Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. ... more Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. The emergence of combination therapy, atezolizumab (anti-PDL1, immune checkpoint inhibitor) and bevacizumab (anti-VEGF) has revolutionised the management of HCC. Despite this breakthrough, the best overall response rate with first-line systemic therapy is only about 30%, owing to intratumoural heterogeneity, complex tumour microenvironment and the lack of predictive biomarkers. Many groups have attempted to classify HCC based on the immune microenvironment and have consistently observed better outcomes in immunologically "hot" HCC. We summarised possible mechanisms of tumour immune evasion based on the latest literature and the rationale for combination/sequential therapy to improve treatment response. Lastly, we proposed future strategies and therapies to overcome HCC immune evasion to further improve treatment outcomes of HCC.
Resting-state functional connectivity MRI has emerged as a powerful tool for mapping large-scale ... more Resting-state functional connectivity MRI has emerged as a powerful tool for mapping large-scale neural networks based on synchronous BOLD signal; however, the neurobiological mechanisms are still unknown. To understand its neural substrates, especially the underlying neurotransmission, we applied pharmacological modulation with a receptor specific agonist and antagonist. Resting and evoked electrophysiology and BOLD signals in rat brains were measured under infusion of α2-adrenergic receptor agonist, medetomidine, the antagonist, atipamezole, and the vehicle individually. Both somatosensory BOLD activation and evoked potential were increased significantly under medetomidine compared to the vehicle while atipamezole slightly decreased both. The interhemispheric correlation at the resting state, in contrast, was suppressed by medetomidine but increased by atipamezole in regions with high receptor densities including the somatosensory cortex and thalamus. No change was seen in the caudate putamen, where receptor occupancy is low. The regional difference in connectivity was not related to cerebral blood flow, indicating that BOLD signal correlation is unlikely due to the vascular effects of the drugs. Resting intracortical recording exhibited agonist/antagonist dependent changes in beta and gamma bands that correlated with the BOLD functional connectivity measure. Our results confirm an important role of the adrenergic system on functional connectivity and suggest a neurotransmission basis of the phenomenon.
Background: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patien... more Background: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. Methods: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. Results: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p b 0.001), with higher proportion of females (70% vs. 54%, p b 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p b 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p b 0.001) and advanced fibrosis (40.3% vs. 17.0%; p b 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. Conclusion: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.
Background and study aims Using personal protective equipment (PPE) can reduce risk of disease tr... more Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Base...
Aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide, especially in Asia, with high m... more Aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide, especially in Asia, with high mortality. Curative options are only available for early-stage HCC, which are usually asymptomatic and best diagnosed through surveillance. Risk factors associated with HCC include liver cirrhosis due to alcohol, chronic viral hepatitis infections and nonalcoholic steatohepatitis. We review the evidence supporting the benefits and drawbacks of HCC surveillance as well as new surveillance modalities. Methods: A MEDLINE and Cochrane Database search with defined search phrases was performed. Studies published from Jan 2000 to Jul 2018 were reviewed and publications focusing on the benefits and harms of HCC surveillance were qualitatively synthesized. Modalities of HCC surveillance were also reviewed. Results: A total of 5 randomized controlled trials (RCTs) and 24 cohort studies with sample size of more than 100 each were selected. Significant mortality reduction was demonstrated in 1 RCT. Cohort studies showed overall improved outcomes in the surveillance group with 61.3%-88% of HCC being detected in an early-stage and with up to 80% eligible for curative treatments. A quarter (27.5%) of the surveillance patients experienced additional scans or procedures due to false-positive results. Combination of ultrasound with alpha-fetoprotein increases HCC detection rate. Novel serum markers and liquid biopsy are attractive tools for surveillance as they are non-invasive and convenient. Conclusion: The current evidence supports HCC surveillance as it detects earlier stage of tumor, allows more curative treatment and improves survival. Further research on hepatocarcinogenesis and novel surveillance modalities will continue to refine surveillance guidelines to reduce HCC-related mortality.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. ... more Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. The emergence of combination therapy, atezolizumab (anti-PDL1, immune checkpoint inhibitor) and bevacizumab (anti-VEGF) has revolutionised the management of HCC. Despite this breakthrough, the best overall response rate with first-line systemic therapy is only about 30%, owing to intratumoural heterogeneity, complex tumour microenvironment and the lack of predictive biomarkers. Many groups have attempted to classify HCC based on the immune microenvironment and have consistently observed better outcomes in immunologically "hot" HCC. We summarised possible mechanisms of tumour immune evasion based on the latest literature and the rationale for combination/sequential therapy to improve treatment response. Lastly, we proposed future strategies and therapies to overcome HCC immune evasion to further improve treatment outcomes of HCC.
Resting-state functional connectivity MRI has emerged as a powerful tool for mapping large-scale ... more Resting-state functional connectivity MRI has emerged as a powerful tool for mapping large-scale neural networks based on synchronous BOLD signal; however, the neurobiological mechanisms are still unknown. To understand its neural substrates, especially the underlying neurotransmission, we applied pharmacological modulation with a receptor specific agonist and antagonist. Resting and evoked electrophysiology and BOLD signals in rat brains were measured under infusion of α2-adrenergic receptor agonist, medetomidine, the antagonist, atipamezole, and the vehicle individually. Both somatosensory BOLD activation and evoked potential were increased significantly under medetomidine compared to the vehicle while atipamezole slightly decreased both. The interhemispheric correlation at the resting state, in contrast, was suppressed by medetomidine but increased by atipamezole in regions with high receptor densities including the somatosensory cortex and thalamus. No change was seen in the caudate putamen, where receptor occupancy is low. The regional difference in connectivity was not related to cerebral blood flow, indicating that BOLD signal correlation is unlikely due to the vascular effects of the drugs. Resting intracortical recording exhibited agonist/antagonist dependent changes in beta and gamma bands that correlated with the BOLD functional connectivity measure. Our results confirm an important role of the adrenergic system on functional connectivity and suggest a neurotransmission basis of the phenomenon.
Background: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patien... more Background: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. Methods: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. Results: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p b 0.001), with higher proportion of females (70% vs. 54%, p b 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p b 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p b 0.001) and advanced fibrosis (40.3% vs. 17.0%; p b 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. Conclusion: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.
Background and study aims Using personal protective equipment (PPE) can reduce risk of disease tr... more Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Base...
Aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide, especially in Asia, with high m... more Aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide, especially in Asia, with high mortality. Curative options are only available for early-stage HCC, which are usually asymptomatic and best diagnosed through surveillance. Risk factors associated with HCC include liver cirrhosis due to alcohol, chronic viral hepatitis infections and nonalcoholic steatohepatitis. We review the evidence supporting the benefits and drawbacks of HCC surveillance as well as new surveillance modalities. Methods: A MEDLINE and Cochrane Database search with defined search phrases was performed. Studies published from Jan 2000 to Jul 2018 were reviewed and publications focusing on the benefits and harms of HCC surveillance were qualitatively synthesized. Modalities of HCC surveillance were also reviewed. Results: A total of 5 randomized controlled trials (RCTs) and 24 cohort studies with sample size of more than 100 each were selected. Significant mortality reduction was demonstrated in 1 RCT. Cohort studies showed overall improved outcomes in the surveillance group with 61.3%-88% of HCC being detected in an early-stage and with up to 80% eligible for curative treatments. A quarter (27.5%) of the surveillance patients experienced additional scans or procedures due to false-positive results. Combination of ultrasound with alpha-fetoprotein increases HCC detection rate. Novel serum markers and liquid biopsy are attractive tools for surveillance as they are non-invasive and convenient. Conclusion: The current evidence supports HCC surveillance as it detects earlier stage of tumor, allows more curative treatment and improves survival. Further research on hepatocarcinogenesis and novel surveillance modalities will continue to refine surveillance guidelines to reduce HCC-related mortality.
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Papers by Ada Chen