Anomalous Pancreaticobiliary Ductal Junction Research Articles

Choledochal cyst in adults: aetiological considerations to intrahepatic involvement

Choledochal cysts are rare anomalies of the biliary tree and their presentation in adults is infrequent. The high incidence of associated anomalous pancreaticobiliary duct junction (APBDJ) has been well documented. However, the prevalence of APBDJ in different anatomic distribution of cysts has yet to be clarified. A total 39 adult patients with choledochal cysts were consecutively enrolled: 22 patients had Todani type I cysts, 16 patients had type IVa cysts, and one patient had a type IVb cyst. No statistical differences were found in age, sex or manifestations. A higher frequency of associated APBDJ was identified in patients with type IVa cyst (100%) than those with type I cyst (P < 0.05). With a mean follow-up of 7.2 years after cyst excision, three patients with type I choledochal cyst and four with type IVa cyst have had episodes of recurrent cholangitis, all accompanied with preoperatively diagnosed APBDJ. Anomalous pancreaticobiliary duct junction has a close relationship with adult choledochal cysts, particularly type IVa. We propose the hypothesis that intrahepatic involvement results from progressive enzymatic destruction. Adult choledochal cysts in association with APBDJ, with or without intrahepatic component, should be carefully monitored.

Double hepatic duct associated with anomalous pancreatobiliary ductal junction

A 58-year-old woman was admitted to a local clinic with the complaint of right subcostal and back pain in October 2002. Wall thickening and a polypoid lesion of the gallbladder were detected by abdominal ultrasonography. She was referred to this hospital for further evaluation of the wall thickening and gallbladder lesion. Abdominal ultrasonography showed a two-chamber gallbladder, the wall of which was thickened and yielded small strong echos, containing a broad-based polypoid lesion 12 mm in diameter. Endoscopic retrograde cholangiography was performed, and revealed a double hepatic duct and an anomalous pancreaticobiliary ductal junction (Fig. 1). The right side hepatic duct joined with the cystic duct, draining into the common bile duct through a narrow segment. Preoperative computed tomography revealed no elevated mucosal lesion in the gallbladder. We performed open cholecystectomy because of suspected gallbladder cancer and to prevent injury to the narrow segment of the biliary duct when performing cholecystectomy from the fundus [1]. Intraoperative cholangiography also showed a double hepatic duct. The resected gallbladder showed hyperplasia with focal regenerative atypia of the mucosa but no carcinoma. The polypoid lesion detected preoperatively was a constriction of the gallbladder. The postoperative course was uneventful. The patient had no right subcostal pain after discharge.

Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study

Anomalous pancreaticobiliary ductal junction, a rare congenital anomaly, is associated with various biliary and pancreatic diseases. The aim of this study was to determine the frequency of anomalous pancreaticobiliary ductal junction in Chinese patients with gallbladder cancer. One thousand eight hundred seventy-six patients underwent ERCP between April 2000 and September 2001 with biliary and pancreatic duct opacification in 1082. Among the latter patients, those with proven gallbladder carcinoma were identified. Anomalous pancreaticobiliary ductal junction was defined as a common channel greater than 15 mm in length or a contractile segment totally distal to the union of the biliary and pancreatic ducts. When the common bile duct appeared to join the main pancreatic duct, the anomalous pancreaticobiliary ductal junction was denoted as B-P subtype; if the main pancreatic duct appeared to join the common bile duct, it was denoted P-B subtype. Fifty-four patients had gallbladder carcinoma, 7 of whom (3 men, 4 women) had anomalous pancreaticobiliary ductal junction (P-B subtype 6, B-P subtype 1). The mean (SD) length of the common channel was 21.0 mm (11.2 mm) with a range of 12 to 45 mm. One patient had early cystic dilation of bile duct. Three other patients had anomalous pancreaticobiliary ductal junction; 1 had an associated choledochal cyst and 2 a normal biliary tree. The overall frequency of anomalous pancreaticobiliary ductal junction was 0.9% (10/1082 cases). The frequency of anomalous pancreaticobiliary ductal junction was significantly higher in patients with gallbladder carcinoma (p < 0.001; OR, 50.7; 95% CI [12.7, 202.3]). Anomalous pancreaticobiliary ductal junction is strongly associated with gallbladder cancer among Chinese patients.

Choledochal cyst due to anomalous pancreatobiliary junction in the adult: sonographic findings.

