好博士·热灌注丨文献微评丨腹腔热灌注化疗（HIPEC）治疗胃癌腹膜转移：现状与未来

根据2020年文献报道，全球胃癌新发病例达109万，在新发癌症中位列第五；死亡病例达77万，居第四位【1，2】。我国超过50万肿瘤患者是胃癌腹膜转移癌患者【3】。其中约20%胃癌患者术前或术中发现有腹膜转移，以及大多数T3或T4晚期胃癌患者根治术后复发有腹膜转移【4】，单纯全身化疗中位生存期仅6–10个月，长期生存极难实现，因此，胃癌腹膜转移曾认为是不可治愈恶性肿瘤。腹腔热灌注化疗（HIPEC）联合肿瘤细胞减灭术（CRS）依托热疗+局部高浓度化疗+机械冲洗+免疫效应四重协同效应，成为这类患者的核心局部治疗手段。结合东西方多项、随机临床对照研究结果，针对CRS+HIPEC治疗胃癌腹膜转移癌的现状与未来简要评述如下。

图：胃癌腹膜转移过程示意图。(A)胃癌原发病灶形成；(B)改变腹膜区域微环境；(C)肿瘤细胞直接侵犯、脱落、种植转移；(D)肿瘤细胞通过血液循环转移；(E)肿瘤细胞通过淋巴循环转移；(F)形成腹膜转移灶。

图片来源：中国科学院网站《自动化所等在胃癌隐匿性腹膜转移智能诊断研究中获进展》

过去：理论基础与早期探索（1980s—2015）

理论基础建立

1980年代，全球共识认为，胃癌腹膜转移属终末期，仅能姑息化疗，无根治手段。Fujimoto、Koga等日本学者率先证实42–43℃高温可增敏铂类、丝裂霉素，由于血-腹膜屏障，腹腔局域给药，能使腹腔药物浓度可达全身静脉给药数十倍，同时大容量灌洗能清除腹腔游离癌细胞，奠定了HIPEC治疗胃癌腹膜转移的理论根基【5～7】。

亚洲早期临床初步获益

亚洲率先开展临床探索：日本早期小随机对照研究显示，根治术后辅助腹腔温热灌注可降低腹膜复发【6，7】；2011年国内杨建平等III期随机临床试验证实，CRS+HIPEC对比单纯手术（CRS），中位生存期从6.5个月提升至11个月，首次提供高级别证据证明HIPEC生存获益【8】。

西方起步、争议并存

欧美起步晚，早期以单中心、回顾性研究为主。2014年一篇综述指出，欧洲内科肿瘤协会（ESMO)，美国国立癌症网络（NCCN），日本胃癌协会（JGCA）胃癌指南仅推荐临床试验内开展CRS+HIPEC，不常规用于临床，核心争议为样本量小、方案不统一、缺乏大型随机对照临床研究数据、手术创伤大、并发症风险高等问题【9】。早期HIPEC方案缺乏统一：灌注时长60分钟为主，药物多用丝裂霉素、顺铂；筛选标准模糊，未建立PCI（腹膜癌指数）分层体系，高肿瘤负荷患者术后获益有限。此阶段研究多为单中心回顾性、小样本，东西方化疗方案差异巨大（亚洲S-1，欧美ECX/FLOT），无统一HIPEC操作规范【9～12】。

现状：分层规范化与证据完善（2016—2025）

患者分层标准确立，PCI成为核心筛选指标

多项研究统一证实PCI≤6、实现CC0完整减瘤是获益核心门槛：

国内CLASS-05 II期研究：腹腔镜CRS+HIPEC，PCI≤6患者中位OS 29个月，PCI＞6仅11个月，差异显著【13】。

德国、法国多中心队列研究结果均提示，PCI过高、无法完全减瘤者难以从HIPEC获益，现已形成术前腹腔镜评估PCI的标准流程【14～17】。

HIPEC灌注时长、方案优化突破

2023年德国单中心回顾研究（Steinhoff等，纳入73例GC-PM）为里程碑【18】：60分钟HIPEC治疗，中位OS 12.86个月，90分钟顺铂灌注组达27.3个月；倾向性匹配后差异有统计学意义（HR=0.2843，P=0.0082），证实延长90分钟热灌注可显著改善特异性生存，2018年后欧美中心逐步将90分钟作为优选方案。

