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We present the case of a boy with antenatally diagnosed bilateral testicular microlithiasis. Following annual surveillance the child developed metachronous bilateral epidermoid cysts. These were subsequently excised with testicular sparing surgery. Currently, there are only three cases of bilateral epidermoid cysts in the paediatric population, and none have been associated with testicular microlithiasis. This reignites the discussion regarding the histogenesis of epidermoid cysts and how its pathophysiology might relate to testicular microlithiasis. [ABSTRACT FROM AUTHOR]

Esophageal atresia (EA) is the most common congenital esophageal disorder. Radiological imaging facilitates diagnosis, surgical interventions, and follow-up. Despite this, standardized monitoring guidelines are lacking. We aimed to: (1) review the literature regarding radiation burden in children with EA; (2) establish the presence of guidelines for diagnosis and follow-up in children with EA. The systematic review was performed according to PRISMA protocol. Two investigators conducted independent searches (PubMed, Ovid, Cochrane Review) and data extraction. Analysis focused on pre- and post-operative imaging type and frequency to determine the radiation burden. Seven studies met the inclusion criteria (337 patients). All authors agreed upon the need to minimize radiation burden, recommending symptoms-guided management, use of dosimeters, and non-radiating imaging. One study identified a median 130-fold increase in cumulative lifetime cancer risk in children with EA compared with other babies in the special care unit. The most common investigations were X-ray and CT (pre-operatively), and X-ray and contrast swallow (post-operatively). Standardized guidelines focused upon the frequency and type of radiological imaging for children with EA are lacking. Children with EA are subjected to more radiation exposure than the general population. Implementation of non-radiating imaging (ultrasonography, manometry) is recommended.

Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called 'Rapid transit constipation (RTC)' first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7-21% of the population, with a higher prevalence in young children and with constipation type dominating in the young. While 60% improve with time, 40% continue with symptoms. First-line therapy for IBS in adults is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols which reduces symptoms in > 70% of patients. In children with functional gastrointestinal disorders, fructose intolerance occurs in 35-55%. Reducing fructose produced significant improvement in 77-82% of intolerant patients. In children with RTC and a positive breath test upon fructose challenge, we found that exclusion of fructose significantly improved constipation, abdominal pain, stool consistency and decreased laxative use. We hypothesise that positive breath tests and improvement of pain and bowel frequency with sugar exclusion diets in RTC suggest these children have IBS-C. These observations raise the possibility that many children with CIC could be treated by reducing fructose early in their diet and this might prevent the development of IBS in later life.

Purpose: Undescended testes (UDT) are subjected to heat stress, which can disturb gonocyte transformation as well as apoptosis. This study aims to describe the apoptosis pathway occurring during minipuberty of children with unilateral (UDT), and to investigate the role of inhibin-B., Methods: Testicular biopsies at unilateral orchidopexy of 10 boys (6-9 months old) with normal inhibin-B (n = 5) or low inhibin-B (n = 5) were selected for immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling) assay. Testicular tubules were labelled with antibodies against Anti-Müllerian hormone (AMH, Sertoli cell marker), mouse Vasa Homolog (MVH) and placental alkaline phosphatase (PLAP) (both germ cell markers), cleaved caspase3 (apoptotic marker), and followed by confocal imaging and cell counting with Fiji/ImageJ. Data were analyzed with GraphPad Prism., Results: In males with low and normal inhibin-B, there was no statistical difference (p > 0.05) in the percentage of testicular tubules containing TUNEL + cells, number of cleaved caspase3 ± germ cells/tubule, total number of germ cells/tubule, and the percentage of fibrotic tubules or number of Sertoli cells/tubule., Conclusions: These results suggest that inhibin-B does not regulate cell death of gonocytes and further studies are required to uncover any role of inhibin-B in gonocyte transformation.

Background/aim: Closure of the processus vaginalis (PV) is considered as the last step of testicular descent. Therefore, patent processus vaginalis (PV), and inguinal hernias are linked to cryptorchidism. As the National Australian incidence of orchidopexy has decreased over the previous 20 years, we aimed to explore the incidence of inguinal herniotomy (including hydrocele) over time in Australia., Methods: The National Department of Human Services (DHS) database, and Bureau of Statistics database were obtained for the years 1998-2017. The numbers of inguinal herniotomies in patients aged 0-4, 5-14 and 15-24 yearswere examined with ethical approval., Results: Over the 20-year period, over 87,000 inguinal herniotomy procedures were performed in males. The incidence per year in males decreased across all ages over the 20-year period, but was most pronounced in infants and toddlers. Similar to males, the incidence in females decreased over time, with the ratio of procedures per head of population decreasing in children under 5 years of age. The ratio of male: females varied according to ages, and was between 2.8 and 6.2 males: 1 female., Conclusion: This study suggests that fewer 0-4-year olds are undergoing inguinal herniotomy, compared with 20 years ago. This is likely due to a change in practice for the management of unilateral symptomatic hernias, from routine bilateral herniotomies, to unilateral surgery. As well as less aggressive surgical intervention for hydroceles in boys., Level of Evidence: III.

