Underlying conditions and surgical procedures that can cause EPI

• Destruction of functioning pancreatic parenchyma and obstruction of the pancreatic duct result in insufficient amounts of enzymes being secreted into the duodenum, and EPI^2,3
• ~6%-22% of patients with CP have EPI at the time of CP diagnosis^4,5
• The probability of developing EPI increases over time to^3,5:
  • 28% at 5 years after onset of CP
  • 50% at 12 years after onset of CP
  • 70% at 20 years after onset of CP
• Onset varies based on etiology, severity, and duration of CP^4,5

• Highly concentrated and viscous pancreatic juice blocks the pancreatic ducts, leading to acinar atrophy, pancreatic fibrosis, and EPI²
• Approximately 90% of patients with CF have EPI⁶

• EPI is a common complication of partial or complete removal of the pancreas, such as pancreatoduodenectomy (Whipple procedure)^7-9
• Frequency and severity of EPI may vary due to underlying condition, type and extent of surgery, and timing of EPI assessment^9,10

• Obstruction of the pancreatic duct by tumors, destruction of the pancreas by tumor growth, and loss of pancreatic tissue from surgery often lead to EPI^2,11
• Unresectable pancreatic cancer: 50%-92% of patients with unresectable pancreatic cancer have EPI^12,13
• Resectable pancreatic cancer (presurgery): 42%-68% of patients with resectable pancreatic cancer have EPI^7,14,15
• Resectable pancreatic cancer (postsurgery): 55%-89% of patients with resectable pancreatic cancer have EPI^14-18

• EPI can be a potential complication of AP and may develop early in the recovery phase or later^19-21
• EPI due to AP may be transient or permanent²¹
• Alcoholic etiology, severity of AP, extent of necrosis, and previous episodes of AP may increase risk in developing EPI²²

• Celiac disease may lead to altered synthesis, storage, and/or secretion of secretin and cholecystokinin (CCK) due to defective postprandial response to intraluminal contents by an atrophic upper intestinal mucosa²³
• Pancreatic dysfunction is generally transient in patients with celiac disease and may improve with a gluten-free diet in most patients²³

• Crohn's disease could lead to EPI via a variety of mechanisms, including²³:
  • Production of pancreatic autoantibodies
  • Damage to the pancreatic duct due to duodenal reflux
  • Scarring or inflammation leading to reduced secretory hormone secretion
• Medications used for the treatment of Crohn's disease have also been found to cause acute pancreatitis²³

• Gastric surgical procedures can result in physiological changes that disrupt neural or hormonal stimulation of pancreatic enzyme secretion or anatomical changes that cause asynchrony between gastric emptying and discharge of bile and pancreatic enzymes, resulting in EPI^24,25
• The prevalence of EPI after gastric surgery may vary widely based on the type and extent of surgery²⁴

• Pancreatic exocrine and endocrine tissue are closely linked both anatomically and physiologically. Conditions that affect one tissue type can cause an impairment in the other^23,26
• Potential causes of EPI in patients with type 1 diabetes include²³:
  • Impaired acinar-islet interaction
  • Diminished trophic effects of insulin
  • Autonomic diabetic neuropathy
  • Diabetic microangiopathy
  • Autoantibodies against exocrine tissue

• Potential causes of EPI in patients with type 2 diabetes could include^27*:
  • Disturbances in the regulation of the islet-acinar axis and lack of trophic effects of insulin
  • Inflammation, fibrosis, and steatosis of the exocrine pancreas

*The cause of EPI in patients with type 2 diabetes is not fully understood.²⁷