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Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain

  • Gyanprakash A. Ketwaroo
  • David Y. GrahamEmail author
Chapter
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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)

Abstract

We describe the rational use of enteric coated and unprotected replacement pancreatic enzymes for treatment of malabsorption due to pancreatic insufficiency and for pancreatic pain. Enteric coated formulations mix poorly with food allowing separation of enzymes and nutrients when emptying from the stomach. The site of dissolution of the enteric coating in the intestine is also unpredictable and enzymes may not be released until the distal intestine. Together, these barriers result in the lack of dose-response such that the strategy of increasing the dosage following a suboptimal effect is often ineffective. The ability to maintain the intragastric pH ≥4 with the combination of proton pump inhibitors and antacids suggests that it should be possible to reliably obtain a good response with uncoated enzymes. We also discuss the recognition, treatment and prevention of nutritional deficiencies associated with pancreatic insufficiency and recommend a test and treat strategy to identify and resolve nutritional deficits. Finally, we focus on mechanisms causing pain that may be amenable to therapy with pancreatic enzymes. Pain due to malabsorbed digestive contents can be prevented by successful therapy of malabsorption. Feedback inhibition of endogenous pancreatic secretion can prevent pain associated with pancreatic secretion but requires use of non-enteric coated formulations.

Keywords

Pancreatic enzymes Pancreatic insufficiency Chronic pancreatitis 

Abbreviations

CCK

Cholecystokinin

CFA

Coefficient of fat absorption

FDA

Food and Drug Administration

INR

International normalized ratio

RBP

Retinol binding protein

Notes

Acknowledgement

Dr. Graham is in part by the Research Service Department of Veterans Affairs and by Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center. The authors acknowledge the excellent advice received from Temitope Osinaiya, DHSc, MS, RD, LDN regarding the nutritional assessment of patients with pancreatic insufficiency.

Competing Interests

Dr. Graham is a consultant for RedHill Biopharma regarding novel H. pylori therapies and has received research support for culture of Helicobacter pylori and is the PI of an international study of the use of antimycobacterial therapy for Crohn’s disease. He is also a consultant for BioGaia in relation to probiotic therapy for H. pylori infection and for Takeda in relation to H. pylori therapies. Dr. Ketwaroo does not have any relevant disclosures.

