The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion.
We report the clinical outcome of more than 800 patients, who underwent continent cutaneous urinary diversion with an ileocecal reservoir (Mainz-pouch I) in two urological tertiary referral centers at a mean follow-up of 7.6 years. Complications related to the continence mechanism (intussuscepted ileal nipple vs. submucosally embedded in situ appendix) and the antirefluxive uretero-intestinal anastomosis (submucosal tunnel vs. serosa-lined extramural tunnel) were recorded retrospectively. Stomal stenosis was observed in 23.5% of the patients with appendix stoma and in 15.3% of the patients with intussuscepted ileal nipple. The incidence of calculi was 10.8% in reservoirs with intussuscepted ileal nipple and 5.6% in reservoirs with appendix stoma. Eleven patients (eight with appendix, three with ileal nipple) required reoperation because of ischemic degeneration of the continence mechanism. The overall continence rate (day and night) was 92.8%. Anastomotic strictures of the afferent limb occurred in 6.5% of renal units (RUs) with a submucosal tunnel and in 5.0% of RUs with a serosa-lined extramural tunnel. Continent cutaneous urinary diversion with an ileocecal pouch is a highly satisfactory and safe option for patients, in whom orthotopic urinary diversion is impossible or contraindicated.
Elective nephron sparing surgery is oncologically safe in select patients with localized renal cell carcinoma more than 4 cm. In our series the selection criterion for choosing elective nephron sparing surgery rather than radical nephrectomy over the years has consistently been safe surgical resectability rather than tumor size. However, there is a correlation between tumor size and unfavorable pathological tumor characteristics, which prompts caution when choosing elective nephron sparing surgery for all large tumors.
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