Why human prepuce is a valuable resource in science? Histological, ultrastructural, immunohistochemical and statistical analysis / ¿Por qué el prepucio humano es un recurso valioso en la ciencia? Análisis histológicos, ultraestructurales, inmunohistoquímicos y estadísticos

SUMMARY: This research was to examine the histological and ultrastructural characteristics of prepuce samples, as well as vimentin and S100 protein localization and statistical analysis. Urologists have long struggled with the prepuce, which is used to treat a variety of urethral problems. Skin biopsies were collected from the prepuce at the moment of circumcision and processed for light microscopy, electron microscope examination, immunohistochemical techniques, and statistical analysis in a total of six boys. Histologically, the prepuce epidermis displayed focal spiky ridges, which are saw-toothed interspersed with sulci, slight hyperpigmentation, looser connective tissue and plentiful vascular components. Immunohistochemically, the existence of melanocytes and Langerhans cells in the epidermis, as well as smooth muscles in the dermis, was stained positively for vimentin. Also, there was a positive reactivity of the Langerhans cells in the epidermis and around Meissner's corpuscles in the dermis for S100 protein staining. Ultrastructurally, the prepuce's intercellular gaps were widened, melanocytes rested on a folded basement membrane, and desmosomal content was reduced, with a prominent active euchromatic nucleus. Cytoplasmic projections were distended and elongated, and the interstitial blood vessels were surrounded by endothelial cells and rested on a basement membrane. There were also minimal collagen fibers in the interstitium. The prepuce's histological and ultrastructural features, as well as immunohistological studies using vimentin and S100 protein as intermediate filaments and statistical analysis, all demonstrated that it is a useful scientific resource.

RESUMEN: El presente trabajo de investigación se realizó para examinar las características histológicas y ultraestructurales de las muestras de prepucio, así como la localización y el análisis estadístico de la vimentina y la proteína S100. Los urólogos han intentado trabajar durante mucho tiempo con el prepucio, que se usa para tratar una variedad de problemas uretrales. Se recolectaron biopsias de piel del prepucio de seis niños en el momento de la circuncisión y se procesaron para microscopía óptica, examen con microscopio electrónico, técnicas inmunohistoquímicas y análisis estadístico. Histológicamente, la epidermis del prepucio mostraba crestas puntiagudas focales, intercaladas con surcos, hiperpigmentación leve, tejido conectivo más laxo y abundantes componentes vasculares. Inmunohistoquímicamente, la existencia de melanocitos y células dendríticas epidérmicas (células de Langerhans), así como músculo liso en la dermis, se tiñeron positivamente para vimentina. Además, hubo una reactividad positiva de las células dendríticas epidérmicas en la epidermis y alrededor de los corpúsculos del tacto (de Meissner) en la dermis para la tinción de la proteína S100. Ultraestructuralmente, los espacios intercelulares del prepucio se ensancharon, los melanocitos descansaban sobre una membrana basal plegada y el contenido desmosómico se redujo, con un núcleo eucromático activo prominente. Las proyecciones citoplasmáticas estaban distendidas y alargadas, y los vasos sanguíneos intersticiales estaban rodeados por células endoteliales y descansaban sobre una membrana basal. También había fibras de colágeno mínimas en el intersticio. Las características histológicas y ultraestructurales del prepucio, así como los estudios inmunohistológicos utilizando vimentina y proteína S100 como filamentos intermedios y el análisis estadístico, demostraron que es un recurso científico útil.

Anatomy of the cutaneous surface of the male genitalia, with elaboration upon the inner preputial coronal-shaft junction.

