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
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 |
Mechanism involved | Pancreatic cancer | Diabetes mellitus | Celiac disease | IBD | GI 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 | √ | √ | √ |
Sign/symptom | Associated findings |
Excessive flatulence | Abdominal bloating or distension, cramps, belching |
Steatorrhea | Fatty, bulky stools; increased bowel movements |
Malnutrition | Weight loss, anorexia, fatigue |
Vitamin D deficiency | Deficient bone mineralization, osteomalacia, osteoporosis |
Vitamin K deficiency | Coagulation abnormalities, ecchymoses, bone metabolism deficiencies |
Vitamin A deficiency | Night blindness, decreased immune competence |
Vitamin E deficiency | Ataxia and peripheral neuropathy |
Hypocalcemia | Muscle spasms, osteomalacia, osteoporosis |
Hypoalbuminemia | Nail leukonychia |
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
Study | Study design, duration (when given), and number of patients | Disease | Results | Adverse effects |
Bruno et al[66] | DBRPC, 8 wk, 24 adults (21 analyzed) | Pancreatic cancer | The 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 adults | Pancreatic cancer | The 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 adults | Pancreatic cancer | Most 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 improved | No descriptions regarding TEAEs |
Ewald et al[49] | DBRPC, 16 wk, 80 adults | Type 1 diabetes | No 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 children | Celiac disease | Significant 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 d | No undesired side effects were reported |
Evans et al[141] | Open-label, up to 4 yr, 20 adults | Celiac disease | Significant 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 adults | Celiac disease | Significant 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 adults | Esophagectomy | Improvement 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 adults | Total gastrectomy | Improved stool consistency (score, 7.6 with PERT vs 9.3 with placebo; P < 0.05), but not the number of bowel movements or abdominal symptoms | No descriptions regarding TEAEs |
Hillman et al[166] | Open-label, 6 mo, 30 adults | Partial gastrectomy | Mean ± 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 adults | Total gastrectomy | Improvement of overall well-being (15/23 with PERT vs 6/24 with placebo; P = 0.006), but no improvement of specific symptom | No descriptions regarding TEAEs |
- Citation: Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23(39): 7059-7076
- URL: https://www.wjgnet.com/1007-9327/full/v23/i39/7059.htm
- DOI: https://dx.doi.org/10.3748/wjg.v23.i39.7059