Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+ CD163+ CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

Does lower urinary tract status affect renal transplantation outcomes in children?

BACKGROUND: Lower urinary tract dysfunction (LUTD), an important cause of end stage renal disease (ESRD) in children, can adversely affect renal graft survival. We compared renal transplant patients with LUTD as primary renal disease to those without LUTD. METHODS: The data of 60 children who underwent renal transplantation (RTx) between 2000 and 2012 were retrospectively reviewed. All patients with LUTD were evaluated with urodynamic tests preoperatively; 15 patients required clean intermittent catheterization and 9 patients underwent augmentation cystoplasty before RTx. RESULTS: There were 25 children with LUTD. The mean follow-up for LUTD (+) and LUTD (-) groups were 63 (22-155) and 101 months (14-124), and graft survival were 76% for LUTD (+) and 80% for LUTD (-), respectively (P = .711). On the other hand, creatinine levels at last follow-up were significantly higher in the LUTD (+) group (1.3 ± 0.3 mg/dL vs 0.96 ± 0.57 mg/dL, P < .001). Infectious complications and postoperative urinary tract infection incidences were also higher in the LUTD (+) group (68% vs 25.7%, P = .002 and 60% vs 11.4%, P < .01). CONCLUSION: UTI is significantly higher after kidney transplantation in patients with LUTD. Despite the higher risk of UTI, renal transplantation can be performed safely in those patients with careful patient selection, preoperative management, and close postoperative follow-up. Restoration of good bladder function is the key factor in the success of kidney transplantation in those patients.

Aortic aneurysms after correction of aortic coarctation: a systematic review.

Despite advanced techniques for surgical or percutaneous therapy coarctation of the aorta continues to carry a high risk of aneurysmal formation. Mortality of these aneurysms ranges between <1 and >90%, reflecting remarkable differences in surgical strategies and the follow-up management of coarctation. We review the frequency, anatomical types, risk factors and mechanisms of aortic aneurysm forming late after surgical or percutaneous therapy of aortic coarctation. We emphasize that aneurysms do not form exclusively at the site of previous intervention, but also at remote locations such as the ascending aorta. Moreover, aneurysm formation may only in part be attributed to a specific technique of coarctation therapy, and we emphasize the role of a bicuspid aortic valve and inherent weakness of the aortic wall as significant risk factors for aneurysm after aortic coarctation. We report the presenting symptoms, follow-up protocols, and imaging criteria for local and proximal aneurysms. Finally, we discuss criteria for prophylactic intervention at the site of such aneurysms, and present therapeutic options for different types of aneurysms. With this systematic review, we wish to provide data for establishing more uniform strategies for preventing, diagnosing and treating aneurysms associated with aortic coarctation.