The number of newly diagnosed prostate cancer cases varies across Asia, with higher mortality‐to‐incidence ratio reported in developing nations. Androgen deprivation therapy (ADT), alone or in ...combination, remains the mainstay of first‐line treatment for advanced prostate cancer. Key findings of extensive research and randomized controlled trials have shaped current clinical practice and influenced clinical guideline recommendations. We describe here the recent trend of ADT in newly diagnosed prostate cancer for Asia focusing on Japan (high‐income country) and Malaysia (middle‐income country) based on the Asian Prostate Cancer (A‐CaP) Study. The combination of radiotherapy and ADT or ADT alone was common in patients with intermediate‐to‐high risk localized and locally advanced disease. For metastatic prostate cancer, maximum androgen blockade (gonadotrophin‐releasing hormone GnRH agonist/antagonist plus antiandrogen) was prevalent among the Japanese patients while primary ADT alone with GnRH agonist/antagonist was widely practiced in the Malaysian cohort. Upfront combined therapy (ADT plus docetaxel or androgen receptor pathway inhibitor) has significantly improved the outcomes of patients with metastatic castration‐naïve prostate cancer. Its application, however, remains low in our cohorts due to patients’ financial capacity and national health insurance coverage. Early detection remains the cornerstone in prostate cancer control to improve treatment outcome and patient survival.
The A‐ Asian Prostate Cancer Study revealed a high proportion of metastatic prostate cancer was reported in Asia, particularly in developing nations. Androgen deprivation therapy, alone or in combination, remains the mainstay of first‐line treatment for advanced prostate cancer.
Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus ...Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC.
We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study.
Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades.
The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.
There is a paucity of information on the use of novel hormonal agents in Southeast Asian patients. We reviewed the clinical roles of novel hormonal therapy (NHT), namely abiraterone acetate (AA), ...enzalutamide, apalutamide and darolutamide, in the management of advanced prostate cancer, and data on its use in Asian patients, in order to extrapolate these findings to the Southeast Asian patient population. There are some differences in the molecular features between the NHTs, which influenced their respective permeabilities through the blood-brain barrier. The Asian sub-analyses of the landmark studies of each NHT were limited. The primary endpoints of the Asian sub-analyses generally reflect the efficacy outcomes of the respective landmark study. Hypertension, fatigue, musculoskeletal disorders, rash, and hot flushes were among the common toxicities observed in Asian patients. Real-world data on AA in the Asian setting is favourable, but data is limited for enzalutamide, apalutamide and darolutamide. Based on the sub-analyses and real-world data, the efficacy and safety of NHTs in the Asian patients showed a similar trend to the respective landmark studies. The lack of clinical trials in the Southeast Asian region hampers the ability to make a robust conclusion on any specific efficacy or safety differences that may be present; clinicians must assume that the broader Asian sub-analyses and real-world data reflects Southeast Asian patients' outcomes.
Recent evidence suggested the link between nephrolithiasis and renal function impairment. We aimed to determine the renal function profile and potential factors associated with reduced renal function ...amongst renal stone formers in multi-ethnic Asians.
We conducted a cross-sectional study involving patients undergoing percutaneous nephrolithotomy between May 2015 and December 2019. Reduced renal function was defined as having estimated glomerular filtration rate < 60 ml/min per 1.73 m2. Renal stone samples were collected and quantified using infrared spectroscopy. Potential factors associated with reduced renal function including age, ethnicity, educational level, history of diabetes, hypertension, gout, hydronephrosis, serum uric acid level, and type of renal stone were evaluated using univariable and multivariable analyses.
A total of 1162 patients from a multi-ethnic population (Malays 67%, Chinese 19%, Indians 13% and indigenous people 1%) with median age of 57 years (Interquartile range 48-64) were enrolled in the study. Almost a third of patients were found with reduced renal function. Multivariable analysis showed that the odds of having reduced renal function increased with age, ethnicity, lower educational level, history of diabetes, hypertension, gout, bilateral hydronephrosis, elevated serum uric acid level and infection stone.
Reduced renal function varies between ethnicities and all age groups of renal stone formers. In addition to age and ethnicity, cardiovascular risk factors including diabetes and hypertension may also need to be taken into account in managing stone patients with reduced renal function.
Background: Frailty is a significant risk factor for recurrent hospital admissions and emergency department presentations. Frail older adults are especially vulnerable to hospital related adverse ...outcomes recognisably functional decline, delirium, institutionalisation and mortality. Fragmentation of care resulting in poorly defined care responsibilities, together with the limitation of community resources to manage acute issues in this group of patients, increase the likelihood of them presenting to an acute care setting.
Methods: A retrospective study evaluated frail older adults seen in an ambulatory Geriatric clinic in a government funded public hospital from 2021 to 2022. The aim of the study was to determine if timely evaluation of acute issues in an ambulatory setting could avoid a hospital admission or an emergency department presentation.
Results: Preliminary data in this study showed that (1) timely review of acute issues (<1 week from presentation) led to avoidance of hospital admission, emergency department presentation as well as admission in the next 30 days; (2) the common presentations successfully managed include worsening behavioral and psychological symptoms of dementia (BPSD), delirium, infections and falls; (3) majority of the patients seen were moderately to severely frail based on their clinical frailty score (CFS). Additionally, there was high level of patient and caregiver satisfaction reported.
Conclusion: This study shows that hospital admissions and emergency department presentations can potentially be avoided in frail older adults whose acute medical issues are recognised and managed early. Important contributing factors to the effective management of these patients include: easy accessibility to the primary geriatrician involved, same day investigations, timely follow ups, good social/family support as well as the engagement of community services. Rapid access frailty clinics, a service model built upon the similar recognition that acute issues in frail older adults needed to be addressed promptly, has been described and shown to have benefit elsewhere. In Singapore, innovations in care delivery both within the hospital and in the community has become ever more crucial with an increasingly frail population and in already overwhelmed healthcare institutions. Rapid access frailty clinics can be a useful hospital-based service delivery model to improve care of our frail older adults.
To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.
We conducted a cross-sectional study of 1054 men with no clinical evidence ...of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.
There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05).
These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.
Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs ...containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.
Matrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous ...malformation (BAVM) patients' tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease.
Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.
MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.
Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers' potential applications as primary medical therapy targets for BAVM patients.
To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in ...a multiethnic Asian setting.
We conducted a cross-sectional study of 1021 men aged 40-79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses.
There were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity.
Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.
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