Keloids in male genitalia-Systematic review and illustrative case report.

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.

[Skin manifestations of the external male genitals]. / Hauterscheinungen des männlichen Genitals.

The urological examination includes the inspection of the external male genitals. Harmless normal variants, such as heterotopic sebaceous glands and pearly penile papules must be differentiated from malignant and infectious manifestations. Lichen sclerosus et atrophicus is a frequent connective tissue disease that can lead to functional impairments and an associated high level of suffering for those affected. Both conservative and invasive treatment options are available. Sexually transmitted diseases, such as syphilis, are gaining increasing importance in routine clinical and daily practice due to the increasing incidence in recent years. An early diagnosis and treatment of malignant neoplasms, such as Queyrat's erythroplasia can be carried out by routine inspection of the genital skin.

Spermatozoa-induced seminal vesiculitis in mice.

BACKGROUND: Seminal vesiculitis is a common inflammation in the male genital tract. Etiologically, microbial infection and non-infectious factors can be responsible for seminal vesiculitis. The pathogenic triggers and mechanisms underlying non-infectious seminal vesiculitis remain unclear. OBJECTIVES: To demonstrate that spermatozoa can induce seminal vesiculitis in mice, which could be attributable to spermatozoa-induced innate immune responses in seminal vesicular epithelial cells. MATERIAL AND METHODS: Spermatozoa from epididymis were injected into seminal vesicles at the tail of the gland. Histopathology of seminal vesicles were examined by hematoxylin-eosin staining. Infiltration of leukocytes were identified by immunohistochemistry. Seminal vesicular epithelial cells were isolated from 5-week-old mice and cell types were detected by immunofluoresence. Western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect protein and gene expression levels. RESULTS: In vivo, local injection of epididymal spermatozoa into seminal vesicles resulted in seminal vesiculitis characterized by tissue swelling and leukocyte infiltration. In vitro, spermatozoa induced the expression of pro-inflammatory cytokines and chemokines, including TNF-α, IL-6, CXCL10, and MCP1, and the activation of NF-κB in seminal vesicular epithelial cells. DISCUSSION AND CONCLUSION: Spermatozoa may induce seminal vesiculitis through the activation of innate immune responses in seminal vesicular epithelial cells, which provide novel insights into the mechanisms underlying non-infectious seminal vesiculitis.

The 2022 revision of the World Health Organization classification of tumors of the urinary system and male genital organs: advances and challenges.

The fifth edition of the World Health Organization (WHO) classification of urinary and male genital organ tumors has been recently published in 2022. The application of molecular profiling has made a substantial impact on the classification of urologic tumors. The new WHO classification introduces a group of molecularly well-defined renal tumor subtypes. The significant changes include addition of a category of "other oncocytic tumors" with oncocytoma/chromophobe renal cell carcinoma (chRCC)-like features, elimination of the subcategorization of type 1/2 papillary RCC, and inclusion of eosinophilic solid and cystic RCC as an independent tumor entity. The WHO/ISUP grading now has been recommended for all RCCs. Major nomenclature changes include replacement of histologic "variants" by "subtypes," "clear cell papillary renal cell carcinoma" to "clear cell renal cell tumor," "TCEB1-mutated RCC" to "ELOC-mutated RCC," "hereditary leiomyomatosis and renal cell carcinoma" to "fumarate hydratase-deficient RCC," "RCC-Unclassified" to "RCC-NOS," "primitive neuroectodermal tumor" to "embryonic neuroectodermal tumor," "testicular carcinoid" to "testicular neuroendocrine tumor," and "basal cell carcinoma of the prostate" to "adenoid-cystic (basal-cell) carcinoma of the prostate." Metastatic, hematolymphoid, mesenchymal, melanocytic, soft tissue, and neuroendocrine tumors are collectively discussed in separate chapters. It has been suggested that the morphological classification of urothelial cancer be replaced with a new molecular taxonomic classification system.

The potential for nanomaterial toxicity affecting the male reproductive system.

With the development of nanotechnology, nanomaterials offer great advantages in a wide variety of industrial and consumer products, and show promise for biomedical applications. However, with these new products, nanomaterial pollutants may enter the human body to cause adverse health effects, including hazards to the male reproductive system. Nanomaterials can enter the body through inhalation, oral exposure, or intravenous injection, and reach the testis via the blood, penetrate the Sertoli cell barrier, and directly or indirectly elicit toxicopathological changes to the testicles. These may then trigger hormone disorders, inhibit spermatogenic cell proliferation, and induce apoptosis, ultimately leading to a decrease in sperm motility and number, ultimately diminishing male reproductive capacity. This review will discuss the toxicological effects of nanomaterials on the male reproductive system, including inflammation, the impact on the hypothalamic-pituitary-gonadal axis (HPG axis), lipid peroxidation, and free ion release relevant to germ cells, Sertoli cell tight junctions, and the gonadal endocrine system. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".

Successful use of dupilumab for the treatment of atopic dermatitis on the genitals, a neglected anatomical site.

Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.

Male genital lichen planus: A retrospective study of 89 cases.

BACKGROUND: Unlike other types of lichen planus (LP), there are no series concerning male genital LP. OBJECTIVE: To describe the clinical characteristics, diagnosis, and response to treatment of male genital LP. PATIENTS AND METHODS: A retrospective study of male patients with genital LP consulting a dermatologist specialized in anogenital diseases between January 2010 and 2019. Demographic data, history, functional signs, clinical characteristics, pathology, complications, and treatment efficacy were collected. RESULTS: Eighty-nine patients were included at four centers. The median age was 51 years. Most patients were uncircumcised and asymptomatic. In 88.8% of cases, only the genital mucosa was involved. Erythema (71%), papules (21.3%), lacy network (15.7%), atrophic lesions (15.7%), erosions (14.6%), and post-inflammatory hyperpigmentation (2.2%) were less frequently observed. Biopsy results confirmed LP in 61.3% of cases but could not rule out other inflammatory genital dermatoses in other cases. Anatomic complications were observed in 30.3% of patients. Topical corticosteroids (TCS) induced remission in most cases. Tacrolimus efficacy was comparable to that of TCS. CONCLUSION: Male genital LP is a rare inflammatory disorder chiefly affecting uncircumcised men. It is found predominantly on the mucosal component of the penis and presents as non-erosive inflammatory balanitis in most cases, with frequent partial or complete remission on treatment with TCS.

Drosophila Accessory Gland: A Complementary In Vivo Model to Bring New Insight to Prostate Cancer.

Prostate cancer is the most common cancer in aging men. Despite recent progress, there are still few effective treatments to cure its aggressive and metastatic stages. A better understanding of the molecular mechanisms driving disease initiation and progression appears essential to support the development of more efficient therapies and improve patient care. To do so, multiple research models, such as cell culture and mouse models, have been developed over the years and have improved our comprehension of the biology of the disease. Recently, a new model has been added with the use of the Drosophila accessory gland. With a high level of conservation of major signaling pathways implicated in human disease, this functional equivalent of the prostate represents a powerful, inexpensive, and rapid in vivo model to study epithelial carcinogenesis. The purpose of this review is to quickly overview the existing prostate cancer models, including their strengths and limitations. In particular, we discuss how the Drosophila accessory gland can be integrated as a convenient complementary model by bringing new understanding in the mechanisms driving prostate epithelial tumorigenesis, from initiation to metastatic formation.

Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism.

OBJECTIVES: Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism. METHODS: A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used. RESULTS: AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT. CONCLUSIONS: No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation.

COVID-19 and male reproductive system: pathogenic features and possible mechanisms.

