Correction of severe thoracolumbar spondylolisthesis (grade 4) secondary to neurofibromatosis with posterior spinal instrumented fusion alone. A case report.

A 15-year-old teenager with Type 1 Neurofibromatosis presented with grade 4 spondylolisthesis over T12/L1 junction resulting paraparesis (Frankel D). Radiograph showed a Cobb angle of 88 degrees. Computed tomography scan showed dysplastic vertebral bodies, pedicles and facet joints of T11, T12 and L1 vertebra with complete T12/L1 facets dislocation. Magnetic resonance imaging confirmed presence of spinal cord compression. He underwent posterior instrumentation and posterolateral fusion (T8 to L4) using hybrid instrumentation. Extensive corticotomy of the posterior elements was followed by the use of large amount of bone graft. Post operatively, his neurology improved markedly back to normal. Radiographs showed a good correction of the deformity. He was immobilized in a thoracolumbar orthosis for six months. A solid posterior fusion was achieved at six months follow up. At 36-month follow up, he remained asymptomatic. This case report illustrates a successful treatment of a grade 4 thoracolumbar spondylolisthesis secondary to neurofibromatosis with posterior spinal fusion alone.

Malignant transformation of mesenchymal hamartoma of the liver: case report and review of the literature.

Here the first case in the literature of both mesenchymal hamartoma and malignant mesenchymoma occurring in a 6-year-old male child, at different times and at different sites in the liver, and also the possible malignant transformation of a mesenchymal hamartoma is reported. The tumor developed from a lesion in the right lobe that was overlooked initially during a left lateral segmentectomy at 18 months of age for a mesenchymal hamartoma. Malignant mesenchymoma is a rare and aggressive tumor. The origin of this tumor is not well understood. There has been no direct support to the hypothesis that malignant mesenchymoma may be the malignant counterpart of mesenchymal hamartoma. The authors provide clinical and histopathologic evidence in our case that suggests the possibility of malignant mesenchymoma arising from a mesenchymal hamartoma. This case emphasizes the need for complete removal of mesenchymal hamartoma and the need for long-term follow-up to detect multifocal lesion or malignant transformation.

Management of Hirschsprung's disease with reference to one-stage pull-through without colostomy.

BACKGROUND/PURPOSE: The authors evaluated the safety and benefits of 1-stage pull-through in comparison with staged repair of Hirschsprung's disease under circumstances prevailing in a developing country. METHODS: Forty-nine patients were treated for Hirschsprung's disease during a 7-year period between January 1991 and March 1998 at our institution, which is a tertiary referral center. Nine patients were excluded from the study, and the medical records of the remaining 40 patients were reviewed. RESULTS: Eighteen patients including 7 neonates underwent 1-stage pull-through, and 22 patients underwent staged correction. There was no mortality for patients undergoing one-stage treatment, but there was 1 death caused by anastamotic leak after a 2-stage repair. There was no substantial difference in the incidence of complications (38.8% v 45.45%) and the need for additional surgical procedures (33.5% v 45.45%) between the 2 groups. Seventy-one percent after 1-stage treatment and 80% after staged treatment had a satisfactory functional result, and the incidence of incontinence was 14% and 10%, respectively. Overall, the incidence of postoperative enterocolitis was low (7.5%). CONCLUSIONS: One-stage correction of Hirschsprung's disease is a safe procedure in all age groups. It offers economical and social advantages to families in developing countries. Benefits of 1-stage treatment include avoidance of multiple operations, elimination of complications associated with a colostomy, shorter duration of hospital stay, and completion of treatment at an earlier age. It is advisable to continue postoperative anal dilatation for a minimum period of 6 months to 1 year to reduce the incidence of enterocolitis.

Scanning electron microscopy shows inhibited gubernacular development in relation to undescended testes in oestrogen-treated mice.

The morphological relationship between transabdominal testicular descent and the 'swelling reaction' of the gubernaculum was investigated in oestrogen-treated fetal mice by using scanning electron microscopy (scanning EM). In addition, flutamide was also administered to pregnant mice to determine whether androgens cause gubernacular growth and transabdominal testicular descent in offspring. In oestrogen-treated fetal mice, scanning EM showed that both the gubernacular 'swelling reaction' and transabdominal testicular descent were inhibited, in addition to inhibition of Müllerian duct regression. The gubernaculum showed a flat, thin bulb (widest diameter 0.25 +/- 0.04 mm) and an elongated cord (1.28 +/- 0.41 mm) after oestrogen treatment in utero, which was significantly different in appearance from that in normal control mice (width 0.44 mm +/- 0.06 mm, p < 0.001; length 0.27 +/- 0.19 mm, p < 0.0001). However, flutamide-treated mice showed much more normal gubernacular enlargement and transabdominal testicular descent. The width of the gubernacular bulb after flutamide exposure was 0.44 +/- 0.05 mm, which was comparable to that in control animals; the length of the intra-abdominal gubernaculum (0.44 +/- 0.15 mm) was slightly longer than in controls (p < 0.02). These results suggest that both the swelling reaction of the gubernaculum and transabdominal testicular migration are blocked by prenatal exposure to oestrogen. However, oestrogen exposure of the fetus does not block the swelling reaction of the gubernaculum by acting as an antiandrogen.

The role of the genitofemoral nerve and calcitonin gene-related peptide in congenitally cryptorchid mutant TS rats.

We investigated whether previous gubernacular denervation in TS rats changes the gubernacular contractile response to or binding capacity of calcitonin gene-related peptide receptors. In TS rats there is excessive calcitonin gene-related peptide in the genitofemoral nerve and 85% of the male rats have cryptorchidism. TS rats and controls underwent genitofemoral nerve transection or sham operation at day 0. On day 3 gubernacula were cultured with or without calcitonin gene-related peptide to observe contractions. Gubernacular frozen sections were incubated with 125iodine calcitonin gene-related peptide with or without unlabeled calcitonin gene-related peptide. Exposed x-ray films were quantified by computerized densitometry. In the sham operated controls contractility increased from 15 to 55% by adding calcitonin gene-related peptide compared with 5% and 10%, respectively, in the TS rats. After genitofemoral nerve denervation exogenous calcitonin gene-related peptide increased contractility to 90% in controls and 75% in TS rats. Previous genitofemoral nerve transection increased specific 125iodine calcitonin gene-related peptide binding 21% in controls and about 100% in TS rats. Genitofemoral nerve transection in TS rats restored gubernacular contractile response to calcitonin gene-related peptide in vitro and doubled the binding capacity of calcitonin gene-related peptide receptors.

Physiological effects in vitro of calcitonin gene-related peptide on gubernacular contractility with or without denervation.

The gubernaculum in neonatal rats has been shown previously by direct observation to contract rhythmically in response to exogenous calcitonin gene-related peptide (CGRP), but the physiological properties of these contractions were unknown. In the first study the authors investigated gubernacular contractility in vitro using a strain gauge to see if there were characteristics of skeletal or smooth muscle. Both the frequency and the amplitude of contractions were significantly enhanced by CGRP, and isotonic tension of the gubernaculum and the duration of contractions were also increased after CGRP. The effect of CGRP on gubernacular contractions appeared several minutes after adding CGRP, and it was independent of the acetylcholine action, which induced only a single twitch response of the gubernaculum. In the second study the authors investigated the effect on gubernacular contractility of prior transection of the genitofemoral nerve (GFN), which contains CGRP. Vigorous contractions occurred in 85% of denervated gubernacular compared with 46% of controls (P < .01). These data provide the first quantitative evidence of rhythmic gubernacular contractions, and suggest that CGRP enhances gubernacular contractility by a direct effect independent of acetylcholine. Further, the contractile properties resemble those of differentiated cardiac muscle or primitive embryonic skeletal muscle. GFN transection enhances the gubernacular contractile response to exogenous CGRP, which is consistent with the GFN being the normal source of CGRP for the gubernaculum in vivo.

Primary neonatal Duhamel procedure using the ENDO GIA stapler.

The technique of performing the Duhamel procedure in the neonate with Hirschsprung's disease using the ENDO GIA stapler (originally designed for laparoscopic surgery) is described. This technique overcomes the problem of conventional staplers being too large to introduce into the neonatal anus.

Bladder, urethral, and vaginal duplication.

The authors report on an infant girl with bladder duplication. There was complete duplication of the bladder, urethra, uterus, and vagina, associated with a urogenital sinus and an anterior ectopic anus. Despite careful attempts at examination, endoscopy, and organ imaging, the anatomy was not completely defined before surgical exploration. A satisfactory cosmetic result and functional lower genitourinary tract has been obtained.

Absence of normal sexual dimorphism of the genitofemoral nerve spinal nucleus in the mutant cryptorchid (TS) rat.

Sexual dimorphism of the genitofemoral nerve spinal nucleus has been demonstrated in normal rodents. Calcitonin gene-related peptide is a neurotransmitter, present in the genitofemoral nerve, that has been implicated in the regulation of gubernacular migration and inguinoscrotal testicular descent. A combination of retrograde fluorescent labelling of the genitofemoral nerve and immunohistochemistry for calcitonin gene-related peptide was used in 1-3-day-old mutant TS rats with 85% incidence of congenital cryptorchidism and an absence of the normal sexual dimorphism of the genitofemoral nerve spinal nucleus was demonstrated. There was no significant difference between male and female nuclei with respect to fluorescent-labelled neurones as well as those immunoreactive for calcitonin gene-related peptide, in contrast to an obvious sexual dimorphism present in normal control animals. This lack of normal sexual dimorphism of the genitofemoral nerve nucleus is likely to be important in the pathogenesis of cryptorchidism in this animal model.

Subureteric Polytef injection in the management of vesico-ureteric reflux in children.

Subureteric Polytef injection is one of the alternatives now available for the management of vesico-ureteric reflux in children. The results of the treatment by one surgeon, over a 2 year period, were studied prospectively in 47 children (60 refluxing units). Following a single injection, reflux was abolished in 49 (82%) ureters and of the 11 failures, 10 ureters showed a reduction of the grade of reflux while one remained unchanged. A repeat injection was performed in nine of these ureters with success in five, persistence in two, and two children are awaiting a follow-up cystogram. The conservative success, with the addition of a second injection, was 90% (54/60). Of the four with unresolved reflux, two have low grade reflux and are free of infection, and two have had a ureteric reimplant, one of which was after a single injection, at the request of the parents. There were no instances of ureteric obstruction. These results show a viable, minimally invasive alternative to open ureteric reimplantation in the management of vesico-ureteric reflux in children.

Calcitonin gene-related peptide receptors in the gubernaculum of normal rat and 2 models of cryptorchidism.

We investigated calcitonin gene-related peptide binding in the gubernaculum from a normal rat, a TS rat (congenitally cryptorchid from unknown causes) and a flutamide rat (cryptorchid secondary to prenatal antiandrogen treatment). Gubernacular sections from 2-day-old male pups were incubated with 125iodine-calcitonin gene-related peptide with various concentrations of unlabeled calcitonin gene-related peptide. After exposure to x-ray film, developed film was quantified by computerized densitometry. The binding analysis showed that concentrations of calcitonin gene-related peptide receptors were 22.9 +/- 2.12, 13.5 +/- 1.70 and 30.3 +/- 2.63 (mean plus or minus standard error of mean, fmol./mg. polymer) for each rat, respectively, and there were significant differences between the normal and TS rats (p < 0.01), and the normal and flutamide rats (p < 0.05). However, there was no significant difference in the dissociation constant among the 3 models. This result shows that deficiency and excess of calcitonin gene-related peptide binding in the gubernaculum are associated with cryptorchidism. Calcitonin gene-related peptide released from the genitofemoral nerve may regulate its own receptor concentration to control gubernacular motility in vivo.

Prenatal androgen blockade with flutamide inhibits masculinization of the genitofemoral nerve and testicular descent.

Prenatal androgen blockade with the antiandrogen flutamide inhibits the inguinoscrotal phase of testicular descent. The evidence suggests that androgens may act indirectly via the sexually dimorphic genitofemoral nerve (GFN) to control this phase. Rats were exposed to flutamide on gestational days 16 through 19. Seven-day-old rats were subjected to retrograde fluorescent labelling of the GFN combined with immunohistochemistry for calcitonin gene-related peptide (CGRP), a neurotransmitter found in the GFN. Fluorescent-labelled and CGRP-immunoreactive neurons in the GFN spinal nucleus were quantified. Sexual dimorphism of the GFN nucleus was absent in the flutamide-treated rats but obviously present in control rats. Furthermore, control male nuclei had 24% more CGRP-immunoreactive neurons and 12% more fluorescent-labelled neurons than did flutamide-treated male nuclei. This study shows that prenatal androgen blockade with flutamide inhibits masculinization of the GFN, with significant reduction of its CGRP content. This supports the proposal that androgens act via the GFN, with CGRP as the second messenger, to control inguinoscrotal testicular descent.

The effect of flutamide on testicular descent in rats examined by scanning electron microscopy.

The effect of prenatal flutamide exposure on testicular descent was investigated by using scanning electron microscopy (SEM) in prenatal and postnatal rats. In 20-day-old fetal rats, SEM showed no significant difference in the degree of gubernacular development or testicular descent relative to the kidney between flutamide-treated (74.5 +/- 2.2 U) and control rats (73.3 +/- 1.5 U); however, there was significant inhibition in oestrogen-treated rats (44.3 +/- 2.2 U) (P < .001). (The distance between the kidney and the bladder neck was standardized to 100 U.) In 5-day-old rats, SEM showed inhibited downward growth of the processus vaginalis in flutamide-treated rats. The length of processus vaginalis below the inguinal ligament was 32.8 +/- 2.4 U in flutamide-treated rats and 51.7 +/- 1.8 U in controls (P < .001). In 30- to 35-day-old mature rats, the frequency of cryptorchidism was 41.3% for flutamide-treated rats and 0% for controls (P < .001). Some cryptorchid testes were located in the lower abdominal cavity (10.9%); others were in the suprainguinal position (26.1%) or on the line of descent in the inguinal region (4.3%). In the flutamide-treated group, no testes were located in the posterior abdominal cavity, near the kidney. These results suggest that transabdominal descent of the testis is independent of androgen action, but that androgens control inguinoscrotal descent of the testis by regulating gubernacular migration and the growth of the processus vaginalis.

Portal hypertension in children--the changing spectrum.

This report is an analysis of changing trends in the etiology and management of portal hypertension (PHT) in childhood. The study compared the 53 admissions to the Royal Children's Hospital from 1971 to 1991 (33 intrahepatic, 20 extrahepatic) with the 77 admissions (22 intrahepatic, 54 extrahepatic, 1 with a congenital anomaly of the mesenteric vein) from the previous 23-year period (1948 to 1971). In addition to the differences in etiology, there has been (1) an increasing role for sclerotherapy as a therapeutic modality (and with this, lessening of the role of surgery), (2) a different approach to investigation (particularly imaging techniques), and (3) the availability of organ transplantation.

Ontogeny of gubernacular contraction and effect of calcitonin gene-related peptide in the mouse.

The mouse gubernaculum undergoes inguinoscrotal migration in the first postnatal week and also shows rhythmic contractions in organ culture in response to calcitonin gene-related peptide (CGRP). This study aimed to investigate the ontogeny of gubernacular contractile activity and effect of CGRP in organ culture in relation to the normal time of migration. Two hundred eighty gubernacula from male mice of 17 and 19 days' gestation, and of postnatal days 0,2,4,7, 10, and 14 were studied. Half were cultured with CGRP 714 nmol/L, and the other half were cultured without CGRP as controls. All were examined daily (for 7 days) for contractions. In the control group, the cumulative percentages of contractile gubernacula increased from 5% to 100% with age; in the CGRP group, these values ranged from 65% to 100%. There were significant differences between the two groups from prenatal day 17 to postnatal day 4 (P values ranged from less than .001 to less than 0.05, respectively). With increasing age in the CGRP group, the highest contractile rates were observed at the fewest number of days in culture. From prenatal day 17 to postnatal day 4, the gubernaculum had increasing endogenous contractility, but there was low endogenous contractility without exogenous CGRP. Contractility of gubernacula was enhanced strongly by exogenous CGRP, and the culture days of the peak contractile rates lined up in the reverse order. These results suggest that the days of optimal gubernacular contraction with CGRP in vitro are in keeping with the days of natural migration in vivo. This is consistent with the hypothesis that CGRP (released from the genitofemoral nerve) is important for gubernacular migration.

