Broderick, Gregory A.

Abstract Introduction Ischemic priapism remains a significant cause of morbidity among men. To date, the precise time when penile ischemia results in permanent, non-reversible cavernosal smooth muscle injury, compromising subsequent erectile integrity, remains ill-defined. Objectives To review the medical literature pertaining to ischemic priapism, focusing on factors that predict the exact timeline of irreversible cavernous tissue injury. Methods A comprehensive literature search was performed. Our search included both publications on animal models and retrospective clinical series through January 2022. Articles were eligible for inclusion if they contained original data regarding nonreversible tissue injury on histology and/or provided a timeline of erectile function loss or preservation and had full text available in English. Results Innovative studies in the 1990s using invitro models with strips of rabbit, rat, canine and monkey corpus cavernosal tissue demonstrated that anoxia eliminated spontaneous contractile activity and reduced tissue responsiveness to electrical field stimulation or pharmacological agents. The same models demonstrated that the inhibitory effects of field stimulated relaxation, were mediated by nitric oxide. Subsequent studies using similar models demonstrated that exposure of corpus cavernosum smooth muscle to an acidotic environment impairs its ability to contract. A pH of 6.9 was chosen for these experiments based on a case series of men with priapism, in whom a mean pH of 6.9 was measured in corporal blood after 4–6 hours of priapism. Invivo animal studies demonstrated that after erection periods of 6–8 hours, microscopy shows sporadic endothelial defects but otherwise normal cavernous smooth muscle. In these studies, greater durations of ischemic priapism were shown to result in more pronounced ultrastructural changes and presumably irreversibility. In studies involving human corporal tissues, samples were obtained from men who had experienced priapism for at least 12 hours. Overall, erectile function outcome data is deficient in priapism reporting, especially within treatment windows less than 6 hours. Some reports on ischemic priapism have documented good erectile function outcomes with reversal by 12 hours. Conclusion Based on our extensive review of animal models and clinical reports, we found that many clinical papers rely on the same small set of animal studies to suggest the time point of irreversible ischemic damage at 4–6 hours. Our review suggests an equal number of retrospective clinical studies demonstrate that ischemic priapism reversed within 6–12 hours may preserve erectile function in many patients.

ABSTRACT Introduction Peyronie's Disease (PD) is characterized by a fibrous scar of the tunica albuginea. PD is typically imaged with 2D ultrasound. We propose a classification system of these ultrasound findings in the evaluation of PD. Objective The purpose of this study is to establish a functional, reproducible sonographic classification system for evaluating PD and to examine the relationship between PD grading and curvature, duration of PD, and vascular erectile status. Methods In our study, 395 patients with PD underwent intracavernous injection with an erectile agent (ICI) followed by Color Doppler Duplex Ultrasound (CDDU). All CDDU studies were performed by a single examiner and all PD grading was done by two independent reviewers using saved images. CCDU findings including peak systolic velocities (PSV) and resistive indices (RIs) were recorded. PD grades of 2D images were classified into three grades: Grade 1 acoustic shadowing without calcification; Grade 2 focal microcalcifications of the tunica, pillars, or septal fibers; Grade 3 confluent calcification of the dorsal, septal, ventral tunica albuginea. Results There were 250 patients classified with Grade 1 (63%) sonographic changes, 75 with Grade 2 (19%), and 70 with Grade 3 (18%). Neither median age nor body mass index (BMI) of the cohorts were significantly different: Grade 1 (59.3 yr), Grade 2 (59 yr) and Grade 3 (60.3 yr), p = 0.711; BMI 27.6, 28.2, 27.7, p = 0.813. Medical risk factors for erectile dysfunction, including hypertension, heart disease, diabetes mellitus, hyperlipidemia, smoking history, and history of prostate surgery were not statistically different for the three cohorts. Most patients had previously used PDE5-Inhibitors (293/395). History and or physical findings of Dupuytren's palmar contracture was noted in 30/395 (7.6%) of men. The median duration of PD was not significantly different in the three cohorts (12, 12, 14 months p = 0.639). Neither CDDU diagnoses (Table 1) nor curvature varied by sonographic grades (Table 2). Conclusions The scar resulting from PD seals together the outer longitudinal and inner circular layers of the tunica albuginea causing deformity of the erect shaft. PD plaques are usually palpable and associated with focal thickening of the tunica. On 2D ultrasound, the typical appearance is an acoustic shadow. Most of our patients presented with Grade I acoustic shadowing and no calcifications 250/395 (63%); on the other hand, 19% had acoustic plaque shadowing and additional findings of focal tunica or deep microcalcifications and 18% had confluent calcification of the dorsal, septal or ventral tunica. We propose a unique and reproducible classification system. This grading system based on grayscale ultrasound of Peyronie's plaques may serve as a paradigm for diagnosis, didactics and integrated research. Disclosure Work supported by industry: no, by N/A.

ABSTRACT Introduction Intracavernosal injections (ICI) are a well-established treatment option with great success rates for men with erectile dysfunction. Unfortunately, the anticipation of pain with injections remains a significant barrier to the use of ICI. Objective This study aims to utilize a standardized verbal pain scale to examine the perception of pre- and post-injection pain in men who are undergoing their first injection with an intracavernosal erectile agent. Thus, inclusion criteria required no previous penile injection of any type, including but not limited to erectile medications and collagenase. Methods We determined a prospective pre-post observational study would be best to examine men undergoing their first ICI. Men who had no previous history of intracavernosal injection of any kind were asked to predict the pain associated with their first ICI with a score of zero to ten. Patients then received a 10 microgram (mcg) injection of prostaglandin E1 (PGE1). Immediately after they received their injection, they were asked to rate the pain they perceived with the injection on the same scale (0-10). The same physician administered pre- and post-injection scales in a standardized fashion. Results A total of 17 of men were asked to rate their pain as discussed in the Methods Section. The average age of men sampled was 61.8 years of age. On review of history, 64.7% of men were found to have used some type of PDE-5 inhibitor before visiting our clinic. The majority of men we saw had erectile dysfunction (70.6%) and/or Peyronie's Disease (58.8%). The average pre-injection prediction pain score was 5.29 +/- 1.90; the average post-injection perceived pain score was 1.21 +/- 0.81. Thus, there was an average decrease of over 4 points in predicted pain versus perceived pain. A two-sample t-test was performed; in addition, a Wilcoxson Signed Rank Test was performed. Both tests showed statistical significance in the difference between pre- and post-injection pain scores (p <0.001). Conclusions We found that patients who are undergoing ICI for their first time have a significantly higher prediction of pain versus perception of pain after the injection. We have utilized this data in our clinic to explain to patients that while the majority of patients predict high pain scores associated with injection, the vast majority of patients report very minimal pain associated with the injection. Patients can be more open-minded to ICI therapy which could help aid them with their erectile status; this can particularly be helpful in patients who want to avoid surgery and in patients who are not good surgical candidates. Disclosure Work supported by industry: no, by N/A.

ABSTRACT Introduction Erectile dysfunction (ED) is a common consequence of Diabetes Mellitus (DM). The medical literature is inconclusive as to which DM related morbidities improve with better glycemic control. Surgical literature often associates infection outcomes with DM and with glycemic control. There is limited research on the relationship between Hemoglobin A1c and severity of vascular ED. Objective To evaluate the relationship between hemoglobin A1c (HbA1c) and severity of vascular ED in men with DM diagnosed with vascular ED by penile color duplex Doppler ultrasound (CDDU). Methods We retrospectively analyzed patients with a history of DM who underwent intracavernous injection followed by CDDU at our institution between 2005 and 2019. CDDU findings including peak systolic velocities (PSV), primary diagnosis after CDDU, and resistive indices (RIs) were recorded. Doppler diagnosis was based on post stimulation PSV and RI. Arterial Insufficiency (AI) was classified as PSV < 25 cm/s (severe), or (moderate) PSV 25-34.9 cm/s with RI ≥ 0.90. Corporal veno-occlusive disease (CVOD) was classified as PSV ≥ 35 cm/s with RI < 0.90. Mixed ED was classified as PSV 25-34.9 cm/s with RI < 0.90. HbA1c was recorded at time of assessment. Among our cohort of 1490 men who had CDDU, 520 had DM: 130 with CDDU diagnosis of ED, 270 with CDDU diagnosis of ED + Peyronie's disease (PD), 94 with PD alone and 26 with normal vascular erections on CDDU and no PD. The 130 patients with DM diagnosed with ED without presence of PD were included in our analysis. We used a Kruskal-Wallis rank sum test to evaluate the overall association between HgA1c and CDDU diagnosis (AI, CVOD, and mixed ED). Spearman rank correlation tests were used to explore the relationship of HbA1C with PSV and RI. Results Among the 130 men with DM + ED without PD, the median age was 61 y (range 20-79 y), 76 (58%) had hypertension, 37 (28%) had heart disease, median BMI was 30.7 kg/m2 (range 21.2-48.9 kg/m2), and median HgbA1C was 7.0 (range 5.0-11.0). PDE-5 inhibitor use was reported in 119/129 (92.2%) and among those who reported using it 108/119 (90.8%) reported PDE-5 inhibitor failure. CDDU diagnoses were 53 (40.8%) AI, 44 (33.8%) CVOD, and 33 (25.4%) mixed vascular (25%). The median (interquartile range) HbA1c was 7.0 (6.1-7.8) in men with AI, 7.1 (6.3-8.0) in men with CVOD, and 6.7 (6.1-7.0) in men with mixed ED. We did not find evidence of a relationship between HbA1c and severity of vascular ED (Kruskal-Wallis test P = 0.25). We also did not find evidence of a correlation of HbA1c with either post-stimulation PSV (Spearman rank correlation = 0.04, P=0.68) or RI (Spearman rank correlation = -0.03, P = 0.79). Conclusions Median HbA1c did not vary with the vascular diagnosis of men with DM + ED (AI vs. CVOD vs. Mixed Vascular). DM is a significant risk factor for ED and HbA1c is used to monitor and advise patients. We found no predictive relationship between HbA1c and type of vascular ED as defined by CDDU. Disclosure No

ABSTRACT Introduction Peyronie's Disease (PD) is a well described pathology affecting up to 5-10% of men. The presence and extent of penile calcifications is an important determinant in disease management. Calcifications have a variety of clinical presentations ranging from microcalcifications to calcified plaques. Calcified plaques were excluded from past Xiaflex clinical trials. Calcified plaques may necessitate plaque excision and grafting (E&G) sometimes combined with inflatable penile prosthesis (IPP) placement, which is more complex than plaque incision and grafting. Peyronie's Disease guidelines recommend color duplex Doppler ultrasound (CDDU) primarily to rule out Erectile Dysfunction. PD pathology such as corporal septal involvement, multifocal calcifications, and circumferential corporal calcification can be difficult to assess on penile ultrasound (PUS) due to acoustic shadowing and device limitations. We describe a series of patients in whom non-contrast CT scan was used to further define calcified or complicated pathology. Objective To describe the role of non-contrast CT scan of the penis for anatomic evaluation and surgical planning in patients with complicated calcified Peyronie's disease. Methods 23 male patients with a diagnosis of PD were evaluated by a single surgeon at a single academic institution between 2017 and 2021. All patients underwent color doppler ultrasound (CDDU) examination with artificial erection via intracavernosal alprostadil injection and were evaluated based on erectile function, plaque dimension, hourglass deformity, plaque septal involvement, and suspected calcification status. Patients with CDDU examination concerning for significant calcification or complexity proceeded to non-contrast CT scan for calcific confirmation and for 3-dimensional evaluation of their PD plaque prior to surgical discussion. Complexity was defined as concern for multifocal calcified plaques (>2), partial/complete circumferential corpus cavernosum involvement, or septal involvement. Results All 23 patients had concerning findings on initial examination for calcified plaque. 9 of 23 (39.1%) patients had exam findings of an hourglass deformity. On CT evaluation, calcification was confirmed in 22 of 23 patients (95.7%). Plaque dimensions on CT scan ranged from 0.4 × 0.2 × 0.5 cm to 4.0 × 2.0 × 1.7 cm. Many of these measurements were approximations due to circumferential calcified plaque. This classic “gull-wing” appearance (Figure 1) was noted in 6 of 23 (26%) patients. 12 of 23 (52.2%) of patients had septal involvement on CT (Figure 2). 8 of 23 patients (34.8%) had significant multifocal disease (Figure 3). 8 of 23 patients (34.8%) decided to proceed with surgical correction via E&G (n = 3), IPP with E&G (n =1), or via IPP with manual remodeling via the Wilson technique (n = 4). Conclusions Non-contrast penile CT scan for evaluation of calcified Peyronie's disease allows for increased accuracy of surgical planning especially when evaluating for multifocal disease, circumferential plaque and/or septal involvement. These elements are critical in being able to provide accurate surgical recommendations and post operative discussions. Disclosure No

