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Sexual Medicine Reviews Jun 2024Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I... (Review)
Review
INTRODUCTION
Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications.
OBJECTIVES
To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications.
METHODS
We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD.
RESULTS
Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results.
CONCLUSION
Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program.
Topics: Humans; Penile Induration; Male; Microbial Collagenase; Penis; Injections, Intralesional
PubMed: 38491199
DOI: 10.1093/sxmrev/qeae004 -
International Journal of Impotence... Mar 2024Adjunctive residual curvature correction by plaque incision and grafting with a sutureless graft during inflatable penile prosthesis (IPP) implantation in patients with...
First worldwide correction of ventral Peyronie's disease utilizing rigicon inflatable penile prosthesis combined with plaque incision & grafting with collagen fleece (PICS-technique) for residual curvature.
Adjunctive residual curvature correction by plaque incision and grafting with a sutureless graft during inflatable penile prosthesis (IPP) implantation in patients with Peyronie's disease (PD) is our preferred technique. The PICS Technique (Penile Implant in Combination with the Sealing Technique) uses a self-adhesive collagen fleece (TachoSil, Corza Medical, MA, USA) to cover the defect after plaque incision. The graft does not require sutures improving operative speed and avoiding needle stick of the implant cylinders. In this article, we present the first known application worldwide of a Rigicon Infla10 X (Rigicon, Ronkonkoma, NY, USA) device to Peyronie's ventral curvature. The patient's residual curvature of 80° after implantation was corrected by PICS through an additional subcoronal incision. At the conclusion of surgery, the penis was totally straight and rigid. No intra- and postoperative complications occurred. At the early follow-up of 12 weeks postoperatively, the patient was able to inflate and deflate the device and sexual intercourse was possible. A combination of the Rigicon Infla10 X and the PICS Technique represents a safe and successful approach for residual curvature correction during IPP in patients with ventral Peyronie's curvature. The Rigicon Infla10 X device showed excellent rigidity, and controlled expansion of the X cylinders means it can be used with the PICS Technique without restrictions. Early results are promising. Long-term follow-up and more patients are needed.
PubMed: 38480871
DOI: 10.1038/s41443-024-00873-y -
The Journal of Urology Apr 2024
Topics: Humans; Testosterone; Androgens; Hypogonadism; Hormone Replacement Therapy
PubMed: 38456434
DOI: 10.1097/JU.0000000000003855 -
Sexual Medicine Reviews Jun 2024Penile induration disease, commonly known as Peyronie's disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous... (Review)
Review
INTRODUCTION
Penile induration disease, commonly known as Peyronie's disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous plaques, penile curvature, and erectile dysfunction. PD is a common male reproductive system disease with a complex etiology involving multiple genes, signaling pathways, and different phenotypes.
OBJECTIVES
The etiology and pathogenesis of PD remain poorly understood, hindering the development of effective treatment strategies. By understanding the underlying mechanisms of PD, we can pave the way for targeted therapies and improved patient outcomes.
METHODS
We reviewed the epidemiology and pathophysiology of PD. We performed database searches on Google Scholar, PubMed, Medline, and Web of Science from inception to September 2023. The literature reviewed included priapism guidelines, review articles, current trial studies, and various literature related to PD.
RESULTS
This article provides a comprehensive overview of the current research progress on the disease, focusing on its genetic factors, signaling pathways, cellular mechanisms, phenotypic manifestations, and therapeutic targets. It can help identify individuals at higher risk, aid in early detection and intervention, and provide insights into fibrosis and tissue remodeling. It can also reveal potential therapeutic targets, guide accurate diagnoses and treatment strategies, and address the impact of the disease on patients' quality of life.
CONCLUSION
By integrating insights from genomics, molecular pathways, clinical phenotypes, and therapeutic potentials, our research aims to achieve a deeper and more comprehensive understanding of PD, propelling the field toward innovative strategies that enhance the lives of those affected by PD. The complex manifestations and pathogenesis of PD necessitate the use of multiple treatment methods for personalized care.
Topics: Humans; Penile Induration; Male; Phenotype; Genomics; Signal Transduction
PubMed: 38456235
DOI: 10.1093/sxmrev/qeae006 -
International Journal of Impotence... Mar 2024Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within... (Review)
Review
Peyronie's disease, a fibroinflammatory disorder, detrimentally impacts the sexual well-being of men and their partners. The manifestation of fibrotic plaques within penile tissue, attributed to dysregulated fibrogenesis, is pathognomonic for this condition. The onset of fibrosis hinges on the perturbation of the equilibrium between matrix metalloproteinases (MMPs), crucial enzymes governing the extracellular matrix, and tissue inhibitors of MMPs (TIMPs). In the context of Peyronie's disease, there is an elevation in TIMP levels coupled with a decline in MMP levels, culminating in fibrogenesis. Despite the scant molecular insights into fibrotic pathologies, particularly in the context of Peyronie's disease, a comprehensive literature search spanning 1995 to 2023, utilizing PubMed Library, was conducted to elucidate these mechanisms. The findings underscore the involvement of growth factors such as FGF and PDGF, and cytokines like IL-1 and IL-6, alongside PAI-1, PTX-3, HIF, and IgG4 in the fibrotic cascade. Given the tissue-specific modulation of fibrosis, comprehending the molecular underpinnings of penile fibrosis becomes imperative for the innovation of novel and efficacious therapies targeting Peyronie's disease. This review stands as a valuable resource for researchers and clinicians engaged in investigating the molecular basis of fibrotic diseases, offering guidance for advancements in understanding Peyronie's disease.
