Masterson, Thomas A.

Abstract Introduction Collagenase clostridium histolyticum (CCH) is the only food and drug administration (FDA) approved intralesional medication for Peyronies Disease (PD). The manufacture instructions recommend a single injection into the plaque at the point of maximal curvature. However, a 2019 survey of the Sexual Medicine Society of North America (SMSNA) found that physicians were utilizing many different injection techniques. It is unknown if one technique is superior. Objective To assess delivery of medication into PD plaques using an invitro model. Methods We obtained PD plaques from men undergoing plaque excision and grafting. Plaques were stored at -80C until ready for use in the lab. We injected the plaques with 0.25ml of Eosin Y, 5 wt. 5% solution in water because this solution is visibly red and similar to the density of CCH. We assess how the dye spread through the plaque in four different injection techniques: single injection, single injection with slow pull back, multiple site injection and lateral injection. All injections were video recorded in real time. Results Dye was retained inside the plaques will all injection techniques, however in all conditions, a significant amount of dye leaked out of the plaques. Multiple injection technique appeared to have the least about of dye leak out of the plaque. Conclusions In all conditions, dye leaked out of the plaques, however the multiple injection technique appears to have deliver the greatest amount Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

Abstract Introduction Peyronie’s disease (PD), estimated to affect around 10% of the male population, is an acquired disorder of penile fibrotic tissue. The only FDA approved medical treatment for PD is Intralesional Collagenase Clostridium Histolyticum (CCh). CCh is a mixture of AUX1 and AUXII, two different forms of collagenase that cleave collage type I and type III, leading to plaque degradation. PD plaques, however, also contain fibrin and calcium which CCh is unable to digest. It is unknown if plaque calcification prevents collagenolysis with CCh. Objective To determine if calcification prevents collageolysis of PD plaques with CCh. Methods Calcified PD plaques were collected from five males undergoing excision and grafting for PD. Control tissue was collected from five males undergoing penile implant surgery for erectile dysfunction, with no known history of PD. Tissue samples were then divided into equal weights and incubated with CCh or PBS for 24 hours. The CCh or PBS was injected into the tissue (control or plaque) to mimic administration of CCH for treatment of PD. Following incubation, the fluid (CCh or PBS) was measured for soluble collagen amount and tissue was subjected to Picrosirius Red and H&E staining. Results There was a higher concentration of soluble collagen in the tissue (control and plaque) incubated in CCh (301ug, SD 21.1) compared to the issue incubated in PBS (32.5ug, SD 3.7) (p=0.02). Additionally, there was less type 1 and 3 collagen present in the CCh condition (mean 0.12, SD=0.08), when compared to the PBS condition (0.44, SD=0.17) (p=0.002). However, when comparing within the CCh condition to look at differences between tissue types (calcified vs. control) no differences were found. There was a similar amount of soluble collagen in the CCh control condition (316ug, SD 35) and the CCh calcified condition (286ug, SD 11) (p=0.06). Similarly, the PBS control condition (30ug, SD17) and the PBS calcified condition (35ug, SD 48) were found to have no significant differences in collagen concentration (p=0.4). Finally, there were no significant differences found in type I/III collagen staining between tissues in the CCh condition, with control (0.08, SD=0.02) and calcified (0.17, SD=0.09) demonstrating no significant difference (p=0.08). Tissues in the PBS condition, control (0.5, SD=0.23) and calcified (0.39, SD=0.39), similarly were not significant (p=0.2) (table 1). Conclusions CCh is capable of breaking down collagen in calcified plaques. Further research into CCh as a treatment option for PD calcified plaques is necessary. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc.