Accuracy of antenatal ultrasound signs in predicting the risk for bowel atresia in patients with gastroschisis.

OBJECTIVE: Evaluate accuracy of prenatal ultrasound findings in predicting the risk of bowel atresia in patients with gastroschisis. METHODS: A retrospective study was conducted on 18 fetuses with a prenatal diagnostic of gastroschisis treated at University hospital of Saint Etienne France between 2002 and 2012. Ultrasound abnormalities were used to classify them into three groups: no ultrasound abnormality (n=4), oligohydramnios (n=9), intra-abdominal bowel dilatation ≥20.5mm (n=5). Postnatal outcomes were compared between groups. The threshold value of 20.5mm for the prediction of atresia was determined through the receiver operator characteristics curve. RESULTS: In the group with oligohydramnios, intra uterine growth restriction were significantly more frequent (p=0.015) and three newborns had serositis including two with secondary complications after the initial surgery. In the group with major intra-abdominal bowel dilatation, all had a narrow defect <10mm significantly more than other fetuses (p=0.002). Intra-abdominal bowel dilatation reaching 20.5mm started at a mean gestational age significantly lower than that of the other fetuses (23.3 versus 29.7 weeks p=0.02). On the five fetuses presented intra-abdominal bowel dilatation ≥20.5mm, four showed atresia and no other newborn has this complication (p=0.0016). The threshold value of 20.5mm has a sensitivity of 100% and a specificity of 92.9%. The area under the curve was equal to 96.4%. CONCLUSION: Intra-abdominal bowel dilatation ≥20.5mm seems to be associated with the risk of postnatal atresia. MRI could help to clarify a complicated or uncertain ultrasound aspect.

Can we select fetuses with intra-abdominal calcification for delivery in neonatal surgical centres?

BACKGROUND: Prenatal ultrasound (US) diagnosis of fetal intra-abdominal calcification (iAC) is frequently caused by an in utero perforation causing meconium peritonitis. Our ability to predict which fetuses will require postnatal surgery is limited. The aim of our study is to correlate iAC and associated US findings with postnatal outcome. METHODS: A single centre retrospective review of all cases of fetal iAC diagnosed between 2004 and 2010 was performed. Maternal demographics, fetal US findings, and outcomes (need for surgery and mortality) were collected. Descriptive and comparative statistical analyses were performed. RESULTS: Twenty-three cases of iAC were identified. There were no cases of fetal demise or postnatal deaths. Three liveborns (13%) required abdominal surgery at a median of 2 days (0-3) for intestinal atresia. US findings of iAC and dilated bowel with (p=0.008) or without (p=0.005) polyhydramnios predicted a need for postnatal surgery as did the combination of iAC, polyhydramnios, and ascites (p=0.008). Conversely, iAC alone or associated with oligohydramnios, polyhydramnios, ascites, or growth restriction did not predict need for postnatal surgery. CONCLUSION: The majority of fetuses with iAC on prenatal US do not require surgery. Associated US findings (bowel dilation) can be used to select fetuses for delivery in neonatal surgical centres.

Outcomes of fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt: a single-institution experience.

PURPOSE: The purpose of this manuscript was to examine the outcomes of patients with lower urinary tract obstruction (LUTO) treated with vesicoamniotic shunt (VAS) to improve the quality of prenatal consultation and therapy. METHODS: The medical records of all patients diagnosed with LUTO at our center between January 2004 and March 2012 were reviewed retrospectively. RESULTS: Of 14 male fetuses with LUTO, all with characteristic ultrasound findings, 11 underwent intervention. One patient received vesicocentesis alone, while 10 had VAS. Two fetuses additionally underwent cystoscopy (one with attempted valve ablation), and two had peritoneoamniotic shunts. Of 16 total VAS, 13 were placed successfully, 8 dislodged (median 7 days), and 1 obstructed (84 days). Two fetuses suffered in utero demise, and two have unknown outcomes. LUTO was confirmed in six of eight live-born fetuses. One patient died in the neonatal period, while seven survived. All six available at follow-up (median 3.7 years), had significant genitourinary morbidity. Five patients had chronic kidney disease, but only one has required dialysis and transplant. Three had respiratory insufficiency, and one required a tracheostomy. CONCLUSION: Despite significant perinatal and long-term morbidity, VAS offers patients faced with a poor prognosis an improved chance of survival. Our results underscore the need for further research into the diagnosis and treatment of LUTO.

Progesterone induced mesenchymal differentiation and rescued cystic dilation of renal tubules of Pkd1(-/-) mice.

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary disease affecting the kidneys, is caused in 85% of cases by mutations in the PKD1 gene. The protein encoded by this gene, polycystin-1, is a renal epithelial cell membrane mechanoreceptor, sensing morphogenetic cues in the extracellular environment, which regulate the tissue architecture and differentiation. However, how such mutations result in the formation of cysts is still unclear. We performed a precise characterization of mesenchymal differentiation using PAX2, WNT4 and WT1 as a marker, which revealed that impairment of the differentiation process preceded the development of cysts in Pkd1(-/-) mice. We performed an in vitro organ culture and found that progesterone and a derivative thereof facilitated mesenchymal differentiation, and partially prevented the formation of cysts in Pkd1(-/-) kidneys. An injection of progesterone or this derivative into the intraperitoneal space of pregnant females also improved the survival of Pkd1(-/-) embryos. Our findings suggest that compounds which enhance mesenchymal differentiation in the nephrogenesis might be useful for the therapeutic approach to prevent the formation of cysts in ADPKD patients.

Gastroschisis with intestinal atresia--predictive value of antenatal diagnosis and outcome of postnatal treatment.

PURPOSE: The purpose of this study is to evaluate (1) the predictive value of fetal bowel dilatation (FBD) for intestinal atresia in gastroschisis and (2) the postnatal management and outcome of this condition. METHODS: A retrospective review of all gastroschisis cases diagnosed in our fetal medicine unit between 1992 and 2010 and treated postnatally in our center was performed. RESULTS: One hundred thirty cases had full postnatal data available. Intestinal atresia was found at surgery in 14 neonates (jejunum, n = 6; ileum, n = 3; ascending colon, n = 3; multiple, n = 2). Polyhydramnios and FBD were more likely in the atresia group compared with infants with no atresia (P = .0003 and P = .005, respectively). Fetal bowel dilatation had 99% negative predictive value (95% confidence interval, 0.9-0.99) and 17% positive predictive value (95% confidence interval, 0.1-0.3) for atresia. Treatment of intestinal atresia included primary anastomosis (n = 5), delayed anastomosis (n = 2), and stoma formation followed by anastomosis (n = 7). Infants with atresia had longer duration of parenteral nutrition, higher incidence of sepsis, and cholestasis compared with infants with no atresia (P = .0003). However, the presence of atresia did not increase mortality. CONCLUSIONS: Polyhydramnios and FBD are associated with atresia. Absence of FBD in gastroschisis excludes intestinal atresia. In our experience, atresia is associated with a longer duration of parenteral nutrition but does not influence mortality. These findings may be relevant for antenatal counseling.

Multiple intestinal atresias associated with angiodysplasia in a newborn.

This is a report describing the association of multiple small bowel atresias with multifocal angiodysplasia of the intestinal wall in a newborn. To the authors' knowledge, such association has never been reported.

Prenatal ultrasound in the prediction of bowel obstruction in infants with gastroschisis.

OBJECTIVE: To assess the value of prenatal ultrasound in predicting bowel obstruction requiring surgery in fetuses with prenatal diagnosis of gastroschisis. METHODS: The database of our center was searched for cases with an antenatal diagnosis of gastroschisis. The ultrasound images were reviewed blindly to assess the presence of intra- or extra-abdominal bowel dilatation. Details of surgical procedures were noted and the discharge letters were obtained. Pediatric follow-up was also obtained from pediatric surgeons, general practitioners or parents. RESULTS: In the 10-year period between November 1998 and September 2008 there were 62 cases with a prenatal diagnosis of gastroschisis. Postnatal outcome was not available for five cases, four pregnancies underwent termination and intrauterine fetal demise occurred in five cases. A final population of 48 liveborn infants was available for analysis. Intra-abdominal bowel dilatation was identified in 14 of these 48 fetuses (29.2%) and extra-abdominal bowel dilatation in 30 (62.5%) fetuses on prenatal ultrasound images. Eight fetuses (16.7%) had bowel obstruction. The relative risk of bowel obstruction with intra-abdominal bowel dilatation was 4.05 (95% CI, 1.12-14.70). On the other hand, the relative risk of bowel obstruction with extra-abdominal bowel dilatation was 1.0 (95% CI, 0.37-3.70). Four babies died, two of whom had intra- and one had extra-abdominal bowel dilatation. CONCLUSIONS: Intra-abdominal dilatation of the bowel on prenatal ultrasound examination appears to predict postnatal bowel obstruction and the need for surgical resection. Extra-abdominal bowel dilatation is observed frequently on prenatal ultrasound scans, but is not predictive of bowel obstruction.

Predicting the outcome of newborns with gastroschisis.

OBJECTIVE: The objective of the study was to determine factors predicting outcome in newborns with gastroschisis. METHODS: A retrospective analysis of 155 consecutive cases admitted from 1 January 1990 to 31 December 2007 was performed. Prenatal ultrasound findings were available for 89 of 155 (57%) patients and were compared with final outcome. Both univariate and multiple regression analyses were used. RESULTS: All patients survived to discharge home. The primary outcome measure was length of stay. Multiple regression identified 4 factors associated with length of stay: (1) gestational age (P = .004), (2) nonelective silo (P < .001), (3) gastrointestinal (GI) complication (intestinal atresia, perforation, or resection) (P < .001), and (4) non-GI anomaly (P = .029). Non-GI anomalies occurred in 17 of 155 (11%) patients and tended to increase the risk of a nonelective silo or GI complication (59% vs 39%, P = .190). Dilated bowel (>10 mm) on prenatal ultrasound was associated with GI complications (22% vs 3%, P = .010). However, 78% of patients with dilated bowel on prenatal ultrasound did not have a GI complication. The absence of dilated bowel on prenatal ultrasound accurately predicted the absence of GI complications in 97% of cases. CONCLUSION: Prematurity, nonelective silo, GI complications, and non-GI anomalies predict the short-term outcome of newborns with gastroschisis. Prenatal ultrasound serves primarily to predict the absence of GI complications.

Prenatal resolution of megacystis possibly caused by spontaneous rupture of posterior urethral valves.

We report herein a case of resolution of severe megacystis, possibly caused by spontaneous rupture of posterior urethral valves during follow-up on a prenatal ultrasound. A 32-year-old woman presented at gestational week 15 for evaluation of fetal bladder enlargement. Prenatal ultrasonography revealed megacystis and posterior urethral dilatation. The longitudinal diameter of the bladder was 25 mm. Megacystis spontaneously resolved at gestational week 16. No association with urinary ascites was observed, and amniotic fluid volume remained normal throughout gestation. A boy was delivered vaginally at week 37. Apgar scores were 8 at 1 minute and 9 at 5 minutes. The neonate voided smoothly. Ultrasonography revealed a thickened bladder wall and normal kidneys and upper urinary tracts. Voiding cystourethrography showed dilatation of the posterior urethra but confirmed normal bladder capacity with smooth voiding and no vesicoureteral reflux. On day 57, remnant valves were incised. Postoperatively, filling cystometry showed a compliant bladder with no involuntary phasic contraction. At 7 months follow-up, the infant was asymptomatic, and ultrasonography showed some improvement of bladder wall thickness. Resolution of megacystis in utero appears to have resulted from spontaneous rupture of the posterior urethral valves. To the best of our knowledge, no similar cases have been previously reported.

Multiple jejunoileal atresia and colonic atresia managed by multiple primary anastomosis with a single gastroperineal transanastomotic tube without stomas.

Multiple jejunoileal atresia is a challenge to the pediatric surgeon. The aim of the study is to preserve bowel length and prevent the long-term complications of short bowel syndrome. The authors present a rare case of combined multiple jejunoileal atresia and colonic atresia managed by 9 primary anastomoses over a gastroperineal transanastomotic tube. This technique avoided the use of stomas and their attendant complications.

Mild pyelectasis diagnosed by prenatal ultrasound is not a predictor of urinary tract morbidity in childhood.

OBJECTIVES: To determine whether children with prenatally diagnosed mild pyelectasis have more urinary tract morbidity during childhood than children without this finding. METHODS: Case-control study in children with pyelectasis (anteroposterior diameter of the fetal renal pelvis of 5-10 mm). A validated questionnaire was sent to the parents of 208 cases and 416 matched controls. RESULTS: The questionnaire was returned by 146 cases and 250 controls. There was a male predominance in the case group (p = < 0.0001). There was no difference in voiding habits or in prevalence of urinary tract infections (UTI). The prevalence of UTI was high: 11.6% in cases and 10.0% in controls. The only difference was a higher prevalence of constipation in the case group (p = 0.003). Postnatally, 41 children had an ultrasound examination and 16 were referred to a paediatrician or urologist: 3 had persisting pyelectasis, 3 had a recurrent UTI and 1 required surgery (a pyeloplasty). Four of the controls were referred to a paediatrician or urologist: 3 had recurrent UTI and 1 had urinary incontinence. CONCLUSION: Children with a mild fetal pyelectasis do not have more urinary tract morbidity during childhood than children without this finding. Therefore, there seems to be no need for additional investigation after birth.

Outcome of fetal pyelectasis diagnosed antenatally.

UNLABELLED: Renal pelvis dilatation is a common anomaly detected at the 20-week anomaly scan. The aim of this study was to evaluate the postnatal outcome of fetal pyelectasis in an unselected obstetric population. This was a retrospective study of fetal pyelectasis detected at midtrimester anomaly scan. Fetal pyelectasis was classified as mild if the anteroposterior renal pelvis diameter measured >5 mm-< or= 7 mm, moderate >7-< or = 10 mm and severe as >10 mm. Persistant fetal pyelectasis was defined as >7 mm in the third trimester. RESULTS: During the study period fetal pyelectasis was identified in 74 women. 6 were excluded, as case records were not available. Mild pyelectasis was identified in 38/67(56.7%), moderate pyelectasis in 20/67(29.8%) and severe pyelectasis in 9/67(13.4%). None of the infants in the mild pyelectasis subgroup required surgery. 3/29(10%) in the moderate and severe pyelectasis subgroup required postnatal surgery. Of the 38 with mild fetal pyelectasis 13.1% had a positive postnatal diagnosis out of which 7.9% had vesico-ureteric reflux, 2.6% renal dysplasia and 2.6% pelvi-ureteric junction (PUJ) stenoses. CONCLUSION: 74% of pregnancies in the mild pyelectasis subgroup demonstrated spontaneous resolution. However persistent mild pyelectasis may lead to postnatal morbidity and should be followed up.

Serial transverse enteroplasty as primary therapy for neonates with proximal jejunal atresia.

Small bowel atresia is associated with a large size discrepancy between the proximal and distal segments of bowel that has traditionally been managed by resection of the dilated segment, tapering enteroplasty, or plication. Longitudinal intestinal lengthening is rarely performed at the time of the initial operation. Many patients with small bowel atresia also have a short length of residual small intestine secondary to in utero resorption. The authors present the clinical application of the novel intestinal lengthening procedure, the serial transverse enteroplasty, in a neonate with proximal jejunal atresia and suggest that it become part of the armamentarium for surgeons treating patients with this anomaly.

Overexpression of RET leads to vesicoureteric reflux in mice.

RET, a tyrosine kinase receptor essential for kidney development, has recently been shown to be important for the formation of the urinary tract. When RET is overexpressed in the HoxB7/Ret transgenic mouse, kidneys are small and cystic, and in some of the mice, the ureters are grossly dilated. Here, we report that the observed ureteral dilatation is associated with the urinary tract abnormality vesicoureteric reflux (VUR), in which urine flows retrogradely from the bladder to the ureter. Reflux was determined in vitro by injecting methylene blue into the bladders of HoxB7/Ret and wild-type mice. At postnatal day 1, 30% of HoxB7/Ret mice had VUR compared with 4% of wild-type mice (P < 0.05). The length of the intravesical ureteral tunnel was shorter in HoxB7/Ret mice compared with wild-type mice, on both the right and the left sides (P < 0.05), suggesting a basis for the higher incidence of VUR in these mutants. At embryonic day 11, the ureteric bud was found to exit more caudally from the mesonephric duct in HoxB7/Ret mice, and this may predispose them to VUR (P < 0.05). Wild-type and HoxB7/Ret mice were tested for reflux at embryonic day 17, and both showed a high frequency of VUR (59 and 75%, respectively). These results suggest that VUR may occur transiently during normal urinary tract development before the ureter has completed its insertion into the bladder. In the HoxB7/Ret mouse, overexpression of RET appears to delay the maturation of the distal ureter, resulting in postnatal VUR. The HoxB7/Ret mouse is thus an important model in which to examine how vesicoureteric reflux arises during urinary tract development.

Congenital segmental dilatation of the colon with anorectal malformation.

Segmental dilatation of the colon is a rare entity. The authors report unique case of segmental dilatation of the cecum and ascending colon with high anorectal malformation in a newborn, and the possible embryogenesis of this condition is discussed.

Embryonic hydromyelia: cystic dilatation of the lumbosacral neural tube in human embryos.

In a large collection of human embryos (the Kyoto Collection of Human Embryos, Kyoto University), we encountered five cases with abnormal dilatation of the neural tube at the lumbosacral level. In these examples, the central canal was enlarged, and the roof plate of the neural tube was extremely thin and expanded. The mesenchymal tissue was scarce or lacking between the roof plate and the surface ectoderm. This type of anomaly was assumed to be formed after neural tube closure and may be an early form of spina bifida. In two of the cases, some abnormal cells were found ectopically between the thin roof plate and the surface ectoderm. Morphologically, these cells resembled those forming spinal ganglia and could be of the neural crest origin. Since neural crest cells are pluripotent and can differentiate into a variety of tissues, such ectopic cells might undergo abnormal differentiation into teratomatous tumors and/or lipomas, which are frequently associated with spina bifida. We also discuss the definition of spina bifida and the classification of neural tube defects from the embryological and pathogenic viewpoints and propose a new classification of neural tube defects.

[Prognostic value of neonatal pyelectasia diagnosed in utero]. / Valutazione prognostica delle pielectasie neonatali diagnosticate in utero.

Sixty-six children (48 male-18 female) with prenatal diagnosis of pyelectasia that was conformed at birth were examined between 1986-1994. All newborns carried out urinalysis and urine culture and performed a renal sonogram to reconfirm the diagnosis at 1 month of age. After 3 month of life the pelvic dilatation was confirmed in 61 patients while 5 showed a complete disappearance, 61 patients underwent micturitional cystography that evidenced 30 renal units (RU) with moderate to severe vesicoureteral reflux. In the patients without reflux, a scintigraphy was carried out with DTPA or MAG 3 and/or IVP and evidenced a functional junctional pathology in 32 RU and an organic junctional pathology in 24 RU, a primary megaureter with pre-vesical stenosis in 6 RU and a pyelo-ureteral complete double system in 4 RU. The patients with organic stenosis or those patients with parenchymal damage due to the vesicoureteral reflux underwent surgical intervention during the 1st year of life while all the remaining patients are continuously monitored to date with biohumoral exams and echography. With these results we can safely confirm the important role of the sonogram in the initial diagnosis of pyelectasia and to its eventual modifications in order to benefit the patients with a nephro-urological pathology and direct them toward a correct follow up.

[The role of transforming growth factor-beta (TGF-beta) in the pathogenesis of primary megaureter. A histological and immunocytochemical study]. / Ruolo del transforming growth factor-beta (TGF-beta) nella patogenesi del megauretere primitivo. Studio istologico ed immunocitochimico.

Histologic and Transforming Growth Factor Beta (TGF-beta) immunostain patterns were sought in resected distal urinary tracts from 17 Primary Megaureter (PM) affected children, referred to surgery. Comparative observations were also carried out on embryonal and fetal ureteral buds of both humans and bovines. A reciprocal resemblance was mainly objectivized between the resected "narrowed" ureters of patients under 18 months, and the fetal ureteral buds at 26th and 38th gestational week. A development delay was irrespectively observed in PM "narrowed" ureters, at the longitudinal muscle-bundles in the parietal juxta-luminal compartment. A consistent TGF-beta immunostain cytoplasmic reaction there selectively depicted the growing mesenchymal lines, including both the undifferentiated single cells and the muscle-like profiled ones. These results agree with very recent reports perspecting a segmental maturation delay as a pathogenetic moment of PM. Because of the acquired potent TGF-beta inhibitory role on myoblasts differentiation, the present study substantiates a persistent TGF-beta role in perinatal ureter dilations.

Ectasia of the rete testis with ipsilateral renal agenesis.

Scrotal masses are a common problem in children. Cystic lesions usually are found to be hydroceles, while solid masses suggest the possibility of neoplasia. A rare cause of a cystic scrotal mass is ectasia of the rete testis. A review of the literature reveals only 1 case similar to the patient herein described. Both patients had agenesis of the ipsilateral kidney, which explained on the basis of the embryologic overlapping of the genitourinary system. Our patient bears clinical similarity to the ACI rat and correlation is made with this animal model system. Excision of the multiloculated rete testis cyst, rather than orchiectomy, appears to be curative.