Effect of Perflubron-induced lung growth on pulmonary vascular remodeling in congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) involves lung hypoplasia and pulmonary hypertension (PH). Post-natal Perflubron ventilation induces lung growth. This phenomenon is called Perflubon-induced lung growth (PILG). However, it does not appear to ameliorate PH in CDH. We aim to determine the effect of PILG on pulmonary vascular remodeling in neonates with CDH and PH requiring extracorporeal membrane oxygenation (ECMO)

Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Neonates: Lessons Learned

Abstract Purpose: We sought to characterize our recent experience with thoracoscopic congenital diaphragmatic hernia (CDH) repair and identify patient selection factors. Methods: 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. Results: 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. Conclusions: 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78119/1/lap.2009.0129.pd

Thoracoscopic Repair of Recurrent Bochdalek Diaphragmatic Hernias in Children

Abstract Background: Recurrent herniation is a well-known complication following the initial repair of congenital diaphragmatic hernias (CDHs). The role of minimally invasive surgical techniques in recurrent CDH remains undefined. The purpose of this study was to evaluate our early experience with thoracoscopic repair compared with traditional open repair in children with recurrent CDH. Subjects and Methods: We retrospectively reviewed all recurrent Bochdalek CDH cases (n=24) managed at a single tertiary-care referral center between January 1990 and March 2011. Children who underwent thoracoscopic repair for recurrent CDH were identified, and their data were compared by the unpaired t test and the two-sided Fisher's exact test, as appropriate, with those of children who underwent open repair. Significance was defined as P<.05. Results: Thoracoscopic repair was attempted in 6 (25%) children with recurrent CDH. Four (67%) repairs were successfully completed without conversion to an open procedure. The mean age at thoracoscopic repair was 11.5 months (range, 8.1?16.1 months). The mean operative time was 191 minutes (range, 94?296 minutes), and all children were extubated within 24 hours. The mean hospital length of stay was 3.75 days (range, 1?6 days). There were no deaths or subsequent recurrences after a mean follow-up of 26.5 months (range, 14.3?41.3 months). There were no statistical differences in any of the measured outcome variables when compared with the open repair group. Conclusions: Our initial experience suggests that thoracoscopic repair is a feasible alternative to open repair in selected children with recurrent Bochdalek diaphragmatic hernias.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98467/1/lap%2E2012%2E0048.pd

Surveillance of fetal lung lesions using the congenital pulmonary airway malformation volume ratio: natural history and outcomes

ObjectivesThe congenital pulmonary airway malformation volume ratio (CVR) is a widely used sonographic measure of relative mass size in fetuses with lung malformations. The purposes of this study were to examine serial CVR measurements to understand longitudinal growth patterns and to determine correlation with postnatal imaging.MethodsAn institutional review boardâ approved retrospective review was performed on fetuses referred for an echogenic lung malformation between 2002 and 2014. For each fetus, the CVR was prospectively calculated using 2D ultrasound and followed with advancing gestation.ResultsBased on 40 fetuses, the mean initial CVR was 0.51â ±â 0.07 at 20.5â ±â 0.3â weeks of gestation. The CVR increased after 24â weeks of gestation (pâ =â 0.0014), peaking at a CVR of 0.96â ±â 0.11 at 25.5â ±â 0.05â weeks, followed by a significant decrease in the CVR to 0.43â ±â 0.07 prior to term (pâ <â 0.0001). However, approximately one third showed no appreciable increase in size. The mean CVR was significantly correlated with postnatal chest computed tomography (CT) size dimensions (pâ =â 0.0032) and likelihood for lung resection (pâ =â 0.0055).ConclusionsFetal lung malformations tend to follow one of two distinct growth patterns, characterized by either (1) a maximal CVR between 25 and 26â weeks of gestation or (2) minimal change in relative growth. The mean CVR correlates with postnatal CT size and operative management. © 2015 John Wiley & Sons, Ltd.What’s already known about the topic?The congenital pulmonary airway malformation volume ratio (CVR) is a common prenatal ultrasound measure of relative mass size in fetuses with lung malformations.The initial CVR and maximum CVR have been shown to be predictive of hydrops and neonatal respiratory compromise, respectively.What does this study add?Gestational age is important when interpreting CVR measurements because two thirds of lesions increase in size at 25â 26â weeks before spontaneous involution occurs.The mean CVR correlates with size measured by postnatal computed tomography scan.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/1/pd4761_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/2/pd4761.pd

Bilateral giant abdominoscrotal hydroceles complicated by appendicitis

Abdominoscrotal hydrocele is a rare entity, with fewer than 100 cases reported in children. Bilateral abdominoscrotal hydroceles are even less common, with 14 cases reported in children. Various complications of abdominoscrotal hydrocele have been reported in the literature. We present a 4-month-old boy with bilateral giant abdominoscrotal hydrocele s who developed appendicitis apparently because of obstruction from the right hydrocele. We discuss the various imaging modalities used to establish the diagnosis and plan the operative approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46717/1/247_2005_Article_1572.pd

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10-8), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH

Fetal Surgery in the Primate 4.0: A New Technique 30 Years Later

IntroductionOpen fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler.ObjectiveIn this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears.MethodsA gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site.ResultsA 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence.ConclusionsThe Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable