SciCombinator

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Concept: Foreskin

229

ABSTRACT Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

Concepts: HIV, Cellular respiration, Foreskin, Penis, Circumcision, Glans penis, Frenulum of prepuce of penis, Foreskin restoration

150

The traditional surgical approach to penile fracture is to perform a circumferential subcoronal degloving incision emergently to repair the injury. This approach necessitates circumcision to avoid foreskin complications. We present four men who had a delayed foreskin-sparing approach and discuss its advantages.

Concepts: Foreskin, Penis, Circumcision, Glans penis, Masturbation, Frenulum of prepuce of penis, Phimosis, Foreskin restoration

149

This paper was aimed to compare the clinical effectiveness and safety of adult male circumcision using the Shang Ring™ (SR) with the no-flip technique compared with Dorsal Slit (DS) surgical method. A single-centered, prospective study was conducted at the West China Hospital, where patients were circumcised using the no-flip SR (n = 408) or the DS (n = 94) procedure. The adverse events (AEs) and satisfaction were recorded for both groups, and ring-removal time and percentage of delayed removals were recorded for the SR group. Finally, complete follow-up data were collected for 76.1% of patients (SR: n = 306; DS: n = 76). The average ring-removal time for the SR group was 17.62 ± 6.30 days. The operation time (P < 0.001), pain scores during the procedure (P < 0.001) and at 24 h postoperatively (P < 0.001), bleeding (P = 0.001), infection (P = 0.034), and satisfaction with penile appearance (P < 0.001) in the SR group were superior to those in the DS group. After two postoperative weeks, the percentage of patients with edema in the SR group (P = 0.029) was higher but no differences were found at 4 weeks (P = 0.185) between the two groups. In conclusions, the no-flip SR method was found to be superior to the DS method for its short operation time (<5 min), involving less pain, bleeding, infection, and resulting in a satisfactory appearance. However, the time for recovery from edema took longer, and patients may wear device for 2-3 weeks after the procedure.

Concepts: Clinical trial, Foreskin, Penis, Circumcision, Brit milah, Phimosis, Preputioplasty, Dorsal slit

141

Genital injury can occur at any age of life but is most common in the pediatric population. Hair-tourniquets and circumcision procedures are the most common causes of penile injury in children. Foreskin trauma, aside from zipper related injuries, is sparsely reported. We describe the case of an 8-year-old male who presented with foreskin entrapment caused by bathing suit mesh. Management and literature review are discussed.

Concepts: Foreskin, Penis, Physical trauma, Circumcision, Glans penis, Masturbation, Frenulum of prepuce of penis, Foreskin restoration

136

Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE®) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE®cream for 7 days before circumcision. We found a significant reduction in mRNA levels of IL-1β, TNF-α, INF-γ, transglutaminase 2 and NOS2 in foreskins treated with OZOILE®in comparison to untreated ones (p< 0.001). No significant differences were observed in NF-κB activation in the specimens obtained from treated and untreated patients. Hence, OZOILE®treatment up-regulated hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF) and E-cadherin gene expression (p< 0.001). The treatment with OZOILE®showed effective results in children affected by BXO by reducing the inflammatory process and stimulating mechanisms for tissue regeneration of the foreskin. A randomized clinical trial on a large number of children affected by BXO might be useful to verify the efficacy of topical treatment with OZOILE®.

Concepts: Inflammation, Cellular differentiation, Anti-inflammatory, Foreskin, Circumcision, Phimosis, Balanitis, Balanitis xerotica obliterans

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WHAT’S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The sensitivity of the foreskin and its importance in erogenous sensitivity is widely debated and controversial. This is part of the actual public debate on circumcision for non-medical reason. Today some studies on the effect of circumcision on sexual function are available. However they vary widely in outcome. The present study shows in a large cohort of men, based on self-assessment, that the foreskin has erogenous sensitivity. It is shown that the foreskin is more sensitive than the uncircumcised glans mucosa, which means that after circumcision genital sensitivity is lost. In the debate on clitoral surgery the proven loss of sensitivity has been the strongest argument to change medical practice. In the present study there is strong evidence on the erogenous sensitivity of the foreskin. This knowledge hopefully can help doctors and patients in their decision on circumcision for non-medical reason. OBJECTIVES: To test the hypothesis that sensitivity of the foreskin is a substantial part of male penile sensitivity. To determine the effects of male circumcision on penile sensitivity in a large sample. SUBJECTS AND METHODS: The study aimed at a sample size of ≈1000 men. Given the intimate nature of the questions and the intended large sample size, the authors decided to create an online survey. Respondents were recruited by means of leaflets and advertising. RESULTS: The analysis sample consisted of 1059 uncircumcised and 310 circumcised men. For the glans penis, circumcised men reported decreased sexual pleasure and lower orgasm intensity. They also stated more effort was required to achieve orgasm, and a higher percentage of them experienced unusual sensations (burning, prickling, itching, or tingling and numbness of the glans penis). For the penile shaft a higher percentage of circumcised men described discomfort and pain, numbness and unusual sensations. In comparison to men circumcised before puberty, men circumcised during adolescence or later indicated less sexual pleasure at the glans penis, and a higher percentage of them reported discomfort or pain and unusual sensations at the penile shaft. CONCLUSIONS: This study confirms the importance of the foreskin for penile sensitivity, overall sexual satisfaction, and penile functioning. Furthermore, this study shows that a higher percentage of circumcised men experience discomfort or pain and unusual sensations as compared with the uncircumcised population. Before circumcision without medical indication, adult men, and parents considering circumcision of their sons, should be informed of the importance of the foreskin in male sexuality.

