Multiple courses of intralesional collagenase injections for Peyronie disease: a retrospective analysis.

BACKGROUND: In the original clinical trials evaluating intralesional collagenase Clostridium histolyticum for Peyronie disease (PD), treatment protocols were limited to 8 injections. AIM: We sought to describe our single-center experience with the use of multiple rounds (>8 injections) of intralesional collagenase in patients with PD. METHODS: We conducted a retrospective analysis of all patients with PD receiving intralesional collagenase injections at our institution from October 2015 through December 2020. Some patients who completed 1 round of treatment elected to undergo additional rounds (16 or 24 injections) based on persistent curvature and presence of penile plaque. Clinical improvement was defined as a 20% reduction in penile curvature from the start of a given round of treatment to the end of that round of treatment. We measured erect penile curvature before and after each round and collected demographics, medical and surgical history, curvature outcomes, and treatment-related adverse events. OUTCOME: The primary outcome was the reduction in penile curvature after multiple rounds of treatment with intralesional collagenase injections in patients with PD. RESULTS: A total of 330 patients underwent intralesional collagenase injections for PD, of whom 229 completed at least 8 injections and underwent pre- and posttreatment erect penile goniometry. An overall 42.8% (98/229), 38.6% (22/57), and 12.5% (1/8) of patients achieved clinical improvement after 1 round of therapy (8 injections), 2 rounds (16 injections), and 3 rounds (24 injections), respectively. Mean degree and mean percentage improvement of penile curvature for the start and end of each round of treatment were 8.3° and 16.4% (after 1 round), 7.2° and 16.8% (after 2 rounds), and 3.3° and 8.1% (after 3 rounds). Bruising was the most common complication, with an incidence of at least 50% in each round. CLINICAL IMPLICATIONS: Knowledge of patient responses to multiple rounds of intralesional collagenase injections may help guide physicians in management and counseling of patients regarding PD treatment options. STRENGTHS AND LIMITATIONS: This is the first study to evaluate multiple rounds (>8 injections) of intralesional collagenase for PD. Limitations include retrospective analysis and smaller sample size among patients undergoing 3 rounds (24 injections). CONCLUSION: For patients who did not achieve clinical improvement after 1 round of treatment, an additional round may be beneficial. However, no real improvement was observed for patients undergoing a third round.

A Novel Technique of Robotic-Assisted Simple Cystectomy During Urinary Diversion for Benign Indications.

BACKGROUND: When urinary diversion is necessary for benign indications, the defunctionalized bladder is at risk of a number of severe complications such as bleeding, pain, pyocystis and secondary urothelial carcinoma. These complications occur in 54%-80% of patients left with native bladder after diversion, and these patients go on to require completion cystectomy 20%-25% of the time. Rowley et al. at the University of Michigan reported their experience in open simple cystectomy in 2011 in a series of 23 patients. This operation, to our knowledge, has not been previously adapted to the robotic platform despite the growing prevalence of robotic surgery including for complex reconstruction and urinary diversion. Here we report our novel adapted technique of performing robotic simple cystectomy in 2 index patients. OBJECTIVE: To visually demonstrate and report our technique of simple cystectomy, utilizing the robotic platform, including outcomes in 2 index patients. METHODS: Two index patients are presented, including outcomes: One female with spinal cord injury, smoking and chronic infections in the setting of suprapubic catheter diversion, and one male with multiply failed local treatments including radiation and cryotherapy for prostate cancer that have resulted in chronic fistula, prior Fournier's gangrene, and sympheseal osteomyelitis. RESULTS: he operations were completed without difficulty, in an expedient fashion (35-48 minutes) and without significant blood loss (10cc or less). The technique is illustrated in the accompanying video. CONCLUSION: This novel adapted robotically-assisted operation appears to be a rapid and reproducible operation that recapitulates the principles of open surgery with little time or blood loss, thus avoiding the morbidity of radical cystectomy or of delayed secondary operations, while at the same time providing all the benefits inherent to a robotic operation. Outcomes appear excellent. Further study is needed.

Intralesional collagenase Clostridium histolyticum for acute phase Peyronie's disease: a single-center, retrospective cohort study.

Background: Peyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12-18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase. Methods: All men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain. Results: Of 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05). Conclusions: This single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings.

Acute Lower Back Pain after Intralesional Injection of Collagenase Clostridium histolyticum for Peyronie's Disease.

PURPOSE: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort. MATERIALS AND METHODS: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities. RESULTS: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac. CONCLUSIONS: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.

3D-printed phantoms to quantify accuracy and variability of goniometric and volumetric assessment of Peyronie's disease deformities.

