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PURPOSE: Ureteroenteric strictures (UESs) are a common and morbid complication of radical cystectomy and urinary diversions. UES occurs in 4% to 25% of all patients undergoing urinary diversion, and anastomotic ischemia is implicated in stricture formation. SPY fluorescence angiography is a technology that can be employed during open surgery that allows for evaluation of ureteral perfusion. MATERIALS AND METHODS: We performed a prospective single-institution study of intraoperative use of SPY for ureteral assessment with a primary outcome of UES incidence compared with a cohort of historic controls prior to the use of SPY during urinary diversion at our institution. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Statistical analysis was performed using χ2 test for UES incidence. Demographics characteristics were analyzed with Wilcoxon rank sum test and χ2 test. RESULTS: A total of 332 patients underwent urinary diversion during the study period. UES occurred in 31 of 277 patients (11.1%) in the control group compared with 1 of 55 patients (1.8%) enrolled in the SPY arm (P = .03). The per-ureter UES rate was 6.7% (33/582) in the control group compared with 0.9% (1/107) in the SPY group. Median follow-up in the SPY group was 17.5 months and 58.6 months in the control group. Median Charlson Comorbidity Index was 5 in the SPY group and 4 in the control group. There were no other significant demographic differences between the study groups. CONCLUSIONS: SPY fluorescent angiography can be used during open urinary diversion to ensure perfusion to ureteroenteric anastomosis. Our single-institution study demonstrates a decreased incidence of UES when ureteral perfusion assessment is performed. CLINICAL TRIAL REGISTRATION NO.: NCT05022199.
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BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has evolved rapidly, and results from the Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) trial bring into question the utility of cytoreductive nephrectomy (CN). The objective of this study was to examine overall survival (OS) and identify risk factors associated with patients less likely to benefit from CN in the targeted therapy era. METHODS: Patients with mRCC undergoing CN from 2005 to 2017 were identified. Kaplan-Meier methods and Cox proportional hazards regression analyses were used to assess OS and risk-stratify patients, respectively, on the basis of preoperative clinical and laboratory data. RESULTS: Six hundred eight patients were eligible with a median follow-up of 29.4 months. Ninety-five percent of the patients had an Eastern Cooperative Oncology Group performance status less than or equal to 1, and 70% had a single site of metastatic disease. In a multivariable analysis, risk factors significantly associated with decreased OS included systemic symptoms at diagnosis, retroperitoneal and supradiaphragmatic lymphadenopathy, bone metastasis, clinical T4 disease, a hemoglobin level less than the lower limit of normal (LLN), a serum albumin level less than the LLN, a serum lactate dehydrogenase level greater than the upper limit of normal, and a neutrophil/lymphocyte ratio greater than or equal to 4. Patients were stratified into 3 risk groups: low (fewer than 2 risk factors), intermediate (2-3 risk factors), and high (more than 3 risk factors). These groups had median OS of 58.9 months (95% confidence interval [CI], 44.3-66.6 months), 30.6 months (95% CI, 27.0-35.0 months), and 19.2 months (95% CI, 13.9-22.6 months), respectively (P < .0001). The median time to postoperative systemic therapy was 45 days (interquartile range, 30-90 days). CONCLUSIONS: Patients with more than 3 risk factors did not seem to benefit from CN. Importantly, OS in this group was equivalent to, if not higher than, OS for patients in the CN plus sunitinib arm of CARMENA, and this raises the possibility that a well-selected population might benefit from CN.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/cirugía , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Selección de Paciente , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/patología , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Supervivencia sin Enfermedad , Femenino , Hemoglobinas/metabolismo , Humanos , Estimación de Kaplan-Meier , Linfocitos/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Nefrectomía/efectos adversos , Neutrófilos/patología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sunitinib/administración & dosificación , Sunitinib/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: In May 2012, the US Preventive Services Task Force assigned prostate-specific antigen-based screening a grade D recommendation, advising against screening at any age. Our objective was to compare prostate cancer characteristics pre- and post-recommendation with an adjusted analysis of our data and a pooled analysis including other primary data sources. METHODS: We identified all incident prostate cancer diagnoses at our institution from 2007 to 2016. Multivariable log binomial regression was used to determine the relative risk (RR) of metastasis at diagnosis, ≥Gleason Group 4, and high D'Amico risk disease pre- versus post-recommendation. The meta-analysis included primary data studies evaluating these outcomes. RESULTS: At our institution, 287 (44.6%) and 224 (48.8%) patients were diagnosed in the pre- and post-cohorts. The RR of metastatic disease at diagnosis did not differ between groups (p = 0.224), nor did the risk of high D'Amico category disease (p = 0.089). The risk of ≥Gleason Group 4 was 1.58 times higher post-recommendation (p = 0.007). The pooled risk of ≥Gleason Group 4 disease was 1.5 (p < 0.001) post-recommendation and was 1.29 (p = 0.006) for high D'Amico risk disease. CONCLUSIONS: While the number of metastatic cases did not differ after the recommendation, the risk of high-grade cancers increased at both a local and aggregated level.
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Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/prevención & control , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Servicios Preventivos de Salud , Neoplasias de la Próstata/diagnóstico , Estados UnidosRESUMEN
BACKGROUND: We performed a comparative survival analysis of patients undergoing robotic-assisted versus laparoscopic or open surgery for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients diagnosed with non-metastatic UTUC undergoing removal of the kidney and/or ureter were identified using Medicare-linked Surveillance, Epidemiology, and End Results Program data (2004-2013). Patients aged 65-85 years were categorized based on surgical approach (open, laparoscopic, or robotic-assisted). Kaplan-Meier methods were used to determine survival (overall and cancer-specific) and intravesical recurrence rates, the former using a propensity score-weighted model. Independent predictors of survival were determined using multivariable Cox proportional hazards regression analysis. RESULTS: We identified a total of 3801 patients meeting the final inclusion criteria: open (n = 1862), laparoscopic (n = 1624), and robotic (n = 315). Robotic surgery was associated with the shortest length of hospital stay (p < 0.001) but highest in-hospital charges (p < 0.001), with no difference in readmission rates (p = 0.964). No difference was found in overall or cancer-specific survival in the robotic cohort when compared with open or laparoscopic surgery. In addition, no difference in the rate of intravesical recurrence was noted in robotic-assisted laparoscopy compared with the other groups. The sole predictor of improved survival was extent of lymphadenectomy, which was highest in the robotic cohort. CONCLUSIONS: Using a large, population-based cancer database, there was no survival difference when a robotic-assisted approach was utilized in patients undergoing surgery for UTUC. These findings are important with the increased use of robotic surgery in the management of UTUC.
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Carcinoma de Células Transicionales/cirugía , Neoplasias Renales/cirugía , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Neoplasias Ureterales/cirugía , Neoplasias de la Vejiga Urinaria/secundario , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/secundario , Femenino , Precios de Hospital , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Laparoscopía/economía , Tiempo de Internación , Metástasis Linfática , Masculino , Readmisión del Paciente , Modelos de Riesgos Proporcionales , Procedimientos Quirúrgicos Robotizados/economía , Programa de VERF , Tasa de Supervivencia , Neoplasias Ureterales/patologíaRESUMEN
We report a new type of carbon nanotube ring (CNTR) coated with gold nanoparticles (CNTR@AuNPs) using CNTR as a template and surface attached redox-active polymer as a reducing agent. This nanostructure of CNTR bundle embedded in the gap of closely attached AuNPs can play multiple roles as a Raman probe to detect cancer cells and a photoacoustic (PA) contrast agent for imaging-guided cancer therapy. The CNTR@AuNP exhibits substantially higher Raman and optical signals than CNTR coated with a complete Au shell (CNTR@AuNS) and straight CNT@AuNP. The extinction intensity of CNTR@AuNP is about 120-fold higher than that of CNTR at 808 nm, and the surface enhanced Raman scattering (SERS) signal of CNTR@AuNP is about 110 times stronger than that of CNTR, presumably due to the combined effects of enhanced coupling between the embedded CNTR and the plasmon mode of the closely attached AuNPs, and the strong electromagnetic field in the cavity of the AuNP shell originated from the intercoupling of AuNPs. The greatly enhanced PA signal and photothermal conversion property of CNTR@AuNP were successfully employed for imaging and imaging-guided cancer therapy in two tumor xenograft models. Experimental observations were further supported by numerical simulations and perturbation theory analysis.
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Oro/química , Hipertermia Inducida/métodos , Nanopartículas del Metal/química , Nanotubos de Carbono/química , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , Campos Electromagnéticos , Oro/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Ratones Desnudos , Neoplasias/diagnóstico , Neoplasias/terapia , Espectrometría Raman , Propiedades de Superficie , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. MATERIALS AND METHODS: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings. RESULTS: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged. CONCLUSIONS: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.
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Carcinoma de Células Transicionales/mortalidad , Selección de Paciente , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Cistectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Background: Tele-cystoscopy involves trained advanced practice providers performing cystoscopy with real-time interpretation by an urologist. The goal of this externally validated care model is to expand the availability of cystoscopy to underserved rural areas. Herein we report on population demographics and describe the socioeconomic benefits of tele-cystoscopy for bladder cancer surveillance. Methods: Using an IRB-approved protocol, patients were consented for dual, sequential cystoscopy wherein they experienced a standard-of-care cystoscopy along with tele-cystoscopy. Patients completed a questionnaire that contained both subjective and objective health and socioeconomic-related questions as well as a satisfaction survey. Patients were also probed about factors associated with transportation to their cystoscopy appointments including gasoline costs, travel time, and time off work. Using the Distressed Community Index, patients were ascribed an economic resource category ranging from prosperous to distressed. Results: In total, 48 patients with a mean age of 55 completed surveys after completing dual cystoscopies. Thirteen patients (27%) were uninsured and 10 patients (20%) had Medicaid as primary insurance. The tele-cystoscopy clinic saved patients an average of 235 miles and 434 min of travel time. In total, 82% of patients resided in a distressed community indicating fewer economic resources. Satisfaction results showed a mean score of 31.38 (out of 32). Conclusions: Patients were satisfied with tele-cystoscopy, noting increased access to health care and fewer disruptions impacting bladder cancer surveillance. Tele-cystoscopy may be a viable option to expand access and improve adherence to guidelines for bladder cancer surveillance, particularly benefiting patients in rural areas and those of lower socioeconomic status.
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While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.
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Tatuaje , Uréter , Neoplasias de la Vejiga Urinaria , Humanos , Persona de Mediana Edad , Uréter/diagnóstico por imagen , Uréter/cirugía , Uréter/patología , Cistectomía , Proyectos Piloto , Anastomosis Quirúrgica/métodos , Estudios RetrospectivosRESUMEN
UNLABELLED: Study Type--Diagnostic (cohort) Level of Evidence: 2b. What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies. OBJECTIVE: ⢠To evaluate the ability of preoperative biopsy to identify high-risk pathological features by comparing pathology from preoperative metastatic site and primary tumour biopsies with nephrectomy pathology in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: ⢠We reviewed clinical and pathological data from patients who underwent biopsy before cytoreductive nephrectomy for mRCC at MD Anderson Cancer Center (MDACC) from 1991 to 2007. ⢠Percutaneous biopsy techniques included fine-needle aspiration, core needle biopsy or a combination of both techniques. RESULTS: ⢠The pathology of 405 preoperative biopsies (239 metastatic site, 166 primary tumour) from 378 patients was reviewed at MDACC before cytoreductive nephrectomy. ⢠The biopsy and nephrectomy specimens had the same histological subtype in 96.0% of clear-cell renal cell carcinomas (RCCs) and 72.7% of non-clear-cell RCCs. ⢠Of 76 nephrectomy specimens where sarcomatoid de-differentiation was identified, only seven (9.2%) were able to be identified from the preoperative biopsy. ⢠In 38.3% of patients, the same Fuhrman grade was identified in both the biopsy and nephrectomy specimens. ⢠A definitive diagnosis of RCC was more likely to be reported in primary tumour biopsies than in metastatic site biopsies. (P < 0.001). CONCLUSIONS: ⢠Preoperative biopsy has limited ability to identify non-clear-cell histological subtype, Fuhrman grade or sarcomatoid features. ⢠When surgical pathology is not available, a biopsy obtaining multiple samples from different sites within the primary tumour should be recommended rather than limited metastatic site biopsy to identify patients for clinical trials.
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Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Riñón/patología , Nefrectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina/normas , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenAsunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirugía , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Neoplasias del Pene/genética , Neoplasias del Pene/patología , Neoplasias del Pene/cirugía , Neoplasias del Pene/virología , Humanos , MasculinoRESUMEN
PURPOSE: As treatment options evolve for metastatic renal cell carcinoma, there is a need for predictive information to help guide therapy. We assessed the accuracy of percutaneous primary tumor biopsy for metastatic renal cell carcinoma by comparing biopsy findings to final nephrectomy pathology in patients undergoing cytoreductive nephrectomy. MATERIALS AND METHODS: Using an institutional database we reviewed the records of patients who underwent percutaneous primary tumor biopsy before cytoreductive nephrectomy. In patients who underwent biopsy elsewhere pathology findings were re-reviewed at our institution. Differences in accuracy based on biopsy technique, imaging modality and biopsy period were determined by chi-square analysis. RESULTS: We identified 166 patients who underwent percutaneous biopsy of the primary tumor before cytoreductive nephrectomy between 1991 and 2007, and had data available for review. Median pathological tumor size was 9.1 cm (range 3 to 32). Median time from biopsy to surgery was 46 days (range 6 to 717). Of 104 patients in whom biopsy was assigned a Fuhrman nuclear grade 33 (31.7%) had the same grade in the nephrectomy specimen, including 74 of 109 (67.9%) when considering only high or low grade. Grade change by more than 2 points was seen in 18 of 104 patients (17.3%). Sarcomatoid features were present in 34 of 166 nephrectomy specimens (20.5%) but only 4 (11.8%) were identified preoperatively. CONCLUSIONS: In patients with metastatic renal cell carcinoma percutaneous renal biopsy has poor accuracy to assess Fuhrman nuclear grade or sarcomatoid features. Physicians should use caution when using biopsy data to guide therapy.
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Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Nefrectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Carcinoma de Células Renales/secundario , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To identify factors in a large cohort of patients with pathologically localized renal cell carcinoma (RCC) that predicted disease progression after surgery, as RCC most commonly presents as a localized tumour which is treated with surgical excision. PATIENTS AND METHODS: Using an institutional database, we identified all patients who underwent radical or partial nephrectomy and had pathologically confirmed pT1 or pT2 RCC. Multivariable stepwise logistic regression analysis was used to calculate an odds ratio corresponding to the odds of progression to metastatic disease during surveillance, based on several clinical and pathological variables. We defined those variables that remained significant on multivariable analysis as risk factors and, based on the number of risk factors, we assessed risk of disease progression. RESULTS: In all, 925 patients were eligible for analysis with a median follow-up of 48.2 months. There was progression to metastatic disease in 53 (5.7%) patients; pT1 in 20/774 (2.6%), pT2 in 33/151 (21.9%). Risk factors included pT2 disease, male gender, symptoms at presentation (local or constitutional), presence of sarcomatoid de-differentiation, and macroscopic necrosis on final pathology. In 177 patients with no risk factors, none progressed; 20 of 618 (3.2%) with one or two risk factors had progression at a median of 37.1 months; 33 of 130 (25.4%) with three or more risk factors progressed at a median of 25.2 months. CONCLUSIONS: We identified five risk factors that can help to predict those patients with pT1 or pT2 RCC at highest risk for disease progression after surgery. The potential for disease progression is exceedingly low in patients with no risk factors and surveillance can be minimized in this group.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Nefrectomía/métodos , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Métodos Epidemiológicos , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , PronósticoRESUMEN
INTRODUCTION: We describe and demonstrate an efficient method for assigning clinic days to urology providers in academic and large urology group practices given their numerous scheduling constraints including evaluation and management visits, office or operating room procedures/surgeries, teaching, trainee mentorship, committee work and outreach activities. METHODS: We propose an integer programming model for scheduling providers for clinic shifts in order to maximize patient access to appointments considering the aforementioned scheduling constraints. We present results for a case study with an academic urology clinic and lessons learned from implementing the model generated schedule. RESULTS: The integer programming model produced a feasible schedule that was implemented after pairwise and 3-way switches among attending providers to account for preferences. The optimized schedule had reduced variability in the number of providers scheduled per shift (standard deviation 1.409 vs 0.999, p=0.01). While other confounding factors are possible we noted a significant increase in the number of encounters after implementing changes from the model (1,370 vs 1,196 encounters, p=0.011). CONCLUSIONS: Optimization models offer an efficient and transferable method of generating a clinic template for providers that takes into account other clinical and academic responsibilities, and can increase the number of appointments for patients. Optimization of schedules may be performed periodically to address changes in providers or provider constraints.
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While several retrospective studies have suggested a possible benefit of lymph node dissection (LND) for patients with clinically node-positive renal cell carcinoma (RCC), the value of LND in patients with clinically node-negative RCC has remained uncertain. LND undoubtedly improves the accuracy of staging and provides better prognostic information; however, much debate surrounds the impact of LND on progression-free and overall survival in patients with RCC. Additionally, the question remains as to whether LND at nephrectomy is associated with increased morbidity. The final results of the European Organisation for Research and Treatment of Cancer (EORTC) randomized phase III trial 30881 demonstrate that complete LND at nephrectomy does not affect the survival of patients with clinical N0M0 RCC. Importantly, no increase in morbidity was noted in patients who underwent an extended LND compared with no LND, indicating that the performance of LND is unlikely to increase the risk to the patient.
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PURPOSE: Gleason sum 7 prostate cancers are a heterogeneous group with diverse tumor behaviors and disease outcomes. Tertiary Gleason patterns are reported with increasing frequency, particularly in prostatectomy pathology reports. We studied the pathological and biochemical outcome following radical prostatectomy in men with Gleason sum 7 and tertiary Gleason pattern 5. MATERIALS AND METHODS: We reviewed 1,110 cases of clinically localized prostate cancer treated with primary radical prostatectomy between January 1998 and August 2006 through a prospectively collected prostate cancer database. Patients who underwent neoadjuvant or adjuvant hormonal deprivation, radiation or systemic chemotherapy were excluded. RESULTS: Of the 1,110 patients 509 had Gleason sum 7 cancer. Tertiary Gleason pattern was present in 66 of 509 cases (13%) and it was absent in 443 (87%). On multivariate analysis tertiary Gleason pattern 5 was associated with higher pT stage (OR 2.55, 95% CI 1.40-4.65) and biochemical recurrence (HR 1.78, 95% CI 1.00-3.17). On subgroup analysis when patients with Gleason sum 3 + 4 + 5 and 4 + 3 + 5 were compared to their respective referent groups without the tertiary Gleason pattern, the 2 groups showed a trend toward higher pathological stage and prostate specific antigen progression. Patients with Gleason sum 3 + 4 with no tertiary pattern had higher PSA recurrence-free probability than those with Gleason sum 3 + 4 + 5 or 4 + 3 and patients with Gleason sum 4 + 3 + 5 had the lowest PSA recurrence-free probability. CONCLUSIONS: In patients with Gleason sum 7 prostate cancer tertiary Gleason grade 5 is significantly associated with higher pT stage and biochemical recurrence. Larger studies are needed to assess the predictive value of tertiary grade compared to other established parameters in predicting the long-term oncological outcome after radical prostatectomy.
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Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , RecurrenciaRESUMEN
Lynch syndrome (LS) is defined by germline mutations in DNA mismatch repair (MMR) genes, and affected patients are at high risk for multiple cancers. Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS. To study the suitability of universal MMR IHC screening for UTUC, we investigated MMR expression and microsatellite status in UTUC in comparison to bladder UC (BUC), and evaluated the clinicopathologic features of UTUC. We found that 9% of UTUC showed MMR IHC loss (8 MSH6 alone; 1 MSH2 and MSH6; 1 MLH1 and PMS2; n=117) compared with 1% of BUC (1 MSH6 alone; n=160) (P=0.001). Of these, 4/10 (40%) of UTUC (3% overall; 3 MSH6 alone; 1 MLH1 and PMS2) and none (0%) of BUC had high microsatellite instability on molecular testing (P=0.03). The only predictive clinicopathologic feature for MMR loss was a personal history of colorectal cancer (P=0.0003). However, UTUC presents at a similar age to colon carcinoma in LS and thus UTUC may be the sentinel event in some patients. Combining our results with those of other studies suggests that 1% to 3% of all UTUC cases may represent LS-associated carcinoma. LS accounts for 2% to 6% of both colorectal and endometrial cancers. As LS likely accounts for a similar percentage of UTUC, we suggest that reflexive MMR IHC screening followed by microsatellite instability testing be included in diagnostic guidelines for all UTUC.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN , Enzimas Reparadoras del ADN/genética , Detección Precoz del Cáncer/métodos , Inmunohistoquímica , Inestabilidad de Microsatélites , Neoplasias Urológicas/genética , Urotelio/química , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Bases de Datos Factuales , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Mutación , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Neoplasias Urológicas/patología , Urotelio/patologíaRESUMEN
The beneficial effect of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma in the immunotherapy era was based on two prospective randomized trials. Unfortunately, such evidence does not yet exist in the present-day period of targeted therapy. Despite this, cytoreductive nephrectomy remains integral in the multimodal management of patients with metastatic renal cell carcinoma. Multiple retrospective studies as well as data from prospective studies examining targeted therapy support the continued use of cytoreductive nephrectomy in the properly selected patient. Ongoing studies will hopefully fine-tune the role and timing of cytoreductive nephrectomy in the context of targeted therapy.
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OBJECTIVES: Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort. MATERIALS AND METHODS: Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death. RESULTS: A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T3), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7 cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001). CONCLUSIONS: Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.