Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.

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Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU. All patients should be tested for their HER-2 status and trastuzumab should be added to a standard fluoropyrimidine/cisplatin regimen in patients with HER-2 positive tumours. Two and three-drug regimens including 5-FU, cisplatin, with or without an anthracycline, as well as irinotecan or docetaxel-containing regimens are reasonable treatment options for HER-2 negative patients.

Aims: At present, clinical success of hepatocyte transplantation as an alternative to whole liver transplantation is hampered by the limited availability of suitable donor organs for the isolation of transplantable hepatocytes. Hence, novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Mesenchymal stem cells (MSCs) from human bone marrow may have the potential to differentiate into hepatocytes in vitro and in vivo. Methods: Isolated MSCs were selected by density gradient centrifugation and plastic adherence, differentiated in the presence of human hepatocyte growth medium and transplanted in immunodeficient Pfp/Rag2 mice. Results: Here, we demonstrate that human MSCs gain in vitro the characteristic morphology and function of hepatocytes in response to specified growth factors. Specifically, preconditioned MSCs store glycogen, synthesise urea and feature the active hepatocyte-specific gene promoter of phosphoenolpyruvate carboxykinase (PCK1). After transplantation into livers of immunodeficient mice, preconditioned MSCs engraft predominantly in the periportal portion of the liver lobule. In situ, the cells continue to store glycogen and express PCK1, connexin32, albumin and the human hepatocyte-specific antigen HepPar1, indicating that the transplanted cells retain prominent qualities of hepatocytes after their regional integration. Conclusion: MSCs derived from human bone marrow may serve as a novel source for the propagation of hepatocyte-like cells suitable for cell therapy in liver diseases.

Pre-differentiation of human MSCs from adipose tissue into hepatocyte-like cells in vitro facilitates long term functional hepatic integration in vivo.

In this randomized controlled multicenter trial, we compared endoscopic variceal banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal varices (diameter >5 mm) without prior bleeding were randomized to VBL (n ‫؍‬ 75) or PPL (n ‫؍‬ 77). The groups were well matched with respect to baseline characteristics (age 56 ؎ 10 years, alcoholic etiology 51%, Child-Pugh score 7.2 ؎ 1.8). The mean follow-up was 34 ؎ 19 months. Data were analyzed on an intention-to-treat basis. Neither bleeding incidence nor mortality differed significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10% (PPL). It was associated with the ligation procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL were similarly effective for primary prophylaxis of variceal bleeding. VBL should be offered to patients who are not candidates for longterm PPL treatment. (HEPATOLOGY 2004;40:65-72.) U pper intestinal hemorrhage is a common and often fatal complication of portal hypertension. It occurs in 30% of patients with cirrhosis, with each bleeding episode bearing a mortality risk of 30% to 50%. 1-3 Thus, prophylactic treatment prior to the first bleeding (i.e., primary prophylaxis) is mandatory in highrisk patients. 4,5 Nonselective ␤-blockers (i.e., propranolol, nadolol)-the current standard prophylaxis-reduce bleeding incidence and bleeding-related mortality. 6 -9 However, pharmacotherapy with ␤-blockers is not optimal: 30% to 40% of patients will not achieve a sufficient reduction of portal pressure to prevent bleeding. 10 -12 Furthermore, contraindications and side effects are common 13,14 and may require withdrawal, which reincreases the risk of bleeding. 15 Therefore, therapeutic alternatives to ␤-blockers are warranted. Due to heterogeneous results, prophylactic endoscopic sclerotherapy is not recommended for the primary prevention of variceal bleeding. 5,7 Compared to injection sclerotherapy, 16 variceal banding ligation (VBL) allows a more rapid and more effective eradication of varices with fewer side effects. 17 To date, only 2 trials comparing VBL with standard treatment (␤-blockers) have been fully published. 13,18 The results of these studies are controversial and partly inconclusive. In the present article, we report on the results of a prospective randomized multicenter trial comparing propranolol (PPL) and banding ligation for the primary prophylaxis of variceal bleeding in patients with cirrhosis.

Background/Aims Patients with cirrhosis are classified in a compensated and a decompensated stage. Portal hypertension is responsible for most of the complications of cirrhosis that mark the transition from compensated to decompensated cirrhosis. The objectives of this study were (a) to analyse survival of the different stages and substages of cirrhosis and (b) to examine the prognostic value of the hepatic venous pressure gradient (HVPG) at each of the stages. Methods A total of 729 patients with suspected cirrhosis underwent routine measurement of portal pressure and systemic haemodynamics between 11/1995 and 12/2004. The primary end-point of the study was death, collected until November 30th, 2006. Multivariable analysis was performed using two models to determine predictors of death at each stage. Results A total of 443 patients were included in the study. The 1-year mortality was 5.4% in compensated and 20.2% in decompensated patients. Compensated patients in stage 1 (no varices) had a longer survival than stage 2 patients (varices present) (P = 0.015). In decompensated patients, survival was not different between stage 3 (ascites, with or without varices) and stage 4 (variceal haemorrhage, with or without ascites). Age and HVPG (cut-off 10 mmHg) were independent predictors of death in compensated patients, whereas MELD was in decompensated patients. Conclusion Survival rates and predictors of death are different between patients with compensated and decompensated cirrhosis. Unlike the Italian cohort staging system, ascites is a better stratifying clinical event than variceal haemorrhage in patients with decompensated cirrhosis. The presence of clinically significant portal hyper-tension has prognostic value in compensated cirrhosis.

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