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Abstract: There is a paucity of data regarding porokeratosis confined to the penis and scrotum. We evaluated our single-institutional experience regarding this entity. We interrogated our pathology archive for all specimens from the penis or scrotum, signed out as porokeratosis between 2000 and 2022. Clinical and histopathological features were reviewed, including the number of cornoid lamella(e) per tissue profile and squamous dysplasia. Nine patients were included in the study. The median age at the time of diagnosis was 51 years. Multiple lesions were present in 3 patients. Six patients had exclusively penile involvement, whereas 2 patients had exclusively scrotal involvement. One patient had multiple lesions consistent with porokeratosis ptychotropica, extending from the scrotum to the buttocks and perineum. Clinically, a collarette of scale was noted in 3 patients and diagnosis of porokeratosis was considered in 1 patient before biopsy. Histopathologically, 2 patients exhibited multiple cornoid lamellae in the same profile and 1 patient had follicular cornoid lamellae. Focal squamous dysplasia was only present in 1 patient. Follow-up was available for 5 patients (median duration: 35 months). In 4 patients, the lesions were removed completely during the shave biopsy procedure. At the past follow-up, there were no signs of recurrence or malignant transformation to squamous cell carcinoma in any patient. Porokeratosis involving the penis and/or scrotum may be elusive to diagnosis based on clinical features alone, emphasizing the role of histopathological examination. Increased awareness of this entity may help better delineate its clinicopathological presentation and appropriate classification., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Purpose: Exploring the therapeutic effect and mechanism of isorhamnetin in the treatment of DMED., Methods: Using a high glucose environment to induce endothelial cells damage in the corpus cavernosum, and combining with intervention agents such as ferroptosis inhibitors to observe the process of cell damage and repair, evaluating cell status through CCK-8 and DAPI; To establish the STZ-induced diabetes rat model and detect the erectile function and tissue changes; Perform transcriptomic sequencing on rat models and samples treated with isorhamnetin to analyze differentially expressed genes and their GO functions; Identify critical pathways by combining with the ferroptosis database; Flow cytometry was used to detect ROS and mitochondrial membrane potential, and RT-PCR was used to verify gene expression, Seahorse detects mitochondrial oxygen consumption rate, revealing the mechanism of action of isorhamnetin., Results: Ferroptosis inhibitors and isorhamnetin can effectively reverse the damage of corpus cavernosum endothelial cells induced by high glucose and ferroptosis agonists. Isorhamnetin has the ability to reinstate the erectile function of diabetic rats, while enhancing the quantity of endothelial cells and refining the morphology of collagen fibers. Immunohistochemistry revealed that ferroptosis existed in the penis tissue of diabetes rats. Transcriptomic analysis showed that isorhamnetin improves gene expression in DM rats by regulating genes such as GFER, IGHM, GPX4 and HMOX1, involving multiple pathways and biological processes. Flow cytometry and RT-PCR confirmed that isorhamnetin can reduce reactive oxygen species levels, restore essential gene expression, improve mitochondrial membrane potential, and alleviate oxidative stress and ferroptosis. Seahorse detection found that isorhamnetin can restore mitochondrial oxygen consumption rate., Conclusion: Isorhamnetin attenuates high glucose damage to cavernous endothelial cells by inhibiting ferroptosis and oxidative stress, restores erectile function and improves tissue morphology in diabetic rats, and its multi-pathway and multi-targeting regulatory mechanism suggests that it is promising to be an effective drug for the treatment of DMED., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Peripheral nerve injury can result in penile cavernosal denervation muscle atrophy, a primary factor in nerve injury erectile dysfunction (NED). While acetylcholine (Ach) is integral to erectile function, its role and mechanisms in NED need further exploration., Objective: To investigate the inhibition of CCMSCs Apoptosis and Protein Degradation Pathway by Ach in NED rat model., Methods: We investigated changes in Ach secretion and receptor expression in an NED rat model, followed by the evaluation of apoptosis and ubiquitin proteasome activation in hypoxic Cavernous smooth muscle cells (CCMSCs) and their co-cultures with Schwann cells (SWCs), under Ach influence. Further, key pathways in NED were identified via high-throughput sequencing, focusing on the p38/MAPK signaling pathway. We examined gene alterations related to this pathway using hypoxic cell models and employed p38 inhibitors to verify protein changes. Our findings in vitro were then confirmed in the NED rat model., Results: Nerve injury led to reduced Ach receptors and associated gene expression. Experimentally, Ach was shown to counteract CCMSC apoptosis and muscle protein degradation via the p38/MAPK pathway. Inhibition of the Ach degradation pathway demonstrated a capacity to slow NED progression in vivo., Discussion and Conclusion: Activation of Ach receptors may decelerate denervation-induced cavernosal muscle atrophy, suggesting a potential therapeutic approach for NED. This study highlights the crucial role of the Ach/p38/MAPK axis in the pathophysiology of penis smooth muscle atrophy and its broader implications in managing NED and male erectile dysfunction., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Frozen section examination (FSE) of the tumor resection margins is important during penile-preserving surgery (PPS) in penile cancer. The margin status will impact on how much penile or urethral tissue is excised. We aim to evaluate the outcomes of intraoperative FSE of resection margins in PPS., Patients and Methods: A retrospective analysis of patients with penile squamous cell carcinoma (SCC) who underwent a FSE of resection margins between 2010 and 2022 was conducted. FSEs were compared with the final histopathological analysis and the Diagnostic Testing Accuracy (DTA): sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated., Results: Overall, 137 FSE were performed. The median (IQR) age was 65 (53-75) years. 118 (86.1%) patients had negative FSE margins, 16 (11.7%) had positive FSE margins and 3 (2.2%) had equivocal (atypical cells) results. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of penile FSE were 66.7%, 100%, 100%, 93.2% and 94% respectively. 18 patients underwent further resection in the same episode due to a positive or equivocal FSE and 12 (66.7%) achieved negative margins. Limitations include the retrospective nature of the study and lack of control arm to compare with., Conclusions: Intraoperative FSE performed at our center for the assessment of penile SCC margins is 66.7% sensitive and 100% specific. FSE should be considered in PPS, as it's an essential and a reliable diagnostic tool in minimizing over-treatment., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4 + T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear., Methods: PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-β-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED., Results: IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED., Conclusions: IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED., (© 2024. The Author(s).)

The prevalence of penile calcification in the population remains uncertain. This retrospective multicenter study aimed to determine the prevalence and characteristics of penile calcification in a large cohort of male patients undergoing non-contrast pelvic tomography. A total of 14 545 scans obtained from 19 participating centers between 2016 and 2022 were retrospectively analyzed within a 3-months period. Eligible scans (n = 12 709) were included in the analysis. Patient age, penile imaging status, presence of calcified plaque, and plaque measurements were recorded. Statistical analysis was performed to assess the relationships between calcified plaque, patient age, plaque characteristics, and plaque location. Among the analyzed scans, 767 (6.04%) patients were found to have at least one calcified plaque. Patients with calcified plaque had a significantly higher median age (64 years (IQR 56-72)) compared to those with normal penile evaluation (49 years (IQR 36-60) (p < 0.001). Of the patients with calcified plaque, 46.4% had only one plaque, while 53.6% had multiple plaques. There was a positive correlation between age and the number of plaques (r = 0.31, p < 0.001). The average dimensions of the calcified plaques were as follows: width: 3.9 ± 5 mm, length: 5.3 ± 5.2 mm, height: 3.5 ± 3.2 mm, with an average plaque area of 29 ± 165 mm² and mean plaque volume of 269 ± 3187 mm³. Plaques were predominantly located in the proximal and mid-penile regions (44.1% and 40.5%, respectively), with 77.7% located on the dorsal side of the penis. The hardness level of plaques, assessed by Hounsfield units, median of 362 (IQR 250-487) (range: 100-1400). Patients with multiple plaques had significantly higher Hounsfield unit values compared to those with a single plaque (p = 0.003). Our study revealed that patients with calcified plaques are older and have multiple plaques predominantly located on the dorsal and proximal side of the penis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Our goal was to identify new Peyronie's disease (PD) subtypes, non-PD penile curvature classifications, and define active (acute) vs stable (chronic) phases of disease using evidence-based analyses., Materials and Methods: A retrospective review was performed of 1098 men who presented with penile deformity, including subjective standardized and nonstandardized questionnaires and objective measures. A second cohort of 719 men who were sent a mailed survey was also utilized for the relapsing/remitting subtype. Statistical analyses were performed to identify clusters of disease characteristics representative of distinct PD and non-PD categorizations, including sensitivity/specificity analyses and subtype comparisons., Results: Comparative analyses identified 4 distinct subtypes of PD: (1) classical and nonclassical, (2) calcifying-moderate/severe calcification, (3) progressive-subjective worsening following disease onset, and (4) relapsing/remitting-reactivation following ≥ 6 months of stability. Additional, non-PD categorizations included congenital (lifelong), maturational (developed around puberty), and trauma induced. Statistical analyses demonstrated unique profiles among each category. Penile pain was not found to be a reliable predictor for disease progression or stability. Stable phase disease (historically "chronic") was variably defined by subtype: classical (≥3 months); progressive, calcifying, or trauma induced (≥12 months + ≥3 months stable OR ≥6 months stable). Similarly, PD subtypes may be assigned at ≥ 3 months following disease onset. A PTNM staging system is proposed to help communicate disease states, in which P = PD component (Ca-calcifying, Cl-classical, P-progressive, R-relapsing/remitting, U-undifferentiated), T = trauma component (0-absent, 1-present), N = non-PD component (C-congenital, M-maturational, U-undifferentiated), and M = mode (0-stable, 1-active); for example, PClT1N0M0 = stable classical PD with prior trauma., Conclusions: The current study provides an evidence-based proposal for the establishment of new PD subtypes and non-PD curvature categorizations as well as a standardized definition for active vs stable phases of disease.

Peyronie's disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie's plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Human mpox, which has spread worldwide since May 2022, is characterized by symptoms involving the genital area; however, its treatment methods and clinical course are not completely understood. Furthermore, penile swelling in human mpox can be difficult to differentiate from cellulitis and antibiotic use has been reported in such cases. Herein, we report a case of human mpox in Japan with prominent penile swelling and persistent penile ulcers that improved without specific treatment. The patient was a Japanese man in his 20s with a history of having sexual intercourse with men frequently. He visited Tokyo Metropolitan Toshima Hospital because of a fever and rash in the genital area. Physical examination revealed vesicles on the limbs, penile pigmentation, and significant penile swelling and redness. There were no signs of cellulitis and symptomatic treatment was initiated with outpatient follow-up. After 7 days, an improving trend in penile swelling, redness, and pain was observed. However, a partially black skin ulcer with exudate was observed at the left coronal sulcus of the penis. Therefore, the symptomatic treatment was continued. On illness day 28, the penile swelling completely improved; however, the penile ulcer and pain persisted, and the exudate was observed again. By illness day 63, the pain in his anogenital area had disappeared, and the penile skin ulcer had healed. The following observations were noted in this case: (i) human mpox can improve without specific treatment such as tecovirimat administration and (ii) skin lesions in the genital area may change over time., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding this report., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetes mellitus commonly causes endothelial cell and smooth muscle cell death in penile cavernous tissue., Aim: The study sought to study the mode of cell death in the penile cavernous tissue in type 1 diabetic rats., Methods: A total of 36 Sprague Dawley rats 10 weeks of age were randomly divided into 2 groups: a normoglycemic group and type 1 diabetic group (intraperitoneal injection of Streptozotocin (STZ), 60 mg/kg). We randomly selected 6 rats from each group for tests at the end of 11, 14, and 18 weeks of age, respectively. All rats were able to eat and drink freely. The ratio of maximum intracavernous pressure to mean arterial pressure, concentration of serum testosterone, level of nitric oxide in the penile cavernosum, and expression of active caspase-1 (pyroptosis) and active caspase-3 (apoptosis) were determined., Outcomes: At the end of weeks 4 and 8 of type 1 diabetes, the proportions of endothelial cells and smooth muscle cells undergoing apoptosis and pyroptosis in penile cavernous tissue are different., Results: The ratio of maximum intracavernous pressure to mean arterial pressure and nitric oxide levels were significantly lower in the 4- and 8-week diabetic groups than in the normoglycemic group (P < .01). Penile endothelial cell pyroptosis (5.67 ± 0.81%), smooth muscle cell apoptosis (23.72 ± 0.48%), total cell pyroptosis (9.67 ± 0.73%), and total apoptosis (10.52 ± 1.45%) were significantly greater in the 4-week diabetic group than in the normoglycemic group (P < .01). The proportion of endothelial cell pyroptosis (24.4 ± 3.69%), endothelial cell apoptosis (22.13 ± 2.43%), total cell pyroptosis (14.75 ± 0.93%), and total apoptosis (14.82 ± 1.08%) in the penile tissues of the 8-week diabetic group were significantly greater than those in the normoglycemic group (P < .01).The 8-week survival proportions of diabetic endothelial cells (38.86 ± 8.85%) and smooth muscle cells (44.46 ± 2.94%) was significantly lower than the 4-week survival proportions of endothelial cells (93.17 ± 8.07%) and smooth muscle cells (75.12 ± 4.76%) (P < .05)., Clinical Translation: Inhibition of cell death by different methods at different stages may be the key to the treatment of type 1 diabetes-induced erectile dysfunction., Strengths and Limitations: The effect of type 1 diabetes on other types of cell death in penile cavernous tissue needs further study., Conclusion: The mode of death of endothelial cells in the cavernous tissue of the penis in the early stage in diabetic rats is dominated by pyroptosis, and the death of smooth muscle cells is dominated by apoptosis. Endothelial cell and smooth muscle cell death are not consistent at different stages of diabetes progression., (© 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.)

Priapism as a complication of scorpionism in children is rare and is categorized as grade II of severity. The pathogenesis is the activation of parasympathetic pathways that stimulate the release of acetylcholine. An 8-year-old boy, a known case of steroid-dependent nephrotic syndrome, presented with a history of persistent penile erection for the previous 12 hours. He had a history of a black scorpion (Heterometrus swammerdami) sting on his right leg 4 days earlier. He was given adequate analgesia, and prazosin was started at 30 µg/kg/dose because of the parasympathetic overactivity. Doppler ultrasonography of the penile shaft showed a bilateral thickened, bulky, and edematous corpus cavernosa and no arterial flow due to venous congestion, suggesting ischemic (low-flow) priapism. Detumescence was not accomplished with saline irrigation and aspiration or with intracorporeal irrigation with phenylephrine. Thus, a distal T-shunt was done. We illustrate an interesting case of scorpion envenomation with delayed ischemic priapism.

Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum., (© 2024. The Author(s).)

Aim: Increased corpus cavernosum smooth muscle cells (CCSMCs) apoptosis in the penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has been found to exert potential antiapoptotic properties. However, whether CSD peptide can alleviate CCSMCs apoptosis and ED in CNI rats remains unknown. The study aimed to determine whether CSD peptide can improve bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processes of CCSMCs., Main Methods: Fifteen 10-week-old male Sprague-Dawley (SD) rats were randomly classified into three groups: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function was assessed and the penis tissue was histologically examined. Furthermore, an in vitro model of CCSMCs apoptosis was established using transforming growth factor-beta 1 (TGF-β1) to investigate the mechanism of CSD peptide in treating BCNI-ED., Key Findings: In BCNI rats, CSD peptide significantly prevented ED and decreased oxidative stress, the Bax/Bcl-2 ratio, and the levels of caspase3. TGF-β1-treated CCSMCs exhibited severe oxidative stress, mitochondrial dysfunction, and apoptosis. However, CSD peptide partially reversed these alterations., Significance: Exogenous CSD peptide could improve BCNI-ED by inhibiting oxidative stress, the Bax/Bcl-2 ratio, and caspase3 expression in penile tissue. The underlying mechanism might involve the regulatory effects of CSD peptide on oxidative stress, mitochondrial dysfunction, and apoptosis of CCSMCs following CNI. This study highlights CSD peptide as an effective therapy for post-radical prostatectomy ED (pRP-ED)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide., Aim: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs)., Methods: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function., Outcomes: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function., Results: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function., Clinical Implications: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment., Strengths and Limitations: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines., Conclusion: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway., (© 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: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine., Case Presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution., Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization., (© 2024. The Author(s).)

