碘油-化疗药乳剂肝动脉化疗栓塞术治疗肝癌的疗效学研究
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摘要
前言
     肝癌是危害人类生命健康的主要恶性肿瘤之一,手术切除为首选的治疗方法,但只有10%~20%的病人适合手术治疗,而80%~90%的病人只能选择以介入治疗为主的其它非手术治疗方法。从八十年代初期日本学者首次报告经肝动脉碘化油栓塞治疗肝癌至今,肝癌的介入治疗得到了广泛的推广。这种广泛推广所带来的后果之一就是介入治疗的不规范,另外,有关肝癌介入治疗的疗效报告又存在着诸多差异。本研究旨在通过对我院介入病房近十年来采用碘油-化疗药乳剂肝动脉化疗栓塞术治疗的部分肝癌病例进行随访观察和临床疗效影响因素的统计分析,从而对肝癌介入治疗方法进行客观的评价,为肝癌的综合治疗提供理论依据。
     实验材料
     中国医科大学附属一院介入病房1991年10月~2000年10月共9年间采用碘油-化疗药乳剂肝动脉化疗栓塞术治疗的原发性肝癌及转移性肝癌病例。符合本研究入组标准的共670例,其中,568例原发性肝癌,均符合原发性肝癌的临床诊断标准,且147例有病理诊断;102例转移性肝癌的病人均有原发肿瘤的手术或活检病理证实。入组病例中,男573例,女97例,男女性别比例为5.9:1。治疗年龄18~78岁,平均年龄55.6岁。所有病人均有完整的影像学检查及介入治疗的病历资料和随访观察结果。
    
     实验方法
     采用Seldinger技术穿刺插管,先行间接门脉造影观察门脉改
    变,再行腹腔动脉造影或肝总动脉造影,明确肝内病灶,然后将导
    管分别插人肿瘤供血动脉。采用丝裂霉素10-20mg、阿霉素20-
    40二g溶于3-4rnl一氟尿呼院中,按 l>2-3的比例加人碘化油,
    充分振荡摇匀制成乳剂后经导管缓慢的推注到病灶局部;对血供
    丰富且肝功能状态较好的病人,加用明胶海绵颗粒进行栓塞。要
    求病人在1-2个月内复查肝功、肝脏CT或肝动脉造影检查,以
    决定是否及如何重复治疗。所有病人进行确切随访,应用SPSS
    10.0统计分析软件,建立数据库并进行统计分析。
     实验结 果
     单因素分析结果,得到与预后相关的因素有14项,但经过多
    因素分析,显示肿瘤类型、包膜、肝外转移、nnssg和重复治疗次
    数与预后显著相关,其中,重复治疗次数为保护性因素,且与疗效
    密切相关。
     本组病例采用KaPIan-Meter法,得出的全组总体L2*j年
    生存率为58.4%,27.1%,13.6%,4.0%。原发性肝癌和转移性
    肝癌的中期(SZ年)疗效大致相同;而转移性肝癌的远期疗效比
    原发性肝癌差。TACE和GS-TACE两种治疗方法的疗效无差
    别,但GS-TACE组术后侧支动脉的发生率万0/282)明显高于
    TACE组p2乃88)。根据血管造影结果,单结节型217例,多结节
    型238例,巨块型170例,弥漫型45例,单结节型中,小肝癌(直径
    $3cm)占52.2%,其中,单结节型肿瘤的生存率最高,弥漫型最
    差。本组间接门脉造影显示门脉癌栓患者132例O9.7%X位于
    门脉主干72例,分支(左、右支广0例,结果证明了门脉癌栓的存
     ·二·
    
    在并非是介人治疗的禁忌证。按照Okuda分期标准,将本组病例
    分为三期,Okud。l期540例,Okud。11期 109 例,Oklld。Ill期ZI
    例,肝动脉化疗栓塞术治疗Okuda期的疗效远远好于Okuda 11。
    Ill期。肝动脉化疗栓塞术后影像学资料完整的病例396例,肝内
    病灶的碘油沉积情况按照CT表现分为三型:密实型门57例X部
    分充填型*17例X稀少型p2例L碘油沉积呈密实型的生存率
    明显高于其它类型。本组重复治疗456例,无重复治疗为214例,
    重复治疗组中治疗次数从2次到12次不等,平均3次p.99次厂
    结果,重复治疗组的生存率高于无重复治疗组,重复治疗次数)4
    次者可以明显提高生存率。我们将1996年1月一2000年10月的
    病例年份分为5组,各组二年生存率随年份呈递增趋势。
     讨 论
     肝癌的介人治疗在肝癌的非手术治疗方面占重要的地位,但
    目前尚缺乏一个统一的化疗栓塞方案。本文通过对大样本的采用
    碘油一化疗药乳剂肝动脉化疗栓塞术治疗的肝癌病例进行随访统
    计分析,从而对肝癌介人治疗的生存率及相关因素进行评价b
     本组病例中,原发性肝癌和转移性肝癌的中期疗效并无显著
    性差异。分析其原因我们发现,本组转移性肝癌病例中,一半以上
    为结肠/直肠癌肝转移,病理类型多为分化程度比较高的腺癌,其
    生物学特性决定了它对肝功能的影响程度低;血管造影经常可以
    看到肿瘤为肝动脉供血,血供尚可,多数有包膜;栓塞治疗后碘油
    沉积也可为密实型和部分充填型,说明了肝动脉化疗栓塞术是转
    移性肝癌有效的治疗方法。按治疗方法的不同本组病例可分成
    TACE和 GS-TACE两组,两组的生存率及术后侧支动脉的发生
    率比较发现,肝动脉化疗栓塞术中明胶海绵的应用并不能明显提
    高栓塞治疗的疗效,并且是侧支动脉形成的诱因之一。我们认为:
    肝动脉化疗栓塞术需要保留一有效的给药途径以便治疗复发或残
     ·3·
    
