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Purpose: Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC. Patients and Methods: A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil*platelet/lymphocyte). Use of Kaplan-Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes. Results: Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168-7.078], 5.623 [2.679-11.801], 3.377 [2.138-5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis. Conclusion: The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.
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The present study aimed to evaluate the influence of pre-treatment neutrophil-to-lymphocyte ratio (NLR) on bladder recurrence in patients with impaired renal function following radical nephrouretectomy (RNU) to treat pure upper tract urothelial carcinoma (UTUC). Retrospective data of 362 patients with pure UTUC who underwent RNU between 2008 and 2019 were analyzed. Kaplan-Meier analyses were performed to evaluate the association of preoperative NLR and estimation of the glomerular filtration rate (eGFR) with intravesical recurrence-free survival (IVRF). Furthermore, multivariate analyses were conducted to determine independent factors for predicting IVRF. In the retrospective cohort study of 362 patients, 103 patients (28%) had intravesical recurrence in a median follow-up of 50.1 months; among those, 85 (83%) developed bladder recurrence within two years after RNU. The Kaplan-Meier analysis indicated that patients exhibiting lower eGFR and higher NLR showed significantly poor IVRF rates (P=0.044). The simultaneous presence of eGFR <45 and NLR >3.8 was an independent factor for the shorter IVRF time in multivariate analysis with Cox's proportional hazards model. Most intravesical recurrences occurred within two years after RNU, particularly in pre-existing poor eGFR patients with preoperative high NLR. Moreover, pre-existing moderate to severe CKD synchronous with pre-operative NLR >3.8 was demonstrated as an independent factor for subsequent bladder recurrence in patients with pure UTUC following RNU. Therefore, such high-risk patients ought to be provided with close bladder monitoring during the follow-up.
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BACKGROUND: To explore the dynamic changes and effects of radical cystectomy on quality of life in muscle-invasive bladder cancer survivors. METHODS: Patients with muscle-invasive bladder cancer were randomly recruited in this study. We used the World Health Organization Quality of Life-Brief questionnaire to assess consecutive patients' quality of life. We applied kernel smoothing to illustrate the dynamic changes of the domain and item scores after treatment. Mixed-effects models were constructed to determine the effects of radical cystectomy on the scores of each item and domain of the World Health Organization Quality of Life-Brief questionnaire after controlling demographic and clinical factors. RESULTS: We collected 397 repeated measurements of the World Health Organization Quality of Life-Brief questionnaire from 109 muscle-invasive bladder cancer patients. Forty-two of them received radical cystectomy. Patients with radical cystectomy exhibited higher levels of education, less co-morbidities (i.e., diabetes and heart diseases), but were associated with more malignancies. Construction of mixed-effects models showed patients with radical cystectomy and those with bladder sparing had similar scores in the three main domains and their items, except that of certain items of physical domain. By applying kernel smoothing method, we found that stage III-IV patients consistently showed higher scores on sleep and rest after radical cystectomy for more than 5 years. In contrast, stage II patients receiving radical cystectomy did not show a higher score on the "sleep and rest" item compared with those with bladder sparing operation. CONCLUSIONS: Radical cystectomy may result in sound sleep and rest, especially in those with stage III-IV bladder cancer.
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Supervivientes de Cáncer , Neoplasias de la Vejiga Urinaria , Cistectomía/métodos , Humanos , Músculos/patología , Invasividad Neoplásica/patología , Calidad de Vida , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: The prognosis of patients undergoing 2-sided radical nephroureterectomies (RNUs) with a residual bladder due to bilateral upper tract urothelial carcinoma (UTUC) is poorly understood. This study was aimed toward surveying the oncology outcomes and prognostic factors that may help in shared decision-making related to bladder preservation in patients preparing to receive 2-sided RNUs. METHODS: Patients with synchronous or metachronous bilateral UTUC who received bilateral RNUs with a residual bladder in our hospital were retrospectively reviewed. Clinical and pathological data were analyzed for potential variables affecting the oncology outcomes. RESULTS: A total of 50 patients were included. The average age at completion of the 2-sided RNU was 62.7 ± 12.4 years, with a mean follow-up of 88.4 ± 59.3 months after the 2-sided RNUs. The medium overall survival was 13.4 ± 1.8 years. Twenty-six patients (52%) had cancer recurrence in the residual bladder, but only 2 (8%) of the recurrences were muscle invasive. The highest UTUC stage was the only predictive factor for cancer-specific survival (CSS) rather than intravesical recurrence. The 5 year CSS rates in patients with the highest UTUC stage ⦠pT2 and ⧠pT3 were 90% and 51%, respectively (p = 0.007). CONCLUSIONS: Risk of cancer recurrence in the residual bladder is high, but does not affect survival outcomes. The highest UTUC stage plays a significant role in cancer-specific survival. With a careful patient surveillance, bladder preservation may be reasonable in patients with bilateral UTUC preparing for 2-sided RNUs.
