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PURPOSE: The modified Glasgow Prognostic Score (mGPS) by measurement of serum C-reactive protein and albumin levels has been shown to provide prognostic value in various cancer types. The purpose of this study was to evaluate whether preoperative assessment of the mGPS predicts patient survival outcome in renal cell carcinoma (RCC). MATERIALS AND METHODS: Clinicopathological and follow-up data in 219 RCC patients, all of whom underwent curative or non-curative nephrectomy, were collected. Overall survival (OS) and cancer-specific survival (CSS) after nephrectomy were evaluated, and univariate and multivariate analyses were conducted to assess the predictive value of the variables, including the mGPS. RESULTS: During the median follow-up of 57 months, 53 patients (24.2%) were deceased within 22 months of the median OS. The 5-year OS rate from nephrectomy was 85.9 and 18.8% in non-metastatic (n = 195) and metastatic (n = 24) patients, respectively. Increasing mGPS was associated with shorter OS in non-metastatic patients (2-year OS rate of 98.2% in mGPS0, 73.3% in mGPS1, and 44.4% in mGPS2; hazard ratio [HR] 9.96, 95% confidence interval [CI] 4.88-20.13, p < 0.001), whereas no significant difference in OS according to the mGPS was seen in metastatic patients (HR 2.01, 95% CI 0.79-5.16, p = 0.137). On multivariate analysis, the mGPS remained as an independent predictor for OS (HR 5.24, 95% CI 1.39-19.77, p = 0.015) and CSS (HR 4.69, 95% CI 1.13-20.96, p = 0.034) in non-metastatic RCC patients. CONCLUSIONS: The mGPS appeared to be a reliable, preoperatively defined predictive marker with widely standardized protocol in non-metastatic RCC, and should therefore be considered in treatment decision making for RCC patients.
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Proteína C-Reactiva/metabolismo , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/cirugía , Neoplasias Renales/sangre , Neoplasias Renales/cirugía , Albúmina Sérica/metabolismo , Anciano , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Nefrectomía , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Tasa de Supervivencia , Carga TumoralRESUMEN
Retroperitoneal tumor is a rare tumor, with an incidence of 0.2 to 0.8%. Among such tumors, the frequency of teratomas ranges from 6 to 18%, and adult cases are extremely rare. We report a mature teratoma that occurred in the retroperitoneum of 43-year-old woman. She experienced back pain and a left adrenal gland mass was detected on computed tomography. Computed tomography and magnetic resonance imaging findings showed a cyst made of fat and calcification, but it was difficult to distinguish retroperitoneal teratoma from adrenal tumor in this case. The tumor was removed, and was mainly composed of a hair ball and fat. Pathological examination showed that the tumor was composed of stratified squamous epithelium, keratinizing component, cartilage, and bronchial epithelium, while no continuity with the adrenal gland was observed. Therefore, the tumor was diagnosed as a retroperitoneal teratoma.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias Retroperitoneales/diagnóstico por imagen , Teratoma/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Neoplasias Retroperitoneales/patología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: We investigated the effect of balloon occluded arterial infusion of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the tumor site without systemic adverse effects, along with concurrent radiation (referred to as the Osaka Medical College regimen) in patients with advanced bladder cancer. MATERIALS AND METHODS: A total of 329 patients (TisN0 16, T2N0 174, T3N0 77, T4N0 22 and TxN+ 40) were assigned to receive the Osaka Medical College regimen. Patients who did not achieve complete response underwent total cystectomy or secondary balloon occluded arterial infusion with an increased amount of cisplatin and/or gemcitabine. RESULTS: The Osaka Medical College regimen allowed 83.6% (276 of 329) of patients in total and 93.6% (250 of 267) of patients with organ confined disease (including T3b) to achieve complete response. Of the patients with a complete response 96% (240 of 250) survived with a functional bladder without evidence of recurrent disease within a mean followup of 159 weeks. Although lymph node involvement, especially N2 stage, was selected as a significant risk factor for treatment failure and survival, it was noteworthy that 61.9% of patients with N1 disease achieved complete response and that the 5-year overall survival rate was 72.2%. No patients had grade III or more severe toxicities. CONCLUSIONS: The Osaka Medical College regimen, a new bladder preservation strategy, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment because of disease stage, age or other factors, and for whom merely palliative therapy would otherwise seem the only option.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Oclusión con Balón , Diálisis Renal , Neoplasias de la Vejiga Urinaria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Terapia Combinada , Cistectomía , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , GemcitabinaRESUMEN
OBJECTIVES: To assess whether bipolar transurethral resection of the prostate (B-TURP) using the TURis system has a similar level of efficacy and safety to that of the traditional monopolar transurethral resection of the prostate (M-TURP), and to evaluate the impact of the TURis system on postoperative urethral stricture rates over a 36-month follow-up period. PATIENTS AND METHODS: A total of 136 patients with benign prostatic obstruction were randomised to undergo either B-TURP using the TURis system or conventional M-TURP, and were regularly followed for 36 months after surgery. The primary endpoint was safety, which included the long-term complication rates of postoperative urethral stricture. The secondary endpoint was the follow-up measurement of efficacy. RESULTS: In peri-operative findings, no patient in either treatment group presented with transurethral resection syndrome, and the decline in levels of haemoglobin and hematocrit were similar. The mean operation time was significantly extended in the TURis treatment group compared with the M-TURP group (79.5 vs 68.6 min; P = 0.032) and postoperative clot retention was more likely to be seen after M-TURP (P = 0.044). Similar efficacy findings were maintained throughout 36 months, but a significant difference in postoperative urethral stricture rates between groups was detected (6.6% in M-TURP vs 19.0% in TURis; P = 0.022). After stratifying patients according to prostate volume, there was no significant difference between the two treatment groups with regard to urethral stricture rates in patients with a prostate volume ≤ 70 mL (3.8% in M-TURP vs 3.8% in TURis), but in the TURis group there was a significantly higher urethral stricture rate compared with the M-TURP group in patients with a prostate volume >70 mL (20% in TURis vs 2.2% in M-TURP; P = 0.012). Furthermore, the mean operation time for TURis was significantly longer than for M-TURP for the subgroup of patients with a prostate volume > 70 mL (99.6 vs 77.2 min; P = 0.011), but not for the subgroup of patients with a prostate volume ≤ 70 mL. CONCLUSION: The TURis system seems to be as efficacious and safe as conventional M-TURP except that there was a higher incidence of urethral stricture in patients with larger preoperative prostate volumes.
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Próstata/cirugía , Resección Transuretral de la Próstata/efectos adversos , Resección Transuretral de la Próstata/métodos , Estrechez Uretral/etiología , Anciano , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Próstata/patología , Hiperplasia Prostática/cirugía , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/cirugíaRESUMEN
A 68-year-old woman, complained of an indolent lump about 60 × 70 mm in size in the left lower back. We conducted a computed tomography scan, which exhibited a hernia of Gerota'sfascia-commonly called superior lumbar hernia. In the right lateral position, the hernia contents were observed to attenuate, hence only closure of the hernial orifice was conducted by using Kugel patch, without removal of the hernia sack. Six months after the surgery, she has had no relapse of the hernia. Superior lumbar hernia, which occurs in an anatomically brittle region in the lower back, is a rare and potentially serious disease. The urologic surgeon should bear in mind this rarely seen entity.
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Hernia/patología , Herniorrafia/instrumentación , Herniorrafia/métodos , Región Lumbosacra/patología , Región Lumbosacra/cirugía , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Mallas Quirúrgicas , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To investigate the treatment outcomes of a single-session high-intensity focused ultrasound (HIFU) using the Sonablate(®) for patients with localized prostate cancer. METHODS: Biochemical failure was defined according to the Stuttgart definition [a rise of 1.2 ng/ml or more above the nadir prostate-specific antigen (PSA)] and the Phoenix definition (a rise of 2 ng/ml or more above the nadir PSA). Disease-free survival rate was defined using the Phoenix criteria and positive follow-up biopsy. RESULTS: A total of 171 patients were identified. Fifty-two (30.4 %) patients were identified to be with D'Amico low risk, 47 (27.5 %) with intermediate risk, and 72 (42.1 %) with high risk. In the median follow-up time of 43 months, there was 44 (25.7 %) and 36 (21.1 %) patients experienced biochemical failure for Stuttgart and Phoenix definition with mean (±SD) time to failure of 17.8 ± 2.1 and 19.4 ± 2.3 months, respectively. A total of 44 (25.7 %) patients were diagnosed as disease failure. Cox multivariate analysis revealed PSA nadir level (PSA cutoff = 0.2 ng/ml; HR = 9.472, 95 % CI 4.527-19.820, p < 0.001) and D'amico risk groups [HR = 3.132 (95 % CI 1.251-6.389), p = 0.033] were the predictor for failure in single-session HIFU. CONCLUSIONS: Single-session HIFU treatment using the Sonablate(®) seems to be potentially curative approach. When treated carefully with neoadjuvant hormonal therapy or preoperative transurethral resection of the prostate, higher-risk disease might be able to choose this minimally invasive procedure as primary therapy.
