In advanced renal cell carcinoma (RCC), surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10) antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14) in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.
Purpose: To compare the efficacy and safety of the electromagnetic lithotripter in the treatment of pediatric lithiasis to that of the earlier electrohydraulic model. Results: In the first group, 21/26 children (80.7%) were stone free at first ESWL session. Colic pain resolved by administration of an oral analgesic in 6 (23%), brief hematuria (< 24 h) resolved with increased fluid intake in 5 (19.2%), while slightly elevated body temperature (< 38°C) occurred in 4 (15.3%). Four children (15.3%) failed to respond to treatment and were treated with ureteroscopy. In the second group 18/19 children were completely stone free at first ESWL session (94.7%). Complications were infrequent and of minor importance: colic pain treated with oral analgesic occurred in 1 (5.26%), brief hematuria (< 24 h), resolved with increased fluid intake in 4 (21%) and slightly elevated body temperature (< 38°C) monitored for 48 hours occurred in 6 (31.5%). Statistical analysis showed that electromagnetic lithotripter is more efficacious and safer than the earlier electrohydraulic model. Conclusions: Technological development not only has increased efficacy and safety of lithotripter devices in treating pediatric lithiasis, but it also provided less painful lithotripsy by eliminating the need for general anesthesia.
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