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1.
PLoS Genet ; 18(9): e1010373, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36095024

RESUMO

Prostate cancer is the most inheritable cancer with approximately 42% of disease risk attributed to inherited factors by studies of twins, indicating the importance of additional genetic screening to identify predisposition variants. However, only DNA damage repair (DDR) genes have been investigated thoroughly in prostate cancer. To determine the comprehensive germline mutation landscape in Chinese prostate cancer patients, we performed whole exome sequencing in 100 Han Chinese patients with prostate cancer in Hong Kong and identified deleterious germline mutations. A total of 36 deleterious germline variants in 25 genes were identified in 29% patients. Variants were found in eight pathways, including DNA methylation, DDR, and tyrosine-protein kinase. These findings were validated in an independent Chinese cohort of 167 patients with prostate cancer in Shanghai. Seven common deleterious-variant-containing genes were found in discovery cohort (7/25, 28%) and validation cohort (7/28, 25%) with three genes not described before (LDLR, MYH7 and SUGCT) and four genes previously reported (FANCI, ITGA6, PABPC1 and RAD54B). When comparing with that of a cohort of East Asian healthy individuals, 12 non-DDR novel potential predisposition genes (ADGRG1, CHD4, DNMT3A, ERBB3, GRHL1, HMBS, LDLR, MYH7, MYO6, NT5C2, NUP98 and SUGCT) were identified using the discovery and validation cohorts, which have not been previously reported in prostate cancer patients in all ethnic groups. Taken together, this study reveals a comprehensive germline mutation landscape in Chinese prostate cancer patients and discovers 12 novel non-DDR predisposition genes to lay the groundwork for the optimization of genetic screening.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias da Próstata , China , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Proteínas Quinases/genética , Tirosina/genética , Sequenciamento do Exoma
2.
Artigo em Inglês | MEDLINE | ID: mdl-39088067

RESUMO

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

3.
BJU Int ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257199

RESUMO

OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

4.
BJU Int ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961793

RESUMO

OBJECTIVES: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. PATIENTS AND METHODS: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. RESULTS: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. CONCLUSION: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.

5.
World J Urol ; 42(1): 547, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331198

RESUMO

OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.


Assuntos
Adjuvantes Imunológicos , Vacina BCG , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/mortalidade , Vacina BCG/uso terapêutico , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Fatores Etários , Resultado do Tratamento , Estudos Retrospectivos , Adjuvantes Imunológicos/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Administração Intravesical , Neoplasias não Músculo Invasivas da Bexiga
6.
World J Urol ; 42(1): 97, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393414

RESUMO

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.


Assuntos
Neoplasias da Próstata , Reto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , Dosagem Radioterapêutica , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
7.
Ann Surg ; 277(1): 50-56, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491983

RESUMO

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.


Assuntos
COVID-19 , Cirurgiões , Humanos , Saúde Mental , SARS-CoV-2 , Pandemias , Depressão/psicologia , Ansiedade/psicologia , Pessoal de Saúde/psicologia , Inquéritos e Questionários , Estresse Psicológico/psicologia
8.
J Intern Med ; 294(6): 775-783, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37849423

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects extra-respiratory systems, with small-scale studies showing worsened male lower urinary tract symptoms (LUTS) after coronavirus disease 2019 (COVID-19). This study explores the correlation between SARS-CoV-2 infection and male benign prostatic hyperplasia (BPH) complications using large-scale real world data. MATERIALS AND METHODS: All male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021 to 2022 were included in this study. Patients with and without positive polymerase chain reaction (PCR) test for SARS-CoV-2 are selected as the exposure group and control group, respectively. Baseline characteristics are retrieved, with propensity score matching performed to ensure balance of covariates between the two groups. BPH complications were then compared and subgroup analyses were performed. RESULTS: After propensity score matching, 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n = 8993). When compared to controls, the SARS-CoV-2 group demonstrated statistically significant higher incidence of retention of urine (4.55% vs. 0.86%, p < 0.001), haematuria (1.36% vs. 0.41%, p < 0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%, p < 0.001), culture-proven bacteriuria (9.02% vs. 1.97%, p < 0.001) and addition of 5ARI (0.50% vs. 0.02%, p < 0.001). Subgroup analysis demonstrated similar differences across different age groups. There are no statistically significance differences in incidence of retention, haematuria, or addition of 5ARI across different COVID-19 severities. CONCLUSIONS: SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.


Assuntos
COVID-19 , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/diagnóstico , Hematúria/etiologia , COVID-19/complicações , Quimioterapia Combinada , SARS-CoV-2 , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/tratamento farmacológico
9.
J Urol ; 210(1): 88-98, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37036248

RESUMO

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Próstata/patologia , Antígeno Prostático Específico/análise , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos
10.
Curr Opin Urol ; 33(6): 482-487, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37646515

RESUMO

PURPOSE OF REVIEW: Urinary incontinence is common postoperative complication following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa). Despite the increasing adoption of RARP in the treatment of high-risk PCa (HRPC), concerns persist regarding the adequacy of reported continence outcomes in this subgroup. This review aims to illuminate the state of continence recovery in HRPC patients post-RARP. RECENT FINDINGS: Urinary continence (UC) recovery rates in HRPC was reported to be lower than the intermediate/low-risk counterparts from 6 to 24 months post-RARP. Predictive models showed that age, obesity, race, disease status, and surgical approaches represent predictors of continence recovery. Special techniques like NeuroSAFE technique and Retzius-Sparing approach also play a role in reducing incontinence also in the high-risk scenario. SUMMARY: RARP for HRPC appears to be associated with worse continence compared with other risk groups. A multimodality approach for prediction and prevention of incontinence after RARP is vital. Further research into this area is necessary to enhance continence recovery outcomes in HRPC patients undergoing RARP.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Incontinência Urinária , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Próstata , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/etiologia , Resultado do Tratamento , Recuperação de Função Fisiológica
11.
Int J Mol Sci ; 25(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38203661

RESUMO

Prostate cancer (PCa) is a prevalent malignant disease and the primary reason for cancer-related mortality among men globally. GLIS1 (GLIS family zinc finger 1) is a key regulator in various pathologies. However, the expression pattern, clinical relevance, and immunomodulatory function of GLIS1 in PCa remain unclear. In this study, GLIS1 was discovered to serve as a key gene in PCa by integrating mRNA and miRNA expression profiles from GEO database. We systematically explored the expression and prognostic values of GLIS1 in cancers using multiple databases. Additionally, we examined the functions of GLIS1 and the relationship between GLIS1 expression levels and immune infiltration in PCa. Results showed that GLIS1 was differentially expressed between normal and tumor tissues in various cancer types and was significantly low-expressed in PCa. Low GLIS1 expression was associated with poor PCa prognosis. GLIS1 was also involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression showed a positive correlation with the infiltration of various immune cells. Moreover, GLIS1 expression was positively associated with various chemokines/chemokine receptors, indicating the involvement in regulating immune cell migration. In summary, GLIS1 is a potential prognostic biomarker and a therapeutic target to modulate anti-tumor immune response in PCa.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/genética , Diferenciação Celular , Movimento Celular , Biomarcadores , Proteínas de Ligação a DNA , Fatores de Transcrição
12.
J Urol ; 207(1): 25-34, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555932

RESUMO

PURPOSE: We performed a systematic review comparing the incidence of infectious complications following transperineal ultrasound-guided prostate biopsy (TPB) in cases utilizing antibiotic prophylaxis (AP) vs cases not utilizing antibiotic prophylaxis (NAP). MATERIALS AND METHODS: The incidences of complications were pooled using the Cochran-Mantel-Haenszel method with the random effect model and expressed as risk ratio (RR). RR higher than 1 indicates an increased risk of complication in patients undergoing TPB without antibiotics. Statistical significance was set at p <0.05 and 95% CI. RESULTS: A total of 1,748 papers were retrieved. After the screening process, 8 studies were included in the quantitative analysis (4 retrospective, and 4 prospective and nonrandomized), reporting on 3,662 patients. A total of 2,368 patients underwent TPB utilizing AP and 1,294 underwent TPB utilizing NAP. The pooled rates of post-biopsy fever from 6 available studies reporting this parameter were 0.69% in the AP group and 0.47% in the NAP group (RR: 1.02, 95% CI: 0.02-44.55, p=0.99). The pooled rates of post-biopsy genitourinary infections from 8 available studies reporting this parameter were 0.11% in the AP group and 0.31% in the NAP group (RR: 2.09, 95% CI: 0.54-8.10, p=0.29). The pooled rates of post-biopsy sepsis over 8 studies reporting this parameter were 0.13% in the AP group and 0.09% in the NAP group (RR: 1.09, 95% CI: 0.21-5.61, p=0.92). The pooled rates of post-biopsy readmission for infections over 8 studies reporting this parameter were 0.13% in the AP group and 0.23% in the NAP group (RR: 1.29, 95% CI: 0.31-5.29, p=0.73). Death due to post-biopsy sepsis did not occur in any study. CONCLUSIONS: This systematic review found no significant difference in infection rate, fever, sepsis or readmission rate after TPB between those cases utilizing AP and those cases without AP.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Próstata/patologia , Antibioticoprofilaxia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Incidência , Masculino , Períneo , Ultrassonografia de Intervenção
13.
J Am Soc Nephrol ; 32(4): 961-971, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33483314

RESUMO

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

14.
Int J Urol ; 29(2): 102-113, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34643976

RESUMO

Urological cancers are common malignancies worldwide. Several conventional models, for example, two-dimensional cell culture and animal models have been used for decades to study tumor genetics. Nonetheless, these methods have limitations in reflecting the real tumor microenvironment in vivo, thereby hindering the development of anti-cancer therapeutic agents. Recently, three-dimensional culture models have gained attention because they can overcome the drawbacks of traditional methods. Above all, three-dimensional organoid models are able to mimic the tumor microenvironment in human bodies more closely as they are able to demonstrate the interactions between cells and extracellular matrix. This type of model has therefore extended our understanding of urological cancers. Tumor cells in organoid models can also be co-cultured with other cellular components, such as peripheral blood lymphocytes, and allow further understanding of the effect of tumor microenvironments on tumor growth. Furthermore, organoid models allow a prolonged culturing period, therefore, tumor evolution, progression and maintenance can also be assessed. Organoid models can be derived from each specific patient, and this facilitates investigation of individual cancer-specific mutations and their subtypes. As a result, the development of personalized medication targeting the signaling pathways or biomolecules of interest will be possible. In the present review, we summarize the development and applications of three-dimensional organoid cultures in urological cancers, mainly focusing on prostate, urinary bladder and kidney cancers, and assess the future prospects of this model.


Assuntos
Neoplasias Renais , Neoplasias Urológicas , Animais , Técnicas de Cultura de Células , Humanos , Masculino , Organoides , Microambiente Tumoral
15.
Int J Mol Sci ; 23(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163181

RESUMO

Polyamines are essential biomolecules for normal cellular metabolism in humans. The roles of polyamines in cancer development have been widely discussed in recent years. Among all, spermine alongside with its acetylated derivative, N1, N12-Diacetylspermine, demonstrate a relationship with the diagnosis and staging of various cancers, including lung, breast, liver, colorectal and urogenital. Numerous studies have reported the level of spermine in different body fluids and organ tissues in patients with different types of cancers. Currently, the role and the underlying mechanisms of spermine in cancer development and progression are still under investigation. This review summarized the roles of spermine in cancer development and as a diagnostic, prognostic and therapeutic tool in various cancers.


Assuntos
Neoplasias/metabolismo , Espermina/análogos & derivados , Espermina/fisiologia , Acetilação , Biomarcadores Tumorais , Humanos , Neoplasias/genética , Neoplasias/terapia , Poliaminas/metabolismo , Prognóstico , Espermidina , Espermina/química , Espermina/metabolismo
16.
Int J Mol Sci ; 23(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35682610

RESUMO

Spermidine/spermine N1-acetyltransferase (SSAT) functions as a critical enzyme in maintaining the homeostasis of polyamines, including spermine, spermidine, and putrescine, in mammalian cells. SSAT is a catalytic enzyme that indirectly regulates cellular physiologies and pathways through interaction with endogenous and exogenous polyamines. Normally, SSAT exhibits only at a low cellular level, but upon tumorigenesis, the expression, protein level, and activities of SSAT are altered. The alterations induce cellular damages, including oxidative stress, cell cycle arrest, DNA dynamics, and proliferation by influencing cellular mechanisms and signaling pathways. The expression of SSAT has been reported in various studies to be altered in different cancers, and it has been correlated with tumor development and progression. Tumor grades and stages are associated with the expression levels of SSAT. SSAT can be utilized as a target for substrate binding, and excreted metabolites may be used as a novel cancer biomarker. There is also potential for SSAT to be developed as a therapeutic target. Polyamine analogs could increase SSAT expression and increase the cytotoxicity of chemotherapy to tumor cells. Drugs targeting polyamines and SSAT expression have the potential to be developed into new cancer treatments in the future.


Assuntos
Neoplasias , Espermidina , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Humanos , Mamíferos/metabolismo , Poliaminas/metabolismo , Espermidina/metabolismo , Espermina/metabolismo
17.
World J Urol ; 39(9): 3127-3138, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32462305

RESUMO

PURPOSE AND OBJECTIVE: We performed a systematic review on COVID-19 and its potential urological manifestations. METHODS: A literature search was performed using combination of keywords (MeSH terms and free text words) relating to COVID-19, urology, faeces and stool on multiple databases. Primary outcomes were the urological manifestations of COVID-19, and SARS-CoV-2 viral RNA detection in urine and stool samples. Meta-analyses were performed when there were two or more studies reporting on the same outcome. Special considerations in urological conditions that were relevant in the pandemic of COVID-19 were reported in a narrative manner. RESULTS: There were a total of 21 studies with 3714 COVID-19 patients, and urinary symptoms were absent in all of them. In patients with COVID-19, 7.58% (95% CI 3.30-13.54%) developed acute kidney injury with a mortality rate of 93.27% (95% CI 81.46-100%) amongst them. 5.74% (95% CI 2.88-9.44%) of COVID-19 patients had positive viral RNA in urine samples, but the duration of viral shedding in urine was unknown. 65.82% (95% CI 45.71-83.51%) of COVID-19 patients had positive viral RNA in stool samples, which were detected from 2 to 47 days from symptom onset. 31.6% of renal transplant recipients with COVID-19 required non-invasive ventilation, and the overall mortality rate was 15.4%. CONCLUSIONS: Acute kidney injury leading to mortality is common amongst COVID-19 patients, likely as a result of direct viral toxicity. Viral RNA positivity was detected in both urine and stool samples, so precautions are needed when we perform transurethral or transrectal procedures.


Assuntos
Injúria Renal Aguda , COVID-19 , SARS-CoV-2/isolamento & purificação , Doenças Urológicas , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Humanos , RNA Viral/urina , Doenças Urológicas/classificação , Doenças Urológicas/terapia , Doenças Urológicas/virologia
18.
World J Urol ; 39(12): 4295-4303, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34031748

RESUMO

PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001). CONCLUSION: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered.


Assuntos
COVID-19/prevenção & controle , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Tempo para o Tratamento , COVID-19/epidemiologia , COVID-19/transmissão , Carcinoma de Células Renais/patologia , Controle de Doenças Transmissíveis , Humanos , Neoplasias Renais/patologia , Nefrectomia , Taxa de Sobrevida
19.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922247

RESUMO

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Espermina/metabolismo , Animais , Humanos , Masculino , Neoplasias da Próstata/metabolismo
20.
Int J Urol ; 26(9): 878-883, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31257704

RESUMO

OBJECTIVE: To investigate the safety and feasibility of robot-assisted single-port radical prostatectomy using the da Vinci single-port surgical system. METHODS: This was a prospective phase 1 clinical study of prostate cancer patients undergoing robot-assisted single-port radical prostatectomy using the da Vinci single-port surgical system. Primary outcome measures included the conversion rate and 30-day complications after surgery. Secondary outcome measures included operative time, blood loss, hospital stay, duration of catheterization, final pathological outcomes and number of lymph nodes yielded at pelvic lymphadenectomy. RESULTS: From February to August 2017, 20 patients were included in the present study. The mean age was 67.7 ± 6.0 years. The mean preoperative prostate-specific antigen level was 15.3 ± 11.3 ng/mL, and the mean prostate size was 36.6 ± 15.5 mL. Preoperatively, 12 (60%) patients had a Gleason score of 6, four (20%) had a Gleason score of 7 and four (20%) had a Gleason score of 8-10. The mean operative time was 208.9 ± 35.2 min, and the mean blood loss was 296.3 ± 220.7 mL. None of the patients required conversion. The mean hospital stay was 5.0 ± 1.7 days. Among the patients, six (15%) had T2a disease, one (5%) had T2b disease, seven (35%) had T2c disease and nine (45%) had T3a disease on final pathology. A mean number of 8.3 ± 7.1 lymph nodes were yielded at pelvic lymphadenectomy. There were no intraoperative complications. The observed postoperative complications were Clavien grade I-II, and all resolved with conservative management. CONCLUSION: Robot-assisted single-port radical prostatectomy using the da Vinci surgical system is safe and technically feasible.


Assuntos
Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação , Idoso , Conversão para Cirurgia Aberta/estatística & dados numéricos , Estudos de Viabilidade , Humanos , Tempo de Internação/estatística & dados numéricos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/instrumentação , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Próstata/patologia , Próstata/cirurgia , Prostatectomia/efeitos adversos , Prostatectomia/instrumentação , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos
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