[Fibroepithelial polyp of the ureter in a child. A case report]. / Polype fibro-épithelial de l'uretère chez l'enfant. À propos d'un cas.

Fibroepithelial polyp of the ureter is benign tumor of mesodermal origin that rarely occurs in children. The most common presenting symptoms are hematuria and flank pain by obstruction of the urinary tract. The etiology of this tumor is not clear. It occurs more frequently in boys and often arises in the proximal ureter and the ureteropelvic junction. The preoperative diagnosis is difficult. We present the case of a 10-year-old boy who had recurrent episodes in the left flank owing to polyps of the lumbar ureter of which the fibroepithelial nature was confirmed by the pathological examination of the surgical specimen. We discuss the clinical presentations, imaging, histological features and treatment options of this unusual tumor through a review of the literature.

Fetal lung growth in congenital diaphragmatic hernia.

BACKGROUND: In spite of significant therapeutic progress, the prognosis of congenital diaphragmatic hernia (CDH) remains pejorative in those forms in which the liver is herniated into the chest. The severity of this malformation relies on the pulmonary hypoplasia due to lung compression by the herniated viscera in the thoracic cavity, particularly the liver. This impaired growth concerns the whole pulmonary tissue, i.e. both the vessels and the alveoli. For the clinician, it is mandatory to know the evolution pattern of the lesions, to define the best time to treat them. AIM AND METHOD: The aim of this work was to study the pulmonary lesions along the gestation in fetuses affected byCDH. This morphological study was carried out on 134 human fetuses aged from 22 to 40 weeks of gestation. Anatomical and histological analysis focused on lung weight, alveolar count and wall thickness of the distal vessels. RESULTS: The results indicate that the pulmonary lesions worsen as the pregnancy continues, particularly beyond 30 weeks of gestation. CONCLUSION: Such an anatomical study should bring to the clinicians useful data to enhance the management of the patients.

Familial malrotation: report of three affected siblings.

We herein report the case of three siblings presenting with intestinal malrotation. Their medical history and circumstances of diagnosis are described. Barium meal demonstrated a minor duodenal anomaly in the mother. As far as we can ascertain, this is the third report of isolated familial malrotation in more than one generation, raising questions about its developmental mechanism. We thus highlight in what circumstances familial investigations should be undertaken in case of malrotation.

Pelvic development in the rabbit embryo: implications in the organogenesis of bladder exstrophy.

Current theses of the development of bladder exstrophy and its variants rely on defective evolution of the urinary tract and cloacal membrane. They do not account satisfactorily for the clinical features reported in children affected by exstrophy, especially the pelvic bone anomaly. We herein describe the normal development of the pelvic ring in the rabbit embryo and its chronological relationship with the lower urinary tract organogenesis. Our results suggest that these events are intricated and allow us to propose a novel mechanism to explain exstrophies.

Uncommon ureteric ectopias: embryological implications.

We herein report two rare ureteric ectopias, one in the uterus, the second in the rectum. These kinds of ectopias are not easily explained with regard to the classic embryological theories of the too-cranial or too-caudal origin of the ureteric bud on the mesonephric duct. We thus set out new explanations consistent with embryological studies on the narrow contact between the developing paramesonephric and mesonephric ducts, and on the so-called cloacal septation.

Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth.

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

Responsiveness of the Cochin rheumatoid hand disability scale after surgery.

OBJECTIVE: To assess the responsiveness of the Cochin functional disability scale for the rheumatoid hand after surgery. METHOD: In a prospective study, patients with rheumatoid arthritis (RA) scheduled for surgery of the wrist and/or fingers were evaluated within 48 h before surgery and at least 6 months after surgery. Clinical outcome measures included duration of morning stiffness, total score for tenderness, total score for swelling, visual analogue scale score for pain in the hands and wrists, a score for overall mobility of the wrist and the fingers, grip and pinch strength, the Hand Functional Index (HFI), the Kapandji index and the Cochin scale. Responsiveness was assessed with the paired t-test, the effect size (ES), the standardized response mean (SRM) and the non-parametric Spearman rank correlation coefficient (r(S)). RESULTS: Fifty patients (42 women) were evaluated twice at an interval of 7.16 +/- 2.10 months (mean +/- s.d.) (range 6-15 months). Thirty-six patients (72%) were very satisfied or satisfied with the results of surgery, seven (14%) were not satisfied or dissatisfied and seven (14%) were dissatisfied or very dissatisfied. The Cochin scale score improved at the second visit (P < 0.0001), with SRM and ES values of 0.66 and 0.58 respectively. The correlation of the change in Cochin score with patient overall satisfaction was r(S) = 0.40. Among the impairment measures, grip strength showed the best responsiveness (SRM = - 0.43, ES = - 0.36, correlation with patient overall satisfaction r(S) = 0.46). The change in Kapandji index had the best correlation (r(S) = 0.51) with patient overall satisfaction but its SRM and ES values were low (- 0.19 and - 0.10 respectively). CONCLUSION: The Cochin scale is responsive and appropriate for the assessment of the effects of surgical treatments on disability in RA hands.

Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy.

The main impediment to effective ex vivo liver gene therapy of metabolic diseases is the lack of experimental work on large animals to resolve such important issues as effective gene delivery, cell-processing techniques, and the development of appropriate vectors. We have used a nonhuman primate, as a preclinical model, to analyze the limiting steps of this approach using recombinant retroviruses. Seven monkeys (Macaca fascicularis) underwent the complete protocol: their left liver lobe was resected, a catheter was placed in the inferior mesenteric vein and connected to an infusion chamber, and the hepatocytes were isolated, cultured, and transduced with a retroviral vector containing the beta-galactosidase gene. The hepatocytes were harvested and returned to the host via the infusion chamber. Biopsies were taken 4-40 days later. No animal was killed in the course of the experiments. They all tolerated the procedure well. We have developed and defined conditions that permit the proliferation and transduction of up to 90% of the plated hepatocytes. A significant proportion of genetically modified cells, representing up to 3% of the liver mass, were safely delivered to the liver via the chamber. Polymerase chain reaction analysis detected integrated viral DNA sequences and quantitative analysis of the in situ beta-Gal-expressing hepatocytes indicated that a significant amount of transduced hepatocytes, up to 2%, had become integrated into the liver and were functional. These results represent substantial advances in the development of the ex vivo approach and suggest that this approach is of clinical relevance for liver-directed gene therapy.

Anatomical basis of surgical repair of hypospadias by spongioplasty.

Despite the numerous surgical procedures reported for hypospadias repair, little attention has been given to the precise assessment of penile anatomy in this malformation. In this study of 51 cases of hypospadias, we describe the particular anatomy of the corpus spongiosum encountered, highlighting its relationships with the other features observed in the different forms of this anomaly. It appears that the level where the corpus spongiosum diverges into two limbs particularly induces the degree of penile curvature that influences the severity in this malformation. We report a new technique of anatomic repair of the penis in hypospadias.

Anomalies of lateralization in man: a case of total situs inversus.

Total or complete visceral situs inversus is the complete inversion of position of the thoracic and abdominal viscera. The aim of this study is to report a case of complete situs inversus and to review our knowledge of the anomalies of lateralization. A case of complete sinus inversus was discovered incidentally during anatomic dissection in a female subject aged 87 years. The thoracic and abdominal organs had a position symmetric with the normal. This was associated with a common mesentery and incomplete rotation of the colon, placing the cecum under the left lobe of the liver. These alimentary anomalies were discovered in adult life during a surgical operation for small intestinal occlusion, as evidenced by the abdominal scar and peritoneal adhesions. No cardiac, pulmonary, splenic or facial sinus anomalies were encountered. The incidence of complete situs inversus is estimated as 1/8000 in the general population. It may be isolated or associated with malformations, especially cardiac or alimentary. It may be discovered in infancy because of associated anomalies but often remains asymptomatic and discovered by chance in adult life. Complete situs inversus may form part of the multiple malformational syndromes such as that of Kartagener, with recessive autosomal transmission (complete situs inversus, bronchiectasis, chronic sinusitis, male infertility), which represents 20-25% of cases of complete situs inversus. In view of the frequency of this type of anomaly, a knowledge of anomalies of lateralization is essential in clinical practice.

In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: feasibility and short-term follow-up.

In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing beta-galactosidase. Transduction efficiency was 75-85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1-2 x 10(7) transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3-4 10(7) hepatocytes by direct intrahepatic injection. All the fetuses survived without side effect. Donor cells were not apparent from histochemical staining and PCR reactions. There was no evidence of inflammatory reaction. These findings indicate that the protocole could be improved by increasing the number of transplanted cells and using specific hepatic promoters in the retroviral vectors to achieve an effective postnatal chimerism.

Anatomic study of the umbilical vein and ductus venosus in human fetuses: ultrasound application in prenatal examination of left congenital diaphragmatic hernia.

For clinicians it is very difficult to evaluate the prognosis of a left congenital diaphragmatic hernia (CDH) at prenatal ultrasound examination. Surgical studies show that the presence of a large part of the liver in the chest is a criterion of poor prognosis. However, ultra-sonography encounters some difficulties in determining the precise position of the liver in the thoracic cavity. The aim of this anatomic study was to define the relationship between the position of the liver and the path of the ductus venosus and of the umbilical v., which are easily recognizable at prenatal sonography. Twenty dead fetuses were used for the study (12 with a left CDH and 8 without). All fetuses underwent radiographic assessment, anatomic dissection and cross-sectional study. The angle between the umbilical v. and the ductus venosus in different planes was measured. The more the liver was in the thorax, the greater was the angle between the ductus venosus and the sagittal plane, and the less the angle between the ductus venosus and the umbilical v. These angles can be easily measured by prenatal ultrasound examination of the fetus. Our findings suggest that it is now possible to offer the clinician a new and reliable way to determine the prognosis of a left CDH before birth.

Surgical approach of an early mammalian embryo: the rabbit model.

We describe an experimental surgical model in early rabbit embryo (12.5 days of gestation). Twenty-one embryos were operated, of which 9 survived the first postoperative week and 5 had normal further growth until term. As far as we can ascertain, this is the first successful report of a surgical approach in early mammalian embryos. We think that this model may be useful for workers involved in the study of early congenital malformations.

Outcome of 116 moderate renal pelvis dilatations at prenatal ultrasonography.

To determine the incidence of urinary tract abnormalities detected in the presence of moderate fetal renal pelvis dilatation, we followed up pre- and postnatally 116 fetuses and children between 1985 and 1995. At prenatal ultrasound, 50 (43%) fetuses showed regressive dilatations, 57 (49%) a stable pattern, and 9 (8%) an evolutive pattern. In the presence of an evolutive dilatation, urinary tract obstruction was present in 8 cases. When a stable pattern was observed, i.e., a patent uropathy was present, surgical correction was performed in 27 of 53 (51%) cases. Regarding the postnatal evolution of 50 prenatal regressive moderate dilatations, we observed in 12 of 50 (24%) vesicoureteric reflux, of which 5 (10%) required surgical correction, and it is concluded that careful and extensive follow-up is mandatory.

Budd-Chiari syndrome following repair of a giant omphalocele.

We report a case of Budd-Chiari syndrome following repair of a giant omphalocele. Thrombosis of hepatic veins and of retrohepatic inferior vena cava may result from direct pressure on the hepatic venous outlet after visceral reduction and final abdominal wall closure.

Preclinical studies for cell transplantation: isolation of primate fetal hepatocytes, their cryopreservation, and efficient retroviral transduction.

Fetal hepatocytes are an attractive target for in utero cellular transplantation. Their use could provide a very efficient way for implanting normal or transduced cells into the livers of affected fetuses. Marking cells with recombinant retroviruses is a powerful tool for evaluating the chimerism of grafted animals. The technique relies on the ex vivo transduction efficiency of the engrafted cells. We have isolated fetal primary hepatocytes from nonhuman primates. The cells were cultured and transduced with a retroviral vector carrying the Escherichia coli beta-galactosidase gene. Optimal gene transfer efficiency was obtained 48-60 hr after plating and was as high as 90%. Cryopreservation had little effect on cell viability and infectivity: The viability of thawed hepatocytes remained high (75-85%) and the infection efficiency was identical to that of freshly isolated cells. Efficient ex vivo retroviral gene transfer into fetal hepatocytes provides an appropriate system for testing allogenic grafting and for modifying immunogenicity of engrafted cells. These results open up new perspectives for cell transplantation through cell banking.

[Hernia in children]. / Hernies de l'enfant.

Congenital hernia seems to be the right term to define "hernia in childhood". Especially in newborn and infant, it is possible to observe numerous different pathologies which have nothing in common apart their congenital origin. Some as inguinal or umbilical hernia are very commonly encountered and others us omphalocele, gastroschisis or diaphragmatic hernia are quite rare and involved in the field of prenatal diagnosis and neonatal surgery.

[Surgical approach on rabbit embryos. A model trial of bladder exstrophy]. / Abord chirurgical d'un embryon de lapin. Essai de modèle d'exstrophie vésicale.

We describe herein a new model of surgical approach of an early mammalian embryo. Indeed the developmental mechanisms of numerous congenital anomalies, such as bladder exstrophy, remain obscure, and progresses in their knowledge must be achieved to propose better treatments. But up to now all the successful reports in experimental models of early produced malformations concerned birds or batracians, whose development is very different from human. We used the rabbit. Twenty-five time matted does were operated at 12.5 days of gestation. Out of their 247 embryos, 99 underwent a surgical procedure. Forty-eight were injured in order to produce an exstrophy. In 18 cases, the embryo extruded from the uterine cavity and could not be reintegrated, and 2 sacs were found empty. The remaining 31 were only exteriorized. Nine additional does received intravenous teratogen at 12.5 days of gestation. In the group of operated embryos we obtained 6 full-term fetuses, one of whom had a cloacal exstrophy. No exstrophy was noted among the intact embryos, neither in the 87 fetuses submitted to the teratogen. We conclude that: it is possible to operate on an early mammalian embryo, and to obtain further growth until term and that the exstrophy we observed in one case resulted from the surgical specific procedure.

Anatomical basis of a common embryological origin for epispadias and bladder or cloacal exstrophies.

Epispadias, bladder exstrophy and its variants are in the first place usually considered as urological anomalies. Embryological theses and therapeutic approaches are mainly based upon this aspect. We challenge this point of view, in order to bring out a new axis of research about this still misknown pathologic field. A review of 16 cases of bladder exstrophy, 6 epispadias cases, and one cloacal exstrophy case, which had never been described before, revealed that the almost constant bony defect of the pelvic ring was linked with the severity of the visceral features, and with the continence status in epispadias cases. The commonly admitted theories about exstrophy development are based on a primary defect of the cloacal membrane. We suggest that the first anomaly could lie in a lack of rotation in the pelvic ring primordia.