Background Primary malignant melanoma of the ureter is extremely rare. Genetic variants to the increased risk of developing the disease have not yet been investigated. Methods Tumour mutation profiling for primary malignant melanoma of the ureter was performed by whole-exome sequencing. Immunohistochemistry was performed to verify histopathological features and the variants of predisposing genes and driver mutation genes. Furthermore, we conducted a literature review and Surveillance, Epidemiology and End Result-based study by searching public databases. Results We identified 38 somatic single nucleotide variants and 9 somatic insertions and deletions (INDELs) in tumour specimens. After filtering with the Cancer Gene Census database, seven predisposing genes and two driver mutation genes were identified. Moreover, the immunohistochemical profile showed that tumour cells were positive for Melan-A, melanoma gp100 human melanoma black 45 (HMB45), S100 beta and P53. The expression levels of two driver mutation genes (phosphatase and tensin homolog (PTEN) and desmoyokin (AHNAK) and five predisposing genes (AT-rich interaction domain 1B (ARID1B), catalase, eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), ANK3 and collagen type I) were significantly downregulated in tumour tissues compared to paracancerous tissues. In the literature review and Surveillance, Epidemiology and End Results-based study, patients with primary malignant melanoma of the urinary tract had worse clinical outcomes than patients with primary urothelial carcinoma after 1:2 propensity score matching (P = 0.010). Additionally, Cox multivariate analysis for patients with primary malignant melanoma of the urinary tract indicated that distant metastasis (hazard ratio = 1.185; P = 0.044) was an independent predictor for overall survival, and tumour focality (hazard ratio = 0.602; P = 0.017) and non-surgery (hazard ratio = 0.434; P = 0.003) were independent factors for tumour progression. Conclusions Our study is the first to provide evidence that the distinct phenotypes of primary malignant melanoma of the ureter may be due to different genetic variations. The prognosis of primary malignant melanoma of the urinary tract was poorer than that of primary urothelial carcinoma of the urinary tract.

carcinogenesis of primary LELC may be due to different genetic variations, including single-nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT-UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this.

Objective. Upper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%–50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted. Here, we aimed at evaluating the efficacy of intravesical instillation for the prevention intravesical recurrence systematically. Methods. In this retrospective cohort study, from October 2006 to September 2017, 158 UUT-UC patients underwent RNU were divided into 4 groups: epirubicin (EPB) instillation group, hydroxycamptothecin (HCPT) instillation group, bacillus Calmette–Guerin (BCG) instillation group, and noninstillation group. Cox univariate and multivariate analyses were employed to identify the risk factors for intravesical recurrence-free survival (IVRFS). The nomogram model was also applied to predict patient outcomes. Subsequently, to evaluate the clinical significance of intravesical instillation comprehensively, several databases including PubMed, Ovid, and Embase were searched and data from published studies with our results were combined by direct meta-analysis. Moreover, a network meta-analysis comparing instillation therapies was conducted to evaluate the clinical efficacy of different instillation drugs. Results. In our retrospective cohort study, the Kaplan–Meier survival curve demonstrated noninstillation groups were associated with worsened IVRFS. Meanwhile, multivariate analysis indicated that intravesical instillation was independent protective factors for IVRFS (hazard ratio [HR] = 0.731). Moreover, calibration plots, receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and the C-index showed the priority of nomogram’s predictive accuracy. Next, direct meta-analysis including 19 studies showed that intravesical instillation could prevent the recurrence of bladder cancer with a pooled risk ratio (RR) estimate of 0.53. Subgroup analysis by study type, year of intravesical recurrence, first instillation time, and instillation times also confirmed the robustness of the results. Moreover, intraoperative instillation was associated with a decrease in the risk of bladder recurrence compared with postoperative instillation. Then, a network meta-analysis including 7 studies indicated that pirarubicin (THP) (surface under the cumulative ranking curve [SUCRA] = 89.2%) is the most effective therapy to reduce the risk of bladder recurrence, followed by BCG (SUCRA = 83.5%), mitomycin C (MMC) (SUCRA = 53.6%), EPB (SUCRA = 52.6%), and HCPT (SUCRA = 5.1%) after the analysis of the value ranking. Conclusions. A maintenance schedule of intravesical instillation prevents the recurrence of bladder cancer after RNU in UUT-UC patients effectively. Large, prospective trials are needed to further confirm its value. Compared with other chemotherapy regimens, THP may be a promising drug with favorable efficacy to prevent bladder recurrence. As included studies had moderate risk of bias, the results of network meta-analysis should be applied with caution.

To get a better understanding of the genetic basis of primary signet ring cell carcinoma (SRCC) of the bladder, which is highly rare and not yet explored. First, by using immunohistochemistry to find histological pathological characteristics.Second, a massively parallel whole-exome sequencing (WES) was performed on a 58-year-old male patient who had painless macroscopic hematuria and was pathologically diagnosed with primary SRCC of the bladder, followed by comparing with genes of ordinary urothelial cancer (UC) from TCGA. Furthermore, a population-based analysis using the SEER database was performed to investigate the prognosis (SRCC vs. UC). We identified 63 copy number variations (CNVs) with gain counts and 181 CNVs with loss counts. Totally 4515 mutations were discovered in C > T with a success rate of greater than 89%. The most frequently mutated pathway was RTK-RAS which has 85 genes involved in carcinogenic signaling. Final screening on predisposing genes is performed after filtering based on ACMG. Moreover, several driver genes, including NBN, KCTD18, SPATA13, ANKRD36, OR2L5, MALRD1, and LSMEM1, were detected. Sanger sequencing of germline DNA revealed the presence of a mutant base A/G of OR2L5 in the sequence, which was discovered for the first time in primary SRCC of the bladder. Furthermore, the immunohistochemical profile showed that primary SRCC of the bladder were positive for CK7, CK20, GATA-3, and expression of CK(AE1/ AE2), EMA, and Ki67. In the SEER-based study, the patients with primary SRCC of the bladder got a worse prognosis compared to those with UC with median months overall survival (OS) 14 vs. 41, respectively, P = 0001, even after adjusting the variables in the Cox regression model, the SRCC of the bladder showed worse survival HR = 1.119, 95% CI = (1.081-1.328), P = 0.0001. These results imply that suppression of potential driver mutations may be a viable adjuvant treatment

Background Aspirin, widely used for the prevention of cardiovascular disease, could reduce the risk of many types of cancer, including colorectal, breast, and pancreatic cancer. Concerns have also been linked to bladder cancer(BCa), but relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. Meanwhile, existing studies focusing on Chinese populations are relatively uncommon, especially for Northeast China. Therefore, this study aims to assess the association of aspirin use with the occurrence and prognosis of BCa in Northeast China. Methods First, we investigated the association between aspirin use and BCa risk in a retrospective cohort study including 1087 patients with BCa from 2002 to 2019 and 1100 healthy persons in the same period as controls. Subsequently, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence and prognosis of BCa by meta-analysis after searching the PubMed, Embase, Cochrane Library, and Google Scholar databases up to March 1, 2020. Results The results of our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (OR = 1.17, p = 0.311). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in male patients (OR = 1.25, p = 0.230) or in female patients (OR = 0.90, p = 0.744). Significant correlations were not found in the age subgroup analysis dividing age into younger or greater than 65, with a pooled OR estimate of 1.25 (p = 0.230) and 0.899 (p = 0.744). In 230 patients who relapsed from the 1087 BCa patients above, no significant relationship was found in the aspirin group (RR = 1.19, p = 0.360), and the sex stratification resulted in the same conclusion; however, in people younger than 68, aspirin seemed to have protective effects (RR = 0.60, p = 0.030). In addition, we performed a meta-analysis after searching several databases, and 10 articles involving 12441 BCa cases met the eligibility criteria, contributing to the analysis of aspirin intake and the incidence of BCa. The combined results indicated that aspirin intake was not associated with the occurrence of BCa (OR = 1.03, p = 0.221). In the subgroup analysis, aspirin intake did not reduce the risk of BCa in male patients (OR = 1.08, p = 0.163), female patients (OR = 0.92, p = 0.441), Asian patients (OR = 1.07; p = 0.088), European patients (OR = 1.12, p = 0.390), or North American patients (OR = 0.99, p = 0.839). At the same time, the study type did not influence the lack of a connection between aspirin intake and the risk of BCa in the cohort study (OR = 1.05; p = 0.176) and case-control study (OR = 1.01; p = 0.797). To explore the impact of aspirin intake on the prognosis of patents with BCa, 8 articles involving 3250 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have a significantly lower risk of BCa recurrence than those without aspirin intake (HR = 0.94, p = 0.718), and a consistent conclusion was also reached for overall survival (HR = 1.04, p = 0.879) and cancer-specific survival (HR = 0.98, p = 0.980) by subgroup analysis. Conclusions Both our retrospective study and literature meta-analysis suggested a lack of a relevant association between the use of aspirin and the risk and prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.