Takehiko Hiroma

Surgical intervention for esophageal atresia in patients with trisomy 18

Trisomy 18 is a common chromosomal aberration syndrome involving growth impairment, various malformations, poor prognosis, and severe developmental delay in survivors. Although esophageal atresia (EA) with tracheoesophageal fistula (TEF) is a potentially fatal complication that can only be rescued through surgical correction, no reports have addressed the efficacy of surgical intervention for EA in patients with trisomy 18. We reviewed detailed clinical information of 24 patients with trisomy 18 and EA who were admitted to two neonatal intensive care units in Japan and underwent intensive treatment including surgical interventions from 1982 to 2009. Nine patients underwent only palliative surgery, including six who underwent only gastrostomy or both gastrostomy and jejunostomy (Group 1) and three who underwent gastrostomy and TEF division (Group 2). The other 15 patients underwent radical surgery, including 10 who underwent single‐stage esophago‐esophagostomy with TEF division (Group 3) and five who underwent two‐stage operation (gastrostomy followed by esophago‐esophagostomy with TEF division) (Group 4). No intraoperative death or anesthetic complications were noted. Enteral feeding was accomplished in 17 patients, three of whom were fed orally. Three patients could be discharged home. The 1‐year survival rate was 17%: 27% in those receiving radical surgery (Groups 3 and 4); 0% in those receiving palliative surgery (Groups 1 and 2). Most causes of death were related to cardiac complications. EA is not an absolute poor prognostic factor in patients with trisomy 18 undergoing radical surgery for EA and intensive cardiac management.

Airway lavage with exogenous surfactant in an animal model of meconium aspiration syndrome

Abstract Background : Meconium aspiration syndrome (MAS) is a major cause of respiratory morbidity and mortality in term infants, and occasionally causes serious respiratory disturbance. Viscous meconium debris in the trachea interferes with ventilation, and chest physiotherapy (CPT) is effective for removing secretions from the trachea. The effects of conventional exogenous diluted surfactant lavage combined with CPT were evaluated in a MAS animal model in a randomized controlled study.

Hernia of the Umbilical Cord and Associated Ileal Prolapse through a Patent Omphalomesenteric Duct: Prenatal Ultrasound and MRI Findings

Background: It is quite unusual for a fistula to communicate directly with the surface of the hernia sac, and associated prolapse of the ileum through a patent omphalomesenteric duct is also extremely rare. Objectives: We report a unique case of a fetus exposed to methimazole in utero, with a hernia of the umbilical cord and associated ileal prolapse through a patent omphalomesenteric duct. Methods and Results: In this case, the umbilical cord was attached to a small unruptured omphalocele, to the right of which a small everted loop of the ileum had evaginated. The hernia sac measured 2.5 cm and contained only ileum. The ileal prolapse was T shaped and had two visible mucosal ostia, and meconium was discharging from the ostium on the oral side. We confirmed that this loop of small bowel had prolapsed through a patent omphalomesenteric duct, which had a fistulous communication with the surface of the hernia sac. This resulted in the misleading prenatal findings on ultrasound and MRI, which were suggestive of a gastroschisis. Such a case with prenatal ultrasound and MRI findings has not been reported previously. Conclusion: The observed congenital anomaly in our fetus might be associated with prenatal exposure to methimazole.

Population‐based study of esophageal and small intestinal atresia/stenosis

The aim of this study was to describe the prevalence of esophageal atresia/stenosis and small intestinal atresia/stenosis in Nagano, Japan, together with associated anomalies, prenatal diagnosis and survival.

Sudden fetal hemorrhage from umbilical cord ulcer associated with congenital intestinal atresia.

There have been several reports of umbilical cord ulcer (UCU) associated with congenital intestinal atresia, many cases of which have been reported with fetal or neonatal death. Herein is described the case of a fetus with jejunal atresia complicated by acute massive intrauterine hemorrhage due to the perforation of UCU resulting in an intact survival. Although the onset of critical condition in the present case was noted due to continuous fetal heart rate (FHR) monitoring, it is necessary to establish the management of congenital intestinal atresia to prevent this life‐threatening fetal hemorrhage.

Monochorionic twin fetuses showing a reversal of donor-recipient phenotypes in severe twin-twin transfusion syndrome without oligo-polyhydramnios sequence

ABSTRACT  Antenatal sonographic diagnosis of twin–twin transfusion syndrome (TTTS) is based on findings of a twin oligo‐polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor‐recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.

Effects of heliox as carrier gas on ventilation and oxygenation in an animal model of piston-type HFOV: a crossover experimental study.

ObjectiveThis study aimed to compare gas exchange with heliox and oxygen-enriched air during piston-type high-frequency oscillatory ventilation (HFOV). We hypothesized that helium gas would improve both carbon dioxide elimination and arterial oxygenation during piston-type HFOV.MethodFive rabbits were prepared and ventilated by piston-type HFOV with carrier 50% helium/oxygen (heliox50) or 50% oxygen/nitrogen (nitrogen50) gas mixture in a crossover study. Changing the gas mixture from nitrogen50 to heliox50 and back was performed five times per animal with constant ventilation parameters. Arterial blood gas, vital function and respiratory test indices were recorded.ResultsCompared with nitrogen50, heliox50 did not change PaCO2 when stroke volume remained constant, but significantly reduced PaCO2 after alignment of amplitude pressure. No significant changes in PaO2 were seen despite significant decreases in mean airway pressure with heliox50 compared with nitrogen50.ConclusionThis study demonstrated that heliox enhances CO2 elimination and maintains oxygenation at the same amplitude but with lower airway pressure compared to air/O2 mix gas during piston-type HFOV.

Early neonatal onset carbamoyl‐phosphate synthase 1 deficiency treated with continuous hemodiafiltration and early living‐related liver transplantation

Takefumi Ishida, Takehiko Hiroma, Yasuhiko Hashikura, Masahisa Horiuchi, Keiko Kobayashi and Tomohiko Nakamura Division of Neonatology, Nagano Children’s Hospital, Nagano, Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Nagano, Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma

Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR‐1/2/3 and PDGFR‐α/β expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post‐resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib. Pediatr Blood Cancer

Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors.

Alagille syndrome is a multisystem developmental disorder characterized by bile duct paucity, congenital heart disease, vertebral anomalies, posterior embryotoxon, and characteristic facial features. Alagille syndrome is typically the result of germline mutations in JAG1 or NOTCH2 and is one of several human diseases caused by Notch signaling abnormalities. A wide phenotypic spectrum has been well documented in Alagille syndrome. Therefore, monozygotic twins with Alagille syndrome provide a unique opportunity to evaluate potential phenotypic modifiers such as environmental factors or stochastic effects of gene expression. In this report, we describe an Alagille syndrome monozygotic twin pair with discordant placental and clinical findings. We propose that environmental factors such as prenatal hypoxia may have played a role in determining the phenotypic severity.