Concepts: Foreskin, Penis, Circumcision, Glans penis, Masturbation, Frenulum of prepuce of penis, Phimosis, Foreskin restoration

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Sexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4(+) T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase in Prevotella, Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection.IMPORTANCE We found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.

Concepts: HIV, Immune system, Inflammation, Sexual intercourse, Foreskin, Penis, Circumcision, Glans penis

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PURPOSE: Men are particularly concerned about pain after circumcision. Concerns about pain can be a reason to decline surgery. Our aim was to assess the severity of postoperative pain and to investigate factors that may influence postoperative pain. MATERIALS AND METHODS: This was a prospective observational cohort study on patients undergoing circumcision. Patients were asked to fill in a questionnaire using visual analogue scales for pain (severity 0-10) on days 1,2,3,7, 21 and to record analgesia used, complications and time off work. Other data recorded were patient age, clinical indication of surgery, foreskin retractility, presence of adhesions and histology. RESULTS: 112 of 211 questionnaires were returned (53.1%). Mean age of patients was 46.4yrs. Commonest clinical indication for circumcision was phimosis (75%). Postoperative pain was scored as mild to moderate (means: 2.4 on days 1-3, 2.1 on day 7 and 0.5 on day 21). Patients younger than 35 yrs of age (p=0.025) and patients with wound infections (p=0.036) had higher pain scores. Only 11 patients (9.8%) had severe pains at any time during the recovery of which 8 had wound problems. The average time off work in the employed population was 6.6 days (SD-6.5), 5 days for light work and 11 days for heavy physical activity. CONCLUSION: Pain following adult circumcision under general anaesthetic administration with intra-operative penile block administration is mild to moderate. Severe pain is rare and mostly related to complications. Younger patients have more discomfort in general.

Concepts: Cohort study, Pain, Foreskin, Penis, Circumcision, Glans penis, Phimosis, Preputioplasty

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Background  In adults, human papillomaviruses (HPV), lichen sclerosus et atrophicus (LSA) and phimosis are considered to be major risk factors for penile cancer. In boys, a possible association between phimosis, LSA and HPV has been suggested. Objective  To investigate the role of HPV in the persistence of phimosis in children. Patients and methods  Out of a cohort of 420 boys presenting with foreskin problems, we prospectively sampled the preputial tissue of 82 patients during circumcision: 46 with steroid-naïve and 36 with steroid-resistant phimosis. All foreskins were assessed clinically and histopathologically with regard to appearance, inflammation, oedema, epithelial degeneration and fibrosis. The viral status of the foreskins was determined by immunohistochemistry and highly sensitive PCR, with subsequent subtyping by DNA hybridization (HPV types 6, 11, 16, 18, 31, 33, 35, 39, 42, 44, 45, 51-54, 56, 58, 59, 61, 62, 66-68, 70, 72, 73, 81-84, 90, 91). Results  The foreskins appeared normal in 62 boys and suggestive of LSA in one single case. Small cracks or white scars were present in seven steroid-naïve and 12 steroid-resistant foreskins. LSA was diagnosed microscopically in two of the steroid-naïve and six of the steroid-pretreated group. No evidence of HPV was found in any of the juvenile foreskins. Conclusions  Our prospective study has provided evidence that HPV is not usually present in the foreskin of boys with persistent phimosis after their first year of life and that topical glucocorticoid treatment failure is not associated with HPV or any specific histopathological changes.

Concepts: Human papillomavirus, Foreskin, Penis, Circumcision, Masturbation, Lichen sclerosus, Phimosis, Preputioplasty

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PURPOSE: Voluntary medical male circumcision (VMMC) has been shown to reduce men’s risk of HIV infection through heterosexual intercourse by ~60% in clinical trials and 73% in post-trial follow-up. In 2007, WHO and UNAIDS recommended countries with low circumcision rates and high HIV prevalence expand VMMC programs as part of their national HIV prevention strategies. Devices for adult/adolescent male circumcision could accelerate the pace of VMMC scale-up. Detailed penile measurements of African males are required for device development and supply size forecasting. MATERIALS AND METHODS: Consenting males undergoing VMMC at three health facilities in Tanzania’s Iringa region underwent measurement of the glans, shaft and foreskin of the penis. Age, Tanner stage, height and weight were recorded. Measurements were analyzed by age categories. Correlations between penile parameters and height, weight and body mass index (BMI) were calculated. RESULTS: In 253 Tanzanian males ages 10-47 years, the mean (SD) penile length of adults was 11.5 (1.6) cm; shaft circumference was 8.7 (0.9) cm; and glans circumference was 8.8 (0.9) cm. As expected, given the variability of puberty, measurements of younger males varied significantly. Glans circumference was highly correlated with height (r=0.80, p<.001) and weight (r=0.81, p<.001). Stretched foreskin diameter was moderately correlated with height (r=0.68, p<.001) and weight (r=0.71, p<.001). CONCLUSIONS: This descriptive study provides penile measurements of males seeking VMMC services in Iringa, Tanzania. It is the first study in a sub-Saharan African population that provides sufficiently detailed glans and foreskin dimensions to inform VMMC device development and size forecasting.

Concepts: HIV, Africa, Foreskin, Penis, Circumcision, Glans penis, Masturbation, Foreskin restoration