- Surgeon-scientistedit
“Evaluation of the Sendai and 2012 International Consensus Guidelines based on cross-sectional imaging findings performed for the initial triage of mucinous cystic lesions of the pancreas: a single institution experience with 114 surgically treated patients.” Or rather “Don Giovanni o sia il conv...more
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A 45-year-old female complained of a painless swelling, which had developed in the epigastric region, and was slowly growing in size over the last one year. The patient had undergone excision of a similar swelling at the same site seven... more
A 45-year-old female complained of a painless swelling, which had developed in the epigastric region, and was slowly growing in size over the last one year. The patient had undergone excision of a similar swelling at the same site seven years ago and was now facing recurrence. Histopathology and immunohistochemical (IHC) examination confirmed the diagnosis of Dermatofibrosarcoma Protuberans.
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While there is an ethical obligation to improve clinical outcomes by developing better therapies, surgical innovation has largely progressed without the strict regulations required of novel pharmaceutical products. We explore the reasons... more
While there is an ethical obligation to improve clinical outcomes by developing better therapies, surgical innovation has largely progressed without the strict regulations required of novel pharmaceutical products. We explore the reasons why new surgical techniques are frequently introduced without the benefit of randomised controlled trials, and present an approach to the ethical evaluation of novel surgical procedures.
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The laparoscopic approach is increasingly adopted for liver resections today especially for lesions located in the left lateral liver section. This study was conducted to determine the impact of the introduction of laparoscopic liver... more
The laparoscopic approach is increasingly adopted for liver resections today especially for lesions located in the left lateral liver section. This study was conducted to determine the impact of the introduction of laparoscopic liver resection (LLR) as a surgical option for suspected small- to medium-sized (<8 cm) tumors located in the left lateral section (LLS). This is a retrospective review of 156 consecutive patients who underwent LLR or open liver resection (OLR) of tumors located in the LLS. The study was divided into 2 consecutive periods (period 1, January 2003 through September 2006, and period 2, October 2006 through April 2014); LLR was available as a surgical option only in the latter period. Comparisons made were LLR versus OLR, LLR versus OLR (in period 2 only), and resections performed in period 1 versus period 2. Forty-two patients underwent LLR with 4 conversions. LLR was significantly associated with a longer median operative time [167.5 minutes (range, 60-525) ...
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High resolution yttrium-90 ((90)Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight... more
High resolution yttrium-90 ((90)Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight capability. However, reconstructed (90)Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by (90)Y PET/CT, which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall, and kidney, supported by angiography and (90)Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT.
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For yttrium-90 ((90)Y) radioembolization, the common practice of assuming a standard 1,000-g lung mass for predictive dosimetry is fundamentally incongruent with the modern philosophy of personalized medicine. We recently developed a... more
For yttrium-90 ((90)Y) radioembolization, the common practice of assuming a standard 1,000-g lung mass for predictive dosimetry is fundamentally incongruent with the modern philosophy of personalized medicine. We recently developed a technique of personalized predictive lung dosimetry using technetium-99m ((99m)Tc) macroaggregated albumin (MAA) single photon emission computed tomography with integrated CT (SPECT/CT) of the lung as part of our routine dosimetric protocol for (90)Y radioembolization. Its rationales are the technical superiority of SPECT/CT over planar scintigraphy, ease and convenience of lung auto-segmentation CT densitovolumetry, and dosimetric advantage of patient-specific lung parenchyma masses. This is a retrospective study of our pulmonary clinical outcomes and comparison of lung dosimetric accuracy and precision by (99m)Tc MAA SPECT/CT versus conventional planar methodology. (90)Y resin microspheres (SIR-Spheres) were used for radioembolization. Diagnostic CT d...
