PURPOSE:To describe the characteristics at presentation and the outcome of elderly patients (> or =70 years old) with HCC, a retrospective analysis using a CLIP database was performed. PATIENTS AND METHODS:The database included 650 patients. Chi2-test, logistic and Cox model were applied. RESULTS:Baseline characteristics and stage were similarly among elderly (n=158) and non-elderly (n=492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p<0.0001). Age and CLIP score were independently predictive of the odds of locoregional treatment. Prognosis was worse for elderly patients with a hazard ratio of death of 1.49 (95% CI 1.20-1.86) at multivariable analysis. The survival difference disappeared when patients were compared within each treatment group, suggesting a close link between undertreatment and shorter survival. CONCLUSION:Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.

To describe the characteristics at presentation and the outcome of elderly patients (≥70 years old) with HCC, a retrospective analysis using a CLIP database was performed. The database included 650 patients. χ2-test, logistic and Cox model were applied. Baseline characteristics and stage were similarly among elderly (n = 158) and non-elderly (n = 492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p < 0.0001). Age and CLIP score were independently predictive of the odds of locoregional treatment. Prognosis was worse for elderly patients with a hazard ratio of death of 1.49 (95% CI 1.20–1.86) at multivariable analysis. The survival difference disappeared when patients were compared within each treatment group, suggesting a close link between undertreatment and shorter survival. Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.

Purpose: To evaluate the effectiveness of partial splenic embolization (PSE) in patients with idiopathic portal hypertension (IPH) in reducing variceal bleeding episodes, splenomegaly and thrombocytopenia. Materials and methods: Six patients (2M, 417, mean age 30.3 years) with IPH presenting with splenomegaly, thrombocytopenia and recurrent variceal bleeding were treated with PSE using gelatin sponge (four patients) or Contour particles (two patients) as embolization material. Results: PSE was performed successfully in all cases; 3F coaxial microcatheters were necessary in two patients due to extreme splenic artery tortuosity. The average amount of devascularized parenchyma at CT I week after PSE was 71%. Splenomegaly and thrombocytopenia improved in all cases, with a mean platelet count increase of 120000/mm(3) and an average 68% reduction of spleen volume at follow up. Variceal bleeding did not recur after PSE. Esophageal or gastroesophageal varices disappeared (one patient) or significantly reduced (five patients) at endoscopic controls. No significant complications were noted. The follow up was of at least 18 months in all patients; mean follow up was 28.2 months. Conclusion: In patients with IPH PSE can be effective in preventing variceal bleedings, in reducing spleen volume and in significantly increasing platelet count; therapeutic results were durable in our population. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

A 76-year-old woman with abdominal pain and diarrhoea developed ascites that did not respond to treatment. There were no signs of liver damage. Abdominal ultrasonography with colour Doppler revealed an arterial-like flow in the enlarged splenic vein. Using selective mesenteric arteriography, we were able to diagnose a shunt between the inferior mesenteric artery and the inferior mesenteric vein. This is an unusual case of ascites due to prehepatic portal hypertension secondary to an extrahepatic arterioportal fistula.

Background Patients with small hepatocellular carcinoma (HCC) are usually treated with hepatic resection or percutaneous ethanol injection (PEI). Goals To compare the effects of hepatic resection versus PEI on survival in a matched case–control study. Study Patients with single-nodule HCC (≤5 cm) who were treated with hepatic resection (cases) or PEI (controls) were eligible. Matching criteria were date of diagnosis, Child–Pugh stage, and age at diagnosis. Kaplan–Meier survival curve of the control group was drawn weighing each stratum by the inverse of its size. Treatments were compared by a stratified Cox's model, adjusted by CLIP score. Results Of 912 patients, 197 were eligible and 82 (17 cases and 65 controls) were matched, creating 17 strata. Nine (53%) cases and 41 (63%) controls died. Cox model showed no survival difference between the two groups; hazard ratio of PEI versus hepatic resection was 1.04 (95% CI = 0.43–2.52). One- and 3-year survival rates in the hepatic resection and PEI groups were 82% versus 91% and 63% versus 65%, respectively. Conclusions Patients with small HCC treated with hepatic resection or PEI have similar survival rates. In view of the higher cost and morbidity of hepatic resection, a prospective randomized study is warranted.