References

  1. Adler G, Mullenhoff A, Bozkurt T, Goke B, Koop I, Arnold R (1988a) Comparison of the effect of single and repeated administrations of a protease inhibitor (Camostate) on pancreatic secretion in man. Scand J Gastroenterol 23(2):158–162PubMedCrossRefGoogle Scholar
  2. Adler G, Mullenhoff A, Koop I, Bozkurt T, Goke B, Beglinger C, Arnold R (1988b) Stimulation of pancreatic secretion in man by a protease inhibitor (camostate). Eur J Clin Investig 18(1):98–104CrossRefGoogle Scholar
  3. Afghani E, Sinha A, Singh VK (2014) An overview of the diagnosis and management of nutrition in chronic pancreatitis. Nutr Clin Pract 29(3):295–311PubMedCrossRefGoogle Scholar
  4. Aloulou A, Puccinelli D, Sarles J, Laugier R, Leblond Y, Carriere F (2008) In vitro comparative study of three pancreatic enzyme preparations: dissolution profiles, active enzyme release and acid stability. Aliment Pharmacol Ther 27(3):283–292PubMedCrossRefGoogle Scholar
  5. Bakowski MT, Prescott P (1997) Patterns of use of pancreatic enzyme supplements in fibrosing colonopathy: implications for pathogenesis. Pharmacoepidemiol Drug Saf 6(5):347–358PubMedCrossRefGoogle Scholar
  6. Beazell JM, Schmidt CR, Ivy AC (1941) The diagnosis and treatment of achylia pancreatica. JAMA 116(25):2735–2739CrossRefGoogle Scholar
  7. Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH (1992) Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion 51(Suppl 1):59–67PubMedCrossRefGoogle Scholar
  8. Benini L, Caliari S, Guidi GC, Vaona B, Talamini G, Vantini I, Scuro LA (1989) Near infrared spectrometry for faecal fat measurement: comparison with conventional gravimetric and titrimetric methods. Gut 30(10):1344–1347PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bernstein CN, Leslie WD, Leboff MS (2003) AGA technical review on osteoporosis in gastrointestinal diseases. Gastroenterology 124(3):795–841PubMedCrossRefGoogle Scholar
  10. Borowitz D, Gelfond D (2013) Intestinal complications of cystic fibrosis. Curr Opin Pulm Med 19(6):676-680. Available from: PM:24060981PubMedCrossRefGoogle Scholar
  11. Borowitz D, Baker RD, Stallings V (2002) Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 35(3):246–259PubMedCrossRefGoogle Scholar
  12. Bruno MJ, Rauws EA, Hoek FJ, Tytgat GN (1994) Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy. Dig Dis Sci 39(5):988–992PubMedCrossRefGoogle Scholar
  13. Chase RF (1905) The therapeutic value of some digestive preparations, and the indications for use of pepsin, in diseases of the stomach. Boston Med Surg J 152:572–574CrossRefGoogle Scholar
  14. Chernick SS, Lepkovsky S, Chaikoff IL (1948) A dietary factor regulating the enzyme content of the pancreas; changes induced in size and proteolytic activity of the chick pancreas by the ingestion of raw soy-bean meal. Am J Phys 155(1):33–41CrossRefGoogle Scholar
  15. Corring T (1973) Mechanism of the exocrine pancreatic secretion in the pig feed-back regulation. Ann Biol Amin Biochim Biophys 13:755–756CrossRefGoogle Scholar
  16. Czako L, Takacs T, Hegyi P, Pronai L, Tulassay Z, Lakner L, Dobronte Z, Boda K, Lonovics J (2003) Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis. Can J Gastroenterol 17(10):597–603PubMedCrossRefGoogle Scholar
  17. Delchier JC, Vidon N, Saint-Marc Girardin MF, Soule JC, Moulin C, Huchet B, Zylberberg P (1991) Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations. Aliment Pharmacol Ther 5(4):365–378PubMedCrossRefGoogle Scholar
  18. Diamond JS, Siegel SA, Kantor JL, Jour DD (1940) The secretin test in the diagnosis of pancreatic diseases with a report of one hundred thirty tests. Am J Dig Dis 7(10):435–442CrossRefGoogle Scholar
