Effects of phlebotomy on the growth of ferric nitrilotriacetate-induced renal cell carcinoma.

The ferric nitrilotriacetate-induced carcinogenesis model is unique in that reactive oxygen species-free radicals are involved in the carcinogenic process. But the effects of iron-withdrawal in the progression of renal cell carcinoma are not well understood. We performed repeated phlebotomies on animals that had been administered ferric nitrilotriacetate in the initiation stage of renal cell carcinoma (phlebotomy group), and compared the development of renal tumors with those not receiving repeated phlebotomies (non-phlebotomy group). Ferric nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a phlebotomy group (21 rats) and a non-phlebotomy group (17 rats). Ten age-adjusted normal rats were also observed as a normal group. Hematocrit was maintained under 25% in the phlebotomy group. Hematocrit levels in the normal group and in the non-phlebotomy group were not significantly different. As a result, the incidence of renal cell carcinoma was not significantly different between phlebotomy and non-phlebotomy animals. However, the total weight of the renal cell carcinoma was significantly heavier in the animals from non-phlebotomy group than in those from the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P &#60; 0.05). The present study demonstrated that phlebotomy after the administration of ferric nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In addition, we showed that iron withdrawal at the promotion stage of carcinogenesis will retard tumor growth.</p

Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

Multilocular Cystic Renal Cell Carcinoma: An Unusual Gross Appearance

Multilocular Cystic Renal Cell Carcinoma (MCRCC) represents a rare variant of clear cell (conventional) renal cell carcinomas. Attributable to its distinct characteristics in prognosis and its natural history, MCRCC was recognised as a separate subtype of renal cell carcinoma in the 2004 WHO classification of adult renal tumors. We report this case of MCRCC from antemortem surgical specimen, due to its unusual gross appearance and a rare clinical entity

Tivozanib in the treatment of renal cell carcinoma

Mehmet Hepgur, Sarmad Sadeghi, Tanya B Dorff, David I Quinn Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA Abstract: Renal cell carcinoma (RCC) is an aggressive malignancy compared to other urological malignancies and has been associated with poor responses to conventional cytotoxic chemotherapy. Interferon-a and interleukin-2 were previously utilized in a limited number of patients with good performance status due to toxicity and safety issues. Over the last decade, through advances in the understanding of the biology and pathology of RCC, the important role of vascular endothelial growth factor (VEGF) in RCC has been identified. Data from randomized trials have led to the approval of first-generation tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib; however, these agents inhibit a wide variety of kinase targets and are associated with a range of adverse effects. More recently, a new generation TKI, axitinib, has been approved by the US Food and Drug Administration. Tivozanib is a novel TKI, which is a potent inhibitor of VEGF-1, VEGF-2, VEGF-3, c-kit, and PDGR kinases, with a more restricted target spectrum. Phase II and III studies have demonstrated significant activity and a favorable safety profile as an initial targeted treatment for advanced RCC. This review examines the emerging data with tivozanib for the treatment of advanced RCC. Preclinical investigations as well as Phase I, II, and III data are examined; data on the comparative benefits of tivozanib are reviewed. Finally, we discuss the future potential of tivozanib in combination, biomarkers associated with tivozanib response, and acquisition of resistance and nonkidney cancer indications. Keywords: targeted therapy, renal cell cancer, tyrosine kinase inhibitor, tivozani

Effect of collecting duct histology on renal cell cancer outcome.

PURPOSE: Collecting duct renal cell carcinoma is a rare entity. Recent surgical series of the condition showed conflicting results. We used an American population based data set to compare the survival experience of patients with collecting duct vs clear cell renal cell carcinoma. MATERIALS AND METHODS: Cases of collecting duct and clear cell renal cell carcinoma were identified in the Surveillance, Epidemiology and End Results program (2001 to 2005). Demographic and pathological characteristics at diagnosis were compared. Differences in disease specific survival were compared with univariate and multivariate Cox regression analysis. RESULTS: A total of 160 collecting duct renal cell carcinoma cases were present in the database from 2001 to 2005. In that time 33,252 clear cell renal cell carcinoma cases were diagnosed. Collecting duct renal cell carcinoma was more common in black than in white patients (23% vs 9%, p <0.001). Collecting duct renal cell carcinoma was more commonly T3+ than T2/T1 (33% vs 18%, p <0.001) and metastatic than regional/local (28% vs 17%, p = 0.001). Nephrectomy rates were similar (84% and 78%, p = 0.06). The 3-year disease specific survival rate was 58% and 79% for collecting duct and clear cell renal cell carcinoma, respectively. On multivariate analysis there was an increased mortality risk in patients with collecting duct vs clear cell renal cell carcinoma (HR 2.42, 95% CI 1.72-3.39, p = 0.001). CONCLUSIONS: Compared to patients with clear cell renal cell carcinoma those with collecting duct renal cell carcinoma have higher stage and are more often black. Even after adjusting for demographic, surgical and pathological factors disease specific survival is significantly worse in patients with collecting duct rather than clear cell renal cell carcinoma. Further research into the biology of this rare tumor is required to explain these results

Gallbladder Metastasis from Renal Cell Carcinoma

A 73-year-old female was operated with radical nephrectomy and cholecystectomy for renal cell carcinoma and suspected gallstones after 9 courses of sunitinib treatment. Gallbladder specimen showed gallbladder metastasis originating from the renal cell carcinoma. Gallbladder metastasis from renal cell carcinoma is rare. Here, we discuss a case of gallbladder metastasis from renal cell carcinoma

Unusual metastasis of papillary renal cell carcinoma to the pyriform sinus: case report

Renal cell carcinoma is the third most common cause of distant metastasis to the head and neck. Renal cell carcinoma metastasis should be considered in differential diagnosis when patients with a clinical history of renal cell carcinoma show a head and neck mass

Bilateral Renal Cell Carcinoma and its Treatment

A report is presented on two cases of bilateral renal cell carcinoma together with a review of the literature. Bilateral renal cell carcinoma is rare and there is much controversy concerning its treatment. Our current experience supports conservative therapy for bilateral renal cell carcinoma

Renal papillary carcinoma developed in a kidney transplant recipient with late IgA-nephropathy

With improvements in immunosuppressive therapy, patient and graft survival in renal transplant recipients have been prolonged. Increasing donor age and patient survival rates have been related to an increase in the number of de novo tumors. Posttransplant malignancy in these patients is an important cause of graft loss and death in these patients. Among cancers occurring after a kidney transplant, renal cell carcinoma is the fifth most common malignancy after lymphoproliferative disorders, and skin, gastrointestinal, and lung cancers. When nonmelanoma skin cancers and in situ carcinoma of the cervix are excluded from malignancies, renal cell carcinoma accounts for 2% of all cancers in the general population, which increases to 5% in solid-organ recipients. The majority of renal cell carcinomas found in transplant recipients develop in the recipient 's native kidneys, but only 9% of tumors develop in the allograft itself. Tumors transmitted by donors represent only 0.02% to 0.2% of cases. Most de novo allograft renal cell carcinomas are single tumors. The mechanisms of development of renal cell carcinoma in renal grafts are not completely understood

Atraumatic Ruptured Giant Renal Tumor

Massive hemoperitoneum due to spontaneous rupture of renal cell carcinoma is a rare presentation during emergency laparotomy. A 60-year-old female patient presented with severe abdominal pain, nausea, vomiting and abdominal distension. A massive hemoperitoneum secondary to ruptured left kidney tumor was found during laparotomy. Histology confirmed a papillary renal cell carcinoma. Ruptured renal cell carcinoma can be a cause of bleeding into the retroperitoneum space. Emergency sonography and laparotomy are advocated for its management. Keywords: Renal cell carcinoma, Rupture, Complex mass, Nephrectomy, Papillar