• M F He, Z W Jiang, Z W Hao, J An, J Zhai, and J K Shen.
• Department of Graduate School, Chengde Medical University, Hebei Chengde 067000, China.
• Zhonghua Wei Chang Wai Ke Za Zhi. 2019 Dec 25; 22 (12): 1196-1204.

AbstractObjective: To systematically evaluate the diagnostic value of optical imaging combined with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy in gastric cancer, and to identify potential factors that would influence diagnostic accuracy. Methods: Study was carried out by searching the electronic database of PubMed, Embase, Medline, Web of Science, and the Cochrane Library with keywords as "gastric/stomach" and "cancer/carcinoma/tumor/tumour/adenocarcinoma/neoplasm" and "sentinel lymph node" and "near-infrared/NIR or fluorescent imaging" and "indocyanine green/ICG" . Literature inclusion criteria: (1) gastric cancer clinical stage was cT0-3; (2) clinical stage determined by at least 2 kinds of imaging modalities; (3) optical imaging (near-infrared or fluorescence imaging) combined with ICG-guided SLN biopsy; (4) prospective study to predict lymph node metastasis; (5) intraoperative or postoperative pathology for all lymph nodes removed; (6) patients number in the literature >10 cases. Exclusion criteria: (1) patients with a history of ICG allergy or chemoradiotherapy; (2) previous history of endoscopic mucosal resection or endoscopic submucosal dissection; (3) patients with a variety of gastrointestinal tumor; (4) case reports, conference abstracts, clinical guidelines, editorials, reviews, meta-analysis and correspondence letters; (5) in vitro or animal experiments; (6) insufficient diagnostic efficacy data. The meta-analysis was performed in the Stata12.0 software using the "bivariate mixed-effects model" combined with the "midas" command to pool the data. Information such as true positive value, false positive value, false negative value, and true negative value of each included articles were extracted. The literature quality assessment map was drawn to describe the overall quality of the articles; the heterogeneity analysis was performed with the forest map, with P<0.01 considered as statistical significance; the funnel plot was used to describe publication bias, with P<0.1 considered as statistically significant. Area under curve (AUC) of summary receiver operator characteristic (SROC) was used to describe the diagnostic accuracy and the AUC closer to 1 indicated higher diagnostic accuracy. If there was heterogeneity (I(2)>50%) among studies, regression analysis and subgroup analysis were performed. P<0.05 was considered as statistically significant. Results: A total of 15 studies (1020 patients) were included. The optical imaging contained near-infrared (NIR) and fluorescent imaging (FI). The diagnostic value of optical imaging combined with ICG-guided SLN biopsy in gastric cancer was as follows: the pooled sensitivity (Sen) was 0.95 (95% CI: 0.82 to 0.99), specificity (Spe) was 1.00 (95% CI: 0.92 to 1.00), positive likelihood ratio (PLR) was 30.39 (95% CI: 9.14 to 101.06), negative likelihood ratio (NLR) was 0.05 (95% CI:0.01 to 0.20), diagnostic odds ratio (DOR) was 225.54 (95% CI: 88.81 to 572.77), AUC was 1.00 (95% CI: 0.99 to 1.00), threshold value was sensitivity=0.95 (95% CI: 0.82 to 0.99) and specificity=1.00 (95% CI: 0.92 to 1.00). Deeks method revealed DOR funnel plot of SLN biopsy was not asymmetrical obviously with significant difference (P=0.01), which indicated remarkable publishing bias. Meta-subgroup analysis showed that compared to FI, NIR imaging had higher sensitivity (0.98 vs. 0.73); compared to 0 minutes, optical imaging performed 20 minutes after ICG injection had higher sensitivity (0.98 vs. 0.70); compared to mean detected number of SLN of 4, mean detected number≥4 had higher sensitivity (0.96 vs. 0.68); compared to HE stain, immunohistochemistry + HE had higher sensitivity (0.99 vs. 0.84); compared to subserous injection of ICG, submucosa injection of ICG had higher sensitivity (0.98 vs. 0.40); compared to injection of 5 g/L ICG, 0.5 g/L and 0.05 g/L had higher sensitivity (0.98 vs. 0.83); compared to cT2-3 tumor, early stage (cT1) tumor had higher sensitivity (0.96 vs. 0.72); compared to ≤ enrolled 26 cases in the study, > 26 cases had higher sensitivity (0.96 vs. 0.65); compared to papers before 2010, papers after 2010 had higher sensitivity (0.97 vs. 0.81); whose differences were all significant. Sensitivity differences between mean tumor diameter of ≤30 cm and >30 cm, open surgery and laparoscopic surgery, lymph node regional dissection and retrieved dissection were not significant (all P>0.05). Conclusions: Optical imaging combined with ICG-guided SLN biopsy is clinically feasible, and especially suitable for early gastric cancer. However, the ICG being used in current studies may be overdosed. Higher sensitivity may be achieved from NIR imaging when compared with FI method.

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