  19. DiMagno EP, Go VL, Summerskill WH (1973) Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 288(16):813–815PubMedCrossRefGoogle Scholar
  20. DiMagno EP, Malagelada JR, Go VL, Moertel CG (1977) Fate of orally ingested enzymes in pancreatic insufficiency comparison of two dosage schedules. N Engl J Med 296(23):1318–1322PubMedCrossRefGoogle Scholar
  21. Dominguez-Munoz JE (2007) Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Curr Gastroenterol Rep 9(2):116–122PubMedCrossRefGoogle Scholar
  22. Dominguez-Munoz JE (2011) Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency: when is it indicated, what is the goal and how to do it? Adv Med Sci 56(1):1–5PubMedCrossRefGoogle Scholar
  23. Dominguez-Munoz JE, Iglesias-Garcia J (2010) Oral pancreatic enzyme substitution therapy in chronic pancreatitis: is clinical response an appropriate marker for evaluation of therapeutic efficacy? JOP 11(2):158–162PubMedGoogle Scholar
  24. Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M, Figueiras A, Vilarino-Insua M (2005) Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency: a randomized, three-way crossover study. Aliment Pharmacol Ther 21(8):993–1000PubMedCrossRefGoogle Scholar
  25. Dominguez-Munoz JE, Iglesias-Garcia J, Vilarino-Insua M, Iglesias-Rey M (2007) 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 5(4):484–488PubMedCrossRefGoogle Scholar
  26. Dreiling DA, Hollander F (1948) Studies in pancreatic function; preliminary series of clinical studies with the secretin test. Gastroenterology 11(5):714–729PubMedGoogle Scholar
  27. Duggan SN, Smyth ND, O’Sullivan M, Feehan S, Ridgway PF, Conlon KC (2014) The prevalence of malnutrition and fat-soluble vitamin deficiencies in chronic pancreatitis. Nutr Clin Pract 29(3):348–354PubMedCrossRefGoogle Scholar
  28. Durie PR, Bell L, Linton W, Corey ML, Forstner GG (1980) Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis. Gut 21(9):778–786PubMedPubMedCentralCrossRefGoogle Scholar
  29. Ebbehoj N, Borly L, Bulow J, Rasmussen SG, Madsen P (1990) Evaluation of pancreatic tissue fluid pressure and pain in chronic pancreatitis a longitudinal study. Scand J Gastroenterol 25(5):462–466PubMedCrossRefGoogle Scholar
  30. Engesser H (1879) Beitrage zur therapeutischen Verwendung der Bauchspeicheldruse von Schlachtthieren und deren praparate. Dtsch Arch Klin Med 24:539–582Google Scholar
  31. Fordtran JS, Morawski SG, Richardson CT (1973) In vivo and in vitro evaluation of liquid antacids. N Engl J Med 288(18):923–928PubMedCrossRefGoogle Scholar
  32. Forsmark CE (2016) Chronic pancreatitis. In: Feldman M, Friedman LS, Brandt LJ (eds) Sleisenger and Fordtran’s gastrointestinal and liver disease, 10th edn. Elsevier Saunders, Philadelphia, p 1020Google Scholar
  33. Franzen D, Went P, Buhlmann U (2008) Fibrosing colonopathy in absence of pancreatic enzyme supplementation in one adult patient with cystic fibrosis. Indian J Gastroenterol 27(3):133–134PubMedGoogle Scholar
  34. Gaia E, Sambatoro A, De Giuli P, Angeli A (2001) Adult fibrosing colonopathy associated with mesalazine treatment. Am J Gastroenterol 96(8):2508–2509PubMedCrossRefGoogle Scholar
  35. Gow R, Bradbear R, Francis P, Shepherd R (1981) Comparative study of varying regimens to improve steatorrhoea and creatorrhoea in cystic fibrosis: effectiveness of an enteric-coated preparation with and without antacids and cimetidine. Lancet 2(8255):1071–1074PubMedCrossRefGoogle Scholar
  36. Graham DY (1977) Enzyme replacement therapy of exocrine pancreatic insufficiency in man relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts. N Engl J Med 296(23):1314–1317PubMedCrossRefGoogle Scholar
