Flutamide-induced hypospadias in rats: A critical assessment.

This paper provides the first detailed description of flutamide-induced hypospadias in the rat based upon wholemount, histologic, three-dimensional reconstruction, scanning electron microscopic, and immunocytochemical analysis. The penile malformations elicited by this potent anti-androgen include a substantial proximal shift in the urethral meatus that clearly conforms to the definition of hypospadias based upon specific morphological criteria for this malformation. Through examination of the normal penile development and flutamide-induced abnormal penile development observed in prenatally oil- and flutamide-treated rats, our analysis provides insights into the morphogenetic mechanism of development of hypospadias. In this regard, a common theme in normal penile development is midline fusion of epithelia followed by removal of the epithelial seam and establishment of midline mesenchymal confluence during development of the penile urethra and prepuce, processes which are impaired as a result of prenatal flutamide treatment. The developmental processes occurring in normal penile development, through comparison with development of female external genitalia and those impaired due to prenatal flutamide treatment, are consistent with critical role of androgen receptors in normal penile development in the rat, and the specific penile abnormalities embodied in flutamide-induced rat hypospadias

Androgen-independent events in penile development in humans and animals.

The common view on penile development is that it is androgen-dependent, based first and foremost on the fact that the genital tubercle forms a penis in males and a clitoris in females. However, critical examination of the complex processes involved in human penile development reveals that many individual steps in development of the genital tubercle are common to both males and females, and thus can be interpreted as androgen-independent. For certain developmental events this conclusion is bolstered by observations in androgen-insensitive patients and androgen receptor mutant mice. Events in genital tubercle development that are common to human males and females include: formation of (a) the genital tubercle, (b) the urethral plate, (c) the urethral groove, (d) the glans, (e) the prepuce and (f) the corporal body. For humans 6 of 13 individual developmental steps in penile development were interpreted as androgen-independent. For mice 5 of 11 individual developmental steps were found to be androgen-independent, which were verified through analysis of androgen-insensitive mutants. Observations from development of external genitalia of other species (moles and spotted hyena) provide further examples of androgen-independent events in penile development. These observations support the counter-intuitive idea that penile development involves both androgen-independent and androgen-dependent processes

Correlation between Penile Length and Anogenital Distance in Term Newborns, Gorgan, 2011

Background and purpose: Anogenital distance is an accepted indicator for endogenous or environmental effects of androgens on development of reproductive system in fetus and newborns. This study was done to determine the relationship between penile length and anogenital distance in Iranian newborns. Material and Methods: In this cross-sectional study stretched penile length (PL) and anogenital distance (AGD) were measured in 427 healthy male newborn infants born in a Teaching Hospital (in north of Iran). Other variables included the age of mothers, and weight, height, and head circumference of neonates. Normal distribution of variables was measured by Shapiro-Wilk and data was analyzed using Pearson Correlation tests Results: The mean of PL was 32.1±3.5 mm and the mean of AGD was 24.5±2.5mm. A weak correlation was observed between PL and AGD (r=0.097, p=0.046). Conclusion: The correlation between penile length and AGD showed that, AGD could be also used in assessing the genital system and even as a common indicator to assess the genital system in both sexes Keywords: penile length, anogenital, distance,term newborn, mal

Conducting interviews about penile cancer: A patient-conducted-interview study

Objectives: Penile cancer is a rare but destructive condition. It has been found to be detrimental to body image, general health and sexual functioning, while increasing anxiety and social problems. The UK now manages penile cancer through specialist multi-disciplinary teams that see at least 25 new patients a year. There is a need to understand patients’ experiences so that treatment can be improved. The aim of this research is to allow patients to participate in the development of a nationwide interview study. Methods: A one-day participative workshop where a range of men diagnosed with penile cancer design and conduct audio and video interviews exploring experiences of treatment within the group. Results: Key themes included the rehabilitation of urinary functioning and strategies for coping with the physical and social impact of treatment. Conclusions: The findings emphasise the importance of day-to-day practicalities for men treated for penile cancer, which can form the basis for larger studies about how to better understand and manage their treatment

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube

Arterial anatomy and arteriographic diagnosis of arteriogenic impotence

One hundred twenty-six bilateral selective arteriographic examinations of the iliopudendal vascular tree were performed after comprehensive multidisciplinary evaluation in patients with chronic erectile dysfunction. Best imaging results were obtained by performing the arteriography under epidural anesthesia after intracavernous injection of a vasoactive drug combination. The arteriography is mandatory prior to revascularization procedures. It is further indicated in primary erectile dysfunction and posttraumatic erectile failure. The importance of cavernosography and selective arteriography in primary erectile dysfunction is stressed. Increasing knowledge about the influence of vasoactive drugs on penile hemodynamics has led to its application in diagnosis and therapy of erectile dysfunction. Pharmacocovernosography, Doppler-ultrasound of penile arteries after intracavernous injection of a vasoactive drug combination, and pharmacoarteriography are refined techniques to prove a vascular etiology of erectile dysfunction. The results of the morphologic studies of the vascular system are correlated with functional testing of erectile capacity by intracavernous application of a papaverinephentolamine drug combination

Malignant priapism due to penile metastases. Case series and literature review

Malignant priapism secondary to penile metastases is a rare condition. This term was originally used by Peacock in 1938 to describe a condition of painful induration and erection of the penis due to metastatic infiltration by a neoplasm. In the current literature there are 512 case reports. The primary tumor sites are bladder, prostate and rectum. The treatment has only palliative intent and consists of local tumor excision, penectomy, radiotherapy and chemotherapy. We present one case of malignant priapism originated from prostate cancer, and two from urothelial carcinoma of the bladder. Different approaches in diagnosis and therapy were performed. The entire three patient reported a relief of the pain following the treatment, with an improvement of their quality of life, even though it was only temporary as a palliative. Malignant priapism is a rare medical emergency. Penile/pelvis magnetic resonance imaging (MRI) scan and corporal biopsies are considered an effective method of diagnosis of the primary organ site.Malignant priapism secondary to penile metastases is a rare condition. This term was originally used by Peacock in 1938 to describe a condition of painful induration and erection of the penis due to metastatic infiltration by a neoplasm. In the current literature there are 512 case reports. The primary tumor sites are bladder, prostate and rectum. The treatment has only palliative intent and consists of local tumor excision, penectomy, radiotherapy and chemotherapy. We present one case of malignant priapism originated from prostate cancer, and two from urothelial carcinoma of the bladder. Different approaches in diagnosis and therapy were performed. The entire three patient reported a relief of the pain following the treatment, with an improvement of their quality of life, even though it was only temporary as a palliative. Malignant priapism is a rare medical emergency. Penile/pelvis magnetic resonance imaging (MRI) scan and corporal biopsies are considered an effective method of diagnosis of the primary organ site