Congenital Diaphragmatic Hernia Defects Research Articles

Synchronous ipsilateral Bochdalek and Morgagni diaphragmatic hernias: a case report

The etiology of congenital diaphragmatic hernia (CDH) is unknown. Phenotypic patterns of CDH defects provide clues about normal diaphragm development and the pathophysiology of CDH. We report a case of a patient who was diagnosed with CDH postnatally and was found on imaging to have simultaneous Bochdalek and Morgagni hernias on the right side. During the operative repair of these defects, an additional left-sided Morgagni-type defect was also found. To the best of our knowledge, this form of CDH has not been previously reported.

Parafollicular C-Cells of the Thyroid are Decreased in Patients with Congenital Diaphragmatic Hernia

Parathyroid and thymic anomalies related to embryonic neural crest dysfunction have been demonstrated in rats with congenital diaphragmatic hernia (CDH). These rats, like infants with CDH, have conotruncal, facial, and other neurocristal defects. The present study examines whether parafollicular C-cells (CC) of the thyroid, whose embryogenesis is related to that of the parathyroids and thymus, might also be abnormal in babies with CDH. Autopsy sections of the thyroids of 12 babies dead from CDH and of 11 controls were stained with anti-calcitonin antibodies. Calcitonin-stained areas and the histological distribution of CC within the thyroid gland were assessed. Mann-Whitney tests were used for comparison, with p<0.05 considered significant. The proportion of stained surface to total thyroid surface was significantly smaller in CDH babies than in controls (0.035±0.030% vs. 0.072±0.052%, p<0.05). A normal central CC location was demonstrated in both groups. Parafollicular thyroid C-cells are deficient in patients with CDH. These findings further support the involvement of neural crest dysregulation in the pathogenesis of CDH and the pertinence of using this experimental model to investigate the human condition. The clinical effects of this anomaly are unknown and probably irrelevant, but they are currently under scrutiny.

Downregulation of FGFRL1 Contributes to the Development of the Diaphragmatic Defect in the Nitrofen Model of Congenital Diaphragmatic Hernia

The nitrofen model of Congenital Diaphragmatic Hernia (CDH) displays a diaphragmatic defect of the Bochdalek-type and has been widely used to investigate the pathogenesis of CDH. However, the exact pathomechanism of the diaphragmatic defect is still poorly understood. Fibroblast growth factor (FGF) receptor-like 1 (FGFRL1), a member of the FGF receptor family, plays a key role in physiological diaphragmatic development. FGFRL1 is expressed in the fetal diaphragm at low levels in early gestation and its expression steadily increases, becoming most pronounced in later gestational stages. It has been reported that FGFRL1 homozygous null mice have thin, partially amuscular diaphragms and die at birth due to respiratory failure. The aim of this study was to investigate the hypothesis that FGFRL1 gene expression in the diaphragm is downregulated during the later gestational stages in the nitrofen CDH model. Timed pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation (D9). Cesarean section was performed on D18 or D21. Fetal diaphragms (n=40) were micro-dissected and divided into CDH group and controls. Total RNA was extracted from the diaphragms and the mRNA levels of FGFRL1 were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression of FGFRL1. Student's t-test and Mann-Whitney test were used, where appropriate. Statistical significance was considered for p<0.05. Relative mRNA expression levels of FGFRL1 were significantly decreased in the CDH group compared to controls on D18 (3.63 ± 1.65 vs. 6.04 ± 3.12, p<0.05) and D21 (1.36 ± 1.01 vs. 2.57 ± 1.34, p<0.05). Immunoreactivity of FGFRL1 was markedly decreased in the diaphragms of the CDH group compared to controls on D18 and D21. Our data provide strong evidence that downregulation of the FGFRL1 gene during the late stages of gestation may contribute to the development of the diaphragmatic defect in nitrofen-induced CDH.

Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Neonates: Lessons Learned

We sought to characterize our recent experience with thoracoscopic congenital diaphragmatic hernia (CDH) repair and identify patient selection factors. We reviewed the medical records of full-term neonatal (<1 month of age) patients who underwent thoracoscopic CDH repair between 2004 and 2008 (n = 15). We obtained data on prenatal diagnosis, characteristics of the CDH and repair, complications, and outcome. All patients were stabilized preoperatively and underwent repair at an average of 5.7 +/- 1.3 days. Six patients were prenatally diagnosed, including the 5 inborn. Thirteen defects were left-sided. All were intubated shortly after birth and 2 required extracorporeal membrane oxygenation (ECMO). Twelve of 15 (80%) patients underwent successful thoracoscopic primary repair, including 1 of the patients who required ECMO prior to repair. Conversion to open repair occurred in 3 of 15 (20%) patients because of the need for patch closure or intraoperative instability. Among those converted to open, all had left-sided CDH defects and 3 had stomach herniation (of 5 such patients). Patients spent an average of 6.9 +/- 1.0 days on the ventilator following repair. The average time until full-enteral feeding was 16.7 +/- 2.25 days, and average length of hospital stay was 23.8 +/- 2.73 days. All patients survived to discharge, and average length of follow-up was 15.3 +/- 3.6 months. Thoracoscopic repair of CDH is a safe, effective strategy in patients who have undergone prior stabilization. Stomach herniation is associated with, but does not categorically predict, conversion to open repair. ECMO use prior to repair should not be an absolute contraindication to thoracoscopic repair.

