Gaetano Capuano

Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma. A Cancer of the Liver Italian Program (CLIP 08)retrospective case-control study

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 Coxs 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.

Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation: A prospective multicenter italian study

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 end-point 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.

Tamoxifen in the Treatment of Hepatocellular Carcinoma: 5-Year Results of the CLIP-1 Multicentre Randomised Controlled Trial

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.

Partial splenic embolization in patients with idiopathic portal hypertension.

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, 4F, 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 1 week after PSE was 71%. Splenomegaly and thrombocytopenia improved in all cases, with a mean platelet count increase of 120,000/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.

Effects of carbonated water on functional dyspepsia and constipation

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.

Nicotinamide methylation in patients with cirrhosis

Methylation reactions play an important role in the transformation of endogenous and exogenous substances. Up to 85% of all transmethylation reactions occur in the liver. Several studies have shown that these metabolic processes are greatly influenced by the presence of hepatic diseases. We investigated the methylation of nicotinamide in 16 control subjects and in 29 patients with cirrhosis (19 Child A, 10 Child B). The basal serum value of N-methyl-nicotinamide was measured in all subjects. In seven controls and in nine patients with cirrhosis (5 Child A and 4 Child B), the serum levels and urinary excretion (5 and 24 h) of N-methyl-nicotinamide were also evaluated after oral administration of nicotinamide (1.5 mg/kg body weight). The basal serum levels of N-methyl-nicotinamide were significantly (p < 0.05) higher in patients with cirrhosis (Child A: median 34 ng/ml, 16th percentile 24, 84th percentile 61; Child B median 45, 16th percentile 34, 84th percentile 81) than in controls (median 22, 16th percentile 13, 85th percentile 28). After the nicotinamide load the urinary excretion and the time course of serum N-methyl-nicotinamide in cirrhosis were also higher (p < 0.05) than in controls (24 h urinary excretion = 66.2 mg +/- 5 S.D. in cirrhosis; 47.2 +/- 10.3 in controls) (area under the serum concentration versus time curve = 68 micrograms.ml-1.min-1 +/- 22 S.D. in cirrhosis; 32 +/- 15 in controls). In conclusion, our results show that cirrhosis does not impair the efficiency of nicotinamide methylation.

Evaluation of Heparin Toxicity in the Isolated and Perfused Rat Liver

A plasma increase of liver enzymes has been recently reported in patients receiving heparin therapy. In this study we have evaluated the toxic effect of heparin infusion in the whole rat and in the isolated and perfused rat liver. No variation of plasma enzymes was observed in heparin-treated rats (10 IU per gram body weight, daily for 12 days). The heparin addition in the perfusion medium (5,000 IU in all) has shown no difference in the kinetics of hepatic enzymes release and in the other parameters of liver function. These data do not confirm a liver-toxic effect of heparin in the rat.

The Cholecystokinin Effect on Human Intestinal Permeability: Influence of Chenodeoxycholic and Ursodeoxycholic Acid Administration

The influence of CDCA and UDCA administration on human intestinal permeability to lactulose, as disclosed by intravenous CCK, has been investigated. For this purpose the fraction of lactulose excreted in the urine during 5 h after an oral load of the disaccharide in hypertonic solution was measured in 12 healthy subjects, with and without intravenous CCK. The lactulose test was performed in each subject before and after a 7-day course of oral CDCA or UDCA (750 mg/day). Under basal conditions CCK induced a 100% increase in lactulose excretion. CDCA treatment further augmented the response to CCK by 33% (p less than 0.001) but UDCA produced no significant change. Finally, the effect of CDCA or UDCA added directly to the lactulose test solution was investigated in 4 subjects following oral and duodenal administration. CDCA only produced an increase in lactulose excretion (more than 100%) when given in hypertonic solution. The possible reasons for these findings are discussed.