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Keywords:

  • Bile duct cancer;
  • Congenital biliary dilatation;
  • Gallbladder cancer;
  • Pancreaticobiliary maljunction

Abstract 

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Clinical practice guidelines on how to deal with pancreaticobiliary maljunction (PBM) were made in Japan in 2012, representing a world first. Using a narrow definition, congenital biliary dilatation involves only Todani type I (except type Ib) and type IV-A, both of which are accompanied by PBM in almost all cases. Prospective ultrasonographic study revealed that the maximum diameter of the common bile duct increased with age. Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of the pancreaticobiliary ducts, a common channel ≥6 mm long and occlusion of communication during contraction of the sphincter of Oddi. Since PBM can be diagnosed by magnetic resonance cholangiopancreatography, multi-planar reconstruction multi-detector row computed tomography and endoscopic ultrasonography, the current diagnostic criteria should be revised to take these diagnostic imaging modalities into consideration. According to a nationwide survey, biliary cancer occurred in 21.6% of adult patients with PBM with biliary dilatation and 42.2% of patients with PBM without biliary dilatation. In biliary cancer associated with PBM without biliary dilatation, 88.1% were gallbladder cancer. Treatment for PBM with biliary dilatation is prophylactic flow-diversion surgery, but further investigations and surveillance studies are needed to clarify the appropriate surgical strategy for PBM without biliary dilatation.


Introduction

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Pancreaticobiliary maljunction (PBM) is a congenital anomaly in which the pancreatic and bile ducts meet anatomically outside the duodenal wall. Normally, the sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. In PBM, the common channel is so long that sphincter action does not directly affect the pancreaticobiliary junction, allowing reciprocal reflux of pancreatic juices and bile. The reflux of pancreatic juices into the biliary tract (pancreatobiliary reflux) provokes higher rates of biliary tract cancer. PBM can be divided into PBM with biliary dilatation (congenital biliary dilatation) and PBM without biliary dilatation [1-3].

The Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) formed a PBM clinical practice guidelines committee, which established clinical practice guidelines on how to deal with PBM, with the support of the Japan Biliary Association in 2012, representing a world first [4, 5]. Since the body of evidence-based literature remained relatively small, the guidelines were created based on the consensus of experts, using the medical literature for reference. These guidelines consisted of 46 clinical questions covering distinct aspects of PBM (concepts and pathophysiology, diagnosis, pancreatobiliary complications, and treatments and prognosis). Created to provide assistance in the clinical practice of PBM, the guideline contents focused on clinical utility, and included general information on PBM to improve recognition of this disease. The present paper describes recent topics and problems in the management of PBM that became apparent during the process of creating the guidelines.

Definition of congenital biliary dilatation

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Congenital biliary dilatation is an uncommon anomaly of the biliary system characterized by localized cystic or fusiform dilatation of the common bile duct with or without intrahepatic biliary dilatation and is associated with pancreaticobiliary maljunction [1]. Congenital biliary dilatation used to be known as “congenital choledochal cyst”, “congenital bile duct dilatation” or “congenital cystic dilatation of the common bile duct” in Western countries.

In 1959, Alonso-Lej et al. [6] classified extrahepatic bile duct cysts into three types: type I, congenital cystic dilatation of the common bile duct where the intrahepatic tree is usually normal; type II, congenital diverticulum of the common bile duct; and type III, choledochocele, a cystic dilatation of the distal segment of the common bile duct protruding into the duodenal lumen. However, bile duct dilatation was found to not be limited to the common bile duct, but instead also present in the intrahepatic bile duct, classification of the disease became more complex.

Todani et al. [7] refined the classification of bile duct cysts into five types and included the concept of PBM. Type IV-A is a congenital biliary dilatation complicated by intrahepatic duct dilatation. Type V involves single or multiple intrahepatic duct dilatations. Pancreaticobiliary maljunction is not included with types II, III or V. Therefore, in a narrow definition, congenital biliary dilatation involves only type I (except type Ib) and type IV-A.

Maximum diameter of the common bile duct in adults and children

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Until now, a bile duct <10 mm has been idiomatically called a “non-dilated bile duct” in adults, but no data have been accumulated. The maximum inner diameter of the common bile duct was recently prospectively examined in consecutive adults over 16 years old using transabdominal ultrasonography (US) [8]. That investigation revealed a mean diameter for the common bile duct of 4.5 ± 1.4 mm (range, 1–14 mm). The relationship between maximum diameter of the common bile duct and age was as follows: adult common bile duct = 2.83 + 0.03 × age. In all age groups but the 20 s and 30 s, there was statistically significant maximum diameter of the common bile duct among each age group. Mean, mode value and median diameter of the common bile duct increased with age as follows: 20 s: 3.9 ± 1.0 mm; 30 s: 3.9 ± 1.2 mm; 40 s: 4.3 ± 1.2 mm; 50 s: 4.6 ± 1.3 mm; 60 s: 4.9 ± 1.4 mm; >70 s: 5.3 ± 1.6 mm (Fig. 1).

figure

Figure 1. Bivariate analysis between age and bile duct diameter in adults [8]. Green: bivariate normal ellipse; red: applying straight line

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In the field of pediatric surgery, a common bile duct <6 mm in diameter has commonly been called a non-dilated bile duct [9], but this has been based not on US, but rather endoscopic retrograde cholangiopancreatography (ERCP) data. Maximum diameter of the common bile duct was also examined in children using US [10]. Maximum diameter of the common bile duct correlated significantly with age in months by polynomial expression degree 2 as follows: pediatric common bile duct = 1.64 + 0.014 Month − (3.26 e–5) (Month − 63.0)2. Mean diameters of the common bile duct were 2.4 mm at 5 years, 3.2 mm at 10 years, and 3.7 mm at 15 years. Upper limits of normal for the common bile duct were further calculated as 3.9 mm, 4.5 mm, and 5.0 mm, respectively (Fig. 2). Mean diameter of the common bile duct also increased significantly with height and body weight. Diameter of the common bile duct thus increases in relation to body growth and is not expressed by one value in the pediatric population.

figure

Figure 2. Bivariate analysis between age and bile duct diameter in children [10]

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These standard values for maximum diameter of the common bile duct in each age will be useful for diagnosing PBM with or without biliary dilatation.

High confluence of pancreaticobiliary ducts

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Some patients with a relatively long common channel are not classified as showing PBM because the sphincter of Oddi includes the pancreaticobiliary ductal junction. As the average length of the common channel was reported as 4.4 mm [11], high confluence of pancreaticobiliary ducts (HCPBD) was defined as a disease state in which the common channel length was ≥6 mm and communication was occluded when the sphincter was contracted (Fig. 3) [12].

figure

Figure 3. (a) Endoscopic retrograde cholangiopancreatography of a patient with high confluence of pancreaticobiliary ducts and a common channel 8 mm in length (arrows). (b) Communication between the pancreatic and bile ducts was interrupted with sphincter contraction [4, 5]

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Reflux of contrast medium into the pancreatic duct was detected in 86% of HCPBD patients who underwent postoperative T-tube cholangiography. Elevated amylase levels in the bile were observed in all cases, although the average levels were significantly lower than those in PBM patients. Gallbladder cancer was associated with 8% of HCPBD patients. Similar to PBM patients, hyperplastic change with increased epithelial cell proliferative activity and K-ras mutations was also detected in the non-cancerous epithelium of the gallbladder of HCPBD patients [3, 13, 14]. A relatively long common channel also appears to be an important risk factor for the development of gallbladder cancer. However, since differences exist between HCPBD and PBM without biliary dilatation in other features, such as the sex most affected, age at diagnosis, bile amylase levels, and incidence of accompanying gallbladder cancer, so HCPBD should at this stage be managed as a disease entity independent of PBM in terms of the appropriate therapeutic strategies.

Revision of diagnostic criteria of PBM

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Diagnostic criteria of PBM were proposed by JSGPM in 1987, and were slightly revised in 1990 [1]. Although no significant changes have been made to the definition of PBM, diagnostic modalities have advanced recently. As no radiological modalities were initially available that could show the status of the pancreaticobiliary junction outside the duodenal wall, PBM was diagnosed when a lack of effect of the sphincter of Oddi on the pancreaticobiliary junction was verified on ERCP, percutaneous transhepatic cholangiography, or operative cholangiography. However, ERCP can cause adverse effects such as pancreatitis.

