Paclitaxel-coated stents to prevent hyperplastic proliferation of ureteral tissue: from in vitro to in vivo.

Ureteric stents have become an indispensable tool in the armamentarium of every urologist. However, they carry their own morbidity resulting mostly from infectious or abacterial fouling and biofilm formation, and/or urothelial hyperplastic reaction. All of these may interact and lead to clinical complications. Many different stent designs and coatings have been proposed. In this study, we focused on the effect of paclitaxel-coated stents on hyperplastic proliferation of ureteral tissue, using as example anastomotic strictures after ureteroureterostomy in a rat model. Human urothelial cells (SV-HUC-1) were used to determine paclitaxel dosages in vitro. Polyurethane stents were coated with a paclitaxel containing biodegradable polymer and studied in a ureteroureterostomy rat model. 48 male 9-week-old Sprague-Dawley rats underwent either sham surgery (n = 16) or ureteroureterostomy with sutured anastomosis, and consecutive stenting with either a paclitaxel-coated or an uncoated stent (16 per group), respectively. The animals received daily intraperitoneal injections of 5-bromo-2-deoxyuridine (20 mg/ml, 100 mg/kg body weight) during the first eight postoperative days, and were sacrificed on day 28. Healing of the ureteral anastomosis and proliferation of urothelial cells was examined histologically and immunohistochemically. In vitro, a concentration of 10 ng/mm2 paclitaxel can be considered as non-toxic, while still exerting an anti-proliferative effect on urothelial cells. Histologically, typical wound healing processes were seen at the site of the ureteral anastomosis in vivo. Proliferation of urothelial cells was significantly lower in animals with paclitaxel-coated stents compared to those with uncoated stents (LI 41.27 vs. 51.58, p < 0.001). Our results indicate that stenting of ureteral anastomoses with paclitaxel-coated stents can reduce hyperplastic proliferation of ureteral tissue. Paclitaxel-coated stents thus might be able to prevent not only scar-induced postoperative stenosis after reconstructive surgery, but also hyperplastic urothelial reaction in non-anastomotic stent patients as part of their inflammatory response to the foreign material.

Ureteral stent encrustation. Pathophysiology.

Ureteral stents are the most commonly used urological implants. They are used for temporary as well as for long-term ureteral stenting. Amongst others, complications of ureteral stenting are encrustation and cellular adherence which, in turn, promotes urinary tract infection and can induce impaired healing in case of ureteral damage. Biofilm formation on urological implants leads to the protection of persisting bacteria from local defense mechanisms, thereby rendering persistent urinary tract infections more common. It seems clear that antibiotics cannot penetrate into biofilms adequately. Also, bacteria persist in biofilms in a state of reduced metabolism which further reduces antibiotic efficacy. Furthermore, bacteria develop resistance more quickly in biofilms. This paper tries to give an overview of the complex pathophysiological mechanisms that underlie stent encrustation as far as we know to date.

[Confocal laser scanning microscopy of the urothelium]. / Konfokale Laserscanningmikroskopie von Urothel.

In order to improve the detection of flat urothelial neoplasia an improvement in optical methods might be helpful. We investigated the use of confocal laser scanning microscopy in a pilot study of specimens with bladder cancer. A total of 35 fresh ex vivo specimens of 20 human bladders of patients who underwent radical cystectomy were examined with a modified confocal laser scanning microscope (670 nm). The field size was 200x200 microm and tissue was investigated up to depths of 120 microm. Resulting data sets were reconstructed three-dimensionally by computer software. Results were compared with conventional histology. Microscopically diseased bladder mucosa showed cytological and histological criteria of malignancy which were readily identifiable by laser scanning microscopy. In all cases we were able to detect the presence of malignancy with the images generated by the confocal laser scanning technique. Atypical cellular structures and subepithelial hypervascularization were prominent features. Carcinoma in situ lesions could also be identified in many cases. Confocal laser scanning microscopy allows the analysis of cellular and epithelial architecture of the urothelium in a detail which is beyond the limitations of conventional endoscopy by white light cystoscopy. Therefore, the principle would probably be of benefit if the technical limitations can be overcome.

[Urological complications after kidney transplantation]. / Urologische Komplikationen nach Nierentransplantation.

Between August 1981 and May 2005, 1065 consecutive kidney transplants were performed at our center; 393 patients (36.9%) developed urological complications in the first 60 postoperative days. Urinary tract infections occurred in 28.5% of all patients. The major urological problems seen were urinary leakage and ureteral obstruction in 6.2% and 1.4% of the patients. Two grafts were lost due to severe urinary leakage. No patient death occurred due to urological complications. The incidence of urological complications is mainly influenced by the surgical procedure of organ retrieval and ureteroneocystostomy. With double-J stenting of the extravesical ureteroneocystostomy, we observed a significantly lower rate of urinary leakage but a higher rate of urinary tract infections in our series. Early diagnosis and treatment of urological complications may prevent further morbidity of our transplant patients.