Background:

Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer’s ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery.

Methods:

MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies’ quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate.

Results:

20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I² = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I² = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I² = 24%), and hospitalization length (MD = −2.07 days; 95% CI = −3.97 to −0.17; P = .03; k = 5; N = 362; I² = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified.

Conclusions:

Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs.

PROSPERO registration:

CRD42018086168.

中文翻译：

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在肿瘤围手术期补充支链氨基酸是否有益：系统评价和荟萃分析

背景：

支链氨基酸（BCAA；亮氨酸、异亮氨酸和缬氨酸）是参与免疫反应的必需氨基酸，可能在蛋白质营养不良和肌肉减少症中起作用。此外，某些肝脏疾病与 Fischer 比率（支链氨基酸与芳香族氨基酸；苯丙氨酸、酪氨酸和色氨酸）的降低有关。我们旨在评估在接受手术的癌症患者中使用支链氨基酸的安全性和有效性。

方法：

检索了 MEDLINE、Embase 和 CENTRAL（开始至 2020 年 7 月 24 日），以寻找在肿瘤围手术期评估 BCAA（单独或组合）的英语随机对照试验 (RCT) 和比较观察性研究。研究选择、数据提取和质量评估一式两份进行。使用 Cochrane 偏倚风险工具评估 RCT 偏倚风险，并使用纽卡斯尔-渥太华量表进行观察性研究的质量评估。适当时进行荟萃分析。

结果：

共纳入 20 篇文章，包括 7 份报告中的 13 项 RCT 和 6 项观察性队列研究，总参与者为 2019 年。在 13 项 RCT 中，77% 涉及肝癌。在大多数 RCT 中，方法学研究质量得分显着的偏倚风险。RCT 的荟萃分析发现，与对照组相比，BCAAs 组术后感染的风险降低了 38%（RR = 0.62；95% CI = 0.44 至 0.87；P  = .006；RCT 数量，k  = 6；总样本）大小，N = 389；I ²  = 0%）。还发现支链氨基酸对腹水有益（RR = 0.55；95% CI = 0.35 至 0.86；P  = .008；k  = 4；N = 296；I ²  = 0%）、体重（MD = 3.24 kg； 95% CI = 0.44 至 6.04；P = .02; k  = 3; N = 196；I ²  = 24%）和住院时间（MD = -2.07 天；95% CI = -3.97 至 -0.17；P  = .03；k  = 5；N = 362；I ²  = 59%）。在死亡率、复发、其他术后并发症（肝功能衰竭、水肿、胸腔积液）、失血量、生活质量、氨水平和凝血酶原时间方面，BCAAs 和对照组之间没有发现差异。没有与支链氨基酸相关的严重不良事件；然而，由于静脉导管，报告了严重的不良事件。没有发现观察性研究的安全问题。

结论：

与对照组相比，肿瘤手术期间的支链氨基酸显示出降低感染和腹水的重要术后发病率的前景。有必要进行更高方法学质量的盲法、安慰剂对照验证性试验，尤其是在最近的 ERAS 计划范围内使用口服、短期富含支链氨基酸的补充剂。

PROSPERO注册：

CRD42018086168。