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The Journal of Sexual Medicine Feb 2019Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate.
AIM
To compare the efficacy of different classes of intralesional therapy with a network meta-analysis (NMA) method.
METHODS
The search was conducted using documents published in PubMed, Scopus, and Web of Science databases until September 30, 2017. We included randomized controlled trials comparing at least 1 intralesional therapy with a placebo therapy or with another drug for the treatment of PD. All intralesional therapies have been considered: collagenase Clostridium histolyticum (CCH), hyaluronic acid, verapamil, and interferon α-2b.
MAIN OUTCOME MEASURE
Outcomes of the study are the mean change in penile curvature (PC) and in erectile function (EF) assessed with the International Index of Erectile Function questionnaire.
RESULTS
In total, 8 comparisons matched with the inclusion criteria, which includes 1,050 patients. With regard to PC (degree) improvement, hyaluronic acid and verapamil showed worse outcomes when compared with CCH (-6.66 and -2.30) and interferon α-2b (-6.75 and -2.38). When considering improvement in EF, hyaluronic acid, verapamil and interferon α-2b showed a slight increase in mean change when compared with CCH (+2.39, +1.77, and +0.65). Moreover, verapamil and interferon α-2b showed slightly worse mean change in comparison to hyaluronic acid (+0.62 and +1.74), whereas interferon α-2b was worse than verapamil (-1.12).
CLINICAL IMPLICATIONS
Based on this NMA, empirical therapy for PD should be avoided to offer the patients the best treatment in terms of level of evidence.
STRENGTHS & LIMITATIONS
In this NMA, we have provided, for the first time, evidence of the efficacy between different intralesional therapies for the treatment of PD. We were not able to compare all specific outcomes (ie, pain, plaque size, patient satisfaction) of PD, because of the lack of homogeneity across relevant studies. Moreover, because of the few included studies, a meta-regression analysis of predictive factors of treatment response was not calculated.
CONCLUSION
This is the first meta-analysis comparing all available intralesional treatments for PD. CCH and interferon α-2b showed the best outcome in terms of PC, whereas hyaluronic acid was most efficient in relation to EF. Russo GI, Cacciamani G, Cocci A, et al. Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis. J Sex Med 2019;16:289-299.
Topics: Adult; Humans; Hyaluronic Acid; Injections, Intralesional; Interferon alpha-2; Male; Microbial Collagenase; Network Meta-Analysis; Penile Erection; Penile Induration; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Verapamil
PubMed: 30692028
DOI: 10.1016/j.jsxm.2018.12.011 -
Progres En Urologie : Journal de... Dec 2020Clinical trials of cell therapy for erectile dysfunction (ED) and Peyronie's disease (PD) were recently conducted after preclinical studies.
INTRODUCTION
Clinical trials of cell therapy for erectile dysfunction (ED) and Peyronie's disease (PD) were recently conducted after preclinical studies.
AIMS
The aims of this study are to give an update on biotherapy for ED and PD and to describe the regulatory framework for these therapies.
MATERIALS AND METHODS
A literature review was performed through PubMed and Clinical.trials.gov addressing cell therapy for ED and PD and using following keywords "erectile dysfunction", "Peyronie's disease", "stem cell", and "platelet-rich plasma".
RESULTS
Preclinical studies in rodent models have shown the potential benefit of cell therapy for ED after radical prostatectomy or caused by metabolic diseases, and PD. The tissues used to obtain the therapeutic product were bone marrow, adipose tissue and blood (PRP, platelet-rich plasma). Mechanism of action was shown to be temporary and mainly paracrine. Four clinical trials were published concerning ED after radical prostatectomy and in diabetic patients and one for PD. Eleven clinical trials including three randomized trials are currently going on. Preclinical and preliminary clinical results suggested the possibility to improve spontaneous erectile function and response to pharmaceutical treatment in initially non-responder patients. This effect is mediated by an improvement of penile vascularization. A reduction of penile curvature without side effect was noted after injections into the plaque of PD patients. Most of these therapeutic strategies using autologous cells were considered as "Advanced Therapy Medicinal Products" with strict regulatory frameworks imposing heavy constraints, in particular in case of "substantial" modification of the cells. The regulatory framework remains unclear and more permissive for PRP and cell therapy processes with extemporaneous preparation/injection and no "substantial" modifications.
CONCLUSIONS
First results on cell therapy for ED and PD are promising. The regulatory framework can significantly change according to cell preparations and origins leading to various constraints. This regulatory framework is crucial to consider for the choice of the procedure.
Topics: Biological Therapy; Clinical Trials as Topic; Erectile Dysfunction; Humans; Male; Penile Induration; Stem Cell Transplantation
PubMed: 32826194
DOI: 10.1016/j.purol.2020.05.002 -
Sexual Medicine Reviews Apr 2024Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase...
INTRODUCTION
Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD.
METHODS
We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie's Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3.
RESULTS
For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies.
CONCLUSION
This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research.
PubMed: 38650382
DOI: 10.1093/sxmrev/qeae025 -
Sexual Medicine Reviews Apr 2020Peyronie's disease is characterized by abnormal healing of the tunica albuginea (TA), resulting in the production of a fibrotic plaque that leads to penile curvature and...
INTRODUCTION
Peyronie's disease is characterized by abnormal healing of the tunica albuginea (TA), resulting in the production of a fibrotic plaque that leads to penile curvature and considerable psychological impact. Precise knowledge of various surgical techniques is of fundamental importance for proper management of the patient.
AIM
To compare results (including surgical success on quality of life and sexual satisfaction and complications) between 2 different techniques: with TA incision vs without TA incision.
METHODS
The search was performed according to PRISMA in PubMed and Embase through September 2018. Key words searched were ["Peyronie" or "Peyronie's disease" or "penile curvature" or "penile induration"] and ["technique" or "surgery" or "surgical"] and ["quality of life" or "sexual quality of life" or "sexual satisfaction" or "outcome" or "outcomes"].
MAIN OUTCOME MEASURE
Thirty-one articles were considered for this review. The main outcomes were reported descriptively.
RESULTS
The most significant results included penile straightening (88.5% vs 70.9% favoring not opening TA), perception of a palpable nodule (13.2% vs 27.4% favoring not opening TA), and loss of sensibility (11% vs 20% favoring not opening TA). Neither a prospective randomized study nor a direct comparison study has been performed for these techniques. There is no consensus among the studies on how to measure results. Subjective criteria were primarily used for evaluation, and there is a paucity of objective tools to quantify the outcomes.
CONCLUSION
There is no consensus on which technique achieves better results or fewer complications; therefore, the decision on which technique to use is a matter of surgeon preference. Studies comparing distinctive techniques and either opening or not opening the tunica albuginea should be performed to support surgical decision making. In addition, guidelines that could assist in the standardization of criteria should be investigated in future studies, with the aim of better evaluating outcomes. Barbosa, ARG, Takemura LS, Cha JD, et al. Surgical Treatment of Peyronie's Disease: Systematic Review of Techniques Involving or Not Tunica Albuginea Incision. Sex Med Rev 2020;8:324-332.
Topics: Humans; Male; Patient Satisfaction; Penile Induration; Quality of Life; Sexual Health; Urogenital Surgical Procedures
PubMed: 31570315
DOI: 10.1016/j.sxmr.2019.08.002 -
Frontiers in Medicine 2022Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in...
BACKGROUND
Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic.
METHODS
We searched the Web of Science, PubMed, Embase, and ClinicalTrials.gov for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity.
RESULTS
Four articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: -318.77, < 0.001) and PDSB (WMD: -1.20, < 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: -0.64, = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, < 0.001].
CONCLUSIONS
The current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.
PubMed: 35252236
DOI: 10.3389/fmed.2022.780956 -
International Journal of Impotence... Jan 2020Several strategies to optimize penile length in the presence of Peyronie's Disease (PD) have been described so far. In case of severe curvature and preserved erectile...
Several strategies to optimize penile length in the presence of Peyronie's Disease (PD) have been described so far. In case of severe curvature and preserved erectile function, plaque incision/excision (PIG/PEG) are advisable in order to maximize penile length, despite the risk of postoperative erectile dysfunction (ED), recurrent curvature, or penile shortening. For men with PD deformities associated to a certain degree of ED several lengthening techniques associated to penile prosthesis (PPI) implantation can be considered. Because of the potential postoperative complications, the indication must be balanced between patient's risk factors and surgeon's experience. Furthermore, adjuvant surgeries, such as prepubic V-Y plasty, suspensory ligament release, suprapubic lipectomy, and ventral phalloplasty, can be performed simultaneously or in a staged fashion to maximize the outcomes. Restoration a decent penile length in the case of a severe PD represents a real challenge for reconstructive surgeons. We present a systematic review of the literature on the current practices for penile lengthening in severe PD, providing the reader with a practical overview on the existing surgical strategies and their surgical and functional outcomes.
Topics: Erectile Dysfunction; Humans; Male; Patient Satisfaction; Penile Erection; Penile Implantation; Penile Induration; Penile Prosthesis; Penis; Postoperative Complications; Postoperative Period; Risk Factors
PubMed: 31481708
DOI: 10.1038/s41443-019-0189-9 -
Sexual Medicine Reviews Oct 2020Evidence for noninvasive management of Peyronie's disease contains many options with varying levels of evidence for each. Many first-line treatments recommended by...
INTRODUCTION
Evidence for noninvasive management of Peyronie's disease contains many options with varying levels of evidence for each. Many first-line treatments recommended by urologists lack strong evidence for their use.
AIM
We summarize the noninvasive (oral medications, topical medications, traction, vacuum erection devices, extracorporeal shock wave therapy, intracavernosal injections and electromotive therapy) treatment options for Peyronie's disease and provide the levels of evidence for each.
METHODS
A literature search of PubMed, EMBASE, Cochrane Library, and ClinicalKey databases was conducted, current up to April 2019.
MAIN OUTCOME MEASURE
For each treatment modality, we measured level of evidence, change in penile curvature, change in erectile function, the percentage of patients with improved angulation, and pain scores.
RESULTS
There is weak evidence to support the use of oral or topical medications. Higher levels of evidence exist for intracavernosal injections and extracorporeal shock wave therapy and may be helpful in certain patient populations.
CONCLUSION
The mechanisms behind Peyronie's disease are not fully understood. Penile injections provide the highest quality of evidence for noninvasive treatment. Ory J, MacDonald L, Langille G. Noninvasive Treatment Options for Peyronie's Disease. Sex Med Rev 2020;8:603-614.
Topics: Disease Management; Evidence-Based Medicine; Humans; Male; Penile Induration; Treatment Outcome
PubMed: 31983573
DOI: 10.1016/j.sxmr.2019.12.002 -
Endocrinology, Diabetes & Metabolism Apr 2021Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the...
INTRODUCTION
Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the tunica albuginea of the penis and fascia of the hand, respectively. Chronic hyperglycaemia due to diabetes mellitus can also lead to tissue injury and fibrosis. A meta-analysis has shown a relationship between Dupuytren disease and diabetes (overall odds ratio, 3.1; 95% confidence interval, 2.7-3.5). This review explores commonalities in the pathogenesis of Peyronie's disease, Dupuytren disease and diabetes.
METHODS
A search of the PubMed database was conducted using the search terms "diabetes" AND "Peyronie's disease"; and "diabetes" AND "Dupuytren."
RESULTS
Genome-wide association and gene expression studies conducted with tissue from people with Peyronie's disease or Dupuytren disease identified signalling pathways associated with wingless-type mammary-tumour virus integration site signalling, extracellular matrix modulation and inflammation. Biochemical studies confirmed the importance of these pathways in the pathogenesis of fibrosis with Peyronie's disease and Dupuytren disease. Dysregulation of matrix metalloproteinase activity associated with extracellular matrix breakdown was implicated in fibroproliferative complications of diabetes and in the aetiology of Peyronie's disease and Dupuytren disease. A notable percentage of people with diabetes have comorbid Peyronie's disease and/or Dupuytren disease.
CONCLUSIONS
Studies have not been performed to identify fibroproliferative pathways that all 3 conditions might have in common, but data suggest that common pathways are involved in the fibroproliferative processes of Peyronie's disease, Dupuytren disease, and diabetes.
