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Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage states exhibited distinct cancer-associated expression profiles, individually contributing to a combined tumor-wide molecular collage. We observed increased plasma cell proportions in diffuse-type tumors associated with epithelial-resident KLF2 and stage-wise accrual of cancer-associated fibroblast subpopulations marked by high INHBA and FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences, demarcating molecular boundaries of PDOs as experimental models. We complemented these findings by spatial transcriptomics, orthogonal validation in independent bulk RNA-sequencing cohorts, and functional demonstration using in vitro and in vivo models. Our results provide a high-resolution molecular resource of intra- and interpatient lineage states across distinct gastric cancer subtypes. Significance: We profiled gastric malignancies at single-cell resolution and identified increased plasma cell proportions as a novel feature of diffuse-type tumors. We also uncovered distinct cancer-associated fibroblast subtypes with INHBA–FAP-high cell populations as predictors of poor clinical prognosis. Our findings highlight potential origins of deregulated cell states in the gastric tumor ecosystem. This article is highlighted in the In This Issue feature, p. 587

Smoke generated by cautery devices used during surgery may contain infective particles and may cause transmission of airborne viruses. This study determines whether live viruses are present in surgical smoke and evaluates the effectiveness of several proposed methods of removal so as to improve safety of healthcare workers.

Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings. This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated. 58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (p = 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (p

Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care.We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472.Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p0·0001) or without (0·704, 0·588-0·843, p0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup IAmong adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without.None.

Introduction Peritoneal carcinomatosis is difficult to treat. Pressurized Intra-Peritoneal Aerosolised Chemotherapy (PIPAC) is a novel method of delivering chemotherapy to the peritoneal cavity, aiming for homogenous and deeper drug distribution. To date, limited chemotherapeutics have been used with promising results. Here, we evaluate the pharmacokinetics, peritoneal tissue drug concentration, penetration, and short-term safety of PIPAC using solvent-based paclitaxel in swine to guide clinical trials. Materials and methods PIPAC solvent-based paclitaxel was administered at 60, 30, and 15mg/m2 for 3 cohorts. Each PIPAC procedure was followed by intravenous (IV) administration of the same dose of solvent-based paclitaxel on Day 7, serving as control for pharmacokinetic comparison in the same pig. Safety and toxicity were evaluated by clinical assessment, blood counts and biochemistry. Blood samples were taken for pharmacokinetic analysis. Peritoneal biopsies were taken to measure tissue paclitaxel concentrations and distribution. Results 12 Yorkshire x Landrace pigs underwent trial procedures. With PIPAC, there was linear pharmacokinetics and lower systemic exposure to paclitaxel compared to IV administration. MALDI-MSI demonstrated concentration of paclitaxel at the peritoneal surface, with estimated 2 mm penetration. PIPAC paclitaxel had favorable toxicity profile. The most significant adverse event was neutropenia which was dose dependent, with absolute neutrophil count Conclusion PIPAC paclitaxel at 15mg/m2 may be considered for a Phase I study.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability. Patients and Methods: We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2. Results: This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r2 = 0.95) and AUC (r2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively. Conclusions: The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases. See related commentary by de Jong et al., p. 1830

Background It has been well-established that primary bariatric surgery is effective in inducing improvement of diabetes and other associated co-morbidities in patients with obesity. Evidence demonstrating the influence of revisional bariatric surgery on this trajectory, however, is lacking. Objectives We performed a systematic review and meta-analysis to examine the impact of revisional bariatric surgery on obesity-related metabolic outcomes. Setting University Hospital, Singapore Methods We examined outcomes of remission and improvement of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea. Revisional surgeries included sleeve gastrectomy, Roux-en-Y gastric bypass, pouch revision, duodenal switch, and minigastric bypass. Results Our search identified 33 relevant studies including a total of 1593 patients. Meta-analysis of proportions demonstrated a 92% improvement in diabetes with 50% achieving remission after revisional bariatric surgery. Of patients, 81% achieved improvement of hypertension with 33% achieving complete remission. In both groups, the highest proportion of improvement was observed after revisional duodenal switch. Although reported by fewer studies, a remission of hyperlipidemia was reported in 37% of patients and improvement of obstructive sleep apnea was seen in 86% of patients. Conclusions Revisional bariatric surgery improves the outcomes of obesity-related co-morbidities and should be considered in patients with persistent metabolic disease after primary bariatric surgery.

The standard recommended treatment of stage IV gastric cancer is palliative chemotherapy. The aim of this study is to evaluate the role of radical gastrectomy with metastasectomy in these patients, as well as to explore the feasibility and safety of a laparoscopic approach. 117 consecutive patients with pathologically proven Stage IV gastric cancer who underwent radical gastrectomy with metastasectomy were enrolled in this study. We evaluated short-term and long-term outcomes, comparing laparoscopic surgery with open surgery by propensity score matching. The 5-year overall survival rate (OSR) was 23.2% and the median survival time (MST) was 19.8 months. After propensity scoring matching, the 5-year OSR and MST of laparoscopy group was 23.4%, 17.9 months and in the open group, it was 25.0%, 22.8 months (p = 0.882). The complication rate was 5.6% in the laparoscopy group and 23.4% in the open group (p = 0.069). In multivariate analysis, adjuvant chemotherapy, chemotherapy cycle, and postoperative complication were independent prognostic factors of overall survival. Radical gastrectomy with metastasectomy could have a potential role in stage IV gastric cancer. Laparoscopic gastrectomy with metastasectomy in selected stage IV gastric cancer patients is safe and feasible.

