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Antibody-drug conjugates (ADCs) have been a significant advancement in cancer therapy, particularly for urothelial cancer (UC). These innovative treatments, originally developed for hematological malignancies, use target-specific monoclonal antibodies linked to potent cytotoxic agents. This rational drug design efficiently delivers cancer cell-killing agents to cells expressing specific surface proteins, which are abundant in UC owing to their high antigen expression. UC is an ideal candidate for ADC therapy, as it enhances on-target efficacy while mitigating systemic toxicity. In recent years, considerable progress has been made in understanding the biology and mechanisms of tumor progression in UC. However, despite the introduction of immune checkpoint inhibitors, advanced UC is characterized by rapid progression and poor survival rates. Targeted therapies that have been developed include the anti-nectin 4 ADC enfortumab vedotin and the fibroblast growth factor receptor inhibitor erdafitinib. Enfortumab vedotin has shown efficacy in prospective studies in patients with advanced UC, alone and in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also demonstrated effectiveness in single-armed studies. This review highlights the mechanism of action of ADCs, their application in mono- and combination therapies, primary mechanisms of resistance, and future perspectives for their clinical use in UC treatment. ADCs have proven to be an increasingly vital component of the therapeutic landscape for urothelial carcinoma, filling a gap in the treatment of this progressive disease.
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TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.
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BACKGROUND: The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. RESULTS: Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. CONCLUSION: A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Puntuación de Riesgo Genético , Estudio de Asociación del Genoma Completo , Estilo de Vida , Neoplasias Renales/genética , República de Corea/epidemiologíaRESUMEN
PURPOSE: To investigate if increased tubular damage biomarker can predict pathologically upstaged renal cell carcinoma (RCC), which may possess sub-radiologic invasive behavior, leading to surrounding tubular damage. MATERIALS AND METHODS: We examined 1563 patients with surgically resected RCC between March 2016 and June 2021 from the prospective database SUPER-RCC-Nx. Exclusion criteria were cancer not originating from the kidneys, benign renal tumor, and end-stage renal disease. RESULTS: Of 1297 patients, 131 had a clinically high T stage (T3-4), whereas 1166 had a low one. Patients with a clinically low T stage were subgrouped into identical-stage (n = 1041) and upstaged (n = 125) groups, who were confirmed as a pathologically high T stage. The upstaged group had older age (p = 0.003), larger tumor size (5.72 ± 3.24 vs. 3.12 ± 2.08, p < 0.001), higher Fuhrman grade (grades 3-4) (57.3% vs. 47.1%, p = 0.032), and higher urine N-acetyl-beta-D-glucosaminidase/creatinine (NAG/Cr) (5.13 ± 4.78 vs. 4.05 ± 2.84, p = 0.026). Tumor size (> 4 cm; odds ratio = 10.2, p < 0.001) and urine NAG/Cr (odds ratio = 1.16, p = 0.003) were independently associated with pathological upstaging in patients with normal renal function, while age and tumor size were significant risk factors in those with decreased renal function. The receiver operating characteristic curve analysis showed that the model using tumor size and urine NAG/Cr strongly predicted pathological upstaging (area under the curve, 0.84). CONCLUSION: Urine NAG/Cr may be a useful biomarker predicting pathologically upstaged RCC. Clinicians should be prudent in making management decisions when a large RCC is accompanied by an increased urine NAG/Cr.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Riñón/patología , Creatinina , Biomarcadores/orinaRESUMEN
Background: Previous studies using the Vesical Imaging Reporting and Data System (VI-RADS) to predict muscle-invasive bladder cancer (MIBC) had some limitations. Most studies were performed with transurethral resection of bladder tumor (TUR-BT) specimens with few samples. This study was conducted to address these shortcomings and confirm the accuracy of VI-RADS for bladder cancer. Methods: This study used data from the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Radical Cystectomy (SUPER-UC-Cx). Patients who underwent multiparametric magnetic resonance imaging (mp-MRI) before radical cystectomy (RC) were included in this study between March 2020 and March 2022. All images were reported by radiologists and reviewed by two urologists. The patient characteristics and clinical information were blinded during the review. The performance of qualitative and quantitative variables in predicting muscle layer invasion or perivesical fat infiltration was verified by receiver operating characteristic (ROC) curve analysis. Results: Of 208 patients, 182 (87.5%) underwent mp-MRI before RC. Twenty-three patients with non-urothelial carcinoma, inappropriate MRI scans, and bladder filling were excluded. Cut-off for muscle invasion, VI-RADS score of 4 had the highest area under the curve (AUC) (sensitivity 0.84; specificity 0.93; accuracy 0.90; positive predictive value (PPV) 0.84; negative predictive value (NPV) 0.93, and AUC 0.88). Cut-off for perivesical fat invasion and VI-RADS score of 5 had the highest AUC (sensitivity, 0.78; specificity, 0.99; accuracy, 0.95; PPV, 0.96; NPV, 0.95; and AUC, 0.89). Conclusions: VI-RADS is a good predictor of bladder cancer staging before RC and is especially helpful in predicting muscle invasion and perivesical fat infiltration.