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Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have... more
Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have advocated an aggressive resectional policy. This approach is no longer appropriate, and the number of PCs detected incidentally has increased. This study reviews the present literature and attempts to provide a management algorithm of pancreatic cysts based on currently available evidence. A Medline search was conducted to identify studies investigating PC, with particular emphasis placed on studies addressing its diagnosis and management. Additional articles were obtained from the reference lists of key articles and recent reviews. Based on current evidence, the optimal management of PC remains an art and should be individualized based on the risk-benefit ratio of surgery, which is influenced by multiple factors, such as the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s potential life expectancy, surgical risk; and malignant potential of the cyst. Our proposed management algorithm is based on an individual&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s predicted risk-benefit ratio of surgery. Prospective evaluation of the algorithm is needed to determine its integrity.
Research Interests: Management, Algorithms, Surgery, Evidence Based Medicine, Natural History, and 15 moreMedicine, Algorithm, Humans, Differential Diagnosis, Decision Tree, Risk factors, Clinical Sciences, Prognosis, Disease Progression, Risk Factors, Management Strategy, The American, Pancreatic Cyst, Pancreatic neoplasms, and pancreatectomy
The aim of this study is to report an update of the surgical experience at a single institution with these unusual tumors. Sixteen consecutive patients who underwent surgery for a pathologically confirmed solid pseudopapillary neoplasm... more
The aim of this study is to report an update of the surgical experience at a single institution with these unusual tumors. Sixteen consecutive patients who underwent surgery for a pathologically confirmed solid pseudopapillary neoplasm (SPPN) were retrospectively reviewed. Fifteen of the patients were female and the median age at diagnosis was 30 years (range, 14-53 years). Abdominal and back pain were the most common presenting symptoms. The tumors appeared on cross-sectional imaging as solid and cystic (n = 14) or cystic (n = 2) masses. The median tumor size was 9.5 cm (range, 5.0-24.0 cm). All 16 patients had curative resections including 3 pancreaticoduodenectomies and 13 distal pancreatectomies. Three patients required extended resections including pancreaticoduodenectomy with portal vein resection, distal pancreatectomy with tranverse colectomy, and distal pancreactomy with omentectomy. Two of the resections were R1 whereas 14 were R0. All patients were alive and disease-free at a median follow-up of 43 months (range, 3-186 months). SPPNs should be considered in young women presenting with a large solid-cystic pancreatic mass. Aggressive en bloc resection should always be attempted including resection of concomitant metastases as patients demonstrate excellent long-term survival even in the presence of distant spread.
Research Interests: Treatment Outcome, Surgical Oncology, Adolescent, Medicine, Humans, and 15 morePancreas, Female, Male, Papillary Squamous Cell Carcinoma, Middle Aged, Adult, Retrospective Studies, Surgical, Pancreaticoduodenectomy, Colectomy, Portal vein, Omentum, Pancreatic neoplasms, Pancreatic pseudocyst, and pancreatectomy
Research Interests: Surgery, Surgical Oncology, Medicine, Humans, Female, and 15 moreMale, Follow-up studies, GIST, Length of Stay, Aged, Middle Aged, Adult, Time Factors, Retrospective Studies, Surgical, Cohort Studies, Paraganglioma, Surgical Treatment, Gastrointestinal Stromal Tumors, and Outcome assessment (Health care)
Research Interests: Nonparametric Statistics, Immunohistochemistry, Humans, Female, Male, and 15 moreClinical Sciences, Aged, Middle Aged, Neoplasm Invasiveness, Adult, Retrospective Studies, Prognosis, Chi Square Distribution, Proportional Hazards Models, Large, Postoperative Complications, Gastrointestinal Stromal Tumors, Gastrectomy, Gastrointestinal surgery, and pancreatectomy
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The Sendai Consensus Guidelines (SCG) were formulated in 2006 and updated in Fukuoka in 2012 (FCG) to guide management of cystic mucinous neoplasms of the pancreas. This study aims to evaluate the clinical utility of the SCG and FCG in... more
