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.

Value of Radiomics of Perinephric Fat for Prediction of Intraoperative Complexity in Renal Tumor Surgery

<b><i>Introduction:</i></b> The aim of this study was to assess the value of computed tomography (CT)-based radiomics of perinephric fat (PNF) for prediction of surgical complexity. <b><i>Methods:</i></b> Fifty-six patients who underwent renal tumor surgery were included. Radiomic features were extracted from contrast-enhanced CT. Machine learning models using radiomic features, the Mayo Adhesive Probability (MAP) score, and/or clinical variables (age, sex, and body mass index) were compared for the prediction of adherent PNF (APF), the occurrence of postoperative complications (Clavien-Dindo Classification ≥2), and surgery duration. Discrimination performance was assessed by the area under the receiver operating characteristic curve (AUC). In addition, the root mean square error (RMSE) and <i>R</i>² (fraction of explained variance) were used as additional evaluation metrics. <b><i>Results:</i></b> A single feature logit model containing “Wavelet-LHH-transformed GLCM Correlation” achieved the best discrimination (AUC 0.90, 95% confidence interval [CI]: 0.75–1.00) and lowest error (RMSE 0.32, 95% CI: 0.20–0.42) at prediction of APF. This model was superior to all other models containing all radiomic features, clinical variables, and/or the MAP score. The performance of uninformative benchmark models for prediction of postoperative complications and surgery duration were not improved by machine learning models. <b><i>Conclusion:</i></b> Radiomic features derived from PNF may provide valuable information for preoperative risk stratification of patients undergoing renal tumor surgery.

Bilateral Renal Tumors in Children: The First 5 Years’ Experience of National Centralization in The Netherlands and a Narrative Review of the Literature

Survival of unilateral Wilms tumors (WTs) is exceeding 90%, whereas bilateral WTs have an inferior outcome. We evaluated all Dutch patients with bilateral kidney tumors, treated in the first five years of national centralization and reviewed relevant literature. We identified 24 patients in our center (2015–2020), 23 patients had WT/nephroblastomatosis and one renal cell carcinoma. Patients were treated according to SIOP-RTSG protocols. Chemotherapy response was observed in 26/34 WTs. Nephroblastomatosis lesions were stable (n = 7) or showed response (n = 18). Nephron-sparing surgery was performed in 11/22 patients undergoing surgery (n = 2 kidneys positive margins). Local stage in 20 patients with ≥1 WT revealed stage I (n = 7), II (n = 4) and III (n = 9). Histology was intermediate risk in 15 patients and high risk in 5. Three patients developed a WT in a treated nephroblastomatosis lesion. Two of 24 patients died following toxicity and renal failure, i.e., respectively dialysis-related invasive fungal infection and septic shock. Genetic predisposition was confirmed in 18/24 patients. Our literature review revealed that knowledge is scarce on bilateral renal tumor patients with metastases and that radiotherapy seems important for local stage III patients. Bilateral renal tumors are a therapeutic challenge. We describe management and outcome in a national expert center and summarized available literature, serving as baseline for further improvement of care.

Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism

<b><i>Background:</i></b> The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. <b><i>Summary:</i></b> HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. <b><i>Key Messages:</i></b> In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.

Surgical treatment of giant renal tumor: a case report

Renal tumors account for 2 to 3 % of all malignant tumors in adults. Of all patients with renal cell carcinoma, 30 to 40 % have advanced forms of the disease. In the literature, the term "giant renal tumor" is used for tumors larger than 20 cm. In this article, we report a case of surgical treatment for a giant malignant kidney tumor.Patient N., female, 54 years old, referred to an outpatient clinic with complaints of a change in the shape of the abdomen on the left with a palpable large tumor, abdominal pain, shortness of breath, weakness, constipation, episodes of blood in the urine and increased blood pressure. Body mass index 30.2 kg/m2. Ultrasound examination revealed a large tumor in the left retroperitoneal space. Laboratory testing of blood, urine was performed, findings were unremarkable. According to the data of magnetic resonance imaging, the left kidney was transformed into a large cystic solid formation, measuring 30.5 х 17.5 х 17.0 cm, heterogeneously accumulating a contrast agent with a solid component. Patient was admitted to the urology department for surgical treatment. We performed radical nephrectomy on the left with thoracolumbar laparotomy access on the left with resection of the 10th rib, resecting the renal tumor with the adrenal gland, total weight of the complex was 10.7 kg. The histological structure was determined as poorly differentiated renal carcinoma with invasion of the perinephric tissue. In the adrenal gland, fields of fresh erythrocytes with an admixture of tumor tissue were noted. Examined lymph node tissue was completely replaced by tumor cells. Postoperative period was characterized by episodes of dynamic intestinal obstruction. The patient was discharged from the department in a satisfactory condition on the 13th day after the operation, but died 1.5 months after discharge, the cause of death has not been established, as no autopsy was performed. Thus, the size of the tumor is not a contraindication to surgical treatment, which improves the survival rate of patients with malignant renal tumors.

Central renal cell carcinoma: a diagnostic dilemma

Centrally Located renal tumor poses a diagnostic challenge to differentiate between renal cell carcinoma and transitional cell carcinoma. Imaging alone is not sufficient to make the diagnosis, some invasive diagnostic investigations are required to ascertain the diagnosis. We present a 60 years old gentleman, who presented dyspepsia and further investigation by contrasted CT kidney revealed a centrally located right renal tumor. Before making a management decision, we performed the right renal biopsy of the tumor which turns out to be a renal cell carcinoma. Henceforth, we performed a robotic-assisted laparoscopic right nephrectomy. A renal biopsy, in this case, assisted to decide only radical nephrectomy instead of radical nephroureterectomy which has higher associated morbidity. Thus, it is important to make confirm by tissue biopsy before deciding on surgery in case of the central renal tumor as this prevents subjecting a patient to under-or overtreatment.