Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study.

BACKGROUND: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population. METHODS: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed. RESULTS: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001). CONCLUSION: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health.

Cu-Catalyzed Cross-Electrophilic Coupling of α-Diazoesters with O-Benzoyl Hydroxylamines for the Synthesis of Unnatural N-Alkyl α-Amino Acid Derivatives.

We describe a Cu-catalyzed cross-electrophilic coupling reaction for synthesizing α-amino acid derivatives from α-diazoesters with O-benzoyl hydroxylamines with Cu(OAc)2 as the catalyst and polymethylhydrosilane (PMHS) as the hydride reagent. Excellent functional group compatibilities were demonstrated. With ethyl 2-diazo-3-oxobutanoate as the precursor, a Cu-acetoacetate complex has been characterized by ESI-MS analysis. Results from the radical trap experiments are consistent with the intermediacy of nitrogen-centered radicals. This strategy offers a simple and inexpensive synthesis of α-amino acid derivatives.

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

Background: In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations. Methods: A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose "Accept Completely" (Option A) or "Accept with Some Reservation" (Option B). Results: The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients. Conclusion: This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.

Risks of metabolic diseases and androgen deprivation therapy for prostate cancer in a Chinese population: a prospective multi-centre cohort study.

PURPOSE: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We are looking into the relationship between ADT and development of metabolic diseases in Chinese patients. METHODS: This is a prospective multi-centre cohort yielded from the READT database (Real-life experience of ADT in Asia), in which patients diagnosed of PCa and offered ADT were prospectively recruited since 2016. Chinese patients recruited from Hong Kong were selected and compared to another cohort of newly diagnosed PCa patients in Hong Kong (HK-Cap database), which was collected prospectively and retrieved retrospectively for this study. Patient outcomes are followed through for 2 years. We compared between the groups the new diagnoses of hypertension, diabetes and hyper-lipidaemia, as well as the initiation of related medication for these conditions. Baseline characteristics including pre-treatment comorbidities, medications and tumour characteristics are documented. RESULTS: 151 patients receiving ADT (from READT database) and 447 patients not receiving ADT (from HK-Cap database) were analysed. ADT is related to higher risks of developing any of concerned medical co-morbidities (23.8% vs 13.0*, p = 0.001) and new-onset DM (16.6% vs 4.4%, p < 0.001). Initiation of new medications is also more common in ADT patients. New anti-hypertensives (37.8% vs 12.5%, p < 0.001), oral hypoglycemic agents (12.6% vs 4.9%, p = 0.001), insulin (4.0% vs 0.05%, p = 0.001) and statin (23.7% vs 12.8%, p = 0.023) are more commonly added in ADT cohort. CONCLUSION: Chinese receiving ADT are exposed to increased risks of new-onset hypertension, diabetes and hyper-lipidaemia, and a higher likelihood of stepping up pharmaceutical control for pre-existing comorbidities. This highlights physicians' role to monitor metabolic profiles in at-risk men upon offering ADT.

Stress and psychological impact on SARS patients during the outbreak.

OBJECTIVE: To examine stress and psychological impact in severe acute respiratory syndrome (SARS) patients during the 2003 outbreak. SARS is a novel, highly infectious pneumonia, and its psychological impact is still unclear. METHOD: At the peak of the outbreak, SARS patients (n = 79) and healthy control subjects (n = 145) completed the Perceived Stress Scale (PSS) and documented a range of psychological responses. Groups were balanced for age, sex, education, and living circumstances. RESULTS: Stress was significantly higher in SARS patients than in healthy control subjects. Stress correlated significantly with negative psychological effects. Of SARS patients, 39% (n = 30) were infected health care workers; these individuals reported significantly more fatigue and worries about health than did other patients. Of patients, 25% (n = 20) requested psychological follow-up. CONCLUSIONS: General stress and negative psychological effects are increased in SARS patients, particularly among infected health care workers. This may increase the risk of mood and stress-related disorders. Functional impairment is apparent in the postrecovery phase.

Psychological effects of the SARS outbreak in Hong Kong on high-risk health care workers.

OBJECTIVE: To quantify stress and the psychological impact of severe acute respiratory syndrome (SARS) on high-risk health care workers (HCWs). METHOD: We evaluated 271 HCWs from SARS units and 342 healthy control subjects, using the Perceived Stress Scale (PSS) to assess stress levels and a structured list of putative psychological effects of SARS to assess its psychological effects. Healthy control subjects were balanced for age, sex, education, parenthood, living circumstances, and lack of health care experience. RESULTS: Stress levels were raised in both groups (PSS = 18) but were not relatively increased in the HCWs. HCWs reported significantly more positive (94%, n = 256) and more negative psychological effects (89%, n = 241) from SARS than did control subjects. HCWs declared confidence in infection-control measures. CONCLUSIONS: In HCWs, adaptive responses to stress and the positive effects of infection control training may be protective in future outbreaks. Elevated stress in the population may be an important indicator of future psychiatric morbidity.

Psychological responses to the SARS outbreak in healthcare students in Hong Kong.

This paper reports a cross-sectional questionnaire study that investigated perceived stress and psychological responses to the SARS outbreak in healthcare students at the height of the outbreak in Hong Kong in 2003. Non-healthcare university students served as controls. All the groups reported high levels of perceived stress. Despite being similarly confident in infection control procedures, nursing students were significantly more stressed than medical students, possibly reflecting a perceived higher risk of infection due to more prolonged contact with patients. Non-healthcare students also had high stress levels due to the perceived risks of dying from SARS, reflecting a fear of the unknown. Suitable psychological and occupational support services should be made available in case of future outbreaks.