Cop+Ed+fisse 2006 87Archivio Italiano di Urologia e Andrologia 2022; 94, 1 ORIGINAL PAPER No conflict of interest declared. Clinically, PD has two distinct phases: inflammatory (acute), when there is pain and the onset and progression of penile deformity; and fibrotic (chronic), when there is stabilization of the penile curvature, cessation of the pain, and possibly the formation of a well-defined plaque on the corpora cavernosa (4). Surgical treatment for PD is reserved for patients who are in the second stage of the disease, with stable tortuosity for at least three to six months. There are basically two types of procedures for correction of penile curvature: tunical shortening and tunical lengthening techniques (5). The latter consists in plaque incision/excision and grafting, following this indication: patients without refractory erectile dysfunction (ED), with curvatures greater than sixty degrees, complex deformities or in patients with smaller curvatures but significant penile shortening for plication procedures (6, 7). The ideal graft should be traction resistant, easy to suture and manipulate, flexible, readily available, cost-effective and with minimal associated morbidity. So far, no mate- rial studied has met all these criteria. Several studies have analyzed the use of autografts, allografts and xenografts. Synthetic grafts are historically not recommended, due to the increased risk of infection, allergic reactions and mate- rial rejection. The use of bioabsorbable synthetic grafts, on the other hand, has been little studied to date (8-11). The aim of this study was to perform a descriptive analy- sis about functional results with the use of a bioab- sorbable graft in the setting of Peyronie's disease surgical treatment. MATERIALS AND METHODS The present study protocol was reviewed and approved by the Institutional Review Board of Hospital Governador Celso Ramos (approval No. 47537021.0.0000.5360). Informed consent was submitted by all subjects when they were enrolled. Psychological counseling was offered to all patients before the surgery, although it was not con- sidered obligatory. A single-center, retrospective cohort study of patients undergoing treatment for Peyronie's dis- ease using a bioabsorbable graft between 2018 and 2021 was conducted. The graft used was the Gore® Bio-A® (W.L. Gore & Associates, Inc. Flagstaff, Arizona, US), com- posed of a network of synthetic polymers (67% of polyg- Objective: Plaque incision and grafting is indicated for patients with Peyronie’s Disease [PD] and severe curvature, complex deformities or for patients with significant penile shortening. To date, no graft studied has been considered ideal. The aim of this study is to conduct a descriptive analysis about functional results with the use of a bioabsorbable graft for PD treatment. Materials and methods: A single-center, retrospective evaluation of a cohort of patients who were treated by plaque incision and grafting with a polyglycolic acid polymer graft (Gore® Bio-A®) between 2018 and 2021 was conducted. Correction of penile curvature was the main outcome. Loss of penile sensitivity, de novo erectile dysfunction and any other adverse event were the secondary endpoints. Results: 14 patients were included in this study (mean age 59.5 ± 7.2 years). The median follow-up time was 12 months (range 3-12). The curvature correction rate was 78.5%. Glans hypoesthesia was present in one of 14 patients (7.1%) and refractory erectile dysfunction was reported in 64.2%. None of the patients presented any major adverse event based on Clavien-Dindo classification. Conclusions: Curvature correction and changes in penile sensi- tivity rates were similar to those found in the literature. No major surgical complications, such as graft rejection, infec- tion, and extrusion, occurred in this sample. Although a popula- tion with a higher prevalence of erectile dysfunction was includ- ed in this sample, higher rates of refractory erectile dysfunction were observed and these findings should be confirmed in further studies. KEY WORDS: Peyronie’s disease; Penile induration; Penile curvature; Erectile dysfunction; Bioabsorbable implants; Polyglycolic acid. Submitted 21 December 2021; Accepted 18 January 2022 INTRODUCTION Peyronie's Disease (PD) is characterized by a disorder of the connective tissue of the penis that affects the tunica albuginea, which can lead to local pain and tortuosity. Although the etiology is unknown, the most accepted hypothesis is repetitive microvascular trauma, leading to inflammation, fibrinogenesis and excessive collagen dep- osition on the tunica albuginea, facilitated by risk factors such as hypertension, diabetes, dyslipidemias, smoking and alcoholism (1-3). The use of a polyglycolic acid polymer graft in Peyronie’s disease - preliminary outcomes Pedro Caetano Edler Zandoná 1, Nivio Pascoal Teixeira 1, Henrique Eduardo Oliveira 1, Jorge Hamilton Soares Garcia 2 1 Department of Urology of Hospital Governador Celso Ramos, Florianópolis, Brazil; 2 Department of Anesthesiology of Hospital Governador Celso Ramos, Florianópolis, Brazil. DOI: 10.4081/aiua.2022.1.87 Summary Archivio Italiano di Urologia e Andrologia 2022; 94, 1 P.C. Edler Zandoná, N.P. Teixeira, H.E. Oliveira, J. Hamilton Soares Garcia 88 lycolic acid and 33% trimethylene carbonate) which are gradually absorbed by the body and registered by ANVISA for use in humans as a soft tissue substitute. The inclusion criteria for this study were all patients undergoing treatment for PD using the Bio-A® graft between 2018 and 2021 at Hospital Governador Celso Ramos, Florianópolis, State of Santa Catarina, Brazil. No exclusion criteria were applied. Data was obtained exclusively from medical charts retro- spective review, and patients’ identity was kept confiden- tial. Curvature correction, was the primary endpoint, characterized by the absence of residual curvature greater than 15 degrees. All patients underwent interview and physical examination during the routine postoperative fol- low-up visits. Patients who reported residual curvature underwent artificial erection in the office to confirm this finding. Secondary endpoints were penile sensory change, postoperative ED and surgical complications (based on Clavien-Dindo classification). The secondary outcomes were also assessed through anamnesis and physical exam- ination performed during routine follow-up visits and described in the patients’ medical chats. Refractory ED, identified pre- or postoperatively, was characterized as the self-reported inability to develop or maintain an erection despite the use of phosphodiesterase type 5 inhibitors (PDE5i). Patients were informed about the risks of erectile function worsening, and the possibility of penile prosthe- sis implantation in a second-stage surgery. Surgical technique was similar in all cases. Under general anesthesia, a subcoronal incision was made and the penis was degloved. An artificial erection was performed at this point and the curvature was identified. In case of dorsal curvatures, the neurovascular bundle was carefully dissect- ed from the corpora caver- nosa. In case of ventral curvature, the urethra was dissected from the corpora cavernosa. Then again, an artificial erection was per- formed to identify the point of greatest curvature of the plaque. An H-inci- sion was then made into the plaque and the defect created was measured to determine the size of the graft. Gore® Bio-A® graft was then placed and fixed over the defect with run- ning sutures of its margins with 3-0 Vicryl (Figure 1). The penis was then cov- ered and a circumcision was performed. The aver- age surgery time was 137.2 (± 19.5 minutes). All patients were dis- charged after 24 hours of the surgery and were pre- scribed 5 mg of tadalafil to use once a day. Statistical analyses were performed using IBM® SPSS® Statistics, version 28.0.0.0. Variables and results related to the primary and secondary out- comes were presented descriptively for each patient. Continuous variables were described in the comparative analysis as the median and respective interquartile range. Categorical variables were described as percentages of the total number of patients. RESULTS Patient characteristics, risk factors and preoperative findings A total of 14 patients were included in this study. The mean age was 59.5 years (± 7.2).Overall, 42.8% (6/14) of patients had hypertension, 21.4% (3/14) diabetes, 42.8% Table 1. Patients characteristics and postoperative outcomes. This table describes important preoperative findings for each patient, as well as the main postoperative outcomes. Patient Age Curvature Curvature Preoperative Curvature Penile Postoperative Surgical number type degree ED correction sensory ED complications change (Clavien-Dindo grade) 1 64 Uniplanar a 65 Yes Yes No Yes Yes (I) 2 64 Uniplanar a 80 No Yes No No No 3 67 Biplanar 80 Yes Yes No Yes No (with ventral component) 4 47 Biplanar b 50 No Yes No Yes No 5 64 Biplanar b 45 No Yes