The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy: A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival. METHODS: This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. RESULTS: A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50 Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). CONCLUSIONS: MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

How-I-do-it: laparoscopic intragastric submucosal dissection (LISD) for gastric and gastro-oesophageal junction early lesions.

PURPOSE: Laparoscopic intragastric submucosal dissection (LISD) is a novel approach to the resection of gastric lesion that are not amenable to conventional endoscopic approaches. The technique permits favourable access to lesions situated at the cardia and angular notch of the stomach, enables en-bloc resection of large areas of tissue, and can prevent the need of formal gastrectomy or oesophagectomy in selected patients. METHODS: All cases were deemed suitable for LISD by a multidisciplinary team panel following endoscopic assessment (using white light enhancement, chromoendoscopy and magnification endoscopy) that was integrated when needed with EUS, CT scan or PET scan. The surgical technique consisted in a 3-port laparoscopic approach; after establishment of pneumoperitoneum, three gastrotomies were performed to enable port insertion into the stomach. Following establishment of stable pneumogastrium, the area of interest was identified, submucosal hyaluronic acid injection performed to provide a cushion in the plane of dissection, and the excision area was circumferentially marked with cautery. Resection was completed using cautery hook, along a plane parallel to the muscolaris propria. After the specimen was extracted in a retrieval bag, intracorporeal single layer running suture closure of gastrotomies was performed. The abdominal wall closed by layers and tap block performed along with local anaesthetic injection on skin incision. Measures were taken to ensure correct orientation of resected specimens prior to fixation. RESULTS: During the study period that spans from 2014 and 2022, a total of 11 patients underwent LISD for limited lesions of the stomach, 10 were located at gastro-oesophageal junction and one at the angular incisura. Four patients were female, seven males. The median age was 74 (46-79) years. R0 resection rate was 54.5%. Mean operative time was 109 min with very low blood loss (10 ml). Mortality rate was 0%, no immediate major complications (Grade II-V Clavien Dindo), including haemorrhage or perforation, occurred in these cases. Two patients developed dysphagia later that was successfully treated with endoscopic balloon dilatations. Median hospital stay was 3 days and median oral intake was on day 1 post-procedural. CONCLUSIONS: Laparoscopic intragastric submucosal dissection is shown to be a safe and effective intervention for the treatment of early gastric cancers in selected patients having undergone deemed not amenable for endoscopic submucosal resection for their technically challenging location. Its application can serve as route to avoid formal surgery and the associated morbidity.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

CagA-ASPP2 complex mediates loss of cell polarity and favors H. pylori colonization of human gastric organoids.

The main risk factor for stomach cancer, the third most common cause of cancer death worldwide, is infection with Helicobacter pylori bacterial strains that inject cytotoxin-associated gene A (CagA). As the first described bacterial oncoprotein, CagA causes gastric epithelial cell transformation by promoting an epithelial-to-mesenchymal transition (EMT)-like phenotype that disrupts junctions and enhances motility and invasiveness of the infected cells. However, the mechanism by which CagA disrupts gastric epithelial cell polarity to achieve its oncogenicity is not fully understood. Here we found that the apoptosis-stimulating protein of p53 2 (ASPP2), a host tumor suppressor and an important CagA target, contributes to the survival of cagA-positive H. pylori in the lumen of infected gastric organoids. Mechanistically, the CagA-ASPP2 interaction is a key event that promotes remodeling of the partitioning-defective (PAR) polarity complex and leads to loss of cell polarity of infected cells. Blockade of cagA-positive H. pylori ASPP2 signaling by inhibitors of the EGFR (epidermal growth factor receptor) signaling pathway-identified by a high-content imaging screen-or by a CagA-binding ASPP2 peptide, prevents the loss of cell polarity and decreases the survival of H. pylori in infected organoids. These findings suggest that maintaining the host cell-polarity barrier would reduce the detrimental consequences of infection by pathogenic bacteria, such as H. pylori, that exploit the epithelial mucosal surface to colonize the host environment.

Near infra-red fluorescence identification of the thoracic duct to prevent chyle leaks during oesophagectomy.

