Chengde Medical University, Chengde, Hebei, China.
Baoding First Central Hospital, Baoding, Hebei, China.
J Surg Oncol. 2018 Dec;118(8):1243-1256. doi: 10.1002/jso.25285. Epub 2018 Oct 31.
This meta-analysis was conducted to evaluate the diagnostic value of near-infrared (NIR) or fluorescent indocyanine green (ICG) guided sentinel lymph node (SLN) mapping in gastric cancer (GC).
This meta-analysis was registered at the PROSPERO. Clinical studies were retrieved from the electronic database Pubmed, Embase, Medline, Web of science, and the Cochrane Library. Quality assessment was conducted by an adapted checklist of QUADAS-2. A bivariate mixed-effects model was used to pool the data. Evaluation of articles quality, analysis for publication bias, summary receiver operator characteristic (SROC) curves, and meta-regression were also performed. Subgroup analysis was used to explain the heterogeneities.
A total of 13 clinical studies (971 patients) were included. The NIR or fluorescent imaging (FI) involved infrared ray electronic endoscopy (IREE), infrared ray laparoscopic system (IRLS), and FI system. Significant evidence of heterogeneity was found for sensitivity and specificity (I = 91.1% and I = 98.2%), respectively. The pooled SLN sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.94(95%CI: 0.80-0.99), 1.00(95%CI: 0.60-1.00), 34.0(95%CI: 9.25-125.29), 0.06(95%CI:0.02-0.22), and 252.50(95%CI: 94.93-671.61), respectively. Area under curve (AUC) of SROC curve was 1.00 (95%CI: 0.99-1.00), and the summary operating point (cut-off value) was SENS = 0.94(95%CI: 0.80-0.99) and SPEC = 1.00(95%CI: 0.60-1.00). Subgroup analysis showed that NIR imaging, imaging performed 20 minutes after intraoperative injection, preoperative injection (especially for FI imaging), stained with immunohistochemistry (IHC) (+hematoxylin-eosin [HE]), cT1 stage, submucosa injection (especially for cT1), mean number of SLN ≥ 5, study size > 26 were associated with higher SLN sensitivity. In terms of ICG concentration, diluted ICG concentration that 0.5 mg/mL (compared with 5 mg/mL) in NIR imaging and 0.05 mg/mL (compared with 0.5 mg/mL) in FI system showed higher sensitivities. However, the differences in tumor diameter (≤30 mm vs >30 mm), gastrectomy methods (opening vs laparoscopy), lymphadenectomy methods (LBD vs pick-up), and publication year (≥2010 vs <2010) did not achieve statistical significance.
ICG combined with NIR or FI guided SLN mapping is technically feasible for GC. Based on the small sample size evidence, the IREE and IRLS devices may have higher sensitivity than FI in current clinical studies; and there may be an excessive ICG concentration used for current SLN mapping in GC. However, well-designed further studies with large sample size are needed to confirm the best procedure and suitable criteria.
MINI-ABSTRACT: This meta-analysis was registered at PROSPERO. Clinical studies on this topic were retrieved from the electronic database Pubmed, Embase, Medline, Web of Science, and the Cochrane Library. The NIR or FI involved IREE, IRLS, and FI techniques. A total of 13 clinical studies (971 patients) were included. Based on the small sample size evidence, NIR or FI ICG guided SLN mapping in GC is technically feasible.
本荟萃分析旨在评估近红外（NIR）或荧光吲哚菁绿（ICG）引导的前哨淋巴结（SLN）在胃癌（GC）中的诊断价值。
本荟萃分析在 PROSPERO 注册。从电子数据库 Pubmed、Embase、Medline、Web of Science 和 Cochrane Library 中检索到临床研究。采用适应性 QUADAS-2 检查表进行质量评估。使用双变量混合效应模型对数据进行汇总。还进行了文章质量评估、发表偏倚分析、汇总受试者工作特征（SROC）曲线和荟萃回归分析。采用亚组分析来解释异质性。
共纳入 13 项临床研究（971 例患者）。NIR 或荧光成像（FI）涉及电子内窥镜近红外射线（IREE）、腹腔镜近红外射线系统（IRLS）和 FI 系统。灵敏度和特异性均存在显著的异质性（I²=91.1% 和 I²=98.2%）。汇总的 SLN 灵敏度（Sen）、特异性（Spe）、阳性似然比（PLR）、阴性似然比（NLR）和诊断优势比（DOR）分别为 0.94（95%CI：0.80-0.99）、1.00（95%CI：0.60-1.00）、34.0（95%CI：9.25-125.29）、0.06（95%CI：0.02-0.22）和 252.50（95%CI：94.93-671.61）。SROC 曲线下面积（AUC）为 1.00（95%CI：0.99-1.00），汇总的工作点（截断值）为 Sen=0.94（95%CI：0.80-0.99）和 Spe=1.00（95%CI：0.60-1.00）。亚组分析表明，NIR 成像、术中注射后 20 分钟进行成像、术前注射（特别是 FI 成像）、免疫组织化学（IHC）染色（+苏木精-伊红[HE]）、cT1 期、黏膜下注射（特别是 cT1）、SLN≥5 个、研究规模>26 与 SLN 灵敏度升高相关。在 ICG 浓度方面，与 5mg/mL 相比，NIR 成像中 0.5mg/mL 稀释的 ICG 浓度和 FI 系统中 0.05mg/mL 稀释的 ICG 浓度显示出更高的灵敏度。然而，肿瘤直径（≤30mm 与>30mm）、胃切除术方法（开腹与腹腔镜）、淋巴结清扫方法（LBD 与 pick-up）和发表年份（≥2010 年与<2010 年）的差异没有统计学意义。
ICG 联合 NIR 或 FI 引导的 SLN 映射在 GC 中是可行的技术。基于小样本量的证据，IREE 和 IRLS 设备在当前临床研究中可能比 FI 具有更高的灵敏度；并且当前 GC 中 SLN 映射可能使用了过高的 ICG 浓度。然而，需要设计进一步的、具有大样本量的研究来证实最佳方法和适用标准。
