Kitamura Morimasa, Hayashi Tomomasa, Suzuki Chiaki, Hirano Shigeru, Tateya Ichiro, Kishimoto Yo, Omori Koichi
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
World J Surg Oncol. 2017 Jan 14;15(1):24. doi: 10.1186/s12957-017-1096-5.
There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding.
We report a case of a 53-year-old woman, who underwent repeated neck dissections and RAI therapy after total thyroidectomy in an outside hospital. Pathology revealed a papillary carcinoma of the tall cell variant. Locoregional recurrence was not under control; therefore, she visited our hospital. Although surgery was performed for locoregional recurrences three times in our hospital, they were not under control and distant metastases were found in the lung and bone a year later. Therefore, although sorafenib was initiated, the locoregional recurrence progressed 6 months later and computed tomography (CT) showed a 7-cm mass in the right subclavicular lesion. Lenvatinib was started at a dose of 24 mg daily. However, although tumor was rapidly reduced, an ulcer occurred in the right subclavicular lesion and was gradually increasing in size. The pulsation of subclavicular artery was found in the deep portion of the ulcer. Therefore, a pectoralis major myocutaneous flap was transplanted to cover the ulcer. Lenvatinib was an antiangiogetic TKI; therefore, it was preoperatively discontinued for 8 days and postoperatively for 12 days. The postoperative course was uneventful.
Fistula formation or bleeding is known to be a severe side effect of antiangiogenic TKIs such as lenvatinib or sorafenib. There is a possibility that severe complications can occur when initiating TKIs in patients whose tumor has invaded into the skin, vessels, trachea, esophagus, and other areas. Therefore, it is necessary to use antiangiogenic TKIs very carefully. It is important to determine the appropriate time to start TKIs; however, there is no established protocol for this, and it is a problem that needs urgent attention.
目前对于局部复发、转移或进展性放射性碘（RAI）难治性分化型甲状腺癌尚无有效的治疗方法。然而，多靶点酪氨酸激酶抑制剂（TKIs）如乐伐替尼或索拉非尼已被批准作为二线靶向治疗用于RAI难治性分化型甲状腺癌患者，这些药物可延长患者生存期。然而，已有数例报道称TKIs会导致致命并发症，如瘘管形成或出血。
我们报告一例53岁女性患者，在外院行全甲状腺切除术后接受了多次颈部淋巴结清扫和RAI治疗。病理显示为高细胞变异型乳头状癌。局部区域复发未得到控制，因此她前来我院就诊。尽管我院对局部区域复发进行了三次手术，但仍未得到控制，一年后发现肺部和骨远处转移。因此，尽管开始使用索拉非尼治疗，但6个月后局部区域复发仍有进展，计算机断层扫描（CT）显示右锁骨下病灶有一个7厘米的肿块。开始每日服用24毫克乐伐替尼。然而，尽管肿瘤迅速缩小，但右锁骨下病灶出现溃疡且面积逐渐增大。在溃疡深部发现锁骨下动脉搏动。因此，移植胸大肌肌皮瓣覆盖溃疡。乐伐替尼是一种抗血管生成的TKI，因此术前停药8天，术后停药12天。术后过程顺利。
已知瘘管形成或出血是乐伐替尼或索拉非尼等抗血管生成TKIs的严重副作用。对于肿瘤已侵犯皮肤、血管、气管、食管及其他区域的患者，开始使用TKIs时有可能发生严重并发症。因此，必须非常谨慎地使用抗血管生成TKIs。确定开始使用TKIs的合适时间很重要；然而，目前尚无既定方案，这是一个亟待关注的问题。
