Optimal ICG dosage of preoperative colonoscopic tattooing for fluorescence-guided laparoscopic colorectal surgery

Abstract

Background Indocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery. Purpose This study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery. Methods Colorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient’s age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM. Results In the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5–1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859). Conclusions Preoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.

Multifunctional Indocyanine Green Applications for Fluorescence-Guided Laparoscopic Colorectal Surgery

“…In colorectal cancer surgery, FLNM helps the surgeon visualize the lymphatic pathway to perform a more accurate dissection of the lymph nodes [30]. The patients' body mass index (BMI) can affect the success of FLNM because higher BMI means more visceral fat tissue and that can disturb the fluorescence signals of lymph nodes that are covered with thick mesenteric fat tissue [10]. FLNM protocols have been introduced from previous studies and summarized in Table 2 [7,8,10,[31][32][33][34][35][36][37][38][39][40][41].…”

“…Nevertheless, the submucosal injection of ICG via preoperative colonoscopy has greater advantages on accurate ICG instillation into the submucosal layer and performing multifunctional applications of ICG. In our recent study, reduced ICG tattooing dosage let cancer be visualized clearly by the NIR system [ 10 ]. In addition, performing the FLNM and intraoperative ICG angiography may not be disturbed with surrounding ICG stained tissues.…”

“…In our clinical experiences with almost 200 patients, we had reduced ICG tattooing dosage by diluting the concentrate, and measured success or failure on each application; fluorescent tumor localization, FLNM, and intraoperative ICG angiography. From the results, we could have established the optimal ICG tattooing protocol; preoperative endoscopic submucosal injection near the tumor at ICG dosage of 0.5 mg, which improve the success rate of FLNM without the interference of fluorescent tumor localization and ICG angiography [ 10 ].…”

“…The patients’ body mass index (BMI) can affect the success of FLNM because higher BMI means more visceral fat tissue and that can disturb the fluorescence signals of lymph nodes that are covered with thick mesenteric fat tissue [ 10 ]. FLNM protocols have been introduced from previous studies and summarized in Table 2 [ 7 , 8 , 10 , 31 - 41 ].…”

“…Thus, it can be suggested that FLNM helps harvest more lymph nodes than the conventional method. Therefore, the successful FLNM could be expected not only to help isolate more lymph nodes but also to effective pathologic isolation of D3 lymph nodes after radical lymphadenectomy [ 10 ].…”