Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

The position of the peritoneal dialysis catheter is not essential for a correct performance.

The success of chronic peritoneal dialysis (PD) is a well-functioning catheter. It is recommended to place the tip of PD access in the intraabdominal deep pelvic area. The authors' objectives were to prove if the PD device should be necessarily located in the pelvic area to function properly, and if the X-ray exploration should be compulsory when blinded implantation technique is used. 42 stable patients on PD were included in the study, infusion and drainage times were recorded and an abdominal X-ray was performed at the same time. Catheter was correctly located in 25 (59.5%) cases and in 17 (40.5%) it was malpositioned. We observed that there were no differences in infusion times, but in the first group drainage was faster than in the second although not significant: infusion 10.5 vs. 10.6 minutes and drainage 14.7 vs. 15.8 minutes. These clinical observations support the fact that catheters' function would not necessarily depend on its intraabdominal position and that a radiological exploration should not be mandatory.

Fasting plasma ghrelin levels increase progressively after biliopancreatic diversion: one-year follow-up.

BACKGROUND: The role of ghrelin in weight control after surgery is not clear. We examined plasma ghrelin and leptin levels in patients with morbid obesity undergoing biliopancreatic diversion (BPD) of Scopinaro. METHODS: 30 adult patients (27 females, 3 males), undergoing elective BPD were recruited from the Hospital Surgery Service. Fasting blood samples for biochemical determinations were drawn before surgery and 1, 3 and 12 months after BPD. Human plasma ghrelin was measured by RIA. RESULTS: During the study period, weight, BMI and serum leptin levels decreased significantly at all sample points compared to preoperative values. Ghrelin plasma levels increased during the study, with statistical significance at 3 months and 1 year after surgery compared with preoperative levels. While leptin changes correlated with changes in BMI, no correlation was found between ghrelin and leptin or BMI changes. CONCLUSION: Plasma ghrelin levels could be decreased in obese patients as a compensatory mechanism to their nutritional state, but our results do not support the postulated beneficial role of ghrelin in the 1-year weight loss after BPD. They rather suggest that weight loss somehow stimulates ghrelin secretion, even in the absence of part of the stomach.

Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients.

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-alpha and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-alpha, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-alpha was found in patients with NASH in hepatic tissue (0.65 +/- 0.54) and in peripheral fat (0.43 +/- 0.45); in the control samples, the mRNA expression was 0.28 +/- 0.32, P <.007, and 0.26 +/- 0.22, P <.018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 +/- 1.81 vs. 1.56 +/- 1.17; P <.05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-alpha in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-alpha mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-alpha system may be involved in the pathogenesis of NASH.

[Surgery of early gastric cancer. Twenty-five year experience]. / Cirugía del cáncer gástrico precoz. Experiencia en 25 años.

AIM: To study the influence of the depth of parietal invasion (mucosal-submucosal), the presence or absence of ganglionic invasion and type of gastrectomy performed (subtotal or total) on survival in patients with early gastric cancer. STUDY DESIGN: Longitudinal study. PATIENTS: A clinical-pathologic study of 101 patients who underwent surgery for early gastric cancer was performed. Probability of survival was estimated using the Kaplan-Meier and logrank tests and multivariate analysis was performed using the Cox test. RESULTS: Mucosal involvement was found in 46 patients (45.5%) and submucosal involvement in 55 patients (54.5%). The presence of ganglionic metastases was greater in tumors reaching the submucosa (14 [25.5%]) than in those limited to the mucosa (4 [8.7%]). Partial gastrectomy was performed according to tumor location in 84 patients (83.2%), total gastrectomy was performed in 16 patients (15.8%) and 1 wedge resection was performed. The mean postoperative follow-up was 84.04 55.89 months (range: 2-264). Comparison of survival in patients with tumors limited to the mucosal or submucosal layers revealed a p-value of 0.06 (NS). Comparison of survival in patients with metastases and in those without metastases revealed a p-value of < 0.0001. Comparison of survival between patients who underwent total gastrectomy and those who underwent partial gastrectomy showed a p-value of 0.38 (NS). Postoperative mortality was nil. Overall survival at 5 years was 79.24% and at 10 years was 68.14%. Multivariate analysis revealed that ganglionic involvement and depth of parietal invasion influenced survival. CONCLUSIONS: Survival is influenced by ganglionic involvement but not by submucosal invasion. Partial gastrectomy may be an appropriate procedure since survival is similar to that associated with total gastrectomy.

Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis?

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity characterized by the presence of steatosis and lobular and/or portal inflammation with or without fibrosis. Patients with non-alcoholic fatty liver and fibrosis on liver biopsy have increased liver-related deaths. METHODS: 181 wedge liver biopsies, taken at the time of bariatric surgery from patients with a mean body mass index (BMI) of 47, were studied. In all cases, the liver biopsy was performed without knowledge of the patient's clinical and biochemical data, which were then examined with univariate and multivariate analysis. RESULTS: Diagnosis of NASH was established in 105 patients (91%); 74 patients (70%) showed mild steatosis, 20 (19%) had moderate inflammation and fibrosis, and 11 (10%) had steatosis with severe fibrosis. None of the liver biopsies showed cirrhosis. Age was the only independent predictor of moderate and severe fibrosis (p = 0.001). CONCLUSIONS: Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.