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Carcinoma de Células Transicionales/cirugía , Neoplasias Renales/cirugía , Nefroureterectomía/métodos , Tratamientos Conservadores del Órgano , Neoplasias Ureterales/cirugía , Anciano , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Tratamientos Conservadores del Órgano/efectos adversos , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/patología , Vejiga UrinariaRESUMEN
OBJECTIVES: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. RESULTS: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). CONCLUSIONS: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.
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BACKGROUND: Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC). METHODS: Hospital-based (n = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T TP53 mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases. RESULTS: In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in TP53 were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC. CONCLUSIONS: Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan. IMPACT: This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.
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Ácidos Aristolóquicos/toxicidad , Arsénico/toxicidad , Carcinoma de Células Transicionales/inducido químicamente , Neoplasias de la Vejiga Urinaria/inducido químicamente , Anciano , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Estudios de Casos y Controles , Aductos de ADN , Femenino , Humanos , Incidencia , Masculino , Clasificación del Tumor , Taiwán/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: The purpose of this study was to evaluate the prognostic values of pathological tumor size and preoperative blood-based inflammation biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: From 2007 to 2017, retrospective data of 449 patients with UTUC who underwent radical nephroureterectomy were assessed. Use of Kaplan-Meier and univariable/multivariable analyses evaluated the effect of preoperative blood-based inflammation biomarkers on overall (OS), cancer-specific (CSS), and progression-free survival (PFS) in pathological tumor sizes > and ≤3 cm. RESULTS: Kaplan-Meier analyses showed that high-level NLR, PLR, or MLR had significantly shorter OS, CSS, and PFS for tumor sizes >3 cm (all P < .05), but not for ≤3 cm. For UTUCs with tumor sizes >3 cm, multivariable analyses showed simultaneously high-level PLR and MLR to be independent predicators of poor OS, CSS, and PFS (all P < .05). Moreover, receiver operating characteristic (ROC) analyses revealed that the predictive accuracy of the combination of PLR and MLR for OS, CSS, and PFS with the area under the ROC curve of 0.836, 0.871, and 0.806, respectively, in tumor sizes >3 cm (all P < .001). CONCLUSIONS: Our study demonstrated that a high-level PLR and MLR can serve as an independent predicator of worse outcomes in UTUCs with tumor sizes >3 cm. This combination can clinically help enhance the prognostic discrimination of UTUCs with tumor sizes >3 cm and further may guide physicians in selecting patients for postoperatively systemic chemotherapy.
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Biomarcadores de Tumor/análisis , Plaquetas/patología , Linfocitos/patología , Monocitos/patología , Nefroureterectomía/mortalidad , Neutrófilos/patología , Neoplasias Urológicas/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Curva ROC , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Urológicas/cirugíaRESUMEN
OBJECTIVES: To determine the optimal surgical timing in high-risk patients with Fournier's gangrene by the Simplified Fournier's Gangrene Severity Index. METHODS: From 1989 to 2018, 118 male patients diagnosed with Fournier's gangrene with complete medical records were retrospectively reviewed. Patients' demographics, laboratory parameters at initial diagnosis, Fournier's Gangrene Severity Index and Simplified Fournier's Gangrene Severity Index, and the time interval from emergency room arrival to surgical intervention were collected. The Fournier's gangrene patients were categorized into low-risk (Simplified Fournier's Gangrene Severity Index ≤2) and high-risk groups (Simplified Fournier's Gangrene Severity Index >2). Differences between the variables within the two groups were analyzed. The optimal surgical timing was analyzed with the receiver operating characteristic curve in high-risk Fournier's gangrene patients. RESULTS: The overall mortality of 118 Fournier's gangrene patients was 14.4%. After risk stratification with the Simplified Fournier's Gangrene Severity Index scoring system, the mortality of low-risk and high-risk Fournier's gangrene patients was 1.3% and 41.0%, respectively. In the high-risk group, the time interval from emergency room arrival to surgical intervention was the only variable with a significant difference between survivors and non-survivors (P = 0.039). The optimal surgical timing was determined at 14.35 h, which allowed the highest sensitivity (0.688) and specificity (0.762) to affect mortality. The mortality was significantly lower in high-risk Fournier's gangrene patients with early surgical intervention compared with late intervention (23.8% vs 68.8%, P = 0.007). CONCLUSIONS: The Simplified Fournier's Gangrene Severity Index is a quick and reliable screening tool for first-line physicians to identify high-risk patients with Fournier's gangrene (Simplified Fournier's Gangrene Severity Index >2) who have poor survival outcomes. We recommended early surgical intervention within 14.35 h to maximize the survival of high-risk Fournier's gangrene patients.
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Gangrena de Fournier/mortalidad , Gangrena de Fournier/cirugía , Enfermedades de los Genitales Masculinos/mortalidad , Enfermedades de los Genitales Masculinos/cirugía , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Gangrena de Fournier/diagnóstico , Enfermedades de los Genitales Masculinos/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Taiwán/epidemiología , Factores de TiempoRESUMEN
Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (pâ¯<â¯0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (pâ¯<â¯0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.
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Disruptores Endocrinos/orina , Contaminantes Ambientales/orina , Hormonas Esteroides Gonadales/sangre , Estrés Oxidativo , Ácidos Ftálicos/orina , Hiperplasia Prostática/sangre , Hiperplasia Prostática/orina , 8-Hidroxi-2'-Desoxicoguanosina , Andrógenos/sangre , Biomarcadores/sangre , Biomarcadores/orina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Estrógenos/sangre , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/sangre , TaiwánRESUMEN
BACKGROUND: This study aimed to evaluate the clinical significance of the preoperative systemic immune-inflammation index (SII) combined with the monocyte-lymphocyte ratio (MLR) for patients with upper-tract urothelial carcinoma (UTUC). METHODS: The clinical data of 424 patients who underwent radical nephroureterectomy from January 2007 to June 2017 were analyzed. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate associations of preoperative systemic immune-inflammatory biomarkers with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Moreover, logistic regression preoperative models were applied to predict advanced disease. RESULTS: Multivariate analyses showed that SII significantly influenced both OS and CSS (both P < 0.05), whereas MLR exhibited the most significant association with OS (P = 0.008). In particular, simultaneously high SII and MLR values correlated significantly with OS, CSS, and PFS (all P < 0.05). Logistic regression preoperative models showed that the combination of high SII and high MLR was a significant predictor of non-organ-confined UTUC (P = 0.001). Furthermore, Kaplan-Meier analysis showed that the combination of high SII and high MLR was significantly linked with poor OS, CSS, and PFS in non-organ-confined UTUC (all P < 0.05). CONCLUSION: The study reviewed serum inflammation biomarkers in a subset of patients with UTUC and demonstrated the ability of combined SII and MLR to predict disease progression and survival. Patients with both high SII and high MLR were significantly more likely to have non-organ-confined disease and poor survival outcomes.
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Biomarcadores de Tumor/análisis , Mediadores de Inflamación/metabolismo , Linfocitos/patología , Monocitos/patología , Nefroureterectomía , Neoplasias Urológicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Urológicas/inmunología , Neoplasias Urológicas/cirugíaRESUMEN
BACKGROUND: To explore the feasibility and long-term outcomes of renal preservation in a retrospective cohort of patients with ureteral urothelial carcinoma undergoing total ureterectomy with ileal-ureteral substitution. METHODS: A retrospective review of the data from patients treated with total ureterectomy with ileal-ureteral substitution from 1988 to 2016 was performed. The pre-operative oncological status, long-term oncological outcome, long-term renal functional outcome, early and late complications were analyzed. RESULTS: A total of eight patients with a median age of 70 years were included. The median follow-up time was 109 months. Six patients had multi-focal tumor involvement over the target ureter, and six patients had bilateral upper tract involvement. Only one patient encountered the upper-tract recurrence. The 2 and 5-year cancer-specific survival rates were 87.5 and 75.0%, respectively. The renal function was well-preserved in most patients, with only one patient needed life-long postoperative hemodialysis. Five patients experienced early complications and four patients experienced late complications. No perioperative mortality happened. CONCLUSIONS: A total ureterectomy with an ileal-ureteral substitution is feasible for treating ureteral urothelial carcinoma when a renal-sparing procedure is indicated. It provides good long-term oncological outcomes over the upper tract, and it also preserves the renal function.
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Íleon/trasplante , Uréter/cirugía , Neoplasias Ureterales/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias Ureterales/mortalidad , Neoplasias de la Vejiga Urinaria , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
PURPOSE: To survey long-term outcomes of dialysis patients with urothelial cancers who have undergone complete urinary tract exenteration (bilateral nephroureterectomy and cystectomy). METHODS: We retrospectively reviewed our patients with urinary tract urothelial cancer. Forty-two dialysis patients who underwent complete urinary tract exenteration were enrolled in our study. Seventeen patients had undergone one-stage complete urinary tract exenteration, and twenty-five patients had undergone multi-stage surgery. We reviewed the demographic, clinical, surgical, and pathological data to determine the clinical and pathologic variables that affected the survival between the two groups. RESULTS: Baseline demographics were comparable in both groups. There was no significant difference in age, American Society of Anesthesiologists class, Charlson index, or body mass index between the two groups. Furthermore, there was no statistically significant difference in estimated blood loss (1280 vs. 1440 ml) or total hospital stay (31 vs. 21 days). Simultaneous upper and lower tract tumors were noted in one-stage CUTE group In comparison with multi-stage surgery, one-stage surgery was associated with a higher complication rate (58.8 vs. 28%). Twenty-two patients were still alive at the end of the study, and 20 had died. The median survival period after confirmation of complete urinary tract exenteration status was 27.5 months. The overall survival was the same between the two groups. The Charlson comorbidity index was a mandatory indicator to predict long-term survival outcome. CONCLUSIONS: In dialysis patients with urothelial cancers who have undergone complete urinary tract exenteration, one-stage complete urinary tract exenteration had a high perioperative complication rate. The Charlson comorbidity index was a mandatory indicator to predict long-term survival outcome.
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Carcinoma de Células Transicionales/cirugía , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Secundarias/cirugía , Neoplasias Urológicas/cirugía , Adulto , Anciano , Comorbilidad , Cistectomía/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Prostatectomía/efectos adversos , Diálisis Renal , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Uréter/cirugíaRESUMEN
Cancer cells initially characterized as sensitive to chemotherapy may acquire resistance to chemotherapy and lead to tumor recurrence through the expansion of drug-resistant population. Acquisition of drug resistance to conventional chemotherapy is a major obstacle in the treatment of recurrent cancer. Here we investigated whether anticancer drugs induced Oct4 expression, thereby contributing to acquired drug resistance and tumor recurrence in bladder cancer. We identified a positive correlation of Oct4 expression with tumor recurrence in 122 clinical specimens of superficial high-grade (stages T1-2) bladder transitional cell carcinoma (TCC). Increased Oct4 levels in bladder tumors were associated with short recurrence-free intervals in the patients. Chemotherapy induced Oct4 expression in bladder cancer cells. Notably, treatment with cisplatin increased CD44-positive bladder cancer cells expressing Oct4, representing cancer stem-like cell subpopulation. Forced expression of Oct4 reduced, whereas knockdown of Oct4 enhanced, drug sensitivity in bladder cancer cells. Furthermore, tumor cells overexpressing Oct4 responded poorly to cisplatin in vivo. In regard to clinical relevance, inhibition of Oct4 by all-trans retinoic acid (ATRA) synergistically increased sensitivity to cisplatin in bladder cancer cells. Furthermore, the combination of cisplatin and ATRA was superior to cisplatin alone in suppressing tumor growth. Therefore, our results provide evidence that Oct4 increases drug resistance and implicate that inhibition of Oct4 may be a therapeutic strategy to circumvent drug resistance.
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Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Factor 3 de Transcripción de Unión a Octámeros/genética , Neoplasias de la Vejiga Urinaria/genética , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Técnicas de Silenciamiento del Gen , Humanos , Receptores de Hialuranos/metabolismo , Ratones , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hypoxia-inducible factor-1α (HIF-1α) can control a transcriptional factor forkhead box P3 (Foxp3) protein expression in T lymphocyte differentiation through proteasome-mediated degradation. In this study, we unveil a reverse regulatory mechanism contributing to bladder cancer progression; Foxp3 expression attenuates HIF-1α degradation. We first demonstrated that Foxp3 expression positively correlates with the metastatic potential in T24 cells and can increase the expression of HIF-1α-target genes, such as vascular endothelial growth factor (VEGF) and glucose transporter (GLUT). Foxp3 protein can bind with HIF-1α, particularly under hypoxia. In vivo ubiquination assay demonstrated that Foxp3 can decrease HIF-1α degradation in a dose-dependent manner. Knocking-down of Foxp3 expression blocks in vivo tumor growth in mice and prolongs mice's survival, which is associated with von Willebrand factor expression. Thirty-three of 145 (22.8 %) bladder tumors exhibit Foxp3 expression. Foxp3 expression is an independent predictor for disease progression in superficial bladder cancer patients (p = 0.032), associated with less number of intratumoral CD8+ lymphocyte. The metaanalysis from 2 published datasets showed Foxp3 expression is positively associated with GLUT-4,-9, and VEGF-A, B-, D expression. This reverse post-translational regulation of HIF-1α protein by Foxp3 provides a new potential target for developing new therapeutic strategy for bladder cancer.
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Biomarcadores de Tumor/metabolismo , Factores de Transcripción Forkhead/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular , Femenino , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Proteolisis , ARN Interferente Pequeño/genética , Análisis de Supervivencia , Ubiquitinación , Regulación hacia Arriba , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
Glycans of prostate-specific antigen (PSA) in prostate cancer were found to be different from that in benign disease. It is difficult to analyze heterogeneous PSA glycoforms in each individual specimen because of low protein abundance and the limitation of detection sensitivity. We developed a method for prostate cancer diagnosis based on PSA glycoforms. Specific glycoforms were screened in each clinical sample based on liquid chromatography-tandem mass spectrometry with ion accumulation. To look for potential biomarkers, normalized abundance of each glycoform in benign prostate hyperplasia (BPH) and in prostate cancer was evaluated. The PSA glycoform, Hex5HexNAc4NeuAc1dHex1, and monosialylated, sialylated, and unfucosylated glycoforms differed significantly between the prostate cancer and BPH samples. The detection sensitivity (87.5%) and specificity (60%) for prostate cancer identification are higher than those of the serum PSA marker. As low as 100 amol PSA could be detected with the ion accumulation method which has not been reported before. The improved detection specificity can help reduce unnecessary examinations.
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Glicopéptidos/aislamiento & purificación , Calicreínas/orina , Antígeno Prostático Específico/orina , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Anciano , Anciano de 80 o más Años , Cromatografía Liquida , Diagnóstico Diferencial , Glicosilación , Humanos , Iones/metabolismo , Calicreínas/sangre , Calicreínas/aislamiento & purificación , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/aislamiento & purificación , Sensibilidad y Especificidad , Espectrometría de Masas en TándemRESUMEN
OBJECTIVES: To validate the predictive value of Fournier's Gangrene Severity Index in patients with Fournier gangrene and to facilitate patient mortality risk-stratification by simplifying the Fournier's Gangrene Severity Index. METHODS: From January 1989 to December 2011, 85 male patients with clinically-documented Fournier's gangrene undergoing intensive treatment and with complete medical records were recruited. The demographic information and nine parameters of Fournier's Gangrene Severity Index were compared between survivors and non-survivors. The parameters that showed a significant difference between the two groups were selected to generate a simplified scoring index. RESULTS: Of the 85 patients recruited, 16 patients died of the disease with mortality rate of 18.8%. The Fournier's Gangrene Severity Index score at initial diagnosis was significantly higher in non-survivors than in survivors. Of the nine parameters of Fournier's Gangrene Severity Index, the scores of serum creatinine level, hematocrit level and serum potassium level were significantly different between the two groups. However, the mean body temperatures, heart rate, respiration rate, white blood cell count, serum sodium and bicarbonate levels were non-significantly different. Of the 12 patients with chronic kidney disease or end-stage renal disease, 10 died of severe sepsis. A simplified scoring index including parameters of creatinine, hematocrit and potassium was generated, which provided sensitivity and specificity of 87% and 77% in predicting patient mortality, respectively. The predictive values of this simplified Fournier's Gangrene Severity Index were shown to be non-inferior to Fournier's Gangrene Severity Index in our patients. CONCLUSIONS: The simplified Fournier's Gangrene Severity Index is easy to use at initial diagnosis, and offers a way to compare outcomes in different clinical populations.
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Gangrena de Fournier/mortalidad , Gangrena de Fournier/fisiopatología , Enfermedades de los Genitales Masculinos/mortalidad , Enfermedades de los Genitales Masculinos/fisiopatología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Gangrena de Fournier/diagnóstico , Enfermedades de los Genitales Masculinos/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/mortalidad , Insuficiencia Renal/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION AND OBJECTIVES: There is a need to improve prescreening determination of prostate cancer to better select patients who need biopsy. Such a strategy properly implemented, will decrease the number of negative biopsies for prostate cancer and in turn better balance the risks and morbidity for patients recommended for biopsy. The aim of study is to investigate Doppler spectral waveform parameters of neurovascular bundle (NVB) vessels and determine differences between benign and malignant pathologies. PATIENTS AND METHODS: We performed a prospective analysis involving 292 patients who received prostate biopsy for elevated prostate-specific antigen (PSA) values or abnormal digital rectal examination, as well as 174 patients with symptomatic benign prostatic hyperplasia. Doppler spectral waveform (DSW) parameters (peak-systolic velocity [PSV], end-diastolic velocity [EDV], and resistive index [RI]) were measured at bilateral NVB vessels through Doppler transrectal ultrasound at the right lateral decubitus position, compared, and analyzed among patients with benign versus malignant histology for each side. RESULTS: Overall, both PSV and EDV at malignant sides were significantly higher than those at benign sides, as well as lower RI (all p-values <0.05, unpaired t-test). In subgroup analysis with 93 patients of serum PSA between 10 and 20 ng/mL and 56 patients with one-side malignancy, higher EDV and lower RI were significantly associated with malignancies (all p<0.05). The values of PSV and EDV rather than RI might be influenced by the patients' position and RI by the prostate volume. CONCLUSIONS: In this study, DSW parameters (mainly EDV and RI) at NVB vessels were significantly associated with prostate cancer, particularly in patients with serum PSA of 10-20 ng/mL. It should be in caution that the patients' position and prostate volume may influence the Doppler signal as demonstrated in the current study. These findings can provide more diagnostic information before prostate biopsy.
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Biopsia/métodos , Neovascularización Patológica/diagnóstico por imagen , Próstata/irrigación sanguínea , Neoplasias de la Próstata/diagnóstico , Ultrasonografía Doppler/métodos , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/irrigación sanguínea , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To determine the impact of earlier ureteral ligation (EUL) during hand-assisted retroperitoneoscopic nephroureterectomy (HARN) for primary renal pelvis urothelial cancer. METHODS: We retrospectively reviewed 240 patients with upper urinary tract urothelial cancer who underwent HARN. Only patients with primary renal pelvis urothelial cancer and complete follow-up with a minimum of 1 year after HARN were enrolled into our study. We defined EUL as ligating the ureter prior to pneumoretroperitoneum and mobilizing the kidney during the surgery. Of these 61 patients, 31 (who composed the study group) underwent EUL, while 30 serving as controls were without ureteral ligation during the surgery. We analyzed intravesical recurrence utilizing log rank testing to assess the significance between the two groups. RESULTS: Clinical parameters were similar between the two groups. The median follow-up after HARN was 39.7 months (range 12-96). There was no significant difference in the rate of intravesical recurrence and cancer-specific survival. However, patients without ligation of the ureter had shorter time to first bladder tumor recurrence (11.7 ± 9.1 months vs. 26.4 ± 19.1 months, p = 0.03). CONCLUSION: EUL during HARN for primary renal urothelial cancer did not affect intravesical recurrence rate or cancer-specific survival.
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Carcinoma/cirugía , Laparoscópía Mano-Asistida , Neoplasias Renales/cirugía , Pelvis Renal/cirugía , Recurrencia Local de Neoplasia , Nefrectomía , Uréter/cirugía , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Supervivencia sin Enfermedad , Laparoscópía Mano-Asistida/efectos adversos , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Pelvis Renal/patología , Ligadura , Masculino , Persona de Mediana Edad , Siembra Neoplásica , Nefrectomía/efectos adversos , Espacio Retroperitoneal/cirugía , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Post-biopsy infection is one of the major concerns of urologists and patients for prostate biopsy. Many efforts have been made to reduce the infection rate. We conducted a study at a single institution with the goal of describing the bacteriology and incidence trends of febrile infections following trans-rectal ultrasound (TRUS)-guided biopsy of the prostate. MATERIALS AND METHODS: From January 1998 to December 2002 (Period 1 of the study), January 2003 to August 2005 (Period 2), September 2005 to October 2007 (Period 3), and November 2007 to December 2009 (Period 4), 1,406 patients underwent prostate biopsy at our hospital. All biopsies were conducted under TRUS guidance without preparation by enemas. Several steps were taken to reduce infectious complications following biopsy, including a shift to levofloxacin prophylaxis starting from Period 3 of our study and thorough instructions in post-biopsy self-care starting from the beginning of Period 4. The incidence and bacteriology of urinary tract infection (UTI) following the prostate biopsies were reviewed from chart records. RESULTS: Twenty-eight of 514 (5.4%), 13 of 276 (4.7%) nine of 274 (3.2%), and three of 342 (0.9%) patients had post-biopsy febrile infections during the four periods of the study, respectively. Fifteen of 28 (53.5%), four of 13 (30.8%), five of nine (55.6%), and zero of three patients, respectively, had positive cultures of blood, urine, or both during the four study periods. Escherichia coli was the pathogen isolated most commonly and ampicillin- and fluoroquinolone-resistant strains of this organism were identified at a high frequency. The times to onset of fever after biopsy in the four study periods were 1.5±1.3 d, 3.7±2.7 d, 2.2±1.6 d, and 2.5±0.9 d, respectively. CONCLUSIONS: Ampicillin- and fluoroquinolone-resistant strains of E. coli were the uropathogenic bacteria identified most commonly after prostate biopsy at our hospital. The incidence of UTI following prostate biopsy can be reduced by explaining instructions for medication and self-care thoroughly to patients undergoing such biopsy.
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Biopsia/efectos adversos , Fiebre/microbiología , Próstata/cirugía , Infecciones Urinarias/etiología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Taiwán/epidemiología , Ultrasonografía Intervencional , Infecciones Urinarias/diagnóstico por imagen , Infecciones Urinarias/epidemiologíaRESUMEN
OBJECTIVE: To test the feasibility of partial nephrectomy using needle arrays under alternating current (AC) electromagnetic field without renal artery clamping. METHODS: We performed an experimental study for partial nephrectomy without renal artery clamping in a porcine model, comparing a new thermal surgery system consisting of an AC electromagnetic field generator and stainless steel needle arrays (using 10 pigs) vs an ultrasonic Harmonic Scalpel (on 8 pigs). Two cm of the upper pole of the kidneys were resected, and then the feasibility, operation time, blood loss, biochemical parameters, pathology, and complications were observed for 14 days. RESULTS: There was no difference by weight in the mean percentage of kidney removed between the 2 groups (8.1 ± 3.4% vs 12.7 ± 5.5%). The estimated blood loss for the partial nephrectomy with electromagnetic thermal surgery system was significantly less compared to the ultrasonic Harmonic Scalpel (53.0 ± 73.0 vs 188.8 ± 49.3 mL). Transection time was shorter with the electromagnetic thermal surgery system (10 vs 12 minutes). Bleeding from the cut surface after partial nephrectomy was noted in 2 pigs (electromagnetic surgery group) and 8 pigs (control group); all the bleeding was controlled with additional monopolar electrocoagulation and sutures. No urinoma was identified in either group when a second laparotomy was performed 2 weeks later. CONCLUSION: Our study of a partial nephrectomy in a porcine model demonstrates that the heat generated by the electromagnetic thermal surgery system is sufficient to coagulate renal parenchyma and to seal off the blood vessels without pedicle clamping.