Endocrine cell carcinoma of the gallbladder with anomalous pancreaticobiliary ductal junction

We experienced a case of endocrine cell carcinoma of the gallbladder with anomalous pancreaticobiliary ductal junction. It is well known that anomalous pancreaticobiliary ductal junction has potentiality to cause gallbladder cancer and that most of the cases are papillary adenocarcinoma or well-differentiated adenocarcinoma. The direct relationship between endocrine cell carcinoma of the gallbladder and anomalous pancreaticobiliary ductal junction has not been elucidated.     

Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union

A total of 96 patients with gallbladder carcinoma in whom direct cholangiography clearly opacified the pancreaticobiliary ductal union and the common channel, and 65 patients with an anomalous union of these two duct systems at a distance greater than 15 mm from the papilla of Vater (normally less than 4.6 +/- 2.2 mm, mean +/- SD) were studied. It was found that this anomalous ductal union occurred in 16.7% of the patients with gallbladder carcinoma in comparison with an incidence of 2.8% among 641 consecutive patients with various hepatobiliary and pancreatic diseases studied by endoscopic retrograde cholangiopancreatography who did not have gallbladder carcinoma. It was also found that gallbladder carcinoma occurred in 24.6% of the 65 cases of anomalous ductal union in comparison with a 1.9% incidence of this cancer among 635 consecutive patients similarly studied and found to have normal ductal union (p less than 0.001). Thus, a close etiologic association was suggested between this anomaly in the terminal segment of the biliary tract and gallbladder carcinoma. Of the 65 patients with anomalous ductal union, 50 had the so-called congenital cystic dilatation of the common bile duct and 15 did not. Five of the 50 (10%) and 11 of the 15 (73.3%) had gallbladder carcinoma (p less than 0.01), and this carcinoma seems to be related to anomalous ductal union rather than to cystic dilatation of the common bile duct. As a tumorigenic factor in this anomaly, regurgitation of pancreatic juice has been stressed.     

先天性胆胰管合流异常与胆囊癌的关联

目的　研讨胆胰管合流异常 (APBDJ)在国人胆囊癌中的发生率及其相关因素 ,并对APBDJ的经内镜逆行胰胆管造影术 (ERCP)诊断标准作初步探讨。方法　 2 0 0 0年 4月至 2 0 0 1年 9月期间 ,1876例患者接受ERCP诊疗 ,其中 10 82例胆管及胰管均显影 ,在这组患者中确定胆囊癌及APB DJ病例。APBDJ的诊断标准是胆、胰管共同通道的长度超过 15mm或壶腹部括约肌收缩段位于胆胰汇合部远侧。根据胆、胰管汇合的形态将其分成 2种类型 :P B型为胰管汇入胆管 ,B P型为胆管汇入胰管。结果　本组共发现胆囊癌 5 4例 ,其中 7例并发APBDJ(男 3例 ,女 4例 ;P B型 6例 ,B P型 1例 ) ,共同通道的平均长度 2 1 0mm(范围 12～ 4 5mm) ,1例尚合并胆管囊肿 ;另有 3例存在APBDJ(1例有胆管囊状扩张 ,2例胆胰管正常 )。APBDJ总发生率为 0 9% (10 / 10 82 ) ,均不合并胆囊结石 ,其在胆囊癌患者中的发生率高 (P <0 0 0 1) ,发病年龄较小 (P =0 0 5 6 )。结论　 (1)国人胆囊癌的发生与先天性胆胰管合流异常有非常密切的关联 ,尤其易发于P B型 ;(2 )APBDJ的ERCP诊断标准可包括胆胰管共同通道长度超过 15mm或壶腹括约肌收缩段位于胆胰汇合部远侧。     

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.     

Type classification of anomalous pancreaticobiliary junction by ERCP

The role of endoscopic retrograde cholangiopancreatography (ERCP) in the preoperative assessment of anomalous pancreaticobiliary junction was retrospectively evaluated in 74 consecutive patients (19 males and 55 females; aged 0–80 years). Sixty-three patients had congenital biliary dilatation and 11 did not. Type classification of congenital biliary dilatation was possible by ERCP alone in 45 patients (71%). The main causes of classification failure were previous bilio-enteric anastomosis and restriction of postural changes during ERCP due to general anesthesia in pediatric patients. Classification of anomalous junction was possible in 69 patients (93%). Technical difficulty in ERCP caused classification failure in 5 patients. Neoplastic lesions were found in 12 patients (16%) and all but 1 were correctly diagnosed by ERCP. We conclude that ERCP plays an important role in the preoperative diagnosis and type classification of anomalous pancreaticobiliary junction and congenital biliary dilatation.     

Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct

OBJECTIVE: In this study, we examined the mutational spectrum of K-ras in cases of gallbladder and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct (AJPBD). METHODS: We examined 35 gallbladders with AJPBD (20 with hyperplasia, 15 with carcinoma) and 38 gallbladders without AJPBD (four normal gallbladders, four with hyperplasia, six with adenoma, 24 with carcinoma). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to detect mutations in codon 12 or 13 of K-ras. RESULTS: In the cases with AJPBD, the prevalences of K-ras mutation were 15% (3/20) in hyperplasia, 60% (6/10) in stage I carcinoma, and 100% (5/5) in stage II-IV carcinoma. In the cases without AJPBD, the prevalences of K-ras mutation were 0% (0/4) in normal gallbladder, 0% (0/4) in hyperplasia, 17% (1/6) in adenoma, 7% (1/16) in stage I carcinoma, and 38% (3/8) in stage II-IV carcinoma. Prevalences of K-ras mutation in hyperplasia and carcinoma with AJPBD were greater than those without AJPBD (p < 0.05). The point mutation of GGT to GAT in codon 12 was frequently observed in the cases with AJPBD. CONCLUSION: These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD.     

Multiseptate gallbladder with anomalous pancreaticobiliary ductal union： A case report

Multiseptate gallbladder, characterized by the presence of multiple septa dividing the gallbladder lumen, is a very extremely rare congenital anomaly of the gallbladder. On the other hand, anomalous pancreaticobiliary ductal union is also one of the congenital anomalous biliary diseases and thought to be related with choledochal cyst or biliary tract malignancies. In this paper, we describe a unique and first patient of multiseptate gallbladder with anomalous pancreaticobiliary ductal union and a review of the literature. To clarify more characters of the multiseptate gallbladder,examination of a larger patient population will be needed and further studies will be required.     

Pancreatic carcinoma associated with anomalous pancreaticobiliary junction

Anomalous pancreaticobiliary junction often leads to biliary tract carcinoma but only rarely to pancreatic carcinoma. We report three cases of pancreatic carcinoma associated with anomalous pancreaticobiliary junction. All three were female with a mean age of 68 years. Carcinomas were located in the pancreatic head (n = 2) or body (n = 1). None had choledochal cyst and one had experienced recurrent acute pancreatitis. All carcinomas were at an advanced stage with a poor prognosis. No unique imaging or histologic findings of the carcinomas could be identified. Attention should be paid to the possibility of pancreatic carcinoma in patients with anomalous pancreaticobiliary junction, particularly in aged patients. Early diagnosis and treatment of anomalous pancreaticobiliary junction may prevent development of pancreatic carcinoma.     

Double cancer of gallbladder and bile duct associated with anomalous junction of the pancreaticobiliary ductal system

We report a case of double cancer of the gallbladder and the common bile duct associated with anomalous junction of the pancreaticobiliary ductal system, and review the literature of similar case reports. A 66-year-old woman was admitted to an associated hospital complaining of upper abdominal pain, and was diagnosed as having pancreatitis. Abdominal imaging revealed an irregularly protruding mass at the body of the gallbladder and an intraluminal protrusion at the lower third of the common bile duct. Endoscopic retrograde cholangiopancreatography also revealed anomalous junction of the pancreaticobiliary ductal system with congenital biliary dilatation of 14 mm in the largest diameter. She underwent surgical resection of the gallbladder, the extrahepatic bile duct and the gallbladder bed of the liver with a dissection of the regional lymph nodes for double cancer of the gallbladder and the bile duct associated with anomalous junction of the pancreaticobiliary ductal system. She is still alive 33 months after surgery without any signs of recurrence. There were 12 patients (including our case) reported in the literature who had double cancer of the gallbladder and the extrahepatic bile duct associated with anomalous junction of the pancreaticobiliary ductal system. Only 33% of these 12 patients had jaundice. Tumors of the 12 patients were commonly early-stage cancer both in the gallbladder (36%) and in the extrahepatic bile duct (73%). Therefore, we concluded that precise preoperative imaging of the total biliary tract should be required in order to detect early-stage cancer in patients with anomalous junction of the pancreaticobiliary ductal system before planning surgical procedures, and consideration should be given to the possibility of multiple occurrences of biliary tract cancers.     

先天性胆胰管合流异常的内镜诊断与治疗

目的探讨ERCP对胆胰管合流异常（APBDJ）的诊断价值与临床处理原则。方法回顾分析近5年来接受ERCP诊疗的患者中,APBDJ的发生情况、分型特点、与合并胆胰疾病的关系,以及内镜下处理的情况。结果探讨ERCP对胆胰管合流异常（APBDJ）的诊断价值与临床处理原则。方法回顾分析近5年来接受ERCP诊疗的患者中,APBDJ的发生情况、分型特点、与合并胆胰疾病的关系,以及内镜下处理的情况。结论ERCP是APBDJ一种直接、可靠的诊断手段;APBDJ与胆囊癌、胆总管囊肿及慢性胰腺炎等症有非常密切的关联;APBDJ患者可根据合并症的具体情况,采取相应的内镜治疗措施。     

Epithelial hyperplasia of the gallbladder in children with anomalous pancreaticobiliary ductal union

BACKGROUND/AIMS: Few data are available on the fate and incidence of epithelial hyperplasia throughout the life of anomalous pancreaticobiliary ductal union (APBD) patients. The pathological study in pediatric APBD patients is less recognized. METHODOLOGY: Ten resected gallbladders obtained from children with APBD and control patients without APBD were examined histologically, and immunohistochemically for the detection of Ki-67 (as a proliferative marker) and p53. K-ras mutations in codon 12 were also examined. Epithelial hyperplasia was classified into high-grade and low-grade hyperplasia. RESULTS: Six (60%) of 10 patients with APBD had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. Diffuse epithelial hyperplasia was observed in 1 (50%) of 2 undilated-type APBD and 5 (63%) of 8 dilated-type. Two (33%) of 6 patients with epithelial hyperplasia exhibited high-grade hyperplasia. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. K-ras mutations and p53 overexpression were not detected in hyperplastic and normal mucosa. CONCLUSIONS: Epithelial hyperplasia of the gallbladder accompanied by increased proliferative activity exists at birth or is acquired in childhood with APBD patients and may be an important factor predisposing to the development of gallbladder carcinoma.     

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)     

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.     

Gallbladder carcinoma associated with anomalous pancreaticobiliary duct junction.

BACKGROUND: Anomalous pancreaticobiliary ductal junction (APBDJ) is believed to be one of the risk factors for gallbladder carcinoma. The present study aims to delineate the gallbladder carcinoma characteristics associated with APBDJ. PATIENTS AND METHODS: Patients with gallbladder carcinoma associated with APBDJ between August 1992 and February 2005 were retrospectively reviewed. Two types of APBDJ classifications were considered: right-angle type (C-P) and acute-angle type (P-C). RESULTS: Ten of 218 patients (4.6%) with gallbladder carcinomas were associated with APBDJ. All patients were female with a mean age of 55.4 years (range 41 to 72 years). Gallstones were absent in nine patients. Seven patients (70%) had the P-C type and three patients (30%) had the C-P type. Survival differences between the P-C type and the C-P type of gallbladder carcinomas were noted (P=0.0269). Patients with incidentally detected gallbladder carcinoma had superior survival (P=0.0316). CONCLUSION: Gallbladder carcinomas associated with APBDJ were significantly related to relatively young female patients without gallbladder stones. Survival outcomes in these patients were not different from those of gallbladder carcinoma without APBDJ. In particular, the P-C type of APBDJ seemed to be more associated with relatively advanced gallbladder carcinomas, and patients with incidentally detected gallbladder carcinomas with APBDJ had superior survival.     

Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer

BACKGROUND/AIMS: Anomalous pancreaticobiliary junction is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between anomalous pancreaticobiliary junction, especially if it is not associated with common bile duct dilatation, and gallbladder carcinoma, we retrospectively reviewed data of 126 patients with gallbladder carcinoma. METHODOLOGY: All these patients had undergone direct cholangiography either by endoscopic retrograde cholangiopancreaticography or percutaneous transhepatic cholangiography. RESULTS: Among 126 patients with gallbladder cancer, 23 patients (18.3%) exhibited anomalous pancreaticobiliary junction. Patients with anomalous pancreaticobiliary junction were younger (mean age: 54 +/- 9.1 years) than patients without anomalous pancreaticobiliary junction (mean age: 65 +/- 9.7 years). The incidence of gallstones in patients with anomalous pancreaticobiliary junction (17%) was significantly lower than in those without this anomaly (64%) (P < 0.01). Among the 23 patients with anomalous pancreaticobiliary junction, 12 patients (52%) had no bile duct dilatation and, 11 patients (48%) had bile duct dilatation in the form of fusiform or cylindrical dilatation. However, no cases with severe cystic dilatation were found. Patients of anomalous pancreaticobiliary junction without common bile duct dilatation had more advanced disease and poor prognosis than those with common bile duct dilatation. CONCLUSIONS: The present study revealed that gallbladder cancer in the patients of anomalous pancreaticobiliary junction without common bile duct dilatation was diagnosed at advanced stage and the prognosis was very poor. Therefore, if a minor abnormality is detected in the wall of acalculous gallbladder on ultrasonography, direct cholangiography should be done to exclude this anomaly.     

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.     

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 Groups 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. Thus no increase of DCA and LCA was found in either the bile from the gall-bladder and the bile duct of APBDJ patients. It is concluded that bile acid plays little role, if any, in the pathogenesis of biliary tract carcinoma in patients with APBDJ.