Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction

BACKGROUND: A reflux of pancreatic juice into the biliary tract caused by pancreaticobiliary maljunction (PBM) has been considered important in the development of biliary tract carcinogenesis in choledochal cysts. We excised extrahepatic bile ducts in patients with choledochal cysts to terminate the reflux of pancreatic juice. We investigated whether this surgery could stop the development of the residual bile duct carcinoma. METHODS: Fifty-six patients with a diagnosis of PBM with choledochal dilatation underwent surgical excision of extrahepatic bile ducts. We applied a person-year method to compare the relative risks (observed number/expected number) of biliary tract carcinoma before and after surgery. RESULTS: In 3 patients, bile duct carcinoma developed in residual dilated segments 19 years 6 months, 8 years 8 months, and 2 years 5 months, respectively, after surgery. Although the relative risk in the post-surgery group was slightly decreased by surgery, it was still high compared with that of the general population. CONCLUSIONS: The incidence of bile duct carcinoma is still high, even after excision of extrahepatic bile ducts in PBM patients with choledochal dilatation. For these patients, careful long-term follow-up is necessary, especially after operations that leave the dilated bile ducts, such as cases of Todani's type IV-A.     

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     

Long-term results after cholecystectomy alone for patients with pancreaticobiliary maljunction without bile duct dilatation

A pancreaticobiliary maljunction (PB-MJ) without bile duct dilatation is relatively rare. The standard treatment for these patients remains controversial. In this study, we followed up the patients with PB-MJ without bile duct dilatation who mainly underwent a cholecystectomy alone. Eighteen adult patients with PB-MJ without bile duct dilatation (8 males and 10 females with a mean age of 54.8 years) were treated surgically. When the diameter of the common bile duct was less than 10 mm, such bile ducts were diagnosed to have no dilatation. The main clinical indications for surgery were cholecystolithiasis in 12 patients, choledocholithiasis in 3, cholecystocholedocholithiasis in 1, and carcinoma of the gallbladder in 2. The amylase levels of gallbladder bile in 14 patients ranged from 115 to 454,000 IU/ml. A simple cholecystectomy was performed in 12 patients, a cholecystectomy with bile duct drainage was performed in 3, a cholecystectomy with a choledochojejunostomy without bile duct resection was performed in 1, and a cholecystectomy with a lymph node dissection was performed in 2. Three patients died of other diseases. The remaining 15 patients have all been doing well for 20-209 months after surgery. In conclusion, a prophylactic resection of the extrahepatic bile duct and biliary diversion could be unnecessary for patients with PB-MJ without bile duct dilatation, when no bile stasis, such as choledocholithiasis, is observed.     

胆管非扩张型胰胆管合流异常诊治的进展

胆管非扩张型胰胆管合流异常 ,是否易引起胆管癌及胆囊癌 ?治疗上是否需要切除胆管、重建胆道的分流术 ?目前无统一的观点。笔者结合近年来的有关文献 ,就胆管非扩张型胰胆管合流异常诊治的进展做一综述。     

Long-term results of treatment for pancreaticobiliary maljunction without bile duct dilatation

HYPOTHESIS: Resection of the gallbladder together with the dilated bile duct is the preferred treatment for pancreaticobiliary maljunction (PBM) with bile duct dilatation, whereas this treatment for PBM without bile duct dilatation is still controversial. DESIGN: Retrospective study of 196 patients from January 1979 to November 2004. SETTING: Two university hospitals. PATIENTS: One hundred ninety-six patients with PBM, 152 (78%) with and 44 (22%) without bile duct dilatation, formed the basis of this study. MAIN OUTCOME MEASURES: The effects of cholecystectomy on long-term results in the patients without bile duct dilatation. RESULTS: Significant differences were observed in patients without bile duct dilatation: patients were older, carcinoma of the gallbladder was more prevalent (19 patients [43.2%] without dilatation vs 9 patients [5.9%] with dilatation), and pancreatic cancer and pancreatitis were also more frequent. Most of their gallbladder carcinomas were found at stage IV (63%). The outcome was very poor in stage IV, whereas 5 patients in stage I and II lived for more than 5 years after surgery. Of the 44 patients without bile duct dilatation, 23 with carcinoma of the gallbladder or pancreas died and the other 2 were lost to follow-up. The remaining 19 patients were alive at the study's conclusion after cholecystectomy without bile duct resection. None of them had bile duct carcinoma at the time of surgery or during the mean follow-up period of 9 years after surgery. CONCLUSIONS: Prophylactic cholecystectomy without bile duct resection is the best treatment option for patients with PBM without bile duct dilatation. Possible association of gallbladder carcinoma should be kept in mind at the time of treatment of patients with PBM when the bile duct is not dilated.     

