John M. Hutson

ANATOMICAL RELATIONSHIP BETWEEN URETHRA AND CLITORIS

PURPOSE We investigated the anatomical relationship between the urethra and the surrounding erectile tissue, and reviewed the appropriateness of the current nomenclature used to describe this anatomy. MATERIALS AND METHODS A detailed dissection was performed on 2 fresh and 8 fixed human female adult cadavers (age range 22 to 88 years). The relationship of the urethra to the surrounding erectile tissue was ascertained in each specimen, and the erectile tissue arrangement was determined and compared to standard anatomical descriptions. Nerves supplying the erectile tissue were carefully preserved and their relationship to the soft tissues and bony pelvis was noted. RESULTS The female urethra, distal vaginal wall and erectile tissue are packed into the perineum caudal (superficial) to the pubic arch, which is bounded laterally by the ischiopubic rami, and superficially by the labia minora and majora. This complex is not flat against the rami as is commonly depicted but projects from the bony landmarks for 3 to 6 cm. The perineal urethra is embedded in the anterior vaginal wall and is surrounded by erectile tissue in all directions except posteriorly where it relates to the vaginal wall. The bulbs of the vestibule are inappropriately named as they directly relate to the other clitoral components and the urethra. Their association with the vestibule is inconsistent and, thus, we recommend that these structures be renamed the bulbs of the clitoris. CONCLUSIONS A series of detailed dissections suggest that current anatomical descriptions of female human urethral and genital anatomy are inaccurate.

Testicular Feminization: A Model for Testicular Descent in Mice and Men

The position of the testis was determined in patients and mice with the testicular feminization (TFM) syndrome, to answer the question, do androgens cause testicular descent? In 16 children with complete or partial TFM syndrome with androgen insensitivity, plus two children with a deficiency of androgen secretion, the testes were at or beyond the internal inguinal ring in 35 out of 36 instances. In male mice with TFM, the testes had descended normally to the internal ring by the time of birth but further descent was absent. These observations suggest testicular descent is a two-stage process comprising transabdominal and transinguinal phases. The first phase is not controlled by androgen, and hence is normal in TFM; by contrast the second phase is androgen-dependent, and absent in TFM. It is speculated that the first phase may be regulated by Müllerian Inhibiting Substance, although this is unproven. Because testicular descent in TFM can be separated into two stages, the TFM mouse should prove a useful model for studying the hormonal control of descent of the testis.

Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group

The term gastrointestinal neuromuscular disease describes a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular, including interstitial cell of Cajal, dysfunction. Such disorders commonly have impaired motor activity, i.e. slowed or obstructed transit with radiological evidence of transient or persistent visceral dilatation. Whilst sensorimotor abnormalities have been demonstrated by a variety of methods in these conditions, standards for histopathological reporting remain relatively neglected. Significant differences in methodologies and expertise continue to confound the reliable delineation of normality and specificity of particular pathological changes for disease. Such issues require urgent clarification to standardize acquisition and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thickness tissue biopsy of bowel or other diagnostic procedures. Such information will also allow increased certainty of diagnosis, facilitating factual discussion between patients and caregivers, as well as giving prognostic and therapeutic information. The following report, produced by an international working group, using established consensus methodology, presents proposed guidelines on histological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology. The report addresses the main areas of histopathological practice as confronted by the pathologist, including suction rectal biopsy and full-thickness tissue obtained with diagnostic or therapeutic intent. For each, indications, safe acquisition of tissue, histological techniques, reporting and referral recommendations are presented.

What is new in cryptorchidism and hypospadias—a critical review on the testicular dysgenesis hypothesis ☆

It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity--the testicular dysgenesis syndrome--leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease.

Incomplete Disappearance of the Processus Vaginalis as a Cause of Ascending Testis

PURPOSE Recently evidence has been accumulating that some undescended testes present later in childhood after apparent normalcy in infancy. These ascending testes appear to explain why a significant number of orchiopexies are performed later in childhood despite the recommendation that surgery for cryptorchidism be performed in infancy. We aimed to determine whether the cause of these ascending testes was persistence of the processus vaginalis. MATERIALS AND METHODS A total of 25 boys 4 to 13 years old with no history of testicular maldescent at birth underwent transscrotal orchiopexy in a 2-year period. A total of 33 orchiopexies was performed (8 bilateral). The spermatic cord was carefully dissected and operative findings of the nature of the spermatic cord were noted. RESULTS In all cases dissection within the spermatic cord revealed a similar finding, namely a fibrous string situated deep to the cremasteric muscle and spermatic fasciae. Transection of this string allowed adequate elongation of the vas deferens and gonadal vessels to permit scrotal placement of the testis. Histological examination revealed characteristic processus vaginalis tissue in which the peritoneal derived mesothelial lining cells were present within a partially obliterated processus vaginalis. CONCLUSIONS Cryptorchidism presenting later in childhood may be an acquired abnormality caused by failure of natural growth of the spermatic cord when the processus vaginalis leaves a fibrous remnant, which prevents normal elongation. These observations suggest that the ascending testis is acquired postnatally and the cause may be related to inguinal hernia.

