Surgery for Peyronie＇s disease

Peymnie＇s disease （PD） is most simply referred to as a fibrotic wound-healing disorder of the tunica albuginea. It is both a physically and psychologically devastating disorder that causes penile deformity, curvature, hinging, narrowing and shortening, which may compromise sexual function. Although a variety of non-surgical treatments have been suggested, none to date offer a reliable and effective correction of the penile deformity. As a result, surgery remains the gold standard treatment option, offering the most rapid and reliable treatment which will be the focus of this article. We review the preoperative evaluation, surgical algorithm, graft materials and postoperative management of PD. Outcomes for tunical shortening, tunical lengthening and penile prosthesis placement for penile straightening are reviewed. Tunica albuginea plication is the preferred method of straightening for men with adequate rigidity and less severe disease defined as curvature less than 70° without narrowing/hinging. Men who have more severe, complex deformity, but maintain strong preoperative erectile function should be considered candidates for straightening with plaque incision or partial excision and grafting. Finally, for those men who have inadequate rigidity and PD, penile prosthesis placement with straightening is the best approach to address both problems.

Extracorporeal shockwave therapy for Peyronie＇s disease： an alternative treatment？

Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent ESWT （group 1）. Fifteen patients matched with the baseline characteristic of the patients in group 1, who received no treatment, were used as the control （group 2）. The patients＇ erectile function （International Index of Erectile Function [IIEF-5] score）, pain severity （visual analog scale）, plaque size and degree of penile angulation were assessed before and after the treatment in group 1 and during the follow-up in group 2. Results： The mean follow-up time was 32 months （range： 6-64 months） in group 1 and 35 months （range： 9-48 months） in group 2. All the patients were available for the follow-up. Considering erectile function and plaque size, no significant changes （P 〉 0.05） were observed in group 1 before or after the ESWT. A total of 39 patients （74%） reported a significant effect in pain relief in group 1 after ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no significant differences were observed between the two groups. In 21 patients （40%） of group 1, the deviation angle was decreased more than 10° with a mean reduction in all patients of 11° （range： 6-20°）. No serious complications were noted considering ESWT procedure. Conclusion： ESWT is a minimally invasive and safe alternative procedure for the treatment of Peyronie＇s disease. However, the effect of ESWT on penile pain, sexual function and plaque size remains questionable.

Peyronie's disease:a silent consequence of diabetes mellitus

Aim： To investigate the clinical characteristics of patients with Peyronie＇s disease （PD） and diabetes mellitus （DM）. Methods： During an 8-year period, a total of 307 men seen at our outpatient clinic were diagnosed with PD. Clinical characteristics, penile deformities and the erectile status of patients with PD and DM together （n = 102） were retrospectively analyzed and compared to patients with PD alone with no risk factors for systemic vascular diseases （n = 97）. Results：The prevalence of PD among men with DM and sexual dysfunction was 10.7 %. The mean age of diabetic patients with PD was （55.9 ± 8.9） years; in the no risk factor group it was （48.5 ± 9.0） years （P 〈 0.05）. The median duration of DM was 5 years. The majority of diabetic patients with PD （56.0 %） presented in the chronic phase （P 〈 0.05）, and they were more likely to have a severe penile deformity （〉 60°） than the no risk factor group （P 〈 0.05）. In the diabetic group, the most common presenting symptom was penile curvature （81.4%）, followed by a palpable nodule on the shaft of the penis （22.5%） and penile pain with erection （14.7%）. A total of 19.6% of patients were not aware of their penile deformities in the diabetic group. Erectile function, provided by history and in response to intracavernosal injection and a stimulation test, was significantly diminished in patients with PD and DM （P 〈 0.05）. Conclusion： DM probably exaggerates the fibrotic process in PD. Diabetic patients with PD have a higher risk of severe deformity and erectile dysfunction （ED）. PD seems to be a silent consequence of DM and should be actively sought in diabetic men. （Asian JAndrol 2006 Jan; 8： 75-79）

Non-surgical therapy of Peyronie＇s disease

The present paper provides a review of the available non-surgical treatments for Peyronie＇s disease （PD）. A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed, and the published results of available treatment options reviewed. The authors＇ recommendations for appropriate non-surgical management of PD are provided. Although there are many published reports that show the efficacy of non-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses the opportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatments for PD.

Tunica albuginea allograft： a new model of LaPeyronie＇s disease with penile curvature and subtunical ossification

The pathophysiology of LaPeyronie＇s disease （PD） is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excisionwith subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat＇s tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograff, and both collagen-Ⅱ- and osteocalcin-positive cells were also noted. Tunica albuginea （TA） allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Surgical treatment of Peyronie＇s disease： choosing the best approach to improve patient satisfaction

Aim： To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyronie＇s disease. Methods： Recent advances in approaches to Peyronie＇s disease are discussed based on the literature and personal experiences. Issues concerning surgical indication, patient selection, surgical techniques, and grafting are discussed. Lengthening procedures on the convex side of the penile curvature by means of grafting offer the best possible gain from a reconstruction standpoint. Penile rectification and rigidity are required to achieve a completely functional penis. Most patients experience associated erectile dysfunction （ED）, and penile straightening alone may not be enough to restore complete function. Twenty-five patients were submitted to total penile reconstruction on length and girth with concomitant penile prosthesis implant. The maximum length restoration was possible and limited by the length of the dissected neurovascular bundle. The mean age was 55.4 years （32-69 years） and the mean angle of curvature 74.2± 22.4° （0-100°）. Pericardial grafting was used to cover the defect. The mean follow-up time was 11.2 ± 5.9 months （3-22 months）. Results： Mean functional penile length gain was 3.40 ＋ 0.73 cm （2-5 cm）. Penile prosthesis maintained the penis straight. No infections occurred. Sexual intercourse was restored in all patients and all reported recovered self-esteem. Conclusion： Improving patient satisfaction with the surgical treatment includes proper preoperative evaluation on stable disease, penile shortening, vascular and erectile status, patient decision and selection as well as extensive discussion on surgical technique for restoring functional penis （length and rigidity）. Length and girth restoration is very important for self-esteem and patient satisfaction.

Penile prosthesis implantation and tunica albuginea incision without grafting in the treatment of Peyronie＇s disease with erectile dysfunction

We evaluated penile prosthesis implantation with tunica albuginea-relaxing incisions without grafting in the treatment of Peyronie＇s disease associated with erectile dysfunction. Between April 2005 and June 2011, 62 patients underwent surgery due to severe Peyronie＇s disease associated with erectile dysfunction. Malleable and inflatable penile prostheses were inserted in 49 and 13 cases, respectively. Penile prostheses were inserted into the corpora cavernosa using the standard ventral approach. After lifting the neurovascular bundle, the tunica albuginea was incised and opened at the plaque region to correct the deformities and to lengthen the penis. Subsequently, the wide neurovascular bundle was replaced, and all incisions of the tunica albuginea were covered to prevent corporal grafting. In the median follow-up of 35 months （range 14-82 months）, the penis was completely straightened in 59 （95%） patients. Numbness of the glans, which the patients found initially upsetting, decreased or disappeared spontaneously 3-6 months later. Penile prosthesis implantation with tunica albuginea incisions is a viable alternative in the treatment of Peyronie＇s disease because the extensive dissection of the neurovascular bundle allows a good approach to the plaque and provides excellent covering of the incised tunica albuginea without additional grafting.

Pentoxifylline treatment and penile calcifications in men Nith Peyronie＇s disease

This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie＇s disease （PD） plaques detected on penile ultrasound at the time of initial presentation. The primary objective was to describe the effect of pentoxifylline （PTX） treatment on subtunical calcifications in men with PD. A PD-specific questionnaire was administered and sonographic evaluations were performed at baseline and follow-up visits. Descriptive statistics and X2 analysis were used to characterize the effect of PTX on calcified tunical plaques. In all, 71 men （mean age： 51.9 years） with PD and sonographic evidence of calcification were identified. Of them, 62 of these men were treated with PTX for a mean duration of I year, and nine with vitamin E or no treatment. Improvement or stabilization in calcium burden at follow-up was noted in 57 （91.9%） of men treated with PTX versus four （44,4%） of those not treated with PTX （P〈0.001）. PTX users were much less likely to have a subjective worsening of their clinical condition （25.0% versus 78.3%, P=0.002）. Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques. A randomized controlled trial is warranted to further explore this effect.

All about Peyronie’s disease

Peyronie’s disease(PD)is an acquired connective tissue disorder of the tunica albuginea of the corpus cavernosum,characterized by excessive fibrosis and plaque formation.PD can result in significant physical and psychological morbidity;as it may prevent intercourse and cause adverse impacts on partner relationships.The exact etiology and pathophysiology remain unclear,and many misconceptions about the disease associations,course and treatment exist.The disease has two distinct stages.The acute stage is characterized by pain,and disease may progress during this stage.Non-surgical managements at this stage aim to alleviate pain and stabilize the disease.Results for non-surgical treatment are often conflicting.The chronic stage occurs 6e12 months later,where pain disappears and the deformity stabilizes.Surgical treatment is reserved for significant deformity or with inability to penetrative intercourse.The choice of the surgical technique depends on the length of the penis,degree of deformity,erectile function,patients’expectations and surgeon’s preference.

Long-term results of the surgical treatment of Peyronie＇s disease with Egydio＇s technique： a European multicentre study

The long-term outcomes of 157 patients affected by Peyronie＇s disease （PD） who underwent penile straightening with Egydio＇s technique between January 2004 and December 2008 are reported. Only patients with PD who were stable for at least 6-12 months prior to surgery were enrolled in this study. Preoperative assessment included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of penile deformity and the peak systolic velocity in the cavernosal arteries and an assessment of erectile function with the administration of the International Index of Erectile Function 5 （IIEF-5） questionnaire. Stretched penile length was recorded pre- and postoperatively. Surgical complications, cosmesis and sexual function, patient satisfaction and postoperative erectile function were assessed postoperatively at 3 months, I year and 2 years, respectively. After a median follow-up period of 20 months （range： 12-24 months）, we found that mild residual curvature （12%） and glans hypoesthesia （3%） were the only causes of partial dissatisfaction. No rejection of the graft was observed. All patients recovered their ability to penetrate with no difficulty. In addition, an intraoperative average increase of 2.5 cm （range： 1.7-4.1 cm） in stretched penile length was recorded, with all patients engaging in penetrative sexual intercourse. In conclusion, this procedure represents a safe and reproducible technique for the correction of penile curvature resulting from PD and yields excellent cosmetic and functional results.

Identification of potential biomarkers of Peyronie's disease

Aim： To identity proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea （TA） as related to Peyronie＇s disease （PD）. Methods： Cells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally- appearing TA of the same patients were designated as NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase chain reaction （RT-PCR） for the expression of monocyte chemoattractant protein 1 （MCP-1）. Crude protein lysates were analyzed by surface-enhanced laser desorption/ionization mass spectrometry （SELDI-MS） with IMAC30-Cu, CM10, and H50 chips. Each lysate was then separated into six fractions, which were further analyzed by SELDI-MS. Results： RT- PCR analysis showed that PT cells expressed higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed that the crude protein lysates of all four cell strains produced similar and reproducible protein profiles on IMAC30-Cu and CM 10 chips. Additional SELDI-MS analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5 kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and 46,9 kDa that were downregulated in PT cells. Conclusion： MCP-1, which is often involved in tissue fibrosis, was expressed at higher levels in PT than that in NT cells. Five potential biomarkers for PD were identified by SELDI-MS analysis. （Asian J Androl 2005 Sep; 7： 237-243）

Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie＇s plaque

Epigenetic modifications, such as histone acetylation/deacetylation, have been shown to play a role in the pathogenesis of fibrotic disease. Peyronie＇s disease （PD） is a localized fibrotic process of the tunica albuginea, which leads to penile deformity. This study was undertaken to determine the anti-fibrotic effect of small interfering RNA （siRNA）-mediated silencing of histone deacetylase 2 （HDAC2） in primary fibroblasts derived from human PD plaque. PD fibroblasts were pre-treated with HDAC2 siRNA and then stimulated with transforming growth factor-p1 （TGF-β1）. Protein was extracted from treated fibroblasts for Western blotting and the membranes were probed with antibody to phospho-Smad2/Smad2, phospho-Smad3/Smad3, smooth muscle α-actin and extracellular matrix proteins, including plasminogen activator inhibitor-β 1, fibronectin, collagen I and collagen IV. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-β1-induced nuclear translocation of Smad2/3 in fibroblasts. Knockdown of HDAC2 in PD fibroblasts abrogated TGF-β1-induced extracellular matrix production by blocking TGF-β1-induced phosphorylation and nuclear translocation of Smad2 and Smad3, and by inhibiting TGF-β1-induced transdifferentiation of fibroblasts into myofibroblasts. Decoding the individual function of the HDAC isoforms by use of siRNA technology, preferably siRNA for HDAC2, may lead to the development of specific and safe epigenetic therapies for PD.

Low-intensity extracorporeal shock wave therapy for Peyronie’s disease:a single-center experience

The aim of this article is to assess the outcomes of a low-intensity extracorporeal shock wave therapy(LiESWT)protocol for the treatment of Peyronie’s disease(PD).Patients treated for PD were prospectively recorded,and data were retrospectively reviewed.Age,characteristics of fibrous plaques,concomitant treatments,International Index of Erectile Function(IIEF-5),Lue score,and pain score on Likert scale were collected.Patients in acute phase of PD and an angulation of<40°were included.The protocol consisted of 6 weekly sessions of 4000 pulses each,applied from different directions,with a maximal power of 20 W and 8 Hz frequency.We included 39 patients(median age:56.8 years,interquartile range[IQR]:35.8–62.2 years).The median number of sessions received per patient was 7.2.After treatment,the median Lue score decreased from 6.8 initially to 3.3(P=0.003),the median Likert pain score dropped from 1.8 to 0.7(P=0.004),the median plaque size was reduced from 2 cm to 1.2 cm(P=0.08),and the median penile curvature diminished from 31°to 17°(P=0.07).On univariate and multivariate analysis,the only predictors of success were younger age(odds ratio[OR]=0.95,P=0.03 and OR=0.91,P=0.04,respectively)and concomitant use of phosphodiesterase-5 inhibitors(PDE5i;OR=0.92,P=0.02 and OR=0.93,P=0.01,respectively).LiESWT had a favorable impact on Lue score and notably penile pain,curvature,plaque size,and erectile function in patients treated for PD during the early inflammatory phase,with no side effects.Younger age and concomitant use of PDE5i were the only success predictors.

A self-reported long-term follow-up of patients operated with either shortening techniques or a TachoSil grafting procedure

The aim of this article is to analyse the long-term results of different surgical techniques for correction of penile deviations in Peyronie＇s disease. Patients who underwent surgery for a penile deviation in Peyronie＇s disease between 1997 and 2007 were included into this study. Cases were retrospectively analysed by chart review. The current situation was evaluated by a 16-item standardized questionnaire addressing penile straightness, sensation, length, sexual function and satisfaction. Ninety patients were contacted with a return rate of 75 （83%） evaluabie questionnaires. Thirty-two patients were operated by shortening techniques （STs） with either Schroeder-Essed （n= 16） or Nesbit （n= 16）. Forty-three were operated by a plaque in-lexcision and defect covering by TachoSil method （TM）. Both groups were similar regarding age （ST 56 years, TM 57 years）, comorbidities, mean preoperative erection hardness score （EHS; 3.1 ST, 3.4 TM） and time of follow-up （total mean, 63 months）. Preoperatively ST patients had significantly less plaques （P〈0.05） and a lower deviation angle in comparison to TM patients （ST 56° versus TM 74°; P〈 0.001）. Still TM patients reported slightly better straightening results, but a significantly lower mean EHS （ST 3.3 versus TM 2.6; P〈0.001） during the follow-up. Satisfaction rates were similar in both groups. In conclusion, both techniques revealed to be safe and sustainable successful in penile straightening with better functional outcome of patients operated by STs.

Use of a lyophilized bovine pericardium graft to repair tunical defect in patients with Peyronie＇s disease： experience in a clinical setting

Many different materials are available for grafting during surgery for Peyronie＇s disease （PD）. To study the outcomes associated with the use of a lyophilized bovine pericardium graft （Peri-Guard） to repair tunical defects in patients with PD, descriptive study of 43 patients with disabling penile curvature was performed. Curvature was measured before and after the intervention using a standardized procedure. Surgical technique was plaque excision and grafting of the tunical defect carried out by a single surgeon. A lyophilized bovine pericardium patch was used for grafting. We measured the change in penile curvature and length, the ability to perform successful sexual intercourse without further pharmacological or surgical treatment, and the satisfaction with treatment. Follow-up data were available for a total of 41 patients. Median age was 50 years （IQR 48-52）; mean follow-up time was 14 ± 6 months. Complete penile straightening was achieved in 33 patients （80.5%） and five patients （12.2%） had curvature under 20. Three months after surgery and stretching therapy, mean （s.d.） flaccid penile length increased from 11.2 ± 2.8 cm to 12.1 ± 2.9 cm （P = 0.062）. Seventy-five percentage of patients reported being able to achieve successful intercourse without further treatment. Eighty-five percentage of patients reported to be satisfied with the treatment. There was no evidence of tissue rejection or infection, and only four patients suffered an adverse event. Plaque excision and grafting of the tunical defect with lyophilized bovine pericardium seems to be a safe and effective treatment for patients with PD.

Effects of patients'understanding and choice of surgical types on postoperative outcomes of Peyronie’s disease:a single-center retrospective study of 108 patients

Surgical correction can be considered for treating patients with a chronic phase of Peyronie’s disease(PD)and persistent penile curvature.In clinical practice,some patients pay too much attention to surgical complications and refuse the recommended feasible surgical types.Meanwhile,they require operations according to their preferences.This study aimed to evaluate the effects of patients’own choice of surgical type on postoperative satisfaction.This retrospective study analyzed data from 108 patients with PD who underwent surgical correction according to doctors’recommendations or patients’own demands.The objective and subjective surgical outcomes were assessed.Patients1 understanding of the disease was analyzed using a questionnaire survey.Objective measurements of surgical outcomes,including penile straightening,penile length,and sexual function,in patients who received the recommended surgery,were similar to those in patients who did not accept the recommended surgery.However,subjective evaluations,including erectile pain,discomfort because of nodules on the penis,and decreased sensitivity in the penis,were more obvious in patients who did not follow doctors’recommendations.In addition,a questionnaire survey showed that understanding PD and the purpose of surgery of patients who did not follow doctors’advice were inappropriate,as they did not conform to the principle of treatment.The present study showed that surgical correction seemed to be an objectively effective option in the management of patients in the stable chronic phase of PD.Low patient satisfaction might be related to patients’lack of correct understanding of the disease and its treatment strategy as well as unrealistic expectations.

Effects of plication procedures in special cases of Peyronie’s disease:a single-center retrospective study of 72 patients

General recommendations regarding surgical techniques are not always appropriate for all Peyronie’s disease(PD)patients.Therefore,the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities.The clinical data from 72 patients who underwent plication procedures were analyzed in this study.Patients were divided into Groups A and B according to the curvature severity(≤60°or>60°)and Groups 1 and 2 according to the duration of disease stabilization(≥3 months or<3 months).At the 1-year follow-up,90.0%(36/40)and 90.6%(29/32)patients reported complete penile straightening,and 60.0%(24/40)and 100.0%(32/32)patients reported penile shortening in Groups A and B,respectively.No curvature recurrence occurred in any patient,and no significant differences were observed in postoperative International Index of Erectile Function–Erectile Function domain(IIEF-EF),erectile pain,sensitivity,or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization.However,the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2(mean±standard deviation[s.d.]:20.9±2.0 months and 14.3±1.2 months,respectively,P<0.001).The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature.In addition,the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.

New insights into the pathogenesis of Peyronie’s disease:A narrative review

Peyronie’s disease(PD)is a benign,progressive fibrotic disorder characterized by scar or plaques within the tunica albuginea(TA)of the penis.This study provides new insights into the pathogenesis of PD based on data from different studies regarding the roles of cytokines,cell signaling pathways,biochemical mechanisms,genetic factors responsible for fibrogenesis.A growing body of literature has shown that PD is a chronically impaired,localized,wound healing process within the TA and the Smith space.It is caused by the influence of different pathological stimuli,most often the effects of mechanical stress during sexual intercourse in genetically sensitive individuals with unusual anatomical TA features,imbalanced matrix metalloproteinase/tissue inhibitor of metalloproteinase(MMP/TIMP),and suppressed antioxidant systems during chronic inflammation.Other intracellular signal cascades are activated during fibrosis along with low expression levels of their negative regulators and transforming growth factor-β1 signaling.The development of multikinase agents with minimal side effects that can block several signal cell pathways would significantly improve fibrosis in PD tissues by acting on common downstream mediators.

Effect of SMAD7 gene overexpression on TGF-β1-induced profibrotic responses in fibroblasts derived from Peyronie＇s plaque

Transforming growth factor-β1 （TGF-β1） has been identified as one of the most important fibrogenic cytokines associated with Peyronie＇s disease （PD）. The mothers against decapentaplegic homolog 7 （SMAD7） is an inhibitory Smad protein that blocks TGF-J3 signaling pathway. The aim of this study was to examine the anti-fibrotic effect of the SMAD7 gene in primary fibroblasts derived from human PD plaques. PD fibroblasts were pretreated with the SMAD7 gene and then stimulated with TGF-β1. Treated fibroblasts were used for Western blotting, fluorescent immunocytochemistry, hydroxyproline determination, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. Overexpression of the SMAD7 gene inhibited TGF-β1-induced phosphorylation and nuclear translocation of SMAD2 and SMAD3, transdifferentiation of fibroblasts into myofibroblasts, and quashed TGF-β1-induced production of extracellular matrix protein and hydroxyproline. Overexpression of the SMAD7 gene decreased the expression of cyclin D1 （a positive cell cycle regulator） and induced the expression of poly （ADP-ribose） polymerase 1, which is known to terminate Smad-mediated transcription, in PD fibroblasts. These findings suggest that the blocking of the TGF-β pathway by use of SMAD7 may be a promising therapeutic strategy for the treatment of PD.

Intraplaque injections of hyaluronic acid for thetreatment of stable-phase Peyronie’s disease:aretrospective single-center experience

Peyronie’s disease(PD)is a condition of penile connective tissue affecting up to 10%of men worldwide.In the complexity ofits management,nonsurgical treatments,such as intraplaque injections,are gaining attention.The current literature shows dataon the efficacy of intraplaque injections of hyaluronic acid(HA)mainly in acute-phase PD.However,data on injections of HA instable-phase PD are lacking.Data for this retrospective study were derived from a prospectively maintained database of privatepatients presenting at a private medical practice affiliated to the University of Naples“Federico II”(Naples,Italy)with stable-phasePD between January 2020 and March 2023.Patients underwent a standard protocol of three injections,each administered at atwo-week interval.During the intervals,patients performed vacuum device therapy,penile stretching,and modeling exercises.Allpatients compiled the Peyronie’s Disease Questionnaire(PDQ)and Global Assessment of Peyronie’s Disease(GAPD)at baselineand 2 weeks after the third injection.A penile Doppler ultrasound was performed 2 weeks after the last injection to record thefinal curvature.Overall,we recruited 62 patients with stable-phase PD and a mean(±standard deviation[s.d.])curvature of52.7°(±9.7°).After 6 weeks,eight(12.9%)patients did not experience any curvature improvement.The remaining 54 patientshad a final mean(±s.d.)curvature of 40.3°(±9.1°)with P<0.001,compared to that before treatment.We found improvement inall PDQ domains(all P≤0.01),and 50(80.6%)patients reported subjective improvement of the penile curvature according to theGAPD.In conclusion,we demonstrated that after three injections of HA administered according to the adopted protocol,patientswith stable-phase PD could experience significant improvements in penile curvature,and physical and psychological consequencesof the disease without significantly relevant side effects.