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BACKGROUND: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. METHODS: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. RESULTS: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. CONCLUSION: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.
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Injúria Renal Aguda , Insuficiência Renal Crônica , Obstrução Uretral , Masculino , Adulto , Criança , Humanos , Lactente , Diálise Renal/efeitos adversos , Progressão da Doença , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Obstrução Uretral/cirurgia , Obstrução Uretral/complicações , Estudos Retrospectivos , Taxa de Filtração Glomerular , Proteinúria/etiologia , Rim , Injúria Renal Aguda/complicaçõesRESUMO
OBJECTIVES: To compare the incidence of benign uretero-enteric anastomotic strictures between open cystectomy, robotic cystectomy with extracorporeal urinary diversion, and robotic cystectomy with intracorporeal urinary diversion. The effect of surgeon learning curve on stricture incidence following intracorporeal diversion was investigated as a secondary outcome. PATIENTS AND METHODS: Patients who underwent radical cystectomy at an academic hospital between 2011 and 2018 were retrospectively reviewed. The primary outcome, incidence of anastomotic stricture over time, was assessed by a multivariable Cox proportional hazards regression. A Cox regression model adjusting for sequential case number in a surgeon's experience was used to assess intracorporeal learning curve. RESULTS: Nine hundred sixty-eight patients were included: 279 open, 382 robotic extracorporeal, and 307 robotic intracorporeal. Benign stricture incidence was 11.3% overall: 26 (9.3%) after open, 43 (11.3%) after robotic extracorporeal, and 40 (13.0%) after robotic intracorporeal. An intracorporeal approach was associated with anastomotic stricture on multivariable analysis (HR 1.66; P = .05). After 75 intracorporeal cases, stricture incidence declined from 17.5% to 4.9%. Higher sequential case volume was independently associated with reduced stricture incidence (Hazard Ratio per 10 cases: 0.90; P = .02). CONCLUSION: An intracorporeal approach to urinary reconstruction following robotic radical cystectomy was associated with an increased risk of benign uretero-enteric anastomotic stricture. In surgeons' early experience with intracorporeal diversion the difference in stricture incidence was more pronounced compared to alternative approaches; however, increased intracorporeal case volume was associated with a decline in stricture incidence leading to a modest difference between the 3 surgical approaches overall.
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Cistectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Derivação Urinária/efeitos adversos , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Cistectomia/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Ureter/cirurgia , Bexiga Urinária/cirurgia , Derivação Urinária/métodosRESUMO
OBJECTIVE: To assess readmission outcomes of a traditional ER pathway as well as a targeted postdischarge intervention aimed at reducing hospital readmissions following RC. METHODS: A prospectively maintained clinical database was used to identify patients undergoing RC before and after implementation of an ER protocol at our institution. An additional intervention aimed at reducing hospital readmission included close postdischarge follow-up and outpatient intravenous hydration (ER+). Inpatient length of stay (LOS) and readmission rates were compared between groups using Wilcoxon Rank Sum and chi-square, respectively. Univariate and multivariate logistic regression was used to identify factors associated with hospital readmission. RESULTS: A total of 320 patients underwent RC, including 111 and 209 patients before and after ER implementation. Median (IQR) LOS decreased from 8.0 (6.0-11.0) days to 5.0 (4.0-7.0) days following ER implementation (P <.0001). Readmissions, however, were unchanged following ER implementation (P = .49). An additional targeted readmission reduction intervention (ER+) was associated with significantly reduced hospital readmissions compared to traditional ER alone (ER+ 5.9%, traditional ER 20.3%, P = .017). CONCLUSION: ER protocols consistently demonstrate reductions in LOS, and should be the standard of care following RC. In order to reduce readmissions, the urologic community must expand beyond traditional ER pathways. We report significant reductions in hospital readmission among RC patients receiving a targeted postdischarge intervention beyond traditional ER alone.