Sclerosing oleogranuloma of the penis is a rare benign condition characterized by the formation of rough and dense infiltrates in the male genital area following injection of foreign materials under the skin for the purpose of augmentation. It predominantly affects males of reproductive age. Diagnosis is based on patients history, examination and histological findings. Treatment involves excision of the granuloma and affected tissues with surgical margins followed by reconstruction of the penis and scrotum. A clinical case of the treatment of giant oleogranuloma of the penis and scrotum in a 21-year-old man clinically manifested by painful multiple lesions under the skin with ulceration along the coronal sulcus, pain, deterioration of the quality of life and cosmetic issues is presented in the article. For surgical treatment, the one-stage Sapozhkov-Reich procedure was performed for the first time at the urology department of the Republican Hospital named after V.A. Baranov, Petrozavodsk. Keywords: sclerosing lipogranuloma of the penis, sclerosing lipogranuloma of the scrotum, penis augmentation, injections into the penis, vaselinome, one-stage Sapozhkov-Reich procedure Author contributions. Simanov R.N. - idea, concept and design of writing the article, literature review, collection and processing of information and materials, description of a clinical case, analysis of patient carts, surgical treatment, writing text and preparing illustrative materials for publication; 60% of the work. Malyshev E.V. - surgical treatment, collection and processing of information, description of a clinical case; 20% of the work. Smirnova D.V. - collection and processing of clinical data, assistance in writing an article, preparation of a description of histological examination and micropreparations, creation of microphotographs, preparation of illustrative materials for publication; 20% of the work.

Competing Interests: The authors have no conflicts of interest regarding this article, and have received no funding for this work.

Background: This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism., Methods: Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed., Results: In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively)., Conclusion: Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.

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.)

Case History: Medical records from a single referral hospital (Davies Veterinary Specialists, Hitchin, UK) were reviewed to identify dogs (n = 8) with preputial cutaneous mast cell tumours (CMCT) that underwent surgical excision and primary preputial reconstruction, preserving the penis and urethra, after clients declined alternatives such as penile amputation and urethrostomy, from June 2017-June 2022., Clinical Findings: Tumours had a median diameter of 21.5 (min 15, max 30) mm, were located cranioventrally (3/8), caudoventrally (1/8), laterally (2/8) and dorsally (2/8) relative to the prepuce and were diagnosed as CMCT based on cytology. No dogs had hepatic or splenic metastasis on cytology but inguinal lymph node metastasis was identified in 3/4 dogs sampled., Treatment and Outcome: The owners of all dogs had declined penile amputation and scrotal urethrostomy. The CMCT were excised and primary reconstruction of the prepuce performed. Surgical lateral margins of 10, 20 or 30 mm were used and the deep margin excised the inner preputial lamina or underlying muscular fascia. The deep margin for caudoventral CMCT involved excision of the underlying SC adipose tissue. Preputial advancement was performed in 3/8 dogs to achieve adequate penile coverage. Histopathology confirmed all CMCT were Kiupel low grade, Patnaik grade II with complete margins in 6/8 dogs but identified metastasis only in one inguinal lymph node from one dog. Two dogs encountered minor complications (infection and a minor dehiscence) and one dog had a major complication (infection with major dehiscence). Median follow-up duration was 125 weeks, excluding one dog with 4 weeks of follow-up. None of the dogs experienced local recurrence or died of mast cell disease during the available follow-up period., Clinical Relevance:  This clinical study evaluated a surgical alternative to penile amputation and advanced reconstructive techniques for Kuipel low/Patnaik grade II preputial CMCT when these procedures were declined by owners. Surgical excision of preputial CMCT with lateral margins of 10, 20 or 30 mm with primary preputial reconstruction is achievable with low morbidity and a good outcome when penile amputation and scrotal urethrostomy is not an option.

The formation of penile keloid after circumcision is an uncommon complication. Herein, we report two pediatric cases of large circumferential keloids that developed post-circumcision and were successfully treated by surgical excision and intralesional triamcinolone injections. In addition, we provide a comprehensive review of the reported cases of penile keloids that developed after circumcision in the literature to highlight the various presentations, treatment options, and outcomes for this condition., (© 2023 Wiley Periodicals LLC.)

Background: Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed as a malignant tumor. While fasciitis ossificans commonly originates from the subcutaneous tissue and can appear throughout the body, it may also arise from extraordinary sites., Case Presentation: We report the first-ever documented case of fasciitis ossificans arising from the penis in a male patient who presented with a tumor on the glans penis. The tumor was surgically resected due to suspicion of penile cancer. Initial histopathological analysis led to a misdiagnosis of squamous cell carcinoma. However, pathological consultation ultimately confirmed the diagnosis of fasciitis ossificans of the penis originating from the glans penis by demonstrating ossification., Conclusion: This case underscores the importance of considering fasciitis ossificans in the differential diagnosis of soft tissue tumors, even in unusual locations such as penile soft tissue., (© 2024. The Author(s).)

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Abstract: Epithelioid hemangioma (EH), also known as angiolymphoid hyperplasia with eosinophilia, is an unusual vascular proliferation that tends to manifest in the head and neck region. Its occurrence on the penis is rare, with only scarce reported cases in the literature. The histopathological examination of this condition poses a challenge because it shares similarities with other entities, such as epithelioid hemangioendothelioma, epithelioid angiosarcoma, cutaneous epithelioid angiomatous nodule, or Kaposi sarcoma (KS). The infrequency of EH in penile locations underscores the need for accurate diagnostic differentiation and tailored treatment strategies for this atypical presentation. This case report highlights a rare instance of multifocal penile EH. The patient's lesions exhibited distinctive histopathologic features, with extensive eosinophilic infiltration, presence of necrosis, and infiltration to subcutaneous fat. The patient was treated with doxorubicin, a chemotherapy drug, with a very good response. This successful therapeutic outcome underscores the potential efficacy of doxorubicin in the management of multifocal penile EH. The comprehensive analysis of this case contributes to our understanding of the clinical presentation, histopathologic features, and treatment modalities for this rare penile tumor, providing valuable insights for future clinical considerations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis' latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

Metastasis to the penis from renal cell carcinoma (RCC) or any other primary cancer site is unusual; when it does occur, it often involves multiple organs. A 75-year-old man presented with penile pain and swelling. Three months earlier, he had open radical nephrectomy with thrombectomy and was diagnosed with clear-cell RCC with tumor thrombosis in the inferior vena cava. The follow-up imaging indicated metastasis to the penis, prompting a total penectomy due to worsening pain. The excised mass displayed features consistent with metastatic RCC. This case underscores the need to consider rare metastatic sites, such as the metastasis of RCC to the penis, in RCC patients.

Background: Swelling of the perineal region in male dogs is most commonly caused by a perineal hernia. Clinical signs associated with perineal hernia are constipation, tenesmus or stranguria. This case report documents a rare cause of perineal swelling created by the growth of a malignant tumour leading to urethral obstruction and subsequent stranguria., Case Presentation: An 11-year-old neutered male German Shepherd was presented for swelling in the perineal region and stranguria for three days. Complete blood count and serum biochemistry were unremarkable. Ultrasound revealed a heterogeneous mass in the perineal region. Retrograde urethrography showed a severe narrowing of the urethra caudal to the pelvis. A fine-needle aspirate of the mass was highly suspicious for liposarcoma. Staging was performed by computed tomography (CT) of the thorax and abdomen. Total penile amputation in combination with pubic-ischial pelvic osteotomy, transposition of the remaining urethra through the inguinal canal, V-Y-plasty cranial to the prepuce and preputial urethrostomy were performed to remove the tumour. Histopathology confirmed a well-differentiated liposarcoma with complete histological margins. Six months after the surgery the dog was doing well and there were no signs indicating local tumour recurrence., Conclusions: Wide surgical excision is generally recommended for soft tissue sarcomas, however this is sometimes not feasible for large tumours. In the case reported here, tumour resection was achieved by a combination of several surgical techniques with a good clinical outcome., (© 2024. The Author(s).)

