Exocrine pancreatic insufficiency – clinical practice in 2024

Czech version

Authors: Petr Dítě ^1,2 ; David Solil ¹; Martina Bojková ^2,3; Marie Přecechtělová ¹; Jiří Dolina ^1,4 ; Bohuslav Kianička ⁵
Published in: Gastroent Hepatol 2024; 78(4): 314-318
Category: Clinical and Experimental Gastroenterology: Review Article
doi: https://doi.org/10.48095/ccgh2024314

Overview

Exocrine pancreatic insufficiency (EPI) is characterized by insufficient secretion of pancreatic digestive enzymes. According to the mechanistic theory, the lack of pancreatic enzymes in the small intestine does not ensure the digestion of food, which is mainly associated with the lack of essential fatty acids and liposoluble vitamins and, as a result, leads to the inability to ensure the nutritional and metabolic needs of the organism. In diagnostics, the standard is determination of fecal elastase. This determination is simple, the limitation is the low sensitivity to determine possible changes in pancreatic function already in the so-called initial stages of the dis ease. An alternative to fecal elastase testing is the use of breath tests using a mixture of triglycerides, radioactively labeled with carbon C13. Although the test is non-invasive, it is time-consuming and more difficult to access. The clinical symptoms of EPI are mainly those related to microbial digestion and subsequent malabsorption/maldigestion of micro- and macronutrients. In addition to the subjective feeling of bloating, borborygmy or osmotic diarrhea, low levels of liposoluble vitamins and some trace elements are frequent findings. Osteoporosis or sarcopenia belong to the picture of EPI. In EPI therapy, diet therapy and pancreatic enzyme replacement are essential approaches. The principle is to administer an adequate dose, especially of pancreatic lipase: 40,000–50,000 units with main meals, with application during meals. Smaller meals (snacks) are substituted with half the dose. The optimal galenic form is capsules with a protective cover, against the inactivation of enzymes by gastric acid, before they enter the duodenum. The galenic form is capsules containing enzymes in microparticles, 1.0–2.0 mm in size, which are released from the capsule upon entering the duodenum. This is the so-called controlled synchronization of the liberalization of the enzymes contained in the capsule. EPI is an underdiagnosed and undertreated condition in the population. The control of patients must therefore include, in addition to the evaluation of the overall clinical condition, the monitoring of changes that may manifest malabsorption. It is recommended to monitor the nutritional status at least once a year, at regular intervals.

Keywords:

exocrine insufficiency – maldigestion – malabsorption – fecal elastase – osteoporosis – osteopenia – pancreatic replacement – microparticle capsules

Sources

1. Whitcomb DC, Duggan SN, Martindale R et al. AGA-PancreasFest joint symposium on exocrine pancreatic insufficiency. Gastro Hep Advances 2023; 2 (3): 395–411. doi: 10.1016/j.gastha. 2022.11.008.

2. de Rijk FEM, van Valdhuisen GL, Besselink MG et al. Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: an international expert survey and case vignette study. Pancreatology 2022; 22 (4): 457–465. doi: 10.1016/j.pan.2022.03.013.

3. Stein J, Jung M, Sziegoleit A et al. Immuno -r eactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 1996; 42 (2): 222–226.

4. Tóth AZ, Szabo A, Hegyi P et al. Detection of human elastase isoforms by the ScheBo pan creatic elastase1 test. Am J Physiol Gastrointest Liver Physiol 2017; 312 (6): G606–G614. doi: 10.1152/ajpgi.00060.2017.

5. Zhan W, Akshintala V, Greer PJ et al. Low serum trypsinogen levels in chronic pancreatitis: correlation with parenchymal loss, exocrine pancreatic insufficieny, and diabetes but not CT-based cambridge severity scores for fibrosis. Pancreatology 2020; 20 (7): 1368–1378. doi: 10.1016/j.pan.2020.08.025.

6. Weintraub A, Blau H, Mussaffi N et al. Exocrine pancreatic function testing in patients with cystic fibrosis and pancreatic sufficiency: a correlation study. J Pediatr Gastroenterol Nutr 2009; 48 (3): 306–310. doi: 10.1097/mpg.0b013e318180af4f.

7. Stevens T, Conwell D, Zuccaro G Jr et al. A prospective crossover study comparing secretin – stimulated endoscopic and Dreiling tube pan creatic function testing in patients evaluated for chronic pancreatitis. Gastrointest Endosc 2008; 67 (3): 458–466. doi: 10.1016/j.gie.2007.07.028.

8. Dominguez-Munoz JE, Iglesias-Garcia J, Vilarino-Insua M et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2007; 5 (4): 484–488. doi: 10.1016/j.cgh.2007.01.004.

9. Dominguez-Munoz JE, Nieto L, Vilarino M et al. Development and diagnostic accuracy of a breath test for pancreatic exocrine insufficiency in chronic pancreatitis. Pancreas 2016; 45 (2): 241–247. doi: 10.1097/MPA.0000000000000434.

10. Toskes T, Dasyam AK, Shah ZK et al. T1 signal intensity ratio of the pancreas as an imaging bio marker for the staging of chronic pancreatitis. Abdom Radiol 2022; 47 (10): 3507–3519. doi: 10.1007/s00261-022-03611-4.

11. Albashir S, Bronner MP, Parsi MA et al. Endoscopic ultrasound, secretin endoscopic pancreatic function test and histology: correlation in chronic pancreatitis. Am J Gastroenterol 2010; 105 (11): 2498–2503. doi: 10.1038/ajg.2010.274.

12. Shetty R, Kumbhar G, Thomas A et al. How are imaging findings associated with exocrine inssuficiency in indiopathic chronic pancreatitis? Indian J Radiol Imaging 2022; 32 (2): 182–190. doi: 10.1055/s-0042-1744138.

13. DeWitt JM, Al-Haddad MA, Easler JJ et al. EUS pancreatic function testing and dynamic pancreatic duct evaluation for the diagnosis of exocrine pancreatic insufficiency and chronic pancreatitis. Gastrointest Endosc 2021; 93 (2): 444–453. doi: 10.1016/j.gie.2020.06.029.

14. Johnson CD, Arbuckle R, Bonner N et al. Quantative assessment of the symptoms and impact of pancreatic exocrine insufficiency (PEI) to inform of the development of patient – reported outcome (PRO) instrument. Patient 2017; 10 (5): 615–628. doi: 10.1007/s40271-017-0233-0.

15. Sikkens EC, Cahen DL, Koch AD et al. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis. Pancreatology 2013; 13 (3): 238–242. doi: 10.1016/j.pan.2013.02.008.

16. Dujsikova H, Dite P, Tomandl J et al. Occu r-r ence of metabolic osteopathy in patients with chronic pancreatitis. Pancreatology 2018; 18 (6): 583–586. doi: 10.1159/000159845.

17. Duggan SN, Smyth ND, Murphy A et al. High prevalence of osteoporosis in patients with chronic pancreatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014; 12 (2): 219–224. doi: 10.1016/j.cgh.2013.06.016.

18. Olesen SS, Buyukuslu A, Kohler M et al. Sarcopenia associates with hospitalization rates and reduced survival in patients with chronic pancreatitis. Pancreatology 2019; 19 (2): 245–251. doi: 10.1016/j.pan.2019.01.006.

19. Fasulo M, Omer E, Kaspar M. Sarcopenia in chronic pancreatitis – prevalence, diag nosis, mechanism and potential therapy. Curr Gastroenterol Rep 2022; 24 (4): 53–63. doi: 10.1007/s11894-022-00837-6.

20. Kuan LL, Dennison D, Garcea G. Prevalence and impact of sarcopenia in chronic pancreatitis. A review of the literature. World J Surgery 2021; 45 (2): 590–597. doi: 10.1007/s00 268-020-05828-0.

21. Ain UQ, Bashir Y, Kelleher L et al. Dietary intake in patients with chronic pancreatitis: a systematic revue and meta-analysis. World J Gastroenterol 2021; 27 (34): 5775–5792. doi: 10.3748/wjg.v27.i34.5775.

22. Ferrucci L, Fabri E. Inflammageing: chronic inflammation in ageing, cardiovascular dis ease, and frailty. Nat Rev Cardiol 2018; 15 (9): 505–522. doi: 10.1038/s41569-018-0064-2.

23. Duggan SN, O‘Keefe S. Nutritional support of chronic pancreatitis. In: The pancreas: an integrated textbook to basic science, medicine, and surgery. New Jersey: John Wiley & Sons 2018: 429–434.

24. Samarasekova E, Mahammed S, Carlisle S et al. Pancreatitis: summary of NICE guidance. BMJ 2018; 362: k3443. doi: 10.1136/bmj.k3443.

25. Shintakuya R, Uemura K, Murakami Y et al. Sarcopenia is closely associated with pancreatic exocrine insufficiency in patientes with pan creatic dis ease. Pancreatology 2017; 17 (1): 70–75. doi: 10.1016/j.pan.2016.10.005.

26. Prado CM, Purcell PA, Alish C et al. Implications of low muscle mass across the continuum of care: a narrative review. Ann Med 2018; 50 (8): 675–693. doi: 10.1080/07853890.2018.1511918.

27. Bear DE, MacGowan L, Elstad M et al. Relationship between skeletal muscle area and density and clinical outcome in adults receiving venovenous extracorporeal membrane oxygenation. Crit Care Med 2021; 49 (4): e350–e359. doi: 10.1097/CCM.0000000000004827.

28. Kordes M, Larsson M, Engstrand L et al. Pancreatic cancer cachexia: three dimensions of a complex syndrome. Br J Cancer 2021; 124 (10): 1623–1636. doi: 10.1038/s41416-021-01301-4.

29. Duggan SN, Smyth ND, O‘Sullivan M et al. The prevalence of malnutrition and fat-soluble vitamin deficiences in chronic pancreatitis. Nutr Clin Pract 2014; 29 (3): 348–354. doi: 10.1177/0884533614528361.

30. de la Iglesia-Garcia D, Huang W, Szatmary P et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic revue and meta-analysis. Gut 2017; 66 (8): 1354–1355. doi: 10.1136/gutjnl-2016-312529.

31. Gan C, Chen YH, Liu L et al. Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta analysis. Oncotarget 2017; 8 (55): 94920–94931. doi: 10.18632/oncotarget.21659.

32. Lohr M, Dominguez-Munoz E, Rosendahl J et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPan EU). United European Gastroenterol J 2017; 5 (2): 153–199. doi: 10.1177/2050640616684695.

33. de Rijk FEM, van Valdhuisen CL, Besselink MG et al. Diagnosis and treatment of exocrine pancreatic insifficiency in chronic pancreatitis: an international expert survey and case vignette study. Pancreatology 2022; 22 (4): 457–465. doi: 10.1016/j.pan.2022.03.013.

34. Gardner TB, Adler DG, Forsmark CE et al. ACG clinical guideline: chronic pancreatitis. Am J Gastroenterol 2020; 115 (3): 322–339. doi: 10.14309/ajg.0000000000000535.

35. Stallings VA, Stark LJ, Robinson KA et al. Evidence-based practice recommendations for the nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc 2008; 108 (5): 832–839. doi: 10.1016/j.jada.2008.02.020.

36. Cruz-Jentoff AJ, Sayer AA. Sarcopenia. Lancet 2019; 393 (10191): 2636–2646. doi: 10.1016/S01 40-6736 (19) 31138-9.

37. Philips ME, Hopper AD, Leeds JS et al. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8 (1): e000643. doi: 10.1136/bmjgast-2021-000643.

38. Vujasinovic M, Nezirevic Dobrijevic L, Asplund E et al. Low bone mineral density and risk for osteoporotic fractures in patients with chronic pancreatitis. Nutrients 2021; 13 (7): 2386. doi: 10.3390/nu13072386.

39. Duggan SN, Chonchubhair HM, Lawal O et al. Chronic pancreatitis: diagnostic dilemna. World J Gastroenterol 2016; 22 (7): 2304–2313. doi: 10.3748/wjg.v22.i7.2304.

40. Lankich PG, Lembcke B, Wemken G et al. Functional reserve capacity of the exocrine pancreas. Digestion 1986; 35 (3): 175–181. doi: 10.1159/000199364.

41. Othman MO, Harb D, Barkin JA. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. Int J Clin Pract 2018; 72 (2): e13066. doi: 10.1111/ijcp.13066.

42. Helander HF, Fandriks L. Surface area of the digestive tract – revisited. Scand J Gastro enterol 2014; 49 (6): 681–689. doi: 10.3109/0036 5521.2014.898326.

ORCID autorů

P. Dítě 0009-0002-3571-8058,

D. Solil 0009-0004-3343-3424,

M. Bojková 0000-0001-7799-2827,

J. Dolina 0000-0002-9061-5273,

B. Kianička 0000-0003-0988-5928.

Doručeno/Submitted: 21. 5. 2024

Přijato/Accepted: 11. 7. 2024

Korespondenční autor

prof. MUDr. Bohuslav Kianička, Ph.D.

II. interní klinika

LF MU a FN u sv. Anny v Brně