Neoadjuvant therapy in renal cell carcinoma with tumor thrombus: A systematic review and meta-analysis.

To evaluate the efficacy, feasibility and safety of neoadjuvant therapy (NAT) for renal cell carcinoma with tumor thrombus (RCC-TT) in terms of response, perioperative and oncological outcomes, and compare the results between neoadjuvant and non-neoadjuvant groups. Overall, 29 single-arm studies and 5 cohort studies were included. Of the 204 patients undergoing NAT, 16.2% were level I, 35.3% level II, 24.0% level III and 18.6% level IV thrombus. Most of patients underwent preoperative targeted therapy, immunotherapy-based combination therapy was applied in 5.4% patients. The total reduction rate of thrombus level was 29.4%. NAT is associated with a shorter operative time, less blood loss (p<0.05 for both). Rate of complications and oncological outcomes were similar between two groups. Overall, 32.1% (34/106) ≥ grade 3 adverse events occurred in patients undergoing NAT. Neoadjuvant therapy is safe and feasible with acceptable perioperative outcomes in RCC-TT.

Corrigendum: No safe renal warm ischemia time-The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury.

[This corrects the article DOI: 10.3389/fmolb.2022.1006917.].

Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma.

Background: Germline pathogenic variants are estimated to affect 3-5% of patients with renal cell carcinoma (RCC). The identification of patients with hereditary RCC is important for cancer screening and treatment guidance. Methods: Whole-exome sequencing (WES) (n=69) or gene panel sequencing containing 139 genes (n=54) related to germline cancer predisposition was used to analyze germline mutations in 123 patients with RCC admitted to Department of Urology, The Third Medical Center of Chinese PLA General Hospital. Chi-square test (χ2) was used to analyze relationship between clinicopathologic parameters and germline mutations. Results: A total of 13 (10.57%) patients carried pathogenic or likely pathogenic germline mutations in 10 cancer predisposition genes, including VHL, FH, FLCN, SDHB, MUTYH, RAD51C, NBN, RAD50, FANCI, and FANCM. A total of 6 of these 10 cancer predisposition genes were associated with maintenance of genomic stability and DNA repair. Patients harboring pathogenic germline mutations tended to have an earlier RCC onset. The prevalence of deleterious mutations was higher in patients with bilateral or multifocal RCC compared to patients without bilateral or multifocal RCC. Patients with non-clear cell RCC (nccRCC) were significantly more likely to have RCC-associated gene mutations. Conclusions: To our knowledge, this is the first report of pathogenic germline mutations in the FANCI and FANCM genes and heterozygous germline missense mutation in exon 5 of the FH gene c.563A>T:p.N188I in RCC. Young RCC patients, patients with bilateral or multifocal RCC, or patients with nccRCC are more likely to have pathogenic/potentially pathogenic germline mutations.

No safe renal warm ischemia time-The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury.

Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney) ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum creatinine (Scr), and kidney tissue samples were harvested to perform Periodic Acid-Schiff (PAS) staining and RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated RNA-Seq results. Our results indicated that there was no absolute safe renal warm ischemia time, and every minute of ischemia increases kidney damage. Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed. Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min warm ischemia. There are two key time intervals in the process of renal ischemia injury, 0 min-16 min (short-term) and 26 min-28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic biomarkers for AKI.

Intermittent hilar occlusion attenuates or prevents renal ischaemia-reperfusion in mice.

BACKGROUND: A minimal decrease in renal function in partial nephrectomy is an important clinical and experimental research objective. We compared the effect of intermittent hilar occlusion (IHO) and continuous hilar occlusion (CHO) on kidney injury and oxidative damage. METHOD: Using CHO or IHO for 24, 30, and 45 min, intraoperative ischaemia, as well as a sham group, were set up in an ischaemia-reperfusion long-term survival mouse model. Renal function, pathological injury, subcellular structure injury, and cell apoptosis were evaluated at 1, 30, and 90 d postoperatively to study the protective effect of IHO. To do so, oxidative damage analysis, antioxidant activities, and ischaemia time dose-response curves on relative acute renal function injury were analysed. RESULTS: All parameters indicated that kidney injury was dramatically attenuated in the IHO groups compared to those in the corresponding CHO groups. Particularly, mice in the IHO 24-min group incurred no tubular injury or renal functional injury; mice in the CHO 30-min group incurred severe acute and chronic kidney injury, but mice in the IHO 30-min group only experienced transient mild renal functional injury. IHO prolonged tolerable ischaemia duration. CONCLUSIONS: IHO can prolong the duration of tolerable ischaemia, at least partly through protecting the kidney from oxidative stress, consequently attenuating or preventing renal ischaemia-reperfusion injury. Reduced kidney injury after ischaemia-reperfusion is linked to a greater maintenance of antioxidant activity and less oxidative damage. The protective effect of IHO can be extremely efficient if properly applied; IHO may avoid renal ischaemia-reperfusion injury during partial nephrectomy.

Papillary renal neoplasm with reverse polarity-a comparative study with CCPRCC, OPRCC, and PRCC1.

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. In this study, we aimed to identify and analyze the clinicopathological, immunohistochemical (IHC), and molecular features of PRNRP in our center and to evaluate its differential diagnosis with other tumors with which it is easily confused: clear cell papillary renal cell carcinoma (CCPRCC), oncocytic papillary renal cell carcinoma (OPRCC), and papillary renal cell carcinoma type 1 (PRCC1). Nephrectomy specimens of PRNRP (n = 15), CCPRCC (n = 11), and OPRCC (n = 12) were retrieved from our pathology archives. We also selected typical cases of PRCC1 (n = 15) as a control group. PRNRP accounted for 3.05% (15/492) of all PRCC cases at our center. The median follow-up period was 41.3 months. All PRNRP cases were pT1N0M0, and only one involved recurrence (1 year after surgery). IHC analysis showed diffuse staining of CK7, EMA, and GATA3 but weak or negative staining of CD10, CD117, p504s, and vimentin in the PRNRP samples and distinctive IHC features in the other three tumor types. KRAS mutation was detected in 4/10 PRNRP cases. Among the 40 most commonly mutated genes identified, 5 (BCLAF1, PDE4DIP, NCOR1, PARP4, and PABPC1) have actionable alterations. Our study supports the suggestion that PRNRP is an entity distinct from CCPRCC, OPRCC, and PRCC1.