BACKGROUND The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors.AIM The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma.PATIENTS AND METHODS IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated.RESULTS Serum IGF-I (70 +/- 10 and 65 +/- 7 vs. 185 +/- 6.4 mug/l, P < 0.001) and IGFBP-3 levels (1225 +/- 113 and 984 +/- 67 vs. 3017 +/- 80 mug/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels in patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r =-0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 +/- 2 vs. 57 +/- 2 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 +/- 0.05 vs. 0.41 +/- 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 +/- 5.6 vs. 42 +/- 6.2 mug/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 +/- 81 vs. 679 +/- 83 mug/l).CONCLUSIONS Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure.

BACKGROUND:In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS:The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS:496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS:the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

Objective The effects of carbonated beverages on the gastrointestinal tract have been poorly investigated. Therefore, this study aims to assess the effect of carbonated water intake in patients with functional dyspepsia and constipation. Methods Twenty-one patients with dyspepsia and secondary constipation were randomized into two groups in a double-blind fashion. One group (10 subjects) drank carbonated water and the other (11 subjects) tap water for almost 15 days. Patients were evaluated for dyspepsia and constipation scores, and underwent a satiety test by a liquid meal, radionuclide gastric emptying, sonographic gallbladder emptying and colonic transit time, using radio-opaque markers. Results The dyspepsia score was significantly reduced with carbonated water (before = 7.9 ± 2.8 vs after = 5.4 ± 1.7;P < 0.05) and remained unmodified after tap water (9.7 ± 5.3 vs 9.9 ± 4.0). The constipation score also decreased significantly (P < 0.05) after carbonated water (16.0 ± 3.9 vs 12.1 ± 4.4;P < 0.05) and was not significantly different with tap water (14.7 ± 5.1 vs 13.7 ± 4.7). Satiety was significantly reduced with carbonated water (before = 447 ± 146 kcal vs after = 590 ± 245;P < 0.01). Gallbladder emptying (delta percent contraction) was significantly improved only with carbonated water (39.9 ± 16.1%vs 53.6 ± 16.7%;P < 0.01). Conclusion In patients complaining of functional dyspepsia and constipation, carbonated water decreases satiety and improves dyspepsia, constipation and gallbladder emptying.

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage. As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with HCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection.

To determine alpha-fetoprotein (AFP) immunogenicity in vivo, the presence of antibodies in sera of 60 hepatocellular carcinoma, 15 liver cirrhosis, and 15 chronic hepatitis patients was evaluated by Western blotting and immunoprecipitation analyses using purified human AFP. High titers of anti-AFP immunoglobulins were detected in 14 hepatocellular carcinomas (P = 0.0006), 3 liver cirrhosis (P = 0.0173), and 1 chronic hepatitis patient, but they were not detected in 40 healthy individuals. Therefore, spontaneous immune responses to AFP are significantly associated to liver diseases (P = 0.0015). Patient immunoglobulins recognized proteic linear epitopes that were cryptic in the native protein, as demonstrated by their restricted reactivity with denatured deglycosylated AFP. Thus, in pathological liver conditions, tolerance to this self-molecule is circumvented. The identification of AFP immunogenic epitopes may contribute to defining novel immunotherapeutic strategies targeting this antigen.

The clinical outcome of cirrhotic patients with hepatocellular carcinoma (HCC) depends both on the residual liver function and tumor characteristics. However, the relative prognostic weight of these variables is not well defined. The aims of this study were to verify the value of known prognostic factors and to devise a prognostic index more sensitive than the commonly used Okuda stage. A retrospective analysis of the cases of HCC diagnosed at 16 Italian institutions from 1990 to 1992 was performed. Overall survival was the only end point used in the analysis. The Cox model, stratified by locoregional treatment, was used for multivariate analyses. The final model was derived from 10 randomly chosen training samples, and the prognostic validity of the Cancer of the Liver Italian Program (CLIP) score was assessed on the corresponding testing samples. Four hundred thirty‐five cases of HCC were collected. As of January 1997, 313 patients (72%) were deceased. Overall median survival was 20 months. At multivariate analysis, independent predictive factors of survival were Child‐Pugh stage, tumor morphology, α‐fetoprotein (AFP), and portal vein thrombosis. A simple scoring system (CLIP score) was thus produced, assigning linear scores (0/1/2) to the covariates. Compared with Okuda stage, the CLIP score, structured as a six‐category tool, has a greater discriminant ability, revealing a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. The CLIP score is a new prognostic system that accounts for both liver function and tumor characteristics. It is easy to calculate and appears to give more precise information than the Okuda stage.

Aims/Methods: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis. belonging to Child class B and C, for 2 years each.Results: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p=0.005), creatinine (p<0.001), varices (p=0.001) and galactose elimination capacity (p<0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the endpoint was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival.Conclusions: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.