Metachronous cancer of gallbladder and pancreas with pancreatobiliary maljunction

Pancreaticobiliary maljunction is a congenital anomaly in which the junction between the pancreatic duct and the common bile duct is located outside the sphincter of Oddi. It is well known that pancreaticobiliary maljunction is frequently associated with carcinoma of thebiliary tract. We report a case of metachronous cancer of the gallbladder and pancreas associated with pancreaticobiliary maljunction and cystic dilatation of common bile duct in a 68-year-old Tunisian woman who underwent a cholecystectomy for acute cholecystitis. The pancreatic tumor was an adenosquamous carcinoma. Pancreaticobiliary maljunction allows for pancreatobiliary or biliopancreatic reflux which may induce biliary tract carcinoma. Few cases of multifocal cancer associated with this anomaly have been reported. The association with pancreatic carcinoma remains rare. Close attention should be given to both the biliary tract system and pancreas during the long-term follow-up of patients with pancreaticobiliary maljunction, especially after they have undergone a choledochojejunostomy.     

Congenital dilatation of the common bile duct and pancreaticobiliary maljunction—clinical implications

Clinical conditions and diagnosis  Congenital dilatation of the common bile duct is a disease in which the extrahepatic bile duct, or both the extra and intrahepatic bile ducts, is dilated in various ways. Pancreaticobiliary maljunction is a disease in which the pancreatic duct meets the bile duct outside of the duodenal wall beyond the sphincter Oddi. Recently, these diseases have been thought to be closely related to each other but to be different malformations. Biliary tract carcinoma, especially bile duct carcinoma, is found in about 30% of patients with congenital dilatation of the bile duct. The concomitance of bile and pancreatic juice and their stasis in the biliary tract induce cellular proliferation and reproduction and stimulate genetic alterations in biliary epithelium, which may play an important role in carcinogenesis of the bile duct. Therapeutic strategies  Endoscopic retrograde cholangiopancreatography is useful for examining pancreaticobiliary maljunction. The operation is dilated bile duct resection and hepaticojejunostomy, which ensure that pancreatic juice and bile do not mix in the bile duct. Gallbladder carcinoma develops in more than 90% of pancreaticobiliary maljunction without bile duct dilatation.     

Precancerous conditions of biliary tract cancer in patients with pancreaticobiliary maljunction: reappraisal of nationwide survey in Japan

It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms. Received: May 1, 2000 / Accepted: September 5, 2000     

Cancer of the gallbladder associated with pancreaticobiliary maljunction without bile duct dilatation in a european patient

A rare case of pancreaticobiliary maljunction (PBM) without dilatation of the biliary tract (DBT) associated with gallbladder carcinoma is described herein. A 62-year-old European woman with a long history of right upper abdominal pain was diagnosed as having PBM without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y hepaticojejunostomy was performed, and subsequent pathological examination of the surgical specimen showed a well differentiated adenocarcinoma of the gallbladder. She had no clinical symptoms for 58 months postoperatively. PBM allows reflux of pancreatic juice into the biliary tract. Recent findings support the idea that epithelial hyperplasia plays an important role in gallbladder carcinogenesis with PBM, and also support the concept that gene mutations are involved in the carcinogenesis of biliary epithelium in patients with PBM. For these reasons, we advocate that resection of the extrahepatic biliary tract in PBM patients without bile duct dilatation, rather than cholecystectomy alone, is the treatment of choice for preventing bile duct carcinoma. Received for publication on Dec. 15, 1999; accepted on Feb. 22, 2000     

Dilatation of the intrahepatic bile duct associated with congenital anomalous junction of the cystic duct--a new disease entity

We describe 3 children with dilatation of the intrahepatic bile duct, who had anomalous junctions of the cystic duct, 2 high and 1 low, without pancreaticobiliary maljunction. They were all male, and underwent excision of the gallbladder and the extrahepatic bile duct followed by a Roux-en-Y hepaticojejunostomy as a definitive surgery. Postoperatively, the dilated intrahepatic bile duct became normal in size. From these 3 cases, we propose a new disease entity—dilatation of the intrahepatic bile duct because of congenital anomalous junction of the cystic duct.     

