Publications by authors named "Nicholas Syn"

107 Publications

Laparoscopic liver resection for huge (≥10 cm) hepatocellular carcinoma: A coarsened exact-matched single-surgeon study.

Surg Oncol 2021 Apr 3;37:101569. Epub 2021 Apr 3.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore. Electronic address:

Introduction: Laparoscopic liver resection (LLR) is increasingly being utilised worldwide for the management of both benign and malignant liver tumours. However, there is limited data to date regarding the safety and feasibility of this approach for huge (≥10 cm) hepatocellular carcinomas (HCCs). We present here our early experience performing LLR for huge HCCs.

Methods: We conducted a retrospective review of 280 consecutive patients who underwent LLR by a single surgeon from 2012 to August 2020.15 patients had a preoperative radiological diagnosis of huge (≥10 cm) HCC. Coarsened exact-matched (CEM) weighting was used to compare them to 101 patients who underwent LLR for non-huge HCC.

Results: After CEM-weighting, both groups were well-balanced for baseline variables. There was no difference in the rates of open conversion. The huge HCC patients had a higher mean Iwate difficulty score than the non-huge HCC patients (9.13 vs 6.53, p = 0.007). As such, the median operating time for the huge HCC group was longer (360 min vs 240min, p = 0.049). However, there were no significant differences in estimated blood loss, proportion of patients requiring blood transfusion, utilization of Pringle maneuver or median Pringle duration. Post-operatively, there were no significant differences in median LOS, overall and major morbidity rates, and 90-day mortality rates between both groups. Median resection margins were also similar for both cohorts.

Conclusion: LLR may be performed successfully for selected patients with huge HCC, with encouraging perioperative outcomes and no compromise in oncologic efficacy.
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http://dx.doi.org/10.1016/j.suronc.2021.101569DOI Listing
April 2021

Learning curves in minimally invasive hepatectomy: systematic review and meta-regression analysis.

Br J Surg 2021 Mar 29. Epub 2021 Mar 29.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.

Background: Minimally invasive hepatectomy (MIH) has become an important option for the treatment of various liver tumours. A major concern is the learning curve required. The aim of this study was to perform a systematic review and summarize current literature analysing the learning curve for MIH.

Methods: A systematic review of the literature pertaining to learning curves in MIH to July 2019 was performed using PubMed and Scopus databases. All original full-text articles published in English relating to learning curves for both laparoscopic liver resection (LLR), robotic liver resection (RLR), or a combination of these, were included. To explore quantitatively the learning curve for MIH, a meta-regression analysis was performed.

Results: Forty studies relating to learning curves in MIH were included. The median overall number of procedures required in studies utilizing cumulative summative (CUSUM) methodology for LLR was 50 (range 25-58) and for RLR was 25 (16-50). After adjustment for year of adoption of MIH, the CUSUM-derived caseload to surmount the learning curve for RLR was 47.1 (95 per cent c.i. 1.2 to 71.6) per cent; P = 0.046) less than that required for LLR. A year-on-year reduction in the number of procedures needed for MIH was observed, commencing at 48.3 cases in 1995 and decreasing to 23.8 cases in 2015.

Conclusion: The overall learning curve for MIH decreased steadily over time, and appeared less steep for RLR compared with LLR.
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http://dx.doi.org/10.1093/bjs/znaa118DOI Listing
March 2021

Response letter to the editor.

Surg Obes Relat Dis 2021 Feb 2. Epub 2021 Feb 2.

National University of Singapore, Singapore.

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http://dx.doi.org/10.1016/j.soard.2021.01.032DOI Listing
February 2021

Publisher Correction: Association between pet ownership and physical activity levels, atopic conditions, and mental health in Singapore: a propensity score-matched analysis.

Sci Rep 2021 Mar 11;11(1):6144. Epub 2021 Mar 11.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Level 10, Singapore, 117549, Singapore.

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http://dx.doi.org/10.1038/s41598-021-85732-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952711PMC
March 2021

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiovascular and Metabolic Outcomes in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

J Am Heart Assoc 2021 Feb 24;10(5):e019463. Epub 2021 Feb 24.

Department of Medicine Yong Loo Lin School of MedicineNational University of Singapore Singapore.

Background Recent studies have increasingly shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta-analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random-effects pairwise meta-analysis model was used to summarize the studies. A total of 8 randomized-controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; <0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of -1.21 kg (<0.001), body mass index of -0.47 kg/m (<0.001), systolic blood pressure of -1.90 mm Hg (=0.04), and fasting plasma glucose of -0.38 mmol/L (=0.05), compared with those without. There were no between-group differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.
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http://dx.doi.org/10.1161/JAHA.120.019463DOI Listing
February 2021

Combined inhibition of PD-1/PD-L1, Lag-3, and Tim-3 axes augments antitumor immunity in gastric cancer-T cell coculture models.

Gastric Cancer 2021 Feb 20. Epub 2021 Feb 20.

Department of Haematology-Oncology, National University Health System (S) Pte Ltd, Level 7, NUHS Tower Block, 1E Kent Ridge Road, Singapore, 119228, Singapore.

Background: Immunotherapy targeting PD-1 provides a limited survival benefit in patients with unresectable advanced or recurrent gastric cancer (GC). Beside PD-L1, the expression of inhibitory ligands such as CEACAM-1 and LSECtin on GC cells account for this limitation. Here we assessed their expression and immune suppressive effect in GC patients.

Methods: Using multiplexed immunohistochemistry staining, we evaluated the distribution of different inhibitory ligands, including PD-L1, CEACAM-1, LSECtin, and MHC class II, in 365 GC patients. We analyzed their correlations and overall survival (OS) based on the expression of each inhibitory ligand and the independent prognostic factors that affect OS. Subsequently, we evaluated the additive effect of anti-PD-1 mAb or anti-PD-L1 mAb with/without anti-Lag-3 mAb with/without anti-Tim-3 mAb in cytotoxic assay using tumor-antigen specific CTL clones against GC cell lines.

Results: Co-expression of the inhibitory ligands for PD-1, Tim-3, and Lag-3 was observed in the largest proportion (34.7%). CEACAM-1, LSECtin, and MHC class II expression showed significant correlation with PD-L1 expression and OS. Multivariable analysis demonstrated that CEACAM-1 low is an independent prognostic factor. Furthermore, combining dual and triple ICIs yielded additive effect on cytotoxicity of CTL clones against each immune inhibitory ligand positive GC cell lines.

Conclusions: Our findings suggested that the expression of inhibitory ligands for Tim-3 and Lag-3 on GC cells serve as potential biomarkers to predict the response to anti-PD-1 therapy and the combinatorial immunotherapy with ICIs targeting for PD-1, Tim-3, and Lag-3 has a therapeutic potential for GC patients.
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http://dx.doi.org/10.1007/s10120-020-01151-8DOI Listing
February 2021

Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma - A meta-analysis and systematic review.

Eur J Surg Oncol 2021 Jan 28. Epub 2021 Jan 28.

Hepatobiliary Surgery and Liver Transplant Unit, Cruces University Hospital, Cruces Plaza, S/N, 48903 Barakaldo, Bizkaia, Spain; BioCruces Research Institute, University of the Basque Country Cruces Plaza, 48903 Barakaldo, Bizkaia, Spain.

This systematic review and meta-analysis aimed to confirm the prognostic value of lymph node ratio (LNR), and determine an optimal LNR cut-off for overall survival (OS) in patients with distal cholangiocarcinoma (DCC) undergoing curative surgery. We additionally aimed to provide a consolidated review of current evidence regarding prognostic significance of positive lymph node count (PLNC) and total lymph node count (TLNC). A systematic search of PubMed, EMBASE and Cochrane Library was conducted from inception to October 2020. Studies were included into meta-analysis if there was histological diagnosis, curative surgery, restriction to DCC and relevant LNR results. Quality assessment was performed using the Newcastle Ottawa Scale. Findings for 1228 patients were pooled across 6 studies. Meta-analysis delineated a dose-effect gradient in which higher LNR cut-offs correlated with larger pooled hazard ratios: 00.2 (HR 3.26; 95% CI 2.07-5.13; p < 0.00001) and LNR>0.4 (HR 3.59; 95% CI 2.31-5.58; p < 0.00001) when compared against a control group of LNR = 0. LNR of 0.2 (HR 2.12; 95% CI: 1.57-2.86; p < 0.0001) was found to be a significant and ideal cut-off for prognostication of poorer OS. A review of current literature reveals an ongoing debate regarding the comparative prognostic value of differing PLNC cut-offs (0/1/3 versus 0/1/4). TLNC of 10-13 is widely reported to be the minimum necessary to ensure improved long term outcomes. PLNC and LNR are strong prognostic factors for OS in DCC. An ideal LNR cut-off of 0.2 is most significantly associated with poorer OS.
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http://dx.doi.org/10.1016/j.ejso.2021.01.004DOI Listing
January 2021

Learning curve of laparoscopic and robotic pancreas resections: a systematic review.

Surgery 2021 Feb 1. Epub 2021 Feb 1.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Lee Kong Chian Medical School, Nanyang Technological University, Singapore; Duke-National University of Singapore Medical School, Singapore. Electronic address:

Background: Minimally invasive pancreatic resection has been shown recently in some randomized trials to be superior in selected perioperative outcomes compared with open resection when performed by experienced surgeons. However, minimally invasive pancreatic resection is associated with a long learning curve. This study aims to summarize the current evidence on the learning curve of minimally invasive pancreatic resection and define the number of cases required to surmount the learning curve.

Methods: A systematic search was performed on PubMed, Embase, Scopus, and the Cochrane database using a detailed search strategy. Studies that did not describe the learning curve were excluded from the study. Data on the method of learning curve analysis, single surgeon versus institutional learning curve, and outcome measures were extracted and analyzed.

Results: A total of 32 studies were included in the pooled analysis: 12 on laparoscopic pancreatoduodenectomy, 9 on robotic pancreatoduodenectomy, 12 on laparoscopic distal pancreatectomy, and 3 on robotic distal pancreatectomy. Sample population was comparable between laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy (median 63 vs 65). Six of 12 studies and 7 of 9 studies used nonarbitrary methods of analysis in laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy, respectively. Operating time was used as the single outcome measure in 4 of 12 studies in laparoscopic pancreatoduodenectomy and 5 of 9 studies in robotic pancreatoduodenectomy. Overall, there was no significant difference between the number of cases required to surmount the learning curve for laparoscopic pancreatoduodenectomy versus robotic pancreatoduodenectomy (laparoscopic pancreatoduodenectomy 34.1 [95% confidence interval 30.7-37.7] versus robotic pancreatoduodenectomy 36.7 [95% confidence interval 32.9-41.0]; P = .8241) and laparoscopic distal pancreatectomy versus robotic distal pancreatectomy (laparoscopic distal pancreatectomy 25.3 [95% confidence interval 22.5-28.3] versus robotic distal pancreatectomy 20.7 [95% confidence interval 15.8-26.5]; P = .5997.) CONCLUSION: This study provides a detailed summary of existing evidence around the learning curve in minimally invasive pancreatic resection. There was no significant difference between the learning curve for robotic pancreatoduodenectomy versus laparoscopic pancreatoduodenectomy and robotic distal pancreatectomy versus laparoscopic distal pancreatectomy. These findings were limited by the retrospective nature and heterogeneity of the studies published to date.
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http://dx.doi.org/10.1016/j.surg.2020.11.046DOI Listing
February 2021

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

J Vasc Interv Radiol 2021 04 29;32(4):576-584.e5. Epub 2021 Jan 29.

Department of Upper Gastrointestinal and Bariatric Surgery, Singapore General Hospital.

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; I = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10-0.83; P = .02; I = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43-1.08; P = .10; I = 0%) and length of hospitalization (mean difference, -0.32; 95% CI, -1.88 to 1.24; P = .69; I = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09-97.98; I = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00-1.28; I = 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.
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http://dx.doi.org/10.1016/j.jvir.2020.12.005DOI Listing
April 2021

Outcomes of left ventricular thrombosis in post-acute myocardial infarction patients stratified by antithrombotic strategies: A meta-analysis with meta-regression.

Int J Cardiol 2021 Apr 4;329:36-45. Epub 2021 Jan 4.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre, Singapore. Electronic address:

Background: Left ventricular thrombus (LVT) formation is a significant complication of acute myocardial infarction (AMI) due to its embolic potential. However, managing LVT requires balancing therapeutic benefits against bleeding risks. Our study provides a risk-benefit analysis of various antithrombotic regimens on long-term outcomes in treating post-AMI LVT patients.

Methods: We conducted a comprehensive literature search in Medline, Embase and SCOPUS up to 1 April 2020. All studies reporting outcomes of post-AMI LVT patients were included.

Results: 17 studies were included in total. Anticoagulation (47-100%) and triple therapy use (38-100%) varied largely across studies. On meta-analysis, administration of anticoagulation (OR 0.14, 95% CI 0.05-0.36, p < 0.001) and triple therapy (OR 0.22, 95% CI 0.07-0.66, p < 0.001) resulted in lower odds of mortality. Neither anticoagulation (p = 0.24) nor triple therapy (p = 0.73) was associated with bleeding. Triple therapy was associated with LVT resolution on meta-analysis (OR 2.53, 95% CI 1.53-4.19, p < 0.001) and regression analysis (OR 1.28, 95% CI 1.03-1.58, p = 0.03). Anticoagulation and triple therapy were independent predictors of systemic embolism ([OR 0.67, 95% CI 0.49-0.93, p = 0.02] and [OR 0.82, 95% CI 0.73-0.93, p = 0.001]) and stroke ([OR 0.62, 95% CI 0.41-0.94, p = 0.03] and [OR 0.73, 95% CI 0.55-0.96, p = 0.03]).

Conclusions: While there is clear therapeutic benefit in anticoagulation for post-AMI LVT, the extent of bleeding risk is uncertain. Future trials are necessary to determine the optimal antithrombotic strategy for post-AMI LVT management.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.087DOI Listing
April 2021

Factors Attracting or Deterring Female Medical Students in Asia From Pursuing a Surgical Career, and the Impact of Surgical Clerkship, Mentorship, and Role Models: A Multicultural Asian Perspective From a National Prospective Cohort Study.

J Surg Res 2021 Apr 23;260:200-209. Epub 2020 Dec 23.

Department of Surgery, University Surgical Cluster, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: Female surgeons are highly underrepresented in Asian countries, where prescriptive gender norms are widespread and more deeply embedded in societies.

Materials And Methods: A nationwide structured questionnaire was completed by 1741 Singaporean third- and fifth-year medical students after the completion of an 8-week general surgery rotation, during 2015-2017. Results were analyzed using mixed-effects hierarchical models which took into account clustering of survey responses under the teaching hospitals which students were posted to and medical students' year of study.

Results: Female medical students had a poorer perception of general surgery than male students (3.22 ± 0.91 versus 3.41 ± 0.89; P < 0.0001) before the clerkship. However, the clerkship improved female students' opinion to a greater extent than male students (+0.84 ± 1.06 versus +0.59 ± 1.03; P < 0.0001), resulting in female and male students having comparable attitudes toward surgery after the clerkship (4.06 ± 0.79 versus 4.00 ± 0.87; P = 0.2435). A total of 40.4% of female students responded that they were inspired to pursue a surgical career after the clerkship, and we identified 13 pedagogical traits of faculty and resident mentors which were associated with female students' career aspirations. Female students were more likely to consider intellectual challenges arising from cases (ratio: 1.045 [95% confidence interval 1.004-1.088, P = 0.0292]) and the presence of role models (ratio: 1.068 [95% confidence interval: 1.020-1.118, P = 0.0048]) as "pull" factors compared with their male contemporaries, but were deterred from a surgical career to a greater extent by eight "push" factors.

Conclusions: A surgical clerkship itself could be regarded as an effective intervention for improving female medical students' enthusiasm for surgery, which may help to address the "pipeline problem" of few female students applying for surgical training after medical school. A greater emphasis on "pull factors" and pedagogical qualities of mentors could be used to improve the clerkship experience, to attract more female students to surgery.
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http://dx.doi.org/10.1016/j.jss.2020.11.053DOI Listing
April 2021

Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review.

J Gastrointest Oncol 2020 Oct;11(5):847-857

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: The role of perioperative or neoadjuvant chemotherapy for locally advanced colon cancer is unclear. Emerging evidence such as the FOXTROT trial is challenging the conventional norm of upfront operation for these patients. However, these trials have yet to reach statistical significance.

Methods: MEDLINE, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI) and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) and observational studies of patients with locally advanced colon cancer were included. The intervention arm was neoadjuvant chemotherapies while the comparator arm was adjuvant chemotherapies. Studies which reported outcomes of interests included overall survival, disease-free survival, R0 resection rate, perioperative complications and adverse effects of chemotherapy were chosen.

Results: We identified five eligible randomized trials and two observational studies, including 29,504 patients. Neoadjuvant therapies exhibited statistically significant improvement in overall survival [hazard ratio (HR) =0.76, 95% confidence interval (CI): 0.65-0.89, P=0.0005], and disease-free survival (HR =0.74, 95% CI: 0.58-0.95, P=0.02). R0 resection rate fell slightly short of significance [odds ratio (OR) =1.86, 95% CI: 0.95-3.62, P=0.07]. Risk of peri-operative complications did not differ between groups when examining abdominal infection [risk ratio (RR) =1.14, 95% CI: 0.59-2.18, P=0.70] and anastomotic leakage (RR =0.83, 95% CI: 0.53-1.31, P=0.42). No statistical differences in complications from chemotherapy were reported.

Conclusions: This meta-analysis highlights the potential survival benefit of neoadjuvant chemotherapy compared to adjuvant chemotherapy for locally advanced colon cancer, without an increase in surgical morbidity. Neoadjuvant or perioperative approaches may be considered an alternative to upfront surgery followed by chemotherapy for locally advanced colon cancer.
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http://dx.doi.org/10.21037/jgo-20-220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657836PMC
October 2020

Association between pet ownership and physical activity levels, atopic conditions, and mental health in Singapore: a propensity score-matched analysis.

Sci Rep 2020 11 16;10(1):19898. Epub 2020 Nov 16.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Level 10, Singapore, 117549, Singapore.

Although existing literature increasingly suggests a positive influence of pet ownership on human physical activity levels, results from many European, American, and Japanese studies have been inconsistent. How pet ownership impacts mental health and atopy is likewise controversial and whether distinct demographic subgroups experience differential effects is unclear. This cross-sectional study surveyed participants (n = 823) via a self-administered online questionnaire. Comparisons of outcomes between pet owners and non-pet owners with subgroup analyses were performed within a propensity score-matched subset (n = 566) of respondents. There were no differences in physical activity levels or mental health scores between pet owners and non-pet owners. In subgroup analyses, compared to non-pet owners, main pet caregivers reported 14.1 (95% CI 2.79-25.3) and 19.0 (95% CI 4.70-33.3) more minutes per week of moderate- and vigorous-intensity physical activity respectively and higher SF-36 emotional well-being (β = 2.7, 95% CI 0.100-5.32) and energy scores (β = 3.8, 95% CI 0.410-7.27). Age was a significant effect modifier of the association between pet ownership and emotional well-being, energy and social functioning scores, with greater scores above the ages of 39, 35 and 39 years old respectively (interaction p = 0.043, 0.044, 0.042). Finally, pet acquisition was associated with worsening of allergic rhinitis, while pet ownership cessation was associated with improvement of allergic rhinitis and eczema symptoms. To our knowledge, this is the first study addressing the public health impact of pet ownership in Southeast Asia and its findings add contextual nuance to suggest potential benefits derived from pet ownership.
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http://dx.doi.org/10.1038/s41598-020-76739-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670461PMC
November 2020

Revisional One-Anastomosis Gastric Bypass After Restrictive Index Surgery-a Metaanalysis and Comparison with Revisional Roux-en-Y Gastric Bypass.

Obes Surg 2021 Mar 6;31(3):949-964. Epub 2020 Nov 6.

Department of Upper Gastrointestinal and Bariatric Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.

Background: One-anastomosis gastric bypass (OAGB) was established as a recognized bariatric procedure in the 2018 International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) position statement. This study evaluates the outcomes of revisional OAGB (rOAGB) after a restrictive index procedure, and to compare it to revisional RYGB (rRYGB).

Methods: A literature search was performed according to the PRISMA guidelines on papers published from inception till February 2020. Original studies involving patients who underwent rOAGB after a primary failed restrictive procedure were included. The primary outcome measured was postrOAGB weight loss. Secondary outcome measures include comorbidity resolution, operative duration, length of stay, morbidity, and mortality.

Results: A total of 21 studies with 1377 patients were included. Five studies compared rOAGB versus rRYGB. Majority of the patients (76%) were female, with mean age of 43.5 years old. Mean body mass index (BMI) before revisional surgery was 41.6 kg/m. The most common biliopancreatic limb length was 200 cm. Percentage of excess weight loss after rOAGB increases to a maximum of 76.0% at 48 months postsurgery. rOAGB resulted in a pooled prevalence of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea resolution of 74.9%, 48.4%, 63.2%, and 75.7% respectively. When compared to rRYGB, rOAGB demonstrated greater weight loss, comparable metabolic syndrome resolution, but with a shorter operating time. Morbidity and mortality rates were low across all studies.

Conclusions: rOAGB has potential as an alternative revisional surgery, with weight loss profiles and rates of metabolic syndrome resolution that are comparable to rRYGB.
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http://dx.doi.org/10.1007/s11695-020-05094-yDOI Listing
March 2021

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

PLoS One 2020 6;15(11):e0241847. Epub 2020 Nov 6.

Division of Surgery, Department of Upper Gastrointestinal & Bariatric Surgery, Singapore General Hospital, Singapore, Singapore.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241847PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647085PMC
January 2021

Vascular Complications of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Regression Analysis.

Crit Care Med 2020 Dec;48(12):e1269-e1277

1Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2Cardiothoracic Intensive Care Unit, Department of Cardiothoracic and Vascular Surgery, National University Heart Centre, National University Hospital, Singapore. 3Saw Swee School of Public Health, National University of Singapore, Singapore. 4SingVaSC, Singapore Vascular Surgical Collaborative, Singapore. 5Cardiovascular Research Institute, National University of Singapore, Singapore. 6Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 7Division of Vascular Surgery, Department of Cardiothoracic and Vascular Surgery, National University Heart Centre, Singapore.

Objectives: Perform a systematic review and meta-analysis of vascular complications associated with extracorporeal membrane oxygenation and identify prognostic and predictive factors.

Data Sources: Systematic search for publications reporting vascular complications on extracorporeal membrane oxygenation, published from 1972 to January 31, 2020, was conducted via PubMed, Scopus, and Embase.

Study Selection: Of 4,076 references screened, 47 studies with 6,583 patients were included in final analyses. Studies with fewer than 10 patients were excluded.

Data Extraction: Relevant data, including demographics, comorbidities, extracorporeal membrane oxygenation and cannulation characteristics, occurrence rates of early and late vascular complications, patient outcomes, and use of distal perfusion cannula, were extracted from selected articles into an excel sheet specifically designed for this review.

Data Synthesis: Random-effects meta-analyses and meta-regression analyses were undertaken. Overall pooled estimate of vascular complications in our meta-analysis was 29.5% (95% CI, 23.6-35.9%). Two-thousand three-hundred forty-seven vascular complications in 6,124 venoarterial extracorporeal membrane oxygenation patients compared with 95 in 459 venovenous extracorporeal membrane oxygenation patients (odds ratio, 2.35; 95% CI, 1.87-2.96; p < 0.0001) were analyzed. Successful weaning off extracorporeal membrane oxygenation occurred in 60.6% of pooled patients; 46.2% were eventually discharged. Pooled prevalences of vascular complications like significant bleeding, limb ischemia, and cannula site bleeding were 15.4% (95% CI, 8.6-23.7%), 12.6% (95% CI, 10.0-15.5%), and 12.6% (95% CI, 9.6-18.5%), respectively. Meta-analysis showed that the use of distal perfusion cannula was associated with lower odds of limb ischemia (odds ratio, 1.93; 95% CI, 1.17-2.47; p = 0.03) Meta-regression showed that male sex, smoking, advanced age, and comorbidities contributed to higher in-hospital mortality, while distal perfusion cannula was protective.

Conclusions: Nearly a third of patients on extracorporeal membrane oxygenation develop vascular complications; elderly males with comorbidities appear vulnerable. The use of distal perfusion cannulas caused significant reduction in limb ischemia and mortality.
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http://dx.doi.org/10.1097/CCM.0000000000004688DOI Listing
December 2020

Surgical Management of Multiple Myeloma With Symptomatic Involvement of the Spine.

Int J Spine Surg 2020 Oct 23;14(5):785-794. Epub 2020 Oct 23.

Department of Orthopaedic Surgery, National University Health System, Singapore.

Introduction: Multiple myeloma (MM) is the most frequent primary malignancy of the spine. We aimed to investigate the clinical presentation, surgical indications and outcomes, complications, survival, and its influencing factors in surgically treated MM patients with symptomatic involvement of the spine (SIS).

Methods: Retrospective analysis of prospectively collected data. Out of 350 MM patients treated at our institution over a period of 12 years (2006-2018), we identified 24 patients who were surgically treated for SIS. We collected data on demographics, clinical presentation, comorbidities, surgical indications, and outcomes and investigated the factors predisposing to postoperative complications and survival.

Results: The median follow-up duration was 85 months; median overall survival (OS) was 50 months. Clinical presentation at admission included pain (88%), sensory and/or motor deficit (67%), and bowel/bladder dysfunction (25%). Symptomatic pathological fractures were seen in 33%. Predominant surgical indications were rapid neurological deterioration with or without spinal cord compression (SCC), followed by mechanical instability. The majority of our patients benefited from surgery in terms of pain reduction in the short term as well as in the long term. There were 21% patients with surgical-related complications (<3 months). Surgical site infections occurred in 17%, without any obvious factors predisposing to infective complications. Neurological deterioration during hospital stay, especially in the presence of motor deficit and/or bowel/bladder dysfunction, significantly reduced OS.

Conclusions: Sudden-onset neurological deterioration was the predominant factor leading to surgery. We achieved good short- and long-term pain reduction. Surgery is a valuable option for MM patients with SIS who present with rapid neurological deterioration with or without SCC and/or mechanical instability.
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http://dx.doi.org/10.14444/7112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671448PMC
October 2020

Validation and comparison of the Iwate, IMM, Southampton and Hasegawa difficulty scoring systems for primary laparoscopic hepatectomies.

HPB (Oxford) 2020 Oct 3. Epub 2020 Oct 3.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore.

Background: Various difficulty scoring systems (DSS) have been formulated to grade the complexity of laparoscopic hepatectomies (LH). This study aims to externally validate and compare 4 contemporary DSS including the Iwate, Institut Mutualiste Montsouris (IMM), Southampton and Hasegawa DSS in predicting the intraoperative technical difficulty and postoperative outcomes after LH.

Methods: Retrospective review of 548 consecutive patients who underwent LH of which 455 met the study inclusion criteria. Outcomes measures of technical difficulty included operation time, Pringles maneuver, blood loss and blood transfusion rate. Postoperative outcomes measured included morbidity, major morbidity and postoperative hospital stay.

Results: There was a statistically significant progressive increase in blood loss, blood transfusion rate, operation time and postoperative stay associated with all 4 DSS. There was also good calibration with respect to blood loss, operation time, Pringles maneuver, open conversion rate, postoperative morbidity, postoperative major morbidity and postoperative stay for all 4 DSS. The Southampton score demonstrated the poorest calibration in terms of operation time and discrimination in terms of application of Pringles maneuver and major morbidity amongst all 4 systems.

Conclusion: All 4 DSS significantly correlated with outcome measures associated with intraoperative technical difficulty and postoperative outcomes. The Southampton DSS was the poorest system in our cohort of patients.
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http://dx.doi.org/10.1016/j.hpb.2020.09.015DOI Listing
October 2020

Impact of liver cirrhosis on the difficulty of minimally-invasive liver resections: a 1:1 coarsened exact-matched controlled study.

Surg Endosc 2020 Sep 24. Epub 2020 Sep 24.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Level 5, 20 College Road, Academia, Singapore, 169856, Singapore.

Introduction: The impact of liver cirrhosis on the difficulty of minimal invasive liver resection (MILR) remains controversial and current difficulty scoring systems do not take in to account the presence of cirrhosis as a significant factor in determining the difficulty of MILR. We hypothesized that the difficulty of MILR is affected by the presence of cirrhosis. Hence, we performed a 1:1 matched-controlled study comparing the outcomes between patients undergoing MILR with and without cirrhosis including the Iwate system and Institut Mutualiste Montsouris (IMM) system in the matching process.

Methods: Between 2006 and 2019, 598 consecutive patients underwent MILR of which 536 met the study inclusion criteria. There were 148 patients with cirrhosis and 388 non-cirrhotics. One-to-one coarsened exact matching identified approximately exact matches between 100 cirrhotic patients and 100 non-cirrhotic patients.

Results: Comparison between MILR patients with cirrhosis and non-cirrhosis in the entire cohort demonstrated that patients with cirrhosis were associated with a significantly increased open conversion rate, transfusion rate, need for Pringles maneuver, postoperative, stay, postoperative morbidity and postoperative 90-day mortality. After 1:1 coarsened exact matching, MILR with cirrhosis were significantly associated with an increased open conversion rate (15% vs 6%, p = 0.03), operation time (261 vs 238 min, p  < 0.001), blood loss (607 vs 314 mls, p  = 0.002), transfusion rate (22% vs 9%, p  = 0.001), need for application of Pringles maneuver (51% vs 34%, p  = 0.010), postoperative stay (6 vs 4.5 days, p  = 0.004) and postoperative morbidity (26% vs 13%, p  = 0.029).

Conclusion: The presence of liver cirrhosis affected both the intraoperative technical difficulty and postoperative outcomes of MILR and hence should be considered an important parameter to be included in future difficulty scoring systems for MILR.
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http://dx.doi.org/10.1007/s00464-020-08018-0DOI Listing
September 2020

Impact of multidisciplinary tumour boards (MTB) on the clinicopathological characteristics and outcomes of resected colorectal liver metastases across time.

World J Surg Oncol 2020 Sep 3;18(1):237. Epub 2020 Sep 3.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore.

Background: Resection of colorectal liver metastases (CLM) has been established as the standard of care. This study aims to compare the change in clinicopathological characteristics of patients who underwent curative resection of CLM across two time periods-2000 to 2010 (P1) and 2011 to 2016 (P2) and evaluate the prognostic impact of these characteristics on survival outcomes.

Methods: Patients who undergo liver resection for CLM at Singapore General Hospital from January 2000 to December 2016 were identified from a prospectively maintained database. The primary end point was overall survival.

Results: There were 183/318 (57.5%) patients and 135/318 (42.5%) patients in P1 and P2, respectively. There was a lower proportion of patients who had nodal metastases from primary colorectal cancer and clinical risk score (CRS) less than 3 in P2 when compared to P1. There was no difference in survival between both time periods. Independent predictors of survival for the cohort were CEA levels ≥ 200 ng/ml, primary tumour grade and lymph nodal status. Independent predictors of poor survival in P1 were poorly differentiated colorectal cancer and nodal metastases while in P2, independent predictors of poor survival were multiple liver metastases and nodal metastases.

Conclusion: Nodal metastases from primary colorectal cancer are an independent predictor of poor survival across time for resectable CLM. Although there is no difference in survival between the two time periods, patients with multiple liver metastases should be carefully considered prior to surgery as it is also an independent predictor of overall survival.
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http://dx.doi.org/10.1186/s12957-020-01984-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650267PMC
September 2020

Early Prediction of Post-hepatectomy Liver Failure in Patients Undergoing Major Hepatectomy Using a PHLF Prognostic Nomogram.

World J Surg 2020 Dec 28;44(12):4197-4206. Epub 2020 Aug 28.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore.

Background: Liver resection (LR) is the main modality of treatment for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). Post-hepatectomy liver failure (PHLF) remains the most dreaded complication. We aim to create a prognostic score for early risk stratification of patients undergoing LR.

Methodology: Clinical and operative data of 472 patients between 2000 and 2016 with HCC or CRLM undergoing major hepatectomy were extracted and analysed from a prospectively maintained database. PHLF was defined using the 50-50 criteria.

Results: Liver cirrhosis and fatty liver were histologically confirmed in 35.6% and 53% of patients. 4.7% (n = 22) of patients had PHLF. A 90-day mortality was 5.1% (n = 24). Pre-operative albumin-bilirubin score (p = 0.0385), prothrombin time (p < 0.0001) and the natural logarithm of the ratio of post-operative day 1 to pre-operative serum bilirubin (SB) (ln(Bil/Bil); p < 0.0001) were significantly independent predictors of PHLF. The PHLF prognostic nomogram was developed using these factors with receiver operating curve showing area under curve of 0.88. Excellent sensitivity (94.7%) and specificity (95.7%) for the prediction of PHLF (50-50 criteria) were achieved at cut-offs of 9 and 11 points on this model. This score was also predictive of PHLF according to Bil > 7 and International Study Group for Liver Surgery criteria, intensive care unit admissions, length of stay, all complications, major complications, re-admissions and mortality (p < 0.05).

Conclusions: The PHLF nomogram ( https://tinyurl.com/SGH-PHLF-Risk-Calculator ) can serve as a useful tool for early identification of patients at high risk of PHLF before the 'point of no return'. This allows enforcement of closer monitoring, timely intervention and mitigation of adverse outcomes.
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http://dx.doi.org/10.1007/s00268-020-05713-wDOI Listing
December 2020

Metabolic outcomes after revisional bariatric surgery: a systematic review and meta-analysis.

Surg Obes Relat Dis 2020 Oct 6;16(10):1442-1454. Epub 2020 Jun 6.

Department of Surgery, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

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.
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http://dx.doi.org/10.1016/j.soard.2020.05.029DOI Listing
October 2020

Survival Advantage of Laparoscopic Versus Open Resection For Colorectal Liver Metastases: A Meta-analysis of Individual Patient Data From Randomized Trials and Propensity-score Matched Studies.

Ann Surg 2020 08;272(2):253-265

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore.

Objective: To perform an individual participant data meta-analysis using randomized trials and propensity-score matched (PSM) studies which compared laparoscopic versus open hepatectomy for patients with colorectal liver metastases (CLM).

Background: Randomized trials and PSM studies constitute the highest level of evidence in addressing the long-term oncologic efficacy of laparoscopic versus open resection for CLM. However, individual studies are limited by the reporting of overall survival in ways not amenable to traditional methods of meta-analysis, and violation of the proportional hazards assumption.

Methods: Survival information of individual patients was reconstructed from the published Kaplan-Meier curves with the aid of a computer vision program. Frequentist and Bayesian survival models (taking into account random-effects and nonproportional hazards) were fitted to compare overall survival of patients who underwent laparoscopic versus open surgery. To handle long plateaus in the tails of survival curves, we also exploited "cure models" to estimate the fraction of patients effectively "cured" of disease.

Results: Individual patient data from 2 randomized trials and 13 PSM studies involving 3148 participants were reconstructed. Laparoscopic resection was associated with a lower hazard rate of death (stratified hazard ratio = 0.853, 95% confidence interval: 0.754-0.965, P = 0.0114), and there was evidence of time-varying effects (P = 0.0324) in which the magnitude of hazard ratios increased over time. The fractions of long-term cancer survivors were estimated to be 47.4% and 18.0% in the laparoscopy and open surgery groups, respectively. At 10-year follow-up, the restricted mean survival time was 8.6 months (or 12.1%) longer in the laparoscopy arm (P < 0.0001). In a subgroup analysis, elderly patients (≥65 years old) treated with laparoscopy experienced longer 3-year average life expectancy (+6.2%, P = 0.018), and those who live past the 5-year milestone (46.1%) seem to be cured of disease.

Conclusions: This patient-level meta-analysis of high-quality studies demonstrated an unexpected survival benefit in favor of laparoscopic over open resection for CLM in the long-term. From a conservative viewpoint, these results can be interpreted to indicate that laparoscopy is at least not inferior to the standard open approach.
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http://dx.doi.org/10.1097/SLA.0000000000003672DOI Listing
August 2020

Current status of laparoscopic liver resection for the management of colorectal liver metastases.

J Gastrointest Oncol 2020 Jun;11(3):526-539

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. The commonest site of spread is the liver, with up to 40% of patients developing colorectal liver metastasis (CLRM) during the course of their lifetime. Significant advances in surgical techniques, as well as breakthroughs in chemotherapy and biologic agents, have resulted in dramatic improvements in prognosis. A multimodal approach comprising of liver resection coupled with systemic therapy offers these patients the best chance of cure. The arrival of laparoscopic liver resection (LLR) within the last 3 decades has added a whole new dimension to the management of this condition. Today, CLRM is one of the most frequent indications for LLR globally. Meta-analyses of retrospective studies and two randomized trials have demonstrated superior short-term outcomes following LLR, with no differences in mortality rates. Oncologically, R0 resection rates are comparable to the open approach, while overall and disease-free survival rates are also similar. As surgeons gain confidence, boundaries are pushed even further. High-volume centers have published their early experiences with complex LLR of recurrent CLRM as well as totally laparoscopic synchronous resection of CRC and liver metastases, with very encouraging results. In the presence of extensive bilobar CLRM, two-stage hepatectomy (TSH) and associating liver partition with portal vein ligation (ALPPS) may be adopted to augment an inadequate future liver remnant to facilitate metastasectomy. Interestingly, the adoption of LLR for these techniques also seem to confer additional benefits. Despite the plethora of advantages, LLR comes with its own unique set of limitations such as a steep learning curve and high cost. The surgical world eagerly awaits the results of prospective trials currently underway in order to further advance the management of this disease.
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http://dx.doi.org/10.21037/jgo.2020.02.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340801PMC
June 2020

Push and pull factors, and the role of residents in nurturing medical students' interest in surgery as a career option in a multicultural Asian context: Results of a prospective national cohort study.

Am J Surg 2020 12 30;220(6):1549-1556. Epub 2020 Apr 30.

Department of Surgery, University Surgical Cluster, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: Studies in Caucasian populations suggest that interest among medical students in pursuing a surgical career is dwindling. We sought to investigate these trends and to evaluate the impact of resident teaching in a multiethnic Asian population.

Study Design: Between 2015 and 2017, 1780 Singaporean third- and fifth-year medical students completed a structured anonymized questionnaire following the completion of an 8-week general surgery rotation. Medical students' impressions of their faculty and resident mentors were analyzed using hierarchical multilevel mixed-effects models.

Results: Respondents' opinions of general surgery improved from 3.31 ± 0.91 points to 4.03 ± 0.83 points on a 5-point Likert scale (P < 0.0001). Medical students were more likely to regard their interaction with residents as a "pull" factor compared to their interaction with faculty members (74.7% vs 65.6%; P < 0.0001). Our analyses revealed 9 statistically-significant "pull" factors and 5 "push" factors which attract or deter Asian medical students from a career in surgery. Comparing the pedagogical qualities of resident and faculty mentors, we found that residents surpassed faculty mentors in 9 domains, had comparable appraisal scores on 3 domains, and fared worse than faculty on 8 domains. Importantly, residents fared better at promoting interest in a surgical career (P = 0.0006) and influencing the career aspirations of medical students (P < 0.0001) compared with faculty members.

Conclusions: To our knowledge, this is the largest study from a Southeast Asian country providing representative sample numbers. With this knowledge of pull and push factors, the surgical clerkship can be improved by emphasizing pull factors and preparing students to cope with the push factors. Finally, our findings suggest that roping in residents as mentors to medical students may improve the pipeline of students interested in pursuing surgery after medical school.
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http://dx.doi.org/10.1016/j.amjsurg.2020.04.036DOI Listing
December 2020

Response to comment on"Survival Advantage of Laparoscopic Versus Open Resection for Colorectal Liver Metastases".

Ann Surg 2020 Jun 24. Epub 2020 Jun 24.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore Duke-NUS Medical School, Singapore, Singapore Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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http://dx.doi.org/10.1097/SLA.0000000000004013DOI Listing
June 2020

Severity of nausea and vomiting in pregnancy and early childhood neurobehavioural outcomes: The Growing Up in Singapore Towards Healthy Outcomes study.

Paediatr Perinat Epidemiol 2021 Jan 23;35(1):98-108. Epub 2020 Jun 23.

Agency for Science, Technology and Research (A*STAR), Singapore Institute for Clinical Sciences (SICS), Singapore, Singapore.

Background: Nausea and vomiting of pregnancy (NVP) affects 50 to 80 per cent of women. The existing literature has examined NVP from the perspective of the mother, and relatively less is known about offspring outcomes.

Objectives: To study the relationships of NVP with social-emotional, behavioural, and cognitive outcomes of the offspring in a multi-ethnic Asian cohort.

