Peking University Third Hospital score: a comprehensive system to predict intra-operative blood loss in radical nephrectomy and thrombectomy.

BACKGROUND: Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon's experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy. METHODS: The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis. RESULTS: The final multivariable model included the following three factors: open operative approach (P < 0.001), Neves classification IV (P < 0.001), inferior vena cava resection (P = 0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280 mL (interquartile range [IQR] 100-600 mL), 1250 mL (IQR 575-2700 mL), 2000 mL (IQR 1250-2900 mL), and 5000 mL (IQR 4250-8000 mL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (P = 0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0 vs. 1 to 3 (P = 0.098). CONCLUSION: We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus.

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) remain poorly understood. Here, we applied whole-exome sequencing on 110 normal-tumor pairs and 42 normal-tumor-thrombus triples, and transcriptome sequencing on 61 tumor-normal pairs and 30 primary-thrombus pairs from 152 Chinese patients with ccRCC. Our analysis reveals that a mutational signature associated with aristolochic acid (AA) exposure is widespread in Chinese ccRCC. Tumors from patients with ccRCC-TT show a higher mutational burden and genomic instability; in addition, mutations in BAP1 and SETD2 are highly enriched in patients with ccRCC-TT. Moreover, patients with/without TT show distinct molecular characteristics. We reported the integrative genomic sequencing of Chinese ccRCC and identified the features associated with tumor thrombus, which may facilitate ccRCC diagnosis, prognosis and treatment.

Body mass index as an independent risk factor for inferior vena cava resection during thrombectomy for venous tumor thrombus of renal cell carcinoma.

OBJECTIVE: To define preoperative clinical and radiographic risk factors for the need of inferior vena cava (IVC) resection in patients with renal cell carcinoma (RCC) and IVC tumor thrombus. METHODS: We reviewed data of 121 patients with renal cell carcinoma and venous tumor thrombus receiving radical nephrectomy and thrombectomy at our institution between 2015 and 2017, and 86 patients with Mayo I-IV level tumor thrombus were included in the final analysis. Clinical features, operation details, and pathology data were collected. Preoperative images were reviewed separately by two radiologists. Univariable and multivariable logistic regression analyses were applied to evaluate clinical and radiographic risk factors of IVC resection. RESULTS: Of the 86 patients, 44 (51.2%) received IVC resection during thrombectomy. In univariate analysis, we found that body mass index (BMI) (odds ratio [OR] = 1.22, P = 0.003), primary tumor diameter (OR = 0.84, P = 0.022), tumor thrombus width (OR = 1.08, P = 0.037), tumor thrombus level (OR = 1.57, P = 0.030), and IVC occlusion (OR = 2.67, P = 0.038) were associated with the need for resection of the IVC. After adjusting for the other factors, BMI (OR = 1.18, P = 0.019) was the only significant risk factor for IVC resection. Multivariable analysis in Mayo II-IV subgroups confirmed BMI as an independent risk factor (OR = 1.26, P = 0.024). A correlation between BMI and the width (Pearson's correlation coefficient [PCC] = 0.27, P = 0.014) and length (PCC = 0.23, P = 0.037) of the tumor thrombus was noticed. CONCLUSION: We identified BMI as an independent risk factor for IVC resection during thrombectomy of RCC with tumor thrombus in a Chinese population. More careful preoperative preparation for the IVC resection and/or reconstruction is warranted in patients with higher BMI.

The survival and prognostic factors of primary testicular lymphoma: two-decade single-center experience.

This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma (PTL) patients. We retrospectively reviewed the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis. The Kaplan-Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival (PFS), overall survival (OS), and determine prognosis predictors. The median follow-up time was 30 months. Median OS and PFS were 96 months and 49 months, respectively. In univariate analysis, advanced Ann Arbor stage (III/IV) (P < 0.001), B symptoms (P < 0.001), and extranodal involvement other than testis (P = 0.001) were significantly associated with shorter OS and PFS. In multivariate analysis, Ann Arbor stage was significantly associated with OS (OR = 11.58, P = 0.049), whereas B symptom was significantly associated with PFS (OR = 11.79, P= 0.049). In the 10 patients with the systemic usage of rituximab, bilateral intervention could improve median OS from 16 to 96 months (P = 0.032). The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.