Top

Published in:

Open Access 01-12-2023 | Motility Disorder | Review

Interstitial cells of Cajal: clinical relevance in pediatric gastrointestinal motility disorders

Authors: Florian Friedmacher, Udo Rolle

Published in: Pediatric Surgery International | Issue 1/2023

Abstract

Interstitial cells of Cajal (ICCs) are pacemaker cells of gastrointestinal motility that generate and transmit electrical slow waves to smooth muscle cells in the gut wall, thus inducing phasic contractions and coordinated peristalsis. Traditionally, tyrosine-protein kinase Kit (c-kit), also known as CD117 or mast/stem cell growth factor receptor, has been used as the primary marker of ICCs in pathology specimens. More recently, the Ca²⁺-activated chloride channel, anoctamin-1, has been introduced as a more specific marker of ICCs. Over the years, various gastrointestinal motility disorders have been described in infants and young children in which symptoms of functional bowel obstruction arise from ICC-related neuromuscular dysfunction of the colon and rectum. The current article provides a comprehensive overview of the embryonic origin, distribution, and functions of ICCs, while also illustrating the absence or deficiency of ICCs in pediatric patients with Hirschsprung disease intestinal neuronal dysplasia, isolated hypoganglionosis, internal anal sphincter achalasia, and congenital smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome.

Cajal RS (1893) Sur les ganglions et plexus nerveux de I’intestin. CR Soc Biol (Paris) 45:217–223

Faussone Pellegrini MS (1985) Ultrastructural peculiarities of the inner portion of the circular layer of the colon. II. Research on the mouse. Acta Anat (Basel) 122:187–192. https://doi.org/10.1159/000146000CrossRefPubMed

Taxi J (1965) Contribution á l’étude des connexions des neurones moteurs du systeme nerveux sutonome. Ann Sci Nat Zool Biol Anim 7:413–674

Taxi J (1952) Cellules de Schwann et “cellules interstitielles de Cajal” au niveau des plexus nerveux de la muscleuse intestinale du Cobaye: retour aux definitions. Arch Anat Micrsc Morphol Exp 41:281–304

Thuneberg L (1982) Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol 71:1–130CrossRefPubMed

Komuro T, Tokui K, Zhou DS (1996) Identification of interstitial cells of Cajal. Histol Histopathol 11:769–786PubMed

Huizinga JD, Thuneberg L, Klüppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 26(373):347–349. https://doi.org/10.1038/373347a0CrossRef

Huizinga JD, Chen JH (2014) Interstitial cells of Cajal: update on basic and clinical science. Curr Gastroenterol Rep 16:363. https://doi.org/10.1007/s11894-013-0363-zCrossRefPubMed

Burns AJ (2007) Disorders of interstitial cells of Cajal. J Pediatr Gastroenterol Nutr 45:S103-106. https://doi.org/10.1097/MPG.0b013e31812e65e0CrossRefPubMed

10.

Rømert P, Mikkelsen HB (1998) c-kit immunoreactive interstitial cells of Cajal in the human small and large intestine. Histochem Cell Biol 109:195–202. https://doi.org/10.1007/s004180050218CrossRefPubMed

11.

Carmona R, Cano E, Mattiotti A, Gaztambide J, Muñoz-Chápuli R (2013) Cells derived from the coelomic epithelium contribute to multiple gastrointestinal tissues in mouse embryos. PLoS One 8:e55890. https://doi.org/10.1371/journal.pone.0055890CrossRefPubMedPubMedCentral

12.

Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (2012) Anoctamins and gastrointestinal smooth muscle excitability. Exp Physiol 97:200–206. https://doi.org/10.1113/expphysiol.2011.058248CrossRefPubMed

13.

Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, Van de Rijn M, West RB, Sarr MG, Kendrick ML, Cima RR, Dozois EJ, Larson DW, Ordog T, Farrugia G (2009) Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 296:G1370-1381. https://doi.org/10.1152/ajpgi.00074.2009CrossRefPubMedPubMedCentral

14.

Torihashi S, Horisawa M, Watanabe Y (1999) c-kit immunoreactive interstitial cells in the human gastrointestinal tract. J Auton Nerv Syst 75:38–50. https://doi.org/10.1016/s0165-1838(98)00174-xCrossRefPubMed

15.

