Terry L. Buchmiller

Standardized reporting for congenital diaphragmatic hernia – An international consensus

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) remains a significant cause of neonatal death. A wide spectrum of disease severity and treatment strategies makes comparisons challenging. The objective of this study was to create a standardized reporting system for CDH. METHODS Data were prospectively collected on all live born infants with CDH from 51 centers in 9 countries. Patients who underwent surgical correction had the diaphragmatic defect size graded (A-D) using a standardized system. Other data known to affect outcome were combined to create a usable staging system. The primary outcome was death or hospital discharge. RESULTS A total of 1,975 infants were evaluated. A total of 326 infants were not repaired, and all died. Of the remaining 1,649, the defect was scored in 1,638 patients. A small defect (A) had a high survival, while a large defect was much worse. Cardiac defects significantly worsened outcome. We grouped patients into 6 categories based on defect size with an isolated A defect as stage I. A major cardiac anomaly (+) placed the patient in the next higher stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78% stage III, 58% stage IV, 39% stage V, and 0% for non-repair. CONCLUSIONS The size of the diaphragmatic defect and a severe cardiac anomaly are strongly associated with outcome. Standardizing reporting is imperative in determining optimal outcomes and effective therapies for CDH and could serve as a benchmark for prospective trials.

Effect of transamniotic administration of epidermal growth factor on fetal rabbit small intestinal nutrient transport and disaccharidase development

As fetal swallowing is documented in utero, supplementation of the ingested amniotic fluid with nutrients or hormones has been postulated as a potential prenatal treatment for intrauterine growth retardation (IUGR). To study the effect of epidermal growth factor (EGF) on the developing fetal small intestine, 12 pregnant rabbits underwent operation on day 24 of a normal 31-day gestation. Bilateral ovarian end fetuses underwent catheterization of their respective amniotic cavities with attachment to a miniosmotic pump. Study fetuses received recombinant human EGF at approximately 300 micrograms/kg/d for 1 week; controls received carrier solution only at an equivalent rate. On gestational day 31, fetuses were delivered by cesarean section and somatic measurements were recorded. The small intestine was harvested and proximal, middle, and distal regions were analyzed for lactase and maltase enzyme activity. Additionally, the uptake of radiolabeled glucose and proline was measured by a standard everted mucosal sleeve technique for each segment. Results were analyzed by Students paired t test and reported as mean +/- SEM. Nine fetal pairs survived (75%). Small intestinal (SI) length was increased in EGF fetuses (54.8 +/- 1.9 cm) versus control (50.4 +/- 2.7 cm) (P = .02). Lactase activity, reported as UE/g protein, was significantly increased in the proximal segments in the EGF-infused fetuses; maltase was significantly increased in both the proximal and middle segments (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Conditional Gata4 deletion in mice induces bile acid absorption in the proximal small intestine

Background and aims The transcription factor GATA4 is expressed throughout most of the small intestine except distal ileum, and restricts expression of the apical sodium-dependent bile acid transporter (ASBT), the rate-limiting intestinal bile acid transporter, to distal ileum. The hypothesis was tested that reduction of GATA4 activity in mouse small intestine results in an induction of bile acid transport in proximal small intestine sufficient to restore bile acid absorption and homeostasis after ileocaecal resection (ICR). Methods Bile acid homeostasis was characterised in non-surgical, sham or ICR mice using two recombinant Gata4 models in which Asbt expression is induced to different levels. Results Reduction of intestinal GATA4 activity resulted in an induction of ASBT expression, bile acid absorption and expression of bile acid-responsive genes in proximal small intestine, and a reduction of luminal bile acids in distal small intestine. While faecal bile acid excretion and bile acid pool size remained unchanged, the bile acid pool became more hydrophilic due to a relative increase in tauro-β-muricholate absorption. Furthermore, proximal induction of Asbt in both Gata4 mutant models corrected ICR-associated bile acid malabsorption, reversing the decrease in bile acid pool size and increase in faecal bile acid excretion and hepatic cholesterol 7α-hydroxylase expression. Conclusions Reduction of intestinal GATA4 activity induces bile acid absorption in proximal small intestine without inducing major changes in bile acid homeostasis. This induction is sufficient to correct bile acid malabsorption caused by ICR in mice.

Impairment of nutrient uptake in a rabbit model of gastroschisis

Infants with gastroschisis (GS) commonly require total parenteral nutrition and prolonged hospitalization because of intestinal dysfunction resulting from dysmotility and/or malabsorption. To investigate prepartum small intestinal (SI) nutrient absorption in GS, a fetal rabbit model was surgically created on gestational day 24 (term, 31 to 33 days) in 11 time-mated New Zealand White does in each left ovarian-end fetus. Each right ovarian-end fetus served as a control (C) and was manipulated only. All does, 10 of 11 GS fetuses (91%), and 8 of 11 C fetuses (73%) survived to gestational day 30. GS fetuses had significantly reduced total body weights, SI weights, and SI lengths compared with C fetuses. Using the everted mucosal sleeve technique, the uptakes of an amino acid (proline) and a sugar (glucose) were determined. The uptakes of proline per milligram SI, proline per centimeter SI, and glucose per milligram SI were significantly impaired in GS fetuses compared with C fetuses (P < .04 by Students paired t test). The uptake of glucose per centimeter SI was also reduced in GS fetuses, but not significantly. Uptake capacities (a measure of the entire SIs ability to absorb a given nutrient) were significantly reduced in GS fetuses compared with C fetuses (proline, 2,670 +/- 612 nmol/min/entire SI v 6,842 +/- 399 nmol/min/entire SI, P < .008 by Students paired t test; glucose, 402 +/- 69 nmol/min/entire SI v 950 +/- 103, P < .008 by Students paired t test).

Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration

Delivery of nutrients to the developing fetal gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. To examine the effect of intrauterine nutrient administration on the uptake capacity of the intestine, 16 maternal rabbits underwent bilateral ovarian-end transamniotic catheter placement on gestational Day 24. Study fetuses received a galactose solution; the contralateral controls received mannitol, a physiologically inert carbohydrate. Infusions were continued until Day 30 when an everted sleeve technique was used to measure radiolabeled uptake of both galactose and glucose in the proximal, middle, and distal small intestine. Mucosal scrapes were obtained, weighed, and the percentage of weight was calculated. Results were analyzed by ANOVA and Students t test with P less than 0.05 being considered significant. There were 2 maternal deaths with 11 fetal pairs surviving (79%). There was increased uptake of galactose in the study fetuses compared to controls reaching significance in the middle and distal segments. Similarly, glucose uptake was significantly increased in the proximal and distal segments. Mucosal weight was increased in all regions, reaching significance in the proximal segment. Total intestinal uptake of galactose and glucose was significantly increased in the study fetuses compared to controls. Intraamniotic galactose infusion caused not only upregulation of its own mucosal transport but also that of glucose, along the entire fetal small intestine, achieving statistical significance particularly in distal segments. Fetal implications for transamniotic feeding are under investigation.

Congenital gastrointestinal pacemaker cell tumor.

The interstitial cells of Cajal complex within the gut wall function as a pacemaker to direct peristalsis. Their neoplastic counterpart is the gastrointestinal pacemaker cell tumor, a spindle and/or epithelioid cell mesenchymal tumor previously known as gastrointestinal stromal tumor or incorrectly called leiomyosarcoma in some cases of older reports. Although numerous cases of gastrointestinal leiomyosarcomas have been documented in the English-language literature, no pediatric case of gastrointestinal stromal tumor or gastrointestinal pacemaker cell tumor has, to our knowledge, been recorded. Herein, we report a case of congenital gastrointestinal pacemaker cell tumor confirmed by immunohistochemistry and electron microscopy in a full-term male newborn.

Scrotal abscess following appendectomy

Abstract. Postoperative infectious complications in children following perforated appendicitis present in diverse ways. We present two unusual complications of appendectomy for perforated appendicitis: an acute scrotum after open and laparoscopic appendectomy. A␣retrospective review of two cases of scrotal abscess following appendectomy at our hospital as well as a MEDLINE search was performed to review the clinical presentation, etiology, type of treatment, and outcome of these patients. Although scrotal inflammation occurring postoperatively in a patient with perforated appendicitis may be due to an incarcerated hernia, it is much more likely to be due to a scrotal abscess. Patients without a patent processus vaginalis or inguinal hernia at initial presentation of peritonitis must be carefully followed in the postoperative period and explored early if testicular or scrotal pain becomes manifest.

Does the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure change outcomes for high-risk patients with congenital diaphragmatic hernia?

PURPOSE In the most severe cases of congenital diaphragmatic hernia (CDH), significant barotrauma or death can occur before advanced therapies such as extracorporeal membrane oxygenation (ECMO) can be initiated. We have previously examined the use of the ex utero intrapartum treatment (EXIT) to ECMO procedure (EXIT with placement on ECMO) in high-risk infants and reported a survival advantage. We report our experience with EXIT to ECMO in a more recent cohort of our patients with most severe CDH. METHODS Every patient with less than 15% predicted lung volume during January 2005 to December 2010 was included. We obtained data on prenatal imaging, size and location of the defect, and survival. RESULTS Seventeen high-risk infants were identified. All 17 (100%) received ECMO and required a patch. Six children were delivered by EXIT to ECMO, and only 2 (33%) survived. An additional patient was delivered by EXIT to intubation with ECMO on standby and died. Of the 10 children who did not receive EXIT, 5 (50%) survived. CONCLUSIONS No clear survival benefit with the use of the EXIT to ECMO procedure was demonstrated in this updated report of our high-risk CDH population. The general application of EXIT to ECMO for CDH is not supported by our results.

Effect of esophageal ligation on small intestinal development in normal and growth-retarded fetal rabbits.

Objective: The uninterrupted passage of amniotic fluid through the gastrointestinal tract is hypothesized to influence both intestinal and overall fetal somatic development. The effect of in utero esophageal ligation (EL) and therefore the exclusion of AF on somatic growth, small intestinal (SI) morphology and proliferation, and the expression of the glucose transporter sodium-glucose cotransporter 1 (SGLT-1) in both normal and intrauterine growth-retarded (IUGR) fetal rabbits were evaluated. Methods: Thirteen pregnant New Zealand white rabbits underwent surgery on day 24 of their normal 31-day gestation. Ipsilateral normal and IUGR fetuses underwent EL; the contralateral normal and IUGR fetuses underwent cervical exploration only forming 4 study groups (control-normal, control-IUGR, EL-normal and EL-IUGR). Rabbits were killed on day 31. Small intestinal villus height was measured, and epithelial cell proliferation was deter mined by proliferating cell nuclear antigen staining. Sodium-glucose cotransporter 1 messenger RNA (mRNA) and protein expressions were analyzed. Statistical analysis was performed using 2-way analysis of variance. Results: Esophageal ligation reduced fetal weight in IUGR by 15% and in normal by 10%. Villus height was significantly reduced in IUGR versus normal in both control and EL (control, P = 0.01; EL, P = 0.05). Intrauterine growth-retarded fetuses had reduced SI proliferation versus normal in both control and EL. Sodium-glucose cotransporter 1 mRNA production in EL fetuses was equal to control fetuses. Esophageal ligation-normal and EL-IUGR fetuses exhibited reduced protein levels and decreased staining for SGLT-1 in villus enterocytes. Conclusions: Amniotic fluid exclusion by in utero EL reduced fetal weight. Small intestinal proliferation was not affected by EL. Although SGLT-1 mRNA and protein were produced in all 4 groups, exposure of the fetal gastrointestinal tract to amniotic fluid appears necessary for proper brush border expression of nutrient transporter proteins.

Effect of esophageal ligation on the development of fetal rabbit intestinal lactase

To investigate the effect of normal fetal swallowing and amniotic fluid ingestion on small intestinal disaccharidase development, 13 pregnant New Zealand White rabbits underwent operation on day 24 of a normal 31-day gestation. The right ovarian fetus in the bicornuate uterus underwent esophageal ligation (EL), while the contralateral left fetus underwent cervical exploration only, and served as the control (C). Rabbits were sacrificed on gestational day 31, fetal somatic measurements obtained, and the midjejunum removed for determination of disaccharidase activity and protein content. There was one maternal death, and 9 of 12 fetal pairs survived the entire study period (75%). Results are reported as mean +/- SEM, analyzed by two-tailed Students t testing with P < .05 being considered significant. Fetal weight was decreased in EL (48.6 +/- 2.7 g) versus C (51.4 +/- 3.2 g) (P = .06). Small intestinal length decreased in EL (49.2 +/- 2.0 cm) versus C (54.9 +/- 1.1 cm) (P = .01). Midjejunal protein content (mg/mL homogenate) was also significantly decreased in EL (38.4 +/- 3.4) versus C (46.2 +/- 3.7) (P = .05). Sucrase activity was not detectable in either group. Lactase activity in jejunal mucosa was not effected when expressed as units of enzyme per milliliter of homogenate (EL = 0.357 +/- 0.03 v C = 0.373 +/- 0.04; P = .70) and units enzyme per gram of protein (EL = 38.8 +/- 4.2 v C = 34.2 +/- 4.6; P = .44). We have confirmed previous studies demonstrating decreases in somatic growth, small intestinal length, and mucosal nutrient transport in rabbit fetuses following esophageal ligation.(ABSTRACT TRUNCATED AT 250 WORDS)