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Assistência ao Convalescente , Cistectomia , Recuperação Pós-Cirúrgica Melhorada , Complicações Pós-Operatórias , Neoplasias da Bexiga Urinária/cirurgia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/tendências , Cistectomia/efeitos adversos , Cistectomia/métodos , Cistectomia/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/tendências , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/normas , Padrão de Cuidado/tendências , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: Bladder cancer management options include open radical cystectomy and robot-assisted radical cystectomy with intracorporeal or extracorporeal urinary diversion. The existing literature shows no difference in the major complication rate between open radical cystectomy and extracorporeal urinary diversion. However, the emerging popularity of intracorporeal urinary diversion has exposed the need to compare a completely intracorporeal method to alternative approaches. To our knowledge the robotic intracorporeal advantage regarding major complications has not yet been established in an evaluation of all 3 modalities. We compared outcomes and complications of open, intracorporeal and extracorporeal cystectomy techniques at a high volume institution. MATERIALS AND METHODS: We queried a prospectively maintained database for patients who underwent radical cystectomy from 2011 to 2018 for an oncologic indication. Perioperative and pathological outcomes, and 30 and 90-day major complications were assessed. Statistical analyses were done using the Pearson chi-square, Kruskal-Wallis and Kaplan-Meier tests, and multivariable regression. RESULTS: A total of 948 patients met the study criteria, including 272, 301 and 375 treated with open radical cystectomy, intracorporeal urinary diversion and extracorporeal urinary diversion, respectively. Median followup was 26 months. Intracorporeal urinary diversion cases had lower estimated blood loss (p <0.001), shorter hospitalization (p <0.001) and a lower ileus rate (p=0.023) than extracorporeal urinary diversion and open radical cystectomy cases. Importantly, intracorporeal urinary diversion was associated with lower 30 and 90-day major complication rates vs extracorporeal urinary diversion and open radical cystectomy (90-day Clavien-Dindo III-V 16.9% vs 24.8% and 26.1%, respectively, p=0.015). There was no significant difference in the readmission rate according to the surgical approach. Multivariable predictors of increased 90-day major complications were patient age, the Charlson Comorbidity Index and operative time. On multivariable analysis intracorporeal urinary diversion was associated with reduced 90-day major complications (OR 0.58, p=0.037). CONCLUSIONS: In a 3-way comparison intracorporeal urinary diversion demonstrated a lower major complication rate and perioperative benefits compared to extracorporeal urinary diversion and open radical cystectomy.
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Cistectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
Immunosuppressive drugs are used in renal transplantation to prevent and treat rejection and their use has traditionally been limited to urologists trained in transplant surgery. However, there are other urologic conditions for which these drugs have proven efficacy. Since transplant surgery has become a small niche subspecialty within urology, most urologists are unfamiliar and uncomfortable with their use. This review will focus on the use of Cyclosporine (CyA), mycophenolate mofetil (MMF), and mammalian target of rapamycin (mTOR) inhibitors in urology outside of solid organ transplant. This includes the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) with CyA as well as the role of CyA in eosinophilic cystitis (EC) and the treatment of retroperitoneal fibrosis (RF) with MMF. Also included is the utilization of mTOR inhibitors in both advanced renal cell carcinoma (RCC) and in patients with tuberous sclerosis complex (TSC) associated angiomyolipoma (AML). Available clinical data on mTOR inhibition in autosomal dominant polycystic kidney disease (ADPKD) is also briefly presented. Specific attention is given to the indications for each agent, the available evidence surrounding their use, and the most common adverse events (AEs) and their subsequent management.
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Background: Ureteroarterial fistula (UAF) is a rare and potentially devastating diagnosis most often associated with a combination of pelvic oncologic or vascular surgery, radiation, and chronic ureteral stents. Herein we discuss a patient with an ileal conduit urinary diversion and left nephroureteral (NU) catheter who presented with gross hematuria and hemodynamic instability. He underwent multiple negative radiologic investigations and his clinical course highlights the need for a high index of suspicion for UAF and multidisciplinary coordination with vascular surgery and interventional radiology. Case Presentation: Our patient is a 64-year-old male with a history of bladder cancer and atrial fibrillation on rivaroxiban who underwent cystoprostatectomy with ileal conduit urinary diversion. His postoperative course was complicated by subsequent mid-distal stricture of his left ureter, which was managed with balloon dilatation and a chronic indwelling NU catheter. He underwent a routine catheter exchange â¼1 year postradical cystectomy and subsequently experienced intermittent gross hematuria. He presented 5 weeks later with profound hematuria and clots through his urostomy accompanied by flank pain, weakness, and tachycardia. Throughout his hospital course he underwent two CT angiograms and a formal provocative angiogram that were all negative. He was taken to the operating room (OR) for attempted antegrade ureteroscopy, which was aborted because of pulsatile bleeding observed upon withdrawal of his stent. In collaboration with vascular surgery, he was eventually taken for provocative angiogram and covered stent graft placement that resolved the hematuria. Conclusion: This case highlights the diagnostic and care coordination challenges in patients with UAF. A high suspicion should be maintained in patients with hematuria and indwelling stents with a history of pelvic surgery and/or radiation.
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Kidney cancer is the eighth most commonly diagnosed cancer in the United States, and nearly one-third of patients have locally advanced or metastatic disease at presentation. Historically, survival outcomes for patients with advanced disease have been poor. In recent years, several novel targeted agents have emerged for the management of advanced renal cell carcinoma that have changed treatment paradigms. At the same time, surgical therapy continues to have a critical role in the management of selected patients. Recent medical and surgical advances have improved the prognosis for patients with a diagnosis of advanced disease. This review provides an overview of the current treatment landscape for patients with advanced renal cell carcinoma.
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Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Metástase Neoplásica , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.
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Portadores de Fármacos/química , Terapia Genética/métodos , Imunoterapia/métodos , Doenças Urológicas/terapia , Agentes Urológicos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Nanopartículas/química , Doenças Urológicas/genética , Doenças Urológicas/imunologia , Urologia/métodosRESUMO
INTRODUCTION: The phenotyping system UPOINT has proven effective in classifying patients with Urologic Pelvic Pain Syndromes in a clinically meaningful way and to guide therapy. While highly successful in men with chronic pelvic pain syndrome (CPPS), UPOINT is more limited in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) since by definition all patients have the urinary and organ specific phenotype. Furthermore, AUA guidelines recommend a sequential tiered approach to therapy rather than the multimodal UPOINT scheme. We sought to modify UPOINT to be more practical and efficacious for IC/PBS. MATERIALS AND METHODS: We developed a new phenotype by removing the urinary and organ specific domains from UPOINT and adding a Hunner's ulcers (U) domain, since these patients benefit from phenotype specific therapies (fulguration, cyclosporine). This yields 'INPUT': infection, neurologic/systemic, psychosocial, ulcers and tenderness of muscles. We applied this system retrospectively to our previously validated upointmd.com IC/PBS database. Symptoms were measured by the Genitourinary Pain Index (GUPI) (valid for men and women). The database was searched for patients with complete data to assess the INPUT domains and include GUPI. Men were included if they reported pain relieved by voiding and/or presence of Hunner's ulcers. Groups were compared with ANOVA, Mann-Whitney, t test or chi squared when appropriate and correlated with Spearman r. RESULTS: There were 239 patients, 154 female (64%) with age range 18-79 (mean 41.8). Incidence of domains was infection 11%, neurologic/systemic 51%, psychosocial 81%, ulcers 18% and tenderness 85%. Mean total domains was 2.46 (range 0-5) and 65% had 2 or 3 positive domains while only 5% had none. There was a stepwise increase in GUPI score with increasing number of positive INPUT domains (ANOVA for differences between groups p < 0.0001. Correlation by Spearman r = 0.355 p < 0.0001). Presence of Hunner's ulcers increased mean symptom score (25.7 versus 29.7, p = 0.004) and indeed each of the domains significantly increased total GUPI score except for Infection. CONCLUSIONS: The INPUT phenotype in IC/PBS appears to replicate the validity and potential clinical utility of UPOINT in CPPS. Patients have a diversity of phenotypes and more positive domains correlate with more severe symptoms. Since 95% of patients have at least 1 positive domain it may benefit patients to receive multimodal therapy up front for these extra domains (eg. pelvic floor physical therapy, fulguration of ulcers) rather than relying on a sequential tiered approach.
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Cistite Intersticial/classificação , Cistite Intersticial/terapia , Fenótipo , Perfil de Impacto da Doença , Adulto , Fatores Etários , Idoso , Análise de Variância , Estudos de Coortes , Cistite Intersticial/genética , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Normal , Medição da Dor , Psicologia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Penile-sparing modalities are gaining widespread adoption for the management of low-stage penile cancer due to an increasing demonstration of sound oncologic, cosmetic, sexual, psychosocial, and quality of life outcomes. This review aims to provide a comprehensive overview of the respective treatment options in the armamentarium of the practicing urologist in dealing with this rare but problematic condition.
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Neoplasias Ósseas/secundário , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Nefrectomia/métodos , Neoplasias Peritoneais/secundário , Idoso , Neoplasias Ósseas/tratamento farmacológico , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/secundário , Feminino , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/fisiopatologia , Recidiva Local de Neoplasia/radioterapia , Neoplasias Peritoneais/tratamento farmacológicoRESUMO
PURPOSE: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. MATERIALS AND METHODS: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. RESULTS: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p <0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). CONCLUSIONS: Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.
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Inibidores de 5-alfa Redutase/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Conduta Expectante , Adulto , Idoso , Esquema de Medicação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling. RESULTS: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.
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Biópsia/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Medição de Risco , Idoso , Progressão da Doença , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/classificação , Ohio/epidemiologia , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.
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Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Conduta Expectante , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Medição de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To analyze trends in perioperative chemotherapy and optimize use of neoadjuvant chemotherapy for bladder cancer. METHODS: From 2005-2012, 284 consecutive patients underwent robot-assisted radical cystectomy at our facility. Patients with disease ≥ T2 and nodal involvement and positive surgical margins were reviewed and considered candidates for referral to medical oncology for chemotherapy. The study was conducted in two phases: phase 1 included 242 consecutive patients between 2005 and 2011, and phase 2 analyzed the effect of changes in 42 patients during a 1-year period (2011-2012). RESULTS: In phase 1, 148 patients (61%) were candidates for neoadjuvant chemotherapy (NAC). Consultation for NAC was sought for 44 patients (29%), and 104 (71%) did not receive consultation. Of the 44 patients, 36% received NAC, 7% refused, 32% were recommended for immediate cystectomy, and 25% did not receive NAC for other reasons. Phase 2 was more stringent, with a multidisciplinary approach. Significant improvement in referral and NAC use was seen. About 78% vs 30% of patients were seen by medical oncology for consideration of NAC before robot-assisted radical cystectomy and 71% vs 36% received NAC compared with phase 1. The NAC utilization rate improved from 10.8% to 55% over 1 year with a diligent multidisciplinary approach. Medical comorbidities were the main reason for patients not receiving adjuvant chemotherapy (AC; 30% and 33%). CONCLUSION: A multidisciplinary approach and coordination of services can help optimize the use of neoadjuvant chemotherapy for bladder cancer.
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Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Quimioterapia Adjuvante , Comorbidade , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Recusa em Tratar , Robótica , Recusa do Paciente ao Tratamento , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
Chlorpyrifos (CPF) is a widely used organophosphorus (OP) pesticide. CPF is bioactivated by cytochrome P450s (CYPs) to the potent cholinesterase inhibitor chlorpyrifos oxon (CPF-O) or detoxified to 3,5,6-trichloro-2-pyridinol (TCPy). Human CYP2B6 has the highest reported Vmax)/Km (intrinsic clearance--CL(int)) for bioactivation while CYP2C19 has the highest reported CL(int) for detoxification of CPF. In this study, 22 human liver microsomes (HLMs) genotyped for common variants of these enzymes (CYP2B6*6 and CYP2C19*2) were incubated with 10 µM and 0.5 µM CPF and assayed for metabolite production. While no differences in metabolite production were observed in homozygous CYP2C19*2 HLMs, homozygous CYP2B6*6 specimens produced significantly less CPF-O than wild-type specimens at 10 µM (mean 144 and 446 pmol/min/mg, respectively). This correlated with reduced expression of CYP2B6 protein (mean 4.86 and 30.1 pmol/mg, for CYP2B6*6 and *1, respectively). Additionally, CYP2B6*1 and CYP2B6*6 were over-expressed in mammalian COS-1 cells to assess for the first time the impact of the CYP2B6*6 variant on the kinetic parameters of CPF bioactivation. The Vmax for CYP2B6*6 (1.05×105 pmol/min/nmol CYP2B6) was significantly higher than that of CYP2B6*1 (4.13×104 pmol/min/nmol CYP2B6) but the K(m) values did not differ (1.97 µM for CYP2B6*6 and 1.84 µM for CYP2B6*1) resulting in CL(int) rates of 53.5 and 22.5 nL/min/nmol CYP2B6 for *6 and *1, respectively. These data suggest that CYP2B6*6 has increased specific activity but reduced capacity to bioactivate CPF in HLMs compared to wild-type due to reduced hepatic protein expression, indicating that individuals with this genotype may be less susceptible to CPF toxicity.