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Fetal Tracheal Occlusion for the Treatment of Congenital Diaphragmatic Hernia

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Abstract

Background

Congenital diaphragmatic hernia (CDH) continues to be associated with significant mortality and morbidity rates despite advances in neonatal care. Fetal intervention for CDH has been studied for 25 years. After initial difficulties encountered with open fetal repair, attention has turned to tracheal occlusion (TO) as a method to correct pulmonary hypoplasia before birth. This article reviews our contribution to this field of research and outlines the current status of this treatment modality.

Materials and Methods

Using the fetal lamb model, we have studied the effects of fetal TO on tracheal fluid pressure, lung growth and type II pneumocyte maturation, and surfactant production. We developed a minimally invasive and reversible technique of TO, using a detachable balloon placed using single-port tracheoscopy. We examined differential lung growth, structural maturation, pulmonary artery remodeling, and lung function during an 8-h resuscitation period in lambs, comparing normal controls, lambs with a surgically created CDH, those with CDH+TO, and those with CDH+TO and release of TO 1 week before delivery. We also studied the potential benefits of maternal betamethasone administration and the administration of surfactant at birth. Using a neonatal piglet model, we examined the effect of postnatal pulmonary distension with perfluorocarbon on lung growth. More recently, we turned to the rat nitrofen-induced CDH model to study the effects of TO on bronchial branching and some molecular markers of lung growth (Shh and LGL1).

Conclusions

Fetal TO is being used to treat human CDH, but its application remains limited by the absence of reliable and widely reproducible prenatal prognostic criteria. A better understanding of the molecular events guiding the lung growth seen with TO may help to refine its use in humans.

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References

  1. Laberge J-M, Sigalet DL, Guttman FM (1995) Congenital diaphragmatic hernia. In Nyhus LM, Condon RE, editors, Hernia, Philadelphia, J.B. Lippincott Company:555–566

  2. Doyle NM, Lally KP (2004) The CDH Study Group and advances in the clinical care of the patient with congenital diaphragmatic hernia. Semin Perinatol 28:174–184

    Article  PubMed  Google Scholar 

  3. Boloker J, Bateman DA, Wung JT, et al. (2002) Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg 37:357–366

    Article  PubMed  Google Scholar 

  4. Chiu PP, Sauer C, Mihailovic A, et al. (2006) The price of success in the management of congenital diaphragmatic hernia: is improved survival accompanied by an increase in long-term morbidity? J.Pediatr.Surg. 41(5):888–892

    Article  Google Scholar 

  5. Kitagawa M, Hislop A, Boyden EA, et al. (1971) Lung hypoplasia in congenital diaphragmatic hernia. A quantitative study of airway, artery, and alveolar development. Br J Surg 58:342–346

    Article  PubMed  CAS  Google Scholar 

  6. Thibeault DW, Haney B (1998) Lung volume, pulmonary vasculature, and factors affecting survival in congenital diaphragmatic hernia. Pediatrics 101:289–295

    Article  PubMed  CAS  Google Scholar 

  7. Morin FC III, Stenmark KR (1995) Persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 151:2010–2032

    PubMed  Google Scholar 

  8. Kays DW, Langham MR, Jr., Ledbetter DJ, et al. (1999) Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg 230:340–348

    Article  PubMed  CAS  Google Scholar 

  9. de Luca U, Cloutier R, Laberge JM, et al. (1987) Pulmonary barotrauma in congenital diaphragmatic hernia: experimental study in lambs. J Pediatr Surg 22:311–316

    Article  PubMed  Google Scholar 

  10. Antunes MJ, Greenspan JS, Cullen JA, et al. (1995) Prognosis with preoperative pulmonary function and lung volume assessment in infants with congenital diaphragmatic hernia. Pediatrics 96:1117–1122

    PubMed  CAS  Google Scholar 

  11. Harrison MR, Ross NA, De Lorimier AA (1981) Correction of congenital diaphragmatic hernia in utero. III. Development of a successful surgical technique using abdominoplasty to avoid compromise of umbilical blood flow. J Pediatr Surg 16:934–942

    Article  PubMed  CAS  Google Scholar 

  12. Laberge J-M (1986) Considering the fetus as a patient. Can Fam Physician 32:2099–2103

    Google Scholar 

  13. Louw JH, Barnard CN (1955) Congenital intestinal atresia; observations on its origin. Lancet 269:1065–1067

    Article  PubMed  CAS  Google Scholar 

  14. Clark RH, Hardin WD Jr, Hirschl RB, et al. (1998) Current surgical management of congenital diaphragmatic hernia: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 33:1004–1009

