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Gastroesophageal Reflux and Cystic Fibrosis

  • Jernej Brecelj
Chapter

Abstract

Cystic fibrosis is an autosomal recessive genetic disease characterized by chronic suppurative lung disease, exocrine pancreatic dysfunction, hepatobiliary disease, gastrointestinal disease, and many other clinical manifestations. Gastroesophageal reflux is a primary phenomenon in cystic fibrosis patients and is more prevalent than in general population. Lung aspirations of duodenogastric fluid are an underestimated risk factor for the lung disease progression. Advanced lung disease additionally increases gastroesophageal reflux risk. Many symptoms and signs of cystic fibrosis are overlapping with those of gastroesophageal reflux disease and are not a prognostic factor for its presence or severity level. Despite a lot of evidence, controversies regarding gastroesophageal reflux disease diagnosis and treatment in cystic fibrosis patients still exist. One of diagnostic challenges is lung aspiration detection. Proton pump inhibitors are the mainstay of the treatment employed in half of all patients. Antireflux operation in selected patients probably slows the decline of lung function. In addition, other topics of interest in cystic fibrosis patients interrelated with gastroesophageal reflux are addressed: respiratory physiotherapy, gastrostomy, and lung transplantation. With the prolongation of life expectancy, late complications of gastroesophageal reflux disease will become more prevalent. Gastroesophageal reflux in cystic fibrosis patients is a challenging field for clinical practice and research.

Keywords

Gastroesophageal reflux disease Cystic fibrosis Combined esophageal multichannel intraluminal impedance-pH monitoring Baseline impedance Gastric emptying Proton pump inhibitors Fundoplication Respiratory physiotherapy Gastrostomy Lung transplantation Barrett’s esophagus 

Abbreviations

BMI

Body mass index

CF

Cystic fibrosis

CFTR

Cystic fibrosis transmembrane conductance regulator

FEV1

Forced expiratory volume in 1 s

GER(D)

Gastroesophageal reflux (disease)

MII-pH

Combined esophageal multichannel intraluminal impedance-pH monitoring

PPI(s)

Proton pump inhibitor(s)