BACKGROUND: Chyle leaks following oesophagectomy are a frustrating complication of surgery with considerable morbidity. The use of near infra-red (NIR) fluorescence in surgery is an emerging technology and the use of fluorescence to identify the thoracic duct has been demonstrated in animal work and early human case reports. This study evaluated the use mesenteric and enteral administration of indocyanine green (ICG) in humans to identify the thoracic duct during oesophagectomy. METHODS: Patients undergoing oesophagectomy were recruited to the study. Administration of ICG via an enteral route or mesenteric injection was evaluated. Fluorescence was assessed using a NIR fluorescence enabled laparoscope system with a visual scoring system and signal to background ratios. Visualisation of the thoracic duct under white light and NIR fluorescence was compared as well as any identification of active chyle leak. Patients were followed up post-operatively for adverse events and chyle leak. RESULTS: 20 patients received ICG and were included in the study. The enteral route failed to fluoresce the thoracic duct. Mesenteric injection (17 patients) identified the thoracic duct under fluorescence prior to white light in 70% of patients with a mean signal to background ratio of 5.35. In 6 participants, a possible active chyle leak was identified under fluorescence with 4 showing active chyle leak from what was identified as the thoracic duct. CONCLUSION: This study demonstrates that ICG administration via mesenteric injection can highlight the thoracic duct during oesophagectomy and may be a potential technology to reduce chyle leak following surgery. CLINICAL TRIAL REGISTRATION: Clinical trials.gov (NCT03292757).

Endoscopic vacuum therapy (EVT) in the management of oesophageal perforations and post-operative leaks.

INTRODUCTION: Oesophageal perforations and post-oesophagectomy anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a novel treatment strategy with the potential to promote healing and ameliorate sepsis. Only two cases of its use have been reported in the UK in the management of oesophageal wall defects, representing a limited aetiological and demographic spectrum. MATERIAL AND METHODS: From May to December 2019, 7 patients aged 27-85 years underwent EVT for disparate oesophageal wall defects. Data regarding technical success and feasibility were analysed. RESULTS: Complete defect resolution was achieved in six cases (86%), requiring median of 13 days of treatment (range 6-23), and necessitating three replacement procedures (range 1-4). Significant improvement in C-reactive protein was achieved in all patients undergoing treatment (p = .015). No severe complications occurred that resulted directly from sponge placement, however two individuals (33%) developed oesophageal stricture necessitating endoscopic balloon dilatation, and one died whilst undergoing treatment. CONCLUSION: In selected patients EVT is a safe, valuable tool for the management of a spectrum of oesophageal wall defects, with the potential to reduce associated morbidity and mortality. While this work significantly expands upon the UK reported experience of EVT, we outline the requirement for a national, prospective registry of EVT use in oesophageal leaks and perforations. ABBREVIATIONS: AL: anastomotic leak; CRP: C-reactive protein; CT: computed tomography; EVT: endoscopic vacuum therapy; HES: hospital episode statistics; OGD: oesophago-gastro-duodenoscopy; SEMS: oesophageal stenting with self-expanding stents; UK: United Kingdom.

Extensive weight loss reduces glycan age by altering IgG N-glycosylation.

BACKGROUND: Obesity, a major global health problem, is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to inflammation and ageing. The prospect of biological age reduction, by changing glycosylation patterns through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. METHODS: IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1680 participants from the TwinsUK cohort. RESULTS: Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG N-glycome that accompanied progressive weight loss during 1-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG N-glycans (adjusted p value range 7.38 × 10-04-3.94 × 10-02). This IgG N-glycan profile is known to be associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease (adjusted p value 1.79 × 10-02) and an increase in digalactosylation (adjusted p value 5.85 × 10-06). CONCLUSIONS: Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced glycan and biological age.

Technique of open and minimally invasive intrathoracic reconstruction following esophagectomy-an expert consensus based on a modified Delphi process.

BACKGROUND: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology. METHODS: The expert panel consisted of specialized esophageal surgeons from 8 European countries. During a two-round Delphi process, a detailed analysis and consensus on key steps of intrathoracic gastric tube reconstruction (IL esophagectomy) was performed. RESULTS: Response rates in Delphi rounds 1 and 2 were 100% (22 of 22 experts) and 83.3% (20 of 24 experts), respectively. Three essential technical areas of intrathoracic gastric tube reconstruction were identified: first, vascularization of the gastric conduit, second, gastric mobilization, tube formation and pull-up, and third, anastomotic technique. In addition, 3 main techniques for minimally invasive intrathoracic anastomosis are currently practiced: (i) end-to-side circular stapled, (ii) end-to-side double stapling, and (iii) side-to-side linear stapled technique. The step-by-step procedural analysis unveiled common approaches but also different expert practice. CONCLUSION: This precise technical description may serve as a clinical guideline for intrathoracic reconstruction after esophagectomy. In addition, the results may aid to harmonize the technical evolution of this complex surgical procedure and thereby facilitate surgical training.

Laparoscopic vs. open feeding jejunostomy insertion in oesophagogastric cancer.

BACKGROUND: Jejunal feeding is an invaluable method by which to improve the nutritional status of patients undergoing neoadjuvant and surgical treatment of oesophageal malignancies. However, the insertion of a feeding jejunostomy can cause significant postoperative morbidity. The aim of this study is to compare the outcomes of patients undergoing placement of feeding jejunostomy by conventional laparotomy with an alternative laparoscopic approach. METHODS: A retrospective review of data prospectively collected at the Oxford Oesophagogastric Centre between August 2017 and July 2019 was performed including consecutive patients undergoing feeding jejunostomy insertion. RESULTS: In the study period, 157 patients underwent jejunostomy insertion in the context of oesophageal cancer therapy, 126 (80%) by open technique and 31 (20%) laparoscopic. Pre-operative demographic and nutritional characteristics were broadly similar between groups. In the early postoperative period jejunostomy-associated complications were noted in 54 cases (34.4%) and were significantly more common among those undergoing open as compared with laparoscopic insertion (38.1% vs. 19.3%, P = 0.049). Furthermore, major complications were more common among those undergoing open insertion, whether as a stand-alone or at the time of staging laparoscopy (n = 11/71), as compared with insertion at the time of oesophagectomy (n = 3/86, P = 0.011). CONCLUSIONS: This report represents the largest to our knowledge single-centre comparison of open vs. laparoscopic jejunostomy insertion in patients undergoing oesophagectomy in the treatment of gastroesophageal malignancy. We conclude that the laparoscopic jejunostomy insertion technique described represents a safe and effective approach to enteral access which may offer superior outcomes to conventional open procedures.

Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: Clinical outcome and cost-effectiveness analyses.

BACKGROUND: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT). METHODS AND FINDINGS: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change. CONCLUSIONS: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Endoscopic mucosal resection of early oesophageal neoplasia in patients requiring anticoagulation: is it safe?

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) has become the standard treatment for early oesophageal neoplasia. The mucosal defect caused by EMR usually takes several weeks to heal. Despite guidelines on high-risk endoscopic procedures in patients on anticoagulation, evidence is lacking whether EMR is safe in such patients. We investigated the immediate and delayed bleeding risk in patients undergoing diagnostic or therapeutic oesophageal EMR comparing patients requiring warfarin anticoagulation with a control group. METHODS: Warfarin was stopped 5 days before the planned EMR and restarted on the evening following the procedure. Patients with high-risk conditions, such as recent pulmonary thromboemboli, received bridging with low molecular weight heparin. All EMRs were performed when the INR was <1.5. Bleeding events on the day of the EMR and within 3 months post-procedure were documented. RESULTS: One hundred and seventeen consecutive patients with early oesophageal neoplasia were included. Sixty-eight EMRs were performed in 15 patients requiring anticoagulation. One patient on warfarin was readmitted 10 days after EMR with haematemesis and melaena. Out of 400 EMRs in 102 controls, 26 immediate bleeding events occurred requiring endoscopic intervention. One delayed bleeding event (melaena) occurred in the control group. The number of bleeding events did not differ between groups [p = 0.99; odds ratio 1.01 (0.30-3.44)], neither for acute (p = 0.76) nor delayed bleeding (p = 0.24). CONCLUSION: EMR of early oesophageal neoplasia can be safely performed in patients requiring anticoagulation when warfarin is discontinued 5 days before the endoscopic intervention and reinstituted on the evening of the procedure day.

Enhanced recovery for esophagectomy: a systematic review and evidence-based guidelines.