No No Yes (I) 6 55 Uniplanar a 60 Yes Yes No Yes d No 7 51 Complex ᶜ 90 No No No No No 8 61 Biplanar 80 Yes Yes No Yes ᵈ No (with ventral component) 9 45 Biplanar ᵇ 90 No Yes No Yes Yes (I) 10 58 Uniplanar ᵃ 50 No No No No No 11 67 Biplanar ᵇ 45 No Yes Yes No No 12 65 Uniplanar ᵃ 60 No Yes No Yes No 13 61 Biplanar ᵇ 50 Yes No Yes Yes ᵈ Yes (I) 14 64 Biplanar ᵇ 60 No Yes No No No ED: erectile dysfunction. a. Uniplanar includes dorsal and lateral and excludes ventral curvatures. b. Biplanar includes dorso-lateral curvatures and excludes biplanar with ventral component curvatures. c. Complex curvatures includes hour-glass and hinge deformities. d. Patients that underwent malleable penile prosthesis implantationn. Figure 1. Gore® Bio-A® graft being placed and secured with running sutures. An H-shaped incision was performed at the point of maximum curvature, after degloving the penis. The defect is measured and the graft is secured with Vicryl 3.0 stitches. 89Archivio Italiano di Urologia e Andrologia 2022; 94, 1 Polyglycolic acid graft in Peyronie’s disease (6/14) smoking habits and 21.4% (3/14) dyslipidemia. Regarding the presence of preoperative ED, 35.7% of patients (5/14) reported impaired erections even with PDE5i before the surgery. On the other hand, 64.3% reported satisfactory erections. The median curvature degree was 60° (range 45-90°). The median time of plaque stability was 36 months (range 12-72). Regarding the cur- vature type, 35.7% (5/14) had uniplanar curvatures (except ventral); 50% (7/14) had biplanar (except ventral) or complex (hourglass or hinge) deformities, and 14.2% (2/14) had curvatures with some ventral component. Surgical outcomes The median follow-up time was 12 months (range 3-12). In terms of curvature correction, 3 of the 14 patients (21.4%) reported residual curvature greater than 15°, that was confirmed after performing artificial erection in the office. The curvature correction rate, therefore, was 78.5% (11/14). Regarding the secondary endpoints, 1 of 14 patients (7.1%) reported glans hypoesthesia. Nine of 14 patients (64.2%) reported refractory ED postoperatively (using 5 mg of tadalafil). Three of the these patients decided to underwent a malleable penile prosthesis implantation after 12 months of the first surgery. Excluding sensory changes and erection impairment, four patients (24.5%) presented minor surgical complications (penile pain and swelling) classified as Clavien-Dindo grade I. None of the patients (0/14) presented major surgical complications, Clavien-Dindo grade ≥ II. Table 1 describes the charac- teristics and postoperative outcomes for each patient. DISCUSSION This study described our initial experience with the Gore® Bio-A® graft, which, to our knowledge, has never been studied for Peyronie’s disease management before. Residual curvature after surgery was a concern, given the physiology of graft integration, which is based on com- plete replacement of the synthetic material by native scar tissue, which could again result in fibrosis and curvature (12, 13). What was obtained, in fact, was a similar rate to that found in other studies, even after 6 months, which is the time described by the manufacturer for complete absorption of the material (13). The European Association of Urology (EAU) 2021 guidelines describe curvature cor- rection average rates (involving different non-comparable studies), or success rates, for porcine intestinal submucosa (SIS) grafts of 83.9% (range 54 -91), 87.4% for bovine pericardium (range 76.5-100) and 81.2% for dermis (range 60-100) (14). Table 2 describes curvature correc- tion rates with different patches. Regarding decreased glans sensitivity, we obtained lower rates compared to those described in other series, such as Chung et al. (15), with 13% impaired sensitivity after der- mis graft, and as Horstmann et al. (16), with 16%, after using TachoSil®, but slightly higher compared to the series by Sansalone et al. (17), with 3%, after bovine pericardium. Table 3 describes penile sensory changes with different patches. This outcome, however, seems to be more related to the technique used for dissection of the neurovascular bundle, rather than to the type of material used (8). Furthermore, a recent study by Terrier JE et al. showed that penile sensory changes tends to decrease in frequency and severity with time, with only rare cases occurring after 12 months (18). In terms of postoperative (de novo) erectile dysfunc- tion, the EAU 2021 guide- lines