三联抗肿瘤疗法预防晚期原发性肝癌肝移植术后肿瘤复发的临床研究

杜国盛; 周林; 石炳毅; 朱志东; 宋继勇

doi:10.3969/j.issn.1674-7445.2014.02.004

三联抗肿瘤疗法预防晚期原发性肝癌肝移植术后肿瘤复发的临床研究

doi: 10.3969/j.issn.1674-7445.2014.02.004

1.
100091 北京, 解放军第309医院全军器官移植研究所肝胆外科（杜国盛、石炳毅、朱志东、宋继勇）
2.
解放军总医院(解放军医学院)（周林，与杜国盛为共同第一作者）

基金项目:

首都临床特色应用研究 Z111107058811008

详细信息

通讯作者:
石炳毅,Email:shibingyi@medmail.com.cn

中图分类号: R617
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- 被引次数: 0
出版历程
- 收稿日期: 2014-01-05
- 网络出版日期: 2021-01-26
- 刊出日期: 2014-03-15

Clinical study of triple anti-tumor therapy for preventing tumor recurrence of terminal primary liver cancer after liver transplantation

1.
Department of Hepatobiliary Surgery, the 309^th Hospital of Chinese People's Liberation Army, Beijing 100091, China

摘要

摘要: 目的初步探讨联合应用西罗莫司、胸腺肽α-1(Tα-1)及槐耳颗粒在预防晚期原发性肝癌(肝癌)肝移植术后肿瘤复发的有效性及安全性。方法联合治疗组为2010年至2012年在解放军第309医院接受肝移植的12例晚期肝癌患者(符合杭州标准)。历史对照组为2002年至2006年在该院接受晚期肝癌肝移植术15例患者,其随访资料完整。术后1个月根据患者的个体差异调整免疫抑制剂的种类或剂量,应用他克莫司(FK506)联合吗替麦考酚酯(MMF),术后1个月逐渐撤出FK506,由西罗莫司替代;术中给予甲泼尼龙500 mg,术后小剂量甲泼尼龙治疗,1周停药,此时开始加用Tα-1及槐耳颗粒。Tα-1用法:先连续皮下注射10 d,每次1.6 mg,每日1次,以后每周2次。槐耳颗粒:每次20 g,每日3次。所有患者均予随访。收集患者术后随访资料,内容包括术后1年血清甲胎蛋白(AFP)变化,术后排斥反应发生情况,肿瘤复发情况及处理方式,生存时间。结果联合治疗组随访8~35个月,中位随访时间18个月,无失访、退组等情况,患者均存活;历史对照组中位随访时间14个月,直至所有患者死亡。联合治疗中2例术后出现肺部孤立性转移灶(单发)和2例术后出现肺部多发转移灶(多发),经γ刀治疗后治愈。历史对照组中术后6个月15例患者中7例复发,术后1年内15例患者全部复发,且全部出现肺部转移,单发6例,多发9例,均死于肿瘤多处转移。结论联合应用西罗莫司、Tα-1及槐耳颗粒在预防晚期肝癌肝移植术后肿瘤复发有显著疗效,能延缓肿瘤的复发,延长患者的生存时间。
- 癌,肝细胞 /
- 肝移植 /
- 西罗莫司 /
- 胸腺肽α-1 /
- 槐耳颗粒 /
- 肿瘤复发
Abstract: Objective To investigate initially the availability and safety of combined application of sirolimus, thymosin α-1(Tα-1) and Huaier granule in preventing tumor recurrence of terminal primary liver cancer(TPLC) after liver transplantation(LT). Methods Combination group included 12 patients with TPLC who underwent LT in the 309^th hospital of Chinese People's Liberation Army from 2010 to 2012(all conform to Hangzhou standard). And historical control group included 15 patients with TPLC underwent LT at the same hospital from 2002 to 2006, whose follow up data was true and precise. During 1 month after LT, the type or dose of immunosuppressors was adjusted according to the individual differences of patients. Tacrolimus(FK506) and mycophenolate mofetil(MMF) were given to patients at first, and FK506 was gradually withdrawn and insteaded by sirolimus at 1 month after LT. Methylprednisolone of 500 mg was given during operation. Then small dose of methylprednisolone was given after operation and withdrawn at 1 week after LT. At the same time Tα-1 and Huaier Granule were added. The Tα-1 was injected for 10 days(1.6 mg per time, once a day), and after that injected twice a week. Huaier granule was given 20 g per time and three times a day. All the patients had been followed up. All the data including serum alpha-fetoprotein(AFP) changes, occurrence of allograft rejection, recurrence and treatment, survival time were collected accurately. Results In the combination group, the 12 cases were followed up for 8-35 months with the median follow up time of 18 months without loss or drop-out. All patients were survived. In the historical control group, the medium follow up time was 14 months till all the patients died. In the combination group, 2 cases developed isolated pulmonary metastasis after LT and 2 cases deveoped multiple pulmonary metastasis. All of the four cases were cured with the treatment of γ-knife. In history control group, 7 cases developed recurrence in 6 months after LT and all of the 15 cases developed recurrence in 1 year after LT. All of the 15 cases developed pulmonary metastasis(6 cases were isolated and 9 cases were multiple). All cases died of multi-section of tumor metastasis. Conclusions Combined application of sirolimus, Tα-1 and Huaier granule have significantly effect on preventing tumor recurrence of TPLC after LT, delaying tumor recurrence and prolonging survival time of patients.
- Carcinoma, Hepatocellular /
- Liver transplantation /
- Sirolimus /
- Thymosin alpha 1 /
- Huaier granule /
- Tumor recurrence

HTML全文

图 1 两组患者术后血清甲胎蛋白水平比较

Figure 1. Comparison of serum AFP level of patients between two groups after transplantation

下载: 全尺寸图片幻灯片

图 2 两组患者的术后复发时间的比较

Figure 2. Comparison of the recurrent time of patients between two groups after transplantation

下载: 全尺寸图片幻灯片

图 3 两组患者的术后存活时间的比较

Figure 3. Comparison of the survival time of patients between two groups after transplantation

下载: 全尺寸图片幻灯片

表 1 两组患者的基线资料比较

Table 1. Comparison of baseline data of patients between two groups(n)

项目	联合治疗组(n=12)	历史对照组(n=15)	P值
肿瘤类型
单发	3	12	>0.05
多发	9	3
肿瘤直径 (cm)
＜5	1	0	>0.05
5～10	6	5
>10	5	10
病理类型
HCC	5	1	>0.05
胆管细胞癌	1	0
HCC伴结节性肝硬化	6	10
HCC伴慢性胆囊炎	0	4
AFP(μg/L)
≤25	2	0	>0.05
＞25	10	15
注：HCC指肝细胞癌(hepatocellular carcinoma)

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