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BACKGROUND: Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. METHODS: This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients' pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. RESULTS: Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2 cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5 min and the estimated blood loss was 100 cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. CONCLUSIONS: The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. TRIAL REGISTRATION: Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371).
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Carcinoma de Células Renales , Fallo Renal Crónico , Neoplasias Renales , Masculino , Femenino , Humanos , Anciano , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Estudios Prospectivos , Nefrectomía , Fallo Renal Crónico/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: To assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients. METHODS: We examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included. RESULTS: Among 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25, p < 0.001), high Fuhrman grade (grade 3-4) (41.7% vs. 55.6%, p < 0.001), and high T stage (T stage 3-4) (9.0% vs. 20.1%, p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5-7) (hazard ratio [HR] 11.9, p < 0.001) and SSIGN (8-10) (HR 69.2, p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75, p = 0.065) showed borderline significance. Kaplan-Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached, p < 0.001). CONCLUSIONS: Among unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Neoplasias Renales/patología , Nefrectomía , Riñón/diagnóstico por imagen , Riñón/fisiología , Riñón/patología , Pronóstico , Ácido Pentético , Estadificación de NeoplasiasRESUMEN
PURPOSE: This study aimed to compare the functional and oncological outcomes of females who underwent uterus-sparing radical cystectomy (USRC) and standard radical cystectomy (SRC). MATERIALS AND METHODS: Between February 2009 and December 2020, 90 female patients who underwent radical cystectomy with urinary diversion were included in this study, comprising the USRC and SRC groups. Functional outcomes were assessed in 63 patients who only underwent radical cystectomy with neobladder formation. Questionnaire scores, clean intermittent catheterization (CIC) rate, and urinary continence rate were analyzed. Oncological outcomes were assessed in 86 patients, regardless of the urinary diversion type. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared. RESULTS: CIC rate was significantly lower in the USRC group than in the SRC group (14.7% vs. 48.0%; p=0.005). The continence rate was significantly higher in the USRC group than in the SRC group (85.3% vs. 40.0%; p=0.001). There were no significant differences in OS (p=0.890), CSS (p=0.700), or RFS (p=0.270) between the two groups. In multivariate analysis, uterine preservation did not significantly increase the hazard ratio (HR) of OS (HR, 0.62; 95% CI, 0.18-2.11; p=0.450), CSS (HR, 0.99; 95% CI, 0.22-4.40; p=0.990), or RFS (HR, 0.46; 95% CI, 0.19-1.11; p=0.840). CONCLUSIONS: USRC resulted in higher continence rates and lower CIC rates than SRC without negatively affecting oncological outcomes. Hence, with thorough deliberation, USRC should be considered for females undergoing radical cystectomy.
