Figure 52-1. A–D: Schematic drawings of the successive stages in the development of the pancreas from the fifth through the

eighth weeks. E–G: Diagrammatic transverse sections through the duodenum and the developing pancreas. Growth and rotations

(arrows) of the duodenum bring the ventral pancreatic bud toward the dorsal bud and they subsequently fuse. The bile duct

initially attaches to the ventral aspect of the duodenum and is carried around to the dorsal aspect as the duodenum rotates. The

main pancreatic duct is formed by the union of the distal part of the dorsal pancreatic duct and the entire ventral pancreatic duct.

The endocrine function of the pancreas begins during gestation, whereas the exocrine function does

not begin until after birth. The first glucagon-producing cells are seen in 3-week-old embryos and the

first islets appear at approximately 10 weeks. During this early developmental period, predominantly

glucagon-positive islet cells initially appear in the tail of the pancreas. Early glucagon-positive

endocrine cells convert to nonepithelial cells and lose connection with the lumen and tight junctions.

Subsequently, there is a major amplification of endocrine cell numbers, particularly B cells, which

produce insulin.

1339

Figure 52-2. Anatomic configuration of the intrapancreatic ductal system. A: The classic anatomy is present in 60% of cases, where

the accessory duct drains into the minor papilla and the main duct drains into the ampulla of Vater. B: The accessory pancreatic

duct is blind and does not drain into the duodenum in 30% of cases. C: A lack of communication between the two ducts, which

occurs in 10% of cases, is referred to as pancreas divisum. When this occurs the main pancreatic duct drains into the duodenum

through the minor papilla. D: Pancreaticogram obtained on ERCP through cannulation of the minor papilla in a patient with

pancreas divisum; the main duct drains into the minor papilla. E: MRCP on the same patient. The main pancreatic duct drains into

the minor papilla and the common bile duct drains into the ampulla of Vater.

Surgical Significance of Congenital Pancreatic Abnormalities

4 Abnormalities in the rotation and fusion of the pancreas during embryonic development can result in

specific congenital anomalies that have surgical significance. In approximately 60% of people, rotation

1340

and fusion occur normally resulting in the classic anatomy seen in Figure 52-2A. The dorsal and ventral

ducts fuse to form the main pancreatic duct which drains the majority of the pancreas into the ampulla

of Vater. The lesser duct, formed from the proximal duct of the dorsal bud, drains into the duodenum at

the minor papilla.

In approximately 30% of cases, the ventral and dorsal ducts fuse and drain normally into the

duodenum at the ampulla of Vater. However, there is atrophy of the accessory or minor duct with a

blind end and drainage into the duodenum (Fig. 52-2B). As this blind duct still communicates with the

main pancreatic duct, this is of little to no clinical significance and most often found only at autopsy.

In 5% to 14% of cases, the fusion of the ventral and dorsal pancreatic ducts is incomplete (Fig. 52-2C–

E).1–3 As a result of the incomplete fusion, the majority of the pancreas is drained into the duodenum

through the minor papilla. This is called pancreas divisum. Only the small remnant duct of the ventral

bud drains the uncinate process into the duodenum via the ampulla of Vater. Whether or not pancreas

divisum causes pancreatitis and abdominal pain is unclear.1,4,5 It is often asymptomatic. However,

mucosal stenosis at the minor papilla may lead to cystic dilatation of the dorsal duct resulting in

pancreatitis and pain.1,6–8 Pancreatitis or abdominal pain due to pancreas divisum is a diagnosis of

exclusion, and other etiologies for the pancreatitis should be thoroughly investigated. If no other causes

of pancreatitis are identified in the setting of abdominal pain, elevated amylase levels, and pancreas

divisum, the anomaly is considered causative and an endoscopic or operative papillotomy of the minor

papilla and accessory duct is indicated. Recurrent acute pancreatitis or chronic pancreatitis with chronic

pain attributed to pancreas divisum is most often seen in young females.

Annular pancreas is a rare congenital anomaly of the pancreas first recognized in 1818. Early autopsy

and surgical series estimate the incidence to be approximately 3 in 20,000.9,10 However, with better

imaging modalities such as computed tomography (CT), magnetic resonance cholangiopancreatography

(MRCP), and endoscopy, the incidence is thought to be closer to 1 in 1,000.11–13 Annular pancreas is

thought to result from abnormal fusion of the ventral pancreatic bud to the duodenum, leading to

improper rotation of the ventral bud around the duodenum.14 This failure of rotation leads to a thin

band of normal pancreatic parenchyma completely surrounding the second portion of the duodenum

(Fig. 52-3A–C). This band is in continuity with the head of the pancreas and causes variable degrees of

duodenal compression and stenosis. This abnormal ring of pancreatic tissue may contain a pancreatic

duct. Therefore, the surgeon must be aware of this anomaly; if annular pancreas is incidentally

encountered during an operation, it should not be divided. Division of the abnormal ring can result in

pancreatic fistula or obstruction of pancreatic ductal drainage.

1341

Figure 52-3. Annular pancreas. A: CT scan of a patient with annular pancreas. There is a ring of pancreatic tissue surrounding the

duodenum, with a narrowed duodenal lumen. B: EGD image in the same patient. Note narrowing of the duodenal lumen with no

mucosal lesion consistent with external compression by the annular pancreas. C: Intraoperative photo of an annular pancreas. Note

the dilated duodenum after the pylorus, the ring of pancreatic tissue surrounding the duodenum just distal to the dilation, and the

decompressed distal duodenum.

Annular pancreas can present at varying time points from in utero to adulthood.13 When diagnosed in

utero, the most common presentation is polyhydramnios due to duodenal obstruction. Newborns present

most commonly with duodenal obstruction shortly after birth, as evidenced by low birth weight and

feeding intolerance. In people who present in utero or in childhood, it is more commonly associated

with other congenital anomalies including Down syndrome, cardiac anomalies, and other intestinal

anomalies. Duodenal bypass (duodenoduodenostomy or gastrojejunostomy) is the treatment of choice in

children.

Fifty percent of cases of annular pancreas occur in adults. Adults are less likely to present significant

obstruction and less likely to require surgical intervention. If they do present with obstruction,

treatment is similar to that in children. In adults, annular pancreas is more commonly associated with

pancreas divisum and pancreatic neoplasia than in children.13 Heterotopic pancreas is pancreatic tissue

outside the bounds of the normal pancreas without anatomic or vascular connections to the pancreas

itself. Heterotopic pancreas occurs in 0.5% to 14% of autopsy series. The heterotopic pancreatic tissue is

functional and can occur in a variety of sites including the stomach, duodenum, ileum, umbilicus, colon,

appendix, gallbladder, and even within a Meckel diverticulum. This tissue is usually submucosal and

uniformly contains acini and ducts. Up to one-third contains islet cells. Heterotopic pancreas is usually

an incidental finding, but can present with ulceration, obstruction, or intussusception, in which case

treatment is directed at the presenting symptoms and may require resection. In incidental and

asymptomatic cases, no treatment is required. The heterotopic pancreas is susceptible to the same

diseases as normal pancreas and can even undergo malignant transformation.15,16

EXOCRINE AND ENDOCRINE STRUCTURE

The exocrine structures of the pancreas account for 80% to 90% of the pancreatic mass while the

endocrine structure accounts for approximately 2% of the pancreatic mass. The remainder of the

pancreas comprises extracellular matrix, blood vessels, and major ductal structures.

Exocrine Structure

The exocrine structure of the pancreas is composed of two main components: the acinar cells and the

ductal network. The acinar cells produce and secrete the enzymes and zymogens responsible for

digestion. The acinar cells are pyramidal cells with an apex that faces the pancreatic ductal network.

Approximately 20 to 40 acinar cells cluster together to form the functional unit called an acinus (Fig.

52-4A,B). Zymogen granules within the acinar cells contain the digestive enzymes for secretion into the

ductal system. Located more centrally within the acinus, the centroacinar cell secretes alkaline fluid (pH

8.0) into the pancreatic ductal system. The acinus drains initially into small intercalated ducts, which

join to form interlobular ducts that also secrete fluid and electrolytes (Fig. 52-4A). These interlobular

ducts form secondary ducts that drain into the main pancreatic ductal system and eventually the

duodenum at the ampulla of Vater.

1342

Figure 52-4. Histologic anatomy of the acinus. A: Low-magnification view of a portion of the pancreas. B: High-magnification

view of a single acinus. The acinar cells, containing zymogen granules, are pyramidal cells with an apex that faces the pancreatic

ductal network. Twenty to 40 acinar cells that cluster together to form the functional unit called an acinus. The centroacinar cell,

also present within the acinus, functions to secrete fluid and electrolytes of the correct pH into the pancreatic ductal system. The

acinus drains into small intercalated ducts, which join to form interlobular ducts that also secrete fluid and electrolytes. These

interlobular ducts form secondary ducts that drain into the main pancreatic duct.

Endocrine Structure

5 The pancreatic islet cells are of neural crest origin and part of the family of amine precursor uptake

and decarboxylation (APUD) cells. Each pancreatic islet is approximately 40 to 900 mm and contains an

average of 3,000 cells. The islets are composed of four cell types. These cell types are differentially

distributed both throughout the pancreas and within the islets. Table 52-1 describes the cell types, their

hormonal products, and their location within the islet and the pancreas.

B (or beta) cells are located centrally within the islets. They constitute approximately 70% of the islet

cell mass. The main secretory product of B cells is insulin, but they also excrete amylin and

cholecystokinin. A (or alpha) cells and F cells are located peripherally within the islets and constitute

10% and 15% of the islet cell mass, respectively. Glucagon is secreted by A cells, which is the major

counter-regulatory hormone to insulin in glucose homeostasis. F cells secrete pancreatic polypeptide. D

cells are evenly distributed throughout the islet and constitute 5% of the islet cell mass.17 They can be

further divided into D cells which secrete somatostatin and D2 cells which secrete vasoactive intestinal

peptide (VIP). E (or epsilon cells) and C cells comprise <1% of the islet mass and secrete substance P

and serotonin. They are of minimal clinical significance.

6 The distribution of endocrine cell types is not uniform throughout the pancreas. B and D cells are

concentrated in the tail of the pancreas, whereas A cells (as well as C and E cells) are evenly distributed

and F cells are concentrated in the pancreatic head and uncinate process. As such, resection of the

pancreatic body and tail removes more of the insulin-producing cells and is more likely to cause

endocrine insufficiency (diabetes). This distribution also has clinical relevance with regard to the

location of endocrine neoplasms when they occur.

The islet cells have a rich blood supply supporting their endocrine role. The afferent arteriole enters

1343