Bilateral Nephroureterectomy Versus Unilateral Nephroureterectomy for Treating De Novo Upper Tract Urothelial Carcinoma After Renal Transplantation: A Comparison of Surgical and Oncological outcomes.

BACKGROUND: There is currently no consensus on the optimal management of de novo unilateral upper tract urothelial carcinoma (UTUC) in renal transplant recipients. We aimed to compare the surgical and oncological outcomes of simultaneous bilateral radical nephroureterectomy (SBRNU) and unilateral radical nephroureterectomy (URNU) to determine the appropriate surgical method. METHODS: Patients who developed de novo UTUC after renal transplantation and underwent surgical treatment at our center were included in the study. Outcomes were compared between the SBRNU group (underwent bilateral RNU within 3 months) and the URNU group using the Mann-Whitney U-test for continuous variables, Pearson's chi-square test for categorical variables, and the log-rank test for survival data. RESULTS: A total of 48 patients were identified, including 21 and 27 patients in the SBRNU and URNU groups, respectively. Comparison of perioperative data showed that the SBRNU group had a significantly longer operative time (P < .001) and hospital stay (P = .040) than the URNU group but no statistically significant difference in the blood loss (P = .171) and morbidity rate (P = .798). After a median follow-up of 65 months, the SBRNU group had a significantly longer disease-free survival (P = .009), longer cancer-specific survival (P = .032), marginally longer overall survival (P = .066), and similar intravesical recurrence-free survival (P = .274) than the URNU group. CONCLUSIONS: Our data suggest that SBRNU contributes to improved survival without significantly compromising the perioperative outcomes compared with URNU. SBRNU can be considered a feasible option for de novo UTUC after renal transplantation in specialized centers. Prospective studies should be conducted to further explore the best treatment options for this group of patients.

Imaging predictors for assessment of inferior vena cava wall invasion in patients with renal cell carcinoma and inferior vena cava tumor thrombus: a retrospective study.

BACKGROUND: Renal cell carcinoma (RCC) has the propensity to lead to venous tumor thrombus (VTT). Nephrectomy with tumor thrombectomy is an effective treatment option but is a technically challenging surgical procedure that is accompanied by a high rate of complications. The aims of this study were to investigate pre-operative imaging parameters for the assessment of inferior vena cava (IVC) wall invasion due to a tumor thrombus in patients with RCC and to identify predictors from the intra-operative findings. METHODS: Clinical and imaging data were collected from 110 patients who underwent nephrectomy with IVC tumor thrombectomy (levels I-IV) for RCC and IVC tumor thrombus at the Peking University Third Hospital between May 2015 and March 2018. Univariable and multivariable logistic regression and receiver operating characteristic curves were used to assess the correlations between pre-operative imaging features and intra-operative macroscopic invasions of the IVC wall by tumor thrombus. RESULTS: Among the 110 patients, 41 underwent partial or segmental resection of IVC. There were univariate associations of pre-operative imaging parameters that could be used to predict the need for IVC resection, including those of the Mayo classification, maximum anterior-posterior (AP) diameter of the renal vein at the renal vein ostium (RVo), maximum AP diameter of the VTT at the RVo and IVC occlusion. For the multivariable analysis, the AP diameter of the VTT at the RVo and IVC occlusion were associated with a significantly increased risk of invasion of the IVC wall by tumor thrombus. The optimum imaging thresholds included an AP diameter of the VTT at the RVo larger than 17.0 mm and the presence of IVC occlusion, with which we predicted invasions of the IVC wall requiring IVC resection. The probabilities of intra-operative IVC resection for patients without both independent factors, with an AP diameter of the VTT at the RVo larger than 17.0 mm, with IVC occlusion, and with both concurrent factors were 5%, 23%, 56%, and 66%, respectively. CONCLUSION: An increase in the AP VTT diameter at the RVo and the presence of complete occlusion of the IVC are independent risk factors for a high probability of IVC wall invasion by tumor thrombus.

Interaction between IGFBP7 and insulin: a theoretical and experimental study.

Insulin-like growth factor binding protein 7 (IGFBP7) can bind to insulin with high affinity which inhibits the early steps of insulin action. Lack of recognition mechanism impairs our understanding of insulin regulation before it binds to insulin receptor. Here we combine computational simulations with experimental methods to investigate the interaction between IGFBP7 and insulin. Molecular dynamics simulations indicated that His200 and Arg198 in IGFBP7 were key residues. Verified by experimental data, the interaction remained strong in single mutation systems R198E and H200F but became weak in double mutation system R198E-H200F relative to that in wild-type IGFBP7. The results and methods in present study could be adopted in future research of discovery of drugs by disrupting protein-protein interactions in insulin signaling. Nevertheless, the accuracy, reproducibility, and costs of free-energy calculation are still problems that need to be addressed before computational methods can become standard binding prediction tools in discovery pipelines.