The Sendai Consensus Guidelines (SCG) were formulated in 2006 and updated in Fukuoka in 2012 (FCG) to guide management of cystic mucinous neoplasms of the pancreas. This study aims to evaluate the clinical utility of the SCG and FCG in the initial triage of all suspected pancreatic cystic neoplasms. Overall, 317 surgically-treated patients with a suspected pancreatic cystic neoplasm were classified according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG)), and according to the FCG as high risk (HR(FCG)), worrisome (W(FCG)), and low risk (LR(FCG)). Cystic lesions of the pancreas (CLP) were classified as potentially malignant/malignant or benign according to the final pathology. The presence of symptoms, proximal lesions with obstructive jaundice, elevated serum carcinoembryonic antigen/carbohydrate antigen 19-9 (CEA/CA 19-9), size ≥3 cm, presence of solid component, main pancreatic duct dilatation, thickened enhancing walls, and change in ductal caliber with distal atrophy were predictive of a potentially malignant/malignant CLP on univariate analyses. The positive predictive value (PPV) and negative predictive value (NPV) of HR(SCG) and HR(ICG2012) for a potentially malignant/malignant lesion was 67 and 88 %, and 88 and 92.5 %, respectively. There were no malignant lesions in both LR groups but some potentially malignant lesions such as cystic pancreatic neuroendocrine neoplasms with uncertain behavior were classified as LR. The updated FCG was superior to the SCG for the initial triage of all suspected pancreatic cystic neoplasms. CLP in the LR(FCG) group can be safely managed conservatively, and those in the HR(FCG) group should undergo resection.
Research Interests: Magnetic Resonance Imaging, Surgical Oncology, Risk assessment, Japan, Adolescent, and 15 moreMedicine, Humans, Triage, Female, Male, Young Adult, Aged, Middle Aged, Adult, Retrospective Studies, Risk Assessment, X ray Computed Tomography, Carcinoembryonic Antigen, Predictive value of tests, and Pancreatic neoplasms
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Research Interests: Hospital Infection, Communicable Diseases, Medicine, Disease Outbreaks, Prospective studies, and 15 moreHumans, Infection Control, Female, Male, Incidence, Clinical Sciences, Aged, Middle Aged, Disease Outbreak, Adult, Management Strategy, Elsevier, Observational Study, Cohort Studies, and Cross Infection
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary... more
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary GCs, GC lines, and non-malignant gastric tissues. We identified ~2000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3). Somatic promoter-associated N-terminal peptides displaying relative depletion in tumors exhibited high-affinity MHC binding predictions and elicited potent T-cell responses in vitro, suggesting a mechanism for reducing tumor antigenicity. In multiple patient cohorts, GCs with high somatic promoter usage also displayed reduced T-cell cytolytic marker expression. Somatic promoters are enriched in PRC2 occupancy, display sensitivity to EZH2 therapeutic inhibition, and are a...
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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... more
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). 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. 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. 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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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... more
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 transfu...
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Research Interests: Clinical Sciences and hpb
The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we... more
The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we investigate the impact of TIBs and their interaction with T cells on HCC patient prognosis. Tissue samples were obtained from 112 patients with HCC from Singapore, Hong Kong and Zurich and analysed using immunohistochemistry and immunofluorescence. RNA expression of CD19, CD8A, IFNG was analysed using quantitative PCR. The phenotype of freshly isolated TILs was analysed using flow cytometry. A mouse model depleted of mature B cells was used for functional study. Tumour-infiltrating T cells and B cells were observed in close contact with each other and their densities are correlated with superior survival in patients with HCC. Furthermore, the density of TIBs was correlated with an enhanced expression of granzyme B and IFN-γ, as well as with reduced t...
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Hepatocellular carcinoma (HCC), which constitutes over 85-90% of all primary liver cancers, is the most predominant type of liver cancer, and the third leading cause of cancer related deaths in the world. While the Asia-Pacific is a... more
Hepatocellular carcinoma (HCC), which constitutes over 85-90% of all primary liver cancers, is the most predominant type of liver cancer, and the third leading cause of cancer related deaths in the world. While the Asia-Pacific is a highly heterogeneous region in geography, ethnicity and in the level of socio-economic development, the main burden of HCC falls in this region and there are compelling reasons and advantages to conduct definitive clinical trials in HCC where it is endemic. The Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group was established in 1997 and has faced and overcome challenges that are inherent in conducting clinical trials in a disparate region. Clinical trial infrastructure is rudimentary at many sites and requires significant effort to be expended on training and monitoring to ensure production of definitive data. The benefits of industrial support of Investigator-Initiated Trials are discussed in the context of the Asia-Pacific. The positive experience of the AHCC trials group would be valuable to any collaborative trials in countries with disparate levels of socio-economic development.
Research Interests: Culture, Developing Countries, International Cooperation, Humans, Asia, and 10 moreHepatocellular Carcinoma, Australasia, Developed Countries, Pacific ocean, Cooperative Behavior, Socioeconomic Factors, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Liver neoplasms, and Medical and Health Sciences
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Several studies published mainly from pioneers and early adopters have documented the evolution of minimally invasive hepatectomy (MIH). However, questions remain if these reported experiences are applicable and reproducible today. This... more
Several studies published mainly from pioneers and early adopters have documented the evolution of minimally invasive hepatectomy (MIH). However, questions remain if these reported experiences are applicable and reproducible today. This study examines the changing trends, safety, and outcomes associated with the adoption of MIH based on a contemporary single-institution experience. This is a retrospective review of 400 consecutive patients who underwent MIH between 2006 and 2017 of which 360 cases (90%) were performed since 2012. To determine the evolution of MIH, the study population was stratified into four equal groups of 100 patients. Analyses were also performed of predictive factors and outcomes of open conversion. Four hundred patients underwent MIH of which 379 (94.8%) were totally laparoscopic/robotic. Eighty-eight (22.0%) patients underwent major hepatectomy and 160 (40.0%) had resection of tumors located in the posterosuperior segments. There were 38 (9.5%) open conversio...
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This study aims to determine the safety and efficacy of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma (rHCC). Twenty patients underwent LRLR for rHCC between 2015 and 2017. The control groups consisted... more
This study aims to determine the safety and efficacy of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma (rHCC). Twenty patients underwent LRLR for rHCC between 2015 and 2017. The control groups consisted of 79 open RLR (ORLR) for rHCC and 185 LLR for primary HCC. We undertook propensity score-adjusted analyses (PSA) and 1:1 propensity score matching (PSM) for the comparison of LRLR versus ORLR. Comparison of LRLR versus LLR was done using multivariable regression models with adjustment for clinically relevant covariates. Twenty patients underwent LRLR with three open conversions (15%). Both PSA and 1:1-PSM demonstrated that LRLR was significantly associated with a shorter stay, superior disease-free survival (DFS) but longer operation time compared to ORLR. Comparison between LRLR versus LLR demonstrated that patients undergoing LRLR were significantly older, had smaller tumors, longer operation time and decreased frequency of Pringle's maneuver...
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The technical complexity of laparoscopic liver resection (LLR) poses unique challenges distinct from open surgery. An objective scoring system was developed that preoperatively quantifies the difficulty of LRR to help guide surgeon... more
The technical complexity of laparoscopic liver resection (LLR) poses unique challenges distinct from open surgery. An objective scoring system was developed that preoperatively quantifies the difficulty of LRR to help guide surgeon decision-making regarding the feasibility and safety of minimally invasive approaches. The aim of this multiinstitutional study was to externally validate this scoring system. Patients who underwent LLR at two institutions were reviewed. LLR difficulty score (LDS) was calculated based on patient, tumor, and anatomic characteristics by two independent, blinded hepatobiliary surgeons. Surrogates of case complexity (e.g., conversion rate, operative time) were used for validation of this index. From 2006 to 2016, 444 LLR were scored as low (n = 94), intermediate (n = 98), and high difficulty (n = 152) with respective conversion rates of 5.3%, 15.7%, and 25%. Cases of higher LDS correlated with larger mean blood loss (203 ml vs. 331 ml vs. 635 ml). Mean operative and Pringle maneuver used were associated with increasing LDS (155 min vs. 202 min vs. 315 min and 14.4% vs. 29.7% vs. 45.1% respectively). These operative surrogates of difficulty correlated significantly with the LDS (all p &lt; 0.0001). This comprehensive external validation of the LDS is robust and applicable in diverse patient populations. This LDS serves as a useful objective predictor of technical difficulty for LLR to help surgeons in selecting patients according to their individual operative experience and is valuable for preoperative risk estimation and stratification in randomized trials.
