Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial
Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial
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DOI：
10.1001/jama.2018.13201
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发表时间：
2018-09-25
影响因子：
120.7
通讯作者：
Gronroos, Juha M.
中科院分区：
文献类型：
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作者：
Salminen, Paulina;Tuominen, Risto;Gronroos, Juha M.
重要性 短期结果支持抗生素作为手术替代治疗无并发症的急性阑尾炎，但长期结果尚不清楚。 目的 确定抗生素治疗无并发症的急性阑尾炎后阑尾炎的晚期复发率。 设计、设置和参与者 对急性阑尾炎 (APPAC) 多中心随机临床试验中的患者进行五年观察性随访，比较阑尾切除术与抗生素治疗，其中530 名年龄在 18 至 60 岁之间、经计算机断层扫描证实为无并发症的急性阑尾炎的患者被随机分配接受阑尾切除术 (n = 273) 或接受抗生素治疗 (n = 257)。初始试验于 2009 年 11 月至 2012 年 6 月在芬兰进行：最后一次随访时间为 2017 年 9 月 6 日。当前分析的重点是评估仅接受抗生素治疗的患者组的 5 年结果。干预措施 开腹阑尾切除术与静脉注射厄他培南抗生素治疗 3 天，然后口服左氧氟沙星和甲硝唑 7 天。主要结果和措施 在本次分析中， 5 年随访时报告的预设次要终点包括抗生素治疗后晚期（1 年后）阑尾炎复发、并发症、住院时间和病假。 结果 在参与试验的 530 名患者（201 名女性；329 名男性）中，273 名患者（中位年龄，35 岁 [IQR，27-46]）被随机接受阑尾切除术，257 名患者（中位年龄，33 岁， [IQR，26-47]）被随机分配接受抗生素治疗。除了 70 名最初接受抗生素治疗但在第一年内接受阑尾切除术的患者 (27.3% [95% CI, 22.0%-33.2%]; 70/256) 之外，另外 30 名接受抗生素治疗的患者 (16.1% [95% CI, 11.2%-22.2%]; 30/186) 在 1 至 5 年内接受了阑尾切除术。阑尾炎复发的累积发生率为 2 年时 34.0% (95% CI, 28.2%-40.1%; 87/256)，3 年时为 35.2% (95% CI, 29.3%-41.4%; 90/256)，37.1% (95% CI, 31.2%-43.3%; 90/256)。 4 年时为 95/256)，S 年时为 39.1% (95% CI，33.1%-45.3%；100/256)。在抗生素组中因复发性阑尾炎而随后接受阑尾切除术的 85 名患者中，76 名患有单纯性阑尾炎，2 名患有复杂性阑尾炎，7 名没有阑尾炎。 5 年时，阑尾切除组的总体并发症发生率（手术部位感染、切口疝、腹痛和梗阻症状）为 24.4%（95% CI，19.2%-30.3%）（n = 60/246），抗生素组为 6.5%（95% CI，3.8%-10.4%）（n = 16/246）（P < .001），手术后计算出 17.9 个百分点（95% CI，11.7-24.1）。各组之间的住院时间没有差异，但病假有显着差异（阑尾切除组多出 11 天）。 结论和相关性 在最初接受抗生素治疗的无并发症急性阑尾炎患者中，5 年内晚期复发的可能性为 39.1%。这项长期随访支持单独使用抗生素治疗作为手术替代治疗无并发症的急性阑尾炎的可行性。
IMPORTANCE Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.OBJECTIVE To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.DESIGN, SETTING, AND PARTICIPANTS Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland: last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.INTERVENTIONS Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.MAIN OUTCOMES AND MEASURES In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.RESULTS Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at S years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%)(n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).CONCLUSIONS AND RELEVANCE Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.