Optimizing management for early-stage esophageal adenocarcinoma: longitudinal results from a multidisciplinary program.

BACKGROUND: The management of early-stage esophageal cancer is nuanced. A multidisciplinary approach may optimize management through selection of candidates for surgical or endoscopic therapies. The objective of this research was to examine long-term outcomes of patients with early-stage esophageal cancer who undergo treatment with endoscopic resection or surgery. METHODS: Data on patient demographics, co-morbidities, pathology results, OS and RFS were obtained for both the endoscopic resection group and esophagectomy group. Univariate analysis of OS and RFS were conducted using the Kaplan-Meier method with calculation of the log-rank test. Multivariate cox-proportional hazards models were created for OS and RFS using a hypothesis-driven approach. A multivariate logistic regression model was created to identify predictors of esophagectomy among patients undergoing initial endoscopic resection. RESULTS: A total of 111 patients were included. The median OS for the surgery group was 67.0 months compared to 74.0 months in the endoscopic resection group (log-rank p = 0.93). The median RFS for the surgery group was 109.4 months compared to 63.3 months in the endoscopic resection group (log-rank p = 0.0127). On multivariable analysis, patients undergoing endoscopic resection had significantly worse RFS (HR 2.55, 95% CI 1.09-6.00; p = 0.032), but equivalent OS (HR 1.03, 95% CI 0.46-2.32; p = 0.941), compared to patients undergoing esophagectomy. High-grade disease (OR 5.43, 95% CI 1.13-26.10; p = 0.035) and submucosal involvement (OR 7.75, 95% CI 1.90-31.40; p = 0.004) were identified as significant predictors of proceeding to esophagectomy. CONCLUSIONS: Through a multidisciplinary approach, patients with early-stage esophageal cancer achieve excellent RFS and OS. Submucosal involvement and high-grade disease place patients at increased risk for local disease recurrence; these patients may undergo endoscopic resection safely if treated with a multidisciplinary approach incorporating endoscopic surveillance and surgical consultation. Further risk-stratification models may enable better patient selection and optimization of long-term outcomes.

The Effect of Covid-19 Pandemic on Current and Future Endoscopic Personal Protective Equipment Practices: A National Survey of 77 Endoscopists.

Introduction: The COVID-19 pandemic has raised awareness about the importance of personal protective equipment (PPE). We aimed to study and compare PPE practices among Canadian endoscopists before and after the COVID-19 pandemic. Methods: A 74-item questionnaire was emailed from June 2020 to September 2020 to practicing endoscopists in Canada. Survey questions collected basic demographics and differences between PPE practices pre- and post-COVID-19. PPE practices were categorized into four endoscopic procedure types including upper or lower endoscopy and diagnostic or interventional. Outcomes for specific procedures were reported as rates, with ranges shown when evaluating all procedure types together. Results: A total of 77 respondents completed the survey with the majority of respondents aged 40 to 49 (44%) and identifying as Gastroenterologists (70%). Gender was evenly split (49% females versus 51% males). In the pre-pandemic era, the majority of endoscopists wore gowns (91 to 94%) and all endoscopists wore gloves (100%). However, the majority of endoscopists did not wear surgical masks (21 to 31%), face shields (13 to 34%), eye protection (13 to 21%), hair protection (11 to 13%), or N95 respirators (2 to 3%). In the post-pandemic era, more surgeons plan on wearing face shields (33 to 47%, P = 0.001 to 0.045), goggles (38.5 to 58.7%, P < 0.001), hair protection (33 to 36%, P = 0.011 to 0.024), and a trend suggests more surgeons will wear surgical masks (51 to 61%, P = 0.163 to 0.333). More endoscopists also plan on wearing N95 respirators during lower endoscopy (6 to 7%, P < 0.005). Conclusion: The COVID-19 pandemic has changed the attitudes of many endoscopists regarding future PPE use in routine endoscopy. Ongoing studies are needed to inform new post-pandemic PPE consensus guidelines.

Variation of Laparoscopic Roux-en-Y Gastric Bypass Techniques: a Survey of 518 Bariatric Surgeons.

INTRODUCTION: Surgical technique varies dramatically in the performance of laparoscopic Roux-en-Y gastric bypass (LRYGB) and these differences can potentially lead to variation in outcomes. The objective of this study was to characterize surgical techniques used during LRYGB. METHODS: An anonymous 44-question survey was distributed by email to all bariatric surgeons with membership in the ASMBS, SAGES, and ACS from April to June 2020. Questions were designed to evaluate surgeon demographics, experience, and variation of techniques. Only surgeons who performed LRYGB within the past year were included for analysis. RESULTS: A total of 534 (18.8%) surgeons responded and the majority (97.0%) reported performing LRYGB in the past year. Surgeons were predominantly from the USA (77.8%). For preoperative work-up, 20.1% performed upper gastrointestinal series while 60.8% performed esophagogastroduodenoscopy. Limb length evaluation revealed mean Roux and biliopancreatic limb lengths of 124.1 ± 29.4 cm and 67.4 ± 32.2 cm, respectively. The gastrojejunostomy was most commonly formed using a linear stapler with handsewn closure of the common enterotomy (53.1%) and the jejunojejunostomy using a linear stapled anastomotic technique with handsewn closure of the common enterotomy (60.6%). The majority of surgeons closed the jejunojejunostomy mesenteric defect (91.1%) and one of the antecolic or retrocolic mesenteric defects (65.1%). Intraoperative leak tests were performed in 95.9% of cases. Only 22.1% of surgeons routinely performed upper gastrointestinal swallow studies postoperatively. CONCLUSIONS: There are wide variations in pre- and intraoperative practice patterns for LRYGB. Further clinical trials designed to evaluate the impact of these practice pattern differences on patient outcomes are warranted.

Characterization of Near-Infrared Imaging and Indocyanine-Green Use Amongst General Surgeons: A Survey of 263 General Surgeons.

BACKGROUND: Near-infrared fluorescence imaging (NIRFI) is an increasingly utilized imaging modality, however its use amongst general surgeons and its barriers to adoption have not yet been characterized. METHODS: This survey was sent to Canadian Association of General Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons members. Survey development occurred through consensus of NIRFI experienced surgeons. RESULTS: Survey completion rate for those opening the email was 16.0% (n = 263). Most respondents had used NIRFI (n = 161, 61.2%). Training, higher volumes, and bariatric, thoracic, or foregut subspecialty were associated with use (P < .001).Common reasons for NIRFI included anastomotic assessment (n = 117, 72.7%), cholangiography (n = 106, 65.8%), macroscopic angiography (n = 66, 41.0%), and bowel viability assessment (n = 101, 62.7%). Technical knowledge, training and poor evidence were cited as common barriers to NIRFI adoption. CONCLUSIONS: NIRFI use is common with high case volume, bariatric, foregut, and thoracic surgery practices associated with adoption. Barriers to use appear to be lack of awareness, low confidence in current evidence, and inadequate training. High quality randomized studies evaluating NIRFI are needed to improve confidence in current evidence; if deemed beneficial, training will be imperative for NIRFI adoption.

Management of choledocholithiasis after Roux-en-Y gastric bypass: a systematic review and pooled proportion meta-analysis.

BACKGROUND: Several therapeutic modalities have been proposed for the management of choledocholithiasis (CDL) following Roux-en-Y gastric bypass (RYGB), yet debate exists regarding the optimal management. The purpose of our study was to review the current literature to compare the efficacy of various techniques in the management of CDL post-RYGB. METHODS: A comprehensive search of multiple databases was conducted. Studies reporting on the management of CDL in patients post-RYGB and including at least 5 patients were eligible for inclusion. The primary outcome was successful stone clearance. Secondary outcomes included procedure duration, length of hospital stay, and adverse events. RESULTS: Of 3259 identified studies, 53 studies involving 857 patients were included in the final analysis. The mean age was 54.4 years (SD 7.05), 78.8% were female (SD 13.6%), and the average BMI was 30.8 kg/m2 (SD 6.85). Procedures described included laparoscopy-assisted ERCP (LAERCP), balloon-assisted enteroscopy (BAE), ultrasound-directed transgastric ERCP (EDGE), laparoscopic common bile duct exploration (LCBDE), EUS-guided intra-hepatic puncture with antegrade clearance (EGHAC), percutaneous trans-hepatic biliary drainage (PTHBD), and rendezvous guidewire-associated (RGA) ERCP. High rates of successful stone clearance were observed with LAERCP (1.00; 95% CI 0.99-1.00; p = 0.47), EDGE (0.97; 95% CI 0.9-1.00; p = 0.54), IGS ERCP (1.00; 95% CI 0.87-1.00), PTHBD (1.0; 95% CI 0.96-1.00), and LCBDE (0.99; 95% CI 0.93-1.00, p < 0.001). Lower rates of stone clearance were observed with BAE (61.5%; 95%CI 44.3-76.3, p = 0.188) and EGHAC (74.0%; 95% CI 42.9-91.5, p = 0.124). Relative to EDGE, LAERCP had a longer procedure duration (133.1 vs. 67.4 min) but lower complication rates (12.8% vs. 24.3%). CONCLUSION: LAERCP and EDGE had high rates of success in the management of CDL post-RYGB. LAERCP had fewer complications but was associated with longer procedure times. BAE had lower success rates than both LAERCP and EDGE.

Gastric ischemic conditioning prior to esophagectomy reduces anastomotic leaks and strictures: a systematic review and meta-analysis.

BACKGROUND: Gastric ischemic conditioning (GIC) is a strategy to promote neovascularization of the gastric conduit to reduce the risk of anastomotic complications following esophagectomy. Despite a number of studies and reviews published on the concept of ischemic conditioning, there remains no clear consensus regarding its utility. We performed an updated systematic review and meta-analysis to determine the impact of GIC, particularly on anastomotic leaks, conduit ischemia, and strictures. METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library was performed on February 5th, 2020 by a university librarian after selection of key search terms with the research team. Inclusion criteria included human participants undergoing esophagectomy with gastric conduit reconstruction, age ≥ 18, N ≥ 5, and GIC performed prior to esophagectomy. Our primary outcome of interest was anastomotic leaks. Our secondary outcome was gastric conduit ischemia, anastomotic strictures, and overall survival. Meta-analysis was performed with RevMan 5.4.1 using a Mantel-Haenszel fixed-effects model. RESULTS: A total of 1712 preliminary studies were identified and 23 studies included for final review. GIC was performed in 1178 (53.5%) patients. Meta-analysis revealed reduced odds of anastomotic leaks (OR 0.67; 95% CI 0.46-0.97; I2 = 5%; p = 0.03) and anastomotic strictures (OR 0.48; 95% CI 0.29-0.80; I2 = 65%; p = 0.005). Meta-analysis revealed no difference in odds of conduit ischemia (OR 0.40; 95% CI 0.13-1.23; I2 = 0%; p = 0.11) and no difference in odds of overall survival (OR 0.54; 95% CI 0.29-1.02; I2 = 22%; p = 0.06). CONCLUSION: GIC is associated with reduced odds of anastomotic leaks and anastomotic strictures and may decrease morbidity in patients undergoing esophagectomy. Further prospective randomized trials are needed to better identify the optimal patient population, timing, and techniques used to best achieve GIC.

Trends and Outcomes of Laparoscopic Sleeve Gastrectomy Between 2015 and 2018 in the USA and Canada.

BACKGROUND: Given there are approximately 100,000 primary laparoscopic sleeve gastrectomy (LSG) procedures performed a year in North America, there is a need to evaluate recent trends in LSG. The objective of this study was to analyze the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to identify trends in technical factors and patient outcomes over time. METHODS: The MBSAQIP prospectively collects data from 854 centers in the USA and Canada. Patients undergoing primary LSG were included. Statistical analysis was performed to characterize trends in patient factors, technical factors, and 30-day postoperative outcomes. RESULTS: A total of 434,030 patients underwent primary LSG. The mean age was 44.2 (SD 12.0) years and mean body mass index was 45.1 (SD 7.8) kg/m2. Baseline demographics did not vary appreciably by year. Operative time decreased from 2015 to 2018 (75.4 to 70.6 min, p < 0.001). Bougie size and stapling distance from the pylorus did not change by year. However, staple line reinforcement (66.8 to 63.2%, p < 0.001) and oversewing of the staple line (23.1 to 20.1%, p < 0.001) were less commonly performed. Postoperatively, from 2015 to 2018, there was a 45.8% relative reduction in leaks (0.48 to 0.26%, p < 0.001). There were also reductions in 30-day major complications (2.87 to 2.28%, p < 0.001), length of stay (1.72 to 1.44 days, p < 0.001), and readmissions (3.39 to 2.77%, p < 0.001). CONCLUSIONS: From 2015 to 2018, there was a decrease in staple line reinforcement and oversewing. These changes correlated with reductions in operative time, length of stay, readmission, and major complications.

Diagnostic accuracy of sentinel lymph node biopsy using indocyanine green in lung cancer: a systematic review and meta-analysis.

OBJECTIVE: The use of sentinel lymph node biopsy (SLNB) has been gaining popularity with the emergence of indocyanine green (ICG) fluorescence imaging. We aimed to systematically review the literature and perform a meta-analysis on the diagnostic accuracy of SLNB using ICG for lung cancer. METHODS: A comprehensive search of MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library using search terms "lung/pulmonary" AND "tumor/carcinoma/cancer/neoplasm/adenocarcinoma/malignancy/squamous/carcinoid" AND "indocyanine green" was completed in June 2018. Articles were selected based on the following inclusion criteria: (1) diagnostic accuracy study design; (2) ICG injected at the tumor site with near-infrared fluorescence imaging identification of sentinel lymph nodes; (3) lymphadenectomy or sampling was performed as the gold standard. RESULTS: Eight primary studies were included with a total of 366 patients. 43.0% of patients were females and the mean tumor size was 2.3 cm. Sentinel lymph nodes were identified with ICG in 251 patients, yielding a pooled identification rate of 0.83 (0.67-0.94). A meta-analysis of seven studies computed a diagnostic odds ratio, sensitivity, and specificity of 177.6 (45.6-691.1), 0.85 (0.71-0.94), and 1.00 (0.98-1.00), respectively. The summary receiver operator characteristic demonstrated an area under the curve of 0.963 (SE = 0.038) and a Q* of 0.91 (SE = 0.057). CONCLUSION: Our review found suboptimal results for the diagnostic accuracy of SLNB using ICG and must be improved before routine clinical use. Further research is required to develop a robust protocol for the use SLNB with ICG for lung cancer.

An Evaluation of the Modern North American Bariatric Surgery Landscape: Current Trends and Predictors of Procedure Selection.

PURPOSE: The last 5 years have produced a dramatic transformation in the landscape of bariatric and metabolic surgery. Yet, while the landscape of bariatric procedures is changing, little is known about these trends or which factors are responsible for their evolution. METHODS: All primary elective laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) cases were extracted from the comprehensive Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data registry from 2015 to 2018. RESULTS: A total of 590,971 patients were identified, with 79.6% being female. Overall, 73.4% of patients underwent LSG. The mean age was 44.5 ± 12.0 years and mean BMI was 45.3 ± 7.9 kg/m2. An increase in proportion of LSG cases was observed and associated with a decrease in LRYGB cases from 2015 to 2018. Multivariable analysis identified dialysis dependence as the greatest predictor of LSG (OR 2.67; 95% CI 2.34-3.04), whereas insulin-dependent diabetes (OR 2.27; 95% CI 2.23-2.32) and gastroesophageal reflux disease (OR 1.52; 95% CI 1.51-1.55) were the two greatest predictors of LRYGB, respectively. Patients offered LSG in 2018 had a near 1.3-fold increase in odds of receiving sleeve gastrectomy vs. those offered surgery in 2015. CONCLUSION: The overall numbers of bariatric cases have increased from 2015 to 2018 and are associated with an increase in proportion of LSG cases and a decrease in proportion of LRYGB cases over time. Factors other than patient comorbidities alone are responsible for the current trends and modern landscape of bariatric surgery.

Intraoperative fluorescence imaging with indocyanine green in hepatic resection for malignancy: a systematic review and meta-analysis of diagnostic test accuracy studies.

BACKGROUND: Fluorescence imaging during hepatic resection has the potential to identify additional malignant tumors, increasing the chance for complete tumor resection. Indocyanine green (ICG) is an FDA approved, fluorescent dye used in a variety of surgical procedures. The objective of this study was to define the sensitivity of intraoperative ICG fluorescent imaging in the detection of hepatic malignancy in adult patients during hepatic resection, which was accomplished by performing a systematic review and meta-analysis. METHODS: The databases Medline, EMBASE, Scopus and Web of Science were assessed in September 2018. Article inclusion criteria was (1) Liver resection for malignancy (2) ICG injected pre or intraoperatively (3) Use of infrared electronic endoscopy or near-infrared fluorescence imaging intraoperatively (4) Patient age ≥ 18 years (5) N > 5 patients (6) Human and English studies only. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines were used for quality assessment. Data synthesis was completed using Meta-Disc and MedCalc software. A DerSimonian-Laird random effects model was used for the meta-analysis. RESULTS: 21 studies and 841 patients were included in our systematic review. Seven studies and 319 patients were included in the meta-analysis. The pooled sensitivity of intraoperative ICG fluorescence was 0.75 (0.71-0.79). Sensitivity for superficial tumors ranged from 0.96 to 1.00. Heterogeneity (I2) was calculated at 65.1%. ICG-related fluorescence imaging detected new malignant tumors not detected by conventional means in 42 of 362 patients across 13 studies. CONCLUSION: The sensitivity of intraoperative ICG-related imaging for superficial tumors is high; however, overall sensitivity is low, at 0.75, suggesting that it would have to be used in combination with current identification methods such as intraoperative ultrasound. Our study also found that intraoperative ICG fluorescence imaging was able to detect additional malignant hepatic tumors in 11.6% of patients.

Idiopathic intracranial hypertension and bariatric surgery: a systematic review

Background: Idiopathic intracranial hypertension (IIH) is a rare condition typically affecting women with obesity who are of child-bearing age. Patients commonly present with headaches, visual disturbances, pulsatile tinnitus and papilledema. The association between IIH and obesity has been well established in the literature, suggesting that weight loss may contribute to improving IIH. For patients with severe obesity for whom conservative management is not successful, bariatric surgery is an effective modality for weight loss. We aimed to systematically review the literature to determine the efficacy of bariatric surgery in the treatment of IIH Methods: We conducted a comprehensive search of MEDLINE, Embase, Scopus, the Cochrane Library and Web of Science (limited to studies in humans published in English between January 1946 and July 2015). Results: Twelve primary studies (n = 39 patients) were included in the systematic review. All patients had a preoperative diagnosis of IIH. Preoperative body mass index (BMI) was 47.4 ± 3.6 kg/m2 ; BMI improved to 33.7 ± 2.1 kg/m2 and 33.9 ± 11.6 kg/m2 at 6 and 12 months postoperatively, respectively. Lumbar puncture opening pressures decreased from 34.4 ± 6.9 cmH2O to 14.0 ± 3.6 cmH2O after surgery. Common symptoms of IIH improved after bariatric surgery: headaches (100% preoperatively v. 10% postoperatively), visual complaints (62% v. 44%), tinnitus (56% v. 3%) and papilledema (62% v. 8%). Conclusion: Bariatric surgery appears to lead to considerable improvement in IIH. Idiopathic intracranial hypertension is not a well-publicized comorbidity of obesity, but its presence may be considered as an indication for bariatric surgery.

Contexte: L'hypertension intracrânienne (HTIC) idiopathique est une affection rare qui touche surtout les femmes atteintes d'obésité en âge de procréer. Les symptômes courants sont des maux de tête, des troubles de la vue, des acouphènes pulsatiles et un oedème papillaire. Le lien entre l'HTIC idiopathique et l'obésité est bien établi dans la littérature, ce qui suggère que la perte de poids pourrait améliorer le tableau clinique de l'HTIC. Pour les patients atteints d'obésité sévère pour lesquels le traitement conservateur ne fonctionne pas, la chirurgie bariatrique est un moyen efficace de perdre du poids. Cette revue systématique de la littérature vise à déterminer l'efficacité de la chirurgie bariatrique dans le traitement de l'HTIC idiopathique. Méthodes: Nous avons interrogé MEDLINE, Embase, Scopus, la Bibliothèque Cochrane et Web of Science (limites : études portant sur les humains publiées en anglais entre janvier 1946 et juillet 2015). Résultats: Douze études primaires (n = 39 patients) ont été incluses dans la revue systématique. Tous les patients avaient un diagnostic préopératoire d'HTIC idiopathique. L'indice de masse corporelle (IMC) préopératoire était de 47,4 ± 3,6 kg/m2 ; l'IMC est passé à 33,7 ± 2,1 kg/m2 6 mois après l'opération, puis à 33,9 ± 11,6 kg/m2 12 mois après l'opération. Les pressions d'ouverture des ponctions lombaires sont passées de 34,4 ± 6,9 cmH2O à 14,0 ± 3,6 cmH2O après l'opération. Les symptômes courants de l'HTIC idiopathique se sont améliorés après la chirurgie bariatrique : maux de tête (100% avant opération c. 10% après), troubles de la vue (62% c. 44%), acouphènes pulsatiles (56% c. 3%) et œdème papillaire (62% c. 8%). Conclusion: La chirurgie bariatrique semble améliorer considérablement les symptômes d'HTIC idiopathique. Cette affection n'est pas une comorbidité bien connue de l'obésité, mais sa présence peut être une indication pour la chirurgie bariatrique comme traitement.

Isolated colonic neurofibroma in the setting of Lynch syndrome: A case report and review of literature.

BACKGROUND: Gastrointestinal neurofibromas are commonly found in patients diagnosed with neurofibromatosis type 1. However, isolated gastrointestinal neurofibromas are a rare entity and only fourteen cases of isolated colorectal neurofibromas have been documented in literature. Isolated gastrointestinal neurofibromas have not been associated with Lynch syndrome (LS). Patients with LS are at an increased risk of colorectal cancer, and are recommended to undergo screening colonoscopy. CASE SUMMARY: A 33-year-old healthy female with a family history of LS was found to have unresectable polyp in the ascending colon on screening colonoscopy suspicious for malignancy. The patient was asymptomatic and had no stigmata of neurofibromatosis. A staging workup for colorectal cancer revealed no evidence of metastatic disease. A discussion with the patient resulted in the decision to undergo a segmental resection with ongoing surveillance. The patient underwent a laparoscopic right hemicolectomy. Histopathology was consistent with a gastrointestinal neurofibroma. Post-operatively, the patient recovered well. She will not require further treatment with regards to her colonic neurofibroma, but will continue to follow-up for ongoing surveillance of her LS. CONCLUSION: We present the first case of an isolated colonic neurofibroma in a patient with LS. This case explores considerations for the management of isolated gastrointestinal neurofibromas given the lack of guidelines in literature.

