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.

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Urine cytology is a common clinical method for the early diagnosis of urologic neoplasms. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence 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. Methods: In this retrospective case-control study, we first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 142 patients with UUT-UC after radical nephroureterectomy (RNU). A nomogram model was established and we evaluated its effectiveness. Subsequently, after searching several databases, including PubMed, Embase, and Ovid, we quantitatively combined our results with the published data in a meta-analysis. Results: Our case-control study demonstrated that patients with muscle-invasive tumors (T2-T4) were more prone to preoperative positive urine cytology than those with non-muscle-invasive tumors (Tis-T1), suggesting that preoperative positive urine cytology may be associated with the aggressive form of UUT-UC. Kaplan-Meier curves demonstrated that the patients with positive urine cytology had significantly poorer intravesical recurrence-free survival (IV-RFS). Additionally, preoperative urine cytology (hazard ratio, HR=3.24) and lymph node status (HR=2.67) were validated as significant independent predictors of intravesical recurrence by multivariate analysis. Nomogram, calibration plots, AUC values and the C-index demonstrated that the predictive accuracy was significantly improved when preoperative urine cytology was combined. Subsequently, adding to our study, 11 eligible articles from 2010 to 2016 containing 2942 patients were sifted out for our meta-analysis. Overall analysis showed that preoperative positive urine cytology was associated with a 56% increased risk of intravesical recurrence (HR=1.56). In the subgroup analysis by region, study type, and sample size, the pooled HR was statistically significant for the Japan subgroup (HR=1.45), China subgroup (HR=1.66), cohort study subgroup (HR=1.44), and case-control study subgroup (HR=1.77), the subgroup with sample size greater than or equal to 100 (HR=1.42), and the subgroup with sample size less than 100 (HR=2.95). Conclusions: Preoperative urine cytology significantly correlated with intravesical recurrence in patients with UUT-UC after RNU, although these results need to be interpreted with caution. Large, prospective trials are required to further confirm its prognostic significance.