Jørgensen Mads Gustaf, Toyserkani Navid Mohammadpour, Hansen Christian Rønn, Hvidsten Svend, Baun Christina, Hejbøl Eva Kildall, Schrøder Henrik Daa, Sørensen Jens Ahm
From the Department of Plastic Surgery and.
Departments of Nuclear Medicine and.
Ann Plast Surg. 2018 Nov;81(5):594-603. doi: 10.1097/SAP.0000000000001537.
Lymphedema is a common and debilitating complication following cancer treatment with surgical lymph node excision and radiotherapy. Currently there are no curative treatments for lymphedema. Animal models that intended to replicate the disease have been inadequate, making a troublesome transition from experimental therapeutic studies into the clinic. It is therefore imperative to establish an experimental animal model that can reliably replicate clinical lymphedema.
To discover the optimal method of lymphedema induction, surgical lymph ablation and irradiation or silicone splint emplacement were combined in 8 experimental groups (n = 4). In total, 32 mice served in this study and were followed for 8 weeks after surgery. Outcomes included micro-computed tomography hind limb volumetry, lymphatic clearance measured with technetium Tc 99m (Tc) human serum albumin lymphoscintigraphy and lymph vessel ectasia quantified with LYVE-1 immunohistochemistry.
All trialed models but one resulted in only transient lymphedema or lasting lymphedema with adverse morbidity. Combined surgical lymph obstruction with 2 fractions of 10-Gy irradiation successfully induced lasting lymphedema without adverse events. Over the 8 weeks' follow-up, limb volumes were significantly increased at all time points (P < 0.001), lymph drainage was impaired (P < 0.001), and lymph vessels were ectatic (P < 0.001), when compared with the unoperated limbs.
The presented model of acquired lymphedema is a reduction and refinement of previous works and can transpose to future observational and interventional studies. In addition, it is shown how Tc-HSA lymphoscintigraphy can quantify lymphatic clearance, which can prove insightful in therapeutic studies aiming to enhance lymphatic drainage.
淋巴水肿是癌症治疗（手术切除淋巴结和放疗）后常见且使人衰弱的并发症。目前尚无治愈淋巴水肿的疗法。旨在复制该疾病的动物模型并不完善，导致从实验性治疗研究向临床应用的转变困难重重。因此，建立一种能够可靠复制临床淋巴水肿的实验动物模型势在必行。
为探寻诱导淋巴水肿的最佳方法，将手术性淋巴切除与放疗或放置硅胶夹板相结合，设置了8个实验组（每组n = 4）。本研究共纳入32只小鼠，术后随访8周。观察指标包括微型计算机断层扫描测量后肢体积、用锝Tc 99m（Tc）人血清白蛋白淋巴闪烁显像术测量淋巴清除率以及用LYVE-1免疫组织化学法定量淋巴管扩张情况。
除一个模型外，所有试验模型均仅导致短暂性淋巴水肿或伴有不良发病率的持续性淋巴水肿。联合手术性淋巴阻塞与两次10 Gy的放疗成功诱导出持续性淋巴水肿且无不良事件发生。在8周的随访期间，与未手术的肢体相比，所有时间点的肢体体积均显著增加（P < 0.001），淋巴引流受损（P < 0.001），且淋巴管扩张（P < 0.001）。
所呈现的获得性淋巴水肿模型是对先前研究的简化和优化，可应用于未来的观察性和干预性研究。此外，还展示了Tc-HSA淋巴闪烁显像术如何量化淋巴清除率，这在旨在增强淋巴引流的治疗研究中可能具有重要意义。