There is no consensus in the literature about the necessity for excision of testicular remnants in the context of surgery for an impalpable testis and testicular regression syndrome (TRS). The incidence of germ cells (GCs) within these nubbins varies between 0 and 16% in previously published series. There is a hypothetical potential future malignancy risk, although there has been only one previously described isolated report of intratubular germ-cell neoplasia. Our aim was to ascertain an accurate incidence of GCs and seminiferous tubules (SNTs) within excised nubbins and hence guide evidence-based practice. The systematic review protocol was designed according to the PRISMA guidelines, and subsequently published by the PROSPERO database after review (CRD42013006034). The primary outcome measure was the incidence of GCs and the secondary outcome was the incidence of SNTs. The comprehensive systematic review included articles published between 1980 and 2016 in all the relevant databases using specific search parameters and terms. Strict inclusion and exclusion criteria were ultilised to identify articles relevant to the review questions. Twenty-nine paediatric studies with a total of 1455 specimens were included in the systematic review. The mean age of the patients undergoing nubbin resection was 33 months and the TRS specimen was more commonly excised from the left (68%). The incidence of SNTs was 10.7% (156/1455) and the incidence of GCs, 5.3% (77/1455). Histological analysis excluding the presence of either SNTs or GCs was consistent with TRS, fibrosis, calcification or haemosiderin deposits. There is limited evidence on subset analysis that GCs and SNTs may persist with increasing patient age. This systematic review has identified that 1 in 20 of resected testicular remnants has viable GCs and 1 in 10 has SNTs present. There is insufficiently strong evidence for the persistence of GCs and SNTs with time or future malignant potential. Intra-abdominal TRS specimens may contain more elements and, therefore, require excision, although this is based on limited evidence. However, there is no available strong evidence to determine that a TRS specimen requires routine excision in an inguinal or scrotal position.

Introduction and Methods: In this review, we describe the common clinical scenarios that may be present to a paediatric surgeon when a patient has a disorder of sex development (DSD). Our aim was to prepare surgeons so that they can respond with correct approaches to diagnose and manage the given situations., Results: DSD present in three distinct clinical situations: in the neonate with some abnormality of the external genitalia; in the child undergoing surgical treatment for inguinal hernia or during open or laparoscopic orchidopexy or during hypospadias correction; and at or after puberty, which may be precocious or delayed or in an adolescent girl with masculinisation at puberty. We describe the clinical features, likely diagnoses and the recommended management pathway in these scenarios.

Background/purpose: Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food., Methods: Patients (n = 10, all males, 9.6 year; 4.25-15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed., Results: Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients., Conclusions: Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption.

Background: Rapid proximal colonic transit with anorectal holdup is a subtype of chronic constipation linked to food intolerance. We aimed to determine the effectiveness of dietary exclusion as a treatment for constipated children with rapid-transit constipation by scintigraphy., Methods: Questionnaires on diet and symptoms were mailed out to 125 children with chronic constipation and rapid proximal colonic transit on nuclear transit study at our institute between 1998 and 2014 years. Patients were given instructions and encouraged to undertake a six-food elimination diet targeting common protein allergens (dairy, wheat, soy, eggs, nuts, seafood). Answers were completed by circling an option or on visual analogue scale. Results were evaluated statistically using GraphPad Prism 6 by a Wilcoxon matched-pairs rank test. P < 0.05 was considered significant., Results: We received 44/125 responses, 26 patients [mean age 11 years (5-21)] had attempted elimination diet and 18 had not. Dairy and wheat were the most common foods eliminated and symptomatic improvement was greater for patients who had completely eliminated foods. Constipation, abdominal pain and pain on defecation were reduced (p < 0.01). Laxative usage decreased, although this was not statistically significant. Families encountered problems with dietary exclusion, particularly expense. Assistance from a dietician or nutritionist was sought by >50 % of families., Conclusion: Dietary exclusion is a promising strategy to treat constipation in children with rapid proximal colonic transit. However, it was hard for many families, demonstrating the need for identifying the cause more specifically and a better set of instructions for the family and/or dietitian to follow.

Background/aim: Undescended testis (UDT) occurs in ~2 % of newborn males, and occasionally these infants also have posterior urethral valve (PUV). The cause of this relationship is uncertain. We aimed to review the literature to identify publications documenting co-occurrence of UDT and PUV, and to summarise the theories of co-occurrence., Methods: A search of the literature (Embase, Medline, Pubmed; 1947-2015) was undertaken to identify publications describing the link between UDT in PUV patients, as well as PUV in UDT patients. Ten publications in English were found with both UDT and PUV: 9 articles describing the frequency of UDT in patients with PUV, and 1 article examining the frequency of PUV in infants with UDT., Results: UDT occurred in 12-17 % of PUV compared with 1-2 % in the control population, consistent with a 10-fold increase. PUV occurred in 1.2 % of UDT patients compared with 0.01 % in the control population, consistent with a 100-fold increase., Discussion: PUV leads to a 10-fold increase in occurrence of UDT, while the presence of UDT causes a 100-fold increase in occurrence of PUV. Four main theories of causation have been proposed, each of which have some merit but little supporting evidence, leaving the cause of simultaneous occurrence of PUV and UDT uncertain.