Introduction Obesity is a risk factor for pregnancy-induced hypertension, preeclampsia, gestational diabetes, and large gestational age pregnancy. Bariatric surgery is widely accepted to treat obesity but associated with small for gestational age fetuses. Objective To report maternal and fetal outcomes after bariatric surgery in morbidly obese Asian females. Setting University Hospital, Singapore. Methods We maintain a prospective cohort of patients who underwent bariatric surgery in our institution. Maternal and fetal outcomes are compared with a control group of 31 pregnancies matched for age, parity, presurgery weight, and year of delivery. Results Twenty-four pregnancies occurred in 16 patients in our postoperative cohort. Morbidly obese women in the control group were more likely to develop gestational diabetes (19.3% versus 5.0%, P = .150) and pregnancy-induced hypertension/preeclampsia (32.2% versus 0%, P = .003) compared with the postoperative group. Of fetuses, 37.5% in the bariatric group had low birth weight compared with only 9.4% fetuses in the control group (P = .016). Preoperative body mass index, short interval between conception and surgery, and poor weight gain during pregnancy did not predict for small for gestational age fetuses. Subsequent weights were available for 37.5% of the children in the surgical cohort and none of these children exhibited growth retardation. Conclusion Bariatric surgery lowers the risk of maternal co-morbidities and large gestational age fetus during pregnancy. Asians are at high risk of small for gestational age pregnancies after bariatric surgery and should undergo close monitoring for fetal growth throughout their pregnancy.

Background The effect of bariatric surgery on improvement and remission of type 2 diabetes (T2D) is well studied. The effect of surgery on glycemic profiles of obese, but nondiabetic individuals is unknown. Objectives We aimed to study changes in glycemic indices in obese nondiabetics undergoing bariatric surgery and correlate fat mass loss with changes in glycemic profiles. Setting University Hospital, Singapore. Methods A prospective database of nonT2D patients who underwent bariatric surgery between April 2009 and December 2014 was analyzed. Changes in weight, fat mass, and glycemic profiles, including glycated hemoglobin, C-peptide levels, and the homeostasis model assessment of insulin resistance were studied at 1- and 3-year follow-up. Results One hundred thirty-three nondiabetics underwent bariatric surgery in the study period. Twenty-nine (21.8%) patients were found to have impaired fasting glycemia. We observed reductions in mean fat mass from 47.4 ± 12.2 kg preoperatively to 27.8 ± 11.6 kg at 1 year. Despite mean fat mass regain to 33.9 ± 19.6 kg at 3 years, homeostasis model assessment of insulin resistance improved from severe insulin resistant state of >5.00 (7.13 ± 11.5) preoperatively to normal ranges of Conclusion Bariatric surgery results in significant sustained weight loss in obese nondiabetics and normalizes glycated hemoglobin and homeostasis model assessment of insulin resistance after surgery. It is a promising modality to prevent or delay the onset of T2D in obese nondiabetic patients. Further studies should be conducted in nondiabetics to assess the efficacy of bariatric surgery in prevention of T2D onset in the longer term.

The aim of the study was to assess the impact of pouch reconstruction on perioperative outcomes, postprandial symptoms, nutritional and anthropometric parameters, and overall quality of life after total gastrectomy for gastric malignancy.The short-term perioperative risks and longer term functional value of creating a small-bowel reservoir after total gastrectomy are contended.A search for randomized and non-randomized studies comparing reconstruction with or without a pouch was conducted. Treatment effects were computed using pairwise random-effects meta-analysis and meta-regression, and the systematic review was conducted in accordance with PRISMA and MOOSE guidelines.A total of 17 randomized trials and 8 observational studies involving 1621 participants were included. Pouch creation is associated with an increased operation time [259.3 vs 235.8 min; weighted mean difference (WMD) 23.5, 95% confidence interval (CI) 9.8-37.2], but not hospitalization duration. There was no difference in overall postsurgical complications, including anastomotic leak and abdominal abscess. Pouch formation markedly reduces the risk of dumping syndrome at 3 to 6 months [8.1% vs 32.4%; risk ratios (RR) 0.36, 95% CI, 0.21-0.60] and 12 to 24 months (2.8% vs 23.6%; RR 0.27, 95% CI, 0.16-0.46). The functional advantages of pouch reconstruction persist at 1 to 2 years, with aggregated data indicating considerably lower risks of esophagitis and heartburn (63% relative reduction), dumping syndrome (73% relative reduction), and food intake disturbance (50% relative reduction). At 12 to 24 months, albumin levels (40.5 vs 37.9 g/L; WMD 2.59, 95% CI, 1.35-3.84) and body mass index (22.2 vs 20.9 kg/m; WMD 1.28, 95% CI, 0.61-1.94) are significantly higher among participants with a pouch.Pouch creation improves long-term functional and nutritional outcomes after total gastrectomy, without greater perioperative morbidity.

Objective Laparoscopic appendectomy is a common operation that is frequently performed by junior surgical residents. We investigated the effect of a structured training program on the proficiency of junior residents in acquiring skills necessary in this operation. Design and Participants This is a randomized pilot trial. Between December 2014 and July 2018, twenty junior residents were recruited for this study. 11 were randomized to receive a structured training program of supervised, task-specific training. Each resident subsequently performed ten cases of laparoscopic appendectomy with their performance assessed for the last 5. The GOALS scale was used as the primary endpoint. Secondary endpoints were perioperative outcomes. The effect of intervention on these outcomes were evaluated assuming a linear mixed effect multi-level model. The study was single-blinded as the assessors did not know which group each resident belonged to. Results There were no statistically significant differences in the total GOALS score or any of its individual domains. After adjusting for the number of operations done within the trial, the mean difference between the total GOALS score was 0.07 (95% CI -0.76 to 0.90, P=0.866). Blood loss, hospital stay and postoperative complication rates were similar. There was suggestion of a shorter operative time (effect estimate -9.03, 95% CI -19.56 to 1.50) in the intervention arm although statistical significance was not achieved. No avoidable adverse events due to this study were recorded. Conclusion Structured training program did not significantly improve surgical performance and outcomes in laparoscopic appendectomy in this pilot trial. Despite these findings, residents can still potentially mount their learning curves in laparoscopy earlier in a safe environment with such a program which is especially important in the era of minimally invasive surgery.

Background Bleeding of the gastrointestinal tract (BGIT) is a common gastrointestinal emergency. There is no consensus whether this condition should be admitted to medical or surgical discipline. Timing of presentation may also impact patient outcomes due to differences in healthcare resource availability. This study thus aims to investigate the impact of admitting discipline and timing of admission on patient outcomes in BGIT. Methods A 2-year tertiary institution database was retrospectively reviewed. Outcome measures included 30-day mortality, 30-day readmissions and rebleeding requiring repeat endoscopic, angiographic or surgical interventions. Secondary outcome measures included time to endoscopy, percutaneous angiographic interventions and surgery. The effect of admission discipline (medical versus surgical) and time of admission (office-hours versus after office-hours) were analysed using a propensity-score-adjusted estimate. Results A total of 1384 patients were included for analysis, medical (n = 853), surgical (n = 530); during office-hours (n = 785) and after office-hours (n = 595). After propensity-score-adjusted analysis, no significant differences in mortality or readmissions were noted between medical or surgical admissions. Patients admitted under surgery were less likely to sustain rebleeding (P = 0.004) for lower BGIT and had an earlier time to endoscopy for upper BGIT (P = 0.04). Patients admitted after office-hours had similar outcomes with those admitted during office hours apart from a delay in time to endoscopy (P = 0.02). Conclusion For BGIT patients, admission to a surgical discipline compared to a medical discipline appeared to have at least equivalent patient outcomes. Patients presenting with BGIT after office-hours were more likely to experience a delay to endoscopy, although it did not affect patient mortality.

Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a novel surgical technique to administer aerosolized chemotherapy into the abdominal cavity as treatment for peritoneal metastasis from various cancers. As the surgery is unique and there are concerns about occupational hazards, specific anaesthetic setup and techniques are required. Notably, our institution’s experience with PIPAC has enlightened us that anaesthesia requirements during PIPAC are generally uncomplicated and that the majority of the patients undergoing PIPAC do not require invasive monitoring, advanced intra or postoperative analgesia like epidurals or PCA. The need for postoperative intensive unit care is also not required in routine PIPAC cases. We describe the anaesthetic considerations involved and the detailed preparation of staff, space, anaesthetic equipment and drugs to facilitate the appropriate modifications for anaesthesia monitoring and maintenance for an elective set up as well as our standard operating procedure for an emergency situation should it arise.

