阑尾炎手术治疗被颠覆了吗?

2015-06-26 MedSci MedSci原创

如果你得了急性阑尾炎,是选择手术切除还是使用抗生素保守治疗?最近,发表于《美国医学会杂志》(JAMA)的一项研究显示,超过七成(73%)非复杂性急性阑尾炎患者可用抗生素治愈。JAMA的这项临床试验从2009年11月开始,到2012年6月份结束,共纳入530名18-60岁经CT确诊为非复杂性急性阑尾炎患者。病人被随机分配到早期急性阑尾炎切除组和抗生素治疗组,随访1年。抗生素治疗组病人接受静脉注射

如果你得了急性阑尾炎,是选择手术切除还是使用抗生素保守治疗?

最近,发表于《美国医学会杂志》(JAMA)的一项研究显示,超过七成(73%)非复杂性急性阑尾炎患者可用抗生素治愈。JAMA的这项临床试验从2009年11月开始,到2012年6月份结束,共纳入530名18-60岁经CT确诊为非复杂性急性阑尾炎患者。病人被随机分配到早期急性阑尾炎切除组和抗生素治疗组,随访1年。抗生素治疗组病人接受静脉注射厄他培南3天(1 g/d),随后7天口服左氧氟沙星(500mg,每日一次)和甲哨唑(500mg,每日三次)。

结果发现,手术治疗组273人中只有1人手术失败,治愈率为99.6%。抗生素治疗组257人中有70人(27%)在一年内阑尾炎复发,需要做阑尾切除手术。在这70人当中有58人(82.9%)为非复杂性急性阑尾炎,7人(10.0%)转变为复杂性急性阑尾炎,5人(7.1%)使用抗生素后急性阑尾炎缓解,但怀疑可能会有阑尾炎复发,进行阑尾切除。手术虽有延迟,但并没有并发症。

研究人员认为经CT确诊的非复杂性急性阑尾炎病人,抗生素治疗虽然没有手术治疗效果好,但是也有73%的患者通过使用抗生素治疗可以痊愈。研究负责人、芬兰图尔库大学医院外科医生Salminen表示,现在只有一小部分阑尾炎患者需要切除手术,即便是那些使用抗生素后再手术的人并没有带来不好的结果。

JAMA的随刊评论给予这项研究很高的评价。杂志副主编Edward Livingston博士认为:“即使手术切除仍是最终(兜底)的选择,但阑尾炎的治疗方针该修改了。CT影像技术使精确诊断成为可能,同时新的抗生素谱覆盖了引起阑尾炎及各种严重并发症的致病体,这些都足以改变疾病的治疗历史。”

对此,有人认为这项研究是颠覆性的,如果真是这样我们可能要重新修改阑尾炎治疗方法。毕竟,只使用抗生素的保守治疗是经济安全的。事实上,100多年来,阑尾切除都是阑尾炎的标准治疗手段。然而,近年来有越来越多的证据表明抗生素可以完全治愈阑尾炎。2014年5月复旦大学附属中山医院发表于《国际外科学杂志》上的一项荟萃分析发现,对于非复杂性急性阑尾炎,在发生复杂性阑尾炎和急性感染方面,保守治疗和手术治疗没有统计学差异;在并发症方面,保守治疗发病率低于手术治疗;但保守治疗在住院时间上长于手术治疗。这项荟萃分析的结果中未包括复发情况。

这是否说明抗生素保守治疗能够颠覆阑尾炎的手术治疗呢?

重新回到这项临床试验,我们发现其中还是有一些疑问。首先,在这次临床试验中对于非复杂性急性阑尾炎患者采用的是开腹手术,而不是微创的腹腔镜手术。如果说研究者是为了让试验结果更利于归纳,那么结果本身是存在缺陷的。其次,我们也注意到抗生素治疗组27%的再手术率,这样的结果或许未必能让人接受。

复旦大学附属中山医院普外科副主任医师吴文川博士表示,阑尾炎手术治疗,不仅仅是基于此次发病所需的治疗,还需要考虑抗生素保守治疗后阑尾炎的再复发;冒着保守治疗失败、潜在危及生命的风险去保留一个退化的阑尾,是得不偿失的,当然,对于极高危病人还是要评估利弊;此外,关注抗生素时代进步的同时,也应该关注微创手术的进步,比如说腹腔镜。吴博士告诉MedSci,在中山医院,急性阑尾炎腹腔镜手术占主导地位后,从急诊室直接入手术室,术后转病房,术后一天半流质,不补液,平均术后2天出院。他认为,对于急性阑尾炎,急诊手术当然不是唯一治疗手段,但会是最干脆、最具费用效果比的选项……在没有更高级别的证据来颠覆时,这就是处理的指导思想。

医学博士Benjamin Davies在福布斯网站撰文指出,考虑到这项研究中27%的复发患者还是得手术,再加上对生活和工作的影响,很难说保守治疗能节省费用。他认为手术治疗99.6%的治愈率比起保守治疗还是有优势的。他引用匹茨堡大学外科教授Brian Zuckerbraum的话说:“我欣赏芬兰这项随机对照试验的严谨,但我还是认为这项研究存在重大问题——我们的大多数急性阑尾炎病例都选择腹腔镜手术,只有极少数才做开腹手术。对我来说,27%的复发率是不可接受的。”

抗生素保守治疗虽然有它的优点,但我们也不得不考虑其中会遇到的问题,比如说炎症复发和并发症等。所以对于急性阑尾炎的治疗,现在谈颠覆,恐怕言之过早。正如《新英格兰医学杂志》旗下期刊观察网急诊医学频道副主编Daniel J. Pallin所说:“对于有些经CT证实的非复杂性阑尾炎患者,抗生素治疗可能是一个合理的选择——根据患者的意愿、个体化的手术风险和其他因素——只要每个人都明白,复发的机会相当高。”


MedSci认为,关于研究设计有几个需要注意的地方:

1.这个研究是非劣效设计,关于非劣效设计最容易引起争议的地方就是非劣效界值的设定了,这关系到最小临床重要差异(minimal clinically important difference ,MCID)的估计。这篇文献的非劣界值设定仅仅根据2012年的一篇meta分析来确定,稍显武断了。

2.RCT研究的患者入选标准设置距离真实世界尚有一定的距离,这篇文章排除了18岁以下或60岁以上患者,CT检查禁忌患者,伴发腹膜炎患者和严重全身性疾病患者,这种较为理想化的研究设定在一定程度上限制了研究结果的外部真实性。

3.并且研究的非劣效终点实际上未能达成,根据阴性结果下结论本身就存在一定的风险
综上,研究中存在颇多局限,需要 新的研究作进一步的探索。

参考资料:

1. Paulina Salminen, Hannu Paajanen, Tero Rautio, et al.Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis. JAMA, June 16, 2015;313(23):2340-2348. doi:10.1001/jama.2015.6154. 

2. GINA KOLATA. Antibiotics Are Effective in Appendicitis, Study Says. The New York Times, June 16, 2015.

3.付亮, 锁涛, 张钰, 鲁超, 宋陆军.保守治疗对比手术治疗急性非复杂性阑尾炎的临床疗效的Meta分析.国际外科学杂志, 2014, 41(5):301-304.

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    2015-07-09 xykzfl

    0

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    2015-07-05 Gsurgeon

    这观点可以

    0

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    2015-06-29 huaxipanxing

    看看

    0

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    2015-06-29 zx890910

    还是蛮有意义的

    0

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    2015-06-28 summer474cn

    我晕

    0

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    2015-06-28 summer474cn

    崩溃!以后普外科医生没有饭吃了

    0

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    2015-06-27 stupidox

    复发率那么高还得手术

    0

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    2015-06-27 18619c0a62m

    ???

    0

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    2015-06-27 18619c0a62m

    不明觉厉

    0

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