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PURPOSE: Urologic surgery involving placement of an indwelling ureteral and/or urethral drain can be associated with significant catheter-related bladder discomfort causing increased postoperative morbidity and opioid medication use. We sought to assess if a single dose of oxybutynin given preoperatively reduces immediate postoperative opioid use in common pediatric urology surgeries. MATERIALS AND METHODS: This single-institution retrospective study identified pediatric patients who underwent surgery on the urinary tract with concomitant placement of a urethral and/or ureteral drain. Patients were given a single weight-based dose of oral oxybutynin in the preoperative area prior to surgery. The primary outcome was receipt of postoperative opioid medication. Multivariable regression analyses were used to assess variables associated with postoperative opioid use. RESULTS: A total of 134 patients were included in our final study population with 42 receiving oxybutynin and 92 who did not. There was no statistical difference between the groups in terms of age, procedure type, anesthesia block, postoperative drain, or intraoperative morphine milligram equivalents per kilogram. Patients who received oxybutynin preoperatively had a decrease in postoperative opioid use (19%) compared to those who did not receive oxybutynin (47%). On multivariable logistic regression analysis, preoperative oxybutynin was associated with a 77% reduced risk of receiving postoperative opioid (odds ratio 0.23, [95% CI 0.09-0.56], P < .001). CONCLUSIONS: For pediatric patients with an indwelling urinary drain after urologic surgery, a single preoperative dose of oxybutynin was significantly associated with lower postoperative utilization of opioids. This relatively low risk intervention can be easily implemented.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Quimioterapia Adjuvante , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Nefrectomia , Ensaios Clínicos como AssuntoRESUMO
SUMMARY: Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME. The spatialTIME package calculates univariate and bivariate spatial statistics (e.g. Ripley's K, Besag's L, Macron's M and G or nearest neighbor distance) and creates publication quality plots for spatial organization of the cells in each tissue sample. The iTIME web application allows users to statistically compare the abundance measures with patient clinical features along with visualization of the TIME for one tissue sample at a time. AVAILABILITY AND IMPLEMENTATION: spatialTIME is implemented in R and can be downloaded from GitHub (https://github.com/FridleyLab/spatialTIME) or CRAN. An extensive vignette for using spatialTIME can also be found at https://cran.r-project.org/web/packages/spatialTIME/index.html. iTIME is implemented within a R Shiny application and can be accessed online (http://itime.moffitt.org/), with code available on GitHub (https://github.com/FridleyLab/iTIME). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Software , Humanos , Análise por Conglomerados , ImunofluorescênciaRESUMO
PURPOSE: Men with nonseminomatous germ cell tumors of the testicle without evidence of residual disease after radical orchiectomy (clinical stage I) are increasingly managed with active surveillance. The guideline-recommended cornerstones of surveillance are conventional serum tumor markers and computerized tomography. The reliability of serum tumor markers as a tool to diagnose early recurrence of clinical stage I nonseminomatous germ cell tumors is unclear. The study objective was to conduct a systematic review of the currently available evidence assessing the reliability of serum tumor markers as a test to diagnose recurrence in patients with clinical stage I nonseminomatous germ cell tumors under active surveillance. MATERIALS AND METHODS: A systematic review was conducted in accordance with PRISMA guidelines, with no language or date restrictions. Studies were included that readily identified the tumor marker status of patients with clinical stage I nonseminomatous germ cell tumors who had a recurrence on active surveillance. The primary outcome was marker positivity at the time of recurrence. Risk of bias assessment was undertaken. RESULTS: A total of 2,157 studies were identified and independently screened by 2 reviewers, with 37 studies ultimately being included. A relatively high risk of bias was identified among the studies, with the vast majority being retrospective series. The total population for the included studies was 8,545 patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, and 2,254 ultimately relapsed. Serum tumor markers were elevated in 28% to 75% of patients at the time of recurrence and were the only indication of recurrence in 4% to 39%. The unavailability of patient-level data is the major limitation to the present findings. CONCLUSIONS: In patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, the use of serum tumor markers cannot obviate the need for computerized tomography. More reliable serum markers are needed in order to limit radiation exposure for these patients.
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Biomarcadores Tumorais/sangue , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Testiculares/sangue , Neoplasias Testiculares/diagnóstico , Conduta Expectante , Humanos , Masculino , Estadiamento de Neoplasias , Reprodutibilidade dos TestesRESUMO
PURPOSE: Our primary objective is to detail the incidence, site, and timing of penile squamous cell carcinoma (pSCC) recurrence after inguinal lymph node dissection (ILND). MATERIALS AND METHODS: We performed a retrospective analysis of 551 patients who underwent ILND for pSCC from 2000 to 2017. The primary outcome was pSCC recurrence after ILND. Recurrences were identified and stratified by site. Timing of recurrence was determined. Multivariable logistic regression analysis determined associations with recurrence. Multivariable Cox regression analysis determined associations with overall survival (OS). Sub-group analysis of the distant recurrences analyzed timing and OS by site of distant recurrence. RESULTS: After ILND pSCC recurred in 176 (31.9%) patients. Median time to recurrence was 10 months for distant recurrences, 12 for inguinal, 10.5 for pelvic, and 44.5 for local. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months of ILND, versus 127 months for local recurrences. Post-ILND recurrence was associated with pN2 (OR 1.99, 95% CI 1.0-4.1), and pN3 (OR 7.2, 95% CI 4.0-13.7). Patients who had local recurrence had similar OS to those without (HR 1.5, 95% CI 0.6-3.8), and worse OS was identified in patients with inguinal (HR 4.5, 95% CI 2.8-7.1), pelvic (HR 2.6, 95% CI 1.5-4.5), or distant (HR 4.0, 95% CI 2.7-5.8) recurrences. Patients with lung recurrences had worse OS than other sites (HR 2.2, 95% CI 1.1-4.3). CONCLUSIONS: Of the patients 31.9% had post-ILND recurrence associated with high pN staging. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months, suggesting surveillance beyond this is low yield. Local recurrences occurred over a longer timeline, emphasizing necessity of long-term surveillance of the primary site.
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Carcinoma de Células Escamosas/cirurgia , Excisão de Linfonodo , Metástase Linfática/terapia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Penianas/cirurgia , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Seguimentos , Humanos , Canal Inguinal , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Estudos RetrospectivosRESUMO
PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.
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Cistectomia , Músculos/efeitos dos fármacos , Terapia Neoadjuvante/estatística & dados numéricos , Neoplasias da Bexiga Urinária/terapia , Bexiga Urinária/patologia , Idoso , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.
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Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Adulto , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Teratoma/patologia , Teratoma/cirurgia , Neoplasias Testiculares/cirurgiaRESUMO
INTRODUCTION To evaluate the educational value of transplant rotation in urology residency. In the United States, exposure to kidney transplantation during urology residency has declined significantly over the past few decades. At our institution, transplantation has been a core component of urology residency since its inception in 1959. MATERIALS AND METHODS: A 15-question anonymous survey was developed. The first 8 questions queried demographics and the last 7 were a set of questions with a Likert Scale response. The survey was electronic- mailed to past and current urology residents who had completed the transplant rotation, dating back to 1972. RESULTS: A total of 61 out of 98 (62%) individuals responded. The majority (59%) were general urologists, and one (2%) had completed a transplant fellowship. In their practices, 17% performed kidney transplants and 28% performed donor nephrectomies. Overall, 100% responded that the skills learned on the transplant rotation were beneficial for urology training, 100% had learned valuable vascular surgical techniques, and 93% felt that urology residents should have clinical transplant experience during their training. There was no statistical difference between the younger and older graduates in Likert scale responses. CONCLUSION: The majority of graduates did not perform transplants in their practice, yet, all of responders agreed that the skills learned on the transplant rotation were beneficial and 93% expressed that urology residents should have clinical transplant experience during residency. Kidney transplantation should be an integral part of urology residency training.
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Internato e Residência , Urologia , Competência Clínica , Bolsas de Estudo , Humanos , Inquéritos e Questionários , Estados Unidos , Urologia/educaçãoRESUMO
INTRODUCTION Perioperative stroke and myocardial infarction are uncommon but devastating thromboembolic complications. There is no comprehensive study detailing these complications for urologic procedures. The primary aim of this study is to determine which urologic procedures and patients carry the highest risk of perioperative stroke and myocardial infarction. MATERIALS AND METHODS: The National Surgical Quality Improvement Program data set was reviewed from 2008-2017. Procedures coded under the urology specialty were included and patients who had a perioperative stroke or myocardial infarction were identified. CPTs were stratified into clinically relevant procedure groups. Two multivariable logistic regression analyses were performed to determine preoperative and procedural risk factors for developing perioperative stroke or myocardial infarction. A multivariable logistic regression analysis was performed to determine the association between these complications and 30-day mortality. RESULTS: A total of 281,744 cases were included, identifying 392 strokes (0.14%) and 1,016 myocardial infarctions (0.36%). Age ≥ 70, hypertension, and disseminated cancer were the strongest preoperative risk factors for perioperative stroke or myocardial infarction. Cystectomy was the highest risk urologic procedure (stroke: OR 3.3, 95%CI 2.3-4.8; MI: OR 7.2, 95%CI 5.6-9.1). Thirty-day mortality was dramatically worse for patients who had a perioperative stroke or myocardial infarction. CONCLUSIONS: Perioperative stroke and myocardial infarction were confirmed to be uncommon but devastating complications of urologic surgery, with incidence of 0.14% and 0.36%, respectively. Cystectomy was the highest risk urologic procedure. Perioperative stroke and myocardial infarction were strongly associated with age ≥ 70, hypertension, and disseminated cancer.
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Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Incidência , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Procedimentos Cirúrgicos Urológicos/efeitos adversosRESUMO
PURPOSE: Physician work relative value units are determined based on operative time, technical skill, mental effort and stress. In theory, work relative value units should account for the operative time involved in a procedure, resulting in similar work relative value units per unit time for short and long procedures. We assessed whether operative time is adequately accounted for by the current work relative value units assignments. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2015 to 2017. The 50 most frequently coded urology CPT codes were included in the study. The primary variable was work relative value units per hour of operative time (work relative value units per hour). Linear regression analysis was used to assess the associations between work relative value units, operative time and the work relative value units per hour variable. RESULTS: A total of 105,931 cases were included in the study. Among the included urology CPTs the median work relative value units was 15.26, median operative time was 48 minutes and median work relative value units per hour was 11.2. CPTs with operative time less than 90 minutes had higher work relative value units per hour compared with longer procedures (12.2 vs 8.7, p <0.001). Univariable analysis revealed that each additional hour of operative time was associated with a decrease in work relative value units per hour by 1.32 (-0.022 per minute, 95% CI -0.037 - -0.001, p <0.001) and that work relative value units were not statistically associated with work relative value units per hour (-0.093, 95% CI -0.193 - 0.007, p=0.07). CONCLUSIONS: This analysis of large population, national level data suggests that the current work relative value units assignments do not proportionally compensate for longer operative times.
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Competência Clínica , Doenças Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Urologistas/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Feminino , Humanos , Masculino , Duração da Cirurgia , Melhoria de Qualidade , Sociedades Médicas , Estados Unidos , UrologiaRESUMO
Malignant Leydig cell tumor is a rare entity that has been previously described as rapidly progressive and uniformly fatal. We present the case of a malignant Leydig cell tumor that presented 14 years after orchiectomy with an isolated retroperitoneal metastasis. Our patient underwent a retroperitoneal lymph node dissection and has been free of recurrence or progression at 12 months of follow up. Additionally, we describe the symptomatic hormone dysfunction experienced by our patient as a result of his tumor.
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Tumor de Células de Leydig/patologia , Recidiva Local de Neoplasia/cirurgia , Orquiectomia/métodos , Neoplasias Retroperitoneais/secundário , Neoplasias Testiculares/patologia , Biópsia por Agulha , Seguimentos , Humanos , Imuno-Histoquímica , Tumor de Células de Leydig/cirurgia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retroperitoneais/cirurgia , Medição de Risco , Neoplasias Testiculares/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Pelvic congestion syndrome (PCS) is a complex condition of the pelvic venous system leading to nonspecific pelvic pain that was initially described in females alone. The underlying abnormalities, though diverse, all result in increased pressure in the left gonadal vein which is transmitted retrograde into the pelvic venous system. Our primary aim was to describe our findings of secondary PCS as a distinct entity from primary PCS in that it has an identifiable vascular etiology and is gender nonspecific. We also aimed to assess the adequacy of late-arterial phase CT urography (CTU) as the initial imaging modality in diagnosing and evaluating secondary PCS. MATERIALS AND METHODS: We retrospectively reviewed 59 patients with PCS, 36 males and 23 females ages 24 to 63, from 2000-2011. To maximize opacification, CTU images were taken in the late-arterial phase with a 35-50 second delay after contrast administration. RESULTS: Review of our cases revealed multiple etiologies for PCS, including: Nutcracker syndrome (19 cases), cirrhosis (17), retroaortic left renal vein (11), tumor thrombosis of the IVC (5), portal vein thrombosis (4), renal cell carcinoma with left renal vein thrombosis (2), and left kidney AVF (1). The most common symptom was unexplained chronic pelvic pain. The patients in our series had clearly identifiable vascular flow abnormalities leading to the development of PCS, and were therefore diagnosed as having secondary PCS. All cases were easily identified utilizing CTU to visualize and measure dilation of the left gonadal vein and pelvic varices. This modality also proved valuable in the identification and management of the various underlying causes of secondary PCS. CONCLUSION: Secondary PCS is distinct from primary PCS in that it arises from clearly identifiable vascular flow abnormalities and occurs in both males and females. The diverse set of underlying etiologies, as well as the resulting congested varices, can be reliably and adequately visualized using CTU as the initial imaging modality.
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Dor Pélvica/etiologia , Pelve/irrigação sanguínea , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/diagnóstico , Veias/fisiopatologia , Adulto , Feminino , Fibrose/complicações , Humanos , Incidência , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Dor Pélvica/epidemiologia , Veia Porta , Síndrome do Quebra-Nozes/complicações , Estudos Retrospectivos , Síndrome , Trombose/complicações , Tomografia Computadorizada por Raios X , Urografia , Doenças Vasculares/etiologiaRESUMO
BACKGROUND: Neoadjuvant cisplatin-containing chemotherapy before radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). However, a large proportion of patients are ineligible for cisplatin. Single-arm phase 2 neoadjuvant immunotherapy trials have reported promising tumor response rates, but interpretation is limited owing to lack of a comparator arm. OBJECTIVE: To compare rates of pathologic downstaging and overall survival between patients receiving neoadjuvant immunotherapy (NAI), neoadjuvant chemotherapy (NAC), or no neoadjuvant therapy (NNAT). DESIGN, SETTING, AND PARTICIPANTS: We identified 18 483 patients in the National Cancer Data Base who were diagnosed with clinically localized MIBC and underwent radical cystectomy from 2014 to 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Nearest-neighbor propensity-score caliper matching was used to create three demographically similar and equally sized cohorts stratified by NAT receipt. Logistic regression was used to examine the association of treatment received with pathologic downstaging to pT0N0 and pT < 2N0. Cox proportional-hazards regression was used to assess the association of treatment received with overall survival (OS). RESULTS AND LIMITATIONS: Propensity score matching yielded three equally sized cohorts without significant differences in baseline characteristics (n = 840). The NAI group had a higher rate of pathologic downstaging to pT0N0 than the NNAT group and a similar rate to the NAC group (NNAT 6.7% vs NAC 26.4%, odds ratio 5.0, 95% confidence interval [CI] 2.9-8.3; NAI 22.5%, odds ratio 4.0, 95% CI 2.4-7.1). The NAI group had better OS than the NNAT group and similar OS to the NAC group (NAC: hazard ratio 0.62, 95% CI 0.42-0.92; NAI: hazard ratio 0.68, 95% CI 0.46-0.97, with NNAT as the reference). The primary limitation is selection bias from confounding by clinical indication. CONCLUSIONS: NAI is a promising alternative to NAC for patients with clinically localized MIBC, as evidenced by similar pathologic downstaging rates and OS benefits in comparison to no NAT. Phase 3 trials should be conducted to test the noninferiority of NAI to NAC. PATIENT SUMMARY: We compared outcomes for patients with muscle-invasive bladder cancer according to whether they received chemotherapy, immunotherapy, or no medical therapy before surgical removal of their bladder. We found that preoperative immunotherapy improved patient survival and regression of the cancer stage in comparison to no medical therapy, similar to the outcomes seen with preoperative chemotherapy. Randomized clinical trials are needed to confirm these findings.
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Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Humanos , Cisplatino/uso terapêutico , Cistectomia/métodos , Imunoterapia , Músculos/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVE: Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. METHODS: Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. RESULTS: NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). CONCLUSION: We developed a simple model that could be used as a screening tool for early palliative care referral.
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Carcinoma de Células Escamosas , Neoplasias Penianas , Masculino , Humanos , Neoplasias Penianas/patologia , Estudos Retrospectivos , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Carcinoma de Células Escamosas/patologia , Planejamento de Assistência ao Paciente , Estadiamento de Neoplasias , PrognósticoRESUMO
INTRODUCTION: In clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary. METHODS: Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley's K analysis, a methodology adapted from ecology. RESULTS: Clustering of CD163+M2 like TAMs into the stromal compartment at the tumor-stroma interface was associated with worse clinical stage (tumor/CD163+nK(75): stage I/II: 4.4 (IQR -0.5 to 5.1); stage III: 1.4 (IQR -0.3 to 3.5); stage IV: 0.6 (IQR -2.1 to 2.1); p=0.04 between stage I/II and stage IV), and worse overall survival (OS) and cancer-specific survival (CSS) (tumor/CD163+nK(75): median OS-hi=149 months, lo=86 months, false-discovery rate (FDR)-adj. Cox p<0.001; median CSS-hi=174 months, lo=85 months; FDR-adj. Cox p<0.001). An RNA-seq differential gene expression score was developed using this geospatial metric, and was externally validated in multiple independent cohorts of patients with ccRCC including: TCGA KIRC, and the IMmotion151, IMmotion150, and JAVELIN Renal 101 clinical trials. In addition, this CD163+ geospatial pattern was found to be associated with a higher TIM-3+ proportion of CD8+T cells, indicative of terminal exhaustion (tumor-core: 0.07 (IQR 0.04-0.14) vs 0.40 (IQR 0.15-0.66), p=0.05). CONCLUSIONS: Geospatial clustering of CD163+M2 like TAMs into the stromal compartment at the tumor-stromal interface was associated with poor clinical outcomes and CD8+T cell terminal exhaustion.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Prognóstico , Linfócitos T CD8-Positivos , Microambiente TumoralRESUMO
Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples. Spatial gene set enrichment analysis (GSEA) and autocorrelation (coupling with high expression) of ligand-receptor transcript pairs were assessed. Multiplex immunofluorescence (mIF) validation was used for significant autocorrelative findings and the cancer genome atlas (TCGA) and the clinical proteomic tumor analysis consortium (CPTAC) databases were queried to assess bulk RNA expression and proteomic correlates. Results: 21 patient samples underwent SMI. Viable tumors following IO harbored more stromal CD8+ T cells and neutrophils than IO naïve tumors. YES1 was significantly upregulated in IO exposed tumor cells. The epithelial-mesenchymal transition pathway was enriched on spatial GSEA and the associated transcript pair COL4A1-ITGAV had significantly higher autocorrelation in the stroma. Fibroblasts, tumor cells, and endothelium had the relative highest expression. More integrin αV+ cells were seen in IO exposed stroma on mIF validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. In CPTAC, collagen IV protein was more abundant in advanced stages of disease. Conclusions: On spatial transcriptomics, COL4A1 and ITGAV were more autocorrelated in IO-exposed stroma compared to IO-naïve tumors, with high expression amongst fibroblasts, tumor cells, and endothelium. Integrin represents a potential therapeutic target in IO treated ccRCC.
RESUMO
INTRODUCTION: Immune checkpoint blockade (ICB) is a rapidly emerging field of oncology that has revolutionized the metastatic renal cell carcinoma (mRCC) treatment. Four recent treatment regimens Nivolumab-Ipilimumab, Pembrolizumab-Axitinib, Nivolumab-Cabozantinib, and Pembrolizumab-Lenvatinib-have demonstrated improved clinical endpoints compared to standard of care and are endorsed by NCCN (2021). However, data on patient-reported outcomes (PROs) for patients receiving these regimens are limited. We conducted a comparative assessment of the quality and standardization of PROs endpoints and data reported for these randomized controlled trials (RCTs). PATIENTS AND METHODS: We systematically identified all RCTs evaluating combination ICB for ccRCC. PROs-specific data were abstracted from the final version of 4 RCT protocols, as well as clinical and PROs specific manuscripts published between April 2018 and April 2021. We used 3 previously published guides standardizing PROs research to objectively score the data: (i) 24-point PROEAS; (ii) 12-point SPIRIT-PRO; and (iii) 14-point CONSORT-PRO. RESULTS: The CheckMate 214, KEYNOTE 426, CheckMate 9ER, and CLEAR studies had PROEAS scores of 88% (21/24), 37% (9/24), 83% (20/24), and 16% (4/24), respectively, and SPIRIT-PRO scores of 50% (6/12), 75% (9/12), 66% (8/12), and 41% (5/12) respectively. The CONSORT-PRO scores were 86% (12/14) for CheckMate 214 and 43% (6/14) for CheckMate 9ER, but scores were not available for the CLEAR and KEYNOTE 426 studies because of a lack of sufficient data. The average SPIRIT-PRO score across the 4 RCTs was 58%, indicating a reasonable adoption of PROs research in data management and analysis. The CheckMate 214 trial had the longest follow-up and most comprehensive published PROs data. CONCLUSION: Our analysis identified the limitations of current PROs data in combination ICB approved for mRCC. This analysis will enable clinicians to better interpret the current PROs results and emphasize the importance of better incorporation of PROs endpoints in future mRCC trial design.