PubMed: 38454161
DOI: 10.1038/s41443-024-00845-2 -
World Journal of Urology Mar 2024Extracorporeal shock wave lithotripsy represents one option for the non-surgical management of Peyronie's disease. Despite promising results, several questions are still...
BACKGROUND
Extracorporeal shock wave lithotripsy represents one option for the non-surgical management of Peyronie's disease. Despite promising results, several questions are still pending. We want to present the long-term results of a retrospective study using high-energy extracorporeal shock wave lithotripsy.
MATERIAL AND METHODS
We evaluated retrospectively 110 patients treated between 1996 and 2020 at the Department of Urology, SLK Kliniken Heilbronn for chronic phase Peyronie's disease using two electromagnetic lithotripters (Siemens Lithostar Plus Overhead Module, Siemens Lithoskop) applying high-energy shock waves under local anesthesia and sonographic or fluoroscopic control. A standardized questionnaire focused on the change in pain, curvature, sexual function and the need of penile surgery.
RESULTS
In 85 of the 110 patients (mean age 54 years) we had sufficient data for evaluation. The median follow-up was 228 (6-288) months. There were no significant complications. Pain reduction was achieved in all patients, 65 (76%) patients were free of pain. Improvement of penile curvature was achieved in 43 patients (51%) ranging from 25% improvement (deflected angle < 30°) to 95% (angle 30-60°). 59 patients (69%) reported problems with sexual intercourse, 40 of those (68%) reported improvement. Only 9 (10.5%) patients underwent surgical correction. We did not observe any significant differences between both electromagnetic devices with stable long-term results.
CONCLUSIONS
High-energy shock wave therapy delivered by two standard electromagnetic lithotripters is safe and efficient providing stable long-term results. In cases with significant plaque formation, the concept of high-energy ESWT should be considered in future studies.
Topics: Male; Humans; Middle Aged; High-Energy Shock Waves; Penile Induration; Retrospective Studies; Lithotripsy; Penis; Pain; Electromagnetic Phenomena; Treatment Outcome
PubMed: 38453751
DOI: 10.1007/s00345-024-04792-x -
The Journal of Sexual Medicine Apr 2024The cavernous nerve (CN) is frequently damaged in prostatectomy and diabetic patients with erectile dysfunction (ED), initiating changes in penile morphology including...
BACKGROUND
The cavernous nerve (CN) is frequently damaged in prostatectomy and diabetic patients with erectile dysfunction (ED), initiating changes in penile morphology including an acute and intense phase of apoptosis in penile smooth muscle and increased collagen, which alter penile architecture and make corpora cavernosa smooth muscle less able to relax in response to neurotransmitters, resulting in ED.
AIM
Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and SHH treatment suppresses penile remodeling after CN injury through an unknown mechanism; we examine if part of the mechanism of how SHH preserves smooth muscle after CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1).
METHODS
Primary cultures of smooth muscle cells were established from prostatectomy, diabetic, hypertension and Peyronie's (control) (N = 18) patients. Cultures were characterized by ACTA2, CD31, P4HB, and nNOS immunohistochemical analysis. Patient smooth muscle cell growth was quantified in response to BMP4 and GREM1 treatment. Adult Sprague Dawley rats underwent 1 of 3 surgeries: (1) uninjured or CN-injured rats were treated with BMP4, GREM1, or mouse serum albumin (control) proteins via Affi-Gel beads (N = 16) or peptide amphiphile (PA) (N = 26) for 3 and 14 days, and trichrome stain was performed; (2) rats underwent sham (N = 3), CN injury (N = 9), or CN injury and SHH PA treatment for 1, 2, and 4 days (N = 9).
OUTCOMES
Western analysis for BMP4 and GREM1 was performed; (3) rats were treated with 5E1 SHH inhibitor (N = 6) or IgG (control; N = 6) for 2 and 4 days, and BMP4 and GREM1 localization was examined. Statistics were performed by analysis of variance with Scheffé's post hoc test.
