Antimicrobial peptides are effector molecules of the innate immune system and contribute to host defense and regulation of inflammation. The human cathelicidin antimicrobial peptide LL-37/hCAP-18 is expressed in leukocytes and epithelial cells and secreted into wound and airway surface fluid. Here we show that LL-37 induces angiogenesis mediated by formyl peptide receptor–like 1 expressed on endothelial cells. Application of LL-37 resulted in neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. The peptide directly activates endothelial cells, resulting in increased proliferation and formation of vessel-like structures in cultivated endothelial cells. Decreased vascularization during wound repair in mice deficient for CRAMP, the murine homologue of LL-37/hCAP-18, shows that cathelicidin-mediated angiogenesis is important for cutaneous wound neovascularization in vivo. Taken together, these findings demonstrate that LL-37/hCAP-18 is a multifunctional antimicrobial peptide with a central role in innate immunity by linking host defense and inflammation with angiogenesis and arteriogenesis
Purpose
To assess the impact that improved detection of non-muscle invasive bladder cancer with hexaminolevulinate (HAL) fluorescence cystoscopy may have on early recurrence rates.
Materials and methods
This prospective, randomized study enrolled 814 patients suspected of having bladder cancer at increased risk for recurrence. All patients underwent white light cystoscopy and mapping of lesions, followed by transurethral resection of the bladder (TURB) where indicated. Patients in the fluorescence group also received intravesical hexaminolevulinate solution at least one hour before cystoscopy to induce fluorescence of cancerous lesions, and underwent additional inspection with blue light before and after TURB. Adjuvant intravesical therapy was based on risk. Follow up cystoscopies at 3, 6 and 9 months were conducted with white light.
Results
Detection was carried out as a within-patient comparison in the fluorescence group. In this group, 286 patients were found to have at least one Ta or T1 tumor (ITT). In 47 (16%), at least one of the tumors was seen only with fluorescence (p=0.001). During the 9 month follow-up period (ITT), there were tumor recurrences in 128/271 patients (47%) in the fluorescence group and 157/280 patients (56%) in the white light group (p=0.026). The relative reduction in recurrence rate was 16%.
Conclusions
HAL fluorescence cystoscopy significantly improves detection of Ta and T1 lesions and significantly reduces the rate of tumor recurrence at 9 months.
Open prostatectomy showed a satisfactory early postoperative outcome with a complication rate that was within the expected range compared to that in the recent literature. It represents an important option in the treatment of patients with significant benign enlargement of the prostate for surgeons with no access to modern techniques, such as holmium laser enucleation of the prostate or laparoscopy.
Purpose
We assessed the impact that hexaminolevulinate fluorescence cystoscopic detection of papillary, non-muscle invasive bladder cancer has on long-term recurrence rates.
Materials and Methods
Long-term follow-up was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study, 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6, and 9 months following the initial resection or until recurrence. A study extension protocol obtained long-term follow-up of these patients.
Results
Follow-up information was obtained for 261 of the 280 (93%) participants in the white light group and 255 of the 271 (94%) participants in the fluorescence group. Median follow-up in the white light and fluorescence groups were 53.0 and 55.1 months, respectively. In the white light and fluorescence groups, 83 (31.8%) and 97 (38%) of the participants remained tumor free, respectively. The median recurrence free survival was 9.6 months in the white light group and 16.4 months in the fluorescence group, p = 0.04. The rates of intravesical therapy were similar in the white light (46%) and fluorescence groups (45%). Cystectomy was performed in 22/280 (7.9%) in the white light group and 13/271 (4.8%) in the fluorescence group, p = 0.16.
Conclusions
Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer recurrence free survival with a trend towards improved bladder preservation.
Early recovery after surgery of patients who underwent radical cystectomy appears to have significant benefits compared to a conservative regimen in terms of postoperative morbidity, quality of life, use of analgesics and time spent in the intermediate care unit.
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