References

  1. 1.
    Elborn JS. Cystic fibrosis. Lancet. 2016;388:2519–31.CrossRefPubMedGoogle Scholar
  2. 2.
    Quinton PM. Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet. 2008;372:415–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Gregory PC. Gastrointestinal pH, motility/transit and permeability in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1996;23:513–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Demeyer S, De Boeck K, Witters P, Cosaert K. Beyond pancreatic insufficiency and liver disease in cystic fibrosis. Eur J Pediatr. 2016;175:881–94.CrossRefPubMedGoogle Scholar
  5. 5.
    Dab I, Malfroot A. Gastroesophageal reflux: a primary defect in cystic fibrosis? Scand J Gastroenterol Suppl. 1988;143:125–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Heine RG, Button BM, Olinsky A, Phelan PD, Catto-Smith AG. Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis. Arch Dis Child. 1998;78:44–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brodzicki J, Trawinska-Bartnicka M, Korzon M. Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis. Med Sci Monit. 2002;8:529–37.Google Scholar
  8. 8.
    Caldaro T, Alghisi F, De Angelis P, Garganese MC, Rea F, Pizzoferro M, et al. Cystic fibrosis: a surgical matter? J Pediatr Surg. 2014;49:753–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Dziekiewicz MA, Banaszkiewicz A, Urzykowska A, Lisowska A, Rachel M, Sands D, et al. Gastroesophageal reflux disease in children with cystic fibrosis. Adv Exp Med Biol. 2015;873:1–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Ledson MJ, Tran J, Walshaw MJ. Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic fibrosis patients. J R Soc Med. 1998;91:7–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sabati AA, Kempainen RR, Milla CE, Ireland M, Schwarzenberg SJ, Dunitz JM, et al. Characteristics of gastroesophageal reflux in adults with cystic fibrosis. J Cyst Fibros. 2010;9:365–70.CrossRefPubMedGoogle Scholar
  12. 12.
    Dimango E, Walker P, Keating C, Berdella M, Robinson N, Langfelder-Schwind E, et al. Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis. BMC Pulm Med. 2014;14:21.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mousa HM, Woodley FW. Gastroesophageal reflux in cystic fibrosis: current understandings of mechanisms and management. Curr Gastroenterol Rep. 2012;14:226–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Blondeau K, Pauwels A, Dupont L, Mertens V, Proesmans M, Orel R, et al. Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;50:161–6.CrossRefPubMedGoogle Scholar
  15. 15.
    D’Ovidio F, Singer LG, Hadjiliadis D, Pierre A, Waddell TK, de Perrot M, et al. Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant. Ann Thorac Surg. 2005;80:1254–60.CrossRefPubMedGoogle Scholar
  16. 16.
    Cucchiara S, Santamaria F, Andreotti MR, Minella R, Ercolini P, Oggero V, et al. Mechanisms of gastro-oesophageal reflux in cystic fibrosis. Arch Dis Child. 1991;66:617–22.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pauwels A, Blondeau K, Dupont LJ, Sifrim D. Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. Am J Gastroenterol. 2012;107:1346–53.CrossRefPubMedGoogle Scholar
  18. 18.
    Kessing BF, Bredenoord AJ, Weijenborg PW, Hemmink GJ, Loots CM, Smout AJ. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am J Gastroenterol. 2011;106:2093–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Farre R, Blondeau K, Clement D, Vicario M, Cardozo L, Vieth M, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60:885–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Brecelj J, Zidar N, Jeruc J, Orel R. Morphological and functional assessment of oesophageal mucosa integrity in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2016;62:757–64.CrossRefPubMedGoogle Scholar
  21. 21.
    Quinton PM. Role of epithelial HCO3 transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol. 2010;299:1222–33.CrossRefGoogle Scholar
  22. 22.
    Abdulnour-Nakhoul S, Nakhoul HN, Kalliny MI, Gyftopoulos A, Rabon E, Doetjes R, et al. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol. 2011;301:83–96.CrossRefGoogle Scholar
  23. 23.
    Woodley FW, Machado RS, Hayes D Jr, Di Lorenzo C, Kaul A, Skaggs B, et al. Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci. 2014;59:623–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Hallberg K, Fandriks L, Strandvik B. Duodenogastric bile reflux is common in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2004;38:312–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Pauwels A, Blondeau K, Mertens V, Farre R, Verbeke K, Dupont LJ, et al. Gastric emptying and different types of reflux in adult patients with cystic fibrosis. Aliment Pharmacol Ther. 2011;34:799–807.CrossRefPubMedGoogle Scholar
  26. 26.
    Hauser B, De Schepper J, Malfroot A, De Wachter E, De Schutter I, Keymolen K, et al. Gastric emptying and gastro-oesophageal reflux in children with cystic fibrosis. J Cyst Fibros. 2016;15:540–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Bendig DW, Seilheimer DK, Wagner ML, Ferry GD, Barrison GM. Complications of gastroesophageal reflux in patients with cystic fibrosis. J Pediatr. 1982;100:536–40.CrossRefPubMedGoogle Scholar
  28. 28.
    Vinocur CD, Marmon L, Schidlow DV, Weintraub WH. Gastroesophageal reflux in the infant with cystic fibrosis. Am J Surg. 1985;149:182–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Gustafsson PM, Fransson SG, Kjellman NI, Tibbling L. Gastro-oesophageal reflux and severity of pulmonary disease in cystic fibrosis. Scand J Gastroenterol. 1991;26:449–56.CrossRefPubMedGoogle Scholar
  30. 30.
    Navarro J, Rainisio M, Harms HK, Hodson ME, Koch C, Mastella G, et al. Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. European Epidemiologic Registry of Cystic Fibrosis. Eur Respir J. 2001;18:298–305.CrossRefPubMedGoogle Scholar
  31. 31.
    Pauwels A, Decraene A, Blondeau K, Mertens V, Farre R, Proesmans M, et al. Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis. Chest. 2012;141:1568–74.CrossRefPubMedGoogle Scholar
  32. 32.
    Reen FJ, Woods DF, Mooij MJ, Adams C, O'Gara F. Respiratory pathogens adopt a chronic lifestyle in response to bile. PLoS One. 2012;7:e45978.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Pauwels A, Verleden S, Farre R, Vanaudenaerde BM, Van Raemdonck D, Verleden G, et al. The effect of gastric juice on interleukin-8 production by cystic fibrosis primary bronchial epithelial cells. J Cyst Fibros. 2013;12:700–5.CrossRefPubMedGoogle Scholar
  34. 34.
    McNally P, Ervine E, Shields MD, Dimitrov BD, El Nazir B, Taggart CC, et al. High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations. Thorax. 2011;66:140–3.CrossRefPubMedGoogle Scholar
  35. 35.
    van der Doef HP, Arets HG, Froeling SP, Westers P, Houwen RH. Gastric acid inhibition for fat malabsorption or gastroesophageal reflux disease in cystic fibrosis: longitudinal effect on bacterial colonization and pulmonary function. J Pediatr. 2009;155:629–33.CrossRefPubMedGoogle Scholar
  36. 36.
    Palm K, Sawicki G, Rosen R. The impact of reflux burden on pseudomonas positivity in children with cystic fibrosis. Pediatr Pulmonol. 2012;47:582–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio. 2012;3:e00251-12.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Robinson NB, DiMango E. Prevalence of gastroesophageal reflux in cystic fibrosis and implications for lung disease. Ann Am Thorac Soc. 2014;11:964–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498–547.CrossRefPubMedGoogle Scholar
  40. 40.
    Wenzl TG, Benninga MA, Loots CM, Salvatore S, Vandenplas Y. Indications, methodology, and interpretation of combined esophageal impedance-pH monitoring in children: ESPGHAN EURO-PIG standard protocol. J Pediatr Gastroenterol Nutr. 2012;55:230–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Shaker A, Stoikes N, Drapekin J, Kushnir V, Brunt LM, Gyawali CP. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve. Am J Gastroenterol. 2013;108:1706–12.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Blondeau K, Mertens V, Vanaudenaerde BA, Verleden GM, Van Raemdonck DE, Sifrim D, et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J. 2008;31:707–13.CrossRefPubMedGoogle Scholar
  43. 43.
    Kazachkov MY, Muhlebach MS, Livasy CA, Noah TL. Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children. Eur Respir J. 2001;18:790–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Hayes D Jr, Kirkby S, KS MC, Mansour HM, Khosravi M, Strawbridge H, et al. Reduction of lipid-laden macrophage index after laparoscopic Nissen fundoplication in cystic fibrosis patients after lung transplantation. Clin Transpl. 2013;27:121–5.CrossRefGoogle Scholar
  45. 45.
    Munck A. Nutritional considerations in patients with cystic fibrosis. Expert Rev Respir Med. 2010;4:47–56.CrossRefPubMedGoogle Scholar
  46. 46.
    Colletti RB, Di Lorenzo C. Overview of pediatric gastroesophageal reflux disease and proton pump inhibitor therapy. J Pediatr Gastroenterol Nutr. 2003;37(Suppl 1):S7–S11.CrossRefPubMedGoogle Scholar
  47. 47.
    2014 Annual Data Report. Bethesda: Cystic Fibrosis Foundation Patient Registry; 2015.Google Scholar
  48. 48.
    Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009;155(Suppl):S73–93.CrossRefPubMedGoogle Scholar
  49. 49.
    Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–72.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373:220–31.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Rowe SM, Heltshe SL, Gonska T, Donaldson SH, Borowitz D, Gelfond D, et al. Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med. 2014;190:175–84.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Boesch RP, Acton JD. Outcomes of fundoplication in children with cystic fibrosis. J Pediatr Surg. 2007;42:1341–4.CrossRefPubMedGoogle Scholar
  53. 53.
    Sheikh SI, Ryan-Wenger NA, McCoy KS. Outcomes of surgical management of severe GERD in patients with cystic fibrosis. Pediatr Pulmonol. 2013;48:556–62.CrossRefPubMedGoogle Scholar
  54. 54.
    Rinsma NF, Farre R, Bouvy ND, Masclee AA, Conchillo JM. The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients. Neurogastroenterol Motil. 2015;27:220–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Tovar JA, Olivares P, Diaz M, Pace RA, Prieto G, Molina M. Functional results of laparoscopic fundoplication in children. J Pediatr Gastroenterol Nutr. 1998;26:429–31.CrossRefPubMedGoogle Scholar
  56. 56.
    Vandenplas Y, Diericx A, Blecker U, Lanciers S, Deneyer M. Esophageal pH monitoring data during chest physiotherapy. J Pediatr Gastroenterol Nutr. 1991;13:23–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Button BM, Heine RG, Catto-Smith AG, Phelan PD, Olinsky A. Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis. Arch Dis Child. 1997;76:148–50.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Phillips GE, Pike SE, Rosenthal M, Bush A. Holding the baby: head downwards positioning for physiotherapy does not cause gastro-oesophageal reflux. Eur Respir J. 1998;12:954–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Button BM, Heine RG, Catto-Smith AG, Olinsky A, Phelan PD, Ditchfield MR, et al. Chest physiotherapy in infants with cystic fibrosis: to tip or not? A five-year study. Pediatr Pulmonol. 2003;35:208–13.CrossRefPubMedGoogle Scholar
  60. 60.
    Doumit M, Krishnan U, Jaffe A, Belessis Y. Acid and non-acid reflux during physiotherapy in young children with cystic fibrosis. Pediatr Pulmonol. 2012;47:119–24.CrossRefPubMedGoogle Scholar
  61. 61.
    McIlwaine PM, Wong LT, Peacock D, Davidson AG. Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis. J Pediatr. 1997;131:570–4.CrossRefPubMedGoogle Scholar
  62. 62.
    McIlwaine M. Chest physical therapy, breathing techniques and exercise in children with CF. Paediatr Respir Rev. 2007;8:8–16.CrossRefPubMedGoogle Scholar
  63. 63.
    McIlwaine M, Button B, Dwan K. Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev. 2015;6:CD003147.Google Scholar
  64. 64.
    Van Ginderdeuren F, Kerckhofs E, Deneyer M, Vanlaethem S, Vandenplas Y. Influence of respiratory physiotherapy on gastro-oesophageal reflux in infants: a systematic review. Pediatr Pulmonol. 2015;50:936–44.CrossRefPubMedGoogle Scholar
  65. 65.
    Freitas DA, Dias FA, Chaves GS, Ferreira GM, Ribeiro CT, Guerra RO, et al. Standard (head-down tilt) versus modified (without head-down tilt) postural drainage in infants and young children with cystic fibrosis. Cochrane Database Syst Rev. 2015;3:CD010297.Google Scholar
  66. 66.
    Rosenblatt RL. Lung transplantation in cystic fibrosis. Respir Care. 2009;54:777–86.CrossRefPubMedGoogle Scholar
  67. 67.
    Zolin A, McKone E, van Rens J, Fox A, Iansa P, Pypops U, et al. ECFSPR annual report 2013. Karup: European Cystic Fibrosis Society; 2016.Google Scholar
  68. 68.
    Vaquero Barrios JM, Redel Montero J, Santos LF. Comorbidities impacting on prognosis after lung transplant. Arch Bronconeumol. 2014;50:25–33.CrossRefPubMedGoogle Scholar
  69. 69.