OBJECTIVE: This article aims to provide the first systematic review of enhanced recovery after surgery (ERAS) programs for esophagectomy and generate guidelines. BACKGROUND: ERAS programs use multimodal approaches to reduce complications and accelerate recovery. Although ERAS is well established in colorectal surgery, experience after esophagectomy has been minimal. However, esophagectomy remains an extremely high-risk operation, commonly performed in patients with significant comorbidities. Consequently, ERAS may have a significant role to play in improving outcomes. No guidelines or reviews have been published in esophagectomy. METHODS: We undertook a systematic review of the PubMed, EMBASE, and the Cochrane databases in July 2012. The literature was searched for descriptions of ERAS in esophagectomy. Components of successful ERAS programs were determined, and when not directly available for esophagectomy, extrapolation from related evidence was made. Graded recommendations for each component were then generated. RESULTS: Six retrospective studies have assessed ERAS for esophagectomy, demonstrating favorable morbidity, mortality, and length of stay. Methodological quality is, however, low. Overall, there is little direct evidence for components of ERAS, with much derived from nonesophageal thoracoabdominal surgery. CONCLUSIONS: ERAS in principle seems logical and safe for esophagectomy. However, the underlying evidence is poor and lacking. Despite this, a number of recommendations for practice and research can be made.

Gender influence on long-term weight loss after three bariatric procedures: gastric banding is less effective in males in a retrospective analysis.

BACKGROUND: Identifying factors that influence weight loss after bariatric surgery is one way to predict a successful surgical outcome. Knowledge of the effect of gender on weight loss after bariatric surgery has not been well demonstrated in the literature despite being noted in every day practice. The aim of this study was to find the influence of gender on long-term weight loss after bariatric surgery. METHODS: A retrospective analysis of data retrieved from a prospectively maintained bariatric database was conducted. RESULTS: The study included 640 consecutive patients. Their mean age was 38 ± 10 years, mean preoperative body mass index was 44.9 ± 8.4 kg/m2, and mean preoperative excess weight (EW %) was 108.3 ± 38.4%. The mean of the average excess weight loss (EWL %) was 43.3 ± 42.4%. Three procedures were utilized: Roux-en-Y gastric bypass (RYGB), vertical banded gastroplasty (VBG), and gastric banding (GB). Both VBG and RYGB induced significantly more EWL % than GB (d = 22.1%, p < 0.001 and d = 16, p = 0.02, respectively). In patients who underwent VBG and GB, males had significantly lower preoperative EW % (Student t = -4.86, p < 0.001, and Student t = 4.69, p < 0.001, respectively), and postoperative mean of the average EWL % (Student t = -2.43, p = 0.016, and Student t = -3.33, p = 0.002, respectively) than females. In patients who underwent RYGB, there were no differences in the preoperative EW % (t = -1.03, p = 0.309) or the mean of the average EWL % (t = 0.406, p = 0.688). The simple linear regression model used to explain the variability in EWL %, accounted for by the variability in the preoperative EW %, was significant (F = 180, p < 0.001). Analysis of the residual errors in predicting the EWL % revealed no significant difference between males and females after VBG and after RYGB (t = 0.117, p = 0.907 and t = 1.052, p = 0.3, respectively), while it was significant after GB (t = -2.999, p = 0.003). CONCLUSION: From our experience, we suggest that GB not to be offered as a first choice for obese male patients.

Alterations in plasma protein N-glycosylation after caloric restriction and bariatric surgery.

BACKGROUND: Protein glycosylation is an enzymatic process known to reflect an individual's physiologic state and changes thereof. The impact of metabolic interventions on plasma protein N-glycosylation has only been sparsely investigated. OBJECTIVE: To examine alterations in plasma protein N-glycosylation following changes in caloric intake and bariatric surgery. SETTING: University of Texas Southwestern Medical Center, US and Oxford University Hospitals, UK. METHODS: This study included 2 independent patient cohorts that recruited 10 and 37 individuals with obesity undergoing a period of caloric restriction followed by bariatric surgery. In both cohorts, clinical data were collated, and the composition of plasma protein N-glycome was analyzed chromatographically. Linear mixed models adjusting for age, sex, and multiple testing (false discovery rate <.05) were used to investigate longitudinal changes in glycosylation features and metabolic clinical markers. RESULTS: A low-calorie diet resulted in a decrease in high-branched trigalactosylated and trisialylated plasma N-glycans and a concomitant increase in low-branched N-glycans in both cohorts. Participants from one cohort additionally underwent a washout period during which caloric intake and body weight increased, resulting in reversal of the initial low-calorie diet-related changes in the plasma N-glycome. Immediate postoperative follow-up revealed the same pattern of N-glycosylation changes in both cohorts-an increase in complex, high-branched, antennary fucosylated, extensively galactosylated and sialylated N-glycans and a substantial decline in simpler, low-branched, core fucosylated, bisected, agalactosylated, and asialylated glycans. A 12-month postoperative monitoring in one cohort showed that N-glycan complexity declines while low branching increases. CONCLUSIONS: Plasma protein N-glycosylation undergoes extensive alterations following caloric restriction and bariatric surgery. These comprehensive changes may reflect the varying inflammatory status of the individual following dietary and surgical interventions and subsequent weight loss.

