urinary tract urothelial carcinoma
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2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Yuto Matsushita ◽  
Yuji Iwashita ◽  
Shunsuke Ohtsuka ◽  
Ippei Ohnishi ◽  
Takashi Yamashita ◽  
...  

Abstract Background DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. Method To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. Results C5-Methyl-2′-deoxycytidine, C5-hydroxymethyl-2′-deoxycytidine (5hmdC), C5-formyl-2′-deoxycytidine, 2′-deoxyinosine, C8-oxo-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman’s rank correlation test revealed a negative correlation between age and 5hmdC levels (r = − 0.46, p = 0.018 and r = − 0.45, p = 0.042, respectively). Conclusions The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0255965
Author(s):  
Sung Han Kim ◽  
Mi Kyung Song ◽  
Ja Hyeon Ku ◽  
Seok Ho Kang ◽  
Byong Chang Jeong ◽  
...  

Background Upper urinary tract urothelial carcinomas are relatively rare and have a cancer-specific survival rate of 20%–30%. The current gold standard treatment for nonmetastatic high-grade urinary tract urothelial carcinoma is radical nephroureterectomy with bladder cuff resection. Objective This study aimed to compare conditional cancer-specific survival between open radical nephroureterectomy and laparoscopic radical nephroureterectomy in patients with nonmetastatic stage pT3-4 or TxN(+) locally advanced urinary tract urothelial carcinoma from five tertiary centers. Methods The medical records of 723 patients were retrospectively reviewed. The patients had locally advanced and nodal staged tumors and had undergone open radical nephroureterectomy (n = 388) or laparoscopic radical nephroureterectomy (n = 260) at five tertiary Korean institutions from January 2000 and December 2012. To control for heterogenic baseline differences between the two modalities, propensity score matching and subgroup analysis were conducted. Conditional survival analysis was also conducted to determine survival outcome and to overcome differences in follow-up duration between the groups. Results During the median 50.8-month follow up, 255 deaths occurred. In univariate analysis, significant factors affecting cancer-specific survival (e.g., age, history of bladder cancer, American Society of Anesthesiologists score, pathological N stage, and presence of lymphovascular invasion and carcinoma in situ) differed in each subsequent year. The cancer-specific survival between patients treated with open radical nephroureterectomy and laparoscopic radical nephroureterectomy was not different between patients with and without a history of bladder cancer. After adjusting baseline differences between the two groups by using propensity score matching, both groups still had no significant differences in cancer-specific survival. Conclusion The two surgical modalities showed no significant differences in the 5-year cancer-specific survival in patients with locally advanced urinary tract urothelial carcinoma.


2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Fan ◽  
Yuanbin Huang ◽  
Shuang Wen ◽  
Qiliang Teng ◽  
Xinrui Yang ◽  
...  

BackgroundUpper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.MethodsWe first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.ResultsFirstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan–Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).ConclusionsPreoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.


2021 ◽  
Vol 10 (19) ◽  
pp. 4474
Author(s):  
Cheng-Ju Ho ◽  
Yu-Hui Huang ◽  
Tzuo-Yi Hsieh ◽  
Min-Hsin Yang ◽  
Shao-Chuan Wang ◽  
...  

Background: Upper urinary tract urothelial carcinoma (UTUC) is the most common malignancy occurring after kidney transplantation (KT) in Taiwan. The aim of this study was to investigate the association between native kidney hydronephrosis and UTUC in post-KT patients. Methods: From 2003 to 2018, we conducted a retrospective cohort study that enrolled 1005 post-KT patients, 67 of whom were subsequently diagnosed with UTUC. We divided patients into two groups based on whether or not they had UTUC. Multivariate analysis and Kaplan-Meier plot were used to evaluate if native kidney hydronephrosis was associated with post-KT UTUC. Results: The total cohort consisted of 612 men (60.9%) and 393 women (39.1%) with a mean age of 48.2 ± 12.0 at KT. The mean follow-up time was 118.6 ± 70.2 months, and mean time from KT to UTUC was 7.53 years. There was a significant gender difference with a female predominance among the UTUC patients (73.1% versus 26.9%, p < 0.001). Native kidney hydronephrosis occurred more frequently in the UTUC group (68.7% versus 4.8%, p < 0.001). Multivariate analysis showed that native kidney hydronephrosis and female gender were significantly associated with UTUC with odds ratios of 35.32 (95% CI, 17.99–69.36; p < 0.001) and 3.37 (95% CI, 1.55–7.29; p = 0.002), respectively. UTUC in the post-KT patients also showed aggressive pathological characteristics and a tendency toward bilateral lesions (41.8%). Conclusions: Native kidney hydronephrosis is significantly associated with post-KT UTUC patients in Taiwan. Native kidney hydronephrosis may be a deciding factor for standard nephroureterectomy and bladder cuff excision in selected patients. Nevertheless, almost half of the patients with kidney hydronephrosis do not present with UTUC at the end of our study.


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