Publications by authors named "Chung Yip Chan"

99 Publications

Impact of non-liver-related previous abdominal surgery on the difficulty of minimally invasive liver resections: a propensity score-matched controlled study.

Surg Endosc 2021 Feb 10. Epub 2021 Feb 10.

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

Introduction: The presence of previous abdominal surgery (PAS) has traditionally been considered to add difficulty to and increase risk of complications of laparoscopic procedures. This study aims to analyse the impact of non-liver-related PAS on the difficulty of minimally invasive liver resections (MILRs).

Materials And Methods: After exclusion of patients with concomitant major surgical procedures as well as previous liver resections, 515 consecutive patients undergoing MILR in Singapore General Hospital from 2006 to 2019 were analysed, consisting of 161 MILR in patients with previous abdominal surgery (WPAS) and 354 MILR in patients without previous abdominal surgery (WOPAS). Propensity score-matched (PSM) comparison was performed between WPAS and WOPAS groups. In addition, subgroup analysis was made comparing previous upper or lower abdominal surgery and open versus minimally invasive approach of PAS. Outcomes measured include those associated with operative difficulty such as open conversion rates, operative time, blood loss, as well as morbidity and mortality rates.

Results: MILR outcomes in patients WPAS are not inferior to those WOPAS. Overall open conversion rate was 8.2%, higher in patients WOPAS compared to patients WPAS (11.9% versus 3.5%, p = 0.015). Operating time (p = 0.942), blood loss (p = 0.063), intraoperative blood transfusion (p = 0.750), length of hospital stay (p = 0.206), morbidity (p = 0.217) and 30- and 90-day mortality (p = 1 & p = 0.367) were comparable between the two groups and subgroup analysis.

Conclusion: Outcomes of MILR in patients with previous non-liver-related abdominal surgery are not inferior to patients without previous abdominal surgery.
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http://dx.doi.org/10.1007/s00464-021-08321-4DOI Listing
February 2021

Preoperative Predictors of Futile Resection of Intraabdominal Extrahepatic Metastases from Hepatocellular Carcinoma.

World J Surg 2021 Apr 31;45(4):1144-1151. Epub 2021 Jan 31.

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

Background: The management of post-liver resection recurrence is often the life-limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post-resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post-metastasectomy.

Methods: We performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution.

Results: Of the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15-89 months). Twenty-one patients (84%) developed recurrence post-metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post-metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9-23.0)) compared to those who did not (89 months (95% CI 24.8-153.1), p = 0.004).

Conclusion: Patients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post-metastasectomy.
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http://dx.doi.org/10.1007/s00268-020-05907-2DOI Listing
April 2021

Is minimally invasive surgery of lesions in the right superior segments of the liver justified? A multi-institutional study of 245 patients.

J Surg Oncol 2020 Dec 16;122(7):1428-1434. Epub 2020 Aug 16.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Controversy exists regarding the safety and feasibility of minimally invasive resection for lesions in segments 7 or 8. We compare outcomes of minimally invasive surgery (MIS) and Open parenchymal sparing liver resections at two high-volume centers.

Methods: From 2003 to 2016 we identified patients who underwent MIS or Open resections for lesions in segments 7 or 8 at two institutions (MSKCC and SGH). Outcomes were compared using univariate and multivariate analyses.

Results: Two-hundred and forty-five patients underwent resection of lesions in segments 7 or 8 (MIS 30% and Open 70%). Compared to the Open group, the MIS group had longer operative time (223 ± 88 vs 188 ± 72 minutes, P = .003), lower blood loss (297 ± 287 vs 448 ± 670 mL, P = .03), and shorter mean length of stay (5.2 ± 7.4 vs 8.3 ± 11.7 days, P < .001), which remained significant on multivariate analysis. No differences in Pringle time, rate of postoperative complications, or R0 resections were detected.

Conclusions: With appropriately selected patients treated by experienced MIS hepatopancreatobiliary surgeons, MIS resection of segments 7 or 8 is safe with similar rates of complications and R0 resections, with significantly less blood loss and shorter length of stay.
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http://dx.doi.org/10.1002/jso.26154DOI Listing
December 2020

Use of Reinforced Staplers Decreases the Rate of Postoperative Pancreatic Fistula Compared to Bare Staplers After Minimally Invasive Distal Pancreatectomies.

J Laparoendosc Adv Surg Tech A 2021 Jan 15. Epub 2021 Jan 15.

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

Postoperative pancreatic fistula (POPF) is the most common and important cause of morbidity after distal pancreatectomy. Various transection and closure techniques of the pancreatic stump have been proposed with no robust evidence unanimously supporting one technique over the other. This study aims to compare the outcomes of minimally invasive distal pancreatectomy (MIDP) performed with reinforced stapler (RS) versus bare stapler (BS) with particular attention to the POPF. Retrospective review of 90 consecutive elective MIDP performed at a single institution between 2014 and 2019 was performed. The primary outcome was POPF as defined by the latest International Study Group of Pancreatic Fistula classification. MIDP with RS was adopted by two surgeons who subsequently performed all their consecutive surgeries with RS. There were 25 and 65 patients who underwent MIDP with RS and BS, respectively. There were 8 (8.9%) open conversions and 17 (18.9%) patients experienced a POPF. Patients who underwent MIDP with RS had a significantly lower POPF rate (4% versus 24.6%,  = .025), lower major (>grade 2) morbidity rate (4% versus 21.5%,  = .046), and lower readmission rate (4% versus 27.7%,  = .014). On multivariate analysis, only the use of BS and obesity (body mass index ≥27.5) was independently associated with the development of a POPF. MIDP performed with RS was associated with a significantly lower rate of POPF, major morbidity, and readmissions compared to BS. The use of RS was protective against POPF.
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http://dx.doi.org/10.1089/lap.2020.0754DOI Listing
January 2021

Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma.

Nat Commun 2021 01 11;12(1):227. Epub 2021 Jan 11.

Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre, Singapore, Singapore.

The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.
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http://dx.doi.org/10.1038/s41467-020-20171-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801667PMC
January 2021

Adoption of Robotic Liver, Pancreatic and Biliary Surgery in Singapore: A Single Institution Experience with Its First 100 Consecutive Cases.

Ann Acad Med Singap 2020 Oct;49(10):742-748

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

Introduction: Presently, robotic hepatopancreatobiliary surgery (RHPBS) is increasingly adopted worldwide. This study reports our experience with the first 100 consecutive cases of RHPBS in Singapore.

Methods: Retrospective review of a single-institution prospective database of the first 100 consecutive RHPBS performed over 6 years from February 2013 to February 2019. Eighty-six cases were performed by a single surgeon.

Results: The 100 consecutive cases included 24 isolated liver resections, 48 pancreatic surgeries (including 2 bile duct resections) and 28 biliary surgeries (including 8 with concomitant liver resections). They included 10 major hepatectomies, 15 pancreaticoduodenectomies, 6 radical resections for gallbladder carcinoma and 8 hepaticojejunostomies. The median operation time was 383 minutes, with interquartile range (IQR) of 258 minutes and there were 2 open conversions. The median blood loss was 200ml (IQR 350ml) and 15 patients required intra-operative blood transfusion. There were no post-operative 90-day nor in-hospital mortalities but 5 patients experienced major (> grade 3a) morbidities. The median post-operative stay was 6 days (IQR 5 days) and there were 12 post-operative 30-day readmissions. Comparison between the first 50 and the subsequent 50 patients demonstrated a significant reduction in blood loss, significantly lower proportion of malignant indications, and a decreasing frequency in liver resections performed.

Conclusion: Our experience with the first 100 consecutive cases of RHPBS confirms its feasibility and safety when performed by experienced laparoscopic hepatopancreatobiliary surgeons. It can be performed for even highly complicated major hepatopancreatobiliary surgery with a low open conversion rate.
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October 2020

Comparison between long and short-term venous patencies after pancreatoduodenectomy or total pancreatectomy with portal/superior mesenteric vein resection stratified by reconstruction type.

PLoS One 2020 5;15(11):e0240737. Epub 2020 Nov 5.

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

Background: Venous reconstruction has been recently demonstrated to be safe for tumours with invasion into portal vein and/or superior mesenteric vein. This study aims to compare the patency between various venous reconstructions.

Methods: This is retrospective study of 76 patients who underwent pancreaticoduodenectomy or total pancreatectomy with venous reconstruction from 2006 to 2018. Patient demographics, tumour histopathology, morbidity, mortality and patency were studied. Kaplan-Meier estimates were performed for primary venous patency.

Results: Sixty-two patients underwent pancreaticoduodenectomy and 14 underwent total pancreatectomy. Forty-seven, 19 and 10 patients underwent primary repair, end-to-end anastomosis and interposition graft respectively. Major morbidity (Clavien-Dindo >grade 2) and 30-day mortality were 14/76(18.4%) and 1/76(1.3%) respectively. There were 12(15.8%) venous occlusion including 4(5.3%) acute occlusions. Overall 6-month, 1-year and 2-year primary patency was 89.1%, 92.5% and 92.3% respectively. 1-year primary patency of primary repair was superior to end-to-end anastomosis and interposition graft (primary repair 100%, end-to-end anastomosis 81.8%, interposition graft 66.7%, p = 0.045). Pairwise comparison also demonstrated superior 1-year patency of primary repair (adjusted p = 0.037). There was no significant difference between the cumulative venous patency for each venous reconstruction method: primary repair 84±6%, end-to-end anastomosis 75±11% and interposition graft 76±15% (p = 0.561).

Conclusion: 1-year primary venous patency of primary repair is superior to end-to-end anastomosis and interposition graft.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240737PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644060PMC
December 2020

Actual 10-year survivors and 10-year recurrence free survivors after primary liver resection for hepatocellular carcinoma in the 21st century: A single institution contemporary experience.

J Surg Oncol 2021 Jan 23;123(1):214-221. Epub 2020 Oct 23.

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

Background: At present, the majority of outcome studies of survival of hepatocellular carcinoma (HCC) post-liver resection (post-LR) present actuarial survival data, which often results in overestimation of survival. We sought to evaluate the actual 10-year survival post-LR for HCC and identify variables that are associated with long-term survival.

Methods: We performed a retrospective review of 600 consecutive patients who underwent primary LR for HCC from 2000 to 2010 at our institution. Twenty-eight patients (4.7%) with 90-day mortality and 125 patients who were lost to follow-up within 10 years were excluded leaving 447 patients who met the study criteria.

Results: There were 140 actual 10-year survivors of which 57 (40.7%) had a recurrence within 10 years. The actual 10-year overall survival (OS) rate of the 447 patients was 31.5% and the actual 10-year recurrence-free survival (RFS) was 18.6%. Multivariate analyses demonstrated that only age >65 years (OR, 0.29; p < .001) (OR, 0.973; p = .041) and presence of cirrhosis (OR. 0.37; p = .005) (OR, 0.31; p = .001) were independent factors negatively associated with actual 10-year OS and actual 10-year RFS, respectively.

Conclusion: Approximately one-third of patients will survive over 10 years after LR for HCC. Amongst these 10-year survivors, 41% had developed recurrent cancer within 10-years of follow-up.
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http://dx.doi.org/10.1002/jso.26259DOI Listing
January 2021

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

Changing trends in the clinicopathological features, practices and outcomes in the surgical management for cystic lesions of the pancreas and impact of the international guidelines: Single institution experience with 462 cases between 1995-2018.

Pancreatology 2020 Dec 28;20(8):1786-1790. Epub 2020 Sep 28.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore.

Introduction: The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice.

Methods: 462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998-2006, 2007-2012 and 2013 to 2018.

Results: Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HR and HR CLP with a corresponding lower proportion of LR and LR being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated.

Conclusions: Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HR and HR CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.
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http://dx.doi.org/10.1016/j.pan.2020.09.019DOI Listing
December 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 Microsurgical Anastomosis of Hepatic Artery on Arterial Complications and Survival Outcomes After Liver Transplantation.

Transplant Proc 2021 Jan-Feb;53(1):65-72. Epub 2020 Sep 18.

Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore; SingHealth Duke-NUS Transplant Centre, Singapore.

Hepatic artery (HA) complications after liver transplant (LT) can lead to biliary complications, graft failure, and mortality. Although microsurgery has been established to improve anastomotic outcomes, it prolongs surgical time and has not reached widespread adoption at all transplant centers. We investigated the incidences of arterial, biliary complications and outcomes after using microsurgery to anastomose HA during LT. Retrospective cohort of consecutive LT performed from 2006 to 2018 was reviewed for operative details and postoperative outcomes. Cox-regression models were used to investigate the relationship between variables and outcomes. Eighty (62.5%) LTs (Group 1) were performed without and compared with 48 (Group 2) with microsurgical anastomosis of HA. Both groups were comparable in terms of arterial and biliary anastomoses performed. Incidence of early HA thrombosis was similar (6.2% vs 2.1%, P = .28). Group 2 had lower incidence of short- and long-term arterial complications, especially amongst living donor liver transplantations (LDLT) (5.3% vs 35.0%, P = .022). On multivariate analysis, microsurgery was associated with lower risk (hazard ratio [HR] 0.09, 95% confidence interval [CI] 0.01-0.71) of, and LDLT had higher risk (HR 4.23, 95% CI 1.46-12.27) of arterial complications. Biliary complications were associated with LDLT (HR 3.91, 95% CI 1.30-11.71) and dual biliary anastomoses (HR 5.26, 95% CI 1.15-24.08) but not with occurrence of HA complications. Worse patient survival was associated with the occurrence of any HA complication (HR 4.11, 95% CI 1.78-9.48). Hepatic arterial complications can be reduced using microsurgical techniques for the anastomosis, resulting in improved patient survival outcomes after liver transplantation.
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http://dx.doi.org/10.1016/j.transproceed.2020.08.017DOI 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

A single institution experience with robotic and laparoscopic distal pancreatectomies.

Ann Hepatobiliary Pancreat Surg 2020 Aug;24(3):283-291

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

Backgrounds/aims: This study aims to describe our experience with minimally-invasive distal pancreatectomies, with emphasis on the comparison between robotic distal pancreatectomy (RDP) and laparoscopic distal pancreatectomy (LDP).

Methods: Retrospective review of 102 consecutive RDP and LDP from 2006 to 2019 was performed.

Results: There were 27 and 75 patients who underwent RDP and LDP, respectively. There were 12 (11.8%) open conversions and 16 (15.7%) patients had major (>grade 2) morbidities. Patients who underwent RDP had significantly higher rates of splenic preservation (44.4% vs. 13.3%, p=0.002), higher rates of splenic-vessel preservation (40.7% vs. 9.3%, p=0.001), higher median difficulty score (5 vs. 3, p=0.002) but longer operation time (385 vs. 245 minutes, p<0.001). The rate of open conversion tended to be lower with RDP (3.7% vs. 14.7%, p=0.175).

Conclusions: In our institution practice, both RDP and LDP were safe and effective. The use of RDP appeared to be complementary to LDP, allowing us to perform more difficult procedures with comparable postoperative outcomes.
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http://dx.doi.org/10.14701/ahbps.2020.24.3.283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452804PMC
August 2020

Validation of the clinical utility of 4 guidelines in the initial triage of mucinous cystic lesions of the pancreas based on cross-sectional imaging: Experience with 188 surgically-treated patients.

Eur J Surg Oncol 2020 11 25;46(11):2114-2121. Epub 2020 Jul 25.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore. Electronic address:

Introduction: Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN.

Methods: One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma.

Results: Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively.

Conclusions: All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.
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http://dx.doi.org/10.1016/j.ejso.2020.07.027DOI Listing
November 2020

Pre-operative Imaging Characteristics in Histology-Proven Resected Intrahepatic Cholangiocarcinoma.

World J Surg 2020 Nov 27;44(11):3862-3867. Epub 2020 Jul 27.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre.

Methods: Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed.

Results: Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group.

Conclusions: A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.
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http://dx.doi.org/10.1007/s00268-020-05698-6DOI Listing
November 2020

Network of clinically-relevant lncRNAs-mRNAs associated with prognosis of hepatocellular carcinoma patients.

Sci Rep 2020 07 7;10(1):11124. Epub 2020 Jul 7.

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

Long non-coding RNAs (lncRNAs) are often aberrantly expressed in Hepatocellular Carcinoma (HCC). We hypothesize that lncRNAs modulate HCC prognoses through differential deregulation of key lncRNAs affecting important gene network in key cancer pathways associated with pertinent clinical phenotype. Here, we present a novel approach integrating lncRNA-mRNA expression profiles with clinical characteristics to identify lncRNA signatures in clinically-relevant co-expression lncRNA-mRNA networks residing in pertinent cancer pathways. Notably one network, associated with poorer prognosis, comprises five up-regulated lncRNAs significantly correlated (|Pearson Correlation Coefficient|≥ 0.9) with 91 up-regulated genes in the cell-cycle and Rho-GTPase pathways. All 5 lncRNAs and 85/91 (93.4%) of the correlated genes were significantly associated with higher tumor-grade while 3/5 lncRNAs were also associated with no tumor capsule. Interestingly, 2/5 lncRNAs that are correlated with numerous genes in this oncogenic network were experimentally shown to up-regulate genes involved in cell-cycle and transcriptional regulation. Another network comprising 4 down-regulated lncRNAs and 8 down-regulated metallothionein-family genes are significantly associated with tumor invasion. The identification of these key lncRNAs signatures that deregulate important network of genes in key cancer pathways associated with pertinent clinical phenotype may facilitate the design of novel therapeutic strategies targeting these 'master' regulators for better patient outcome.
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http://dx.doi.org/10.1038/s41598-020-67742-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341759PMC
July 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

Critical Appraisal of the Impact of Individual Surgeon Experience on the Outcomes of Minimally Invasive Distal Pancreatectomies: Collective Experience of Multiple Surgeons at a Single Institution.

Surg Laparosc Endosc Percutan Tech 2020 Aug;30(4):361-366

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital.

Background: Presently, there are limited studies analyzing the learning experience of minimally invasive distal pancreatectomies (MIDPs) and these frequently focused on a single surgeon or institution learning curve. This study aims to critically analyze the impact of individual surgeon experience on the outcomes of MIDP based on the collective experiences of multiple surgeons at a single institution.

Methods: A retrospective review of 90 consecutive MIDP from 2006 to 2018 was performed. These cases were performed by 13 surgeons over various time periods. The cohort was stratified into 4 groups according to individual surgeon experience. The case experience of these surgeons was as follows: <5 cases (n=8), 6 to 10 cases (n=2), 11 to 15 cases (n=2), and 30 cases (n=1).

Results: The distribution of the 90 cases were as follows: experience <5 cases (n=44), 6 to 10 cases (n=20), 11 to 15 cases (n=11), and 15 cases (n=15). As individual surgeons gained increasing experience, this was significantly associated with increasingly difficult resections performed, increased frequency of the use of robotic assistance and decreasing open conversion rates (20.5% vs. 100% vs. 9.1% vs. 0%, P=0.038). There was no significant difference in other perioperative outcomes. These findings suggest that the outcomes of MIDP in terms of open conversion rate could be optimized after 15 cases. Subset analyses suggested that the learning curve for MIDP of low difficulty was only 5 cases.

Conclusion: MIDP can be safely adopted today and the individual surgeon learning curve for MIDP of all difficulties in terms of open conversion rate can be overcome after 15 cases.
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http://dx.doi.org/10.1097/SLE.0000000000000800DOI Listing
August 2020

Predictors of post-operative complications after surgical resection of hepatocellular carcinoma and their prognostic effects on outcome and survival: A propensity-score matched and structural equation modelling study.

Eur J Surg Oncol 2020 09 2;46(9):1756-1765. Epub 2020 Apr 2.

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

Introduction: Although hepatectomy is the mainstay of curative therapy for hepatocellular carcinoma (HCC), post-operative complications remain high. Presently there is conflicting data on the impact of morbidity on oncologic outcomes. We sought to identify predictors for the occurrence of post-hepatectomy complications, as well as to analyse the impact on overall survival (OS) and recurrence-free survival (RFS).

Materials And Methods: We performed a retrospective review of 888 patients who underwent resection for HCC from 2001 to 2016 in our institution.

Results: A total of 237 patients (26.7%) developed 254 complications of Clavien-Dindo Grade ≥2. Hepatitis B (p = 0.0397), elevated ASA score (p = 0.0002), higher platelet counts (p = 0.0277), raised pre-operative APRI scores (p = 0.0105) and bloodloss (p < 0.0001) were independently associated with the development of complications. After propensity-score matching, 458 patients were compared in a 1:1 ratio (229 with complications versus 229 without). Patients with complications had significantly longer median length of stay (9 days [IQR 7-15] versus 6 days [IQR 5-8], p < 0.0001), higher 90-day mortality rates as well as inferior OS (p = 0.0139), but there was no difference in RFS (p = 0.4577). Age (p = 0.0006), elevated Child Pugh points (p < 0.0001), microvascular invasion (p = 0.0002), multifocal tumours (p = 0.0002), R1 resection (p = 0.0443) and development of complications (p = 0.0091) were independent predictors of inferior OS.

Conclusion: Post-operative morbidity affected both short-term and OS outcomes after hepatectomy for HCC. Hepatitis B, higher ASA scores, elevated preoperative APRI and increased blood loss were found to predict a higher likelihood of developing complications. This may potentially be mitigated by careful patient selection and adopting strict measures to minimise intraoperative bleeding.
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http://dx.doi.org/10.1016/j.ejso.2020.03.219DOI Listing
September 2020

Impact of First Assistant Surgeon Experience on the Perioperative Outcomes of Laparoscopic Hepatectomies.

J Laparoendosc Adv Surg Tech A 2020 Apr 28;30(4):423-428. Epub 2020 Feb 28.

Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore.

This study aims to evaluate the impact of first assistant surgeon experience on the outcomes of laparoscopic hepatectomies in a university-affiliated teaching hospital. This is a retrospective study comparing outcomes of laparoscopic hepatectomies with first assistant surgeons of varying experience levels. Three hundred and eighty-five consecutive laparoscopic hepatectomies performed in a tertiary university-affiliated teaching hospital from 2012 to 2018 were included and stratified into three cohorts-Group 1 in which assistants were residents, Group 2 for fellows, and Group 3 for attendings. Baseline clinicopathologic variables and outcome measures were analyzed using the augmented inverse probability of treatment weighting approach, which is a propensity score-based method that combines aspects of covariate adjustment and inverse probability weighting. Group 3 comprised a greater proportion of advanced- and expert-level surgeries based on the Iwate criteria; 33.8%, 32.2%, and 46.0% of patients underwent advanced- and expert-level surgeries in Groups 1, 2, and 3, respectively. Group 3 had consistently higher operative times as well as more frequent use and longer duration of Pringle's maneuver ( < .05). The median operative times for Groups 1, 2, and 3 were 195, 195, and 290 minutes, respectively. Pringle's maneuver was applied in 26.9%, 33.9%, and 60.2% of patients with a corresponding median duration of 35, 36, and 45 minutes, respectively. None of the other perioperative and postoperative outcomes demonstrated statistically significant differences. With an appropriate selection of cases, participation of residents as first assistants in laparoscopic hepatectomies can be encouraged without compromise in perioperative outcomes.
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http://dx.doi.org/10.1089/lap.2019.0701DOI Listing
April 2020

Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial.

HPB (Oxford) 2020 Sep 30;22(9):1250-1257. Epub 2020 Jan 30.

Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; National Heart Research Institute Singapore, National Heart Centre, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore; The Hatter Cardiovascular Institute, University College London, London, UK; Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taiwan; Tecnologico de Monterrey, Centro de Biotecnologia-FEMSA, Nuevo Leon, Mexico. Electronic address:

Objective: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC).

Methods: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients.

Results: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints.

Conclusion: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy.
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http://dx.doi.org/10.1016/j.hpb.2019.12.002DOI Listing
September 2020

Outcome of minimally invasive liver resection for extrapancreatic biliary malignancies: A single-institutional experience.

J Minim Access Surg 2021 Jan-Mar;17(1):69-75

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

Background: Minimally invasive liver resection (MILR) has been increasingly adopted over the past decade, and its application has been expanded to the management of extrapancreatic biliary malignancies (EPBMs). We aimed to evaluate the peri- and post-operative outcome of patients undergoing MILR for suspected EPMB.

Methods: Forty-four consecutive patients who underwent MILR with a curative intent for EPBM at Singapore General Hospital between 2011 and 2018 were identified from a prospectively maintained surgical database. Clinical and operative data were analysed and compared to provide information and make comparisons on peri- and post-operative outcomes.

