Review
Copyright ©The Author(s) 2017.
World J Gastroenterol. Oct 21, 2017; 23(39): 7059-7076
Published online Oct 21, 2017. doi: 10.3748/wjg.v23.i39.7059
Table 1 Causes of exocrine pancreatic insufficiency
Definite association with EPI
Chronic pancreatitis
Pancreatic tumor/cancer
Cystic fibrosis
Pancreatic resection
Pancreatic hemochromatosis
Mechanisms associated with EPI not fully identified
Type 1 and 2 diabetes
Type 3c (pancreatogenic) diabetes
Gastrointestinal diseases
Celiac disease
Inflammatory bowel disease
Crohn’s disease
Ulcerative colitis
Gastrointestinal surgery
Aging
Table 2 Factors involved with exocrine pancreatic insufficiency in different medical conditions[1,16,77,78,107,129,131,133,143,144,152-154,164]
Mechanism involvedPancreatic cancerDiabetes mellitusCeliac diseaseIBDGI surgery
Normal pancreas
Abnormal pancreas
Low or absent pancreatic enzyme production
Lack of stimulus for pancreatic enzyme production
Postcibal asynchrony
Pancreatic or biliary tract abnormalities
GI malabsorption
Table 3 Common signs and symptoms of exocrine pancreatic insufficiency[1,14-16,18,19,22]
Sign/symptomAssociated findings
Excessive flatulenceAbdominal bloating or distension, cramps, belching
SteatorrheaFatty, bulky stools; increased bowel movements
MalnutritionWeight loss, anorexia, fatigue
Vitamin D deficiencyDeficient bone mineralization, osteomalacia, osteoporosis
Vitamin K deficiencyCoagulation abnormalities, ecchymoses, bone metabolism deficiencies
Vitamin A deficiencyNight blindness, decreased immune competence
Vitamin E deficiencyAtaxia and peripheral neuropathy
HypocalcemiaMuscle spasms, osteomalacia, osteoporosis
HypoalbuminemiaNail leukonychia
Table 4 Symptoms and tests used in the diagnosis of exocrine pancreatic insufficiency[2,16,23,24]
Clinical symptoms
Steatorrhea
Diarrhea
Flatulence
Weight loss
Laboratory findings
Fecal fat > 7 g/d on a 100-g fat/d diet
Inconvenient; special high-fat diet and prolonged collection of feces
Considered gold standard
An abnormal coefficient of fat absorption is not specific for EPI
Fecal elastase-1 level ≤ 200 μg/g stool; < 100 μg/g stool = severe EPI
Simple, convenient, and widely available
Measured on a random stool sample
Liquid stools may lead to falsely low results due to dilution
Less accurate in mild stages of disease
Positive qualitative fecal fat (Sudan III) staining
Special high-fat diet
Less accurate; semi-quantitative microscopic method
Insensitive for mild disease
Fecal chymotrypsin ≤ 6 U/g stool
Less sensitive than fecal elastase for mild EPI
Fluorescein dilaurate (pancreolauryl test)
Easy to perform
Not widely available
13C-mixed triglyceride breath test
Well established
Not widely available
Imaging/endoscopy
Pancreatic duct dilatation
Main pancreatic duct calculi
Endosonographic criteria of chronic pancreatitis
Secretin-enhanced diffusion-weighted magnetic resonance cholangiopancreatography imaging
New
Not widely available
Table 5 Pancreatic enzyme replacement therapy clinical trials
StudyStudy design, duration (when given), and number of patientsDiseaseResultsAdverse effects
Bruno et al[66]DBRPC, 8 wk, 24 adults (21 analyzed)Pancreatic cancerThe mean absolute difference for PERT vs placebo in percentage change in body weight was 4.9% (P = 0.02); other outcomes were numerically improved with PERT vs placebo [fat absorption coefficient, 12% increase vs 8% decrease (P = 0.13); stool frequency, decrease of 1/d vs increase of 2/d (P = 0.07)]No treatment-related AEs
Woo et al[70]DBRPC, 8 wk, 67 adultsPancreatic cancerThe mean change in body weight at 8 wk was similar with PERT vs placebo (-1.49% vs -2.99%; P = 0.381), but the mean change in nutritional status was superior with PERT vs placebo in the subset of patients with cancer of the pancreatic head (PG-SGA score, -42.65% vs 32.93%; P = 0.039)Three patients died [PERT group, 2/34 (6%); placebo group, 1/33 (3%)]
There were no PERT-related serious AEs
Perez et al[60]Open-label, 12 adultsPancreatic cancerMost patients with moderate to severe fat (6/7) or protein (3/3) malabsorption improved, but no patients with mild fat or protein (0/8) malabsorption improvedNo descriptions regarding TEAEs
Ewald et al[49]DBRPC, 16 wk, 80 adultsType 1 diabetesNo significant change in HbA1c, fasting glucose, or postprandial glucose; increase in mean vitamin D from baseline to week 16 (PERT, from 54.1 to 59.4 nmol/L; placebo, 60.2 to 62.7 nmol/L)TEAEs occurred in 33 patients (84.6%) in PERT group and in 35 (85.4%) in PBO group; most frequent AEs were headache, infection, pain, diarrhea, and dyspepsia
Carroccio et al[150]DBRPC, 2 mo, 40 childrenCeliac diseaseSignificant mean ± SD weight gain in first 30 d (1131 ± 461 g with PERT vs 732 ± 399 g with placebo; P < 0.006), not significant at 60 dNo undesired side effects were reported
Evans et al[141]Open-label, up to 4 yr, 20 adultsCeliac diseaseSignificant increase in fecal elastase from median of 90 μg/g to 365 μg/g (P < 0.0001) and improvement in chronic diarrhea with reduction in median stool frequency from 4/d to 1/d (P ≤ 0.0001), but no weight increase (P = 0.3)No descriptions regarding TEAEs
Leeds et al[135]Open-label, up to 2 yr, 20 adultsCeliac diseaseSignificant improvement in chronic diarrhea with reduction in median stool frequency from 4/d to 1/d (P ≤ 0.0001), but no weight increase (P = 0.3)No descriptions regarding TEAEs
Huddy et al[181]Open-label, 10 adultsEsophagectomyImprovement in diarrhea and steatorrhea (9/10), increased weight (7/10)Nausea in 1 patient
Armbrecht et al[183]DBRPC crossover trial, 2 wk (plus 1-wk washout), 15 adultsTotal gastrectomyImproved stool consistency (score, 7.6 with PERT vs 9.3 with placebo; P < 0.05), but not the number of bowel movements or abdominal symptomsNo descriptions regarding TEAEs
Hillman et al[166]Open-label, 6 mo, 30 adultsPartial gastrectomyMean ± SE weight gain of 6.73 ± 0.77 (P < 0.001), mean ± SE decrease in steatorrhea of 49.7% ± 7.7% (P < 0.001)No descriptions regarding TEAEs
Brägelmann et al[184]DBRPC, 14 d, 52 adultsTotal gastrectomyImprovement of overall well-being (15/23 with PERT vs 6/24 with placebo; P = 0.006), but no improvement of specific symptomNo descriptions regarding TEAEs