肝内胆管结石与肝内胆管癌相关性研究进展

肝内胆管结石是指发生于左、右肝管汇合部之上的结石,在我国是一种常见的胆道良性疾病。肝内胆管癌是第二常见的肝脏原发性恶性肿瘤,其发生可能与肝内胆管结石、原发性硬化性胆管炎、先天性胆管囊性扩张症、乙肝与丙肝病毒感染以及胆道寄生虫病等有关。鉴于我国肝内胆管结石具有高发的特点,其在诱发肝内胆管癌中的作用及潜在机制应予高度重视。从病理解剖来看,与肝内胆管结石相关的肝内胆管癌包含了从胆管内乳头状肿瘤（IPNB）、胆管上皮内瘤变（BilIN）到胆管癌不同阶段的特征。从分子层面来看,肝内胆管癌组织中炎症因子的过表达及转录因子、生长因子的功能紊乱,诱导了正常胆管上皮细胞的癌变。同时,肿瘤微环境中免疫细胞分群的变化进一步加重了肿瘤的恶性行为。这些特点提示结石对所在胆管部位的慢性机械及炎症刺激是造成胆管上皮癌变的重要原因。针对肝内胆管癌恶性程度高、治疗效果差的特点,有关肝内胆管结石诱发胆管癌的具体机制需要更多、更深入的研究,以便在早期发现胆管细胞癌变的证据及潜在的药物靶点,做到早期干预,提高这类病人的治疗效果及远期预后。     

肝内胆管结石合并肝内胆管癌诊治28例分析

目的 总结分析肝内胆管结石合并肝内胆管癌的诊治经过,以提高对该病的诊治水平.方法 回顾性分析2005-2008年收治经病理证实的28例肝内胆管结石合并肝内胆管癌的临床资料.结果 本组病例中术前诊断率为28.6%(8/28);根治性手术率75.0%(21/28),中位存活时间30个月;姑息性手术率17.9%(5/28),中位存活时间8个月;探查活检术率7.1%(2/28),分别存活2个月和4个月.结论 肝内胆管癌的发生与肝内胆管结石有关,合并结石的肝内胆管癌的早期诊断率低,预后差;应重视肝内胆管结石的早期根治性治疗;姑息性手术可提高肝内胆管癌患者的生活质量.     

肝内胆管结石并肝内胆管癌

回顾性分析1973～1995年我科经手术治疗肝内胆管结石327例及经病理证实并发肝内胆管癌7例，占2．14％。而肝内胆管癌并肝内胆管结石率为50％(7／14)。7例中男性3例，女性4例。年龄35～88岁。发病时同为2天至11年。临床表现主要为疼痛、发热、黄疸。诊断靠B超、CT和探查。6例经治后1年内死亡．仅1例左半肝切除后存活至今已5年。文中就发生率、病因、诊断和治疗进行了分析和讨论。     

肝内胆管结石并肝内胆管癌6例分析

肝内胆管结石并肝内胆管癌少见,近来有少许报道,作者统计两家医院自1986年3月至1997年6月共收治肝内胆管结石494例,其中合并肝内胆管癌6例,现分析报道如下。临床资料1.一般资料:男5例,女1例,年龄31～63岁,平均49岁。发热4例,腹痛6例,黄疸5例,腹块1例,胆外瘘1例,肝大2例,发现结石至发现胆管癌时间8个月至12年,平均31年。2.辅助检查:血ＷＢＣ升高2例,ＳＧＰＴ升高2例,ＡＫＰ升高6例,ＡＦＰ升高1例,ＣＥＡ升高2例。5例Ｂ超示肝内胆管结石3例,肝内外均有结石2例,肝内外胆管癌1例;5例ＣＴ示肝内外胆管结石3例,肝内胆管癌、肝内外胆管癌各1例;3例…     

肝胆管结石合并肝内胆管癌15例临床分析

目的探讨肝胆管结石合并肝内胆管癌的诊治经验。方法回顾性分析两院在1996年1月至2005年12月,15例肝胆管结石合并肝内胆管癌的临床资料,并对其诊断、治疗和预后进行总结。结果15例肝内胆管癌的发生率占同期肝内胆管结石患者的4.3%(15/350)。术前诊断率为40%(6/15)。5例行根治性切除(33.3%),术后平均生存27个月。姑息性手术治疗10例,术后平均生存8个月。结论对50岁以上,病史较长,反复胆管炎发作,短期内消瘦,进行性黄疸加重的肝胆管结石病人,应高度警惕并发胆管癌可能。提高疗效的关键是早期诊断,早期治疗,争取根治性切除。     

