Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox.

INTRODUCTION: Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders. METHODS: We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis. RESULTS: The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV. CONCLUSIONS: Our study shows that height is an independent prognostic factor of resectable lung cancer.

Multimodal treatment confers best overall survival results in patients with huge hepatocellular carcinoma: a systematic review and network meta-analysis.

BACKGROUND: Huge (>10 cm) hepatocellular carcinoma is burdened by elevated mortality due to its peculiar characteristics and delayed diagnosis. Liver resection is considered the gold standard although survival is poor. Recently, some different strategies have been evaluated to improve results in tumor recurrence and survival. The aim of this research is to identify which strategy offers the best results in terms of overall survival for resectable huge hepatocellular carcinoma. METHODS: A systematic review and network meta-analysis of 13 studies was conducted from PubMed, Embase, Scopus, Cochrane Library, and Web of Science databases including research comparing two or more treatments to manage huge hepatocellular carcinoma. Results were synthesized through forest plots and risk of bias assessed with the CINeMA framework as recommended. RESULTS: The association of liver resection and transcatheter arterial chemoembolization confers a significant improvement in survival compared to liver resection alone (HR: 0.55) while transcatheter arterial chemoembolization, radioembolization, and ethanol ablation alone were associated to decreased overall survival. Within-study bias, indirectness and incoherence were the domains mainly affected by concerns in risk of bias analysis. CONCLUSION: Multimodal treatment including liver resection and transcatheter arterial chemoembolization increases survival in patients with resectable huge hepatocellular carcinoma.

Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

How to deal with right hepatic artery coming from the superior mesenteric artery during minimally invasive pancreaticoduodenectomy: A systematic review.

BACKGROUND: Anatomical variations in the liver arterial supply are quite common and can affect the surgical strategy when performing a minimally invasive pancreaticoduodenectomy (MIPD). Their presence must be preemptively detected to avoid postoperative liver and biliary complications. DATA SOURCES: Following the PRISMA guidelines and the Cochrane protocol we conducted a systematic review on the management of an accessory or replaced right hepatic artery (RHA) arising from the superior mesenteric artery when performing an MIPD. RESULTS: Five studies involving 118 patients were included. The most common reported management of the aberrant RHA was conservative (97.0%); however, patients undergoing aberrant RHA division without reconstruction did not develop liver or biliary complications. No differences in postoperative morbidity or long-term oncological related overall survival were reported in all the included studies when comparing MIPD in patients with standard anatomy to those with aberrant RHA. CONCLUSIONS: MIPD in patients with aberrant RHA is feasible without increase in morbidity and mortality. As preoperative strategy is crucial, we suggested planning an MIPD with an anomalous RHA focusing on preoperative vascular aberrancy assessment and different strategies to reduce the risk of liver ischemia.

The Association between Oxytocin and Lower Limb Osteoarthritis: A Prospective Cohort Study.

Oxytocin (OT), a neuropeptide best known for its role in emotional and social behaviors, has been linked to osteoarthritis (OA). This study aimed to investigate the serum OT level in hip and/or knee OA patients and to study its association with disease progression. Patients from the KHOALA cohort with symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) scores of 2 and 3) and follow-up at 5 years were included in this analysis. The primary endpoint was structural radiological progression, which was defined as an increase of at least one KL point at 5 years. Logistic regression models were used to estimate the associations between OT levels and KL progression while controlling for gender, age, BMI, diabetes and leptin levels. Data from 174 hip OA patients and 332 knee OA patients were analyzed independently. No differences in OT levels were found between the 'progressors' and 'non-progressors' groups among the hip OA patients and knee OA patients, respectively. No statistically significant associations were found between the OT levels at baseline and KL progression at 5 years, the KL score at baseline or the clinical outcomes. Higher structural damage at baseline and severe structural progression of hip and knee osteoarthritis did not appear to be associated with a low serum OT level at baseline.

Endoplasmic reticulum-mitochondria miscommunication is an early and causal trigger of hepatic insulin resistance and steatosis.

BACKGROUND & AIMS: Hepatic insulin resistance in obesity and type 2 diabetes was recently associated with endoplasmic reticulum (ER)-mitochondria miscommunication. These contact sites (mitochondria-associated membranes: MAMs) are highly dynamic and involved in many functions; however, whether MAM dysfunction plays a causal role in hepatic insulin resistance and steatosis is not clear. Thus, we aimed to determine whether and how organelle miscommunication plays a role in the onset and progression of hepatic metabolic impairment. METHODS: We analyzed hepatic ER-mitochondria interactions and calcium exchange in a time-dependent and reversible manner in mice with diet-induced obesity. Additionally, we used recombinant adenovirus to express a specific organelle spacer or linker in mouse livers, to determine the causal impact of MAM dysfunction on hepatic metabolic alterations. RESULTS: Disruption of ER-mitochondria interactions and calcium exchange is an early event preceding hepatic insulin resistance and steatosis in mice with diet-induced obesity. Interestingly, an 8-week reversal diet concomitantly reversed hepatic organelle miscommunication and insulin resistance in obese mice. Mechanistically, disrupting structural and functional ER-mitochondria interactions through the hepatic overexpression of the organelle spacer FATE1 was sufficient to impair hepatic insulin action and glucose homeostasis. In addition, FATE1-mediated organelle miscommunication disrupted lipid-related mitochondrial oxidative metabolism and induced hepatic steatosis. Conversely, reinforcement of ER-mitochondria interactions through hepatic expression of a synthetic linker prevented diet-induced glucose intolerance after 4 weeks' overnutrition. Importantly, ER-mitochondria miscommunication was confirmed in the liver of obese patients with type 2 diabetes, and correlated with glycemia, HbA1c and HOMA-IR index. CONCLUSIONS: ER-mitochondria miscommunication is an early causal trigger of hepatic insulin resistance and steatosis, and can be reversed by switching to a healthy diet. Thus, targeting MAMs could help to restore metabolic homeostasis. LAY SUMMARY: The literature suggests that interactions between the endoplasmic reticulum and mitochondria could play a role in hepatic insulin resistance and steatosis during chronic obesity. In the present study, we reappraised the time-dependent regulation of hepatic endoplasmic reticulum-mitochondria interactions and calcium exchange, investigating reversibility and causality, in mice with diet-induced obesity. We also assessed the relevance of our findings to humans. We show that organelle miscommunication is an early causal trigger of hepatic insulin resistance and steatosis that can be improved by nutritional strategies.

Rate of post-bariatric hypoglycemia using continuous glucose monitoring: A meta-analysis of literature studies.

AIMS: Hypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM). DATA SYNTHESIS: Studies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%-63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%-34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71-3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: -1.4%-12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013). CONCLUSIONS: PBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.

Role of Branched-Chain Amino Acid Metabolism in Type 2 Diabetes, Obesity, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease.

Branched-chain amino acids (BCAAs) include leucine, isoleucine, and valine. Mammalians cannot synthesize these amino acids de novo and must acquire them through their diet. High levels of BCAAs are associated with insulin resistance; type 2 diabetes; obesity; and non-metabolic diseases, including several forms of cancer. BCAAs-in particular leucine-activate the rapamycin complex1 mTORC1, which regulates cell growth and metabolism, glucose metabolism and several more essential physiological processes. Diets rich in BCAAs are associated with metabolic diseases (listed above), while diets low in BCAAs are generally reported to promote metabolic health. As for the dysregulation of the metabolism caused by high levels of BCAAs, recent studies propose that the accumulation of acyl-carnitine and diacyl-CoA in muscles alters lipid metabolism. However, this suggestion is not broadly accepted. On clinical grounds, pre- and post-operative metabolic profiles of candidate patients for bariatric surgery are being used to select the optimal procedure for each individual patient.

Gut Microbiota Host-Gene Interaction.

Studies carried out in the last ten years have shown that the metabolites made up from the gut microbiota are essential for multiple functions, such as the correct development of the immune system of newborns, interception of pathogens, and nutritional enrichment of the diet. Therefore, it is not surprising that alteration of the gut microbiota is the starting point of gastrointestinal infection, obesity, type 2 diabetes, inflammatory bowel disease, colorectal cancer, and lung cancer. Diet changes and antibiotics are the major factors damaging the gut microbiota. Early exposure of the newborns to antibiotics may prevent their correct development of the immune system, exposing them to pathogen infections, allergies, and chronic inflammatory diseases. We already know much on how host genes, microbiota, and the environment interact, owing to experiments in several model animals, especially in mice; advances in molecular technology; microbiota transplantation; and comparative metagenomic analysis. However, much more remains to be known. Longitudinal studies on patients undergoing to therapy, along with the identification of bacteria prevalent in responding patients may provide valuable data for improving therapies.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Mesenchymal Stem Cells and Platelet Rich Plasma Therapy to Treat Leak After Sleeve Gastrectomy.

BACKGROUND: One of the most feared and life-threatening complications after sleeve gastrectomy (SG) is staple line leak, with an incidence between 1 and 4%. Stable patients may be managed conservatively, with antibiotics, percutaneous drainage and endoscopy-based treatment. We propose mesenchymal stem cells (MSC) and platelet rich plasma (PRP) therapy as an innovative technique to treat leak after SG. MATERIAL AND METHODS: Bone marrow MSCs is obtained by centrifugation of tibial puncture specimen. A peripheral whole blood sample is retrieved from the patient and centrifuged to obtain PRP. During endoscopy, the first 10 mL are injected in 4quadrants (equal volume) in the submucosae around the internal orifice. The second 10 mL are injected in the wall of the fistula tract. RESULTS: The immediate course following the endoscopy was uneventful in both reported cases. The leaks healed in 30 and 42 D, respectively. Oral nutrition was progressively started during the third WK and fourth WK following the injection for both patients. No adverse event was noted during the follow-up period. CONCLUSION: The management of fistulas post SG is controversial and actual available treatments present a relatively prolonged healing time. MSC administration retains a high potential value in the treatment of these fistulas. Further studies and wider clinical trials are mandatory to determine the impact of MSC administration.

The 'TRIANGLE Operation' by Laparoscopy: Radical Pancreaticoduodenectomy with Major Vascular Resection for Borderline Resectable Pancreatic Head Cancer.

BACKGROUND: It has recently been shown that the 'triangle operation'1 may be associated with margin-free resection in selected patients with borderline resectable pancreatic cancer after neoadjuvant chemotherapy. Such a procedure consists of en bloc removal, following the adventitial plane of the whole mesopancreas from the triangular space delimited by the superior mesenteric artery, hepatic artery, and portal vein.2-11 In this video, we show how to safely perform this procedure by laparoscopy. METHODS: A 70-year-old male with persistent back pain and significant loss of weight underwent a computed tomography that showed a 3 cm mass of the uncinate process of the pancreas with involvement of the superior mesenteric artery and venous axis. The biopsy, performed at the time of endoscopic retrograde cholangiopancreatography, showed an adenocarcinoma of the pancreas. Cancer antigen (CA) 19-9 was in the normal range. The patient received eight cycles of neoadjuvant chemotherapy (FOLFIRINOX). The chemotherapy induced a major tumoral radiological response with tumoral shrinkage, however the preoperative computed tomography showed persistent infiltration of the mesopancreas behind the superior mesenteric artery and venous axis. A radical laparoscopic pancreaticoduodenectomy with portal vein resection was performed, including the complete clearing of the superior mesenteric artery and the right side of the celiac trunk, as in the 'triangle operation'. Venous reconstruction was achieved with an end-to-end 5/0 polypropylene running suture with growth factor, while intestinal reconstruction was achieved with an end-to-side hepaticojejunal anastomosis, a double purse-string pancreaticogastrostomy, and side-to-side mechanical linear gastrojejunostomy. The specimen was removed via a short Pfannenstiel incision. RESULTS: Operative time was 7 h and 15 min, and blood loss was 150. Frozen sections of the superior mesenteric artery margins were negative for tumoral cells. On postoperative day 5, the patient had a hematemesis with bleeding from the pancreaticogastrostomy, which was treated endoscopically. Hospital stay was 16 days. Histopathological examination showed a well-differentiated adenocarcinoma of the pancreas [ypT3 N1 (3/36) R0]. CONCLUSION: The 'triangle operation' for borderline resectable pancreatic head cancer can be achieved safely by laparoscopy in carefully selected patients.1-11 Proven experience in both open and laparoscopic pancreatic surgery is mandatory.

Is nonanatomic rectal resection a valid therapeutic option for rectal gastrointestinal stromal tumors? A proposed decision algorithm.

BACKGROUND AND OBJECTIVES: The best surgical approach to rectal gastrointestinal stromal tumors (GISTs) is still debated, and both nonanatomic rectal resection (NARR) and anatomic rectal resection (ARR) are applied. The aim of this study was to evaluate the feasibility and oncological outcomes of NARR and ARR for rectal GISTs (R-GISTs). METHODS: Through a large French multicentre retrospective study, 35 patients were treated for R-GIST between 2001 and 2013. Patients who underwent NARR and ARR were compared. RESULTS: There were 23 (65.7%) patients in group ARR and 12 (34.3%) in group NARR. Significantly more patients in the group with ARR had a neoadjuvant treatment (86%) with tyrosine kinase inhibitor (TKI) (imatinib) compared to those with NARR (25%) (p < .01). The median preoperative tumor size was significantly different between the groups without and with neoadjuvant TKI: 30 ± 23 mm versus 64 ± 44.4 mm, respectively (p < .001). Overall postoperative morbidity was 20% (n = 7) (26% for ARR vs. 8% for NARR; p = .4). After a median follow-up of 60.2 (3.2-164.3) months, the 5-year disease-free survival rates were 79.5% (confidence interval [CI] 95%: 54-100) for the NARR group and 68% (CI 95%: 46.4-89.7) for the ARR group (p = .697), respectively. CONCLUSION: The use of NARR for small R-GIST's does not seem to impair the oncological prognosis.

An In Vitro Model to Investigate the Role of Helicobacter pylori in Type 2 Diabetes, Obesity, Alzheimer's Disease and Cardiometabolic Disease.

Helicobacter pylori (Hp) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the Hp cell filtrate (Hpcf) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer's diseases, and cardiometabolic disease. Here, we demonstrate how Hp may modulate these traits. Hp induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by Hp. Furthermore, Hp modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the Hp toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how Hp may potentially manipulate them.

Defining Global Benchmarks in Bariatric Surgery: A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

OBJECTIVE: To define "best possible" outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). BACKGROUND: Reference values for optimal surgical outcomes in well-defined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. METHODS: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. RESULTS: Patients were mainly females (78%), aged 38±11 years, with a baseline BMI 40.8 ±â€Š5.8 kg/m. Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade ≥IIIa complication rate, 5.5% readmission rate, and comprehensive complication index ≤33.73 in the subgroup of patients presenting at least 1 grade ≥II complication. CONCLUSION: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in quality-improvement cycle.ClinicalTrials.gov Identifier NCT03440138.

Assessment of Liver Graft Steatosis: Where Do We Stand?

The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively "the ideal method" to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.

Bax inhibitor-1 protects from nonalcoholic steatohepatitis by limiting inositol-requiring enzyme 1 alpha signaling in mice.

Endoplasmic reticulum (ER) stress is activated in nonalcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation, and cell death underlie the transition from steatosis to steatohepatitis (nonalcoholic steatohepatitis; NASH). B-cell lymphoma 2 (BCL2)-associated X protein (Bax) inhibitor-1 (BI-1), a negative regulator of the ER stress sensor, inositol-requiring enzyme 1 alpha (IRE1α), has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH because of unrestrained IRE1α signaling. ER stress was induced in wild-type and BI-1-/- mice acutely by tunicamycin (TM) injection (1 mg/kg) or chronically by high-fat diet (HFD) feeding to determine NAFLD phenotype. Livers of TM-treated BI-1-/- mice showed IRE1α-dependent NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation, hepatocyte death, fibrosis, and dysregulated lipid homeostasis that led to liver failure within a week. The analysis of human NAFLD liver biopsies revealed BI-1 down-regulation parallel to the up-regulation of IRE1α endoribonuclease (RNase) signaling. In HFD-fed BI-1-/- mice that presented NASH and type 2 diabetes, exaggerated hepatic IRE1α, X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP) expression was linked to activated NLRP3 inflammasome and caspase-1/-11. Rises in interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein 1 (MCP1), chemokine (C-X-C motif) ligand 1 (CXCL1), and alanine transaminase (ALT)/aspartate transaminase (AST) levels revealed significant inflammation and injury, respectively. Pharmacological inhibition of IRE1α RNase activity with the small molecules, STF-083010 or 4µ8c, was evaluated in HFD-induced NAFLD. In BI-1-/- mice, either treatment effectively counteracted IRE1α RNase activity, improving glucose tolerance and rescuing from NASH. The hepatocyte-specific role of IRE1α RNase activity in mediating NLRP3 inflammasome activation and cell death was confirmed in primary mouse hepatocytes by IRE1α axis knockdown or its inhibition with STF-083010 or 4µ8c. CONCLUSION: Targeting IRE1α-dependent NLRP3 inflammasome signaling with pharmacological agents or by BI-1 may represent a tangible therapeutic strategy for NASH. (Hepatology 2018).

Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire.

INTRODUCTION: Obesity can lead to pelvic floor disorders, interfering with women's sexual life; Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association-Revised (PISQ-IR) is a new instrument to measure sexual life in women with pelvic floor disorders. AIMS: To assess the utility of using PISQ-IR in morbidly obese women undergoing bariatric surgery and to show the improvement of bariatric surgery on sexuality. METHODS: This prospective monocentric study included all women who underwent bariatric surgery from June 2016-May 2017. Sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) was performed by 1 surgeon, and data were collected by 1 researcher. Demographics, medical history, number of deliveries, and type of bariatric surgery (SG or RYGB) were collected at baseline. At the 1-year follow-up consultation, postoperative complications, percentage of total body weight loss (TWL) and percentage excess weight loss were assessed. Questionnaires were given at baseline and at 1-year follow-up. MAIN OUTCOME MEASURES: Postoperative complications and total weight loss were measured at the 1-year follow-up. Sexual activity, using the PISQ-IR, and pelvic organ prolapse, urinary incontinence, and anal incontinence, using the urinary symptom profile and PFDI (Pelvic Floor Distress Inventory) 20, were compared before surgery and at 1-year follow-up. RESULTS: 72 patients were included at baseline, 54 (75%) were considered for final analysis (30 RYGB and 24 SG), and 51 patients were considered for PISQ-IR. The mean preoperative body mass index was 41 ± 5.4 kg/m2, and mean age was 43 ± 11.8 years. Both procedures induced an important weight loss (mean TWL of 33%) and had a similar percentage of TWL for each procedure: 31 (15-46) for SG vs 34 (9-51) for RYGB. 9 patients (17 [6%]) became sexually active 1 year after surgery. For the sexually inactive population after 1 year, there was no differences in the PISQ-IR in the follow-up. When body mass index loss was >13 kg/m2, a higher percentage of the sexually active population improved their different scores, and there were significant results for both global quality of life and desire (P = .026 and .046). The other questionnaires showed a significant decrease in urinary incontinence symptoms (P < .001) associated with weight loss, whereas there was no difference in terms of pelvic organ prolapse or anal incontinence. CONCLUSION: PISQ-IR is a useful instrument to measure sexual function regarding pelvic floor disorders. Bariatric surgery improves sexual activity in obese women 1 year after surgery. Treacy PJ, Mazoyer C, Falagario U, et al. Sexual Activity After Bariatric Surgery: A Prospective Monocentric Study Using the PISQ-IR Questionnaire. J Sex Med 2019;16:1930-1937.