Multiorgan dysfunction is the main characteristic of severe COVID-19 patients and the involvement of male reproductive system may occur among these patients. Although there is a limited evidence to confirm the orchitis and virus presence in the semen of patients, there are concerns about the transmission of virus through the semen. In addition, reduced fertility or infertility can be seen as consequences of severe COVID-19 in recovered subjects. In this study, we aimed to review articles related to COVID-19 and male reproductive system to find the possible underlying mechanisms of SARS-CoV-2 in affecting male fertility. The following keywords of SARS-CoV-2, COVID-19, testis, orchitis, semen, angiotensin-converting enzyme 2 (ACE2), hypothalamic-pituitary-testicular (HPT) axis, Hypothalamus, etc., were defined to find the related publications from standard search engines, e.g., PUBMED, SCOPUS, Google Scholar. According to studies, COVID-19 occurs in severe patients as respiratory disease, along with multi-organ failure. The most important mechanisms are classified as direct and indirect pathogenesis of SARS-CoV-2. The presence of ACE2 on the cell surface of various cells in testis increases the risk of direct infection by this virus. SARS-CoV-2 also affects the testis through the cytokine storm. In addition, the important role of HPT axis dysregulation through impaired Leydig cells and hypothalamus should be considered. Using antiviral and immunomodulatory therapy can be harmful for testis function. Further investigations are required to investigate potential mechanisms of male infertility in survivals of COVID-19. Since involvement of testis is essential for fertility, increasing the knowledge of health system may improve the outcomes.

Pyrethroids Toxicity to Male Reproductive System and Offspring as a Function of Oxidative Stress Induction: Rodent Studies.

Pyrethroids may be related to male reproductive system damage. However, the results of many previous studies are contradictory and uncertain. Therefore, a systematic review and a meta-analysis were performed to assess the relationship between pyrethroid exposure and male reproductive system damage. A total of 72 articles were identified, among which 57 were selected for meta-analysis, and 15 were selected for qualitative analysis. Pyrethroid exposure affected sperm count (SMD= -2.0424; 95% CI, -2.4699 to -1.6149), sperm motility (SMD=-3.606; 95% CI, -4.5172 to -2.6948), sperm morphology (SMD=2.686; 95% CI, 1.9744 to 3.3976), testis weight (SMD=-1.1591; 95% CI, -1.6145 to -0.7038), epididymal weight (SMD=-1.1576; 95% CI, -1.7455 to -0.5697), and serum testosterone level (SMD=-1.9194; 95% CI, -2.4589 to -1.3798) in the studies of rats. We found that gestational and lactational exposure to pyrethroids can reduce sperm count (SMD=1.8469; 95% CI, -2.9010 to -0.7927), sperm motility (SMD=-2.7151; 95% CI, -3.9574 to -1.4728), testis weight (SMD=-1.4361; 95% CI, -1.8873 to -0.9848), and epididymal weight (SMD=-0.6639; 95% CI, -0.9544 to -0.3733) of F1 offspring. Exposure to pyrethroids can increase malondialdehyde (SMD=3.3451; 95% CI 1.9914 to 4.6988) oxide in testes and can reduce the activities of glutathione (SMD=-2.075; 95% CI -3.0651 to -1.0848), superoxide dismutase (SMD=-2.4856; 95% CI -3.9612 to -1.0100), and catalase (SMD=-2.7564; 95% CI -3.9788 to -1.5340). Pyrethroid exposure and oxidative stress could damage male sperm quality. Gestational and lactational pyrethroid exposure affects the reproductive system of F1 offspring.

Effect of COVID-19 on Male Reproductive System - A Systematic Review.

Background: Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men. Objective: To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system. Methods: We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included. Results: We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA. Conclusion: The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.

A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly.

Tel Hashomer camptodactyly syndrome is a long-known entity characterized by camptodactyly with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases. Currently, the genetic basis for this disorder is unknown, thus there is a possibility that this clinical presentation may be contained within another genetic diagnosis. Here, we present a multiplex family with a previous clinical diagnosis of Tel Hashomer camptodactyly syndrome. Whole exome sequencing and pedigree-based analysis revealed a novel hemizygous truncating variant c.269_270dup (p.Phe91Alafs*34) in the FGD1 gene (NM_004463.3) in all three symptomatic patients, congruous with a diagnosis of Aarskog-Scott syndrome. Our report adds to the limited data on Aarskog-Scott syndrome, and emphasizes the importance of unbiased comprehensive molecular testing toward establishing a diagnosis for genetic syndromes with unknown genetic basis.

The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility.

PURPOSE: The present study aims to summarize the current understanding of probable mechanisms and claims of adverse effects of SARS-CoV-2 on male fertility potential. METHODS: Our search was including original articles, reviews, guidelines, letters to the editor, comments on guidelines, and editorials, regarding the male reproductive system. We used the words SARS-CoV-2, coronavirus, severe acute respiratory syndrome coronavirus 2, "2019 ncov," testis, sperm, male factor infertility, fertility treatment, semen, assisted reproductive technology (ART), sexual transmission, and ACE2. RESULTS: Data showed coronavirus affects men more than women because of more expression of 2019 nCoV receptors (ACE2 and TMPRSS2) in testicular cells. Also, "Bioinformatics Analysis" suggests that sperm production may be damaged, since "Pseudo Time Analysis" has shown disruption in spermatogenesis. "Gene Ontology" (GO) showed an increase in viral reproduction and a decrease in sperm production-related terms. Recently, SARS-COV-2 mRNA and protein were detected in the semen of patients that had recovered from SARS-CoV-2 infection. Therefore, the probable disruption of blood-testis barrier (BTB) in febrile diseases is suspected in the acute phase of the disease enabling viral entry into the testes. Not only is spermatogenesis disturbed, but also disturbs gonadotropin, androgens, and testosterone secretion during SARS-CoV-2 infection. No sexual transmission has been reported yet; however, detection of the virus in semen still makes the sexual transmission an open question. CONCLUSION: There is a concern that male fertility may be disturbed after the SARS-CoV-2 infection. Therefore, follow-up of the reproductive functions and male fertility may be necessary in recovered cases, especially in aged men.

Delayed genital necrosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C.

INTRODUCTION: Genital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history. METHODS: We identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases. RESULTS: Of 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49-64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60-108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 ∗109/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8-180). CONCLUSION: GN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.

Ultrasound aspects of symptomatic versus asymptomatic forms of male accessory gland inflammation.

BACKGROUND: The ultrasound (US) evaluation of the male sex accessory gland inflammation (MAGI) helps the clinicians to understand the severity of this condition, allowing them to distinguish the uncomplicated form (prostatitis) from the complicated ones (prostate-vesiculitis and prostate-vesiculitis-epididymitis), as well as the unilateral from the bilateral forms, the fibrosclerotic and the hypertrophic-congestive form. OBJECTIVE: This retrospective study aimed to evaluate the US features of MAGI patients with active symptoms compared to patients without sexual, voiding, and ejaculatory dysfunction. MATERIALS/METHODS: To achieve this aim, an analysis of the prevalence of MAGI US criteria was carried out on a very large series of over 500 patients diagnosed with MAGI classified according to the different symptom profile evaluated through a dedicated questionnaire (previously conceived and published by our group) arbitrarily named "structured interview about MAGI" (SI-MAGI) for sexual, voiding, and ejaculatory disorders reported by these patients. RESULTS: The results of this study revealed that US criteria most frequently detected in patients with severe urinary symptoms were the presence of areas of high echogenicity (almost exclusively in the periurethral prostatic zone) together with the presence of single or multiple areas of acinar ectasia of the prostate. The presence of seminal vesicles with polycyclic areas within the glandular lumen separated by hyperechoic septa represented US criterion most frequently detected in patients with severe spontaneous or post-ejaculate pain. Finally, US criterion most frequently detected in patients with severe sexual dysfunction was the dilation of the periprostatic venous plexus, suggesting the hypothesis of a possible alternative therapeutic approach. CONCLUSION: The data of the present study suggest that symptoms may associate with US signs in patients with MAGI. Also, specific US signs may associate with specific symptoms. Further studies are needed to understand whether patients with specific US signs may in turn benefit from a personalized therapeutic choice.

SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre-existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID-19.