Prognostic value of preoperative radiographic perinephric fat features in renal cell carcinoma patients undergoing surgery.

BACKGROUND: We aimed to assess the prognostic importance of perinephric fat features in images of patients with non-metastatic renal cell carcinoma (RCC) undergoing surgery. METHODS: We enrolled RCC patients who underwent surgical treatment between 2011 and 2019. Two characteristics, including perinephric fat thickness and perinephric fat stranding, were evaluated using preoperative computed tomography or magnetic resonance images. The association between perinephric fat characteristics and disease progression was examined by Kaplan-Meier survival analysis and Cox regression model. RESULTS: In a multivariate Cox proportional hazards model adjusting for tumor stage, intratumoral necrosis, and neutrophil-to-lymphocyte ratio, we found that patients in the thin perinephric fat group (<1 cm) had a poorer progression-free survival (PFS) compared to the thick perinephric fat group (≥1 cm) (HR 2.8; 95% CI 1.175-6.674, p = 0.02). Additionally, the fat stranding group had a poorer PFS than the non-stranding group (HR 3.852; 95% CI 1.082-13.704, p = 0.037). The non-stranding with thick perinephric fat group exhibits the highest cumulative PFS while the stranding with thin perinephric fat group has the lowest cumulative PFS. In receiver operating characteristic curve analysis, combing these two perinephric fat characteristics with tumor stage can achieve a better discriminatory power than tumor stage alone. CONCLUSIONS: Our study indicates that the evaluation of image-based perinephric fat features is a simple, straightforward, reproducible tool for predicting RCC prognosis and may assist in preoperative risk stratification.

Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review).

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of ß­human chorionic gonadotropin (ß­hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since ß­hCG­targeting vaccines have failed in an early phase II trial, it is crucial to obtain a better understanding of the molecular pathogenesis of trophoblastic differentiation in human cancer. The present review summarizes the clinical and translational research on this topic with the aim of accelerating the development of an effective targeted therapy. Ectopic expression of ß­hCG promotes proliferation, migration, invasion, vasculogenesis and epithelial­mesenchymal transition (EMT) in vitro, and enhances metastatic and tumorigenic capabilities in vivo. Signaling cascades modulated by ß­hCG include the TGF­ß receptor pathway, EMT­related pathways, the c­MET receptor tyrosine kinase and mitogen­activated protein kinase/ERK pathways, and the SMAD2/4 pathway. Taken together, these findings indicated that TGF­ß receptors, c­MET and ERK1/2 are potential therapeutic targets. Nevertheless, further investigation on the molecular basis of aberrant trophoblastic differentiation is mandatory to improve the design of precision therapy for this aggressive type of human cancer.

Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P = .017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P = 0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma.

OBJECTIVES: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. RESULTS: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). CONCLUSIONS: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.