Abstract
Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of vomiting in infants. Despite numerous hypotheses, the aetiopathogenesis of IHPS is not fully understood. Genetic, extrinsic and hormonal factors have been implicated in the pathogenesis of the disease. Furthermore, abnormalities of various components of the pyloric muscle such as smooth muscle cells, growth factors, extracellular matrix elements, nerve and ganglion cells, synapses, nerve supporting cells, neurotransmitters and interstitial cells of Cajal have been reported. Recently, genetic studies have identified susceptibility loci for IHPS and molecular studies have concluded that smooth muscle cells are not properly innervated in IHPS.
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References
Abel RM (1996) The ontogeny of the peptide innervation of the human pylorus, with special reference to understanding the aetiology and pathogenesis of infantile hypertrophic pyloric stenosis. J Pediatr Surg 31(4):490–497
Abel RM (2000) Hunterian Lecture. The ontogeny of the peptide innervation of the human pylorus with special reference to understanding the aetiology and pathogenesis of infantile hypertrophic pyloric stenosis. Ann R Coll Surg Engl 82(6):371–377
Alarotu H (1956) The histopathologic changes in the myenteric plexus of the pylorus in hypertrophic pyloric stenosis of infants (pylorospasm). Acta Paediatr Suppl 45(Suppl 107):1–131
Applegate MS, Druschel CM (1995) The epidemiology of infantile hypertrophic pyloric stenosis in New York State, 1983 to 1990. Arch Pediatr Adolesc Med 149(10):1123–1129
Barbosa IM, Ferrante SM et al (2001) Role of nitric oxide synthase in the etiopathogenesis of hypertrophic pyloric stenosis in infants. J Pediatr (Rio J) 77(4):307–312
Belding HH, Kernohan JW (1953) A morphological study of the myenteric plexus with special reference to changes in hypertrophic pyloric stenosis. Surg Gynecol Obstet 97:323–334
Bleicher MA, Shandling B et al (1978) Increased serum immunoreactive gastrin levels in idiopathic hypertrophic pyloric stenosis. Gut 19(9):794–797
Callahan MJ, McCauley RG et al (1999) The development of hypertrophic pyloric stenosis in a patient with prostaglandin-induced foveolar hyperplasia. Pediatr Radiol 29(10):748–751
Capon F, Reece A et al (2006) Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16p12-p13 and evidence for genetic heterogeneity. Am J Hum Genet 79(2):378–382
Carter CO (1961) The inheritance of congenital pyloric stenosis. Br Med Bull 17(3):251–254
Carter CO, Evans KA (1969) Inheritance of congenital pyloric stenosis. J Med Genet 6:233–254
Cass DT, Zhang AL (1991) Extracellular matrix changes in congenital hypertrophic pyloric stenosis. Pediatr Surg Int 6:190–194
Cekada S, Kilvain S et al (1999) Partial trisomy 13q22–>qter and monosomy 18q21–>qter as a result of familial translocation. Acta Paediatr 88(6):675–678
Choi KM, Gibbons SJ et al (2007) Regulation of interstitial cells of Cajal in the mouse gastric body by neuronal nitric oxide. Neurogastroenterol Motil 19(7):585–595
Chung E, Curtis D et al (1996) Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis. Am J Hum Genet 58(2):363–370
Cooper WO, Griffin MR et al (2002) Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med 156(7):647–650
Cooper WO, Ray WA et al (2002) Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol 100(1):101–106
Dahshan A, Donovan KG et al (2006) Helicobacter pylori and infantile hypertrophic pyloric stenosis: is there a possible relationship? J Pediatr Gastroenterol Nutr 42(3):262–264
Daniel EE, Tomita T et al (1992) Sphincters: normal function-changes in diseases. CRC press, Boca Raton
Danzer E, Schier F et al (2000) Smith-Lemli-Opitz Syndrome: case report and literature review. J Pediatr Surg 35(12):1840–1842
Dick AC, Ardill J et al (2001) Gastrin, somatostatin and infantile hypertrophic pyloric stenosis. Acta Paediatr 90(8):879–882
Dieler R, Schroder JM et al (1990) Infantile hypertrophic pyloric stenosis: myopathic type. Acta Neuropathol 80(3):295–306
Dodge JA (1970) Production of duodenal ulcers and hypertrophic pyloric stenosis by administration of pentagastrin to pregnant and newborn dogs. Nature 225(5229):284–285
Dodge JA (1996) Study of breast feeding and hypertrophic pyloric stenosis does not conflict with others. BMJ 312(7047):1674
Everett KV, Capon F et al (2008) Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16q24. Eur J Hum Genet 16(9):1151–1154
