大腸癌のERASプロトコールのコクランレビュー

大腸癌のERAS（Enhanced Recovery after Surgery）プロトコールのコクランレビュー論文を紹介します。

Spanjersberg WR, Reurings J, Keus F, van Laarhoven CJ: Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev. 2011;2:CD007635.

大腸癌ではERASの臨床研究が数多く行われています。ERASプロトコールと通常のプロトコールのランダム化比較試験のメタ分析になります。

結果は、ERAS群で合併症が有意に少なく、入院期間が約3日間、有意に短いとなっています。ただし、重症の合併症が減少したから合併症が少ないのではないとのことです。再入院率は両群で同じで、その他のアウトカムはメタ分析を行うのが困難でした。

これよりERASで入院期間が短くなることは確かです。ただし、著者の結論は、ERASは安全そうにみえますが、研究の質が低いことや他のアウトカムが不足していることより、ERASを標準とするにはまだ根拠が不十分ということです。

ERASの他のメタ分析ではERASは有効と結論付けていますが、コクランの結論はそれに比べると弱いです。

例えば、Varadhan KK, Neal KR, Dejong CH, Fearon KC, Ljungqvist O, Lobo DN: The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr. 2010 Aug;29(4):434-40.

これは論文の選択基準が異なること（コクランではERASの7要素以上で4論文、Clin NutrではERASの4要素以上で6論文）が最も大きいです。しかし、利益相反の違いも無視できません。コクランでは利益相反は全くありませんが、Clin Nutrでは6人の著者中4人に利益相反があります。そのためにより有効という結論になっている可能性があります。

コクランのメタ分析は厳しめの結論となることが多いですが、信頼性は他のメタ分析より高いことが多いと私は感じています。

Abstract
BACKGROUND: In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo-)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common.

OBJECTIVES: We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo-)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced.

SEARCH STRATEGY: To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS.

SELECTION CRITERIA: We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo-) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included.

DATA COLLECTION AND ANALYSIS: Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I(2)).

MAIN RESULTS: 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD -2.94 days; 95% CI -3.69 to -2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta-analysis, but seemed to favour ERAS.

AUTHORS' CONCLUSIONS: The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed.