scholarly journals Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations

2021 ◽  
Vol 11 (11) ◽  
pp. 1147
Author(s):  
Ekaterina Laukhtina ◽  
Ursula Lemberger ◽  
Andreas Bruchbacher ◽  
Dafina Ilijazi ◽  
Stephan Korn ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Expression ◽  
Urothelial Carcinoma ◽  
Clinical Decision Making ◽  
Histone Methyltransferase ◽  
Tumor Location ◽  
Upper Tract Urothelial Carcinoma ◽  
Survival Outcomes ◽  
Upper Tract ◽  
Mutational Status

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.

scholarly journals Bladder Recurrence Following the Treatment of Upper Tract Urothelial Carcinoma

2021 ◽  
Author(s):  
Takarn Itsaranujareankul ◽  
Kanrapee Nuwatkrisin ◽  
Kamol Panumatrassamee ◽  
Dutsadee Sowanthip ◽  
Julin Opanuraks ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Tumor Location ◽  
Upper Tract Urothelial Carcinoma ◽  
P Value ◽  
Distal Ureter ◽  
Upper Tract ◽  
History Of ◽  
The Mean ◽  
Bladder Recurrence

Objective: Although, upper tract urothelial carcinoma (UTUC) is rare it is associated with a high mortality rate and frequently, followed by bladder recurrence after radical surgery. Hence, this study aimed to identify the rate of bladder recurrence and its predictive factors.Material and Methods: We reviewed the medical records of 104 patients, who were diagnosed with UTUC and had radical nephroureterectomy (RNU), at the King Chulalongkorn Memorial Hospital. We excluded patients who have concurrent bladder cancer, or had a history of bladder cancer. Various clinicopathological factors were analyzed using the log-rank test and Cox proportional hazard model.Results: The mean age at diagnosis of UTUC was 68 years, and one-third of the patients were diagnosed with pathological T3 (33.7%). The mean follow-up duration was 56 months. Bladder recurrence occurred in 39 out of 104 patients (37.5%), and the median time to recurrence was 5.8 months (interquartile range 3.6 to 11.0 months). Tumor location in the distal ureter (p-value=0.038) and history of diagnostic ureteroscopy (p-value=0.004) were significantly associated with bladder recurrence in the univariate model. However, only the history of diagnostic ureteroscopy remained significant in the multivariate analysis (p-value=0.023).Conclusion: Bladder recurrence, following RNU, occurs in one-third of patients. Potential predictive factors may include history of diagnostic ureteroscopy, and the tumor location being in the distal ureter.

Survival outcomes for patients with localised upper tract urothelial carcinoma managed with non-definitive treatment

2017 ◽  
Vol 121 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Jamil S. Syed ◽  
Kevin A. Nguyen ◽  
Alfredo Suarez-Sarmiento ◽  
Katelyn Johnson ◽  
Michael S. Leapman ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Definitive Treatment ◽  
Survival Outcomes ◽  
Upper Tract

Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population‐based analysis

2020 ◽  
Vol 27 (11) ◽  
pp. 966-972 ◽  
Author(s):  
Alessandro Veccia ◽  
Alessandro Antonelli ◽  
Alberto Martini ◽  
Ugo Falagario ◽  
Giuseppe Carrieri ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Population Based ◽  
Upper Tract Urothelial Carcinoma ◽  
Survival Outcomes ◽  
Upper Tract

scholarly journals Risk factors and survival outcomes of metachronous contralateral upper tract urothelial carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kan Wu ◽  
Jiayu Liang ◽  
Yiping Lu
Keyword(s):  
Risk Factors ◽  
Bladder Cancer ◽  
Regression Model ◽  
Urothelial Carcinoma ◽  
Large Population ◽  
Multivariable Analysis ◽  
Population Based ◽  
Upper Tract Urothelial Carcinoma ◽  
Competing Risk ◽  
Upper Tract

Abstract Because population-based risk estimates for metachronous contralateral UTUC are lacking. In this study, we aimed to evaluate the risk and survival of metachronous contralateral upper tract urothelial carcinoma (UTUC) on a large population-based level. A total of 23,075 patients were identified from the Surveillance, Epidemiology, and End Results database (1973–2015), 144 (0.6%) patients developed metachronous contralateral UTUC (median of 32 months after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.1%, 1.6%, and 2.6%, respectively. We applied Fine and Gray’s competing risk regression model to determine the risk factors of a new contralateral, metachronous UTUC. The competing risk regression model demonstrated that older age (hazard ratio [HR] 0.75; 95% CI 0.67–0.85) and larger tumor size (HR 0.61; 95% CI 0.39–0.97) were associated with a significantly decreased risk of metachronous contralateral UTUC. However, bladder cancer presence was an independent risk factor for the development of contralateral tumors (HR 2.42; 95% CI 1.73–3.37). In addition, we demonstrated developing contralateral UTUC was not associated with poor prognosis by using Kaplan–Meier and multivariable analysis. Our findings suggest that metachronous contralateral UTUC is comparatively rare, and has not impact on survival. Importantly, patients with younger age, small tumours, and the presence of bladder cancer were more likely to develop a contralateral tumor, which may provide a rationale for lifelong surveillance in high-risk patients.

Impact of Tumor Location on Prognosis for Patients with Upper Tract Urothelial Carcinoma Managed by Radical Nephroureterectomy

2010 ◽  
Vol 57 (6) ◽  
pp. 1072-1079 ◽  
Author(s):  
Jay D. Raman ◽  
Casey K. Ng ◽  
Douglas S. Scherr ◽  
Vitaly Margulis ◽  
Yair Lotan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Location ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Upper Tract

Risk factors for bladder cancer recurrence survival in patients with upper-tract urothelial carcinoma

2018 ◽  
Vol 104 (6) ◽  
pp. 451-458 ◽  
Author(s):  
Yu-Peng Wu ◽  
Yun-Zhi Lin ◽  
Min-Yi Lin ◽  
Ting-Ting Lin ◽  
Shao-Hao Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards Model ◽  
Upper Tract Urothelial Carcinoma ◽  
Intravesical Therapy ◽  
Low Grade ◽  
High Grade ◽  
Upper Tract ◽  
Bladder Cancer Recurrence

Purpose: The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC). Methods: We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS. Results: In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016). Conclusions: Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.

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