Treatment Of Congenital Diaphragmatic Hernia Research Articles

The Use of Inhaled Nitric Oxide in Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is a complex congenital defect of the diaphragm that allows abdominal contents to herniate into the chest cavity, altering pulmonary development, and leading to pulmonary hypoplasia and hypertension. Patient presentation is variable in severity, making management difficult. Many common management strategies have improved the survival rate of infants with CDH, including gentle ventilation and permissive hypercapnia. Inhaled nitric oxide (iNO) is a potent, pulmonary vasodilator that has shown to improve oxygenation while decreasing pulmonary pressure in infants with pulmonary hypertension. While many institutions utilize iNO in the treatment of pulmonary hypertension, the role of iNO as a treatment for CDH is controversial. The purpose of this literature review is to establish a better understanding of CDH including embryology, patient presentation, and management strategies, and to analyze the use and effect of iNO on patients in this population. A systemic search of PubMed, CINHAL, and Medline was performed to identify research articles studying the use of iNO on patients with pulmonary hypertension secondary to CDH. Three studies were utilized in this review to assess the current use and effectiveness of iNO in patients with CDH. This review summarized the pathophysiology, embryology, patient presentation, and management strategies, as well as reviewed literature on the effectiveness of iNO on pulmonary hypertension secondary to CDH. Further research is indicated to determine alternative treatment modalities and establish evidence-based practice protocols to standardize care in infants with CDH.

Surgical Complications in Children with CDH: A Multivariate Analysis

IntroductionSeveral medical and surgical improvements in the treatment of congenital diaphragmatic hernia (CDH) patients have led to a higher survival rate. However, some of these improvements also lead to an increased morbidity rate. This study aims to determine the contribution different medical and surgical treatments have had on the development of surgical complications.MethodAll CDH patients treated in a single centre between 2000 and 2015 were retrospectively evaluated. Multivariate logistic regression was used to estimate the independent effects of several treatment options that could influence the surgical outcome by adjustment for multiple risk factors.ResultsSixty of the 197 surgically repaired CDH patients had surgical complications. There were more haemorrhagic complications in the ECMO compared to non-ECMO group (27% vs. 2%, p < 0.001). The use of inhaled nitric oxide was also significantly related to haemorrhage (OR = 13.0 (95% CI 1.1–159)). After adjustment for other risk factors, chylothorax was neither significantly associated with ECMO treatment (OR = 1.6 (95% CI 0.5–5.2) nor with patch repair (OR = 2.1: 95% CI 0.7–6.1). A recurrence occurred more often in patients with pulmonary hypertension (OR = 10.0 (95% CI 1.5–65.8) and after treatment with an abdominal patch (OR = 11.3: 95% CI 1.5–84.4).ConclusionECMO treatment and the inhalation of nitric oxide are used in the most severe CDH patients but are associated with a higher risk on surgical haemorrhage. The recurrence rate is associated with both the use of an abdominal patch and the presence of pulmonary hypertension, regardless of medical treatment.

Polydopamine Functionalization: A Smart and Efficient Way to Improve Host Responses to e-PTFE Implants

Among the different materials used as protheses for the treatment of Congenital Diaphragmatic Hernia, expanded polytetrafluoroethylene (e-PTFE) plays a leading role owing to its mechanical properties as explained in the first part of this review. However, this material is poorly cell adhesive, which is expected for its contact on the abdominal face, but should display specific tissue adhesion on its thoracic exposed faced. A side specific functionalization method is hence required. The deposition of a nanosized polydopamine film on PTFE is known to be possible but immersion of the e-PTFE membrane in an aerated dopamine solution leads to a functionalization not only on both faces of the membrane but also in its porous volume. The fact that polydopamine also forms at the water/air interface has allowed to transfer a polydopamine film on only one face of the e-PTFE membrane. The deposition method and applications of such Janus like membranes are reviewed in the second part of the review.

Sildenafil for Antenatal Treatment of Congenital Diaphragmatic Hernia: From Bench to Bedside.

Persistent pulmonary hypertension (PPH) is one of the main causes of mortality and morbidity in infants affected by congenital diaphragmatic hernia (CDH). Since the structural changes that lead to PPH take place already in utero, a treatment starting in the prenatal phase may prevent the occurrence of this complication. To summarize the development process of antenatal sildenafil for CDH. The pharmacokinetics and efficacy of sildenafil have been assessed in the rat and the rabbit model. The transfer of the drug through the human placenta has been measured with the ex-vivo placenta perfusion model. Results from this experiment are being incorporated in a pregnancy-physiologically based pharmacokinetic (p- PBPK) model. A phase I-IIb placental transfer and safety study is ongoing. Sildenafil administration to pregnant rats and rabbits led to therapeutic foetal drug levels without maternal and foetal toxicity, although it was associated with impaired vascular development in foetuses with nonhypoplastic lungs. Peak concentrations and 24-hour exposure were higher in pregnant rabbits compared to nonpregnant ones. In rat and rabbit foetuses with CDH, sildenafil rescued the lung vascular anomalies and partially improved parenchymal development. Sildenafil crossed the human placenta at a high rate ex-vivo, independently from the initial maternal concentration. There is preclinical evidence that maternally administered sildenafil prevents the vascular changes that lead to PPH in CDH newborns. The phase I/IIb clinical study together with the p-PBPK model will define the maternal dose needed for a therapeutic effect in the foetus. Foetal safety will be investigated both in the clinical study and in the sheep. The final step will be a multicentre, randomized, placebo-controlled trial.

Impact of nutrition in the treatment of congenital diaphragmatic hernia.

The optimum enteral (EN) and parenteral nutrition (PN) regimens during acute management of congenital diaphragmatic hernia (CDH) remain unclear. We examined the effects of EN and PN on weight gain in CDH patients. A multicenter retrospective cohort study of neonates with CDH (born 2006-2010; n = 105) who survived to discharge was conducted. Patients were divided as receiving PN ≥ or <50 kcal/kg/day at 1 week of age, and EN ≥ or <60 kcal/kg/day at 2 weeks of age. Changes in bodyweight at 30, 60, and 90 days of age were compared. The higher EN group (n = 39) had greater mean weight gain than the lower EN group (n = 66; 90 days: 2,501 g, 95% CI: 2,294-2,710 g vs 1,706 g, 95% CI: 1,553-1,861 g; P <0.001). When patients received lower EN, the higher PN group (n = 24) had greater mean weight gain than the lower PN group (n = 42; 90 days: 1,768 g, 95% CI: 1,574-1,961 g vs 1,411 g, 95% CI: 1,264-1,558 g; P = 0.004). The amount of EN in the acute phase of CDH management is essential for weight gain during infancy. When patients are intolerant to adequate EN, supportive PN is also essential.

Allogenic tissue-specific decellularized scaffolds promote long-term muscle innervation and functional recovery in a surgical diaphragmatic hernia model

Congenital diaphragmatic hernia (CDH) is a neonatal defect in which the diaphragm muscle does not develop properly, thereby raising abdominal organs into the thoracic cavity and impeding lung development and function. Large diaphragmatic defects require correction with prosthetic patches to close the malformation. This treatment leads to a consequent generation of unwelcomed mechanical stress in the repaired diaphragm and hernia recurrences, thereby resulting in high morbidity and significant mortality rates. We proposed a specific diaphragm-derived extracellular matrix (ECM) as a scaffold for the treatment of CDH. To address this strategy, we developed a new surgical CDH mouse model to test the ability of our tissue-specific patch to regenerate damaged diaphragms. Implantation of decellularized diaphragmatic ECM-derived patches demonstrated absence of rejection or hernia recurrence, in contrast to the performance of a commercially available synthetic material. Diaphragm-derived ECM was able to promote the generation of new blood vessels, boost long-term muscle regeneration, and recover host diaphragmatic function. In addition, using a GFP + Schwann cell mouse model, we identified re-innervation of implanted patches. These results demonstrated for the first time that implantation of a tissue-specific biologic scaffold is able to promote a regenerating diaphragm muscle and overcome issues commonly related to the standard use of prosthetic materials. Statement of significanceLarge diaphragmatic hernia in paediatric patients require application of artificial patches to close the congenital defect. The use of a muscle-specific decellularized scaffold in substitution of currently used synthetic materials allows new blood vessel growth and nerve regeneration inside the patch, supporting new muscle tissue formation. Furthermore, the presence of a tissue-specific scaffold guaranteed long-term muscle regeneration, improving diaphragm performance to almost complete functional recovery. We believe that diaphragm-derived scaffold will be key player in future pre-clinical studies on large animal models.

Rising Postoperative C-Reactive Protein in Congenital Diaphragmatic Hernia: Sepsis or Inflammation?

This study aims to determine the incidence of sepsis in neonates operated for congenital diaphragmatic hernia and ascertain if the level or pattern of C-reactive protein (CRP) could be used to differentiate neonates with sepsis from noninfective inflammation. This study suggests that CRP patterns within the first 48-hours after surgical intervention for congenital diaphragmatic hernia could be used to differentiate neonates with noninfective inflammation from sepsis. A larger, multicentric study is needed to differentiate sepsis from inflammation on the basis of CRP rise and thereby help in avoiding unnecessary use of antibiotics.

Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia.

BackgroundCongenital diaphragmatic hernia (CDH) is a fetal defect comprising an incomplete diaphragm and the herniation of abdominal organs into the chest cavity that interfere with fetal pulmonary development. Though the most promising treatment for CDH is via interventional fetoscopic tracheal occlusion (TO) surgery in-utero, it has produced mixed results due to the static nature of the inserted occlusion. We hypothesize that a suitable noninvasively-actuatable, cyclic-release tracheal occlusion device can be developed to enable dynamic tracheal occlusion (dTO) implementation.ObjectiveTo conduct an in-vitro proof-of-concept investigation of the construction of thermo-responsive polymer valves designed for targeted activation within a physiologically realizable temperature range as a first step towards potential development of a noninvasively-actuatable implantable device to facilitate dynamic tracheal occlusion (dTO) therapy.MethodsSix thermo-responsive polymer valves, with a critical solution temperature slightly higher than normal physiological body temperature of 37°C, were fabricated using a copolymer of n-isopropylacrylamide (NIPAM) and dimethylacrylamide (DMAA). Three of the valves underwent ethylene oxide (EtO) sterilization while the other three served as controls for EtO-processing compatibility testing. Thermal response actuation of the valves and their steady-state flow performances were evaluated using water and caprine amniotic fluid.ResultsAll six valves consisting of 0.3-mole fraction of DMAA were tested for thermal actuation of caprine amniotic fluid flow at temperatures ranging from 30–44°C. They all exhibited initiation of valve actuation opening at ~40°C with full completion at ~44°C. The overall average coefficient of variation (CV) for the day-to-day flow performance of the valves tested was less than 12%. Based on a Student t-test, there was no significant difference in the operational characteristics for the EtO processed versus the non-EtO processed valves tested.ConclusionsWe successfully fabricated and demonstrated physiological realizable temperature range operation of thermo-responsive polymer valves in-vitro and their suitability for standard EtO sterilization processing, a prerequisite for future in-vivo surgical implantation testing.

180: Outcome after fetoscopic tracheal occlusion treatment of congenital diaphragmatic hernia

180: Outcome after fetoscopic tracheal occlusion treatment of congenital diaphragmatic hernia

Long-term Quality of Life in Neonatal Surgical Disease.

This prospective observational study was designed to assess Pediatric Quality of Life (PedsQL) after surgical treatment for congenital diaphragmatic hernia (CDH), esophageal atresia/tracheoesophageal fistula (EA/TEF), Hirschsprung disease (HD), gastroschisis (GAS), omphalocele (OMP), and necrotizing enterocolitis (NEC). Improvements in neonatal and surgical care have led to increased survival for many newborn conditions. Quality of life in these patients is seldom explored in a longitudinal manner. We hypothesized that age-adjusted physical and psychosocial scores would improve over time, but with diagnosis-dependent variation. Data were collected from 241 patients (CDH = 52; EA/TEF = 62; HD = 46; GAS = 32; OMP = 26; NEC = 23) in an institutional Clinical Outcomes Registry (COR) from 2012 to 2017. Aggregate physical, psychosocial, and overall PedsQL scores were determined for each diagnosis. Spline regression models were created to model scores as a function of age. Physical scores trended up for all diagnoses except CDH and NEC beyond age 10. Psychosocial scores trended up for all diagnoses except NEC and EA/TEF beyond age 10. Beyond age 12, CDH, GAS, and HD patients had overall scores within the normal range, while NEC, OMP, and EA/TEF patients had scores similar to children with chronic medical illness. Variation exists in long-term PedsQL scores after neonatal surgery for selected, complex disease. Beyond age 12, quality of life is significantly impaired in NEC, moderately impaired in OMP and EA/TEF, and within normal range for CDH, HD, and GAS patients at the population level. These data are relevant to prenatal and perioperative discussions with patients and families.

Thoracoscopic repair of congenital diaphragmatic hernia in neonates: a report of 47 cases

To review the application of thoracoscopic repair for treatment of congenital diaphragmatic hernia in neonates, so as to improve the cure rate. Clinical data of 47 neonates with congenital diaphragmatic hernia receiving thoracoscopic repair from June 2012 to June 2017 were reviewed. The admission age, gestational age, birth weight, timing of diagnosis, hernia location, clinical manifestation, surgical timing, surgical method, operation time, postoperative mechanical ventilation time of patients were analyzed. There were 42 cases of left diaphragmatic hernia and 5 cases of right diaphragmatic hernia. Thirteen cases were diagnosed prenatally. Primary diaphragmatic repair was successfully accomplished under thoracoscope in 45 neonates without perioperative complications, while 2 patients were converted to open surgery. The average operation time was (63±13) min (42-150 min), the average blood loss was (3.0±1.7) mL (1.0-9.0 mL), and the average postoperative mechanical ventilation time was (3.9±1.4) d (2.0-11.0 d). Two patients died and the treatment was withdrawn in 3 patients with an overall cure rate of 89.4% (42/47). Thoracoscopic repair is effective and can be used as first-choice treatment of diaphragmatic hernia in neonates.

Pediatric thoracoscopic repair of congenital diaphragmatic hernias.

Congenital diaphragmatic hernia (CDH) is a rare congenital disease requiring neonatal surgical treatment. The traditional surgical management of CDH consists of diaphragmatic repair by laparotomy. Thoracoscopic repair techniques have been well described for CDH with late presentation. Nevertheless, its feasibility for CDH treatment in neonates emerged only the past few years because the use of thoracoscopy with carbon dioxide insufflation remains controversial in these patients more vulnerable to hypothermia and acidosis. However, we think that thoracoscopy can be safely used to repair CDH in selected patients and the major limiting factor is pulmonary hypoplasia. Some patients should be excluded based on their higher potential need for patch closure with its technical difficulty and increased operative time. The close collaboration between pediatric surgeon, anesthetist and neonatologist is essential. We discuss here the patient selection criteria, expose the pre- and post-operative management, the procedure steps; regarding to our experience we deliver some tips to achieve the safest surgical procedure for the pediatric patient.

Multicentral study of thoracoscopic treatment of congenital diaphragmatic hernia

Multicentral study of thoracoscopic treatment of congenital diaphragmatic hernia

Progress of antenatal medication on treatment of congenital diaphragmatic hernia with pulmonary hypoplasia

Progress of antenatal medication on treatment of congenital diaphragmatic hernia with pulmonary hypoplasia

Predictors of prognosis in neonates with congenital diaphragmatic hernia: experience of 12 years

Introduction: Congenital diaphragmatic hernia (CDH) is a severe malformation, displaying relevant mortality and morbidity rates in newborns.Aim: To characterize clinically and demographically all neonatal cases of CDH admitted to a level III Neonatal Intensive Care Unit during a 12-year period and to evaluate the predictive value of baseline characteristics on mortality and morbidity at discharge.Methods: Maternal/infant clinical and electronic records were ret-rospectively reviewed. All neonates with posterolateral CDH admitted between January 2003 and December 2014 were included.Results: Fifty-three newborns were included. Overall mortality during hospitalization was 22/53 (41.5%). Clinical characteristics associated with mortality were the presence of intrathoracic liver (p = 0.005), intrathoracic stomach (p = 0.015), elevated arterial pCO2 or lower pH values at admission (respectively, p = 0.001 and p < 0.001), pre-ductal oxygen saturation < 85% at admission (p = 0.012) and surgical repair with prosthetic patch (p = 0.041). Morbidity at discharge was reported in 7 (22.6%) survivors. Stomach herniation and sepsis were associated with higher morbidity (respectively, p = 0.012 and p = 0.029). In a logistic regression, patch repair was the only variable with predictive value for death during hospitalization, with an odds ratio (OR) of 15 (95% CI 0.98-228.9), and intrathoracic stomach was a predictor of morbidity at discharge (OR = 15.7, 95% CI 1.4-174.2).Conclusion: Structural characteristics, namely defect size and presence of intrathoracic stomach, remain the primary determinants of neonatal prognosis in CDH. Although post-natal approaches have progressively proven their value in increasing survival and improving management of high-risk cases, future researches should continue focusing on the definition of foetal anatomical markers of severity and prenatal treatment of CDH.

A comparison of clinical outcomes between endoscopic and open surgery to repair neonatal diaphragmatic hernia.

OBJECTIVE:The objective of this study is to evaluate the clinical efficacies of open versus endoscopic surgery in the treatment of congenital diaphragmatic hernia (CDH) and investigate the feasibility and safety of endoscopic surgery as an alternative to open surgery in these cases.PATIENTS AND METHODS:A retrospective analysis was performed from June 2002 to February 2014. A total of 59 cases were attempted. The neonates were divided into either an endoscopic or open surgery group. The pre-, intra- and post-operative data on the neonates were analysed, and the surgery-related complications, survival rates and recurrence rates were compared between the two groups.RESULTS:Demographic characteristics were not significantly different between the two groups. Compared with open group, the hospital stay and post-operative mechanical ventilation time were significantly shorter, while surgery duration was significantly longer in the endoscopic surgery group. The recurrence rate was higher and the survival rate was lower in the endoscopic surgery group with no statistically significant and the recurrence rate has decreased over the past 5 years.CONCLUSIONS:We have demonstrated that the endoscopic surgery is safe and effective for repairing CDH. The endoscopic surgery is a minimally invasive procedure with fast post-operative recovery and a good cosmetic outcome.

IS-7 Current strategy and outcome in the treatment of congenital diaphragmatic hernia : A report from a single institute(International Session II)

IS-7 Current strategy and outcome in the treatment of congenital diaphragmatic hernia : A report from a single institute(International Session II)

Diagnosis and treatment of congenital diaphragmatic hernia

Congenital diaphragmatic hernia(CDH)is one of the critical congenital malformations disease which caused the defects of the diaphragmatic hernia, the hernia of the abdominal viscera into the thoracic cavity and the dysplasia of the lung because of the abnormal development of the embryo.The degree of pulmonary hypoplasia determined the curative effect of surgical treatment, so it is a key problem to improve the condition of pulmonary hypoplasia in treatment of CDH.Now it is feasible to make early prenatal diagnosis, predict outcomes and select the best operative opportunity of CDH with ultrasonography.It is a trend to treat CDH with endoscopic surgery of the minimally invasive operation.This article focuses on the latest diagnostics, treatment and new research progress of CDH, and summarized as follows. Key words: Congenital diaphragmatic hernia; Child; Pulmonary hypoplasia; Fetus; Diagnosis; Surgery; Endoscopic surgery

Computed Tomographic Study of the Pediatric Diaphragmatic Growth: Application to the Treatment of Congenital Diaphragmatic Hernia.

Background The prosthesis commonly used for the treatment of congenital diaphragmatic hernia (CDH) lacks elasticity to replace the diaphragm's mechanical properties and does not follow the natural growth of the child treated. Objective To determine the appropriate properties required for the prostheses, a CT study on healthy patients was conducted. Methods Two methods of diaphragmatic surface analysis are assessed: the diaphragmatic surface is either estimated using surface 2D estimations (method 1), or calculated using length measures on thoracoabdominal CT scans from children (method 2). Patients are divided into two groups depending on their age: group 1: n = 9; median age: 2.0 months (0.1-9.5); group 2: n = 9; median age: 182.6 months (158.5-235.5). Growth factor between the two groups is calculated and the two methods are statistically compared. Results The ratio group 2/group 1 of the diaphragmatic surfaces was 4.3 ± 0.2 on the left side and 4.0 ± 0.2 on the right side for method 1, and 5.1 ± 0.2 on the left side and 5.1 ± 0.3 on the right side for method 2. The difference in the median values between both methods is statistically significant for both the left and right sides (p = 0.022 and p = 0.002, respectively). Hence, the two methods cannot be used exchangeably. Conclusion The treatment of CDH with large defect remains a challenge because of the high incidence of hernia recurrence probably due to prosthesis defect; thus it is important to estimate the diaphragmatic surface precisely. We aim to develop a prosthesis material that can be commonly used and found a mean diaphragmatic growth factor of approximately 4 to 5 from early childhood to adolescence.

Применение имплантов в коррекции диафрагмальной грыжи у новорожденных

Применение имплантов в коррекции диафрагмальной грыжи у новорожденных