A 6-week-old Boy with Apnea and Abdominal Distention

A 6-week-old Boy with Apnea and Abdominal Distention

Predictors of gastroesophageal reflux in neonates with congenital diaphragmatic hernia

Purpose Gastroesophageal reflux (GER) is observed in 22% to 81% of neonates with congenital diaphragmatic hernia (CDH). The purpose of this study was to identify factors that may predict GER requiring fundoplication in neonates with CDH. Methods A retrospective chart review was performed on all neonates with CDH treated at our hospital from June 1997 to June 2005. Preoperative respiratory status, side of the CDH, and method of repair were assessed as predictors of GER and the need for fundoplication. Results Of the 42 patients with CDH, 3 died before intervention, leaving 39 patients eligible for study. All but 1 patient survived until discharge. Twenty-one (54%) developed GER of whom 9 (23%) required fundoplication. Although the side of the CDH was not a determinant of GER or the need for fundoplication, patch repair and the need for extracorporeal life support were determinants of both. Conclusions Gastroesophageal reflux is common among babies with CDH, although symptoms often resolve without surgical intervention. Infants with CDH defects requiring a patch repair and those requiring advanced physiologic support, especially extracorporeal life support, are likely to develop severe GER necessitating fundoplication. Early recognition and treatment of GER among high-risk patients may shorten hospital stay and minimize patient morbidity. Early fundoplication should be considered for those patients at the highest risk.

Implantation of a cone-shaped double-fixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia

Background Large defects in patients with congenital diaphragmatic hernia (CDH) are frequently closed with a polytetrafluoroethylene patch (PTFE). Intraoperative problems include lack of abdominal domain for the reduction of organs and closure of the abdominal wall. Main surgical postoperative complication is the recurrence of the hernia. We suggest a new and easy method of patch implantation, improving these problems, and report first follow-up results. Methods In our clinic, 103 children with CDH were treated, and 87 children underwent reconstruction of the diaphragm in the 5 years between 1998 and 2002. In 52 patients, a patch implantation had to be performed. We have been optimizing our complete pediatric and surgical procedure and present a new standardized technique of preparation and implantation of a PTFE patch. The flat patch is folded to a 90° cone. The cone is fixed in its form with few single stitches. It is implanted with an overlapping border of 1 cm circumferentially. The border is separately fixed with absorbable single stitches to keep from rolling up. The rough side of the patch points toward the rim of the diaphragm to enable ingrowth of the connective tissue. In a 1-year follow-up study, the recurrences in the 3 following groups of PTFE patches were studied: conventional implantation (simple patch without overlapping border), patch with separately fixed overlapping border, and cone-shaped patch with overlapping separately fixed border. Results Thirty-three patients were included in the study. After conventional PTFE-patch implantation, 6 (46%) of 13 patients developed reherniation. After PTFE-patch implantation with separately fixed overlapping border, 1 (11%) of 9 patients had a recurrent hernia. In the group with the PTFE-cone implantation, 1 (9%) of 11 patients developed a recurrence. Meanwhile, another 20 CDH patients received implantation of a cone-shaped patch, and no further recurrence occurred up to now. With the additional space (20 mL) provided by the cone-shaped patch, the closure of the abdomen was easier, and the fundus had intraoperatively a physiological position. Conclusion This optimized patch implantation technique in large diaphragmatic defects offers considerable advantages especially regarding recurrence of the hernia and closure of the abdomen, which are currently the most challenging surgical problems. 1. The cone-shaped 3-dimensional patch increases abdominal capacity. 2. Redundant chest capacity is reduced, and the reconstructed diaphragm shows a physiological shape. 3. The dome of the patch allows a physiological position of the gastric fundus and a normal Hiss angle, thus preventing gastroesophageal reflux. 4. Additional safety of the implantation is achieved by separate fixation of the overlapping border of the cone, preventing recurrence.

Abdominal muscle flap repair for large defects of the diaphragm

Repair of a large diaphragmatic defect in congenital diaphragmatic hernia (CDH) and eventration of the diaphragm (DE) is difficult, especially when this is an unexpected finding at surgery. A patch of synthetic material may not be available at short notice, especially in developing countries. We describe the repair of nine such defects by using an abdominal muscle flap comprising the transversus abdominis and internal oblique muscles based on the intercostal and subcostal vessels. Although reports of similar flap repairs have been published in the literature [1-5], these employed a subcostal incision for abdominal entry, which we believe jeopardizes the flap's vascularity. Thus, we prefer to use an upper abdominal midline incision for abdominal entry in all cases of CDH and DE.

Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation.

Congenital diaphragmatic hernia (CDH) is a significant clinical problem in which a portion of the diaphragmatic musculature fails to form, resulting in a hole in the diaphragm. Here we use animal models of CDH to test two hypotheses regarding the pathogenesis. First, the origin of the defect results from the malformation of the amuscular mesenchymal component of the primordial diaphragm rather than with the process of myogenesis. Second, the defect in the primordial diaphragmatic tissue is not secondary to defects in the developing lung. In c-met(-/-) mouse embryos, in which diaphragm muscle fibers do not form because of a defect in muscle precursor migration, the amuscular substratum forms fully. We show that a defect characteristic of CDH can be induced in the amuscular membrane. In Fgf10(-/-) mouse embryos that have lung agenesis we show that the primordial diaphragm does not depend on signals from lung tissue for proper development and that diaphragmatic malformation is a primary defect in CDH. These data suggest that the pathogenesis of CDH involves mechanisms fundamentally different from previously proposed hypotheses.

Nutritional morbidity in survivors of congenital diaphragmatic hernia

Purpose: The purpose of this report is to detail the nutritional sequelae seen in survivors of congenital diaphragmatic hernia (CDH) followed in a multidisciplinary clinic. Methods: Data on 121 surviving CDH patients seen between 1990 and 2000 were collected. Regression analysis was used to determine the impact of factors such as Apgar score, birth weight, extracorporeal membrane oxygenation (ECMO), and patch repair on outcomes associated with nutritional morbidity. Results: There were 100 left and 21 right CDH defects. Mean birth weight and 5-minute Apgar score were 3.1 kg (±0.8) and 6.8(±2), respectively. Extracorporeal membrane oxygenation was required in 43 (36%) patients and patch repair in 39 (32%). A gastrostomy was required in 39 (32%) patients and a fundoplication in 23 (19%) patients. The side of the defect did not affect the frequency of these procedures. Fifty-six percent of patients were below the 25th percentile for weight during most of their first year. Regression analysis found that duration of ventilation (P <.001) and the presence of a patch repair (P =.03) were independent variables predictive of failure to thrive thereby requiring a gastrostomy tube. Patch repair also was predictive of need for subsequent fundoplication caused by gastroesophageal reflux (P <.001). Twenty-nine patients (24%) had severe oral aversion. Risk factors were prolonged ventilation (P =.001) and oxygen requirement at discharge (P =.015). Two thirds of these patients subsequently improved. Conclusions: Nutritional problems continue to be a source of morbidity for survivors of CDH, particularly in the first year of life. Not surprisingly, patients who had prolonged intubation and prosthetic material at the gastroesophageal junction fared worse. Despite aggressive nutritional management, 56% of the population remained below the twenty-fifth percentile for weight. These data show the need for careful nutritional assessment in all CDH patients, especially those at high risk for malnutrition. J Pediatr Surg 36:1171-1176. Copyright © 2001 by W.B. Saunders Company.

Associated malformations and chromosomal defects in congenital diaphragmatic hernia.

In order to determine the frequency of associated malformations and chromosomal defects in patients with congenital diaphragmatic hernia (CDH) our experiences with CDH during the last 8 years (1985-1993) were reviewed. During the study period, 33 fetuses (prenatal group) with CDH were examined at our level III ultrasound department. In the same period 11 neonates (postnatal group) were admitted to our pediatric surgical unit after postnatal diagnosis of a CDH. Those cases had not been suspicious for CDH during prenatal level I scan. In 24 (72.7%) of the cases with CDH seen prenatally, at least one or more extradiaphragmatic malformations could be detected. Most of them affected the cardiovascular, skeletal, genitourinary and nervous system. Six (18.1%) fetuses had chromosomal abnormalities, especially trisomy 18. In contrast to these findings just 4 of the 11 babies (36.3%) seen postnatally had associated malformations and all of them had a normal chromosome set. Survival rate of fetuses with CDH and associated anomalies (7.1%) was poor, in contrast to those with an isolated CDH (43.7%). Prenatal ultrasound investigations being suspect for CDH should encourage the clinician to make further diagnostical efforts. This includes detailed ultrasound examination and cytogenetic analysis. Associated malformations as well as chromosomal defects are often present in affected patients.