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1.
Investig Clin Urol ; 61(2): 127-135, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32158963

RESUMO

Purpose: This study aimed to evaluate the feasibility of pan-cancer panel analysis for locally advanced prostate cancer in the Korean population. Materials and Methods: We analyzed 20 patients with locally advanced prostate cancer who underwent radical prostatectomy. A pan-cancer panel (1.9 Mbp) developed by Seoul National University Hospital (SNUH), composed of 183 target genes, 23 fusion genes, and 45 drug target regions was used for this analysis. We compared the SNUH pan-cancer panel results with The Cancer Genome Atlas (TCGA) database to search for different mutations in the Korean population. Clinical data were analyzed with univariate and multivariate analysis, and p-values <0.05 were considered statistically significant. Kaplan-Meier curve and log-rank tests were performed to evaluate survival. Results: The average age of the patients and initial prostate-specific antigen values were 69.3±7.8 years and 66.3±16.9 ng/dL, respectively. Average sequencing depth was 574.5±304.1×. Ninety-nine genetic mutations and 5 fusions were detected. SPOP (25%), KMT2D (20%), and BRAF (15%) were frequently detected. ERG fusions were recurrently detected in 20% of the patients, with SLMAP and SETD4 as novel fusion partners. BRAF mutation was frequently detected in this study, but not in the TCGA database. Multivariate analysis showed BRAF mutation as an independent prognostic factor for biochemical recurrence (hazard ratio, 9.84; p=0.03). Conclusions: The pan-cancer panel comprising genes related to prostate cancer is a useful tool for evaluating genetic alterations in locally advanced prostate cancers. Our results suggest that the BRAF mutation is associated with biochemical recurrence in the Korean population.

2.
Eur Urol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31980309

RESUMO

BACKGROUND: Active surveillance (AS)/watchful waiting (WW) strategy for localized prostate cancer (PCa) is increasingly and broadly endorsed as a preferred option for initial treatment of men with very low- and low-risk PCa, but outcomes can be difficult to analyze in traditional, population-based registries. The recently released Surveillance, Epidemiology, and End Results (SEER) Prostate with WW dataset provides an opportunity to understand national patterns and trends in AS/WW, but the data source itself has not been well described. OBJECTIVE: To provide a comprehensive description of this dataset and investigate possible biases due to missing data. DESIGN, SETTING, AND PARTICIPANTS: The SEER is a population-based epidemiologic registry in the USA. Newly diagnosed PCa patient data were collected from 18 SEER registries between 2010 and 2015, with inclusion of a new treatment variable for AS/WW. We identified 316 724 patients in the entire cohort and 257 060 men with clinically localized PCa (T1-2N0M0). INTERVENTION: Various primary treatments for PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The degree of missing data for each variable was measured. In order to investigate possible bias due to missing data for cancer characterization, we compared two versions of the data: one that excluded cases with missing data and one dataset generated applying multiple imputations. RESULTS AND LIMITATIONS: Only 46% of cases had complete data on basic cancer characteristics for risk stratification. The excluded dataset (N=118 821) differed significantly from the multiple imputation dataset (N=257 060) in the distribution of every reported variable (all p<0.001). The dataset does not distinguish WW from AS, which is a limitation. CONCLUSIONS: While the SEER Prostate with WW dataset offers a new method to describe treatment trends for men with PCa, including the use of AS/WW, the amount of missing data should not be ignored. PATIENT SUMMARY: While the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting dataset offers a new method to describe treatment trends for men with prostate cancer, including the use of active surveillance, it has a significant amount of missing data, which can be a source of potential bias if not addressed properly.

3.
Investig Clin Urol ; 61(1): 19-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942459

RESUMO

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients. Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT). Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125-0.958). Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.

4.
Investig Clin Urol ; 61(1): 107-113, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942470

RESUMO

Purpose: Although percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model. Materials and Methods: A novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach. Results: When the temperature of the outer wall of the renal artery was maintained at 90℃ for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70℃ to 90℃ and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining. Conclusions: This animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use.

6.
J Nucl Med ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806771

RESUMO

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.

7.
Am J Kidney Dis ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31866225

RESUMO

RATIONALE & OBJECTIVE: Living kidney donors may have a higher risk for death and kidney failure. This study aimed to investigate the long-term mortality experience of living kidney donors compared with members of the general public in Korea who underwent voluntary health examinations. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We first calculated standardized mortality ratios for 1,292 Korean living kidney donors who underwent donor nephrectomy between 1982 and 2016 and 72,286 individuals who underwent voluntary health examinations between 1995 and 2016. Next we compared survival between the 1,292 living kidney donors and a subgroup of the health examination population (n=33,805) who had no evident contraindications to living kidney donation at the time of their examinations. Last, a matched comparator group was created from the health examination population without apparent contraindication to donation by matching 4,387 of them to donors (n=1,237) on age, sex, body mass index, estimated glomerular filtration rate, urine dipstick albumin excretion, previously diagnosed hypertension and diabetes, and era. EXPOSURES: Donor nephrectomy. OUTCOMES: All-cause mortality and other clinical outcomes after kidney donation. ANALYTICAL APPROACH: First, standardized mortality ratios were calculated separately for living kidney donors and the health examination population standardized to the general population. Second, we used Cox regression analysis to compare mortality between living kidney donors versus the subgroup of the health examination population without evident donation contraindications. Third, we used Cox regression analysis to compare mortality between living kidney donors and matched comparators from the health examination population without apparent contraindication to donation. RESULTS: The living kidney donors and health examination population had excellent survival rates compared with the general population. 52 (4.0%) of 1,292 kidney donors died during a mean follow-up of 12.3±8.1 years and 1,072 (3.2%) of 33,805 in the health examiner subgroup without donation contraindications died during a mean follow-up of 11.4±6.1 years. Donor nephrectomy did not elevate the hazard for mortality after multivariable adjustment in kidney donors and the 33,805 comparators (adjusted HR, 1.01; 95% CI, 0.71-1.44; P=0.9). Moreover, living donors showed a similar mortality rate compared with the group of matched healthy comparators. LIMITATIONS: Donors from a single transplantation center. Residual confounding owing to the observational study design. CONCLUSIONS: Kidney donors experienced long-term rates of death comparable to nondonor comparators with similar health status.

8.
Urol Int ; : 1-6, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694041

RESUMO

OBJECTIVE: The aim of this study was to evaluate the feasibility of including patients with biopsy Gleason score (bGS) 3 + 4 prostate cancer in an active surveillance (AS) protocol. METHODS: A total of 615 patients underwent a radical prostatectomy and satisfied the following requirements: prostate-specific antigen ≤10 ng/dL, clinical stage T1c or T2a, 2 or fewer positive biopsy cores, and bGS 6 or 3 + 4 prostate cancer. The patients were divided into two groups according to their bGS (bGS 6 group, n =534; bGS 3 + 4 group, n = 81). RESULTS: The adverse pathological features were significantly higher in the bGS 3 + 4 group (16.7 vs. 49.4%, p< 0.001). Biochemical recurrence (BCR)-free survival was also significantly lower in this group (p < 0.001). In a multivariate analysis, clinical stage (odds ratio [OR] 2.026, p =0.007), maximum percentage of biopsy core involvement (OR 1.015, p = 0.014), and bGS (OR 1.913, p = 0.030) were independent risk factors for adverse pathological features. However, the bGS was the only variable to forecast BCR (hazard ratio 3.567, p < 0.001). CONCLUSIONS: A bGS 3 + 4 was the leading risk factor for a worse postoperative prognosis. Therefore, patients with a bGS 3 + 4 are not appropriate candidates for AS.

9.
Medicine (Baltimore) ; 98(40): e17377, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577742

RESUMO

BACKGROUND: E-cadherin has emerged as a prognostic factor of urothelial cell carcinoma. In the present work we investigate the relationship between expression of E-cadherin and clinical outcomes, following radical nephroureterectomy for upper tract urothelial cell carcinoma. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases to identify eligible studies published until July 2017. RESULT: Six studies were included in the meta-analysis, with a total of 1014 patients. The pooled hazard ratio (HR) for recurrence-free survivor was 0.69 (95% confidence interval [CI], 0.44-1.09, I = 63%, P = .04). Also, reduced E-cadherin was not significantly associated with poor cancer-specific survivor (pooled HR, 1.40; 95% CI, 0.66-1.43, I = 54%, P = .11). The pooled HR for overall survivor was not statistically significant (pooled HR, 0.68; 95% CI, 0.32-1.46, I = 80%, P = .007). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis. CONCLUSIONS: Reduced E-cadherin expression did not appear to be significantly associated with disease prognosis after nephroureterectomy in the meta-analysis. However, further high quality, prospective studies are warranted to better address this issue.


Assuntos
Caderinas/biossíntese , Neoplasias Urológicas/patologia , Urotélio/patologia , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Recidiva Local de Neoplasia , Nefroureterectomia , Estudos Observacionais como Assunto , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Urológicas/mortalidade
10.
Sci Rep ; 9(1): 15268, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649294

RESUMO

This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.

11.
Front Oncol ; 9: 859, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552183

RESUMO

We evaluated prognostic risk factors of recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) outcomes in patients with non-metastatic renal cell carcinoma (nmRCC) after curative nephrectomy during long-term follow-up. The medical records of 4,260 patients with nmRCC who underwent curative nephrectomy between 2000 and 2012 from five Korean institutions and follow-up after postoperative 1 month until December 2017 were retrospectively analyzed for RFS, MFS, OS, and CSS. During the median 43.86 months of follow-up, 342 recurrences, 127 metastases, and 361 deaths, including 222 cancer-specific deaths, were reported. In addition to the unreached median survival of RFS and MFS, the median OS and CSS times were 176.75 and 227.47 months, respectively. Multivariable analyses showed that nephrectomy type (laparoscopy vs. open), pathological T stages, and nuclear grade were common significant risk factors for survival, and the baseline ASA, hemoglobin, and pathological N stage were common factors only for RFS, OS, and CSS (p < 0.05). Further, tumor necrosis for MFS; platelet count, extent (partial vs. radical) of surgery, and lymphovascular invasion for RFS; baseline diabetes, hypertension, age, body mass index, extent of surgery, and pathological sarcomatoid differentiation for OS; and baseline diabetes, hypertension, body mass index, and pathological sarcomatoid differentiation for CSS were additionally significant risk factors (p < 0.05). RFS, MFS, OS, and CSS were significantly different depending on the pathological T stages (p < 0.05). In conclusion, this large-numbered, long-term follow-up study revealed significant factors affecting the survival of patients with nephrectomized nmRCC.

12.
Dis Markers ; 2019: 6702964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534562

RESUMO

Introduction: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase (AST)/alanine transaminase (ALT)) and postoperative outcome in patients with urothelial cell carcinoma (UC) treated with radical cystectomy. Materials and Methods: We analyzed the clinical and pathological data of 771 patients who underwent radical cystectomy for bladder UC. Patients were divided into two groups according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed using the Kaplan-Meier method and Cox regression hazard models for patients' cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In addition, propensity score matching of 1 : 1 was performed between the two groups. Results: Median follow-up was 84.0 (36-275) months. Mean age was 64.8 ± 10.0 years. According to the receiver operating characteristic (ROC) analysis, the optimal threshold of the AST/ALT ratio was 1.1. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in CSS and OS (all P < 0.001). Also, RFS (P = 0.001) in the Cox regression models of clinical and pathological parameters was used to predict CSS, OS, and AST/ALT ratio (HR 2.15, 95% CI 1.23-3.73, P = 0.007) and pathological T stage (HR 4.80, 95% CI 1.19-19.28, P = 0.003). To predict OS and AST/ALT ratio (HR 2.05, 95% CI 1.65-2.56, P < 0.001), pathological T stage (HR 2.96, 95% CI 0.57-17.09, P = 0.037) and positive lymph node (HR 1.71, 95% CI 1.50-1.91, P = 0.021) were determined as independent prognostic factors. Conclusion: Preoperative AST/ALT ratio could be an independent prognostic factor in patients with UC treated with radical cystectomy.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Neoplasias da Bexiga Urinária/sangue , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
13.
J Clin Med ; 8(9)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540394

RESUMO

We sought to evaluate the association of postoperative acute kidney injury (AKI) adjusted for parenchymal mass reduction with long-term renal function in patients undergoing partial nephrectomy. A total of 629 patients undergoing partial nephrectomy were reviewed. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria, by using either the unadjusted or adjusted baseline serum creatinine level, accounting for renal parenchymal mass reduction. Estimated glomerular filtration rates (eGFRs) were followed up to 61 months (median 28 months) after surgery. The primary outcome was the functional change ratio (FCR) of eGFR calculated by the ratio of the most recent follow-up value, at least 24 months after surgery, to eGFR at 3-12 months after surgery. Multivariable linear regression analysis was performed to evaluate whether unadjusted or adjusted AKI was an independent predictor of FCR. As a sensitivity analysis, functional recovery at 3-12 months after surgery compared to the preoperative baseline was analyzed. Median parenchymal mass reduction was 11%. Unadjusted AKI occurred in 16.5% (104/625) and adjusted AKI occurred in 8.6% (54/629). AKI using adjusted baseline creatinine was significantly associated with a long-term FCR (ß = -0.129 ± 0.026, p < 0.001), while unadjusted AKI was not. Adjusted AKI was also a significant predictor of functional recovery (ß = -0.243 ± 0.106, p = 0.023), while unadjusted AKI was not. AKI adjusted for the parenchymal mass reduction was significantly associated with a long-term functional decline after partial nephrectomy. A creatinine increase due to remaining parenchymal ischemic injury may be important in order to predict long-term renal functional outcomes after partial nephrectomy.

14.
J Clin Med ; 8(10)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554223

RESUMO

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal dysfunction after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) and CKD upstaging were compared between general anesthetic agent groups (propofol, sevoflurane, and desflurane). Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs. sevoflurane; propofol vs. desflurane; sevoflurane vs. desflurane; propofol vs. volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of new-onset CKD between groups up to 36 months after nephrectomy. Propofol was associated with a lower incidence of AKI (propofol 23.2% vs. sevoflurane 39.5%, p = 0.004; vs. propofol 21.0% vs. desflurane 34.3%, p = 0.031), a lower incidence of CKD upstaging (propofol 27.2% vs. sevoflurane 58.4%, p < 0.001; propofol 32.4% vs. desflurane 48.6%, p = 0.017) and better three-year renal survival after nephrectomy compared to sevoflurane or desflurane group (Log-rank test propofol vs. sevoflurane p < 0.001; vs. desflurane p = 0.015) after matching. Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching (p < 0.001). There were no significant differences between sevoflurane and desflurane. However, subgroup analysis of partial nephrectomy showed a significant difference only in CKD upstaging. In conclusion, propofol, compared to volatile agents, could be a better general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. However, limitations of the retrospective study design and inconsistent results of the subgroup analysis preclude firm conclusions.

15.
BMC Cancer ; 19(1): 897, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500577

RESUMO

BACKGROUND: We evaluated the clinical efficacy and prognosis of muscle-invasive bladder cancer according to the basal/squamous-like (BASQ) classification system based on immunohistochemical staining [CK5/6(+), CK14(+), GATA3(-), and FOXA1(-)]. METHODS: One hundred patients diagnosed with muscle-invasive bladder cancer (cT2-4 N0-3 M0) were included in the study. All patients underwent radical cystectomy after transurethral removal of bladder tumor. Immunostaining was performed for CK5/6, CK14, FOXA1, and GATA3 antibodies on tissue microarray slides, and expression patterns were quantitatively analyzed using a scanning program. RESULTS: The median follow-up time was 77.4 (interquartile range: 39-120.9) months. The mean age of the patients was 65.1 ± 11.2 years. FOXA1 or CK14 expression greater than 1% was respectively positively and negatively correlated with overall survival (OS; p = 0.011 and p = 0.042, respectively), cancer-specific survival (CSS; p = 0.050 for both), and recurrence-free survival (RFS; p = 0.018 and p = 0.040, respectively). For CK5/6+ and GATA3- or FOXA1- expression, 10% CK5/6+ cells were negatively correlated with OS (p = 0.032 and p = 0.039, respectively) and with RFS in combination with FOXA1- only (p = 0.050). CONCLUSIONS: In this study, CK14 expression was associated with a poor prognosis. The new classification system of bladder cancer based on molecular characteristics is expected to helpful tool for the establishment of personalized treatment strategies and associated prediction of therapeutic responses.


Assuntos
Biomarcadores Tumorais/análise , Queratina-14/análise , Neoplasias Musculares/secundário , Neoplasias de Células Escamosas/secundário , Neoplasias da Bexiga Urinária/patologia , Idoso , Cistectomia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Queratina-14/genética , Queratinas/análise , Queratinas/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/metabolismo , Neoplasias Musculares/cirurgia , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/cirurgia , Prognóstico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/cirurgia
16.
Stud Health Technol Inform ; 264: 1506-1507, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438204

RESUMO

In this study, we built a multi-center integrated database platform of localized prostate cancer and developed biochemical recurrence (BCR) prediction system with Gradient Boosted Regression model using Korean Prostate Cancer Registry (KPCR) database. This platform will facilitate clinical management of patients with prostate cancer, and it will also help develop appropriate treatment of prostate cancer.


Assuntos
Neoplasias da Próstata , Bases de Dados Factuais , Humanos , Masculino , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia
17.
J Cancer ; 10(10): 2237-2242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258727

RESUMO

Purpose: To evaluate the prognostic value of early postoperative prostate specific antigen (PSA) levels after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) in prostate cancer patients with lymph node invasion (LNI). Materials and Methods: The retrospective analysis involved 96 patients who had a diagnosis of LNI with available data on the first PSA level at postoperative 6 weeks after RP and PLND between 2002 and 2014 at our institution. PSA persistence was defined as PSA ≥ 0.1 ng/ml at 6 weeks after surgery. Radiographic progression was defined as positive imaging during follow-up after the onset of biochemical recurrence, consisting of a bone scan and/or computed tomography (CT) and/or magnetic resonance imaging and/or 18F-(2-deoxy-2-fluoro-D-glucose positron emission tomography/CT scan. Comparative analysis of patients with and without PSA persistence was done, and Kaplan-Meier curve analysis with log-rank test and Cox proportional hazard regression models assessed radiographic progression free survival (PFS). Results: Fifty two (54.2%) patients displayed PSA persistence. Kaplan-Meier curve analysis showed significantly decreased 5-year radiographic PFS (64.2% vs. 93.2%, log-rank, p=0.009) in the PSA persistence group compared to the no PSA persistence group. In a multivariate analysis, PSA persistence was a statistically significant predictor of radiographic PFS. Conclusions: Early assessment of PSA after surgery is important for predicting radiographic progression in node-positive prostate cancer patients. Risk stratification based on the early PSA value after surgery would be helpful to identify patients who may benefit from early adjuvant therapies.

18.
Investig Clin Urol ; 60(4): 235-243, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294132

RESUMO

Purpose: To establish a prospective, comprehensive, multidisciplinary, bio-bank linked genitourinary cancer cohort based on standard real practice. Materials and Methods: We established the Seoul National University Prospectively Enrolled Registry for Genitourinary Cancer (SUPER-GUC), a prospective cohort clinical database and bio-specimen repository system for prostate cancer (SUPER-PC), renal cell carcinoma (SUPER-RCC), and urothelial cancer (SUPER-UC) at a high-volume, tertiary institution. Each cohort consists of several sub-cohorts based on treatment or disease status. Detailed longitudinal clinical information, and general and disease specific patient-reported outcomes are captured. We use the same evaluation format and questionnaires for all participating departments. Patients' blood, urine, tumor, and normal tissues are collected. The number of registered patients and their basic characteristics are summarized. For the surgical sub-cohort, study participation, bio-specimen, and tissue banking rates are analyzed. Results: Since March 2016, 11 sub-cohorts for all disease statuses have been opened, ranging from low-risk localized to metastatic disease. SUPER-PC, SUPER-RCC, and SUPER-UC enrolled 929, 796, and 1,221 patients, respectively. Study participation, bio-sampling, and fresh frozen tumor banking rates of surgical sub-cohorts were 89.0% to 93.1%, 91.2% to 99.1%, and 56.9% to 79.1%, respectively. Conclusions: SUPER-GUC is a study platform for comparative outcome, quality-of-life, and translational (genetics, biomarkers) research for genitourinary cancer.

19.
J Clin Med ; 8(7)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331003

RESUMO

The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38-0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen.

20.
Eur Urol ; 76(6): 743-751, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31345635

RESUMO

BACKGROUND: Valid health utility values are essential for comparative effectiveness analyses. However, subjective utilities in long-term survivors of prostate cancer (PCa) with various oncological and functional outcomes have not been well described. OBJECTIVE: To quantify utilities in long-term survivors of PCa using the standard gamble method, generally regarded as the approach best grounded in economic theory. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study nested within a prospective cohort-Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Overall, 1884 (59.7%) of 3155 active participants across all disease states returned the questionnaire. INTERVENTION: Various primary treatments for PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Utility values for PCa health, sexual function, urinary function, bowel function, and overall health were measured, based on patients' conditions at the time of the survey. Bias correction methods were employed. RESULTS AND LIMITATIONS: After exclusion of incomplete or disqualified data, 1740 (92.3% of responding) patients were included in the final analysis. The mean age was 73.1 ±â€¯8.2 yr at a median of 9 yr (interquartile range: 6-11) since diagnosis. Mean utilities for PCa health and overall health were 0.934 ±â€¯0.120 and 0.960 ±â€¯0.100, respectively. After bias correction by probability weighting function, utilities were 0.866 ±â€¯0.154 and 0.897 ±â€¯0.142, and by mixed model correction, 0.845 ±â€¯0.186 and 0.884 ±â€¯0.176, respectively. Measured utilities were similarly high for specific functional outcomes, even with bias corrections. Survivorship bias and skewed proportion of disease status due to natural history of PCa were potential limitations. CONCLUSIONS: Standard gamble-based utilities in long-term survivors of PCa were much higher than those determined previously. The results indicate substantial human resilience: most PCa patients adapt to their health status over time even if they experience incomplete functional recovery and would not take risk in pursuit of better quality of life. PATIENT SUMMARY: We elicited health utilities (measures of quality of life) among long-term survivors of prostate cancer using the most robust method. These were much higher than previously reported values that were based on theoretical scenarios or indirect methods. Long-term survivors of prostate cancer may adapt well to their health conditions over time even if they experience disease-specific or functional problems.

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