Original Title: Uso del verde de indocianina en cirugía colorrectal y hepato-biliopancreática

Authors' objectives: To study the efficacy and safety of the use of CIV by means of FIS, which can be integrated into laparoscopic or robotic surgical equipment, in comparison with the usual procedures, in colorectal and hepatobiliopancreatic surgery requiring resection, both in oncologic and non-oncologic patients, from the perspective of the Spanish National Health System (SNHS).

Authors' results and conclusions: RESULTS: The preliminary literature search identified 90 systematic reviews and meta-analyses (26 in Medline and 64 in EMBASE) on the use of ICG in colorectal and hepatobiliopancreatic pathology during the period 2007- 2021. After excluding duplicates (n=37), by title and abstract (n=32), and for other causes (n=17), 4 systematic reviews with meta-analysis (MA) were finally included in the analysis. Inclusion criteria were: systematic reviews and/or meta-analyses analysing the safety and effectiveness of the use (as a unique augmentation or reinforcement to standard treatment or diagnostic technique) of ICG via FIS during a surgical intervention or diagnostic procedure in patients over 18 years of age of both sexes undergoing colorectal and/or hepatobiliopancreatic surgery. In this review of reviews, the effects of the use of ICG via FIS in the following clinical conditions are analysed: prevention of anastomotic leakage by fluorescence angiography in colorectal surgery (2 SR), fluorescence imaging-guided hepatectomies for liver tumors (1 SR) and fluorescence cholangiography in cholecystectomies (1 SR). The quality of the SRs was assessed with the AMSTAR2 tool. Out of the 4 SRs included, 3 were of low quality and 1 critically low. As a tool to assess the risk of bias of the RCTs, the 2 SRs that included them used the Risk of Bias tool of the Cochrane Collaboration. One of the SRs additionally used the Jadad scale to assess the methodological quality of the RCTs. For the non-experimental observational studies, 1 SR used the MINORS tool (methodological index for non-randomized studies), 2 used the Newcastle-Ottawa Scale (NOS) and one used the Cochrane ROBINS-I tool (Risk of Bias in Non-Randomized Studies of Interventions). The 2 included RCTs did not receive the same overall assessment in the 2 SRs that analysed them, which did agree in considering a high risk of detection bias due to blinding of the outcome. The non-experimental observational studies were of very heterogeneous quality, characterised by small sample size, retrospective designs and short-term follow-up. There was great variability in the selection and collection of the effectiveness and safety outcome variables described by the authors, which in the case of the 2 SR that evaluated anastomotic leaks (AL) in colorectal surgery is illustrated by the coincidence between both analyses in only one effectiveness outcome variable (the rate of AL, which was also not defined in the same way in both studies), out of a total of 14 outcome variables described in the 2 SR. In the 4 SRs evaluated, there is a lack of systematic and homogeneous collection of robust data on the safety of the ICG application procedure. Only one of the SRs evaluated in this report collected specific information on possible adverse effects (AE) of ICG administration. The assessment of complications related to administration procedures was very heterogeneous in the 4 reviews examined in this report. The comparators used in each surgical setting were the usual standard techniques with no other dye than ICG used. A random-effects model was applied in the MAs if the heterogeneity between studies was considered high (with different heterogeneity thresholds depending on the authors), otherwise a fixed-effect model was used. 3 of the SRs performed some form of sensitivity analysis (according to quality or type of primary study) and subgroup analysis (according to certain clinical characteristics of patients or geographical origin of the study). Indocyanine green fluorescence angiography for prevention of anastomotic leak in colorectal surgery Two low-quality systematic reviews (SR) were selected with 21 common primary studies analysed in both papers (2 of them RCTs; the rest observational studies mostly retrospective) and 12 analysed only in one or the other of the reviews (7 of them without control group, analysed in one of the SR), evaluating the safety and effectiveness of indocyanine green fluorescein angiography (ICG-FA) compared to the non-use of this technique in the prevention of AL in colorectal surgery. One of the reviews collected specific information on possible AEs of the dye, but not on possible complications of the dye administration procedure or other safety variables, while the other review did not collect information on AEs related to the dye, but provided non-specific information on the complications suffered by patients (global and severe) without specifying their definition in detail. Although in both reviews the authors consider that the use of ICG-FA seems to suggest a decrease in the rate of AF, this is not homogeneous in all patients, but according to one of the SRs it would decrease especially in patients with low/ultra-low rectal resection. On the other hand, the other SR additionally concludes that the rate of AL would increase in those patients whose anastomosis line is modified after evaluation with ICG-FA. This other SR also considers that ICG-FA could reduce the overall complication rate, the severe complication rate and the reoperation rate while it could increase the postoperative ileus rate. The low quality of the 2 reviews and the limitations and heterogeneity of the studies do not allow us to draw solid conclusions on the safety and efficacy of ICG-FA for the prevention of anastomotic leakage (AL) in colorectal surgery. Indocyanine green fluorescence imaging-guided hepatectomy for liver tumors A single low-quality SR analysed the effectiveness and safety of hepatectomy of liver tumors guided by fluorescence imaging with VIC (ICG-FIGH) versus traditional hepatectomy (TH). This review included 6 retrospective cohort studies. No specific information on possible AEs of the dye was collected. The authors concluded that blood loss, hospital stay length (in this case with significant heterogeneity) and overall postoperative complication rate were lower in the ICG-FIGH group of patients compared to TH group. They found no differences in surgery duration, blood transfusion, R0 resection (with disease-free margins) and 1-year recurrence rate. The low quality of the SR, the limited number of primary studies included and their low quality do not allow conclusions to be drawn on the effectiveness and safety of ICG-FIGH versus TH. Indocyanine green dye fluorescent cholangiography A critically low-quality SR comparing the effectiveness and safety of ICG fluorescence cholangiography (ICG-FC) and traditional standard intraoperative cholangiography (IOC) in the definition of extrahepatic biliary anatomy in patients undergoing cholecystectomy by minimal access surgery was selected. This SR included 7 primary studies: 6 case-control and 1 randomised case-control. The primary outcome variable was the percentage of visualisation of the cystic duct, common bile duct, cystic duct -common bile duct junction and common hepatic duct. The authors reported non-specific information on possible complications suffered by the patients and did not collect specific data on possible AEs of the dye. The authors found no significant difference in the visualisation rate of the cystic duct, common bile duct cystic duct -common bile duct junction between ICG-FC compared to IOC. According to the authors, ICG-FC provided a statistically significant better visualisation of the common hepatic duct compared to IOC. Due to the small number and low quality of available studies, no solid conclusions can be drawn on the safety and effectiveness of ICG-FC and traditional standard IOC in defining extrahepatic biliary anatomy in patients undergoing cholecystectomy by minimal access surgery. CONCLUSIONS: The scarce evidence available and its limited quality do not allow us to draw solid conclusions on the use of ICG-FA compared to the non-use of this technique for the prevention of anastomotic leakage in colorectal surgery. The scarce evidence available and its limited quality do not allow us to draw solid conclusions on the use of ICG-FIGH compared to TH in liver tumor resection surgery. The limited evidence available and its limited quality do not allow to draw strong conclusions on the use of ICG-FC compared to IOC in the definition of extrahepatic biliary anatomy in non-oncological patients undergoing cholecystectomy by minimal access surgery. No evidence has been found on the safety and effectiveness of ICG in other clinical scenarios such as tumor identification, lymphadenectomy, sentinel node and lymphatic mapping in colorectal and hepatobiliopancreatic surgery. No evidence has been found on the cost-effectiveness of the use of ICG using FIS nor on the impact of its widespread implementation on the organisation and operation of surgical services that provide care for patients undergoing colorectal or hepatobiliopancreatic surgery. The enormous difficulty in standardising the protocol for the application of ICG using FIS in the different clinical situations in which its safety and effectiveness is being studied, as well as the problems in designing and conducting high-quality studies, suggest that mechanisms should be established to facilitate a rigorous protocol accepted by all the actors involved in this field.

Authors' methods: A systematic review (SR) of systematic reviews was performed. The available scientific evidence collected from systematic reviews and meta-analyses was reviewed. A specific search strategy was designed to locate the studies of interest in the period from January 1, 2007 to May 31, 2021. Two reviewers independently selected the studies by reading the titles and abstracts retrieved from the literature search, extracted data from the included studies, and assessed the quality of the studies using the AMSTAR-2 tool. Evidence tables were developed from the data extraction forms.

Project Status: Completed

Year Published: 2022

URL for published report: https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=detalle&id=1102

Requestor: Spanish Ministry of Health

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Spain

Organisation Name: Agencia de Evaluacion de Tecnologias Sanitarias

Contact Address: Instituto de Salud "Carlos III", Calle Sinesio Delgado 6, Pabellon 4, 28029 Madrid, Spain. Tel: +34 9 1 822 2005; Fax: +34 9 1 387 7841;

Contact Name: Luis M. Sánchez Gómez

Contact Email: luism.sanchez@isciii.es

Copyright: <p>Agencia de Evaluacion</p>