  37. Graham DY (1979) An enteric-coated pancreatic enzyme preparation that works. Dig Dis Sci 24(12):906–909PubMedCrossRefGoogle Scholar
  38. Graham DY (1982) Pancreatic enzyme replacement: the effect of antacids or cimetidine. Dig Dis Sci 27(6):485–490PubMedCrossRefGoogle Scholar
  39. Graham DY, Dore MP (2018) Update on the use of vonoprazan: a competitive acid blocker. Gastroenterology 154(154):462–466PubMedCrossRefGoogle Scholar
  40. Graham DY, Sackman JW (1982) Mechanism of increase in steatorrhea with calcium and magnesium in exocrine pancreatic insufficiency: an animal model. Gastroenterology 83(3):638–644PubMedGoogle Scholar
  41. Graham DY, Sackman JW (1983) Solubility of calcium soaps of long-chain fatty acids in simulated intestinal environment. Dig Dis Sci 28(8):733–736PubMedCrossRefGoogle Scholar
  42. Graham DY, Tansel A (2018) Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 16(6):800–808PubMedCrossRefGoogle Scholar
  43. Green GM, Lyman RL (1972) Feedback regulation of pancreatic enzyme secretion as a mechanism for trypsin inhibitor-induced hypersecretion in rats. Proc Soc Exp Biol Med 140(1):6–12PubMedCrossRefGoogle Scholar
  44. Gubergrits N, Malecka-Panas E, Lehman GA, Vasileva G, Shen Y, Sander-Struckmeier S, Caras S, Whitcomb DC (2011) A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. Aliment Pharmacol Ther 33(10):1152–1161PubMedCrossRefGoogle Scholar
  45. Harris R, Norman AP, Payne WW (1955) The effect of pancreatin therapy on fat absorption and nitrogen retention in children with fibrocystic disease of the pancreas. Arch Dis Child 30(153):424–427PubMedPubMedCentralCrossRefGoogle Scholar
  46. Heijerman HG, Lamers CB, Bakker W (1991) Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis. Ann Intern Med 114(3):200–201PubMedCrossRefGoogle Scholar
  47. Heubi JE, Schaeffer D, Ahrens RC, Sollo N, Strausbaugh S, Graff G, Jain R, Witte S, Forssmann K (2016) Safety and efficacy of a novel microbial lipase in patients with exocrine pancreatic insufficiency due to cystic fibrosis: a randomized controlled clinical trial. J Pediatr 176:156–161e1PubMedCrossRefGoogle Scholar
  48. Hobbs PM, Johnson WG, Graham DY (2016) Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes. World J Gastrointest Pharmacol Ther 7(3):370–386PubMedPubMedCentralCrossRefGoogle Scholar
  49. Hunt JN (1983) Mechanisms and disorders of gastric emptying. Annu Rev Med 34:219–229PubMedCrossRefGoogle Scholar
  50. Hunt JN, Knox MT (1968) Control of gastric emptying. Am J Dig Dis 13(4):372–375PubMedCrossRefGoogle Scholar
  51. Hunt RH, Cederberg C, Dent J, Halter F, Howden C, Marks IN, Rune S, Walt RP (1995) Optimizing acid suppression for treatment of acid-related diseases. Dig Dis Sci 40(2 Suppl):24S–49SPubMedCrossRefGoogle Scholar
  52. Ianiro G, Pecere S, Giorgio V, Gasbarrini A, Cammarota G (2016) Digestive enzyme supplementation in gastrointestinal diseases. Curr Drug Metab 17(2):187–193PubMedPubMedCentralCrossRefGoogle Scholar
  53. Ihse I, Lilja P, Lundquist I (1979) Trypsin as a regulator of pancreatic secretion in the rat. Scand J Gastroenterol 14(7):873–880PubMedCrossRefGoogle Scholar
  54. Jones DB, Howden CW, Burget DW, Kerr GD, Hunt RH (1987) Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. Gut 28(9):1120–1127PubMedPubMedCentralCrossRefGoogle Scholar
  55. Jordan PH Jr, Grossman MI (1959) Effect of dosage schedule on the efficacy of substitution therapy in pancreatic insufficiency. Gastroenterology 36(4):447–451PubMedCrossRefGoogle Scholar
