Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
JAMA Otolaryngol Head Neck Surg. 2017 Feb 1;143(2):125-130. doi: 10.1001/jamaoto.2016.2895.
Adult laryngotracheal stenosis (LTS) is typically managed surgically, but some patients fail treatment because of rapid restenosis or granulation tissue formation. The need for frequent surgery or tracheostomy reduces the quality of life in these patients and poses a significant challenge for the treating physician. New adjuvant treatments are required to reduce the surgical burden of this condition.
To examine whether patients with rapidly recurrent nonvasculitic LTS who fail surgical management of their stenosis (ie, requiring dilation more frequently than every 6 months) experience longer intervals between surgical procedures when receiving adjuvant treatment with low-dose methotrexate.
DESIGN, SETTING, AND PARTICIPANTS: This study was a retrospective case series study of patients treated with methotrexate from January 2014 to January 2016 at a tertiary academic medical center. Participants were 10 patients with LTS without any diagnosis of vasculitis or granulomatous disease who underwent low-dose methotrexate therapy.
Once-weekly treatment with oral methotrexate, 15 or 20 mg.
The mean number of days between operations before and after starting methotrexate therapy was compared. Clinical courses and adverse effects of each patient were also reviewed.
Among 10 patients, the mean (SD) age at the outset of study inclusion was 52 (19) years; 8 were female and 2 were male. All 10 patients experienced some clinical improvement. Three patients who were previously tracheostomy dependent were able to be decannulated. Two other patients who were tracheostomy dependent and had failed endoscopic management of their granulation tissue had complete resolution. In 6 patients who underwent at least 1 surgical procedure before and after the initiation of methotrexate treatment, the mean (SD) interval between operations increased from 61 (35) days (95% CI, 26-96 days) before starting methotrexate therapy to 312 (137) days (95% CI, 175-449 days) after starting methotrexate therapy, for an absolute difference of 251 (58) days (95% CI, 193-309 days). The median number of days between surgical procedures was 44 days before starting methotrexate therapy and 289 days after starting methotrexate therapy. Adverse effects observed included mild hair thinning and onychomycosis in 2 patients and herpes zoster infection in 1 patient.
Low-dose methotrexate appears to be an effective adjunct to surgery in select patients with LTS that is resistant to surgical management and leads to a substantial increase in the number of days between surgical procedures. The patient and clinician must be aware of the adverse effects of methotrexate therapy and balance these factors against the risk of poorly controlled airway stenosis. Randomized, placebo-controlled, double-blind trials are needed to examine whether the clinical efficacy in this series of patients translates to a larger population.
成人喉气管狭窄(LTS)通常采用手术治疗,但由于再狭窄或肉芽组织形成迅速,一些患者治疗失败。由于需要频繁手术或气管切开术,这些患者的生活质量降低,并给治疗医生带来了重大挑战。需要新的辅助治疗方法来减轻这种疾病的手术负担。
研究在接受低剂量甲氨蝶呤辅助治疗后,因狭窄而再次接受手术治疗的非血管炎 LTS 患者(即,需要每 6 个月以上进行扩张术),手术间隔是否更长。
设计、地点和参与者:这是一项回顾性病例系列研究,于 2014 年 1 月至 2016 年 1 月在一家三级学术医疗中心对接受甲氨蝶呤治疗的患者进行了研究。参与者为 10 名非血管炎或肉芽肿性疾病诊断的 LTS 患者,接受低剂量甲氨蝶呤治疗。
每周一次口服甲氨蝶呤,剂量为 15 或 20mg。
比较开始甲氨蝶呤治疗前后手术间隔的平均天数。还回顾了每位患者的临床过程和不良反应。
在 10 名患者中,研究开始时的平均(SD)年龄为 52(19)岁;8 名女性,2 名男性。所有 10 名患者均有一定程度的临床改善。3 名以前依赖气管切开术的患者能够拔管。另外 2 名依赖气管切开术且肉芽组织内镜治疗失败的患者完全缓解。在至少接受过 1 次手术的 6 名患者中,在开始甲氨蝶呤治疗之前和之后,手术间隔的平均(SD)天数从 61(35)天(95%CI,26-96 天)增加到开始甲氨蝶呤治疗后 312(137)天(95%CI,175-449 天),绝对差异为 251(58)天(95%CI,193-309 天)。开始甲氨蝶呤治疗前手术间隔的中位数为 44 天,开始甲氨蝶呤治疗后为 289 天。观察到的不良反应包括 2 名患者出现轻度脱发和甲真菌病,1 名患者出现带状疱疹感染。
低剂量甲氨蝶呤似乎是一种有效的手术辅助治疗方法,适用于对手术治疗有抵抗力且导致手术间隔显著增加的 LTS 患者。患者和临床医生必须意识到甲氨蝶呤治疗的不良反应,并将这些因素与气道狭窄控制不良的风险进行权衡。需要进行随机、安慰剂对照、双盲试验,以检验该系列患者的临床疗效是否适用于更大的人群。