Slow-transit constipation (STC) is a newly described subtype of intractable constipation in children which we originally identified with deficiency of substance P in axons supplying the proximal colonic muscle. When nuclear transit studies became available, the patients were found to have slow proximal colonic transit, and responded to antegrade enemas. Using the appendicostomy, we found that there was reduced frequency in propagating sequences throughout the colon. We began testing whether transcutaneous electrical stimulation (TES) could improve motility and symptoms, and over several trials have now shown that TES is remarkably effective in treating children with STC, with long-lasting effects. TES holds promise for treating STC, as well as a range of gastrointestinal motility disorders.

Testicular descent occurs in two morphologically distinct phases, each under different hormonal control from the testis itself. The first phase occurs between 8 and 15 weeks when insulin-like hormone 3 (Insl3) from the Leydig cells stimulates the gubernaculum to swell, thereby anchoring the testis near the future inguinal canal as the foetus grows. Testosterone causes regression of the cranial suspensory ligament to augment the transabdominal phase. The second, or inguinoscrotal phase, occurs between 25 and 35 weeks, when the gubernaculum bulges out of the external ring and migrates to the scrotum, all under control of testosterone. However, androgen acts mostly indirectly via the genitofemoral nerve (GFN), which produces calcitonin gene-related peptide (CGRP) to control the direction of migration. In animal models the androgen receptors are in the inguinoscrotal fat pad, which probably produces a neurotrophin to masculinise the GFN sensory fibres that regulate gubernacular migration. There is little direct evidence that this same process occurs in humans, but CGRP can regulate closure of the processus vaginalis in inguinal hernia, confirming that the GFN probably mediates human testicular descent by a similar mechanism as seen in rodent models. Despite increased understanding about normal testicular descent, the common causes of cryptorchidism remain elusive.

Objective: In developing countries like Bangladesh, delayed presentation for disorders of sex development (DSD) is common, and provides some special problems for management. There remains significant controversy about appropriate sex assignment in this group. We aimed, therefore, to assess gender identity (GI) in 50 consecutive patients with DSD presenting to a referral centre in Chittagong, Bangladesh, and correlate it with Prader score, to see if the latter could be used to predict GI., Methods: A cross-sectional, case-control study of 50 consecutive children with DSD and 50 children with vascular anomalies was conducted in the Pediatric Surgical Clinic, Chittagong Medical College and Hospital. After informed consent, patients and controls provided oral answers to a GI questionnaire and had a detailed history and physical examination. Sex-typed activities were assessed by observations of a structured toy play and the child's selection of a toy to keep. Both patients and parents then completed the Child Game Participation Questionnaire., Results: There were no differences in age (2-16 years, mean 8.74) between controls and DSD patients (11 46, XX DSD, 32 46, XY DSD, 4 MGD, 3 ovo-testicular DSD). Fifteen of the DSD patients (30 %) came from consanguineous marriages and only 2 of the control patients had consanguinity of their parents. For the 13-question GI interview, there was no overall difference between DSD cases and controls. For the 46, XX DSD subgroup, there was a significantly higher score (11.1 ± 7.1) compared with control girls (4.5 ± 4.7) (p < 0.05), while for DSD and control boys, there was a positive correlation with age and GI (p < 0.01). Prader score correlated with GI score in both control (r = 0.91) and DSD patients (r = 0.75) (p < 0.01), DSD girls played significantly less with girls' toys than controls (p < 0.01), but there was no differences for the boys. Composite scores on GI and gender-related behaviour correlated with Prader score for DSD patients (r = 0.61) (p < 0.01)., Conclusion: This study supports the view that GI and gender-role behaviour should be assessed routinely in DSD patients presenting after the neonatal period, so that sex assignment is in accordance with behaviour. Prader scores showed a good correlation with GI and gender role behaviour.

Testicular descent is a complex developmental process involving anatomical and hormonal regulation. The gubernaculum undergoes a "swelling reaction" during the transabdominal phase and is mainly under the control of Insulin-Like Peptide 3 (INSL-3) and Mullerian Inhibitory Substance/Anti-Mullerian Hormone (MIS/AMH). The second phase of testicular descent is regulated by androgens and calcitonin gene-related peptide (CGRP) release from the sensory nucleus of the genitofemoral nerve (GFN). In rodents, the active proliferation of the gubernacular tip and cremaster muscle, its rhythmic contraction, as well as the chemotactic gradient provided by the CGRP result in eventual migration of the testis into the scrotum. This review illustrates the structural aspects and hormonal control of cremaster muscle development to better understand the mechanism of testicular descent in normal rodents and humans, compared to diseased rodent models. The analysis showed the cremaster muscle is formed from mesenchymal differentiation of the gubernacular tip and is not a direct passive extension of internal oblique muscle. Cremaster muscle matures slower than other body muscles, and the persistence of immature myogenic proteins seen in cardiac muscle allows rhythmic contraction to guide the testis into the scrotum. Finally, remodelling of the cremaster muscle enables gubernacular eversion. Further understanding of the molecular regulators governing the structural and hormonal changes in the cremaster muscle may lead to new advances in the treatment of undescended testes.

