ObjectivesThe risk factors for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC) are currently inconsistent and unclear. In this study, we aimed to identify these risk factors and develop a grading system for EUR.MethodsWe retrospectively analyzed 220 patients who underwent RNU for UTUC in our center from January 2009 to December 2020. Overall survival (OS) and extraurothelial recurrence-free survival (EURFS) were compared using the Kaplan–Meier curve with a log-rank test. Univariate and multivariate Cox regression models were applied to identify the independent risk factors related to EUR.ResultsThe median follow-up period was 42 (range: 2–143) months. Of the 220 patients, 61 patients developed EUR in our cohort, which had worse survival outcome. Multivariate Cox regression analysis showed pathologic stage, lymph node (LN) status, lymphovascular invasion (LVI), Ki-67, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were independent risk factors for EUR. The Kaplan–Meier curves revealed a significant difference in EUR among the three risk groups.ConclusionOur study suggests that pathologic stage, LN status, LVI, Ki-67, NLR, and PLR are independent risk factors for EUR in UTUC patients after RNU. The development of a grading system for EUR risk stratification may assist urologists in making clinical decisions regarding the management of UTUC.

With the development of NK cell-directed therapeutic strategies, the actual effect of NK cells on the cellular SIV DNA levels of the virus in SIV-infected macaques in vivo remains unclear. In this study, five chronically SIVmac239-infected, treatment-naïve rhesus macaques were euthanized, and the blood, spleen, pararectal/paracolonic lymph nodes (PaLNs), and axillary lymph nodes (ALNs) were collected. The distributional, phenotypic, and functional profiles of NK cells were detected by flow cytometry. The highest frequency of NK cells was found in PBMC, followed by the spleen, while only 0~0.5% were found in LNs. Peripheral NK cells also exhibited higher cytotoxic potential (CD56− CD16+ NK subsets) and IFN-γ-producing capacity but low PD-1 and Tim-3 levels than those in the spleen and LNs. Our results demonstrated a significant positive correlation between the frequency of NK cells and the ratios of cellular SIV DNA/RNA in HLADR− CD4+ T cells (r = 0.6806, p < 0.001) in SIV-infected macaques, despite no discrepancies in the cellular SIV DNA or RNA levels that were found among the blood, spleen, and LNs. These findings showed a profile of NK cell frequencies and NK cytotoxicity levels in different immune organs from chronically SIVmac239-infected, treatment-naïve rhesus macaques. It was suggested that NK cell frequencies could be closely related to SIV DNA/RNA levels, which could affect the transcriptional activity of SIV proviruses. However, the cytotoxicity effect of NK cells on the latent SIV viral load in LNs could be limited due to the sparse abundance of NK cells in LNs. The development of NK cell-directed treatment approaches aiming for HIV clearance remains challenging.

ObjectiveWe aimed to evaluate the effect of the timing of diagnostic ureteroscopy (URS) on intravesical recurrence (IVR) following radical nephroureterectomy (RNU).Patients and methodsThe clinical data of 220 patients with upper tract urothelial carcinoma (UTUC) treated with RNU at our center from June 2010 to December 2020 were retrospectively analyzed. According to the timing of the URS, all patients were divided into three groups: the no URS group, the 1-session group (diagnostic URS immediately followed by RNU), and the 2-session group (RNU after diagnostic URS). Additionally, we analyzed IVR-free survival (IVRFS) using the Kaplan-Meier and Cox proportional regression methods.ResultsThe median follow-up period of these 220 patents was 41 (range: 2-143) months. Among them, 58 patients developed IVR following RNU. Kaplan-Meier curve displayed a significantly higher IVR rate in both treatment groups than in the no-URS group (p=0.025). In the subgroup of patients with renal pelvis cancer, the incidence of IVR was significantly higher in both treatment groups than in the group without URS (p=0.006). In univariate Cox proportional regression analysis, the two treatment groups were risk factors for IVR compared to the no-URS group [p=0.027, hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.08-3.46]. The two-stage group (p=0.032, HR: 1.98, 95% CI: 1.08-3.65), positive urine pathology (p&lt;0.001, HR: 8.12, 95% CI: 3.63-18.15), adjuvant chemotherapy (p&lt;0.001, HR: 0.20, 95% CI: 0.10-0.38), and positive margin (p&lt;0.0001, HR: 7.50, 95% CI: 2.44-23.08) were all identified as independent predictors in the multivariate.ConclusionThis study revealed that delayed RNU following diagnostic URS may increase the risk of postoperative IVR in patients with UTUC, preoperatively positive uropathology, and positive surgical margin were risk factors for IVR after RNU, while early postoperative chemotherapy may effectively prevent IVR. Delay of RUN after URS could increase the risk of IVR.

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