Current Status of Endoscopic Vacuum Therapy in the Management of Esophageal Perforations and Post-Operative Leaks.

Esophageal wall defects, including perforations and postoperative leaks, are associated with high morbidity and mortality and pose a significant management challenge. In light of the high morbidity of surgical management or revision, in recent years, endoscopic vacuum therapy (EVT) has emerged as a novel alternative treatment strategy. EVT involves transoral endoscopic placement of a polyurethane sponge connected to an externalized nasogastric tube to provide continuous negative pressure with the intention of promoting defect healing, facilitating cavity drainage, and ameliorating sepsis. In the last decade, EVT has become increasingly adopted in the management of a diverse spectrum of esophageal defects. Its popularity has been attributed in part to the growing body of evidence suggesting superior outcomes and defect closure rates in excess of 80%. This growing body of evidence, coupled with the ongoing evolution of the technology and techniques of deployment, suggests that the utilization of EVT has become increasingly widespread. Here, we aimed to review the current status of the field, addressing the mechanism of action, indications, technique methodology, efficacy, safety, and practical considerations of EVT implementation. We also sought to highlight future directions for the use of EVT in esophageal wall defects.

PYY plays a key role in the resolution of diabetes following bariatric surgery in humans.

BACKGROUND: Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied. METHODS: Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. FINDINGS: We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. INTERPRETATION: This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction.

AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Steroid hormones and bile acids are potent regulators of hepatic carbohydrate and lipid metabolism. Steroid 5ß-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. METHODS: Human liver biopsies were obtained from 34 obese patients and AKR1D1 mRNA expression levels were measured using qPCR. Genetic manipulation of AKR1D1 was performed in human HepG2 and Huh7 liver cell lines. Metabolic assessments were made using transcriptome analysis, western blotting, mass spectrometry, clinical biochemistry, and enzyme immunoassays. RESULTS: In human liver biopsies, AKR1D1 expression decreased with advancing steatosis, fibrosis and inflammation. Expression was decreased in patients with type 2 diabetes. In human liver cell lines, AKR1D1 knockdown decreased primary bile acid biosynthesis and steroid hormone clearance. RNA-sequencing identified disruption of key metabolic pathways, including insulin action and fatty acid metabolism. AKR1D1 knockdown increased hepatocyte triglyceride accumulation, insulin sensitivity, and glycogen synthesis, through increased de novo lipogenesis and decreased ß-oxidation, fueling hepatocyte inflammation. Pharmacological manipulation of bile acid receptor activation prevented the induction of lipogenic and carbohydrate genes, suggesting that the observed metabolic phenotype is driven through bile acid rather than steroid hormone availability. CONCLUSIONS: Genetic manipulation of AKR1D1 regulates the metabolic phenotype of human hepatoma cell lines, driving steatosis and inflammation. Taken together, the observation that AKR1D1 mRNA is down-regulated with advancing NAFLD suggests that it may have a crucial role in the pathogenesis and progression of the disease.

Oligometastatic recurrence of an oesophageal adenocarcinoma at a chest drain site following radical treatment: palliative treatment or resection?

A 62-year-old female patient diagnosed with oesophageal adenocarcinoma underwent radical treatment consisting of neoadjuvant chemotherapy and oesophagectomy with no major complications. Eleven months later, she re-presented with a mass at one of the chest drain sites. A PET-CT scan and biopsy demonstrated this to be a single recurrence of the oesophageal adenocarcinoma. Excision of the metastatic lesion was considered as per metachronous single site metastasis. However, the operation was postponed due to acute kidney injury. Restaging after 6 weeks revealed progressive metastatic disease. The patient underwent palliative therapy and passed away soon after. Oesophageal cancer recurrence has a very poor prognosis, and factors such as the disease-free interval, site of recurrence and tumour pathological factors must be considered when stratifying for suitability for metastasectomy. A period of watchful waiting followed by restaging is essential to rule out patients with indolent metastatic disease.