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Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Femenino , Cistectomía/efectos adversos , Cistectomía/métodos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Resultado del Tratamiento , ÚteroRESUMEN
Upper tract urothelial carcinoma (UTUC) occurs in urothelial cells from the kidney and the ureters. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker for pancreatic and gastrointestinal cancers, and its high levels are associated with poor prognosis in bladder cancer. In this study, prospective patients enrolled in the registry of Seoul National University were retrospectively examined to determine the clinical significance of CA 19-9 in UTUC. In 227 patients, high serum CA 19-9 levels reflected a high tumor burden represented by high T and N stages, leading to adverse prognosis in metastasis-free or overall survival. Subsequently, propensity score matching analysis showed that the CA 19-9 level is an independent prognostic factor of UTUC.
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BACKGROUND: Non-muscle invasive bladder cancer can be controlled by transurethral resection of bladder (TURB), but suffers from frequent recurrences in 60-70% of cases. Although, recurrence interval after TURB influences treatment course and prognosis, its implication and risk factors have not been fully elucidated. We evaluated the risk factors of early (within 1 yr) and late (after 1 yr) recurrence of pTa bladder cancer and clinical significance of recurrence interval on disease progression and overall survival. METHODS: In this study, pTa bladder cancer patients enrolled in prospective patient registry system of Seoul National University, SUPER-UC, were retrospectively examined to determine the clinical risk factors for recurrence and its significance regarding to recurrence interval. A total of 1067 bladder cancer patients who underwent TURB between March 20 and June 2021 were included and classified into three groups of no recurrence, early, or late recurrence to be comparatively analyzed. RESULTS: Early recurrence was associated with poorer cystectomy-free survival and overall survival than late recurrence. Risk factors for early recurrence included a high number of previous TURB, tumor multiplicity, tumor location, tumor shape, incompleteness of TURB, and high tumor grade. Otherwise, late recurrence was associated with low-grade tumors with insufficient TURB depth. CONCLUSION: Patients with risk factors for early recurrence should be closely followed up with special cautions.
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Neoplasias de la Vejiga Urinaria , Cistectomía , Humanos , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: To demonstrate the safety and feasibility of synchronous unilateral nephrectomy and contralateral heminephrectomy in extremely severe autosomal dominant polycystic kidney disease (ADPKD), which corresponds to the Mayo imaging classification classes 1D and 1E. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent unilateral nephrectomy and contralateral heminephrectomy at the Seoul National University Hospital (Seoul, Korea) between May 1, 2016 and August 1, 2021. The preoperative kidney volume was calculated using the ellipsoid equation (length×width×thickness×π/6). The Mayo imaging classification was determined by height-adjusted total kidney volume and age. Using a midline vertical incision, heminephrectomy was performed first by horizontal transection, followed by contralateral nephrectomy. Hilar vessel clamping or resection-bed suturing was not required. RESULTS: In all, nine patients with ADPKD of the highest severity (Mayo class 1D/1E) underwent unilateral heminephrectomy and contralateral nephrectomy for the most common cause of severe abdominal discomfort and malnutrition. All nine patients had end-stage renal disease with hypertension and anemia. The median preoperative total kidney volume was 10,905.8 mL (interquartile range [IQR], 8,170.4-16,227.6 mL). The median operation time was 140 minutes (IQR, 125-185 min) and the median estimated blood loss was 250 mL (IQR, 200-425 mL). Eight of the nine patients were discharged without ICU care or any complications. Delayed pseudoaneurysm occurred in one case and was successfully managed by embolization. All patients were symptom-free for a median follow-up period of 2 years. CONCLUSIONS: Synchronous unilateral nephrectomy and contralateral heminephrectomy are safe and feasible treatment options for severe bilateral ADPKD.
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Riñón Poliquístico Autosómico Dominante , Estudios de Factibilidad , Femenino , Humanos , Riñón/cirugía , Masculino , Nefrectomía/efectos adversos , Nefrectomía/métodos , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the ability of the G8 assessment to predict postoperative complications in older adults undergoing major uro-oncologic surgery in comparison with the Charlson Comorbidity Index (CCI). MATERIALS AND METHODS: The study included patients ≥65 years old who underwent major uro-oncologic surgery between December 2017 and December 2019 and were enrolled in the Seoul National University Prospectively Enrolled Registry for Genitourinary Cancer (SUPER-GUC). Odds ratio (OR) smoothing was used to visualize risk according to G8 scores. Chi-square tests were used to compare postoperative complication rates according to G8 score or CCI category. RESULTS: A total of 657 patients undergoing radical prostatectomies (n = 372, 56.6%), partial/radical nephrectomies (n = 149, 22.7%), radical cystectomies (n = 76, 11.6%), and nephroureterectomies (n = 60, 9.1%) were included. Complication rates did not significantly differ between patients with CCI scores ≥1 and those with CCI scores of 0 (15.0% vs. 12.4%, p = 0.34). However, the complication rate was significantly higher in patients with G8 scores ≤14 than in those with G8 scores >14 (18.1% vs. 10.5%, p = 0.005). When the OR smoothing curve was used to divide patients into three groups based on G8 scores of <10, 10-14, and > 14, we observed significant differences in complication rates among the groups (37.5% vs. 16.9%. vs. 10.5%; p = 0.001). CONCLUSION: The G8 can aid in predicting postoperative complications in patients ≥65 years old. Comprehensive geriatric assessment is warranted in patients with G8 scores ≤14 prior to major uro-oncologic surgery. Older patients with G8 scores <10 should be counseled regarding the very high risk of surgery.
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Cistectomía , Evaluación Geriátrica , Anciano , Comorbilidad , Cistectomía/efectos adversos , Humanos , Masculino , Oncología Médica , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: We aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods. MATERIALS AND METHODS: Label-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer. RESULTS: Comparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology. CONCLUSION: The results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Biomarcadores de Tumor/metabolismo , Humanos , Proteómica/métodos , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
INTRODUCTION: We investigated the efficacy of a urethral catheter alone for intraperitoneal perforation during transurethral resection of bladder tumor (TURBT). PATIENTS AND METHODS: We retrospectively evaluated the medical records of 4,543 patients who underwent TURBT from January 2000 to December 2017 using the Clinical Data Warehouse system. The clinicopathologic characteristics, recurrence-free survival, and progression-free survival were compared between the patient groups with intraperitoneal perforation treated with the Foley catheter alone, extraperitoneal perforation, and matched control TURBT. RESULTS: Intraperitoneal perforation and extraperitoneal perforation were observed in 16 (35.6%) and 29 (64.4%) patients, respectively. In the intraperitoneal perforation group, 11 (68.8%), 2 (12.5%), and 3 (18.8%) patients were treated with the Foley catheter alone, additional percutaneous drainage, and delayed open surgery, respectively. The use of the Foley catheter alone in patients with intraperitoneal perforation of smaller size than the cystoscope or no pelvic radiotherapy history showed improved efficacy without sequelae or therapeutic delay. One of the 2 patients with the size of the intraperitoneal perforation larger than the cystoscope was successfully treated with the Foley catheter alone, whereas the other patient underwent delayed surgical repair. There was no difference in recurrence-free survival and progression-free survival of the intraperitoneal perforation treated with the Foley catheter alone compared to those of the matched control TURBT (p = 0.909, p = 0.518) and the extraperitoneal perforation (p = 0.458, p = 0.699). CONCLUSIONS: Intraperitoneal perforation rarely occurred during TURBT. In the case of intraperitoneal perforation of size smaller than cystoscopy or without pelvic radiotherapy history, treatment with the Foley alone showed successful improvement and safe oncological results. Therefore, treatment with the urethral catheter alone can be carefully considered when an intraperitoneal perforation smaller than the cystoscope size or without pelvic radiotherapy history occurs.
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Cistectomía/métodos , Complicaciones Intraoperatorias/terapia , Neoplasias de la Vejiga Urinaria/cirugía , Vejiga Urinaria/lesiones , Cateterismo Urinario , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peritoneo , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Preoperative renal function is associated with worse outcomes in patients undergoing radical nephroureterectomy (RNU). The purpose of this systemic review and meta-analysis was to determine the association of preoperative renal function with oncological outcome in patients who underwent RNU. We searched articles published up to March 2021 in PubMed, Scopus, and Embase by combining "urothelial carcinoma", "radical nephroureterectomy", and "estimated glomerular filtration rate". We also manually screened the reference list for publications following general guidelines recommended by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The relationship between preoperative renal function and survival was expressed as overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). This review and meta-analysis included 13 studies involving a total of 4668 patients who received RNU. Pooled analysis showed significant negative association of preoperative renal function with PFS (HR: 1.51, 95% CI: 1.23-1.80, p < 0.00001), CSS (HR: 1.63, 95% CI: 1.38-1.92, p < 0.00001), and OS (HR: 1.22, 95% CI: 1.10-1.35, p < 0.00001). Patients with upper tract urothelial carcinoma (UTUC) who received RNU showed a significant negative association of preoperative renal function with survival.
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This study aims to investigate the clinical role of preoperative pyuria for predicting bacillus Calmette-Guérin (BCG) unresponsiveness in non-muscle invasive bladder cancer (NMIBC). We performed a logistic regression analysis on 453 patients with NMIBC who were treated with BCG immunotherapy after a transurethral resection of bladder tumours, to evaluate predictive factors of BCG unresponsiveness. We also analysed univariate and multivariable survival data to estimate the prognostic impact of pyuria. Of the total study population, 37.6% (170/453) of patients had BCG unresponsiveness. A multivariable logistic regression analysis revealed that a history of upper urinary tract cancer (odds ratio (OR): 1.86, 95% confidence interval (CI): 1.04-3.32, p-value = 0.035) and the presence of pyuria (OR: 1.51, 95% CI: 1.01-2.27, p = 0.047) and tumour multiplicity (OR: 1.80, 95% CI: 1.18-2.75, p-value < 0.001) were significant predictors of BCG unresponsiveness. A Cox proportional hazards analysis model showed that pyuria was a significant prognostic factor for progression-free survival (hazard ratio: 4.51, 95% CI: 1.22-16.66, p = 0.024). A history of upper urinary tract cancer and the presence of pyuria and tumour multiplicity are predictive markers of BCG unresponsiveness. For patients with NMIBC who have preoperative pyuria, treatment using BCG should be considered cautiously.
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We evaluated the expression of PDLIM2 in human kidney cancer cell lines from primary or metastatic origins and found that PDLIM2 expression was highly elevated in metastatic kidney cancers. We evaluated the effect of PDLIM2 inhibition by RNA interference method. PDLIM2 knockdown showed the decreased proliferation and metastatic character in human metastatic kidney cancer cells. By repeated round of orthotopic injection of RenCa mouse kidney cancer cell line, we obtained metastatic prone mouse kidney cancer cell lines. PDLIM2 expression was highly expressed in these metastatic prone cells comparing parental cells. In addition, we evaluated the in vivo efficacy of PDLIM2 knockout on the tumor formation and metastasis of kidney cancer cells using a PDLIM2 knockout mice. The experimental metastasis model with tail vein injection and orthotopic metastasis model injected into kidney all showed reduced lung metastasis cancer formation in PDLIM2 knockout mice comparing control Balb/c mice. Overall, our findings indicate that PDLIM2 is required for cancer formation and metastasis in metastatic kidney cancer, indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer.
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PURPOSE: The current stratification of risk groups regarding recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) is problematic. We aimed to assess the long-term outcome and risk of multiple, recurrent, and large (≥3 cm) Ta, G1/G2 tumors after transurethral resection of the bladder tumor (TURBT). MATERIALS AND METHODS: We categorized 1,621 patients with NMIBC who underwent TURBT into four risk groups according to the European Association of Urology (EAU) guidelines as follows: low-risk, intermediate-risk, high-risk, and study group. The overall, cancer-specific, disease recurrence-free, and disease progression-free survival rates were estimated by using the Kaplan-Meier method. Then, the impact of risk group was assessed by using a multivariable Cox regression model. RESULTS: The study group comprised 52 patients (3.2%) within a mean follow-up of 64.8 months. The disease recurred and progressed in 41 (78.8%) and 7 (13.5%) patients, respectively. Among the four groups, the study group showed the highest risk for 10-year recurrence after TURBT. The disease progression risk in the study group was between that of the intermediate- and high-risk groups. Cancer-specific and all-cause deaths occurred in one and four patients in the study group, respectively. The study group had a higher risk for disease recurrence than did the high-risk group; however, it did not have a higher risk for disease progression than in the high-risk group. CONCLUSIONS: Multiple, recurrent, and large (≥3 cm) Ta, G1/G2 tumors carry a higher risk for disease recurrence, but not progression, than in the EAU high-risk group of NMIBC.
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Carcinoma de Células Transicionales/patología , Progresión de la Enfermedad , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Neoplasias de la Vejiga Urinaria/patología , Adyuvantes Inmunológicos/uso terapéutico , Anciano , Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mialgia/patología , Estadificación de Neoplasias , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Medición de Riesgo/métodos , Tasa de Supervivencia , Carga Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
PURPOSE: To evaluate the clinical impact of strict selection criteria for active surveillance (AS) of prostate cancer in a Korean population. MATERIALS AND METHODS: A single-center, prospectively collected AS cohort from December 2016 to February 2019 was used. Following pre-determined criteria, patients were categorized into "strict AS" and "non-strict AS" groups. Clinicopathological progression-free survival (PFS) and treatment-free survival (TFS) of the two groups were compared using the Kaplan-Meier curve and log-rank test. Age-adjusted hazard ratios for clinicopathological progression was calculated using Cox proportional regression analysis. RESULTS: Of 54 eligible patients, 25 and 29 were assigned to "strict AS" and "non-strict AS," respectively. Clinicopathological progression and definitive treatment rates were 24.0% (6 of 25 patients) vs. 51.7% (15 of 29 patients) and 32.0% (8 of 25 patients) vs. 62.1% (18 of 29 patients) in "strict AS" and "non-strict AS" groups. Progress to high-risk cancer (pathologic T3 or surgical Gleason Grade 2 over) in radical prostatectomy was higher in "non-strict AS" than "strict AS". PFS (mean 34.6±2.9 mo vs. 22.6±2.7 mo; p=0.025) and TFS (mean 31.8±3.2 mo vs. 19.6±2.4 mo; p=0.018) favor the "strict AS" group than "non-strict AS" group. Age-adjusted hazard ratio for clinicopathological progression of strict criteria was 0.36 (95% confidence interval, 0.14-0.94; p=0.04). CONCLUSIONS: PFS and TFS were better in the "strict AS" group than in the "non-strict AS" group. This finding should be informed to relevant patients during decision making and considered in Korean guidelines.
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Selección de Paciente , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Espera Vigilante , Anciano , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Prostatectomía , República de Corea , Medición de RiesgoRESUMEN
Several studies founded that preoperative renal insufficiency is associated with a higher risk of upper tract urothelial carcinoma recurrence and mortality than normal renal function patients. However, previous studies were all retrospective; no study focused on urothelial carcinoma in the bladder and metastasis-free survival (MFS). Herein, we examined the prognostic impact of preoperative renal insufficiency on the oncologic outcomes of patients with urothelial carcinoma in the bladder after radical cystectomy. We used data from 262 patients prospectively collected from a radical cystectomy cohort between March 2016 and February 2021. The patients were divided into those with a preoperative glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 (renal insufficiency; n=66) and those with a GFR ≥60 mL/min/1.73 m2 (control; n=196). We investigated MFS, cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier curves and Cox proportional hazard regression were used to estimate the prognostic impact of renal insufficiency. The mean MFS was significantly shorter in the renal insufficiency group than in the control group (36.58±3.09 months vs. 47.37±1.87 months); however, OS and CSS were not significantly different. T stage ≥3 (hazard ratio [HR]: 2.79), lymph node positivity (HR: 2.261), and renal insufficiency (HR: 2.04) were significant independent predictors of MFS. Preoperative renal insufficiency was an independent prognostic factor for worse MFS. Well-designed randomized clinical trials and translational studies are needed to clarify the mechanism of relationship between preoperative renal insufficiency and MFS.