    Fisichella PM, Davis CS, Gagermeier J, Dilling D, Alex CG, Dorfmeister JA, et al. Laparoscopic antireflux surgery for gastroesophageal reflux disease after lung transplantation. J Surg Res. 2011;170:e279–86.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Benden C, Aurora P, Curry J, Whitmore P, Priestley L, Elliott MJ. High prevalence of gastroesophageal reflux in children after lung transplantation. Pediatr Pulmonol. 2005;40:68–71.CrossRefPubMedGoogle Scholar
  71. 71.
    Gasper WJ, Sweet MP, Hoopes C, Leard LE, Kleinhenz ME, Hays SR, et al. Antireflux surgery for patients with end-stage lung disease before and after lung transplantation. Surg Endosc. 2008;22:495–500.CrossRefPubMedGoogle Scholar
  72. 72.
    Mendez BM, Davis CS, Weber C, Joehl RJ, Fisichella PM. Gastroesophageal reflux disease in lung transplant patients with cystic fibrosis. Am J Surg. 2012;204:e21–6.CrossRefPubMedGoogle Scholar
  73. 73.
    Braun AT, Merlo CA. Cystic fibrosis lung transplantation. Curr Opin Pulm Med. 2011;17:467–72.PubMedGoogle Scholar
  74. 74.
    Davis RD Jr, Lau CL, Eubanks S, Messier RH, Hadjiliadis D, Steele MP, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003;125:533–42.CrossRefPubMedGoogle Scholar
  75. 75.
    Zheng C, Kane TD, Kurland G, Irlano K, Spahr J, Potoka DA, et al. Feasibility of laparoscopic Nissen fundoplication after pediatric lung or heart-lung transplantation: should this be the standard? Surg Endosc. 2011;25:249–54.CrossRefPubMedGoogle Scholar
  76. 76.
    Culhane S, George C, Pearo B, Spoede E. Malnutrition in cystic fibrosis: a review. Nutr Clin Pract. 2013;28:676–83.CrossRefPubMedGoogle Scholar
  77. 77.
    Woestenenk JW, Castelijns SJ, van der Ent CK, Houwen RH. Nutritional intervention in patients with cystic fibrosis: a systematic review. J Cyst Fibros. 2013;12:102–15.CrossRefPubMedGoogle Scholar
  78. 78.
    Oliver MR, Heine RG, Ng CH, Volders E, Olinsky A. Factors affecting clinical outcome in gastrostomy-fed children with cystic fibrosis. Pediatr Pulmonol. 2004;37:324–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Grime CJ, Greenaway C, Clarke S, Balfour-Lynn IM. Critical timing of gastrostomy insertion in a child with cystic fibrosis. Paediatr Respir Rev. 2015;16(Suppl 1):19–21.PubMedGoogle Scholar
  80. 80.
    Ledder O, Oliver MR, Heine RG, Graham J, Volders E, Robinson PJ. Clinical audit results in earlier nutritional intervention in malnourished children with cystic fibrosis with improved outcome. J Paediatr Child Health. 2015;51:988–93.CrossRefPubMedGoogle Scholar
  81. 81.
    Morton A, Wolfe S. Enteral tube feeding for cystic fibrosis. Cochrane Database Syst Rev. 2015;4:CD001198.Google Scholar
  82. 82.
    Best C, Brearley A, Gaillard P, Regelmann W, Billings J, Dunitz J, et al. A pre-post retrospective study of patients with cystic fibrosis and gastrostomy tubes. J Pediatr Gastroenterol Nutr. 2011;53:453–8.PubMedGoogle Scholar
  83. 83.
    Kakade M, Coyle D, McDowell DT, Gillick J. Percutaneous endoscopic gastrostomy (PEG) does not worsen vomiting in children. Pediatr Surg Int. 2015;31:557–62.CrossRefPubMedGoogle Scholar
  84. 84.
    Heuschkel RB, Gottrand F, Devarajan K, Poole H, Callan J, Dias JA, et al. ESPGHAN position paper on management of percutaneous endoscopic gastrostomy in children and adolescents. J Pediatr Gastroenterol Nutr. 2015;60:131–41.CrossRefPubMedGoogle Scholar
  85. 85.
    Munck A. Cystic fibrosis: evidence for gut inflammation. Int J Biochem Cell Biol. 2014;52:180–3.CrossRefPubMedGoogle Scholar
  86. 86.
    Holt EW, Yimam KK, Liberman MS. Esophageal adenocarcinoma in a 40-year-old man with cystic fibrosis: coincidence or not? Ochsner J. 2013;13:252–5.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Hassall E, Israel DM, Davidson AG, Wong LT. Barrett’s esophagus in children with cystic fibrosis: not a coincidental association. Am J Gastroenterol. 1993;88:1934–8.PubMedGoogle Scholar
  88. 88.
    Miller R, Bourke S, Immanuel A, Metcalfe S. Subtotal esophagectomy for carcinoma in a patient with cystic fibrosis. A A Case Rep. 2016;6:394–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Gastroenterology, Hepatology and NutritionUniversity Children’s Hospital LjubljanaLjubljanaSlovenia
  2. 2.Department of Pediatrics, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia

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