  56. Julapall VR, Graham DY (2005) Appropriate use of intravenous proton pump inhibitors in the management of bleeding peptic ulcer. Dig Dis Sci 50(7):1185–1193CrossRefGoogle Scholar
  57. Kalser MH, Leite CA, Warren WD (1968) Fat assimilation after massive distal pancreatectomy. N Engl J Med 279(11):570–576PubMedCrossRefGoogle Scholar
  58. Kattwinkel J, Agus SG, Taussig LM, di Sant’Agnese PA, Laster L (1972) The use of L-arginine and sodium bicarbonate in the treatment of malabsorption due to cystic fibrosis. Pediatrics 50(1):133–137PubMedGoogle Scholar
  59. Keller J, Layer P (2005) Human pancreatic exocrine response to nutrients in health and disease. Gut 54(Suppl 6):vi1–v28PubMedCrossRefGoogle Scholar
  60. Keller J, Runzi M, Goebell H, Layer P (1997) Duodenal and ileal nutrient deliveries regulate human intestinal motor and pancreatic responses to a meal. Am J Phys 272(3 Pt 1):G632–G637Google Scholar
  61. Ketwaroo G, Brown A, Young B, Kheraj R, Sawhney M, Mortele KJ, Najarian R, Tewani S, Dasilva D, Freedman S, Sheth S (2013) Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis. Am J Gastroenterol 108(8):1360–1366PubMedPubMedCentralCrossRefGoogle Scholar
  62. Kirchheiner J, Glatt S, Fuhr U, Klotz U, Meineke I, Seufferlein T, Brockmoller J (2009) Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol 65(1):19–31PubMedCrossRefGoogle Scholar
  63. Kuhn RJ, Eyting S, Henniges F, Potthoff A (2007) In vitro comparison of physical parameters, enzyme activity, acid resistance, and pH dissolution characteristics of enteric-coated pancreatic enzyme preparations: implications for clinical variability and pharmacy substitution. J Pediatr Pharmacol Ther 12(2):115–128PubMedPubMedCentralGoogle Scholar
  64. da la Iglesia-García D, Huang W, Szatmary P, Baston-Rey I, Gonzalez-Lopez J, Prada-Ramallal G, Mukherjee R, Nunes QM, Dominguez-Munoz JE, Sutton R (2017) Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut 66(8):1354–1355PubMedGoogle Scholar
  65. da la Iglesia-García D, Vallejo-Senra N, Iglesias-Garcia J, Lopez-Lopez A, Nieto L, Dominguez-Munoz JE (2018) Increased risk of mortality associated with pancreatic exocrine insufficiency in patients with chronic pancreatitis. J Clin Gastroenterol 52(8):e63–e72PubMedCrossRefGoogle Scholar
  66. Layer P, Keller J (1999) Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease. J Clin Gastroenterol 28(1):3–10PubMedCrossRefGoogle Scholar
  67. Layer P, Go VL, DiMagno EP (1986) Fate of pancreatic enzymes during small intestinal aboral transit in humans. Am J Phys 251(4 Pt 1):G475–G480Google Scholar
  68. Liener IE, Goodale RL, Deshmukh A, Satterberg TL, Ward G, DiPietro CM, Bankey PE, Borner JW (1988) Effect of a trypsin inhibitor from soybeans (Bowman-Birk) on the secretory activity of the human pancreas. Gastroenterology 94(2):419–427PubMedCrossRefGoogle Scholar
  69. Lindkvist B, Dominguez-Munoz JE, Luaces-Regueira M, Castineiras-Alvarino M, Nieto-Garcia L, Iglesias-Garcia J (2012) Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis. Pancreatology 12(4):305–310PubMedCrossRefGoogle Scholar
  70. Lindkvist B, Phillips ME, Dominguez-Munoz JE (2015) Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: prevalence and diagnostic use. Pancreatology 15(6):589–559PubMedCrossRefGoogle Scholar
  71. Littman A, Hanscom DH (1969) Current concepts: pancreatic extracts. N Engl J Med 28(4):201–204CrossRefGoogle Scholar
  72. Louie DS, May D, Miller P, Owyang C (1986) Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats. Am J Physiol 250(2 Pt 1):G252–G259PubMedGoogle Scholar
  73. Lowe ME, Whitcomb DC (2015) Next generation of pancreatic enzyme replacement therapy: recombinant microbial enzymes and finding the perfect lipase. Gastroenterology 149(7):1678–1681PubMedCrossRefGoogle Scholar
  74. Marotta F, O’Keefe SJ, Marks IN, Girdwood A, Young G (1989) Pancreatic enzyme replacement therapy: importance of gastric acid secretion, H2-antagonists, and enteric coating. Dig Dis Sci 34(3):456–461PubMedCrossRefGoogle Scholar
  75. Meyer JH (1980) Gastric emptying of ordinary food: effect of antrum on particle size. Am J Phys 239(3):G133–G135Google Scholar
  76. Meyer JH, Lake R (1997) Mismatch of duodenal deliveries of dietary fat and pancreatin from enterically coated microspheres. Pancreas 15(3):226–235PubMedCrossRefGoogle Scholar
  77. Meyer JH, Elashoff J, Porter-Fink V, Dressman J, Amidon GL (1988) Human postprandial gastric emptying of 1-3-millimeter spheres. Gastroenterology 94(6):1315–1325PubMedCrossRefGoogle Scholar
  78. Mossner J (1991) Treatment of pain in chronic pancreatitis with pancreatic enzymes another point of view. In: Lankisch PG (ed) Pancreatic enzymes in health and disease. Springer-Verlag, Berlin, pp 103–112CrossRefGoogle Scholar
  79. Mullady DK, Yadav D, Amann ST, O’Connell MR, Barmada MM, Elta GH, Scheiman JM, Wamsteker EJ, Chey WD, Korneffel ML, Weinman BM, Slivka A, Sherman S, Hawes RH, Brand RE, Burton FR, Lewis MD, Gardner TB, Gelrud A, DiSario J, Baillie J, Banks PA, Whitcomb DC, Anderson MA (2011) Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut 60(1):77–84PubMedCrossRefGoogle Scholar
  80. Owyang C, Louie DS, Tatum D (1986a) Feedback regulation of pancreatic enzyme secretion suppression of cholecystokinin release by trypsin. J Clin Invest 77(6):2042–2047PubMedPubMedCentralCrossRefGoogle Scholar
  81. Owyang C, May D, Louie DS (1986b) Trypsin suppression of pancreatic enzyme secretion differential effect on cholecystokinin release and the enteropancreatic reflex. Gastroenterology 91(3):637–643PubMedCrossRefGoogle Scholar
  82. Pelley JR, Gordon SR, Gardner TB (2012) Abnormal duodenal [HCO3-] following secretin stimulation develops sooner than endocrine insufficiency in minimal change chronic pancreatitis. Pancreas 41(3):481–484PubMedCrossRefGoogle Scholar
  83. Poulsen JL, Olesen SS, Malver LP, Frokjaer JB, Drewes AM (2013) Pain and chronic pancreatitis: a complex interplay of multiple mechanisms. World J Gastroenterol 19(42):7282–7291PubMedPubMedCentralCrossRefGoogle Scholar
  84. Prescott P, Bakowski MT (1999) Pathogenesis of fibrosing colonopathy: the role of methacrylic acid copolymer. Pharmacoepidemiol Drug Saf 8(6):377–384PubMedCrossRefGoogle Scholar
  85. Prieto G, Perez-Moneo B, Molina M, Ramos E, Sarria J, Larrauri J, Tovar JA (2009) Fibrosing colonopathy associated with treatment with enteric-coated mesalazine pills. Inflamm Bowel Dis 15(10):1452–1453PubMedCrossRefGoogle Scholar
  86. Ramesh H, Reddy N, Bhatia S, Rajkumar JS, Bapaye A, Kini D, Kalla M, Thorat V (2013) A 51-week, open-label clinical trial in India to assess the efficacy and safety of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Pancreatology 13(2):133–139PubMedCrossRefGoogle Scholar
  87. Rausch U, Weidenbach H, Adler G, Kern HF (1987) Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor II regulation of total protein and individual enzyme biosynthesis. Cell Tissue Res 249(1):63–67PubMedCrossRefGoogle Scholar
  88. Regan PT, Malagelada JR, DiMagno EP, Go VL (1979) Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. Gastroenterol 77(2):285–289CrossRefGoogle Scholar
  89. Rogers CL (2013) Nutritional management of the adult with cystic fibrosis – part I. Pract Gastroenterol 113(1):10–24Google Scholar