肝内胆管结石合并肝内胆管癌的诊断分析

目的：分析肝内胆管结石合并肝内胆管癌的相关因素,提高术前诊断率。方法：1997年1月至2003年9月本院肝内胆管结石合并肝内胆管癌资料较齐全病人13例,与同期肝内胆管结石手术病人20例进行回顾性比较分析,采用单因素及多因素分析的方法,研究肝内胆管结石合并肝内胆管癌的相关因素,结果：单因素分析显示年龄,病程,6月内胆管炎发作次数,血CEA,血CA199,肝内占位与肝内胆管结石合并肝内胆管癌有关,进一步通过多元逐步回归分析发现肝内占位为肝内胆管结石合并肝内胆管癌的独立因素,结论 对年龄高,病程长,近期内反复姨作病人进行血CEA,血CA199,CT,MRI等检查,有利于提高肝内胆管结石合并肝内胆管癌的术前诊断率。     

肝内胆管结石合并肝内胆管癌的病因及其防治

本文报道肝内胆管结石伴发肝内胆管癌１０例，迟发性肝胆管癌３例，占同期肝内胆管结石病例的３．５％，癌肿均发生结石胆道处，以左肝多见。病程１－４０年，平均１６年；３例这发性肝内胆管癌分别发生于取石后６、７、１１年，平均８年。认为肝内结石、胆管炎、胆汁淤积是诱发肝内胆管癌的重要因素。早期治疗肝内胆管结石及胆管狭窄，、通畅胆汁此流、控制感染是这癌发生手重要措施；早期诊断、根治性切除可获得良好疗效。对左肝结     

肝内胆管结石合并胆管癌38例临床分析

目的 探讨肝内胆管结石合并胆管癌的诊断、治疗以及微创外科时代肝部分切除在肝内胆管结石治疗中的意义.方法 分析我院收治的38例胆管结石并胆管癌患者的临床资料.结果 我院1998年3月至2011年12月间,胆管癌的患者为225例,同期肝胆管结石患者2333例.手术切除组21例,平均生存时间为32.9个月,1、2、3年生存率分别为85.71%、71.43%、52.38%;介入治疗组13例,平均生存时间为6.85个月,0.5、1、2年生存率分别为46.15%、7.69%、0.结论 肝内胆管结石长期的炎症、反复的感染、胆汁淤积等因素是肝内胆管癌发生的重要因素.肝部分切除不仅能够去除结石、预防结石复发,对于预防胆管癌变亦具有重要的意义.     

肝内胆管结石合并胆管癌相关因素探讨

目的 探讨肝内胆管结石合并胆管癌相关临床因素及其演变过程.方法 对420例肝内胆管结石接受手术的患者进行调查,内容包括年龄、合并肝病、胆道感染病程等.对80 例疑有胆管癌者,术中于胆镜下钳取结石部位胆管炎症粘膜组织或切除肝脏标本,进行DNA 含量及Agnor 颗粒计数分析.结果 年龄>50 岁,合并丙肝或乙肝、肝硬化、胆道感染史>10 年的47 例患者发现胆管癌7 例(14.8%).DNA 含量及Agnor 颗粒计数:单纯增生与轻、中、重度非典型增生及高、中、低分化胆管癌均数逐渐升高.单纯增生组与轻度非典型增生组差异无显著性(P>0.05).其余各两组差异均有统计学意义(P<0.05).结论 胆管结石合并胆管癌发生的可能机制是反复炎症刺激原胆管上皮增生、化生原癌形成的演变过程.     

肝内胆管结石合并肝内胆管癌的诊断和外科治疗

肝内胆管结石是临床上常见疾病,而并发肝内胆管癌(intrahepatic cholangiocarcinoma)的发生率为肝内胆管结石病的4％-1O％,因此肝内胆管结石合并肝内胆管癌的病人并不少见。由于对其认识尚不充分,术前确诊率低,相当一部分病人在术中才能确诊,     

肝内胆管癌的诊断与治疗(附12例报告)

目的探讨肝内胆管癌发病的诊治方法。方法对我院1990年1月至2003年3月经手术和病理证实的12例肝内胆管癌病例资料进行回顾性分析。结果早期症状无特异性，AFP检查均为阴性，血CEA检查升高显著3例，4例术前诊断为肝内胆管癌，8例误诊，本组行根治性切除5例(41．6％)，姑息性手术7例。结论肝内胆管癌误诊率高，根治性手术率低，熟悉本病的临床特征，B超检查仍是首选方法。术中病理学检查是避免误诊漏诊的重要方法，根治性手术切除是本病最有效的治疗方法。     

影响肝内胆管细胞癌预后高危因素的临床回顾分析

目的 探究影响肝内胆管细胞癌(ICC)手术预后的可能因素,为进一步改善ICC的预后提供借鉴.方法 对2009年1月至2011年12月期间103例行根治性手术切除的ICC病人临床病理特征进行生存率、无瘤生存率的单因素分析,并通过Cox多因素分析得到有独立意义的预后指标.结果 103例ICC病人术后1年、3年生存率为77.70％、45.76％,无瘤生存率为67.65％、40.75％.单因素分析提示性别、肿瘤数目、肿瘤大小、脉管侵犯、淋巴结转移、术前CEA影响病人的无瘤生存率及生存率.Cox多因素分析提示脉管侵犯、淋巴结转移和术前癌胚抗原(CEA)是影响ICC病人生存的独立因素;肿瘤大小、神经束侵犯、脉管侵犯和术前CEA是影响ICC病人无瘤生存的独立因素.结论 ICC的局部侵犯和淋巴结转移是影响ICC病人预后的重要因素,如何进一步规范ICC的治疗,包括术前评估、术中手术方式(是否需常规的淋巴结清扫)、术后辅助方案的制定,需要多中心随机对照研究结果的支持.     

Anatomic and molecular pathology of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor of the liver, and ICC is reportedly increasing recently. ICC is usually adenocarcinoma with variable desmoplastic reaction, although there are several special or unusual histological features. ICC may arise at the large intrahepatic bile duct near the hepatic hilus and also from the bile ductules at the border of the hepatic parenchyma. On the anatomical level, the pathology of ICC differs depending on the region from which the ICC arises. At the large intrahepatic bile duct, ICC presents papillary growth and periductal infiltration. Some cases show extensive papillary growth and intraluminal spread with marked gastroenteric metaplasia. Mucus core protein 1 is expressed in aggressive ICC. ICC arising from ductules shares phenotypes of hepatocellular carcinoma. ICC in chronic biliary diseases, particularly arising in hepatolithiasis, presents precancerous lesions that include biliary epithelial dysplasia, as well as in-situ carcinoma. Chronic advanced hepatitis C is one of the background diseases of ICC. Chronic inflammation, with the upregulation of cyclooxygenase-2 and growth factors, and the formation of reactive oxygen species are one of the causative factors in the DNA damage of biliary epithelial cells. K-ras mutation and aberrant expression of p53 are found in one-third of ICCs. The latter may be due to mdm-2 upregulation. Hepatocyte growth factor/met and interleukin 6 (IL6)/IL6 receptor are involved in cell proliferation/mitoinhibition and apoptosis in ICC. Fibrous stroma formation and invasion involve the proliferation of -smooth muscle antigen-positive stromal cells, and cell-to-cell and cell-to-matrix interactions involving E-cadherin/catenin and CD44 and matrix proteinases may be involved in the invasion of ICC. Evasion of immune surveillance involving the Fas/FasL system is important in the malignant progression of ICC. Further molecular and genetic studies are mandatory to evaluate the pathogenesis and progression of ICC.     

Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma

Background/Purpose. We retrospectively investigated the clinicopathologic features and outcome of 51 patients who underwent hepatectomy for intrahepatic cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the potential prognostic factors for long-term survival. Methods. There were 27 men and 24 women, with a mean age of 63.7 years. The surgical procedures were extended right or left hepatectomy (15 cases), right or left hepatectomy (19 cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy (7 cases). The macroscopic findings of the excised tumor showed the mass-forming (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the intraductal growth (IG) type (7 cases). Results. The patients with the MF type had a significantly higher incidence of lymph node metastasis (44.8%), as compared to those with the PI or IG type (15.0%). Two patients who died of hepatic failure during their hospital stay were excluded from this survival study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The patients with the IG type had the best outcome, followed by those with the PI type and MF type. The survival rates with or without lymph node metastasis were 9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively (P 0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%) survived for more than 5 years after operation. The gross appearance of these tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in 1. Except for one case with the PI-type tumor, lymph node metastasis was not observed. All of the 5-year survivors underwent curative resection and none of them had any positive surgical margin. Conclusion. Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.     

Metastatic colon cancer from intrahepatic cholangiocarcinoma

A 62-year-old man had been followed because of an elevated serum level of carcinoembryonic antigen without the detection of any cancer lesions. However, there was a sudden increase in the serum level of carcinoembryonic antigen, and abdominal imagings showed a hepatic tumor with peripheral intrahepatic bile duct dilatation, and a submucosal tumor at the sigmoid colon with intact mucosa. Histopathological findings showed that the hepatic tumor had perineural invasion, suggesting an intrahepatic cholangiocarcinoma, and that the colon tumor infiltrated the submucosa, while its mucosa was intact. Both tumors showed similar pathological features and were positive for cytokeratin 20 and 7. These findings suggested intrahepatic cholangiocarcinoma with metastatic sigmoid colon cancer.     

腹腔镜手术治疗胆囊结石合并胆总管结石术后结石复发危险因素的meta分析

目的:采用meta分析的方法系统评价腹腔镜手术治疗胆囊结石合并胆总管结石术后复发的相关危险因素。方法:计算机检索PubMed、Cochrane Library、Embase、中国生物医学文献数据库、中国知网、维普、万方等数据库,收集截至2019年10月公开发表的研究腹腔镜治疗胆囊结石合并胆总管取石术后结石复发危险因素的相关文章,采用RevMan 5.3软件进行meta分析。结果:共纳入12项研究、1 658例患者。meta分析结果显示,复发组中有碎石手术史患者的比例高于未复发组(OR=4.41,95%CI=2.63~7.38,P<0.01);复发组中合并胆管炎、胰腺炎患者的比例高于未复发组(OR=3.40,95%CI=2.25~5.13,P<0.01);复发组中合并胆囊管扩张患者的比例高于未复发组(OR=4.08,95%CI=2.81~5.93,P<0.01);复发组中合并胆总管扩张患者的比例高于未复发组(OR=4.12,95%CI=2.96~5.75,P<0.01);复发组中合并胆总管直径>1.0 cm患者的比例高于未复发组(OR=4.96,95%CI=3.59~6.86,P<0.01);腹腔镜胆囊切除联合胆道镜胆总管切开取石组的复发比例低于腹腔镜胆囊切除联合十二指肠镜乳头切开取石组(OR=0.27,95%CI=0.09~0.81,P<0.05)。结论:既往碎石史、合并胆管炎与胰腺炎、胆囊管扩张、胆总管直径>1 cm、内镜乳头切开术均是促进腹腔镜胆囊切除联合胆道镜胆总管切开取石术后结石复发的危险因素。     

Hepatolithiasis and intrahepatic cholangiocarcinoma: carcinogenesis based on molecular mechanisms

Hepatolithiasis is more frequently seen in East Asian countries than in Western countries, and it is well known to represent a high-risk state for intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma is an aggressive tumor that shows a dismal outcome even after resection. Cancer results from multistep carcinogenesis; however, the precise molecular mechanisms involved in the genetic alterations in cancer remain unknown. The accumulation of alterations in cancer-related genes leads to disruptions in cell-cycle regulation and also to continuous cell proliferation. The present review provides an overview of cancer-related genes in intrahepatic cholangiocarcinogenesis arising in hepatolithiasis. Further study of molecular mechanisms in hepatolithiasis-related intrahepatic cholangiocarcinoma, and the delineation of the influence of the genes involved should lead to our understanding of cholangiocarcinogenesis.     

肝内胆管细胞癌的外科治疗进展

肝内胆管细胞癌(ICC)具有显著的局部播散和淋巴道转移的特性.治愈ICC的惟一选择是根治性手术,应行规则性肝切除或扩大肝切除;是否常规清扫淋巴结以及淋巴结清扫的范围目前研究较多,结论有待进一步证实.姑息性切除仍然可以改善部分病人的预后.再次手术对于术后"超过一年"的部分肝内复发病人也有较好的疗效.肝移植仅适用于高度选择的早期病人或者谨慎的临床试验,并建议联合术后放化疗等以改善预后.     

Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma

Background

Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.

Methods

Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.

Results

Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3–5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2–4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).

Conclusions

Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.     

Recurrence after surgical resection of intrahepatic cholangiocarcinoma

We aimed to assess the patterns of recurrence after surgery for intrahepatic cholangiocarcinoma (ICC) and the outcomes of treatment in patients with recurrence. From 1981 to 1999, 123 patients with ICC underwent hepatectomy. The 3-year and 5-year survival rates were significantly higher in patients after curative resection (n = 56; 53%, 50%) than in patients after noncurative resection (n = 67; 7%, 2%; P < 0.0001). In 54 patients followed-up after curative resection, the rate of recurrence after surgery was 46%. The recurrences were in the liver (56%), abdomen (disseminated; 24%), and lymph nodes (20%). The rates of recurrence were significantly higher in patients with various classifications of mass-forming ICC tumors (P = 0.039) than in those with other types of tumors, and in patients with tumors over 3 cm in greatest diameter than in those with tumors 3 cm or less (P = 0.006). Hepatic recurrence, abdominal dissemination, and intraductal recurrence were significantly related to tumors that included mass-forming ICC (P = 0.002), tumors that included periductal infiltrating ICC (P = 0.009), and tumors that included intraductal growth ICC (P = 0.038), respectively. Seven patients with recurrence underwent radiation, chemotherapy, immunotherapy, or surgical resection. Only 2 patients, with intrahepatic metastasis and intraductal recurrence, respectively, had good outcomes after surgery. The effectiveness of other treatments has not been established.