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Purpose: Injectable collagenase Clostridium histolyticum has been an effective and well-tolerated nonsurgical treatment option for the management of Dupuytren contracture of the hand. The purpose of this study was to determine the efficacy of collagenase injection and adverse event rate in patients who had undergone previous collagenase treatment., Methods: A retrospective chart review was performed on 332 patients treated with collagenase injection for Dupuytren contracture by three fellowship-trained hand surgeons at a single institution from 2009 to 2019. Fifty-nine joints in 45 patients underwent repeat collagenase therapy for recurrent contracture in the same digit. Pretreatment and posttreatment total metacarpophalangeal and proximal interphalangeal joint flexion contractures were recorded, with complete correction defined as <5° residual digital flexion contracture. Postmanipulation skin tears and adverse events were recorded. A comparison was made between average contracture improvement after initial collagenase injection and that after repeat injection., Results: Forty-five patients with an average duration of 30 months (range, 6-73 months) between initial and repeat collagenase therapies were identified. The mean improvement after first collagenase injection was 45° ± 24° (39° for metacarpophalangeal joint and 50° for proximal interphalangeal joint) compared with a mean improvement of 43° ± 23° (41° for metacarpophalangeal joint and 44° for proximal interphalangeal joint) after second injection. Although similar complete correction rates and skin tear rates (32.2 % for initial and 30.5% for repeat) were observed between initial (80%) and repeat injections (73%), the occurrence of adverse events was 3 times higher (3.4% for initial and 10.2% for repeat) in the latter group., Conclusions: Collagenase treatment of Dupuytren contracture yields effective total flexion contracture correction. Repeat collagenase treatment of previously treated digits yields similar deformity correction and complete correction rates but a higher incidence of adverse events., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Treatments for Dupuytren's contracture include limited fasciectomy and collagenase injection. Comparisons of the effectiveness of these treatments have been limited., Methods: We performed an unblinded, multicenter, pragmatic, two-group, randomized, controlled noninferiority trial comparing collagenase injection with limited fasciectomy in persons with moderate Dupuytren's contracture. The primary outcome was the score on the Patient Evaluation Measure-Hand Health Profile (PEM), a questionnaire for assessing hand health as reported by the patient, at 1 year after treatment. Scores on the PEM range from 0 to 100, with higher scores indicating worse outcomes. The prespecified noninferiority margin was 6 points., Results: A total of 672 persons (336 per group) were assigned to receive collagenase injection or to undergo limited fasciectomy. The primary analysis included 599 persons: 314 in the collagenase group and 285 in the limited-fasciectomy group. The mean score on the PEM at 1 year was 17.8 among the 284 patients with available data in the collagenase group and 11.9 among the 250 patients with available data in the limited-fasciectomy group (estimated difference, 5.9 points; 95% confidence interval [CI], 3.1 to 8.8; one-sided P = 0.49 for noninferiority). Among the patients with available data (229 patients in the collagenase group and 197 patients in the limited-fasciectomy group), the estimated difference in the mean score on the PEM at 2 years was 7.2 points (95% CI, 4.2 to 10.9). Moderate or severe complications of treatment occurred in 1.8% of the patients in the collagenase group and in 5.1% of those in the limited-fasciectomy group; recurrent contracture resulted in reintervention in 14.6% and 3.4%, respectively., Conclusions: Collagenase injection was not noninferior to limited fasciectomy with respect to the score on the PEM at 1 year after treatment. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme; DISC ISRCTN Registry number ISRCTN18254597.)., (Copyright © 2024 Massachusetts Medical Society.)

Collagenase Clostridium histolyticum (CCh), the first approved non-surgical treatment for Peyronie's disease (PD), was withdrawn from the European, Canadian, and Asian markets due to poor demand and lack of government reimbursement options. We sought to assess insurance approval rates and usage of CCh across Canada to understand the factors that led to its withdrawal. Data on patients prescribed CCh for PD or Dupuytren's contracture was obtained through collaboration with BioScript Solutions to assess the association of variables with insurance approval and prescription filling. We identified 3297 insurance coverage applications for Xiaflex® from April 2018 to June 2020. Of all applications for PD, 92.9% applications were approved while 7.1% were rejected. Despite the withdrawal of CCh from Canadian markets, coverage application approval rates for 2018, 2019, and 2020 were 86.5%, 90.1%, and 89.1%, respectively. Of 2921 approved applications, 88.8% prescriptions were filled. For the 376 rejected applications, 66.4% of prescriptions were filled. Overall, 90% of the cost of Xiaflex® was covered in Canada among those with extended health benefits, with an out-of-pocket expense of $210.4. Insurance coverage requests for Xiaflex® were approved at a high rate in Canada with approved patients being very likely to proceed with therapy, despite interprovincial variation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The purpose of this study was to determine the perioperative complication rate of surgical fasciectomy following previous treatment with collagenase clostridium histolyticum (CCH) treatment in patients with Dupuytren disease., Methods: A retrospective review of all patients at a large health system undergoing CCH treatment and subsequent limited surgical fasciectomy for recurrence on the same digit between 2010 and 2020 was performed. Fifty-two patients with 62 affected digits met inclusion criteria, and cases were reviewed for preoperative demographics, treatment characteristics, clinical outcomes, and perioperative complications., Results: Fifty-five digits in 48 patients were treated with CCH and underwent subsequent limited surgical fasciectomy. Of all digits in the present study, 3 (6.3%) had a documented surgical complication following open surgical fasciectomy. There were zero postoperative infections, vascular injuries, or tendon injuries. The rate of nerve injury was 2.1%. The rate of postoperative skin necrosis was 4.2%. These rates were comparable or lower than those of historical published data., Conclusions: The rate of perioperative complications in patients undergoing limited surgical fasciectomy after previous CCH treatment is low. The findings of this study will aid the counseling of Dupuytren patients in deciding whether to pursue treatment with CCH versus open surgical fasciectomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest and received no funding to conduct this study. Because this is a retrospective review, this article does not contain any studies with human or animal subjects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024. The Author(s).)

Background: Testosterone plays an important role in collagen metabolism, transforming growth factor-β1 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 (β = -0.02; R 2  = 0.06; p = 0.14) or percent (β = 0.0; R 2  = 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 (β = 5.7; R 2  = 0.34; p < 0.01)., Conclusion: Neither total testosterone nor hypogonadism is associated with a degree of improvement after collagenase clostridium histolyticum treatment., (© 2023 American Society of Andrology and European Academy of Andrology.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP)., Method: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated., Results: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm 2 , 12.4/5.3mN/mm 2 , 22.2/9.7mN/mm 2 , and 33.3/15.5mN/mm 2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm 2 , 6.5/2.9mN/mm 2 , 12.2/5.7mN/mm 2 , and 15.4/7.7mN/mm 2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003)., Interpretation: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP., (© 2023 Mac Keith Press.)

Purpose: The objective of this systematic review and meta-analysis was to synthesize the available randomized controlled trial data comparing needle fasciotomy and collagenase treatment for single-digit Dupuytren contractures with a minimum of 3-year follow-up and determine whether one treatment is superior regarding contracture correction and functional outcomes., Methods: A systematic review and meta-analysis was conducted by searching four databases for randomized controlled trials investigating the single-digit treatment outcomes for Dupuytren contracture comparing collagenase treatment and needle fasciotomy with a minimum of 3-year follow-up. The risk of bias of included studies was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using a random effects model in anticipation of unobserved heterogeneity. The primary outcome measure was contracture recurrence. Secondary outcome measures included final fixed flexion contracture (FFC), Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores, and Unité Rhumatologique des Affections de la Main (URAM) scores., Results: After screening 264 articles, 4 randomized clinical trials were eligible for final inclusion. One trial had a high risk of bias, and two trials had some concern for bias. The final meta-analysis included 347 patients, 169 who underwent collagenase treatment and 178 who underwent needle fasciotomy. No significant differences were noted between the groups in contracture recurrence, FFC, and URAM scores. The pooled data showed a higher QuickDASH score in the collagenase treatment group compared with the needle fasciotomy group, but the observed difference was less than what would be expected to be clinically relevant., Conclusions: Needle fasciotomy and collagenase treatment have similar outcomes with regards to contracture recurrence, final FFC, QuickDASH scores, and URAM scores for the single-digit treatment for Dupuytren contracture at a minimum of 3-year follow-up. Relevant factors that may be considered during the shared decision-making process for treatment selection include surgeon and patient preferences, costs of treatment, and the disparate complication profiles of these two treatments., Type of Study/level of Evidence: Therapeutic II., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: Since Food and Drug Administration approval of collagenase Clostridium histolyticum for Peyronie's disease, there has been significant debate regarding its role and comparable efficacy to surgery., Materials and Methods: A randomized, controlled trial was performed of Peyronie's disease men treated with either collagenase C histolyticum + RestoreX penile traction therapy + sildenafil or penile surgery + RestoreX penile traction therapy + sildenafil, with 3-month data presented. Primary objectives were overall satisfaction, subjective changes in erectile function, penile sensation, penile length, and changes in the International Index of Erectile Function-Erectile Function Domain score. Secondary outcomes included objective changes in length, curve, adverse events, and other standardized and nonstandardized questionnaires., Results: A total of 40 men were enrolled, with 38 (collagenase C histolyticum group = 19, surgery group = 19) completing treatment and having 3-month data available. All demographic and clinicopathological variables were similar between groups. Following treatment, 50% of men in the collagenase C histolyticum group reported being very satisfied (vs 21% in the surgery group, P = .08) and noted better subjective erectile function (100% vs 68%, P = .03) and penile length (88% vs 16%, P < .0001), lesser impacts on penile sensation (75% vs 11% no change, P < .001), and similar International Index of Erectile Function-Erectile Function Domain changes (+1.5 vs +2.5, P = .91). Objectively, men in the surgery group had greater curve improvements (84% vs 54%, P < .01) and higher rates of adverse events (50 vs 13 events, P < .001) but decreased penile length (-0.5 cm vs +1.0 cm, P < .01)., Conclusions: At 3 months posttreatment, collagenase C histolyticum + RestoreX penile traction therapy + sildenafil results in lesser curve improvements but greater penile length and fewer adverse events, including impacts on subjective erectile function and sensation, than men treated with surgery.

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.

