In vitro fusion of human inguinal hernia with associated epithelial transformation.

The processus vaginalis (PV) is a peritoneal diverticulum which forms to allow descent of the fetal testis to the scrotum. During human development fusion and obliteration of the PV often fails to occur with the result that inguinal hernias are the most prevalent congenital abnormality requiring surgery in childhood. Androgen is proposed to regulate testicular descent via the genitofemoral nerve which releases the neuropeptide calcitonin gene-related peptide (CGRP). It is possible that subsequent fusion of the PV and tissue remodelling following descent is indirectly controlled by androgen via CGRP action. An organ culture assay was developed to assess fusion of the PV taken from inguinal herniotomy in infants. Fusion was induced in vitro by CGRP but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone in equimolar concentrations. Fusion was accompanied by transformation of the epithelium, as shown by staining of intermediate filament proteins, cytokeratin and vimentin. Localization studies for CGRP receptors on 25 specimens indicated CGRP acts on mesenchymal fibroblasts but not directly on PV epithelium suggesting an indirect pathway. Hepatocyte growth factor/scatter factor was found to induce fusion of PV and may be involved as an intermediate molecule in the fusion cascade. This study represents the first approach to understanding the humoral control and underlying mechanism by which the PV fuses.

Exogenous calcitonin gene-related peptide can change the direction of gubernacular migration in the mutant trans-scrotal rat.

PURPOSE: The mutant trans-scrotal (TS) rat shows unilateral or bilateral suprainguinal testes in more than 70% of males. Calcitonin gene-related peptide (CGRP) has been proposed as the neurotransmitter released from the genitofemoral nerve (GFN), which controls gubernacular migration to the bottom of the scrotum during inguinoscrotal descent. Results of previous studies in this rat suggest a down-regulation of CGRP receptors in gubernaculum occurring caused by excess release of the neuropeptide from the GFN. The aim of this study was to test the hypothesis that division of the GFN in neonatal TS rats, potentially allowing the gubernaculum to become sensitive to CGRP, followed by exogenous CGRP injections, would change the direction of gubernacular migration and the final position of the testis. METHODS: Four study groups were used: group 1 (n = 43), sham operation, in which the peritoneal cavity was opened and the left genitofemoral nerve was exposed but not divided, and oil injections into left hemiscrotum; group 2 (n = 70), division of left GFN and CGRP injections into left hemiscrotum; group 3 (n = 36), sham operation and CGRP injections into left hemiscrotum; group 4 (n = 30), division of left GFN and oil injections into left hemiscrotum. RESULTS: In group 2 (GFN division and CGRP injection), 18 testes were located in a position not previously described in this model. In 16 (23%) rats, the testis was located at the entrance of the internal inguinal ring with the gubernaculum directed down toward the scrotum. This contrasts with the normal position of the testis in the superficial inguinal pouch, where the testis is located superficial to the external oblique muscle, with the gubernaculum directed craniolaterally. In two (3%) rats, there was incomplete descent of the testis. In group 3 (sham operation and CGRP injection), two (6%) testes were located at the internal ring. The remaining testes in the above groups and all of the testes in groups 1 and 4 were found in either the superficial inguinal pouch, completely descended, or adherent to scar tissue. CONCLUSIONS: These findings suggest that division of the GFN in neonatal TS rats followed by CGRP injections into the scrotum can change the direction of gubernacular migration in the TS rat. The effectiveness of this experimental model is limited by the inability to accurately localize injected CGRP into the scrotum.

Testicular and paratesticular tumours in children: 30 years' experience.

BACKGROUND: Testicular or paratesticular tumours in children are rare, making it difficult to achieve the best management for these life-threatening diseases. The aim of this study is to review patients during a 30-year period with these tumours and assess clinical aspects to improve management. METHODS: The records of 68 patients from 1967 to 1996 were reviewed with respect to age at diagnosis, affected sites, presentation, clinical diagnosis, operation, pathology and prognosis. RESULTS: The most common presentation was a painless scrotal mass (84%). The most common testicular tumour was mature teratoma (n = 27) followed by yolk sac tumour (n = 17). Thirteen patients had paratesticular rhabdomyosarcoma. Two teratocarcinomas, three leydig cell tumours, two sertoli cell tumours, one granulosa cell tumour, one fibroma, one gonadoblastoma, and one secondary tumour from acute myeloid leukaemia were found also. Testis-sparing surgery was performed in 21 of 33 patients with benign tumours (27 teratoma, three leydig cell tumours, two sertoli cell tumours, one fibroma), which caused no recurrence. Only two patients with rhabdomyosarcoma and one with mixed germ cell tumour died of their disease. CONCLUSION: Recent combined therapy with surgery and chemotherapy against primary testicular and paratesticular tumours has improved prognosis. Testis-sparing surgery should be considered for benign tumours.

Ventriculo-peritoneal shunts in children reveal the natural history of closure of the processus vaginalis.

PURPOSE: Little information is known about the natural history of closure of the processus vaginalis. The authors studied children who had ventriculoperitoneal shunts to determine the natural history of closure of the processus vaginalis and to better understand the role of intraabdominal pressure in the etiology of congenital inguinal hernia. MATERIALS AND METHODS: A retrospective review of all children undergoing insertion of ventriculoperitoneal shunts between 1985 and 1995 at the Royal Children's Hospital was undertaken. In each case, the sex, the cause of hydrocephalus, the age at insertion of the shunt, and the subsequent development of an inguinal hernia or hydrocele was recorded. RESULTS: There were 430 children in the study. An inguinal hernia developed in 15% of children after insertion of a ventriculoperitoneal shunt, and a hydrocele developed in an additional 6% of boys. Inguinal hernias were bilateral in 47% of boys and 27% of girls. The incidence of subsequent development of an inguinal hernia or hydrocele was closely related to the age of insertion of the ventriculoperitoneal shunt, being 30% during the last 8 weeks of gestation and the first few months of life, then falling quite sharply to reach about 10% at 1 year. CONCLUSIONS: The high occurrence of inguinal hernias and hydroceles after ventriculoperitoneal shunt insertion supports the role of raised intraabdominal pressure in the etiology of these conditions. It appears that raised intraabdominal pressure is associated with an increased incidence of clinical hernias, but not with increased incidence of patency of the processus vaginalis. The development of an inguinal hernia or hydrocele after insertion of a ventriculoperitoneal shunt can be used as an indirect marker of patency of the processus vaginalis at the time of insertion of the shunt. From this, we propose that the processus vaginalis remains patent in at least 30% of children in the first few months of life, after which time the patency rate appears to fall off quite sharply.

Does the gubernaculum migrate during inguinoscrotal testicular descent in the rat?

BACKGROUND: The role of the gubernaculum in descent of the testis is controversial. The mechanism of testicular descent has been studied in the rat, because inguino-scrotal descent occurs postnatally in this species. Several authors have claimed that the cremasteric sac forms by eversion of the gubernacular cone, whereby regression of the extra-abdominal part of the gubernaculum creates a space into which the gubernacular cone everts to form the processus vaginalis within the scrotum. This postulated lack of any gubernacular migration phase contrasts with the situation in the human, where gubernacular migration appears to be an integral component of testicular descent. This study was designed to determine in the rat whether there is any gubernacular migration toward the scrotum during testicular descent, or whether eversion of the cremasteric sac alone could account for the extension of this sac into the bottom of the scrotum. METHODS: Oblique sagittal sections of the inguino-perineal region were taken from rats aged 21 days of gestation and days 1, 3, 4, 6, 8, and 10 days postnatally. Histological sections were examined and the following measurements were obtained: gubernacular cone height, gubernaculum-scrotum distance, processus vaginalis length, and pubic symphysis-anus distance. RESULTS: The gubernaculum was not in close proximity to the developing scrotum at any age. After 21 days of gestation, there was little evidence of a substantial gubernacular bulb distal to the processus vaginalis. At all ages the gubernacular cone height was significantly less than the distance from the gubernaculum to the scrotum. CONCLUSIONS: These results show that the gubernaculum does not develop in close proximity to the developing scrotum. Even if complete eversion of the gubernaculum takes place, the gubernaculum would still fail to reach the bottom of the scrotum. It is proposed that gubernacular eversion is more apparent than real and that some degree of gubernacular migration is needed for complete extension of the cremasteric sac to the bottom of the scrotum.

Handlebar injuries in children: patterns and prevention.

BACKGROUND: Bicycle handlebar injuries in children are a significant cause of abdominal trauma. The present study documents 32 children with handlebar injuries who were managed at the Royal Children's Hospital over a 5-year period, and suggests a design change to bicycle handlebars which may reduce the severity of injury. METHODS: A retrospective review of all the children admitted to the Royal Children's Hospital with handlebar injuries between January 1990 and January 1995 was undertaken. The age, sex, nature of injury, length of hospital stay and management were recorded. RESULTS: Thirty-two children with blunt abdominal trauma or lacerations resulting from handlebar injuries were identified. Injuries included: splenic trauma (9); liver trauma (4); traumatic pancreatitis (3); transection of the pancreas (2); renal contusions (2); duodenal haematoma (1); and bowel perforation (3). In addition, there were three urethral injuries and five lacerations involving the abdominal wall and inguino-scrotal region. The presence of external bruising was a poor indicator of underlying brgan damage. Thirteen operations were performed and the mean hospital stay for the series was 9 days. CONCLUSIONS: Handlebar injuries are a significant cause of both blunt abdominal trauma and lacerations to the contact area. The infrequent finding of external bruising in the presence of major organ damage suggests that, although the velocity at impact may be relatively low, the small cross-sectional area of the end of the handlebar is a major factor contributing to organ damage. Moreover, we suspect that the high proportion of lacerations observed in this type of trauma result from the sharp metallic end of the handlebar cutting through the soft rubber handle. Manufacturers of bicycles should be made aware of these findings and should adjust the design of the handlebars accordingly.

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.

Exogenous calcitonin gene-related peptide can induce the testis to cross the scrotal septum.

OBJECTIVES: To determine: (i) whether the pattern of gubernacular migration can be changed by local injections of calcitonin gene-related peptide (CGRP) in rats with a normal testicular position, (ii) the effects of both endogenous and exogenous CGRP on contralateral gubernacular migration and (iii) whether the scrotal septum acts as a barrier to prevent gubernacular migration. MATERIALS AND METHODS: Four groups of neonatal rats were used, all of which underwent right orchidectomy with: group 1 (29 rats) division of the genitofemoral nerve (GFN) on both sides; group 2 (31 rats) division of the left GFN; group 3 (31 rats) division of the left GFN and injections of oil into the right hemiscrotum; and group 4 (34 rats) division of the left GFN and injections of CGRP into the right hemiscrotum. After 26-38 days, the rats were killed and the testicular positions determined. RESULTS: In rats receiving no injections (groups 1 and 2), the testes were oriented further to the right side where the right GFN was not divided (group 2). With the addition of oil into the right hemiscrotum where the right GFN was not divided (group 3), the testes were oriented further to the left compared with those in group 2. Injections of CGRP into the right hemiscrotum in the presence of an intact right GFN (group 4) resulted in more testes where the axis was orientated to the right side of the scrotum compared with the other groups with an intact right GFN (groups 1 and 3) but this was not reflected in the mean distance from the midline, which was similar among these groups. A significant number of testes in groups 1, 2 and 4 crossed the midline. CONCLUSIONS: The presence of an intact GFN on the right side where the left nerve was divided provides a directional signal influencing migration of the contralateral gubernaculum to the right side of the scrotum. Oil injected into the scrotum interferes with the normal concentration gradient of CGRP released from the right GFN, resulting in gubernacular migration further toward the left side. CGRP injections were poorly localized to the right hemiscrotum, resulting in gubernacular migration toward in some and away from the site of injection in others. The midline scrotal septum is not a barrier to gubernacular migration and most likely forms as a secondary event following descent of the testis.

Is the ascending testis actually 'stationary'? Normal elongation of the spermatic cord is prevented by a fibrous remnant of the processus vaginalis.

The processus vaginalis (PV) forms as a peritoneal diverticulum within the gubernaculum testis to allow the testis to exit from the abdominal cavity. Failure of its closure leads to inguinal hernias and hydroceles. Ascending testis, which is likely to be an acquired form of undescended testis, may also be part of the spectrum of failure of regression of the PV. At orchidopexy for cryptorchidism in older boys with a history of a scrotal testis in infancy, we find that the PV persists as a fibrous string, preventing normal elongation of the vas deferens and gonadal vessels with increasing size of the boy. We propose that the ascending testis is actually 'stationary', and is caused by persistence of a fibrous remnant of the PV. Seen in this light, ascending testes are directly related to inguinal hernias.

Genital anomalies in human and animal models reveal the mechanisms and hormones governing testicular descent.

A systematic examination of the conditions characterized by the presence of genital anomalies in humans, noting in each condition the position of the gonad, the nature of the gubernaculum and cranial suspensory ligament can provide valuable information regarding the mechanisms controlling the final position of the gonads. In conditions where MIS is absent, the gubernaculum is "feminized', resulting in a testis in the position normally occupied by an ovary or an abnormally mobile testis that can prolapse to the inguinal region. In conditions of androgen insensitivity the testis is located in the inguinal region, indicating that the first phase of descent is normal but that inguinoscrotal descent has failed to occur. Ovarian descent fails to occur in congenital adrenal hyperplasia, despite exposure of the developing fetus to high levels of androgens, indicating that androgen alone does not control gonadal descent. Moreover, ovarian descent fails to occur despite androgen-dependent regression of the cranial suspensory ligament. The correlation between the degree of Müllerian duct retention and scrotal position in mixed gonadal dysgenesis further strengthens the hypothesis that the first stage of testicular descent is controlled by MIS. The study of genital anomalies suggests that MIS controls the swelling reaction in the male gubernaculum, which is responsible for the first phase of testicular descent to the inguinal region. The second or inguinoscrotal phase of descent is androgen-dependent. Regression of the cranial suspensory ligament is also androgen-dependent: however, it is the gubernaculum and not the presence or absence of the cranial suspensory ligament which controls testicular descent. A combined knowledge of the hormonal basis controlling sexual differentiation and the biphasic model of testicular descent enables the clinician to accurately predict the internal anatomy of these complex sexual anomalies.