INTRODUCTION: Descriptions of the penile prepuce in anatomical and clinical texts either omit details or contain a small, yet potentially serious, error with regard to the manner of its attachment to the penis. OBJECTIVE: This study sought to cast light on a ubiquitous but poorly understood and under-appreciated structure, while correcting a long-standing mistake in the medical literature. STUDY DESIGN: The foreskins of five male stillborn babies were dissected and carefully examined. Tissue from the apposing surfaces of the various regions of the inner and outer prepuce surfaces and the transition zone itself were collected, embedded in paraffin, sectioned, stained, examined and photographed under microscopy. RESULTS: Contradicting the prevailing descriptions in the literature that the inner prepuce is a single, uniform sheath, this study's observations and histological findings demonstrated that it actually splits into separate laminae that connect distally to the shaft at the base of the corona and proximally with the shaft fascia, respectively (Figure). DISCUSSION: The penile prepuce is a discrete and deceptively complex part of the male anatomy, yet key details of its interposing surfaces are inaccurately described or entirely omitted in the literature. Understanding the normal anatomy of the prepuce is critically relevant, particularly for urologists and others involved in the performance of circumcision. For example, avoiding potentially catastrophic avulsion of the inner preputial remnant beyond the coronal sulcus during circumcision and accurate assessment of tissue positioning prior to penile reconstruction in cases of hypospadias. CONCLUSION: The findings of this study correct a misunderstanding in the anatomy of the prepuce.

Terminal innervation of the male genitalia, cutaneous sensory receptors of the male foreskin.

PURPOSE: Understanding the types of sensory nerve termini within the glabrous skin of the human male foreskin could throw light on surgical outcomes and therapeutic possibilities for the future. Various receptor types sense changes in temperature, position, pressure, pain, light touch, itch, burning and pleasurable sexual sensations. Similarities and differences in innervation characteristics and density might become apparent when the glans penis is compared with homologous structures in the female genitalia. The aim of this study is to document the presence and characteristics of cutaneous sensory receptors in the human penile foreskin using a histopathological study of the nerve termini to achieve a more complete understanding of sensory experiences. METHODS: Foreskin samples were obtained from ten boys (aged 1-9 years) who had undergone circumcision. Informed consent was obtained from the parent/legal guardian. The samples were examined after modified Bielschowsky silver impregnation of neural tissue, and immunocytochemistry against gene protein product (PGP) 9.5 and neuron-specific enolase (NSE). RESULTS: PGP 9.5 appeared to be the most sensitive neural marker. Free nerve endings were identified in the papillary dermis visualized as thin fibers, mostly varicose, with either branched or single processes, either straight or bent. Two types of sensory corpuscle were identified: capsulated and non-capsulated. Meissner-like corpuscles were located in the papillary dermis. Capsulated corpuscles resembled typical Pacinian corpuscles, comprising a single central axon surrounded by non-neural periaxonic cells and lamellae. The capsulated corpuscles were strongly positive for PGP 9.5 and NSE. CONCLUSIONS: Free nerve endings, Meissner's corpuscles and Pacinian corpuscles are present in the human male foreskin and exhibit characteristic staining patterns.

Redundant prepuce increases the odds of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Some published evidence has revealed that the dendritic cells can interact with pathogens that exist in the inner foreskin. This information provides a new vision that pathogens could play a role through the redundant prepuce; numerous studies have failed to find pathogens in prostates of patients who had chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have reported an association between foreskin length and CP/CPPS. Hence, we conducted a retrospective case-control study of clinical data from 322 CP/CPPS patients (case group) and 341 nonCP/CPPS patients (control group). Demographic characteristics, lifestyle factors, and foreskin lengths were collected and analyzed. Multivariate logistic regression was adopted to calculate the odds of foreskin length for CP/CPPS. According to the multivariate logistic regression results, when the foreskin length covered up more than half of the glans penis, the odds for CP/CPPS were higher with an increased foreskin (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.04-2.66). In comparison, when the glans penis was completely covered by the foreskin, the OR value increased to 1.86 (95% CI, 1.2-2.88). The study results showed an association between foreskin length and the odds of CP/CPPS. When the foreskin length covered up more than half of the glans penis, there were greater odds for CP/CPPS. This possible mechanism might result from interaction between pathogens and DCs in the inner foreskin, consequently activating T-cells to mediate allergic inflammation in the prostate and producing the autoimmunizations causing CP/CPPS.

Canine perineal hypospadias / Hipospadia perineal canina

Canine hypospadias is a rare condition that can occur in male and female dogs. Affected animals may present signs of urinary incontinence, recurrent urinary tract infections, periurethral dermatitis or can remain asymptomatic. Periurethral hypospadias in a 14-week-old mongrel dog and its surgical repair are addressed.

Hipospadia canina é uma condição rara que pode ocorrer em cães machos e fêmeas. Animais afetados podem apresentar sinais de incontinência urinária, infecções recorrentes do trato urinário, dermatite periuretral ou podem permanecer assintomáticos. Hipospadia periuretral em cão de 14 semanas de idade, sem raça definida, e sua reparação cirúrgica são abordadas.

Cutaneous corpuscular receptors of the human glans clitoris: descriptive characteristics and comparison with the glans penis.

INTRODUCTION: The female genital sensory pathways that initiate sexual arousal reflexes begin with cutaneous corpuscular receptors in the glabrous genital skin, including those of the glans clitoris. AIM: The aim of this study is to characterize the corpuscular receptors of the glans clitoris. In addition, we compared basic features with the receptors of the glans penis. MAIN OUTCOME MEASURE: Number of stained receptors. METHODS: Five cadaveric vulvectomy specimens and four cadaveric penile specimens were used. They were serially sectioned and stained with hematoxylin and eosin. Selected blocks were stained with Masson's trichrome, and immunohistochemical staining was done with neuronal markers S-100 and neurofilament. RESULTS: Using the three stains, we identified an abundance of corpuscular receptors within the glans clitoris, as compared with the surrounding prepuce. These receptors were of varied arrangements, situated in the subepithelial tissues of the glans clitoris. They were indistinguishable from the receptors of the glans penis. The number of receptors per 100× high-powered field ranged from 1 to 14, whereas the receptor density in the glans penis ranged from 1 to 3. A second type of receptor, the Pacinian corpuscle, was identified within the suspensory ligament along the trunks of the dorsal nerve but not within the glans itself. CONCLUSIONS: The glans clitoris is densely innervated with cutaneous corpuscular receptors, and these receptors are morphologically similar to the corpuscular receptors of the glans penis. The glans clitoris has greater variability in receptor density compared with the glans penis.

Inter-rater reliability of self-reported response on foreskin status in questionnaire among Japanese adult men.

OBJECTIVES: To determine whether foreskin status is a measurable marker for evaluating the effect of the foreskin on sexually transmitted infections. METHODS: Inter-rater comparison of the responses on foreskin status and circumcision in a self-report questionnaire with the findings of a physical examination by an experienced well-trained urologist was performed for patients who visited a healthcare facility in Kanagawa, Japan. Foreskin status was defined using a five-point graphical scale based on the degree to which the foreskin covers the foreskin and the glans penis in a non-erectile condition: type 1, a fully exposed glans penis; types 2-4, the glans penis partly covered by the foreskin and type 5, phimosis. Linear weighted κ and per cent agreement were used to evaluate the reliability of responses. RESULTS: Among 188 participants who were evaluated about their foreskin status, linear weighted κ and per cent agreement were 0.74% and 68.4%, respectively. Linear weighted κ improved from 0.74 to 0.80 when the number of categories was changed to three. All the self-reported responses on circumcision were in agreement with the findings of the physical examination. Seventeen participants (9.0%) had been circumcised, and among them, three (17.6%) had approximately one-half of their glans penis covered by the foreskin. In 90 among the 171 uncircumcised participants (52.6%), the foreskin did not cover the glans penis. CONCLUSIONS: The self-reported response on foreskin status in this questionnaire has sufficient reliability to replace physical examination, and this questionnaire can facilitate further studies about the effect of foreskin on sexually transmitted infections.

How willing are men who have sex with men in China to be circumcised for the sake of protecting his female sex partner?

INTRODUCTION: The HIV prevalence among men who have sex with men (MSM) is increasing sharply in China. Many MSM have female sexual partners, representing a bridge of transmitting HIV to the general population. Circumcision reduces the risk of HIV prevention via heterosexual intercourse. AIM: The study investigated the prevalence and factors related to willingness to undergo circumcision when MSM were informed that circumcision could reduce risk of heterosexual HIV transmission. METHODS: An anonymous cross-sectional survey was conducted in Jiangsu, China. A total of 157 MSM with bisexual behaviors in the last six months were recruited using snowball sampling. MAIN OUTCOME MEASURES: Self-reported circumcision status and foreskin conditions were recorded. HIV-related knowledge, risk perceptions, risky sexual behaviors, cognitive and behavioral intention factors regarding circumcision were assessed. RESULTS: Among all respondents, 5.7% were circumcised. In the uncircumcised subsample, the willingness to be circumcised increased from 8.1% to 35.1% after they were informed about the 50% risk reduction effect of circumcision regarding heterosexual HIV transmission. Risk behaviors, uncertainty about the prevalence of HIV among MSM, perception of overly long foreskin, peer's suggestion, disagreement with the statements "MSM in general are not willing to be circumcised" and "circumcisions are for children, not for adults" and self-efficacy for circumcision were significantly associated with willingness for circumcision given the hypothetical risk reduction effect (OR = 2.37 and 3.11, respectively, P < 0.05). Perception of overly long foreskin, self-efficacy, and having used a condom in the last episode of sex with a woman remained significantly associated with the conditional willingness for circumcision in the multivariate analysis (OR = 3.03, 2.84 and 2.42, respectively, P < 0.05). CONCLUSIONS: Interventions promoting circumcision among bisexual MSM, based on the risk reduction effect on heterosexual HIV transmission, are likely to be successful. Such programs should focus on increasing self-efficacy and may consider utilizing a peer educator approach.

HIV-1 transmission in the male genital tract.

HIV-1 is mainly a sexually transmitted infection, and epithelial surfaces covering genital mucosa are the primary site of HIV-1 transmission. Although male circumcision was reported to reduce male acquisition of HIV-1 by 60%, the initial mechanisms of HIV-1 transmission in the male genitals remain elusive. We established two novel models of the adult human foreskin epithelium that allowed for polarized infection via the mucosal pole with either HIV-1-infected cells that are present in all secretions vectorizing HIV-1 or cell-free HIV-1. Efficient HIV-1 transmission occurs following 1 hr of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs form conjugates with T-cells, thereby transferring HIV-1. Seminal plasma from HIV-negative men mixed with cervico-vaginal secretions from HIV-positive women, which mimics the in-vivo mixture of these genital fluids during woman-to-man HIV-1 sexual transmission, decreases HIV-1 infection at the foreskin. Our results rationalize at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.

The role of the foreskin in male circumcision: an evidence-based review.

HIV sexual transmission via the male genital tract remains poorly defined. Male circumcision was shown to reduce female-to-male transmission in Africa, providing a clue that the foreskin plays a role in the route of transmission. Scientific data in four categories relating to how the foreskin might affect HIV transmission is summarized: (i) surface area, (ii) microbiologic environment, (iii) HIV-1-susceptible cells, and (iv) tissue structure. The relative contribution of each of these areas is yet unknown, and further studies will be crucial in understanding how male circumcision affects HIV transmission in men.

Absence of lymphatic vessels in human dental pulp: a morphological study.

Few and controversial data are available in the literature regarding the presence of lymphatic vessels in the human dental pulp. The present study was designed to examine morphologically the existence of a lymph drainage system in human dental pulp. Human dental pulp and skin sections were immunohistochemically stained with specific antibodies for lymphatic endothelium (D2-40, LYVE-1, VEGFR-3 [vascular endothelial growth factor receptor-3], and Prox-1), with the pan-endothelial markers CD31 and von Willebrand factor (vWF), and with the blood-specific marker CD34. Several blood vessels were identified in human pulps and skin. Lymphatic vessels were found in all human skin samples but in none of the pulps examined. Western blotting performed on human dermis and on pulps treated with collagenase (to remove odontoblasts) confirmed these results. Transmission electron microscopy indicated that vessels which, by light microscopy, appeared to be initial lymphatic vessels had no anchoring filaments or discontinuous basement membrane, both of which are typical ultrastructural characteristics of lymphatic vessels. These results suggest that under normal conditions human dental pulp does not contain true lymphatic vessels. The various theories about dental pulp interstitial fluid circulation should be revised accordingly.

Metaplasia mucinosa de pene asociada a balanitis de Zoon / Mucinous Metaplasia of the Penis Associated With Zoon’s Balanitis

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Fimose: conceitos e atualidades / Phymosis: concepts and uptodates

Fimose é condição comum nos consultórios pediátricos. Por tratar-se, possivelmente, de evento fisiológico na vida da criança e, muitas vezes, não precisar de tratamento é fundamental diferenciar as situações patológicas e fisiológicas. Este artigo trata de questões como conceitos, classificação e indicações para o tratamento clínico ou cirúrgico. Explorando opções desses tratamentos, discutimos o sucesso e as principais complicações dos mesmos. Além disso, faz-se breve análise da relação custo-benefício entre os tratamentos.

Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters).

INTRODUCTION: Male circumcision reduces HIV acquisition in men. We assessed whether foreskin surface area was associated with HIV acquisition prior to circumcision. METHODS: In two randomized trials of male circumcision, the surface area of the foreskin was measured after surgery using standardized procedures. Nine hundred and sixty-five initially HIV-negative men were enrolled in a community cohort who subsequently enrolled in the male circumcision trials, provided 3920.8 person-years of observation prior to circumcision. We estimated HIV incidence per 100 person-years prior to circumcision, associated with foreskin surface area categorized into quartiles. RESULTS: Mean foreskin surface area was significantly higher among men who acquired HIV (43.3 cm2, standard error 2.1) compared with men who remained uninfected (36.8 cm, standard error 0.5, P = 0.01). HIV incidence was 0.80/100 person-years (8/994.9 person-years) for men with foreskin surface areas in the lowest quartile (< or =26.3 cm2), 0.92/100 person-years (9/975.3 person-years) with foreskin areas in the second quartile (26.4-35.0 cm2), 0.90/100 person-years (8/888.5 person-years) with foreskin area in the third quartile (35.2-45.5 cm2) and 2.48/100 person-years (23/926.8 person-years) in men with foreskin surfaces areas in the highest quartile (>45.6 cm2). Compared with men with foreskin surface areas in the lowest quartile, the adjusted incidence rate ratio of HIV acquisition was 2.37 (95% confidence interval 1.05-5.31) in men with the largest quartile of foreskin surface area. CONCLUSION: The risk of male HIV acquisition is increased among men with larger foreskin surface areas.

Foreskin length in uncircumcised men is associated with subpreputial wetness.

This study was performed to identify possible factors associated with penile wetness, defined as the observation of a diffuse homogenous film of moisture on the surface of the glans and coronal sulcus, in men attending a sexually transmitted infection clinic. Genital examination was undertaken in 422 uncircumcised men and any degree of subpreputial wetness observed was recorded. The degree of visibility of the urinary meatus on direct inspection was also assessed. Subjects were asked whether they retracted the foreskin while urinating and how long since they had last passed urine. Penile wetness was observed in 13.0% of the men and was more common in those whose foreskin covered the urinary meatus on direct inspection (17.4% vs. 4.9%) and those with balanitis (33.3%). On multivariate analysis, penile wetness was independently associated with balanitis, non-specific urethritis/chlamydia, reporting sex with another man and having a visible urinary meatus on direct inspection. Penile wetness was not associated with retracting the foreskin while passing urine or duration since last passed urine. Men with a foreskin covering the urinary meatus on direct observation should be advised about the benefits of good genital hygiene if penile wetness was observed.