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This study aims to evaluate the safety and feasibility of laparoscopic minor hepatectomy (LMH) in elderly patients with hepatocellular carcinoma (HCC). A total of 40 consecutive elderly (≥ 70 years) patients were compared with 94 young... more
This study aims to evaluate the safety and feasibility of laparoscopic minor hepatectomy (LMH) in elderly patients with hepatocellular carcinoma (HCC). A total of 40 consecutive elderly (≥ 70 years) patients were compared with 94 young patients (&lt; 70 years). The 40 patients were also compared with 85 consecutive elderly patients who underwent open minor hepatectomies (OMH). After 1:1 propensity-score matching (PSM), 32 LMHs were compared with 32 OMHs in elderly patients. Comparison between the baseline characteristics of elderly and young HCC patients showed that elderly patients were significantly more likely to have comorbidities, ASA score &gt; 2, non-hepatitis B, previous liver resection and larger tumor size. Comparison between perioperative outcomes demonstrated that elderly patients were significantly more likely to have a longer operation time, increased blood loss, increased need for blood transfusion, longer Pringles duration and longer postoperative stay. Comparison between LMH and OMH in elderly patients demonstrated no significant difference in baseline characteristics except the LMH cohort were significantly more likely to have &gt; 1 comorbidity, higher platelet count and lower median AFP level. Comparison between outcomes before and after PSM demonstrated that LMH was associated with longer operation time, increased blood loss, longer Pringles duration but decreased postoperative pulmonary complications and shorter postoperative stay compared to OMH. LMH is safe and feasible in elderly patients with HCC. However, LMH in elderly patients is associated with poorer perioperative outcomes compared to LMH in young patients. Comparison between LMH and OMH in elderly patients demonstrated advantages in terms of decreased pulmonary complications and shorter length of stay at the expense of increased operation time and blood loss.
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Spontaneous rupture of Hepatocellular Carcinoma (srHCC) is a life-threatening emergency. We sought to identify the pre-operative predictors of early tumor recurrence/mortality including the role of inflammatory indices after partial... more
Spontaneous rupture of Hepatocellular Carcinoma (srHCC) is a life-threatening emergency. We sought to identify the pre-operative predictors of early tumor recurrence/mortality including the role of inflammatory indices after partial hepatectomy for srHCC. Between 2000-2015, 79 patients with srHCC were identified to have undergone upfront partial hepatectomy following srHCC. Clinicopathologic data were retrospectively analyzed to identify pre-operative predictors of early (&lt;1 year) recurrence and mortality. Seventy-nine patients were identified to have undergone partial hepatectomy for srHCC. The 1-year mortality and 1-year recurrence rate in our series was 30.3% and 41.8% respectively. On multivariate analyses, free tumor rupture and a tumor size &gt; 10 cm were identified to be independent predictors of early recurrence while an alpha fetoprotein (AFP) &gt; 200 ng/mL was an independent predictor of early mortality. Neutrophil-to-lymphocyte ratio &gt; 3 and prognostic nutritional index &lt; 40 were predictors of early recurrence while PLR &gt; 180 was a predictor of early mortality on univariate analyses but not multivariate analyses. Tumor size &gt; 10 cm, free tumor rupture, and an AFP &gt; 200 ng/mL were useful predictors in avoiding &quot;futile surgery&quot; in patients with srHCC undergoing a partial hepatectomy. Preoperative inflammatory markers appear to be less useful as predictors of early recurrence/mortality in this cohort of patients.