Keloid is the maximum expression of pathological fibroproliferative skin wound healing, whose pathophysiology is not yet fully understood. Its occurrence in the perineum and genitalia is uncommon. A systematic review was carried out regarding the occurrence and treatment of keloids on the penis. An illustrative case was also reported. The review used the PRISMA checklist and was registered in PROSPERO. The entire literature period up to April 2023 was searched in the EMBASE/Elsevier, Cochrane, Scopus, Medline, BVS, SciELO, and Lilacs databases. The inclusion criteria embraced primary studies, clinical trials, prospective or retrospective cohorts, case series, case-control studies and case reports. Three hundred and sixty-one studies were found and 12 of them were included, consisting of 9 case reports and 3 case series. The most common triggering factor for keloid formation was circumcision, in 11 of the cases, of which more than half occurred in prepubescent children. Several therapies, associated or isolated, were used to treat the cases. Only one of the reported patients had scar recurrence after surgical treatment. Studies with better scientific evidence are needed to understand the involvement of keloids in male genitalia. However, keloid formation in this topography is rare, making it difficult to carry out more elaborate studies., (© 2024 The Wound Healing Society.)

Purpose: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls., Methods: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM)., Results: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%., Conclusion: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages., (© 2023 The Japanese Urological Association.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was firstly identified in China and has been declared a global pandemic. Several serious extrapulmonary manifestations due to SARS-CoV-2 infection have also been reported and associated with hypercoagulability thrombotic vasculopathy. In addition, cases of Mycobacterium-leprae infection have also been known associated with blood coagulation abnormality., Methods: Here, we report a 56-year-old male with coronavirus disease-19 (COVID-19) with concomitant leprosy infection with manifestation of glans penile necrosis, presented to the emergency department with acute penile pain. This case is unique because no occlusion blood flow to the penile was observed in the radiographic imaging. We described the potential pathophysiology in this case through a literature review., Results: The patient received treatment according to the COVID-19 protocol and was given low molecular weight heparin (LMWH) therapy for 4 days. During the follow up, the clinical and functional condition of the penis showed significant improvement., Conclusions: Microthrombus involvement, platelet abnormalities and impaired hemostasis due to SARS-CoV-2 and leprosy co-infection are the hypothesis in this case report., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Ismy J et al.)

Computed tomography (CT) may show a variety of scrotal and penile pathologic finding, but is usually not used as a first-line imaging due to its limited soft tissue contrast. Nonetheless, there are three main scenarios for imaging of the scrotum and penis with CT. Pathologies may be found incidentally in patients undergoing abdominal and pelvic CT scanning for different reasons. In emergency settings, CT is frequently performed, and the recognition of scrotal and penile pathologies by the reporting radiologist is crucial to ensure optimal patient treatment and outcome. If MRI scanning cannot be performed due to contraindications or is unavailable in resource, limited CT may be used for the further characterization of scrotal and penile pathology found on ultrasound. This pictorial review wants to familiarize general and emergency radiologists with the anatomy and possible pathological findings of the scrotum and penis on CT., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Objective: Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours., Methods: Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information., Results: Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis., Conclusions: Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO 2 -OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO 2 -OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO 2 -OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO 2 -OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO 2 -OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Abstract: A 71-year-old man, presenting with complaints of burning sensation and pain during urination, finally diagnosed with prostate carcinoma. Ultrasonography of the abdomen and pelvis revealed prostatomegaly. Serum PSA level was elevated, and TRUS-guided biopsy demonstrated acinar adenocarcinoma (Gleason score: 5 + 4 = 9). 68 Ga-PSMA-11 PET/CT for initial staging showed PSMA-avid enlarged prostate, pelvic lymphadenopathy, and focal PSMA uptake in the left side of the shaft of the penis. The patient also underwent a 64 CuCl 2 PET/CT, which demonstrated similar findings of enlarged prostate and adenopathy with focally increased tracer uptake in the shaft of the penis coinciding with the lesion observed on 68 Ga-PSMA-11 PET/CT, thereby detecting a rare metastatic site from carcinoma prostate., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest All authors must disclose any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.

Background: Penile cancer is rising in most European countries. Several risk factors have been identified, namely human papillomavirus (HPV) infection. However, the exact role of HPV in penile cancer carcinogenesis is still unknown. Clarifying the contribution of HPV in penile cancer is crucial as it may improve prevention and treatment strategies., Objective: To describe the characteristics of patients with penile cancer and penile intraepithelial neoplasia (PeIN), evaluate the prevalence of HPV-DNA in tumour tissue and identify differences between patients with and without HPV-DNA., Methods: A retrospective observational study including patients with histological diagnosis of penile squamous cell carcinoma (SCC) or PeIN between 2012 and 2021 in a university hospital was carried out. HPV analysis was performed using Anyplex™ II HPV28 Detection that detects and identifies 28 HPV types. (sensitivity of 95.9%)., Results: A total of 25 patients were included. Most of the tumours identified were invasive SCC (n = 11) and SCC in situ (PeIN 3) (n = 8). PeIN1/2 was found in the remaining six patients. HPV-DNA was tested in all tissue specimens and was detected in 18 of them. High risk HPV DNA was identified in all positive HPV samples, except one. HPV types included in the nonavalent HPV vaccine were identified in 16 of the 18 samples positive for HPV-DNA. Stratifying patients according to HPV-DNA detection, we found that patients with HPV-DNA were younger (57.5 years vs. 70 years, p = 0.047), less likely to have phimosis (5.8% vs. 42.9%, p = 0.022) and more likely to have PeIN lesions than invasive SCC (85.7% vs. 27.8%, p = 0.025)., Conclusion: This study shows a prevalence of HPV-DNA in penile SCC and premalignant lesions of 45.5% and 92.9%, respectively. Identifying HPV involvement in SCC and PeIN pathology has the potential to guide treatment and enhance follow-up strategies., (© 2023 European Academy of Dermatology and Venereology.)

Purpose: To review the evidence for radiotherapy in the management of primary penile cancer, either as brachytherapy or external beam radiation, and the role of external beam radiotherapy in node positive penile cancer., Methods: English language literature was reviewed for the past 3 decades. As penile cancer is uncommon in developed nations, high quality evidence to guide management is limited. Single institution reports often span decades during which time staging systems and treatments have evolved, reducing their relevance to current practice. Successful clinical trials require collaboration not only among disciplines but also among multiple institutions and nations., Results: Radiotherapy is a definitive organ-preserving option for T1-T2 penile cancers. Interstitial brachytherapy is associated with penile preservation in 85% of men at 5 years, maintained in 70% by 10 years. Results of external radiotherapy are not quite as promising but nonetheless 60% of men will have an intact penis at 5 years. Inguino-pelvic external radiotherapy has been reported to increase overall survival when delivered as adjuvant treatment for men with pN3 groin but pN0 pelvic nodes, and improve disease specific survival for those with involved pelvic nodes. InPACT (ECOG-ACRIN&#95;8134) is investigating the role of inguino-pelvic chemo-radiotherapy for men with pN3 inguinal nodes but imaging negative pelvic nodes., Conclusions: Radiotherapy has a well-defined role to play in treatment of squamous cell cancers of other sites, such as vulva, anal canal, uterine cervix and head and neck malignancies. Emerging data support the incorporation of radiotherapy into treatment paradigms for penile cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing ( P <0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P <0.001), p53 overexpression (26/42; P <0.001), and hotspot mutations in TP53 (32/42; P <0.001), CDKN2A (26/42; P <0.001) or both (21/42; P =0.003) in the adjacent SCC. Cytoplasmic p16 ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P <0.001) occurred adjacent to verrucous or papillary SCC (17/21; P <0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P <0.004). Undifferentiated p16 ink4a -negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS ., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)