RESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with nonmetastatic muscle-invasive bladder cancer (MIBC) confers an absolute survival benefit of 5%-10%. There is evidence that molecular differences between tumors may impact response to therapy, highlighting a need for clinically validated biomarkers to predict response to NAC. MATERIALS AND METHODS: Four bladder cancer cohorts were included. Inverse probability weighting was used to make baseline characteristics (age, sex and clinical tumor stage) between NAC-treated and untreated groups more comparable. Molecular subtypes were determined using a commercial genomic subtyping classifier. Survival rates were estimated using weighted Kaplan-Meier curves. Cox proportional hazards models were used to evaluate the primary and secondary study end points of overall survival (OS) and cancer-specific survival, respectively. RESULTS: A total of 601 patients with MIBC were included, of whom 247 had been treated with NAC and RC, and 354 underwent RC without NAC. With NAC, the overall net benefit to OS and cancer-specific survival at 3 years was 7% and 5%, respectively. After controlling for clinicopathological variables, nonluminal tumors had greatest benefit from NAC, with 10% greater OS at 3 years (71% vs 61%), while luminal tumors had minimal benefit (63% vs 65%) for NAC vs non-NAC. CONCLUSIONS: In patients with MIBC, a commercially available molecular subtyping assay revealed nonluminal tumors received the greatest benefit from NAC, while patients with luminal tumors experienced a minimal survival benefit. A genomic classifier may help identify patients with MIBC who would benefit most from NAC.
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Cisplatino/uso terapéutico , Invasividad Neoplásica/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Anciano , Biomarcadores de Tumor , Quimioterapia Adyuvante , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
PURPOSE: The utility of blue light cystoscopy (BLC) in patients receiving bacillus Calmette-Guérin (BCG) during post-treatment cystoscopy is not well understood. Our objective was to determine if BLC improves recurrence detection in patients with non-muscle invasive bladder cancer (NMIBC) undergoing BCG. MATERIALS AND METHODS: Using the prospective multi-institutional Cysview® Registry (2014-2019), patients with NMIBC who received BCG within 1 year prior to BLC were identified. Primary outcomes were recurrences and whether lesions were detected on white light cystoscopy (WLC), BLC or both. We calculated the percentage of cystoscopies with recurrences that were missed with WLC alone. The cystoscopy-level BLC false-positive rate was the proportion of cystoscopies with biopsies only due to BLC suspicious lesions without recurrence. RESULTS: Of 1,703 BLCs, 282 cystoscopies were in the analytic cohort. The overall recurrence rate was 45.0% (127). With only WLC, 13% (16/127) of recurrences would have been missed as 5.7% (16/282) of cystoscopies performed had recurrence only identified with BLC. Among 16 patients with recurrence missed with WLC, 88% (14) had carcinoma in situ. The cystoscopy-level BLC false-positive rate was 5% (15). CONCLUSIONS: BLC helped detect recurrences after recent BCG that would have been missed with WLC alone. Providers should consider BLC for high-risk patients undergoing BCG and should discuss the risk of false-positives with these patients. As clinical trials of novel therapies for BCG-unresponsive disease increase and there are no clear guidelines on BLC use for post-treatment cystoscopies, it is important to consider how variable BLC use could affect enrollment in and comparisons of these studies.
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Vacuna BCG/uso terapéutico , Cistoscopía/métodos , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Biopsia , Carcinoma in Situ/tratamiento farmacológico , Femenino , Humanos , Masculino , Estudios Prospectivos , Sistema de Registros , Estados UnidosRESUMEN
OBJECTIVES: To evaluate the role of blue-light cystoscopy (BLC) in detecting invasive tumours that were not visible on white-light cystoscopy (WLC). PATIENTS AND METHODS: Using the multi-institutional Cysview registry database, patients who had at least one white-light negative (WL-)/blue-light positive (BL+) lesion with invasive pathology (≥T1) as highest stage tumour were identified. All WL-/BL+ lesions and all invasive tumours in the database were used as denominators. Relevant baseline and outcome data were collected. RESULTS: Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL-/BL+, of those, 55 (7%) lesions were invasive (48 T1, seven T2; 47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). In all, 21/47 (45%) patients had WL-/BL+ concommitant carcinoma in situ and/or another T1 lesions. Of 22 patients with a WL-/BL+ lesion who underwent radical cystectomy (RC), high-risk pathological features leading to RC was only visible on BLC in 18 (82%) patients. At time of RC, 11/22 (50%) patients had pathological upstaging including four (18%) with node-positive disease. CONCLUSIONS: A considerable proportion of invasive lesions are only detectable by BLC and the rate of pathological upstaging is significant. Our present findings suggest an additional benefit of BLC in the detection of invasive bladder tumours that has implications for treatment approach.
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Cistoscopía , Neoplasias de la Vejiga Urinaria , Cistectomía , Humanos , Sistema de Registros , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Telomerase reverse transcriptase (TERT) promoter mutations have been implicated in urothelial carcinogenesis and are present in 60-80% of conventional and variants of urothelial carcinomas. We investigated the prevalence of TERT promoter mutations in 46 cases of bladder nonurachal adenocarcinoma, 30 cases of urothelial carcinoma with glandular differentiation, 24 cases of nephrogenic adenoma, eight cases of villous adenoma, 31 cases of florid cystitis glandularis, and 20 cases of intestinal metaplasia of the bladder. TERT promoter mutations were detected in 33% of adenocarcinomas of urinary bladder and in 67% of urothelial carcinomas with glandular differentiation. All 30 cases of urothelial carcinoma with glandular differentiation harbored identical TERT promoter mutation in both glandular and urothelial carcinoma components from the same tumor, suggesting a common clonal origin. TERT promoter mutations were absent in nephrogenic adenoma, villous adenoma, florid cystitis glandularis, and intestinal metaplasia of the bladder. TERT promoter mutation analysis may be a useful ancillary study in the differential diagnosis.
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Adenocarcinoma/genética , Carcinoma de Células Transicionales/genética , Telomerasa/genética , Neoplasias de la Vejiga Urinaria/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Regiones Promotoras Genéticas/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
INTRODUCTION: Residual retrocrural disease in testis cancer following chemotherapy is a surgical challenge. We sought to assess the outcomes and evolution with surgical management of residual retrocrural disease. MATERIALS AND METHODS: We identified 2,788 testicular cancer patients from 1990 to 2010 who underwent retroperitoneal surgery for metastatic testicular cancer at our institution. Patients who also underwent postchemotherapy staged or concurrent retrocrural dissections were stratified for analysis. Surgical approach, clinical characteristics, additional procedures, complications and outcomes were evaluated. RESULTS: Retrocrural dissection was performed in 211 patients. Histology of retrocrural disease demonstrated teratoma in 72%, necrosis in 15.2%, active germ cell cancer in 8.1% and malignant transformation in 2.4%. Our preferred surgical approach to the retrocrural space has evolved over time. Earlier approaches from 1990 to 1995 favored a single thoracoabdominal incision (17, 25%), midline transabdominal incision (22, 32.4%), or with a concurrent or staged thoracotomy (29, 42.6%). A transabdominal/transdiaphragmatic approach at the time of midline retroperitoneal lymph node dissection has been used more frequently in 55% of contemporary cases, decreasing the need for thoracotomies. Patients undergoing a transabdominal/transdiaphragmatic approach had fewer complications (p=0.006) and required fewer associated procedures (p=0.001) and a shorter length of stay (5 vs 6 days, p=0.184). CONCLUSIONS: Metastatic testis cancer to the retrocrural space is surgically challenging however complete resection is needed to maintain an expected excellent oncologic outcome. Coordination between urological and thoracic surgeons for an individualized approach is important. We have found that a transabdominal/transdiaphragmatic approach where appropriate has resulted in fewer complications.
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Neoplasias del Mediastino/cirugía , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Retroperitoneales/cirugía , Neoplasias Testiculares/cirugía , Adulto , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Neoplasias del Mediastino/secundario , Metástasis de la Neoplasia , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Retroperitoneales/secundario , Neoplasias Testiculares/patologíaRESUMEN
Urothelial carcinoma of the urinary bladder is a heterogeneous disease with multiple possible treatment modalities and a wide spectrum of clinical outcome. Treatment decisions and prognostic expectations hinge on accurate and precise staging, and the recently published American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition, should be the basis for staging of urinary bladder tumours. It is unfortunate that the International Union Against Cancer (UICC) 8th edition failed to incorporate new data which is considered in the AJCC 8th edition. Thus, the AJCC 8th edition is the focus of this review. Several critical changes and clarifications are made by the AJCC 8th edition relative to the 7th edition. Although the most obvious changes in the 8th edition are in the N (i.e. perivesical lymph node involvement now classified as N1) and M (i.e. M1 is subdivided into M1a and M1b) categories, several points are clarified in the T category (e.g. substaging of pT1 should be attempted). Further optimisation, however, is required. No particular method of substaging pT1 is formally recommended. In this review, these modifications are discussed, as well as points, which require further study and optimisation.
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Carcinoma de Células Transicionales/patología , Estadificación de Neoplasias/métodos , Neoplasias de la Vejiga Urinaria/patología , HumanosRESUMEN
Environmental factors that play a role in the urothelial carcinogenesis have been well characterized. Current research is continuously exploring potential heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable disease that increases the risk for a variety of cancers, including urothelial carcinomas. Screening of patients with known Lynch syndrome is important to evaluate for development of new primary tumors. Further study may provide more information on what level of follow-up each patient needs. Recent data suggest that mismatch repair mutations confer a greater risk for urothelial cancer. Additional large patient series as well as advancement of molecular testing may provide triage for Lynch syndrome patients in regards to the frequency and type of screening best suited for individual patient.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Neoplasias de la Vejiga Urinaria/genética , Biomarcadores de Tumor/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Detección Precoz del Cáncer , Humanos , Tamizaje Masivo , Inestabilidad de Microsatélites , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/epidemiología , Síndromes Neoplásicos Hereditarios/genética , Vigilancia de la Población , Pronóstico , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
OBJECTIVE: To update previously reported outcomes of modified-template post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in appropriately selected patients with metastatic non-seminomatous germ cell tumour (NSGCT), as our previous report was criticised for short follow-up and so we now provide a long-term update on this cohort. PATIENTS AND METHODS: In all, 100 patients with normal serum markers after cisplatin-based chemotherapy and residual retroperitoneal tumour underwent modified PC-RPLND between 1991 and 2004. Using a prospectively managed institutional testicular cancer database, long-term follow-up was obtained. RESULTS: As previously reported, 43 patients underwent a right-modified template, 18 patients underwent a full-left-modified template, and 39 patients underwent a left-modified template. The updated long-term median follow-up for the entire cohort is 125 months. Seven patients developed recurrent disease with a median (range) time to recurrence of 11 (6-102) months, and one patient died from recurrent disease in the chest 4 years after surgery. All recurrences were outside the boundaries of a full-bilateral template RPLND, with the most common location of recurrence being the chest. The 5- and 10-year recurrence-free survival rates were 93% and 92%, respectively. The overall survival at 10 years was 99%. CONCLUSIONS: In appropriately selected patients with low-volume disease before and after chemotherapy, a modified template has durable long-term efficacy without risk of in-field recurrences at a median follow-up of 125 months.
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Protocolos de Quimioterapia Combinada Antineoplásica , Escisión del Ganglio Linfático , Neoplasia Residual/patología , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Retroperitoneales/patología , Espacio Retroperitoneal/patología , Neoplasias Testiculares/patología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasia Residual/mortalidad , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/terapia , Estudios Retrospectivos , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To determine TERT promoter mutation status as well as the expression of PAX8, GATA3, p63, p40, p53 and uroplakin III in 17 patients with the upper urinary tract sarcomatoid urothelial carcinoma. METHODS & RESULTS: TERT C228T mutations were found in six of 17 cases (35%). p53 was expressed in 77% of these tumors. PAX8, GATA3, p40 and uroplakin III are less frequently expressed. Lymph node metastases were present in ten cases (59%). Eight patients (47%), including all three patients with TERT mutation, died of cancer within 2 years after surgery. CONCLUSION: Sarcomatoid carcinoma of the upper urinary tract is an aggressive tumor and the presence of TERT mutation may portend poor prognosis.
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Carcinoma/genética , Mutación , Regiones Promotoras Genéticas , Telomerasa/genética , Neoplasias Uretrales/genética , Neoplasias Urológicas/genética , Anciano , Anciano de 80 o más Años , Biomarcadores , Carcinoma/metabolismo , Carcinoma/mortalidad , Carcinoma/patología , Femenino , Factor de Transcripción GATA3/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factor de Transcripción PAX8/metabolismo , Pronóstico , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Uretrales/metabolismo , Neoplasias Uretrales/mortalidad , Neoplasias Uretrales/patología , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patologíaRESUMEN
AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/mortalidad , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Estudios de Cohortes , Cistectomía , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/mortalidad , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , GemcitabinaRESUMEN
PURPOSE: Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes 3 cycles of bleomycin, etoposide and cisplatin (BEP x3) or 4 cycles of etoposide and cisplatin (EP x4). We examine differences in active cancer in the retroperitoneum between patients receiving BEP x3 compared to EP x4. MATERIALS AND METHODS: The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received BEP x3 or EP x4 induction chemotherapy before retroperitoneal lymph node dissection. The primary outcome of interest was retroperitoneal histology. The association between the use of bleomycin in the induction regimen with active cancer in the retroperitoneal specimen was tested using a propensity score adjusted analysis. RESULTS: A total of 179 men (79%) received BEP x3 while 47 (21%) received EP x4. Median age of the bleomycin, etoposide and cisplatin group was 27 years (range 15 to 50) vs 30 years (range 18 to 71) in the etoposide and cisplatin group. The incidence of active cancer in the retroperitoneal specimen at post-chemotherapy retroperitoneal lymph node dissection was significantly higher in the EP x4 group compared to the BEP x3 group (31.9% vs 7.8%, p <0.01). This significant difference in the bleomycin, etoposide and cisplatin vs etoposide and cisplatin groups remained in the propensity adjusted analysis (22.9% vs 7.8%, p=0.015). CONCLUSIONS: There was a higher incidence of active cancer in the retroperitoneal specimen in good risk patients who received 4 cycles of induction etoposide and cisplatin chemotherapy compared to 3 cycles of bleomycin, etoposide and cisplatin in this retrospective analysis. The overall burden of treatment may be higher for men receiving EP x4 for induction chemotherapy.
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Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/uso terapéutico , Escisión del Ganglio Linfático , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Espacio Retroperitoneal/patología , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Adolescente , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada , Etopósido/administración & dosificación , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Testiculares/patología , Adulto JovenRESUMEN
OBJECTIVES: To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). PATIENTS AND METHODS: A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. RESULTS: Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. CONCLUSIONS: While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.
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Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Cistectomía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Small cell carcinoma is an aggressive malignancy often associated with dismal prognosis due to the presence of advanced disease. Small cell malignancies, initially described in the lung (small cell carcinoma of the lung), can occur in extrapulmonary sites, such as prostate (small cell carcinoma of the prostate) and bladder (small cell carcinoma of the bladder), with similar clinicopathologic outcomes. There has been a paradigm shift in the management of small cell carcinoma of the lung from initial surgical treatment to use of chemotherapy followed by local therapies. Such treatment modalities have been applied to small cell carcinoma of the prostate and the bladder, with promise in improving patient survival. Use of platinum-based combination chemotherapy followed by surgical resection and/or radiation offers the most benefit. Further investigation at the molecular level may offer targeted therapies earlier in the course of the disease.
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Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/terapia , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia , Carcinoma de Células Pequeñas/etiología , Femenino , Humanos , Masculino , Neoplasias de la Próstata/etiología , Neoplasias de la Vejiga Urinaria/etiologíaRESUMEN
AIM: To evaluate a three-tiered prognostic stratification using one, two to five and >five positive lymph nodes (LNs) and this nodal staging system performs across different pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. METHODS: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4-141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratification. RESULTS: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratification in patients with: one positive LN, two to five positive LNs or >five positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratification in the three groups was also verified irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confirmed the findings when controlling for demographic features and known pathologic risk factors. CONCLUSION: Three-tiered nodal classification system using the number of metastatic LNs (one, two to five and >five) stratifies patients with lymphatic disease into distinct prognostic groups.
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Ganglios Linfáticos/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Cistectomía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Primary renal extra-osseous osteosarcoma is an exceedingly rare and deadly kidney neoplasm with only 27 reported cases to date. Extra-osseous osteosarcoma is a mesenchymal sarcoma that produces osteoid, but has no skeletal or periosteal involvement and most commonly arises in the lower extremities. Yet, it can arise in other locations such as the kidney. Extra-osseous osteosarcoma behaves as a separate entity from osseous osteosarcoma and should be treated as such. The treatment is surgical resection. Five year overall survival is 46% for local and 10% for metastatic disease. Additionally, 45%-50% of patients experience disease recurrence. We present a 77-year-old woman who underwent work up for recurrent gross hematuria and subsequently underwent radical nephroureterectomy for presumed upper tract urothelial cell carcinoma. However, pathologic analysis revealed a diagnosis of primary renal extra-osseous osteosarcoma. She is alive with no evidence of disease 30 months after surgery.
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Neoplasias Renales/patología , Osteosarcoma/patología , Anciano , Femenino , Hematuria/etiología , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/cirugía , Nefrectomía , Osteosarcoma/complicaciones , Osteosarcoma/cirugía , Uréter/cirugíaRESUMEN
Rare earth metal magnets (Buckyballs and similar products) remain an important public health risk for children. We report the presentation, course, and treatment of a boy who inserted a string of 30 magnets through his urethra into his bladder and review the diagnostic as well as the therapeutic options for foreign bodies inserted into the pediatric urogenital tract.
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Cuerpos Extraños/diagnóstico por imagen , Imanes , Vejiga Urinaria/diagnóstico por imagen , Niño , Humanos , Masculino , RadiografíaRESUMEN
The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014-2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.
RESUMEN
Nearly 40% of patients with non-invasive bladder cancer will progress to invasive disease despite locally-directed therapy. Overcoming the bladder permeability barrier (BPB) is a challenge for intravesical drug delivery. Using the fluorophore coumarin (C6), we synthesized C6-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface modified with a novel cell penetrating polymer, poly(guanidinium oxanorbornene) (PGON). Addition of PGON to the NP surface improved tissue penetration by 10-fold in intravesically-treated mouse bladder and ex vivo human ureter. In addition, NP-C6-PGON significantly enhanced intracellular uptake of NPs compared to NPs without PGON. To examine biological activity, we synthesized NPs that were loaded with the histone deacetylase (HDAC) inhibitor belinostat (NP-Bel-PGON). NP-Bel-PGON exhibited a significantly lower IC50 in cultured bladder cancer cells, and sustained hyperacetylation, when compared to unencapsulated belinostat. Xenograft tumors treated with NP-Bel-PGON showed a 70% reduction in volume, and a 2.5-fold higher intratumoral acetyl-H4, when compared to tumors treated with unloaded NP-PGON. FROM THE CLINICAL EDITOR: These authors demonstrate that PLGA nanoparticles with PGON surface functionalization result in greatly enhanced cell penetrating capabilities, and present convincing data from a mouse model of bladder cancer for increased chemotherapy efficacy.
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Portadores de Fármacos/química , Inhibidores de Histona Desacetilasas/administración & dosificación , Ácidos Hidroxámicos/administración & dosificación , Nanopartículas/química , Sulfonamidas/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Línea Celular Tumoral , Portadores de Fármacos/metabolismo , Sistemas de Liberación de Medicamentos , Femenino , Inhibidores de Histona Desacetilasas/farmacocinética , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Ácidos Hidroxámicos/farmacocinética , Ácidos Hidroxámicos/uso terapéutico , Ratones , Nanopartículas/metabolismo , Poliglactina 910/química , Poliglactina 910/metabolismo , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapéutico , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Urotelio/efectos de los fármacos , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
BACKGROUND: Biodynamic signatures (temporal patterns of microscopic motion within a 3-dimensional tumor explant) offer phenomic biomarkers that are highly predictive for therapeutic response. OBJECTIVE: By utilizing motility contrast tomography, which provides a simple, fast assessment of motion patterns in living tissue, we evaluated the predictive accuracy of a biodynamic drug response classifier in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). DESIGN, SETTING, AND PARTICIPANTS: One hundred five consecutive bladder cancer patients suspected of having MIBC were screened in a multi-institutional prospective observational study (NCT03739177) from July 2018 to June 2020, of whom, 30 completed NAC and radical cystectomy. INTERVENTION(S): Biodynamic signatures from treatment-naïve fresh bladder tumor specimens obtained after transurethral resection were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin per institutional guidelines and were followed through radical cystectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: A 4-level classifier was developed to predict pathologic complete response (pCR) vs. incomplete response utilizing a one-left-out cross-validation protocol to minimize over-fitting. Area under the curve evaluated predictive utility. RESULTS: Thirty percent (9 of 30) achieved pCR. Utilizing the 4-level classifier, biodynamically "favored" (scoring ≥ 3) and "strongly favored" (scoring 4) regimens accurately predicted pCR at rates of 66.7% (4 of 6 patients) and 100% (4 of 4 patients), respectively. Biodynamically "favored" scores predicted pCR with 88% sensitivity and 95% negative predictive value, P < 0.0001. Only 5.0% (1 of 20 patients) achieved pCR from regimens scoring 1 or 2, indicating poor to no response from NAC. Area under the receiver operating curve was 96% (95% Confidence Interval: 79%-99%, P < 0.0001). Future direction involves validating this model prospectively. PRINCIPAL CONCLUSIONS: Biodynamic scoring accurately predicts response in MIBC patients receiving NAC and holds promise to substantially improve the scope of appropriate management intervention.
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Cisplatino , Neoplasias de la Vejiga Urinaria , Humanos , Cisplatino/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/patología , Cistectomía/métodos , Músculos/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Invasividad Neoplásica , Estudios RetrospectivosRESUMEN
OBJECTIVES: To evaluate whether a restaging transurethral resection of bladder tumor (TURBT) is necessary in high-risk nonmuscle invasive bladder cancer (NMIBC) if the initial TURBT was performed using blue light (BL) technology. METHODS AND MATERIALS: Using the multi-institutional Cysview registry between 2014 and 2021, all consecutive adult patients with known NMIBC (Ta and T1 disease) who underwent TURBT followed by a restaging TURBT within 8 weeks were reviewed. Patients were stratified according to their initial TURBT, BL vs. white light (WL), and compared to determine rates of residual disease and upstaging. Univariate analysis was performed using Mann-Whitney U and chi-square tests, with P < 0.05 considered significant. RESULTS: Overall, 115 patients had TURBT for NMIBC followed by a restaging TURBT within 8 weeks and were included in the analysis. Patients who underwent BL compared to WL for their initial TURBT had higher rates of benign pathology on restaging TURBT, although this was not statistically significant (47% vs. 30%; Pâ¯=â¯0.08). Of patients with residual tumors on restaging TURBT, there were no differences in rates of Ta (22% vs. 26.5%; Pâ¯=â¯0.62), T1 (22% vs. 26.5%; Pâ¯=â¯0.62), or CIS (5.5% vs. 13%; Pâ¯=â¯0.49) when the initial TURBT was done using BL compared to WL. Rates of upstaging to muscle invasive disease were also not different when initial TURBT was performed using BL compared to WL (3% vs. 4%; Pâ¯=â¯0.78). CONCLUSIONS: TURBT using BL does not reduce rates of residual disease or risk of upstaging on restaging TURBT in Ta or T1 disease. Thus, a restaging TURBT is still necessary even if initial TURBT was performed using BL.