Publications by authors named "Shridhar Iyer"

Background: Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC.

Methods: HCC tumor samples were classified into "low" or "normal/high" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues.

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Article Synopsis
  • - The study analyzed data from the United Network for Organ Sharing between 2000 and 2022 to evaluate how the causes of liver disease impact liver transplantation outcomes for individuals with hepatocellular carcinoma (HCC), focusing on differences between men and women.
  • - Findings revealed that nonalcoholic steatohepatitis (NASH) is the fastest-growing cause of liver disease in women and has surpassed chronic hepatitis C as the leading cause for both genders on transplant waitlists.
  • - Women with HCC experience longer wait times for liver transplants and have lower rates of receiving transplants compared to men, though they tend to have better posttransplant survival rates when suffering from NASH-related HCC.
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Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS.

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Background: Endoscopic retrograde cholangiopancreatography is a common procedure performed for choledocholithiasis and gallstone pancreatitis. Although a relatively low risk procedure, it is not without its complications. Cases of impacted Dormia baskets during stone retrieval have been reported, but these are usually retrieved surgically during the same setting.

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Unlabelled: Laparoscopic donor right hepatectomy (LDRH) is a technically challenging procedure. There is increasing evidence demonstrating the safety of LDRH in high-volume expert centers. We report our center's experience in implementing an LDRH program in a small- to medium-sized transplantation program.

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Pheochromocytomas (PCC) are rare and functional neuroendocrine tumors developing from adrenal chromaffin cells. Predicting malignant behavior especially in the absence of metastasis can be quite challenging even in the era of improved understanding of the molecular mechanisms involved in PCCs. Currently, two histopathological grading systems Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) score are used in clinical practice, but these are subject to significant interobserver variability.

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IL-17-producing CD8 (Tc17) T cells have been shown to play an important role in infection and chronic inflammation, however their implications in hepatocellular carcinoma (HCC) remain elusive. In this study, we performed cytometry by time-of-flight (CyTOF) and revealed the distinctive immunological phenotypes of two IFNγ and IFNγ Tc17 subsets that were preferentially enriched in human HCC. Single-cell RNA-sequencing analysis further revealed regulatory circuits governing the different phenotypes of these Tc17 subsets.

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Background: Evidence for use of graft from older donors in living donor liver transplantation (LDLT) has been conflicting. This study aims to clarify the impact of donor age on recipient morbidity and mortality after adult LDLT.

Methods: A total of 90 live liver donors and recipients who underwent primary adult-to-adult LDLT were divided into three groups according to donor age: donors in 20s (D-20s) group, donors in 30s and 40s (D-30s and 40s) group and donors in 50s & 60s (D-50s and 60s) group.

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Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations.

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Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours.

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Background And Aims: Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated.

Approach And Results: We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses.

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Introduction: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme.

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Background: The volume-outcome relation for complex surgical procedures such as living donor liver transplantation (LDLT) generally favors high volume (HV) centers. It is important for low to medium volume (MV) centers to evaluate their centers' performance against HV centers to allow early detection and correction of potential systemic issues. There is a dearth of national and international comprehensive registries for LDLT that may allow reasonable risk-adjusted comparisons for benchmarking.

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Purpose Of The Systematic Review: To determine the efficacy and safety of percutaneous trans-hepatic balloon and/or stent angioplasty (PTA) in the management of portal vein (PV) stenosis following paediatric liver transplantation.

Methods: Articles were included from a systematic search of Medline, Embase, Cochrane CENTRAL, ClinicalTrials.gov and International Clinical Trials Registry from inception to the 29th of August 2020.

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Article Synopsis
  • * Approximately 11.6% of patients showed preoperative PVT, which was linked to higher overall mortality (HR 1.45) and graft loss (HR 1.58), especially in more severe cases (grade 3 and 4 PVT).
  • * The findings suggest that patients with pre-transplant PVT face higher risks of post-operative PVT, and preventive anticoagulation might help improve their outcomes post-transplant.
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Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations.

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Background And Aim: Hepatocellular carcinoma (HCC) is a significant global problem. With advances in HCC diagnosis and therapy, our hypothesis is that there are significant differences in the clinical characteristics and treatment of HCC over the years.

Methods: Patients with HCC between 1980 and 2018 from three major tertiary hospitals in Singapore were enrolled into a Research Electronic Data Capture database.

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Background: Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program.

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Background: Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries. The impact of various policies restricting LT on outcomes of potential LT candidates is unclear.

Methods: We studied all patients on the nationwide LT waitlists in Hong Kong and Singapore between January 2016 and May 2020.

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Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology.

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The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome.

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Phenomenon: Research literacy remains important for equipping clinicians with the analytical skills to tackle an ever-evolving medical landscape and maintain an evidence-based approach when treating patients. While the role of research in medical education has been justified and established, the nuances involving modes of instruction and relevant outcomes for students have yet to be analyzed. Institutions acknowledge an increasing need to dedicate time and resources towards educating medical undergraduates on research but have individually implemented different pedagogies over differing lengths of time.

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Background: The application of intra-operative blood salvage autotransfusion(IBSA) in liver transplantation(LT) for hepatocellular carcinoma(HCC) remains controversial due to the theoretical risk of tumour cell(TC) reintroduction. Current studies evaluating for presence of TC are limited by suboptimal detection techniques. This study aims to analyze the presence of TC in HCC LT autologous blood using microfluidics technology.

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