RESUMEN
BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.
Asunto(s)
Humanos , Carcinoma de Células Renales , Estudios de Cohortes , Supervivencia sin Enfermedad , Epigenómica , Estudios de Seguimiento , Riñón , Metilación , Análisis Multivariante , Metástasis de la Neoplasia , Fenotipo , Dedos de ZincRESUMEN
BACKGROUND: To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). METHODS: We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I–II and stage III. Kidney function, and survival outcomes were compared between groups. RESULTS: We included 1,756 patients with CKD I–II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I–II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I–II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122–0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086–1.172; P = 0.117). CONCLUSION: PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.
Asunto(s)
Humanos , Carcinoma de Células Renales , Riñón , Métodos , Nefrectomía , Insuficiencia Renal , Insuficiencia Renal Crónica , Tasa de SupervivenciaRESUMEN
BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212–7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079–16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.
Asunto(s)
Humanos , Ciclo Celular , Replicación del ADN , Expresión Génica , Modelos Logísticos , Ganglios Linfáticos , Clasificación del Tumor , Metástasis de la Neoplasia , Anafilaxis Cutánea Pasiva , Próstata , Antígeno Prostático Específico , Hiperplasia Prostática , Neoplasias de la Próstata , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN MensajeroRESUMEN
PURPOSE: The aim of this study is to investigate the criteria of biochemical recurrence (BCR) and follow-up periods and methods with and without blood and imaging test of urologic oncology before established guidelines of prostate cancer in Korea. MATERIALS AND METHODS: In December 2015, we sent the questionnaire to urologic oncologist in academic hospital and received the answer from 108 urologic oncologist (50%). Also, we analyzed the data of 1,141 patients underwent radical prostatectomy in 2005 from Korean Medical Insurance. RESULTS: In follow-up, 72 physicians (66.7%) performed blood test every 3 months, 51 physicians (47.2%) performed imaging study in case of BCR. Bone scan was the most common imaging study in the follow-up (74 physicians, 68.5%). But, bone scan was only performed in case of BCR (43 physicians, 39.8%). The criteria of BCR was PSA 0.2 ng/mL (75 physician, 69.4%), 76 physicians (70.4%) was performed different follow-up according to risk of patients. In Korean Medical Insurance data analysis, PSA were performed average 2 times every year and magnetic resonance imaging, computed tomography, Bone scan were performed average 0.1, 0.2, 0.1 times every year, respectively. CONCLUSIONS: The criteria of BCR and the follow-up of prostate cancer patients in Korea were similar Korean prostate cancer guidelines. Blood and imaging test might be increased compared to 10 years ago, it is necessary to compare the Korean Medical Insurance data between 10 years ago and present.
Asunto(s)
Humanos , Diagnóstico , Estudios de Seguimiento , Pruebas Hematológicas , Seguro , Corea (Geográfico) , Imagen por Resonancia Magnética , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Recurrencia , Estadística como AsuntoRESUMEN
The aim of the present multi-institutional study was to assess the influence of the American Society of Anesthesiologists Physical Status (ASA-PS) classification on adjuvant chemotherapy eligibility and survival in a multi-institutional cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed data from 416 patients who underwent RNU for UTUC at four Korean institutions between 2001 and 2013. The ASA-PS classification was obtained from the anesthesia chart. Locally advanced UTUC was defined as ≥ pT3 and/or pN1 disease. The influence of ASA-PS score on survival was evaluated by Kaplan-Meier analyses and a multivariate Cox regression model. Patients with a higher ASA-PS class were less likely to be eligible for adjuvant chemotherapy in locally advanced UTUC (P = 0.016). Kaplan-Meier estimates showed that the high-risk ASA-PS group has a poorer overallsurvival (OS) and cancer-specific survival (CSS) compared to low risk ASA-PS groups in both the total and locally advanced UTUC cohorts. Based on multivariate Cox regression analysis, the high-risk ASA-PS category was an independent predictor for overall mortality (OM) (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.017–3.619; P = 0.044) and cancer-specific mortality (CSM) (HR, 2.120; 95% CI, 1.023–4.394; P = 0.043). In conclusion, high-risk ASA-PS score was independently associated with a lower survival rate in patients with UTUC after RNU. However, the influence of ASA-PS classification on survival was limited to locally advanced UTUC. The lower eligibility of patients in the high-risk ASA category for adjuvant chemotherapy may contribute to the lower survival rate in this group.
Asunto(s)
Humanos , Anestesia , Quimioterapia Adyuvante , Clasificación , Estudios de Cohortes , Mortalidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996–2000, n = 897), group 2 (2001–2005, n = 1,018), group 3 (2006–2010, n = 1,043), and group 4 (2011–2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period.
Asunto(s)
Humanos , Índice de Masa Corporal , Calcio , Diabetes Mellitus , Diagnóstico , Hipertensión , Incidencia , Corea (Geográfico) , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Sodio , Ácido Úrico , UrolitiasisRESUMEN
PURPOSE: To determine the malignant potential in clinically localised small renal cell carcinoma (RCC) (≤4cm) in patients using postoperative pathologic outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of 2,085 patients in 7 urology centres with clinical T1a RCC who underwent nephrectomy. The pathologic upstaging group (PUG) was defined by pathologic T3a after the operation. Multivariate analyses were used to examine predicting factors for the risk of PUG. Next, Kaplan-Meier analysis was used to examine the PUG for worse recurrence-free survival during the follow-up period. RESULTS: The PUG had 73 patients (3.5%); they were older and had a larger tumour size than the other patients (all p<0.001). After adjusting for clinical characteristics, age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02–1.06) and tumour size greater than 3 cm (OR, 1.94; 95% CI, 1.21–3.11) were found to be independent predictors for the PUG after nephrectomy. Furthermore, the PUG had worse recurrence-free survival during the follow-up period. CONCLUSIONS: In this multi-institution analysis, RCC 3 cm or greater in older patients had a high malignant potential compared to relatively small tumours in younger patients. These results may be helpful for stratifying patients to manage small renal masses.
Asunto(s)
Humanos , Carcinoma de Células Renales , Estudios de Seguimiento , Estimación de Kaplan-Meier , Análisis Multivariante , Nefrectomía , Estudios Retrospectivos , UrologíaRESUMEN
Many tumor markers in relation to renal cell carcinoma (RCC) have been evaluated for detecting and monitoring diseases outcomes. However, none of these biomarkers reported to date has shown sufficient sensitivity and specificity for as a detector and prognosticator of the whole spectrum of RCC in routine clinical practice. The limited value of the established prognostic markers requires analysis of new molecular parameters of interest in predicting the prognosis of RCC patients; in particular, the high-risk patient groups at risk of recurrence and progression. Abnormal methylation of CpG islands can efficiently repress transcription of the associated gene in a manner akin to mutations and deletions. Recent progress in the understanding of epigenetic modification and gene silencing has provided new opportunities for the detection, treatment, and prevention of cancer. Methylation is an important molecular mechanism in RCC and could be used as a diagnostic and prognostic marker. Aberrant patterns of epigenetic modification would be, in near future, crucial parameters in cancer diagnosis, prognosis and a good target for developing novel therapies while maintaining the quality of life. This review discusses the epigenetic issues involved in the detection and prediction of prognosis in RCC.
Asunto(s)
Humanos , Biomarcadores , Carcinoma de Células Renales , Islas de CpG , Diagnóstico , Epigenómica , Silenciador del Gen , Metilación , Pronóstico , Calidad de Vida , Recurrencia , Sensibilidad y Especificidad , Biomarcadores de TumorRESUMEN
This study aimed to evaluate the efficacy, safety, and tolerability of 2-cycled neoadjuvant sunitinib therapy (NST) in patients with inoperable metastatic renal cell carcinoma (mRCC). Between 2009 and 2012, 14 patients with inoperable mRCC from 5 Korean academic centers were prospectively enrolled after collecting their clinicopathological data and completing health-related questionnaires. The best overall response (BOR), safety profile, and changes in quality of life during NST were assessed using the RECIST criteria (version 1.0), CTCAE criteria (version 4.0), and the Cancer Quality of Life Questionnaire (QLQ-C30). Among the 14 patients, 9 patients (64.3%) experienced partial response or stable disease state, and 5 patients (35.7%) did not complete treatment, with 1 case of disease progression (7.1%), 3 grade 3 adverse events (21.4%), and 1 voluntary withdrawal (7.1%). Four patients (28.6%) were successfully converted to an operable state and underwent surgery after NST. The BOR for the primary renal lesions was 22.2%, with a median 1.3-cm diameter reduction (range: 0–2.8 cm) from a baseline diameter of 10.3 cm (range: 6.6–15.8 cm). The other 18 measurable metastatic lesions exhibited a BOR of 55.6%. The QLQ-C30 questionnaire results revealed significant improvements in the quality of life domain, although we observed significant increases in the scores for fatigue, nausea and vomiting, and the financial effects of NST (P < 0.05). Two-cycle NST provided limited efficacy for resectability of inoperable mRCC, despite mild improvements in the BOR of the primary lesion and quality of life (Clinical Trial Registry 1041140-1).
Asunto(s)
Humanos , Carcinoma de Células Renales , Progresión de la Enfermedad , Fatiga , Terapia Molecular Dirigida , Estudios Multicéntricos como Asunto , Náusea , Terapia Neoadyuvante , Metástasis de la Neoplasia , Estudios Prospectivos , Calidad de Vida , Criterios de Evaluación de Respuesta en Tumores Sólidos , VómitosRESUMEN
The prognostic significance of age in renal cell carcinoma (RCC) is a subject of debate. The aim of the present multi-institutional study was to evaluate the impact of age on clinicopathological features and survival in a large cohort of patients with RCC. A total of 5,178 patients who underwent surgery for RCC at eight institutions in Korea between 1999 and 2011 were categorized into three groups according to age at diagnosis as follows: young age (< 40 years, n = 541), middle-age (≥ 40 and < 60 years, n = 2,551), and old age (≥ 60 years, n = 2,096) groups. Clinicopathological variables and survival rates were compared between the three groups. Young patients had lower stage tumors with a low Fuhrman grade, a lower rate of lymphovascular invasion than patients in the other age groups. Regarding histologic type, the young age group had a lower percentage of clear cell histology and a greater incidence of Xp11.2 translocation RCC. Kaplan-Meier estimates showed that cancer-specific survival was significantly better in the young age group than in the other groups (log rank test, P = 0.008). However, age at diagnosis was not an independent predictor of survival in multivariate analysis. In conclusion, young age at diagnosis was associated with favorable pathologic features, although it was not an independent prognostic factor for survival in patients with surgically-treated RCC. Age itself should not be regarded as a crucial determinant for the treatment of RCC.
Asunto(s)
Humanos , Carcinoma de Células Renales , Estudios de Cohortes , Diagnóstico , Incidencia , Corea (Geográfico) , Análisis Multivariante , Nefrectomía , Recurrencia , Tasa de SupervivenciaRESUMEN
Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P or =10 ng/mL), a Gleason score> or =8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.
Asunto(s)
Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Expresión Génica , Calicreínas/sangre , Proteínas Asociadas a Microtúbulos/metabolismo , Clasificación del Tumor , Reacción en Cadena de la Polimerasa , Próstata/patología , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Neoplasias de la Próstata/sangreRESUMEN
Dietary and lifestyle modifications are widely prescribed to prevent recurrence of urolithiasis, although little is known about the clinical and demographic factors associated with patient compliance and urinary metabolic changes. The present study assessed the clinical and demographic factors influencing compliance with a modified diet and lifestyle in first-time ureteric stone formers as well as determined the effects of compliance on urinary stone risk factors. We retrospectively reviewed the medical records of 53 patients presenting with ureteric calcium stones. Using a self-completed questionnaire, patients were classified according to compliance with seven recommendations for modifying diet and lifestyle into good compliance group (complied with > or = three recommendations) and poor compliance group. Before (on a random diet) and after prescribing the modifications, 24 hour urine samples were collected from those in the good and poor compliance group. The stone size at presentation and initial treatment modality were closely associated with patient compliance (P=0.019, P=0.027, respectively). Citrate excretion significantly increased in the good compliance group after adopting modifications (P=0.012), whereas the poor compliance group did not show a statistically significant difference. Moreover, patients in the poor compliance group showed significantly increased urinary calcium excretion by the end of the study (P=0.040). After adjustments for age, sex, body mass index, and metabolic abnormality status, poor compliance was found to be an independent risk factor for persistence or development of hypocitraturia (OR: 3.885; 95% CI: 1.102~13.694; P=0.035). In conclusion, our results imply that patient education programs regarding diet and lifestyle should be tailored to the individual's clinical and demographic characteristics.
Asunto(s)
Humanos , Índice de Masa Corporal , Calcio , Ácido Cítrico , Adaptabilidad , Demografía , Dieta , Estilo de Vida , Registros Médicos , Cooperación del Paciente , Educación del Paciente como Asunto , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Uréter , Cálculos Urinarios , Urolitiasis , Encuestas y CuestionariosRESUMEN
The aim of the present study was to investigate sex- and age-associated clinico-metabolic characteristics of urinary stone patients. A retrospective review was performed on data from 2,009 consecutive patients presenting with their first urinary stone episode between 2005 and 2013. Of the 2,009 patients, 1,426 (71.0%) satisfied the inclusion criteria and were enrolled in the study. Patients were grouped by age ( or =60 years old) and sex. The medical history and 24 hr urinary chemistry results of each patient were obtained. The mean age of the 165 (11.6%) patients aged 60 or over was 65.5 +/- 4.2 years. Body mass index was greater in elderly females than in younger females (p=0.031). After stratification by sex and age, lower urinary excretion of calcium and uric acid was a protective factor for both sexes among the elderly (p<0.05, each, respectively). Low urine pH was a common risk factor for both sexes among the elderly (p=0.013 in males, p=0.047 in females, respectively), whereas lower citrate excretion was a risk factor for only the elderly female group (p=0.004). With regard to urinary metabolic abnormalities, elderly females showed higher incidence of hypocitraturia compared to younger females (p=0.049). In conclusion, this study demonstrated the sex- and ageassociated clinico-metabolic characteristics of urinary stone patients. Thus, it is important to tailor metabolic evaluation and medical prevention therapies for patient according to sex and gender characteristics.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Índice de Masa Corporal , Calcio , Química , Ácido Cítrico , Concentración de Iones de Hidrógeno , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Ácido Úrico , Cálculos Urinarios , UrolitiasisRESUMEN
DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, the association between GATA-binding protein 5 (GATA5) methylation and carcinogenesis of various types of tumors was investigated. The aim of the present study was to evaluate the effect of GATA5 methylation status on clinicopathological features and prognosis in primary non-muscle invasive bladder cancer (NMIBC) patients with a long-term followup period. The GATA5 methylation status was determined for 171 human bladder specimens (eight normal controls [NCs] and 163 primary NMIBC patients) using quantitative pyrosequencing analysis. The primary NMIBC tissues were obtained from patients who underwent transurethral resection (TUR) for histologically diagnosed transitional cell carcinomas between 1995 and 2012 at Chungbuk National University Hospital. GATA5 methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates showed significant differences in tumor recurrence and progression according to GATA5 methylation status (each p<0.05). Our results show that increased methylation of GATA5 was significantly associated with not only aggressive characteristics but also poor prognosis in primary NMIBC patients. Alteration of GATA5 methylation might be used as a biomarker for prognosis of NMIBC patients. However, prospective and functional investigations are necessary to clarify the role of GATA5 methylation in future clinical management of patients with NMIBC.
Asunto(s)
Humanos , Carcinogénesis , Carcinoma de Células Transicionales , Metilación de ADN , Epigenómica , Estudios de Seguimiento , Metilación , Pronóstico , Estudios Prospectivos , Recurrencia , Neoplasias de la Vejiga Urinaria , Vejiga UrinariaRESUMEN
PURPOSE: We assessed the impact of transobturator tape (TOT) treatment on overactive bladder (OAB) symptoms with a particular focus on nocturia in patients with mixed urinary incontinence (MUI). MATERIALS AND METHODS: In this retrospective cohort study, the medical records of 237 women who underwent TOT surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had preoperative nocturia. Patients with neurological diseases or sleep disorders that could affect the voiding pattern were excluded. Patients who were being treated with anticholinergics and antidiuretic hormones were also excluded, which left 70 subjects eligible for analysis. Pre- and postoperative evaluations consisted of a physical examination, 3-day frequency-volume chart, and health-related quality of life questionnaires (King's health questionnaire, overactive bladder symptom score, and OAB-questionnaire). RESULTS: TOT treatment resulted in an overall significant improvement in OAB symptoms including nocturia. Frequency-volume charts revealed that TOT treatment significantly decreased the actual number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in the entire cohort. However, in a subgroup of women with nocturnal polyuria, there was no significant change in ANV or NBCi after the sling operation. Correlation analysis of the whole cohort revealed that the postoperative changes in NBCi correlated positively with postoperative changes in ANV. The nocturia-persisting group was more likely to have nocturnal polyuria and lower preoperative functional bladder capacity compared with the nocturia-improved group (p=0.024 and p=0.023, respectively). CONCLUSIONS: Our results demonstrated that the TOT procedure resulted in an overall significant improvement in OAB symptoms including OAB-related nocturia in patients who presented with MUI.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Nocturia/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Cabestrillo Suburetral , Resultado del Tratamiento , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Hiperactiva/fisiopatología , Incontinencia Urinaria de Esfuerzo/fisiopatología , Urodinámica/fisiologíaRESUMEN
PURPOSE: To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters. MATERIALS AND METHODS: A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)2D3 and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included. RESULTS: 1,25(OH)2D3 level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)2D3 levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)2D3 level (beta=0.259, p<0.001) and serum PTH level (beta=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)2D3 had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)2D3 (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001). CONCLUSION: 1,25(OH)2D3 was closely correlated with urinary calcium excretion, and high 1,25(OH)2D3 levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)2D3 was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)2D3 might be important intrinsic factor for altered calcium regulation in SFs.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calcio/metabolismo , Cálculos Renales , Modelos Lineales , Análisis Multivariante , Oportunidad Relativa , Hormona Paratiroidea/sangre , Vitamina D/análogos & derivadosRESUMEN
The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance < or =60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Causalidad , Supervivencia sin Enfermedad , Tasa de Filtración Glomerular , Incidencia , Recurrencia , Insuficiencia Renal/diagnóstico , Reproducibilidad de los Resultados , República de Corea/epidemiología , Medición de Riesgo , Sensibilidad y Especificidad , Urolitiasis/diagnósticoRESUMEN
The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance < or =60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Causalidad , Supervivencia sin Enfermedad , Tasa de Filtración Glomerular , Incidencia , Recurrencia , Insuficiencia Renal/diagnóstico , Reproducibilidad de los Resultados , República de Corea/epidemiología , Medición de Riesgo , Sensibilidad y Especificidad , Urolitiasis/diagnósticoRESUMEN
PURPOSE: The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC. MATERIALS AND METHODS: The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. RESULTS: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05). CONCLUSIONS: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.
Asunto(s)
Humanos , Cromosomas Humanos Par 9 , Genes Supresores de Tumor , Estimación de Kaplan-Meier , Pérdida de Heterocigocidad , Membrana Mucosa , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Vejiga Urinaria , Neoplasias de la Vejiga UrinariaRESUMEN
PURPOSE: Epigenetic alterations such as abnormal DNA methylation are associated with many human cancers. Differences in methylation patterns between neoplastic and normal cells can be used to detect cancer. The aim of the present study was to evaluate the effectiveness of detecting Adenomatous polyposis coli (APC) hypermethylation by quantitative pyrosequencing for discriminating between normal and prostate cancer (PCa) cells and for predicting tumor behaviors. MATERIALS AND METHODS: A total of 218 human prostate tissues obtained from our institute were assessed: 106 specimens of benign prostatic hyperplasia (BPH) and 112 specimens of PCa. The methylation status of APC was analyzed by quantitative pyrosequencing. The association between the APC methylation level and clinicopathological parameters was explored. RESULTS: The level of APC methylation was significantly higher in PCa specimens than in BPH specimens (33.3%+/-20.7% vs. 1.3%+/-1.8%, p<0.001). The sensitivity and specificity of APC methylation status in discriminating between PCa and BPH reached 89.3% and 98.1%, respectively. Similar results were obtained after stratification by stage, Gleason score, and prostate-specific antigen level. The APC methylation level correlated positively with Gleason score (p trend=0.016). There was no association between the APC methylation level and the PSA level or staging. CONCLUSIONS: Our results demonstrate that APC methylation is associated with PCa and its aggressive tumor features.