    留的肿瘤组织;同时,本组病例中应用的明胶海?
Preface
    liver neoplasm is one of the most common malignant tumors that threaten the health of human. Surgical resection currently is considered to be the only preferred treatment, unfortunately, only a small number of patients are suitable candidates for such resection. Transcatheter arterial chemoembolization ( TACE) has become the first choice of palliative treatment for 80% -90% unresectable liver neoplasms. Since the transcatheter arterial embolization was first introduced by Nakamura et al in 1980s, it has now been widely used with the development of radiographic diagnosis and interventional therapeutic equipment, which brings two problems to the interventional treatment of liver neoplasms: the absence of a acceptance criterion and the variety of efficacy. The purpose of our study was to assess the efficacy of TACE using lipiodol - chemotherapeutic drugs emulsion by following liver neoplasms cases in our interventional ward and analysis some correlative factors and to provide a theoretical basis for treatment o
    f liver neoplasms.
    Materials
    From October 1991 to October 2000, 670 patients with primary
    
    
    hepatocellular carcinoma ( PHC ) or metastatic hepatic cancer ( MHC) were enrollded in a retrospective trial of TACE, of which PHC 568 cases and MHC 102 cases. All PHC were diagnosed by clinical diagnosis criteria, including 147 cases of pathologic diagnosis, while MHC were diagnosed by the original tumors. There were 573 men and 97 women, with a mean age of 55.6 years (range, 18-78 years). All cases had complete radiographic, following and clinical data.
    Methods
    Using the Seldinger technique and catheterizing the femoral arter-y, indirect portal vein angiography and hepatic arterial angiography was performed in turn. The embolization emulsion, mixed with MMC 10-20mg, ADM 20 -40mg, 5 - FU 3 - 4ml and ildized oil 8 -15ml, was injected through the catheter. 1 - 3mm gelatin sponge (GS) particles were used in patients with better liver function and rich blood - supplyment tumors. Cases received reexamination of liver function, hepatic CT or DSA to determine whether and how to perform retreatment. Statistical analysis employed SPSS software.
    Results
    Univariate analysis showed 14 parameters were significant prognostic factors. However, multivariate analysis showed that tumor type, encapsulant, extrahepatic involvement, HBsAg and treatment times were significant factors. The overall commulative survival rates for 1, 2, 3 and 5 years were 58. 4% , 27. 1% , 13. 6% and 4. 0% respectively.
    The mid - term efficacy of PHC and MHC was almost the same,
    
    but the long - term efficacy of MHC is lower. According to the different regimens, all cases were divided into two groups: TACE (simple embolization by emulsion) and GS -TACE (embolization by emulsion and GS). The efficacy between two groups had no defferences. But the postembolization occurrence of collateral arterial in GS - TACE group was higher than TACE group. According DSA, nodular 217 cases, multinodular 238 cases, massive 170 cases and diffuse 45 cases. Among them, the survival rate of nodular was the highest. Portal vein tumor thrombus 132 cases. By Okuda criterion, Okuda I were 540 cases, Okuda II 109 cases, Okuda III 21 cases. The TACE efficacy of Okuda I is the best. The lipiodol uptake pattern of postembolization consisted of denseness, partretention and sparseness. The denseness survived the longest as a whole. Retreatment can improve the survival rate, furthermore, retreatment times >4 times is the highest. Our study also showed that the 1 year survival rate increased along with the years.
    Discussion
    Our study showed that the mid - term efficacy of PHC and MHC after TACE was almost the same. Analysis the original tumors of MHC, we found that half of the cases were from colonic or rectal carcinoma, pathological type of most of them were highly differenttiative adenocarcinoma, which influenced the liver function lower; DSA often showed hepatic arterial supplying the tumors and encapsulant; CT of postembolization showed lipiodol uptake as
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