Purpose: Adult slow-transit constipation (STC) occurs predominantly in females and is associated with low numbers of substance P (SP)-containing nerves in colonic circular muscle., Aim: To determine if reduced SP nerves is female predominant in paediatric STC., Methods: Children with STC were identified from records of more than 600 nuclear transit studies (NTS) and intestinal biopsies done for intractable chronic constipation between November 1998 and March 2009. Colonic seromuscular biopsies collected from hepatic and splenic flexures, and sigmoid colon were processed for immunohistochemistry. Nerve fibre density in circular muscle containing SP was measured qualitatively by a pathologist., Results: Eighty-eight children with chronic constipation had both NTS and intestinal biopsies. Seventy-eight children (52 M; age 2-15.5 years; mean 7.7 years) had STC diagnosed by NTS. SP was reduced in 10/26 girls, but only 11/52 boys., Conclusion: In this sample, STC was more common in boys than girls. However, in girls with STC, SP deficiency occurred in 40%, when compared with 20% of boys. During puberty, the percentage of girls with reduced SP decreased, whilst the percentage of boys increased. These results suggest that STC is heterogeneous and that there are some gender differences, the implication of which requires further investigation.

Purpose: Transcutaneous electrical stimulation (TES) speeds up colonic transit in children with slow-transit constipation (STC). This study examined if concurrent upper gastrointestinal dysmotility (UGD) affected response to TES., Methods: Radio-nuclear transit studies (NTS) were performed before and after TES treatment of STC as part of a larger randomised controlled trial. UGD was defined as delayed gastric emptying and/or slow small bowel transit. Improvement was defined as increase of ≥1 Geometric Centre (median radiotracer position at each time [small bowel = 1, toilet = 6])., Results: Forty-six subjects completed the trial, 34 had NTS after stimulation (21 M, 8-17 years, mean 11.3 years; symptoms >9 years). Active stimulation increased transit in >50% versus only 25% with sham (p = 0.04). Seventeen children also had UGD. In children with STC and either normal upper GI motility (NUGM) and UGD, NTS improved slightly after 1 month (57 vs. 60%; p = 0.9) and more after 2 months (88 vs. 40%; p = 0.07). However, mean transit rate significantly increased with NUGM, but not UGD (5.0 ± 0.2: 3.6 ± 0.6, p < 0.01)., Conclusion: Transcutaneous electrical stimulation was beneficial for STC, with response weakly associated with UGD. As measured by NTS, STC children with NUGM responded slightly more, but with significantly greater increased transit compared to those with UGD. Higher numbers are needed to determine if the difference is important.

The sitz or plastic marker study for colonic transit has been around for many years. It is applicable where an X-ray machine exists, is widely used and is accepted as the gold standard for diagnosing constipation. Recently, radiopharmaceutical methods have been developed. The theme of this review is their possible roles in the assessment of paediatric bowel motility disorders in patients presenting to paediatric surgeons. This review presents data on total and segmental transit in normal adults and children and comparing the two techniques in adults. Reliability and reproducibility are presented. Normative data for colonic transit in adults and children are discussed and parameters for assessing abnormal transit are reviewed. Normal colonic transit takes 20-56 h. Plastic marker studies are more readily accessible, but the assessment may be misleading with current methods. Plastic markers show faster transit than scintigraphy. It is difficult to compare the two techniques because methods of reporting are different. Using scintigraphy, repeatability is good. Separation of normal from slow transit in the ascending colon is apparent at 24 and 48 h, but the determination of transit through the distal colon/rectum in adults may require studies of more than 7 days. In conclusion, plastic marker studies and scintigraphy show similar transit rates in young adults and children. However, scintigraphy has advantages of allowing transit through the stomach and small intestine to be measured and has proved useful in the diagnostic workup of children with intractable constipation.

Background: Slow transit constipation (STC) is a form of chronic constipation characterised by prolonged passage of faecal matter through the colon. It is diagnosed by demonstrating delayed colonic transit on gastrointestinal transit studies. Traditionally, radio-opaque marker studies are performed. Recently, radioisotope nuclear transit studies (NTS) have been used in our centre to assess gastrointestinal transit time. This study aimed to evaluate if there are changes in colonic transit in STC children resistant to standard medical treatment over a prolonged period., Methods: Children with STC resistant to standard medical therapy for > or =2 years who had undergone two separate NTS to assess their colonic transit (where the first study had identified slow colonic transit without anorectal retention) were identified after ethical approval. The geometric centre (GC) of radioisotope activity at 6, 24, 30 and 48 h was compared in the two transit studies to determine if changes occurred., Results: Seven children (4 males) with proven STC resistant to standard medical therapy and two transit studies performed at different times were identified. Mean age was 7.0 years (5.4-10.8 years) at first study, and 11.4 years (9.7-14.2 years) at second study, with a mean of 4.4 years (1-8.5 years) between studies. There was no significant difference in colonic transit at any timepoint in the two tests (paired t test)., Conclusions: We conclude that nuclear transit studies are reproducible in assessing slow colonic transit in children with treatment-resistant STC and demonstrate that conventional medical treatment over many years has no effect on underlying colonic motility.

Unlabelled: Chronic constipation in children is common and produces significant morbidity. Identification of the site of dysmotility in constipation may determine the cause and permit directed management. Scintigraphy differentiates constipated patients with anorectal hold-up from those with colonic slowing. Adults with colonic slowing demonstrate variation in the site of hold-up. However, in children with colonic slowing, variability in the site of hold-up has not been investigated., Purpose: The current study aimed to characterise colonic transit patterns in 64 children with chronic idiopathic constipation., Methods: Scintigraphic images were grouped visually by their transit patterns. Intra-observer variation was assessed. Scintigraphic data were analysed quantitatively., Results: Visual analysis of scintigraphy studies demonstrated normal transit (11/64), anorectal hold-up (7/64) and slow colonic transit (46/64). Transit characteristics in the slow transit group demonstrated three possible subgroups: pancolonic slowing (28/46), discrete hold-up in the transverse colon (10/46) and abnormal small and large bowel transit (8/46). Kappa testing demonstrated consistent characterisation (k = 0.79). Statistical analysis of scintigraphic data demonstrated highly significant differences from normal (P < 0.001) in the subgroups., Conclusion: Scintigraphy demonstrates three possible transit patterns in children with chronic constipation secondary to slow colonic transit.

Constipation is a common problem in children, with childhood prevalence estimated at between 1 and 30%. It accounts for a significant percentage of referrals to paediatricians and paediatric gastroenterologists. It commonly runs in families, suggesting either an underlying genetic predisposition or common environmental factors, such as dietary exposure. The peak age for presentation of constipation is shortly after toilet training, when passage of hard stools can cause pain on defecation, which then triggers holding-on behaviour in the child. At the time of the next call to stool the toddler may try to prevent defecation by contraction of the pelvic floor muscles and anal sphincter. Unless the holding-on behaviour is quickly corrected by interventions to soften faeces and prevent further pain, the constipation can very rapidly become severe and chronic. Until recently, this mechanism was thought to be the only significant primary cause of constipation in childhood. In this review, we will summarise recent evidence to suggest that severe chronic constipation in children may also be due to slowed colonic transit.

Interstitial cells of Cajal (ICC) act as pacemaker in gastrointestinal smooth muscle. In animals, small bowel dilatation produces a reduction in ICC numbers and in pacemaker function. With resolution of dilatation, ICC numbers and pacemaking function are partially restored. In human colonic disease states, dilatation is associated with dysmotility. The effect of dilatation on ICC distribution has not previously been examined in the human colon. Tissues from a neonate with colonic atresia and a 17-year-old adolescent with acquired megasigmoid were fixed, sectioned and incubated with anti cKit antibodies followed by fluorescent secondary antibodies. Distended and non-distended segments of colon were examined for ICC distribution using immunohistochemistry to c-Kit. Images were obtained with confocal microscopy. In both patients, there was a marked reduction in cKit-immunoreactive cells in the circular muscle and the myenteric plexus of the distended colon compared to the distal non-distended colon. Dilatation of the human colon is associated with a marked reduction in ICC. A resulting loss of pacemaker function could contribute to dysmotility associated with distension. Further studies assessing pacemaking function in human subjects and investigating reversibility of ICC disruption may allow new therapeutic strategies.

Recent studies of testicular descent suggest not only that the gubernaculum does not initially attach to the scrotum, but also that it must migrate from the groin. Two findings suggest that the gubernaculum may behave like an embryonic limb bud during this phase. First, the active growth centre is at the distal tip of the gubernaculum. Secondly, the gubernaculum is loose in the subcutaneous tissues beneath Scarpa's fascia. The free protrusion of the gubernaculum from the abdominal wall was so reminiscent of a developing embryonic limb bud, we thought that the biological controls of both processus may be similar. This review examines what is known about vertebrate limb bud development, and compares the mechanisms to what has recently been discovered in the gubernaculum. The hypothesis that both processes may be similar is initially consistent with the current facts, encouraging us to investigate this further experimentally.

