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Abstract Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it’s necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Abstract Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan–Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression‐free survival, cancer‐specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K‐AKT‐mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT‐mTOR pathway. Furthermore, the overexpression of NTRK3 in UM‐UC‐14 cells promoted AKT‐mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT‐mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Abstract To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.