the results of any new diagnostic tests for pancreatic cancer be compared with these clinical findings.

Treatment of Small Hepatocellular Carcinoma Associated with Cirrhosis by Percutaneous Ethanol Injection: A Trial with a Comparison Group

BACKGROUND Ethanol injection has been reported to be effective in the treatment of hepatocellular carcinoma, but no controlled randomized trials have been performed. We therefore performed a trial comparing ethanol injection with an untreated, matched historical comparison group in the treatment of hepatocellular carcinoma. METHODS From 1992 to 1993, 35 patients (14 Childs A and 21 Childs B cirrhosis) with small (< 4 cm) hepatocellular carcinoma associated with cirrhosis were treated by ethanol injection. Each patient was matched with an untreated case (followed up during the period 1984-89) for variables known to have independent prognostic value (age, Childs classification, number of lesions, alpha-fetoprotein, and modality of diagnosis). RESULTS The 1-, 2-, and 3-year survival rates of ethanol-treated patients were 86% (95% confidence interval (CI), 69-94), 53% (95% CI, 34-68), and 33% (95% CI, 15-52), whereas the survival rates of the comparison group were 75% (95% CI, 56-85), 26% (95% CI, 13-41), and 14% (95% CI, 5-27) (P = 0.01). The 1-, 2-, and 3-year survival rates of Childs A were 100%. 87% (95% CI, 30-97), 71% (95 CI, 33-90), 71% (95% CI, 33-90) in the ethanol-treated patients and 92 (95% CI, 59-99), 43% (95% CI, 23-73), and 21% (95% CI, 23-72) in untreated patients. The 1-, 2-, and 3-year survival of Childs B patients were 76% (95% CI, 59-97), 32% (95% CI, 13-53), and 9% (95% CI, 0.8-33) in the treated group and 61% (95% CI, 40-83), 14% (95% CI, 3-32), and 9% (95% CI, 1-26) in the treated group. CONCLUSIONS These data suggest that ethanol injection prolongs the life of patients with hepatocellular carcinoma associated with Childs A cirrhosis but seems not to influence the survival of Childs B patients.

Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: Survival rate and prognostic factors

BACKGROUND The role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial. AIMS To evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival. METHODS From 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model. RESULTS The cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values >2mg/dl compared to patients with values <2mg/dl (Hazard ratio 3.84; CI 95% 1.70-8.66; p-value=0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20-7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18-7.05; p-value 0.02) are correlated with a worse outcome. CONCLUSIONS TACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin <2mg/dl were identified as predictors of survival.

Ultrasonographic and radionuclide detection of hepatocellular carcinoma in cirrhotics with low alpha-fetoprotein levels

A total of 67 cirrhotic patients with clinically suspected neoplastic degeneration and low alpha‐fetoprotein levels were assessed prospectively with ultrasound and gold (198Au) scintigraphy. Ultrasound showed space‐occupying lesions in 22 of the 24 patients who had a final diagnosis of hepatocellular carcinoma (HCC) (sensitivity, 95.8%) and excluded the presence of HCC in 37 of the 43 patients with cirrhosis only (specificity, 86.0%; efficiency, 90.8%). Scintigraphy demonstrated a cold defect in 22 of the 24 patients who had a final diagnosis of HCC (sensitivity, 95.8%) and excluded the presence of HCC in 22 of the 43 patients with cirrhosis only (specificity, 51.1%; efficiency, 69.8%). It was concluded that the most accurate screening plain in cirrhotic patients suspected of having HCC with alpha‐fetoprotein values below 500 mg/ml would consist of ultrasonography followed, as clinically indicated, by ultrasonographic or laparoscopic guided biopsy.