Large Congenital Diaphragmatic Hernia Research Articles

Split abdominal wall muscle flap repair vs patch repair of large congenital diaphragmatic hernias

Purpose Large congenital diaphragmatic hernias are commonly repaired with a prosthetic patch. We hypothesized that a split abdominal wall muscle flap would reduce the risk of recurrence. Methods A retrospective review of neonates with congenital diaphragmatic hernia in whom primary repair was not possible was performed. Kaplan-Meier analyses and Cox proportional hazards modeling were performed. Results Of 153 patients, 46 could not have repair with primary closure of the diaphragm. Thirty-three survived to discharge and were subjected to analysis for recurrence. Ten underwent repair with a patch, whereas 23 had a muscle flap (internal oblique and transversalis) patch. The groups were similar with regard to demographics, need for extracorporeal membrane oxygenation, repair on extracorporeal membrane oxygenation, and size of the defect. Fifty percent of patch repairs recurred with a median time of 0.5 years. Only one (4.3%) of the patients who had muscle flap patch developed a recurrence. This was significant on Kaplan-Meier analysis ( P = .0009) and had a hazard ratio of 14.3 on Cox regression ( P = .018). Median follow-up exceeded 4 years. No children required surgery for an abdominal wall hernia. Conclusions The split abdominal wall muscle flap allows for closure of large congenital diaphragmatic hernia defects with autologous tissue. This approach is associated with significantly fewer recurrences than patch repairs.

Large diaphragmatic defect: are skeletal deformities preventable?

The aim of study was to compare growth, nutritional status and incidence of chest wall deformities and scoliosis in survivors of large congenital diaphragmatic hernia (CDH) defect (Gore-Tex patch reconstruction) with survivors with smaller defects and primary reconstruction. An anthropometric study of 53 children who underwent CDH repair in neonatal period was carried out. Weight, height, and skin-fold thickness were measured, scoliosis and chest wall deformity were evaluated. Body mass index (BMI) and thoracic index (TI) were calculated using standard rules. The measured data were compared with national population standard with the use of standard deviation score (SDS). According to the type of diaphragmatic reconstruction, the patients were divided into two groups [Gore-Tex patch (10) versus primary repair (43)]. Student t test and Fisher exact tests were used for statistical analysis. Pectus excavatum was found in 25 (47%) patients, poor posture in 33% and significant scoliosis in 5%. Compared with the population norm, CDH children had a significantly lower body height SDS (mean -0.39, p<0.05), weight SDS (mean -0.75, p<0.001), BMI (mean SDS -0.68, p<0.001) and lower TI (mean SDS -0.62, p<0.01). Gore-Tex versus primary repair group significantly differed in incidence of pectus excavatum and BMI (PE: p=0.027, BMI SDS: p=0.016). A majority of anthropometric parameters (weight, height, thoracic index, and thorax circumference) and incidence of scoliosis and poor posture in children after Gore-Tex patch reconstruction did not significantly differ from children after primary repair. The differences in some anthropometric parameters (weight, BMI, and TI) and in the skeletal deformity suggest that the CDH not only disturbs normal lung growth, but also seems to have implications on some other aspects of somatic development. Whether these changes could be related to the type of diaphragmatic reconstruction or rather to the size of the defect remains uncertain.

Absorbable Versus Nonabsorbable Mesh Repair of Congenital Diaphragmatic Hernias in a Growing Animal Model

The repair of large congenital diaphragmatic hernia frequently results in patch disruption and recurrence as patients grow in size. Absorbable meshes allow for ingrowth of endogenous tissue as they are degraded, providing a more natural and durable repair. The aim of this study was to compare the characteristics of the new diaphragmatic tissue between an absorbable biologic mesh and a nonabsorbable mesh for repairing diaphragmatic hernia in a growing animal model. The left hemi-diaphragm of twenty 2-month-old Yucatan pigs was nearly completely resected. Small intestinal submucosa (SIS; Cook Biotech, Lafayette, IN) and expanded polytetrafluoroethylene (ePTFE; W.L. Gore & Associates, Flagstaff, AZ) were randomly assigned to cover the defect in 10 animals each, and were survived for 6 months. During necropsy, newly formed diaphragmatic tissue was evaluated and compared between the two groups. At necropsy, the animals had tripled their weight. Patch disruption and herniation occurred in 3 animals in the ePTFE group and none in the SIS group. The SIS mesh had better integration to the chest wall (2.8 ± 0.2 versus 1.3 ± 0.3), more muscle growth within the newly formed diaphragmatic tissue (1.9 ± 0.2 versus 0.4 ± 0.2), and less fibrotic tissue (2.1 ± 0.5 versus 3.4 ± 0.4) than ePTFE. There was no difference between SIS and ePTFE in terms of adhesion scores to the lung (2 ± 0.4 versus 2.4 ± 0.4) and liver (1.8 ± 0.3 versus 2.2 ± 0.5). SIS allows for tissue ingrowth from surrounding tissue as it degrades, providing a more durable repair with 30% less incidence of herniation in a porcine model. As the diaphragm grows, SIS resulted in a more natural repair of the defect with more tissue growth, better tissue integration, and a comparable adhesion formation to ePTFE.

Characterization of the chromosome 1q41q42.12 region, and the candidate gene DISP1, in patients with CDH.

Cytogenetic and molecular cytogenetic studies demonstrate association between congenital diaphragmatic hernia (CDH) and chromosome 1q41q42 deletions. In this study, we screened a large CDH cohort (N=179) for microdeletions in this interval by the multiplex ligation-dependent probe amplification (MLPA) technique, and also sequenced two candidate genes located therein, dispatched 1 (DISP1) and homo sapiens H2.0-like homeobox (HLX). MLPA analysis verified deletions of this region in two cases, an unreported patient with a 46,XY,del(1)(q41q42.13) karyotype and a previously reported patient with a Fryns syndrome phenotype [Kantarci et al., 2006]. HLX sequencing showed a novel but maternally inherited single nucleotide variant (c.27C>G) in a patient with isolated CDH, while DISP1 sequencing revealed a mosaic de novo heterozygous substitution (c.4412C>G; p.Ala1471Gly) in a male with a left-sided Bochdalek hernia plus multiple other anomalies. Pyrosequencing demonstrated the mutant allele was present in 43%, 12%, and 4.5% of the patient's lymphoblastoid, peripheral blood lymphocytes, and saliva cells, respectively. We examined Disp1 expression at day E11.5 of mouse diaphragm formation and confirmed its presence in the pleuroperitoneal fold, as well as the nearby lung which also expresses Sonic hedgehog (Shh). Our report describes the first de novo DISP1 point mutation in a patient with complex CDH. Combining this finding with Disp1 embryonic mouse diaphragm and lung tissue expression, as well as previously reported human chromosome 1q41q42 aberrations in patients with CDH, suggests that DISP1 may warrant further consideration as a CDH candidate gene.

Outcomes after muscle flap vs prosthetic patch repair for large congenital diaphragmatic hernias

Background Repair of large congenital diaphragmatic hernia (CDH) defects still pose a significant challenge, as the defects cannot be repaired primarily. Two techniques have been widely used: autologous anterior abdominal wall muscle flap and prosthetic patch. The latter has been used more often. Our goal was to compare the short-term and long-term outcomes of these 2 approaches. Methods This is a retrospective review of all neonates undergoing CDH repair at our institution from 1969 to 2006. Results Of 188 children undergoing surgery for CDH, primary repair could not be accomplished in 51 infants (27%). Nineteen had muscle flap repair, and 32 had prosthetic patch repair (Gore-Tex [W.L. Gore and Associates, Flagstaff, AZ], n = 15; Marlex [Bard Inc, Cranston, NJ], n = 9; Surgisis [Cook, Bloomington, IN], n = 5; SILASTIC [Dow Corning, Midland, MI], n = 3). There was no significant difference in gestational age or birth weight between groups. Three patients developed an abdominal wall defect at the muscle flap donor site, but none required surgical intervention. Chest wall deformities were found in 9 patients, 3 after a muscle flap and 6 after a prosthetic patch ( P = .7). Postoperative bowel obstruction occurred in 3 muscle flap patients and 1 patch patient ( P = .2). There were 10 recurrences among survivors: 2 after a muscle flap and 8 after a prosthetic patch ( P = .3) There were 2 deaths among the muscle flap patients (10%), and 3 deaths among the prosthetic patch repair patients (9%) ( P = .1). Results were confirmed after controlling for age and comorbidities between both groups in a multivariate logistic regression. Conclusion These results suggest that autologous anterior abdominal wall muscle flap and prosthetic patch repairs provide similar short-term and long-term outcomes.

Evaluation of diaphragmatic hernia repair using PLGA mesh–collagen sponge hybrid scaffold: an experimental study in a rat model

Patch closure is necessary to achieve tension-free repair in large congenital diaphragmatic hernia. However, the use of prosthetic material may lead to granulation, allergic reaction, infection, recurrence of hernia, and thoracic deformity. Tissue engineering may become an alternative treatment strategy for diaphragmatic hernia repair, since the regenerated autologous tissue is expected to grow potentially without rejection or infection. We evaluated the efficacy of diaphragmatic hernia repair in a rat model using a poly-lactic-co-glycolic acid (PLGA) mesh-collagen sponge hybrid scaffold, designed for in situ tissue engineering. Twenty-four F344 female rats were used. Oval-shaped defects were surgically created in the left diaphragm and repaired with three different grafts, including PLGA mesh in group 1 (n = 7), PLGA mesh-collagen sponge hybrid scaffold in group 2 (n = 7), and PLGA mesh-collagen sponge hybrid scaffold seeded with bone marrow-derived mesenchymal stem cells (MSCs) in group 3 (n = 10). The animals were killed at 1, 2, and 3 months after operation. The specimens were examined macroscopically and microscopically. No recurrence or eventration was observed. In all animals, autologous fibrous tissue with vascularization was generated at the graft site. Although no muscular tissue was detected, scattered desmin-positive cells were observed in groups 2 and 3. The 'neodiaphragm' in groups 2 and 3 was significantly thicker compared with that in group 1. There was no significant difference in the 'neodiaphragm' between groups 2 and 3. The PLGA mesh-collagen sponge hybrid scaffold provided better promotion of autologous in situ tissue regeneration in the diaphragm, suggesting its potential application to diaphragmatic repair in place of other prosthetic patches.

Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia

Purpose Many different prosthetic materials have been used for repair of large posterolateral congenital diaphragmatic hernias (CDH), with high recurrence rates for hernias that cannot be primarily repaired. Since 1993, we have used a composite patch of Gore-Tex/Marlex to repair large CDHs and hypothesized that this repair leads to fewer recurrences. Methods This is a retrospective review of 137 consecutive patients with CDH cared for at a single institution from 1993 to 2004. Data collected include timing and method of repair and use of extracorporeal membrane oxygenation. Outcomes include hernia recurrence, complications, and death. Results One hundred thirty-seven patients with CDH were analyzed. Repair was not attempted in 12 because of disease severity. Primary repair was accomplished in 79 and 46 required patch repair. Of the 46 patients with patch repairs, 32 required extracorporeal membrane oxygenation, and 18 died before discharge. Of the 28 patch repair survivors, 1 (3.57%) developed a recurrence over a median follow-up of 47 months (range, 2-115 months). Overall survival was 77%. Conclusions Gore-Tex/Marlex composite patch repair of large CDHs in this complex patient population results in a lower recurrence rate than has been reported for other types of prosthetic diaphragm repair.

The split abdominal wall muscle flap repair for large congenital diaphragmatic hernias on extracorporeal membrane oxygenation

Background Numerous techniques exist for repairing large congenital diaphragmatic hernias (CDHs) including prosthetic patches, tissue-engineered grafts, and various muscle flaps. A split abdominal wall muscle flap is a simple, durable way to repair a large diaphragmatic hernia. This technique has not gained widespread use, and some have suggested that it would be inappropriate in the setting of extracorporeal membrane oxygenation (ECMO) because of bleeding risk. We present our series of diaphragmatic hernias with a focus on those repaired with the split abdominal wall technique while on ECMO. Methods A retrospective, single-institution chart review was performed on all patients who underwent surgical repair for CDH over 6 years beginning in August 2000. Results Seventy-five patients underwent repair. Sixteen were performed with patients on ECMO. Of these, 4 were closed primarily, 7 used a prosthetic patch, and 5 used a split abdominal wall muscle flap. Two patients in the prosthetic group developed a recurrent hernia, and 2 required reoperation for bleeding while on ECMO. No reoperations for bleeding were required in the abdominal muscle flap group. Conclusions The split abdominal wall muscle flap can be safely performed on anticoagulated patients. We believe it is a practical option for repairing large CDHs.

Reversed latissimus dorsi muscle flap for repair of recurrent congenital diaphragmatic hernia

Background/Purpose: Neonates with large congenital diaphragmatic hernias (CDH) require prosthetic patch closure of the defect because of the paucity of native diaphragmatic tissue. As the child grows, patch separation can occur necessitating reoperation. Use of vascularized autologous tissue may decrease the incidence of reherniation as tissue incorporation and growth may be improved. The authors report our early experience using a local muscle advancement flap with microneural anastomosis for those children in whom reherniation develops after prosthetic patch placement. Methods: Seven patients with CDH (6 left and 1 right) whose synthetic diaphragmatic patch separated from the chest wall resulting in a clinically significant recurrent hernia were followed up with prospectively. After dissecting the ipsilateral latissimus dorsi off the chest wall and dividing the thoracodorsal neurovascular bundle (based on its lumbar blood supply), the synthetic patch was removed via an eighth intercostal incision. The muscle flap was placed into the hemithorax through the bed of the tenth rib and sutured in place over a Vicryl mesh scaffold. The thoracodorsal nerve was anastomosed to the phrenic nerve. Functional analysis of the flap was performed in 4 patients. Results: Age at placement of the muscle graft ranged from 2 months to 48 months (median, 24 months). There has been no evidence of reherniation after placement of the muscle graft. Long-term outcome and functional analysis of the flap was available in 4 patients (mean, 19 months). Two infants had fluoroscopic and sonographic evidence of nonparadoxical neodiaphragmatic motion. In one of these, electromyographic evidence of function was documented with a phrenic nerve conduction velocity of 22 meters per second. The third infant showed no evidence of neodiaphragmatic motion, and the fourth infant had paradoxical motion. Conclusions: This is the first direct documentation of phrenic nerve function in an infant with CDH. An innervated reversed latissimus dorsi (RLD) flap reconstruction for recurrent CDH provides an alternative to prosthetic patch repair. This technique offers the advantages of autologous vascularized tissue with potential phrenic nerve innervation and physiologic neodiaphragmatic motion. J Pediatr Surg 38:296-300. Copyright 2003, Elsevier Science (USA). All rights reserved.

Vascular changes with in utero correction of diaphragmatic hernia

In utero surgical correction of fetal diaphragmatic hernia is a new therapeutic alternative for selected prenatally diagnosed patients. With increasing experience, the authors have found that fetuses with herniation of the liver through the diaphragmatic defect have a high incidence of perioperative death. The hypothesis was that reduction of the liver during fetal diaphragmatic hernia repair caused distortion of fetal vascular anatomy resulting in fetal demise. To study this, the authors performed angiograms through the umbilical vein in fetal and neonatal cadavers, with and without diaphragmatic hernias, and simulated in utero repair. Large fetal congenital diaphragmatic hernias can be associated with dramatic changes in the vascular anatomy of the liver. The liver does not simply rotate up into the chest through a diaphragmatic defect; instead, the liver more likely develops in the chest, with its vascular anatomy situated accordingly. Attempts to reduce a herniated liver can result in significant distortion of the fetal vasculature, leading to fetal death. Techniques to prevent vascular compromise during hepatic manipulation may improve the outcome for fetuses during in utero repair of diaphragmatic hernias.

Antenatal glucocorticoid corrects pulmonary immaturity in experimentally induced congenital diaphragmatic hernia in rats.

Congenital diaphragmatic hernia, a highly lethal condition, displays at term the pulmonary biochemical and morphologic immaturity characteristic of premature delivery. We hypothesized that antenatal glucocorticoid, now the standard treatment to prevent hyaline membrane disease in premature human beings, might correct the parameters of the pulmonary biochemical and morphologic immaturity in severe congenital diaphragmatic hernia. A total of 112 fetal rats with or without nitrofen-induced congenital diaphragmatic hernias from 34 pregnancies were treated antenatally with either saline or dexamethasone. Antenatal dexamethasone increased the lung disaturated phosphatidylcholine content, reduced the lung glycogen concentration, reduced the saccular septal thickness, and increased the mean saccular size and volume fraction of saccules in the lungs of rats with large congenital diaphragmatic hernia in comparison with similar rats not so treated. All differences were statistically significant. Antenatal glucocorticoid therapy was efficacious in treating rats with nitrofen-induced congenital diaphragmatic hernia. This encouraging finding warrants further investigation in a large animal model with surgically created congenital diaphragmatic hernia.

Anterolateral Diaphragmatic Hernia: Is it a Morgagni Hernia?

Three unusual cases of large anterolateral congenital diaphragmatic hernia are described with emphasis on its embryogenesis. This type of diaphragmatic defect is rare and underemphasized. Its clinical spectrum ranges from the asymptomatic case to those with acute respiratory distress. It may present itself as a solitary defect or as part of a more complex association such as the thoracoabdominal syndrome. This defect should be differentiated from Morgagni (and other anterior) diaphragmatic hernias by its size and lateral extension and the presence of left pulmonary hypoplasia. Treatment is by primary operative repair, and prognosis depends on the presence and severity of associated malformations.

Biochemical immaturity of lungs in congenital diaphragmatic hernia

Neonates with congenital diaphragmatic hernia (CDH) continue to have unacceptably high mortality rates. To better understand the associated pulmonary pathology we measured biochemical parameters of lung maturity in neonatal rats with or without congenital diaphragmatic hernia created by maternal feeding of a single dose of nitrofen on day 9.5 or day 11.5 of gestation. Lungs from neonatal rats with large CDH (n = 9, 5 right-sided, 4 left-sided) had a significantly lower lung weight ( P = .0001), lung weight/body weight ratio ( P = .0001), disaturated phosphatidylcholine (DSPC) per microgram DNA ( P < .005), total DSPC ( P = .0001), total DNA ( P < .05), protein per microgram DNA ( P < .05), and total protein content ( P < .005) when compared with lungs from the litter mates without congenital diaphragmatic hernia (n = 10). The lungs of rats with hernia also had significantly higher DNA concentrations ( P < .05) and glycogen concentrations ( P < .05). These data demonstrate that lungs in neonatal rats with large CDH are biochemically immature. Treatment directed toward correcting the pulmonary biochemical immaturity of affected fetuses before birth may improve the prognosis for these babies.

Use of abdominal wall muscle flap in repair of large congenital diaphragmatic hernia

Occasionally a congenital diaphragmatic defect is too large to be repaired in the conventional manner. With the use of a subcostal incision for exposure a pedicle flap of abdominal wall muscle can be used to give a strong repair with no significant deformity of the rib cage or abdominal wall.