Magnetic resonance cholangiopancreatography (MRCP) has become popular as a non-invasive method for obtaining high-quality images of the pancreaticobiliary tree, and is replacing diagnostic ERCP for many pancreatobiliary diseases. Many PBM cases can be diagnosed on MRCP based on findings of an anomalous union between the common bile duct and pancreatic duct in addition to a long common channel. MRCP is thus useful for diagnosing children and screening for PBM. However, accurate diagnosis of PBM is difficult in cases with a relatively short common channel [4, 5].

Pancreaticobiliary maljunction can be diagnosed if the junction outside the wall can be depicted by high-resolution multi-planar reconstruction multi-detector row computed tomography. Three-dimensional drip infusion cholangiography computed tomography images can define biliopancreatic reflux in PBM, and the morphology of the intra- and extra-hepatic ducts [4, 5].

Because of its high resolution, endoscopic US (EUS) can be used to diagnose PBM by depicting the pancreaticobiliary junction outside the duodenal wall. In addition to the pancreatic and bile ducts, the muscularis propria of the duodenum and pancreatic parenchyma can be examined by EUS, confirming that the pancreaticobiliary junction lies outside the duodenal wall irrespective of the length of the common channel. Furthermore, the bile duct and gallbladder can be studied in detail in a series of scans following the diagnosis of PBM [4, 5].

The current diagnostic criteria should thus be revised to take these diagnostic imaging techniques into consideration.

Biliary cancer associated with PBM

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Clinical features particularly focusing on the associated biliary cancers were clarified, using data from 2,561 PBM patients with and without biliary dilatation collected by the JSGPM and the Committee for Registration, at 141 medical institutions during the 18 years from 1 January 1990 to 31 December 2007 [15, 16].

Biliary cancer occurred in 21.6% of adult patients with PBM with biliary dilatation and 42.2% of adult patients with PBM without biliary dilatation. In patients with biliary cancers in association with PBM, the location ratio of the bile duct cancer and gallbladder cancer were 32.1% and 62.3% in PBM patients with biliary dilatation, and were 7.3% and 88.1% in PBM patients without biliary dilatation, respectively. Regarding the occurrence rate of each biliary cancer, bile duct cancer was seen in 6.9% and gallbladder cancer was seen in 13.4% in patients with PBM with biliary dilatation, and in 3.1% and 37.4% in patients with PBM without biliary dilatation, respectively (Fig. 4). Hence, the location of biliary cancers differs between adult patients with and without biliary dilatation, but gallbladder cancer is significantly predominant. Interestingly, cancer incidence rates in Japan reported by The Japan Cancer Surveillance Research Group [17] showed biliary tract (gallbladder and bile duct) neoplasm occurring at a rate of 14.1 per 100,000 population. The overall incidence of biliary cancers with PBM is more than 200 times higher compared to the risk in the general population, even in bile duct cancer associated with patients without biliary dilatation.

figure

Figure 4. Location of biliary tract cancer in adult pancreaticobiliary maljunction (PBM) patients according to biliary dilatation [16]. *Cancer incidence: Cancer Control and Information Services, National Cancer Center, Japan

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In addition, focusing on the location of the bile duct cancer, total occurrence rates of intrahepatic and hepatic duct cancer were 8.6% in bile duct cancer patients with PBM with biliary dilatation and 37.5% in bile duct cancer patients with PBM without biliary dilatation (Fig. 5). Significant differences in the location of bile duct cancer were found between adult PBM patients with and without biliary dilatation.

figure

Figure 5. Location of bile duct cancer according to biliary dilatation [16]

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Regarding the associated age of cancer onset, in patients with PBM with biliary dilatation, mean age of patients with biliary cancer was approximately 10 years older than that of patients without biliary cancer (benign, 41.3 ± 17.2 years; gallbladder cancer, 60.1 ± 10.4 years; bile duct cancer, 52.0 ± 15.0 years). Likewise, in patients with PBM without biliary dilatation, mean age of patients with biliary cancer was also approximately 10 years older than that of patients without biliary cancer (benign, 47.7 ± 16.1 year; gallbladder cancer, 58.6 ± 9.6 years; bile duct cancer, 63.3 ± 10.6 years). However, these patients may develop biliary cancers 15–20 years earlier than patients without PBM [17].

Regarding the coexistence of biliary stones, the incidence of concomitant stones in adult patients with associated biliary cancers was 13.0% in patients with PBM with biliary dilatation and 10.6% in patients with PBM without biliary dilatation; lower than the ratio in the biliary cancer population without PBM [18].

Regarding amylase levels, in the gallbladder, amylase levels of cancer patients with PBM with biliary dilatation were significantly lower than those of benign patients with PBM with biliary dilatation, although amylase levels of cancer patients with PBM without biliary dilatation were similar to those of benign patients with PBM without biliary dilatation. In cancer patients, no significant differences in amylase levels were apparent regardless of biliary dilatation. In the bile duct, no significant differences were observed between any groups.

The former period was defined between 1990 and 1999, and the latter period was between 2000 and 2007. In the former period, the frequency of biliary cancer was 19.2% in patients with PBM with biliary dilatation, and 41.3% in patients with PBM without biliary dilatation. In the latter period, the frequency of biliary cancers was significantly increased to 25.0% in patients with biliary dilatation. In patients with PBM without biliary dilatation, the frequency of biliary cancers was also increased from 41.3% to 44.8% in the latter period. In patients with PBM with biliary dilatation, the ratio of biliary cancer localization differed significantly between the former and latter periods. In particular, the frequency of bile duct cancer was increased in the latter period (9.3%) compared with the former period (5.5%). In patients with PBM without biliary dilatation, the ratio of biliary cancer localization also differed between the former and latter periods. Frequencies of bile duct cancer (from 2.7% to 3.6%) and gallbladder combined bile duct cancer (from 1.1% to 3.0%) tended to increase in the latter period.

Surgical strategy of PBM without biliary dilatation

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Once the diagnosis of PBM is established, immediate prophylactic surgical treatment is recommended before the onset of malignant changes. Cholecystectomy and resection of the extrahepatic bile duct, as so-called “flow-diversion surgery”, is an established method of standard surgical treatment for PBM with biliary dilatation. However, whether prophylactic resection of the extrahepatic bile duct should be performed for PBM patients without biliary dilatation remains controversial.

Considering that 88.1% of biliary cancers associated with PBM without biliary dilatation were gallbladder cancer [15, 16], and histopathological features such as hyperplasia, metaplasia, and dysplasia with occasional K-ras and/or p53 gene mutations are detected in noncancerous lesions of the gallbladder epithelium [19, 20], prophylactic cholecystectomy is strongly recommended to prevent gallbladder cancer in PBM patients without biliary dilatation. Many institutions have been performing prophylactic cholecystectomy alone, and no bile duct cancer has been reported to develop in such patients, even after a long-term postoperative follow-up [21, 22].

However, some surgeons have recommended that both the extrahepatic bile duct and gallbladder should be excised in PBM patients without biliary dilatation, because of the risk of developing bile duct cancer. An analysis of 1361 PBM patients described bile duct cancer as a complication with an incidence of 4.0% in PBM patients without biliary dilatation, similar to the 5.2% incidence in PBM patients with biliary dilatation [23]. In addition, the incidence of bile duct cancer in PBM patients, even those without biliary dilatation, is extremely high when compared with the incidence of biliary tract cancer in the general population. Indeed, the histopathological changes of carcinogenesis observed in PBM patients with biliary dilatation, such as K-ras and/or p53 gene mutations, are also reportedly seen in PBM patients without biliary dilatation [24]. Moreover, the development of bile duct cancer in PBM patients without biliary dilatation who have undergone cholecystectomy alone without bile duct resection has been reported [25].

The Japanese clinical practice guidelines for PBM, as an answer to the clinical question of operative procedures for PBM without biliary dilatation, state that “There is no fixed strategy on the prophylactic resection of the extrahepatic bile duct for prevention of bile duct cancer” [4, 5]. In the clinical practice guidelines for the management of biliary tract and ampullary carcinomas, both of these opinions are mentioned, but no recommendations are given [18].

Conclusions

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References

Several advances in diagnostic imaging and understanding of the pathophysiology of PBM have been made, and the current diagnostic criteria should be revised accordingly. Further investigations and surveillance studies are needed to clarify appropriate surgical strategies for PBM without biliary dilatation.

References

  1. Top of page
  2. Abstract 
  3. Introduction
  4. Definition of congenital biliary dilatation
  5. Maximum diameter of the common bile duct in adults and children
  6. High confluence of pancreaticobiliary ducts
  7. Revision of diagnostic criteria of PBM
  8. Biliary cancer associated with PBM
  9. Surgical strategy of PBM without biliary dilatation
  10. Conclusions
  11. Conflict of interest 
  12. References
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