1.Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development
John M. WOLPERT ; Caroline PRESSON ; Nathaniel KIMBALL ; Benjamin LIN ; Luis BRANDI ; Naseem HELO ; Werner T. W. de RIESE
Investigative and Clinical Urology 2024;65(4):334-341
Purpose:
Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique.
Materials and Methods:
Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ.
Results:
Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001).
Conclusions
The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.
2.Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma
Kelly M MAHURON ; Kevin M SULLIVAN ; Matthew C HERNANDEZ ; Yi-Jen CHEN ; Joseph CHAO ; Laleh G MELSTROM ; I. Benjamin PAZ ; Jae Yul KIM ; Rifat MANNAN ; James L. LIN ; Yuman FONG ; Yanghee WOO
Journal of Gastric Cancer 2024;24(3):267-279
Purpose:
The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type.
Materials and Methods:
We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications.
Results:
Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients.All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients.Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months.
Conclusions
Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.
3.Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Jin Hean KOH ; Claire Yi Jia LIM ; Lucas Tze Peng TAN ; Ching-Hui SIA ; Kian Keong POH ; Vijay Kumar SHARMA ; Leonard Leong Litt YEO ; Andrew Fu Wah HO ; Teddy WU ; William Kok-Fai KONG ; Benjamin Yong Qiang TAN
Journal of Stroke 2024;26(3):371-390
Background:
and Purpose Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke.
Methods:
Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR).
Results:
From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients.
Conclusion
Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.
4.Surgical margins assessment reduces re-excision rates in breast-conserving surgery.
Chang Yi WOON ; Serene Si Ning GOH ; Lin Seong SOH ; Chloe Fu Cui YEO ; Marc Weijie ONG ; Benjamin WONG ; Joelle Hoi Ting LEONG ; Jerry Tiong Thye GOO ; Clement Luck Khng CHIA
Annals of the Academy of Medicine, Singapore 2023;52(1):48-51
6.Safety attitudes, burnout and well-being among healthcare workers during the COVID-19 pandemic: an Indo-Pacific regional cross-sectional study.
Abhiram KANNEGANTI ; Benjamin Yong Qiang TAN ; Nik Hisamuddin NIK AB RAHMAN ; Aloysius Sheng-Ting LEOW ; Max DENNING ; Ee Teng GOH ; Lucas Jun HAO LIM ; Ching-Hui SIA ; Ying Xian CHUA ; James KINROSS ; Melanie TAN ; Li Feng TAN ; Yi Min WAN ; Arvind SHARMA ; Rivan DANUAJI ; R N KOMAL KUMAR ; Chew Keng SHENG ; Cheah Phee KHENG ; Sarah Shaikh ABDUL KARIM ; Mohd Najib ABDUL GHANI ; Suhaimi MAHMUD ; Yiong Huak CHAN ; Vijay Kumar SHARMA ; Kang SIM ; Shirley Beng SUAT OOI
Singapore medical journal 2023;64(11):667-676
INTRODUCTION:
The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety.
METHODS:
A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR).
RESULTS:
We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR.
CONCLUSION
Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
Humans
;
Cross-Sectional Studies
;
Pandemics
;
COVID-19/epidemiology*
;
Burnout, Psychological
;
Health Personnel
7.Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.
Jiacai CHO ; Joanne LEE ; Ching-Hui SIA ; Chieh Sian KOO ; Benjamin Y Q TAN ; Weizhen HONG ; Ellie CHOI ; Xueying GOH ; Louis CHAI ; Nisha Suyien CHANDRAN ; Horng Ruey CHUA ; Bernard P L CHAN ; Mark MUTHIAH ; Ting Ting LOW ; Eng Soo YAP ; Manjari LAHIRI
Singapore medical journal 2023;64(6):349-365
INTRODUCTION:
We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.
METHODS:
We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.
RESULTS:
169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.
CONCLUSION
Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Humans
;
Asian People
;
COVID-19/complications*
;
Inflammation/complications*
;
SARS-CoV-2
;
Thrombosis
8.Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion
Isabel SIOW ; Benjamin Y.Q. TAN ; Keng Siang LEE ; Natalie ONG ; Emma TOH ; Anil GOPINATHAN ; Cunli YANG ; Pervinder BHOGAL ; Erika LAM ; Oliver SPOONER ; Lukas MEYER ; Jens FIEHLER ; Panagiotis PAPANAGIOTOU ; Andreas KASTRUP ; Maria ALEXANDROU ; Seraphine ZUBEL ; Qingyu WU ; Anastasios MPOTSARIS ; Volker MAUS ; Tommy ANDERSON ; Vamsi GONTU ; Fabian ARNBERG ; Tsong Hai LEE ; Bernard P.L. CHAN ; Raymond C.S. SEET ; Hock Luen TEOH ; Vijay K. SHARMA ; Leonard L.L. YEO
Journal of Stroke 2022;24(1):128-137
Background:
and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT.
Methods:
This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH).
Results:
Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not asComorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013).
Conclusions
Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.
9.Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin TANG ; Kai En CHAN ; Jingxuan QUEK ; Jieling XIAO ; Phoebe TAY ; Margaret TENG ; Keng Siang LEE ; Snow Yunni LIN ; May Zin MYINT ; Benjamin TAN ; Vijay K SHARMA ; Darren Jun Hao TAN ; Wen Hui LIM ; Apichat KAEWDECH ; Daniel HUANG ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J SANYAL ; Mark MUTHIAH ; Cheng Han NG
Clinical and Molecular Hepatology 2022;28(3):483-496
Background/Aims:
Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.
Methods:
Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.
Results:
From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.
Conclusions
This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.
10.The Association of Obstructive Sleep Apnea With Breast Cancer Incidence and Mortality: A Systematic Review and Meta-analysis
Dominic Wei TING YAP ; Nicole Kye WEN TAN ; Benjamin Kye JYN TAN ; Yao Hao TEO ; Veronique Kiak MIEN TAN ; Anna SEE ; Song Tar TOH
Journal of Breast Cancer 2022;25(3):149-163
Purpose:
Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship.
Methods:
We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse varianceweighted meta-analysis and performed pre-specified subgroup analyses.
Results:
We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03–1.80; N = 6, I 2 = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98–1.87; N = 5, I 2 = 96%) and 1.57 (95% CI, 1.14–2.18; N = 4; I 2 = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA.
Conclusion
This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.

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