Super-selective robot-assisted partial nephrectomy using near-infrared flurorescence versus early-unclamping of the renal artery: results of a prospective matched-pair analysis

ABSTRACT Introduction Super-selective clamping of tumor-specific segmental arteries was developed to eliminate ischemia of the remnant kidney while limiting hemorrhage during partial nephrectomy. The objective is to evaluate the benefice of super-selective clamping on renal functional outcome, compared to early-unclamping of the renal artery. Materials and Methods From March 2015 to July 2016, data from 30 patients undergoing super-selective robot-assisted PN (RAPN) for a solitary tumor by a single surgeon were prospectively collected. Tumor devascularization was assessed using indocyanine green near-infrared fluorescence. A matched-pair analysis with a retrospective cohort undergoing early-unclamping was conducted, adjusting on tumor complexity and preoperative eGFR. Perioperative, oncologic and functional outcomes using DMSA-renal scintigraphy were assessed. Multivariate analysis was performed to identify predictors of postoperative renal function and de novo chronic kidney disease (CKD). Results Super-selective RAPN was successful in 23/30 patients (76.7%), 5 requiring secondary main artery clamping due to persistent tumor fluorescence. Matched-pair analysis showed similar operating time, blood loss, positives margins and complication rates. Super-selective clamping was associated with an improved eGFR variation at discharge (p=0.002), 1-month (p=0.01) and 6-month post-op (-2%vs-16% p=0.001). It also led to a better relative function on scintigraphy (46%vs40% p=0.04) and homolateral eGFR (p=0.04), and fewer upstaging to CKD stage ≥3 (p=0.03). On multivariate analysis, super-selective clamping was a predictor of postoperative renal function. Conclusion Super-selective RAPN leads to an improved preservation of renal function and a reduced risk of de novo CKD stage≥3, while keeping the benefit of main artery clamping on perioperative outcomes.

Analysis of various potential prognostic markers and survival data in clear cell renal cell carcinoma

ABSTRACT Purpose Clear cell renal cell cancers frequently harbor Von Hippel-Lindau gene mutations, leading to stabilization of the hypoxia-inducible factors (HIFs) and their target genes. In this study, we investigated the relationship between vascular endothelial growth factor (VEGF), HIF-1α, HIF-2α, p53 positivity, microvessel density, and Ki-67 rates with prognostic histopathologic factors (Fuhrman nuclear grade, stage, and sarcomatoid differentiation) and survival in clear cell renal cell carcinomas. Material and Methods Seventy-two nephrectomy specimens diagnosed as clear cell renal cell carcinoma between 2000 and 2012 were reevaluated. Immunohistochemically VEGF, HIF-1α, HIF-2α, p53, CD34 (for microvessel density evaluation), and Ki-67 antibodies were applied to the tumor areas. The relationships of these antibodies with prognostic factors and survival rates were evaluated with statistical analyses. Results Mean survival time was 105.6 months in patients with ccRCC. Patients with high expression of VEGF, HIF-1α and HIF-2α positivity, a high Ki-67 proliferation index, and a high microvessel density evaluation score had a shorter survival time (p<0.05). Conclusions Our findings supported that with the use of these immunohistochemical markers, prognosis of renal cell carcinoma may be predicted at the first step of patient management. New treatment modalities targeted to HIF-1α and HIF-2α might be planned as well as VEGF-targeted therapies in the management of clear cell renal cell carcinomas.

Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model

OBJECTIVE: To evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model. MATERIALS AND METHODS: Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test. RESULTS: The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 +/- 9.9% vs. 77.4 +/- 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 +/- 0.7 mm for the RFA only group and 8.5 +/- 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 +/- 3.9% in no-therapy group, 10.3 +/- 4.5% in the RFA only group, and 2.1 +/- 0.7% in the RFA with DAAP group (ANOVA, p < 0.001). CONCLUSION: Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

Vascular Endothelial Growth Factor - Its Relation to Neovascular ization and Their Significance as Prognostic Factors in Renal Cell Carcinoma

Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low ascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.

Hallazgos con ecografía Doppler color y tomografía computada helicoidal en tumores renales: relación entre volumen y grado de neovascularización / Renal tumors: correlation of volume with neovascularity by means of color Doppler, US and helical CT

Entre julio de 1997 y agosto de 1998, se analizaron en nuestro Servicio 23 neoplasias renales de distinta histología que fueron estudiadas mediante ecografía convencional, Doppler color, Power Doppler y tomografía computada helicoidal, obteniéndose en todos los casos confirmación antomopatológica. Basándonos en sus características volumétricas, los tumores se clasificaron en tres grupos. A la vez, se utilizó Doppler color como power Doppler para caracterizar el tipo e intensidad de neuvascularización tumoral, para obtener distintos registros espectorales, arteriales y venosos, y para calcular las diferentes velocidades de flujo con sus índices de resistencia. Se realizó TC helicoidal, antes y después de la inyección de contraste yodado endovenoso, con el objeto de establecer una correlación entre el volumen ecográfico y el obtenido por tomografía, así como observar los diferentes tipos de realce vascular tumoral y entablar una relación con los hallazgos obtenidos mediante Doppler color y Power Doppler. Los hallazgos deberán ampliarse a un mayor número de casos pero los resultados iniciales indican una importante correlación entre el volumen tumoral y el grado de vascularización en el examen Doppler color, especialmente en tumores de pequeño volumen, con un predominio del patrón hipovascular de los mismos. También se observó un aporte importante de este último en la caracterización de los tumores renales en relación con su histopatología

Vascularity of solid renal masses: role of pulsed and color doppler U.S.

The vascularity of 18 renal masses [11 malignant and 7 benign lesions] was investigated prospectively by duplex Doppler ultrasound. The results were correlated to pathologic [17/18], US [18/18] and CT findings [10/18]. With the use of a cut off peak systolic frequency of 2.5 KHz, seven of eleven malignant lesions demonstrated abnormal high frequency tumor signals [63.6% sensitivity]. Only one false positive result of a benign renal mass [inflammatory] demonstrated peak systolic frequency shifts over 2.5 KH [specificity 85.7%]. Doppler shifted signals can help in the differential diagnosis of renal masses