药物形成主流组合：欧美顺铂+多柔比星，亚洲多西他赛；同时硫代硫酸钠用于顺铂肾脏保护的标准化流程落地，降低围术期肾毒性。

多模式综合治疗成型：转化+HIPEC+手术

新辅助全身+腹腔双向转化治疗成为主流：

国内浙江肿瘤中心前瞻性队列【19】：先全身+腹腔新辅助化疗降期，再行CRS+HIPEC，转化手术组中位OS 21.1个月，单纯姑息化疗组仅10.8个月。

2023年德国GASTRIPEC III期随机试验【20】：整体人群CRS±HIPEC总生存期无差异（均14.9个月），但CC0完整减瘤亚组加用HIPEC显著延长无远处转移生存期，明确了HIPEC获益人群仅限彻底减瘤患者，解释既往研究矛盾结果。

微创HIPEC普及、安全性提升

腹腔镜CRS（L-CRS）联合术后多次、序贯HIPEC（术后第1，3，5天）方案成熟【13，21】。CLASS-05研究显示微创术后并发症仅20%，重度并发症10%，中位住院8天，大幅降低传统开放手术创伤，适合局限腹膜转移年轻患者【13】。

东西方证据差异

亚洲多中心前瞻性研究整体阳性【22】；欧美大型III期（GASTRIPEC）总体阴性，但亚组获益明确【23】；指南更新为选择性用于低PCI、完整减瘤人群，仅限专科腹膜肿瘤中心开展，不再全盘否定HIPEC对于胃癌腹膜转移治疗效果【24～27】。

未来：精准化、个体化与新技术融合

□ 精准筛选病例与分子分层治疗

液体活检（腹腔游离肿瘤细胞、ctDNA）预判腹膜微转移，提前筛选高危根治术后需预防性HIPEC人群【28～30】。

分子分型指导：HER2阳性患者联合曲妥珠单抗联合腹腔治疗，已有回顾性数据显示生存延长；腹膜型、印戒细胞癌亚组定制灌注药物方案，打破“一刀切”模式【31，32】。

□ HIPEC方案持续迭代

延长灌注90分钟方案开展多中心随机验证，确认长期生存获益【33，34】。

腹腔靶向、免疫药物联合热灌注：如卡妥索单抗用于恶性腹水，腹腔PD-1抑制剂联合热疗协同杀伤腹腔微转移灶【35～38】。

加压腹腔气溶胶化疗（PIPAC）作为不耐受手术或失去手机会患者的姑息替代，同步开展对比研究【39～41】。

□ 大型III期临床试验提供一级证据

多项全球多中心随机试验正在推进：欧洲PERISCOPE II、GASTRICH，国内HIPEC-01、HIPEC-02，对比“转化+CRS+HIPEC”与单纯全身化疗，有望改写全球胃癌指南，统一东西方治疗标准【42～44】。

□  预防型HIPEC成为热点

针对T3/T4浆膜侵犯、腹腔细胞学阳性（无肉眼腹膜转移）高危胃癌，预防性HIPEC降低术后腹膜复发；德国PREVENT III期FLOT联合预防性HIPEC研究正在入组，有望将HIPEC适应症从晚期转移拓展至局部高危可切除胃癌【45～47】。

□ 微创与智能化治疗

机器人CRS联合术中实时测温、均匀灌注系统，保证腹腔药物温度稳定；人工智能基于PCI、血常规、肿瘤标志物构建预后模型，精准预测患者能否从HIPEC获益，避免无效手术与灌注带来的创伤【48～52】。

过去，认为胃癌腹膜转移属于不可治愈，针对HIPEC治疗胃癌腹膜转移充满争议。现在，分层筛选、90分钟延长灌注、转化联合CRS+HIPEC的综合模式已标准化；低PCI、完整减瘤（CC0）患者可获得翻倍生存期。未来将走向分子精准分层、免疫/靶向联合、预防性应用、微创智能化，通过大型随机试验统一全球治疗规范，彻底改写胃癌腹膜转移“不可治愈”的传统认知；但该疗法仍需多团队（MDT）协作，在具备腹膜肿瘤专科资质中心开展，严格把握手术减瘤与患者筛选指征。

专家简介

刘博士M.D.,Ph.D.

专业学会会员

美国细胞学会American Society for Cell Biology(2006-至今)

美国心脏学会American Heart Association(2006-至今)

美国胸科学会American Thoracic Society(1997-至今)

2023-2025.5副教授美国迈阿密大学心血管内科

1999-2023助/副教授美国内布拉斯加大学医学中心呼吸与重症科

1996-1999博士后美国内布拉斯加大学医学中心呼吸与重症科

1992-1995医学硕士第四军医大学西京医院呼吸内科(孙滨教授)

1986-1992临床医师沈阳军区总医院呼吸内科

1981-1986医学学士第四军医大学医疗系

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