Per-oral endoscopic myotomy versus laparoscopic Heller's myotomy plus Dor fundoplication in patients with idiopathic achalasia: 5-year follow-up of a multicentre, randomised, open-label, non-inferiority trial.

However, post-procedural gastro-oesophageal reflux was more common after POEM at 2 years.

然而，在术后2年，经口内镜下肌切开术（POEM）后的胃食管反流现象更为常见。

Here we report 5-year follow-up data.

这里我们报告了5年的随访数据。

Methods

This study is a multicentre, randomised, open-label, non-inferiority trial performed at eight centres in six European countries (Germany, Italy, Czech Republic, Sweden, the Netherlands, and Belgium).

这项研究是一项多中心、随机、开放标签、非劣效试验，在六个欧洲国家（德国、意大利、捷克共和国、瑞典、荷兰和比利时）的八个中心进行。

Patients with symptomatic primary achalasia were eligible for inclusion if they were older than 18 years and had an Eckardt symptom score higher than 3.

如果患者年龄超过18岁且Eckardt症状评分高于3分，则有症状的原发性食管失弛缓症患者符合纳入标准。

Patients were randomly assigned (1:1; randomly permuted blocks of sizes 4, 8, or 12) to undergo either POEM or LHM plus Dor fundoplication.

患者被随机分配（1:1；随机排列的4、8或12大小的区块）接受POEM或LHM加Dor抗反流术。

The primary endpoint was clinical success, defined by an Eckardt symptom score of 3 or less without the use of additional treatments, at 2 years, and was reported previously.

主要终点是临床成功，定义为在不使用额外治疗的情况下，2年时Eckardt症状评分达到3分或以下，并已先前报告。

Prespecified secondary endpoints at 5 years were clinical success; Eckardt symptom score; Gastrointestinal Quality of Life Index score; lower oesophageal sphincter function by high-resolution manometry; and parameters of post-procedural reflux (reflux oesophagitis according to the Los Angeles classification; pH-metry, and DeMeester clinical score).

预设的次要终点在5年时包括临床成功；Eckardt症状评分；胃肠道生活质量指数评分；通过高分辨率测压法评估的下食管括约肌功能；以及术后反流参数（根据洛杉矶分类的反流性食管炎；pH监测和DeMeester临床评分）。

We hypothesised that POEM would be non-inferior (with a non-inferiority margin of -12·5 percentage points) to LHM plus Dor fundoplication with regards to clinical success.

我们假设经口内镜下括约肌切开术（POEM）在临床成功率方面不会逊色于腹腔镜下 Heller 肌切开术加Dor 基底折叠术（LHM plus Dor fundoplication），非劣效性边界设定为-12.5个百分点。

All analyses were performed on a modified intention-to-treat(mITT) population, which included all patients who underwent the assigned procedure.

所有分析均在改良意向治疗（mITT）人群中进行，该人群包括所有接受了指定手术的患者。

This study is registered with ClinicalTrials.gov (NCT01601678) and is complete.

该研究已在ClinicalTrials.gov注册（NCT01601678），研究已完成。

Results

Between Dec 7, 2012, and Oct 9, 2015, 241 patients were randomly assigned (120 to POEM and 121 to LHM) and 221 had the assigned treatment (112 POEM and 109 LHM; mITT). 5-year follow up data were available for 90 (80%) patients in the POEM group and 87 (80%) patients in the LHM group.

在2012年12月7日至2015年10月9日期间，241名患者被随机分配（120名接受POEM治疗，121名接受LHM治疗），并有221名患者接受了指定的治疗（POEM组112名，LHM组109名；mITT）。

Clinical success rate at 5 years was 75·0% (95% CI 66·2 to 82·1) after POEM and 70·8% (61·7 to 78·5) after LHM (difference 4·2 percentage points [95% CI -7·4 to 15·7]).

在经口内镜下食管括约肌切开术（POEM）后，5年的临床成功率达到了75.0%（95%置信区间66.2至82.1），而在拉德手术（LHM）后为70.8%（95%置信区间61.7至78.5），两者之间的差异为4.2个百分点（95%置信区间-7.4至15.7）。

The mean Eckardt symptom score decreased from baseline to 5 years in both groups and the overall difference in mean scores was -0·29 (95% CI -0·62 to 0·05).

两组的平均Eckardt症状评分从基线到5年都有所下降，总体平均分数差异为-0.29（95%置信区间-0.62至0.05）。

Change in Gastrointestinal Quality of Life Index scores, as well as in integrated relaxation pressure on manometry, from baseline to 5 years, did not differ significantly between the groups.

从基线到5年，胃肠道生活质量指数评分以及在压力测量上的综合放松压力的变化，在各组之间没有显著差异。

At 5 years, 26 (41%) of 63 patients after POEM and 18 (31%) of 58 patients after LHM had reflux oesophagitis (difference 10·2 percentage points [95% CI -7·0 to 26·8]).

在5年时，63名POEM术后患者中有26名（41%），58名LHM术后患者中有18名（31%）出现反流性食管炎（差异10.2个百分点[95% CI -7.0至26.8]）。

Significant oesophagitis (Los Angeles classification grade B, C, or D) was observed in nine (14%) of 63 patients after POEM and in four (7%) of 58 patients after LHM. pH-metry was performed in 81 (37%) of 221 patients, with higher mean acid exposure time for POEM (10·2% [95% CI 7·6 to 14·2]) than for LHM (5·5% [3·1 to 11·8]).

在63名接受POEM治疗的患者中有9名（14%）和在58名接受LHM治疗的患者中有4名（7%）观察到显著的食管炎（洛杉矶分级B、C或D）。

Significantly more patients in the POEM than in the LHM group had abnormal acid exposure time at 5 years (>4·5%; 28 [62%] of 45 vs 11 [31%] of 36; difference 31·7 percentage points [95% CI 9·8 to 50·5]).

在5年时，与LHM组相比，POEM组有显著更多的患者酸暴露时间异常（>4.5%；45名中的28名[62%]对比36名中的11名[31%]；差异31.7个百分点[95%置信区间 9.8至50.5]）。

The presence of reflux symptoms at 5 years was similar in both groups, with a mean DeMeester clinical score of 1·3 (95% CI 1·0 to 1·6) after POEM and 1·1 (0·9 to 1·4) after LHM.

5年后，两组患者的反流症状出现频率相似，经口内镜下食管括约肌切开术(POEM)后的DeMeester临床评分平均为1.3（95%置信区间1.0至1.6），而经手助下食管肌层切开术(LHM)后的评分为1.1（0.9至1.4）。

The complications of peptic stricture, Barrett's oesophagus, and oesophageal adenocarcinoma were not reported.

未报告消化性狭窄、Barrett食管和食管腺癌等并发症。

interpretation

Our long-term results support the role of POEM as a less invasive myotomy approach that is non-inferior to LHM in controlling symptoms of achalasia.

我们的长期结果支持POEM作为一种微创的肌切开术，其在控制贲门失弛缓症症状方面不亚于LHM。

Gastro-oesophageal reflux was common in both groups, but with a tendency towards higher rates in the POEM group.

胃食管反流在两组中都很常见，但在POEM组中倾向于有更高的发生率。

Thus, patients should be provided with the advantages and disadvantages of each approach in decision making.

因此，在决策过程中，应向患者提供每种方法的优缺点。

funding

European Clinical Research Infrastructure Network, Hamburgische Stiftung für Wissenschaften, Entwicklung und Kultur Helmut und Hannelore Greve, Dr med Carl-August Skröder Stiftung, Dr Gerhard Büchtemann Stiftung, Agnes-Graefe Stiftung, Georg und Jürgen Rickertsen Stiftung, Reinhard Frank Stiftung, Johann Max Böttcher Stiftung, Richard und Annemarie Wolf Stiftung, Olympus Europa, German Society for Gastroenterology and Metabolism and Olympus Europe Foundation, United European Gastroenterology Week, Olympus EuroNOTES Research Fund Program, Harvard Catalyst, the Harvard Clinical and Translational Science Center, and Harvard University and its affiliated academic health-care centres.

欧洲临床研究基础设施网络、汉堡科学、发展和文化基金会Helmut und Hannelore Greve、卡尔-奥古斯特·施罗德博士基金会、格尔哈德·比希特曼博士基金会、阿格内斯-格雷费基金会、格奥尔格和尤尔根·里克特森基金会、赖因哈德·弗兰克基金会、约翰·马克斯·博特希尔基金会、理查德和安内玛丽·沃尔夫基金会、奥林巴斯欧洲、德国胃肠病学和代谢学会及奥林巴斯欧洲基金会、欧洲胃肠病学周、奥林巴斯EuroNOTES研究基金计划、哈佛催化器、哈佛临床与转化科学中心以及哈佛大学及其附属的学术医疗中心。