To define indications for percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and cirrhosis. Survival rates were determined in 746 patients who had undergone PEI (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and 0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and 0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of severe complications and a 0.1% mortality rate. PEI proved safe, effective, and repeatable and had a low cost. Survival after PEI was comparable to that after surgery, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.

To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.

The aim of this study was to investigate in a retrospective setting the patients' profile and results of those undergoing surgery for hepatocellular carcinoma (HCC) in high-volume surgical centers throughout the world. Whether surgery for HCC is a suitable approach and for which subset of patients is still controversial. The EASL/AASLD (European Association for the Study of Liver Disease/American Association for the Study of Liver Disease) guidelines, based on the Barcelona Clinic Liver Cancer (BCLC) classification, leave little room for hepatic resection; inversely, other reports promote its wider application. On the basis of the network "Hepatocellular Carcinoma: Eastern & Western Experiences," data for 2046 consecutive patients resected for HCC in 10 centers were collected. According to the BCLC classification, 1012 (50%) were BCLC 0-A, 737 (36%) BCLC B, and 297 (14%) BCLC C. Analysis of overall survival and disease-free survival and multivariate analysis of prognostic factors were performed. The 90-day mortality rate was 2.7%. Overall morbidity was 42%. After a median follow-up of 25 months (range, 1-209 months), the 1-, 3-, and 5-year overall survival rates were 95%, 80%, and 61% for BCLC 0-A; 88%, 71%, and 57% for BCLC B; and 76%, 49%, and 38% for BCLC C (P = 0.000). The 1-, 3-, and 5-year disease-free survival rates were as follows: 77%, 41%, and 21% for BCLC 0-A; 63%, 38%, and 27% for BCLC B; and 46%, 28%, and 18% for BCLC C (P = 0.000). The multivariate analysis identified bilirubin, cirrhosis, esophageal varices, tumor size, and macrovascular invasion to be statistical and independent prognostic factors for overall survival. This large multicentric survey shows that surgery is in current practice widely applied among patients with multinodular, large, and macrovascular invasive HCC, providing acceptable short- and long-term results and justifying an update of the EASL/AASLD therapeutic guidelines in this sense.

Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (Hepatology 2007;45:725–734.)

HEPATOCELLULAR carinoma (HCC) is one of the most frequently occurring tumors in humans, with more than 250,000 new cases per year diagnosed in the world.¹ It generally grows in a cirrhotic liver, and its incidence in patients with this condition is 3%.² This strict association has led some authors to consider the cirrhotic liver to be a preneoplastic condition.³ These factors, and the fact that the liver cirrhosis itself significantly reduces life expectancy, contribute to the ongoing controversy about the optimal therapeutic approaches to HCCs. The double aims of curative therapy for the tumor and the preservation of as much functioning liver parenchyma as possible are the priorities of any treatment modality for HCCs in patients with liver cirrhosis.