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Neoplasias de la Próstata/cirugía , Ultrasonido Enfocado Transrectal de Alta Intensidad , Anciano , Humanos , Masculino , Resultado del Tratamiento , Ultrasonido Enfocado Transrectal de Alta Intensidad/métodosRESUMEN
OBJECTIVE: To examine the association between the body mass index (BMI) and the risk of survival, and to evaluate whether tumor characteristics differ by BMI in patients with upper tract urothelial carcinoma (UTUC) managed by surgery. METHODS: A clinical series on 876 patients with localized UTUC following nephroureterectomy with a bladder cuff, with data from Osaka Medical College registry (discovery cohort) and the Nagoya group (validation cohort) was examined. In addition to analyzing the overall survival and cancer-specific survival (CSS), the survival impact adjusted by pathological variables was also assessed by the BMI group. RESULTS: The percentage of high risk features including positive lymphovascular invasion was doubled in the discovery cohort compared to the validation cohort. The group of BMI ≥ 25 kg/m2 was associated with improved CSS in the discovery cohort (p = 0.004), and this tendency was verified in the validation cohort (p = 0.006). Nonproportional hazards existed for the group of BMI ≥ 25 kg/m2 and the BMI 18.5-25 kg/m2 relative to the group of BMI < 18.5 kg/m2, with a change in the CSS hazard. In multivariable Cox models, the BMI group had a superior predictive value compared with other pre-clinical factors both in the discovery cohort (HR = 3.85, p = 0.01; 95%CI: 0.09-0.73) and the validation cohort (HR = 1.56, p = 0.01; 95%CI: 0.45-0.91). When adjusted by lymphovascular invasion, the concordance of the model proposed by the discovery cohort (0.52) challenged in the validation cohort was 0.59. CONCLUSIONS: We found a clinically relevant signature for high risk patients with BMI grouping. Further research is necessary on whether tailoring recommendations for weight and nutrition management to tumor characteristics will improve outcomes.
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Background: There is emerging evidence that radiographic progression-free survival (rPFS) is highly correlated with overall survival (OS), potentially serving as an indicator of treatment outcome for castration-resistant prostate cancer (CRPC). The objective of this study is to assess rPFS and prostate specific antigen (PSA) response in sequential treatment using androgen signaling inhibitors (ASIs) including abiraterone and enzalutamide in newly diagnosed CRPC. Methods: Propensity score matching was performed to reduce bias by confounding factors between first-line ASIs. The primary endpoints of the study included rPFS, time to PSA progression (TTPP), and PSA response. Results: A paired-matched group of 184 patients were identified. From the initiation of first-line ASIs, there was no significant difference in rPFS, TTPP, and PSA response between treatment arms. From the initiation of second-line ASIs, enzalutamide following abiraterone consistently exhibited longer rPFS (median: 7 and 15 months, p = 0.04), TTPP, and better PSA response compared to the reverse, whereas OS did not reach significance (median: 14 and 23 months, p = 0.35). Conclusion: Although the effect of ASIs as the first line was similar, the extent of cross-resistance might differ towards less resistance in enzalutamide following abiraterone than the reverse.
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This study aimed to assess the clinical value of C-reactive protein-albumin ratio (CAR) at the initiation of first-line treatment for castration-resistant prostate cancer (CRPC). We identified 221 CRPC patients treated with either androgen-signaling inhibitors (ASIs: abiraterone and enzalutamide) or docetaxel as the first-line treatment. The value of CAR was evaluated at the initiation of first-line treatment. The optimal cutoff value of CAR for the prediction of lethality was defined by the receiver operating characteristic curve and the Youden Index. The primary endpoints of the study included overall survival (OS) and cancer-specific survival (CSS). The median age was 74 years. The optimal cutoff value of CAR in newly diagnosed CRPC patients was 0.5 (CAR > 0.5: n = 77 and CAR ≤ 0.5: n = 144). The 3-year OS and CSS rate in patients with CAR > 0.5 were significantly lower than those with CAR ≤ 0.5 (OS: 30.9% vs 55.5%, p < 0.001) (CSS: 42.5% vs 65.4%, p < 0.001). A multivariate analysis consistently demonstrated that CAR was an independent predictor for both OS and CSS. When stratified by the first-line treatments, patients with CAR > 0.5 has significantly shorter CSS than those with CAR ≤ 0.5 in abiraterone (median of 23 vs 49 months, p < 0.001) and enzalutamide (median of 23 vs 41 months, p = 0.0016), whereas no difference was observed in patients treated with docetaxel as the first-line treatment (median of 34 and 37 months, p = 0.7708). Despite the limited cohort size and retrospective design, increased CAR seemed to serve as an independent predictor of OS and CSS for patients newly diagnosed with CRPC.
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Albúminas/análisis , Antineoplásicos/uso terapéutico , Proteína C-Reactiva/análisis , Neoplasias de la Próstata Resistentes a la Castración , Anciano , Antagonistas de Andrógenos/uso terapéutico , Androstenos/uso terapéutico , Benzamidas , Docetaxel/uso terapéutico , Humanos , Masculino , Nitrilos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. METHODS: To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB patients, were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. RESULTS: Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0.001). CONCLUSIONS: The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB.
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Biomarcadores de Tumor/genética , Carcinoma/genética , MicroARNs/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Humanos , Masculino , MicroARNs/metabolismo , Análisis de Supervivencia , Transcriptoma , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
BACKGROUND: No standard chemotherapy regimen for advanced urothelial cancer has been established, except for cisplatin-based regimens. We report the case of a patient with double primary cancer, urothelial carcinoma of the upper urinary tract and colorectal cancer, who underwent oxaliplatin-based chemotherapies. CASE PRESENTATION: A 56-year-old Japanese man presented to our hospital with the diagnosis of a left renal pelvic tumor and rectal cancer. Several examinations including ureteroscopic biopsy and computed tomography-guided biopsy were performed; however, the diagnosis of renal pelvic cancer could not be made. Because the rectal cancer had been growing during the course of examination, he underwent five cycles of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan. The volumes of both the rectal cancer and renal pelvic tumor drastically decreased. He then underwent pelvic evisceration with colostomy and ureterocutaneostomy. The histological diagnosis of the renal pelvic tumor was urothelial carcinoma. He is free of disease at 12 months after the treatment. CONCLUSIONS: To the best of our knowledge, this is the first report describing a remarkable response to fluorouracil, leucovorin, oxaliplatin, and irinotecan therapy for renal pelvic cancer. We suggest fluorouracil, leucovorin, oxaliplatin, and irinotecan is an effective therapy for patients with advanced urothelial cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/tratamiento farmacológico , Pelvis Renal/patología , Terapia Neoadyuvante , Neoplasias Urológicas/tratamiento farmacológico , Urotelio/patología , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carcinoma de Células Renales/patología , Colostomía/métodos , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Inducción de Remisión , Resultado del Tratamiento , Ureterostomía/métodosRESUMEN
BACKGROUND: We vigorously reviewed patients' operation record who had adhesion of the Denonvilliers' fascia and found out most of these patients had prostatic bleeding after prostatic gland biopsies. We examined the magnitude of prostatic bleeding and frequency after biopsies and the relationship with oncological outcomes. MATERIALS AND METHODS: A total of 285 patients were selected for the final analyses. Inclusion criteria were as follows: receiving MRI three weeks after biopsiesand laparoscopic radical prostatectomy within 300 days after biopsy. We divided the patients into two groups with (group A) or without (group B) prostatic bleeding. We examined the magnitude of prostatic bleeding after biopsies and the relationship with operation time (OT), positive surgical margin (PSM), biochemical recurrence (BCR) and other factors. Furthermore, we created a logistic-regression model to derive a propensity score for prostatic bleeding after biopsies, which included all patient and hospital characteristics as well as selected interaction terms, and we examined the relationship with PSM and BCR. RESULTS: In all patients, the OT in the group B was shorter than the group A (p < 0.001). Prostatic bleeding was associated with PSM (p=0.000) and BCR (p=0.036). In this propensity-matched cohort, 11 of 116 patients in the group B had PSM as compared with 36 of 116 patients from group A (match-adjusted odds ratio, 4.30; 95%CI confidence interval, 2.06 to 8.96; P=0.000). In addition, eight of 116 patients in group B encountered BCR, as compared with 18 of 116 patients in group A (match-adjusted odds ratio, 2.48; 95%CI, 1.03 to 5.96; P=0.042). Kaplan-Meier analysis in the propensity matching cohort showed a significant biochemical recurrence-free survival advantage for being free of prostate bleeding after biopsies. CONCLUSIONS: Our findings in the present cohort should help equip surgeons to pay attention to careful excision especially for those who experienced deferred prostatic bleeding.
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Biopsia/efectos adversos , Laparoscopía/efectos adversos , Recurrencia Local de Neoplasia/diagnóstico , Hemorragia Posoperatoria/etiología , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa.
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Tejido Adiposo/citología , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Apoptosis/genética , Western Blotting , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Exosomas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Células del Estroma/citología , Proteína bcl-X/metabolismoRESUMEN
BACKGROUND: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology, recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, still ranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity are needed. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamic diagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or 2nd-transurethelial resection (TUR). MATERIALS AND METHODS: The present study was performed from October 2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white light and blue light followed by the resection of tumors identified. Resections were performed from bladder mucosa areas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by random biopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivity and specificity. RESULTS: A total of 147 specimens extracted from 25 patients were included in the analysis. Some 45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55 specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was 52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5% (19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases. CONCLUSIONS: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.
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Carcinoma in Situ/diagnóstico , Luz , Neoplasias de los Músculos/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Fármacos Fotosensibilizantes , Neoplasias de la Vejiga Urinaria/diagnóstico , Anciano , Anciano de 80 o más Años , Vacuna BCG/uso terapéutico , Carcinoma in Situ/terapia , Terapia Combinada , Cistectomía/métodos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de los Músculos/terapia , Invasividad Neoplásica , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, ß-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model.
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Administración Intravesical , MicroARNs/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Animales , Apoptosis , Línea Celular , Línea Celular Tumoral , Movimiento Celular , Femenino , Humanos , Ratones , Ratones Desnudos , MicroARNs/administración & dosificación , Trasplante de Neoplasias , Transducción de Señal , Transfección , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom surgery after neoadjuvant chemotherapy would otherwise be necessary, and also facilitate potential cure in patients for whom, otherwise, merely palliative treatment would seem the only option.
Asunto(s)
Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada/métodos , Desoxicitidina/análogos & derivados , Metástasis Linfática/radioterapia , Recurrencia Local de Neoplasia/terapia , Neoplasias de la Vejiga Urinaria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Oclusión con Balón , Cisplatino/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Dosificación Radioterapéutica , Diálisis Renal/métodos , Neoplasias de la Vejiga Urinaria/patología , GemcitabinaRESUMEN
OBJECTIVE: To assess whether bipolar transurethral resection of the prostate using the TURis (Olympus, Tokyo, Japan) system demonstrates comparable efficacy and safety reporting 36 months of follow-up findings. METHODS: The trial was registered at University hospital Medical Information Network Clinical Trials Registry in Japan (trial number UMIN 000010801). Patients were randomly selected to undergo transurethral resection of the prostate using either the TURis or the conventional monopolar technique. Primary end points were safety according to operation time, decline of sodium and hemoglobin levels, clot retention, and catheterization time. Secondary end points were efficacy findings for patients after 36 months of follow-up. RESULTS: A total of 136 patients were enrolled. Mean operation times were significantly prolonged in the TURis group (68.4 and 79.5 minutes for monopolar and TURis groups, respectively; P = .048). No significant differences in the decline of hemoglobin, hematocrit, and perioperative transfusion rates between groups were seen, whereas clot retention (grade 2) after the treatment seemed to occur more often in the monopolar group (7 of 62 [12.3%] in monopolar group vs 1 of 63 [1/8%] in TURis group; P = .061). No case presented symptomatic transurethral resection syndrome in either groups. CONCLUSION: Continued efficacy at 36 months after the treatment could be confirmed for the first time in TURis system, which also seems to be preferable as they produced more clinically favorable outcomes. Nevertheless, the TURis system required significantly more resection time, which might not entirely be a panacea for the treatment of benign prostatic obstruction, especially for patients having larger prostatic volumes.