Evaluating the safety of intragastric balloon: An analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program.

BACKGROUND: Laparoscopic bariatric surgery (LBS) is effective for severe obesity but is invasive and costly. Intragastric balloons (IGBs) are increasingly popular as an alternative to LBS with modest short-term weight loss. However, IGBs are associated with complications and a comparison of the safety of IGB to LBS is warranted. OBJECTIVES: The objective of this study was to compare the safety profile of IGB with LBS through analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. SETTING: The MBSAQIP collects data from 791 bariatric surgery centers in the United States and Canada. METHODS: A propensity-matched analysis was performed between IGB and LBS. Multivariable logistic regression analysis was performed to determine if IGBs were independently associated with adverse outcomes. RESULTS: A total of 145,408 patients were included, of which 144,627 (99.5%) underwent LBS and 781 (0.5%) underwent IGB therapy. With one-to-one propensity score matching, 684 pairs of IGB and LBS patients were selected. Multivariable logistic regression found that IGB (odds ratio 1.97, confidence interval 1.10-3.52, P = .023) was independently predictive of 30-day adverse outcomes. This was due to a significantly higher nonoperative reintervention rate in the IGB cohort (4.2% versus 1.0%, P < .001) from early balloon removal (2.8%). CONCLUSIONS: In this propensity-matched analysis, IGBs were associated with a higher adverse event rate than LBS, due to a 4-times higher nonoperative reintervention rate. The utility of IGB as a primary weight loss intervention should be reconsidered due to its poor safety profile compared with LBS.

The utility of routine esophagogastroduodenoscopy before laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The routine use of esophagogastroduodenoscopy (EGD) before laparoscopic Roux-en-y gastric bypass (LRYGB) is debatable. Various studies have reported high diagnostic yield of routine EGD before LRYGB to detect pathologies that could alter surgical management. However, other studies have found that preoperative EGD did not identify significant pathologies that changed clinical management; therefore, it is not indicated in asymptomatic patients. OBJECTIVES: We aimed to study the utility of routine EGD in patients before LRYGB. SETTING: Academic teaching hospital, (Royal Alexandra Hospital, Canada). METHODS: A retrospective review of patients undergoing LRYGB with 1 surgeon at our hospital from May 2014 to March 2016 was completed. EGD findings were compared with surgical gastrojejunal specimen pathology and postoperative complications. RESULTS: There were 116 patients who underwent EGD before LRYGB with 113 reported EGDs, of which 46.0% were normal, 40.7% had findings that did not result in a change of management, and 13.3% had findings resulting in a change of management. In the gastrojejunal specimen, 16 patients (14.2%) were found to have chronic gastritis. The relative risk of patients having gastrojejunal gastritis was 5.1 (P<.0005) for patients with gastritis on EGD and 5.1 (P<.0005) for patients with Helicobacter pylori infection on EGD. After surgery, 18 patients (15.9%) had complications. Preoperative EGD findings were not associated with postoperative complications. CONCLUSION: Based on the findings from this study, we recommend using less invasive screening in the routine workup of patients awaiting LRYGB and reserving EGD for symptomatic patients.

Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus.

The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription-translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short- to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of the hippocampus.

The proteomic landscape of the suprachiasmatic nucleus clock reveals large-scale coordination of key biological processes.

The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry. Of the 2112 proteins that were accurately quantified, 20% (421 proteins) displayed a time-of-day-dependent expression profile. Within this time-of-day proteome, 11% (48 proteins) were further defined as circadian based on a sinusoidal expression pattern with a ∼24 h period. Nine circadianly expressed proteins exhibited 24 h rhythms at the transcript level, with an average time lag that exceeded 8 h. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated light-to-dark and dark-to-light transitions, and was enriched for proteins involved in several key biological pathways, most notably, mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. These insights into the proteomic landscape of the SCN will facilitate a more integrative understanding of cellular control within the SCN clock.

