[Peculiarities of angiogenesis in clear cell renal cancer]. / Osobennosti angiogeneza pri svetlokletochnom rake pochki.

A literature search was conducted to review papers on the results of studies of clear cell renal cancer (CCRC) vascularization. Numerous data on the relationship between tumor pathogenesis and its vascularization have been revealed, which indicates the multifactorial nature of CCRC development and the significant role of angiogenesis in this process. It should be taken into account that patients with CCRC may have impaired vessel formation even before tumor development. To evaluate normal and pathologic angiogenesis, a pathohistologic study using immunohistochemistry is certainly necessary. Due to the significant role of angiogenesis in the development and course of CCRC, the use of drugs that suppress the formation of the vascular network in the tumor is relevant and advisable. To date, many drugs have been developed and introduced into clinical practice to inhibit angiogenesis. However, such drugs have not lived up to the expectations placed due to the frequent and rapidly developing drug resistance. Timely detection of pre-tumor and tumor processes, as well as effective treatment of cancer, including CCRC, is possible only with close cooperation between pathomorphologists and oncologists.

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma.

Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three-dimensional light-sheet microscopy. Here, we used the diagnosing immunolabeled paraffin-embedded cleared organs pipeline for tissue clearing, immunolabeling, and three-dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE-1, which targets lymphatic vessels, were examined by calculating three-dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin-fixed paraffin-embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three-dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K-mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High-end tissue clearing techniques and volumetric immunohistochemistry enable three-dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.

Depiction rate of feeding arteries of renal cell carcinoma on four-dimensional computed tomography angiography.

PURPOSE: To retrospectively evaluate the depiction rate of feeding arteries in biopsy-proven clear cell renal cell carcinoma (CCRCC) on four-dimensional computed tomography angiography (4D-CTA) images. MATERIALS AND METHODS: This study included 22 patients with 22 CCRCC and 30 feeding arteries treated with transcatheter renal artery embolization. The depiction rate of the feeding arteries on preprocedural 4D-CTA was evaluated. Images were acquired by 320-row multi-detector computed tomography (CT) 15‒36 s after starting to inject a contrast agent (600 mg/kg iodine) intravenously into patients at 2.1 s intervals (11 phases). Two board-certified radiologists retrospectively assessed the feeder depiction rate in all 11 phases with reference to the procedural images as the gold standard. Discrepancies were resolved by consultation with a third radiologist. RESULTS: Among the feeders, 11 (36.7%) were segmental or lobar, and 19 (63.3%) were interlobar or arcuate arteries. The feeder depiction rate was the highest (25 [83.3%] of 30) in the 5th phase (delay, 23.4 s) where the gap in contrast enhancement between the renal artery and cortex was the largest. This was followed by the 6th (23 [76.7%] of 30), 4th (22 [73.3%] of 30]), and 7th (21 [70.0%] of 30) phases. The overall rate of depicting feeding arteries in the 11 phases of 4D-CTA was 28 (93.3%) of 30. CONCLUSIONS: The depiction rate of CCRCC feeding arteries including lobar or smaller artery branches by 4D-CTA was favorable. The feeding arteries were optimally visualized during the phase with the largest contrast gap between the renal artery and cortex.

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.

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