Characteristics and outcome of children with renal tumors in the Netherlands: The first five-year’s experience of national centralization

Around 6% of all childhood malignancies represent renal tumors, of which a majority includes Wilms tumor (WT). Although survival rates have improved over the last decades, specific patients are still at risk for adverse outcome. In the Netherlands, since 2015, pediatric oncology care for renal tumors has been centralized in the Princess Máxima Center for Pediatric Oncology. Here, we describe experiences of the first 5 years of centralized care and explore whether this influences the epidemiological landscape by comparing data with the Netherlands Cancer Registry (NCR). We identified all patients <19 years with a renal mass diagnosed between 01-01-2015 and 31-12-2019 in the Princess Máxima Center. Epidemiology, characteristics and management were analyzed. We identified 164 patients (including 1 patient who refused consent for registration), in our center with a suspicion of a renal tumor. The remaining 163 cases included WT (n = 118)/cystic partially differentiated nephroblastoma (n = 2)/nephrogenic rests only (n = 6) and non-WT (n = 37). In this period, the NCR included 138 children, 1 17-year-old patient was not referred to the Princess Máxima Center. Central radiology review (before starting treatment) was performed in 121/163 patients, and central pathology review in 148/152 patients that underwent surgery. Treatment stratification, according to SIOP/EpSSG protocols was pursued based on multidisciplinary consensus. Preoperative chemotherapy was administered in 133 patients, whereas 19 patients underwent upfront surgery. Surgery was performed in 152 patients, and from 133 biomaterial was stored. Centralization of care for children with renal tumors led to referral of all but 1 new renal tumor cases in the Netherlands, and leads to referral of very rare subtypes not registered in the NCR, that benefit from high quality diagnostics and multidisciplinary decision making. National centralization of care led to enhanced development of molecular diagnostics and other innovation-based treatments for the future.

Creation of synthetic contrast-enhanced computed tomography images using deep neural networks to screen for renal cell carcinoma

Objectives: To elucidate if synthetic contrast enhanced computed tomography (CECT) images created from plain CT images using deep neural networks (DNN) could be used for screening, clinical diagnosis, and postoperative follow up of small diameter renal tumors by comparing the concordance rate between real and synthetic CECT images and the diagnoses according to 10 urologists. Methods: This retrospective, multicenter study included 155 patients (artificial intelligence training cohort [n=99], validation cohort [n=56]) who underwent surgery for small-diameter (≤40 mm) renal tumors, with the pathological diagnosis of renal cell carcinoma, during 2010 to 2020. Preoperatively, dynamic plain CT and CECT images were obtained. We created a learned DNN using pix2pix. We examined the quality of the synthetic CECT images created using this DNN and compared them with real CECT images using the zero mean normalized cross correlation parameter. We assessed concordance rates between real and synthetic images and diagnoses according to 10 urologists by creating a receiver operating characteristic curve and calculating the area under the curve (AUC). Results: The synthetic CECT images were highly concordant with the real CECT images, regardless of the existence or morphology of the renal tumor. Regarding the concordance rate, a greater AUC was obtained with synthetic CECT (AUC=0.892) than with only CT (AUC=0.720; p<0.001). Conclusions: This study is the first to use DNN to create a high-quality synthetic CECT image that was highly concordant with a real CECT image. Synthetic CECT images could be used for urological diagnoses and clinical screening.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Percutaneous Cryoablation of Renal Tumors: Initial Indian Experience

Objective The purpose of this study was to report short-term outcomes of cryoablation of early-stage renal tumors (T1a and T1b) at a tertiary hospital in India. Methods This was a retrospective study of consecutive patients who underwent cryoablation for renal cell carcinoma (RCC) from November 2018 to June 2020. Cryoablation was performed under combined ultrasound and computed tomography guidance using a helium-argon cryoablation system. Tumor number, size, location, nephrometry score, relationship of the tumor with pelvicalyceal system, and adjacent organs were tabulated, and technical and clinical success evaluated. Early and late recurrence and complications were also assessed. Results Eleven patients (median age: 62 years) with 11 tumors underwent cryoablation. The mean tumor size was 2.58 cm (range: 1.62–5.62 cm) with 10 lesions being T1a and one lesion T1b. Tissue sampling was done in 9/11 patients, 3 were papillary RCC and the rest, clear cell RCC. In two patients, the tumor was completely endophytic, three patients had partially endophytic tumors while 6 patients had exophytic lesions. The median nephrometry score was 6 (range: 4–11, Mode 4). Technical success was achieved in all patients. Complete response was achieved in 81% (9/11) of the patients at 1-month follow-up. Median follow-up period was 6 months. Two patients showed residual disease on follow-up imaging at 1 and 3 months, respectively. Conclusion Cryoablation is a promising, relatively new minimally invasive therapy for treating small renal tumors in India. It is safe, technically feasible, and shows excellent short-term efficacy.

Endovascular Rescue for Renal Artery Pseudoaneurysms following Minimally Invasive Robot-Assisted Partial Nephrectomy—A Case Series

Nephron sparing surgery or partial nephrectomy has been employed ever since in cases of renal tumors with an aim to preserve the function of residual kidney. Lately, there has been increasing adoption in robot-assisted techniques for partial nephrectomy. However, renal surgeries of any kind have always been a hazard for postoperative vascular complications owing to high vascularity of the renal tissues, of which renal artery pseudoaneurysm is one of the most fatal complications. We present a case series where highly super-selective embolization rescues the patient and augments the nephron sparing nature of the precise robot-assisted partial nephrectomy.