Bates David O
Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, United Kingdom.
Pathophysiology. 2010 Sep;17(4):289-94. doi: 10.1016/j.pathophys.2009.10.006. Epub 2009 Dec 5.
Breast cancer related lymphoedema (BCRL), the chronically swollen arm of patients that have been treated for breast cancer, is no longer considered to be a result of lymphatic obstruction as recent studies have identified failing peripheral lymphatic function as a principal contributing factor. The aetiology and pathophysiology that results in this lymphatic failure is not clearly understood, but it can occur with minimal or even in some cases no damage to the axillary lymph nodes, and evidence suggests that some patients are pre-disposed to develop the disease, and have poor lymphatic function in their non-affected arms. It has been shown that interstitial forces such as hydrostatic pressure, and interstitial fluid velocity, can regulate both lymph flow, and lymph formation, and there is good evidence that interstitial forces are dysregulated in lymphoedema patients. Here I outline a hypothesis for how dysregulation of interstitial parameters could contribute to the generation of breast cancer related lymphoedema, by combining disparate strands of current evidence on the molecular and physiological control of interstitial and lymph flows. One mechanism by which lymphoedema could be generated is that a reduction in interstitial velocity results in increased VEGF-C production, which in low flow conditions, instead of acting on the lymphatics to increase pumping and lymphangiogenesis, acts on vasculature to increase fluid filtration. The resulting increase in interstitial pressure restores flow, but at the expense of increased volume and hence oedema. The evidence supporting the hypothesis and possible tests of it are presented and discussed.
乳腺癌相关淋巴水肿（BCRL），即接受过乳腺癌治疗的患者长期肿胀的手臂，不再被认为是淋巴阻塞的结果，因为最近的研究已确定外周淋巴功能衰竭是一个主要促成因素。导致这种淋巴功能衰竭的病因和病理生理学尚不清楚，但它可能在腋窝淋巴结极少受损甚至在某些情况下没有受损的情况下发生，并且有证据表明一些患者易患此病，其未受影响的手臂淋巴功能也较差。研究表明，诸如静水压力和组织间液流速等组织间力可以调节淋巴流动和淋巴生成，并且有充分证据表明淋巴水肿患者的组织间力失调。在此，我通过结合目前关于组织间液和淋巴流动的分子和生理控制的不同证据，概述一个关于组织间参数失调如何导致乳腺癌相关淋巴水肿的假说。淋巴水肿可能产生的一种机制是，组织间液流速降低导致VEGF-C生成增加，在低流量条件下，VEGF-C不是作用于淋巴管以增加泵血和淋巴管生成，而是作用于血管系统以增加液体滤过。由此导致的组织间液压力升高恢复了流动，但以体积增加和水肿为代价。文中展示并讨论了支持该假说的证据及其可能的检验方法。
