MRI延迟期强化扫描与MSCT在诊断肝内胆管细胞癌中的应用

目的比较MRI延迟期强化扫描与MSCT在诊断肝内胆管细胞癌(ICC)中的应用价值。方法以2015年3月至2021年5月125例疑似ICC患者为研究对象,均给予MRI延迟期强化扫描与MSCT检查,并经术中病理学确诊。比较MRI延迟期强化扫描与MSCT检查结果与病理学检查结果的一致性;以病理学检查结果为标准,比较MRI延迟期强化扫描与MSCT检查对ICC的诊断效能及诊断价值;进一步对ICC的病理类型进行分类,比较MRI延迟期强化扫描与MSCT检查对导管状腺癌的诊断效能及鉴别价值。结果MRI延迟期强化扫描结果与病理学检查结果的一致性(Kappa=0.642)高于MSCT(Kappa=0.464);MRI延迟期强化扫描诊断ICC的灵敏度为91.25%,大于MSCT的80.00%(P<0.05);MRI延迟期强化扫描诊断ICC的AUC为0.812,大于MSCT的0.733(P<0.05);MRI延迟期强化扫描结果与病理学检查结果的一致性(Kappa=0.715)高于MSCT(Kappa=0.399);MRI延迟期强化扫描诊断导管状腺癌的准确度为88.75%,高于MSCT的76.25%(P<0.05);MRI延迟期强化扫描诊断导管状腺癌的AUC为0.890,大于MSCT的0.717(P<0.05)。结论MRI延迟期强化扫描对ICC的诊断价值及诊断灵敏度较高,且对导管状腺癌具有鉴别价值。

Oncogenic potential of IDH1R132C mutant incholangiocarcinoma development in mice

AIM: To investigate whether IDH1R132 C mutant in combination with loss of p53 and activated Notch signaling promotes intrahepatic cholangiocarcinoma(ICC) development.METHODS: We applied hydrodynamic injection and sleeping beauty mediated somatic integration to induce loss of p53(via sh P53), activation of Notch [via intracellular domain of Notch1(NICD)] and/or overexpression of IDH1R132 C mutant together with the sleeping beauty transposase into the mouse liver. Specifically, we co-expressed sh P53 and NICD(sh P53/NICD, n = 4), sh P53 and IDH1R132C(sh P53/IDH1R132 C, n = 3), NICD and IDH1R132C(NICD/IDH1R132 C, n = 4), as well as NICD, sh P53 and IDH1R132C(NICD/sh P53/IDH1R132 C, n = 9) in mice. Mice were monitored for liver tumor development and euthanized at various time points. Liver histology was analyzed by hematoxylin and eosin staining. Molecular features of NICD/sh P53/IDH1R132 C ICC tumor cells were characterized by Myc tag, Flag tag, Ki-67, p-Erk and p-AKT immunohistochemical staining. Desmoplastic reaction in tumor tissues was studied by Picro-Sirius red staining.RESULTS: We found that co-expression of sh P53/NICD, sh P53/IDH1R132 C or NICD/IDH1R132 C did not lead to liver tumor formation. In striking contrast, coexpression of NICD/sh P53/IDH1R132 C resulted in ICC development in mice(P < 0.01). The tumors could be identified as early as 12 wk post hydrodynamic injection. Tumors rapidly progressed, and by 18 wk post hydrodynamic injection, multiple cystic lesions could be identified on the liver surface. NICD/sh P53/IDH1R132 C liver tumors shared multiple histological features of human ICCs, including hyperplasia of irregular glands. Importantly, all tumor cells were positive for the biliary epithelial cell marker cytokeratin 19. Extensive collagen fibers could be visualized in tumor tissues using Sirus red staining, duplicating the desmoplastic reaction observed in human ICC. Tumors were highly proliferative and expressed ectopically injected genes. Together these studies supported that NICD/sh P53/IDH1R132 C liver tumors were indeed ICCs. Finally, no p-AKT or p-ERK positive staining was observed, suggesting that NICD/sh P53/IDH1R132 C driven ICC development was independent of AKT/m TOR and Ras/MAPK signaling cascades. CONCLUSION: We have generated a simple, nongermline murine ICC model with activated Notch, loss of p53 and IDH1R132 C mutant. The study supported the oncogenic potential of IDH1R132 C.

TβR Ⅰ和Smad4在肝内胆管细胞癌中的表达及意义

目的探讨转化生长因子β(TGF-β)通路中的转化生长因子βⅠ型受体(TβRⅠ)和Smad4蛋白在肝内胆管细胞癌组织中的表达及其可能的作用机制。方法应用免疫组织化学EnVision二步法,检测19例正常肝组织肝内胆管细胞,33例肝内胆管细胞癌组织中TβRⅠ、Smad4蛋白的表达情况。结果 33例肝内胆管细胞癌组织中TβRⅠ和Smad4蛋白的阳性表达率分别为30.30%、24.24%,19例正常肝组织肝内胆管细胞中TβRⅠ和Smad4蛋白的阳性表达率分别为68.42%、63.16%,肝内胆管细胞癌组织中TβRⅠ和Smad4表达明显低于正常肝组织肝内胆管细胞,差异有统计学意义(P<0.01)。肝内胆管细胞癌组织中TβRⅠ蛋白表达与Smad4蛋白表达呈正相关(r=0.232 4,P<0.01)。结论 TβRⅠ和Smad4蛋白在肝内胆管细胞癌组织中的表达与肝内胆管细胞癌的发生、发展密切相关。

CA19-9、CA125和CEA联合检测在AFP阴性的ICC鉴别诊断中的效果

目的:探究CA19-9(血清癌抗原19-9)、CA125(癌抗原125)和CEA(癌胚抗原)联合检测在AFP(甲胎蛋白)阴性的ICC(肝内胆管细胞癌)鉴别诊断中的效果。方法:收集某院2015年12月~2017年12月收治的92例ICC患者,根据AFP的阳阴性,分甲组(阴性组n=46)和乙组(阳性组n=46)。用微粒子酶联免疫分析法对CEA、CA125、CA19-9进行检测,比较血清肿瘤标记物及其诊断效能。结果:与乙组CEA、CA125、CA19-9水平比较,甲组较高,具有统计学差异,P<0.05;根据CEA、CA125、CA19-9截断点可知CEA的正确率、特异度、灵敏度分别是60.9%、65.2%、59.2%;CA125的分别是65.2%、69.6%、56.5%,CA19-9的分别是68.5%、76.1%、60.9%。结论:AFP阴性的ICC患者进行CEA、CA125、CA19-9检测,可有效提高ICC患者的诊断准确率,效果确切,值得借鉴。

异柠檬酸脱氢酶基因突变在肝内胆管癌中的作用

异柠檬酸脱氢酶（IDH）是肝内胆管癌（ICC）中最常见的基因变异之一。在ICC和其他恶性肿瘤中，突变翻译后的IDH酶可产生异常代谢产物羟戊二酸（2-HG），并取代正常代谢产物a酮戊二酸（a-KG），从而抑制多量a-KG依赖的双加氧酶活性，导致细胞分化改变，肿瘤形成。本文对ICC中IDH基因突变作用的研究进展进行综述。