Ureterocystoplasty: an extraperitoneal, urothelial bladder augmentation technique.

A technique of bladder augmentation is described in which the dilated ureter draining a unilateral, poorly functioning kidney is used to augment a small capacity, non-compliant bladder. This extraperitoneal bladder augmentation technique has been used in three boys with a history of congenital obstruction of the posterior urethra and ipsilateral vesicoureteric reflux.

The relationship among calcitonin gene-related peptide, androgens and gubernacular development in 3 animal models of cryptorchidism.

The relationship among calcitonin gene-related peptide (CGRP), a neurotransmitter in the genitofemoral nerve, androgens and gubernacular development was studied using rats treated prenatally with the antiandrogen flutamide and the mutant cryptorchid TS rat. We compared these 2 groups with the testicular feminization mouse with androgen insensitivity. Gubernacula from male TS rats and flutamide-treated rats were maintained in organ culture and examined for contractile response to CGRP. Controls were gubernacula from normal rats and vehicle-treated rats, respectively. TS rat gubernacula have an inhibited contractile response to CGRP, whereas flutamide-treated rat gubernacula have an exaggerated response. A similar exaggerated response to CGRP has previously been demonstrated in testicular feminization mouse gubernacula. These results revealed abnormalities in gubernacular contractile response to CGRP in these cryptorchid animal models, implying that CGRP and gubernacular contractility may have key roles in mediating normal inguinoscrotal testicular descent.

Exogenous calcitonin gene-related peptide causes gubernacular development in neonatal (Tfm) mice with complete androgen resistance.

It has been proposed that testicular descent is controlled indirectly by androgens acting on the central nervous system to mediate migration of the gubernaculum to the scrotum. Accumulating evidence suggests that the genitofemoral nerve may release a newly described neurotransmitter, calcitonin gene-related peptide (CGRP) to stimulate gubernacular motility during migration. This study aimed to determine whether exogenous CGRP could stimulate gubernacular migration in mice with complete androgen resistance (testicular feminization mouse [Tfm]). CGRP was injected into the right groin of neonatal Tfm mice at 2-day intervals until 2 weeks of age, when the length of the processus vaginalis was measured under a dissecting microscope. The processus vaginalis length in normal male littermates was 5.9 +/- 1.8 mm (mean +/- SD) while in the female it was 1.2 +/- 0.9 mm. Exogenous CGRP had no effect on either of these. In Tfm males CGRP caused a significant increase in the length of the processus vaginalis on the injected side (2.3 +/- 0.8 mm) compared with the uninjected side (1.4 +/- 1.0 mm). These results are consistent with the hypothesis that CGRP can replace, at least partially, the effect of androgens on gubernacular migration.

Calcitonin gene-related peptide stimulates motility of the gubernaculum via cyclic adenosine monophosphate.

Calcitonin gene-related peptide (CGRP), N-truncated CGRP fragments CGRP 8-37 and [Tyr0]-CGRP 28-37, and dibutyryl cyclic adenosine monophosphate (DBcAMP) were studied for their effects on the neonatal male mouse gubernaculum in organ culture. Rhythmic contractions were shown in 18% of control gubernacula, which were enhanced with CGRP, inhibited by CGRP 8-37 and not affected by [Tyr0]-CGRP 28-37. A total of 60 gubernacula was exposed to increasing concentrations of DBcAMP and the percentage of gubernacula showing rhythmic contractions increased from 18 to 60%. These studies demonstrate that the neonatal mouse gubernaculum exhibits endogenous contractility that can be enhanced with CGRP or DBcAMP. These results suggest that cyclic adenosine monophosphate may act as the intracellular second messenger for receptor bound CGRP in the gubernaculum. This finding is consistent with the hypothesis that CGRP from the genitofemoral nerve provides directional, chemotactic guidance for inguinoscrotal gubernacular migration during testicular descent.