Calcitonin gene-related peptide (CGRP) released from the genitofemoral nerve (GFN) is proposed to control gubernacular migration to the scrotum during inguinoscrotal descent. As previous studies suggested that both CGRP and androgens are necessary to stimulate gubernacular elongation and proliferation, this study aimed to test whether CGRP perturbed growth of the gubernaculum by exogenous injection in a rat model of GFN blockade with an intact androgen pathway. Sprague-Dawley rats (day 0, n = 34) were injected with capsaicin (sensory neurotixin) or vehicle. CGRP (25 microl of 2 x 10 5 molar concentration) Or castor oil was administered at the umbilicus 24 h later, then every other day thereafter for 10 days. Groups of rats were sacrified on days 8 and 28, and the tip of the gubernaculunx was identified in relation to the scrotum and umbilicus. The length of the processus vaginalis (PV) was measured. In group 1 (capsaicin and CGRP), at 8 days of age (n = 8) the testes were found in the intraabdominal or suprainguinal position in 87.5% (14 testes) and the tip of the gubernaculum was oriented more laterally than normal. However the mean PV length was 5.1 mm, which was shorter than control groups (9-10.8 mm) (P < 0.001, t-test). On the other hand, at day 28, the testes were located proximal to the internal inguinal ring in 66.7% (8 testes) with their gubernacular tip oriented in part towards the umbilicus. The mean of the PV length was 12.2 mm, which was significantly decreased compared to other groups (P < 0.001, t-test). In group 2 (capsaicin and castor oil) and group 3 (vehicle and CGRP) the testes of one rat in each group at 28 days of age were located in the abdomen at the internal inguinal ring with the distal gubernacular attachment lying free and directed caudally towards the scrotum, while the rest of the testes were found in the normal location. These findings suggest that chemical interruption of sensory nerves followed by CGRP injections in rats can perturb gubernacular growth and can change the direction of migration.

This paper reviews the history of clitoral surgery throughout the twentieth century. The changing operations, from amputation through to attempts to produce a normal clitoris mirror the changing attitudes and available knowledge. It also examines the current issues that arise out of available data on long-term outcomes of clitoroplasty.

Germ cell development is an active process in normal testes during the first 4 years after birth, with transformation of the neonatal gonocytes into adult dark spermatogonia and then primary spermatocytes. The hormonal regulation of these changes is not fully understood, with evidence both for and against a role for gonadotrophins and androgens. Early surgical intervention in infancy aims to prevent or reverse germ cell maldevelopment. Although hormonal treatment for maldescent has been shown to be ineffective, there is still controversy over whether it may be useful as an adjunct to surgery to stimulate germ cells. Current evidence suggests that hormonal therapy may not stimulate transformation of neonatal gonocytes but may trigger prepubertal mitosis of primary spermatocytes. Further studies are required to determine the role of hormone treatment on germ cell development.

The relationship of the testis to the peritoneal cavity, and hence its position as an intraperitoneal or extraperitoneal organ, remains controversial. Adult anatomy texts favour an extraperitoneal position during and after testicular descent, whereas journal articles favour an intraperitoneal position. Interestingly, there is no similar debate around the position of the ovary despite the common origin of each as indifferent gonads. Through direct observation and the literature review, we aimed to determine whether the testis should be considered an intraperitoneal or an extraperitoneal organ. The anatomical and embryological literature relevant to human and animal models was reviewed. Direct dissections were made in rats (n=8) during foetal development, postnatally, and in mature animals, allowing comparison of foetus with adult and male with female. The position of the human testis was also recorded in various pathological states. Direct dissection in rats reveals an intraperitoneal testis on a mesorchium during both foetal and postnatal life. Intraperitoneal testes are demonstrated in humans in cases of gastroschisis (where the testis may protrude through the periumbilical defect with the bowel), testicular torsion (where the testis is mobile within the peritoneum), and bell clapper testis (where the testes are identifiable as intraperitoneal). We conclude that the foetal testis is an intraperitoneal organ. In the adult rat the testis remains intraperitoneal. The postnatal human testis is intraperitoneal. The adult human testis is intraperitoneal but may appear extraperitoneal. The apparent discrepancy between the adult testis being intraperitoneal or extraperitoneal is likely to result from differences in the relative size of the tunica vaginalis between infant boys and elderly men.

Children with Down syndrome have an increased risk of cryptorchidism, but the reported incidence is unclear. In a proportion of these children, the testes are within the scrotum at birth but later appear to have ascended to an ectopic position. Records of patients diagnosed with trisomy 21 who had surgery for undescended testes in two tertiary paediatric centres over a 10-year period were examined. Information on liveborn males with Down syndrome was obtained from the Victorian Genetic Registry, and then the incidence of congenital and acquired undescended testes was determined. The incidence of undescended testes in Down syndrome was found to be 6.52% (24/368), with 4.35% (16/368) being acquired undescended or ascending testes. In conclusion, there is an increased incidence of cryptorchidism in Down syndrome; in particular, there is a significant proportion of acquired undescended testes.

Meckel's diverticulum is the most common congenital gastrointestinal anomaly. (99m )Technetium pertechnetate imaging (Meckel's scan) is the best noninvasive method used to diagnose this condition when heterotopic gastric mucosa (HGM) is present. Although cimetidine enhancement has been shown to improve sensitivity of the Meckel's scan, ranitidine enhancement has also been advocated; however, this recommendation is based on unpublished data. Thirty-seven children with confirmed Meckel's diverticulum were reviewed retrospectively. Of eight children with HGM in the Meckel's diverticulum who presented with profuse rectal bleeding and underwent the conventional Meckel's scan, three of them (37.5%) had a false negative study. Ranitidine, when administered either intravenously or orally for 24 h prior to the Meckel's scan, enhanced the sensitivity of this test to 87.5% in our patient cohort.

Ultrasonography (US) was used to study intussusceptions prospectively at Kiyama Hospital in 1999 and 2000 under the classification of small bowel intussusception (SBI) and large bowel or ileo-ileo-colic intussusception (LBI). The clinical features, management, outcome and etiology were analyzed. All LBIs and SBIs with ischemic symptoms and SBIs complicated by LBI were treated by enema reduction, whereas SBIs considered to be nonischemic were observed. SBI was seen in 21 patients with a mean age of 62.6+/-31.2 months. Four cases (19.0%) were diagnosed during the course of LBI. US showed mesenteric lymphoid hyperplasia in 15 (71.4%). Hydrostatic enema reduction was successful in 9/9, and SBI reduced naturally in the other 12 (benign SBI). LBI occurred in 38 patients with a mean age of 27.8+/-21.2 months. Mesenteric lymphoid hyperplasia was observed in 29 (76.3%). Hydrostatic enema reduction was successful in 37/38. SBI occurs more frequently and in a wider age group than previously considered. Many SBIs reduced naturally, suggesting that they were only transient invagination phenomena and should be called benign SBI. The frequent association of SBI with LBI and also the frequent association of mesenteric lymphoid hyperplasia with both SBI and LBI seem the key to the pathophysiology of intussusception.

The embryology of the normal esophagus and trachea is controversial. There are two main opinions regarding the role played by the tracheoesophageal (TE) septum. Similar controversy exists in explaining the embryology of anomalous TE development, mainly due to a lack of embryos demonstrating these anomalies at critical stages during development. Proposed theories can be divided into four main groups: intraembryonic pressure; epithelial occlusion; differential growth; and vascular occlusion. More recently, a new theory has been described based on analysis of anomalous TE development in adriamycin (doxorubicin)-exposed rat embryos. Impaired tracheal development, with the foregut developing into the trachea rather than the esophagus and associated with development of a dorsal pouch from the upper part of the foregut, gave rise to esophageal atresia with distal TE fistula. On the other hand, development of a ventral upper foregut pouch led to tracheal atresia. A laryngotracheo-esophageal cleft may result if no upper foregut pouches develop, with differentiation of the ventral half of the foregut into trachea and the dorsal half into esophagus. This review describes the basic theories of normal and abnormal TE development in mammalian embryos and presents new data related to this abnormality.

The role of the processus vaginalis (PV) during inguinoscrotal testicular descent remains controversial. Some authors propose passive dragging of the PV by the migrating testis, while others suggest active elongation. In addition, the exact site of growth is unknown. Our aim was to determine whether the PV actively proliferates at its tip or stretches passively during the inguinoscrotal phase of descent in the rat. Gubernacula were removed from Sprague-Dawley (SD) rats and congenitally-cryptorchid TS mutants. Animals (at days 3, 7, 10, and 11) were treated with bromo-uridine deoxyribose (BUdR) 2 h before death. BUdR incorporation into newly-synthesised DNA served as a marker for cell division. The gubernacula were processed for haematoxylin and eosin and immunoperoxidase staining. Three sites were examined: (1) the tip of the PV on either side of the gubernacular bulb; (2) the proximal gubernacular cord; and (3) the proximal parietal PV. At each site, 50 adjacent cells were counted and the number of positive cells recorded. The highest BUdR labelling in SD rats was at the tip (site 1) on day 3 (17/50) compared with sites 2 (11/50) and 3 (9/50) (P < 0.05). Labelling decreased by 7 and 11 days to similar levels in all three sites. In TS rats, labelling rates were lower at day 3 and were highest at the tip at day 11. These results suggest active growth of the caudal tip of the PV during testicular descent. In normal rats, the growth rate slows as the testis approaches the scrotum. By contrast, in TS rats growth continued longer. We propose that the PV elongates actively from the tip to allow the intraperitoneal testis to leave the abdomen in a special peritoneal diverticulum.

After surgical management of their oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF), most patients exhibit evidence of gastro-oesophageal reflux (GOR) and many have oesophagitis. However, the aetiology of the GOR is still controversial. This study was undertaken to document whether there are congenital abnormalities in the intra-abdominal oesophagus and the hiatus in the fetal rat with OA and TOF following exposure to adriamycin (ADR). Time-pregnant rats were injected daily with either saline or 2 mg/kg ADR intraperitoneally on gestational days (GD) 6-9. The fetuses (n = 56) from 8 litters were harvested on GD 21 for examination. The length of the oesophagus between the diaphragmatic crura and the gastro-oesophageal junction (GOJ) and the sizes of the stomach and the oesophageal hiatus were measured under a dissecting microscope. The length of the oesophagus between the diaphragmatic crura and the GOJ in the ADR-treated fetuses (0.85 +/- 0.37 mm) was significantly shorter than in control fetuses (2.41 +/- 0.32 mm) (P < 0.0001). The size of the stomach in ADR-treated fetuses (5.30 +/- 1.01 mm) was significantly smaller than in the controls (8.07 +/- 0.49 mm) (P < 0.001). Moreover, the size of the oesophageal hiatus in ADR-treated fetuses (1.16 +/- 0.43 mm) was markedly larger than in the controls (0.32 +/- 0.1 mm) (P < 0.0001). These results showed that the congenital abnormalities in ADR-treated rat fetuses may account for the oesophageal functional disorders seen after surgical correction in patients who have OA and TOF.

