目的:淋巴水肿是淋巴结清扫和放疗等癌症治疗的常见并发症。这是一种病理性组织变化的衰弱状况,阻碍了有效的治愈性治疗并危及患者的生活质量。已经进行了各种尝试来预防淋巴水肿的发展,并改善了病理学的发生率。然而,它在癌症幸存者中仍然很普遍。在本文中,我们回顾了分子疗法和立即手术淋巴重建作为淋巴结清扫术后治疗策略。具体来说,我们讨论了在淋巴水肿动物模型和临床试验中已证明有效的亲淋巴管生成分子,并回顾了目前可用的即时淋巴重建的显微外科技术。
方法:在PubMed,Embase,科克伦图书馆,和谷歌学者到2022年5月。分别进行分子疗法和显微外科技术的快速淋巴重建。用于(1)非手术方法的搜索术语包括\'淋巴管生成\',\'淋巴水肿\',\'生长因子\',和“基因治疗”。用于(2)手术方法的搜索术语包括\'淋巴水肿\',\'淋巴结切除术\',\'淋巴管\',\'初级预防\',和“显微外科手术”。
结果:各种具有治疗潜力的前淋巴管生成因子包括VEGF-C,VEGF-D,HGF,bFGF,PDGF,IGF,维甲酸,Ang-1,S1P,TLR4和IL-8。用于预防继发性淋巴水肿的显微外科淋巴重建包括淋巴静脉吻合术(LYMPHA),血管化淋巴结转移,和淋巴间置性皮瓣转移(LIFT),有希望的临床结果。
结论:随着对淋巴管生成途径和淋巴水肿病理学的认识不断提高,以及恢复淋巴通道的显微外科技术的进步,分子和手术方法可能是淋巴水肿一级预防的一种有前途的方法。
OBJECTIVE: Lymphedema is a common complication of cancer treatment, such as lymphadenectomy and radiation therapy. It is a debilitating condition with pathologic tissue changes that hinder effective curative treatment and jeopardize patients\' quality of life. Various attempts to prevent the development of lymphedema have been made, with improvements in the incidence of the pathology. However, it is still prevalent among survivors of cancer. In this paper, we review both molecular therapeutics and immediate surgical lymphatic reconstruction as treatment strategies after lymphadenectomy. Specifically, we discuss pro-lymphangiogenic molecules that have proved efficient in animal models of lymphedema and clinical trials, and review currently available microsurgical techniques of immediate lymphatic reconstruction.
METHODS: A literature search was conducted in PubMed, Embase, Cochrane Library, and Google Scholar through May 2022. Searches were done separately for molecular therapeutics and microsurgical techniques for immediate lymphatic reconstruction. Search terms used for (1) non-surgical methods include \'lymphangiogenesis,\' \'lymphedema,\' \'growth factor,\' and \'gene therapy.\' Search terms used for (2) surgical methods include \'lymphedema,\' \'lymph node excision,\' \'lymphatic vessels,\' \'primary prevention,\' and \'microsurgery.\'
RESULTS: Various pro-lymphangiogenic factors with therapeutic potential include VEGF-C, VEGF-D, HGF, bFGF, PDGF, IGF, Retinoic acid, Ang-1, S1P, TLR4, and IL-8. Microsurgical lymphatic reconstruction for prevention of secondary lymphedema includes lymphovenous anastomosis, vascularized lymph node flap transfer, and lymph-interpositional flap transfer, with promising clinical outcomes.
CONCLUSIONS: With growing knowledge of the lymphangiogenic pathway and lymphedema pathology and advances in microsurgical techniques to restore lymphatic channels, molecular and surgical approaches may represent a promising method for primary prevention of lymphedema.