Symptomatic Pancreas Divisum: Recurrent Acute Pancreatitis in a 23-Year-Old Man

Discussion

Pancreas divisum is the most common congenital anomaly of the pancreas, with a reported worldwide prevalence of 2.9%.^1-4 The prevalence of pancreas divisum in Western countries ranges from 8% to 12.6%, but it is much less prevalent in Asian countries, with a 1% to 2% prevalence, meaning it is much more common in the white population.⁵

Pathophysiology

The pancreas is formed by the rotation of the ventral pancreatic bud and its subsequent fusion with the dorsal pancreatic bud at the junction of the foregut and midgut (Figure 1).^3,6 The ducts in the ventral and dorsal pancreatic buds fuse to form the main pancreatic duct. Failure of the distal portion of the dorsal duct to involute will result in the formation of the accessory duct.^3,6 The characteristic anatomy of pancreas divisum is the failure of the dorsal and pancreatic ducts to fuse into 1 duct that drains into the major duodenal papilla (major duct, Wirsung duct).⁷ Instead, the dorsal pancreatic duct, which drains the dorsal head, tail, and body of the pancreas, communicates with the intestinal lumen through the minor duodenal papilla (minor duct, Santorini duct), and becomes the major drainage route for the pancreas.^2,6,8,9 The ventral duct continues to drain through the major duodenal papilla along with the common bile duct.⁷

Pancreas divisum commonly presents as 2 variations: complete divisum or incomplete divisum. Complete pancreas divisum is described as complete separation or absolute lack of fusion between the dorsal and ventral pancreatic ducts and occurs in 70% of cases.¹⁰ Incomplete pancreas accounts for 20% to 25% of cases and is characterized by the existence of a small communicating branch between the dorsal and ventral pancreatic ducts, but with most pancreatic exocrine secretions routed through the minor duodenal papilla (Figure 2).^6,10,11 The smaller aperture of the minor duodenal papilla increases resistance to outward flow of pancreatic exocrine secretions and can result in significant back pressure within the pancreas, which may lead to the development of pancreatitis.⁶

Most patients with symptomatic pancreas divisum are categorized into recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain.¹ However, evidence suggests that only 10% of people with pancreas divisum are symptomatic, meaning most people with the condition do not experience any adverse effects from their anomalous anatomy.^1,9,12,13 Therefore, the role of pancreas divisum and pancreatitis remains somewhat controversial, since many who have pancreas divisum do not experience any abdominal or pancreatic pain. Instead, pancreas divisum is thought to be a predisposing factor to pancreatitis opposed to a causal factor. Most individuals with pancreas divisum are asymptomatic, and the anomalous anatomy usually is uncovered in symptomatic individuals after investigating other more common causes of pancreatitis such as alcohol consumption and gallstones. Some researchers have described pancreas divisum as an independent risk factor for pancreatitis, specifically associated with recurrent acute pancreatitis, chronic pancreatitis, or chronic abdominal pain.^4,5,7,10

Other investigators have also noted the association of pancreas divisum and idiopathic pancreatitis with cystic fibrosis transmembrane conductance regulator gene (CFTR) or serine protease inhibitor, Kazal-type 1 gene (SPINK1) mutations.^5,7 Mutations in CFTR may be associated with a predisposition to pancreatitis in patients with pancreas divisum.¹ In fact, a recent study suggests that pancreas divisum may not be a sole cause of pancreatitis but act as a cofactor alongside predisposing genetic mutations.¹⁴ Approximately 22% of patients with clinical symptoms associated with pancreas divisum have mutations in CFTR.¹⁵ One study found that persons with pancreas divisum had a greater risk of other pancreaticobiliary abnormalities such as pancreaticobiliary maljunction, intraductal papillary mucinous neoplasm, pancreaticobiliary cancer, and others.⁹

It has been suggested that complete pancreas divisum might be a factor that promotes oncogenesis.⁹ An incidence of 11.1% to 12.5% of pancreatic tumors in the setting of pancreas divisum has been reported, with most being ductal carcinomas and intraductal papillary mucinous neoplasms.¹¹ Invasive ductal carcinomas associated with pancreas divisum usually arise from the dorsal pancreas usually due to chronic pancreatitis. The pathogenesis of intraductal papillary mucinous neoplasm in pancreas divisum warrants further investigation.¹¹ Therefore, if pancreas divisum and pancreatitis is present, genetic testing to investigate an alternative explanation for idiopathic pancreatitis should be explored, because endoscopic repair or treatment under those circumstances may not confer benefit to the patient.⁷ If mutations are not present, therapy targeted to mitigate the progression into chronic pancreatitis should be considered.