  90. Sander-Struckmeier S, Beckmann K, Janssen-van SG, Pollack P (2013) Retrospective analysis to investigate the effect of concomitant use of gastric acid-suppressing drugs on the efficacy and safety of pancrelipase/pancreatin (CREON(R)) in patients with pancreatic exocrine insufficiency. Pancreas 42(6):983–989PubMedCrossRefGoogle Scholar
  91. Scharpé S, Uyttenbroeck W, Samyn N (1997) In: Lauwers A, Scharpé S (eds) Pancreatic enzyme replacement. Taylor Francis, London, pp 187–221Google Scholar
  92. Shiratori K, Chen YF, Chey WY, Lee KY, Chang TM (1986) Mechanism of increased exocrine pancreatic secretion in pancreatic juice-diverted rats. Gastroenterology 91(5):1171–1178PubMedCrossRefGoogle Scholar
  93. Sikkens EC, Cahen DL, Eijck C, Kuipers EJ, Bruno MJ (2012) Patients with exocrine insufficiency due to chronic pancreatitis are undertreated: a Dutch national survey. Pancreatology 12(1):71–73PubMedCrossRefGoogle Scholar
  94. Sikkens EC, Cahen DL, Koch AD, Braat H, Poley JW, Kuipers EJ, Bruno MJ (2013) The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis. Pancreatology 13(3):238–242PubMedCrossRefGoogle Scholar
  95. Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM (2017) Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 23(39):7059–7076PubMedPubMedCentralCrossRefGoogle Scholar
  96. Slaff J, Jacobson D, Tillman CR, Curington C, Toskes P (1984) Protease-specific suppression of pancreatic exocrine secretion. Gastroenterology 87(1):44–52PubMedCrossRefGoogle Scholar
  97. Smith JL, Jiang CL, Hunt JN (1984) Intrinsic emptying pattern of the human stomach. Am J Phys 246(6 Pt 2):R959–R962Google Scholar
  98. Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton H (2008) Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc 108(5):832–839PubMedCrossRefGoogle Scholar
  99. Stein J, Jung M, Sziegoleit A, Zeuzem S, Caspary WF, Lembcke B (1996) Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 42(2):222–226PubMedGoogle Scholar
  100. Struyvenberg MR, Martin CR, Freedman SD (2017) Practical guide to exocrine pancreatic insufficiency – breaking the myths. BMC Med 15(1):29PubMedPubMedCentralCrossRefGoogle Scholar
  101. Trang T, Chan J, Graham DY (2014) Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century. World J Gastroenterol 20(33):11467–11485PubMedPubMedCentralCrossRefGoogle Scholar
  102. Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman M (2018) Diagnostic performance of measurement of fecal elastase-1 in detection of exocrine pancreatic insufficiency – systematic review and meta-analysis. Clin Gastroenterol Hepatol 16(8):1220–1228.e4PubMedPubMedCentralCrossRefGoogle Scholar
  103. Veeger RW, AbelsS J, Hellemans N, Nieweg HO (1962) Effect of sodium bicarbonate and pancreatin on the absorption of vitamin B12 and fat in pancreatic insufficiency. N Engl J Med 267:1341–1344PubMedCrossRefGoogle Scholar
  104. van Velzen D, Ball LM, Dezfulian AR, Southgate A, Howard CV (1996) Comparative and experimental pathology of fibrosing colonopathy. Postgrad Med J 72(Suppl 2):S39–S48PubMedGoogle Scholar
  105. Weber AM, Roy CC, Chartrand L, Lepage G, Dufour OL, Morin CL, Lasalle R (1976) Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis. Gut 17(4):295–299PubMedPubMedCentralCrossRefGoogle Scholar
  106. White JV, Guenter P, Jensen G, Malone A, Schofield M (2012) Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). JPEN J Parenter Enter Nutr 36(3):275–283CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Medicine, Michael E. DeBakey VA Medical CenterBaylor College of MedicineHoustonUSA

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