Ackerman Jaeger, Kent Sean, Walker Paul
Department of Otolaryngology, Loma Linda University, Loma Linda, CA, USA.
Ann Otol Rhinol Laryngol. 2020 Jul;129(7):657-661. doi: 10.1177/0003489420902161. Epub 2020 Feb 10.
Medullary thyroid carcinoma (MTC) accounts for 1% to 2% of thyroid cancers in the United States. When identified early, total thyroidectomy is most often curative. However, in advanced disease, more aggressive treatment such as laryngectomy and esophagectomy may be indicated. Postsurgical fistula formation and leak is a potential complication in such cases. These fistulas are most likely to occur at the anastomotic site in cases of laryngectomy or esophagectomy. Concomitant chemotherapy and radiation increase this risk. Tyrosine kinase inhibitors (TKI) such as Cabozantinib are used as therapy for metastatic MTC. These drugs have previously been associated with dehiscence of anastomotic sites in the gastrointestinal tract. While previously identified in the bowel, this report represents the first documented case of gastropharyngeal anastomosis leak described in the context of TKI use for head and neck cancer.
We present the case of a 72-year-old male previously diagnosed with MTC. His gastropharyngeal anastomosis status-post laryngopharyngectomy and gastric pull up had been stable for 23 years. Over the past year, he developed back pain and was found to have spinal metastases of MTC. He was subsequently started on Cabozantinib to slow the progression of the disease. Within months of starting this TKI, a bleeding pharyngocutaneous fistula developed at the anastomosis site of the gastric pull up and pharynx. Upon discontinuation of Cabozantinib, the fistula healed with no further complications.
To our knowledge, this is the first documented case of gastropharyngeal anastomotic leak related to TKI use. A causal relationship is highly plausible given the previously stable anastomosis and the suspicious advent of complications within months of initiation of this new drug. While previously limited to cases of intraabdominal bowel dehiscence, this report now suggests that wound dehiscence must be considered a known side effect of TKIs throughout the gastrointestinal tract, including the gastropharynx. As such, the risk of anastomotic dehiscence should be discussed with the patient prior to starting a TKI.
在美国，甲状腺髓样癌（MTC）占甲状腺癌的1%至2%。早期确诊时，全甲状腺切除术通常可治愈。然而，对于晚期疾病，可能需要更积极的治疗，如喉切除术和食管切除术。术后瘘管形成和渗漏是此类病例的潜在并发症。这些瘘管最有可能发生在喉切除术或食管切除术的吻合部位。同时进行化疗和放疗会增加这种风险。酪氨酸激酶抑制剂（TKI）如卡博替尼被用作转移性MTC的治疗药物。这些药物此前曾与胃肠道吻合部位裂开有关。虽然此前在肠道中已被发现，但本报告是首次记录在使用TKI治疗头颈癌背景下发生胃咽吻合口漏的病例。
我们报告一例72岁男性，此前被诊断为MTC。他在接受喉咽切除术和胃上提术后胃咽吻合口状况稳定了23年。在过去一年中，他出现背痛，被发现患有MTC脊柱转移。随后他开始服用卡博替尼以减缓疾病进展。在开始使用这种TKI后的几个月内，胃上提术与咽部的吻合部位出现了出血性咽皮瘘。停用卡博替尼后，瘘管愈合，未出现进一步并发症。
据我们所知，这是首例记录在案的与使用TKI相关的胃咽吻合口漏病例。鉴于此前吻合口稳定，且在开始使用这种新药后的几个月内出现可疑并发症，因果关系非常合理。虽然此前仅限于腹腔内肠道裂开的病例，但本报告现在表明，伤口裂开必须被视为TKI在整个胃肠道（包括胃咽部）的已知副作用。因此，在开始使用TKI之前，应与患者讨论吻合口裂开的风险。
