BR55 Ultrasound Molecular Imaging of Clear Cell Renal Cell Carcinoma Reflects Tumor Vascular Expression of VEGFR-2 in a Patient-Derived Xenograft Model.

Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients' ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors were analyzed at D0, D1, D3, D7 and D11, and compared with IHC staining for the VEGFR-2 and CD34. Significant Pearson correlation coefficients were observed between the area under the curve (AUC) and the CD34 (0.84, p < 10-4), and between the VEGFR-2-specific signal obtained by USMI and IHC (0.72, p < 10-4). USMI with BR55 could provide instant, quantitative information on tumor VEGFR-2 expression to characterize renal masses non-invasively.

Surgical and oncological management of renal medullary carcinoma in a young patient: a case report.

Renal medullary carcinoma (RMC) is a rare form of renal cell carcinoma that has a poor prognosis. It is known to be associated with sickle cell trait or disease, although the exact underlying mechanisms are still unclear. The diagnosis is made through immunochemical staining for SMARCB1 (INI1). In this report, we present a case of a 31-year-old male patient with sickle cell trait who was diagnosed with stage III right RMC. Despite the poor prognosis, the patient survived for a remarkable duration of 37 months. Radiological assessment and follow-up were primarily performed using 18F-FDG PET/MRI. The patient underwent upfront cisplatin-based cytotoxic chemotherapy before surgical removal of the right kidney and retroperitoneal lymph node dissection. Identical adjuvant chemotherapy was administered post-surgery. Disease relapses were detected in the retroperitoneal lymph nodes; these were managed with chemotherapy and surgical rechallenges. We also discuss the oncological and surgical management of RMC, which currently relies on perioperative cytotoxic chemotherapy strategies, as there are no known alternative therapies that have been shown to be superior to date.

Primary Renal Tumour Response in Patients Treated with Nivolumab for Metastatic Renal Cell Carcinoma: Results from the GETUG-AFU 26 NIVOREN Trial.

Primary tumour response may impact therapeutic strategies in metastatic renal cell carcinoma (mRCC) but remains unknown in the era of immune checkpoint inhibitors. We aimed to describe the response of the primary tumour in patients who did not undergo upfront cytoreductive nephrectomy (uCN) and were treated with nivolumab in the GETUG-AFU-26 NIVOREN phase 2 trial. Primary tumour response was prospectively assessed, as well as the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Among 720 patients, 111 did not undergo uCN, mainly patients with intermediate (45%) and poor (49%) International mRCC Database Consortium (IMDC) risk. In the 111 patients, nivolumab was used in the second line for 63% of patients and the third line or more for 37%, with an ORR of 16% (95% confidence interval [CI] 1025%); with a median follow-up of 24.5 mo (95% CI 21.6-27.1), median PFS was 2.7 mo (95% CI 2.5-4.0) and median OS was 15.9 mo (95% CI 9.5-19.8). A total of 67 patients had an evaluable primary renal lesion, four of whom (6%) experienced shrinkage of more than 30%. Overall, patients who did not undergo uCN had adverse baseline characteristics and nivolumab activity against the primary tumour was limited. PATIENT SUMMARY: In this report, we observed that nivolumab was associated with a limited response of the primary tumour in previously treated patients with metastatic kidney cancer.

Comorbidity and frailty assessment in renal cell carcinoma patients.

PURPOSE: Renal cell carcinoma (RCC) incidence has considerably increased during the last decades without any real impact on age-standardized mortality. It questions the relevance of aggressive treatments carrying potential side effects. Conservative management should be considered for frail patients. Comorbidity and frailty assessment in RCC patients is paramount before engaging a treatment. METHODS: Narrative, non-systematic review based on PubMed and EMBASE search with the terms "renal neoplasm", "elderly, frail", "comorbidities", "active surveillance", "metastatic". The selection was restricted to articles written in English. RESULTS: Comorbidity and frailty assessment go along with the cancer-specific aggressivity and intervention risks assessment. In localized disease, several standardized algorithms offer patient health evaluation to define how suitable the patient would be for curative treatment. The pre-operative American Society of Anesthesiologists and the age-adjusted Charlson's scores are the most widely used. At the metastatic stage, drug combinations based on immunotherapies and targeted therapies improved cancer outcomes at the price of significant toxicities. Frail patients are not always suitable for such strategies. Commonly used scores like the International Metastatic RCC Database Consortium or Memorial Sloan Kettering Cancer Center integrate features to define patients' risk groups, more specifically the Karnofsky Performance Score is an easy way to document the frailty. CONCLUSIONS: Comorbidity and frailty have to be assessed at any stage of the RCC disease based on a standardized scoring system to define the most suitable treatment strategy ranging from surveillance to aggressive treatment.

Comparison of the iliac, vaginal and umbilical graft extraction in robot-assisted laparoscopic living donor nephrectomy.

PURPOSE: To compare different extractions routes for robot-assisted living donor nephrectomy in terms of post-operative pain and renal function recovery. METHODS: Live donor kidney transplantation data from our institution were reviewed from November 2011 to March 2017. Postoperative pain was estimated using cumulative painkillers consumption. Variables were compared between the 3 groups with ANOVA for continuous data, χ2 test for categorial data. A survival analysis with Kaplan-Meier curve assessing time to transplant recipient nadir was performed to compare the renal function recovery. RESULTS: Sixty-three RLDN were performed (23 iliac, 23 vaginal and 17 umbilical extractions). There was no significant difference between the three groups in terms of operative time, blood lost, warm ischemia time, cumulative painkiller consumption and renal function recovery time. Postoperative complications for Umbilical, Vaginal and Iliac were, respectively, of 0, 3 and 1. No major difference was found between the 3 groups beside a slightly longer hospital stay in the iliac group. CONCLUSION: Iliac incision might impact post-operative pain with a moderate but significant longer hospital stay. Vaginal extraction is an option when cosmetic outcomes present a real demand. The three options appeared to be safe and should be discussed with the patient in regard of the surgeon experience.

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management.

Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role of CAIX as a marker for diagnosis, prognosis, treatment monitoring and molecular imaging, and the potential target for therapeutic strategies.