腹膜转移癌腹腔化疗的创新与挑战

冯欣滢, 王冰, 刘培峰

  1. 1.上海交通大学医学院附属仁济医院，上海市肿瘤研究所，肿瘤系统医学全国重点实验室，上海 200032
    2.上海交通大学医学院附属仁济医院中心实验室，上海 2000127
  • 收稿日期:2024-08-01 修回日期:2024-09-11 出版日期:2024-09-30 发布日期:2024-10-11
  • 通信作者: 刘培峰（ORCID: 0000-0001-7733-2511），研究员、博士研究生导师。
  • 作者简介:冯欣滢（ORCID: 0009-0000-7261-5248），硕士在读。
    刘培峰，研究员、博士研究生导师，上海市肿瘤研究所副所长，肿瘤系统医学全国重点实验室项目负责人，中国抗癌协会青年理事会常务理事，上海生物医学工程学会理事，《肿瘤》副主编，Nano Research、View编委。曾荣获国家“万人计划”青年拔尖人才、上海青年拔尖人才计划等荣誉。主要从事纳米药物载体的构建和新型抗肿瘤药物的开发研究，多项研究成果在Nature Biomedical Engineering、Advanced Materials、Angewandte Chemie International Edition、Accounts of Chemical Research等国际期刊上发表。主持多项国家级科研项目，并获得多项发明专利。
  • 基金资助:
    国家自然科学基金面上项目(32371468)

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摘要/Abstract

摘要：

腹膜转移癌是指从原发部位扩散至腹膜的恶性肿瘤，常见于胃癌、结直肠癌、卵巢癌及腹膜假黏液瘤（pseudomyxoma peritonei，PMP）等多种癌症类型的晚期阶段。腹膜转移癌的复发率和死亡率高，严重危害人类健康，通常在根治术后或晚期腹膜转移阶段采用以化疗为主的姑息性治疗方案。腹膜转移癌治疗的难点在于缺少靶向治疗药物以及药物较难透过血-腹膜屏障，以致全身治疗效果欠佳。腹腔化疗（intraperitoneal chemotherapy，IPC）作为一种重要的临床治疗手段，在腹膜转移癌的治疗中具有广阔的应用前景。近年来，腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）、腹腔加压气溶胶（pressurized intraperitoneal aerosol chemotherapy，PIPAC）等IPC技术的革新和新型药物的出现显著延长了患者的生存期。然而，腹膜转移癌的多样性和复杂性使临床IPC在给药方式、药物类型和剂量等治疗策略上仍然存在差异性和疗效不确定性。尽管已经制定了基于循证医学证据的指南和推荐治疗策略，但是仍需要通过更多的临床试验和更高级别的循证医学证据来进一步支持这些方案。本文对IPC的发展历程和最新进展进行归纳总结，对比分析手术治疗联合传统IPC、HIPEC及PIPAC等治疗手段的疗效，并对近期开展的IPC技术的研究进展进行汇总。此外，在IPC技术的临床应用方面，本文详细阐述其在胃癌、结直肠癌、妇科肿瘤、PMP、胆管癌及胰腺癌等疾病中的应用。针对IPC技术的局限性，提出纳米药物的创新开发有望为腹膜转移癌的治疗提供更安全有效的选择。综上所述，本文通过梳理IPC研究的最新进展、不足和未来发展方向，以期为腹膜转移癌更有效的临床治疗提供可行性方向。

关键词: 腹膜转移癌, 腹腔化疗, 腹腔热灌注化疗, 腹腔加压气溶胶, 纳米药物, 靶向治疗

Abstract:

Peritoneal metastatic carcinoma refers to the spread of malignant tumors from the primary site to the peritoneum. It is commonly observed in the advanced stages of various cancer types, including gastric cancer, colorectal cancer, ovarian cancer and pseudomyxoma peritonei (PMP). Peritoneal metastatic carcinoma seriously impair human health due to their high recurrence and mortality rates, and palliative treatment based on chemotherapy is usually provided after radical surgery or in the advanced stage of peritoneal metastases. The difficulties in the treatment of peritoneal metastatic carcinoma are the lack of targeted drugs and the difficulty of drugs to cross the blood-peritoneal barrier, resulting in poor systemic effects. Intraperitoneal chemotherapy, as an important therapeutic means, has a broad application prospect in the treatment of peritoneal metastatic carcinoma. In recent years, innovations in intraperitoneal chemotherapy techniques such as hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC) and the development of novel drugs have significantly improved patients' quality of life. The development of novel drugs has significantly improved patient survival. However, the diversity and complexity of these diseases have led to clinical variability and uncertainty in the efficacy of intraperitoneal chemotherapy in terms of treatment strategies such as mode of administration, drug type and dose. Although evidence-based guidelines and recommended treatment strategies have been developed, there is a need to further support these regimens through additional clinical trials and higher levels of evidence-based medicine. This review summarized the development history and recent advances in intraperitoneal chemotherapy, compared and analyzed the treatments such as surgery combined with traditional IPC, HIPEC and PIPAC, and summarized the research progress of recently conducted intraperitoneal chemotherapy techniques; moreover, in terms of the clinical application of intraperitoneal chemotherapy techniques, this paper elaborated on its use in diseases such as gastric cancer, colorectal cancer, gynecological oncology, PMP, cholangiocarcinoma and pancreatic cancer. For the limitations of intraperitoneal chemotherapy technology, it is proposed that the innovative development of nanomedicine is expected to provide a safer and more effective option for the treatment of peritoneal metastatic carcinoma. In conclusion, this review summarized the latest progress, shortcomings and future development of intraperitoneal chemotherapy, with the aim of providing a feasible direction for more effective clinical treatment of peritoneal metastatic carcinoma.

Key words: Peritoneal metastatic carcinoma, Intraperitoneal chemotherapy, Hyperthermic intraperitoneal chemotherapy, Pressurized intraperitoneal aerosol chemotherapy, Nano-drug, Targeted therapy

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