Synchronous primary gallbladder and pancreatic cancer associated with congenital biliary dilatation and pancreaticobiliary maljunction
© The Author(s). 2017
Received: 28 August 2017
Accepted: 27 October 2017
Published: 2 November 2017
Synchronous double cancer of the gallbladder and pancreas that is associated with congenital biliary dilatation (CBD) and pancreaticobiliary maljunction (PBM) is extremely rare. PBM is frequently reported in Asia, particularly in Japan. We report a surgical case of synchronous double cancer in a patient with primary gallbladder and pancreatic cancer.
Presentation of case
A 72-year-old woman with epigastralgia underwent subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection for synchronous primary gallbladder and pancreatic head cancer. Histopathological examination revealed moderately differentiated ductal adenocarcinoma of the pancreatic head and well-differentiated tubular adenocarcinoma at the bottom of the gallbladder.
Synchronous gallbladder and pancreatic cancer is extremely rare. It is necessary to determine the optimal surgical course taking into consideration the degree of tumor progression. This is the second case of synchronous primary gallbladder and pancreatic cancer associated with CBD accompanied by PBM.
Congenital biliary dilatation (CBD) is a congenital malformation involving both extrahepatic bile duct dilatation and pancreaticobiliary maljunction (PBM) .
It is well known that PBM is frequently associated with carcinoma of the biliary tract [2, 3]. PBM includes abnormal connection between the pancreatic duct and the common bile duct outside of the duodenal wall, which leads to the reciprocal reflux of pancreatic juices and bile. The normal intra-pancreatic pressure is higher than in the bile duct , and pancreatic juice reflux into the biliary tract is confirmed by the presence of activated pancreatic enzymes amylase and lipase . It is thought that the reflux of pancreatic juice into the bile duct and the repeated cycle of biliary epithelium breakdown and regeneration leads to carcinogenesis [6, 7]. Abnormal expression and/or mutation of some oncogenes and cancer suppressor genes occurs during each step of carcinogenesis . Continuous chronic inflammation causes mutations in genes, such as K-ras and p53, that are associated with carcinogenesis and gallbladder cancer [9–11]. As a result, patients with CBD have a high rate of biliary tract cancers. In Western countries, the rate of biliary tract cancer concurrent with CBD is 20%, but this rate is based on very few cases (n = 20) . In Japan, a large-scale survey of 2561 patients was undertaken that looked at the incidence of biliary tract cancer concurrent with CBD. The survey found that biliary tract cancer occurs in 21.6% of adult patients with CBD . The main malignancies are gallbladder cancer (62.3%), bile duct cancer (32.1%), and gallbladder plus bile duct cancer (4.7%), indicating that gallbladder cancer is the most frequently found in association with this condition . On the other hand, the evidence for carcinogenesis in pancreatic carcinoma associated with PBM is still lacking. Furthermore, there has been only one other published case of synchronous double cancer consisting of gallbladder cancer and pancreatic cancer associated with CBD. We report herein an interesting and rare case of the above.
In June 2016, a 72-year-old woman was admitted to the hospital complaining of epigastralgia; however, physical examination did not reveal any abnormalities. Her laboratory tests revealed a normal complete blood count and normal liver function. The serum carcinoembryonic antigen level was 9.3 ng/mL (normal range, < 5 ng/mL), the carbohydrate antigen 19-9 (CA19-9) level was 1084 U/mL (normal range, < 37 U/mL), and the duke pancreatic monoclonal antigen type 2 (DUPAN-2) level was 140 U/mL (normal range, < 150 U/mL). The patient had no history of pancreatitis, pancreatic stone, and cholangitis.
Postoperative adjuvant chemotherapy was not performed because of the anticipated impact on quality of life after surgery. Eight months after surgery, she died due to peritoneal dissemination recurrence.
CBD is thought to occur in the development of PBM; however, the pathogenesis of CBD is unknown . The incidence of CBD appears to be higher in Oriental than in Occidental populations . Approximately, one in every 1000 persons is affected by this disease in Japan . In Western countries, CBD occurs in one of every two million births and in every 50,000−150,000 individuals [17–19].
It is important to diagnose bile duct dilation taking into account bile duct diameter, dilated site, and expanded form. Since bile duct diameter varies with age, it is necessary to refer to the upper limit value of the bile duct diameter by age . In our case, the diameter of the bile duct was 32 mm, which extended beyond the upper limit of age.
Todani et al.  reported that the reflux of bile may activate pancreatic enzymes, which can cause chronic inflammation and metaplastic epithelial change in the pancreatic duct, and pancreatic cancer may eventually develop. In our case, pancreatic ductal adenocarcinoma developed independently of IPMN in the pancreatic duct, which is an important consideration for future cases. Branch duct type IPMN (BD-IPMN) is associated with concomitant pancreatic carcinogenesis [22–24]. However, the exact diagnosis between pancreatic cancer derived from IPMN and concomitant pancreatic cancer with IPMN is difficult, when IPMN is close to pancreatic cancer histopathologically. Yamaguchi et al.  reported that approximately one third of pancreatic cancers derived from IPMN are mucinous carcinoma, and most pancreatic cancers concomitant with IPMN are tubular adenocarcinoma, which are similar to ordinary pancreatic cancers.
Characteristics of reported patients with pancreatobiliary maljunction and double cancer of the pancreas and gallbladder
Synchronous (GBC, PC, BDC)
Metachronous (GBC then PC)
Metachronous (GBC then PC)
Synchronous (GBC, PC)
Synchronous (GBC, PC)
8 months, death
In summary, pancreatic carcinoma associated with PBM is a rare event. PBM is closely related to chronic pancreatitis, but the actual relationship between pancreatic carcinoma and CBD accompanied by PBM is unclear, due to lack of sufficient data [3, 26]. Funabiki et al.  reported that the incidence of pancreatic cancer is higher in patients with PBM than in patients without PBM. They suspected that the reflux of bile into the pancreatic duct may cause chronic inflammation and cancer of the pancreas. The frequency of pancreatic cancer with PBM is 0.8%, which is relatively lower than biliary tract cancer. However, the incidence of pancreatic cancer in Japan is 16.2 per 100,000 of the population; therefore, 0.8% is 49.4 times higher than the carcinogenic risk in the general population . The present case suggests that patients with CBD accompanied by PBM should be monitored for synchronous cancer of the pancreaticobiliary system and the appropriate surgical procedure should be selected on a per patient basis.
The authors received no financial support for the preparation of this case report.
HM is the first author of this manuscript and the corresponding author. HI, HM, and NK collected the clinical data. TS and MT revised the manuscript. All authors read and approved the final manuscript.
All authors are members of the Japan Surgical Society and the Division of Department of Surgery, Shiga University of Medical Science, Shiga, Japan, Setatsukinowa-chou, Ootsu, Shiga 520-2192, Japan.
Ethics approval and consent to participate
Consent for publication
The patient has consented to the publication of these features of her case, and her identity has been protected.
The authors declare that they have no competing interests.
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