Anomalous biliary drainage associated with pancreaticobiliary maljunction and nondilatation of the common bile duct

A case report is presented of an infant with jejunal atresia and hyperbilirubinemia with diagnosed pancreaticobiliary maljunction without choledochal dilatation. Common channel insertion was into the third portion of the duodenum.     

胰胆管合流异常对胆囊损伤的实验研究

胰胆管合流异常(anomalous pancreaticobiliaryductal union,APBDU)时主胰管与胆总管汇合成过长的共同通道,胆汁和胰液互流,引起多种胰胆系统病变.APBDU胆管癌的发生率高于正常人,且发生年龄也比正常人提前.尽管对APBDU进行了大量研究,其机制还未完全明了.以往的研究大多限于临床病例资料回顾,已有的动物模型与人类的生理解剖结构有较大差异~([1]).     

胰胆管合流异常之胆囊炎患者胆囊黏膜增殖性变化

目的 观察合并胰胆管合流异常之胆囊炎患者胆囊黏膜增殖性的变化.方法 对照观察4年间胰胆管合流异常与胰胆管汇合部正常之成人胆囊炎患者中的胆囊黏膜增殖细胞核抗原(proliferating cell nuclear antigen.PCNA)染色切片,比较两者间增殖性的差异.结果 4年内通过术中胆道造影及内镜逆行胰胆管造影检查检出17例胆囊炎合并胰胆管合流异常患者,其增殖细胞核抗原阳性率为(32.05±5.17)%;而另17例经检查明确胰胆管汇合部正常之成人胆囊炎患者则为(24.16±6.33)%;精确卡方检验显示两组间胆囊黏膜增殖性差异有统计学意义(P＜0.01).结论 胆囊炎患者胆囊黏膜增殖性在合并胰胆管合流异常者高于胰胆管汇合部正常者.     

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     

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.     

肌球蛋白在胰胆管合流异常患儿胆总管平滑肌中表达的改变

目的:观察胰胆管合流异常(PBM)患儿胆总管平滑肌肌球蛋白重链(MHC)与磷酸化肌球蛋白20 kD轻链(P-MLC20)表达的情况.方法:收集16例儿童PBM胆总管标本,以16例新生儿尸体胆总管标本为对照,免疫组化染色后用图像分析系统检测分析两种组织中MHC和P-MLC20表达;用Western blot法检测两种组织中P-MLC20的蛋白表达.结果:MHC与P-MLC20蛋白表达免疫组化图像分析系统定量分析结果显示,除两者的平均光密度(MOD)组间无差异外(均P＞0.05),PBM组两者的平均阳性面积比例(MLI)与阳性染色得分(MQS)均明显高于对照组(均P＜0.05);Western blot显示PBM组中P-MLC20蛋白表达量较对照组明显增高(P＜0.05).结论:PBM患儿胆总管平滑肌MHC与P-MLC20蛋白表达增高,该改变可能导致了胆总管平滑肌的收缩力代偿性增加.     

p53 gene mutation and p53 protein overexpression in a patient with simultaneous double cancer of the gallbladder and bile duct associated with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. We present a case of simultaneous double cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice, intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8. The bile duct cancer revealed a well-differentiated adenocarcinoma without mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53 gene in non-cancerous epithelia. In contrast, only the mucosa of the common channel had p53 protein accumulation and high cell proliferation activity. Therefore, the genetic pathway might be the same in both the gallbladder and bile duct cancer, and a high potential for carcinogenesis might be present in the epithelium of the common channel in patients with PBM.     

Advanced bile duct carcinoma in a 15-year-old patient with pancreaticobiliary maljunction and congenital biliary cystic disease

We report a case of advanced bile duct carcinoma arising in a 15-year-old female with pancreaticobiliary maljunction and congenital biliary cystic disease. Pancreaticoduodenectomy and partial resection of the liver was performed. Surgical and histopathological findings indicated advanced tubular adenocarcinoma, classified as final stage IVb according to the General rules for surgical and pathological studies on cancer of the biliary tract proposed by the Japanese Society of Biliary Surgery, 5th edition, and stage IV according to the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC), 6th edition. She underwent chemotherapy with gemcitabine HCl after discharge. She died of cachexia 14 months after the surgery. Although it is well known that biliary malignancies arise frequently in patients with pancreaticobiliary maljunction, it is uncommon for advanced bile duct carcinoma to occur in a 15-year-old female. We should pay attention to the possibility of biliary malignancy in patients with pancreaticobiliary maljunction and congenital biliary cystic disease, even when the patients are juveniles.     

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

We report a 64-year-old woman with double cancer of the gallbladder and the common bile duct associated with anomalous junction of the pancreaticobiliary ductal system. Eleven previous cases have been reported to date. From analysis of the 12 cases reviewed, including our patient, double cancer of the gallbladder and the common bile duct accompanied by anomalous junction of the pancreaticobiliary ductal system is characterized by the predominance of well-differentiated and superficial cancer.     

A case report of gallbladder cancer and pancreas cystic neoplasm associated with pancreaticobiliary maljunction

Introduction and importancePancreaticobiliary maljunction (PBM) is a rare congenital anomaly that is frequently associated with carcinoma of the biliary tract. However, there is still no clear evidence that PBM is associated with pancreatic tumors. Here we describe a case of gallbladder cancer and intraductal papillary mucinous neoplasm (IPMN) that is associated with PBM.Case presentationA 72-year-old man underwent a cholecystectomy with hepatectomy (S4a + S5) and regional lymph node dissection for gallbladder adenocarcinoma invading the front lobe branch of the hepatic artery. A pylorus-preserving pancreaticodudenectomy was also performed for pancreatic IPMN.Clinical discussionPresence of mucin type 6 (MUC6) -positive pyloric gland metaplasia in both the dilated pancreatic duct and the gallbladder background mucosa suggests that pancreatic IPMN and gallbladder cancer may have a common phenotypic origin. Additionally, analysis of 41 reported cases of pancreatic cancer associated with PBM revealed that in all metachronous multiple cancer cases, biliary tract cancer preceded the pancreatic cancer with congenital biliary dilatation accompanied by PBM. The analysis also revealed an increased proportion of pancreatic cancer cases with PBM in patients who had not undergone a flow diversion procedure located in pancreatic head.ConclusionWe show an interesting relationship between pancreatic/gallbladder cancer and PBM. More comprehensive evaluations of the whole pancreaticobiliary system in follow-up of patients with PBM is required to understand the full extent of this relationship.     

Cell kinetic study of the gallbladder epithelium, with special reference to the pancreaticobiliary maljunction

The bromodeoxyuridine labelling index (BrdU-LI), ornithine decarboxylase (ODC) activity, and bile elements in the gallbladder were examined in 23 patients to investigate cell kinetics and oncogenesis in gallbladder epithelium with pancreaticobiliary maljunction (PBMJ). The patients were classified into five groups: group I (4 patients without biliary disorder), group II (8 patients with cholecystolithiasis), group III (4 patients with PBMJ), group IV (3 patients with gallbladder cancer and PBMJ), and group V (4 patients with gallbladder cancer). In non-cancerous epithelium, the BrdU-LI in groups III (2.88±3.07%), IV (4.92±2.73), and V (5.93±2.08) was significantly higher than in group I (0.06±0.12), and the ODC activity in groups III (7.83±6.82 pmole CO₂/h per mg protein), IV (17.21±9.44), and V (11.27±12.33) was also significantly higher than that in group I (1.39±1.78). Both BrdU-LI and ODC activity were high in epithelium showing metaplasia in 3 patients from groups III and IV. In groups I and II, the lithocholic acid (LCA) fraction showed a positive correlation with BrdU-LI (correlation coefficient, 0.90) and ODC activity (correlation coefficient, 0.91). From these results, it can be concluded that the gallbladder epithelium in patients with PBMJ, and its metaplastic changes, show an increase in cell proliferation, which is important in the progression of cancer.     

胰胆管合流异常合并胆囊床迷走胆管致术后胆汁漏

LG是治疗胆囊结石和慢性胆囊炎的有效方法。回顾性分析2012年8月解放军第八十八医院收治的1例因胰胆管合流异常以及胆囊床迷走胆管致LC术后胆汁漏、腹腔感染患者的临床资料,旨在探讨比类疾病的正确诊断和治疗方法。     

Surgical treatment for anomalous arrangement of the pancreaticobiliary duct with nondilatation of the common bile duct

Background/purpose

For anomalous arrangement of the pancreaticobiliary duct (AAPBD) with nondilatation of the common bile duct (CBD), the optimal surgical procedure remains controversial. The authors investigated which procedure would be most effective for AAPBD with nondilatation of the CBD.

Methods

The authors encountered 60 children with AAPBD in our institution between 1979 and 2002. Six of the 60 were classified as the nondilated type (CBD diameter; less than 8 mm), whereas the other 54 were classified as the dilated type (CBD diameter; more than 9 mm). Amylase levels in serum, CBD, and gallbladder were examined. Cellular activity of the resected gallbladder was examined for the incidence of hyperplasia and Ki-67 labeling index (Ki-67 LI).

Results

The amylase level in the nondilated type was elevated as in the dilated type. Epithelial hyperplasia of the gallbladder was present in 4 of the 6 with the nondilated type (67%). 10 of the 20 with the dilated type (50%), and none of the 6 controls (0%). The Ki-67 LI of the dilated type was significantly higher than that of control.

Conclusions

A free reflux of pancreatic juice into the biliary system was found regardless of dilatation, and cellular proliferative activity of the gallbladder mucosa was increased in both the nondilated and dilated type. Therefore, excision of the extrahepatic bile duct including cholecystectomy is recommended for AAPBD with nondilatation of the CBD.