Bochdalek-type Congenital Diaphragmatic Hernia Research Articles

Safe thoracoscopic repair of recurrent congenital diaphragmatic hernia after initial open abdominal repair.

The optimal surgical approach for recurrent congenital diaphragmatic hernia (CDH) remains controversial. We compared the surgical outcomes of a thoracoscopic approach versus an open abdominal approach for recurrent CDH after initial abdominal open repair. The subjects of this comparative study were patients who underwent open abdominal or thoracoscopic surgery for recurrent CDH following an initial open abdominal repair. Among 166 patients with Bochdalek-type CDH, 15 underwent reoperation for recurrent CDH following an open abdominal repair. Seven patients underwent open abdominal surgery (group O) and eight underwent thoracoscopic surgery (group T). The operative duration was similar for the two groups, with less blood loss (17.2ml/kg vs. 1ml/kg, P = 0.001) and fewer intraoperative complications in the T group (n = 6 vs. n = 0 cases, P = 0.001). There was no significant difference in the number of postoperative complications (n = 1 vs. n = 1, P = 1.0) or in the number of patients with a second CDH recurrence (n = 2 vs. n = 1, P = 0.569) between the two groups. Thoracoscopic surgery is preferable to the open surgical approach for recurrent CDH following an initial abdominal open repair.

Novel abdomino-pelvic anomalies in Kagami-Ogata syndrome

Kagami-Ogata syndrome (KOS) is a rare genomic imprinting disorder of chromosome 14 with characteristic facial features, a small, bell-shaped thorax, muscular hypotonia, and abdominal wall defects. We present a case of a kidney incarcerated in a posterolateral Bochdalek type congenital diaphragmatic hernia (CDH), intestinal malrotation and stage 2 rectocele in KOS. Successful repair of CDH and malrotation was achieved with Ladd's procedure, CDH repair, Nissen fundoplication and gastrostomy tube placement. She had no post-operative complications and is currently tolerating 100% enteral feeds. CDH, intestinal malrotation and rectocele have not been previously reported in KOS. Despite overall poor prognosis, KOS patients with CDH and malrotation can be repaired successfully with improvement in quality of life.

The management of Bochdalek congenital diaphragmatic hernia: a single center experience and review of the literature

Objectives: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly of the diaphragm with pulmonary hypoplasia and persistent pulmonary hypertension and has serious consequences. Despite recent diagnosis and treatment strategies, CDH is still a challenging condition. We aim to present our clinical experiences of CDH, and review of the literature. Methods: Data of CDH patients who were operated in our clinic between January 2010 and September 2018 were obtained from the patient's chart. The clinical course and results of the patients with Bochdalek type CDH were reviewed. Results: We performed diaphragmatic closure in 16 patients with Bochdalek CDH during study period. Fourteen (82%) cases were diagnosed antenatally. In 5 (29%) patients, preoperative pulmonary hypertension developed and nitric oxide was administered. Twelve of the sixteen patients (75%) underwent primary repair and 4 of them underwent prosthetic patch. Three patients were repaired thoracoscopically. Five (31%) patients died due to severe persistent pulmonary hypertension on postoperative period. There was no recurrence in our patients who were followed-up for a mean of 27 months. Conclusion: In the management of Bochdalek CDH, the clinical success has been increasing in parallel with the important developments with the application of new treatment modalities in the neonatal intensive care units and new surgical techniques in recent years.

Congenital diaphragmatic eventration and hernia sac compared to CDH with true defects: a retrospective cohort study

