肝细胞癌肝内微转移的研究

目的 探讨肝细胞癌肝内微转移分布的规律。方法 选择无临床肝内转移且无门静脉主干或一级分支内瘤栓、切缘充分的单发肝细胞癌切除标本43例为研究对象。用立体定位全取材切片和黑色素瘤抗原（MAGE）及甲胎蛋白（AFP）抗体免疫组化染色技术寻找肝内的微转移。结果 58．7％（25／43）的患者肝内微转移阳性，59．3％（179／302）的转移灶为门静脉内的微瘤栓。微转移距原发灶的最远距离可达4．7cm，P95为2．5cm。单因素分析显示，微转移的发生与血清AFP水平、原发瘤直径、包膜完整性和Edmondson分级相关（χ^2或t值分别为11．50，2．465，12．17和16．59，P〈0．05）。多因素分析显示，原发瘤直径和包膜完整性是独立影响因素（Wald值为7．903和3．858，P〈0．05）。在HE染色微转移阴性的切片中AFP染色阳性率为9．3％，MAGE为7．0％，至少有一项阳性者为14．0％。结论 （1）肝细胞癌肝内转移是较为普遍的现象，大部分位于原发瘤附近，主要形式为门静脉内的微瘤栓。（2）无临床转移的单发肝癌的理想手术切缘应为2．5cm，并应根据肿瘤的生物学特性进行调整。（3）AFP和MAGE免疫组化染色有利于肝内微转移的检出。

A study on the intrahepatic micrometastases in the vicinity of solitary hepatocellular carcinoma

Objective To study the intrahepatic micrometastases surrounding solitary hepatocellular carcinoma (HCC). Methods Forty-three solitary HCC patients without tumor thrombus in the main portal vein or its first branch were collected. Specimens with safe margins were made into multiple sections stained with HE and antibodies against alpha-fetoprotein (AFP) or melanoma-associated antigen (MAGE ) for intrahepatic metastases. Results Twenty-five ( 58.7% ) patients were found with micrometastases. Among 302 micrometastatic foci, 179 foci (59.3%) were within the portal vein. The spread distances were up to 4. 7 cm with the P95 being 2. 5 cm. With univariate analysis, preoperative serum AFP, the size, capsule status and Edmondson grade of primary tumor were found to be significant factors associating with intrahepatic micrometastases (x2 or t values 11.50,2.465,12. 17 and 16.59, P<0.05). With multivariate analysis, the size and capsule status of primary tumor independently affected intrahepatic micrometastases ( Wald values 7.903 and 3.858, P < 0. 05). Among HE stain negative sections the micrometastases positive rate was 9. 3% against AFP, 7. 0% against MAGE and 14. 0% against at least one of them. Conclusions ( 1) Intrahepatic micrometastases are common in HCC with the main form of microscopic tumor emboli in portal vein. (2) The surgical margin of 2. 5 cm is necessary for hepactomy with the adjustment according to the tumor' s clinicopathological features. Most patients need postoperative adjuvant therapy. (3) Immunohistochemical detection of intrahepatic micrometastases against AFP and MAGE is feasible in HCC patients.