The crystal structure of Aquifex aeolicus prephenate dehydrogenase reveals the mode of tyrosine inhibition.

TyrA proteins belong to a family of dehydrogenases that are dedicated to l-tyrosine biosynthesis. The three TyrA subclasses are distinguished by their substrate specificities, namely the prephenate dehydrogenases, the arogenate dehydrogenases, and the cyclohexadienyl dehydrogenases, which utilize prephenate, l-arogenate, or both substrates, respectively. The molecular mechanism responsible for TyrA substrate selectivity and regulation is unknown. To further our understanding of TyrA-catalyzed reactions, we have determined the crystal structures of Aquifex aeolicus prephenate dehydrogenase bound with NAD(+) plus either 4-hydroxyphenylpyuvate, 4-hydroxyphenylpropionate, or l-tyrosine and have used these structures as guides to target active site residues for site-directed mutagenesis. From a combination of mutational and structural analyses, we have demonstrated that His-147 and Arg-250 are key catalytic and binding groups, respectively, and Ser-126 participates in both catalysis and substrate binding through the ligand 4-hydroxyl group. The crystal structure revealed that tyrosine, a known inhibitor, binds directly to the active site of the enzyme and not to an allosteric site. The most interesting finding though, is that mutating His-217 relieved the inhibitory effect of tyrosine on A. aeolicus prephenate dehydrogenase. The identification of a tyrosine-insensitive mutant provides a novel avenue for designing an unregulated enzyme for application in metabolic engineering.

Crystal structure of prephenate dehydrogenase from Aquifex aeolicus. Insights into the catalytic mechanism.

The enzyme prephenate dehydrogenase catalyzes the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate for the biosynthesis of tyrosine. Prephenate dehydrogenases exist as either monofunctional or bifunctional enzymes. The bifunctional enzymes are diverse, since the prephenate dehydrogenase domain is associated with other enzymes, such as chorismate mutase and 3-phosphoskimate 1-carboxyvinyltransferase. We report the first crystal structure of a monofunctional prephenate dehydrogenase enzyme from the hyper-thermophile Aquifex aeolicus in complex with NAD+. This protein consists of two structural domains, a modified nucleotide-binding domain and a novel helical prephenate binding domain. The active site of prephenate dehydrogenase is formed at the domain interface and is shared between the subunits of the dimer. We infer from the structure that access to the active site is regulated via a gated mechanism, which is modulated by an ionic network involving a conserved arginine, Arg250. In addition, the crystal structure reveals for the first time the positions of a number of key catalytic residues and the identity of other active site residues that may participate in the reaction mechanism; these residues include Ser126 and Lys246 and the catalytic histidine, His147. Analysis of the structure further reveals that two secondary structure elements, beta3 and beta7, are missing in the prephenate dehydrogenase domain of the bifunctional chorismate mutase-prephenate dehydrogenase enzymes. This observation suggests that the two functional domains of chorismate mutase-prephenate dehydrogenase are interdependent and explains why these domains cannot be separated.

The crystal structure of a novel SAM-dependent methyltransferase PH1915 from Pyrococcus horikoshii.

The S-adenosyl-L-methionine (SAM)-dependent methyltransferases represent a diverse and biologically important class of enzymes. These enzymes utilize the ubiquitous methyl donor SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids. Here we present the crystal structure of PH1915 from Pyrococcus horikoshii OT3, a predicted SAM-dependent methyltransferase. This protein belongs to the Cluster of Orthologous Group 1092, and the presented crystal structure is the first representative structure of this protein family. Based on sequence and 3D structure analysis, we have made valuable functional insights that will facilitate further studies for characterizing this group of proteins. Specifically, we propose that PH1915 and its orthologs are rRNA- or tRNA-specific methyltransferases.