ABSTRACT Introduction Peyronie's Disease (PD) is characterized by a fibrous scar of the tunica albuginea. PD is typically imaged with 2D ultrasound. We propose a classification system of these ultrasound findings in the evaluation of PD. Objective The purpose of this study is to establish a functional, reproducible sonographic classification system for evaluating PD and to examine the relationship between PD grading and curvature, duration of PD, and vascular erectile status. Methods In our study, 395 patients with PD underwent intracavernous injection with an erectile agent (ICI) followed by Color Doppler Duplex Ultrasound (CDDU). All CDDU studies were performed by a single examiner and all PD grading was done by two independent reviewers using saved images. CCDU findings including peak systolic velocities (PSV) and resistive indices (RIs) were recorded. PD grades of 2D images were classified into three grades: Grade 1 acoustic shadowing without calcification; Grade 2 focal microcalcifications of the tunica, pillars, or septal fibers; Grade 3 confluent calcification of the dorsal, septal, ventral tunica albuginea. Results There were 250 patients classified with Grade 1 (63%) sonographic changes, 75 with Grade 2 (19%), and 70 with Grade 3 (18%). Neither median age nor body mass index (BMI) of the cohorts were significantly different: Grade 1 (59.3 yr), Grade 2 (59 yr) and Grade 3 (60.3 yr), p = 0.711; BMI 27.6, 28.2, 27.7, p = 0.813. Medical risk factors for erectile dysfunction, including hypertension, heart disease, diabetes mellitus, hyperlipidemia, smoking history, and history of prostate surgery were not statistically different for the three cohorts. Most patients had previously used PDE5-Inhibitors (293/395). History and or physical findings of Dupuytren's palmar contracture was noted in 30/395 (7.6%) of men. The median duration of PD was not significantly different in the three cohorts (12, 12, 14 months p = 0.639). Neither CDDU diagnoses (Table 1) nor curvature varied by sonographic grades (Table 2). Conclusions The scar resulting from PD seals together the outer longitudinal and inner circular layers of the tunica albuginea causing deformity of the erect shaft. PD plaques are usually palpable and associated with focal thickening of the tunica. On 2D ultrasound, the typical appearance is an acoustic shadow. Most of our patients presented with Grade I acoustic shadowing and no calcifications 250/395 (63%); on the other hand, 19% had acoustic plaque shadowing and additional findings of focal tunica or deep microcalcifications and 18% had confluent calcification of the dorsal, septal or ventral tunica. We propose a unique and reproducible classification system. This grading system based on grayscale ultrasound of Peyronie's plaques may serve as a paradigm for diagnosis, didactics and integrated research. Disclosure No

ABSTRACTBackgroundIntracavernosal injections (ICI) are a well-established treatment option for men with erectile dysfunction (ED); however, the anticipation of pain with injection remains a significant barrier to the use of ICI.AimTo evaluate the patient-anticipated degree of pain versus the experienced degree of pain pre- and post-ICI in men undergoing their first injection with an erectile agent.MethodsWe studied 51 patients who underwent their first ICI in our men’s health clinic. Anticipated needle-associated pain was judged with a pre-injection score, and pain experienced during the injection was judged with a post-injection score. All patients graded their pre- and post-ICI pain using a standard 10-point scale (0–10).OutcomesPre- and post-ICI pain was defined with the visual analogue scale (0–10) in men undergoing their first penile injection.ResultsMedians and interquartile ranges (IQRs) of the patients’ age [65 years (54.5–68.0)], pre-injection pain [5 (4–7)], and post-injection pain [1 (1–2)] were recorded. Most men in the study had erectile dysfunction (68.6%) and/or Peyronie’s Disease (64.7%). The average pre-injection prediction pain score was 5.45 ± 2.15; the average post-injection perceived pain score was 1.20 ± 0.73. Thus, there was an average discrepancy of over 4 points in predicted pain vs perceived pain. A paired t-test was performed which showed a statistically significant difference between pre- and post-injection scores (P < .05). A Wilcoxson Signed Rank Test showed statistical significance in the difference between pre- and post-injection pain scores (P < .05).Clinical ImplicationsICI is a safe, effective treatment for patients with ED and is associated with significantly less pain than is anticipated by patients.Strengths & LimitationsThis is the first report to describe the discrepancy between pre-ICI anticipated pain and post-ICI experienced pain. Limitations include an overall small sample size.ConclusionPatients experience significantly less pain with ICI than they anticipate having. This represents an important factor to consider when counseling patients about available ED treatments.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor’s complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.