Propranolol as an Alternative Treatment Option for Pediatric Lymphatic Malformation
Propranolol as an Alternative Treatment Option for Pediatric Lymphatic Malformation
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DOI：
10.1620/tjem.229.61
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发表时间：
2013-01-01
影响因子：
2.2
通讯作者：
Kondo, Naomi
中科院分区：
文献类型：
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作者：
Ozeki, Michio;Kanda, Kaori;Kondo, Naomi
淋巴管畸形（LM），以前被称为淋巴管瘤，是一种罕见的先天性淋巴系统畸形，其治疗仍然具有挑战性。普萘洛尔（β受体阻滞剂）最近被开发为婴儿血管瘤的一线治疗药物。我们的研究旨在评估普萘洛尔对儿童LM的作用及其有效性与血管内皮生长因子（VEGF）家族成员（VEGF-A，C和D）之间的关系。入组了6例日本LM患者（年龄范围：10个月至19岁; 2例巨囊性、2例微囊性和2例混合型）。以2 mg/kg/天剂量经口给予普萘洛尔。普萘洛尔对LM的疗效通过MRI成像计算的体积变化率和症状改善来评价。在所有患者中，没有明显的副作用。患者3和5被归类为客观应答者，在24周时肿瘤体积分别减少30.6%和22.9%。患者1显示肿瘤体积减小8%，患者6显示症状改善，因此，两者均被归类为最小应答者。另外两名患者被归类为无应答者。LM组的血浆VEGF-A、C和D水平显著高于对照组（通过Mann-Whitney检验，所有P < 0.01）。VEGF-A和D水平在24周时显著低于治疗前（P = 0.031，Wilcoxon配对检验为0.047）。虽然这种治疗方法还需要进一步的试验，但我们认为普萘洛尔可能是难治性LM的一种替代治疗选择。
Lymphatic malformation (LM), which was previously termed lymphangioma, is a rare congenital malformation of the lymphatic system and its treatment is still challenging. Propranolol (beta blocker) has been recently developed as a first-line treatment of infantile hemangioma. Our study aimed to assess the effect of propranolol on pediatric LM and the relationship between its effectiveness and vascular endothelial growth factor (VEGF) family members (VEGF-A, C and D). Six Japanese patients with LM (age range: 10 months-19 years old; 2 macrocystic, 2 microcystic and 2 combined type) were enrolled. Oral propranolol was administered at 2 mg/kg/day. The efficacy of propranolol for LM was evaluated by the rate of volume change as calculated from MRI imaging and by symptomatic improvement. In all patients, there were no significant side effects. Patients 3 and 5 were classified as objective responders with tumor volume reduction of 30.6% and 22.9%, respectively, at 24 weeks. Patient 1 showed 8% tumor volume reduction and patient 6 showed symptomatic improvement, hence, both were classified as minimal responders. The other two patients were classified as non-responders. Plasma VEGF-A, C, and D levels were significantly higher in the LM group than in the controls (all P < 0.01 by Mann-Whitney test). VEGF-A and D levels at 24 weeks were significantly lower than those at pre-treatment (P = 0.031, 0.047 by Wilcoxon matched pairs test). Though further trials with this treatment must be carried out, we propose that propranolol may be an alternative therapy option for intractable LM.