Preferable operative age of choledochal dilation types to prevent patients with pancreaticobiliary maljunction from developing biliary tract carcinogenesis

BACKGROUND: Pancreaticobiliary maljunction (PBM), which frequently accompanies choledochal dilation, is a high risk factor for biliary tract (gallbladder, bile duct) carcinoma because of the continuous reflux of pancreatic juice into the biliary tract. The aim of this study was to clarify the preferable operative age in PBM patients for the prevention of biliary tract carcinogenesis, with reference to the dilation types of bile ducts. METHODS: There were 165 PBM patients in total studied, including 92 pediatric patients (< or =15 y) (cystic, 63; spindle-like, 29; nondilation, 0) and 73 adult patients (>15 y) (cystic, 45; spindle-like, 18; nondilation, 10) who underwent operative excision of extrahepatic bile ducts or cholecystectomy. We investigated incidence by age of biliary tract malignancies and the risk according to types of dilation. RESULTS: In the pediatric group, no carcinoma case could be found preoperatively or postoperatively (mean follow-up period, 11.7 y). In the adult group, bile duct carcinomas could be detected in 6 cases of a cystic type (6 of 45; 13.3%) (3 preoperative, 3 postoperative). Among the bile duct carcinoma cases, the youngest patient was a 21-year-old woman who had undergone excision of an extrahepatic bile duct 3 years previously. Gallbladder carcinomas were detected in 16 patients: 3 of 45 cystic (6.7%), 6 of 18 spindle-like (33.3%), and 8 of 10 nondilation (80.0%), in whom the youngest patient was a 41-year-old woman with a spindle-like type. CONCLUSIONS: To prevent biliary tract carcinogenesis in PBM patients, cystic-dilated choledochus should be excised in childhood before the development to a precancerous stage. In spindle-like and nondilation types, cholecystectomy is absolutely necessary in early adulthood before age 40.     

Epithelial cell proliferation activity of the biliary ductal system with congenital biliary malformations

Congenital biliary malformations such as anomalous arrangement of the pancreaticobiliary ductal system (AAPB), congenital cystic dilatation of the common bile duct (CCDB), and congenital biliary strictures at the hepatic hilum (CBSH) are newly designated disease entities and are frequently found in adult patients with biliary malignancy such as gallbladder carcinoma, common bile duct carcinoma, and intrahepatic bile duct carcinoma. In the present study, the relationship of these malformations and biliary malignancy was investigated. We studied 61 gallbladders of patients with AAPB and 56 gallbladders of patients without AAPB; 16 common bile ducts of patients with CCDB (12 with AAPB and 4 without AAPB) and 11 gallbladders of patients without CCDB; and 17 intrahepatic bile ducts of patients with CBSH and 6 intrahepatic bile ducts of patients without CBSH. Tissue sections from the mucosa of the gallbladder, common bile duct, and intrahepatic bile duct were stained for proliferating cell nuclear antigen (PCNA). The PCNA labeling indexes of patients with these malformations were significantly higher than those of patients without these malformations (P < 0.05). Cell proliferation of the epithelia in the biliary ductal system in patients with these congenital biliary malformations was accelerated. Consequently, these congenital malformations appear to be an important risk factor for the occurrence of biliary malignancy. Received for publication on Feb. 15, 1999; accepted on March 29, 1999     

Invasive cholangiocarcinoma identified in congenital biliary dilatation in a 3-year-old boy

We herein report a 3-year-old male demonstrating invasive cholangiocarcinoma (CC) associated with congenital biliary dilatation (CBD). A 3-year-old Japanese boy was admitted to our hospital with abdominal pain and vomiting. Computed tomography and magnetic resonance imaging demonstrated a dilated extrahepatic bile duct. A diagnosis of Todani's type 1a CBD was made.Intraoperative cholangiography demonstrated the presence of pancreaticobiliary maljunction but could not reveal any tumor lesion in the bile duct. The excision of extrahepatic bile duct and gallbladder and Roux-en-Y hepaticojejunostomy were performed. On gross inspection, we could not find any tumor lesion in the resected specimen.However, the postoperative histopathologic examinations confirmed the presence of well-differentiated tubular adenocarcinoma with lymphovascular invasion. Most of the carcinoma remained within the mucosal layer, and the carcinoma was identified at both the distal and proximal surgical margins of the bile duct. We scheduled additional surgery to eradicate the residual carcinoma, but informed consent for the extra surgery could not be obtained.A close follow-up with abdominal computed tomography has been going on without either additional surgery or adjuvant chemotherapy about for 1 year. The patient has so far been clinically doing well without any obvious symptoms of recurrent disease. To our knowledge, this report is the youngest case of CC associated with CBD.     

