Evaluation of submicron particle docetaxel directly injected into uro-oncologic xenografts.

360 Background: We evaluated intratumoral (IT) injection of submicron particles of pure docetaxel (NanoDoce) into clear cell renal carcinoma (768-O [R]), transitional cell bladder carcinoma (UM-UC-3 [B]) and prostate carcinoma (PC-3 [P]) xenografts implanted into immunocompromised rats and mice. Methods: Animals received IT NanoDoce and IV docetaxel per Table. Treatments were 7 days apart. Animals were followed up to 60 days post-treatment initiation. Tumor size, clinical signs and body weight were assessed 2-3 times per week. In the 786-O and UM-UC-3 studies, tumor site tissues were analyzed for docetaxel levels and H&E and IHC (CD11b, CD45r) was evaluated. Results: Tumor volume decreases with 2 and 3 doses of NanoDoce were significantly greater than (R, B) or similar (P) to IV docetaxel and better than vehicle (p < 0.05). High tissue levels of docetaxel were detected in all NanoDoce-treated animals with evaluable tumor tissue. In these animals, histology confirmed tumor volume findings; IHC showed (peri)tumor-infiltrating immune cells in all NanoDoce-treated animals. Comparators exhibited limited to no infiltration. NanoDoce-treated UM-UC-3 tumor injection sites were typically cleared of tumor and contained lymphoid structures. No lymphoid structures were seen in comparators and all had residual tumor. Conclusions: Local presence of persistent, therapeutic levels of docetaxel from IT NanoDoce creates a unique disruption of the tumor microenvironment. IT injection of NanoDoce may kill tumor cells through direct and indirect means. NanoDoce directly inhibits tumor cell mitosis, and in reducing tumor burden, indirectly promotes immune cell-mediated tumor clearance. Clinical testing of NanoDoce in urogenital tumors is underway. [Table: see text]

A case of transitional cell bladder carcinoma prolapsed from the external urethral orifice: A 6-year follow-up after percutaneous suprapubic bladder

A 30-year-old female was admitted in emergency with acute urinary retention due to bladder tumour prolapsed from the external urethral orifice. The patient underwent immediate endoscopic surgery via suprapubic percutaneous approach. The histological examination confirmed a superficial highly differentiated transitional cell bladder carcinoma. During the 6-year follow-up no evidence of local recurrence or metastatic tumor spread was revealed. The comprehensive Medline search confirmed that this is the fourth case of bladder tumor prolapsed from the external urethral orifice, reported so far. The case deserves the interest of practicing urologists because of the exceptional rarity of the entity and the unconventional treatment approach which involves using a percutaneous suprapubic endoscopic technique. Based on the results achieved, we can recommend this unconventional endoscopic approach as specifically indicated in certain situations. .