Evaluation of the benefit of using a combination of autologous platelet rich-plasma and hyaluronic acid for the treatment of Peyronie’s disease

Background: Platelet-Rich Plasma (PRP) has been successfully used for different medical conditions, to help regenerate fibrotic or inflammatory tissues. Peyronie’s disease (PD) could be a target for such treatment. In this study, PRP in combination with hyaluronic acid (HA) is proposed as an innovative treatment for this condition. Objectives: To assess the effects of repeated intralesional injections inside the tunica albuginea (TA) with a combination of PRP and HA in PD patients. Design, setting, and participants: 90 patients, naive of any prior interventional treatment, were injected with 8 ml of PRP combined with HA directly in the diseased area of TA under ultrasound (US) guidance. Injections were repeated 4 times within 2 months. Additional monthly sessions were done, if necessary. Outcome measurements and statistical analysis: Penile deformation, TA thickening, presence and size of calcifications, and questionnaires evaluating both PD and sexual function. Global results were classified into satisfactory improvement (I+) unsatisfactory (I-) and unchanged (U). Results and limitations: Angulation and thickening were both significantly improved after 4 sessions and continuously improved with the number of sessions, to achieve a mean final improvement of 39.65 +/-24.83% (p<0.001) (CI 14.26;18.82) and 26.23+/-10.29% (p<0.001) (CI 0.99;1.22), respectively . Younger patients achieved better results. 73.3% of the patients belonged to I+ group; 67.8% felt an improvement, 62.2% a decrease of their deformation, 46.7% had easier sexual intercourses and 70% judged the treatment as positive. Limitations included the absence of a control group. Conclusions: Repeated intralesional injections of PRP-HA improve significantly penile deformation and thickening of the TA. This fully natural treatment may stand as a first line treatment of PD. Patient summary: We evaluated here an innovative treatment of Peyronie’s disease using intralesional injections of Platelet-Rich Plasma mixed with hyaluronic acid. We observed a significant improvement of the deformation in 70% of the cases without any serious adverse events. Correspondence to: Ronald Virag MD, Centre d’Exploration et Traitement de l’Impuissance (CETI) Paris, France, E-mail : rvirag@wanadoo.fr Received: June 11, 2017; Accepted: July 05, 2017; Published: July 08, 2017 Introduction The treatment of penile deformities first described in 1743 by King Louis XV’s first surgeon François Gigot de Lapeyronie [1] has gained much interest especially for non-surgical procedures [2]. An increasing knowledge of the pathophysiology [3] of the disease has urged clinical researchers to propose intralesional treatments [4] such as verapamil [5] and interferon alpha 2B [6] which remain off label, or collagenase clostridium histolycum (CCH) ( Xiapex®) which obtained an FDA approval [7] for Peyronie’s disease (PD). The interesting improvement rates observed with these treatments are challenged by side effects such as corporeal ruptures for CCH, flu-like symptoms for interferon alpha 2B, or penile bruising, dizziness and nausea for verapamil. Moreover, a wider use of Xiapex® is to date limited by the high cost of the compound. More recently, Hyaluronic Acid (HA) (7) and Botulinum toxin [8] have also been proposed with the purpose of counteracting tunica fibrosis, the final issue of the pathological process of PD, before the deposit of calcifications [4]. We hypothesized that regenerative medicine could help stop the process and restore function. Although stem cell therapy for erectile dysfunction (ED) [9] and PD [10] has become a wide subject of research in animal studies with rising hopes for future treatments with adipose derived stem cells (ADSC’s), we did not find in the literature any mention of the potential use of autologous platelet-rich plasma (PRP) in both ED and PD. PRP is prepared from autologous blood after centrifugation with an adequate medic al device giving a plasma with a higher platelet concentration than baseline. [VDF2] PRP is a source of platelets growth factors (GFs). In situ activation of platelets induces the orchestrated release of several growth factors such as FGF(fibroblast growth factor), PGDF (platelet-derived growth factor), IGF (insulin-like growth factor), VEGF (vascular endothelial growth factor), and TGF-b (transforming growth factor) [11]. Platelet GFs are signals that regulate cell growth and division, as well as synthesis of extracellular matrix for tissue regeneration. On the other hand, plasma is a source of proteins such as fibrinogen, vitronectin and fibronectin which play a key role in the Virag R (2017) Evaluation of the benefit of using a combination of autologous platelet rich-plasma and hyaluronic acid for the treatment of Peyronie’s disease Volume 1(1): 2-8 Sex Health Issues, 2017 doi: 10.15761/SHI.1000102 regulation of cell-cell interaction and cell spatial organization [12]. Autologous PRP has been widely and safely used in many disciplines including orthopaedics, maxillofacial surgery, plastic and reconstructive surgery [13]. Adding thrombin to PRP produces a platelet gel which can be used as biological glue. One of us (RV) has been using it during graft procedures for PD surgery (unpublished data). From these early experiences, we became interested in an intralesional non-surgical use of PRP for PD. Okabe et al. [13] have shown experimentally that the addition of HA to PRP enhanced its regenerative potential, acting as a biological scaffold . The combination of PRP and HA, now facilitated by the availability of the new medical device CellularMatrix, encouraged us to conduct a first trial on 13 patients with PD [14]. Preliminary data from this case series indicated that patients experienced a significant improvement of their condition, both functionally and anatomically. Stimulated by these early encouraging results, we designed a new study using extensive clinical (the Peyronie’s disease questionnaire PDQ), echographic and photographic assessments as outcome measures in 90 patients whose results we report here are, to the best of our knowledge, the first in the English literature. Patients and methods Between July 2014 and November 2016, 90 patients (aged 25 to 77y, median 56) complaining of penile deformations and/or curvatures linked to the presence of plaques palpated in the tunica albuginea (TA), and who had not received any previous local treatment were enrolled in this study. All patients gave written informed consent. Patient’s evaluation criteria Patient’s eligibility was assessed on the basis of the onset and duration of the disease, initial local trauma, and presence of ED assessed by the IIEF-5 [15]. PDQ questionnaires [16] evaluate symptom’s bother. Deformation, consisting of curvatures (angulation in degrees) and/or shaft strictures was measured on photographs of fully erected penis [7]. Duplex ultrasound (DUS) (General Electric Logic F8 with an L12 RS probe) measurements of the thickening of the TA and presence of calcifications were assessed by one of us (HS) with a fixed protocol at each session of treatment (see appendix 1). In addition, patients responded to a self-administered questionnaire.