Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

A 10-Year Review of Collagenase Versus Fasciectomy in the Treatment of Dupuytren Contracture.

BACKGROUND: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy. METHODS: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital. RESULTS: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence. CONCLUSIONS: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy.

The action of microbial collagenases in dentinal matrix degradation in root caries and potential strategies for its management: a comprehensive state-of-the-art review.

Conventional views associate microbial biofilm with demineralization in root caries (RC) onset, while research on their collagenases role in the breakdown of collagen matrix has been sporadically developed, primarily in vitro. Recent discoveries, however, reveal proteolytic bacteria enrichment, specially Porphyromonas and other periodontitis-associated bacteria in subgingivally extended lesions, suggesting a potential role in RC by the catabolism of dentin organic matrix. Moreover, genes encoding proteases and bacterial collagenases, including the U32 family collagenases, were found to be overexpressed in both coronal and root dentinal caries. Despite these advancements, to prove microbial collagenolytic proteases' definitive role in RC remains a significant challenge. A more thorough investigation is warranted to explore the potential of anti-collagenolytic agents in modulating biofilm metabolic processes or inhibiting/reducing the size of RC lesions. Prospective treatments targeting collagenases and promoting biomodification through collagen fibril cross-linking show promise for RC prevention and management. However, these studies are currently in the in vitro phase, necessitating additional research to translate findings into clinical applications. This is a comprehensive state-of-the-art review aimed to explore contributing factors to the formation of RC lesions, particularly focusing on collagen degradation in root tissues by microbial collagenases.

Long-term recurrence of Dupuytren's disease treated with clostridium histolitycum collagenase. Surgical treatment and anatomopathological study.

OBJECTIVE: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase. MATERIALS AND METHODS: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment. RESULTS: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy. CONCLUSIONS: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection. LEVEL OF EVIDENCE: III.

Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

Peyronie's disease response to intralesional collagenase clostridium histolyticum therapy is independent of baseline testosterone.

BACKGROUND: Testosterone plays an important role in collagen metabolism, transforming growth factor-ß1 expression, and wound healing, which are all critical factors in pathogenesis of Peyronie's disease. Some clinical studies have suggested an association between Peyronie's disease and hypogonadism. OBJECTIVE: We sought to investigate whether baseline total testosterone levels influence response to intralesional collagenase clostridium histolyticum in Peyronie's disease. METHODS: A retrospective review of patients receiving collagenase clostridium histolyticum injections with available total testosterone levels within 1 year of initial injection was conducted at a single institution. Baseline demographics, hypogonadal status, total testosterone, number of collagenase clostridium histolyticum cycles, and pre- and post-treatment degrees of curvature were collected. Hypogonadism was defined as total testosterone <300 ng/dL. RESULTS AND DISCUSSION: Thirty-six men were included with mean age of 58.2 years (SD 10.4) and mean body mass index 26.8 (SD 3.2). The mean total testosterone was 459.2 ng/dL (SD 144.0), and four (11.1%) were hypogonadal. Mean pre-treatment curvature was 47.6°, and mean post-treatment curvature was 27.8°, with mean improvement of 19.9° (40.1%). Hypogonadal status was not significantly associated with more severe curvature, 46.4° among hypogonadal men as to 57.5° among eugonadal men (p = 0.32). On linear regression analysis, total testosterone did not significantly predict improvement in degrees (ß = -0.02; R2 = 0.06; p = 0.14) or percent (ß = 0.0; R2 = 0.05; p = 0.18). Improvement in neither degrees nor percent differed significantly by hypogonadal status (p = 0.41 and 0.82, respectively). The cycle number did significantly predict greater improvement in curvature on both univariate and multivariate analyses (ß = 5.7; R2 = 0.34; p < 0.01). CONCLUSION: Neither total testosterone nor hypogonadism is associated with a degree of improvement after collagenase clostridium histolyticum treatment.

Changes in Point of Maximal Curvature During Collagenase Clostridium Histolyticum Injections for Peyronie's Disease.

OBJECTIVE: To determine change in the point of maximal curvature (POMC) during Collagenase Clostridium histolyticum (CCH) injections for Peyronie's disease (PD). METHODS: A prospective database has been maintained of all men undergoing CCH injections since March 2014. For the current study, data were abstracted on the POMC with each curve assessment and correlated with demographic and clinical factors. Maximal changes were defined as the largest change in POMC from baseline. RESULTS: Six hundred and eighteen men underwent ≥1 series of CCH, with 313 having a baseline and subsequent POMC measurements available. Median baseline curvature was 60.0° and POMC 2.8 cm. Among 189 men who were satisfied or completed 8 CCH injections, the median improvement in penile curvature was -27.5° (40.9%). The median maximal change in POMC during CCH treatment was 1.0 cm (interquartile range, 0.5, 1.8). Overall, 55.6% had changes in POMC of ≥1 cm, 23.6% ≥2 cm, 8.9% ≥3 cm, and 3.8% ≥4 cm. Multivariate logistic regression identified ventral curvature as a predictor of larger change in POMC, after controlling for other variables. Study limitations included the observational, non-randomized study design and potential for intra- and inter-individual measurement variability. Strengths are the inclusion of an all-comer population, large series, prospective database, and routine objective assessments. CONCLUSION: Approximately half of men with PD undergoing CCH experience ≥1 cm of change in POMC during the treatment course, with nearly 1/4 experiencing ≥2 cm. Findings suggest that patients may benefit from repeat curvature assessments with each CCH series to optimize accuracy of drug administration.

Risk Factors for Penile Fracture After Intralesional Collagenase Clostridium histolyticum in Peyronie's Disease.

OBJECTIVE: To evaluate risk factors leading to corporal rupture after Collagenase Clostridium histolyticum (CCh). Peyronie's disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional CCh is the only FDA-approved medication for PD, however, it can lead to corporal rupture, a potential surgical emergency. METHODS: We retrospectively reviewed medical records from Veterans diagnosed with PD who were under treatment with CCh using the Veterans Administration Informatics and Computing Infrastructure (VINCI). Using International Classification of Diseases and Current Procedural Terminology codes, we identified men who suffered a corporal rupture after CCh. Individual charts were reviewed to determine potential risk factors and events leading to corporal rupture. RESULTS: We identified 17,647 veterans who were diagnosed with PD, of which 8.7% (1541) received at least one injection of CCh for PD. Of them, 0.7% (11/1541) veterans suffered corporal rupture. Within these 11 patients, the median number of CCH injections was 6 with a median initial curvature of 35°. Fracture occurred at a median of 8days after CCH injection. The majority of fractures were secondary to spontaneous erections or sexual intercourse. Finally, six patients had their fracture repaired surgically while the remaining were managed conservatively. CONCLUSION: Most fractures occurred within 2weeks of CCh injections and were associated with sexual intercourse and spontaneous morning erections.

The Discontinuation Rate With Collagenase Clostridium histolyticum for Peyronie's Disease in a High-volume Practice Is Unexpectedly High: Identifying Opportunities for Patient Care Improvement.

OBJECTIVE: To elucidate reasons for premature discontinuation of Collagenase Clostridium histolyticum (CCH) injections for the treatment of penile curvature associated with Peyronie's disease. METHODS: A database of men who underwent CCH injections at a single institution was queried to identify men who completed fewer than 8 injections. Chart review was conducted to identify reasons for treatment discontinuation. When this could not be identified, patients were contacted first via the online patient portal and next by phone. RESULTS: Of 406 patients who underwent CCH treatment, 133 did not complete 8 injections (32.8%). The most common reasons for discontinuation were satisfactory curve reduction (27%), unsatisfactory curve reduction (21%), bothersome side effect (15%), and pursuit of surgery (12%). Other less common reasons included other health concerns, pausing treatment due to the COVID-19 pandemic, high cost, transferring care elsewhere, and lack of awareness that more injections were indicated. CONCLUSION: We present the largest series of patients to date dedicated to evaluation of CCH discontinuation. We find that up to 1/3 of patients who begin CCH injections will not complete the full treatment course. Understanding the reasons for discontinuation can help providers better stratify patients for CCH treatment vs other modalities. In addition, as previous studies indicate curvature improvements are equally likely to be seen in the final four injections as the first four, our data points to the potential impact of improved patient education for individuals who discontinue due to unsatisfactory curve reduction.

New protocol in the treatment of Peyronie's disease by combining platelet-rich plasma, percutaneous needle tunneling, and penile modeling: Preliminary results.

INTRODUCTION: Intra-lesional injections of collagenase (Xiapex®) were the only non-invasive treatment option for Peyronie's disease (PD), until their withdrawal from the European market. OBJECTIVE: To evaluate the feasibility, efficacy, and safety of a combined treatment of percutaneous needle tunnelling (PNT) with penile modelling (PM) and the injection of platelet-rich plasma (PRP) under general anesthesia in the treatment of PD. PATIENTS AND METHOD: A prospective case series study included patients with PD in a stable phase who underwent this procedure between March 2020 and January 2023. The main outcome was an improvement in curvature. RESULT: Thirty-six patients underwent this novel approach for the treatment of PD. The pretreatment mean±standard deviation (SD) curvature degree was 57.5±20.61° (range 20-90°). After the protocol, the mean curvature degree was 40.86±25.13° (range 0-90°). The curvature angle improved significantly (P=0.0001), with a mean improvement difference of 16.85±14.81° (range 0-50°) and a mean improvement percentage of 47.7±40.29% (range 0-100%). CONCLUSION: Our preliminary experience suggests that PNT and PRP injections with PM are effective and safe for the treatment of penile deformity of PD. LEVEL OF EVIDENCE: 4: case series study.

A contemporary assessment of the evaluation and management of patients presenting to a tertiary medical center with Peyronie's disease.

Peyronie's disease continues to be poorly understood. We characterize the presenting features of Peyronie's disease within a large cohort and elucidate the factors that correlate with surgical intervention. Univariate and multivariate analyses were performed on 1483 consecutive patients to assess pre-operative predictors of surgical intervention for Peyronie's disease. Overall, 1263 patients met inclusion criteria. Mean age was 55.4 ± 11.1 years with a mean duration of disease at presentation of 33.2 ± 42.5 months. Mean primary curvature was 49.8 ± 20.8°. Primary ventral curvature was present in 11.4% and 36.5% of patient had a multiplanar curvature. During penile duplex ultrasound evaluation indentation/narrowing deformities were appreciated in 76.0%, hourglass deformity in 10.1%, and hinge effect in 33.0% of patients. Calcification was seen in 30.1% of patients. Operative intervention occurred in 35.3% of patients. Degree of primary curvature (1.03 OR, p < 0.001), hourglass deformity (1.82 OR, p = 0.01), decreased tunical elasticity (1.20 OR, p = 0.03), and prior intralesional collagenase clostridium histolyticum injections (2.94 OR, p < 0.001) predicted surgical correction on multivariate analysis. Compared to historical studies, we found a higher incidence of severe degree of curvature (27.5% >60°), indentation deformities, hinge-effect, multiplanar curvature and penile calcifications. Ultimately, predictors of surgical intervention included those with worse erectile function and more severe characteristics.

Collagenase clostridium histolyticum injection versus limited fasciectomy for the treatment of Dupuytren's disease: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: The aim of the present study is to systematically review the literature on well-selected comparative studies for meta-analysis on outcome differences between collagenase clostridium histolyticum (CCH) injection and limited fasciectomy (LF) for Dupuytren's disease. MATERIALS AND METHODS: PubMed/Medline, Embase, and the Cochrane Library were searched for comparative studies assessing differences in outcomes of CCH and LF. Effect estimates were pooled across studies using random effects models and presented as weighted mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: A total of 11 studies encompassing 1'051 patients was included (619 patients in the CCH and 432 in the LF group). The residual contracture at a minimal average follow-up of three months was higher in the CCH group than in the LF group (27.8 vs. 16.2°, MD 11.6°, 95% CI [8.7, 14.5°], p < 0.001). The recurrence rate was significantly higher in the CCH group (25.8 vs. 9.3%, OR 5.2, 95% CI [1.5, 18.8], p = 0.01) while the rate of severe complications was significantly higher in the LF group (0.3 vs. 7.3%, OR 0.12, 95% CI [0.03, 0.42], p = 0.001). CONCLUSIONS: Evidence of the present study confirms that CCH injection has a higher rate of disease recurrence whereas LF carries a higher risk for severe complications. It's imperative that the trade-off between these aspects is considered, keeping in mind that CCH injections may be repeated in case of disease recurrence without increasing procedure related risks, especially in complex cases.

A survey of exposure to the use of Xiaflex for the treatment of Peyronie's disease among United States urology residency programs.

Xiaflex® (collagenase clostridium histolyticum) is a Food and Drug Administration-approved treatment for patients with Peyronie's disease. Despite its approval and implementation, there is concern that urologists in training are offered minimal exposure to its use. Thus, the purpose of this study was to evaluate the exposure of urology residents to Peyronie's disease and its management, particularly Xiaflex®. A Google Forms survey regarding the exposure of residents to Peyronie's disease and use of Xiaflex® was created and disseminated through email to urology programs. Overall, 47 institutional responses were received. At 45 institutions (95.7%), residents receive training in directly evaluating and caring for patients with Peyronie's disease. At 46 institutions (97.9%), residents receive training in observing and/or performing surgical procedures for Peyronie's disease. Residents at 31 institutions (66.0%) receive observational or procedural training for non-surgical management of Peyronie's disease, specifically Xiaflex®. Residents receive non-surgical training from an academic faculty who is fellowship trained in sexual medicine at 25 institutions and an academic faculty not trained in sexual medicine at six institutions. There exists a glaring disparity in residency exposure to Xiaflex®. Further research is warranted to elucidate how programs can provide residents with further exposure to the use of Xiaflex® in patients with Peyronie's disease.

Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series.

BACKGROUND: The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie's disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. AIM: The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. METHODS: Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. OUTCOMES: Changes in penile curvature, Peyronie's Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. RESULTS: A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was -25.0° in the ventral cohort vs -24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was -35.0° in the ventral cohort vs -25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie's Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. CLINICAL IMPLICATIONS: Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. STRENGTHS AND LIMITATIONS: Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. CONCLUSION: CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

Long-term clinical outcome of collagenase clostridium histolyticum treatment is independent of Dupuytren Diathesis Score.

Collagenase clostridium histolyticum (CCH) is a pharmaceutical, non-surgical treatment option for Dupuytren Disease. However, recurrence is common, and predictors of treatment outcome of CCH treatment are largely unknown. In this retrospective study, we analysed the possible correlation between Abe's Dupuytren Diathesis Score (DDS) and recurrence after treatment with CCH. In a total of 74 patients, with an average follow-up of 5 years, we found an overall recurrence rate of 67% after 5y but no correlation with DDS. Sub-scale analysis indicated that the presence of knuckle pads was associated with a reduced recurrence risk. Patient satisfaction after CCH was high. Deriving from our data, there is no correlation between DDS and recurrence following CCH treatment. Therefore, at this moment, we do not advocate the use of the DDS when informing patients about recurrence rates after CCH treatment. Level of evidence: IV: therapeutic cohort study.

Significant Geographic Variation in Access to Certified Collagenase Clostridium histolyticum Injectors for Peyronie's Disease Throughout the United States.

INTRODUCTION: We characterize the geographic distribution of providers trained to inject Clostridium histolyticum and identify areas with low provider availability. METHODS: We utilized a publicly available search tool to identify clinical sites offering Clostridium histolyticum in the US The data gathered included the provider's name, specialty, address, and whether the site was considered high-volume (ie, administer ≥20 Clostridium histolyticum injections per year). Data were compared to the AUA Census. RESULTS: In total, 2,388 clinical sites offering Clostridium histolyticum were identified. A total of 894 sites (37%) were high-volume sites. The mean number of locations offering Clostridium histolyticum per 100,000 state residents was 0.69 (SD 0.27). Georgia (1.28), Rhode Island (1.13), and Alaska (1.10) had the highest number, whereas New Mexico (0.10), Maine (0.22), and Delaware (0.30) had the lowest. The mean proportion of urologists providing Clostridium histolyticum to total urologists was 0.17 (SD 0.07). The 3 states with the highest proportion were Georgia (0.37), Alaska (0.31), and Utah (0.30), whereas New Mexico (0.03), Maine (0.05), and Vermont (0.06) had the lowest. CONCLUSIONS: States with low numbers of clinical sites offering Clostridium histolyticum per 100,000 residents relative to other states also had a low total ratio of urologists offering Clostridium histolyticum as a treatment. There is room for urologists in these states and others to expand their practice to offer Clostridium histolyticum and improve patient access to this important nonsurgical treatment option.

Delayed vascular complication after collagenase injection for Dupuytren disease.

BACKGROUND: Vascular adverse events after collagenase injection for Dupuytren disease are absent in large trials and systematic reviews. The aim of this study is to present a case series of delayed vascular complications after collagenase treatment. METHODS: A prospective evaluation of 1181 consecutively treated patients at one orthopedic department identified three patients reporting symptoms of possible vascular complication. Baseline demographics and description of symptoms were collected, with a physical examination documenting extension deficit and neurovascular status. All patients completed the Cold Intolerance Symptom Severity (CISS) scale (range 4-100, lower is better) and underwent Doppler sonography examination of the digital arteries. RESULTS: All patients were treated in the small finger and two had an isolated proximal interphalangeal joint contracture. All patients had a delayed presentation of a few months, with episodes of white discoloration of the treated finger relieved within 30 min and associated with variable pain, paresthesia, stiffness and weakness. Two of the patients reported cold exposure as an episode trigger and had a pathological CISS score (40 and 36, respectively). Doppler sonography identified a nonpatent ulnar digital artery in one patient. CONCLUSIONS: Delayed vascular complication after collagenase treatment is rare, but surgeons and patients should be aware of the risk, especially when treating the small finger.