Papillary carcinoma of the extrahepatic bile duct: characteristic features and implications in surgical treatment

BACKGROUND: Papillary carcinoma of the extrahepatic bile duct presents clinically and histologically distinct features relevant to surgical decision-making. STUDY DESIGN: Serial sections of 15 specimens of resected papillary carcinoma of the bile duct were histologically examined to determine mode of spread, possibility of multicentric tumor origins, and coincidence with other neoplastic lesions. The presence of anomalous pancreaticobiliary ductal union was also investigated. These characteristics were considered with regard to surgical treatment. RESULTS: Three patients displaying pancreaticobiliary maljunction and one of three patients with a long common channel (> or = 8 mm) exhibited multicentric tumors. Eight patients (53%) demonstrated superficial spread along a mean length of 37.8 mm (range, 5 to 67 mm) of bile duct mucosa. Multicentric tumors developed synchronously in 4 patients, while metachronous tumors were identified in three patients displaying tumor histology similar to the primary lesions. Two of these three underwent successful repeated resection. Concomitant neoplastic lesions in the biliary tract were identified as mucosal dysplasia in four patients and cholangiocellular carcinoma of the liver in two. All tumors but one were removed via hepatic lobectomy or pancreatoduodenectomy, or both, resulting in a 5-year survival rate of 60%. CONCLUSIONS: Aggressive resection offers clear survival benefits for patients presenting with tumors displaying extensive superficial spread or multicentric origins. Closer attention should be paid to long common channels in relation to carcinogenesis of the bile duct, in addition to pancreaticobiliary maljunction. The risk of secondary tumor development remains, particularly in patients with pancreaticobiliary maljunction even after excision of the tumor-bearing extrahepatic bile duct.     

Metachronous double cancer of the gallbladder and pancreas associated with pancreaticobiliary maljunction

A 50-year-old Japanese woman complained of abdominal and back pain. Ten years previously she had undergone cholecystectomy, choledochectomy, and Roux-en-Y choledochojejunostomy for gallbladder cancer associated with pancreaticobiliary maljunction without bile duct dilatation. On the present admission, ultrasonography (US) and computed tomography (CT) demonstrated a large mass, 60 mm in size, in the pancreatic tail. Endoscopic retrograde cholangiopancreatography (ERCP) showed obstruction of the main pancreatic duct in the tail of the pancreas and revealed that the pancreatic duct was joined to the bile duct 25 mm above the papilla of Vater. The patient underwent distal pancreatectomy, splenectomy, left adrenalectomy, and partial gastrectomy. Histological examination revealed moderately differentiated ductal adenocarcinoma that had invaded to the proper muscle of the stomach. Double cancer of the gallbladder and pancreas in a patient with pancreaticobiliary maljunction is rare. Although the etiology of cancer of the pancreas associated with pancreaticobiliary maljunction is unclear, we should pay close attention to the pancreas as well as the biliary tract during the long-term follow-up of patients with pancreaticobiliary maljunction after they have undergone a choledochojejunostomy.     

Spontaneous necrosis of gallbladder carcinoma in patient with pancreaticobiliary maljunction

While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma. Received: August 8, 2000 / Accepted: October 26, 2000     

A case of a rare anomaly of the common bile duct associated with an abnormal arrangement of the pancreaticobiliary ductal union

A 39 year-old Japanese female patient with a duplication of the distal portion of the common bile duct is presented herein. Moreover, an abnormal arrangement of the pancreaticobiliary ductal union, congenital biliary dilatation and carcinoma of the gallbladder were all demonstrated by cholangiographic and endoscopical studies. The patient underwent radical surgery for advanced adenosquamous carcinoma of the gallbladder, and her postoperative course was satisfactory. A reflux of pancreatic juice into the bile duct was demonstrated, but it was eliminated and considered to be a contributory etiologic factor of the gallbladder carcinoma.     

选择性术中胆道造影在腹腔镜胆囊切除术中的价值

目的:探讨选择性术中胆道造影在腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)中的应用价值。方法:回顾分析231例术前诊断为胆囊结石、胆囊息肉样病变的患者于LC术中经胆道造影发现胆道病变、变异的临床资料。结果:225例造影成功,成功率97.4%。术中胆道造影发现胆囊管残石3例,胆总管结石12例,胆管损伤4例,胰胆管汇合异常14例,胆囊管异常开口12例,右侧副肝管4例,胆总管憩室1例,十二指肠乳头旁憩室6例,Mirizzi综合征5例,右肝内钙化灶2例。结论:LC术中行胆道造影不仅能发现术前未确诊的胆总管结石、胆囊管结石,而且利于胆管变异、胰胆管汇合异常及乳头旁憩室的诊断。     

Association of extrahepatic bile duct duplication with pancreaticobiliary maljunction and congenital biliary dilatation in children: a case report and literature review

We herein report a case of cystic-type congenital biliary dilatation (CBD) in whom an extremely rare anomalous duplication of the common bile duct and pancreaticobiliary maljunction were diagnosed intraoperatively by meticulous surgical manipulations via conventional open surgery. By performing a dissection at the outer epicholedochal layer of the cyst, a thin cord-like structure shown to be the distal part of the common bile duct was identified. A further exploration revealed that the most distal (extra- and intrapancreatic) part of the common bile duct was duplicated, and each branch of the duct was connected to the main and accessory pancreatic ducts. The experience with our case and a literature review showed that extrahepatic bile duct duplication is generally associated with pancreaticobiliary maljunction and CBD. We conclude that an extremely careful exploration with delicate and meticulous surgical manipulation is essential to identify these morphological anomalies and prevent intraoperative and postoperative complications of CBD, such as pancreatic duct injury or pancreatitis.     

Extracystic biliary carcinoma associated with anomalous pancreaticobiliary junction and cysts

Anomalous pancreaticobiliary junction with cystic dilatation of the biliary tract is usually associated with carcinoma arising from the cyst wall. We report an extracystic location of biliary carcinoma in the presence of anomalous pancreaticobiliary junction and cysts in a patient with obstruction of the origin of the left hepatic duct who underwent hepatobiliary resection. Cholangiocarcinoma was found to have arisen in a noncystic left hepatic duct, in conjunction with cystic dilatation involving both the cystic and common bile ducts. The present case supports a relationship between anomalous pancreaticobiliary junction and biliary carcinogenesis that may affect the extracystic biliary tree.     

Double common bile duct: a case report and a review of the Japanese literature

BACKGROUND: A double common bile duct (DCBD) is a rare congenital anomaly. We report the case of a 60-year-old Japanese female, whose common bile duct divided into 2 channels and both channels opened individually into the second portion of the duodenum. This is the fourth reported case of DCBD with a choledochal cyst and pancreaticobiliary maljunction (PBM). METHODS: A review of the literature revealed that DCBD is more frequently diagnosed in Oriental people. We reviewed 47 cases of DCBD reported in the Japanese literature. RESULTS: Among these, cholelithiasis was found in 27.7%, a choledochal cyst in 10.6%, PBM in 29.8%, and cancers in 25.5%. Cancer and PBM were the 2 most serious concomitant conditions. The incidence and type of complicating cancer and PBM varied according to the site of the opening of the accessory common bile duct (ACBD). Concomitant gastric cancer was frequently noted when the ACBD opened into the stomach, whereas cancer of the biliary system was common when the ACBD opened into the second portion of the duodenum or the pancreatic duct. PBM was observed only in those patients in whom the ACBD opened into the second portion of the duodenum or the pancreatic duct. Therefore the treatment and prognosis of DCBD is influenced by the site of opening of the ACBD. CONCLUSIONS: In DCBD, the opening site of the ACBD was considered to have close implications for the type of concomitant cancer and concomitant PBM that would appear.     

A case of a rare anomaly of the common bile duct associated with an abnormal arrangement of the pancreaticobiliary ductal union

A 39 year-old Japanese female patient with a duplication of the distal portion of the common bile duct is presented herein. Moreover, an abnormal arrangement of the pancreaticobiliary ductal union, congenital biliary dilatation and carcinoma of the gallbladder were all demonstrated by cholangiographic and endoscopical studies. The patient underwent radical surgery for advanced adenosquamous carcinoma of the gallbladder, and her postoperative course was satisfactory. A reflux of pancreatic juice into the bile duct was demonstrated, but it was eliminated and considered to be a contributory etiologic factor of the gallbladder carcinoma.     

End-to-side choledochoduodenostomy: A widely applicable procedure for biliary reconstruction

End-to-side choledochoduodenostomy was originally used for reconstruction between the duodenum and the biliary tree in iatrogenic bile duct stricture. However, we believe the procedure could be applied for various biliary disorders. We have recently shown the high carcinogenicity of biliary epithelium in patients with pancreaticobiliary maljunction, and consequently we recommend excision of the bile duct, along with appropriate reconstruction of the biliary system to divert the flow of pancreatic juice from bile fluid, to prevent carcinoma in biliary epithelium even in patients without dilatation of the bile duct. The conditions causing primary or recurrent bile duct stones must be removed. We employed this procedure for biliary reconstruction in 42 patients with pancreatico-biliary maljunction and in 30 patients with various benign biliary diseases, such as bile duct stones and benign biliary stenosis. We also used the procedure for palliation in 6 patients with malignant tumors around the head of the pancreas. Among these 78 patients over 20 years, we experienced 5 cases of reflux cholangitis with anastomotic stenosis, for which conservative dilatation was required. This procedure of end-to-side choledochoduodenostomy could be widely applicable for biliary reconstruction in terms of its being simplicity, minimal invasiveness and the establishment of a single physiological route for bile flow into the duodenum.     

Pancreaticobiliary maljunction and carcinogenesis to biliary and pancreatic malignancy

Background  It is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is synonymous with “abnormal junction of the pancreaticobiliary ductal system”, “anomalous arrangement of pancreaticobiliary ducts”, “anomalous union of bilio-pancreatic ducts”, etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually. Biliary carcinogenesis  The most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic. K-ras gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of p53 gene and overexpression of p53 protein are also found in the cancerous and noncancerous lesions. These changes are called “hyperplasia–carcinoma sequence”. Treatment  Total excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.     

Biliary carcinogenesis in pancreaticobiliary maljunction

The coexistence of bile duct carcinoma in choledochal cysts is well known. With large number of cases of congenital bile duct dilatation and pancreaticobiliary maljunction (PBM), it is now apparent that gallbladder carcinoma is more frequent in PBM without bile duct dilatation. The incidence of Gallbladder cancer in choledochal cyst and bile duct cancer in PBM, regardless of the presence of bile duct dilatation is significantly higher than that in control patients with biliary cancer but without PBM. A recent survey shows that the incidence of bile duct cancer in PBM without dilatation is equivalent to that of gallbladder cancer and bile duct cancer in patients with choledochal dilatation. Pathology in PBM is a result of reflux of pancreatic juice and stasis of the mixture in the biliary system. Carcinogenic factors thus present in the biliary contents induce epithelial changes in the biliary tract. In the biliary contents, activated pancreatic enzymes and secondary or deconjugated bile acids are markedly increased and they irritate the biliary mucosa. Mutagens are proven to form in the bile of PBM. In the epithelia of PBM, hyperplasia, metaplasia, and dysplasia are often found, and proliferative activity is increased; furthermore, K-ras gene mutation and overexpression of p53 protein are demonstrated. As for treatment of PBM, whether it is symptomatic or not, an operative procedure, is necessary, to prevent carcinogenic changes in the gallbladder and bile duct. Regardless of whether dilatation is present or not, total excision of the extrahepatic bile duct, along with gallbladder, is the treatment of choice, followed by hepaticojejunostomy or hepaticoduodenostomy.