Long-Term Outcomes of Laser Incision and Triamcinolone Injection for the Management of Ureteroenteric Anastomotic Strictures.

Purpose: Benign ureteroenteric anastomotic stricture (UEAS) is a common postoperative complication after urinary diversion with an incidence of 3%-10%. Our objective is to report long-term follow-up of our technique for endoscopically managing UEAS after cystectomy. Materials and Methods: Patients with endoscopically managed benign UEAS after cystectomy were included. Intervention entailed anetegrade flexible ureteroscopy with biopsy followed by laser incision of the stricture and of periureteral and peri-ileal tissues 1 cm below and 1 cm above the stricture into fat. Triamcinolone injection was then performed, followed by balloon dilation of the incised area to 24F. Parallel Double-J ureteral stents or upside down nephrostomy tubes were placed for 6 weeks. CT scans were obtained at 3 months and 1 year after surgery, and renal ultrasound at 6 and 9 months, and then annually. Results: Twenty-one patients, and a total of 24 UEAS were treated. Urinary diversion included ileal conduit (n = 12), neobladder (n = 7), and Indiana pouch (n = 2). Twenty out of 24 strictures had no recurrence, including three patients who had bilateral disease, yielding an overall success rate of 83.3%. The remaining three patients with recurrence had evidence of stricture within 3 months. Follow-up ranged from 8 to 102 months, with a median of 30 months. Conclusions: Patients treated endoscopically for UEAS have been shown to have acceptable immediate success with less morbidity when compared with ureteral reimplantation. Our technique of laser incision, triamcinolone injection, balloon dilation, and temporary stent placement has a success rate of over 80% and is unique in that long-term data confirms the durability of this endoscopic procedure.

CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.

The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo. Similarly, treatment of BR5-1-derived tumors with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis and necrosis, reduction in intraperitoneal dissemination, and selective reduction of intratumoral FoxP3(+) regulatory T cells (Treg). Compared with controls, CXCR4 blockade greatly increased T-cell-mediated antitumor immune responses, conferring a significant survival advantage to AMD3100-treated mice. In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model. Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.