Background & Aims Metaplasia and dysplasia in the corpus are reportedly derived from de-differentiation of chief cells. However, the cellular origin of metaplasia and cancer remained uncertain. Therefore, we investigated whether pepsinogen C (PGC) transcript–expressing cells represent the cellular origin of metaplasia and cancer using a novel Pgc-specific CreERT2 recombinase mouse model. Methods We generated a Pgc-mCherry-IRES-CreERT2 (Pgc-CreERT2) knock-in mouse model. Pgc-CreERT2/+ and Rosa-EYFP mice were crossed to generate Pgc-CreERT2/Rosa-EYFP (Pgc-CreERT2/YFP) mice. Gastric tissues were collected, followed by lineage-tracing experiments and histologic and immunofluorescence staining. We further established Pgc-CreERT2;KrasG12D/+ mice and investigated whether PGC transcript–expressing cells are responsible for the precancerous state in gastric glands. To investigate cancer development from PGC transcript–expressing cells with activated Kras, inactivated Apc, and Trp53 signaling pathways, we crossed Pgc-CreERT2/+ mice with conditional KrasG12D, Apcflox, Trp53flox mice. Results Expectedly, mCherry mainly labeled chief cells in the Pgc-CreERT2 mice. However, mCherry was also detected throughout the neck cell and isthmal stem/progenitor regions, albeit at lower levels. In the Pgc-CreERT2;KrasG12D/+ mice, PGC transcript–expressing cells with KrasG12D/+ mutation presented pseudopyloric metaplasia. The early induction of proliferation at the isthmus may reflect the ability of isthmal progenitors to react rapidly to Pgc-driven KrasG12D/+ oncogenic mutation. Furthermore, Pgc-CreERT2;KrasG12D/+;Apcflox/flox mice presented intramucosal dysplasia/carcinoma and Pgc-CreERT2;KrasG12D/+;Apcflox/flox;Trp53flox/flox mice presented invasive and metastatic gastric carcinoma. Conclusions The Pgc-CreERT2 knock-in mouse is an invaluable tool to study the effects of successive oncogenic activation in the mouse corpus. Time-course observations can be made regarding the responses of isthmal and chief cells to oncogenic insults. We can observe stomach-specific tumorigenesis from the beginning to metastatic development.

Introduction: There is a dearth of literature on frailty specifically in elderly (aged ≥65 years) gastric cancer patients undergoing gastrectomy. We aim to assess the effects of frailty on postoperative outcomes. Methods: A review of a prospective database was performed from November 2011 to April 2019. Frailty was assessed by multidimensional frailty score (MFS). Outcomes assessed were early postoperative complications and mortality, and length of stay. Results: 289 patients were included. The mean age was 77.3 (range 66–94) years. 183 (63.3%) were males and 172 (59.5%) had early cancer. 275 (95.2%) underwent minimally invasive gastrectomy. 79 (27.3%) patients suffered early postoperative complications, with 47 (16.3%) suffering from Clavien-Dindo grade ≥2 complications. One-year, 90-day, 30-day, and inhospital mortality were 6.6, 1.4, 0.7, and 0%, respectively. 111 (38.4%) of patients were classified as “frail” based on MFS > 5. “Frail” patients were associated with higher 1-year mortality (odds ratio (OR) 4.51, 95% CI 1.57–12.98, p = 0.005) on univariate analysis. On multivariate analysis, “frail” patients did not have significantly increased 1-year mortality. However, when definition of “frail” was changed from MFS > 5 to MFS > 6, frailty was significantly associated with increased 1-year mortality (OR 3.73, 95% CI 1.11–12.53, p = 0.033). Conclusions: Elderly gastric cancer patients undergoing gastrectomy with MFS > 5 do not have increased mortality risk. The influence of frailty on postoperative outcomes may vary based on the risk of the surgical procedure.

Introduction: A Dieulafoy lesion is a large tortuous submucosal arteriole protruding through a small mucosal defect.1 It is uncommon but potentially life threatening.2 Endoscopic hemostasi...

Changes in body composition after bariatric surgery such as a sustained loss of body fat are often associated with an inevitable loss of fat free mass. This can contribute to an undesirable disturbance in resting metabolic rate and weight maintenance. Our aim was to study changes in body composition in a multiethnic Asian cohort following bariatric surgery and to identify differences between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. A retrospective review of prospectively collected data on 295 patients who underwent either laparoscopic sleeve gastrectomy (256 patients) or laparoscopic Roux-en-Y gastric bypass (39 patients) was performed. Body composition variables were measured with the analyzer, GAIA 359 PLUS, which included the parameters; total body weight, body mass index, excess weight, basal metabolic rate, fat-free mass, fat mass, and total body water. There were no statistical differences in gender, ethnicity, age, weight, height, and body mass index between laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. At each time point (6, 12, 24, and 36 months) post-operation, there was no significant differences in % total body weight loss, basal metabolic rate, fat mass, fat percentage, and total body water between sleeve gastrectomy and bypass patients. There was significant difference (p

Endoscopic therapy remains the cornerstone of hemostasis for gastrointestinal bleeding. In situations where hemostasis cannot be achieved via endoscopic or radiological methods, surgery is necessary. Traditional open surgery for bleeding gastric ulcers can be very morbid and unsuitable especially in hemodynamically unstable patients in extremis. We describe a minimally invasive, transgastric approach for underrunning and closure of Cameron ulcers. Our patient is a 75-year-old Chinese lady, who presented to the emergency department with fresh melena. She was hemodynamically unstable with severe metabolic acidosis. CT angiography revealed blood clots within the stomach, with no active blush. On urgent gastroscopy, large blood clots obscured the site of hemorrhage. A Mallory-Weiss tear was noted. Our patient subsequently underwent a successful single-incision laparoscopic transgastric (SLT) underrunning and closure of two Cameron ulcers. Our patient had an uneventful recovery and subsequently underwent a successful laparoscopic para-esophageal hernia repair on postoperative day 9. A SLT approach is a suitable minimally invasive option for the surgical management of hemostasis and closure of bleeding gastric ulcers not amenable to endoscopic or radiological interventions.

Laparoscopic gastrectomy (LG) is now a widely accepted treatment option for gastric cancer. However, there is insufficient evidence for LG for advanced gastric cancer (AGC). Many retrospective studies have shown that LG for AGC is safe and feasible, but very few studies have shown the actual outcome in general practice. The aim of this study is to analyze our last 15 years of experience in LG for AGC. This is a retrospective review from May 2003 to May 2017 in Seoul National University Bundang Hospital. A total of 1592 patients who had LG for AGC were enrolled of which 109 patients with open conversion were excluded. We evaluated the short-term and long-term oncologic outcomes of LG for AGC. A total of 1483 patients were analyzed. There were 432 cases of total gastrectomy, 982 cases of distal gastrectomy, and 69 cases of proximal gastrectomy. The total complication rate was 9.1% (135/1483), which included wound-related complications (0.7%), postoperative bleeding (0.5%), anastomosis or stump leakage (2.2%), intestinal obstruction (0.9%), pancreatic fistula (0.1%), intra-abdominal abscess (1.6%), and lung morbidity (3.0%). The rate of Clavien-Dindo grade 3 and above complications was 4.9%. Age was the only significant risk factor in multivariate analysis (OR 1.02; 95% CI, 1.01–1.04, P = 0.01). 5-year overall survival stratified by stage was as follows: stage IB 88.9%, stage IIA 88.7%, stage IIB 84.2%, stage IIIA 71.7%, stage IIIB 56.8%, stage IIIC 45.4%, and stage IV 25%. Total recurrence rate was 14.4%, which included local recurrence (1.1%) and distant metastases (13.3%). During our 15 years of experience, we have successfully performed 1483 cases of AGC with laparoscopy. Our results showed short-term and long-term oncologic outcomes that were comparable with other studies. LG is safe and feasible in general practice for advanced gastric cancer when performed by experienced surgeons.

Prevalence of obesity in Asia has been on the increasing trend, with corresponding increase in utilisation of bariatric surgery. The objective of this study was to examine differences in weight loss outcomes following bariatric surgery between Asian ethnicities. A retrospective database review was conducted of patients undergoing primary laparoscopic sleeve gastrectomy between 2009 and 2013 in 14 centres from Singapore, Malaysia, Taiwan, Hong Kong, Japan, Korea, India, Australia, Switzerland, and the USA. All patients with available follow-up data at 12 months and 36 months post-surgery were included in this study. Outcome measures used were percentage excess weight loss (%EWL) and percentage total weight loss (%TWL). Differences in outcomes between ethnicities were analysed after adjusting for age, gender, baseline body mass index (BMI), and presence of diabetes. The study population (n = 2150) consisted of 1122 Chinese, 187 Malays, 309 Indians, 67 Japanese, 259 Koreans, and 206 Caucasians. 67.1% were female and 32.9% were male. Mean age was 37.1 ± 11.2 years. Mean pre-operative BMI was 40.7 ± 8.1 kg/m2. With the Caucasian population as reference, Japanese had the best %TWL (3.90, 95% CI 1.16–6.63, p

Incidence of non-alcoholic fatty liver disease (NAFLD) is on the rise and is one of the most common causes of chronic liver disease worldwide. Obesity and metabolic syndrome are considered the most significant risk factors. Bariatric surgery is the only treatment modality in morbid obesity which allows long-term weight loss with improvement in associated co-morbid conditions. However, the effects of bariatric surgery on NAFLD are not well established. NAFLD fibrosis score (NFS) is a validated non-invasive scoring system used to assess advanced fibrosis. We used the NFS to analyse the impact of weight loss on NAFLD following sleeve gastrectomy.174 patients who underwent bariatric surgery between 2010 and 2016 were retrospectively reviewed. Multivariate analysis was performed using pre-operative patient characteristics, biochemical markers and TANITA body analysis measurements to determine significant risk factors for NFS 0.675. Additionally, the NFS was calculated at 6 months, 1 year and 2 years post-operatively to determine correlation with weight loss.Pre-operatively, 13.8% of our patients had significant fibrosis by NFS. Mean change in NFS was - 0.46 ± 1.02, - 0.55 ± 0.98 and - 0.55 ± 1.12 at 6 months, 1 year and 2 years respectively. This was significantly correlated with percent of total weight loss with R coefficients of 0.253, 0.292 and 0.274 respectively (P 0.05). 79.2% of patients with NFS 0.675 achieved resolution by 2 years post-operatively.Based on our study, we conclude that sleeve gastrectomy may be a viable treatment option for management of NAFLD in the obese.

165 Background: The addition of intraperitoneal (IP) paclitaxel (PTX) to systemic chemotherapy comprising taxane/fluoropyrimidine doublet has shown promising results for patients with gastric cancer (GC) and peritoneal metastases (PM). However, this has not been studied in combination with platinum/fluoropyrimidine doublet which is the current standard-of-care for metastatic GC. We conducted a prospective phase 2 trial of IP PTX with capecitabine and oxaliplatin (XELOX) in patients with GCPM. Methods: The trial enrolled 44 patients with GCPM who received treatment comprising IP PTX (40mg/m2 on day 1,8), PO capecitabine (1000mg/m2 twice daily from day 1-14) and IV oxaliplatin (100mg/m2 on day 1) in 21-day cycles. Patients with synchronous GCPM were eligible for conversion surgery comprising radical gastrectomy if they had good response after chemotherapy, negative cytology on 2 consecutive peritoneal fluid assessments, no extraperitoneal metastasis and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were also compared with a retrospective cohort of 39 patients with GCPM who received identical systemic chemotherapy (SC) comprising platinum/fluoropyrimidine agents alone. Results: The median OS for the IP and SC groups was 14.6 and 10.6 months (HR 0.44; 95% CI, 0.26-0.74; P=0.002). The 1-year OS was 67.8% in the IP group and 32.3% in the SC group (Logrank p

Highlights • Discussion on minimally invasive approaches to acute groin hernia surgery. • Technical ‘tips and tricks’ for emergency laparoscopic repair of femoral hernia. • Review of the current literature., Introduction Femoral hernias frequently present with incarceration, resulting in obstruction and strangulation. Laparoscopic groin hernia repairs have been shown in the elective setting to be an effective alternative to open repair. Acute incarceration of groin hernia with obstruction, though previously seen as a relative contraindication, has been increasingly repaired with minimally invasive techniques, with the potential benefit of avoiding the morbidity associated with a laparotomy. Presentation of case and discussion We describe a case of an acutely incarcerated femoral hernia with intestinal obstruction that was repaired using the totally extra-peritoneal approach. A releasing incision was performed to facilitate reduction of hernia prior to mesh repair. Diagnostic laparoscopy through a separate incision was then performed. Conclusion This modification of the TEP repair technique for the acutely incarcerated and obstructed femoral hernia serves to minimise potential contamination by keeping the pre-peritoneal plane strictly separate from the intra-peritoneal space.

This article was updated to correct Do Joong Park’s name: Do Joong (given name) Park (family name).

360 Background: PIPAC is a novel, laparoscopic intraperitoneal chemotherapy delivery technique which aims to improve on hyperthermic intraperitoneal chemotherapy (HIPEC), ameliorating drug distribution and tissue penetration. Thus far, PIPAC has been conducted with oxaliplatin chemotherapy in Europe, at an arbitrary dose of 92mg/m2; 150mg/m2 was found to be intolerable. We conducted a dose-escalation phase 1 study to establish the safety, tolerability and recommended phase 2 dose (RP2D) for PIPAC in Asian patients. Methods: This phase 1 study of oxaliplatin administered via PIPAC was designed as a traditional 3+3 dose escalation study for patients with predominant peritoneal metastasis from a gastrointestinal primary tumor, after failure of standard therapies. Dose levels were planned at 45, 60, 90 and 120mg/m2. Repeat doses of PIPAC were permitted, 6 weeks apart. Dose limiting toxicities (DLT) were defined as any clinically relevant grade 3 adverse events occurring within 28 days after PIPAC. Results: This study included 16 patients (25 PIPAC procedures; 8 gastric, 4 colorectal and 1 gallbladder, pancreas and appendix cancer each). Median age was 62 years, with a median peritoneal carcinomatosis index (PCI) score of 17 (range 1 - 39). Two patients developed pancreatitis (grade 2 and 3) on day 6 and day 9 after PIPAC administration at the dose cohort of 45mg/m2, necessitating cohort expansion to 6 patients. One patient was noted to have asymptomatic grade 3 hyperamylasemia (90mg/m2 cohort). There were no other DLTs and all 3 patients in the highest dose cohort (120mg/m2) tolerated PIPAC well. Nine patients who underwent a 2nd PIPAC procedure had a decrease in PCI score from 18.4 to 15.5; one patient at 120mg/m2 had an improvement in PCI from 30 to 12. Conclusions: The RP2D of PIPAC with oxaliplatin is 120mg/m2. Single agent PIPAC is well tolerated, and future studies with PIPAC must consider a bi-directional approach with the incorporation of systemic therapy, with either chemotherapy or immunotherapy to improve efficacy. Clinical trial information: NCT03172416.

Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain. A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888). Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD—2.47 days, 95% CI − 3.06 to − 1.89, P

Despite the high incidence of reflux esophagitis, there are few reports of antireflux modifications for minimally invasive Ivor-Lewis esophagectomy. We present the case of a 63-year-old man with mid-thoracic esophageal squamous cell carcinoma who underwent minimally invasive Ivor-Lewis esophagectomy after neoadjuvant chemoradiotherapy. Laparoscopic dissection, gastric tube creation, and mobilization was performed. Thoracoscopic esophageal dissection, subcarinal, paraesophageal and diaphragmatic lymphadenectomy were performed, followed by esophagogastric anastomosis with double seromuscular flap reconstruction to recreate the lower esophageal sphincter. The operation was completed in 618 minutes with 200 mL blood loss and the patient recovered uneventfully. A morphologic sphincter was seen on postoperative contrast study.

BackgroundPressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel laparoscopic intraperitoneal chemotherapy technique, with advantages such as homogeneous distribution of aerosol and deeper tissue penetration. Thus far, PIPAC oxaliplatin has been administered at an arbitrary dose of 92 mg/m2.AimWe aim to determine the dose-related safety profile and tolerability of PIPAC oxaliplatin using an evidence-based approach. The secondary aim is to evaluate clinic-pathologic response and the pharmacokinetic profile.MethodsThis is a phase I 3+3 dose escalation study for gastric and colorectal cancer with predominant peritoneal metastasis starting at a dose of 45 mg/m2. Safety is assessed according to Clavien-Dindo Classification and Common Terminology Criteria for Adverse Events (version 4.0). Clinico-pathologic response is assessed using the Peritoneal Regression Grading Score, Peritoneal Cancer Index, and Response Evaluation Criteria In Solid Tumour criteria (version 1.1). Pharmacokinetic analysis is performed using Inductively Coupled Plasma-Mass Spectrometry assay. This trial is registered on ClinicalTrials.gov (NCT03172416).ConclusionsThis phase I study can provide the scientific basis to identify the optimal dose for PIPAC with oxaliplatin such that the benefits of this novel and promising intraperitoneal chemotherapy delivery technique can be maximized.

Single-incision laparoscopic hepatic resection has been attracting increased attention from the surgical community in recent years. While there have been reports and studies on this procedure, none has suggested the possibility of doing repeated hepatic resections via a single incision. This report on three such cases aims to determine the feasibility and safety of this approach for such patients. Three patients who had previously had liver resections underwent single-incision laparoscopic hepatic resection in our center. Patient demographics, type of port and instruments used, operating time, complications and incision length were collected. The operating time in each case was less than 230 min. The incision length for the single-port device was 3.5 cm or less. The length of hospital stay was less than 5 days in each case. Intra-operative blood loss was limited to 250 mL in each case. There were no immediate postoperative complications related to hepatic resection. Single-incision laparoscopic hepatic resection is feasible for selected patients who have had previous hepatic resections. Because the port entry site for the single-incision laparoscopic approach is usually slightly larger than that for the conventional approach, it is safer in re-resection cases where there may be adhesions from previous surgery. Other possible benefits, such as cosmesis and reduced port-associated morbidity, are mainly related to the use of only one small incision.

Background Per-Oral Endoscopic Myotomy (POEM) has been adopted as a treatment option for Achalasia, with similar efficacy and safety profile as laparoscopic Heller Myotomy. However, issues of acid reflux and reflux oesophagitis have often plagued these patients. We aim to evaluate the clinical outcomes and resolution of reflux disease among individuals post-POEM. Methods A prospective review was performed for all patients who have undergone POEM from January 2014 to December 2017, with individuals analysed at the 1 year mark post-POEM. Subjective assessment of reflux was performed using self-administered questionnaires, with 24h pH impedence test and high resolution manometry providing objective correlation. Results Forty-three individuals underwent POEM during the 4 year period. The median age was 52 years (range, 24–78), with half being males (53.5%). The individuals had a median ASA score of 2 (range, 1–3). Majority of the individuals had type II achalasia (58.1%) followed by type I (34.9%) and type III (7%). Patients presented with dysphagia (88.4%) and reflux (10%); symptomatic for a median of 36 months (range, 3–540). One-third required the use of proton pump inhibitors (PPI) for symptomatic relief, with 35% receiving prior interventions for achalasia. These patients had a median Integrated Relaxation Pressure (IRP) of 23.6 mmHg (range, 4.6–160) and a median Eckardt score of 6 (range, 1 -11). One-third developed complications such as mucosal injury (18.6%), carbon dioxide pneumoperitoneum (16.3%) and bleeding (4.7%). The median length of stay was 3 days (range, 1–6). At the 1 year mark, 86% reported improvement in dysphagia (p: 0.043) with 66% having reduction in ratings for their severity (p: 0.002) and frequency (p: 0.05) of reflux. The median IRP (23 vs 13 mmHg) was also significantly lower (p: 0.005). However, only 38.5% correlated with a normal acid exposure on the impedence test (p: 0.592). Conclusion POEM is a promising solution in the management of achalasia given good clinical response for dysphagia and reflux. However, excessive lower oesophageal acid exposure may still be present in almost half of these patients, which may be alleviated with the use of long term use of PPI. Disclosure All authors have declared no conflicts of interest.

Single-port endo-laparoscopic surgery has gained support in the surgical community because it is perceived to offer a better postoperative outcome as it requires only a single incision. We write this prospective observational study to ascertain the feasibility and safety of this technique in patients otherwise requiring two operations. Five patients who underwent double procedures with a single-port device were reviewed: Case 1, a transabdominal preperitoneal hernia repair and gastric wedge resection; Case 2, cholecystectomy and diaphragmatic hernia repair; Case 3, oophorectomy and incisional hernia repair; Case 4, anterior resection of the rectum and hepatic segmentectomy; and Case 5, left adrenalectomy and cholecystectomy. Patient demographics, type of port used, operative time, complications and incision length were collected. Mean operative time for the cases ranged from 100 to 315 min. Incision length for the single-port device was 2 cm. In Case 2, an additional 5-mm port was used and an intraoperative complication involving a laceration of the liver occurred during the suturing of the gallbladder fundus. An additional 8-cm lower abdominal incision (Pfannenstiel) was required in Case 4 to complete the colonic anastomosis and for specimen retrieval. Single-port endo-laparoscopic surgery is a feasible and safe technique for approaching double procedures. It drastically reduces the number of scars that a double procedure creates, and if difficulty arises, another port can always be added to ease the operation. It can also potentially reduce the number of admissions and anesthesia that a patient undergoes.