Characterization of Peyronie's disease (PD) involves manual goniometry and penile length measurement. These techniques neglect volume loss or hourglass deformities. Inter-provider variability complicates accuracy. Using 3D-printed models, we aimed to evaluate measurement accuracy and variability and establish computational assessment workflows. Five digital phantoms were created: 13.0 cm cylinder, 13.0 cm hourglass cylinder, 15.0 cm cylinder with 40° angulation, 12.0 cm straight penis, and 12.9 cm PD penis with 68° angulation and hourglass. Lengths, volumes, and angles were determined computationally. Each phantom was 3D-printed. Ten urology providers determined lengths, angles, and volumes with measuring tape, goniometer, and volume calculator. Provider versus computational measurements were compared to determine accuracy using t-tests or Wilcoxon rank-sum tests. No significant differences were observed between manual assessment of length of penile models and designed length in penile models. Average curvature angles from providers for bent cylinder and PD phantoms were 38.3° ± 3.9° (p = 0.25) and 57.5°â€†±â€†7.2° (p = 0.006), respectively. When assessing for volume, hourglass cylinder and bent cylinder showed significant differences between designed volume and provider averages. All assessments of length, angle, and volume showed significant provider variability. Our results suggest manual measurements suffer from inaccuracy and variability. Computational workflows are useful for improved accuracy and volume assessment.

Measurement accuracy of 3-Dimensional mapping technologies versus standard goniometry for angle assessment.

BACKGROUND: A specific aspect of the hypospadias phenotype that may contribute to long-term outcomes is the presence of ventral penile curvature and the adequacy of its surgical correction. The current gold standard to assess this angle is intraoperative goniometry of an erect penis. 3-dimensional (3D) mapping technologies may overcome the limitations of these traditional methods through their combination of digital image and geometric replication to produce consistent 3D digital forms of a physical structure. The aim of this study is to evaluate the measurement accuracy and reliability of handheld 3D mapping technologies versus standard goniometry for angle assessment in a laboratory setting. METHODS: Blocks with specified angles (10-45°) were printed using a Zortrax M200 3D printer (±0.2% accuracy). Following the completion of standardized training, blinded participants measured each block angle using a baseline digit goniometer. Additionally, complete digital models of the blocks were created using 3D mapping technologies. Structured light scanning was completed using an Artec Space Spider and Artec Studio 13. Traditional photogrammetry was completed using a Canon Eos Rebel T5i DSLR camera and Agisoft Metashape Pro. Photogrammetry with a 3D camera was completed using the VECTRA H1 and VECTRA Analysis Module. All 3D models were imported into the software Autodesk Inventor in which automated angle measurements through the central plane were obtained. Statistical analysis was performed to determine the accuracy, precision and reliability of each modality using SAS 9.4 software. The reliability of goniometry and each mapping technology was evaluated using two-way random effect models with absolute agreement. RESULTS: Six 3D printed blocks were evaluated. 5 digital models per block were created using each of the 3 mapping technologies. Inter-rater reliability of goniometry was moderate (ICC 0.76, 95% CI 0.46, 0.92), whereas all mapping technologies demonstrated excellent test-retest reliability: structured light scanning (ICC 0.99; 95% CI 0.999, 0.999); traditional photogrammetry (0.99; 0.99, 0.99); 3D camera (0.99; 0.99, 0.99). Mean angle measurements and standard error for each angle and modality are provided in the table. CONCLUSIONS: This study demonstrated excellent accuracy, precision and reliability of off-the-shelf, handheld 3D mapping technologies and moderate reliability for goniometry when applied to measurements of angulation in a laboratory setting. The described methods developed in the laboratory for optimization of angle analysis from 3D models are an important step toward reliable, reproducible phenotypic analysis of congenital genitourinary conditions in future intraoperative and database development applications.

Deletion of the von Hippel-Lindau Gene in Hemangioblasts Causes Hemangioblastoma-like Lesions in Murine Retina.

von Hippel-Lindau (VHL) disease is an autosomal-dominant tumor predisposition syndrome characterized by the development of highly vascularized tumors and cysts. LOH of the VHL gene results in aberrant upregulation of hypoxia-inducible factors (HIF) and has been associated with tumor formation. Hemangioblastomas of the central nervous system and retina represent the most prevalent VHL-associated tumors, but no VHL animal model has reproduced retinal capillary hemangioblastomas (RCH), the hallmark lesion of ocular VHL. Here we report our work in developing a murine model of VHL-associated RCH by conditionally inactivating Vhl in a hemangioblast population using a Scl-Cre-ERT2 transgenic mouse line. In transgenic mice carrying the conditional allele and the Scl-Cre-ERT2 allele, 64% exhibited various retinal vascular anomalies following tamoxifen induction. Affected Vhl-mutant mice demonstrated retinal vascular lesions associated with prominent vasculature, anomalous capillary networks, hemorrhage, exudates, and localized fibrosis. Histologic analyses showed RCH-like lesions characterized by tortuous, dilated vasculature surrounded by "tumorlet" cell cluster and isolated foamy stromal cells, which are typically associated with RCH. Fluorescein angiography suggested increased vascular permeability of the irregular retinal vasculature and hemangioblastoma-like lesions. Vhl deletion was detected in "tumorlet" cells via microdissection. Our findings provide a phenotypic recapitulation of VHL-associated RCH in a murine model that may be useful to study RCH pathogenesis and therapeutics aimed at treating ocular VHL.Significance: This study describes a model that phenotypically recapitulates a form of retinal pathogenesis that is driven by genetic loss of the VHL tumor suppressor, providing a useful tool for its study and therapeutic intervention. Cancer Res; 78(5); 1266-74. ©2018 AACR.