Topics: Chronic Disease; Diabetes Complications; Diabetes Mellitus; Dupuytren Contracture; Extracellular Matrix; Fascia; Female; Fibrosis; Genome-Wide Association Study; Hand; Humans; Hyperglycemia; Male; Matrix Metalloproteinases; Penile Induration; Penis; Signal Transduction
PubMed: 33855203
DOI: 10.1002/edm2.195 -
Sexual Medicine Reviews Apr 2021Collagenase Clostridium histolyticum (CCH) is an injectable agent used to treat Peyronie's disease (PD) by enzymatically degrading the interstitial collagen in plaques.... (Review)
Review
INTRODUCTION
Collagenase Clostridium histolyticum (CCH) is an injectable agent used to treat Peyronie's disease (PD) by enzymatically degrading the interstitial collagen in plaques. CCH has been administered via multiple treatment protocols, in combination therapies, to patients with varying curvatures and in both the acute and stable phases of this condition.
OBJECTIVES
To review the current literature and provide an update on CCH as an injectable therapy for PD, as a singular therapy or in conjunction with combination therapies, and its associated complications. We provide a brief background of PD treatments, evaluate CCH efficacy in penile curvature reduction and subjective improvement in a variety of protocols, and compare combination therapies (penile traction, sildenafil), plaque location, and efficacy in both acute and stable diseases.
METHODS
We performed a systematic review of the existing PubMed literature pertaining to CCH injection therapy in the treatment of PD and compared the effectiveness to different treatment modalities.
RESULTS
CCH is a safe and effective injectable agent for all curvature directions in both acute and stable PD. It can be used in conjunction with multiple penile modeling techniques, in combination with sildenafil, and following a shortened administration protocol. Moderate to severe treatment-related adverse events occur at a rate of 9% and are typically managed conservatively.
CONCLUSION
Intralesional injections of CCH are FDA approved as a nonsurgical treatment for men with PD. The IMPRESS trials were instrumental in demonstrating the efficacy and safety of CCH and provided a standard protocol for administration. Additional studies are required to optimize treatment protocols and use in combination therapies. Further investigation of patients with ventral curvatures, hourglass deformities, and those in acute phase is needed. Natale C, McLellan D, Yousif A, et al. Review of Intralesional Collagenase Clostridium Histolyticum Injection Therapy and Related Combination Therapies in the Treatment of Peyronie's Disease (an Update). Sex Med 2021;9:340-349.
Topics: Humans; Injections, Intralesional; Male; Microbial Collagenase; Penile Induration; Penis; Treatment Outcome
PubMed: 32199788
DOI: 10.1016/j.sxmr.2020.01.005 -
International Journal of Impotence... Sep 2022Severe Peyronie's disease (PD) and concomitant erectile dysfunction (ED) may require plaque incision/excision and grafting (PIG) as an adjunct to penile prosthesis... (Review)
Review
Severe Peyronie's disease (PD) and concomitant erectile dysfunction (ED) may require plaque incision/excision and grafting (PIG) as an adjunct to penile prosthesis implantation (IPP). Currently, there is no available consensus on the best graft material to use. Our aim was to systematically review graft materials used as patches following PIG + IPP. Literature search was performed in March 2021. Only original articles in English with a series of 10 or more patients were included. Overall, a total of 17 studies were included, corresponding to a cohort of 662 patients. The mean age ranged from 45 to 65 years and most patients had curvatures >45°. Average penile lengthening ranged from 1 to 3.5 cm, average residual curvatures from 0 to 20% and decreased glans sensitivity from 0 to 20%. Eighty to 100% of patients were satisfied with cosmetic and functional results. PIG + IPP with the use of various grafts offers promising results for the treatment of patients suffering from severe PD with concomitant ED. Unfortunately, the absence of high quality and comparative studies makes it difficult to establish the optimum graft. Therefore, the level of experience of the surgical team with one or more methods should guide their choice.
Topics: Erectile Dysfunction; Humans; Male; Penile Implantation; Penile Induration; Penile Prosthesis; Penis
PubMed: 34718344
DOI: 10.1038/s41443-021-00479-8