Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Elastography to Evaluate the Early Effects of Bariatric Surgery on Nonalcoholic Fatty Liver Disease.

Background: Bariatric surgery is the most effective treatment for morbid obesity and reduces the severity of nonalcoholic fatty liver disease (NAFLD) in the long term. Less is known about the effects of bariatric surgery on liver fat, inflammation, and fibrosis during the early stages following bariatric surgery. Aims: This exploratory study utilises advanced imaging methods to investigate NAFLD and fibrosis changes during the early metabolic transitional period following bariatric surgery. Methods: Nine participants with morbid obesity underwent sleeve gastrectomy. Multiparametric MRI (mpMRI) and magnetic resonance elastography (MRE) were performed at baseline, during the immediate (1 month), and late (6 months) postsurgery period. Liver fat was measured using proton density fat fraction (PDFF), disease activity using iron-correct T1 (cT1), and liver stiffness using MRE. Repeated measured ANOVA was used to assess longitudinal changes and Dunnett's method for multiple comparisons. Results: All participants (Age 45.1 ± 9.0 years, BMI 39.7 ± 5.3 kg/m2) had elevated hepatic steatosis at baseline (PDFF >5%). In the immediate postsurgery period, PDFF decreased significantly from 14.1 ± 7.4% to 8.9 ± 4.4% (p = 0.016) and cT1 from 826.9 ± 80.6 ms to 768.4 ± 50.9 ms (p = 0.047). These improvements continued to the later postsurgery period. Bariatric surgery did not reduce liver stiffness measurements. Conclusion: Our findings support using MRI as a noninvasive tool to monitor NAFLD in patient with morbid obesity during the early stages following bariatric surgery.

Laparoscopic completion gastrectomy: A single-institution case series and systematic review of the literature.

INTRODUCTION: Completion gastrectomy with lymphadenectomy for remnant gastric cancer (RGC) is currently the gold standard for patients with resectable disease. Multiple surgical approaches can be adopted; however, there exists no agreement on the best choice due to the low incidence of RGC. With its anticipated increase in prevalence, we thus sought to evaluate the feasibility and efficacy of the laparoscopic approach versus conventional laparotomy via a pooled analysis of existing literature. METHODS: A retrospective review of five consecutive patients who underwent laparoscopic completion gastrectomy from August 2017 to June 2022 was performed following Institutional Review Board waiver. A comprehensive systematic review of literature on laparoscopic completion gastrectomy from the Pubmed, Embase, MEDLINE, Web of Science and Cochrane databases was conducted to supplement the experience from our institution. RESULTS: Four patients had prior benign gastric disease and one had prior gastric cancer. Two patients experienced severe postoperative complications but there were otherwise no reports of conversion to laparotomy or mortality. Mean operative duration was 295 minutes. Mean duration to oral intake and discharge was 6.8 and 14.6 days respectively. Results from our pooled analysis of 591 cases suggested that the laparoscopic approach was associated with longer operative durations but delivered fewer postoperative complications, shorter duration to dietary resumption and shorter lengths of stay over conventional laparotomy. CONCLUSION: Laparoscopic completion gastrectomy is indeed a more challenging procedure due to the presence of dense adhesions from previous surgery. However, the procedure can be performed safely with superior outcomes as compared to conventional laparotomy.

Revisional Surgery or Pharmacotherapy for Insufficient Weight Loss and Weight Regain After Primary Bariatric Procedure: a Descriptive Study.

PURPOSE: Bariatric surgery is the most effective and durable treatment option for clinically severe obesity. Unfortunately, some degree of weight regain (WR) is common after nadir weight is achieved. Pharmacotherapy and revision surgery are potential options to treat this phenomenon. We aim to determine the efficacy of both approaches in patients with WR versus insufficient weight loss (IWL). MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database of patients who underwent bariatric surgery from 2008 to 2018 with IWL or WR. RESULTS: Of 422 patients with WR or IWL after bariatric surgery, 150 patients were placed on pharmacotherapy and 27 underwent revisional surgeries. Mean age of patients was 41.4 years and mean BMI was 42.1 kg/m2. The most common conversion surgery was LSG to RYGB. % Total weight loss (TWL) was higher in IWL group (23.8% ± 11.0) compared to WR group (17.2% ± 7.9) in revisional surgery (p = 0.02). The converse was observed for pharmacotherapy, with %TWL 1.9% in the WR group compared to 0.7% in the IWL group (p = 0.0067). CONCLUSION: Patients with IWL or WR had modest weight loss with adjunctive use of pharmacotherapy after primary bariatric surgery. Conversely, revisional surgery is an effective treatment for both IWL and WR.

Endoscopic internal drainage with double pigtail stents for upper gastrointestinal anastomotic leaks: suitable for all cases?

BACKGROUND/AIMS: Surgeons and endoscopists have started to use endoscopically inserted double pigtail stents (DPTs) in the management of upper gastrointestinal (UGI) leaks, including UGI anastomotic leaks. We investigated our own experiences in this patient population. METHODS: From March 2017 to June 2020, 12 patients had endoscopic internal drainage of a radiologically proven anastomotic leak after UGI surgery in two tertiary UGI centers. The primary outcome measure was the time to removal of the DPTs after anastomotic healing. The secondary outcome measure was early oral feeding after DPT insertion. RESULTS: Eight of the 12 patients (67%) required only one DPT, whereas four (33%) required two DPTs. The median duration of drainage was 42 days. Two patients required surgery due to inadequate control of sepsis. Of the remaining 10 patients, nine did not require a change in DPT before anastomotic healing. Nine patients were allowed oral fluids within the 1st week and a soft diet in the 2nd week. One patient was allowed clear oral feeds on the 8th day after DPT insertion. CONCLUSION: Endoscopic internal drainage is becoming an established minimally invasive technique for controlling anastomotic leak after UGI surgery. It allows for early oral nutritional feeding and minimizes discomfort from conventional external drainage.

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15-0.85; P = .02; I2 = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10-0.83; P = .02; I2 = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43-1.08; P = .10; I2 = 0%) and length of hospitalization (mean difference, -0.32; 95% CI, -1.88 to 1.24; P = .69; I2 = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09-97.98; I2 = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00-1.28; I2 = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.

Small hiatal hernia and postprandial reflux after vertical sleeve gastrectomy: A multiethnic Asian cohort.

BACKGROUND: Laparoscopic vertical sleeve gastrectomy (LSG) is a popular bariatric procedure performed in Asia, as obesity continues to be on the rise in our population. A major problem faced is the development of de novo gastroesophageal reflux disease (GERD) after LSG, which can be chronic and debilitating. In this study, we aim to assess the relationship between the presence of small hiatal hernia (HH) and the development of postoperative GERD, as well as to explore the correlation between GERD symptoms after LSG and timing of meals. In doing so, we hope to gain a better understanding about the type of reflux that occurs after LSG and take a step closer towards effectively managing this difficult to treat condition. METHODS: We retrospectively reviewed data collected from patients who underwent LSG in our hospital from Dec 2008 to Dec 2016. All patients underwent preoperative upper GI endoscopy, during which the identification of hiatal hernia takes place. Patients' information and reflux symptoms are recorded using standardized questionnaires, which are administered preoperatively, and again during postoperative follow up visits. RESULTS: Of the 255 patients, 125 patients (74%) developed de novo GERD within 6 months post-sleeve gastrectomy. The rate of de novo GERD was 57.1% in the group with HH, and 76.4% in the group without HH. Adjusted analysis showed no significant association between HH and GERD (RR = 0.682; 95% CI 0.419 to 1.111; P = 0.125). 88% of the patients who developed postoperative GERD reported postprandial symptoms occurring only after meals, and the remaining 12% of patients reported no correlation between the timing of GERD symptoms and meals. CONCLUSION: There is no direct correlation between the presence of small hiatal hernia and GERD symptoms after LSG. Hence, the presence of a small sliding hiatal hernia should not be exclusion for sleeve gastrectomy. Electing not to perform concomitant hiatal hernia repair also does not appear to result in higher rates of postoperative or de novo GERD.

Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy.

BACKGROUND: Plasma concentrations of branched-chain amino acids (BCAAs) are elevated in obese individuals with insulin resistance (IR) and decrease after bariatric surgery. However, the metabolic mechanisms are unclear. OBJECTIVES: Our objectives are to compare leucine kinetics between morbidly obese and healthy-weight individuals cross-sectionally, and to prospectively evaluate changes in the morbidly obese after sleeve gastrectomy. We hypothesized that leucine oxidation is slower in obese individuals and increases after surgery. METHODS: Ten morbidly obese [BMI (in kg/m2) ≥32.5, age 21-50 y] and 10 healthy-weight participants (BMI <25), matched for age (median ∼30 y) but not gender, were infused with [U-13C6] leucine and [2H5] glycerol to quantify leucine and glycerol kinetics. Morbidly obese participants were studied again 6 mo postsurgery. Primary outcomes were kinetic parameters related to BCAA metabolism. Data were analyzed by nonparametric methods and presented as median (IQR). RESULTS: Participants with obesity had IR with an HOMA-IR (4.89; 4.36-8.76) greater than that of healthy-weight participants (1.32; 0.99-1.49; P < 0.001) and had significantly faster leucine flux [218; 196-259 compared with 145; 138-149 µmol · kg fat-free mass (FFM)-1 · h-1], oxidation (24.0; 17.9-29.8 compared with 16.1; 14.3-18.5 µmol · kg FFM-1 · h-1), and nonoxidative disposal (204; 190-247 compared with 138; 129-140 µmol · kg FFM-1 · h-1) (P < 0.017 for all). After surgery, the morbidly obese had a marked improvement in IR (3.54; 3.06-6.08; P = 0.008) and significant reductions in BCAA concentrations (113; 95-157 µmol/L) and leucine oxidation (9.37; 6.85-15.2 µmol · kg FFM-1 · h-1) (P = 0.017 for both). Further, leucine flux in this group correlated significantly with IR (r = 0.78, P < 0.001). CONCLUSIONS: BCAA oxidation is not impaired but elevated in individuals with morbid obesity. Plasma BCAA concentrations are lowered after surgery owing to slower breakdown of body proteins as insulin's ability to suppress proteolysis is restored. These findings suggest that IR is the underlying cause and not the consequence of elevated BCAAs in obesity.

Resolution of Erosive Esophagitis After Conversion from Vertical Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, there is one shortcoming of LSG in the long-term follow-up, and this is the onset of gastro-esophageal reflux disease (GERD) and erosive esophagitis (EE). Conversion to Roux-en-Y gastric bypass (RYGB) is considered an option in patients unresponsive to medical therapy. Currently, there is no evidence of EE improvement or resolution after conversion surgery. In this study, we objectively evaluate the effectiveness of RYGB in management of EE with upper endoscopy (EGD) to identify the significant variables in patients with GERD symptoms post LSG refractory to medical therapy and require conversion surgery. METHODS: Over a period of 11 years (2008-2019) at Singapore General Hospital, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had conversion surgery to RYGB for refractory GERD and EE after LSG. Patient's endoscopic findings and demographic and anthropometric data were analyzed. RESULTS: We identified a total of 14 patients who underwent LSG to RYGB conversions for endoscopic proven erosive esophagitis in our unit during the study period. Eight patients (57.1%) had concurrent hiatal hernia repaired. Nine (64.3%) patients were females. The median age of patients in this cohort was 44 (range 30-61) years. Mean weight and BMI were 87.7 kg (± 19.2) and 32.8 (± 3.09) kg/m2, respectively, on the day of conversion surgery. The median time between LSG and revision to RYGB was 36 (range 6-68) months. Seven patients (50%) had complete resolution of GERD symptoms after conversion, and 6 patients (42.9%) had partial resolution. Six out of 7 patients had complete resolution of EE. There were 4 anastomotic strictures (28.6%). Older patients, Indian ethnicity, present of hiatal hernia and lower weight loss after initial LSG were more likely to undergo conversion surgery. CONCLUSION: Conversion to RYGB after LSG is clinically relevant and may be a feasible solution if patients have ongoing GERD refractory to medical therapy. Ninety-three percent of our patients achieved complete resolution of their GERD symptoms and significant improvement of erosive esophagitis with significant weight loss after conversion. This study has important implications as LSG is increasingly being performed and a proportion of these will need revision surgery for various reasons, particularly GERD which is extremely prevalent.

Associations of Bariatric Interventions With Micronutrient and Endocrine Disturbances.

Importance: Few studies have described the longitudinal trajectories of serum levels of micronutrients whose deficiencies are associated with serious sequelae following bariatric procedures, such as anemia, osteoporotic fractures, and neuropathies. Furthermore, previous studies comparing laparoscopic sleeve gastrectomy (LSG) vs Roux-en-Y gastric bypass (LRYGB) or one-anastomosis gastric bypass (OAGB) procedures may have been limited by selection and confounding biases. Objective: To appraise the spectrum and temporal course of micronutrient deficiencies associated with bone metabolism and erythropoiesis after LSG vs OAGB or LRYGB procedures, using the propensity score as a balancing score. Design, Setting, and Participants: This prospective, longitudinal comparative effectiveness study was conducted at a high-volume bariatric unit in Singapore from September 1, 2008, to November 30, 2017, with a cutoff date for analysis of September 2018. Patients who underwent adjustable gastric banding, biliopancreatic diversion procedures, and intragastric balloon procedures were excluded. All other patients who underwent bariatric procedures were included. Data were analyzed from September 23 to 30, 2018. Main Outcomes and Measures: Serial assessment of 13 biochemical parameters at 12 time points for up to 5 years after bariatric procedure. Inverse probability-of-treatment weights were used to obtain estimates of the mean associations of variables assessed with the bariatric surgical interventions. Longitudinal trajectories were analyzed using mixed-effects generalized linear models to apportion the temporal variation of serum micronutrients into fixed-effects and random-effects components. Results: A total of 688 patients were included in this study, of whom 499 underwent LSG (mean [SD] age, 41.5 [11.3] years; 318 [63.7%] women) and 189 underwent OAGB or LRYGB (mean [SD] age, 48.6 [9.4] years; 112 [59.3%] women). There were no differences during follow-up among patients who underwent LSG vs those who underwent OAGB or LRYGB in intact parathyroid hormone levels (mean difference, 7.05 [95% CI, -28.67 to 42.77] pg/mL; P = .70), serum 25-hydroxyvitamin D levels (mean difference, -0.72 [95% CI, -1.56 to 0.12] ng/mL; P = .09), or phosphate levels (mean difference, 0.006 [95% CI, -0.052 to 0.064] mg/dL; P = .83). Hemoglobin levels were a mean 0.63 (95% CI, 0.41 to 0.85) g/dL higher among patients who underwent LSG compared with those who underwent OAGB or LRYGB (P < .001), despite no differences in iron concentration levels (mean difference, 1.50 [95% CI, -1.39 to 4.39] µg/dL; P = .31), total iron-binding capacity (mean difference, 4.36 [95% CI, -5.25 to 13.98] µg/dL; P = .37), or ferritin levels (mean difference, 3.0 [95% CI, -13.0 to 18.9] ng/mL; P = .71). Compared with patients who underwent LSG procedures, patients who underwent OAGB or LRYGB had higher folate levels (mean difference, 2.376 [95% CI, 1.716 to 3.036] ng/mL; P < .001) but lower serum magnesium levels (mean difference, -0.25 [95% CI, -0.35 to -0.16] mg/dL; P < .001) and zinc levels (mean difference, -7.58 [95% CI, -9.92 to -5.24] µg/dL; P < .001). Conclusions and Relevance: These findings suggest that LSG vs OAGB or LRYGB procedures have differential associations with various micronutrient and metabolic parameters. These differences should be recognized in guidelines for postbariatric nutritional surveillance and prevention.

Randomized control trial comparing an Alvarado Score-based management algorithm and current best practice in the evaluation of suspected appendicitis.

BACKGROUND: An objective algorithm for the management of suspected appendicitis guided by the Alvarado Score had previously been proposed. This algorithm was expected to reduce computed tomography (CT) utilization without compromising the negative appendectomy rate. This study attempts to validate the proposed algorithm in a randomized control trial. METHODS: A randomized control trial comparing the management of suspected acute appendicitis using the proposed algorithm compared to current best practice, with the rate of CT utilization as the primary outcome of interest. Secondary outcomes included the percentage of missed diagnosis, negative appendectomies, length of stay in days, and overall cost of stay in dollars. RESULTS: One hundred sixty patients were randomized. Characteristics such as age, ethnic group, American Society of Anesthesiologist score, white cell count, and symptom duration were similar between the two groups. The overall CT utilization rate of the intervention arm and the usual care arm were similar (93.7% vs 92.5%, p = 0.999). There were no differences in terms of negative appendectomy rate, length of stay, and cost of stay between the intervention arm as compared to the usual care arm (p = 0.926, p = 0.705, and p = 0.886, respectively). Among patients evaluated with CT, 75% (112 out of 149) revealed diagnoses for the presenting symptoms. CONCLUSION: The proposed AS-based management algorithm did not reduce the CT utilization rate. Outcomes such as missed diagnoses, negative appendectomy rates, length of stay, and cost of stay were also largely similar. CT utilization was prevalent as 93% of the study cohort was evaluated by CT scan. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT03324165, Registered October 27 2017).

Preoperative Weight Loss via Very Low Caloric Diet (VLCD) and Its Effect on Outcomes After Bariatric Surgery.

INTRODUCTION: The effect of preoperative weight loss via very low caloric diet (VLCD) on long-term weight loss post-bariatric surgery (BS) is conflicting. We analysed its impact on weight loss and other outcomes post-BS. METHODS: Patients (n = 306) who underwent sleeve gastrectomy or gastric bypass from 2008 to 2018 were studied. VLCD was prescribed for 14 days preoperatively. Patients were followed up for 5 years. Postoperative weight loss was compared in patients with preoperative weight gain or weight loss < 5% (WL < 5%), and weight loss ≥ 5% (WL ≥ 5%). Preoperative WL compared weight before and after VLCD; postoperative WL compared post-VLCD weight and follow-up weight. Total weight loss (TWL) encompassed pre- and postoperative WL. RESULTS: WL was < 5% in 87.3% and ≥ 5% in 12.7%. There was no significant difference in complication rate, duration of surgery or length of stay, regardless of surgical type. Patients with WL < 5% lost more weight postoperatively compared with WL ≥ 5% for up to 60 months (%postoperative WL at 1 month: WL < 5% = 13.7%, WL ≥ 5% = 10%, p = <0.001; 60 months: WL < 5% = 30.6%, WL ≥ 5% = 23.9%, p = 0.041). However, when TWL and percentage of excess body mass index loss (%EBMIL) were measured, there was no difference beyond 6 months. A predictive multivariable model for 1-year %EBMIL was formed. Significant variables included pre-VLCD BMI and preoperative WL, and the relationship between the two. CONCLUSION: Preoperative WL via VLCD was associated with reduced postoperative WL after BS, with no significant effect on complications, long-term TWL or %EBMIL. This challenges the notion that preoperative WL via VLCD should be mandated for better postoperative outcomes.

A functional network of gastric-cancer-associated splicing events controlled by dysregulated splicing factors.

Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor-normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and stringent filtering, and also identified 8 differentially expressed splicing factors (SFs). The TA ASEs occurred in genes primarily involved in cytoskeletal organization. We constructed a correlative network between TA ASE splicing ratios and SF expression, replicated it in independent gastric cancer data from The Cancer Genome Atlas and experimentally validated it by knockdown of the nodal SFs (PTBP1, ESRP2 and MBNL1). Each SF knockdown drove splicing alterations in several corresponding TA ASEs and led to alterations in cellular migration consistent with the role of TA ASEs in cytoskeletal organization. We have therefore established a robust network of dysregulated splicing associated with tumor invasion in gastric cancer. Our work is a resource for identifying oncogenic splice forms, SFs and splicing-generated tumor antigens as biomarkers and therapeutic targets.

Attitudes and perceptions of the general public on obesity and its treatment options in Singapore.

Data on attitudes and perceptions towards obesity are lacking in Asia. Participants who attended an obesity public forum were surveyed concerning obesity and its treatment options. Although obesity is generally accepted as a disease with biological underpinnings such as hormonal imbalances and slow metabolic rate, it is also regarded as an issue of personal responsibility. 65.1% believed that weight-loss medications are dangerous. 20.6% thought that pharmacotherapy is effective for weight loss, whereas 41.1% were unsure. Most believed that bariatric surgery could improve health (81.9%) and diabetes control (74.0%) although 64.1% were unsure of its risks.

Correlation Between Symptomatic Gastro-Esophageal Reflux Disease (GERD) and Erosive Esophagitis (EE) Post-vertical Sleeve Gastrectomy (VSG).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, there is one shortcoming of LSG in the long-term follow-up and this is the onset of GERD and erosive esophagitis (EE). Current evidence of the effect of SG on GERD did not consolidate to a consensus. In this study, we objectively evaluate the incidence of EE 1 year post-LSG with upper endoscopy (EGD) and try to identify the significant variables and possible underlying mechanisms of the EE post-LSG. METHODS: Over a period of 5 years (2011-2016) at Singapore General Hospital, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had LSG by a single surgeon who routinely performed EGD pre-operative and 1 year post-operative to assess EE and hiatal hernia. Patient's endoscopic findings and demographic and anthropometric data were analyzed. RESULTS: We identified a total of 97 obese patients who underwent LSG at our hospital by studied surgeon. Sixty-three patients (64.9% of original sample) were finally evaluated in the present study, 40 (59.7%) of whom were female. The mean (range) age of patients was 38.2 (18-66) years, and mean BMI was 36.3 ± 4.1 kg/m2. Median time to follow-up EGD was 13 months (range, 12-15). Following LSG, there was a significant decrease in both BMI (42.1 ± 1.2 vs. 29.9 ± 1.0 kg/m2) and percentage excess weight loss of 56.6 ± 3.6%. The prevalence of EE on endoscopy increased from 9 (14.3%) to 28 (44.4%) patients. Of which 15 (23.8%) were grade A, 11 (17.5%) were grade B, and 2 (3.2%) were grade C. There was no correlation between GERD symptoms with EE; however, our study found a trend suggesting higher prevalence of EE with a sleeve diameter measuring > 2 cm wide (p = 0.069). CONCLUSION: Although LSG is effective in treating obesity and its metabolic syndromes, the prevalence of EE increased significantly 1 year after the surgery. Since we do not fully understand the long-term impact of chronic esophagitis in post-sleeve population, we recommend follow-up EGD assessment post-operatively and treat the esophagitis if present.

Comprehensive Assessment of the Effects of Sleeve Gastrectomy on Glucose, Lipid, and Amino Acid Metabolism in Asian Individuals with Morbid Obesity.

BACKGROUND: Obesity-induced insulin resistance leads to abnormalities in glucose, lipid, and amino acid metabolism. Our study examined the differences in insulin-mediated glucose, amino acid, and lipid metabolism between morbidly obese subjects with non-obese controls and the associated changes following sleeve gastrectomy (SG). METHODS: Non-obese controls and individuals with morbid obesity and scheduled for SG were recruited. Metabolic assessments were performed for all subjects at baseline and at 6 months after SG for eight subjects. The hyperinsulinemic-euglycemic clamp technique together with comprehensive metabolomic profiling was used to quantify insulin-mediated glucose, amino acid, and lipid metabolism. RESULTS: Eleven morbidly obese non-diabetic subjects scheduled for SG and nine non-obese controls were recruited. Compared to controls, obese subjects had significantly lower glucose uptake (4.4 ± 0.6 vs. 17.3 ± 2.4 mg/kg FFM/min per µU/mL·100) and higher concentration of branched-chain amino acids (BCAAs, 332.5 ± 26.8 vs. 235.3 ± 11.0 µM), non-esterified fatty acid (52.9 ± 9.9 vs. 25.6 ± 6.7 µM), and lipid-related acylcarnitines (intermediate chain 389.8 ± 32.5 vs. 285.9 ± 20.5; long chain 301.7 ± 22.1 vs. 236.0 ± 13.3 nM) during insulin clamp. Body weight significantly reduced at 6 months after bariatric surgery (92.5 ± 6.3 vs. 115.2 ± 6.9 kg), together with improvements in insulin-mediated glucose uptake, and suppression of BCAAs, non-esterified fatty acids, and lipid-related metabolites. CONCLUSIONS: Morbid obesity in Asian individuals was associated with impairment in the regulatory actions of insulin on glucose, amino acid, and lipid metabolism, and these obesity-induced regulatory dysfunctions improved significantly 6 months after SG.

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.

Promoter elements play important roles in isoform and cell type-specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and nonmalignant gastric tissues. We identified nearly 2,000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3). Somatic promoter-associated N-terminal peptides displaying relative depletion in tumors exhibited high-affinity MHC binding predictions and elicited potent T-cell responses in vitro, suggesting a mechanism for reducing tumor antigenicity. In multiple patient cohorts, gastric cancers with high somatic promoter usage also displayed reduced T-cell cytolytic marker expression. Somatic promoters are enriched in PRC2 occupancy, display sensitivity to EZH2 therapeutic inhibition, and are associated with novel cancer-associated transcripts. By generating tumor-specific isoforms and decreasing tumor antigenicity, epigenomic promoter alterations may thus drive intrinsic tumorigenesis and also allow nascent cancers to evade host immunity.Significance: We apply epigenomic profiling to demarcate the promoter landscape of gastric cancer. Many tumor-specific promoters activate different promoters in the same gene, some generating pro-oncogenic isoforms. Tumor-specific promoters also reduce tumor antigenicity by causing relative depletion of immunogenic peptides, contributing to cancer immunoediting and allowing tumors to evade host immune attack. Cancer Discov; 7(6); 630-51. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 539.

Factors associated with and consequences of open conversion after laparoscopic distal pancreatectomy: initial experience at a single institution.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is increasingly adopted today. This study aims to determine factors associated with and consequences of open conversion after LDP. METHODS: Retrospective review of the first 40 consecutive LDP performed for pancreatic tumors from 2006 to 2015 was performed. Individual surgeon volume was stratified by ≤5 versus >5 cases and institution experience was stratified by two time periods 2006-2010 and 2011-2015. RESULTS: Two high-volume surgeons performed 19 cases with an average case volume of ≥2/year whereas 10 low-volume surgeons performed 21 cases with an average case volume of <1/year. Median age of patients was 57.6 (range, 21-78) years. LDP was performed for malignancy in four (10%) patients. The median tumor size was 25 (range, 8-75) mm. Eight patients (20%) underwent subtotal pancreatectomies and seven (17.5%) had concomitant surgeries. Eleven (27.5%) LDP were spleen-saving procedures. Ten (25%) procedures were converted to open. Twenty-nine (72.5%) patients experienced 90-day/in-hospital morbidity of which eight (20%) were major (>grade II). There were 24 (60%) pancreatic fistulas of which 10 (25%) were grade B. Univariate analyses demonstrated that splenectomy (10 (34.5%) versus 0, P = 0.025), individual surgeon volume (<5 cases) (8 (38.1%) versus 2 (10.15%), P = 0.044) and institution experience (5 (55.6%) versus 5 (16.1%), P = 0.016) were factors associated with open conversion after LDP. Open conversion was associated with an increased rate of intra-operative blood transfusion (P = 0.053). CONCLUSIONS: Splenectomy, institution experience and individual surgeon volume were the factors associated with open conversion after LDP.

Laparoscopic wedge resection for suspected large (≥5 cm) gastric gastrointestinal stromal tumors.

BACKGROUND: Laparoscopic wedge resection (LWR) for small gastric gastrointestinal stromal tumors (GIST) is now widely accepted, but its application for large GISTs remains controversial. This study aims to evaluate the feasibility and safety of LWR for suspected large (≥5 cm) gastric GISTs. METHODS: Retrospective review of 82 consecutive patients who underwent attempted LWR for suspected gastric GIST. LWR for large (≥5 cm) (n = 23) tumors was compared with LWR for small (<5 cm) tumors (n = 59). The 23 patients with LWR for large tumors were also compared to 36 consecutive patients who underwent open wedge resection (OWR) for large tumors. RESULTS: Comparison between patients who underwent LWR for large versus small tumors demonstrated that resection of large tumors was associated with a longer operating time. There was no difference in other perioperative outcomes, and oncological outcomes such as frequency of close margins (≤1 mm) and recurrence-free survival. Comparison between patients who underwent LWR versus OWR for large tumors showed that LWR was associated with decreased median time to fluid or solid diet, shorter postoperative stay but longer operating times. There was no difference in oncological outcomes. CONCLUSION: LWR for suspected large gastric GIST is feasible and safe. It is associated with similar short-term outcomes with LWR for small tumors and favorable short-term outcomes over OWR for large tumors without compromising on oncological outcomes.