Specificities of the diagnostics and therapy of exocrine pancreatic insufficiency
Authors:
Petr Dítě 1
; I. Novotný 2; P. Kocna 3; M. Bojková 4; T. Kupka 4; H. Nechutová 5; Bohuslav Kianička 5
Authors place of work:
Akademické centrum gastroenterologie a gastroonkologie OU Ostrava, vedoucí pracoviště prof. MUDr. Petr Dítě, DrSc.
1; Gastroenterologické oddělení Masarykova onkologického ústavu Brno, vedoucí pracoviště MUDr. Milana Šachlová, CSc. et Ph. D.
2; Ústav lékařské biochemie a laboratorní diagnostiky 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Tomáš Zima, DrSc., MBA
3; Interní klinika Lékařské fakulty OU a FN Ostrava, přednosta doc. MUDr. Arnošt Martínek, CSc.
4; Gastroenterologické oddělení II. interní kliniky Lékařské fakulty MU a FN u sv. Anny Brno, přednosta prof. MUDr. Miroslav Souček, CSc.
5
Published in the journal:
Vnitř Lék 2013; 59(1): 65-70
Category:
Review
Summary
Exocrine pancreatic insufficiency develops steadily; however, the initial reduction in secretion is practically not diagnosable. More advanced stages, which usually replicate morphological changes, can be determined with tests which asses the exocrine pancreatic capacity. Substantial damage of the pancreas and replacement of viable parenchyma with connective tissue is accompanied by the occurrence of steatorrhoea. This corresponds to a reduction in exocrine pancreatic secretion below 10% of physiological secretion. Exocrine pancreatic secretion tests are still not sufficiently sensitive for diagnosing early stages of pancreas defects and thus are not suitable for diagnostics. Furthermore, detecting reduced exocrine secretion does not provide any information about the aetiology of the disease, e.g. inflammation/tumor. The most precise test is a costly examination, including a stimulation of the gland with enterohormones; however, breath tests are usually recommended for the assessment of exocrine insufficiency therapy. Exocrine pancreatic insufficiency therapy consists of administering drugs containing pancreatin (amylase, lipase, and peptidase) to patients diagnosed with steatorrhoea, manifest pancreatic insufficiency. As standard, capsules containing microparticles of 1–2mm are recommended. They have a protective coating that prevents inactivation in the microparticles of the contained enzymes by gastric hydrochloric acid. The drug should be administered during each meal, i.e. several times a day. The most common mistake during pancreatic enzyme therapy is underdosage. The following rule applies to patients with digestive insufficiency: 40,000–50,000 UNT of lipase are to be administered during “main meals” and 25,000 UNT of lipase during morning or afternoon snacks. The drug should be taken during the meal; insufficient treatment and dosage are associated with insufficient digestion and absorption of a number of substances and also with pancreatic malabsorption.
Key words:
pancreatic secretion – pancreatic enzymes – pancreatin – pancreatic secretion tests
Zdroje
1. Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005; 54: (Suppl. 6): vi1–vi28.
2. Moreau H, Sauniere JF, Gargouri Y et al. Human gastric lipase: variations induced by gastrointestinal hormones and by pathology. Scand J Gastroenterol 1988; 23: 1044–1048.
3. Carriere F, Barrowman JA, Verger R et al. Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterology 1993; 105: 876–878.
4. Layer P, von der Ohe MR, Holst JJ et al. Altered postprandial motility in chronic pancreatitis: role of malabsorption. Gastroenterology 1997; 112: 1624–1634.
5. Lankisch PG, Lembcke B, Wemken G et al. Functional reserve capacity of the exocrine pancreas. Digestion 1986; 35: 175–181.
6. Layer P, Peschel S, Schlesinger T et al. Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion. Am J Physiol 1990; 258: G196–G201.
7. Layer P, Schlesinger T, Groger G et al. Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum. Pancreas 1993; 8: 426–432.
8. Read NW, McFarlane A, Kinsman RI et al. Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 1984; 86: 274–280.
9. Layer P, Jansen JB, Cherian L et al. Feedback regulation of human pancreatic secretion. Effects of protease inhibition on duodenal delivery and small intestinal transit of pancratic enzymes. Gastroenterology 1990; 98: 1311–1319.
10. Layer P, Go VL, DiMagno EP. Fate of pancreatic enzymes during small intestinal aboral transit in humans. Am J Physiol 1986; 251: G475–G480.
11. Holtmann G, Kelly DG, Sternby B et al. Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes. Am J Physiol 1997; 273: G553–G558.
12. Whitcomb DC, Lowe ME. Human pancreatic digestive enzymes. Dig Dis Sci 2007; 52: 1–17.
13. Zentler-Munro PL, Fitzpatrick WJ, Batten JC et al. Effect of intrajejunal acidity on aqueous phase bile acid and lipid concentrations in pancreatic steatorrhoea due to cystic fibrosis. Gut 1984; 25: 500–507.
14. Bruno MJ. Maldigestion and exocrine pancreatic insufficiency after pancreatic resection for malignant disease: pathophysiology and treatment. Pancreatology 2001; 1: (Suppl. 1): 55–61.
15. Kalivianakis M, Minich DM, Bijleveld CM et al. Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids. Am J Clin Nutr 1999; 69: 127–134.
16. Dítě P, Dastych M, Novotný I et al: Changes in serum levels of zinc, selenium, copper and magnesium in individuals with chronic alcoholic and chronic idiopathic pancreatitis. Progress in Medicine 2011; 26: 181–185.
17. Montalto G, Soresi M, Carroccio A et al. Lipoproteins and chronic pancreatitis. Pancreas 1994; 9: 137–138.
18. Gullo L, Tassoni U, Mazzoni G et al. Increased prevalence of aortic calcification in chronic pancreatitis. Am J Gastroenterol 1996; 91: 759–761.
19. Haaber AB, Rosenfalck AM, Hansen B et al. Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency. Int J Pancreatol 2000; 27: 21–27.
20. Dujsíková H, Novotný I, Tomandl J et al. Chronická pankreatitida a skelet. Vnitř Lék 2010; 56: 656–662.
21. Ewald N, Raspe A et al. Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentration in patients with diabetes mellitus. Eur J Med Res 2009;14: 118–122.
22. Gullo L, Simoni P. A study of pancreatic function among subjects over ninety years of age. Pancreatology 2009; 9: 240–244.
23. Dobrilla G. Management of chronic pancreatitis. Focus on enzyme replacement therapy. Int Pancreatol 1989; 5: (Suppl.): 17–29.
24. Mundlos S, Kuhnelt P, Adler G. Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholestery octanoate breath test. Gut 1990; 31: 1324–1328.
25. Bruno MJ, Haverkort EB, Tijssen GP et al. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998; 42: 92–96.
26. Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M et al. Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency: a randomized, threeway crossover study. Aliment Pharmacol Ther 2005; 15: 993–1000.
27. Keller J, Layer P. Pancreatic enzyme supplementation therapy. Curr Treat Options Gastroenterol 2003; 6: 369–374.
28. Delchier JC, Vidon N, Saint-Marc Girardin MF et al. Fate of orally ingested enzymes in pancreatic insufficiency:comparison of two pancreatic enzyme preparations. Aliment Pharmacol Ther 1991; 5: 365–378.
29. Lohr MJ, Hummel FM, Pirilis KT et al. Properties of different pancreatin preparations used in pancreatic exocrine insufficiency. Eur J Gastroenterol Hepatol 2009; 4: 1024–1031.
30. Sikkens ECM, Cahen DL, Knipers EJ et al. Pancreatic enzyme replacement therapy in chronic pancreatitis. Best Practice Res Clin Gastroent 2010; 24: 337–347.
31. Waljee AK, DiWagno MJ, Wu BU et al. Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis. Aliment Pharmacol Ther 2009; 29: 235–246.
32. Bruno MJ, Borm JJ, Hoek FJ et al. Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis. Dig Dis Sci 1998; 43: 203–213.
33. Layer P, Keller J. Lipase supplementation therapy: standards, alternatives, and perspectives. Pancreas 2003; 26: 1–7.
34. Dominguez-Munoz JE, Birckelbach U, Glasbrenner B et al. Effect of oral pancreatic enzyme administration on digestive function in healthy subjects: comparison between two enzyme preparations. Aliment Pharmacol Ther 1997; 11: 403–408.
35. Halm U, Loser C, Lohr M et al. A double--blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency. Aliment Pharmacol Ther 1999; 13: 951–957.
36. Meyer JH, Elashoff. J Human postprandial gastric emptying of 1–3 milimeter spheres. Gastroenterology 1988; 94: 114–119.
37. Ramo OJ, Puolakkainen PA, Seppala K et al. Self-administration of enzyme substitution in the treatment of exocrine pancreatic insufficiency. Scand J Gastroenterol 1989; 24: 688–692.
38. Stead RJ, Skypala I, Hodson ME et al. Enteric coated microspheres of pancreatin in the treatment of cystic fibrosis: comparison with standard enteric coated preparation. Thorax 1987; 42: 533–537.
39. Regan PT, Malagelada JR, DiMagno EP et al. Comparative effects of antacids, cimetidine and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency. N Engl J Med 1977; 297: 854–858.
40. Stevens T, Conwell DL, Whitcomb DC et al. Pancreatic exocrine function tests. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, March 2012.
41. Kocna P. Dechové testy – moderní, neinvazivní diagnostika. Interní medicína 2006; 8: 336–341.
42. Braden B. 13C breath tests for the assessment of exocrine pancreatic function. Pancreas 2010; 39: 955–959.
43. Nakamura H, Morifuji M, Murakami Y et al. Usefulness of a 13C-labeled mixed triglyceride breath test for assessing pancreatic exocrine function after pancreatic surgery. Surgery 2009; 145: 168–175.
44. Ishii Y, Kohno T, Ito A et al. Measurement of extra-pancreatic secretory function by 13C-dipeptide breath test. Transl Res 2007; 149: 298–303.
45. Krechler T, Kocna P, Vaníčková Z et al. Stanovení elastázy I ve stolici – využití v diagnostice chronické pankreatitidy. Čas Lék Čes 2006; 145: 480–483.
46. Kocna P, Kohout P Clinical, therapeutical and economical benefit of exocrine pancreatic function tests. Pancreatology 2012; 25: (Suppl.): 44.
47. Smyth RL, van Velzen D, Smyth AR et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 1994; 8: 85–86.
48. Raimondo M, DiMagno EP. Lipolytic activity of bacterial lipase survives better than that of porcine lipase in human gastric and duodenal content. Gastroenterology 1994; 107: 231–235.
49. Suzuki A, Mizumoto A, Rerknimitr R et al. Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs. Gastroenterology 1999; 116: 431–437.
50. Suzuki A, Mizumoto A, Sarr MG et al. Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: a new therapy of steatorrhea? Gastroenterology 1997; 112: 2048–2055.
51. Kuhel DG, Zheng S, Tso P et al. Adenovirus--mediated human pancreatic lipase gene transfer to rat bile: gene therapy of fat malabsorption. Am J Physiol Gastrointest Liver Physiol 2000; 279: G1031–G1036.
52. Maeda H, Danel C, Crystal RG. Adenovirus – mediated transfer of human lipase complementary DNA to the gallbladder. Gastroenterology 1994; 106: 1638–1644.
Štítky
Diabetology Endocrinology Internal medicineČlánok vyšiel v časopise
Internal Medicine
2013 Číslo 1
Najčítanejšie v tomto čísle
- Drug induced osteoporosis
- Specificities of the diagnostics and therapy of exocrine pancreatic insufficiency
- Risk factors for relapsing and severe Clostridium difficile infection
- Outcomes of Catheter Ablation of Atrial Fibrillation in Patients over 65 Years of Age