Congenital diaphragmatic eventration (CDE) and congenital diaphragmatic hernia (CDH) with or without hernia sac are three different types of congenital diaphragmatic malformations, which this study evaluates. All surgically treated patients with CDE or Bochdalek type CDH between 2000 and 2016 were included in this retrospective analysis. Demographics, CDH-characteristics, treatment, and clinical outcome were evaluated. In total, 200 patients were included. Patients with an eventration or hernia sac had no significant differences and were compared as patients without a true defect to patients with a true defect. The 1-year survival of patients with a true defect was significantly lower than patients with no true defect (76% versus 97%, p = 0.001). CDH with no true defect had significantly better short-term outcomes than CDH with true defect requiring patch repair. However, at 30 days, they more often required oxygen supplementation (46% versus 26%, p = 0.03) and had a higher recurrence rate (8% versus 0%, p = 0.006) (three eventration and two hernia sac patients). Conclusion: Patients without a true defect seem to have a more similar clinical outcome than CDH patients with a true defect, with a better survival. However, the recurrence rate and duration of oxygen supplementation at 30 days are higher than CDH patients with a true defect.What is Known:• Congenital diaphragmatic hernia with or without hernia sac and congenital diaphragmatic eventration (incomplete muscularization) are often treated similarly.• Patients with hernia sac and eventration are thought to have a relatively good outcome, but exact numbers are not described.What is New:• Congenital diaphragmatic eventration and patients with hernia sac seem to have a more similar clinical outcome than Bochdalek type CDH with a true defect.• Patients without a true defect (eventration or hernia sac) have a high recurrence rate.

Early surgical complications after congenital diaphragmatic hernia repair by thoracotomy vs. laparotomy: A bicentric comparison

PurposeThe surgical strategy for congenital diaphragmatic hernia (CDH) repair remains debated and mainly depends on the training and preference of the surgeon. Our aim was to evaluate the occurrence and nature of surgical reinterventions within the first year of life, following repair through thoracotomy as compared to laparotomy. MethodsThis is a retrospective bi-centric cohort study comparing postero-lateral thoracotomy (n = 55) versus subcostal laparotomy (n = 62) for CDH repair (IRB: MP001882). We included neonates with isolated, left-sided, Bochdalek-type CDH who were operated on between 2000 and 2017, and had a minimum follow-up of 1 year. Excluded were patients treated prenatally and/or had extra-corporeal membrane oxygenation. Outcomes were occurrence and nature of surgical reinterventions and mortality by 1 year of life. ResultsBoth groups had comparable neonatal severity risk profiles. The overall surgical reintervention rate by 1 year of age was higher in the thoracotomy group (29.1% vs. 6.5%; p = 0.001), mainly because of a higher prevalence of acute bowel complications (18.1% vs. 3.2%; p = 0.012) requiring surgery, such as perforation, obstruction and volvulus. At 1 year of follow-up, groups were similar in terms of recurrence (5.5% vs. 1.6%; p = 0.341), surgical interventions related to severe gastroesophageal reflux disease (3.6% vs. 1.6%; p = 0.600) and mortality (5.5% vs. 6.6%; p = 1.000). ConclusionPostnatal CDH repair through thoracotomy was associated with a higher rate of surgical reinterventions within the first year of life, especially for severe acute gastro-intestinal complications. There seemed to be no difference in recurrence and mortality rate. Type of StudyRetrospective Comparative Cohort Study. Level of EvidenceLevel III.

Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice.

Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4(Cre);Wt1(fl/fl) embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism.

Thoracoscopic repair of congenital diaphragmatic hernia with countermeasures against reported complications for safe outcomes comparable to laparotomy.

Thoracoscopic repair is the preferred treatment for congenital diaphragmatic hernia (CDH); however, several complications, including visceral injury, hypercapnia, and a high incidence of recurrence, have been reported. The purpose of this study was to evaluate the efficacy of countermeasures against these complications at ensuring safe thoracoscopic repair. Between January 2000 and December 2014, 40 patients with Bochdalek-type CDH were treated. Of these, 24 patients met the defined criteria for this study, 8 of whom underwent thoracoscopic repair beginning in January 2010 (TS group) and 16 underwent laparotomy before December 2009 (LT group). Perioperative variables and postoperative complications were compared between the groups. Countermeasures against adverse events in the TS group included an endoscopic surgical spacer to prevent visceral injury, intrapulmonary percussive ventilation to avoid hypercapnia, pausing CO2 insufflation to reduce tension during the repair, and prioritizing patch repair in cases of strong tension at the defect. Primary closure was performed in 4 of 8 cases in the TS and 11 of 16 cases in the LT group. There was no visceral injury or conversion to laparotomy in the TS group. The mean operative duration was significantly longer (212 vs. 115 min, respectively, p = 0.0001), and the mean blood loss was significantly less in the TS than in the LT group (1.0 vs. 10.1 mL, respectively, p = 0.01). The intraoperative minimum arterial pH and maximum pCO2 were similar between the groups. All patients survived, and none experienced recurrence. Our countermeasures to complications of thoracoscopic repair may contribute to safe outcomes equivalent to those of laparotomy in patients meeting our criteria.

