Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan

We reviewed the records of 64 patients with resected intrahepatic cholangiocarcinoma (ICC) according to the macroscopic classification proposed by the Liver Cancer Study Group of Japan, in which ICC is classified into three types based on the macroscopic appearance of the cut sur-face of the tumor: mass-forming, periductal-infiltrating, and intraductal growth types. There were 24 patients with the periductal-infiltrating type, 28 with the mass-forming type, and 12 with the intraductal growth type. The mass-forming type essentially showed expansive growth irrespective of hilar invasion. The periductal-infiltrating type of tumor exhibited diffuse infiltration along the portal pedicle, and preoperative planning of the resection procedure was similar to that for primary bile duct carcinoma of the hepatic confluence. Vascular resection and reconstruction was required in some patients with advanced disease. In the intraductal growth type of tumor, precise determination of tumor extent was difficult because of the ambiguity caused by abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Percutaneous transhepatic cholangioscopy provided the most reliable information for designing the operative procedure. The macroscopic classification is useful for preoperative diagnosis of tumor extent and for planning the surgical procedure. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Extended resection for intrahepatic cholangiocarcinoma in Japan

To elucidate surgical outcome after extended sugery for intrahepatic cholangiocarcinoma (ICC), we retrospectively allocated 83 patients who had undergone resection to a standard surgery group (n = 56), in which the patients had undergone hepatectomy alone or hepatectomy with bile duct resection, and an extended surgery group (n = 27), in which the patients had undergone the standard operation combined with vessel resection and/or pancreatectomy. The incidence of mass-forming plus periductal-infiltrating type lesions (P = 0.0129), lymph node metastasis (P = 0.0005), noncurative resection (P < 0.0001), mortality within 30 days and within 1 year after surgery (P = 0.0392, P = 0.0010), local recurrence (P = 0.0439), and peritoneal disseminated recurrence (P = 0.0241) was significantly higher in the extended surgery group than in the standard surgery group. The 5-year survival rate was significantly higher in the standard surgery group (30%) than in the extended surgery group (10%; P = 0.0061). The mortality rate within 1 year after extended surgery was significantly higher in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0032), and long-term (5-year) survival in the extended surgery group was significantly lower in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0253). We conclude that extended surgery does not improve the curative resection rate or the surgical outcome of ICC, and that extended surgery is not indicated for patients with infiltrating-spread type tumors. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Intrahepatic cholangiocarcinoma in Thailand

Intrahepatic cholangiocarcinoma is defined as adenocarcinoma originating from bile ductules and segmental and lobar intrahepatic ducts. Four types of surgical pathology have been identified in the Khon Kaen endemic area in Thailand: peripheral, type I; intermediate, type II; central, type III; and diffuse, type IV. We report our experience with intrahepatic cholangiocarcinoma with emphasis on the surgical pathology, operative procedure, and associated survival time. We reviewed the records of patients treated for cholangiocarcinoma at Srinagarind Hospital from January 1, 1992 to February 28, 1997. There was a total of 411 patients, and 138 were intrahepatic and non-jaundiced. Tumors in the proximity of the gray zone i.e., portal, periportal with jaundice, were excluded. Patient profiles, surgical pathology, operative procedure, postoperative morbidity, and mortality were recorded. The data were analyzed using Kaplan-Meier survival curves. Of the 138 patients with intrahepatic disease who were non-jaundiced, 116 had type I, 10 had type II–III, and 12 had type IV. The wear ages of the patients were: 53.0, SE 9.2 years in type I; 57.1, SE 4.6 years in type II–III, and 50.2, SE 9.2 years in type IV. The male-to-female ratios in the three groups were 1.4 : 1, 1.5 : 1, and 5 : 1, respectively. The mean survival times in the three groups were 556, SE 63 days 374, SE 149 days and 97, SE 35 days. Most of the surgical procedures were tumor excisions (108/138). Right hepatectomy was performed in 63 patients, extended right hepatectomy in 8, left hepatectomy in 18, and extended left hepatectomy in 1. Palliative procedures were performed in the other patients because tumors were in both lobes. The mean survival time was 582 days (SE, 75), for right lobe surgery; 458 days (SE, 89) for left lobe surgery; and 127 days (SE, 58) for the other procedures. Mean survival time was 1039 days (SE, 201) in tumor stage III, 773 days (SE, 123) in stage IVa, and 382 days (SE, 60) in stage IVb. There were no significant differences in survival time according to age or sex. The results of surgery in type I and type II-III were better than the results in type IV. Survival time after right hepatectomy was better than that after left hepatectomy, although without statistical significance, but survival time was significantly better after both operations than after palliative procedures. The results of surgery according to pathological staging showed that survival time in stage III was better than that in either stage IVa or IVb, but only the difference from stage IVb was significant. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Surgical management of intrahepatic cholangiocarcinoma: A 31-year experience

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival. Received for publication on May 8, 1997; accepted on July 3, 1997     

Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan

As a result of an increasing number of studies on the surgical treatment of intrahepatic cholangiocarcinoma (ICC), knowledge of its biological characteristics has been accumulating. We analyzed the clinicopathological features and outcome of 36 of 48 surgical patients with histologically proven ICC (75.0%) who underwent hepatic resection between March 1979 and July 1998. According to tumor location, 12 patients had the central type and 24, the peripheral type. The incidence of portal vein tumor thrombus and lymph node metastasis was higher in the central type than in the peripheral type. All 12 patients with the central type had stage IV disease, and none of them underwent complete resection, whereas 12 of the 24 patients with peripheral type tumors had stage IV disease; complete resection was achieved in 12 of the 24 patients with peripheral type tumors (50%). Outcome after resection was significantly poorer in the patients with the central type. The macroscopic type of lesion in the resected specimens was the mass-forming type in 15 patients (41.7%), the mass-forming + periductal-infiltrating type in 15 patients (41.7%), the periductal-infiltrating type in 3 patients (8.3%) and the intraductal growth type in 3 patients (8.3%). The macroscopic tumor type was associated with mode of tumor spread and outcome. All 3 patients with the intraductal growth type are alive without tumor recurrence 26–138 months after surgery. The survival rate was much higher in the patients with the mass-forming type than in those with the mass-forming + periductal-infiltrating type. Importantly, the outcome in the 17 patients who underwent resection for stage IV-B disease and who accounted for 47.2% of patients with resection in the present series was very poor, almost the same as that in the 12 patients who did not undergo resection. By selecting patients based on the biological characteristics of the tumor and taking into account patients' quality of life, complete surgical resection can be performed safely and is associated with long-term survival. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

周围型肝内胆管细胞癌的诊断和治疗

目的 探讨周围型肝内胆管细胞癌(PICC)的诊断及外科治疗，提高其诊治水平。方法 总结分析1991～2000年间我科收治的46例PICC病人诊断、治疗及预后的资料。结果 (1)本病早期无特异性临床表现，部分病例可并存乙型肝炎(20％)、肝硬化(45％)，部分伴有肝内胆管结石(20％)，血清AFP升高(30％)；(2)影像学检查：B超、CT、MRI的诊断率分别为90．0％、95．4％及100．0％；(3)手术切除率为64．0％．全组病例的1、3、5年生存率分别为60．0％、33．0％及26．0％；(4)生存5年以上的12例病人中，直径≤3cm的小肝癌9例，包膜完整的肿块型直径位于3～5cm肝癌3例，术后均辅助性放射治疗和选择性肝动脉灌注化疗。结论影像学检查能在早、中期提供临床线索，但缺乏特异性血清肿瘤标志物，治愈性切除术加辅助治疗可获得良好生存率。     

肝内胆管细胞癌诊治策略

肝内胆管细胞癌（intrahepatic cholangiocarcinoma, ICC）的生物学特性与肝细胞癌和肝外胆管癌存在显著差异,早期缺乏明显临床表现。因此,对合并高危因素的人群进行定期筛查,有助于ICC的早期诊断和及时治疗。现有ICC分期系统为预后评估提供了临床依据,但是在影响病人预后因素方面尚存在分歧,有待大规模前瞻性研究提供循证医学证据,进一步修订、完善分期系统。以手术为主的综合治疗是ICC的主流治疗模式,根治性切除和淋巴结清扫有助于提高疗效、改善病人预后,非手术治疗方法的不断进展可使无法手术或术后复发ICC病人临床获益。     

末梢型肝内胆管细胞癌的诊断及外科治疗效果分析

目的 探讨末梢型肝内总胆管细胞癌（PIHCC）的诊断及外科治疗结果,以提高其诊治水平。方法 回顾性分析1970－1999年间外科治疗的20例PIHCC患者诊断、治疗及预后的资料。结果 （1）本病缺乏特异性临床表现,部分病例可并发乙型肝炎（35．0％）、肝硬化（45．0％）和血清AFP升高（25．0％）;（2）影像学检查：B超、CT、MRI及ECT的诊断率分别为90．0％（18／20）、94．4％（17／18）、3／3及4／3;（3）手术切除率为60％,全组病例的1、3、5年生存率分别为55．0％（11／20）、35．0％（7／20）及20．0％（4／20）,其中肝切除术病例分别为83．3％（11／12）、58．3％（7／12）、33．3％（4／12）;（4）生存5年以上的4例患者中,直径≤3cm的小肝癌3例、包膜完整的结节型大肝癌1例,且术后均辅助选择性肝动脉灌注化疗,有助于生存率的提高。结论 本病缺乏特异性血清肿瘤标志物,治愈性切除术（包括术后辅助治疗）可获得良好生存率。     

Intrahepatic cholangiocarcinoma in Korea

We reviewed surgically treated patients with intrahepatic cholangiocarcinoma to evaluate the clinical and pathologic features of intrahepatic cholangiocarcinoma that may affect long-term survival in Korean patients with the disease. Between 1990 and 1997, 28 patients with intrahepatic cholangiocarcinoma underwent laparotomy. Resection was performed in 25 patients, and wedge resection alone in 3 patients. The liver resections consisted of right lobectomy in 5 patients, right trisegmentectomy in 1, left lobectomy in 7, extended left lobectomy in 3, hepatopancreatoduodenectomy in 2, and segmentectomy in 7. Curative resection was performed in 15 patients. Histological sections of all resected specimens were immunohistochemically stained with p53 and Ki-67 monoclonal antibodies to assess the biological behavior of the tumor cells. Cumulative survival rate and clinicopathological factors that may influence the prognosis, including biological markers (p53, Ki-67), were analyzed statistically. Patients who underwent curative resection survived significantly longer than patients who underwent noncurative resection. The median survival time of the patients who underwent curative resection was 24 months (mean, 34 ± 8 months), with 1-, 2-, and 3-year survival rates of 66.6%, 44.4%, and 35.6%, respectively. The median survival time of the patients who underwent noncurative resection was 3 months (mean, 8 ± 3 months), with 1- and 2-year survival rates of 26.7% and 13.4%, respectively. Univariate analysis showed that positive regional lymph nodes correlated significantly with poor outcome (P = 0.004) and that curative resection significantly correlated with better prognosis (P = 0.001). Age, sex, tumor size, degree of cell differentiation, gross type of tumor, and p53 and Ki-67 labeling index were not significantly correlated with outcome. Our findings support the concept that aggressive liver resection, along with regional lymph node dissection, be recommended for long-term survival. The validity of molecular biologic tumor markers (p53, Ki-67) as prognostic factors has not yet been clearly demonstrated. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

末梢型肝内胆管细胞癌的诊治分析

目的探讨末梢型肝内胆管细胞癌的诊断和治疗方法，评价淋巴清扫在末梢型肝内胆管细胞癌手术中的意义。方法回顾性分析我院1993年1月至2003年4月手术治疗28例末梢型肝内胆管细胞癌的临床资料，对发病特点，症状体征，影像学检查，病理特点和手术治疗效果进行分析。结果单因素生存分析显示手术切除组1，3，5年生存率分别为78．9％，36．8％，21．1％，未切除组15．8％，0，0，两组有显著性差异（P〈0．001）。进行淋巴结清扫组1，3，5年生存率分别为100％，60％，40％，未进行淋巴结清扫切除组为55．5％，11．1％，0，两组有显著性差异（P〈0．001）。合并门静脉癌栓组1，3，5年生存率分别为50％，0，0，未合并门静脉癌栓组为86．7％，46．7％，26．7％，两组有显著性差异（P=0．004）。而COX比例风险回归模型多因素分析显示手术切除和淋巴清扫与预后显著相关，而门静脉癌栓与生存没有显著相关性。结论淋巴转移，手术切除是影响生存的主要因素，手术切除能改善预后，术中进行肝门淋巴脂肪清扫能提高术后生存率。     

Serosal invasion in TNM staging of mass-forming intrahepatic cholangiocarcinoma

Background/Purpose The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer. Methods Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors. Results By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV. Conclusions Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.     

p27kip1在胆管癌组织中的表达与临床病理特征的相关性研究

目的探讨细胞周期抑制蛋白p27kip1在胆管癌组织中的表达及与胆管癌各项临床病理特征的关系。方法采用免疫组化法检测43例胆管癌组织及10例伴慢性胆管炎的胆管壁组织中p27kip1的表达,结合临床病理资料进行回顾性分析。结果①p27kip1在胆管癌组织中的阳性表达率为30.23%(13/43),而在伴慢性炎症的胆管组织中阳性表达率为80.00%(8/10),差异有统计学意义(P<0.05)。②p27kip1蛋白表达与胆管癌的分化程度及临床分期呈显著相关(P<0.05)。结论胆管癌中p27kip1蛋白低表达可能与胆管癌的发生发展有关,检测p27kip1的表达对胆管癌的预测有一定的参考价值。     

8-Nitroguanine在肝吸虫相关性肝内胆管癌中的表达以及意义

目的 探讨8-Nitroguanine在伴有肝吸虫感染的肝内胆管细胞癌（ICC）中的表达以及意义。方法 应用酶联接免疫吸附试验（ELISA）检测2016年1月-2018年6月我院18例行根治性手术的伴肝吸虫感染的ICC患者癌组织、癌旁组织和正常肝组织中8-Nitroguanine的表达情况。同样用ELISA方法检测患者术前血清及18例肝吸虫性胆管炎和健康志愿者中8-Nitroguanine的表达情况;体外培养胆管癌RBE细胞,按梯度浓度处理细胞,计算半抑制浓度,并以该浓度处理细胞24 h,侵袭实验检测RBE细胞侵袭能力的变化。结果 在18例伴有肝吸虫感染的ICC患者中,8-Nitroguanine在肿瘤组织中表达水平显著高于癌旁组织和正常肝组织（P < 0.001）,后两者差异无统计意义（P > 0.05）。伴有肝吸虫感染的ICC患者术前血清中8-Nitroguanine的表达水平与肝吸虫性胆管炎患者和健康志愿者无明显差异（P > 0.05）。8-Nitroguanine对RBE细胞的增殖能力具有浓度依赖性抑制作用,8-Nitroguanine处理后RBE细胞的侵袭能力无明显改变（P > 0.05）。结论 8-Nitroguanine与肝吸虫感染相关性ICC的关系密切,可能在癌变阶段发挥关键作用。     

肝癌衍生生长因子在原发性肝内胆管细胞癌中的表达及其临床意义

目的探讨肝癌衍生生长因子(HDGF)与原发性肝内胆管细胞癌(PICC)预后的关系。 方法选择2011年1月至2014年12月共55例肝内胆管细胞癌手术标本和30例非癌变标本,进行免疫组织化学(IHC)染色及评估、全RNA提取、逆转录PCR(RT-PCR)以及结果判定。 结果特异性HDGF染色主要存在于良性和恶性上皮细胞的细胞核和细胞质中。52.7%(29/55)的PICC提示细胞核HDGF EI 2级。对比之下,非癌变标本的细胞核HDGF蛋白表达EI 2级率是33.3%(10/30)。核HDGF表达与PICC的T分类、N分类和肿瘤分化密切相关(P<0.01)。Log-rank检验显示,在PICC中高HDGF表达组生存期短,而低HDGF表达组生存期长。 结论PICC中核HDGF水平升高,并与PICC的TNM分期、肿瘤分化、PICC的生存期有关。HDGF可能是PICC预后的独立预测因素。     

血清维生素D对晚期肝内胆管癌病人预后及化疗敏感度预测价值研究

目的 评估血清维生素D水平对无法进行手术的晚期肝内胆管癌病人的预后和化疗敏感度的预测价值.方法 回顾性分析海军军医大学第三附属医院收治的41例无法手术的晚期肝内胆管癌病人的临床资料,按照实体瘤评价标准(RECIST 1.1版)对病人化疗情况进行分析.采用受试者工作特征曲线(ROC),单因素及多因素分析以及生存曲线明确血...     

肝内胆管癌淋巴结清扫的热点与争议

肝内胆管癌是一种高度侵袭性的恶性肿瘤,近年来发病率逐年升高,根治性手术切除被认为是可能治愈的唯一方法.淋巴结转移是手术预后的高危因素,在肝内胆管癌根治性切除术中,淋巴结清扫问题仍存在很多争议,其中淋巴结清扫与否,淋巴结清扫的方式和范围,以及清扫的意义和价值更是当下研究的热点.本文就肝内胆管癌淋巴结清扫的热点与争议进行了...     

Development and validation of a machine learning-based nomogram for prediction of intrahepatic cholangiocarcinoma in patients with intrahepatic lithiasis

BackgroundAccurate diagnosis of intrahepatic cholangiocarcinoma (ICC) caused by intrahepatic lithiasis (IHL) is crucial for timely and effective surgical intervention. The aim of the present study was to develop a nomogram to identify ICC associated with IHL (IHL-ICC).MethodsThe study included 2,269 patients with IHL, who received pathological diagnosis after hepatectomy or diagnostic biopsy. Machine learning algorithms including Lasso regression and random forest were used to identify important features out of the available features. Univariate and multivariate logistic regression analyses were used to reconfirm the features and develop the nomogram. The nomogram was externally validated in two independent cohorts.ResultsThe seven potential predictors were revealed for IHL-ICC, including age, abdominal pain, vomiting, comprehensive radiological diagnosis, alkaline phosphatase (ALK), carcinoembryonic antigen (CEA), and cancer antigen (CA) 19-9. The optimal cutoff value was 2.05 µg/L for serum CEA and 133.65 U/mL for serum CA 19-9. The accuracy of the nomogram in predicting ICC was 82.6%. The area under the curve (AUC) of nomogram in training cohort was 0.867. The AUC for the validation set was 0.881 from The Second Affiliated Hospital of Wenzhou Medical University, and 0.938 from The First Affiliated Hospital of Fujian Medical University.ConclusionsThe nomogram holds promise as a novel and accurate tool to predict IHL-ICC, which can identify lesions in IHL in time for hepatectomy or avoid unnecessary surgical resection.     

肿瘤负荷评分在获得根治性切除肝内胆管癌患者预后预测中的价值

目的 研究肿瘤负荷评分(tumor burden score,TBS)对肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)患者根治性切除术后预后的预测价值。方法 回顾性分析2005年1月至2011年12月在复旦大学附属中山医院肝肿瘤外科连续收治的322例行根治性切除术的ICC患者资料,随访截止至2014年4月。采用ROC曲线评价TBS预测总体生存率(OS)的准确性。多因素Cox回归分析影响ICC患者预后的独立因素。结果 中位随访时间44.0个月(范围2.7～100.5)。TBS将322例ICC患者分为低、中和高三个预后风险组(104例、176例和42例)。TBS与血清CA199(P=0.004)、术前中性粒细胞/淋巴细胞比值(NLR,P=0.001)、淋巴细胞/单核细胞比值(LMR,P<0.001)、肿瘤最大径(P<0.001)、肿瘤数目(P=0.001)、淋巴结转移(P<0.001)及TNM分期(P<0.001)显著相关。TBS预测ICC患者术后5年OS的曲线下面积(AUC)为0.632(P<0.001),高于NLR≥2...     

基于MRI影像组学及临床特征预测肿块型肝内胆管细胞癌的术后生存时间

目的 探讨影响肿块型肝内胆管细胞癌（mass-forming intrahepatic cholangiocarcinoma,MFICC）患者手术切除预后的相关因素。方法 回顾性收集2015年10月至2017年5月杭州市第三人民医院行外科手术切除治疗的MF-ICC患者42 例,均经病理学检查证实为MF-ICC。所有患者术前1 个月内行肝脏MRI平扫+增强检查,应用GE-AK软件标注MRI增强平衡期（magnetic resonance-equilibrium phase,MREP）图像上肿瘤病灶并提取9个量化的一阶影像组学特征,纳入临床特征10个指标。电话随访并记录患者术后生存时间,行Cox回归模型分析。结果 MRI影像组学特征及临床特征与MF-ICC患者术后生存具有明显相关性,大血管侵犯（HR 1.532,95%CI 2.245～9.328,P=0.025）、淋巴结肿大（HR 1.273,95%CI 1.352～5.463,P=0.042）和均匀度（HR 2.475,95%CI 3.226～12.001,P=0.002）是影响MF-ICC患者术后生存的不良预后因素。结论 MRI影像组学特征（均匀度）和临床特征（大血管侵犯和淋巴结肿大）是与MF-ICC患者术后总生存时间相关的独立危险因素,提示影像组学特征（均匀度）是具有临床应用前景的生物学特征。     

淋巴细胞和C反应蛋白比值在肝内胆管癌根治性手术预后中的意义

目的 淋巴细胞和C反应蛋白比值(LCR)是一种炎症评分,本研究旨在分析LCR评分在肝内胆管癌(ICC)患者行根治性切除术预后中的价值.方法 回顾性选取咸阳市中心医院2015年1月至2020年12月经病理确诊为ICC的157例患者为研究对象,收集患者的年龄、性别、白蛋白(ALB)、总胆红素(TBIL)、血管侵犯、肿瘤大小...