Diagnosis and Management of Pancreatic Exocrine Insufficiency in Chronic Pancreatitis

A Practical Protocol

J. Enrique Domínguez-Muñoz

Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

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J. Enrique Domínguez-Muñoz,

J. Enrique Domínguez-Muñoz

Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

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Book Editor(s):J. Enrique Domínguez-Muñoz MD, PhD,

J. Enrique Domínguez-Muñoz MD, PhD

Director

Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

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First published: 16 April 2021

https://doi.org/10.1002/9781119570097.ch38

Summary

Pancreatic exocrine insufficiency (PEI) defines the clinical situation in which pancreatic secretion of enzymes and bicarbonate is insufficient to ensure normal digestion of the ingested food, leading to symptoms and/or nutritional deficiencies. Prevalence of PEI in chronic pancreatitis is mainly related to the severity of the disease. PEI presents clinically as an intestinal malabsorption syndrome. Diagnosis of PEI is needed for appropriate management of patients with chronic pancreatitis. In clinical practice, PEI may be diagnosed by means of tests evaluating digestion, mainly that of fat, as well as tests quantifying pancreatic secretion of enzymes. Nutritional therapy and pancreatic enzyme replacement therapy are the two pillars of PEI therapy. PEI is a complication of chronic pancreatitis. Appropriate treatment of PEI is therefore mandatory to avoid complications and death related to malnutrition.

References

DiMagno EP, Go VL, Summerskill WH. Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973; 288(16): 813–815.
10.1056/NEJM197304192881603
CAS PubMed Web of Science® Google Scholar
Benini L, Amodio A, Campagnola P, et al. Fecal elastase-1 is useful in the detection of steatorrhea in patients with pancreatic diseases but not after pancreatic resection. Pancreatology 2013; 13(1): 38–42.
10.1016/j.pan.2012.11.307
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol 2011; 26(Suppl 2): 12–16.
10.1111/j.1440-1746.2010.06600.x
PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Phillips M. Nutritional therapy in chronic pancreatitis. Gastroenterol Clin North Am 2018; 47(1): 95–106.
10.1016/j.gtc.2017.09.004
PubMed Web of Science® Google Scholar
Stallings VA, Stark LJ, Robinson KA, et al. 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 2008; 108(5): 832–839.
10.1016/j.jada.2008.02.020
PubMed Web of Science® Google Scholar
Huang W, de la Iglesia-García D, Baston-Rey I, et al. Exocrine pancreatic insufficiency following acute pancreatitis: systematic review and meta-analysis. Dig Dis Sci 2019; 64(7): 1985–2005.
10.1007/s10620-019-05568-9
PubMed Web of Science® Google Scholar
Vujasinovic M, Valente R, Del Chiaro M, et al. Pancreatic exocrine insufficiency in pancreatic cancer. Nutrients 2017; 9(3): 183.
10.3390/nu9030183
Web of Science® Google Scholar
Straatman J, Wiegel J, van der Wielen N, et al. Systematic review of exocrine pancreatic insufficiency after gastrectomy for cancer. Dig Surg 2017; 34(5): 364–370.
10.1159/000454958
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford) 2009; 11(Suppl 3): 3–6.
10.1111/j.1477-2574.2009.00132.x
PubMed Google Scholar
Vujasinovic M, Valente R, Thorell A, et al. Pancreatic exocrine insufficiency after bariatric surgery. Nutrients 2017; 9(11): 1241.
10.3390/nu9111241
PubMed Web of Science® Google Scholar
Tseng DSJ, Molenaar IQ, Besselink MG, et al. Pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer: a systematic review. Pancreas 2016; 45(3): 325–330.
10.1097/MPA.0000000000000473
CAS PubMed Web of Science® Google Scholar
Beger HG, Poch B, Mayer B, Siech M. New onset of diabetes and pancreatic exocrine insufficiency after pancreaticoduodenectomy for benign and malignant tumors: a systematic review and meta-analysis of long-term results. Ann Surg 2018; 267(2): 259–270.
10.1097/SLA.0000000000002422
PubMed Web of Science® Google Scholar
Deprez PH, Sempoux C, De Saeger C, et al. Expression of cholecystokinin in the duodenum of patients with coeliac disease: respective role of atrophy and lymphocytic infiltration. Clin Sci (Lond) 2002; 103(2): 171–177.
10.1042/cs1030171
CAS PubMed Web of Science® Google Scholar
Mohapatra S, Majumder S, Smyrk TC, et al. Diabetes mellitus is associated with an exocrine pancreatopathy: conclusions from a review of literature. Pancreas 2016; 45(8): 1104–1110.
10.1097/MPA.0000000000000609
PubMed Web of Science® Google Scholar
Hardt PD, Ewald N. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes? Exp Diabetes Res 2011; 2011: 761950.
10.1155/2011/761950
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Alvarez-Castro A, Lariño-Noia J, et al. Endoscopic ultrasonography of the pancreas as an indirect method to predict pancreatic exocrine insufficiency in patients with chronic pancreatitis. Pancreas 2012; 41(5): 724–728.
10.1097/MPA.0b013e31823b5978
PubMed Web of Science® Google Scholar
Dominguez-Muñoz JE, Iglesias-Garcia J, Castiñeira Alvariño M, et al. EUS elastography to predict pancreatic exocrine insufficiency in patients with chronic pancreatitis. Gastrointest Endosc 2015; 81(1): 136–142.
10.1016/j.gie.2014.06.040
PubMed Web of Science® Google Scholar
Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United Eur Gastroenterol J 2017; 5(2): 153–199.
10.1177/2050640616684695
PubMed Web of Science® Google Scholar
Dominguez-Munoz JE, Drewes AM, Lindkvist B, et al. Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis. Pancreatology 2018; 18(8): 847–854.
10.1016/j.pan.2018.09.016
PubMed Web of Science® Google Scholar
Lindkvist B, Phillips ME, Domínguez-Muñoz JE. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: prevalence and diagnostic use. Pancreatology 2015; 15(6): 589–597.
10.1016/j.pan.2015.07.001
CAS PubMed Web of Science® Google Scholar
Partelli S, Frulloni L, Minniti C, et al. Faecal elastase-1 is an independent predictor of survival in advanced pancreatic cancer. Dig Liver Dis 2012; 44(11): 945–951.
10.1016/j.dld.2012.05.017
CAS PubMed Google Scholar
Johnson CD, Williamson N, Janssen-van Solingen G, et al. Psychometric evaluation of a patient-reported outcome measure in pancreatic exocrine insufficiency (PEI). Pancreatology 2019; 19(1): 182–190.
10.1016/j.pan.2018.11.013
PubMed Web of Science® Google Scholar
Johnson CD, Arbuckle R, Bonner N, et al. Qualitative assessment of the symptoms and impact of pancreatic exocrine insufficiency (PEI) to inform the development of a patient-reported outcome (PRO) instrument. Patient 2017; 10(5): 615–628.
10.1007/s40271-017-0233-0
PubMed Web of Science® Google Scholar
Barkin JA, Barkin JS. Chronic pancreatitis and bone disease. J Clin Densitom 2020; 23(2): 237–243.
10.1016/j.jocd.2019.08.004
PubMed Web of Science® Google Scholar
Tignor AS, Wu BU, Whitlock TL, et al. High prevalence of low-trauma fracture in chronic pancreatitis. Am J Gastroenterol 2010; 105(12): 2680–2686.
10.1038/ajg.2010.325
PubMed Web of Science® Google Scholar
Shintakuya R, Uemura K, Murakami Y, et al. Sarcopenia is closely associated with pancreatic exocrine insufficiency in patients with pancreatic disease. Pancreatology 2017; 17(1): 70–75.
10.1016/j.pan.2016.10.005
CAS PubMed Web of Science® Google Scholar
Olesen SS, Büyükuslu A, Køhler M, et al. Sarcopenia associates with increased hospitalization rates and reduced survival in patients with chronic pancreatitis. Pancreatology 2019; 19(2): 245–251.
10.1016/j.pan.2019.01.006
PubMed Web of Science® Google Scholar
de la Iglesia D, Vallejo-Senra N, López-López A, et al. Pancreatic exocrine insufficiency and cardiovascular risk in patients with chronic pancreatitis: a prospective, longitudinal cohort study. J Gastroenterol Hepatol 2019; 34(1): 277–283.
10.1111/jgh.14460
PubMed Web of Science® Google Scholar
de la Iglesia-Garcia D, Vallejo-Senra N, Iglesias-Garcia J, et al. Increased risk of mortality associated with pancreatic exocrine insufficiency in patients with chronic pancreatitis. J Clin Gastroenterol 2018; 52(8): e63–e72.
10.1097/MCG.0000000000000917
PubMed Web of Science® Google Scholar
D'Haese JG, Ceyhan GO, Demir IE, et al. Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life. Pancreas 2014; 43(6): 834–841.
10.1097/MPA.0000000000000131
PubMed Web of Science® Google Scholar
Dominguez-Muñoz JE. Diagnosis and treatment of pancreatic exocrine insufficiency. Curr Opin Gastroenterol 2018; 34(5): 349–354.
10.1097/MOG.0000000000000459
PubMed Web of Science® Google Scholar
Kamath MG, Pai CG, Kamath A, Kurien A. Comparing acid steatocrit and faecal elastase estimations for use in M-ANNHEIM staging for pancreatitis. World J Gastroenterol 2017; 23(12): 2217–2222.
10.3748/wjg.v23.i12.2217
PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Nieto L, Vilariño M, et al. Development and diagnostic accuracy of a breath test for pancreatic exocrine insufficiency in chronic pancreatitis. Pancreas 2016; 45(2): 241–247.
10.1097/MPA.0000000000000434
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Malfertheiner P. Optimized serum pancreolauryl test for differentiating patients with and without chronic pancreatitis. Clin Chem 1998; 44(4): 869–875.
10.1093/clinchem/44.4.869
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, Iglesias-Rey M. ¹³C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2007; 5(4): 484–488.
10.1016/j.cgh.2007.01.004
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Martinez SM, Leodolter A, Malfertheiner P. Quantification of pancreatic zinc output as pancreatic function test: making the secretin–caerulein test applicable to clinical practice. Pancreatology 2004; 4(1): 57–62.
10.1159/000077026
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Hardt DP, Lerch MM, Löhr MJ. Potential for screening for pancreatic exocrine insufficiency using the fecal elastase-1 test. Dig Dis Sci 2017; 62(5): 1119–1130.
10.1007/s10620-017-4524-z
CAS PubMed Web of Science® Google Scholar
Löser C, Möllgaard A, Fölsch UR. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Gut 1996; 39(4): 580–586.
10.1136/gut.39.4.580
CAS PubMed Web of Science® Google Scholar
Chowdhury SD, Kurien RT, Ramachandran A, et al. Pancreatic exocrine insufficiency: comparing fecal elastase 1 with 72-h stool for fecal fat estimation. Indian J Gastroenterol 2016; 35(6): 441–444.
10.1007/s12664-016-0714-4
PubMed Web of Science® Google Scholar
Symersky T, van der Zon A, Biemond I, Masclee AA. Faecal elastase-I: helpful in analysing steatorrhoea? Neth J Med 2004; 62(8): 286–289.
CAS PubMed Web of Science® Google Scholar
Lindkvist B, Domínguez-Muñoz JE, Luaces-Regueira M, et al. Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis. Pancreatology 2012; 12(4): 305–310.
10.1016/j.pan.2012.04.006
CAS PubMed Web of Science® Google Scholar
Adler G, Mundlos S, Kühnelt P, Dreyer E. New methods for assessment of enzyme activity: do they help to optimize enzyme treatment? Digestion 1993; 54(Suppl 2): 3–9.
10.1159/000201095
CAS PubMed Web of Science® Google Scholar
Kühnelt P, Mundlos S, Adler G. [Effect of pellet size of a pancreas enzyme preparation on duodenal lipolytic activity.] Z Gastroenterol 1991; 29(9): 417–421.
PubMed Google Scholar
Czakó L, Takács T, Hegyi P, et al. Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis. Can J Gastroenterol 2003; 17(10): 597–603.
10.1155/2003/515848
PubMed Web of Science® Google Scholar
Duggan SN, O'Sullivan M, Hamilton S, et al. Patients with chronic pancreatitis are at increased risk for osteoporosis. Pancreas 2012; 41(7): 1119–1124.
10.1097/MPA.0b013e31824abb4d
PubMed Web of Science® Google Scholar
Duggan SN, Smyth ND, O'Sullivan M, et al. The prevalence of malnutrition and fat-soluble vitamin deficiencies in chronic pancreatitis. Nutr Clin Pract 2014; 29(3): 348–354.
10.1177/0884533614528361
CAS PubMed Web of Science® Google Scholar
Duggan S, O'Sullivan M, Feehan S, et al. Nutrition treatment of deficiency and malnutrition in chronic pancreatitis: a review. Nutr Clin Pract 2010; 25(4): 362–370.
10.1177/0884533610373772
PubMed Web of Science® Google Scholar
Mirtallo JM, Forbes A, McClave SA, et al. International consensus guidelines for nutrition therapy in pancreatitis. JPEN J Parenter Enteral Nutr 2012; 36(3): 284–291.
10.1177/0148607112440823
CAS PubMed Web of Science® Google Scholar
Boivin M, Lanspa SJ, Zinsmeister AR, et al. Are diets associated with different rates of human interdigestive and postprandial pancreatic enzyme secretion? Gastroenterology 1990; 99(6): 1763–1771.
10.1016/0016-5085(90)90485-J
CAS PubMed Web of Science® Google Scholar
Holtmann G, Kelly DG, Sternby B, DiMagno EP. Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes. Am J Physiol 1997; 273(2 Pt 1): G553–G558.
CAS PubMed Web of Science® Google Scholar
Suzuki A, Mizumoto A, Sarr MG, DiMagno EP. Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: a new therapy of steatorrhea? Gastroenterology 1997; 112(6): 2048–2055.
10.1053/gast.1997.v112.pm9178698
CAS PubMed Web of Science® Google Scholar
Singh S, Midha S, Singh N, et al. Dietary counseling versus dietary supplements for malnutrition in chronic pancreatitis: a randomized controlled trial. Clin Gastroenterol Hepatol 2008; 6(3): 353–359.
10.1016/j.cgh.2007.12.040
CAS PubMed Web of Science® Google Scholar
Dutta SK, Hlasko J. Dietary fiber in pancreatic disease: effect of high fiber diet on fat malabsorption in pancreatic insufficiency and in vitro study of the interaction of dietary fiber with pancreatic enzymes. Am J Clin Nutr 1985; 41(3): 517–525.
10.1093/ajcn/41.3.517
CAS PubMed Web of Science® Google Scholar
Lordan JT, Phillips M, Chun J-Y, et al. A safe, effective, and cheap method of achieving pancreatic rest in patients with chronic pancreatitis with refractory symptoms and malnutrition. Pancreas 2009; 38(6): 689–692.
10.1097/MPA.0b013e3181a5edf8
PubMed Web of Science® Google Scholar
Meier R, Ockenga J, Pertkiewicz M, et al. ESPEN guidelines on enteral nutrition: pancreas. Clin Nutr 2006; 25(2): 275–284.
10.1016/j.clnu.2006.01.019
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Iglesias-García 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, three-way crossover study. Aliment Pharmacol Ther 2005; 21(8): 993–1000.
10.1111/j.1365-2036.2005.02390.x
CAS PubMed Web of Science® Google Scholar
Seiler CM, Izbicki J, Varga-Szabó L, et al. Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther 2013; 37(7): 691–702.
10.1111/apt.12236
CAS PubMed Web of Science® Google Scholar
Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005; 54(Suppl 6): vi1–vi28.
10.1136/gut.2005.065946
CAS PubMed Web of Science® Google Scholar
de la Iglesia-García D, Huang W, Szatmary P, et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut 2017; 66(8): 1354–1355.
PubMed Web of Science® Google Scholar
Ramesh H, Reddy N, Bhatia S, et al. 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 2013; 13(2): 133–139.
10.1016/j.pan.2013.01.009
CAS PubMed Web of Science® Google Scholar
Greer JB, Greer P, Sandhu BS, et al. Nutrition and inflammatory biomarkers in chronic pancreatitis patients. Nutr Clin Pract 2019; 34(3): 387–399.
10.1002/ncp.10186
CAS PubMed Web of Science® Google Scholar
Winny M, Paroglou V, Bektas H, et al. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis. Surgery 2014; 155(2): 271–279.
10.1016/j.surg.2013.08.012
PubMed Web of Science® Google Scholar
Dutta SK, Rubin J, Harvey J. Comparative evaluation of the therapeutic efficacy of a pH-sensitive enteric coated pancreatic enzyme preparation with conventional pancreatic enzyme therapy in the treatment of exocrine pancreatic insufficiency. Gastroenterology 1983; 84(3): 476–482.
10.1016/0016-5085(83)90070-7
CAS PubMed Web of Science® Google Scholar
Guarner L, Rodríguez R, Guarner F, Malagelada JR. Fate of oral enzymes in pancreatic insufficiency. Gut 1993; 34(5): 708–712.
10.1136/gut.34.5.708
CAS PubMed Web of Science® Google Scholar
Domínguez-Muñoz JE, Iglesias-García J, Iglesias-Rey M, Vilariño-Insua M. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut 2006; 55(7): 1056–1057.
10.1136/gut.2006.094912
CAS PubMed Web of Science® Google Scholar
Ní Chonchubhair HM, Bashir Y, Dobson M, et al. The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI). Pancreatology 2018; 18(4): 379–385.
10.1016/j.pan.2018.02.010
PubMed Web of Science® Google Scholar
El Kurdi B, Babar S, El Iskandarani M, et al. Factors that affect prevalence of small intestinal bacterial overgrowth in chronic pancreatitis: a systematic review, meta-analysis, and meta-regression. Clin Transl Gastroenterol 2019; 10(9): e00072.
10.14309/ctg.0000000000000072
PubMed Web of Science® Google Scholar

Clinical Pancreatology for Practising Gastroenterologists and Surgeons, Second Edition