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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 -
Asian Journal of Andrology 2020With the onset of a metabolic syndrome epidemic and the increasing life expectancy, erectile dysfunction (ED) has become a more common condition. As incidence and...
With the onset of a metabolic syndrome epidemic and the increasing life expectancy, erectile dysfunction (ED) has become a more common condition. As incidence and prevalence increase, the medical field is focused on providing more appropriate therapies. It is common knowledge that ED is a chronic condition that is also associated with a myriad of other disorders. Conditions such as aging, diabetes mellitus, hypertension, obesity, prostatic hypertrophy, and prostate cancer, among others, have a direct implication on the onset and progression of ED. Characterization and recognition of risk factors may help clinicians recognize and properly treat patients suffering from ED. One of the most reliable treatments for ED is penile prosthetic surgery. Since the introduction of the penile prosthesis (PP) in the early seventies, this surgical procedure has improved the lives of thousands of men, with reliable and satisfactory results. The aim of this review article is to characterize the epidemiology of men undergoing penile prosthetic surgery, with a discussion about the most common conditions involved in the development of ED, and that ultimately drive patients into electing to undergo PP placement.
Topics: Diabetes Complications; Diabetes Mellitus; Erectile Dysfunction; Humans; Hypertension; Impotence, Vasculogenic; Male; Pelvic Bones; Penile Implantation; Penile Induration; Penile Prosthesis; Penis; Prostatectomy; Prostatic Neoplasms; Radiation Injuries; Radiotherapy; Reoperation; Spinal Cord Injuries; Vascular Diseases; Wounds and Injuries
PubMed: 31793443
DOI: 10.4103/aja.aja_124_19 -
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 -
World Journal of Urology May 2024Platelet-rich plasma (PRP) as a regenerative therapy has gained interest in the field of andrology for the treatment of erectile dysfunction (ED) and Peyronie's disease...
PURPOSE
Platelet-rich plasma (PRP) as a regenerative therapy has gained interest in the field of andrology for the treatment of erectile dysfunction (ED) and Peyronie's disease (PD). This systematic review aims to critically evaluate the current evidence on the use of PRP for these conditions.
METHODS
We performed a systematic literature search according to the PRISMA guidelines using PubMed and Scopus databases in December 2023. Studies were included if they evaluated the effect of PRP therapy for ED or PD in humans.
RESULTS
We identified 164 articles, 17 of which were included, consisting of 11 studies on ED, 5 studies on PD, and 1 study on both. We included four randomized controlled trials, 11 prospective cohort studies, and three retrospective cohort studies including a total of 1099 patients. The studies on ED and PD generally showed small to moderate benefits with mild and transient side effects and no major adverse events were reported. General limitations included variations in PRP protocols, small sample sizes, short follow-up periods, and lack of control groups except in the three randomized trials on ED and the one on PD.
CONCLUSION
The literature on PRP therapy in andrology is limited and difficult to interpret due to variations in protocols and methodological drawbacks. Further research is necessary to determine the optimal preparation and treatment protocols for PRP therapy and clarify its effectiveness in andrology.
Topics: Humans; Penile Induration; Platelet-Rich Plasma; Male; Erectile Dysfunction
PubMed: 38811395
DOI: 10.1007/s00345-024-05065-3 -
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 -
International Journal of Molecular... Jan 2023Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted... (Review)
Review
Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.
Topics: Male; Humans; Penile Induration; Penis; Penile Erection; Injections; Stem Cells
PubMed: 36614220
DOI: 10.3390/ijms24010777 -
Progres En Urologie : Journal de... Sep 2020The efficiency of extracorporeal shock waves (SW) for Peyronie's disease (PD) is controversial.
INTRODUCTION
The efficiency of extracorporeal shock waves (SW) for Peyronie's disease (PD) is controversial.
METHODS
A systematic review of the literature published between 2000 and 2019 was conducted using the PRISMA methodology. We used Medline data with the following.
KEYWORDS
"extracorporeal shock wave therapy" ; "Peyronie's disease"; "Sexuality"; Penile erection.
RESULTS
Thirteen articles were selected. Our review showed that SW were beneficial in terms of pain. Regarding plaques size and penile curvature, the results remain divergent.
CONCLUSION
SW may be useful in the management of pain in selected patients with PD. Its effectiveness on plaques size and penile curvature needs to be demonstrated through controlled and randomized trials. The population has to be targeted, and the treatment protocol must also be standardized.
Topics: Extracorporeal Shockwave Therapy; Humans; Male; Penile Induration
PubMed: 32370921
DOI: 10.1016/j.purol.2020.04.003 -
The Journal of Sexual Medicine Feb 2022Congenital penile curvature (CPC) is corrected surgically by various corporoplasty or tunica albuginea plication techniques, but the optimal surgical approach is not...
BACKGROUND
Congenital penile curvature (CPC) is corrected surgically by various corporoplasty or tunica albuginea plication techniques, but the optimal surgical approach is not well-defined.
AIM
To provide a comprehensive evaluation of the published literature pertaining to outcomes with penile plication and corporoplasty techniques for surgical management of CPC. To determine if plication or corporoplasty offers superior outcomes in surgical correction of CPC.
METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist. The following databases were queried from inception to March 18, 2020 to search for studies describing surgical treatment of CPC: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.
OUTCOMES
Objective and subjective postoperative outcomes including penile straightening, shortening, penile sensory changes, and reoperation rates for both corporoplasty and tunica albuginea plication were summarized.
RESULTS
Fifty-five articles comprising 2,956 patients with CPC who underwent a plication procedure (n = 1,375) or corporoplasty (n = 1,580) were included. The definition of "treatment success" varied widely and most often involved subjective patient reporting (22 studies; 40%) or objective assessment (15 studies; 27%). We considered curvature correction to be satisfactory if there was self-reported patient satisfaction or residual curvature after correction of <20˚. Reported rates of successful straightening ranged from 75 to 100% and 73 to 100% for plication and corporoplasty, respectively. A comprehensive and accurate assessment of surgical outcomes for CPC correction, such as satisfactory penile straightening, reoperation rates, glans sensory changes, and other complications was limited by significant inter-study heterogeneity with respect to the reporting of treatment outcomes.
CLINICAL IMPLICATIONS
While both plication and corporoplasty appear to be safe and effective options in the treatment of CPC, definitive conclusions cannot be drawn with respect to treatment superiority due to low-quality study design, methodology flaws, and significant heterogeneity in reporting.
STRENGTH & LIMITATIONS
This report represents the most comprehensive review of CPC surgical management. However, there is a significant lack of standardization in the reporting of treatment outcomes for CPC, thereby limiting the reliability of the published data summarization encompassed by our review.
CONCLUSION
Both plication and corporoplasty demonstrate high success rates and relatively low complication rates in the treatment of CPC, albeit with low-level evidence available in most research publications. Robust comparison of the surgical techniques used to correct CPC is limited by significant variation in reporting methods used in the literature. C. J. Britton, F. A. Jefferson, B. L. Findlay, et al. Surgical Correction of Adult Congenital Penile Curvature: A Systematic Review. J Sex Med 2022;19:364-376.
Topics: Adult; Humans; Male; Patient Satisfaction; Penile Induration; Penis; Reproducibility of Results; Treatment Outcome
PubMed: 34996726
DOI: 10.1016/j.jsxm.2021.11.017 -
Actas Urologicas Espanolas Jun 2020Reduction in penile size is due to numerous conditions including Peyronie's disease, previous penile surgeries, diabetes, trauma, erectile dysfunction, pelvic surgery,...
INTRODUCTION
Reduction in penile size is due to numerous conditions including Peyronie's disease, previous penile surgeries, diabetes, trauma, erectile dysfunction, pelvic surgery, and aging. Elasticity of the tunica albuginea is adversely affected by any of the above. Fibrosis then triggers progressive erectile dysfunction OBJECTIVES: When a penile prosthesis is indicated, it is important to determine whether the penis has already diminished in size prior to insertion of the implant. Because a prosthesis only provides axial rigidity and is not associated with the enlargement of the penis, reflection of strategies to simultaneously enlarge the size of the penis while implanting a device is recommended.
MATERIAL AND METHODS
A systematic review of current scientific literature regarding procedures and tactics currently available for penile implants and enlargement was conducted.
RESULTS
The literature demonstrates that the evolution of penile implant surgery, accompanied by consideration of enlargement, has evolved through 5 fundamental techniques: Incision with Grafting; Sliding with Grafting; Modified Sliding without Grafting (MoST); Multiple Slit without Grafting (MUST); and the Egydio Paradigm for Tunica Expansion Procedures (TEP), a further evolution of previous strategies to achieve state of the art penile implantation accompanied by maximum penile enlargement. Evolving technology of tunica expansion procedures has led to diminution of the size of tunica defects and avoidance of grafts to prevent bulging and indentation, while developing solutions to preserve the strength of the tunica albuginea for firm positioning of the cylinders in the interior of the corpora cavernosa.
CONCLUSIONS
The evolution of these techniques is the transformation of larger tunica defects into smaller ones. While grafts are often used to reinforce the penile structure due to large defects, multiple incisions of the tunica albuginea are gaining popularity to promote girth and length enlargement without grafts and without the loss of tunica strength necessary to support the cylinders inside the corpora.
Topics: Humans; Male; Organ Size; Penile Implantation; Penile Prosthesis; Penis; Prosthesis Design; Urologic Surgical Procedures, Male
PubMed: 32278614
DOI: 10.1016/j.acuro.2019.10.015