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Presently, the adoption of laparoscopic hepatectomy is rapidly increasingly worldwide. However, the application of robotic hepatectomy (RH) remains limited and its role remains undefined today. A retrospective review of 43 consecutive... more
Presently, the adoption of laparoscopic hepatectomy is rapidly increasingly worldwide. However, the application of robotic hepatectomy (RH) remains limited and its role remains undefined today. A retrospective review of 43 consecutive patients who underwent RH at two institutions in the Singapore Health Services Group. Forty-three consecutive patients underwent 48 resections during the study period. Seven (16.3%) patients underwent major resections and seven (16.3%) underwent right posterior sectionectomies. Nineteen (44.2%) patients had tumours located in the difficult posterosuperior segments, five had multiple resections and three underwent repeat resections for recurrent tumours. RH was performed for malignant tumours in 32 (74%) patients and 16 (37.2%) had cirrhosis. Seven RH was performed with other concomitant procedures including three colectomies, three hilar lymphadenectomies and one portal vein ligation. The median operation time was 360 min (range 75-825) and the median ...
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Chronic inflammation induced by chronic hepatitis B virus (HBV) infection increases the risk of hepatocellular carcinoma (HCC). However, little is known about the immune landscape of HBV-related HCC and its influence on the design of... more
Chronic inflammation induced by chronic hepatitis B virus (HBV) infection increases the risk of hepatocellular carcinoma (HCC). However, little is known about the immune landscape of HBV-related HCC and its influence on the design of effective cancer immunotherapeutics. We interrogated the immune microenvironments of HBV-related HCC and non-viral-related HCC using immunohistochemistry and cytometry by time-of-flight (CyTOF). On identifying unique immune subsets enriched in HBV-related HCC, we further interrogated their phenotypes and functions using next-generation sequencing (NGS) and in vitro T-cell proliferation assays. In-depth interrogation of the immune landscapes showed that regulatory T cells (T) and CD8 resident memory T cells (T) were enriched in HBV-related HCC, whereas Tim-3CD8 T cells and CD244 natural killer cells were enriched in non-viral-related HCC. NGS of isolated T and T from HBV-related HCC and non-viral-related HCC identified distinct functional signatures asso...
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Laparoscopic liver resection has been gaining momentum, and it has become an accepted practice after the two international consensus conferences where experts worked up guidelines to standardize this approach and improve its safety.... more
Laparoscopic liver resection has been gaining momentum, and it has become an accepted practice after the two international consensus conferences where experts worked up guidelines to standardize this approach and improve its safety. However, most laparoscopic hepatectomies were performed in patients with liver metastases. The concurrent presence of liver cirrhosis with hepatocellular carcinoma (HCC) poses a great challenge to clinicians trying to establish a routine use of laparoscopic liver resection for HCC. The first Asia Pacific consensus meeting on laparoscopic liver resection for HCC was held in July 2016 in Hong Kong. A group of expert liver surgeons with experience in both open and laparoscopic hepatectomy for HCC convened to formulate recommendations on the role and perspective of laparoscopic liver resection for primary liver cancer. The recommendations consolidate the most recent evidence pertaining to laparoscopic hepatectomy together with the latest thinking of practici...
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As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models... more
As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing. Patient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD- (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated. Similar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other ...
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Yttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which... more
Yttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response. Time-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE. TILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8 T cells, CD56 NK cells and CD8 CD56 NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GBCD8 T cells to the Y90-RE-treated tumours. When comparing PBMCs befor...
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Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with... more
Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0...
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Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways... more
Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10-6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The...
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Liver resection is a major curative option in patients presenting with hepatocellular carcinoma. An inadequate functional liver remnant is a major limiting factor precluding liver resection. In recent years, hypertrophy of the functional... more
Liver resection is a major curative option in patients presenting with hepatocellular carcinoma. An inadequate functional liver remnant is a major limiting factor precluding liver resection. In recent years, hypertrophy of the functional liver remnant after selective internal radiation therapy hypertrophy has been observed, but the degree of hypertrophy in the early postselective internal radiation therapy period has not been well studied. We conducted a prospective study on patients undergoing unilobar, Yttrium-90 selective internal radiation therapy for hepatocellular carcinoma to evaluate early hypertrophy at 4-6 weeks and 8-12 weeks after selective internal radiation therapy. In the study, 24 eligible patients were recruited and had serial volumetric measurements performed. The median age was 66 years (38-75 years). All patients were either Child-Pugh Class A or B, and 6/24 patients had documented, clinically relevant portal hypertension; 15 of the 24 patients were hepatitis B p...
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Mirizzi syndrome (MS) occurs when gallstone impaction in Hartmann's pouch results in extrinsic obstruction of the common bile duct, and fistulation may occur. We retrospectively reviewed electronic records of patients surgically... more
Mirizzi syndrome (MS) occurs when gallstone impaction in Hartmann's pouch results in extrinsic obstruction of the common bile duct, and fistulation may occur. We retrospectively reviewed electronic records of patients surgically treated for MS from November 2001 to June 2012. Patient presentations, diagnostic methods, treatments and complications were recorded. Sixty-four patients were grouped according to a classification proposed by Beltran et al. [World J Surg 2008; 32: 2237-2243]. Forty-three (66.2%), 18 (27.7%) and 3 (4.6%) patients were classified as types I, II, and III respectively. Magnetic-resonance-cholangiopancreaticography was the most sensitive imaging modality, suggesting MS in 24 (88.9%), followed by CT scan (40%) and ultrasonography (11.4%). Forty-four underwent Endoscopic-retrograde-cholangiopancreaticography and 29 (65.9%) suggested the presence of MS. MS was accurately diagnosed pre-operatively in 48 (73.8%) patients. In type I, 40 (93.0%) patients underwent ...
Research Interests:
Most studies analyzing the learning experience of laparoscopic liver resection (LLR) focused on the experience of one or two expert pioneering surgeons. This study aims to critically analyze the impact of individual surgeon experience on... more
Most studies analyzing the learning experience of laparoscopic liver resection (LLR) focused on the experience of one or two expert pioneering surgeons. This study aims to critically analyze the impact of individual surgeon experience on the outcomes of LLR based on the contemporary collective experiences of multiple surgeons at single institution. Retrospective review of 324 consecutive LLR from 2006 to 2016. The cases were performed by 10 surgeons over various time periods. Four surgeons had individual experience with &amp;amp;amp;amp;lt;20 cases, four surgeons with 20-30 cases, and two surgeons with &amp;amp;amp;amp;gt;90 cases. The cohort was divided into two groups: comparing a surgeon&amp;amp;amp;amp;#39;s experience between the first 20, 30, 40, and 50 cases with patients treated thereafter. Similarly, we performed subset analyses for anterolateral lesions, posterosuperior lesions, and major hepatectomies. As individual surgeons gained increasing experience, this was significantly associated with older patients being operated, decreased hand-assistance, larger tumor size, increased liver resections, increased major resections, and increased resections of tumors located at the posterosuperior segments. This resulted in significantly longer operation time and increased use of Pringle maneuver but no difference in other outcomes. Analysis of LLR for tumors in the posterosuperior segments demonstrated that there was a significant decrease in conversion rates after a surgeon had experience with 20 LLR. For major hepatectomies, there was a significant decrease in morbidity, mortality, and length of stay after acquiring experience with 20 LLR. LLR can be safely adopted today especially for lesions in the anterolateral segments. LLR for lesions in the difficult posterosuperior segments and major hepatectomies especially in cirrhosis should only be attempted by surgeons who have acquired a minimum experience with 20 LLR.