describe average rates of 21.9% (range 7-54) for porcine intestinal submu- cosal grafts (SIS), 26.5% (range 0-50) for bovine pericardium, and 20.5% (range 7-67) for autolo- gous dermis (14). Other series, as Fabiani et al. (19, 20), report even lower rates, with 5.8% and 7.2% of ED after buccal mucosa graft. In our cohort, we found higher rates of refractory erectile dysfunc- tion (Table 4). However, a possible selec- tion bias must be consid- ered, as 35.7% of patients (5/14) reported impaired erectile function prior to the surgical procedure. In this study, all patients were enrolled to undergo curva- ture correction surgery – Table 2. Curvature correction with different patches. This table describes the curvature correction rates, expressed as weighted average, with grafts that are frequently used worldwide, along with the rate found with Gore®Bio-A®. Author, year EAU 2021 average rates for EAU 2021 average rates EAU 2021 average rates Zandoná et al. (2021) – and graft used porcine intestinal submucosa (SIS)a for bovine pericardiuma for Dermisa Gore® Bio-A® patch Curvature/deformity correction 83.9% (54-91) 87.4% (76.5-100) 81.2% (61-100) 78.5% a. Data are expressed as weighted average and range in parenthesis (from different non-comparable studies). Table 4. De novo erectile dysfunction with different patches. This table describes the rates of postoperative erectile function worsening with different grafts, that are frequently used worldwide, along with the rate found with Gore®Bio-A®. Author, year EAU 2021 average rates for EAU 2021 average rates Fabiani et al. (2016/2021) Zandoná et al. (2021) – and graft used porcine intestinal submucosa (SIS)a for bovine pericardiuma buccal mucosa patch Gore® Bio-A® patch De novo erectile dysfunction 21.9% (7-54) 26.5% (0-50) 5.8%/ 7.2% 64.2% a. Data are expressed as weighted average and range in parenthesis (from different non-comparable studies). Table 3. Penile sensory changes with different patches. This table describes the rates of penile numbness, or penile hypoesthesia with grafts that are frequently used worldwide, along with the rate found with Gore®Bio-A®. Author, year Chung et al. (2011) - Horstmann et al. (2011) - Sansalone et al. (2011) - Zandoná et al. (2021) - and graft used dermis graft Tachosil® bovine pericardium Gore® Bio-A® patch Penile Hypoesthesia 13% 16% 3% 7.1% a. Data are expressed as weighted average and range in parenthesis (from different non-comparable studies). Archivio Italiano di Urologia e Andrologia 2022; 94, 1 P.C. Edler Zandoná, N.P. Teixeira, H.E. Oliveira, J. Hamilton Soares Garcia 90 plaque incision and grafting – as a first-stage procedure. Although penile prosthesis implantation can be offered as a second procedure, it’s possible to perform both surgeries at the same time, even with the use of grafts, for patients at high-risk of developing refractory ED (14). The absence of major surgical complications, especially graft rejection, infection or extrusion, seems to be a char- acteristic of bioabsorbable materials, as opposed to syn- thetic grafts. We know that the incorporation process, comprising graft cell infiltration, neovascularization, and collagen deposition, which occurs in bioabsorbable mate- rials, seems to lead to a lower risk of infection and ero- sion, compared to encapsulation, which occurs with the use of non-absorbable materials (21, 22). This study has some limitations, and therefore it should be interpreted with caution. The "self-reported" assess- ment of patients regarding erectile dysfunction, residual curvature and sensitivity change parameters, although described and recognized in the literature, is based on a subjective parameter and, therefore, reduces the statisti- cal value and the possibility of extrapolating the results (23). The loss of follow-up of patients in the expected returns after surgery, largely due to the COVID-19 pan- demic and cancellation of elective appointments, also had a negative impact on the results of this sample. CONCLUSIONS In this study, it was possible to demonstrate our initial experience with the use of Gore® Bio-A® graft. The rates of curvature correction and change in glans sensitivity were similar to those found in the literature. The rates of major complications related to the graft, as rejection, infection, and extrusion, were negligible in this sample. Although a population with a higher prevalence of erectile dysfunction was included in this sample, higher rates of refractory erec- tile dysfunction were observed and these findings should be confirmed in further studies. We believe that this study brings the perspective that similar bioabsorbable grafts can be used as an alternative in PD’s treatment, although prospective studies with a larger population and longer fol- low-up are needed to validate such findings. REFERENCES 1. Devine Jr CJ, Somers KD, Jordan SG, Schlossberg, SM. Proposal: trauma as the cause of the Peyronie’s lesion. J Urol. 1997; 157: 285. 2. Kadioglu A, Tefekli A, Erol B, et al. A retrospective review of 307 men with Peyronie’s disease. J Urol. 2002; 168:1075. 3. Rhoden EL, Riedner CE, Fuchs SC, et al. A cross-sectional study for the analysis of clinical, sexual and laboratory conditions associat- ed to Peyronie’s disease. J Sex Med. 2010; 7:1529. 4. Ralph D, Gonzalez-Cadavid N, Mirone V, et al. The management of Peyronie’s disease: evidence-based 2010 guidelines. J Sex Med, 2010. 7:2359. 5. Chung E, Ralph D, Kagioglu A, et al. Evidence-based management guidelines on Peyronie’s disease. J Sex Med. 2016; 13:905. 6. Mulhall J, Anderson M, Parker M. A surgical algorithm for men with combined Peyronie’s disease and erectile dysfunction: function- al and satisfaction outcomes. J Sex Med. 2005; 2:132. 7. Zaid UB, Alwaal A, Zhang X, Lue TF. Surgical management of Peyronie’s disease. Current Urol Rep. 2014; 15:446. 8. Garcia-Gomez B, Ralph D, Levine L, et al. Grafts for Peyronie's disease: a comprehensive review. Andrology. 2018; 6:117-126. 9. Carson CC, Levine LA. Outcomes of surgical treatment of Peyronie's disease. BJU Int. 2014; 113:704-13. 10. Schiffman ZJ, Gursel EO, Laor E. Use of Dacron patch graft in Peyronie disease. Urology. 1985; 25:38. 11. Faerber GJ, Konnak JW. Results of combined Nesbit penile pli- cation with plaque incision and placement of Dacron patch in patients with severe Peyronie’s disease. J Urol. 1993; 149:1319. 12. Klinge U, Schumpelick V, Klosterhalfen B. Functional assessment and tissue response of short- and long-term absorbable surgical meshes. Biomaterials. 2001; 22:1415. 13. Yeo KK, Park TH, Park JH, et al. Histologic changes of implant- ed gore bio-a in an experimental animal model. Biomed Res Int. 2014; 2014:167962. 14. Salonia A, Bettocchi C, Carvalho J, et al. Guidelines on Sexual and Reproductive Health. Edn. presented at the EAU Annual Congress Milan 2021. ISBN 978-94-92671-13-4. 15. Chung E, Clendinning E, Lessard L, Brock G. Five-year follow- up of Peyronie’s graft surgery: outcomes and patient satisfaction. J Sex Med. 2011; 8:594. 16. Horstmann M, Kwol M, Amend B, et al. A self-reported long- term follow-up of patients operated with either shortening techniques or a TachoSil grafting procedure. Asian J Androl. 2011; 13:326. 17. Sansalone S, Garaffa G, Djinovic R, et al. Long-term results of the surgical treatment of Peyronie’s disease with Egydio’s technique: a European multicentre study. Asian J Androl. 2011; 13:842. 18. Terrier JE, Tal R, Nelson CJ, Mulhall JP. Penile Sensory Changes After Plaque Incision and Grafting Surgery for Peyronie’s Disease. J Sex Med. 2018; 15:1491. 19. Fabiani A, Servi L, Fioretti F, et al. Buccal mucosa is a promis- ing graft in Peyronie’s disease surgery. Our experience and a brief lit- erature review on autologous grafting materials. Arch Ital Urol Androl. 2016; 88:115-21. 20. Fabiani A, Fioretti F, Pavia MP, et al. Buccal mucosa graft in surgical management of Peyronie's disease: Ultrasound features and clinical outcomes. Arch Ital Urol Androl. 2021; 93:107-110. 21. Trabuco EC, Zobitz ME, Klingele CJ, Gebhart JB. Effect of host response (incorporation, encapsulation, mixed incorporation and encapsulation, or resorption) on the tensile strength of graft-rein- forced repair in the rat ventral hernia model. Am J Obstet Gynecol. 2007; 197: 638.e1. 22. Klinge U, Klosterhalfen B, Müller M, Schumpelick V. Foreign body reaction to meshes used for the repair of abdominal wall her- nias. Eur J Surg. 1999; 165:665. 23. Revicki DA, Cella D, Hays RD, et al. Responsiveness and mini- mal important differences for patient reported outcomes. Health Qual Life Outcomes. 2006; 4:70. Correspondence Pedro Caetano Edler Zandoná, MD (Corresponding Author) uropedrozandona@gmail.com pedrozandona@outlook.com Rua Esteves Júnior, 574, ap 105, 88015-130 Florianópolis, Santa Catarina (Brazil) Nivio Pascoal Teixeira, MD - nivio@uromed.com.br Henrique Eduardo Oliveira, MD - henriqueoliveira02@hotmail.com Jorge Hamilton Soares Garcia, MD - jorge@anestesiologistas.com.br