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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.
Investig Clin Urol ; 61(2): 136-145, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32158964

RESUMO

Purpose: To evaluate the impact of perioperative blood transfusion (PBT) on oncologic outcomes after surgery in patients with nonmetastatic renal cell carcinoma (RCC). Materials and Methods: This retrospective review included 2,329 patients who underwent partial or radical nephrectomy for localized RCC in a single institution from 2000 to 2014. PBT was defined as transfusion of allogeneic packed red blood cells (pRBCs) during nephrectomy or within the preoperative or postoperative hospitalization period. Oncologic outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Results: PBT was performed in 275 patients (11.8%). In the multivariable logistic regression analysis, symptomatic presentation, advanced age at surgery, higher preoperative serum creatinine, and lower preoperative hemoglobin were independent preoperative risk factors for PBT (all p<0.05). Kaplan-Meier plots revealed that transfused patients showed poorer 5-year RFS (65.1% vs. 91.2%, p<0.001), OS (71.4% vs. 92.8%, p<0.001), and CSS (74.0% vs. 95.5%, p<0.001) than nontransfused patients. However, in the multivariable Cox regression analyses, PBT was not significantly associated with RFS, OS, or CSS. In multivariable analyses involving transfused patients only (n=275), an higher number of pRBC units was an independent predictor of worse OS (hazard ratio [HR], 1.043; 95% confidence interval [CI], 1.008-1.078; p=0.016) and CSS (HR, 1.066; 95% CI, 1.033-1.100; p<0.001). Conclusions: The results of this study are inconclusive in that the influence of PBT on survival outcomes could not be determined in the multivariate analysis. However, increasing pRBC units in transfused patients might be a concern in light of worse OS and CSS. Therefore, efforts to limit PBT overuse seem necessary to improve postoperative survival in patients with RCC.

3.
Nanotechnology ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32182601

RESUMO

Electrochemical water splitting represents an ideal strategy for producing clean hydrogen as an energy carrier that serves as an alternative to fossil fuels. As an effective method for hydrogen production, an efficient inexpensive multifunctional electrocatalyst with high durability is designed. Herein, we describe the heterostructural design of a three-dimensional catalytic network with self-embedded CoNi2S4 nanograins grown on electrospun carbon nanofibers (CoNi2S4-CNFs) with anchored thin-layer reduced graphene oxide. This is achieved via facile electrospinning followed by carbonization, low temperature sulfidation, and surface functionalization. As a bifunctional catalyst, CoNi2S4-CNFs exhibited robust high activity toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline medium. The anchored ultrathin graphene oxide layer promoted the stability and durability of the catalytic network with an efficient path for the transportation of electrons. The rGO-anchored CoNi2S4-CNFs yielded overpotential values of 228 mV and 205 mV for the HER and OER, respectively, that drive a current density of 20 mA cm-2 in an alkaline medium. Notably, the excellent electrochemical properties are attributed to the functional effect of the CoNi2S4 on the CNF network. The ultrathin feature of rGO improved the durability of the catalytic network. Moreover, using the rGO-anchored CoNi2S4-CNFs as a cathode and anode in a two-electrode water splitting system required a cell voltage of only 1.55 V to reach a current density of 10 mA cm-2. These CNFs exhibited an outstanding durability for 48 h. The present work offers new insight for the design of a catalytic network with a non-noble metal catalyst that exhibits excellent electrocatalytic activity and durability on the metal sulfides in overall water splitting.

4.
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.

5.
J Cancer Res Clin Oncol ; 146(1): 187-196, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606760

RESUMO

PURPOSE: No study has evaluated the prognostic impact of the age-adjusted Charlson comorbidity index (AACI) in those with renal cell carcinoma (RCC). This study aimed to evaluate the utility of the AACI for predicting long-term survival in patients with surgically treated non-metastatic clear cell RCC (ccRCC). METHODS: Data from 698 patients with non-metastatic ccRCC who underwent radical or partial nephrectomy as primary therapy from a multi-institutional Korean collaboration between 1988 and 2015 were retrospectively analyzed. Clinicopathological variables and survival outcomes of those with AACI scores ≤ 3 (n = 324), 4-5 (n = 292), and ≥ 6 (n = 82) were compared. RESULTS: Patients with a high AACI score were older and more likely to be female. They were also more likely to have diabetes or hypertension, a worse Eastern Cooperative Oncology Group performance status, and lower preoperative hemoglobin, albumin, serum calcium, and serum total cholesterol levels. Regarding pathologic features, a high AACI score was associated with advanced stage. Kaplan-Meier analyses revealed that AACI ≥ 6 was associated with shorter cancer-specific (log-rank test, P < 0.001) and overall survival (log-rank test, P < 0.001), but not with recurrence-free survival (log-rank test, P = 0.134). Multivariate Cox regression analyses identified an AACI score as an independent predictor of overall survival (hazard ratio, 6.870; 95% confidence interval, 2.049-23.031; P = 0.002). The AACI score was a better discriminator of overall survival than the Charlson comorbidity index score. CONCLUSIONS: AACI scores may enable more tailored, individualized management strategies for patients with surgically treated non-metastatic ccRCC.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/cirurgia , Comorbidade , Intervalo Livre de Doença , Feminino , Indicadores Básicos de Saúde , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia/estatística & dados numéricos , Valor Preditivo dos Testes , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida
6.
Nutr Cancer ; 72(1): 88-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31155957

RESUMO

Purpose: To investigated the prognostic significance of the geriatric nutritional risk index (GNRI) in patients with surgically treated clear cell renal cell carcinoma (ccRCC).Patients and methods: We retrospectively selected 4,591 consecutive patients with surgically treated ccRCC from a multi-institutional Korean collaboration between 1988 and 2015. The clinical significance of the GNRI as a continuous and categorical variable was determined.Results: Preoperative low GNRI was significantly associated with older age, low body mass index, presence of diabetes, poor performance status, and presence of symptoms at diagnosis, as well as pathologic features such as aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, sarcomatous differentiation, and tumor necrosis. A low GNRI was significantly associated with a short recurrence-free survival (RFS) in localized (pT1-2N0M0) ccRCC and cancer-specific survival (CSS) in the entire cohort, and with short RFS and CSS in the subgroup analysis according to age categories (≤65 and >65 years). Multivariate Cox regression analysis showed that preoperative GNRI, as a continuous or categorical variable, was an independent predictor of RFS and CSS.Conclusion: Malnutrition as assessed by the preoperative GNRI is associated with aggressive tumor characteristics and poor survival in patients with surgically treated ccRCC.

7.
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.

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.
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
14.
Front Oncol ; 9: 679, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403033

RESUMO

Purpose: We aimed to evaluate and compare relative impacts of various second-line treatments on overall survival (OS) in metastatic urothelial carcinoma (mUC). Method: A literature search was conducted in PubMed, Embase, and the Cochrane Library for all articles published prior to December 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Seven randomized controlled trials with phase III design that met study eligibility criteria were selected for final analysis. A Bayesian framework network meta-analysis (NMA) was applied to indirectly compare the effect of each treatment on OS. Results: In NMA, atezolizumab (HR, 0.90; 95% CI, 0.57-1.40) and pembrolizumab (HR, 0.77, 95% CI, 0.48-1.20) showed no significant effect on OS improvement compared to vinflunine. Gemcitabine/paclitaxel combination (HR, 1.30; 95% CI, 0.80-1.90) and lapatinib (HR, 0.95; 95% CI, 0.57-1.60) was not significantly associated with OS improvement compared to atezolizumab and best supportive care, respectively. However, results of rankograms revealed that pembrolizumab and atezolizumab were the first and second rank therapeutic agents for OS improvement in post-platinum mUC. Conclusions: Our NMA results are inconclusive. The optimal second-line treatment for OS improvement could not be determined because there were no significant OS differences among evaluated therapeutic agents. However, the use of immunotherapeutic agents such as atezolizumab and pembolizumab may have priority for improving OS in second-line setting of mUC.

15.
Urol Int ; 103(3): 291-296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31461728

RESUMO

PURPOSE: There are only a few studies on characteristics and outcomes of late recurrence (LR) of urothelial carcinoma of bladder (UCB) after radical cystectomy (RC). The objective of this study was to assess characteristics and oncological outcomes of such LR that developed 5 years after RC. MATERIALS AND METHODS: We retrospectively reviewed 570 patients who underwent RC and bilateral regional lymphadenectomy for UCB at our institution. Comparisons of post-recurrence disease-specific survival (DSS) according to the timing of recurrence and the site of recurrence were performed using Kaplan-Meier survival curves and log-rank test. Cox regression model was fitted to assess factors for post-recurrence DSS. RESULTS: Disease recurrence occurred in 214 (37.5%) patients, including 20 (9.3%) who had LRs. Median time from RC to recurrence was 13.0 (interquartile range 6.0-32.0) months. There were no significant differences in clinicopathological factors between early- and late-recurrence groups. Post-recurrence 5-year DSS was not significantly different (21.6 vs. 14.1%, p = 0.344) between early- and late-recurrence groups. However, it was worse in the nonurothelial recurrence group compared to that in the urothelial recurrence group (14.0 vs. 19.4%, p = 0.056). Older age (HR 1.03, 95% CI 1.01-1.05, p = 0.001), nonorgan-confined disease at RC (HR 1.73, 95% CI 1.15-2.61, p = 0.008), and lymph node invasion (HR 1.58, 95% CI 1.01-2.45, p = 0.043) were significant predictors for post-recurrence 5-year DSS. CONCLUSIONS: LR after RC with lymphadenectomy is not common. However, it cannot be overlooked. LR had similar characteristics to early recurrence. Interestingly, the time to recurrence did not affect post-recurrence survival.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Cistectomia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Cistectomia/métodos , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
16.
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.

17.
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.

18.
Anal Chim Acta ; 1077: 150-159, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31307704

RESUMO

In this article, we demonstrate the potentiostatic electrodeposition of poly(3,4-ethylenedioxythiophene) (PEDOT) on reduced graphene oxide (RGO) to develop a nanocomposite-modified electrode that separates three coexisting biofluids - ascorbic acid (AA), dopamine (DA), and uric acid (UA) - in a 0.1 M Phosphate buffer solution at a physiological pH (7.4). The texture, physicochemical properties, and electrochemical behavior of the PEDOT-RGO were explored using UV-visible spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, electron microscopic techniques, and electrochemical impedance spectroscopy (EIS). A PEDOT-RGO/GCE was evaluated with respect to a bare GCE, RGO/GCE, and PEDOT/GCE for the simultaneous sensing of AA, DA, and UA. The difference in voltammetric peak potentials was about 180 mV between AA and DA and 120 mV between DA and UA. The differential pulse voltammetric sensor provided a linear calibration for a wide concentration range (0.1-907 µM for AA, 0.1-901 µM for DA, and 0.1-701 µM for UA) with detection limits of 1.5 µM, 0.6 µM, and 0.2 µM for AA, DA, and UA, respectively. The developed sensor was validated by the detection of AA, DA, and UA in a vitamin C tablet, a dopamine hydrochloride injection, and human serum samples.


Assuntos
Ácido Ascórbico/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/química , Dopamina/sangue , Grafite/química , Nanocompostos/química , Polímeros/química , Ácido Úrico/sangue , Ácido Ascórbico/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Carbono/química , Dopamina/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/síntese química , Humanos , Limite de Detecção , Oxirredução , Polímeros/síntese química , Reprodutibilidade dos Testes , Ácido Úrico/química
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.
J Geriatr Oncol ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31235435

RESUMO

OBJECTIVE: To develop a Korean version of the G-8 questionnaire validated with Korean patients over 70 years-of-age who were scheduled to undergo cancer surgery. MATERIALS AND METHODS: We conducted a translation study over a nine-month period from February to November 2017. Permission was received to use the original version of the G-8 questionnaire for forward translation into Korean and reconciliation, for backward translation of the translated Korean version into English, for cognitive debriefing, and final proofreading. These steps were performed in the order of translation and then language validation. Forward translation was performed independently by two translators who were fluent in Korean and English. The cognitive debriefing was carried out through interviews with ten Korean nurses who cared for the patients surveyed. RESULTS: In the forward translation, "mobility" was replaced by "degree of activity". During the reconciliation, the difference in meaning between the terms "loss of appetite" and "severe," as determined by the two translators, was adjusted. Moreover, to achieve more natural Korean expression, some revisions were made to the questions and answers. In the backward translation, most of the forward translations were accepted without any objection. During the final proofreading, no difficulties were found in understanding the questionnaire's content, and most terms were deemed easy to understand. CONCLUSION: This Korean version of the G-8 questionnaire has been validated in accordance with appropriate procedures. Therefore, the questionnaire is appropriate for use as a geriatric screening tool for older patients with cancer in Korea.

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