    Article  PubMed  CAS  Google Scholar 

  15. Adzick NS, Harrison MR, Glick PL et al. (1986) Fetal surgery in the primate III. Maternal outcome after fetal surgery. J Pediatr Surg 21:477–480

    PubMed  CAS  Google Scholar 

  16. Adzick NS, Outwater KM, Harrison MR, et al. (1985) Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis. J Pediatr Surg 20:673–680

    Article  PubMed  CAS  Google Scholar 

  17. Harrison MR, Adzick NS, Longaker MT, et al. (1990) Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax. N Engl J Med 322:1582–1584

    Article  PubMed  CAS  Google Scholar 

  18. Harrison MR, Langer JC, Adzick NS, et al. (1990) Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience. J Pediatr Surg 25:47–55

    Article  PubMed  CAS  Google Scholar 

  19. Harrison MR, Adzick NS, Flake AW et al. (1993) Correction of congenital diaphragmatic hernia in utero: VI. Hard-earned lessons. J Pediatr Surg 28:1411–1417

    Google Scholar 

  20. Albanese CT, Lopoo J, Goldstein RB, et al. (1998) Fetal liver position and perinatal outcome for congenital diaphragmatic hernia. Prenat Diagn 18:1138–1142

    Article  PubMed  CAS  Google Scholar 

  21. Harrison MR, Adzick NS, Bullard KM, et al. (1997) Correction of congenital diaphragmatic hernia in utero VII: a prospective trial. J Pediatr Surg 32:1637–1642

    Article  PubMed  CAS  Google Scholar 

  22. Wigglesworth JS, Desai R, Hislop AA (1987) Fetal lung growth in congenital laryngeal atresia. Pediatr Pathol 7:515–525

    Article  PubMed  CAS  Google Scholar 

  23. Adzick NS, Harrison MR, Glick PL, et al. (1984) Experimental pulmonary hypoplasia and oligohydramnios: relative contributions of lung fluid and fetal breathing movements. J Pediatr Surg 19:658–665

    Article  PubMed  CAS  Google Scholar 

  24. Alcorn D, Adamson TM, Lambert TF, et al. (1977) Morphological effects of chronic tracheal ligation and drainage in the fetal lamb lung. J Anat 123(Pt 3):649–660

    PubMed  CAS  Google Scholar 

  25. Moessinger AC, Harding R, Adamson TM, et al. (1990) Role of lung fluid volume in growth and maturation of the fetal sheep lung. J Clin Invest 1270–1277

  26. Hashim E, Laberge J-M, Chen M-F, et al. (1995) Reversible tracheal obstruction in the fetal sheep: effects on tracheal fluid pressure and lung growth. J Pediatr Surg 30:1172–1177

    Article  PubMed  CAS  Google Scholar 

  27. Wilson JM, DiFiore JW, Peters CA (1993) Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: possible application for congenital diaphragmatic hernia. J Pediatr Surg 28:1433–1439

    Article  PubMed  CAS  Google Scholar 

  28. DiFiore JW, Fauza DO, Slavin R, et al. (1994) Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg 29:248–256

    Article  PubMed  CAS  Google Scholar 

  29. Piedboeuf B, Laberge JM, Ghitulescu G, et al. (1997) Deleterious effect of tracheal obstruction on type II pneumocytes in fetal sheep. Pediatr Res 41(4 Pt 1):473–479

    Article  PubMed  CAS  Google Scholar 

  30. Finkelstein JN (1990) Physiologic and toxicologic responses of alveolar type II cells. Toxicology 60:41–52

    Article  PubMed  CAS  Google Scholar 

  31. Bin SW, Piedboeuf B, Laberge JM, et al. (1997) The effects of tracheal occlusion and release on type II pneumocytes in fetal lambs. J Pediatr Surg 32:834–838

    Article  Google Scholar 

  32. Avery ME (1995) Historical overview of antenatal steroid use. Pediatrics 95:133–135

    PubMed  CAS  Google Scholar 

  33. Kay S, Laberge JM, Flageole H, et al. (2001) Use of antenatal steroids to counteract the negative effects of tracheal occlusion in the fetal lamb model. Pediatr Res 50:495–501

    Article  PubMed  CAS  Google Scholar 

  34. Harrison MR, Adzick NS, Flake AW, et al. (1996) Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg 31:1339–1348

    Article  PubMed  CAS  Google Scholar 

  35. Harrison MR, Mychaliska GB, Albanese CT, et al. (1998) Correction of congenital diaphragmatic hernia in utero IX: fetuses with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion. J Pediatr Surg 33:1017–1022

    Article  PubMed  CAS  Google Scholar 

  36. Harrison MR, Sydorak RM, Farrell JA, et al. (2003) Fetoscopic temporary tracheal occlusion for congenital diaphragmatic hernia: prelude to a randomized, controlled trial. J.Pediatr.Surg 38:1012–1020

    Article  PubMed  Google Scholar 

  37. Flageole H, Evrard VA, Vandenberghe K, et al. (1997) Tracheoscopic endotracheal occlusion in the ovine model: technique and pulmonary effects. J Pediatr Surg 32:1328–1331

    Article  PubMed  CAS  Google Scholar 

  38. White RI, Jr., Kaufman SL, Barth KH, et al. (1979) Embolotherapy with detachable silicone balloons: technique and clinical results. Radiology 131:619–627

    PubMed  Google Scholar 

  39. Bealer JF, Skarsgard ED, Hedrick MH, et al. (1995) The ‘PLUG’ odyssey: adventures in experimental fetal tracheal occlusion. J Pediatr Surg 30:361–364

    Article  PubMed  CAS  Google Scholar 

  40. Bratu I, Flageole H, Laberge J-M, et al. (1999) Lung growth and structural development after reversible fetal tracheal occlusion in diaphragmatic hernia. Surg Forum 50:569–570

    Google Scholar 

  41. Flageole H, Evrard VA, Piedboeuf B, et al. (1998) The plug-unplug sequence: an important step to achieve type II pneumocyte maturation in the fetal lamb model. J Pediatr Surg 33:299–303

    Article  PubMed  CAS  Google Scholar 

  42. Bratu I, Flageole H, Laberge JM, et al. (2001) Surfactant levels after reversible tracheal occlusion and prenatal steroids in experimental diaphragmatic hernia. J Pediatr Surg 36:122–127

    Article  PubMed  CAS  Google Scholar 

  43. Bratu I, Flageole H, Laberge JM et al. (001) Pulmonary structural maturation and pulmonary artery remodeling after reversible fetal ovine tracheal occlusion in diaphragmatic hernia. J Pediatr Surg 36:739–744

    Google Scholar 

  44. Bratu I, Flageole H, Laberge JM, et al. (2004) Lung function in lambs with diaphragmatic hernia after reversible fetal tracheal occlusion. J Pediatr Surg 39:1524–1531

    Article  PubMed  Google Scholar 

  45. Cloutier M, Seaborn T, Piedboeuf B, et al. (2005) Effect of temporary tracheal occlusion on the endothelin system in experimental cases of diaphragmatic hernia. Exp Lung Res 31:391–404

    Article  PubMed  CAS  Google Scholar 

  46. Butter A, Bratu I, Flageole H, et al. (2005) Fetal tracheal occlusion in lambs with congenital diaphragmatic hernia: role of exogenous surfactant at birth. Pediatr Res 58:689–694

    Article  PubMed  Google Scholar 

  47. Ijsselstijn H, Zimmermann LJ, Bunt JE et al. (1998) Prospective evaluation of surfactant composition in bronchoalveolar lavage fluid of infants with congenital diaphragmatic hernia and of age-matched controls. Crit Care Med 26:573–580

    Google Scholar 

  48. McCabe AJ, Wilcox DT, Holm BA, et al. (2000) Surfactant—a review for pediatric surgeons. J Pediatr Surg 35:1687–1700

    Article  PubMed  CAS  Google Scholar 

  49. Lally KP, Lally PA, Langham MR, et al. (2004) Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia. J Pediatr Surg 39:829–833

    Article  PubMed  Google Scholar 

  50. Pranikoff T, Gauger PG, Hirschl RB (1996) Partial liquid ventilation in newborn patients with congenital diaphragmatic hernia. J Pediatr Surg 31:613–618

    Article  PubMed  CAS  Google Scholar 

  51. Nobuhara KK, Fauza DO, DiFiore JW, et al. (1998) Continuous intrapulmonary distension with perfluorocarbon accelerates neonatal (but not adult) lung growth. J Pediatr Surg 33:292–298

    Article  PubMed  CAS  Google Scholar 

  52. Hirschl RB, Philip WF, Glick L, et al. (2003) A prospective, randomized pilot trial of perfluorocarbon-induced lung growth in newborns with congenital diaphragmatic hernia. J Pediatr Surg 38:283–289

    Article  PubMed  Google Scholar 

  53. Butter A, Piedboeuf B, Flageole H, et al. (2005) Postnatal pulmonary distension for the treatment of pulmonary hypoplasia: pilot study in the neonatal piglet model. J Pediatr Surg 40:826–831

    Article  PubMed  Google Scholar 

  54. Cilley RE, Zgleszewski SE, Krummel TM, et al. (1997) Nitrofen dose-dependent gestational day-specific murine lung hypoplasia and left-sided diaphragmatic hernia. Am J Physiol 272(2 Pt 1):L362–L371

    PubMed  CAS  Google Scholar 

  55. Losty PD, Pacheco BA, Manganaro TF, et al. (1996) Prenatal hormonal therapy improves pulmonary morphology in rats with congenital diaphragmatic hernia. J Surg Res 65:42–52

    Article  PubMed  CAS  Google Scholar 

  56. Guarino N, Oue T, Shima H, et al. (2000) Antenatal dexamethasone enhances surfactant protein synthesis in the hypoplastic lung of nitrofen-induced diaphragmatic hernia in rats. J Pediatr Surg 35:1468–1473

    Article  PubMed  CAS  Google Scholar 

  57. Kitano Y, Davies P, von Allman D, et al. (1999) Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia. J Appl Physiol 87:769–775

    PubMed  CAS  Google Scholar 

  58. Yoshizawa J, Chapin CJ, Sbragia L, et al. (2003) Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats. Am J Physiol Lung Cell Mol Physiol 285:L344–L353

    PubMed  CAS  Google Scholar 

  59. Baird R, Khan N, Flageole H, et al. (2006) Lung branching in the nitrophen rat model of congenital diaphragmatic hernia with or without tracheal occlusion. J Surg Res 130:284–285

    Article  Google Scholar 

  60. Baird R, Khan N, Laberge J-M et al. (2006) Tracheal occlusion upregulates late gestation lung-l (LGLl), but not sonic Hedgehog (Shh) expression in the fetal rat. Annual Meeting of the Canadian Association of Paediatric Surgeons.

  61. Baird R, Khan N, Laberge J-M et al. (2006) Altered LGL1 expression suggests diaphragmatic hernia contributes to pulmonary hypoplasia in Nitrofen-fed rats. Annual Meeting of the American Thoracic Society

  62. Baird R (2006) Morphologic and molecular investigation of pulmonary branching in the Nitrofen-rat model of congenital diaphragmatic hernia with or without tracheal occlusion. Masters Thesis, McGill University

  63. Harrison MR, Keller RL, Hawgood SB, et al. (2003) A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med 349:1916–1924

    Article  PubMed  CAS  Google Scholar 

  64. Deprest J, Jani J, Van Schoubroeck D, et al. (2006) Current consequences of prenatal diagnosis of congenital diaphragmatic hernia. J Pediatr Surg 41:423–430

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors recognize the contribution of the many collaborators mentioned in the text or listed as co-authors in the publications quoted, as well as the essential part played by the surgical residents/fellows who performed most of the experiments. Support from Dr. Bruce Williams, Surgeon-in-Chief at the Montreal Children’s Hospital, was also essential throughout this period.

Various funding sources have made this work possible, including the Montreal Children’s Hospital Research Institute, the Medical Research Council of Canada (now the Canadian Institutes for Health Research), the Quebec Lung Association, the Fonds de Recherche en Santé du Québec, the Canadian Association of General Surgeons Research Fund, the Foundation for Research into Children’s Diseases, and the Pediatric Surgery Research and Education Fund of the Montreal Children’s Hospital.

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Correspondence to Jean-Martin Laberge.

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Laberge, JM., Flageole, H. Fetal Tracheal Occlusion for the Treatment of Congenital Diaphragmatic Hernia. World J Surg 31, 1577–1586 (2007). https://doi.org/10.1007/s00268-007-9074-7

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