Results: A total of 26, 5 and 13 patients underwent MILR for intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PHC) and gallbladder carcinoma (GBCA), respectively. Six major hepatectomies were performed, of which one was laparoscopic assisted and another was robot assisted. Ten patients underwent posterosuperior segmentectomies. There was one open conversion. The mean operative time was 266.5 min, and the mean blood loss was 379 ml. The mean length of hospital stay was 4.7 days with no incidences of 30- and 90-day mortality. The rate of recurrence-free survival (RFS) was 75% (at least 12-month follow-up). There was a significantly higher rate of robot-assisted procedures in patients undergoing MILR for GBCA/PHC as compared to ICC (P = 0.034). Patients undergoing posterosuperior segmentectomies required longer operative time (P = 0.018) with an increased need for (P = 0.001) and duration of (P = 0.025) Pringles manoeuvre. There were no differences in operative time, blood loss, morbidity, mortality or RFS between the above groups.

Conclusion: Minimally invasive surgery can be adopted safely with a low open conversion rate for EPBMs.
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http://dx.doi.org/10.4103/jmas.JMAS_247_19DOI Listing
January 2020

Repeat liver resection versus salvage liver transplant for recurrent hepatocellular carcinoma: A propensity score-adjusted and -matched comparison analysis.

Ann Hepatobiliary Pancreat Surg 2019 Nov 29;23(4):305-312. Epub 2019 Nov 29.

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

Backgrounds/aims: Repeat liver resection (RLR) and salvage liver transplantation (SLT) are viable treatment options for recurrent hepatocellular carcinoma (HCC). With possibly superior survival outcomes than RLR, SLT is however, limited by liver graft availability and poses increased perioperative morbidity. In this study, we seek to compare the outcomes of RLR and SLT for patients with recurrent HCC.

Methods: Between 1999 and 2018, 94 and 16 consecutive patients who underwent RLR and SLT respectively were identified. Further retrospective subgroup analysis was conducted, comparing 16 RLR with 16 SLT patients via propensity-score matching.

Results: After propensity-score adjusted analyses, SLT demonstrated inferior short-term perioperative outcomes than RLR, with increased major morbidity (57.8% vs 5.4 %, =0.0001), reoperations (39.1% vs 0, <0.0001), renal insufficiency (30.1% vs 3%, =0.0071), bleeding (19.8% vs 2.2%, =0.0289), prolonged intensive care unit stay (median=4 vs 0 days, <0.0001) and hospital stay (median=19.8 vs 7.1days, <0.001). However, SLT showed significantly lower recurrence rate (15.4% versus 70.3%, =0.0005) and 5-year cumulative incidence of recurrences (19.4% versus 68.4%, =0.005). Propensity-matched subgroup analysis showed concordant findings.

Conclusions: While SLT offers potentially reduced risks of recurrence and trended towards improved long-term survival outcomes relative to RLR, it has poorer short-term perioperative outcomes. Patient selection is prudent amidst organ shortages to maximise allocated resources and optimise patient outcomes.
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http://dx.doi.org/10.14701/ahbps.2019.23.4.305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893044PMC
November 2019

Minimally invasive major hepatectomies: a Southeast Asian single institution contemporary experience with its first 120 consecutive cases.

ANZ J Surg 2020 04 12;90(4):553-557. Epub 2019 Nov 12.

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

Background: The role of minimally invasive major hepatectomy (MIMH) remains controversial and questions remain about its safety and reproducibility outside expert centres. This study examines the changing trends, safety and outcomes associated with the adoption of MIMH based on a contemporary single institution experience.

Methods: This study is a review of 120 consecutive patients who underwent MIMH between 2011 and 2018. To determine the evolution of MIMH, the study population was stratified into four equal groups of patients. Both conventional major hepatectomies (CMHs) (≥3 segments) and technical major hepatectomies (right anterior and posterior sectionectomies) were included.

Results: There were 70 CMHs and 50 technical major hepatectomies. Seven MIMHs were laparoscopic-assisted and 113 (94.2%) were totally laparoscopic/robotic. There were 10 (8.3%) open conversions. Comparison across the four groups demonstrated that with increasing experience, there was a significant trend in a higher proportion of higher American Society of Anesthesiologists score patients, increasing frequency of CMH performed, increasing frequency of multifocal tumours resected, decreasing use of laparoscopic-assisted approach and decrease in blood loss.

Conclusion: MIMH can be adopted safely today with a low open conversion rate. Over time with increasing experience, we performed MIMH with increasing frequency in higher risk patients and in patients with multifocal tumours but with a decrease in median estimated blood loss.
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http://dx.doi.org/10.1111/ans.15563DOI Listing
April 2020

Novel method of intraoperative liver tumour localisation with indocyanine green and near-infrared imaging.

Singapore Med J 2019 Nov 4. Epub 2019 Nov 4.

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

Introduction: Fluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection.

Methods: From 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0-3 or Day 4-7.

Results: Among 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0-3 and Day 4-7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events.

Conclusion: ICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis.
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http://dx.doi.org/10.11622/smedj.2019137DOI Listing
November 2019

Effect of surgical delay on survival outcomes in patients undergoing curative resection for primary hepatocellular carcinoma: Inverse probability of treatment weighting using propensity scores and propensity score adjustment.

Surgery 2020 02 31;167(2):417-424. Epub 2019 Oct 31.

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

Background: The evidence is conflicting regarding the effect of delays from the time of diagnosis to surgery on the survival in patients with hepatocellular carcinoma. We sought to investigate the impact of time to surgery on overall survival for patients who underwent curative resection for primary hepatocellular carcinoma.

Methods: We performed a retrospective review of all patients who underwent liver resection for primary hepatocellular carcinoma between the years 2000 and 2015. Using 30-, 60-, and 90-day cutoffs, we investigated the effect of time to surgery on survival outcomes by dichotomizing the patients and using inverse probability of treatment weighting to ensure comparability. We also investigated time to surgery in prognostic subgroups by modeling the statistical interaction between time to surgery and the relevant prognostic variable in multivariable Cox models.

Results: A total of 863 patients underwent liver resection for primary hepatocellular carcinoma during the study period. Using 30-, 60-, and 90-day cutoffs, time to surgery did not have a significant bearing on overall survival. For elderly patients (>70 years), patients with Child-Pugh B liver disease, American Society of Anesthesiologists status 2/3, tumor size >5cm, tumor size ≥10cm and presence of extrahepatic invasion, hazard ratio decreased and overall survival improved as time to surgery increased. However, for patients with liver cirrhosis or portal hypertension, increasing time to surgery was found to portend higher risks of death.

Conclusion: Time to surgery does not have a significant bearing on overall survival, and modest delays even appear to be associated with improved survival in specific subsets of patients. The importance of these findings is that patients with hepatocellular carcinoma should be fully optimized before and not rushed to surgery because of concerns of tumor progression and a diminished survival.
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http://dx.doi.org/10.1016/j.surg.2019.09.022DOI Listing
February 2020

Changing trends and outcomes associated with the adoption of minimally invasive pancreatic surgeries: A single institution experience with 150 consecutive procedures in Southeast Asia.

J Minim Access Surg 2020 Oct-Dec;16(4):404-410

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

Background: Minimally invasive pancreatic surgeries (MIPS) are increasingly adopted worldwide. However, it remains uncertain if these reported experiences are reproducible throughout the world today. This study examines the safety and evolution of MIPS at a single institution in Southeast Asia.

Methods: This is a retrospective review of 150 consecutive patients who underwent MIPS between 2006 and 2018 of which 135 cases (90%) were performed since 2012. To determine the evolution of MIPS, the study population was stratified into 3 equal groups of 50 patients. Comparison was also made between pancreatoduodenectomies (PD), distal pancreatectomies (DP) and other pancreatic surgeries.

Results: One hundred and fifty patients underwent MIPS (103 laparoscopic, 45 robotic and 2 hand-assisted). Forty-three patients underwent PD, 93 DP and 14 other MIPS. There were 21 (14.0%) open conversions. There was an exponential increase in caseload over the study period. Comparison across the 3 time periods demonstrated that patients were significantly more likely to have a higher American Society of Anesthesiologists score, older, undergo PD and a longer operation time. The conversion rate decreased from 28% to 0% and increased again to 14% across the 3 time periods. Comparison between the various types of MIPS demonstrated that patients who underwent PD were significantly older, more likely to have symptomatic tumours, had longer surgery time, increased blood loss, increased frequency of extended pancreatectomies, increased frequency of hybrid procedures, longer post-operative stay, increased post-operative morbidity rate and increased post-operative major morbidity rate.

Conclusion: The case volume of MIPS increased rapidly at our institution over the study period. Furthermore, although the indications for MIPS expanded to include more complex procedures in higher risk patients, there was no change in key perioperative outcomes.
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http://dx.doi.org/10.4103/jmas.JMAS_127_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597893PMC
October 2019