High recurrence rate in thoracoscopic repair of Bochdalek type congenital diaphragmatic hernia

Background: This study aims to determine the possible causes of high recurrence in thoracoscopic repair of congenital diaphragmatic hernia. Methods: Medical records of 14 children (8 boys, 6 girls; mean estimated gestational age of 38.2 weeks; range 36 to 40 weeks) who underwent thoracoscopic repair of Bochdalek type congenital diaphragmatic hernia in our clinic between August 2006 and August 2010 were retrospectively analyzed. Data including demographic characteristics, intraoperative details and respiratory status of the patients were reviewed in terms of recurrence. Results: Only one patient died due to pulmonary hypertension. The mean follow-up was four years (range, 3 to 7 years). Recurrence was seen in five patients. No significant difference in the parameters evaluated was found between the groups. Conclusion: Because of the high recurrence rate after thoracoscopic repair of the congenital diaphragmatic hernia, care must be taken to select the low risk patient for recurrence.

Defining “liver-up”: does the volume of liver herniation predict outcome for fetuses with isolated left-sided congenital diaphragmatic hernia?

PurposeThe aim of the study was to evaluate the relationship between the degree of liver herniation and mortality or need for extracorporeal membrane oxygenation (ECMO) in isolated left-sided congenital diaphragmatic hernia (CDH). MethodsThis is a retrospective review of all fetuses with isolated left-sided Bochdalek-type CDH evaluated at our center with ultrafast fetal magnetic resonance imaging between January 2004 and December 2010. Percentage of liver herniation was defined as the ratio of herniated liver volume to total fetal liver volume. The liver/thoracic volume ratio was defined as the ratio of herniated liver volume to total thoracic volume. Data were analyzed using receiver operating characteristic curves and Fisher's Exact and Mann-Whitney U tests. ResultsFifty-three fetuses with isolated left-sided CDH were evaluated. Fetuses with “liver-up” (n = 32) and “liver-down” (n = 21) anatomy had similar rates of mortality (25% vs 14%, P = .49) and ECMO use (41% vs 29%, P = .40). The accuracy of liver-up (a dichotomous variable) to predict mortality or need for ECMO was 49% and 53%, respectively. Percentage of liver herniation greater than 21% was associated with mortality (P < .001) or need of ECMO (P < .001), with an accuracy of 87% and 79%, respectively. Liver/thoracic volume ratio of greater than 14% was also associated with mortality or ECMO use (P < .001 and P = .01, respectively), with an accuracy of 85% and 72%, respectively. ConclusionIncreased amounts of liver herniation in fetuses with isolated left-sided CDH are associated with higher rates of mortality or the need for ECMO support. Quantification of liver herniation (a continuous variable) is superior to overall liver herniation as a dichotomous variable (liver-up vs liver-down) in the prediction of perinatal morbidity and mortality.

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

Background/PurposeAlthough intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome. MethodsRetrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test. ResultsOf 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%). ConclusionsPatients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.

Up-regulation of COUP-TFII gene expression in the nitrofen-induced hypoplastic lung

Purpose Recent studies have suggested that the retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The exact mechanism by which nitrofen acts in the RSP remains unclear. Targeted ablation of COUP-TFII, a gene encoding a transfactor regulated by the RSP, has been shown to cause Bochdalek-type congenital diaphragmatic hernia. It has been shown that COUP-TFII has 2 main roles in the RSP, (i) repressing the RSP by directly sequestering retinoid X receptors, thereby preventing heterodimerization to retinoid acid receptors and inhibiting gene transcription, and (ii) modulating the transcriptional activity of GATA proteins. We designed this study to investigate the gene expression of COUP-TFII in the nitrofen-induced hypoplastic lung. Materials and Methods Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9 of gestation. Fetuses were harvested and lungs were dissected on day 15 (D15), D18, and D21 and divided into 2 groups: control (n = 9) and nitrofen (n = 9). Real-time reverse transcription–polymerase chain reaction was performed to evaluate the relative mRNA levels of COUP-TFII expression in the hypoplastic lung. Results The relative mRNA levels of COUP-TFII at D15 was significantly increased in the nitrofen group (0.76 ± 0.53) compared to controls (0.45 ± 0.05) ( P < .01). The expression levels of COUP-TFII at D18 and D21 were not significantly different between the nitrofen group and controls. Conclusions Our results provide evidence for the first time that the pulmonary gene expression of COUP-TFII is up-regulated in the early stages of lung development in the nitrofen-induced hypoplastic lung. We speculate that up-regulation of COUP-TFII gene expression during the stage of branching lung morphogenesis may cause pulmonary hypoplasia by repressing RSP.

Late Presentation of Bochdalek-Type Congenital Diaphragmatic Hernia in Children: A 23-Year Experience at a Single Center

The purpose of this article is to report on our 23-year experience of treating children with late-presenting congenital diaphragmatic hernia (CDH), focusing on diagnostic difficulties, associated anomalies, and morbidity. We reviewed 19 children in whom Bochdalek-type CDH was diagnosed after the neonatal period, between 1983 and 2005. There were 14 boys and 5 girls, with a mean age of 18.3 months (range, 5 weeks-14 years). Ten (52.6%) of the patients presented with respiratory symptoms and five (26.3%) with gastrointestinal symptoms. The diagnosis of CDH was based on the findings of chest X-rays, gastrointestinal tract contrast radiographs, and computerized tomography findings. The CDH was on the left side in 16 patients and on the right side in three patients. A hernia sac was present in seven (36.8%) patients. The only postoperative complications were intestinal obstruction caused by adhesions, incisional hernia, and eventration of the diaphragm in one patient each. None of the patients died within this study period. The possibility of a delayed presentation of CDH should be considered in the differential diagnosis of recurrent non-specific respiratory or gastrointestinal tract symptoms in a child. A plain roentgenogram with a swallowed nasogastric tube might assist in the diagnosis. Early surgical correction of the diaphragmatic defect is crucial for preventing life-threatening complications.

Mouse lackingCOUP-TFIIas an animal model of Bochdalek-type congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH), a life-threatening anomaly, is a major cause of pediatric mortality. Although the disease was described >350 years ago, the etiology of CDH is poorly understood. Here, we show that tissue-specific null mutants of COUP-TFII exhibit Bochdalek-type CDH, the most common form of CDH. COUP-TFII, a member of orphan nuclear receptors, is expressed in regions critical for the formation of the diaphragm during embryonic development. Ablation of COUP-TFII in the foregut mesenchyme, including the posthepatic mesenchymal plate (PHMP), results in the malformation of the diaphragm and the failure of appropriate attachment of the PHMP to the body wall. Thus, both the stomach and liver enter the thoracic cavity, leading to lung hypoplasia and neonatal death. Recently a minimally deleted region for CDH has been identified on chromosome 15q26.1-26.2 by CGH array and FISH analysis. COUP-TFII is one of the four known genes residing within this critical region. Our finding suggests that COUP-TFII is a likely contributor to the formation of CDH in individuals with 15q deletions, and it may also be a potential contributor to some other Bochdalek-type of CDH.

Survival in neonatal congenital hernia without extracorporeal membrane oxygenation support

The experience with high-risk congenital diaphragmatic hernia (CDH) at an institution that does not offer extracorporeal membrane oxygenation (ECMO) was reviewed. Between January 1, 1983 and December 31, 1993, 38 children presented with Bochdalek-type CDH. Excluded were two infants with lethal cardiac anomalies and four presenting after 4 hours of age. Thus, the authors identified 32 high-risk patients. All had early respiratory distress and were intubated within 5 hours of birth. Sixteen were inborn; 16 were referred to the Izaak Walton Killam Children's Hospital (IWK) within 24 hours of birth. There were 19 males and 13 females. Three died before surgery could be attempted. Twenty-two survived, giving an overall survival rate of 69% (22 of 32). For 28 of the 32, the best preoperative postductal Pao 2 (BPDPao 2) was recorded. Fifteen of the 28 children had a BPDPao 2 of greater than 100 mm Hg. Survival in this group was 14 of 15 (93%). Thirteen of the 28 patients had a BPDPao 2 of less than 100 mm Hg. Survival in this group was 5 of 13 (38%). These survival rates are comparable to those of centers offering ECMO. BPDPao 2 appears to be a useful discriminating variable.