Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2019; 11(3): 250-263
Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.250
Near-infrared fluorescence guided esophageal reconstructive surgery: A systematic review
Elke Van Daele, Yves Van Nieuwenhove, Wim Ceelen, Christian Vanhove, Bart P Braeckman, Anne Hoorens, Jurgen Van Limmen, Oswald Varin, Dirk Van de Putte, Wouter Willaert, Piet Pattyn
Elke Van Daele, Yves Van Nieuwenhove, Wim Ceelen, Oswald Varin, Dirk Van de Putte, Wouter Willaert, Piet Pattyn, Department of Gastrointestinal Surgery, Ghent University Hospital/Ghent University, Ghent B-9000, Belgium
Christian Vanhove, Department of Electronics and information systems, Ghent University, Ghent B-9000, Belgium
Bart P Braeckman, Department of Biology, Ghent University, Ghent B-9000, Belgium
Anne Hoorens, Department of Pathology, Ghent University Hospital/Ghent University, Ghent B-9000, Belgium
Jurgen Van Limmen, Department of Anaesthesiology, Ghent University Hospital/ Ghent University, Ghent B-9000, Belgium
Author contributions: Van Daele E, Pattyn P, Van Nieuwenhove Y and Ceelen W designed the research; Van Daele E and Pattyn P performed the research and analysed the data; Van Daele E, Van Nieuwenhove Y and Ceelen W wrote the paper; Van Daele E and Ceelen W performed the statistical analysis; Vanhove C, Braeckman BP, Hoorens A, Van Limmen J, Varin O, Willaert W and Van de Putte D contributed to the manuscript reviewing and editing;
Supported by “ Kom op tegen Kanker” (Stand up to Cancer), the Flemish cancer society which has no role in the design of the study, nor in the collection, analysis or interpretation of the data or in the manuscripts’ writing.
Conflict-of-interest statement: The authors declare no conflicting interests related to this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Elke Van Daele, MD, Surgeon, Department of Gastrointestinal Surgery, Ghent University Hospital/Ghent University, University Hospital 2K12 IC, C. Heymanslaan 10, Ghent B-9000, Belgium.
Telephone: +32-9-3320829 Fax: +32-9-3323891
Received: November 27, 2018
Peer-review started: November 27, 2018
First decision: January 4, 2019
Revised: January 21, 2019
Accepted: January 29, 2019
Article in press: January 30, 2019
Published online: March 15, 2019
Research background

After an esophagectomy, the stomach is most commonly used to restore continuity of the upper gastrointestinal tract. These esophago-gastric anastomoses are prone to serious complications such as leakage associated with high morbidity and mortality. The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicled gastric tube (GT). Clinical judgment is unreliable in determining GT perfusion.

Research motivation

An objective, validated, and reproducible method to evaluate tissue perfusion at the anastomotic site is urgently needed. Based on the current literature we believe Indocyanine green fluorescence angiography (ICGA) is an easy and cheap assessment tool for GT perfusion, that might predict and therefore alter a potentially bad outcome.

Research objectives

This study aimed to systematically review the literature on feasibility and effectiveness of ICGA use as a method to evaluate graft perfusion and as a predictor of AL after esophageal reconstructive surgery. Additionally, current methods to quantify ICGA in esophageal reconstructive surgery were reviewed.

Research methods

This study was designed according to the PRISMA guidelines and registered in the PROSPERO database. Pubmed and Embase were independently searched by 2 reviewers for studies presenting data on intraoperative ICGA GT perfusion assessment during esophago-gastric reconstruction after esophagectomy. Relevant outcomes such as feasibility, complications, intraoperative surgical changes based on ICGA findings, quantification attempts, anatomical data and the impact of ICGA on postoperative anastomotic complications, were collected by 2 independent researchers. The quality of the included articles was assessed based on the MINORS criteria. The 19 included studies presented data on 1192 esophagectomy patients, in 758 patients ICGA was used perioperative to guide esophageal reconstruction.

Research results

The 19 included studies for qualitative analyses all described ICGA as a safe and easy. AL occurred in 13.8% of the entire cohort, 10% in the ICG guided group and 20.6% in the control group (P < 0.001). When poorly perfused cases are excluded from the analyses, the difference in AL was even larger (AL well-perfused group 6.3% vs control group 20.5%, P < 0.001). The AL rate in the group with an altered surgical plan based on the ICG image was 6.5%, similar to the well perfused group (6.3%) and significantly less than the poorly perfused group (47.8%) (P < 0.001), suggesting that the technique is able to identify and alter a potential bad outcome.

Research conclusions

ICGA is a safe, feasible and promising method for perfusion assessment. Based on this review a bolus dose of 2.5 mg is a sufficient optimal dose for visualization of esophagogastric anastomotic perfusion. The differences in AL rate between the well perfused and poor perfused AS clearly suggest that a good fluorescent signal is a predictor of good outcome. The AL rate in the group with an altered surgical plan based on the ICG image was similar to the well perfused group and significantly less than the poorly perfused group, suggesting that the technique is able to predict and remedy a potentially worse outcome.

Research perspectives

A few authors have attempted to quantify the method, but rarely in oesophageal surgery and without comparison with a golden standard method, stressing the need for objective quantification of the ICGA with validated cutoff levels for sufficient graft perfusion in esophageal surgery. No studies mentioned validation of the method. Therefore, we propose a clinical study that validates imaging-based perfusion assessment of the stomach graft using tissue, serum, and cellular hallmarks of hypo-perfusion and hypoxia during esophagectomy. The study is registered in as NCT03587532 and is currently recruiting. This easy and safe new technique of perioperative perfusion assessment has the potential to reduce AL rate and its associated mortality, but randomized trials are needed to confirm these retrospective results. At present, there are no ongoing randomized trials listed on clinical Potentially because a prospective randomized study comparing ICGA guided surgery versus non ICGA guided surgery implies a large sample size demanding a large multicentre study.