Methods: In the Growing Up in Singapore Towards Healthy Outcomes prospective mother-offspring cohort study, mothers responded to a structured NVP questionnaire at 26-28 weeks' gestation (n = 1172) and participants with severe NVP were confirmed using medical records. Children underwent multiple neurodevelopmental assessments throughout childhood. We conducted multivariable regressions with post-estimation predictive margins to understand the associations of NVP with offspring neurobehavioural outcomes, which included 1-year Infant-Toddler Social and Emotional Assessment, 1.5-year Quantitative Checklist for Autism in Toddlers, 2-year Bayley Scales of Infant and Toddler Development, 2- and 4-year Child Behavior Checklist, and 4.5-year Kaufman Brief Intelligence Test. Analyses were adjusted for household income, birth variables, maternal mental health, and other relevant medical variables. Cohen's d effect sizes were calculated using standardised mean differences (μ ).

Results: Mothers were categorised into no (n = 296, 25.3%), mild-moderate (n = 686, 58.5%), and severe NVP (n = 190, 16.2%), of whom 67 (5.7%) required admission. Compared to children of mothers who had no or mild-moderate NVP, children with exposure to severe NVP exhibited more externalising behaviours (μ 2.0, 95% CI 0.3, 3.6; Cohen's d = 0.33) and social communication difficulties before 2 years (μ 4.1, 95% Cl 0.1, 8.0; Cohen's d = 0.38), both externalising (μ 1.5, 95% CI 0.4, 2.6; Cohen's d = 0.43) and internalising behaviours at 2 years (μ 1.2, 95% CI 0.1, 2.2; Cohen's d = 0.35), and only internalising behaviours after 2 years (μ 1.1, 95% CI 0.4, 2.0; Cohen's d = 0.37).

Conclusions: Severe NVP is highly prevalent in this Asian cohort and may be adversely associated with multiple offspring neurobehavioural outcomes.
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http://dx.doi.org/10.1111/ppe.12703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116637PMC
January 2021

Development, internal validation and calibration of a risk score to predict survival in patients with -mutant non-small cell lung cancer.

J Clin Pathol 2021 Feb 23;74(2):116-122. Epub 2020 Jun 23.

Department of Hematology-Oncology, National University Cancer Institute, Singapore

Aims: EGFR tyrosine kinase inhibitors (TKIs) are first-line molecularly targeted therapies in patients with advanced non-small cell lung cancer (NSCLC) who carry sensitising mutations, due to its superior survival outcomes compared with conventional chemotherapy regimens. In this study, we sought to identify clinical, immune and biochemical variables with prognostic significance in this patient subgroup and incorporate them into a nomogram-based risk score.

Methods: A total of 199 patients with mutation-positive, advanced NSCLC (defined as stage IV at initial diagnosis or incurable disease recurrence) treated with first-line EGFR TKI therapy were retrospectively profiled. Univariable and multivariable survival analyses were conducted, with variables from the multivariable model with the highest Harrell's Concordance (C) Index selected for inclusion in the subsequent survival nomogram. Internal validation and internal calibration of our prognostic nomogram were also performed.

Results: Serum lactate dehydrogenase (LDH) and lung/pleural metastasis were independent predictors of unfavourable overall survival in all three multivariable models. A survival nomogram was generated based on the multivariable model with the highest Harrell's C Index, incorporating the following 11 variables: white cell count, haemoglobin, LDH, neutrophil/lymphocyte ratio, ethnicity (Chinese vs non-Chinese), Karnofsky-Performance Status (score of '90-100' or '70-80' vs '0-60'), Charlson Comorbidity Index (≥3, or 2, or 1 vs 0), neurological symptoms, brain, lung/pleural and adrenal metastases.

Conclusion: We identified serum LDH as an independent predictor of unfavourable clinical outcomes in patients with advanced, mutation-positive NSCLC. We further developed a robust nomogram-based risk score that incorporates clinical, biochemical and immune variables that can provide more targeted prognostication and management in this patient subgroup.
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http://dx.doi.org/10.1136/jclinpath-2020-206754DOI Listing
February 2021

Associations of Bariatric Interventions With Micronutrient and Endocrine Disturbances.

JAMA Netw Open 2020 06 1;3(6):e205123. Epub 2020 Jun 1.

Department of Upper Gastrointestinal and Bariatric Surgery, Singapore General Hospital, Singapore.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.5123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284307PMC
June 2020

Minimally Invasive Versus Open Pancreatectomies for Pancreatic Neuroendocrine Neoplasms: A Propensity-Score-Matched Study.

World J Surg 2020 09;44(9):3043-3051

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, 20 College Road, Academia Level 5, Singapore, 169856, Singapore.

Background: Pancreatic neuroendocrine neoplasms (PNENs) are increasingly prevalent with modern imaging, and surgical excision remains mainstay of treatment. This study aims to perform a propensity-score-matched (PSM) comparison of perioperative and oncologic outcomes following minimally invasive pancreatectomy (MIP) versus open pancreatectomy (OP) for PNEN.

Methods: A retrospective review was performed on patients who underwent curative-intent surgery for PNEN at Singapore General Hospital from 1997 to 2018. A 1:1 PSM was performed between MIP and OP, after which both groups were balanced for baseline variables.

Results: We studied 134 patients who underwent surgery (36 MIP and 98 OP) for PNEN. Propensity-score-matched comparison between 35 MIP and 35 OP patients revealed that the MIP group had a longer operating time (MD = 75.0, 95% CI 15.2 to 134.8, P = 0.015), lower intraoperative blood loss (MD = - 400.0, 95% CI - 630.5 to - 169.5, P = 0.001), shorter median postoperative stay (MD = - 1.0, 95% CI - 1.9 to - 0.1, P = 0.029) and shorter median time to diet (MD = - 1.0, 95% CI - 1.9 to - 0.1, P = 0.039). There were no differences between both groups for short-term adverse outcomes and oncologic clearance. Overall survival (HR = 0.84, 95% CI 0.28 to 2.51, P = 0.761) and disease-free survival (HR = 0.57, 95% CI 0.20 to 1.64, P = 0.296) were comparable.

Conclusion: MIP is a safe and feasible approach for PNEN and is associated with a lower intraoperative blood loss, decreased postoperative stay and time to oral intake, at the expense of a longer operative time compared to OP.
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http://dx.doi.org/10.1007/s00268-020-05582-3DOI Listing
September 2020