Peritoneal recurrence after gastrectomy for gastric cancer is common and the prognosis is dismal. Recent evidence suggests that extensive peritoneal lavage with large volume of normal saline after surgery before abdominal closure can reduce the risk of peritoneal recurrence and improve overall survival. This study aims to evaluate the benefit of extensive intraoperative peritoneal lavage. This is a prospective, open-label, multicentre randomised controlled trial involving 15 international centres in China, Korea, Japan, Malaysia and Singapore. Patients with cT3/4 stomach cancer undergoing curative resection are randomised to either extensive peritoneal lavage (10 l of saline) or standard lavage (≤2 l of saline). The primary outcome is overall survival and secondary outcomes include disease-free survival and peritoneal recurrence. The minimum sample size is 600 subjects with 300 per arm completing 3 years follow-up. The data will be analysed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance.

The preoperative use of gastroscopy for patients undergoing bariatric surgery remains controversial. We aim to evaluate the diagnostic yield of gastroscopy and the clinical significance in asymptomatic individuals undergoing bariatric surgery in Asia. We retrospectively reviewed the medical records of all patients undergoing gastroscopy prior to bariatric surgery at the National University Hospital and Khoo Teck Puat Hospital, Singapore, between Jan 2006 and June 2013. Gastroscopy findings were classified into four groups: group 1 (normal study), group 2 (abnormal findings that do not modify surgical approach), group 3 (abnormal findings that modify surgical approach) and group 4 (absolute contraindications to immediate surgery). During the study period, 208 asymptomatic individuals were evaluated by gastroscopy prior to bariatric surgery. Gastroscopy was normal in 70 (33.6 %). Group 2 comprised 67 (32.2 %) patients with mild gastritis or oesophagitis. Group 3 included 69 (33.2 %) patients diagnosed with erosive gastritis or oesophagitis, peptic ulcer disease, hiatal hernia or mass lesions. There were 2 patients (1.0 %) in group 4. One patient had a gastro-oesophageal junction adenocarcinoma, and 1 had a gastrointestinal stroma tumour. In group 3, modification of surgical approach included concurrent hiatal hernia repair, institution of medical therapy with delay in surgery, further evaluation of mass lesions and change in choice of surgical procedures. Routine gastroscopy for asymptomatic bariatric patients has a high diagnostic yield. Given the high percentage of patients with clinically important lesions, our current experience supports the use of routine preoperative gastroscopy prior to bariatric surgery in Singapore.

Conventional laparoscopic cholecystectomy is the gold standard surgical treatment for symptomatic gallstones. Surgeons have attempted to minimize the number of incisions via single-incision laparoscopic cholecystectomy (SILC), which offers benefits including improved cosmesis, possibly less postoperative pain, and improved patient satisfaction. However, studies show that there is an increased risk of operative complications—in particular bile duct injuries. We report 500 consecutive cases of SILC performed without bile duct injury. A retrospective study of 500 continuous cases of SILC performed by the same surgeon at a single institution was conducted. Data on patient demographics, operative details, and postoperative outcomes were collected and evaluated. Detailed analysis of surgical techniques specifically to reduce bile duct injury was performed and described in this study. In total, 500 patients underwent SILC during the study period. Eight patients needed additional ports to complete the surgery, while one was converted to an open surgery. No serious intraoperative complications, such as bile duct injury, were encountered. Our experience shows that with due care and caution during SILC, with particular attention towards achieving the critical view of safety and a standardized technique, bile duct injury in SILC can be avoided.

With widespread acceptance of laparoscopic surgery, efforts are aimed to minimize further surgical trauma. The last decade has seen a few novel approaches, such as mini-laparoscopy, needlescopic surgery, natural orifice translumenal endoscopic surgery (NOTES), and single-port endo-laparoscopic surgery (SPES). The latter two methods are the most recent surgical innovations that have heralded the trend toward scarless and less invasive surgery. While current clinical application of NOTES requires significant improvement in technique and technology, SPES can be performed with the refinement of existing laparoscopic instruments and is gaining popularity among surgeons and patients. SPES was first performed and reported as early as 1992 by Pelosi, which were single-puncture laparoscopic appendectomy and hysterectomy. Since then, many case reports and case series have emerged in the fields of gastrointestinal, urological, and gynecological surgery using the reduced port technique. In this chapter we will review and discuss the prevailing controversies in SPES for combined surgical procedures. For the purpose of this chapter, we will use the term SPES, even though there are several accepted definitions and no agreement among the surgical community regarding the best term.