EARLY BILE DUCT CARCINOMA

The clinocopathologic features of seven patients with early bile duct carcinoma are reported. Early bile duct carcinoma has been defined as bile duct carcinoma limited to the bile duct wall. The seven patients included six men and one woman ranging in age from 44 to 77 years. Six patients complained of jaundice and the other presented with right hypochondralgia. Ultrasonography showed a dilated proximal bile duct in the seven with a polypoid mass in three. Computerized tomography showed a dilated biliary tree in the seven together with a polypoid mass in two. Direct visualization of the bile duct with endoscopic retrograde cholangiography and/or percutaneous transhepatic cholangiography showed a polypoid tumour of the bile duct and a dilated proximal biliary tree in all seven. Each of the seven polypoid tumours were well differentiated papillary or tubular adenocarcinoma restricted to the bile duct wall with minimal stromal invasion. There was neither any lymph node metastasis nor perineural invasion. Five of the seven patients were doing well at 24–112 months after a complete resection. One patient died from multiple liver metastases 21 months after intervention. The other patient died from other diseases 138 months after operation. These seven cases can be classified as early bile duct carcinoma due to both the limited invasion and favourable prognosis. The clinical features of the seven patients were quite similar to those of usual bile duct carcinoma. However there are still no proper diagnostic clues for early bile duct carcinoma and these patients represent fortunate cases that clinicians happened to discover by chance.     

ARE SECONDARY BILE ACIDS IN CHOLEDOCHAL CYSTS IMPORTANT AS A RISK FACTOR IN BlLlARY TRACT CARCINOMA?

Since secondary bile acids have mutagenic potency and choledochal cyst patients with or without cyst-enterostomy have a high risk of developing bile duct carcinoma, we examined the hypothesis that secondary bile acids are elevated in the choledochal cyst and possibly cause biliary tract carcinoma. Eleven choledochal cyst patients with or without previous cyst-enterostomy or biliary tract carcinoma, seven patients with biliary tract carcinoma not associated with choledochal cyst and five patients with cholecystolithiasis were examined. Samples were directly needle aspirated from the cyst or by cannulating a tube into the common bile duct through the cystic duct. The concentrations of each bile acid in these samples were quantified by gas-liquid chromatography and compared. Neither the relative composition nor the absolute concentration of secondary bile acids (deoxycholic acid, lithocholic acid) elevated in patients with choledochal cyst compared with the values in the non-choledochal cyst patients with or without biliary tract carcinoma. The presence of biliary tract carcinoma or previous cyst-enterostomy did not affect the concentrations of secondary bile acids. The results suggest that the factor other than secondary bile acids can be primarily responsible for the high risk of bile duct carcinoma in patients with choledochal cyst.     

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.     

Anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract

A rare case of anomalous arrangement of the pancreaticobiliary ductal system without dilatation of the biliary tract (AAPBDS without DBT) associated with mucosal dysplasia of the biliary duct is described herein. A 53 year old male with a long history of diarrhea and right upper abdominal pain was diagnosed as having AAPBDS without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y hepatico-jejunostomy was performed and subsequent pathological examination of the surgical specimens showed mucosal hyperplasia of the gall-bladder and mucosal dysplasia of the biliary duct. Considering the dysplastic changes of the biliary duct as seen in our case, and the high incidence of AAPBDS without DBT developing into carcinoma of the biliary duct, being 12.2 per cent, we suggest that pancreaticobiliary ductal diversion with excision of the gall-bladder and biliary duct should also be performed for AAPBDS without DBT. However, further pathological investigations concerning the excised biliary duct in AAPBDS without DBT will be need to be carried out.     

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     

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct(type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the doudenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.     

原发性肝癌合并胆管内癌栓12例临床分析

目的探讨原发性肝癌继发胆管癌栓的临床特点和诊治要点。方法回顾性分析1990～2003年12例HCC伴癌栓的外科治疗情况。结果本组原发性肝癌合并胆管内癌栓的发生率为4．69％(12／256)．术前确诊牢为25％(3／12)．肝癌切除加胆管癌栓清除术8例,肝癌切除加肝外胆管切除．胆肠内引流1例．单纯胆总管切开取栓术3例。术后1年生存率66．7％(8／12)．3年生存率25％(3／12),其中1例生存已超过5年。结论原发性肝癌伴胆管内癌栓十分少见．术前易误诊．手术治疗不失为一种积极有效的治疗方法。     

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.     

Preoperative cholangiography of the caudate lobe: Surgical anatomy and staging for biliary carcinoma

The biliary branches of the caudate lobe (B1) join the right hepatic duct, the left hepatic duct, the confluence of these ducts, and/or the right posterior segmental bile duct. Therefore, in the preoperative staging of biliary tract carcinoma it is important to delineate the anatomy of B1 and the extent of cancer spread into B1. Tube cholangiography through percutaneous transhepatic biliary drainage or selective cholangiography by percutaneous transhepatic cholangioscopy enables us to obtain fine images of B1. We have developed cholangiography in the cephalad anterior oblique position to visualize B1 more clearly and distinctly. Four separate types of biliary branches are identified in the caudate lobe: (1) A duct running from the cranial portion of the right caudate lobe along the inferior vena cava to the hepatic hilus (B1r); (2) a duct from the cranial portion of the left caudate lobe to the hepatic hilus (B1ls); (3) a duct from the left lateral part of the left caudate lobe to the hepatic hilus (B1li); and (4) a duct from the caudate process to the hepatic hilus (B1c). The findings of the root of B1 in resected patients with biliary tract carcinoma were classified into four groups: not stenotic, short segmental stenosis, long segmental stenosis, and poorly imaged. A study of 64 branches of B1 in 42 resected patients with biliary tract cancer revealed carcinoma invasion in or near the root of B1 in all patients with poorly imaged or long segmental stenosis of B1, and in 33% of those with short segmental stenosis of B1.     

Indication for and problems of hepatopancreatoduodenectomy for carcinoma of the biliary tract based on the statistical registry in Japan

Hepatopancreatoduodenectomy (HPD) as radical surgery for advanced carcinoma of the biliary tract was previously eschewed due to the high rate of postoperative complications. However, recently many institutes have performed it due to the improvement of operative procedures, such as hepatectomy and pancreatoenterostomy, and of pre-intra-postoperative management. Four hundred and sixty-five patients undergoing HPD were registered in Japan during the past 10 years, of whom 355 had carcinoma of the gallbladder and 110 carcinoma of the bile duct. The 30-day operative mortality rate was 9.2% (43 patients). The 5-year survival rates according to the Kaplan-Meier method was 18.1% (32 patients). Survival rates of those with ss and se or si gallbladder cancer were 36% and more than 10%, respectively, but that of those with se or si bile duct cancer was less than 6%. Only 3 patients with 16 lymph node metastases survived for more than 5 years. Fewer patients with biliary infiltration survived for more than 5 years compared with those with hepatic infiltration in carcinoma of the gallbladder. For such patients, extended surgery combining so-called total resection of the hepatoduodenal ligament is thought necessary.     

原发性肝癌伴胆管癌栓致阻塞性黄疸的外科治疗

目的探讨原发性肝癌伴胆管癌栓致阻塞性黄疸的外科手术治疗及其治疗效果。方法回顾性对15例原发性肝癌伴胆管癌栓致阻塞性黄疸行外科手术治疗的总结和分析。结果行左半肝切除 胆总管切开取癌栓术5例,行肿瘤切除 胆总管切开取癌栓术7例,行胆总管切开取癌栓 肝总动脉结扎3例,术后随访2年,平均生存时间为14.5个月,最长存活23个月。结论外科治疗明显提高了患者生活质量,延长了生存时间。     

Status of surgical treatment of biliary tract cancer

Complete surgical resection of biliary tract carcinoma remains the best treatment. The Japanese Society of Biliary Surgery has organized a registry project and established a classification of biliary tract carcinoma. We report here the status of biliary surgery in Japan. For hilar bile duct carcinoma, major hepatectomy is needed to increase the resection rate, and total caudate lobectomy is required for curative resection. The 5-year survival rate was 39.1%. Middle and distal bile duct carcinomas were treated with pancreatoduodenectomy (PD) or pylorus-preserving PD (PPPD) or bile duct resection alone. The 5-year survival rate was 44.0%. The treatment of gallbladder carcinoma with pT1 lesions is cholecystectomy. The treatment of pT2 lesions is extended cholecystectomy or various hepatectomy with or without extrahepatic bile duct resection along with lymphadenectomy. Treatment of pT3 and pT4 lesions includes hepatectomy with or without bile duct resection, combined with vascular resection, extended lymphadenectomy, and autonomic nerve dissection. Several groups in Japan have performed hepatopancreatoduodenectomy. The 5-year survival rate of pT1, pT2, pT3, and pT4 were 93.7, 65.1, 27.3, and 13.8%. PD or PPPD is the standard operation for carcinoma of the papilla of Vater. The 5-year survival rate was 57.5%.     

胆道癌NDPK/nm23的表达及意义

目的　研究转移抑制基因ＮＤＰＫ／ｎｍ２３ 在胆道良恶性病变中的表达及与转移性的关系。方法　４３ 例胆囊腺癌,２０ 例胆管癌,８ 例胆囊腺瘤和５ 例胆囊炎的石蜡包埋组织切片,经免疫胶体金方法（ＩＧＳＳ）染色,并在显微镜下计数阳性细胞。结果　胆囊腺癌中ＮＤＰＫ 在转移性及非转移性肿瘤中的表达率分别为２３．５％ （４／１７） ,和３４．６％（９／２６） ,两者间无显著性差异（ Ｐ＞ ０．０５）,而胆管癌中分别为１４．３％（１／７）和４６．１％ （６／１３）,两者间有显著性差异（ Ｐ＜ ０．０５）。ＮＤＰＫ在良恶性病变中的表达无显著性差异,并与肿瘤的病理分级无关。结论　ｎｍ２３ 基因可能在胆囊腺癌和胆管癌的转移过程中起不同的调节作用,其表达程度与胆管癌的转移呈负相关而与胆囊腺癌的转移无关。     

Clinical problems in the surgical treatment of pancreaticobiliary maljunction

The results of surgical treatment of pancreaticobiliary maljunction at our department are described. The 67 patients who underwent surgery for this disease were divided by age into an adult group (45 patients, aged 16 years and over) and a pediatric group (22 patients, aged less than 16 years). The incidence of concomitant carcinoma before surgery and the incidence and severity of postoperative cholangitis were compared between these two groups. In addition, the cell proliferating activity of the biliary tract epithelium in cancer-free patients was compared between the two groups, using the proliferating cell nuclear antigen labeling index (PCNA LI). Ten patients (all adults) were diagnosed with cancer (gallbladder carcinoma in 7 and bile duct carcinoma in 3) before surgery. The surgical techniques used for reconstruction in the cancer-free patients were: in the adult group, hepaticoduodenostomy in 9 patients, Roux-en-Y hepaticojejunostomy in 17, jejunal interposition in 8, and another technique in 1. In the pediatric group, hepatico-duodenostomy was performed in 17 patients. Roux-en-Y hepaticojejunostomy in 3, and jejunal interposition in 2. Postoperative cholangitis occurred in 6 adults (including 2 with severe form) and 1 child (mild case). The PCNA LI of the biliary tract epithelium was high compared to control findings in the biliary tract epithelium of 10 adult patients without pancreaticobiliary maljunction. In the adult group with dilated extrahepatic bile ducts (n=10 examined) this index was 11.4% for the bile duct epithelium (control, 1.5%) and 12.7% for the gallbladder epithelium (control, 1.4%). In the adult group with non-dilated extrahepatic bile ducts (n=5 examined) it was 5.9% for the bile duct epithelium and 13.1% for the gallbladder epithelium. In the pediatric group (n=10 with extrahepatic bile duct dilatation) it was 7.5% for the bile duct and 9.7% for the gallbladder epithelium. (Differences from control values were all significant.) These results suggest that surgery for this disease should be performed as early as possible and that extrahepatic bile duct excision and biliary reconstruction should be performed whether or not extrahepatic bile ducts are dilated.     

Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice

We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 ± 10%) 3 months after the surgery compared with the preoperative PS (70 ± 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2–25 months). With respect to tumor location, the median survival time was 4 months (range, 2–25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12–22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection. Received: September 5, 2000 / Accepted: November 8, 2000     

胆管癌患者胆汁脱落细胞端粒酶活性和p53基因突变检测的临床意义

目的探讨胆汁中端粒酶活性和P53基因突变在胆管癌早期诊断中的价值。方法应用重复片段扩增法(TRAP)和PCR-SSCP-银染法检测、分析30例胆管癌患者及10例良性胆道疾病患者胆汁脱落细胞的端粒酶活性及P53基因突变情况。结果胆管癌组端粒酶阳性表达率60%,P53基因突变率50%,良性胆道疾病组无端粒酶活性表达及P53基因突变,两者比较有显著性差异(P<0.05)。胆管癌组胆汁细胞学检查分级和端粒酶活性及p53基因突变差异均有显著性(P<0.05)。胆管癌组胆汁端粒酶活性和p53基因突变之间有正相关关系(P<0.05)。结论胆汁中端粒酶活性和P53基因联合检测有助于胆管癌的诊断。     

胆汁CA19—9检测对胆道癌诊断价值的探讨

目的 探讨胆汁ＣＡ１９－９在胆道良恶性病变的诊断价值。方法 本研究选择手术及病理证实的胆道恶性肿瘤２６例，胆道良性病变９２例，正常健康人１３例，采用ＲＩＡ同时联合检测胆汁ＣＡ１９－９、ＣＥＡ，进行定量分析。结果ＣＡ１９－９的含量分界值为１２０００ｕ／ｍｌ，其敏感性，特异性分别为９２．３１％，７２．８３％；胆汁ＣＥＡ水平分界值为４９０ｎｇ／ｍｌ，其相应指标分别为５７．６９％、７８．２６％。胆汁ＣＡ１     

Small cell carcinoma of the cystic duct: A case report

Small cell carcinoma usually involves the lung and rarely affects the biliary tract, especially the cystic duct. In this article we report a case of small cell carcinoma of the cystic duct in a 46-year-old Japanese man. The patient presented with abdominal pain and jaundice. Imaging showed a small nodule in the cystic duct invading the common bile duct with dilatation of the proximal biliary tree. The hepatic artery and portal vein were free from invasion. Extended right hepatic lobectomy, cholecystectomy, and resection of the extrahepatic proximal bile ducts were performed together with lymph node dissection under the tentative diagnosis of carcinoma of the cystic duct. Histopathologic examination of the resected specimen revealed small cell carcinoma arising in the cystic duct and extending into the common bile duct. The postoperative clinical course was uneventful, and the patient is doing well without any signs of recurrence 1 year after the operation. To our knowledge this is the first documented case of a small cell carcinoma arising in the cystic duct.     

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.     

NON-IATROGENIC TRAUMA TO THE EXTRAHEPATIC BlLlARY TRACT

Between 1980 and 1991, 15 cases of non-iatrogenic extrahepatic biliary tract trauma have been managed at Westmead and the Royal Canberra Hospitals. There were seven cases of gall-bladder injury and eight bile duct injuries. Four cases resulted from penetrating trauma whereas 11 resulted from blunt trauma. Associated injuries were common. Cholecystectomy was the preferred method of management for gall-bladder injuries whereas the bile duct injuries were managed by a variety of techniques. There were three deaths in the series, mostly related to associated injuries. Bile duct injuries were associated with longer hospitalization than gallbladder injuries.