Exocrine pancreatic insufficiency with maldigestion is caused by a deficiency of pancreatic enzymes production due to fibrotic replacement of normal pancreatic tissue or loss of pancreatic parenchyma. This condition is major consequence of chronic pancreatitis, but may also follow pancreatic resections. In pancreatic resections, the development of exocrine insufficiency depends on the type and the extension of resection, on the associated bowel resection, and on individual factors.

Digestion is often impaired after pancreaticoduodenectomy, and patients may experience steatorrhea and weight loss. This condition is often transient, and depends more on bowel resection than on the loss of pancreatic parenchyma. The duodenum, in fact, functions as an intestinal pacemaker and activates pancreatic enzymes. Most patients return to a normal bowel and pancreatic function within few months. Long-term exocrine insufficiency may depend on anastomosis failure with subsequent pancreatic duct obstruction and secondary chronic pancreatitis. signs of exocrine insufficiency are not present until 85 to 90% of the pancreas is unable to secrete enzymes. After left pancreatectomy, exocrine isufficiency is uncommon. 

Total pancreatectomy is invariably associated with exocrine insufficiency and impairment of gastrointestinal motility. However, these conditions tend to ameliorate over time (with an appropriate replacement therapy) such that the reported 1-year quality of life seems to be comparable to patients who underwent pancreaticoduodenectomy.

Symptoms of exocrine pancreatic insufficiency are mainly related to lipids and protein maldigestion, and include (in a variable degree) malabsorption, diarrhea, steatorrhea, and weight loss. Recurring abdominal pain  may be present. Breakdown of carbohydrates can be partially taken over by amylase in the saliva and enzymes in the small intestine; while breakdown of proteins may be partially taken over by gastric peptidase and enteropeptidase. Deficiency of liposoluble vitamins is usually present.

Quantification of exocrine pancreatic insufficiency requires functional tests. Among them, determination of fecal elastase-1, fecal chymotripsin, and stool fat content are the most widely available. 

The mainstays of exocrine pancreatic insufficiency treatment are a balanced low-fat diet, supplementation with trace elements and vitamins, and enzyme replacement therapy. A pancreatic enzyme preparation (pancreatine) contains lipases, alpha-amylase, and proteases. The strenght of the preparation is defined as the content of lipase per capsule (microspheres or minimicrospheres), where 10.000 = 10.000 lipase units. Up to 40.000 lipase units per capsule are commercially available. 

The capsules must be taken with meals or immediately thereafter. Enzyme preparations are acid-resistant and become activated under basic pH, in the small intestine. Nevertheless, proton-pump inhibitors may be associated to maximize their activation, especially in the case of gastric hyperacidity. Therapeutic success is primarily determined on a clinical basis.