Three cases of urethral stricture due to balanitis xerotica obliterans (BXO) after hypospadias repair are reported. The first patient showed white, dense scarring on the prepuce before the hypospadias repair and developed a stricture of the urethra after the operation. The second and the third were uneventful for 6 and 2 years, respectively, after the hypospadias repair, and then developed urethral strictures. Pathologic diagnosis of the stenotic lesion is essential. Complete excision of the affected urethra with topical steroid ointment or sublesional triamcinolone injection is recommended for this condition. Although the complication of BXO after hypospadias repair is rare (3 out of 796 cases with hypospadias in our series), surgeons need to be aware of this condition as a cause for late onset of urethral problems.

The management of a baby born with a major disability presents one of the most significant ethical problems faced at the end of the second millenium. These problems concern the individual baby and its family, but society as a whole is and must be involved in their resolution. This article explores these issues as they impact on the contemporary surgeon confronted with changing medical, technical, and ethical considerations.

Adriamycin is teratogenic if given to pregnant rats. A wide range of anomalies involving the gastrointestinal, renal, and cardiovascular systems has been described, similar to the VATER association, yet it is not known if they are identical to the human pattern. The aim of this study was to document the visceral anomalies in rat fetuses exposed to adriamycin and to determine their similarities with the congenital defects in humans with the VATER association. The results revealed a spectrum of very similar anomalies. Furthermore, the characteristics of the tracheo-oesophageal anomalies had a lot of features in common with the human pattern. We conclude that the adriamycin-treated fetal rat is an excellent model for studying the VATER association.

Although the aetiology of oesophageal dysmotility after repair of oesophageal atresia and tracheo-oesophageal fistula (OA-TOF) remains controversial, oesophageal dysmotility also is present in isolated TOF or OA before surgery, suggesting a congenital cause. Our previous work with a model of OA-TOF in fetal rats demonstrated an abnormality in the course and branching pattern of the vagus nerve. However, little is known about the intramural nervous components of the atretic oesophagus. The intrinsic innervation of the atretic oesophagus was examined by immunohistological staining to see if there is an abnormality that might account for dysmotility. OA-TOF was induced in fetal rats by injecting adriamycin intraperitoneally into pregnant rats. Forty-eight controls, 40 OA-TOF, and 6 treated fetuses without OA-TOF were recovered. Whole-mount preparations of each oesophagus were stained with fluorescent antibodies against neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). Compared with control fetuses, the density of the nerve plexus, ganglia, and number of cell bodies per ganglion immunostained by NSE, VIP, or SP was significantly reduced in OA-TOF fetuses. CGRP-immunoreactive nerve fibres in the oesophageal wall of both control and OA-TOF animals were found to be connected with extrinsic nerve bundles. No plexus-like nerve fibre network was observed. The results of the present study demonstrated significant abnormalities of the intramural nervous components of the oesophagus in OA-TOF fetal rats, involving both the excitatory (SP-labelled) and inhibitory (VIP-labelled) intramural nerves. These abnormalities may underlie the oesophageal dysmotility seen in OA-TOF patients.

In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0-4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%-21% throughout the colon, and VIP was 39% in the caecum and 63%-65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%-6% and the VIP population was also low (22%-33%). After 3 weeks of age, the populations had stabilised at 18%-26% for SP and 52%-62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres.

A modified labioplasty to improve the cosmetic appearance after feminizing genitoplasty is described. Good results were obtained in all five patients in whom the technique was utilized.

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.

Associated congenital anomalies have emerged as the most significant prognostic factor in babies born with oesophageal atresia and/or tracheo-oesophageal fistula (OA-TOF). The most frequently encountered groups of anomalies are cardiovascular (CV) and gastrointestinal, the former being more significant from a prognostic point of view. Some, such as a right-sided aortic arch (RAA), vascular ring, or major heart defects, may alter the timing and surgical approach for the repair of OA-TOF or adversely affect the prognosis. The rat fetal OA model induced by adriamycin (Adr) has been described previously. In the present experiments, information was sought regarding the incidence and type of CV abnormalities in fetal rats obtained from Adr-treated dams. OA-TOF was induced in 24 of 36 fetal rats from Adr-treated dams. DV abnormalities were found in 18 (75%) OA-TOF fetuses and 10 (83%) Adr-treated fetuses without OA-TOF. The difference was not significant (P >0.05). The most frequently found anomalies were ventricular and atrial septal defects. A RAA was present in 8/36 fetuses and a double aortic arch in 2/36. A patent ductus arteriosus was present in all treated fetuses compared with two-thirds of controls. The findings in the present study emphasise the importance of CV anomalies in association with OA, and reinforce the value of the Adr-induced rat fetal OA model by adding to our knowledge of the basic embryogenesis of both OA and CV anomalies.