The ontogeny of mullerian inhibiting substance in the gonads of the chicken

Mullerian inhibiting substance (MIS) was studied in the testis, ovary, and ovotestis of the domestic fowl, from early embryonic development to adulthood by a graded organ-culture method using the urogenital ridge of a 14.5 day fetal rat. The chick testis had high levels of MIS from 8 days of embryonic development (4-5+) until sexual maturity, when activity declined (2+) but persisted throughout adulthood. The right gonad (ovotestis) of the hen showed moderate levels of MIS activity from 8 to 12 days of embryonic life (1-3+) before its normal involution by the time of hatching (21 days). The left gonad (ovary) of the hen also produced MIS at levels similar to that seen in the testis. Activity was high during embryonic development (4+) and after hatching, and persisted in the adult hen at diminished levels (2+). MIS production by the female gonads explains regression of the right Mullerian duct, but the mechanisms that allow preservation of the left duct remain unexplained. Evidence suggests that ovarian estrogens may interact with MIS at the receptor level to protect the left Mullerian duct. MIS persists in the sexually mature gonads of both the hen and cockeral, long after the Mullerian duct has regressed, suggesting a wider role for this substance in reproductive physiology.

Copy Number Variation in Patients with Disorders of Sex Development Due to 46,XY Gonadal Dysgenesis

Disorders of sex development (DSD), ranging in severity from mild genital abnormalities to complete sex reversal, represent a major concern for patients and their families. DSD are often due to disruption of the genetic programs that regulate gonad development. Although some genes have been identified in these developmental pathways, the causative mutations have not been identified in more than 50% 46,XY DSD cases. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to analyse copy number variation in 23 individuals with unexplained 46,XY DSD due to gonadal dysgenesis (GD). Here we describe three discrete changes in copy number that are the likely cause of the GD. Firstly, we identified a large duplication on the X chromosome that included DAX1 (NR0B1). Secondly, we identified a rearrangement that appears to affect a novel gonad-specific regulatory region in a known testis gene, SOX9. Surprisingly this patient lacked any signs of campomelic dysplasia, suggesting that the deletion affected expression of SOX9 only in the gonad. Functional analysis of potential SRY binding sites within this deleted region identified five putative enhancers, suggesting that sequences additional to the known SRY-binding TES enhancer influence human testis-specific SOX9 expression. Thirdly, we identified a small deletion immediately downstream of GATA4, supporting a role for GATA4 in gonad development in humans. These CNV analyses give new insights into the pathways involved in human gonad development and dysfunction, and suggest that rearrangements of non-coding sequences disturbing gene regulation may account for significant proportion of DSD cases.

Abnormalities of testicular descent

Testicular descent occurs in two stages. The transabdominal phase (8–15 weeks) is controlled by enlargement of the caudal genito-inguinal ligament (gubernaculum) and regression of the cranial ligament. Insulin-like 3 from the Leydig cell appears to be the prime stimulator of gubernacular growth, augmented by Müllerian inhibiting substance/anti-Müllerian hormone. Testosterone causes regression of the cranial ligament. The inguinoscrotal phase (25–35 weeks) requires the migration of the gubernaculum from the groin to the scrotum; this migration is guided by the genito-femoral nerve releasing calcitonin gene-related peptide under the influence of androgen. The neonatal gonocyte transforms into a type A spermatogonium at 3–12 months of age, a step that is now known to be crucial for subsequent fertility, as the stem cells for spermatogenesis are created in this structure. This step is blocked in undescended testis and, hence, orchidopexy is currently recommended at 6–12 months of age. Congenital cryptorchidism is caused by the failure of gubernacular migration to the scrotum (1%–2%) but we now recognise that another 1%–2% of boys have acquired cryptorchidism, secondary to the failure of spermatic cord elongation with growth of the boy. These latter cases come to operation at 5–10 years of age. Surgery remains the mainstay of treatment, as hormonal therapy has not been proven to be effective, presumably because testicular descent is a complex anatomical mechanism.

Pilot study using transcutaneous electrical stimulation (interferential current) to treat chronic treatment-resistant constipation and soiling in children.

Background:  Chronic constipation in children may have organic or behavioral causes. The purpose of the present study was to investigate the effect of treatment with transcutaneous electrical stimulation (using interferential current) in children with chronic treatment‐resistant constipation with proven organic disorders.

Fecal incontinence after the surgical treatment of Hirschsprung disease

We examined 60 children 8.9 years (+/- 2.6 years) after surgical treatment of Hirschsprung disease to determine the extent of fecal incontinence. Thirty-two children (53%) had significant fecal soiling and 16 (27%) less severe soiling. The prevalence of incontinence did not diminish with increasing age.