Hirschsprung Disease

Chapter
First Online:
Part of the Clinical Gastroenterology book series (CG)

Abstract

Over the past century dramatic advances have been made in Hirschsprung disease diagnosis, surgical management, developmental biology, and genetics. Ongoing studies provide new hope that we will be able to reduce HSCR incidence, prevent HAEC, replace missing enteric neurons using stem cells, image the ENS intra-operatively, improve surgical techniques, and incorporate genetics into clinical practice.

Keywords

Ganglion Cell Down Syndrome Abdominal Distension Enteric Nervous System Bowel Perforation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Sieber WK. Hirschsprung’s disease. Curr Probl Surg. 1978;15(6):1–76.PubMedCrossRefGoogle Scholar
  2. 2.
    Skinner MA. Hirschsprung’s disease. Curr Probl Surg. 1996;33(5):389–460.PubMedCrossRefGoogle Scholar
  3. 3.
    Dasgupta R, Langer JC. Hirschsprung disease. Curr Probl Surg. 2004;41(12):942–88.PubMedCrossRefGoogle Scholar
  4. 4.
    Martucciello G. Hirschsprung’s disease, one of the most difficult diagnoses in pediatric surgery: a review of the problems from clinical practice to the bench. Eur J Pediatr Surg. 2008;18(3):140–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Coran AG, Teitelbaum DH. Recent advances in the management of Hirschsprung’s disease. Am J Surg. 2000;180(5):382–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45(1):1–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Suita S, Taguchi T, Ieiri S, Nakatsuji T. Hirschsprung’s disease in Japan: analysis of 3852 patients based on a nationwide survey in 30 years. J Pediatr Surg. 2005;40(1):197–201. discussion 201–192.PubMedCrossRefGoogle Scholar
  8. 8.
    Haricharan RN, Georgeson KE. Hirschsprung disease. Semin Pediatr Surg. 2008;17(4):266–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Godbole K. Many faces of Hirschsprung’s disease. Indian Pediatr. 2004;41(11):1115–23.PubMedGoogle Scholar
  10. 10.
    Ikeda K, Goto S. Diagnosis and treatment of Hirschsprung’s disease in Japan. An analysis of 1628 patients. Ann Surg. 1984;199(4):400–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Singh SJ, Croaker GD, Manglick P, et al. Hirschsprung’s disease: the Australian Paediatric Surveillance Unit’s experience. Pediatr Surg Int. 2003;19(4):247–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Klein MD, Coran AG, Wesley JR, Drongowski RA. Hirschsprung’s disease in the newborn. J Pediatr Surg. 1984;19(4):370–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Kim AC, Langer JC, Pastor AC, et al. Endorectal pull-through for Hirschsprung’s disease-a multicenter, long-term comparison of results: transanal vs transabdominal approach. J Pediatr Surg. 2010;45(6):1213–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen F, Winston 3rd JH, Jain SK, Frankel WL. Hirschsprung’s disease in a young adult: report of a case and review of the literature. Ann Diagn Pathol. 2006;10(6):347–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Wald ER, Di Lorenzo C, Cipriani L, Colborn DK, Burgers R, Wald A. Bowel habits and toilet training in a diverse population of children. J Pediatr Gastroenterol Nutr. 2009;48(3):294–8.PubMedCrossRefGoogle Scholar
  16. 16.
    van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol. 2006;101(10):2401–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Hackam DJ, Reblock KK, Redlinger RE, Barksdale Jr EM. Diagnosis and outcome of Hirschsprung’s disease: does age really matter? Pediatr Surg Int. 2004;20(5):319–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Teitelbaum DH, Cilley RE, Sherman NJ, et al. A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes. Ann Surg. 2000; 232(3):372–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Diamond IR, Casadiego G, Traubici J, Langer JC, Wales PW. The contrast enema for Hirschsprung disease: predictors of a false-positive result. J Pediatr Surg. 2007;42(5):792–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Surana R, Quinn FMJ, Puri P. Neonatal intestinal perforation in Hirschsprung’s disease. Pediatr Surg Int. 1994;9:501–2.Google Scholar
  21. 21.
    Newman B, Nussbaum A, Kirkpatrick Jr JA. Bowel perforation in Hirschsprung’s disease. AJR Am J Roentgenol. 1987;148(6):1195–7.PubMedGoogle Scholar
  22. 22.
    Bell MJ. Perforation of the gastrointestinal tract and peritonitis in the neonate. Surg Gynecol Obstet. 1985;160(1):20–6.PubMedGoogle Scholar
  23. 23.
    Metaj M, Laroia N, Lawrence RA, Ryan RM. Comparison of breast- and formula-fed normal newborns in time to first stool and urine. J Perinatol. 2003;23(8):624–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Tunc VT, Camurdan AD, Ilhan MN, Sahin F, Beyazova U. Factors associated with defecation patterns in 0-24-month-old children. Eur J Pediatr. 2008;167(12):1357–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Bekkali N, Hamers SL, Schipperus MR, et al. Duration of meconium passage in preterm and term infants. Arch Dis Child Fetal Neonatal Ed. 2008; 93(5):F376–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Ameh N, Ameh EA. Timing of passage of first meconium and stooling pattern in normal Nigerian newborns. Ann Trop Paediatr. 2009;29(2): 129–33.PubMedCrossRefGoogle Scholar
  27. 27.
    Weaver LT, Lucas A. Development of bowel habit in preterm infants. Arch Dis Child. 1993;68(3 Spec No):317–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Reding R, de Ville de Goyet J, Gosseye S, et al. Hirschsprung’s disease: a 20-year experience. J Pediatr Surg. 1997;32(8):1221–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Jung PM. Hirschsprung’s disease: one surgeon’s experience in one institution. J Pediatr Surg. 1995; 30(5):646–51.PubMedCrossRefGoogle Scholar
  30. 30.
    Rahman N, Chouhan J, Gould S, et al. Rectal biopsy for Hirschsprung’s disease–are we performing too many? Eur J Pediatr Surg. 2010;20(2):95–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Martucciello G, Pini Prato A, Puri P, et al. Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth International Symposium on Hirschsprung’s disease and related neurocristopathies. J Pediatr Surg. 2005;40(10):1527–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Kapur RP. Practical pathology and genetics of Hirschsprung’s disease. Semin Pediatr Surg. 2009; 18(4):212–23.PubMedCrossRefGoogle Scholar
  33. 33.
    de Lorijn F, Kremer LC, Reitsma JB, Benninga MA. Diagnostic tests in Hirschsprung disease: a systematic review. J Pediatr Gastroenterol Nutr. 2006;42(5):496–505.PubMedCrossRefGoogle Scholar
  34. 34.
    Buder E, Meier-Ruge WA. Twenty years diagnostic competence center for Hirschsprung disease in Basel. Chirurg. 2010;81(6):572–6.CrossRefGoogle Scholar
  35. 35.
    Rees BI, Azmy A, Nigam M, Lake BD. Complications of rectal suction biopsy. J Pediatr Surg. 1983; 18(3):273–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Santos MM, Tannuri U, Coelho MC. Study of acetylcholinesterase activity in rectal suction biopsy for diagnosis of intestinal dysganglionoses: 17-year experience of a single center. Pediatr Surg Int. 2008;24(6):715–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Hall NJ, Kufeji D, Keshtgar A. Out with the old and in with the new: a comparison of rectal suction biopsies with traditional and modern biopsy forceps. J Pediatr Surg. 2009;44(2):395–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Alizai NK, Batcup G, Dixon MF, Stringer MD. Rectal biopsy for Hirschsprung’s disease: what is the optimum method? Pediatr Surg Int. 1998;13(2–3): 121–4.PubMedCrossRefGoogle Scholar
  39. 39.
    Kobayashi H, Li Z, Yamataka A, Lane GJ, Miyano T. Rectal biopsy: what is the optimal procedure? Pediatr Surg Int. 2002;18(8):753–6.PubMedGoogle Scholar
  40. 40.
    Puffenberger EG, Kauffman ER, Bolk S, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. 1994;3(8): 1217–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Torfs CP (1998) An epidemiological study of Hirschsprung disease in a multiracial California population. The Third International Meetings: Hirschsprung disease and related neurocristopathies. Evian, FranceGoogle Scholar
  42. 42.
    Spouge D, Baird PA. Hirschsprung disease in a large birth cohort. Teratology. 1985;32(2):171–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Koh CE, Yong TL, Fenton EJ. Hirschsprung’s disease: a regional experience. ANZ J Surg. 2008;78(11): 1023–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Schoellhorn J, Collins S. False positive reporting of Hirschsprung’s disease in Alaska: an evaluation of Hirschsprung’s disease surveillance, birth years 1996–2007. Birth Defects Res A Clin Mol Teratol. 2009;85(11):914–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Meza-Valencia BE, de Lorimier AJ, Person DA. Hirschsprung disease in the U.S. associated Pacific Islands: more common than expected. Hawaii Med J. 2005;64(4):96–8. 100–101.PubMedGoogle Scholar
  46. 46.
    Rajab A, Freeman NV, Patton MA. Hirschsprung’s disease in Oman. J Pediatr Surg. 1997;32(5):724–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990;46(3):568–80.PubMedGoogle Scholar
  48. 48.
    Pini Prato A, Musso M, Ceccherini I, et al. Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association. Medicine (Baltimore). 2009; 88(2):83–90.CrossRefGoogle Scholar
  49. 49.
    Sarioglu A, Tanyel FC, Buyukpamukcu N, Hicsonmez A. Hirschsprung-associated congenital anomalies. Eur J Pediatr Surg. 1997;7(6):331–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Abbag FI. Congenital heart diseases and other major anomalies in patients with Down syndrome. Saudi Med J. 2006;27(2):219–22.PubMedGoogle Scholar
  51. 51.
    Skaba R. Historic milestones of Hirschsprung’s disease (commemorating the 90th anniversary of Professor Harald Hirschsprung’s death). J Pediatr Surg. 2007;42(1):249–51.PubMedCrossRefGoogle Scholar
  52. 52.
    Swenson O, Bill Jr AH. Resection of rectum and rectosigmoid with preservation of the sphincter for benign spastic lesions producing megacolon; an experimental study. Surgery. 1948;24(2):212–20.PubMedGoogle Scholar
  53. 53.
    Marquez TT, Acton RD, Hess DJ, Duval S, Saltzman DA. Comprehensive review of procedures for total colonic aganglionosis. J Pediatr Surg. 2009;44(1):257–65. discussion 265.PubMedCrossRefGoogle Scholar
  54. 54.
    Langer JC. Response to Dr Swenson’s article: Hirschsprung’s disease—a complicated therapeutic problem: some thoughts and solutions based on data and personal experience over 56 years. J Pediatric Surg. 2004;39(10):1449–53.CrossRefGoogle Scholar
  55. 55.
    Teitelbaum DH, Coran AG. Primary pull-through for Hirschsprung’s disease. Semin Neonatol. 2003;8(3): 233–41.PubMedCrossRefGoogle Scholar
  56. 56.
    Rangel SJ, de Blaauw I. Advances in pediatric colorectal surgical techniques. Semin Pediatr Surg. 2010;19(2):86–95.PubMedCrossRefGoogle Scholar
  57. 57.
    De La Torre L, Langer JC. Transanal endorectal pull-through for Hirschsprung disease: technique, controversies, pearls, pitfalls, and an organized approach to the management of postoperative obstructive symptoms. Semin Pediatr Surg. 2010;19(2):96–106.CrossRefGoogle Scholar
  58. 58.
    Georgeson KE, Robertson DJ. Laparoscopic-assisted approaches for the definitive surgery for Hirschsprung’s disease. Semin Pediatr Surg. 2004;13(4):256–62.PubMedCrossRefGoogle Scholar
  59. 59.
    Shinall Jr MC, Koehler E, Shyr Y, Lovvorn 3rd HN. Comparing cost and complications of primary and staged surgical repair of neonatally diagnosed Hirschsprung’s disease. J Pediatr Surg. 2008;43(12): 2220–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Pastor AC, Osman F, Teitelbaum DH, Caty MG, Langer JC. Development of a standardized definition for Hirschsprung’s-associated enterocolitis: a Delphi analysis. J Pediatr Surg. 2009;44(1):251–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Vieten D, Spicer R. Enterocolitis complicating Hirschsprung’s disease. Semin Pediatr Surg. 2004; 13(4):263–72.PubMedCrossRefGoogle Scholar
  62. 62.
    Bush TG, Savidge TC, Freeman TC, et al. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell. 1998;93(2):189–201.PubMedCrossRefGoogle Scholar
  63. 63.
    Bjerknes M, Cheng H. Modulation of specific intestinal epithelial progenitors by enteric neurons. Proc Natl Acad Sci USA. 2001;98(22):12497–502.PubMedCrossRefGoogle Scholar
  64. 64.
    Van Landeghem L, Mahe MM, Teusan R, et al. Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions. BMC Genomics. 2009;10:507.PubMedCrossRefGoogle Scholar
  65. 65.
    Savidge TC, Newman P, Pothoulakis C, et al. Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology. 2007;132(4):1344–58.PubMedCrossRefGoogle Scholar
  66. 66.
    Murphy F, Puri P. New insights into the pathogenesis of Hirschsprung’s associated enterocolitis. Pediatr Surg Int. 2005;21(10):773–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Mattar AF, Coran AG, Teitelbaum DH. MUC-2 mucin production in Hirschsprung’s disease: possible association with enterocolitis development. J Pediatr Surg. 2003;38(3):417–21. discussion 417–421.PubMedCrossRefGoogle Scholar
  68. 68.
    Ruhl A. Glial cells in the gut. Neurogastroenterol Motil. 2005;17(6):777–90.PubMedCrossRefGoogle Scholar
  69. 69.
    Neunlist M, Van Landeghem L, Bourreille A, Savidge T. Neuro-glial crosstalk in inflammatory bowel disease. J Intern Med. 2008;263(6):577–83.PubMedCrossRefGoogle Scholar
  70. 70.
    Genton L, Kudsk KA. Interactions between the enteric nervous system and the immune system: role of neuropeptides and nutrition. Am J Surg. 2003; 186(3):253–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Veiga-Fernandes H, Coles MC, Foster KE, et al. Tyrosine kinase receptor RET is a key regulator of Peyer’s patch organogenesis. Nature. 2007;446(7135): 547–51.PubMedCrossRefGoogle Scholar
  72. 72.
    Cheng Z, Wang X, Dhall D, et al. Splenic lymphopenia in the endothelin receptor B-null mouse: implications for Hirschsprung associated enterocolitis. Pediatr Surg Int. 2011;27(2):145–50.PubMedCrossRefGoogle Scholar
  73. 73.
    Marty TL, Seo T, Sullivan JJ, Matlak ME, Black RE, Johnson DG. Rectal irrigations for the prevention of postoperative enterocolitis in Hirschsprung’s disease. J Pediatr Surg. 1995;30(5):652–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Momoh JT. Hirschsprung’s disease: problems of diagnosis and treatment. Ann Trop Paediatr. 1982; 2(1):31–5.PubMedGoogle Scholar
  75. 75.
    Rescorla FJ, Morrison AM, Engles D, West KW, Grosfeld JL. Hirschsprung’s disease. Evaluation of mortality and long-term function in 260 cases. Arch Surg. 1992;127(8):934–41. discussion 941–932.PubMedCrossRefGoogle Scholar
  76. 76.
    Sherman JO, Snyder ME, Weitzman JJ, et al. A 40-year multinational retrospective study of 880 Swenson procedures. J Pediatr Surg. 1989;24(8):833–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Menezes M, Puri P. Long-term outcome of patients with enterocolitis complicating Hirschsprung’s disease. Pediatr Surg Int. 2006;22(4):316–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Haricharan RN, Seo JM, Kelly DR, et al. Older age at diagnosis of Hirschsprung disease decreases risk of postoperative enterocolitis, but resection of additional ganglionated bowel does not. J Pediatr Surg. 2008;43(6):1115–23.PubMedCrossRefGoogle Scholar
  79. 79.
    Niramis R, Watanatittan S, Anuntkosol M, et al. Quality of life of patients with Hirschsprung’s disease at 5–20 years post pull-through operations. Eur J Pediatr Surg. 2008;18(1):38–43.PubMedCrossRefGoogle Scholar
  80. 80.
    Menezes M, Corbally M, Puri P. Long-term results of bowel function after treatment for Hirschsprung’s disease: a 29-year review. Pediatr Surg Int. 2006; 22(12):987–90.PubMedCrossRefGoogle Scholar
  81. 81.
    Gunnarsdottir A, Sandblom G, Arnbjornsson E, Larsson LT. Quality of life in adults operated on for Hirschsprung disease in childhood. J Pediatr Gastroenterol Nutr. 2010;51(2):160–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci. 2007;8(6):466–79.PubMedCrossRefGoogle Scholar
  83. 83.
    Newgreen D, Young HM. Enteric nervous system: development and developmental disturbances–part 1. Pediatr Dev Pathol. 2002;5(3):224–47.PubMedGoogle Scholar
  84. 84.
    Newgreen D, Young HM. Enteric nervous system: development and developmental disturbances–part 2. Pediatr Dev Pathol. 2002;5(4):329–49.PubMedCrossRefGoogle Scholar
  85. 85.
    Gariepy CE. Intestinal motility disorders and development of the enteric nervous system. Pediatr Res. 2001;49(5):605–13.PubMedCrossRefGoogle Scholar
  86. 86.
    Gershon MD. Lessons from genetically engineered animal models. II. Disorders of enteric neuronal development: insights from transgenic mice. Am J Physiol. 1999;277(2 Pt 1):G262–7.PubMedGoogle Scholar
  87. 87.
    Burzynski G, Shepherd IT, Enomoto H. Genetic model system studies of the development of the enteric nervous system, gut motility and Hirschsprung’s disease. Neurogastroenterol Motil. 2009;21(2):113–27.PubMedCrossRefGoogle Scholar
  88. 88.
    Jain S, Naughton CK, Yang M, et al. Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis. Development. 2004;131(21):5503–13.PubMedCrossRefGoogle Scholar
  89. 89.
    Gianino S, Grider JR, Cresswell J, Enomoto H, Heuckeroth RO. GDNF availability determines enteric neuron number by controlling precursor proliferation. Development. 2003;130(10):2187–98.PubMedCrossRefGoogle Scholar
  90. 90.
    Medhus AW, Bjornland K, Emblem R, Husebye E. Motility of the oesophagus and small bowel in adults treated for Hirschsprung’s disease during early childhood. Neurogastroenterol Motil. 2010; 22(2):154–60. e149.PubMedCrossRefGoogle Scholar
  91. 91.
    Medhus AW, Bjornland K, Emblem R, Husebye E. Liquid and solid gastric emptying in adults treated for Hirschsprung’s disease during early childhood. Scand J Gastroenterol. 2007;42(1):34–40.PubMedCrossRefGoogle Scholar
  92. 92.
    Miele E, Tozzi A, Staiano A, Toraldo C, Esposito C, Clouse RE. Persistence of abnormal gastrointestinal motility after operation for Hirschsprung’s disease. Am J Gastroenterol. 2000;95(5):1226–30.PubMedCrossRefGoogle Scholar
  93. 93.
    Faure C, Ategbo S, Ferreira GC, et al. Duodenal and esophageal manometry in total colonic aganglionosis. J Pediatr Gastroenterol Nutr. 1994;18(2):193–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Staiano A, Corazziari E, Andreotti MR, Clouse RE. Esophageal motility in children with Hirschsprung’s disease. Am J Dis Child. 1991;145(3):310–3.PubMedGoogle Scholar
  95. 95.
    Frykman PK, Lindsley EH, Gaon M, Farkas DL. Spectral imaging for precise surgical intervention in Hirschsprung’s disease. J Biophotonics. 2008; 1(2):97–103.PubMedCrossRefGoogle Scholar
  96. 96.
    Fu M, Sato Y, Lyons-Warren A, et al. Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Development. 2010;137(4):631–40.PubMedCrossRefGoogle Scholar
  97. 97.
    Hannon RJ, Boston VE. Discordant Hirschsprung’s disease in monozygotic twins: a clue to pathogenesis? J Pediatr Surg. 1988;23(11):1034–5.PubMedCrossRefGoogle Scholar
  98. 98.
    Siplovich L, Carmi R, Bar-Ziv J, Karplus M, Mares AJ. Discordant Hirschsprung’s disease in monozygotic twins. J Pediatr Surg. 1983;18(5):639–40.PubMedCrossRefGoogle Scholar
  99. 99.
    Hotta R, Natarajan D, Thapar N. Potential of cell therapy to treat pediatric motility disorders. Semin Pediatr Surg. 2009;18(4):263–73.PubMedCrossRefGoogle Scholar
  100. 100.
    Druckenbrod NR, Epstein ML. Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors. Development. 2009;136(18):3195–203.PubMedCrossRefGoogle Scholar
  101. 101.
    Lindley RM, Hawcutt DB, Connell MG, Edgar DH, Kenny SE. Properties of secondary and tertiary human enteric nervous system neurospheres. J Pediatr Surg. 2009;44(6):1249–55. discussion 1255–1246.PubMedCrossRefGoogle Scholar
  102. 102.
    Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N. Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology. 2009;136(7): 2214–25. e2211–2213.PubMedCrossRefGoogle Scholar
  103. 103.
    Thapar N. New frontiers in the treatment of Hirschsprung disease. J Pediatr Gastroenterol Nutr. 2009;48 Suppl 2:S92–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Gastroenterology, Hepatology, and NutritionWashington University School of MedicineSt. LouisUSA

Personalised recommendations