Hagger R, Gharaie S, Finlayson C, Kumar D (1998) Distribution of the interstitial cells of Cajal in the human anorectum. J Auton Nerv Syst 73:75–79. https://doi.org/10.1016/s0165-1838(98)00038-1CrossRefPubMed

16.

Faussone-Pellegrini MS, Cortesini C (1985) Ultrastructural features and localization of the interstitial cells of Cajal in the smooth muscle coat of human esophagus. J Submicrosc Cytol 17:187–197PubMed

17.

Benarroch EE (2007) Enteric nervous system: functional organization and neurologic implications. Neurology 69:1953–1957. https://doi.org/10.1212/01.wnl.0000281999.56102.b5CrossRefPubMed

18.

McCann CJ, Hwang SJ, Bayguinov Y, Colletti EJ, Sanders KM, Ward SM (2013) Establishment of pacemaker activity in tissues allotransplanted with interstitial cells of Cajal. Neurogastroenterol Motil 25:e418-428. https://doi.org/10.1111/nmo.12140CrossRefPubMedPubMedCentral

19.

Klüppel M, Huizinga JD, Malysz J, Bernstein A (1998) Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Dev Dyn 211:60–71. https://doi.org/10.1002/(SICI)1097-0177(199801)211:1%3c60::AID-AJA6%3e3.0.CO;2-5CrossRefPubMed

20.

Torihashi S, Ward SM, Sanders KM (1997) Development of c-kit-positive cells and the onset of electrical rhythmicity in murine small intestine. Gastroenterology 112:144–155. https://doi.org/10.1016/s0016-5085(97)70229-4CrossRefPubMed

21.

Lecoin L, Gabella G, Le Douarin N (1996) Origin of the c-kit-positive interstitial cells in the avian bowel. Development 122:725–733. https://doi.org/10.1242/dev.122.3.725CrossRefPubMed

22.

Young HM, Ciampoli D, Southwell BR, Newgreen DF (1996) Origin of interstitial cells of Cajal in the mouse intestine. Dev Biol 180:97–107. https://doi.org/10.1006/dbio.1996.0287CrossRefPubMed

23.

Beckett EA, Ro S, Bayguinov Y, Sanders KM, Ward SM (2007) Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract. Dev Dyn 236:60–72. https://doi.org/10.1002/dvdy.20929CrossRefPubMed

24.

Kenny SE, Connell G, Woodward MN, Lloyd DA, Gosden CM, Edgar DH, Vaillant C (1999) Ontogeny of interstitial cells of Cajal in the human intestine. J Pediatr Surg 34(8):1241–1247. https://doi.org/10.1016/s0022-3468(99)90160-4CrossRefPubMed

25.

Ward SM, Ordög T, Bayguinov JR, Horowitz B, Epperson A, Shen L, Westphal H, Sanders KM (1999) Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves. Gastroenterology 117:584–594. https://doi.org/10.1016/s0016-5085(99)70451-8CrossRefPubMed

26.

Wester T, Eriksson L, Olsson Y, Olsen L (1999) Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry. Gut 44:65–71. https://doi.org/10.1136/gut.44.1.65CrossRefPubMedPubMedCentral

27.

Gomez-Pinilla PJ, Gibbons SJ, Sarr MG, Kendrick ML, Shen KR, Cima RR, Dozois EJ, Larson DW, Ordog T, Pozo MJ, Farrugia G (2011) Changes in interstitial cells of cajal with age in the human stomach and colon. Neurogastroenterol Motil 23:36–44. https://doi.org/10.1111/j.1365-2982.2010.01590.xCrossRefPubMed

28.

Keith A (1915) The Cabendish lecture: on a new theory of the causation of enterostasis. Lancet 186:371–375. https://doi.org/10.1016/S0140-6736(01)53737-XCrossRef

29.

Yamamoto M (1977) Electron microscopic studies on the innervation of the smooth muscle and the interstitial cell of Cajal in the small intestine of the mouse and bat. Arch Histol Jpn 40:171–201. https://doi.org/10.1679/aohc1950.40.171CrossRefPubMed

30.

Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM (1995) c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res 280:97–111. https://doi.org/10.1007/BF00304515CrossRefPubMed

31.

Ward SM, Burns AJ, Torihashi S, Sanders KM (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 480:91–97. https://doi.org/10.1113/jphysiol.1994.sp020343CrossRefPubMedPubMedCentral

32.

Sanders KM, Ward SM (2006) Interstitial cells of Cajal: a new perspective on smooth muscle function. J Physiol 576:721–726. https://doi.org/10.1113/jphysiol.2006.115279CrossRefPubMedPubMedCentral

33.

Komuro T (2006) Structure and organization of interstitial cells of Cajal in the gastrointestinal tract. J Physiol 576:653–658. https://doi.org/10.1113/jphysiol.2006.116624CrossRefPubMedPubMedCentral

34.

Huizinga JD, Hussain A, Chen JH (2021) Interstitial cells of Cajal and human colon motility in health and disease. Am J Physiol Gastrointest Liver Physiol 321:G552–G575. https://doi.org/10.1152/ajpgi.00264.2021CrossRefPubMed

35.

Mitsui R, Komuro T (2003) Distribution and ultrastructure of interstitial cells of Cajal in the gastric antrum of wild-type and Ws/Ws rats. Anat Embryol (Berl) 206:453–460. https://doi.org/10.1007/s00429-003-0323-8CrossRefPubMed

36.

Seki K, Komuro T (2002) Distribution of interstitial cells of Cajal and gap junction protein, Cx 43 in the stomach of wild-type and W/Wv mutant mice. Anat Embryol (Berl) 206:57–65. https://doi.org/10.1007/s00429-002-0279-0CrossRefPubMed

37.

Horiguchi K, Semple GS, Sanders KM, Ward SM (2001) Distribution of pacemaker function through the tunica muscularis of the canine gastric antrum. J Physiol 537:237–250. https://doi.org/10.1111/j.1469-7793.2001.0237k.xCrossRefPubMedPubMedCentral

38.

Ishikawa K, Komuro T (1996) Characterization of the interstitial cells associated with the submuscular plexus of the guinea-pig colon. Anat Embryol (Berl) 194:49–55. https://doi.org/10.1007/BF00196314CrossRefPubMed

39.

Berezin I, Huizinga JD, Daniel EE (1988) Interstitial cells of Cajal in the canine colon: a special communication network at the inner border of the circular muscle. J Comp Neurol 273:42–51. https://doi.org/10.1002/cne.902730105CrossRefPubMed

40.

Mazet B, Raynier C (2004) Interstitial cells of Cajal in the guinea pig gastric antrum: distribution and regional density. Cell Tissue Res 316:23–34. https://doi.org/10.1007/s00441-003-0835-9CrossRefPubMed

41.

Rumessen JJ, Thuneberg L, Mikkelsen HB (1982) Plexus muscularis profundus and associated interstitial cells. II. Ultrastructural studies of mouse small intestine. Anat Rec 203:129–146. https://doi.org/10.1002/ar.1092030112CrossRefPubMed

42.

Blair PJ, Bayguinov Y, Sanders KM, Ward SM (2012) Interstitial cells in the primate gastrointestinal tract. Cell Tissue Res 350:199–213. https://doi.org/10.1007/s00441-012-1468-7CrossRefPubMedPubMedCentral

43.

Zhou DS, Komuro T (1992) Interstitial cells associated with the deep muscular plexus of the guinea-pig small intestine, with special reference to the interstitial cells of Cajal. Cell Tissue Res 268:205–216. https://doi.org/10.1007/BF00318788CrossRefPubMed

44.

Vanderwinden JM, Rumessen JJ, Bernex F, Schiffmann SN, Panthier JJ (2000) Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit(W-lacZ) mice. Cell Tissue Res 302:155–170. https://doi.org/10.1007/s004419900170CrossRefPubMed

45.

Rogers DC, Burnstock G (1966) The interstitial cell and its place in the concept of the autonomic ground plexus. J Comp Neurol 126:255–284. https://doi.org/10.1002/cne.901260207CrossRefPubMed

46.

Cook RD, Burnstock G (1976) The ultrastructure of Auerbach`s plexus in the guinea pig. II Non-neuronal elements J Neurocytol 5:195–206. https://doi.org/10.1007/BF01181656CrossRefPubMed

47.

Imaizumi M, Hama K (1969) An electron microscopic study on the interstitial cells of the gizzard in the love bird (Uronloncha domestica). Z Zellforsch Mikrosk Anat 97:351–357. https://doi.org/10.1007/BF00968841CrossRefPubMed

48.

Gabella G (1972) Fine structure of the myenteric plexus in the guinea-pig ileum. J Anat 111:69–97PubMedPubMedCentral

49.

Faussone-Pellegrini MS (1992) Histogenesis, structure and relationships of interstitial cells of Cajal (ICC): from morphology to functional interpretation. Eur J Morphol 30:137–148PubMed

50.

Rumessen JJ, Mikkelsen HB, Qvortrup K, Thuneberg L (1993) Ultrastructure of interstitial cells of Cajal in circular muscle of human small intestine. Gastroenterology 104:343–350. https://doi.org/10.1016/0016-5085(93)90400-7CrossRefPubMed

51.

Faussone-Pellegrini MS, Thuneberg L (1999) Guide to the identification of interstitial cells of Cajal. Microsc Res Tech 47:248–266. https://doi.org/10.1002/(SICI)1097-0029(19991115)47:4%3c248::AID-JEMT4%3e3.0.CO;2-WCrossRefPubMed

52.

Mazzia C, Porcher C, Julé Y, Christen MO, Henry M (2000) Ultrastructural study of relationships between c-kit immunoreactive interstitial cells and other cellular elements in the human colon. Histochem Cell Biol 113:401–411. https://doi.org/10.1007/s004180000154CrossRefPubMed

53.

Hagger R, Finlayson C, Jeffrey I, Kumar D (1997) Role of the interstitial cells of Cajal in the control of gut motility. Brit J Surg 84:445–450PubMed

54.

Rumessen JJ, Thuneberg L (1991) Interstitial cells of Cajal in the human small intestine. Ultrastructural identification and organization between the main smooth muscle layers. Gastroenterology 100:1417–1431CrossRefPubMed

55.

Rumessen JJ, Thuneberg L (1996) Pacemaker cells in the gastrointestinal tract: interstitial cells of Cajal. Scand J Gastroenterol 216:82–94. https://doi.org/10.3109/00365529609094564CrossRef

56.

Komuro T, Tokui K, Zhou DS (1996) Identification of the interstitial cells of Cajal. Histol Histopathol 11:769–786PubMed

57.

Christensen J, Rick GA, Lowe LS (1992) Distributions of interstitial cells of Cajal in the stomach and colon of cat, dog, ferret, opossum, rat, guinea pig and rabbit. J Auton Nerv Syst 37:47–56. https://doi.org/10.1016/0165-1838(92)90144-6CrossRefPubMed

58.

Christensen J (1992) A commentary on the morphological identification of interstitial cells of Cajal in the gut. J Auton Nerv Syst 37:75–88. https://doi.org/10.1016/0165-1838(92)90236-aCrossRefPubMed

59.

Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K, Nishikawa S (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116:369–375. https://doi.org/10.1242/dev.116.2.369CrossRefPubMed

60.

Ward SM, Burns AJ, Torihashi S, Harney SC, Sanders KM (1995) Impaired development of interstitial cells and intestinal electrical rhythmicity in steel mutants. Am J Physiol 269:C1577-1585. https://doi.org/10.1152/ajpcell.1995.269.6.C1577CrossRefPubMed

61.

Horisawa M, Watanabe Y, Torihashi S (1998) Distribution of c-kit immunopositive cells in normal human colon and in Hirschsprung’s disease. J Pediatr 33:1209–1214. https://doi.org/10.1016/s0022-3468(98)90152-xCrossRef

62.

Horie K, Fujita J, Takakura K, Kanzaki H, Suginami H, Iwai M, Nakayama H, Mori T (1993) The expression of c-kit protein in human adult and fetal tissue. Hum Reprod 8:1955–1962. https://doi.org/10.1093/oxfordjournals.humrep.a137967CrossRefPubMed

63.

Sanders KM (1996) A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 111:492–515. https://doi.org/10.1053/gast.1996.v111.pm8690216CrossRefPubMed

64.

Horiguchi K, Komuro T (1998) Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats. Cell Tissue Res 293:277–284. https://doi.org/10.1007/s004410051119CrossRefPubMed

65.

Isozaki K, Hirota S, Nakama A, Miyagawa J, Shinomura Y, Xu Z, Nomura S, Kitamura Y (1995) Disturbed intestinal movement, bile reflux to the stomach, and deficiency of c-kit-expressing cells in Ws/Ws mutant rats. Gastroenterology 109:456–464. https://doi.org/10.1016/0016-5085(95)90333-xCrossRefPubMed

66.

Burns AJ, Herbert TM, Ward SM, Sanders KM (1997) Interstitial cells of Cajal in the guinea-pig gastrointestinal tract as revealed by c-Kit immunohistochemistry. Cell Tissue Res 290:11–20. https://doi.org/10.1007/s004410050902CrossRefPubMed

67.

Komuro T, Zhou DS (1996) Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine. J Auton Nerv Syst 61:169–174. https://doi.org/10.1016/s0165-1838(96)00078-1CrossRefPubMed

68.

Nemeth L, Puri P (2001) Three-dimensional morphology of c-kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Lab Med 125:899–904. https://doi.org/10.5858/2001-125-0899-TDMOCKCrossRefPubMed

69.

Fekete E, Resch BA, Benedeczky I (1995) Histochemical and ultrastructural features of the developing enteric nervous system of the human foetal small intestine. Histol Histopathol 10:127–134PubMed

70.

Mebis J, Penninckx F, Geboes K, Eggermont E, Desmet V (1990) Neuropathology of Hirschsprung’s disease: en face study of microdissected intestine. Hepatogastroenterology 37:596–600PubMed

71.

Wang XY, Sanders KM, Ward SM (1999) Intimate relationship between interstitial cells of Cajal and enteric nerves in the guinea-pig small intestine. Cell Tissue Res 295:247–256. https://doi.org/10.1007/s004410051231CrossRefPubMed

72.

Ward SM (2000) Interstitial cells of Cajal in enteric neurotransmission. Gut 47:iv40-43. https://doi.org/10.1136/gut.47.suppl_4.iv40CrossRefPubMedPubMedCentral

73.

Rolle U, Nemeth L, Puri P (2002) Nitrergic innervation of the normal gut and in motility disorders of childhood. J Pediatr Surg 37:551–567. https://doi.org/10.1053/jpsu.2002.31610CrossRefPubMed

74.

Wedel T, Krammer HJ, Kühnel W, Sigge W (1998) Alterations of the enteric nervous system in neonatal necrotizing enterocolitis revealed by whole-mount immunohistochemistry. Pediatr Pathol Lab Med 18:57–70CrossRefPubMed

75.

Ferri GL, Botti PL, Vezzadini P (1982) Peptide-containing innervation of the human intestinal mucosa. An immunocytochemical study on whole-mount preparations. Histochemistry 76:413–420. https://doi.org/10.1007/BF00543961CrossRefPubMed

76.

Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T (2010) The London classification of gastrointestinal neuromuscular pathology: report on behalf of the gastro 2009 international working group. Gut 59:882–887. https://doi.org/10.1136/gut.2009.200444CrossRefPubMed

77.

Friedmacher F, Puri P (2013) Classification and diagnostic criteria of variants of Hirschsprung’s disease. Pediatr Surg Int 29:855–872. https://doi.org/10.1007/s00383-013-3351-3CrossRefPubMed

78.

Yamataka A, Kato Y, Tibboel D, Murata Y, Sueyoshi N, Fujimoto T, Nishiye H, Miyano T (1995) A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung’s disease. J Pediatr Surg 30:441–444. https://doi.org/10.1016/0022-3468(95)90051-9CrossRefPubMed

79.

Yamataka A, Ohshiro K, Kobayashi H, Fujiwara T, Sunagawa M, Miyano T (1997) Intestinal pacemaker C-KIT+ cells and synapses in allied Hirschsprung’s disorders. J Pediatr Surg 32:1069–1074. https://doi.org/10.1016/s0022-3468(97)90401-2CrossRefPubMed

80.

Vanderwinden JM, Rumessen JJ, Liu H, Descamps D, De Laet MH, Vanderhaeghen JJ (1996) Interstitial cells of Cajal in the colon and in the Hirschsprung’s disease. Gastroenterology 111:901–910. https://doi.org/10.1016/s0016-5085(96)70057-4CrossRefPubMed

81.

Rolle U, Piotrowska AP, Nemeth L, Puri P (2002) Altered distribution of interstitial cells of Cajal in Hirschsprung disease. Arch Pathol Lab Med 126:928–933. 10.5858/2002-126-0928-ADOICO

82.

Piotrowska AP, Solari V, de Caluwe D, Puri P (2003) Immunocolocalization of the heme oxygenase-2 and interstitial cells of Cajal in normal and aganglionic colon. J Pediatr Surg 38:73–77. https://doi.org/10.1053/jpsu.2003.50014CrossRefPubMed

83.

Newgreen D, Young HM (2002) Enteric nervous system: development and developmental disturbances–part 2. Pediatr Dev Pathol 5:329–349. https://doi.org/10.1007/s10024-002-0002-4CrossRefPubMed

84.

Taguchi T, Suita S, Masumoto K, Nada O (2003) Universal distribution of c-kit-positive cells in different types of Hirschsprung’s disease. Pediatr Surg Int 19:273–279. https://doi.org/10.1007/s00383-002-0931-zCrossRefPubMed

85.

Gfroerer S, Rolle U (2013) Interstitial cells of Cajal in the normal human gut and in Hirschsprung disease. Pediatr Surg Int 29:889–897. https://doi.org/10.1007/s00383-013-3364-yCrossRefPubMed

86.

Bettolli M, De Carli C, Jolin-Dahel K, Bailey K, Khan HF, Sweeney B, Krantis A, Staines WA, Rubin S (2008) Colonic dysmotility in postsurgical patients with Hirschsprung’s disease. Potential significance of abnormalities in the interstitial cells of Cajal and the enteric nervous system. J Pediatr Surg 43:1433–1438. https://doi.org/10.1016/j.jpedsurg.2007.10.067CrossRefPubMed

87.

Newman CJ, Laurini RN, Lesbros Y, Reinberg O, Meyrat BJ (2003) Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung’s disease. Pediatr Surg Int 19:662–668. https://doi.org/10.1007/s00383-003-1026-1CrossRefPubMed

88.

Taguchi T, Suita S, Masumoto K, Nagasaki A (2005) An abnormal distribution of C-kit positive cells in the normoganglionic segment can predict a poor clinical outcome in patients with Hirschsprung’s disease. Eur J Pediatr Surg 15:153–158. https://doi.org/10.1055/s-2005-837612CrossRefPubMed

89.

Coyle D, Kelly DA, O’Donnell AM, Gillick J, Puri P (2016) Use of anoctamin 1 (ANO1) to evaluate interstitial cells of Cajal in Hirschsprung’s disease. Pediatr Surg Int 32:125–133. https://doi.org/10.1007/s00383-015-3822-9CrossRefPubMed

90.

Meier-Ruge W (1971) Casuistic of colon disorder with symptoms of Hirschsprung’s disease. Verh Dtsch Ges Pathol 55:506–510PubMed

91.

Puri P, Lake BD, Nixon HH, Mishalany H, Claireaux AE (1977) Neuronal colonic dysplasia: an unusual association of Hirschsprung’s disease. J Pediatr Surg 12:681–685. https://doi.org/10.1016/0022-3468(77)90393-1CrossRefPubMed

92.

Fadda B, Maier WA, Meier-Ruge W, Schärli A, Daum R (1983) Neuronal intestinal dysplasia. Critical 10-years’ analysis of clinical and biopsy diagnosis. Z Kinderchir 38:305–311. https://doi.org/10.1055/s-2008-1059994CrossRefPubMed

93.

Bruder E, Meier-Ruge WA (2007) Intestinal neuronal dysplasia type B: how do we understand it today? Pathologe 28:137–142. https://doi.org/10.1007/s00292-007-0894-xCrossRefPubMed

94.

Montedonico S, Cáceres P, Muñoz N, Yáñez H, Ramírez R, Fadda B (2011) Histochemical staining for intestinal dysganglionosis: over 30 years experience with more than 1,500 biopsies. Pediatr Surg Int 27:479–486. https://doi.org/10.1007/s00383-010-2849-1CrossRefPubMed

95.

Schäppi MG, Staiano A, Milla PJ, Smith VV, Dias JA, Heuschkel R, Husby S, Mearin ML, Papadopoulou A, Ruemmele FM, Vandenplas Y, Koletzko S (2013) A practical guide for the diagnosis of primary enteric nervous system disorders. J Pediatr Gastroenterol Nutr 57:677–686. https://doi.org/10.1097/MPG.0b013e3182a8bb50CrossRefPubMed

96.

Martucciello G, Pini Prato A, Puri P, Holschneider AM, Meier-Ruge W, Jasonni V, Tovar JA, Grosfeld JL (2005) 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 40:1527–1531. https://doi.org/10.1016/j.jpedsurg.2005.07.053CrossRefPubMed

97.

Rolle U, Piaseczna-Piotrowska A, Puri P (2007) Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood. Pediatr Surg Int 23:1139–1152. https://doi.org/10.1007/s00383-007-2022-7CrossRefPubMed

98.

Taguchi T, Masumoto K, Ieiri S, Nakatsuji T, Akiyoshi J (2006) New classification of hypoganglionosis: congenital and acquired hypoganglionosis. J Pediatr Surg 41:2046–2051. https://doi.org/10.1016/j.jpedsurg.2006.08.004CrossRefPubMed

99.

Rolle U, Yoneda A, Solari V, Nemeth L, Puri P (2002) Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis. J Pediatr Surg 37:709–714. https://doi.org/10.1053/jpsu.2002.32259CrossRefPubMed

100.

Friedmacher F, Puri P (2012) Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis. Pediatr Surg Int 28:765–771. https://doi.org/10.1007/s00383-012-3123-5CrossRefPubMed

101.

Doodnath R, Puri P (2009) Internal anal sphincter achalasia. Semin Pediatr Surg 18:246–248. https://doi.org/10.1053/j.sempedsurg.2009.07.006CrossRefPubMed

102.

Gosemann JH, Puri P (2011) Megacystis microcolon intestinal hypoperistalsis syndrome: systematic review of outcome. Pediatr Surg Int 27:1041–1046. https://doi.org/10.1007/s00383-011-2954-9CrossRefPubMed

103.

Berdon WE, Baker DH, Blanc WA, Gay B, Santulli TV, Donovan C (1976) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls. AJR Am J Roentgenol 126:957–964. https://doi.org/10.2214/ajr.126.5.957CrossRefPubMed

104.

Rolle U, O’Briain S, Pearl RH, Puri P (2002) Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy. Pediatr Surg Int 18:2–5. https://doi.org/10.1007/s003830200001CrossRefPubMed

105.

Puri P, Lake BD, Gorman F, O’Donnell B, Nixon HH (1983) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a visceral myopathy. J Pediatr Surg 18:64–69. https://doi.org/10.1016/s0022-3468(83)80275-9CrossRefPubMed

Title: Interstitial cells of Cajal: clinical relevance in pediatric gastrointestinal motility disorders
Authors: Florian Friedmacher
Udo Rolle
Publication date: 01-12-2023
Publisher: Springer Berlin Heidelberg
Keywords: Motility Disorder
Motility Disorder
Published in: Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-023-05467-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Interstitial cells of Cajal: clinical relevance in pediatric gastrointestinal motility disorders

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2023

The 30th international meeting of the pediatric colorectal club

Staged surgical approach of neonates with esophageal atresia and tracheoesophageal fistula from low- and middle-income countries

Delayed primary anastomosis for repair of long-gap esophageal atresia: technique revisited

Robot-assisted laparoscopic varicocelectomy in a pediatric population

Oncologic safety of Carrel patch hepaticojejunostomy for treating cystic-type choledochal cyst in children based on 20-plus years follow-up

Height-based formulas for predicting intravascular length of tunnelled neck central venous catheter in paediatric population