Adult cases of choledochal cyst due to anomalous pancreaticobiliary duct junction have been rarely reported. At present, sonography (US) is the first tool for diagnosing biliary disorders. The aim of this study was to reevaluate the US findings of choledochal cysts due to anomalous pancreaticobiliary duct junction in adults. We reviewed the clinical manifestations and US findings of 12 such adult cases confirmed by endoscopic retrograde cholangiopancreatic ductography (ERCP). Patients were assigned to three groups: (a) associated with biliary carcinoma (two cases), (b) associated with choledocholithiasis (one case), and (c) not associated with other abdominal diseases (nine cases). Patients in group c were asymptomatic, and the lesions were detected incidentally detected by US. In contrast, patients in group a sought medical care because of symptoms such as jaundice and those in group b sought medical attention because of abdominal pain. The diameter of a dilated bile duct on US was considerably less than that of ERCP (ERCP: 26-58 mm, mean = 37.6 mm; US: 13-32 mm, mean = 21.8 mm). Its diameter changed significantly under probe compression when the dilated bile duct took a purely cystic form but changed very little when it took a tubular form. Unlike cases in children, adult cases of choledochal cyst are generally asymptomatic. Careful US observation of the bile duct is thus expected to detect asymptomatic adult choledochal cysts cases. Cyst diameter can change significantly under probe compression, so it is important not to compress the bile duct during routine US examination.

Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreaticobiliary duct

Anomalous junction of pancreaticobiliary duct (AJPBD) patients has an increased risk of gallbladder and bile duct carcinomas. However, the relevance of carcinoma with AJPBD is not fully clarified. We performed analysis of loss of heterozygosity (LOH) at p53 locus and immunohistochemistry of p53 and K- ras gene mutation in five cases of gallbladder carcinoma associated with AJPBD. LOH of p53 locus and overexpression of p53 were detected in two out of five (40%) and five out of five (100%), respectively, in the present study. K-ras gene mutation at codon 12 and 13 was not detected (0%, 0/5). These results suggest that aberrations of p53 are involved in carcinogenesis of gallbladder carcinoma associated with AJPBD. Next, in order to find the genetic events besides K- ras mutation and overexpression of mutant p53 in this disease, LOH analysis was performed using 72 microsatellite markers. High frequency of allelic loss (>50%) was found on 2p (81.8%), 4p (50%), 4q (50%), 8q (60%), 9q (50%), 10p (50%), 14p (60%), 14q (50%), 16p (60%), 19p (50%), 21p (50%) and Xp (66.6%). The highest deletion regions on chromosome 2p24 (3/3, 100%), 14q22 (3/4, 75%) and 21q22 (3/4, 75%) were found. The present study suggests that gallbladder carcinoma associated with AJPBD has high frequent allelic loss and has two new regions which may harbor putative tumor suppressor genes.

Precancerous conditions of gallbladder carcinoma: overview of histopathologic characteristics and molecular genetic findings.

Two distinct epithelial lesions (dysplasia and adenoma) and one high-risk condition (anomalous pancreatico-biliary ductal junction; APBDJ) are currently recognized as premalignant stages of gallbladder carcinogenesis. In addition to clinicopathologic observations, recent molecular genetic studies have provided further insight into the pathogenesis and biological behavior of these precursor lesions. In this review, we concentrate on describing the histopathologic and clinicopathologic background and recent molecular genetic findings for each of these putative precursor lesions.

Endoscopic therapy in anomalous pancreatobiliary duct junction

Anomalous pancreaticobiliary duct junction is associated with bile duct strictures, pancreatitis, choledochal cysts, and biliary carcinoma. Limited data are available for outcomes of endoscopic therapy. Review of 7537 patients undergoing endoscopic retrograde cholangiopancreatography from 1988 to 1997 yielded 18 patients with anomalous pancreaticobiliary duct junction. Therapeutic responses were tallied by chart review and phone calls. There were 13 women and 5 men, with a mean age of 36 years. Twelve patients had no ductographic evidence of pancreatitis and 6 had chronic pancreatitis. Seven had choledochal cysts. Fifteen patients (83%) underwent endoscopic biliary sphincterotomy, two of whom underwent repeat endoscopic biliary sphincterotomy for recurrence of symptoms. The other therapies included stent placement for benign biliary strictures in 5 patients, lithotripsy of pancreatic stones in 1 patient, and choledochal cyst removal in 4 patients. Three cases with malignant biliary strictures are excluded from endoscopic outcome studies. The 12 patients with pancreatitis had a mean of 2.0 episodes per year before any treatment. After endoscopic therapy 7 patients had no further episodes of pancreatitis, whereas 5 patients had further episodes, with a mean of one additional attack per year, over 3 years mean follow-up. Patients with anomalous pancreaticobiliary duct junction have complex pathology associated with strictures, choledochal cysts, pancreatitis, and malignancies. Endoscopic therapy appeared to benefit 13 of 15 patients without malignant disease with elimination of or decreased frequency of pancreatitis. Endoscopic therapy appears to be a logical first step in the management of most symptomatic patients with anomalous pancreaticobiliary duct junction.

Carcinogenesis in the biliary system associated with APDJ.

Anomalous pancreaticobiliary ductal junction (APDJ) is a rare congenital anomaly which is considered to be an etiological factor in the development of carcinoma of the biliary tract. It is generally accepted that pancreatic juice reflux into the biliary tract due to APDJ is one of the etiologies of biliary tract cancers. Refluxing pancreatic juice results in changes of bile and induces chronic inflammation and increased cellular proliferation, leading to epithelial hyperplasia, metaplasia, and carcinoma of the biliary tract. K-ras mutations are more prevalent in the carcinomas of biliary tract associated with APDJ compared with those without APDJ. There is no difference in the overexpression of p53 between biliary tract carcinomas associated with APDJ and those unassociated with APDJ. Further studies are needed to evaluate the role of cytokines and growth factors in carcinogenesis of the biliary system associated with APDJ.

Cellular kinetics and gene mutations in gallbladder mucosa with an anomalous junction of pancreaticobiliary duct.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. We have reported the characteristic pathology, cellular kinetics, and gene mutations to clarify the mechanism of carcinogenesis in gallbladder mucosa with AJPBD. A comprehensive review of the literature was undertaken, with referencing of major articles on the subject. A sequence of hyperplastic changes, with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma is important in carcinogenesis of gallbladder mucosa with AJPBD. p53 mutations may contribute to the transition from premalignancy to malignancy in the early stage of carcinogenesis of the gallbladder mucosa, regardless of the presence of AJPBD. The specific mutation of GGT-to-GAT in codon 12 of K-ras may play an important role in carcinogenesis of gallbladder mucosa with AJPBD.

Double Cancer of the Gallbladder and Common Bile Duct Associated with an Anomalous Pancreaticobiliary Ductal Junction Without a Choledochal Cyst: Report of a Case

Double Cancer of the Gallbladder and Common Bile Duct Associated with an Anomalous Pancreaticobiliary Ductal Junction Without a Choledochal Cyst: Report of a Case

Altered bile composition in the gallbladder and the common bile duct of patients with anomalous pancreaticobiliary ductal junction

Altered bile composition in the gallbladder and the common bile duct of patients with anomalous pancreaticobiliary ductal junction

Carcinoma in adenoma of the gallbladder in a patient with anomalous pancreaticobiliary ductal junction

We present a case of carcinoma in adenoma of the gallbladder with anomalous pancreaticobiliary ductal junction (APBDJ) in a 60-year-old Japanese woman. The patient had no abdominal symptoms. Serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, elastase 1, and α-fetoprotein were all within normal limits. Ultrasonography demonstrated two irregular hyperechoic lesions of the gallbladder. Computed tomography showed two soft-tissue density masses in the gallbladder. Endoscopic retrograde cholangiopancreatography showed APBDJ and two protruding lesions in the gallbladder. Angiography displayed a hypervascular lesion fed by the cystic artery. The patient underwent total cholecystectomy; the diagnosis of the intraoperative frozen section was well differentiated adenocarcinoma with possible mucosal invasion. Amylase level in the gallbladder bile was 90600 IU/l. Macroscopically, there were two polyps in the gallbladder. The larger one, 3.5 cm in diameter, was adenocarcinoma in adenoma, and the smaller one, an inflammatory polyp. We briefly discuss the relationship among adenoma, adenocarcinoma of the gallbladder, and APBDJ.

Anomalous pancreaticobiliary ductal junction without dilatation of the choledochus

A case of anomalous pancreaticobiliary ductal junction is reported in which the choledochus was not dilated but had significant histopathologic changes in its wall. This case suggests that early operative resection of the choledochus is indicated even if choledochal dilatation is minimal in order to prevent the occurrence of carcinoma in the long term.

Primary Carcinoma of the Gallbladder Associated with Anomalous Pancreaticobiliary Ductal Junction

Anomalous pancreaticobiliary ductal junction (APBDJ) is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between APBDJ and gallbladder carcinoma, we retrospectively reviewed data of 57 patients with gallbladder carcinoma. Of these patients, 25 had undergone endoscopic retrograde cholangiopancreaticography (ERCP) and four (16%) exhibited APBDJ. The age of those patients with APBDJ was 58.0 +/- 8.6 years and that of the patients without APBDJ was 59.2 +/- 3.1 years. Two (50.0%) of the APBDJ patients had gallstones and 47.6% of the patients without APBDJ had gallstones. The mean length of the common channel was 30 mm (range 22-38). The mode of ductal junction was three pancreatic-biliary types and one biliary-pancreatic type. One patient had an associated choledochal cyst. All the four patients with APBDJ had advanced gallbladder cancers. Consideration of gallbladder carcinoma in the patients with APBDJ may improve early detection and their survival rate.

Comparative studies of epidermal growth factor, epidermal growth factor receptor, K-ras, and P53 in gallbladder carcinomas with and without an anomalous junction of pancreticobiliary duct

AIM: We reported a 6 to 10 times higher incidence of gallstone disease in curatively gastrectomized patients for cancer (Gastroenterology 104: A362, 1993) and a possible factor for the lithogenesis to be bile infection (Gastroenterology 106: A340, 1994). The aim of this study is to experimentally investigate whether bile infection and postgastrectomy gallstone disease is related with methods of gastrectomy for cancer, i.e., a conservative pylorus-preserving gastrectomy (PPG) and a radical Billroth II subtotal gastrectomy (B-II). METHOD: Five mongrel dogs underwent PPG with the truncal vagi and the hepatic branch intact and 6 dogs underwent B-I1 with wide bursectomy and bilateral truncal vagotomy. Other 6 dogs undergoing only laparotomy (sham operation) were served as the controls. The dogs were maintained with an ordinary laboratory canine diet for 1 year. Gallbladder (GB) bile was collected by sterile fine needle puncture during laparotomy at the time of surgery, 6 months and 12 months. The obtained bile was cultured for bacteriology and analyzed for chemical constituents. Bile acids were quantified by GLC. The presence or absence of gallstone (GS) was consecutively examined by ultrasound at 2 week intervals and by inspection of the aspirated bile. GS's were examined with infrared spectral analysis for classification. RESULTS: The PPG and control dogs incurred no bile infection nor gallstone disease. Three Of the 6 B-II dogs incurred bile infection (E. coli, Bacteroides and Enterococcus). GS's (black stones containing calcium bilirubinate) developed in 3 of the 6 B-II dogs (1 identified at 6 months and 2 at 12 months). Two of the 3 B-II dogs with GS were with bile infection but one without. Total bile acids and bile acid fractions did not significantly differ among the three animal groups. Free bile acids was detected in all of the B-II dogs and in 2 of the 5 PPG dogs but in none of the control dogs. Lithogenicity calculated was within the micellar zone for all dogs. CONCLUSION: Calcium bilirubinate stone developed only in the B-II gastrectomized dogs. Positive bacterial culture and detection of free bile acids were most common in the B-II dogs, which suggested that (1) bile infection is involved in postgastrectomy gallstone disease, (2) B-II subtotal gastrectomy is more liable to bile infection and gallstone disease and (3) PPG may preserve a better sphincter of Oddi motor function, thereby preventing retrograde biliary infection. COMPARATIVE STUDIES OF EPIDERMAL GROWTH FACTOR, EPIDERMAL GROWTH FACTOR RECEPTOR, K-RAS, AND P53 IN GALLBLADDER CARCINOMAS WITH AND WITHOUT AN ANOMALOUS JUNCTION OF PANCREATICOBILIARY DUCT. Keiji Hanada, Masaki Itoh, Kiyomu Fujii, Akira Tsuchida, Shouhei Ishimaru, Manabu Hirata, Toshiyasu Iwao, and Goro Kajiyama. First Dept. of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan. AIMS. Previously, we reported that mutations of Kras and p53 contributed to carcinogenesis in gallbladder mucosa with an anomalous junction of the pancreaticobiliary duct (AJPBD). In this study, we examined the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR), and mutations of K-ras or p53in gallbladder carcinoma with and without AJPBD. METHODS. We used l0 gallbladder carcinomas with AJPBD (Group A), and 25 gallbladder carcinomas without AJPBD (Group B). EGF and EGFR were examined using immnohistochemistry. Genomic DNA was extracted from routinely processed tissues. Polymerase chain reaction (PCR) restriction fragment length polymorphism was performed for mutations of K-ras. Mutations of p53 were examined using PCR single strand conformation polymorphism. RESULTS. The percentage of immunoreactivity for EGF and EGFR in Group A (70%) was higher than that in Group B (40%). The incidence of mutation of Kras in Group A (30%) was higher than that in Group B (7%). As for p53, although mutations were found in only exon 7 and 8 in Group A, they were found in exon 5, 6, and 7 in Group B. CONCLUSIONS. i) The autocrine loop of EGF and EGFR may play an important role in tumor growth of gallbladder carcinomas associated with AJPBD. 2) Mutations of K-ras may strongly contribute to carcinogenesis of gallbladder carcinomas associated with AJPBD. 3) Mutation spots of p53 in gallbladder carcinomas associated with AJPBD may be different from that in gallbladder carcinomas without AJPBD.

Biliary bile acids in the gall-bladder and the common bile duct of patients with anomalous pancreaticobiliary ductal junction.

The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) with or without choledochal cyst (CC) has been well documented. Twenty-two patients with APBDJ were divided into three groups: Group A, four patients not associated with CC and biliary tract carcinoma; Group B, 13 patients with CC but without biliary tract carcinoma; and Group C, five patients with biliary tract carcinoma (four with and one without CC). Profiles of bile acids in the gall-bladder and/or common bile duct were analysed in these patients and compared with those in the control patients with cholecystlithiasis to examine the hypothesis that the levels of deoxycholic acid (DCA) and lithocholic acid (LCA) are elevated in patients with APBDJ because these secondary bile acids are mutagenic. Bile acids were quantified by gas-liquid chromatography. Total bile acid concentration in the gall-bladder bile was significantly lower in any group with APBDJ than that of controls. In the gall-bladder, increased proportion of chenodeoxycholic acid (CDCA) in Group A and B, decreased proportion of DCA in Group B and increased proportion of cholic acid (CA) in Group C were found in bile. In the bile duct, total bile acid concentration and proportion of DCA were significantly low in bile from Group C and decreased proportion of DCA and increased proportion of CDCA were found in bile from Group B. In both the gall-bladder and hepatic bile, proportion of LCA was not significantly different between any intergroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Discordance for anomalous pancreaticobiliary ductal junction and congenital biliary dilatation in a set of monozygotic twins

A pair of monozygotic twins, 2-year-old Japanese girls, discordant for both anomalous pancreaticobiliary ductal junction and congenital biliary dilatation, are reported. The pathogenesis of the disease is discussed in relation to the occurrence of discordant monozygotic twins.

Clinical and experimental studies on the activation mechanism of pancreatic enzymes refluxing into the biliary tract with an anomalous pancreatico-biliary ductal junction : H. Narita, T. Hashimoto, T. Suzuki, et al. J Jpn Soc Pediatr Surg 26:609–615, (May), 1990

Clinical and experimental studies on the activation mechanism of pancreatic enzymes refluxing into the biliary tract with an anomalous pancreatico-biliary ductal junction : H. Narita, T. Hashimoto, T. Suzuki, et al. J Jpn Soc Pediatr Surg 26:609–615, (May), 1990

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

A high incidence of inflammation and carcinoma of the biliary tract in patients with anomalous pancreaticobiliary ductal junction has been well documented. The change in biliary phospholipids as a result of the reflux of pancreatic juice into the biliary tract through anomalous pancreaticobiliary ductal junction may be responsible for it. We developed a new method of analysis of phospholipid classes using aminopropyl Bond Elut cartridge for extraction and high-performance liquid chromatography for separation. Satisfactory recovery was achieved (i.e., more than 95% for both phosphatidylcholine and lysophosphatidylcholine). With this method, the bile of 11 patients with anomalous pancreaticobiliary ductal junction was examined. The concentration and proportion of lysophosphatidylcholine in bile were much higher in the presence of anomalous pancreaticobiliary ductal junction than in controls (3.44 +/- 1.50 mmol/L vs. 0.52 +/- 0.25 mmol/L, 60.0% +/- 31.0% vs. 2.3% +/- 1.4% in gallbladder bile; p less than 0.001). In contrast, the concentration of phosphatidylcholine and the sum of phosphatidylcholine and lysophosphatidylcholine in gallbladder bile significantly decreased (p less than 0.001), but in hepatic bile they did not. An inverse correlation was found between the proportion of lysophosphatidylcholine and phospholipid concentration in gallbladder bile. Phospholipase A2 and amylase activities in bile were markedly high. Increased total fatty acid concentration and proportion of unsaturated fatty acid in bile were found. Total bile acid concentration in gallbladder bile was significantly lower than in controls. These results suggest that a considerable amount of lysophosphatidylcholine, which is known to have a cytotoxic effect, isp reduced by phospholipase A2 in refluxing pancreatic juice, and an increased concentration of lysophosphatidylcholine gives rise to cell damage causing mucosal hyperplasia and metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction