**5. Etiology**

*Pediatric Surgery, Flowcharts and Clinical Algorithms*

cholangiographic images [4–8].

**3. Incidence**

early infancy [10, 17].

**4. Pathology**

The anatomist Abraham Vater first described the normal anatomy of the bile ducts and the fusiform dilatation of the common bile duct (CBD) in 1723 [1]. Then, Doctor Halliday Douglas first described clinically CBD dilatation in 1852. Douglas had detected a large tenderness cystic mass on the right upper quadrant by physical examination of a 17-year-old girl who had an intermittent right-sided pain, obstructive jaundice, and fever complaints in her history. Despite performing external drainage promptly, she died within 1 month. Subsequently, Douglas detected a CC with her autopsy [2]. In 1894, British surgeon William Swain performed the first successful operation in a 17-year-old girl presented with CC, by anastomosing the jejunum to a giant CC. This patient had been reported 2 months later with no jaundice. In 1922, Golder McWhorter underwent hepaticoduodenostomy after excising the CC in a 49-year-old patient who had complaints since infancy. In 1959, Alanso-Lej and colleagues first published the series of CCs. In this publication, they reviewed 94 cases, published previously, together with their own 2 cases and classified the congenital cystic dilatations of the bile ducts anatomically for the first time [3]. In 1977, Todani and colleagues modified the classification of CCs according to

CCs are more common in Asian populations with an incidence of 1 in 13,000, even 1:1000 in Japan [9], versus 1 in 100,000–150,000 in Western populations [10]. The reason for this Asian preponderance is still unknown [11]. Although predominately diagnosed in children, CCs are found with increasing frequency in

Grossly, CCs appear as a diffuse dilatation of the bile ducts [18]. In the congenital dilatations of the bile ducts, the cyst wall thickness is between 2 and 7 mm in diameter and usually involves an inflammatory reaction (80%) [18] that becomes severe after 10 years of age. Cysts, especially infected, are usually being adherent to the surrounding tissues. Bile ducts and columnar epithelium can be seen in the microscopic examination of the cyst wall. Choledochocele that is covered with duodenal mucosa appears different from other types of CCs according to epithelial histology. Liver biopsy findings usually vary with the age in patients with CC. Although, newborn liver is mostly normal, mild periportal fibrosis may be seen in older children. Varying degrees of histological hepatic changes severity may be seen in most patients with CC when it is diagnosed [19]. Higher degree of liver damage associates with the presence of an anomalous pancreaticobiliary ductal union (APBDU), more severe symptoms, type IVa CC, and younger age [19–21]. It has been observed by investigating liver biopsies that most of these changes resolve after surgical excision; however, preoperative portal fibrosis and central venous distension may remain stable or increase in severity [19]. It is considered that carcinoma of the cyst wall may develop due to recurrent chronic inflammation attacks.

adults such that adults comprise the majority of patients in recent series [12, 13], which in part may be due to the increased use of diagnostic imaging [14]. In both adult and children [15], females are higher risk for the disease with a nearly 4:1 female preponderance [10, 16]. Nearly, 80% of CCs are diagnosed in

**2. History**

**88**

Despite the existence of numerous theories and laboratory works to explain the etiology of the disease, the exact etiology remains incompletely understood. Initial theories, put forward in this regard, were congenital weakness of the choledochal wall, distal obstruction, oligoganglionosis, and disturbances in the process of recanalization. However, more accepted theories have been produced parallel to the progress in radiological imaging methods [24, 25]. Today, there are two main theories that are widely accepted; (1) reflux of trypsin and other pancreatic enzymes to the bile ducts due to an APBDU; (2) obstruction of distal CBD [26–28]. The idea that the choledochal and pancreatic ducts' abnormality about joint and angle was first reviewed by Babbitt in 1969, and subsequently many number of studies, supporting this view, were made [22, 23, 29–32]. A normal pancreaticobiliary junction usually has an acute angle between the CBD and the pancreatic duct [33] and is located within the duodenal wall [34]. The common channel (distance from between the junction of the CBD and the pancreatic duct to ampulla Vater) length is 4 mm or less, normally. In patients with CCs, this distance (common channel length) increases 5–20 mm [22, 23, 35, 36] that makes the common channel longer [37]. Okada defined it as "common channel syndrome" [36, 38]. It is considered that an abnormal long common channel (especially >15 mm proximal to ampullary sphincter) [39, 40] causes the pancreatic duct communicating with the choledochal duct without the support of ampulla Vater's circular muscular layer (sphincter of Oddi) [41], which protects the biliary tree from reflux of pancreatic enzymes and bile [34]. Another observation is that the junction angle of the two ducts that should be acute normally, however, is close to 90° in these patients. It also causes the pancreatic fluids to flow into the CBD due to the higher pressure of pancreatic duct (**Figure 1**) [41]. Eventually, it is considered that APBDU has a tendency to cause reflux of the pancreatic enzyme into biliary tree with consequent biliary duct inflammation and increased duct pressure, leading to duct wall damage and cystic changes [42, 43]. In animal models of murine APBDU, this mechanism has also been demonstrated [44, 45]. APBDU is seen in up to 90% of patients with CC [25, 46], compared with 2% in the general population [10] and this seems to have important clinical implications. In a comparison of APBDU-associated CC versus non-APBDU-associated CC, APBDU-associated CC patients were significantly more likely to have evidence of pathologically confirmed inflammation including hepatitis, cholangitis, and pancreatitis [47, 48]. However, APBDU is not enough to explain the etiology of all CCs, such as diverticular cyst (type II), where the bile ducts were normal except cyst and the cyst is considered to be a sequel of an intrauterine CC rupture, such as meconium pseudocyst [28]. Additionally, type V CCs are possibly due to dysfunctional remodeling of the ductal plate during embryogenesis [40, 49].

In addition, it is considered that primary strictures of the CBD may also play a role in the development of CCs. The types of the CCs are determined according to the location, severity, and length of the stricture. Detection of these strictures preoperatively is important because treating the CC without addressing the stricture may lead to recurrent episodes of cholangitis. This mechanism has been under estimated and is now believed to be more significant in the pathophysiology of CCs [50].

#### **Figure 1.** *Anomalous pancreaticobiliary union.*

The association of CC with congenital anomalies remains ambiguous. Previous reports have demonstrated an association of pediatric CC and congenital anomalies. Murphy et al. reported in 2012 that screening for cardiac anomalies may be prudent in CC patients [51]. Other reports have postulated an association of CC with duodenal atresia, colonic atresia, gastroschisis, annular pancreas, and pancreatic cysts [10, 52–57].