Factors affecting the development of the processus vaginalis in the rat.

PURPOSE: We examined the factors that influence development of the processus vaginalis in the rat. MATERIALS AND METHODS: Neonatal Sprague-Dawley rats 0 to 3 days old underwent distal or proximal gubernaculotomy, unilateral orchiectomy or proximal genitofemoral nerve transection. At ages 28 to 60 days the rats were sacrificed, position of the testis was noted and length of the processus vaginalis was measured. RESULTS: There was no development of the processus vaginalis after distal gubernaculotomy. Proximal gubernaculotomy enabled the processus vaginalis to achieve a mean length similar to that of controls (p = 0.06) when the testis descended into the scrotum. Mean length of the processus after proximal gubernaculotomy with an abdominal testis, surgical orchiectomy and torsion of the testis after proximal gubernaculotomy was similar (p = 0.9) but less than that of controls (p < 0.05). Proximal division of the genitofemoral nerve produced variable results depending on how and when the surgical procedure was performed, and whether the psoas muscle was divided. CONCLUSIONS: Distal attachment of the gubernaculum is essential for normal development of the processus vaginalis. Distal gubernaculotomy prevents development of the processus vaginalis because of mechanical disruption of the gubernaculum. Proximal attachment is not essential for normal development of the processus vaginalis but it serves to anchor the testis to the region of the internal inguinal ring, allowing intra-abdominal pressure to facilitate descent of the testis. In the presence of an innervated gubernaculum the processus vaginalis achieves greater length when the testis descends into the scrotum, suggesting that its complete development demands the presence of a testis in the sac. The timing of genitofemoral nerve division may be crucial in determining the subsequent effect on the development of the processus vaginalis and testicular descent, since programming of the gubernaculum by calcitonin gene-related peptide released from the genitofemoral nerve appears to occur just before birth in the rat.

The genitofemoral nerve may link testicular inguinoscrotal descent with congenital inguinal hernia.

The genitofemoral nerve (GFN) hypothesis for inguinoscrotal testicular descent proposes that calcitonin gene-related peptide (CGRP), released from the genitofemoral nerve, controls the migration of the gubernaculum from the inguinal region to the scrotum between 26 and 40 weeks of gestation. The processus vaginalis provides a channel through which the testis descends from the abdomen to the scrotum. Following descent of the testis the processus vaginalis undergoes luminal obliteration and disappearance between the internal inguinal ring and the upper pole of the testis. The mechanism underlying closure of the processus is unknown and failure for it to occur normally results in congenital inguinal hernia, scrotal hydrocele and possibly even an 'ascending' testis. Recent work in our laboratory suggests that CGRP, released from the genitofemoral nerve, may cause fusion and disappearance of the processus vaginalis. We propose that abnormalities in the GFN link a spectrum of disorders encompassing congenital undescended testis, inguinal hernia, scrotal hydrocele and ascending testis.

Retrograde balloon dilatation for primary pelvi-ureteric junction stenosis in children.

OBJECTIVE: To evaluate the efficacy of retrograde balloon dilatation for primary pelvi-ureteric junction (PUJ) stenosis (RBDP) in children. PATIENTS AND METHODS: Sixteen children (12 boys, four girls; mean age 29 months) with primary PUJ stenosis initially underwent RBDP. A double-pigtail catheter was left in the ureter for 6 weeks to provide drainage. The initial diagnosis of PUJ stenosis and the subsequent post-operative assessment were both made by diuretic renography in almost all patients. All children were followed up for between 9 and 38 months (mean 25) after the procedure. RESULTS: RBDP was unsuccessful in nine of 17 renal units. In three of these, failure was caused by inability to pass the catheter through the PUJ or vesico-ureteric junction (VUJ). In six cases, failure was caused by recurrent or persistent stenosis. In eight of 17 renal units, RBDP was successful in relieving the stenosis. The morbidity from the procedure was minimal. CONCLUSIONS: Long-term follow-up revealed a significant failure rate for RBDP, caused by the inability to pass the catheter through the VUJ or PUJ, or persistent and/or recurrent stenosis. Recurrent stenosis may result from excessive dilatation which traumatizes the PUJ and causes subsequent scarring. Failure to overcome the stenosis is thought to be caused by a large redundant renal pelvis, producing 'kinking' of the upper ureter. In these cases, only reduction pyeloplasty may be successful in relieving the obstruction.