Ser Yee Lee
Email Address
gmsleesy@nus.edu.sg
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Publication High Endothelial Venules and Pancreatic Ductal Adenocarcinoma: A potential game changer(Elsevier B.V., 2019) Chai, S.M.; Lee, S.Y.; DUKE-NUS MEDICAL SCHOOLPublication Impact of multidisciplinary tumour boards (MTB) on the clinicopathological characteristics and outcomes of resected colorectal liver metastases across time(BioMed Central Ltd, 2020) Chen, L.; Syn, N.L.; Goh, B.K.P.; Cheow, P.C.; Raj, P.; Koh, Y.; Chung, A.; Lee, S.Y.; Ooi, L.L.; Chan, C.Y.; Teo, J.Y.; DUKE-NUS MEDICAL SCHOOLBackground: 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. © 2020 The Author(s).Publication Central hepatectomy for centrally located malignant liver tumors: A systematic review(2014) Lee, S.Y.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREAim: To study whether central hepatectomy (CH) can achieve similar overall patient survival and disease-free survival rates as conventional major hepatectomies or not. Methods: A systematic literature search was performed in MEDLINE for articles published from January 1983 to June 2013 to evaluate the evidence for and against CH in the management of central hepatic malignancies and to compare the perioperative variables and outcomes of CH to lobar/extended hemihepatectomy. Results: A total of 895 patients were included from 21 relevant studies. Most of these patients who underwent CH were a sub-cohort of larger liver resection studies. Only 4 studies directly compared Central vs hemi-/extended hepatectomies. The range of operative time for CH was reported to be 115 to 627 min and Pringle's maneuver was used for vascular control in the majority of studies. The mean intraoperative blood loss during CH ranged from 380 to 2450 ml. The reported morbidity rates ranged from 5.1% to 61.1%, the most common surgical complication was bile leakage and the most common cause of mortality was liver failure. Mortality ranged from 0.0% to 7.1% with an overall mortality of 2.3% following CH. The 1-year overall survival (OS) for patients underwent CH for hepatocellular carcinoma ranged from 67% to 94%; with the 3-year and 5-year OS having a reported range of 44% to 66.8%, and 31.7% to 66.8% respectively. Conclusion: Based on current literature, CH is a promising option for anatomical parenchymal-preserving procedure in patients with centrally located liver malignancies; it appears to be safe and comparable in both perioperative, early and long term outcomes when compared to patients undergoing hemi-/extended hepatectomy. More prospective studies are awaited to further define its role. © 2014 Baishideng Publishing Group Inc.Publication Clinicopathological-Associated Regulatory Network of Deregulated circRNAs in Hepatocellular Carcinoma(MDPI, 2021-06-01) Han, Jian; Thurnherr, Thomas; Chung, Alexander YF; Goh, Brian KP; Chow, Pierce KH; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Lim, Tony KH; Chong, Samuel S; Ooi, London LPJ; Lee, Caroline G; Assoc Prof Guat Lay, Caroline Lee; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); CANCER SCIENCE INSTITUTE OF SINGAPORE; NUS GRADUATE SCHOOL; DUKE-NUS MEDICAL SCHOOL; PAEDIATRICSHepatocellular carcinoma (HCC) is one of the most common and lethal cancers world-wide. Here, we present a novel strategy to identify key circRNA signatures of clinically relevant co-expressed circRNA‐mRNA networks in pertinent cancer‐pathways that modulate prognosis of HCC patients, by integrating clinic‐pathological features, circRNA and mRNA expression profiles. Through further integration with miRNA expression profiles, clinically relevant competing‐endog-enous‐RNA (ceRNA) networks of circRNA‐miRNA‐mRNAs were constructed. At least five clinically relevant nodal‐circRNAs, co‐expressed with numerous genes, were identified from the circRNA‐mRNA networks. These nodal circRNAs upregulated proliferation (except circRaly) and transformation in cells. The most upregulated nodal‐circRNA, circGPC3, associated with higher-grade tumors and co‐expressed with 33 genes, competes with 11 mRNAs for two shared miRNAs. circGPC3 was experimentally demonstrated to upregulate cell‐cycle and migration/invasion in both transformed and non‐transformed liver cell‐lines. circGPC3 was further shown to act as a sponge of miR‐378a‐3p to regulate APSM (Abnormal spindle‐like microcephaly associated) expression and modulate cell transformation. This study identifies 5 key nodal master circRNAs in a clinically relevant circRNA‐centric network that are significantly associated with poorer prognosis of HCC patients and promotes tumorigenesis in cell‐lines. The identification and characterization of these key circRNAs in clinically relevant circRNA‐mRNA and ceRNA networks may facilitate the design of novel strategies targeting these important regulators for better HCC prognosis.Publication Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma(Springer Science and Business Media LLC, 2021-12) Nguyen, Phuong HD; Ma, Siming; Phua, Cheryl ZJ; Kaya, Neslihan A; Lai, Hannah LH; Lim, Chun Jye; Lim, Jia Qi; Wasser, Martin; Lai, Liyun; Tam, Wai Leong; Lim, Tony KH; Wan, Wei Keat; Loh, Tracy; Leow, Wei Qiang; Pang, Yin Huei; Chan, Chung Yip; Lee, Ser Yee; Cheow, Peng Chung; Toh, Han Chong; Ginhoux, Florent; Iyer, Shridhar; Kow, Alfred WC; Young Dan, Yock; Chung, Alexander; Goh, Brian KP; Albani, Salvatore; Chow, Pierce KH; Zhai, Weiwei; Chew, Valerie; Assoc Prof Wei Chieh Kow; MEDICINE; SURGERY; MICROBIOLOGY AND IMMUNOLOGY; DUKE-NUS MEDICAL SCHOOL; BIOCHEMISTRY; RISK MANAGEMENT INSTITUTEAbstractThe 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.Publication Highly deregulated lncRNA LOC is associated with overall worse prognosis in Hepatocellular Carcinoma patients(IVYSPRING INT PUBL, 2021-01-01) Lim, Lee Jin; Ling, Lay Hiang; Neo, Yu Pei; Chung, Alexander YF; Goh, Brian KP; Chow, Pierce KH; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Lim, Tony KH; Chong, Samuel S; Ooi, London LPJ; Lee, Caroline G; Assoc Prof Guat Lay, Caroline Lee; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); NUS GRADUATE SCHOOL; DUKE-NUS MEDICAL SCHOOL; PAEDIATRICS; BIOCHEMISTRYAlthough numerous long non-coding RNAs (lncRNAs) were reported to be deregulated in Hepatocellular Carcinoma (HCC), experimentally characterized, and/or associated with patient's clinical characteristics, there is, thus far, minimal concerted research strategy to identify deregulated lncRNAs that modulate prognosis of HCC patients. Here, we present a novel strategy where we identify lncRNAs, which are not only de-regulated in HCC patients, but are also associated with pertinent clinical characteristics, potentially contributing to the prognosis of HCC patients. LOC101926913 (LOC) was further characterized because it is the most highly differentially expressed amongst those that are associated with the most number of clinical features (tumor-stage, vascular and tumor invasion and poorer overall survival). Experimental gain- and loss-of-function manipulation of LOC in liver cell-lines highlight LOC as a potential onco-lncRNA promoting cell proliferation, anchorage independent growth and invasion. LOC expression in cells up-regulated genes involved in GTPase-activities and downregulated genes associated with cellular detoxification, oxygen- and drug-transport. Hence, LOC may represent a novel therapeutic target, modulating prognosis of HCC patients through up-regulating GTPase-activities and down-regulating detoxification, oxygen- and drug-transport. This strategy may thus be useful for the identification of clinically relevant lncRNAs as potential biomarkers/targets that modulate prognosis in other cancers as well.Publication Author Correction: Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma (Nature Communications, (2021), 12, 1, (227), 10.1038/s41467-020-20171-7)(Nature Research, 2021-02-23) Nguyen, Phuong H. D.; Ma, Siming; Phua, Cheryl Z. J.; Kaya, Neslihan A.; Lai, Hannah L. H.; Lim, Chun Jye; Lim, Jia Qi; Wasser, Martin; Lai, Liyun; Tam, Wai Leong; Lim, Tony K. H.; Wan, Wei Keat; Loh, Tracy; Leow, Wei Qiang; Pang, Yin Huei; Chan, Chung Yip; Lee, Ser Yee; Cheow, Peng Chung; Toh, Han Chong; Ginhoux, Florent; Iyer, Shridhar; Kow, Alfred W. C.; Young Dan, Yock; Chung, Alexander; Bonney, Glen K.; Goh, Brian K. P.; Albani, Salvatore; Chow, Pierce K. H.; Zhai, Weiwei; Chew, Valerie; MEDICINEThe original version of this Article omitted from the author list the 25th author Glen K. Bonney, who is from ‘Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore’. Consequently, the following was added to the Author Contributions: ‘G.K.B recruited patients, provided samples and discussed the data. F.G. provided analysis support for immunomics data.’ The original version of this Article also contained an error in the author affiliations. Affiliation 12 incorrectly read ‘Department of Medicine, Yong Loo Lin School of Medicine, National University Hospital Singapore, Singapore, Singapore’. In addition, the original version of this Article contained an error in the author affiliations. Yock Young Dan was incorrectly associated with Division of Gastroenterology and Hepatology, National University Hospital Singapore, Singapore, Singapore. These errors have now been corrected in both the PDF and HTML versions of the Article. © 2021, The Author(s).Publication Repeat liver resection versus salvage liver transplant for recurrent hepatocellular carcinoma: A propensity score-adjusted and -matched comparison analysis.(The Korean Association of Hepato-Biliary-Pancreatic Surgery, 2019-11) Guo, Yuxin; Tan, Ek-Khoon; Syn, Nicholas L; Krishnamoorthy, Thinesh-Lee; Tan, Chee-Kiat; Lim, Reina; Lee, Ser-Yee; Chan, Chung-Yip; Cheow, Peng-Chung; Chung, Alexander YF; Jeyaraj, Prema Raj; Goh, Brian KP; Prof Chee Kiat Kenneth Tan; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLBACKGROUNDS/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 %, p=0.0001), reoperations (39.1% vs 0, p<0.0001), renal insufficiency (30.1% vs 3%, p=0.0071), bleeding (19.8% vs 2.2%, p=0.0289), prolonged intensive care unit stay (median=4 vs 0 days, p<0.0001) and hospital stay (median=19.8 vs 7.1days, p<0.001). However, SLT showed significantly lower recurrence rate (15.4% versus 70.3%, p=0.0005) and 5-year cumulative incidence of recurrences (19.4% versus 68.4%, p=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.Publication Hepatic adenoma mimicking a metastatic lesion on computed tomography-positron emission tomography scan(2013) Lim, D.; Lee, S.Y.; Lim, K.H.; Chan, C.Y.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREPositron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is an imaging modality which reflects cellular glucose metabolism. Most malignant cells accumulate and trap 18F-FDG, allowing the visualisation of increased uptake. It is hence widely used to differentiate malignant from benign lesions. "False positive" findings of hepatic lesions have been described in certain instances such as hepatic abscesses, but are rare in cases involving hepatocellular adenomas. To our knowledge, there have been only 7 reports in the English literature documenting PET-avid hepatocellular adenomas; 6 of the 7 reports were published in the last 3 years with the first report by Patel et al. We report the case of a 44-year-old Chinese female patient with a history of cervical adenocarcinoma, referred for a hepatic lesion noted on a surveillance computed tomography (CT) scan. A subsequent CT-PET performed showed a hypermetabolic lesion (standardized uptake value 7.9) in segment IVb of the liver. After discussion at a multidisciplinary hepato-pancreato-biliary conference, the consensus was that of a metastatic lesion from her previous cervical adenocarcinoma, and a resection of the hepatic lesion was performed. Histology revealed features consistent with a hepatocyte nuclear factor-1 α inactivated steatotic hepatocellular adenoma. © 2013 Baishideng. All rights reserved.Publication Spontaneous regression of pancreatic cancer: A case report and literature review(Elsevier Ltd, 2018) Chin, K.M.; Chan, C.Y.; Lee, S.Y.; DUKE-NUS MEDICAL SCHOOLIntroduction Spontaneous regression of cancer is defined as the partial or complete disappearance of malignant disease without treatment, or in the presence of therapy that is deemed inadequate to exert an influence on malignant disease, as composed by Tilden Everson and Warren Cole in the 1960s. It has been a topic of major interest in the field of medical and surgical oncology. It is poorly understood and scantily documented. Factors associated and postulated pathogeneses are at best, hypothetical. Presentation of case We report a case of spontaneous resolution of a head of pancreas carcinoma in a 77-year-old gentleman after a myocardial infarction event delayed planned surgery. Discussion A literature review of previously reported cases of spontaneous regression of pancreatic cancer was performed. The possible predisposing factors to spontaneous regression of pancreatic and other forms of malignancies was reviewed. Conclusion This is a novel case of spontaneous regression of pancreatic carcinoma after an episode of myocardial infarction. The pathophysiology to spontaneous resolution of cancer is not well understood, may be multifactorial and requires further study © 2017 The Authors