Hiroomi Okuyama

Anomalies of the tracheobronchial tree in patients with esophageal atresia

To examine associated anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea, and their clinical consequences, bronchoscopic examination and follow-up studies were performed in 32 patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) over a 5-year period. To evaluate structural abnormalities of trachea, the ratio of circumferential length of cartilaginous trachea to circumferential length of membranous trachea (C:M ratio) was determined before surgical repair. In patients examined before and after surgical repair, the motion of the posterior tracheal wall was observed under spontaneous respiration. Fifteen of the 32 patients (47%) had abnormalities of the tracheobronchial tree such as ectopic right upper bronchus (12), congenital bronchial stenosis (4), and absence of the right upper bronchus (2). The C:M ratio of the 27 patients with EA (2.0 +/- 0.6) was significantly lower than that of controls (3.0 +/- 0.3); the ratio for the 10 cases with ectopic right upper bronchus (1.7 +/- 0.4) was significantly lower than that of other cases (2.2 +/- 0.5). The C:M ratio for the 12 patients who had atelectasis (1.7 +/- 0.3) was significantly lower than that of the 15 who did not have atelectasis (2.2 +/- 0.6). Of 24 infants, nine had bulging of the posterior tracheal wall synchronized with expiration, and their C:M ratio (1.8 +/- 0.2) was significantly lower than that of the 15 patients without bulging (2.2 +/- 0.6). These data show an association between anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea in patients with EA. Because these abnormalities may be related to the occurrence of respiratory disorders such as tracheomalacia and atelectasis, early bronchoscopic examination, including measurement of the C:M ratio and observation of the motion of the posterior tracheal wall under spontaneous respiration, may be useful in the care of patients with EA.

Re-evaluation of stomach position as a simple prognostic factor in fetal left congenital diaphragmatic hernia: a multicenter survey in Japan

To document outcome and to explore prognostic factors in fetal left congenital diaphragmatic hernia (CDH).

Prenatal diagnosis of congenital diaphragmatic hernia and perinatal care: assessment of lung hypoplasia

To assess the severity of lung hypoplasia, we have attempted to measure the lung thorax transverse area ratio (L/T) by using ultrasonic echography and to select immediate surgery after delivery by caesarean section. The evaluation of L/T for an index of lung hypoplasia was made by arterial blood gas data and clinical courses. Of 14 fetuses diagnosed, 13 had left sided CDH and one right sided case, from 11 to 38 weeks of pregnancy, 10 cases survived. The L/T in 14 fetuses with CDH was from 0.08 to 0.36 (mean 0.2 +/- 0.073) and was significantly lower than that of the controls. L/T was correlated best with data of arterial pH, PCO2, preductal A-aDO2 before operation and the duration of mechanical ventilation in survivors. Although L/T was also significantly low in the cases with severe grade, diaphragmatic patch closure and ECMO therapy, no significant differences were noted in L/T between survivors and non-survivors. These results indicated that L/T may predict the severity of lung hypoplasia in CDH and that the combination of perinatal management bases on prenatal diagnosis of CDH and ECMO support may improve the outcome of fatal CDH with severe lung hypoplasia.

Experience in tracheobronchial reconstruction with a costal cartilage graft for congenital tracheal stenosis

Although successful surgical management of congenital tracheal stenosis has been reported, it is still controversial as to the best operative procedure. Eleven infants with congenital tracheal stenosis were evaluated to confirm the efficacy of tracheobronchial reconstruction with costal cartilage graft. Symptoms ranged from recurrent respiratory infection to severe respiratory failure. All infants had other congenital anomalies in addition to tracheal stenosis. Notably, five infants had pulmonary artery sling and four infants had patent ductus arteriosus. Definitive diagnosis was made by bronchoscopy, results of which showed complete tracheal rings in all patients with severely compromised tracheobronchial lumens. Five infants had elongated stenosis involving nearly the whole length of the trachea, and five infants had segmental stenosis involving nearly one half the length of the trachea. One infant had bilateral stenosis of the main bronchi. Early experience included two deaths from problems related to the repair. The involvement of the carina and the distal portion of the trachea was associated with increased complications and a higher mortality rate. Currently, our preferred technique facilitated by extracorporeal membrane oxygenation (ECMO) includes carinal reconstruction with a thin-wall intraluminal stent. Bronchoscopy is essential for accurate intraoperative incision of the trachea, post-operative airway management for several weeks, and removal of the intraluminal stent.

A comparison of the efficacy of pyloromyotomy and pyloroplasty in patients with gastroesophageal reflux and delayed gastric emptying

PURPOSE Delayed gastric emptying (DGE) in children with gastroesophageal reflux (GER) is often treated with a gastric emptying procedure. Although pyloroplasty is the most common gastric emptying procedure performed, pyloromyotomy is easier to perform and is associated with less morbidity. The aim of this study was to compare the efficacy of pyloromyotomy and pyloroplasty in children with DGE and GER undergoing a fundoplication. MATERIALS AND METHODS We reviewed the charts of 54 patients with DGE who underwent pyloromyotomy (n = 29), or pyloroplasty (n = 25) along with a fundoplication. A technetium 99-labeled sulfur colloid liquid-phase gastric emptying study (GES) was performed in the pre- and early postoperative period (within 6 months after operation). Normal stomach emptying was defined as greater than 40% at 1 hour. Comparisons were made with regard to postoperative complication rate, incidence of redo fundoplication, length of postoperative hospital stay, and pre- and postoperative GES. RESULTS The pyloroplasty and pyloromyotomy group were comparable in terms of age, sex, operative indications, and neurological status. There was no significant difference in the GES between the two groups preoperatively. There was a trend toward a decreased incidence of early postoperative complications including gas bloat, wound infection, pneumonia, dysphagia, bowel obstruction and dumping syndrome in the pyloromyotomy (8, 28%) when compared with the pyloroplasty group (12, 48%, P = .10). The mean postoperative hospital stay was 10.6 +/- 1.4 days for the pyloroplasty group and 7.6 +/- 1.0 days for the pyloromyotomy group (P + .08). The incidence of a redo fundoplication was 8% in the pyloroplasty and 7% in the pyloromyotomy group. Postoperative gastric emptying increased significantly in both groups (pyloroplasty group, from 18.1 +/- 3.1 to 49.5 +/- 7.9%, P = .0005; pyloromyotomy group, from 19.3 +/- 2.1 to 41.2 +/- 3.7%, P = .0001). There was no significant difference in the postoperative GES between the two groups (P = .289). CONCLUSION Both pyloroplasty and pyloromyotomy performed in conjunction with a fundoplication resulted in a significant increase in early postoperative gastric emptying. There was no advantage of pyloroplasty over pyloromyotomy during this follow-up period. These data suggest that pyloromyotomy is an effective gastric emptying procedure in children with GER and DGE.

Prenatal diagnosis of abdominal wall defects and their prognosis

To determine whether associated anatomic features may be useful in predicting fetal prognosis, 43 fetuses who had ultrasonographic evaluation for abdominal wall defects during a 13-year period were reviewed. Thirty-one fetuses had omphalocele and were classified into three groups according to fetal ultrasonography results: ruptured omphalocele with exposed liver, giant omphalocele with exposed liver, and small omphalocele without liver herniation. Twelve fetuses had gastroschisis. Ten of the 12 fetuses with gastroschisis survived; one died in utero. Nine of the 12 with a small omphalocele survived. Ten of 12 fetuses with giant omphalocele survived, but six of the seven with ruptured omphalocele died of pulmonary hypoplasia and respiratory insufficiency. Ruptured omphalocele recognized in utero was accompanied by intrauterine growth retardation and liver herniation and frequently was associated with deformity of the spine, diaphragmatic defects, vesicointestinal fissure, and meningocele. These results indicated that, together with the deformity of the spine, rupture and absence of the covering membrane with an exposed liver (noted through fetal ultrasonography) may suggest a poor prognosis because of pulmonary hypoplasia.

The effect of epidermal growth factor on bacterial translocation in newborn rabbits

PURPOSE Epidermal growth factor (EGF), which is present in breast milk, has both trophic and maturational effects on intestinal mucosa. The aim of this study is to determine the effect of EGF on spontaneous intestinal bacterial translocation (BT) in formula-fed newborn rabbits, who have a high incidence of BT compared with breast-fed newborn rabbits. METHODS Sixty-one rabbit pups were divided into three groups: EGF(-), n=24, EGF(+), n=22, and breast-fed animals, n=15. Both the EGF(-) and EGF(+) groups were gavage fed a standard artificial formula three times daily. EGF was administered subcutaneously three times daily (1.5 microg/g body weight per day) in the EGF(+) group. The breast-fed group was fed by their mothers ad libitum. At 7 days of age, all rabbits were killed, and the mesenteric lymph nodes (MLN), liver, and spleen were cultured qualitatively for bacterial growth, while the cecum and ileum were quantitatively cultured. To determine the effect of EGF on mucus-producing cells, goblet cell numbers in the small intestine were quantified histologically. RESULTS There was no BT to MLN, spleen, or liver in the breast-fed group. The incidence of BT to MLN and spleen was significantly lower in the EGF(+) compared with EGF(-) group; (EGF[+]: MLN, 45%; spleen, 32%; Liver, 27%; EGF[-]: MLN, 79%; Spleen 67%; Liver 29%; in EGF[+] MLN and Spleen P<.05 vEGF[-]). There was no significant difference in cecal and ileal bacterial colonization between the EGF(+) and EGF(-) groups. The number of goblet cells in the small intestine was significantly lower in the EGF(-) group compared with the EGF(+) group as follows: EGF(+), 14+/-3; EGF(-), 9+/-3; breast-fed, 11+/-5 goblet cells per 100 epithelial cell nuclei; P=.013. CONCLUSIONS (1) EGF caused a significant decrease in spontaneous bacterial translocation in formula-fed newborn rabbits and was associated with an increase in the goblet cell number of the small intestine. (2) These changes occurred in spite of the fact that no changes in small bowel bacterial colonization were observed. (3) These results suggest, but do not prove, that EGF may provide protection for neonates from gut origin infection by improving the mucosal barrier function through increased goblet cell production, thus decreasing the incidence of spontaneous bacterial translocation in the newborn.

Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.

Summary Induced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment.

The current profile and outcome of congenital diaphragmatic hernia: a nationwide survey in Japan.

BACKGROUND/PURPOSE Few nationwide surveys have been reported regarding the perinatal status, clinical course and postnatal outcome of cases with congenital diaphragmatic hernia (CDH). The aim of this study was to review the current profile and the outcomes of a large cohort of CDH cases in Japan. METHODS A nationwide retrospective cohort study was conducted on neonates diagnosed to have CDH between January 2006 and December 2010. The questionnaires were sent to 159 representative regional institutions and 109 (68.6%) institutions responded to the preliminary survey which had 674 cases. Eleven institutions which had 60 CDH neonates did not respond to the second questionnaire, and 26 institutions had no cases. Finally, 614 CDH neonates from 72 institutions had been collected and were used in the detailed survey. The perinatal status, clinical course and the postnatal outcome were reviewed. Survival was defined as infants alive at hospital discharge, at the time of transfer or still in the hospital at the time of questionnaire, which was confirmed during the period from July 2011 to November 2011 by the investigators. RESULTS Four hundred sixty-three (75.4%) of 614 CDH neonates survived in this study. The overall survival rate of neonates with isolated CDH was 84.0%. A total of 444 (72.0%) patients were prenatally diagnosed, and had a survival rate of 70.8%. Four hundred thirty-three (70.9%) patients were treated with high-frequency oscillatory ventilation (HFOV) as the initial ventilation, 344 (56.0%) patients received inhaled nitric oxide (iNO) and 43 (7.0%) required extracorporeal membrane oxygenation (ECMO). The overall survival rates of the CDH neonates who had been treated using HFOV, iNO and ECMO were 74.3%, 68.3% and 37.2%, respectively. CONCLUSIONS This study demonstrated that the current status for CDH treatment in Japan and the overall survival rate were comparable to those of recent reports from other countries.

Meconium-related ileus in extremely low-birthweight neonates: etiological considerations from histology and radiology.

Background:  A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low‐birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live‐birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium‐related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified.