Clinical experience of intrahepatic cholangiocarcinoma associated with hepatolithiasis

Between 1960 and 1986, seven patients with intrahepatic cholangiocarcinoma and one patient with intrahepatic bile duct adenoma, related to hepatolithiasis, were seen among 112 cases of hepatolithiasis. Histopathologically, the tumors associated with hepatolithiasis arose from the periphery of the stone-containing bile duct, spread chiefly along the luminal surface, and invaded the ductal wall or periductal tissue. The tumors showed papillary to papillo-tubular proliferation and were diagnosed as the intraductal or periductal spreading type of cholangiocarcinoma. In addition, atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that chronic relapsing cholangitis in patients with hepatolithiasis can induce progressive changes to atypical epithelial hyperplasia which may develop into cholangiocarcinoma.     

肝内胆管结石并肝内胆管癌临床病理特征与外科治疗

目的 提高肝内胆管结石并肝内胆管癌（HLAIHCC）的诊治水平。方法回顾性分析珠江医院1993年1月至2004年11月26例HLAIHCC病人的病理及治疗。结果胆管癌发生处大多都有结石。大体分为三型：包块型、胆管周围浸润型与胆管内生长型，病理检查均为腺癌。17例病人行肝切除或广泛的肝切除和（或）肝外胆管切除，切除率65．4％，1年及5年生存率分别为82．3％和11．7％。结论肝内胆管癌与肝内胆管结石所引起的刺激、炎症、感染有一定关系，积极的手术切除是HLAIHCC理想的治疗方案。     

肝胆管结石合并胆管癌的临床特点及防治

目的 探讨肝内胆管结石合并肝内胆管癌的临床特点及其防治.方法 对1990-2009年肝内胆管结石伴肝内胆管癌84例的临床资料进行回顾性研究.结果 肝内胆管结石合并肝内胆管癌的发生率占同期肝内胆管结石病例的4.6%(84/1840),术前明确诊断47例;肿瘤均发生于含结石的胆管处,以左肝多见;病程1～40年,平均18年.20例迟发性肝内胆管癌发生于取石后6-16年,平均9年.临床表现为久治不愈的肝脓肿、难以控制的肝内感染、肝内阻塞性进行性黄疸和影像学提示结石部位的肿瘤性改变.84例中晚期病例65例(65/84,77.4%).行根治性切除者仅35例,姑息性切除26例,射频消融4例,单纯活检19例.结论 (1)肝内胆管结石并发肝内胆管癌的概率较高.(2)对所有肝内占位性病变行术前、术中活检是避免误漏诊的重要方法.(3)早期诊断者行根治性切除可获得良好疗效.(4)对肝内结石伴胆管狭窄、肝段萎缩纤维化者行病灶肝段切除对继发胆管癌有预防作用.     

结石与非结石性肝内胆管癌肝切除术的围手术期管理差异

肝胆管结石是指发生在左右肝管汇合部以上的结石病。该病可引起胆道梗阻及胆汁淤积,继而增加结石的发生率,而机械梗阻及反复炎症刺激将加重胆道梗阻,从而引起一系列严重的并发症,如胆管炎、肝萎缩、肝硬化等,甚至诱发胆管癌变。肝内胆管癌（ICC）是常见的肝脏恶性肿瘤,其起源于肝内胆管上皮,有着恶性程度高、手术根治率低、术后复发率高、预后差等特点,因此也成为影响国民健康的重大疾病。ICC的病因目前尚未明确,众多研究表明,肝胆管结石是ICC的高危因素之一,在结石长期的机械刺激及慢性炎症刺激下,胆管上皮沿着增生修复、不典型性增生、癌前病变的方向发展,并在此基础上,最终演变成ICC。因此,根据致病因素与结石相关程度将ICC分为结石性肝内胆管癌（HICC）和非结石性肝内胆管癌（NHICC）。外科手术仍是ICC的主要治疗方式,早期根治性肝切除术可有效提高ICC患者的总体生存率,改善预后。作为肝内胆管结石的高发地区,近年来HICC在我国的发病率也随之攀升,因而针对HICC的综合管理具有十分重要的临床意义。基于上述背景,本文以HICC为中心,归纳出HICC与NHICC的围手术期处理要点差异,以期为HICC患者在整个肝切除术的围手术期内提供个体化、精准化的围手术期管理方式,从而达到提高诊断率、精准治疗、加速康复、改善预后的目的。     

CK7和CK20在肝内胆管癌及肝内胆管结石旁胆管组织中的表达

目的：探讨细胞角蛋白7（CK7）、细胞角蛋白20（CK20）在肝内胆管癌及肝内胆管结石旁胆管组织中的表达及临床意义。方法：免疫组织化学方法检测30例肝内胆管癌、例肝内胆管结石旁胆管组30织及15例正常肝内胆管组织中的CK7、CK20表达。结果：CK7在肝内胆管癌、正常肝内胆管组织中的阳性表达率分别为96.7%（29/30）、13.3%（2/15）,差异有统计学意义（P〈0.01）;CK20在肝内胆管癌组织、正常肝内胆管组织中阳性表达率分别为43.3%（13/30）、（1/15）,差异有统计学意义（P〈0.01）。CK76.7%在肝内胆管结石旁胆管组织阳性表达率为76.6%（23/30）,与正常肝内胆管组织阳性表达率13.3%（2/15）比较,差异有统计学意义（P〈0.05）。CK20在肝内胆管结石旁胆管组织阳性表达率为6.7%（2/30）,与正常肝内胆管组织阳性表达率6.7%（1/15）比较,差异无统计学意义（P〉0.05）。结论：CK7和CK20可能成为肝内胆管癌特异性肿瘤标志物。     

肝内胆管结石并胆管癌的临床病理和生化特征分析

目的探讨肝内胆管结石并胆管癌的临床病理和生化特征。方法选取我院收治的12例肝内胆管癌和同期良性病变（肝内胆管结石14例,肝外胆管结石30例,结石性胆囊炎40例）患者病例资料,通过多因素logistic回归分析模型探讨乙型肝炎病毒标志物检测,血清非特异性肿瘤标志物（CA19—9、CA125、CEA和AFP）检测,肝内胆管结石等10项影响因素对肝内胆管癌患病率的影响。结果本次研究所纳入病例,肝内胆管癌患者的乙肝病毒携带率或慢性乙肝患病率（33.3％）均明显高于同期的肝外胆管结石和结石性胆囊炎患者（P〈0．05）;多因素Logistic回归模型显示：肝内胆管结石（OR=1．05,CI为0．92～1．38,P=0．023）,乙肝病毒感染（OR=1．02,95％CI为0．78。1．31,P=0．02）;ICC患者血清高于参考值的CA19—9和黄疸指数对回归方程亦有贡献（P〈0．05）。结论乙型肝炎病毒感染,肝内胆管结石,高于参考值的CA19—9和黄疸指数可能作为提示诊断肝内胆管癌的辅助指标。     

肝内胆管癌的大体类型与细胞来源的关系

肝内胆管癌是原发性肝癌的一个重要组成部分,其发生发展的机制复杂.从细胞层面来分析,目前已被发现可能的来源有胆管上皮细胞、肝干细胞、肝细胞.从大体类型来分析,可将其分为以下三类:肿块型、管壁浸润型、腔内型.临床研究表明,不同类型的肝内胆管癌不仅形态学上有差异,患者的临床表现、治疗及预后差异也较大.因此,为探求肝内胆管癌的大体类型与细胞来源的关系,进一步研究清楚其相关发生机制及预后影响因素,笔者特就两者关系进行综述.     

Morphological studies on the pathogenesis and treatment of hepatolithiasis

Review of 108 patients with hepatolithiasis showed a recent increase of primary intrahepatic gallstones. 55 per cent of cases with hepatolithiasis had their gallstones in the left intrahepatic bile ducts. Clinicopathological study on the resected hepatic specimens of 33 patients revealed numerous intrahepatic periductal glandular formations. Periductal glandular formations were classified into the intramural and extramural glands. The mucous substances which might had been released from the periductal glands seemed to play a role in the formation of stones in combination with bilirubin pigments, cholesterin, bacterial organisms, cellular debris and other bile component. Intrahepatic gallstones and extramural glands were seen in the intrahepatic segment and area ducts. The defunctionalized atrophic hepatic lobe or segment should be resected in order to remove the calculi completely and to prevent the recurrence.     

�ε��ܽ�ʯ�ϲ����ܰ����ٴ�����

目的 探讨肝胆管结石合并胆管癌的诊治经验。方法 总结1981～2002年第三军医大学西南医院收治的48例肝胆管结石合并胆管癌病人的临床资料。结果 术前CT检查诊断正确率为80％(28／35)。其中60．7％为肝内病变；超声检查诊断率为57．8％(26／45)，其肝门病变的诊断正确率为53.8％。根治性手术13例，病理诊断为胆管腺癌及黏液癌。随访22例，根治组平均存活25个月，姑息治疗组平均存活12个月。结论 胆管癌的发生与肝胆管结石有关；伴有结石的胆管癌疗效较差，应重视胆管结石的早期根治性治疗，以防止胆管癌的发生；姑息性手术可提高生活质量。     

胆管上皮细胞与胆管癌细胞的核浆比值和嗜银核仁形成区相关蛋白的定量研究

采用图像分析技术定量分析胆管癌细胞与肝胆管结石所致胆管上皮不典型增生细胞核浆比值与核仁形成区相关蛋白的关系。结果显示：高、中、低分化胆管癌细胞与肝胆管结石胆管上皮单纯性增生细胞的核浆比值有显著性差异（Ｐ＜０．０１）；高分化与低分化胆管癌细胞核浆比值和嗜银核仁形成区相关蛋白计数有显著性差异（Ｐ＜０．０１）；但高分化胆管癌细胞与胆管上皮不典型增生细胞核浆比值无显著性差异（Ｐ＞０．０５）。由此提示，肝胆管结石所致胆管上皮增生可能是胆管癌的一种癌前病变。     

Histologic bile duct invasion by a mass-forming intrahepatic cholangiocarcinoma

Abstract. Background/Purpose: Although curative surgical resection provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma, the presence of bile duct invasion decreases postoperative survival rates in patients with mass-forming intrahepatic cholangiocarcinoma. We carried out this study to determine a surgical strategy for patients with bile duct invasion of these tumors. Methods: Forty-one patients with mass-forming intrahepatic cholangiocarcinoma were classified as either having bile duct invasion (n= 26) or not having bile duct invasion (n= 15). Clinicopathologic findings, including postoperative outcomes, were compared between these two groups. Results: Perineural invasion, lymphatic invasion, and a positive resection margin were more frequent in patients with ductal invasion. Patients with ductal invasion had lower survival rates than those without ductal invasion. Conclusions: Intraoperative frozen section examination of the bile duct stump to confirm a clear resection margin is required in patients with mass-forming tumors. Resection of the extrahepatic bile duct should be considered when tumor cells are identified at the surgical margin of the resected bile duct. Received: October 30, 2001 / accepted: November 16, 2001     

Hepatolithiasis in the hepatic hilum mimicking hilar cholangiocarcinoma: Report of a case

We report a rare case of hepatolithiasis, which was diagnosed as hilar cholangiocarcinoma and treated with hepatectomy and extrahepatic bile duct resection. A 59-year-old woman presented to a local hospital with liver dysfunction. Diagnostic imaging revealed a biliary stricture at the hepatic hilum and middle bile duct. Hilar cholangiocarcinoma was diagnosed, and she was referred to our hospital for definitive surgical treatment. She underwent left hepatic trisectionectomy, total caudate lobectomy, and extrahepatic bile duct resection. Gross examination of the resected specimen revealed intrahepatic stones firmly adherent to the bile duct wall. Pathological examination revealed no malignant lesions. The epithelium of the bile duct was absent underneath the stone, and the boundary between the stone and bile duct wall was ill defined. To our knowledge, this is the first case report of hepatolithiasis with a biliary stricture caused by peculiar stone formation, mimicking hilar cholangiocarcinoma.     

Intrahepatic calculi associated with cholangiocarcinoma

A unique case of hepatolithiasis associated with cholangiocarcinoma is described. The intrahepatic calculi consisted mainly of cholesterol rather than calcium bilirubinate. A bacteriological study of the intrahepatic and gallbladder bile was negative, though bacterial infection of the bile duct has been considered a main factor responsible for formation of intrahepatic calculi.     

Intrahepatic calculi associated with cholangiocarcinoma

A unique case of hepatolithiasis associated with cholangiocarcinoma is described. The intrahepatic calculi consisted mainly of cholesterol rather than calcium bilirubinate. A bacteriological study of the intrahepatic and gallbladder bile was negative, though bacterial infection of the bile duct has been considered a main factor responsible for formation of intrahepatic calculi.     

肝胆管结石病并发肝胆管癌CEA表达的研究

作者采用高灵敏度的免疫组化ＳＰ法对９例胆管癌（ＣＣ），１００例肝胆管结石病（ＨＬ）及１５例正常肝胆组织的癌胚原（ＣＥＡ）表达进行，结果发现正常胆管不表达ＣＥＡ；９例ＣＣ的ＣＥＡ阳性率为１００％，呈阳性较高的非规则性分布；１００例ＨＬ中伴异型曾生的有２７例，其ＣＥＡ阳性率为５９．３％。呈极性分布，表明组织ＣＥＡ的检测将有助于ＨＬ并发ＣＣ的诊断，对对于ＨＬ胆管增生性病变性质的判别具有一定的参考价值。     

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.     

肝内胆管结石合并肝胆管癌：附24例报告

目的探讨肝内胆管结石与肝胆管癌发生的关系及提高早期诊断的措施。方法回顾性分析近20年收治的24例肝内胆管结石并发肝胆管癌患者的临床资料。结果肝内胆管结石并肝内胆管肿瘤在所有肝内胆管结石的病例中占2．8％（24／860），癌肿均发生于含结石胆管处，部分切片中可见癌与不同程度的胆管上皮不典型增生同时存在。术前B超、CT和MRI／MPCP对肝内胆管结石并发肝占位病变诊断率分别为40．9％（9／22），53．8％（7／13）和66．7％（4／6）；手术切除率70．8％（17／24），根治性切除率为33．3％（8／24）例，姑息切除率为37．5％（9／24）。术后1．3年生存率：根治组为62．5％，25．0％，姑息性组为33．3％，11．1％，活检组为0％。结论长期肝内胆管结石反复发作是引起胆管癌发生的重要原因；结石型肝内胆管癌的延误诊断率高、根治性切除率低、预后差。重视结石型肝胆管癌临床延误诊断的原因并采取相应的避免措施有助于早期诊断。     

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 duodenal 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.     

�ε��ܽ�ʯӰ��ѧ��ϼ���ѡ������

??Selection and evaluation of different imaging technology for hepatolithiasis REN Ke??ZHANG Xin. Department of Radiology?? the First Hospital of China Medical University??Shenyang110001??China
Corresponding author??REN Ke??E-mail??renke815@sina.com
Abstract Color ultrasound is a common examination method??suitable for the screening of stones. CT plain scan can diagnose high density stones??difficult to find isodense stones.Enhanced CT can find most stones of hepatic bile duct and the complications??such as liver abscess and intrahepatic cholangiocarcinoma.Plain MRI can display the stones in bile duct and the dilation of the distal duct.It’s helpful to find the abnormal signal in liver.Enhanced MRI can find intrahepatic lesions??such as liver abscess and intrahepatic cholangiocarcinoma??and also has some diagnosis value for the inflammation and tumor of bile duct. MRCP can display the biliary tree and the obstruction site??while have to combine with enhanced CT or MRI in the diagnosis of common hepatic duct and common bile duct lesions.     

Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver.

A variable proportion of bile duct adenomas of the liver are still confused with metastatic well-differentiated adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct tumors that were composed almost entirely of clear cells that closely mimicked metastatic renal cell carcinoma. They were interpreted as atypical bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell cholangiocarcinoma and 13 conventional bile duct adenomas were examined. The clear cell cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical bile duct adenomas expressed cytokeratin (CK) 7, p53 protein, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA); they were negative for CK20, vimentin, Hep Par 1, chromogranin, and prostatic specific antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical bile duct adenoma displayed luminal immunoreactivity for villin. With the exception of Ki-67 reactivity, the 13 conventional bile duct adenomas and the clear cell cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell bile duct adenomas. The absence of an extrahepatic primary tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell bile duct adenoma. The differential diagnosis with clear cell hepatocellular carcinoma and metastatic clear cell carcinomas is discussed.