Everett KV, Chioza BA et al (2008) Genome-wide high density SNP-based linkage analysis of infantile hypertrophic pyloric stenosis identifies loci on chromosomes 11q14-q22 and Xq23. Am J Hum Genet 82:756–762
Farrugia G, Szurszewski JH (1999) Heme oxygenase, carbon monoxide, and interstitial cells of Cajal. Microsc Res Tech 47(5):321–324
Finsen VR (1979) Infantile hypertrophic pyloric stenosis—unusual familial incidence. Arch Dis Child 54(9):720–721
Friesen SR, Boley JO et al (1956) The myenteric plexus of the pylorus: its early normal development and its changes in hypertrophic pyloric stenosis. Surgery 39(1):21–29
Gentile C, Romeo C et al (1998) A possible role of the plasmalemmal cytoskeleton, nitric oxide synthase, and innervation in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study. Pediatr Surg Int 14(1–2):45–50
Grochowski J, Szafran H et al (1980) Blood serum immunoreactive gastrin level in infants with hypertrophic pyloric stenosis. J Pediatr Surg 15(3):279–282
Guarino N, Shima H et al (2000) Glial-derived growth factor signaling pathway in infantile hypertrophic pyloric stenosis. J Pediatr Surg 35(6):835–839
Guarino N, Shima H et al (2000) Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 16(4):282–284
Guarino N, Yoneda A et al (2001) Selective neurotrophin deficiency in infantile hypertrophic pyloric stenosis. J Pediatr Surg 36(8):1280–1284
Hambourg MA, Mignon M et al (1979) Serum gastrin levels in hypertrophic pyloric stenosis of infancy. Response to a gastrin secretion test. Arch Dis Child 54(3):208–212
Hanquinet S, Damry N et al (1995) Gastric outlet obstruction: unusual ultrasonographic findings in the pyloric and antral regions. Pediatr Radiol 25(Suppl 1):S163–S166
Heller A, Seidel J et al (2000) Molecular cytogenetic characterisation of partial trisomy 9q in a case with pyloric stenosis and a review. J Med Genet 37(7):529–532
Hodgson SV, Berry AC et al (1995) Two brothers with an unbalanced 8;17 translocation and infantile pyloric stenosis. Clin Genet 48(6):328–330
Holland AJ, Freeman JK et al (1997) Idiopathic focal foveolar hyperplasia in infants. Pediatr Surg Int 12(7):497–500
Huang LT, Tiao MM et al (2006) Low plasma nitrite in infantile hypertrophic pyloric stenosis patients. Dig Dis Sci 51(5):869–872
Huang PL, Dawson TM et al (1993) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75(7):1273–1286
Huizinga JD (2001) Physiology and pathophysiology of the intersitial cell of cajal: from bench to bedside II. Gastric motility: lessons from mutant mice on slow waves and innervation. Am J Physiol Gastrointest Liver Physiol 281:1129–1134
Hummer-Ehret BH, Rohrschneider WK et al (1998) Eosinophilic gastroenteritis mimicking idiopathic hypertrophic pyloric stenosis. Pediatr Radiol 28(9):711–713
Iino S, Horiguchi K (2006) Interstitial cells of cajal are involved in neurotransmission in the gastrointestinal tract. Acta Histochem Cytochem 39(6):145–153
Jablonski J, Gawronska R et al (2006) Study of insulin-like growth factor-1 (IGF-1) and platelet-derived endothelial cell growth factor (PDEGF) expression in children with infantile hypertrophic pyloric stenosis. Med Sci Monit 12(1):CR27–CR30
Jackson L, Kline AD et al (1993) de Lange syndrome: a clinical review of 310 individuals. Am J Med Genet 47(7):940–946
Jona JZ (1978) Electron microscopic observations in infantile hypertrophic pyloric stenosis (IHPS). J Pediatr Surg 13(1):17–20
Kim S, Chung CJ et al (1997) Coexisting hyperplastic antral polyp and hypertrophic pyloric stenosis. Pediatr Radiol 27(12):912–914
Kobayashi H, Miyahara K et al (2001) Pyloric stenosis: new histopathologic perspective using confocal laser scanning. J Pediatr Surg 36(8):1277–1279
Kobayashi H, O’Briain DS et al (1994) Defective cholinergic innervation in pyloric muscle of patients with hypertrophic pyloric stenosis. Pediatr Surg Int 9:338–341
Kobayashi H, O’Briain DS et al (1994) Selective reduction in intramuscular nerve supporting cells in infantile hypertrophic pyloric stenosis. J Pediatr Surg 29(5):651–654
Kobayashi H, O’Briain DS et al (1995) Immunochemical characterization of neural cell adhesion molecule (NCAM), nitric oxide synthase, and neurofilament protein expression in pyloric muscle of patients with pyloric stenosis. J Pediatr Gastroenterol Nutr 20(3):319–325
Kobayashi H, Wester T et al (1997) Age-related changes in innervation in hypertrophic pyloric stenosis. J Pediatr Surg 32(12):1704–1707
Komuro T (2006) Structure and organization of interstitial cells of Cajal in the gastrointestinal tract. J Physiol 576(Pt 3):653–658
Kusafuka T, Puri P (1997) Altered messenger RNA expression of the neuronal nitric oxide synthase gene in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 12(8):576–579
LaFerla G, Watson J et al (1986) The role of prostaglandins E2 and F2 alpha in infantile hypertrophic pyloric stenosis. J Pediatr Surg 21(5):410–412
Langer JC, Berezin I et al (1995) Hypertrophic pyloric stenosis: ultrastructural abnormalities of enteric nerves and the interstitial cells of Cajal. J Pediatr Surg 30(11):1535–1543
Latchaw LA, Jacir NN et al (1989) The development of pyloric stenosis during transpyloric feedings. J Pediatr Surg 24(8):823–824
Louik C, Mitchell AA (2003) Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol 101(4):816 author reply 816-7
MacMahon B (2006) The continuing enigma of pyloric stenosis of infancy: a review. Epidemiology 17(2):195–201
Mahon BE, Rosenman MB et al (2001) Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. J Pediatr 139(3):380–384
Malmfors G, Sundler F (1986) Peptidergic innervation in infantile hypertrophic pyloric stenosis. J Pediatr Surg 21(4):303–306
Mercado-Deane MG, Burton EM et al (1994) Prostaglandin-induced foveolar hyperplasia simulating pyloric stenosis in an infant with cyanotic heart disease. Pediatr Radiol 24(1):45–46
Mitchell LE, Risch N (1993) The genetics of infantile hypertrophic pyloric stenosis. A reanalysis. Am J Dis Child 147(11):1203–1211
Miyazaki E, Yamataka T et al (1998) Active collagen synthesis in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 13(4):237–239
Moazam F, Rodgers BM et al (1978) Fasting and postprandial serum gastrin levels in infants with congenital hypertrophic pyloric stenosis. Ann Surg 188(5):623–625
Ng E, Shah VS (2008) Erythromycin for the prevention and treatment of feeding intolerance in preterm infants. Cochrane Database Syst Rev(3): CD001815
Nielsen JP, Haahr P et al (2000) Infantile hypertrophic pyloric stenosis. Decreasing incidence. Dan Med Bull 47(3):223–225
Nielsen OS (1956) Histological changes of the pyloric myenteric plexus in infantile pyloric stenosis; studies on surgical biopsy specimens. Acta Paediatr 45(6):636–647
O’Neill JA, Rowe MI et al (1998) Pediatric surgery. Mosby, St Louis
Ohshiro K, Puri P (1998) Increased insulin-like growth factor-I mRNA expression in pyloric muscle in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 13(4):253–255
Ohshiro K, Puri P (1998) Increased insulin-like growth factor and platelet-derived growth factor system in the pyloric muscle in infantile hypertrophic pyloric stenosis. J Pediatr Surg 33(2):378–381
Ohshiro K, Puri P (1998) Pathogenesis of infantile hypertrophic pyloric stenosis: recent progress. Pediatr Surg Int 13(4):243–252
Okazaki T, Yamataka A et al (1994) Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis. J Pediatr Surg 29(5):655–658
Okazaki T, Yamataka A et al (1994) Abnormal distribution of synaptic vesicle proteins in infantile hypertrophic pyloric stenosis. J Pediatr Gastroenterol Nutr 18(2):254–255
Oue T, Puri P (1999) Abnormalities of elastin and elastic fibers in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 15(8):540–542
Panteli C, Filippopoulos A et al (2008) Infantile pyloric stenosis: Interstitial cells of Cajal, nitric oxide or both? 9th EUPSA Congress. Istanbul, Turkey
Paulozzi LJ (2000) Is Helicobacter pylori a cause of infantile hypertrophic pyloric stenosis? Med Hypotheses 55(2):119–125
Persson S, Ekbom A et al (2001) Parallel incidences of sudden infant death syndrome and infantile hypertrophic pyloric stenosis: a common cause? Pediatrics 108(4):E70
Piotrowska AP, Solari V et al (2003) Distribution of heme oxygenase-2 in nerves and interstitial cells of Cajal in the normal pylorus and in infantile hypertrophic pyloric stenosis. Arch Pathol Lab Med 127(9):1182–1186
Pisacane A, de Luca U et al (1996) Breast feeding and hypertrophic pyloric stenosis: population based case-control study. BMJ 312(7033):745–746
Porcher C, Orsoni P et al (1999) Distribution of heme oxygenase 2 in nerves and c-kit(+) interstitial cells in human stomach. Histochem Cell Biol 112(4):317–322
Publicover NG, Hammond EM et al (1993) Amplification of nitric oxide signaling by interstitial cells isolated from canine colon. Proc Natl Acad Sci USA 90:2087–2091
