Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial.

BACKGROUND: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. METHODS: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. FINDINGS: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. INTERPRETATION: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. FUNDING: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.

Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis.

OBJECTIVE: Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. DESIGN: This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14+CD16- monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis. RESULTS: The algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively.The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort.The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and specificity 95.8% in the discovery cohort and 97.6%, 99% and 89.6% in the validation cohort. This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score and aspartate aminotransferase (AST)-to-platelet ratio and was comparable to ultrasound two-dimensional shear wave elastography. CONCLUSIONS: The proposed novel liquid biopsy is accurate, sensitive and specific in diagnosing the presence and severity of NASH or liver fibrosis and is more reliable than currently used biomarkers. CLINICAL TRIALS: Discovery multicentre cohort: Bariatric Surgery versus Non-Alcoholic Steatohepatitis, BRAVES, ClinicalTrials.gov identifier: NCT03524365.Validation multicentre cohort: Liquid Biopsy for NASH and Fibrosis, LIBRA, ClinicalTrials.gov identifier: NCT04677101.

Y Not Roux-en-Y?: Resolution of Barrett's Esophagus After Surgical Conversion of Gastric Sleeve in Two Patients.

Esophageal lesions ranging from erosive esophagitis to Barrett's esophagus (BE) eventually develop months-years after sleeve gastrectomy (SG), representing a significant post-surgical issue in GI practice. Roux-en-Y gastric bypass (RYGB) conversion is a widespread and effective method of managing reflux and esophageal complications following SG. Although some studies using a limited sample size have demonstrated that RYGB performed as a primary procedure may regress BE presumably by reducing reflux, whether the same may apply to RYGB performed as revision surgery after SG has scarcely been addressed in the literature. Though histological regression of BE following primary RYGB occurs in 51.9% of patients, with regression of Barrett's dysplasia in 50% of cases, revisional RYGB yields a remission rate as high as 81.8% for Barrett's metaplasia and 100% for dysplastic lesions, although the number of subjects in the published studies are very small. We report two patients who developed GERD and BE following SG with complete regression 12 months after conversion to RYGB in both subjects, confirming the substantially greater proportion of BE resolution in patients undergoing RYGB as revision surgery following SG.

Novel Modality of Endoluminal Anastomotic Integrity Assessment with Fluoroangiography After Left-sided Colorectal Resections.

BACKGROUND: Several methods have been described for the intraoperative evaluation of colorectal anastomotic integrity. Technological evolution has allowed to progress from basic mechanical methods to the use of more sophisticated techniques. This study describes a novel endoluminal modality of colorectal anastomotic assessment through the use of a Disposable Rigid Scope Introducer (DRSI) also allowing for intraoperative endoluminal perfusion evaluation by indocyanine green (ICG) fluoroangiography in patients undergoing left-sided colorectal resection. METHODS: The DRSI consists of an endoluminal introducer device made up of an insertion tube and port connected to an insufflation bulb to manually insufflate the sigmoid and rectum and is compatible with any laparoscopic camera, also allowing for ICG fluoroangiography for perfusion purposes. RESULTS: The DRSI was successfully used to assess anastomotic integrity after left-sided colorectal resections performed in 16 consecutive patients. The DRSI allowed to visualize by fluoroangiography the quality of tissue perfusion at the anastomotic site in all cases, contributing to the decision of avoiding loop ileostomies in low rectal resections. In 2 cases, the DRSI showed the presence of significant anastomotic bleeding which was successfully controlled by laparoscopic suture placement. No adverse event resulted from the use of this device. CONCLUSIONS: The DRSI combines direct endoluminal visualization of the anastomosis together with real-time evaluation of its blood flow. This device holds great potential for prompt intraoperative detection of anastomotic alterations, possibly reducing the risk of postoperative anastomotic bleeding or leaks related to mechanical construction/perfusion issues. Potential advantages of this device warrant larger cohort studies and prospective randomized trials.

Coincidental or Causal? Concurrence of Colorectal Carcinoma with Primary Breast Cancer.

Multiple primary malignant neoplasms (MPMN) represent the occurrence of a second malignancy in the same patient within 6 months after the detection of first primary (synchronous) tumor, or > 6 months after primary detection (metachronous). We present a case of a patient treated for carcinoma of the breast who developed a metachronous primary malignancy in the colorectal tract. These tumors were histologically different with distinct immune-histochemical parameters. The association between breast and colon cancer is well documented in the literature with several studies reporting the coexistence of common extrinsic and genetic predisposing factors. Although rare, MPMN are becoming more common due to the increased number of elderly cancer survivors, improved diagnosis and enhanced awareness. The association between colorectal and breast cancer should not be dismissed merely as metastasis since there is good precedent for the co-occurrence of these primary tumors.

Small intestinal metabolism is central to whole-body insulin resistance.

OBJECTIVE: To assess the role of jejunum in insulin resistance in humans and in experimental animals. DESIGN: Twenty-four subjects undergoing biliopancreatic diversion (BPD) or Roux-en-Y gastric bypass (RYGB) were enrolled. Insulin sensitivity was measured at baseline and at 1 week after surgery using oral glucose minimal model.We excluded the jejunum from intestinal continuity in pigs and created a jejunal loop with its vascular and nerve supply intact accessible from two cutaneous stomas, and reconnected the bowel with an end-to-end anastomosis. Glucose stable isotopes were given in the stomach or in the jejunal loop.In vitro studies using primary porcine and human hepatocytes or myoblasts tested the effects of plasma on gluconeogenesis or glucose uptake and insulin signalling. RESULTS: Whole-body insulin sensitivity (SI∙104: 0.54±0.12 before vs 0.82±0.11 after BPD, p=0.024 and 0.41±0.09 before vs 0.65±0.09/pM/min after RYGB, p=not significant) and Glucose Disposition Index increased only after BPD. In pigs, insulin sensitivity was significantly lower when glucose was administered in the jejunal loop than in the stomach (glucose rate of disappearance (Rd) area under the curve (AUC)/insulin AUC∙10: 1.82±0.31 vs 2.96±0.33 mmol/pM/min, p=0.0017).Metabolomics showed a similar pattern before surgery and during jejunal-loop stimulation, pointing to a higher expression of gluconeogenetic substrates, a metabolic signature of impaired insulin sensitivity.A greater hepatocyte phosphoenolpyruvate-carboxykinase and glucose-6-phosphatase gene expression was elicited with plasma from porcine jejunal loop or before surgery compared with plasma from jejunectomy in pigs or jejunal bypass in humans.Stimulation of myoblasts with plasma from porcine jejunal loop or before surgery reduced glucose uptake, Ser473-Akt phosphorylation and GLUT4 expression compared with plasma obtained during gastric glucose administration after jejunectomy in pigs or after jejunal bypass in humans. CONCLUSION: Proximal gut plays a crucial role in controlling insulin sensitivity through a distinctive metabolic signature involving hepatic gluconeogenesis and muscle insulin resistance. Bypassing the jejunum is beneficial in terms of insulin-mediated glucose disposal in obesity. TRIAL REGISTRATION NUMBER: NCT03111953.

GORD and Barrett's oesophagus after bariatric procedures: multicentre prospective study.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) after bariatric surgery is a debated topic. This study investigated the prevalence of GORD and associated oesophageal complications following bariatric procedures-namely, adjustable gastric banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB). METHODS: This was a prospective multicentre study designed to evaluate the long-term effects of bariatric surgery on GORD. Patients were studied at baseline, at >10 years following AGB, SG, and RYGB, and at >3 years following OAGB (due to the more recent recognition of OAGB as a standard bariatric procedure). Patients were assessed by endoscopy and GORD symptom evaluation. RESULTS: A total of 241 patients were enrolled. A minimum follow-up of 10 years was completed by 193 patients following AGB (57 patients), SG (95 patients), and RYGB (41 patients), and of >3 years by 48 subjects following OAGB. GORD symptoms increased following AGB and SG (from 14 to 31.6 per cent and from 26.3 to 58.9 per cent, respectively; P < 0.0001), improved following RYGB (from 36.6 to 14.6 per cent; P < 0.0001), and were unchanged following OAGB. The overall prevalence of erosive oesophagitis was greater in the SG group (74.7 per cent) than in the AGB (42.1 per cent), RYGB (22 per cent), and OAGB (22.9 per cent) groups (P < 0.0001). Barrett's oesophagus was found only in patients who had SG (16.8 per cent). Biliary-like gastric stagnation was found in a greater proportion of SG and OAGB patients (79.7 and 69.4 per cent, respectively) than in other treatment groups (P < 0.0001). The prevalence of biliary-type reflux into the oesophagus was higher in patients who underwent SG (74.7 per cent), compared with other treatment groups. CONCLUSION: Bariatric surgery leads to gastro-oesophageal complications of variable severity, particularly SG, which can result in a large proportion of patients developing Barrett's oesophagus.

Gastro-oesophageal reflux disease (GORD)-related oesophageal sequelae following bariatric surgery confirm the importance of postoperative endoscopic surveillance in early detection of such conditions. Sleeve gastrectomy was shown to be correlated with the highest prevalence of GORD, biliary-type gastric and oesophageal reflux, and erosive oesophagitis. This, in turn, appeared to be responsible for the high number of cases of Barrett's oesophagus found in this group of patients. Adjustable gastric banding displayed minimal effectiveness in terms of weight loss, along with a high number of reoperations, also due to band-related complications. The study showed one-anastomosis gastric bypass to be associated with a high percentage of subjects who developed often severe inflammation of the gastrojejunal anastomosis or of the gastric pouch, as a consequence of chronic biliary-type duodenogastric reflux. Finally, our results suggest that Roux-en-Y gastric bypass could represent the most 'reliable' bariatric procedure in terms of GORD resolution, and the only operation not requiring any reintervention in our cohort of patients. Each surgical procedure leads to gastro-oesophageal modifications of variable extent, which need to be taken into consideration when selecting the designated bariatric operation.

Duodenal-jejunal bypass improves nonalcoholic fatty liver disease independently of weight loss in rodents with diet-induced obesity.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation, and insulin resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD, and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear whether such effects result from reduced weight, from a lower calorie-intake, or from the direct influence of surgery on mechanisms contributing to NAFLD. We aimed to investigate whether gastrointestinal (GI) bypass surgery could induce direct effects on hepatic fat accumulation and insulin resistance, independently of weight reduction. Twenty Wistar rats on a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham operation and were pair fed (PF) for 15 wk after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling, and gluconeogenesis in liver and muscle. Despite no differences in body weight and calorie intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin sensitivity, and enhanced lipid droplet degradation. In both tissues, DJB increased insulin signaling, whereas hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of NAFLD that share a mutual pathway, in which perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases.NEW & NOTEWORTHY Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of nonalcoholic fatty liver disease that share a mutual pathway, in which perilipin-2 seems to be the main player. Our study supports further investigation into the role of proximal small intestine exclusion in the pathophysiology of nonalcoholic fatty liver disease to uncover less invasive treatments that mimic the effects of metabolic surgery and aims to prevent and treat metabolic liver disease.

The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery.

Neurotensin is a peptide with effects on appetite and intestinal lipid absorption. Experimental data suggest a role in glucose homeostasis, while human data is missing. Here, 20 morbidly obese subjects either underwent biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB) in a randomized fashion. Before and 1 year after surgery, anthropometric data, body composition, clinical biochemistry, insulin sensitivity by means of euglycemic hyperinsulinemic clamps (HEC) and fasting plasma proneurotensin 1-117 were analyzed. Plasma proneurotensin increased significantly more 1 year after BDP than RYGB (P = 0.028), while weight loss was comparable. After metabolic surgery, proneurotensin correlated positively with insulin sensitivity (M-value) (r = 0.55, P < 0.001), while an inverse relationship with fasting glucose, HOMA-IR and HbA1c was observed (P < 0.05 for all components). After adjustment for age and gender, proneurotensin and BMI remained independently related with delta of M-value (ß = 0.46 and ß = 0.51, P < 0.05, resp.). From these data we conclude that proneurotensin positively correlates with insulin sensitivity uniquely after weight loss induced by metabolic surgery in humans. BDP leads to a stronger increase in the anorexigenic peptide compared to RYGB.

Point shear-wave elastography in chronic pancreatitis: A promising tool for staging disease severity.

BACKGROUND: Objectives: ElastPQ®-pSWE is an ultrasound technique developed to stage disease severity in patients with chronic liver diseases. Little data is available about its application to the pancreas. We aimed to assess the feasibility and reproducibility of pancreatic stiffness (PS) measurements in patients with chronic pancreatitis and their relationship with clinical and laboratory data. MATERIAL AND METHODS: 52 consecutive patients with chronic pancreatitis (CP) (40 males; median age 60 years) underwent hepatic and pancreatic pSWE. Liver stiffness was measured by transient elastography, 42 healthy subjects being controls (25 males; median age 54 years). Pancreatic pSWE inter-observer agreement was analyzed by intraclass correlation coefficient (ICC). The effects of clinical, laboratory and US data on PS measurements were evaluated by linear regression. RESULTS: pSWE was feasible in all the CP patients, but one. Pancreatic stiffness was significantly higher in CP patients than healthy controls (4.3 ± SD 2.4 vs. 2.8 ± SD 1.1 kPa, respectively, p = 0.001). Significantly higher values in the CP group were observed in patients with longer disease duration (>10 vs. ≤10 years) (5.8 ± SD 4 vs. 3.9 ± SD 1.5 kPa, respectively, p = 0.01), on chronic analgesic drugs (6.0 vs. 3.5 kPa, p < 0.05) and with lower body weight (p < 0.05, r = -0.38). At multivariate analysis all the three variables resulted independently associated to the pancreatic stiffness value. The ICC for PS was 0.77. CONCLUSIONS: ElastPQ®-pSWE is promising and reproducible in assessing pancreatic stiffness, which mainly reflects disease length and severity. Accordingly, its use is of potential value in stratifying CP patients by identifying those with a more serious degree of disease.

Lipidomic Changes in Skeletal Muscle in Patients after Biliopancreatic Diversion.

The mechanisms behind the fast improvements of insulin sensitivity and release of the diabetic metabolic state after bariatric surgery are still not completely understood. To further elucidate the effects on the individual cellular level, we applied mass spectrometry to investigate the changes in the lipidomic profile of skeletal muscle cells before and after biliopancreatic diversion in six patients. We found a decrease in lipid storage species, mainly triacylglycerides (e. g., TAG 52:2 from 19.84 to 13.26 mol%; p=0.028), and an increase in structural and signaling lipids, including phosphatidylcholines [PC 36:2 (18:1/18:1) from 0.12 to 0.65 mol%; p=0.046], phosphatidylinositols (PI 36:2 from 0.008 to 0.039 mol%; p=0.046), and cardiolipins (CL 72:8 from 0.16 to 1.22 mol%; p=0.043). The proportional increase in structural lipids was directly and the decrease in TAGs was inversely correlated to improved post-operative insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Thus, short-term recovery of insulin sensitivity after biliopancreatic diversion may, beside gut hormonal adaptation, mechanical factors, shifts in the gut microbiome, and changes in bile acid and phospholipid metabolism, additionally be attributed to a metabolic recovery of skeletal muscle cells, reflected by normalization of the cellular lipidomic profile. Further studies are needed to investigate whether improved insulin sensitivity of skeletal muscle might be directly associated with the degradation of ectopic triglycerides, thereby reducing the reservoir of lipotoxic intermediates, which might interfere with insulin signaling and hamper mitochondrial metabolism.

Autoimmune gastritis: relationships with anemia and Helicobacter pylori status.

BACKGROUND: Autoimmune gastritis (AIG) is a gastric pathologic condition affecting the mucosa of the fundus and the body and eventually leading to hypo-achlorhydria. AIMS: We report our clinical and pathological experience with AIG. METHODS: Data from patients with a diagnosis of AIG seen in the period January 2002-December 2012 were retrieved. Only patients with complete sets of biopsies were analyzed. RESULTS: Data from 138 patients were available for analysis. Pernicious anemia was present in 25% of patients, iron deficiency anemia was found in 29.7% of patients, hypothyroidism in 23% of patients, type 1 diabetes in 7.9% of patients, and vitiligo in 2.8% of patients. Parietal cell antibodies were positive in 65% of patients, and no patient had serology positive for celiac disease. All gastric biopsies showed glandular atrophy associated with enterochromaffin-like (ECL)-cells hyperplasia, features limited to the mucosa of the fundus and body, and focal glandular intestinal metaplasia. Helicobacter pylori was negative in all cases. CONCLUSIONS: AIG was strongly associated with anemia; atrophy, intestinal metaplasia and ECL hyperplasia in the gastric fundus and body are hallmarks of this condition.

Learning curve for laparoscopic sleeve gastrectomy: role of training in a high-volume bariatric center.

BACKGROUND: Since the great diffusion of laparoscopic treatment of obesity, there is a growing interest concerning the learning process for those surgeons who undertake the bariatric activity. However, papers analyzing the learning curve (LC) for sleeve gastrectomy (SG) are still scarce. This study aims to investigate whether the LC for SG of a novice bariatric surgeon might be positively influenced by the training in a high-volume bariatric center (HVBC). METHODS: Between October 2010 and January 2014, 128 patients underwent SG by the same young surgeon who previously attended a 2-year training in a HVBC. His LC has been divided into three consecutive periods: in the first period (1st-47th SGs) he operated in the HVBC, while in the second (48th-88th SGs) and third period (89th-128th SGs) he moved to a novel department where surgical and ancillary staff were initially not confident with bariatric procedures but progressively owned the proper experience. Preoperative characteristics, operative data, complications and postoperative results of the three periods were compared. RESULTS: Mean follow-up was 1 year. Preoperative patients' characteristics were homogeneous. No significant differences have been registered among the three periods concerning operative data, mortality, intra- and post-operative complications, weight loss outcomes and comorbidities' resolution. Post-operative follow-up rates at 6 and 12 months were 98.4 and 92.1 %, respectively. CONCLUSIONS: Long-lasting fellowship in a HVBC might allow the novel bariatric surgeon to safely and proficiently overcome the LC for SG, even in a new established bariatric setting.

Spider surgical system versus multiport laparoscopic surgery: performance comparison on a surgical simulator.

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience.

Can virtual reality simulators be a certification tool for bariatric surgeons?

BACKGROUND: Construct validity of virtual laparoscopic simulators for basic laparoscopic skills has been proposed; however, it is not yet clear whether the simulators can identify the actual experience of surgeons in more complex procedures such as laparoscopic Roux-en-Y gastric bypass. This study tested the ability of the Lap Mentor simulator to recognize the experience in advanced laparoscopic procedures and to assess its role in the certification of bariatric surgeons. METHODS: Twenty surgeons were divided into two groups according to their experience in laparoscopic and bariatric surgery. The general group included 10 general surgeons performing between 75 and 100 nonbariatric laparoscopic procedures. The bariatric group included 10 bariatric surgeons performing between 50 and 100 laparoscopic bariatric procedures. Participants were tested on the simulator in one basic task (task 1: eye-hand coordination) and in two tasks of the gastric bypass module (task 2: creation of the gastric pouch; task 3: gastrojejunal anastomosis). RESULTS: Comparing the groups, no significant differences were found in task 1. Analyzing the results from the gastric bypass module (bariatric vs. general), in task 2, significant differences (p < 0.05) were found in the median volume of the gastric pouch (21 vs. 48 cm(3)), in the percentage of fundus included in the pouch (8.4 vs. 29.4 %), in the complete dissection at the angle of His (10 vs. 3), and in safety parameters. In task 3, significant differences were found in the size and position of enterotomies. CONCLUSIONS: The Lap Mentor may be proposed as a certification tool for bariatric surgeons because it also recognizes their specific skills in the technical details of the procedure that affect long-term results. Furthermore, the possibility of analyzing the performance in detail can help define areas where the surgeon is lacking. These findings indicate a potential role of the Lap Mentor in tailoring the training to maximize improvement.

Sleeve gastrectomy and one-year outcomes: Impact on cardiovascular, renal and metabolic parameters.

Background: Cardiovascular and renal diseases represent a major determinant for the morbidity and mortality associated with obesity and type 2 diabetes mellitus (T2DM). Bariatric surgery is considered one of the few treatments with the potential to reverse cardiovascular, renal and metabolic disease. Methods: Prospective study of patients undergoing sleeve gastrectomy collecting pre- and post-surgery creatinine, eGFR, glucose, insulin, total, LDL/HDL cholesterol, triglycerides, parathyroid hormone, vitamin D3, C- Reactive Protein (CRP), blood count, weight, body mass index (BMI), bilateral carotid intima media thickness (IMT), flow-mediated dilation (FMD) and epicardial adipose tissue (EAT). Measurements were compared at 1 year follow up. Results: 24 patients were included in the study. Cardiovascular parameters, as HDL-cholesterol (p = 0.002), IMT (p = 0.003), EAT (p < 0.001) and FMD (p = 0.001) showed significant improvement after surgery. Secondary renal outcomes including Vitamin D3 (p < 0.0001), Calcium (p = 0.006), RBCs (p = 0.007), HCO3- (p = 0.05) also ameliorated as well as BMI (p < 0.001). Conclusions: Sleeve gastrectomy has a positive impact on cardiovascular, renal, and metabolic parameters in patients with morbid obesity, suggesting it may halt the progression of these diseases even in the preclinical stage. Further research is needed to explore the long-term effects underlying these improvements.

From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance.

BACKGROUND: The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex-vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease. METHODS: Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents. KEY RESULTS: Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction-relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF-1 was detected in both muscle and mucosa. CONCLUSION & INFERENCES: The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.

Upcoming Italian clinical practice guidelines on endoscopic bariatric treatment of overweight and obesity: design and methodological aspects.

Obesity/overweight and its complications are a growing problem in many countries. Italian Society of Bariatric and Metabolic Surgery for Obesity (Società Italiana di Chirurgia dell'Obesità e delle Malattie Metaboliche-SICOB) decided to develop the first Italian guidelines for the endoscopic bariatric treatment of obesity. The creation of SICOB Guidelines is based on an extended work made by a panel of 44 members and a coordinator. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide the aims, reference population, and target health professionals. Clinical questions have been created using the PICO (patient, intervention, comparison, outcome) conceptual framework. We will perform systematic reviews, formal meta-analyses, and network meta-analyses for each PICO and critical outcomes aimed at assessing and rating the efficacy and safety of endoscopic bariatric procedures in comparison with either no interventions, lifestyle interventions, or approved anti-obesity treatments in trials with a follow-up of at least 52 weeks. For PICO on temporary endoscopic bariatric treatments, we will also consider RCT with a minimum duration of 6 months. The panel proposed 8 questions, organized into four domains: A. Indication for endoscopic bariatric surgery; B. Revisional surgery; C. Temporary gastric and duodenal-jejunal procedures; D. Endoscopic diagnosis/treatment of bariatric and metabolic surgery complications. These guidelines will apply to patients aged ≥ 14 years) with body mass index (BMI) ≥ 27 kg/m2 and requiring endoscopic bariatric surgery or endoscopic diagnostic and/or therapeutic procedures. The areas covered by the clinical questions included indications of endoscopic bariatric surgery, types of surgery, revisional surgery, and management of bariatric and metabolic surgery complications.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

BACKGROUND & AIMS: Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. PATIENTS AND METHODS: Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. RESULTS: Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. CONCLUSIONS: In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications.