Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery?

According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.     

Non-oxidative metabolism of ethanol by rat pancreatic acini.

BACKGROUND: The pathogenesis of alcoholic pancreatitis may involve the metabolism of ethanol (via oxidative and non-oxidative pathways) within the pancreas. The aims of this study were to determine the rate of non-oxidative metabolism in isolated rat pancreatic acini and to compare this to the rate of ethanol oxidation. METHODS: Pancreatic acini were isolated from male Sprague-Dawley rats and incubated with (14)C-ethanol. Radiolabelled fatty acid ethyl esters (non-oxidative metabolites) were isolated from lipid extracts by thin-layer chromatography. Radiolabelled acetate (oxidative metabolite) was isolated from the incubation medium by ion-exchange chromatography. RESULTS: Non-oxidative metabolism by isolated pancreatic acini was demonstrated. At 50 and 100 mmol/l ethanol, fatty acid ethyl ester concentrations were 49.6 +/- 13.3 and 199 +/- 93 micromol/l, respectively. These levels have previously been shown to result in tissue injury. Non-oxidative metabolism was increased 9-fold by addition of oleic acid and inhibited by the lipase inhibitor, tetrahydrolipstatin, by 91.05 +/- 1.99%. The rate of oxidative metabolism was 21-fold higher than that of non-oxidative metabolism. CONCLUSIONS: Intact pancreatic cells metabolize ethanol by the non-oxidative pathway, generating fatty acid ethyl esters at a rate sufficient to cause pancreatic damage. Oxidative metabolism of ethanol occurs at a much higher rate and may also play a role in pancreatitis.     

Mitral valve repair for dilated cardiomyopathy: predictive role of right ventricular dysfunction.

AIMS: To evaluate the impact of right ventricular (RV) dysfunction on early and mid-term outcome of patients with ischaemic or dilated cardiomyopathy (DCM) undergoing mitral valve annuloplasty. METHODS AND RESULTS: From January 1997 to December 2005, 111 patients with DCM (89 ischaemic, 22 non-ischaemic) were enrolled in this retrospective study. Mean age was 67 +/- 10 years. Average pre-operative NYHA class was 3.0 +/- 0.6. Tricuspid annular plane systolic excursion (TAPSE), tricuspid annular pleak systolic velocity (TAPSV), and RV fractional area change were considered as an index of RV function. A strong relationship between TAPSE and TAPSV were found (r = 0.76). Thirty-day mortality was 10.8%. Five-year survival and possibility to be alive in NYHA classes I-II were 66.5 +/- 5.0 and 59.5 +/- 5.0%. TAPSE, TAPSV, and MV coaptation depth (MVCD) were found to be risk factors for worse early and mid-term outcome; functional class impaired mid-term outcome. ROC analysis identified TAPSE < or = 12 mm, TAPSV < or = 10 cm/s, and MVCD>10 mm as predictive cut-offs. CONCLUSION: Pre-operative assessment of some echocardiographic parameters (TAPSE, TAPSV) is very easy, low cost, and provides accurate information on RV function. A good pre-operative clinical compensation has to be necessarily reached before the operation. MVCD should be evaluated to decide surgical strategy (repair or replace).     

Dose- and time-dependent changes in plasma catecholamines in response to endotoxin in conscious rats

Time- and dose-dependent changes in plasma catecholamines, heart rate, and blood pressure were studied in response to sublethal doses of intravenous (i.v.) bacterial endotoxin in conscious male rats. Hypotension occurred with high endotoxin (1,000 micrograms/kg), whereas hypertension occurred in the low-dose group (10 micrograms/kg). All groups had significant tachycardia, which was dose and time dependent, but heart rate was unchanged for the first 2 hr in the low-dose groups (100 and 10 micrograms/kg). Plasma levels of norepinephrine (NE) and epinephrine (E) increased with both dose and time and there was significant interaction of dose and time effects. NE levels increased maximally at 0.5 hr following the highest dose of endotoxin and remained elevated during the protocol. Plasma E levels were maximal at 0.5 hr in the high-dose group, but then declined while remaining significantly higher than the 10 and 100 micrograms/kg endotoxin-treated groups for the duration of the protocol. Peak E levels in the 100 and 10 micrograms/kg group occurred at 3.0 hr and then decreased at the 6.0 hr time. Significant increases in plasma catecholamines and heart rate with endotoxin in the absence of significant hypotension present the possibility that factors other than blood pressure may be mediating efferent sympathetic outflow in endotoxicosis.     

Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells.

We studied the correlation between dexamethasone (Dex) induced growth effects and modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433 ovarian cancer cells. These cells express specific high and low affinity 125I-EGF binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but increases the number of both the high and the low affinity EGFR in a dose dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex treatment consistently with Northern blot studies. The mitogenic activity of EGF in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the Dex induced growth effects occur independently of EGFR expression.     

Ultrasound evaluation of centenarians' gallbladder

Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in centenarians compared to the other groups. There was a negative correlation between age and axial length (transverse diameter), age and width and age and common bile duct (CBD) diameter in the elderly group only. Conclusions: The study of gallbladder function in elderly people and centenarians is important because this parameter is related to the quality of digestion and absorption of many alimentary substances as well as to the formation of cholesterol gallstones. We found that gallbladder functions in centenarians are almost normal with respect to the elderly and adults. Contractility was higher than in our elderly sample. This fact ensures a correct concentration of bile salts and a good intestinal transit rate. It may represent one of the factors allowing for good digestive function in these subjects, which contributes to their health status.     

Efficacy and tolerability of antibiotics in patients undergoing H. pylori eradication

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is one of the most common gastrointestinal diseases. An increasing number of people undergo different treatment options. Unfortunately, H. pylori therapy may be troublesome for drug side effects and inefficacious for resistance to antibiotics. METHODOLOGY: One hundred and ninety-three (193) H. pylori-positive patients were randomly assigned to one of the following 7-day treatments: Group A (N = 64): amoxicillin, clarithromycin and rabeprazole; Group B (N = 64): tinidazole, clarithromycin and ranitidine bismuth citrate; Group C (N = 65): tinidazole, clarithromycin and rabeprazole Eradication was assessed by 13C-Urea Breath Test 6-8 weeks after the end of the therapy. Not-eradicated patients underwent a second cycle with tinidazole, tetracycline, bismuth and rabeprazole. All patients were asked to complete a validated questionnaire regarding presence and intensity of drug side effects. RESULTS: One hundred and eighty-eight out of the 193 H. pylori-positive patients (96%) completed therapy. No significant difference in eradication rates was observed among the three groups both in intention to treat analysis and in per protocol analysis. No significant difference in incidence of side effects occurred among groups after the first-line regimens: 48% in group A, 44% in group B and 46% in group C. Twenty-two out of the 193 enrolled subjects (11%) were not eradicated after the first-line therapy. Among them, 86% were successfully eradicated by the tinidazole, tetracycline, bismuth and rabeprazole therapy. Moreover, during quadruple therapy, a higher prevalence and intensity of side effects than in each one of the groups submitted to the first-line triple therapy was observed. CONCLUSIONS: This study shows that triple rabeprazole-based eradicating regimens are effective and safe. Incidence of side effects seems low and similar in different three-drug regimens used. Quadruple therapy, which appear highly efficacious as a second line therapy, is associated with a significantly higher incidence of side effects when compared to first-line treatment.