RESULTS
BMP4 increased patient smooth muscle cell growth, and GREM1 decreased growth. In rats, BMP4 treatment via Affi-Gel beads and PA increased smooth muscle at 3 and 14 days of treatment. GREM1 treatment caused increased collagen and smooth muscle at 3 days, which switched to primarily collagen at 14 days. CN injury increased BMP4 and GREM1, while SHH PA altered Western band size, suggesting alternative cleavage and range of BMP4 and GREM1 signaling. SHH inhibition in rats increased BMP4 and GREM1 in fibroblasts.
CLINICAL IMPLICATIONS
Understanding how SHH PA preserves and regenerates penile morphology after CN injury will aid development of ED therapies.
STRENGTHS AND LIMITATIONS
SHH treatment alters BMP4 and GREM1 localization and range of signaling, which can affect penile morphology.
CONCLUSION
Part of the mechanism of how SHH regulates corpora cavernosa smooth muscle involves BMP4 and GREM1.
Topics: Animals; Humans; Male; Middle Aged; Rats; Bone Morphogenetic Protein 4; Cells, Cultured; Cytokines; Erectile Dysfunction; Hedgehog Proteins; Intercellular Signaling Peptides and Proteins; Muscle, Smooth; Myocytes, Smooth Muscle; Penile Induration; Penis; Prostatectomy; Rats, Sprague-Dawley
PubMed: 38451321
DOI: 10.1093/jsxmed/qdae016 -
The Journal of Sexual Medicine Apr 2024Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora...
BACKGROUND
Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment.
AIM
We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment.
METHODS
Corpora cavernosa of Peyronie's disease (control), prostatectomy, and diabetic ED patients were obtained (N = 30). Adult Sprague Dawley rats (n = 90) underwent (1) CN crush (1-7 days) or sham surgery; (2) CN injury and BMP4, GREM1, or mouse serum albumin (control) treatment via Affi-Gel beads or peptide amphiphile (PA) for 14 days; (3) 5E1 SHH inhibitor, IgG, or phosphate-buffered saline (control) treatment for 2 to 4 days; or (4) CN crush with mouse serum albumin or SHH for 9 days.
OUTCOMES
Immunohistochemical and Western analysis for BMP4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed.
RESULTS
BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic, and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 treatment (P = .02) and increased 61.3% with CN injury and GREM1 treatment (P = .005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2 days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling.
CLINICAL IMPLICATIONS
A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies.
STRENGTHS AND LIMITATIONS
The relationship between SHH, BMP4, GREM1, and collagen is complex in the penis.
CONCLUSION
BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED.
Topics: Animals; Humans; Male; Middle Aged; Rats; Bone Morphogenetic Protein 4; Collagen; Cytokines; Disease Models, Animal; Erectile Dysfunction; Hedgehog Proteins; Intercellular Signaling Peptides and Proteins; Penile Induration; Penis; Prostatectomy; Rats, Sprague-Dawley; Signal Transduction
PubMed: 38451311
DOI: 10.1093/jsxmed/qdae015 -
Journal of the West African College of... 2023Colour duplex Doppler is a noninvasive tool for the evaluation of the vascular mechanism of erectile dysfunction (ED). It can be used to determine the integrity of the...
BACKGROUND
Colour duplex Doppler is a noninvasive tool for the evaluation of the vascular mechanism of erectile dysfunction (ED). It can be used to determine the integrity of the vascular mechanism and to differentiate between arterial and venous insufficiency.
OBJECTIVES
To identify the vasculogenic causes of ED and subclassify them into arteriogenic, venogenic, or mixed to assist in predicting the clinical outcome.
MATERIALS AND METHODS
A retrospective study was conducted at the Department of Radiology, ABUTH Zaria, from records of patients who had presented to the Doppler suite with symptoms of ED available between July 2020 and August 2022.
RESULTS
A total of 23 patients were involved in this study. The age range was 25-66 years. The majority of the patients were seen in age groups 51-60 years and 41-50 years with 48% (11) and 22% (5), respectively. Only 3 (13%) of the patients were found to have normal penile Doppler study, 12 (52%) patients were found to have arteriogenic, and another 4 (17.4%) patients were found to have venogenic cause. In four (17.4%) patients, there was mixed/inconclusive picture. Among the nine (39%) patients with Peyronie's disease, only one showed normal Doppler study. The incidence of vasculogenic cause of ED was found to increase with age.
CONCLUSIONS
The colour Doppler study is an important noninvasive nonionizing radiation tool for swift evaluation of penile erectile function and, thus, helps in classifying ED causes into structural, vascular, or possibly psychogenic, hence guiding the clinicians on the therapeutic options.
PubMed: 38449545
DOI: 10.4103/jwas.jwas_71_23 -
The Journal of Urology May 2024
Randomized Controlled Trial
PubMed: 38447151
DOI: 10.1097/JU.0000000000003896