Rintoul JR, Kirkman NF (1961) The myenteric plexus in infantile hypertrophic pyloric stenosis. Arch Dis Child 36:474–480
Rogers IM (2006) The true cause of pyloric stenosis is hyperacidity. Acta Paediatr 95:132–136
Rogers IM, Drainer IK et al (1979) Serum cholecystokinin, basal acid secretion, and infantile pyloric stenosis. Arch Dis Child 54(10):773–775
Rogers IM, Drainer IK et al (1975) Plasma gastrin in congenitial hypertrophic pyloric stenosis. A hypothesis disproved. Arch Dis Child 50(6):467–471
Rogers IM, Macgillion F et al (1976) Congenital hypertrophic pyloric stenosis: a gastrin hypothesis pursued. J Pediatr Surg 11(2):173–176
Romeo C, Santoro G et al (2007) Sarcoglycan immunoreactivity is lacking in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study. Pediatr Med Chir 29(1):32–37
Saps M, Di Lorenzo C (2008) Gastric motility. In: Kleinman R, Goulet OG, Mieli-Vergani G, Sanderson I (eds) Walker’s Pediatric gastrointestinal disease, vol 1. McGraw-Hill, New York, pp 187–193
Saur D, Vanderwinden JM et al (2004) Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis. Proc Natl Acad Sci USA 101(6):1662–1667
Shen Z, She Y et al (1990) Immunohistochemical study of peptidergic nerves in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 5:110–113
Sherwood W, Choudhry M et al (2007) Infantile hypertrophic pyloric stenosis: an infectious cause? Pediatr Surg Int 23(1):61–63
Shima H, Ohshiro K et al (2000) Increased local synthesis of epidermal growth factors in infantile hypertrophic pyloric stenosis. Pediatr Res 47(2):201–207
Shima H, Puri P (1999) Increased expression of transforming growth factor-alpha in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 15(3–4):198–200
Shinohara K, Shimizu T et al (1998) Correlation of prostaglandin E2 production and gastric acid secretion in infants with hypertrophic pyloric stenosis. J Pediatr Surg 33(10):1483–1485
Snyder JD, Rosenblum N et al (1987) Pyloric stenosis and eosinophilic gastroenteritis in infants. J Pediatr Gastroenterol Nutr 6(4):543–547
Sommerfield T, Chalmers J et al (2008) The changing epidemiology of infantile hypertrophic pyloric stenosis in Scotland. Arch Dis Child 93(12):1007–1011
Sorensen HT, Norgard B et al (2002) Maternal smoking and risk of hypertrophic infantile pyloric stenosis: 10 year population based cohort study. BMJ 325(7371):1011–1012
Sorensen HT, Skriver MV et al (2003) Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides. Scand J Infect Dis 35(2):104–106
Spitz L, Kaufmann JC (1975) The neuropathological changes in congenital hypertrophic pyloric stenosis. S Afr J Surg 13(4):239–242
Spitz L, Zail SS (1976) Serum gastrin levels in congenital hypertrophic pyloric stenosis. J Pediatr Surg 11(1):33–35
Stromer MH (1995) Immunocytochemistry of the muscle cell cytoskeleton. Microsc Res Tech 31(2):95–105
Subramaniam R, Doig CM et al (2001) Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis. J Pediatr Surg 36:616–619
Svenningsson A, Lagerstedt K et al (2008) Absence of motilin gene mutations in infantile hypertrophic pyloric stenosis. J Pediatr Surg 43(3):443–446
Tam PK (1986) An immunochemical study with neuron-specific-enolase and substance P of human enteric innervation—the normal developmental pattern and abnormal deviations in Hirschsprung’s disease and pyloric stenosis. J Pediatr Surg 21(3):227–232
Vanderwinden JM, Liu H et al (1996) Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology 111(2):279–288
Vanderwinden JM, Mailleux P et al (1992) Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. N Engl J Med 327(8):511–515
Ward SM (2000) Interstitial cells of Cajal in enteric neurotransmission. Gut 47:iv40–iv43
Wattchow DA, Cass DT et al (1987) Abnormalities of peptide-containing nerve fibers in infantile hypertrophic pyloric stenosis. Gastroenterology 92(2):443–448
Wiley JW (2007) The many faces of nitric oxide: cytotoxic, cytoprotective or both. Neurogastroenterol Motil 19:541–544
Yamataka A, Fujiwara T et al (1996) Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis. J Pediatr Surg 31(1):96–98 discussion 98-9
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Panteli, C. New insights into the pathogenesis of infantile pyloric stenosis. Pediatr Surg Int 25, 1043–1052 (2009). https://doi.org/10.1007/s00383-009-2484-x
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DOI: https://doi.org/10.1007/s00383-009-2484-x