Genetic Evidence of Causal Relation Between Intestinal Glucose Absorption and Early Postprandial Glucose Response: A Mendelian Randomization Study.

The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1,547 subjects with class II/III obesity from the Atlas Biologique de l'Obésité Sévère cohort, the study uses SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype serves as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-min postload glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results show that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of -0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study links a 1-SD decrease in SGLT1 expression to a Δ30 glucose reduction of -0.097 mmol/L. MR analysis parallels these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decrease of -0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early postload glucose response. This finding has a potential translational impact on managing early glucose response to prevent or treat type 2 diabetes.

Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery.

BACKGROUND & AIMS: The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery. METHODS: Participants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60 months after surgery. We calculated the fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI), Hepatic fibrosis score (HFS), Fibrotic NASH index (FNI), and Liver risk score (LRS) at each time point, and compared their performances for predicting significant fibrosis (F ≥ 2) and its resolution following surgery. RESULTS: At baseline, 2436 patients had liver biopsy, including 261 (10.7 %) with significant fibrosis. Overall, 672 patients had pre- and post-operative biopsies (564 at M12 and 328 at M60). The fibrosis stage decreased at M12 and M60 (p < 0.001 vs M0). Resolution of significant fibrosis occurred in 58/121 (47.9 %) at M12 and 32/50 (64 %) at M60. The mean value of all tests decreased after surgery, except for FIB-4. Performances for predicting fibrosis resolution was higher at M60 than at M12 for all tests, and maximal at M60 for FNI and LRS: area under the curve 0.843 (95%CI 0.71-0.95) and 0.92 (95%CI 0.84-1.00); positive likelihood ratio 3.75 (95 % CI 1.33-10.59) and 4.58 (95 % CI 1.65-12.70), respectively. CONCLUSIONS: Results showed the value and limits of non-invasive tests for monitoring the evolution of liver fibrosis after an intervention. Following bariatric surgery, the best performances to predict the resolution of significant fibrosis were observed at M60 with tests combining liver and metabolic traits, namely FNI and LRS.

Recurrence After Surgery for Primary Hyperparathyroidism in 517 Patients With Multiple Endocrine Neoplasia Type 1: An Association Francophone de Chirurgie Endocrinienne and Groupe d'étude des Tumeurs Endocrines study.

OBJECTIVE: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. BACKGROUND: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. METHODS: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. RESULTS: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). CONCLUSIONS: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.

Combining diabetes, sex, and menopause as meaningful clinical features associated with NASH and liver fibrosis in individuals with class II and III obesity: A retrospective cohort study.

OBJECTIVE: Steatotic liver disease (SLD) is frequent in individuals with obesity. In this study, type 2 diabetes (T2D), sex, and menopausal status were combined to refine the stratification of obesity regarding the risk of advanced SLD and gain further insight into disease physiopathology. METHODS: This study enrolled 1446 participants with obesity from the ABOS cohort (NCT01129297), who underwent extensive phenotyping, including liver histology and transcriptome profiling. Hierarchical clustering was applied to classify participants. The prevalence of metabolic disorders associated with steatohepatitis (NASH) and liver fibrosis (F ≥ 2) was determined within each identified subgroup and aligned to clinical and biological characteristics. RESULTS: The prevalence of NASH and F ≥ 2 was, respectively, 9.5% (N = 138/1446) and 11.7% (N = 159/1365) in the overall population, 20.3% (N = 107/726) and 21.1% (N = 106/502) in T2D patients, and 3.4% (N = 31/920) and 6.1% (N = 53/863) in non-T2D patients. NASH and F ≥ 2 prevalence was 15.4% (33/215) and 15.5% (32/206) among premenopausal women with T2D vs. 29.5% (33/112) and 30.3% (N = 36/119) in postmenopausal women with T2D (p < 0.01); and 21.0% (21/100) / 27.0% (24/89) in men with T2D ≥ age 50 years and 17.9% (17/95) / 18.5% (17/92) in men with T2D < age 50 years (NS). The distinct contribution of menopause was confirmed by the interaction between sex and age with respect to NASH among T2D patients (p = 0.048). Finally, several NASH-associated biological traits (lower platelet count; higher serum uric acid; gamma-glutamyl transferase; aspartate aminotransferase) and liver expressed genes AKR1B10 and CCL20 were significantly associated with menopause in women with T2D but not with age in men with T2D. CONCLUSIONS: This study unveiled a remarkably high prevalence of advanced SLD after menopause in women with T2D, associated with a dysfunctional biological liver profile.

Risk-Benefit Balance of Simultaneous Gastric Bypass or Sleeve Gastrectomy and Concomitant Cholecystectomy: A Comprehensive Nationwide Cohort of 289,627 Patients.

OBJECTIVE: To assess the relevance of concomitant laparoscopic metabolic bariatric surgery (MBS) and cholecystectomy. BACKGROUND: Because of the massive weight loss it induces, MBS is associated with an increase in the frequency of gallstones. However, no consensus yet exists on the risk-to-benefit ratio of a concomitant cholecystectomy (CC) during MBS to prevent long-term biliary complications. METHODS: This nationwide retrospective cohort research was conducted in 2 parts using information from a national administrative database (PMSI). The 90-day morbidity of MBS with or without CC was first compared in a matched trial (propensity score). Second, we observed medium-term biliary complication following MBS when no CC had been performed during MBS up to 9 years after MBS (minimum 18 months). RESULTS: Between 2013 and 2020, 289,627 patients had a sleeve gastrectomy (SG: 70%) or a gastric bypass (GBP: 30%). The principal indications of CC were symptomatic cholelithiasis (79.5%) or acute cholecystitis (3.6%). Prophylactic CC occurred only in 15.5% of the cases. In our matched-group analysis, we included 9323 patients in each arm. The complication rate at day 90 after surgery was greater in the CC arm [odds ratio=1.3 (1.2-1.5), P <0.001], independently of the reason of the CC. At 18 months, there was a 0.1% risk of symptomatic gallstone migration and a 0.08% risk of biliary pancreatitis. At 9 years, 20.5±0.52% of patients underwent an interval cholecystectomy. The likelihood of interval cholecystectomy decreased from 5.4% per year to 1.7% per year after the first 18 months the whole cohort, risk at 18 months of symptomatic gallstone migration was 0.1%, of pancreatitis 0.08%, and of angiocholitis 0.1%. CONCLUSION: CC during SG and GBP should be avoided. In the case of asymptomatic gallstones after MBS, prophylactic cholecystectomy should not be recommended.

Surgery for Primary Aldosteronism in France From 2010 to 2020 - Results from the French-Speaking Association of Endocrine Surgery (AFCE): Eurocrine Study Group.

OBJECTIVE: Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020. BACKGROUND: Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers. METHODS: Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database. RESULTS: Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs. CONCLUSIONS: These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse.

Impact of Robotic Assistance on Complications in Bariatric Surgery at Expert Laparoscopic Surgery Centers: A Retrospective Comparative Study With Propensity Score.

OBJECTIVE: To investigate the way robotic assistance affected rate of complications in bariatric surgery at expert robotic and laparoscopic surgery facilities. BACKGROUND: While the benefits of robotic assistance were established at the beginning of surgical training, there is limited data on the robot's influence on experienced bariatric laparoscopic surgeons. METHODS: We conducted a retrospective study using the BRO clinical database (2008-2022) collecting data of patients operated on in expert centers. We compared the serious complication rate (defined as a Clavien score≥3) in patients undergoing metabolic bariatric surgery with or without robotic assistance. We used a directed acyclic graph to identify the variables adjustment set used in a multivariable linear regression, and a propensity score matching to calculate the average treatment effect (ATE) of robotic assistance. RESULTS: The study included 35,043 patients [24,428 sleeve gastrectomy (SG); 10,452 Roux-en-Y gastric bypass (RYGB); 163 single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S)], with 938 operated on with robotic assistance (801 SG; 134 RYGB; 3 SADI-S), among 142 centers. Overall, we found no benefit of robotic assistance regarding the risk of complications (average treatment effect=-0.05, P =0.794), with no difference in the RYGB+SADI group ( P =0.322) but a negative trend in the SG group (more complications, P =0.060). Length of hospital stay was decreased in the robot group (3.7±11.1 vs 4.0±9.0 days, P <0.001). CONCLUSIONS: Robotic assistance reduced the length of stay but did not statistically significantly reduce postoperative complications (Clavien score≥3) following either GBP or SG. A tendency toward an elevated risk of complications following SG requires more supporting studies.

Scope of prophylactic lymph node dissection in the surgical treatment of differentiated thyroid cancer. Recommendations of the AFCE (Association francophone de chirurgie endocrinienne) with the SFE (Société française d'endocrinologie) and the SFMN (Société française de médecine nucléaire).

Prophylactic lymph node dissection is considered only for papillary cancers. It is not indicated for vesicular cancers or oncocytic cancers, nor should it entail a secondary surgical intervention in the event of an incidental discovery of papillary cancer on a thyroidectomy specimen. Prophylactic lymph node dissection means a cervical lymph node dissection in the absence of any pre- or intraoperative evidence (biological, cytological, histological, clinical or ultrasound) of lymph node metastases. There is currently no evidence in the literature that prophylactic central dissection improves overall survival, which is similar for N0 and NX patients. Yet although prophylactic lymph node dissection is not justified by overall survival, it does seem to reduce the risk of locoregional recurrence in the case of micro-N1, and it allows occult metastases to be detected and a tumour to be reclassified. This enables patients at risk of recurrence to be more surely identified and therapeutic strategy and follow-up adapted accordingly. Prophylactic homolateral central lymph node dissection is warranted for papillary cancers with largest ultrasound diameter 4cm and above and/or with intraoperative macroscopic evidence of perithyroid tissue invasion. The benefits and risks of lymph node dissection must be assessed and discussed on a case-by-case basis. Only a central lymph node dissection homolateral to the tumour is recommended, except for bilateral or isthmic cancers, for which a prophylactic bilateral central lymph node dissection may be considered. This bilateral lymph node dissection incurs an increased risk of complications (parathyroids, recurrent laryngeal nerve). Prophylactic lateral lymph node dissection is not recommended.

Impact of Lymph Node Dissection on Postoperative Complications of Total Thyroidectomy in Patients with Thyroid Carcinoma.

Background: Lymph node dissection (LND) in primary treatment of differentiated thyroid carcinoma is controversial. The aim of our retrospective study was to analyse the risk factors of post-thyroidectomy complications and to assess the morbidity of lymph node dissection, especially in the central neck compartment, since prophylactic central lymph node dissection has not been proven to bring an overall survival benefit. Methods: We performed a retrospective analysis of postoperative complications from 1547 consecutive patients with differentiated thyroid carcinoma in an academic department of endocrine surgery over a period of 10 years. Results: A total of 535 patients underwent lymph node dissection, whereas the other 1012 did not. The rate of postoperative hypoparathyroidism was higher in patients with LND (17.6% vs. 11.4%, p = 0.001). No significant difference in the rate of permanent hypoparathyroidism (2.4% vs. 1.3%, p = 0.096) was observed between these two groups. A multivariate analysis was performed. Female gender, ipsilateral and bilateral central LND (CLND), parathyroid autotransplantation, and the presence of the parathyroid gland on the resected thyroid were associated with transient hypoparathyroidism. Bilateral CLND and the presence of the parathyroid gland on specimen were associated with permanent hypoparathyroidism. The rate of transient recurrent laryngeal nerve (RLN) injury (15.3% vs. 5.4%, p < 0.001) and permanent RLN injury (6.5% vs. 0.9%, p < 0.001) were higher in the LND group. In multivariate analysis, ipsilateral and bilateral lateral LND (LLND) were the main predictive factors of transient and permanent RLN injury. Bilateral RLN injury (2.6% vs. 0.4%, p < 0.001), chyle leakage (2.4% vs. 0%, p < 0.001), other nerve injuries (2.2% vs. 0%, p < 0.001), and abscess (2.4% vs. 0.5%, p = 0.001) were higher in the patients with LND. Conclusions: The surgical technique and the extent of lymph node dissection during surgery for thyroid carcinoma increase postoperative morbidity. A wider knowledge of lymph-node-dissection-related complications associated with thyroid surgery could help surgeons to carefully evaluate the surgical and medical therapeutic options.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Surgical treatment.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French-speaking Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the surgical management of thyroid nodules.

Data-driven subgroups of type 2 diabetes, metabolic response, and renal risk profile after bariatric surgery: a retrospective cohort study.

BACKGROUND: A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. METHODS: We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). FINDINGS: At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8-11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6-22·7; p=0·0070). INTERPRETATION: Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery. FUNDING: Agence Nationale de la Recherche, Investissement d'Avenir, Innovative Medecines Initiative, Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.

Salvage Robotic Roux-en-Y Fistulojejunostomy for Chronic Gastro-Colic Fistula After Laparoscopic Sleeve Gastrectomy.

Roux-en-Y fistulojejunostomy (RYFJ) has been proposed as a surgical option for the treatment of a chronic fistula after sleeve gastrectomy but can be technically challenging. The robotic approach in bariatric surgery has emerged as a new rapidly evolving technology and allows performing more complex surgical procedures. Here we present the case of a 42-year-old man referred to our university tertiary center for a chronic gastro-colic fistula after laparoscopic SG who underwent a salvage robotic RYFJ. The aim of this video is to present our management of a chronic gastro-colic fistula after laparoscopic SG demonstrating the technical advantages of a robotic approach to a RYFJ.

Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model.

The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the one anastomosis gastric bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces similar beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the length of biliary and common limbs in the weight loss and metabolic effects that occur upon OAGB. OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss.NEW & NOTEWORTHY Common limb mediates postprandial glucose metabolism change after gastric bypass whereas biliary limb contributes to weight loss.

Circular Stapled Laparoscopic Oesophagojejunal Anastomosis for Treating Large Gastrojejunal Leak After Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.

After Roux-en-Y gastric bypass, leaks from gastro-jejunostomies represent serious morbidity. Situations where large defects develop on small gastric pouches present particular surgical challenges. Here, we report the case of a 43-year-old female who presents with a large gastric leak after conversion of sleeve gastrectomy to Roux-en-Y gastric bypass due to staple lines having crossed. The aim of this video is to present the management of gastrojejunal leak after Roux-en-Y gastric bypass and technical features of circular stapled laparoscopic oesophagojejunal anastomosis.

Malignant Leakage After Sleeve Gastrectomy: Endoscopic and Surgical Approach.

PURPOSE: Gastric leak occurs after sleeve gastrectomy (SG) in 2% of cases. Most staple-line disruptions (SLD) can be successfully treated with first-line endoscopic procedures. Less favorable situations may lead to more complex therapeutic strategies, like conversion to Roux-en-Y gastric bypass (RYGBP). The aim of our study is to predict the factors of endoscopic treatment failure and to assess the safety of conversion to RYGBP. METHODS: We included all patients treated in two centers of academic excellence (n = 100) between 2013 and 2017 who had a malignant SLD after SG. A "malignant" leakage met one of the following poor prognosis criteria suggested in the literature: unsuccessfully treated by the first-line endoscopic treatment; generalized peritonitis; anatomical anomalies; gastro-cutaneous or gastro-pleural fistula (GCF/GPF); or chronic leaks (> 4 weeks). RESULTS: No deaths occurred during the follow-up (20 ± 12 months). The endoscopy reported an anatomically abnormal gastric tube in 35 (35%) patients (stenosis [n = 21 (21%)], twist [n = 9 (9%)], or both [n = 5 (5%)]). We could maintain the SG in place in 92% of cases without stenosis, twist, or GCF/GPF. Conversion to RYGBP due to leakage was necessary in 37 (37%) patients. Stenosis, twist, or GCF/GPF significantly prevented healing in multivariate analysis (respectively: p = 0.020, OR = 0.17, and p < 0.001, OR = 0.07-logistic regression). CONCLUSION: Endoscopy is the treatment of choice for the management of chronic leaks after SG. The association of anatomical anomalies and GCF/GPF should lead to consideration of conversion to RYGBP.

Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis.

BACKGROUND AND AIMS: Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver samples, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH. METHODS: We performed a prospective study of 180 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network histologic scores. The patients underwent bariatric surgery at a single center in France and were followed for 5 years. We obtained liver samples from 125 of 169 patients (76%) having reached 1 year and 64 of 94 patients (68%) having reached 5 years after surgery. The primary endpoint was the resolution of NASH without worsening of fibrosis at 5 years. Secondary end points were improvement in fibrosis (reduction of ≥1 stage) at 5 years and regression of fibrosis and NASH at 1 and 5 years. RESULTS: At 5 years after bariatric surgery, NASH was resolved, without worsening fibrosis, in samples from 84% of patients (n = 64; 95% confidence interval, 73.1%-92.2%). Fibrosis decreased, compared with baseline, in samples from 70.2% of patients (95% CI, 56.6%-81.6%). Fibrosis disappeared from samples from 56% of all patients (95% CI, 42.4%-69.3%) and from samples from 45.5% of patients with baseline bridging fibrosis. Persistence of NASH was associated with no decrease in fibrosis and less weight loss (reduction in body mass index of 6.3 ± 4.1 kg/m2 in patients with persistent NASH vs reduction of 13.4 ± 7.4 kg/m2; P = .017 with resolution of NASH). Resolution of NASH was observed at 1 year after bariatric surgery in biopsies from 84% of patients, with no significant recurrence between 1 and 5 years (P = .17). Fibrosis began to decrease by 1 year after surgery and continued to decrease until 5 years (P < .001). CONCLUSIONS: In a long-term follow-up of patients with NASH who underwent bariatric surgery, we observed resolution of NASH in liver samples from 84% of patients 5 years later. The reduction of fibrosis is progressive, beginning during the first year and continuing through 5 years.

Differential unfolded protein response in skeletal muscle from non-diabetic glucose tolerant or intolerant patients with obesity before and after bariatric surgery.

AIMS: Not all people with obesity become glucose intolerant, suggesting differential activation of cellular pathways. The unfolded protein response (UPR) may contribute to the development of insulin resistance in several organs, but its role in skeletal muscle remains debated. Therefore, we explored the UPR activation in muscle from non-diabetic glucose tolerant or intolerant patients with obesity and the impact of bariatric procedures. METHODS: Muscle biopsies from 22 normoglycemic (NG, blood glucose measured 120 min after an oral glucose tolerance test, G120 < 7.8 mM) and 22 glucose intolerant (GI, G120 between 7.8 and 11.1 mM) patients with obesity were used to measure UPR activation by RTqPCR and western blot. Then, UPR was studied in biopsies from 7 NG and 7 GI patients before and 1 year after bariatric surgery. RESULTS: Binding immunoglobulin protein (BIP) protein was ~ 40% higher in the GI compared to NG subjects. Contrastingly, expression of the UPR-related genes BIP, activating transcription factor 6 (ATF6) and unspliced X-box binding protein 1 (XBP1u) were significantly lower and C/EBP homologous protein (CHOP) tended to decrease (p = 0.08) in GI individuals. While BIP protein positively correlated with fasting blood glucose (r = 0.38, p = 0.01), ATF6 and CHOP were associated with G120 (r = - 0.38 and r = - 0.41, p < 0.05) and the Matsuda index (r = 0.37 and r = 0.38, p < 0.05). Bariatric surgery improved metabolic parameters, associated with higher CHOP expression in GI patients, while ATF6 tended to increase (p = 0.08). CONCLUSIONS: CHOP and ATF6 expression decreased in non-diabetic GI patients with obesity and was modified by bariatric surgery. These genes may contribute to glucose homeostasis in human skeletal muscle.

[What is the position of bariatric surgery in the treatment of non-alcoholic steatohepatitis?] / Quelle place pour la chirurgie bariatrique dans le traitement de la stéatohépatite non alcoolique ?

Bariatric surgery is indicated for patients with BMI≥35kg/m2 and associated steatohepatitis. Bariatric surgery induces NASH disappearance for nearly 80% of patients after 1 year of follow up. Bariatric surgery is associated with low morbidity and mortality if patients are well selected. Bariatric surgery is contraindicated in patients with cirrhosis. Long-term data are needed to determine the risk of recurrence of NASH. The extension of indications for bariatric surgery to patients with BMI less than 35kg/m2 will depend on the results of randomized trials.

NIFT-P: Are they indolent tumors? Results of a multi-institutional study.

BACKGROUND: Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists. METHODS: All patients from 9 high-volume endocrine surgery departments who underwent surgery between 2005 and 2015 and whose final surgical pathology revealed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (>10 mm) were included in this study. The primary outcome was to determine the potential for recurrent disease in these patients. RESULTS: Among the 363 patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 76% were female with a median age of 50 years (5-86 years); 345 patients (95%) underwent total thyroidectomy. A total of 65 patients had an associated micropapillary thyroid carcinoma. In the group of 133 patients who underwent prophylactic lymph node dissection (37%), 1 patient had a micrometastasis but with an associated micropapillary thyroid carcinoma. Over a median follow-up period of 5 years, 1 patient with an associated micropapillary thyroid carcinoma had recurrent disease at 6 years. All patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features without micropapillary thyroid carcinoma had no lymph node metastasis or recurrent disease. CONCLUSION: We found that noninvasive follicular thyroid neoplasm with papillary-like nuclear features presents with indolent behavior. However, the identification of an associated micropapillary thyroid carcinoma should be carefully evaluated because it could be a factor for lymph node metastasis and/or of recurrence.

Management of Acute Gallstone Cholangitis after Roux-en-Y Gastric Bypass with Laparoscopic Transgastric Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: The incidence of biliary lithiasis is increased after bariatric surgery due to rapid weight loss [1]. Trans-oral endoscopic management in cases of common bile duct gallstone complication is not possible in patients with Roux-en-Y gastric bypass (RYGB) due to the modified anatomy. Access to the biliary tree after RYGB with a classical direct surgical approach of common bile duct and choledocoscopy can be used, but may be complicated in situations of acute cholangitis because of the fragility of common duct, or in cases of previous cholecystectomy. Multiple alternatives have been described, such as percutaneous transhepatic cholangiography or laparoscopic transgastric endoscopic retrograde cholangiopancreatography (LTG-ERCP) [2, 3]. The aim of this video was to present the management of common bile duct gallstone complication after RYGB and the technical features of LTG-ERCP [4]. METHODS: We present the case of a 79-year-old woman (98 kg, BMI 40.2 kg/m2) with a 24-month history of RYGB, who presented with gallstone cholangitis and septic shock. Imaging revealed a 16-mm dilatation of the common bile duct upstream of a biliary gallstone. A previous history of laparotic cholecystectomy leads us to favor LTG-ERCP. RESULTS: We present the step-by-step LTG-ERCP technique. The laparoscopic procedure started with an excluded stomach dissection and gastrostomy on the great curvature at 10 cm from the pylorus with a 15-mm extra-long port. The placement of the gastrotomy should be carefully chosen with respect to the antrum, in order to provide straightforward access to the pylorus. The transgastric endoscopic procedure should include sphincterotomy (if not formerly performed) and gallstone removal. The patient experienced no specific complication of LTG-ERCP. Control of sepsis was favorable with adapted antibiotic treatment. Hepatic cytolysis and cholestasis normalized within postoperative day 3. Postoperative imaging showed a reduction of the common bile duct diameter to 12 mm. The patient required hemodialysis because of acute kidney injury. She finally left the hospital on postoperative day 16. CONCLUSIONS: LTG-ERCP is a safe and feasible alternative for gallstone cholangitis management in patients with RYGB. This procedure should be recommended for cases of cholangitis rather than laparoscopic choledocoscopy or a percutaneous transhepatic approach, especially in cases of prior cholecystectomy, or in patients where the BMI remains high. LTG-ERCP should be performed in a referral center by a skilled endoscopist and surgeon following a standardized technique.