Chapter 66
Diagnosis and Management of Pancreatic Exocrine Insufficiency in Pancreatic Cancer
Sarah Powell-Brett, Keith J. Roberts,
Keith J. Roberts
Queen Elizabeth Hospital, Birmingham, UK
University of Birmingham, Birmingham, UK
Search for more papers by this authorSarah Powell-Brett, Keith J. Roberts,
Keith J. Roberts
Queen Elizabeth Hospital, Birmingham, UK
University of Birmingham, Birmingham, UK
Search for more papers by this authorBook 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
Search for more papers by this authorFirst published: 16 April 2021
Summary
Pancreatic exocrine insufficiency (PEI) is a significant contributor to weight loss and malnutrition in pancreatic cancer, with over 80% of those with pancreatic cancer having lost weight by the time of diagnosis and over one-third having lost more than 10% of their body weight. For recognizable symptoms to occur in patients with PEI, the ingested food must overwhelm the enzymatic capacity of exocrine pancreatic secretion. An effective mechanism for diagnosing and quantifying PEI in pancreatic cancer is essential to assess the need for, correct dosage of, and efficacy of pancreatic enzyme replacement therapy (PERT) in order to prevent malabsorption/malnutrition and the associated complications and enable patients to undergo chemotherapy and/or surgery if appropriate. The treatment of PEI revolves around the exogenous replacement of the required enzymes with administration of PERT.
References
- Gilliland, TM, Villafane-Ferriol N, Shah KP, et al. Nutritional and metabolic derangements in pancreatic cancer and pancreatic resection. Nutrients 2017; 9(3): 243.
- Sikkens ECM, Cahen DL, de Wit J, et al. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol 2014; 48(5): e43–e46.
- Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 2016; 41(3): 211–218.
- Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11(5): 325–337.
- Miyamoto R, Oda T, Hashimoto S, et al. Platelet × CRP multiplier value as an indicator of poor prognosis in patients with resectable pancreatic cancer. Pancreas 2017; 46(1): 35–41.
- Tahergorabi Z, Khazaei M, Moodi M, Chamani E. From obesity to cancer: a review on proposed mechanisms. Cell Biochem Funct 2016; 34(8): 533–545.
- Permert J, Larsson J, Westermark GT, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med 1994; 330(5): 313–318.
- Bartel MJ, Asbun H, Stauffer J, Raimondo M. Pancreatic exocrine insufficiency in pancreatic cancer: a review of the literature. Dig Liver Dis 2015; 47(12): 1013–1020.
- Tseng DS, 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.
- Nordback I, Parviainen M, Piironen A, et al. Obstructed pancreaticojejunostomy partly explains exocrine insufficiency after pancreatic head resection. Scand J Gastroenterol 2007; 42(2): 263–270.
- Sato N, Yamaguchi K, Yokohata K, et al. Short-term and long-term pancreatic exocrine and endocrine functions after pancreatectomy. Dig Dis Sci 1998; 43(12): 2616–2621.
- Roeyen G, Jansen M, Ruyssinck L, et al. Pancreatic exocrine insufficiency after pancreaticoduodenectomy is more prevalent with pancreaticogastrostomy than with pancreaticojejunostomy. A retrospective multicentre observational cohort study. HPB (Oxford) 2016; 18(12): 1017–1022.
- Singh VK, Haupt ME, Geller DE, et al. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23(39): 7059–7076.
- Vujasinovic M, Valente R, Del Chiaro M, et al. Pancreatic exocrine insufficiency in pancreatic cancer. Nutrients 2017; 9(3): 183.
- Kodama M, Tanaka T. Residual function of exocrine pancreas after operation for chronic pancreatitis by N-benzoyl-l-tyrosyl-p-aminobenzoic acid test (NBT-PABA test). Digestion 1984; 30(1): 41–46.
- Tanaka T, Ichiba Y, Fujii Y, et al. Clinical and experimental study of pancreatic exocrine function after pancreaticoduodenectomy for periampullary carcinoma. Surg Gynecol Obstet 1988; 166(3): 200–205.
- Roberts KJ, Schrem H, Hodson J, et al. Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy. HPB (Oxford) 2017; 19(10): 859–867.
- Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic consequences of (regional) total pancreatectomy. Ann Surg 1991; 214(2): 131–140.
- Del Chiaro M, Rangelova E, Segersvärd R, Arnelo U. Are there still indications for total pancreatectomy? Updates Surg 2016; 68(3): 257–263.
- Parsaik AK, Murad MH, Sathananthan A, et al. Metabolic and target organ outcomes after total pancreatectomy: Mayo Clinic experience and meta-analysis of the literature. Clin Endocrinol 2010; 73(6): 723–731.
- DiMagno EP, Go VL, Summerskill WH. Relations between pancreatic enzyme ouputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973; 288(16): 813–815.
- Dominguez-Munoz JE. Diagnosis and treatment of pancreatic exocrine insufficiency. Curr Opin Gastroenterol 2018; 34(5): 349–354.
- 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.
- 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.
- Lindkvist B, Phillips ME, Dominguez-Munoz JE. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: prevalence and diagnostic use. Pancreatology 2015; 15(6): 589–597.
- 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.
- 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.
- 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.
- 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.
- 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.
- Gooden HM, White KJ. Pancreatic cancer and supportive care: pancreatic exocrine insufficiency negatively impacts on quality of life. Support Care Cancer 2013; 21(7): 1835–1841.
- van Dijk SM, Heerkens HD, Tseng DSJ, et al. Systematic review on the impact of pancreatoduodenectomy on quality of life in patients with pancreatic cancer. HPB (Oxford) 2018; 20(3): 204–215.
- Heerkens HD, van Berkel L, Tseng DSJ, et al. Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications. HPB (Oxford) 2018; 20(2): 188–195.
- Okumura S, Kaido T, Hamaguchi Y, et al. Visceral adiposity and sarcopenic visceral obesity are associated with poor prognosis after resection of pancreatic cancer. Ann Surg Oncol 2017; 24(12): 3732–3740.
- Sugimoto M, Farnell MB, Nagorney DM, et al. Decreased skeletal muscle volume is a predictive factor for poorer survival in patients undergoing surgical resection for pancreatic ductal adenocarcinoma. J Gastrointest Surg 2018; 22(5): 831–839.
- Choi MH, Yoon SB, Lee K, et al. Preoperative sarcopenia and post-operative accelerated muscle loss negatively impact survival after resection of pancreatic cancer. J Cachexia Sarcopenia Muscle 2018; 9(2): 326–334.
- Dominguez-Munoz JE, Hardt PD, 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.
- 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.
- Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005; 54(Suppl 6): 1–28.
- Lohr JM, Dominguez-Munoz JE, 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.
- 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.
- Dominguez-Munoz 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.
- 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(16): 854–858.
- 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(1): 203–213.
- Meyer JH, Elashoff J, Porter-Fink V, et al. Human postprandial gastric emptying of 1-3-millimeter spheres. Gastroenterology 1988; 94(6): 1315–1325.
- Meyer JH. Gastric emptying of ordinary food: effect of antrum on particle size. Am J Physiol 1980; 239(3): G133–G135.
- Meyer JH, Lake R. Mismatch of duodenal deliveries of dietary fat and pancreatin from enterically coated microspheres. Pancreas 1997; 15(3): 226–235.
- Meyer JH, Hlinka M, Kao D, et al. Gastric emptying of oil from solid and liquid meals. Effect of human pancreatic insufficiency. Dig Dis Sci 1996; 41(9): 1691–1699.
- 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.
- Gianotti L, Besselink MG, Sandini M, et al. Nutritional support and therapy in pancreatic surgery: a position paper of the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2018; 164(5): 1035–1048.
- Corey M, McLaughlin FJ, Williams M, Levison H. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol 1988; 41(6): 583–591.
- Landers A, Muircroft W, Brown H. Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer. BMJ Support Palliat Care 2016; 6(1): 75–79.
- Subramaniam S, Nobar N, Besherdas K. PWE-217 Pancreatic enzyme replacement therapy in chronic pancreatitis and pancreatic cancer: are we getting it right? Gut 2015; 64: 307–308.
- 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.
- Domínguez-Muñoz JE, Nieto-Garcia L, López-Díaz J, et al. Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis. BMC Cancer 2018; 18(1): 534.
- Woo SM, Joo J, Kim SY, et al. Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial. Pancreatology 2016; 16(6): 1099–1105.
- Braga M, Cristallo M, De Franchis R, et al. Pancreatic enzyme replacement therapy in post-pancreatectomy patients. Int J Pancreatol 1989; 5(Suppl): 37–44.
- Landers A, Brown H, Strother M. The effectiveness of pancreatic enzyme replacement therapy for malabsorption in advanced pancreatic cancer, a pilot study. Palliat Care 2019; 12:1178224218825270.
- Roberts KJ, Bannister CA, Schrem H. Enzyme replacement improves survival among patients with pancreatic cancer: results of a population based study. Pancreatology 2019; 19(1): 114–121.
- Sikkens ECM, Cahen DL, van Eijck C, et al. The daily practice of pancreatic enzyme replacement therapy after pancreatic surgery: a northern European survey. Enzyme replacement after surgery. J Gastrointest Surg 2012; 16(8): 1487–1492.
