胰胆管合流异常与胆胰肿瘤发生的研究进展

近年来，随着磁共振胰胆管成像( magnetic resonance cholangiography,MRCP) 和内镜逆行性胆管胰管造影术( endoscopic retrograde cholangiopancreatography, ERCP)等影像学检查的广泛应用，胰胆管合流异常(pancreaticobiliary realjunction，PBM)病例的检出率有较大幅度提高，PBM与胆胰部疾病的相关性也越来越引起重视。胰胆管合流异常的概念首先由Kozumi和Kodama于1916年提出，他们是从先天性胆管囊肿的病例中发现胰胆管汇合的异常。直到1969年，Babbitt等从病因学方面报道了PBM与先天性胆总管囊肿的相关性后，PBM才开始作为一个独立的疾病诊断，无论其是否合并有胆管囊肿。随后的研究也表明，PBM不仅与先天性胆总管囊肿有关，还与胆道结石、胆囊炎、急慢性胰腺炎等多种疾病的发生相关。最近许多研究者发现PBM与胆胰部恶性肿瘤的发生有着密切的关系[2，3]，这为研究胆胰肿瘤发生的机制提供了新的思路，现综述如下。     

儿童胆总管囊肿51例ERCP分析

目的 了解儿童胆总管囊肿的分型、胆管胰管汇合方式与胆总管囊肿形态关系,及胆总管囊肿并发症发生率,探讨儿童胆总管囊肿ERCP检查的诊断价值. 方法 回顾分析1998年6月至2003年3月长海医院ERCP检查诊断儿童先天性胆总管囊肿51例图像及随访资料. 结果 成功行ERCP 45例,行逆行胆管造影(ERC)6例.胆总管囊肿分型,Ⅰ型41例,其中Ⅰ a 17例,Ⅰ b 10例,Ⅰ c 14例.Ⅳ型10例,其中Ⅳa 8例、Ⅳb 2例.合并胰胆管合流异常37例,占82.2%,合流方式为B-P型21例,P-B型16例.并选定Ⅰ c型为胆总管柱状扩张组;Ⅰ a+Ⅰ b+Ⅳ型均为囊状扩张组,对照分析,柱状扩张中P-B型占80%,囊状扩张中B-P型占70.4%.合并有胆道结石8例,胰管扩张2例.测量胰胆管合流异常共同管长度=0.5 cm 4例,>0.5cm且<1.5 cm 20例,≥1.5 cm 13例.14例随访病例中,未发现急性胰腺炎及出血、穿孔等严重并发症. 结论 儿童先天性胆总管囊肿Ⅰ型最多见,且大多数合并胰胆管合流异常.胆管柱状扩张中P-B型较常见,胆管囊状扩张中B-P型较常见.ERCP检查对儿童胆总管囊肿诊断安全有效.     

小儿先天性胆管扩张症的基础研究

先天性胆管扩张症(congenital biliary dilatation,CBD)又常称为先天性胆总管囊肿(congenital choledochal cyst,CCC),近期许多研究表明本病大多有胰胆管合流异常(pancreaticobiliary maljunction,PBM),而且亚洲国家发病率较西方国家高,婴幼儿及童年时期发现诊断为CBD者约占2/3.目前对本病的诊断和治疗已不存在困难,关键是如何预防CBD的发生,因而对CBD的形成机制和病因研究以及远期癌变问题已成为现今基础研究的主要问题.     

胰胆管合流异常与胆管囊肿的关系及诊治进展

胰胆管合流异常( pancreaticobiliary maljunction,PBM)是指胰管和胆管在十二指肠壁外合流,通常明显伴有一个长的共同通道.由于胰胆汇合部失去Oddi括约肌的控制,胰液和胆汁的逆流持续发生,导致胆道和胰腺的各种病理变化.PBM和胆管囊肿(choledochal cyst,CC)的关系密切,但两者之间的病因学关系仍然不清楚.另外,PBM被认为是导致胆道肿瘤的高危因素.虽然共同管长度和胆汁淀粉酶是诊断PBM的重要依据,并且完全胆囊、囊肿切除,肝管空肠Roux-Y吻合术这一术式已被广泛采用,但仍存有争议.现就PBM与CC的关系研究进展作一综述.     

小儿先天性胆管扩张症的基础研究

先天性胆管扩张症(congenital biliary dilatation,CBD)人们又常称为先天性胆总管囊肿(congenital choledochal cyst,CCC),近期许多研究表明本病大多有胰胆管合流异常(pancreaticobil-iary maljunction,PBM),而且亚洲国家发病率较西方国家高,婴幼儿及童年时期发现诊断为CBD者约占2/3。目前对本病的诊断和治疗已不存在困难,关键是如何预防CBD的发生,因而对CBD的形成机制和病因研究以及远期癌变问题已成为现今基础研究的主要问题。一、动物模型的制作自1969年Bakitt通过胰胆管造影首次提出“胰胆管合流异常”的概念以来[1],人们先后已…     

胰胆管合流异常与胰胆管疾病的关系

自Babbitt[1]1969年首次报道胰胆管合流异常(anomalouspancreaticobiliary ductal uion,APBDU)以来,人们发现APBDU与许多胆道及胰腺疾病密切相关。近年来,随着MRCP、ER-CP、PTC等影像学技术的发展和广泛应用,有关的报道逐渐增多[2],对APBDU又有了更进一步的认识。APBDU的基本概念解剖学上APBDU是指胰胆管共同通道在十二指肠壁外合流,造成共同通道过长,使十二指肠乳头括约肌的作用不能影响到整个合流部,胆汁、胰液相互逆流而引起胆道及胰腺的各种疾病。APBDU分为两型:①P-C型,即胰管注入胆总管型;②C-P型,即胆总管注入胰…     

成人先天性胆管扩张症与胰腺炎发作的关系

目的探讨先天性胆管扩张症(CCC)与胰腺炎发作的关系及其外科治疗方法。方法回顾性分析1997年6月—2005年12月期间收治的17例CCC患者的临床资料。17例患者术前均经B超和磁共振胰胆管造影(MRCP)检查明确诊断,其中4例行腹部CT检查,术中造影检查6例,2例行内镜下胰胆管造影(ERCP)。结果先天性胆管扩张症Ⅰ型10例,Ⅱ型4例,Ⅲ型1例,Ⅳ型1例,Ⅴ型1例;其中14例合并胆囊、胆管结石(11例为泥沙样色素结石,3例为胆固醇结石),5例合并慢性胆囊炎,1例合并胆囊息肉,10例合并胰胆管合流异常(APBJ),10例(58.8%)合并胰腺炎发作。行胆总管囊肿切除和胆肠内引流手术治疗14例,行保留幽门胰十二指肠切除术1例,行胆囊切除术加T管引流术2例。术后随访中14例无胰腺炎发作,2例仍有胰腺炎发作,1例意外死亡。结论合并有APBJ和泥沙样结石的CCC患者容易发生急性胰腺炎,对CCC合并APBJ患者行胆总管囊肿切除、胆囊切除术和胆道Roux-en-Y内引流术可减少胰腺炎发作。     

术中造影在先天性胆总管囊肿根治切除术中的应用价值

目的探讨术中胆道造影在确立胆总管囊肿的病理特征与胆胰管合流异常的价值 ,并用于指导术式选择。方法对胆总管囊肿患儿进行术中胆胰管造影检查 ,记录胆管病变形态和胆胰管合流异常类型。结果 82例胆总管囊肿按Todani分型 :Ⅰa型 35例、Ⅰb型 9例、Ⅰc型 2 8例及Ⅳ型 10例。确定胆胰管合流异常 73例 ,按Komi分类 :Ⅰ型 37例、Ⅱ型 30例及Ⅲ型 6例。 4 4例胆管囊状扩张中胆胰管合流异常Ⅰ型 33例 ,2 9例胆管梭形扩张中Ⅱ型 2 1例 ,2 1例合并有胰腺炎发作者中胆胰管合流异常Ⅱ型 17例。 14例合并肝内胆管狭窄者同时行胆管成形术。结论术中造影简便易行 ,可以明确诊断 ;不同的胆胰管合流异常类型可导致不同形式的胆胰管病变 ;对术中指导根治切除囊肿、避免损伤胆胰管连接部和处理肝内胆管狭窄有重要参考价值。     

胰胆管合流异常的病理特征与诊治进展

胰胆管合流异常 (pancreaticobiliary maljunction,PBM)是胰管和胆总管异常汇合的一种先天性畸形 [1 ]。从 1916年 Kizu-mi首先提出 PBM这一概念 ,至 1978年日本学者因此成立“胰胆管合流异常研究会”,PBM已日渐引起国内外广泛关注 ,对PBM基础及临床的研究正逐步深入。1　PBM的病理特征约 75 %的正常人胆总管与主胰管在十二指肠粘膜下汇合成共通管 ,并随着年龄逐渐增长。共通管周围及近端具有 Oddi氏括约肌 ,其中胆总管括约肌部分恒定存在 ,在神经与体液双重因素的调节下可控制胆汁的正常排出 ,亦可防止胰液逆流入胆管。据 1991年日…     

胰胆管合流异常合并胆道肿瘤的诊断与治疗

目的 阐述胰胆管合流异常这种解剖学异常的临床分型与其所导致胆道肿瘤的关系，探讨如何选择适当的、合理的手术治疗。方法 回顾性分析我院自1979年12月至2001年10月间所收治的64例胰胆管合流异常症病人的临床表现、影像学特点和分型与其合并胆道肿瘤的关系。结果 本组病人中：胰管型(P-C型)28例，合并胆道肿瘤11例；胆管型(C-P型)32例，合并胆道肿瘤8例；共同通道型4例，胆道肿瘤2例。结论 胰胆管合流异常同胆道肿瘤的发生关系密切。胰、胆管合流异常病人的临床分型不同，所导致的胆道肿瘤发生的可能性不同。     

胰胆管合流异常与胰腺炎发病的关系

目的探讨无胆管扩张型的胰胆管合流异常与急性胰腺炎的发病关系。方法回顾分析1995年1月—2004年1月期间经影像学检查确认的72例无胆管扩张型的胰胆管合流异常病例。结果无胆管扩张型的胰胆管合流异常的发生率为2.7%。逆行胰胆管造影检查发现率为2.5%、术中胆道造影发现率为2.8%、磁共振胆胰管成像发现率为2.4%。72例中胰管汇入胆总管型43例、胆总管汇入胰管型29例。本组急性胰腺炎的发生率为35%,胆囊结石的发生率为74%。结论具有无胆管扩张型的胰胆管合流异常者急性胰腺炎的发生率很高;反复发作胰腺炎而无明显诱因时,应考虑有胰胆管合流异常的存在;胆囊切除术是预防胰腺炎的有效方法。     

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.     

Congenital choledochal dilatation with emphasis on pathophysiology of the biliary tract.

Of 37 patients with congenital choledochal dilatation, aged 8 days to 12 years, who had undergone excision with Roux-en-Y hepaticojejunostomy, 26 patients could be analyzed for morphologic abnormalities and pathophysiology of the biliary tract. Of the 26 patients with congenital choledochal dilatation, 25 (96.2%) had an abnormal choledochopancreaticoductal junction. Of the 12 patients with cystic-type choledochal dilatation, 10 had the C-P type of abnormal choledochopancreaticoductal junction, and of the 13 patients with fusiform-type choledochal dilatation, nine had the P-C type. The amylase levels in the choledochal cyst and the gallbladder were elevated regardless of the form of choledochal dilatation. An adenocarcinoma in a cystic choledochal dilatation was found in one child. Therefore, longstanding inflammation of the biliary tract caused by the reflux of pancreatic juice might be one of the factors in carcinogenesis in the biliary tract. This free reflux of pancreatic juice was demonstrated not only by amylase levels in the biliary tract but also by intraoperative biliary manometry. This reflux might be explained by the lack of sphincter function at the junction of the common bile and pancreatic ducts.     

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.     

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??Etiology relationship and principles of treatment of pancreatic and biliary anomalous junction and choledochal cyst LI Long, ZHANG Jin-shan. Pediatrics Surgery of Capital Institute, Beijing 100020, China
Corresponding author: LI Long, E-mail??zjs851@163.com
Abstract Choledochal cyst (CC) is a pathologic condition characterized by varying degrees of congenital dilatation of the biliary system. Most of the reported cases come from Asia and its etiology remains unclear. Some people suggested that CC is a result of weakness of the wall and the distal obstruction of the common bile duct. But its underlying precise mechanisms remain unclear. The pathogenetic implications of pancreaticobiliary maljunction (PBM) is a popular hypothesis: In PBM, the common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall; in such cases, sphincter action does not functionally affect the junction. As the hydropressure within the pancreatic duct is usually greater than in the bile duct, pancreatic juice frequently refluxes into the biliary duct (pancreatobiliary reflux) in PBM, resulting in the incidence of lesion in the wall of the common bile duct and dilatation of the common bile duct. Currently, most scholars tend to believe the ectopic hepatic diverticulum may cause the primitive common bile duct and common channel to become stretched, producing a long common bile duct and a long common channel. If growth of the epithelium in the common bile duct fails to keep up with the anomalous elongation during embryonic, the duct may become attenuated, resulting in stenosis and weakness of the wall, and eventually dilatation. In treatment, the cyst excision with Roux-en-Y hepatoenterostomy is the standard surgical method for choledochal cyst. To reduce the post-operative complications, doctors need to learn about the changes of the biliary system, deal with the abnormality in the intrahepatic bile duct, pancreatic duct and common channel. Laparoscopic surgery has become a successful method in treatment of choledochal cyst.     

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.     

Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis

BACKGROUND: Pancreaticobiliary maljunction (PBM) is frequently associated with congenital choledochal cyst (CCBD), but differs in embryonic cause and clinical features. It is thought to develop as a misarrangement of the embryonic connections in the pancreaticobiliary ductal system, with the terminal bile duct joined to one of the ducts of the ventral pancreas. Clinical aspects are intermittent abdominal pain, relapsing acute pancreatitis, jaundice, cholangitis, and gallbladder cancer. In patients with PBM and CCBD, primary bile duct stones, acute cholangitis, and bile duct cancer are considered to result from cholestasis, regurgitation of pancreatic juice, and reciprocal reflux of bile and pancreatic juice. The mixture of bile and pancreatic juice due to recipocal reflex very likely plays an important role in biliary carcinogenesis. PATIENTS AND METHODS: We reviewed the pathophysiological and clinical aspects and biliary carcinogenesis in 250 PBM patients (169 with benign hepatobiliary and pancreatic disease, 81 with malignancy). RESULTS: PBM patients show elevated cellular proliferation activity in the gallbladder epithelia. A number of oncogenes and tumor suppressor genes have been identified and implicated in carcinogenesis, particularly the K- ras oncogene and the p53 suppressor gene. Some K- ras mutations do not appear essential for hyperplasia but may be an early event in carcinogenesis. The p53 mutations are involved in carcinogenesis in the biliary epithelium in PBM patients.     

Anomalous union of the pancreaticobiliary duct without choledochal cyst: is cholecystectomy alone sufficient?

Purpose

Anomalous union of the pancreaticobiliary duct (AUPBD) is frequently associated with choledochal cyst and biliary tract cancers. Management of AUPBD with choledochal cyst consists of extrahepatic bile duct excision and cholecystectomy. In cases of AUPBD without choledochal cyst, cholecystectomy alone is usually recommended. This study aimed to evaluate the occurrence of biliary tract cancer in AUPBD patients in order to assess the validity of the currently recommended operative management.

Methods

Of a total of 10,255 endoscopic retrograde cholangiopancreatography cases performed at two Korea University hospitals from 2001 to 2010, 55 (0.54 %) cases of AUPBD were identified. Patients with AUPBD were divided according to its subtype (P-C union and C-P union) and the presence of choledochal cyst for analysis. The occurrence of benign and malignant disease was evaluated and compared between the groups.

Results

Gallbladder stones were more frequently found in AUPBD patients without choledochal cyst (p?=?0.032). Biliary tract cancer occurred more frequently in P-C union (p?=?0.050), especially the common bile duct cancer (p?=?0.023). When analyzed according to the presence of choledochal cyst, biliary tract cancer occurred more frequently in AUPBD patients without choledochal cyst (p?=?0.005), with bile duct cancer being significantly more common (p?=?0.015). However, there was no difference in the presence of gallbladder cancer between the two groups (p?=?0.318).

Conclusions

Since cancers of the biliary tract occur more frequently in the AUPBD group without choledochal cyst, cholecystectomy alone may not be protective of the future occurrence of bile duct cancers, and thus, vigilant surveillance is necessary in this population group.     

Prophylactic excision of the gallbladder and bile duct for patients with pancreaticobiliary maljunction.

HYPOTHESIS: Pancreaticobiliary maljunction (PBM) is a high-risk factor for biliary tract carcinogenesis because of a continuous reflux of pancreatic juice into the biliary tract. It remains to be disclosed whether we should perform prophylactic excision of gallbladders and bile ducts. DESIGN: A person-year method. SETTING: A university hospital. PATIENTS: We studied 68 patients with PBM treated between August 1, 1974, and December 31, 1999. MAIN OUTCOME MEASURES: Relative risks (observed number-expected number ratios) of gallbladder and bile duct carcinomas according to type of bile duct dilation (ie, cystic dilation, diffuse dilation, and nondilation). RESULTS: Observed number-expected number ratios of gallbladder carcinomas were high: 291.3 in 43 patients with cystic dilation, 167.2 in 16 patients with diffuse dilation, and 419.6 in 7 patients with nondilation. Observed number-expected number ratios of bile duct carcinomas were 194.2 in 43 patients with cystic dilation before surgery and 142.8 in 39 patients with cystic dilation after long postsurgical follow-up. All these values were statistically significant (P<.01). CONCLUSIONS: The gallbladder carries a high risk for carcinogenesis in all types of dilation in patients with PBM. The bile duct carcinomas of PBM were exclusively identified by the type of cystic dilation. Prophylactic cholecystectomy should be recommended for all dilation types, and prophylactic excision of bile ducts including cholecystectomy should be performed in patients with PBM and cystic dilation. Complete excision of extrahepatic dilated bile ducts and careful follow-up for carcinogenesis in residual dilated bile ducts should be recommended for patients with PBM and cystic dilation.     

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.