Indocyanine green fluorescence in gastrointestinal surgery: Appraisal of current evidence

Table 1 Studies on liver segmentation and mapping using direct staining technique

Ref.	Country	Study type	Patient	Camera device	ICG dose and time	Guide/approach	Target liver	Success rate	Procedure time
Qian et al[16], 2022	China	Prospective cohort	Grp A: 10. Grp C: 20	-	0.0125 mg/mL, up to 10 mL	DSA: Hepatic artery. USG: Portal vein	Grp A: Seg, sub-seg. Grp C: Seg	Grp A: 80 %. Grp C: 60 %	Grp A: 305.3 ± 23.2 min. Grp C: 268.4 ± 34.7 min
Li et al[17], 2021	Taiwan	Prospective cohort	8	Karl storz, Pinpoint Stryker	Conc -0.125 mg/mL, rate of 1 mL/min	DSA: Hepatic artery	Segment bisegment	100%	DSA: 32.7 +/5.3 min, operative time: 242 +/118 min
Lan et al[18], 2022	China	Retrospective cohort	24	Pinpoint Stryker	5 mL of 0.025 mg/mL	Glissonian pedicle approach	Hemiliver: 10. Left lateral: 7. Segment: 7	79.40%	Staining time: 25.92 ± 14.64, operative time: 334.17 ± 98.65
Xu et al[15], 2020	China	Retrospective cohort	9	Pinpoint Stryker	0.025 mg/mL, 5-10 mL	Intraoperative ultrasound. Glissonian pedicle approach	Segment, section	56%	Median operative time: 260 min (range 150-360 min)
Ueno et al[13], 2019	Japan	Prospective cohort	10	Pinpoint Stryker	0.125 mg/mL, 2 mL ICG, 2 mL Indigo carmine, 1 mL Sonazoid embolic agent-Gelatin particles	DSA	Segment	100%	IVR procedures- 41 (30-102) min. Median operating time with IVR time: 432 min
Ueno et al[14], 2018	Japan	Prospective cohort	5	Pinpoint Stryker	0.125 mg/mL, 2 mL ICG, 2 mL Indigo carmine, 1 mL Sonazoid embolic agent-Gelatin particles	DSA	Segment	100%	Operative time: 432 (293-572) min
Aoki et al[11], 2010	Japan	Prospective cohort	81	PDE: 2	5 mg/mL	IOUS	Segment. Sub-segment	73/81 (90.1%)	NA

ICG: Indocyanine green; IOUS: Intraoperative ultrasound; DSA: Digital subtraction angiography; USG: Trans abdominal ultrasound; NA: Not available; PDE: Photodynamic eye.

Table 2 Studies on liver segmentation and mapping using counterstaining technique

Ref.	Country	Study type	Patients	Camera device	ICG dose and time	Approach	Target liver	Success rate	Median (range) operative time, in minutes
Funamizu et al[21], 2021	Japan	Retrospective cohort	74	Viscera Elite II, Olympus, Pinpoint, Stryker, Hopkins II, Karl storz	0.5 mg	Glissonian pedicle approach	Monosegmectomy	100%	351
Xu et al[15], 2020	China	Retrospective cohort	27	Pinpoint, Stryker	2.5 mg/mL	Glissonian pedicle approach	Hemiliver. Section. Segment	52%	260 (150-360)
Uchiyama et al[19], 2011	Japan	Prospective cohort	22	PDE; Hamamatsu Photonic	0.5 mg/kg	CE-IOUS: Glissonian pedicle approach	Hemiliver: 8. Section: 8. Segment: 6	100%	280 (140-380)
Berardi et al[20], 2021	Japan	Retrospective cohort	86 patients: HCC: 55; CRLM: 31	Viscera Elite II, Olympus, Pinpoint, Stryker, Hopkins II, Karl storz	0.5 mg	Glissonian approach	Section: 14. Segment: 56. Sub-segment: 16	98.80%	328 (270-437)

ICG: Indocyanine green; HCC: Hepatocellular carcinoma; CRLM: Colorectal liver metastasis; CE-IOUS: Contrast enhanced intraoperative ultrasound.

Table 3 Studies on hepatic tumor detection with indocyanine green fluorescence

Ref.	Country	Study type	Patients	Device	ICG dose and time	Tumor detection rate	New lesions	Correlation with histology	Micro metastases detection
Cai et al[24], 2023	China	Retrospective cohort	Total: 86. HCC: 52, CRLM: 34	Pinpoint, Stryker	Dose: 0.5 mg/kg, ICG < 7: 5 d prior; ICG > 7: 7 d prior	96%	8	Positive (P = 0.001)	False positive: 3/8 (37.5 %)
Franz et al[23], 2021	Germany	Prospective cohort	Total: 18. HCC: 9, CRLM: 4, IHCC: 2	Firefly, DaVinci NIR-ICG, Karl storz	Dose: 0.5 mg/kg, 2-14 d prior	100%	27.8	-	False positive: 39%
Piccolo et al[25], 2021	Italy	Prospective cohort	Total lesions: 29. HCC: 14, CRLM: 13, IHCC: 1, non-CRLM: 1	NIR-ICG, Karl storz	0.5 mg/kg, HCC/IHCC: 7 d prior; CRLM: 5 d prior	ICG: 100%, LUS: 72.4%	-	R0: 100%	-
Marino et al[27], 2020	Spain	Retrospective cohort	Total lesions: 59. HCC: 23, CRLM: 27, IHCC: 6, hemangioma: 2, steatosis: 1	Davinci- Firefly	0.5 mg/kg 5 d prior	52/59 (88.1%)	6 (11.5%)	R0: 100%	False positive: 3/52
Zhou et al[29], 2019	China	Retrospective cohort	ICG: 21, IOUS: 21	Pinpoint, Stryker	0.25 mg/kg 3-5 d prior	100%	-	-	NA
Terasawa et al[26], 2017	Japan	Prospective cohort	Total lesions: 59. CRLM: 46, HCC: 7, others: 6	Pinpoint, Stryker	0.5 mg/kg body within 3 d	45/53 (85%)	22/45	R0: 100%	True negative: 100%
Kudo et al[30], 2014	Japan	Prospective cohort	Total lesions: 32. HCC: 16, CRLM: 16	Olympus	0.5 mg/kg within 14 d	23/32 (71.8%)	-	-	-

ICG: Indocyanine green; HCC: Hepatocellular carcinoma; CRLM: Colorectal liver metastasis; IHCC: Intrahepatic cholangiocarcinoma; CE-IOUS: Contrast enhanced intraoperative ultrasound; ICG: Indocyanine green; LUS: Laparoscopic ultrasound; NA: Not available.

Table 4 Studies on lymphatic mapping in esophageal and gastric surgery

Ref.	Country	Study type	Patient	Device	ICG dose and time	Surgery	Results	Long term outcome
Esophageal
Hachey et al[48], 2016	United States	Prospective PFS	EAC: 9	NOVADAQ, Stryker	2.5 mg/mL, 1 cc, 4 sites, endoscopic injection diluted with sterile water/HSA 25%	Ivor Lewis esophagectomy	6/9 patients showed 2-6 regional NIR +	NA
Park et al[49], 2018	Korea	Prospective PFS	ESCC, cT1: 29	Firefly, Da Vinci	0.5 mg/m, 0.5 m: Each quadrant 1 d prior	Robotic Mckeown esophagectomy	High NPV	NA
Stomach
Chen et al[58], 2020	China	RCT	ICG 129; non-ICG: 129	NOVADAQ, Stryker	Submucosal endoscopic 1 d prior 2 mL, 0.5 mL/quadrant 0.625 mg/m	Laparoscopic distal and total gastrectomy	Lymph node yield, mean ± SD: ICG: 50.5 ± 15.9; non-ICG: 42.0 ± 10.3	3-yr: DFS: 81.4% vs 68.2%; OS: 86.0% vs 73.6%
Park et al[51], 2020	Korea	Prospective feasibility study, PSM	ICG: 20; non-ICG: 60	NOVADAQ, Stryker	Endoscopic sub-mucosal 0.1 mg/mL, 1 mL 5 sites	Laparoscopic distal gastrectomy, station 6 dissection	ICG vs non-CIG lymph node yield 30.15 vs 32.55, bleeding events 4 (20.0) vs 41 (68.3)	NA
Cianchi et al[53], 2020	Italy	Retrospective, PSM	ICG: 37; non-ICG: 37	Firefly, Da Vinci	Endoscopic sub-mucosal 0.1 mg/mL, 0.5 mL, 4 quatrants	Robotic distal or total gastrectomy	Operative time mean ± SD: 293.1 ± 6 vs 321.2 ± 77.8 harvested lymph nodes: vs 50.8 ± 17	NA
Ushimaru et al[52], 2019	Japan	Retrospective, PSM	ICG: 84; non-ICG: 84	NIR, Karl storz	Endoscopic submucosal 0.05 mg/mL, 10 mL, 4 sites	Laparoscopic distal gastrectomy	Operative time mean ± SD: 206.1 ± 5.0 vs 237.0 ± 5.0, harvested lymph nodes: 47.5 vs 42.6	NA

ICG: Indocyanine green; PSM: Propensity score matching; PFS: Progression free survival; HAS: Human albumin solution; ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma; DNIR: Near infra-red; DFS: Disease free survival; OS: Overall survival; NA: Not available.

Table 5 Studies on sentinel nodal navigation in early gastric cancer

Ref.	Country	Study type	Patient	ICG dose	Surgery	Mean SN yield	Results	Long term outcome
Isozaki et al[56], 2019	Japan	Multicenter retrospective cohort	100	Intraop endoscopic submucosal 1 mL 2.5% ICG 4 sites wait 15 min. Sentinel node biopsy followed by frozen	Open SNNS/DiG WDG: 3; 1/2 DG: 18; PPG: 19; SG: 31; LR: 29	3.8	Sensitivity: 85.7%. Specificity: 98.9%. Accuracy: 98%	5-yr OS: 89.6%. Gastric cancer specific survival: 98.5%
An et al[54], 2020	Korea	Multicenter RCT	580 patients; LSG: 292; LSNNS: 245	Dual tracer, ICG 2.5 mg/mL, 2 ml, and 99mTc-HSA, 2 mL	LSG group: Open: 3; LSG: 266. LSNNS group: LSNNS: 210	9	SBD: SB nodes: 59.7%; hot nodes: 23.4%; hot and green: 12%; green nodes: 4.9%. Operative time: LSG: 180 min; LSNNS: 192.5 min. Upstaging: 7.4%	NA
Miyashiro et al[55], 2014	Japan	Multicenter RCT	440 patients suspended	Serosal injection 4-5 mL, 25 mg/5 mL ICG	Sentinel node biopsy followed by gastrectomy with lymphadenectomy	4	False negative: 46.4%	NA

RCT: Randomized controlled trial; ICG: Indocyanine green; SNSS: Sentinel node navigation surgery; WDG: Wide-extent distal gastrectomy; LR: Local resection of stomach; SG: Segmental gastrectomy; PPG: Pylorus preserving gastrectomy; OS: Overall survival; DiG: Diminished gastrectomy; SBD: Sentinel basin dissection; HN: Hot nodes; SB: Sentinel basin; LSG: Laparoscopic standard gastrectomy; LSNNS: Laparoscopic sentinel node navigation surgery.