Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

Long-Term Results at 10 Years of Pouch Resizing for Roux-en-Y Gastric Bypass Failure

Background: Roux-en-Y gastric bypass (RYGB) is currently one of the most performed bariatric procedures and it is associated with rapid weight loss. However, weight loss failure and weight regain after RYGB occurs in approximately 30% and 3-5% of patients, respectively, and represent a serious issue. RYGB pouch resizing is a surgical option that may be offered to selected patients with RYGB failure. The aim of this study is to assess long-term results of pouch resizing for RYGB failure. Materials and Methods: From February 2009 to November 2011, 20 consecutive patients underwent gastric pouch resizing for RYGB failure in our tertiary bariatric center. The primary outcome was the rate of failure (%EWL < 50% with at least one metabolic comorbidity) after at least 10 years from pouch resizing. Gastroesophageal Reflux Disease (GERD) was also assessed. Results: Twenty patients (18 women (90%)) were included and seventeen (85%) joined the study. The failure rate of pouch resizing was 47%. Mean %EWL and mean BMI were 47%, and 35.1 kg/m(2), respectively. Some of the persistent co-morbidities further improved or resolved after pouch resizing. Seven patients (41%) presented GERD requiring daily PPI with a significantly lower GERD-HQRL questionnaire score after pouch resizing (p < 0.001). Conclusion: Pouch resizing after RYGB results in a failure rate of 47% at the 10-year follow-up while the resolution of comorbidities is maintained over time despite a significant weight regain

A case report of liver transplantation following a biliopancreatic diversion: A friendly cohabitation?

Abstract Today, bariatric surgery has become the main therapeutic means to fight against the escalating increase in obesity, worldwide. Besides that, non-alcoholic steatohepatitis has inflated its indication for liver transplantation. Liver transplant surgeons are prone to face more and more patients with such background. Here, we described the first case of liver transplantation for hepatocellular carcinoma in a patient with previous history of biliopancreatic diversion with duodenal switch. Biliopancreatic diversion with duodenal switch is nowadays an uncommon bariatric surgery but use to be a second stage surgery following sleeve gastrectomy. Liver transplantation can be challenging as such bariatric procedure reshape the digestive anatomy and can also be responsible for malnutrition. Without such complication and in a center specialized in bariatric surgery and liver transplantation, such cases can be successful and should not alarm liver transplant surgeons. In our case, the bariatric anatomy was conserved, and the liver transplantation was successful, without difficulty of the post-operative immunosuppressive treatment. However, long term follow-up showed an exacerbation of the sarcopenia level and establish even more the need for an association of a well-planned physical and nutritional rehabilitation in the peri-operative period in such candidate

Results ofstandard stapler closure of pancreatic remnanat after distal spleno-pancreatectomy for adenocarcinoma

Background/Aim: The purpose of this study was to evaluate the results of stapled closure of the pancreatic remnant after cold-knife section of the pancreatic isthmus and distal pancreatectomy for adenocarcinoma. Methods: A retrospective evaluation of 57 consecutive patients undergoing distal spleno-pancreatectomy for adenocarcinoma was performed. The pancreatic isthmus was systematically straight-sectioned with a cold knife, and the remnant was stapled close without additional stitches or adjuncts. The study’s main endpoints were postoperativemortality, the occurrence of a pancreatic fistula, the need for a re-operation, the postoperative length of stay in the hospital, the rate of re-admission, and late survival. Results: Postoperative mortality was absent. Seventeen patients (29.8%) presented a pancreatic fistula of grade A in seven cases (41.2%), grade B in eight cases (47.1%), and grade C in two cases (11.8%). Re-operation was required in the two patients (3.5%) with grade C fistula in order to drain an intra-abdominal abscess. The mean postoperative length of stay in the hospital was 15 days (range, 6–62 days). No patient required re-admission. Twenty-nine patients (50.8%) were alive and free from disease, respectively, 12 patients (21.1%) at 12 months, 13 patients (22.8%) at 60 months, and four patients (7.0%) at 120 months from the operation. The remaining patients died of metastatic disease 9–37 months from the operation. Lastly, disease-related mortality was 49.1%. Conclusion: Stapler closure of the pancreatic remnant allows good postoperative results, limiting the formation of pancreatic fistula to the lower limit of its overall reported incidence

B-type natriuretic peptide as a biochemical marker of left ventricular diastolic function: Assessment in asymptomatic patients 1 year after valve replacement for aortic stenosis.

Objectives: Left ventricular (LV) diastolic dysfunction after aortic valve replacement (AVR) carries a substantial risk of development of heart failure and reduced survival. In addition to echocardiography, B-type natriuretic peptide (BNP) provides a powerful incremental assessment of diastolic function. This study evaluates BNP as a marker of LV diastolic dysfunction in a cohort of patients with preserved LV ejection fraction who underwent AVR for pure aortic stenosis and the relationship between BNP values and the grade of LV diastolic dysfunction. Methods A total of 113 patients were included in the study. Echocardiographic evaluation was performed preoperatively, 5 days postoperatively and at 12-month follow-up, to assess LV dimensional and functional parameters. Diastolic function was labelled as normal, mild, moderate or severe dysfunction. Concomitantly, BNP levels were evaluated. Results Mild to severe diastolic dysfunction occurred preoperatively in all patients. At 12-month follow-up, 65 (62.5%) patients had mild and 25 (24.1%) moderate to severe diastolic dysfunction. BNP values, categorized for quartile distribution, correlated with diastolic dysfunction grade (P < 0.001 for each comparison). At receiver operating characteristic analysis, the BNP level of 120 pg/ml was 91% sensitive and 85% specific for diastolic disease, while 300 pg/ml was 80% sensitive and 91% specific for moderate or severe diastolic dysfunction. Twelve months after AVR, BNP values were strongly correlated with the significant echocardiographic parameters suggestive of diastolic dysfunction (P ≤ 0.006 in all cases). Conclusions The BNP level following AVR is related to diastolic disease severity and may complement echocardiographic evaluation when symptoms are unclear and LV function is difficult to interpret

An analysis of surgical anatomy of the gastric fundus in bariatric surgery: Why the gastric pouch expands? A point of technique

AbstractIn bariatric surgery, it is essential to completely release the Fundus in order to create a narrow gastric pouch. The upper part of the fundus is located above the omental bursa and is therefore retro-peritoneal. In order to release this completely, not only does the arterial supply to the fundus need to be divided to visualise the left diaphragmatic pillar, but the right attachment beginning at the left diaphragmatic pillar and running towards the fundus needs to be divided. This minimal dissection is compensated by further dissection at the level of the left diaphragmatic pillar and traction on the stomach from right to left during the final division stapling division process. The surgeon still has the impression of having released the posterior aspect of the Fundus, exposing the pillar of the diaphragm, although in fact part of the Fundus still remains adherent to the diaphragm and is therefore not released