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OBJECTIVES: To assess intrarenal pressures (IRPs) and complication rates after flexible ureteroscopy (fURS), and to assess factors that contribute to raised IRPs and postoperative complications. PATIENTS AND METHODS: After informed consent patients underwent fURS under general anaesthesia. The transducer of a 0.3556 mm (0.014â³) pressure guidewire was placed in the renal pelvis for live recording of IRPs. The fURS procedures were performed in a routine manner under antibiotic cover with the aim of dusting the calculus to completion. The operating surgeon was blinded to the live-recorded IRPs. RESULTS: A total of 40 fURS procedures were performed in 37 patients (26 male and 11 female). The mean age was 50.5 years. As a cohort, the mean of average IRPs was 34.8 mmHg and the mean of maximal IRPs was 128.8 mmHg. Pearson's correlation showed a significant inverse correlation between the mean IRP and age (r[38]: -0.391, P = 0.013). Three cases experienced postoperative deviations from uncomplicated recovery, with two being hypotensive and one case being both hypotensive and hypoxic. Three cases returned to the emergency department within 30 days of surgery, with two cases of flank pain and one case of urosepsis with positive urine cultures. The patient presenting with urosepsis had exhibited IRPs exceeding the mean. CONCLUSION: The IRPs changed significantly from normal baseline levels during routine fURS. The mean IRP during fURS correlates with patient age, but not with other factors. The IRP may be related to increased complication rates at fURS. Understanding factors that influence IRP will allow urologists to better manage this intraoperatively.
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Cálculos Renais , Ureteroscopia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Ureteroscópios , Cálculos Renais/cirurgia , Pelve Renal , UrologistasRESUMO
OBJECTIVE: To compare clinical outcomes of single-use endoscopes with those of reusable endoscopes to better define their role within urology. METHODS: A systematic search of electronic databases was performed. All studies comparing the clinical outcomes of participants undergoing urological procedures with single-use endoscopes to those of participants treated with reusable endoscopes were included. Results are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. RESULTS: Twenty-one studies in 3943 participants were identified. Six different single-use flexible ureteroscopes and two different single-use flexible cystoscopes were assessed. There were no differences in mean postoperative infection rates (4.0% vs 4.4%; P = 0.87) or overall complication rates (11.5% vs 11.9%; P = 0.88) between single-use and reusable endoscopes. For patients undergoing flexible ureteroscopy there were no differences in operating time (mean difference -0.05 min; P = 0.96), length of hospital stay (LOS; mean difference 0.06 days; P = 0.18) or stone-free rate (SFR; 74% vs 74.3%; P = 0.54) between the single-use and reusable flexible ureteroscope groups. CONCLUSION: This study is the largest to compare the clinical outcomes of single-use endoscopes to those of reusable endoscopes within urology, and demonstrated no difference in LOS, complication rate or SFR, with a shorter operating time associated with single-use flexible cystoscope use. It also highlights that the cost efficiency and environmental impact of single-use endoscopes is largely dependent on the caseload and reprocessing facilities available within a given institution. Urologists can therefore feel confident that whether they choose to 'use' or to 'reuse' based on the financial and environmental implications, they can do so without negatively impacting patient outcomes.
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Ureteroscopia , Urologia , Humanos , Ureteroscopia/métodos , Reutilização de Equipamento , Desenho de Equipamento , UreteroscópiosRESUMO
OBJECTIVE: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades. METHODS: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study. RESULTS: Invasive bladder cancer age-standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non-bladder cancer-specific deaths in older people, there was no change in the bladder cancer-specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not. CONCLUSIONS: Invasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor. PATIENT SUMMARY: We looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously.
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Sistema de Registros , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Incidência , Taxa de Sobrevida , Pessoa de Meia-Idade , Austrália do Sul/epidemiologia , AdultoRESUMO
OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Espectroscopia de Luz Próxima ao Infravermelho , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodosRESUMO
BACKGROUND: Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB. METHODS: A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB. RESULTS: 361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations. CONCLUSION: Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.
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Períneo , Próstata , Retenção Urinária , Humanos , Masculino , Retenção Urinária/etiologia , Retenção Urinária/prevenção & controle , Próstata/patologia , Neoplasias da Próstata/patologia , Antagonistas Adrenérgicos alfa/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversosRESUMO
To document the histological changes observed in renal units subjected to elevated intrarenal pressures (IRPs) and postulate the possible mechanisms of infectious complications after ureteroscopy. MATERIALS AND METHODS: Ex vivo studies were performed on porcine renal models. Each ureter was cannulated with a 10-F dual-lumen ureteric catheter. A pressure-sensing wire was inserted through one lumen and with the sensor positioned in the renal pelvis for IRP measurement. Undiluted India ink stain was irrigated through the second lumen. Each renal unit was subjected to ink irrigation at target IRPs of 5 (control), 30, 60, 90, 120, 150, and 200 mmHg. Three renal units were subjected to each target IRP. After irrigation, each renal unit was processed by a uropathologist. Macroscopically, the amount of renal cortex stained by ink was calculated as a percentage of the total perimeter. Microscopically, presence of ink reflux into collecting ducts or distal convoluted tubules, and pressure-related features, was noted at each IRP. RESULTS: Signs of pressure, as represented by collecting duct dilatation, was first observed at 60 mmHg. Ink staining was consistently observed in the distal convoluted tubules at IRPs ≥60 mmHg, and all renal units above this pressure showed renal cortex involvement. At ≥90 mmHg, ink staining was observed in venous structures. At 200 mmHg, ink staining was observed in supportive tissue, venous tributaries in the sinus fat, peritubular capillaries, and glomerular capillaries. CONCLUSION: Using an ex vivo porcine model, pyelovenous backflow occurred at IRPs of ≥90 mmHg. Pyelotubular backflow occurred when irrigation IRPs were ≥60 mmHg. These findings have implications for the development of complications after flexible intrarenal surgery.
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OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.
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Hidrogéis , Neoplasias da Próstata , Humanos , Masculino , Próstata , Neoplasias da Próstata/cirurgia , Radiometria , Dosagem Radioterapêutica , RetoRESUMO
OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.
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Biópsia Guiada por Imagem , Neoplasias da Próstata , Masculino , Humanos , Biópsia Guiada por Imagem/métodos , Estudos Prospectivos , Biópsia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Próstata/patologia , Antígeno Prostático Específico , Gradação de TumoresRESUMO
BACKGROUND: To determine the utility of diagnostic 18F-DCPyL PSMA-PET/CT to aid management of men with highly suspicious multiparametric MRI prostate (PIRAD 4-5 lesions) and discrepant negative prostate biopsy. METHODS: A multicentre prospective consecutive case series was conducted (2018-2021), recruiting men with prior mpMRI prostate PIRADS 4-5 lesions and negative prostate biopsy. All men had 18F-DCPyL PSMA-PET/CT with subsequent management based on the concordance between MRI and PET: (1) Concordant lesions were biopsied using in-bore MRI targeting; (2) PSMA-PET/CT avidity without MRI correlate were biopsied using cognitive/software targeting with ultrasound guidance and (3) Patients with negative PET/CT were returned to standard of care follow-up. RESULTS: 29 patients were recruited with 48% (n = 14) having concordant MRI/PET abnormalities. MRI targeted biopsy found prostate cancer in six patients, with grade groups GG3 (n = 1), GG2 (n = 1), GG1 (n = 4) found. Of the 20 men who PSMA-PET/CT avidity and biopsy, analysis showed higher SUVmax (20.1 vs 6.8, p = 0.036) predicted prostate cancer. Of patients who had PSMA-PET avidity without MRI correlate, and those with no PSMA-PET avidity, only one patient was subsequently found to have prostate cancer (GG1). The study is limited by small size and short follow-up of 17 months (IQR 12.5-29.9). CONCLUSIONS: PSMA-PET/CT is useful in this group of men but requires further investigation. Avidity (higher SUVmax) that correlates to the mpMRI prostate lesion should be considered for targeted biopsy.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Compostos Radiofarmacêuticos , Imageamento por Ressonância Magnética , Neoplasias da Próstata/patologia , BiópsiaRESUMO
The South West Oncology Group's 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear.Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy.Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35-49) RFS at five years in the control arm and 60% RFS (53-67 95% CI) in the maintenance arm (p < 0.0001). Only 16% of patients in the treatment arm received all of the scheduled maintenance courses of BCG.The study's seminal results correlate with contemporary systematic review and have guided international guidelines.
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Carcinoma in Situ , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Urologia , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vacina BCG/uso terapêutico , Bexiga Urinária/patologia , Administração Intravesical , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Imunoterapia , Recidiva Local de Neoplasia/patologia , Adjuvantes Imunológicos/uso terapêuticoRESUMO
PURPOSE: Robot-assisted radical prostatectomy (RARP) is associated with poorer postoperative urinary continence in older men. However, published studies reporting conflicting results have design limitations with insufficient data at the extremes of age. The purpose of this study was to assess the effect of age on post-RARP urinary continence. MATERIALS AND METHODS: This study included 5,648 patients from 2 prospective Australian databases who underwent a primary RARP for prostate cancer between 2008 and 2019. Significant urinary bother and pad-usage were evaluated 12 months post-RARP by EPIC-26 (Expanded Prostate Cancer Index Composite) questionnaires, independently collected by third parties. Multivariable logistic regression was used to investigate the relationship between continence and age. RESULTS: Percentages of significant bother increased with age: 4.2%, 6.8% 9.1% and 12.9% at age groups <55, 55-64, 65-74 and ≥75 years, respectively. Compared with men aged 65-69 years, the odds of significant bother in patients <55 years was significantly lower (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.32-0.75, p=0.001). Corresponding OR found no significant difference in bother in patients ≥70 (OR 1.24, 95% CI 0.94-1.63, p=0.13) or ≥75 years (OR 1.41, 95% CI 0.88-2.25, p=0.16). Pad-free rates markedly decreased with age: 86%, 79%, 68% and 50% at ages, <55, 55-64, 65-74 and ≥75 years, respectively. Corresponding social continence (0-1 pads/day) rates also decreased with age: 98%, 96%, 92% and 85%. CONCLUSIONS: Urinary bother and pad-usage post-RARP are excellent in young men but worsen with age. Older patients were only slightly more likely to be "significantly bothered" by incontinence despite higher pad-usage.
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Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Idoso , Austrália/epidemiologia , Pré-Escolar , Humanos , Masculino , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Non-muscle-invasive bladder cancer (NMIBC) represents a significant global therapeutic challenge, particularly in the era of Bacillus Calmette-Guérin (BCG) shortage. High-risk NMIBC can progress to muscle invasive or metastatic disease in 25% of patients. Optimal treatment selection, according to risk stratification, is imperative. International guidelines slightly differ in their categorisation of low, intermediate and high-risk NMIBC. Nonetheless, a single post-operative instillation of chemotherapy with Mitomycin C (MMC) or Gemcitabine improves relapse-free survival (RFS) in low-risk NMIBC. Induction and maintenance intravesical BCG remains the historical gold standard for patients with intermediate or high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current BCG shortage. Both intravesical MMC and Gemcitabine have been associated with similar efficacy to BCG, albeit in smaller studies. MMC may also be manipulated using a variety of methods to potentiate its effects. BCG treatment delivery may also be modified without affecting efficacy through dose reduction and abbreviation or omission of maintenance therapy. Preliminary data also highlight that directly proceeding to radical cystectomy may not adversely affect long-term quality of life measures. Access to new systemic and intravesical therapies must be prioritised for patients with BCG recurrent or unresponsive disease. When used in conjunction with molecularly defined biomarkers, these agents herald the potential for improved survival outcomes and alleviation of the current BCG shortage.
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Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Feminino , Humanos , Masculino , Mitomicina/uso terapêutico , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: Feeling depressed and lethargic are common side effects of prostate cancer (PCa) and its treatments. We examined the incidence and severity of feeling depressed and lack of energy in patients in a population based PCa registry. METHODS: We included men diagnosed with PCa between 2015 and 2019 in Victoria, Australia, and enrolled in the Prostate Cancer Outcomes Registry. The primary outcome measures were responses to two questions on the Expanded Prostate Cancer Index Composite (EPIC-26) patient reported instrument: problems with feeling depressed and problems with lack of energy 12 months following treatment. We evaluated associations between these and age, cancer risk category, treatment type, and urinary, bowel, and sexual function. RESULTS: Both outcome questions were answered by 9712 out of 12,628 (77%) men. 981 patients (10%) reported at least moderate problems with feeling depressed; 1563 (16%) had at least moderate problems with lack of energy and 586 (6.0%) with both. Younger men reported feeling depressed more frequently than older men. Lack of energy was more common for treatments that included androgen deprivation therapy than not (moderate/big problems: 31% vs. 13%), irrespective of disease risk category. Both outcomes were associated with poorer urinary, bowel, and sexual functional domain scores. CONCLUSIONS: Self-reported depressive feelings and lack of energy were frequent in this population-based registry. Problems with feeling depressed were more common in younger men and lack of energy more common in men having hormonal treatment. Clinicians should be aware of the incidence of these symptoms in these at-risk groups and be able to screen for them.
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Antagonistas de Androgênios , Neoplasias da Próstata , Idoso , Antagonistas de Androgênios/uso terapêutico , Emoções , Humanos , Masculino , Estudos Prospectivos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/terapia , Qualidade de Vida , Sistema de Registros , AutorrelatoRESUMO
PURPOSE OF REVIEW: This review highlights the emerging role of genetics-lead medicine (GLM) in prostate cancer. We describe the benefits of GLM integration into prostate cancer screening, diagnosis and management. Imaging techniques enhancing prostate cancer detection are advancing concurrently, facilitating strategic active surveillance protocols for appropriately selected patients. We aim to improve clinician awareness of the role of GLM in current and future practice. RECENT FINDINGS: We explore recent literature advancing the role of GLM in prostate cancer detection and management, particularly as this coexists with the development of imaging technology. Our current understanding of germline mutations implicated in familial prostate cancer development is summarized. We describe how these developments are being utilized to inform screening, surveillance and the development of novel therapies. We summarize current guidelines and explore factors inhibiting optimal implementation of recommendations in clinical practice. SUMMARY: Integration and further development of genetics-lead medicine in the detection, surveillance and management of prostate cancer will improve clinical outcomes for men at risk of aggressive disease as a result of familial predispositions to prostate cancer. This review summarizes the pertinent developments in the field including improving clinician awareness to facilitate implantation of these strategies into current clinical practice.
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Neoplasias da Próstata , Detecção Precoce de Câncer , Mutação em Linhagem Germinativa , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Conduta ExpectanteRESUMO
PURPOSE OF REVIEW: Many clinical trials are currently underway to target the epigenome of castration-resistant prostate cancer. In this review, we summarize the major epigenetic alterations that occur during prostate cancer progression, describe their biological consequences, and highlight potential of therapies that target epigenetic regulators for use in patients. RECENT FINDINGS: Epigenetic alterations frequently occur in tumour suppressor genes, DNA repair genes, and genes that regulate cell proliferation and differentiation. Unlike genetic alterations, epigenetic changes are reversible, making them promising targets for cancer therapy. Epigenetic regulators can be divided into three broad groups: writers, readers, and erasers , each with specific drug targets that are being assessed in phase I and II clinical trials for prostate cancer. CBP/p300, and BRD4 are coregulators of the androgen receptor and inhibit androgen signalling, making bromodomain extra-terminal inhibitors and CBP/p300 inhibitors attractive targets in prostate cancer. Enhancer of zeste homolog 2, a histone methyltransferase, is also a potential target in castrate-resistant prostate cancer. An emerging direction is to combine epigenetic inhibitors with other compounds to enhance their efficacy. SUMMARY: Preclinical studies indicate that the epigenome is a potential target in prostate cancer, and clinical trials are testing multiple agents that target the epigenome in different ways. However, the process of translating these therapies into the clinic is ongoing and none have yet been approved for castrate-resistant prostate cancer.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/uso terapêutico , Proliferação de Células , Epigênese Genética , Humanos , Masculino , Proteínas Nucleares/genética , Proteínas Nucleares/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/uso terapêuticoRESUMO
The lockdown measures of the ongoing COVID-19 pandemic have disengaged patients with cancer from formal health care settings, leading to an increased use of social media platforms to address unmet needs and expectations. Although remote health technologies have addressed some of the medical needs, the emotional and mental well-being of these patients remain underexplored and underreported. We used a validated artificial intelligence framework to conduct a comprehensive real-time analysis of two data sets of 2,469,822 tweets and 21,800 discussions by patients with cancer during this pandemic. Lung and breast cancer are most prominently discussed, and the most concerns were expressed regarding delayed diagnosis, cancellations, missed treatments, and weakened immunity. All patients expressed significant negative sentiment, with fear being the predominant emotion. Even as some lockdown measures ease, it is crucial that patients with cancer are engaged using social media platforms for real-time identification of issues and the provision of informational and emotional support.
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COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/normas , Saúde Mental/estatística & dados numéricos , Neoplasias/psicologia , Pandemias/prevenção & controle , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/transmissão , Conjuntos de Dados como Assunto , Medo/psicologia , Humanos , Disseminação de Informação/métodos , Oncologia/normas , Oncologia/tendências , Neoplasias/diagnóstico , Neoplasias/imunologia , Neoplasias/terapia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Mídias Sociais/estatística & dados numéricos , Telemedicina/normas , Telemedicina/tendênciasRESUMO
Zinc inhibits replication of the SARS-CoV virus. We aimed to evaluate the safety, feasibility, and biological effect of administering high-dose intravenous zinc (HDIVZn) to patients with COVID-19. We performed a Phase IIa double-blind, randomized controlled trial to compare HDIVZn to placebo in hospitalized patients with COVID-19. We administered trial treatment per day for a maximum of 7 days until either death or hospital discharge. We measured zinc concentration at baseline and during treatment and observed patients for any significant side effects. For eligible patients, we randomized and administered treatment to 33 adult participants to either HDIVZn (n = 15) or placebo (n = 18). We observed no serious adverse events throughout the study for a total of 94 HDIVZn administrations. However, three participants in the HDIVZn group reported infusion site irritation. Mean serum zinc on Day 1 in the placebo, and the HDIVZn group was 6.9 ± 1.1 and 7.7 ± 1.6 µmol/l, respectively, consistent with zinc deficiency. HDIVZn, but not placebo, increased serum zinc levels above the deficiency cutoff of 10.7 µmol/l (p < .001) on Day 6. Our study did not reach its target enrollment because stringent public health measures markedly reduced patient hospitalizations. Hospitalized COVID-19 patients demonstrated zinc deficiency. This can be corrected with HDIVZn. Such treatment appears safe, feasible, and only associated with minimal peripheral infusion site irritation. This pilot study justifies further investigation of this treatment in COVID-19 patients.
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Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Zinco/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Injeções Intravenosas , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Projetos Piloto , Respiração Artificial , Zinco/administração & dosagemRESUMO
OBJECTIVE: Fenestrated endovascular aneurysm repair has yet to gain widespread adoption owing to the technical complexity and increased risk of complications. Three-dimensional (3D) printed templates to guide fenestrated physician-modified stent grafts (PMSGs) are a novel technique that may have the potential to increase the accuracy of fenestration alignment, and to disrupt both the cost and timing of the current commercial fenestrated endograft supply chain. We have conducted a critical appraisal of the emerging literature to assess this. METHODS: A systematic literature search was performed using PubMed and OVID Medline as guided by the PRISMA statement on April 30, 2020. We used "3D printing" and "physician modified" or "surgeon modified" and all related search terms. We identified 50 articles which met our search criteria. None articles were included as being of direct relevance to 3D-printed template-assisted PMSGs for fenestrated endovascular aneurysm repair. Abstracts were screened individually by each investigator to ensure relevance. RESULTS: Nine relevant articles were identified for critical analysis. These included one technical report, five case reports or series, two prospective trials, and one letter to the editor. CONCLUSIONS: These 3D-printed templates are a promising new avenue to assist with the placement of fenestrations in PMSGs, particularly in urgent or emergent cases where custom fenestrated endografts are unavailable, with larger scale studies warranted. Further work to validate the key stages of the template workflow are required, as well as further investigation into the most suitable manufacturing and distribution methods before the mainstream implementation of this novel technique.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Desenho Assistido por Computador , Procedimentos Endovasculares/instrumentação , Impressão Tridimensional , Desenho de Prótese , Stents , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Modelos Anatômicos , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Resultado do TratamentoRESUMO
OBJECTIVE: To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). METHODS: We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. RESULTS: Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. CONCLUSION: This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.
Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Uretra/patologia , Bexiga Urinária/patologia , Idoso , Anastomose Cirúrgica , Biópsia , Tomada de Decisão Clínica , Tomada de Decisão Compartilhada , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Terapia de Salvação , Ultrassonografia , Uretra/cirurgia , Bexiga Urinária/cirurgiaRESUMO
PURPOSE: To determine how members of the Société Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. METHODS: A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. RESULTS: In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; all ps < 0.001), followed by searching journals and textbook including the online versions (62%; all ps < 0.001). Overall, 6% of the respondents reported no time/interest for CME during the pandemic. Although most urologists report using only one platform for their CME (26.6%), the majority reported using ≥ 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. CONCLUSION: During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods.