Research Article: Development and Congenital Anomalies of the Pancreas

Date Published: May 14, 2011

Publisher: Hindawi Publishing Corporation

Author(s): Hiroyuki Tadokoro, Masaru Takase, Bunsei Nobukawa.


Understanding how the pancreas develops is essential to understand the pathogenesis of congenital pancreatic anomalies. Recent studies have shown the advantages of investigating the development of frogs, mice, and chickens for understanding early embryonic development of the pancreas and congenital anomalies, such as choledochal cysts, anomalous pancreaticobiliary junction, annular pancreas, and pancreas divisum. These anomalies arise from failure of complete rotation and fusion during embryogenesis. There are many theories in the etiology of congenital anomalies of the pancreas. We review pancreas development in humans and other vertebrates. In addition, we attempt to clarify how developmental failure is related to congenital pancreatic anomalies.

Partial Text

In the 19th century, early embryonic development of the pancreas in mammals and other vertebrates was investigated. Many histological studies of human and other mammalian embryos have confirmed that the ventral pancreatic anlage occurs in a paired condition [1–7]. It is believed that the ventral pancreatic anlage is initially paired, with the left lobe subsequently disappearing during development [1, 2, 8, 9]. Recent research has examined pancreas development using animal models. It has become clear that early pancreas development in humans closely resembles that of mice and frogs [9, 10], whereas in chickens and frogs, the left ventral anlage persists, and the two ventral buds fuse together and become part of the mature organ [10, 11]. It is considered that mammals, birds, reptiles, and amphibians have similar development [12].

Ventral (caudal) and dorsal (cranial) outpouchings develop at the junction of the foregut and midgut during the fourth week of gestation. The dorsal diverticulum forms the dorsal portion of the pancreas, and the ventral diverticulum forms the liver, gallbladder, bile ducts, and ventral pancreas. As the foregut elongates, the developing ventral pancreas, gallbladder, and bile duct rotate clockwise posterior to the duodenum and join the dorsal pancreas in the retroperitoneum. The ventral pancreatic duct and the common bile duct (CBD) are linked by their embryonic origins, which results in the adult configuration of their common entrance into the duodenum at the major papilla [16]. The ventral pancreatic bud fuses with the dorsal bud at approximately the seventh week of gestation. During the eighth week of gestation, the remaining portion of the ventral diverticulum separates into the pars cystica and pars hepatica [17]. The pars cystica forms the cystic duct and gallbladder. The pars hepatica branches to form the two major lobes of the liver. The proliferation is followed by vacuolation, and the coalescence of the ensuing lacunae produces a tubular biliary duct system. The pars cystica vacuolates and expands, and the stalk becomes the cystic duct. This structure is initially hollow, then solid (by proliferation of epithelial lining), and recanalization occurs by vacuolation of this expanded epithelium [18].

Choledochal cysts are a well-known anomaly that appears as dilatation of extra- or intrabiliary trees. Choledochal cysts have been classified into five subtypes radiologically by Todani et al. [32], which is a modification of the Alonso-Lej classification [33]. Choledochal cysts, which are rare and more common in female than male patients, occur in approximately 1 : 100,000–150,000 live births in Western countries [34]. Choledochal cysts are much more prevalent in Asia than in Western countries. Approximately 33%–50% of reported cases come from Japan, where the frequency in some studies has approached one case per 1000 population [35].

APBJ is a rare congenital anomaly in which the pancreatic and biliary ducts join outside the duodenal wall [13]. APBJ is diagnosed when the pancreatic duct joins the bile ducts 1-2 cm proximal to the sphincter of Oddi [24–27, 40]. The incidence of APBJ has been reported to be 1.5–3.0% in patients who are undergoing endoscopic retrograde cholangiopancreatography (ERCP) for various reasons [24, 41, 42]. It is well known that APBJ is commonly associated with congenital bile duct dilatation and carcinoma of the bile duct and gallbladder. The reason for biliary carcinogenesis in such patients has been ascribed to reflux and stasis of bile mixed with pancreatic juice in the dilated bile duct and gallbladder [43, 44]. The incidence of gallbladder carcinoma and biliary tract cancer in APBJ without bile duct dilatation is 36.1% and 4.0%, respectively, according to the register of the Japanese Study Group on Pancreaticobiliary Maljunction over the past 10 years [45].

Annular pancreas is a rare congenital anomaly in which a ring of pancreatic tissue surrounds the duodenum. It is estimated that it occur in one of every 12,000–15,000 live births [48]. The annular pancreatic tissue forms a complete (25%) or partial (75%) ring around the descending duodenum [49, 50]. The incidence of annular pancreas has been reported to be 0.005%–0.015% in autopsy cases in adults [51]. It is frequently associated with other congenital abnormalities such as esophageal atresia, imperforate anus, congenital heart disease, malrotation of the midgut, and Down syndrome.

Pancreas divisum is the most common congenital anomaly of the pancreas. The ventral and dorsal ducts fail to fuse together, resulting in pancreas divisum [56] (Figure 4(b)). The body, tail, and part of the head of the pancreas (dorsal pancreas) drain through Santorini’s duct into the minor papilla, while another part of the head (ventral pancreas) drains through Wirsung’s duct into major papilla. This anomaly is found with an incidence of 3%–7% in patients who are undergoing ERCP and in approximately 9% of autopsy cases [16]. The cause of this anomaly is unknown. A short and rudimentary ventral duct in pancreas divisum is thought to be caused by hypoplasia of the ventral pancreas.

Embryonic development of the pancreas in various species offer suggestions about the development and congenital anomalies of the pancreas in humans.




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