Background: Despite many available treatments for Peyronie's disease (PD), practice patterns of available therapeutics are not well characterized., Objective: We conducted a national survey of urologists to characterize real-world practice patterns of PD management and to characterize the use of therapies discouraged by the American Urological Association guidelines on PD management., Materials and Methods: A 34-item survey was distributed via RedCap to urologists who treat patients with PD in all American Urological Association sections. Questions elicited demographic information as well as practices in the diagnosis and treatment of PD. Comparisons were made with Pearson's chi-squared test. The primary outcome was reported use of therapies discouraged by the American Urological Association guidelines on PD., Results: A total of 145 respondents completed the survey, of whom 19% were fellowship trained in andrology/sexual medicine, 36% practiced in an academic setting, and 50% had at least 20 years in practice. Only 60% of respondents reporting performing in-office curvature assessment prior to commencing intralesional injection or surgical treatment, with higher prevalence in andrology/sexual medicine fellowship-trained versus non-fellowship-trained urologists (85% vs. 54%, p = 0.003). The most popular treatment modalities were collagenase clostridium histolyticum (61% of respondents), phosphodiesterase-5 inhibitors (54%), and penile traction (53%). Twenty-one percent of respondents reported currently using a treatment that is explicitly discouraged by the American Urological Association guidelines (extracorporeal shockwave therapy for curvature, L-carnitine, omega-3 fatty acids, or vitamin E)., Discussion: Patients seeking PD treatment may be offered different therapies, some of which are not evidence-based, depending on the treating urologist. This study is limited by self-selection and response bias. Its strength is that it represents a cross-sectional overview of real-world practice patterns in PD management, which has not been previously described., Conclusions: A significant proportion of urologists reported PD management practices that are not evidence-based and not guideline-supported., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Dupuytren disease creates thickened cords of the palmar fascia, leading to progressive flexion contractures that severely hinder hand function. Collagenase clostridium histolyticum (CCH) injection is a common, minimally invasive alternative to surgical excision of these cords. The impact of CCH injection on the histological architecture of Dupuytren cords has not been studied extensively. Methods: A series of 10 CCH-injected cords were evaluated histologically. Cellularity, architecture, and connective tissue organization were compared against uninjected Dupuytren cords and normal palmar fascia. Results: No significant histopathological differences between CCH-injected and CCH-uninjected cords were identified. Conclusions: Dupuytren cords do not demonstrate histological changes with prior exposure to CCH.

The efficacy of many non-surgical treatments for Peyronie's disease is unclear. This systematic review aims to critically assess the currently available options and provide a recommendation for treatment based on this. A systematic literature search utilising the Medline (Pubmed), Embase, global health and Cochrane library databases was conducted up to May 2021. All randomised controlled trials assessing non-surgical treatment modalities for Peyronie's Disease were included. Individual study risk of bias was evaluated using the Cochrane tool and GRADE was used to assess evidence strength. Outcome measures were the change in penile curvature (degrees), plaque size (volume or size), International Index of Erectile Function score, pain scores and change in penile length. Prospero registration number: CRD42017064618. Amongst the 5549 articles identified, 41 studies (42 reports) were included. Seven different oral treatment options including vitamin E supplementation showed evidence for improving outcomes such as penile curvature and plaque size. Of the intralesional treatments, Collagenase Clostridium Histolyticum showed evidence for improving penile curvature (Range: 16.3-17 degrees, moderate level certainty of evidence). Intralesional Interferon demonstrated some improvement in curvature (Range: 12-13.5 degrees), plaque size (Range: 1.67-2.2 cm 2 ) and pain, whilst intralesional calcium channel blockers such as Verapamil showed variable evidence for changes in the plaque size and pain. Extracorporeal Shockwave Therapy consistently demonstrated evidence for improving penile pain in stable disease, and two mechanical traction devices improved curvature. Iontophoresis, topical medications, and combination therapies did not demonstrate any consistent improvements in outcome measures. Intralesional options demonstrate the best potential. Overall, results varied with few high-quality randomised trials present., (© 2022. The Author(s).)

Introduction: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture., Materials and Methods: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance., Results: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05)., Conclusions: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates following treatment. A number of nonsurgical modalities have been discussed in the past and continue to appear in discussions among hand surgeons, despite highly variable and often poor or no long-term clinical data. This article reviews many of the pharmacotherapies discussed in the treatment of Dupuytren disease and novel therapies used in inflammation and fibrosis that offer potential treatment options., (Copyright © 2023. Published by Elsevier Inc.)

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.

Collagenase clostridium histolyticum (CCH) is an injectable therapy targeting collagen present in penile plaques in Peyronie's disease (PD). Data comparing CCH to penile surgery are limited, and long-term therapeutic outcomes are unknown. This retrospective analysis used a US claims database (January 2014-June 2017) to determine the percentage of men with subsequent penile surgery among those who initially received CCH (n = 1227) or surgery (index treatment; n = 620) for PD. Eligible patients were aged ≥18 years with continuous enrollment ≥6 months before and ≥12 months after index treatment date. During 12 months of post-index treatment follow-up, fewer patients with PD initially treated with CCH (4.6% [56/1227]) had subsequent penile surgery versus those initially treated with penile surgery (10.3% [64/620]; p < 0.0001). Mean ± SD time to first subsequent surgery after initial PD treatment was longer in the CCH versus surgery cohort (7.7 ± 3.0 vs 1.7 ± 3.2 months). The likelihood of subsequent surgery varied by initial surgery type: 18.2% after plaque incision or excision with grafting; 11.6% after penile implant; and 8.2% after tunical plication. Patients with PD who received CCH first were less likely to undergo subsequent surgery compared with those who received surgery first within a 12-month post-treatment follow-up., (© 2022. The Author(s).)

Background: In this randomized controlled trial, the authors compared the recurrence of Dupuytren disease at 3 years following needle fasciotomy or collagenase injection treatment for isolated metacarpophalangeal joint contractures., Methods: The study was conducted between 2013 and 2015. The study design was a single-center, randomized controlled clinical trial with an independent blinded observer. Patients were randomized between collagenase clostridium histolyticum injections (Xiapex) and percutaneous needle fasciotomy (collagenase clostridium histolyticum versus percutaneous needle fasciotomy). A total of 36 patients were followed in the percutaneous needle fasciotomy group and 32 in the collagenase clostridium histolyticum group., Results: Patients who were treated with collagenase clostridium histolyticum had a significantly lower recurrence rate than patients treated with percutaneous needle fasciotomy during the 3-year period ( P = 0.007). Of the 36 patients who were followed in the percutaneous needle fasciotomy group, 17 (47%) had recurrence of extension deficit or progression of the disease leading to further treatment. Of the 32 patients who were followed in the collagenase clostridium histolyticum group, six (19%) had recurrence or progression. No serious adverse event was reported in any of the patients., Conclusions: In this randomized controlled trial, we found less recurrence and progression of Dupuytren disease using collagenase injection as compared to percutaneous needle fasciotomy 3 years following treatment for isolated metacarpophalangeal joint contractures., Clinical Question/level of Evidence: Therapeutic, I., Competing Interests: Disclosure : The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No funding was received for this work ., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Peyronie's disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional collagenase Clostridium histolyticum (CCh) is effective in noncalcified PD; however, its effectiveness in calcified PD is not well characterized., Objective: To assess curvature improvement in calcified PD plaques treated with CCh., Design, Setting, and Participants: We prospectively evaluated men with calcified PD electing CCh treatment at our institution from October 2018 to November 2020. We assessed curvature with artificial erection and goniometer before and at least 3 mo after treatment. We classified the type of plaque calcification based on ultrasound., Intervention: Intralesional CCh. Each treatment cycle consisted of two CCh injections (0.58 mg) into the plaque at the point of maximal penile curvature. The second injection was performed 72 h to 1 wk later, after which participants began modeling. All men were intended to receive a total of eight injections in four cycles, each 6 wk apart., Outcome Measurements and Statistical Analysis: Change in penile curvature after CCh was measured. We assessed for differences in outcomes based on the number of injections and type of calcification. Unless otherwise specified, data are presented as medians (interquartile range)., Results and Limitations: Sixty men with calcified PD elected CCh; 47 had complete follow-up data. Thirty-nine men completed treatments with eight injections, while the remaining discontinued after a median of five (four to six) injections. There was no difference in response between type 2 and type 3 plaques. Curvature significantly improved by 17.5° (37.5-10.0°) in patients who completed treatment and by 15.0° (20.0-0.0°) in those who discontinued. Limitations include a small sample., Conclusions: Men with calcified PD plaques improve with CCh treatment and show similar improvements regardless of calcification type., Patient Summary: In this study, we evaluated the efficacy of collagenase Clostridium histolyticum (CCh) treatment in calcified Peyronie's disease (PD) plaques. We found that treatment in calcified plaques demonstrated significant improvement in curvature and the grading of calcification did not impact the degree of curvature improvement. We conclude that participants with calcified PD plaques can benefit from nonsurgical CCh treatment., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To report outcomes of a novel collagenase clostridium histolyticum (CCH) injection protocol., Methods: A prospective, sequential database was maintained of all Peyronie's men undergoing CCH injections since 2015. Our protocol has evolved to include changes with injection technique, timing, aggressive modeling/traction, and wrapping. Results of the "traditional" and "novel" techniques were compared using two definitions: "most recent" assessment and final assessments among men who "completed eight (injections) or were satisfied.", Results: A total of 509 men underwent greater than or equal to 1 CCH series (traditional, n = 280; novel n = 229). Baseline demographic/clinicopathologic characteristics were similar between groups. Results demonstrated significantly greater curve improvements with the novel technique ("most recent" median 30° vs 20° or 46% vs 28%; "completed eight or satisfied" 34° vs 20° or 58% vs 30%). Using the "completed eight or satisfied" definition, 94% vs 66% of men achieved greater than or equal to 20% improvement (odds ratio 7.6), and 60% vs 24% achieved greater than or equal to 50% improvements (odds ratio 5.0) in the novel cohort (all P < .0001). Importantly, the International Index of Erectile Function Erectile Function Domain score was unchanged, and subjective erectile function (50% vs 5%, P < .0001) and sensation improved (17% vs 8% improved, P = .01) with the new protocol. The novel cohort also reported higher rates of surgery prevention (53% vs 18%), restored/facilitated penetration (57% vs 21%), and hematomas (56% vs 26%), necessitating changes to wrapping procedures (all P < .0001)., Conclusions: Use of the novel CCH protocol results in significant improvements with curvature without negatively impacting erectile function or sensation. Given its specialized nature, it is not recommended for low-volume CCH injectors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Peyronie's disease treatments is changing again due the interruption of Xiapex® distrubution in Europe. There are many reasons that can be referred to this event. In this editorial we would like to shed light on the current cost items relating to treatment with collagenase clostridium histolyticum (CCH). The inaccessibility of the drug has seen both an increase in surgery for the treatments of both PD and Dupuytren's disease and an interruption of therapies in patients who had not completed their therapeutic cycle. Considering the aforementioned concerns, we would like to invite researchers dealing with PD to conduct studies with the available CCH products in collaboration with the drug companies in order to give again an efficacious treatment for PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: With numerous treatment modalities available, it is unclear whether the treatment of recurrent Dupuytren disease is as effective as its initial treatment. We aimed to investigate the outcomes of management of recurrent Dupuytren contracture., Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, Embase, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials were searched from their inception to April 2020. Studies of patients aged above 18 years undergoing treatment for recurrent Dupuytren contractures were included. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment. The study was registered with Open Science Foundation., Results: A systematic review identified 12 studies: 311 patients with 224 affected digits-index (n = 5; 2.2%), long (n = 17; 7.6%), ring (n = 57; 25.4%), small (n = 112; 50%), and unspecified (n = 33; 14.7%); of these, there were 76 metacarpophalangeal joints (MCPJ; 45.5%), 90 proximal phalangeal joints (PIPJ; 53.9%), and 1 distal interphalangeal joint (0.6%). Previous treatment included the following: percutaneous needle aponeurotomy (n = 103 of 311 patients; 33.1%), collagenase clostridium histolyticum-injection (CCH; n = 75 of 311; 24.1%), limited fasciectomy (LF) ± skin graft (n = 83 of 311; 26.7%), fasciotomy (n = 1 of 311; 0.3%), and unspecified (n = 64 of 311; 20.6%). Recurrence was treated by percutaneous needle aponeurotomy (n = 68 of 311 patients; 21.9%); CCH injection (n = 53 of 311; 17.0%); aponeurotomy or dermofasciectomy or LF (n = 176 of 311; 56.6%); ray/digit amputation (n = 8 of 311; 2.6%); and PIPJ arthrodesis (n = 6 of 293; 2.0%). Range of motion was improved by 23.31° (95% confidence interval [CI] = 13.13°-33.50°; I 2 = 67%; P = .05) and 15.49° (95% CI = 2.67°-28.31°; I 2 = 76%; P = .01) for MCPJ and PIPJ, respectively., Conclusions: There is low level of evidence that both surgical and nonsurgical treatments provide clinically important improvements for recurrent Dupuytren contracture.

Purpose: To compare collagenase injection with surgical fasciectomy in Dupuytren disease (DD) for the prevalence of contracture in treated fingers 5 years after treatment., Methods: This was a single-center, comparative cohort study comprising 2 cohorts of patients treated for DD in 1 or more of 3 ulnar fingers with collagenase injection (159 patients) or surgical fasciectomy (59 patients). At 5 years after treatment, 13 collagenase-treated and 8 fasciectomy-treated patients had undergone subsequent treatment on the treated fingers and were considered to have current contracture. Of the remaining patients, 112 collagenase-treated patients (128 hands, 180 fingers) and 46 fasciectomy-treated patients (49 hands, 63 fingers) attended follow-up evaluation performed by 2 independent examiners (participation rate 84% and 93%, respectively). We defined current contracture in a treated finger as an active extension deficit of ≥20° in the metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint or a total (MCP + PIP) active extension deficit (TAED) of ≥30°. We used linear mixed models to analyze differences between the cohorts over time., Results: In the collagenase cohort, current contracture was present in 45 (25%) MCP and 60 (33%) PIP joints, and in the fasciectomy cohort, current contracture was present in 12 MCP (19%) and 30 PIP (48%) joints; a TAED of ≥30° was present in 79 (44%) of the collagenase-treated and 30 (48%) of the fasciectomy-treated fingers. In MCP and PIP joints with ≥20° pretreatment contracture, complete correction was observed in 82 (56%) MCP and 30 (30%) PIP joints in the collagenase cohort and 23 (70%) MCP and 5 (16%) PIP joints in the fasciectomy cohort. There was no statistically significant difference between the 2 cohorts in the TAED change over time., Conclusions: In patients with DD, collagenase injection and surgical fasciectomy improved finger joint contracture over the pretreatment status but had a high prevalence of joint contracture in the treated fingers 5 years after treatment., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To compare clinical outcomes and patient satisfaction rates between intralesional verapamil (ILV) and collagenase Clostridium histolyticum (CCH) injections in males with Peyronie's disease (PD)., Materials and Methods: Following ethics approval, PD patients were prospectively enrolled in this open-label non-blinded study. Patients were randomised to receive ILV or CCH injections with penile remodelling every fortnightly for 6 courses. Patient demographics, change in penile curvature, International Index of Erectile Function-15 and Peyronie's Disease Questionnaire (PDQ) scores as well as overall patient satisfaction and Patient Global Impression of Improvement (PGI-I) scores were recorded at pre-treatment and 6-, 12- and 24-month post-treatment., Results: A total of 50 males were recruited and divided into ILV (n=25) and CCH (n=25) groups. The mean changes in penile curvature were -16.8 (standard deviation [SD] 7.65) degrees in ILV and -28.2 (SD 11.5) degrees in CCH groups (p<0.01). Patients in the CCH group scored better than the ILV group on the PDQ psychosexual symptoms (-2.14 vs. -2.9; p<0.01) and symptom bother score (-3.88 vs. -4.16; p=0.08). Minor treatment-related adverse events were more common in the CCH group. The overall satisfaction rate on a 5-point scale was 4.1 in ILV and 4.5 in CCH groups, and there was no statistically significant difference in the PGI-I scores between the 2 groups (p=0.14)., Conclusions: CCH therapy is more effective than ILV to treat a carefully selected group of males with PD, with a reasonable safety profile and a higher high level of patient satisfaction rate in the short term., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

This systematic review investigates complications and recurrence of Dupuytren's contracture in metacarpophalangeal joints (MCPJs) and/or proximal interphalangeal joints (PIPJs) of fingers treated with collagenase clostridium histolyticum (CCH). A review of the literature on Dupuytren's disease was performed using PRISMA guidelines. Included publications described complications and/or recurrences for contractures ≥20° in MCPJs and/or PIPJs treated with CCH. Successful treatments reduced contractures to ≤5° immediately. Treatment-related adverse events (AEs) were classified as minor, major surgical, and major nonsurgical. Contracture recurrence involved return of fixed-flexion contracture ≥20° in a successfully treated finger in patients with ≥12 months of follow-up. Of 2675 patients (3753 joints), 94% experienced ≥1 treatment-related AE, most commonly peripheral edema (64%), pain in extremity (53%), and contusion (51%). Major surgical complications occurred in 9 patients (1.0%). Major nonsurgical complications occurred in 2 patients, specifically nonrupture tendon injury and anaphylaxis. Of 1488 patients (2069 joints), recurrences were reported in 23% of successfully treated joints (n = 466; 20% MCPJs, 28% PIPJs), on average 12 to 24 months after treatment. MCPJs achieved greater success than PIPJs in initial contracture reduction (77% versus 36%). CCH is a safe, effective treatment to improve hand function in Dupuytren's contracture. Most AEs are minor and self-resolving, although the risk of major AEs still exists. Following treatment, 23% of successfully treated joints experience recurrence, typically within 12 to 24 months but sometimes as early as 6 months. Surgeons are encouraged to discuss these risks with patients for shared decision-making regarding optimal treatment modalities.

Intralesional Collagenase Clostridium histolyticum (CCh) was the first non-surgical therapy approved for Peyronie's disease (PD). However, CCh's cost and poor market uptake has led to its discontinuation in Europe and Canada. In Canada, Xiaflex® is the trade name for CCh and it is produced by Paladin Labs Inc, an operating company of Endo International. The paper aims to better understand Canadian CCh providers' perspectives regarding its treatment efficacy and the potential impact of its discontinuation. All Xiaflex®-approved Canadian providers were asked to complete an anonymous 21-question survey using an online platform. Analysis consisted of descriptive statistics. Outcomes of interest included previous experience with CCh, protocols utilized, experience with insurance coverage, clinical and patient-reported outcomes, and provider perspectives on the discontinuation of CCh. Overall response rate was 48.3% (29/60). A total of 89% of respondents were male, 61% were in practice more than 10 years, 32% were in an academic practice, and 46% had completed an Andrology/Sexual Medicine fellowship. A total of 93% of respondents felt that CCh was superior to other intralesional therapies for PD. In all, 86% reported a patient satisfaction rate of at least 50%, and the majority (75%) saw a clinically meaningful response. Only 7% expressed difficulty obtaining insurance coverage, with many providers (71%) achieving an insurance approval rate between 75 and 100%. Only 54% of respondents reported that they would continue treating PD in light of CCh's discontinuation, and 96% felt that CCh's discontinuation represents a loss to Canadian patients. In light of CCh's discontinuation, most (79%) are now more likely to offer surgical treatment. In conclusion, most CCh providers found CCh to be effective and were dismayed by its discontinuation. The survey demonstrated that due to the withdrawal of CCh from Canada, physicians' abilities to offer effective medical therapy may become limited, with more providers offering surgical options for PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Breast cancer is the most common malignancy among women worldwide. As survival rates increase, breast reconstruction and quality of life gain importance. Of all women undergoing breast reconstruction, approximately, 70% opt for silicone implants and 50% of those develop capsular contracture, the most prevalent long-term complication. The collagenase of the bacterium Clostridium histolyticum (CCH) showed promising results in the therapy of capsule contracture; however, its influence on residual cancer cells is unknown. The aim of this study was to investigate whether CCH-treatment negatively impacts breast cancer cells in vitro and in vivo., Methods: MDA-MB-231 and MCF-7 cells were used in this study. In vitro, we tested the influence of CCH on proliferation, wound healing, migration and cell cycle by MTT-assay, scratch-assay, transwell-migration-assay, and flow cytometry. In vivo, solid tumors were induced in immune-deficient mice. CCH was injected into the tumors and tumor growth and metastasis formation was monitored by caliper measurement, in vivo bioluminescence imaging and histology. Gene expression analysis was performed by microarray including 27,190 genes., Results: CCH-incubation led to a dose-dependent reduction in proliferation for both cell lines, while wound healing was reduced only in MDA-MB-231 cells. No morphological alterations were monitored in cell cycle or apoptosis. In vivo, bioluminescence imaging and histology did not show any evidence of metastasis. Although CCH led to changes in gene expression of breast cancer cells, no relevant alterations in metastasis-related genes were monitored., Conclusion: CCH has no impact on tumor growth or metastasis formation in vitro and in vivo. This paves the way for first clinical trials., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Introduction: Across many cultures, penis size has been associated with virility, and concerns about penile length are commonplace. Peyronie's disease (PD) is a known acquired cause of penile shortening., Objectives: This paper describes the psychosocial impacts of penile length on men and their partners, both generally and in men with PD, and evaluates the effect of PD treatments (eg, collagenase clostridium histolyticum , surgery, mechanical therapy) on this outcome measure., Methods: A PubMed database search was performed for English language articles through July 2021. Main outcome measures were association of penile length with emotional well-being, selfesteem, and relationship satisfaction in men with PD, and change from baseline penile length after treatment., Results: Shortened penile length caused by PD can negatively impact patient and partner quality of life, including effects on body image, emotional well-being, sexual function, and interpersonal relationships. In men with PD, studies have demonstrated an association between loss of penile length and emotional problems, reduced satisfaction with sexual performance, poor self-esteem, depression, and relationship difficulties. Loss of penile length can frequently occur after surgery for PD (including plication, plaque incision/excision with grafting, and penile implant). Advanced surgical techniques may preserve/increase penile length, but the increased risks associated with these complex procedures must be carefully considered. Treatment with collagenase clostridium histolyticum does not appear to negatively impact penile length, and 5-year follow-up data suggest potential longterm posttreatment improvements in this outcome measure. Penile traction therapy, either alone or as adjunctive therapy, may increase penile length in men with PD, but nonadherence may limit improvement., Conclusion: Changes in penile length are important to many men, particularly those with PD, and should be considered during PD treatment selection. Penile length should be measured objectively before and after treatment for PD and should be included as an outcome measure in future studies on treatment effectiveness. Goldstein I, Gelbard MK, Lipshultz LI. Clinical Significance of Shortened Penile Length and Alterations in Penile Length Following Treatment for Peyronie's Disease. Sex Med Rev 2022;10:409-420., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

This study compared hand function and the cost-effectiveness of treatment between collagenase Clostridium histolyticum (CCH) injection and limited fasciectomy for patients with Dupuytren's contracture (DC). The CeCORD-J study is a prospective, multicenter, non-randomized controlled, observational study of two parallel groups. Participants were DC patients with multiple affected fingers, including flexion contracture of the proximal interphalangeal (PIP) joint. The primary outcome was the Hand10 score, as a patient-reported outcome measure (PROM). We set secondary outcomes of EQ-5D-5L (QOL) score, degree of extension deficit, and direct cost. Propensity score adjustment was used to balance differences in patient characteristics between groups. Participants comprised 52 patients in the Collagenase group and 26 patients in the Surgery group. There were no significant differences in the Hand10 and QOL scores between the two groups at 26 weeks. Mean direct cost was 248,000 yen higher in the Surgery group than in the Collagenase group. Extension deficit angle of the PIP joint was significantly larger in the Collagenase group at 26 weeks. Although the Collagenase group showed dominance in cost-effectiveness, there was no significant difference between the two groups in hand function at 26 weeks., (© 2022. The Author(s).)

Background: Dupuytren contracture (DC) treatment with collagenase clostridium histolyticum (CCH) has lower associated treatment costs than fasciectomy, but real-world, postprocedure return-to-function data are limited. Methods: This retrospective study used a US claims database and included adults treated for DC with CCH or fasciectomy (first treatment = index date), who had continuous health plan enrollment ≥360 days preindex and ≥90 days postindex (ie, 90-day follow-up). Analgesic use and physical therapy (PT) and occupational therapy (OT) visits during the follow-up were used as surrogate markers for return-to-function. Results: Overall, 1654 and 2745 patients were included in the CCH and fasciectomy cohorts, respectively. A significantly lower percentage of patients in the CCH versus fasciectomy cohort used opioid analgesics (32.3% vs 82.7%; P < .0001), used nonsteroidal anti-inflammatory drugs (8.6% vs 17.2%; P < .0001), or had ≥1 DC-specific PT or OT visit during follow-up (PT, 38.9% vs 45.3% [ P < .0001]; OT, 32.8% vs 38.0% [ P = .0006]). The mean number of DC-specific PT and OT visits (PT, 2.5 vs 6.4 [ P < .0001]; OT, 1.4 vs 1.9 [ P < .0001]) per patient was significantly lower in the CCH versus fasciectomy cohort. Conclusions: This analysis using surrogate markers suggests that CCH treatment may allow earlier return-to-function than fasciectomy in adults treated for DC.

Background: The primary objective of this study was to assess patient preferences for collagenase Clostridium histolyticum (CCH) treatment versus limited surgical fasciectomy in a cohort that has undergone both treatments for Dupuytren contracture. Methods: We retrospectively identified 68 patients who have undergone both limited surgical fasciectomy and CCH treatment for digital flexion contractures from Dupuytren disease. Patients were contacted by telephone and asked whether they preferred surgery or CCH treatment for their Dupuytren contracture. Multivariable logistic regression was used to determine factors associated with preference for surgery versus CCH treatment. Results: Of the 68 patients who were treated with both CCH and surgery, 37 patients (54.4%) preferred CCH treatment over surgery, 26 (38.2%) preferred surgery over CCH treatment, and 5 (7.4%) were unable to decide. Patients expressed common themes of the perceived ease of recovery following CCH treatment versus the perceived durability of contracture correction with surgery. Preference for surgical fasciectomy over CCH treatment was associated with lower American Society of Anesthesiologists Physical Status Classification (ASA) [odds ratio (OR): 0.32, 95% confidence interval (CI): 0.14-0.75]. The order of treatment was also associated with the treatment preference; treatment with surgery after CCH compared to treatment with CCH after surgery was associated with a preference for surgery (OR: 6.51, 95% CI: 2.15-19.7). Conclusions: In a cohort of patients who have undergone both treatments, patients were divided in their preferences, with a slight majority preferring CCH treatment over surgery. Treatment recommendations should be individualised to each patient's long-term goals and expectations. Level of Evidence: Level III (Therapeutic).

Treatments for Peyronie's Disease (PD) include oral medications, intralesional injections, and surgery. Collagenase Clostridium histolyticum (CCh) is the only FDA-approved treatment for PD. We sought to examine current trends in treatment of PD across the United States. Using data in the MarketScan Database, we conducted a retrospective study of men with PD in the United States. Cases were identified by ICD-9 and 10 codes, and treatments were identified using NDC and CPT codes. Treatment rates were analyzed using a linear regression model, and a Cox proportional hazard function test was performed for time-to-treatment analysis. About 27.8% of men with PD were treated within a year of diagnosis. The annual treatment rate increased from 23.2 to 35.4%, and intralesional injection was the most used treatment. Over the study period, the percentage of men receiving treatment with oral medication increased from 0.66 to 20.5%, while the use of intralesional injection and surgery decreased. Increased odds of treatment were observed in men 45-54 years (odds ratio [OR] 1.35; 95% confidence interval [CI], 1.21-1.50; p = 0) and in the southern region (OR 1.48; 95% CI, 1.39-1.56; p = 0). Trends in treatment of PD have changed over time. Intralesional injection remains the most used treatment option for men with PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Collagenase injection is a relatively new, minimally invasive treatment option for Dupuytren disease. Most literature focusses on quantitative outcome measures, such as degree of residual contracture and recurrence. The patient experience of the treatment has rarely been explored. This study sought to explore patients' experiences of the treatment process, including their reasons for seeking and choosing the treatment., Methods: A qualitative descriptive design was used to explore patients' experiences. Seven patients (aged 57 to 81 years) who had received collagenase treatment for Dupuytren disease engaged in individual, semistructured interviews. Interviews were audio recorded, transcribed verbatim, and analyzed thematically., Results: Thematic analysis revealed that Dupuytren disease was an obstacle to doing things, but not a barrier. Patients "went with the flow" of treatment, often taking a passive approach to their health care decisions. Patients found the collagenase injections to be extremely painful, but worth it. They had a varied knowledge of the disease and treatment., Conclusions: Patients were pleased with the results of the collagenase treatment, even if the finger was not completely straight or there was recurrence. The quick recovery and minimal complications were positive factors; however, the injections were extremely painful and could deter patients from future treatment. This research highlighted that a number of patients had low health literacy regarding their condition, and this affected their expectations of treatment outcomes and future treatment seeking. There are opportunities for health professionals to improve health literacy for people with Dupuytren disease, possibly in a group setting., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Purpose: Over the past decade, collagenase treatment and needle fasciotomy (NF) have gained widespread popularity in the treatment of Dupuytren contracture. This prospective study was designed to compare the results of these treatments in terms of clinical and patient-reported outcomes., Methods: A prospective, randomized, controlled trial included patients with a contracture of 20° or more in a single metacarpophalangeal joint. Patients were allocated to treatment with either NF or collagenase Clostridium histolyticum. The primary outcome was a reduction in the metacarpophalangeal joint contracture to less than 5°. Secondary outcomes included recurrence, the presence of Dupuytren cords, and changes in patient-reported outcomes. The participants were examined 5 years after the intervention., Results: The study cohort comprised 156 patients divided into 2 equally sized groups. After 5 years, data were collected from 143 (92 %) of the initially enrolled participants. The mean time for the clinical follow-up was 5.1 years. In the remaining cohort without a second procedure, 51% (23 patients) in the collagenase Clostridium histolyticum group and 47% (27 patients) in the NF group still had extension deficits of less than 5°. Among the participants with a successful initial procedure, the recurrence rate was 56% (36 patients) in the collagenase Clostridium histolyticum group and 45% (30 patients) in the NF group. There were no differences between the 2 treatments in regard to passive joint extension, reduction of contracture, range of motion, or patient-reported outcomes., Conclusions: The 5-year outcomes for NF are similar to those for collagenase in terms of sustained correction, recurrence, presence of Dupuytren cords, and patient-reported outcomes for the treatment of metacarpophalangeal joint contractures., Type of Study/level of Evidence: Therapeutic I., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Over the past decade, there have been several advancements in the technologies available to treatment erectile dysfunction and Peyronie's disease. Vacuum erection devices, penile traction devices, low-intensity extracorporeal shockwave therapy, and penile prosthesis surgery have evolved and are changing the way we treat men's health. Although significant improvements have been made, further work is needed to standardize treatment, create universal algorithms for technological applications, and simply their use., (Copyright © 2021 Elsevier Inc. All rights reserved.)