PROSPERO

International prospective register of systematic reviews

Indocyanine green for intraoperative sentinel lymph node mapping in esophageal cancer:
a systematic review and meta-analysis
Julio Jimenez Lillo, Eduardo Villegas Tovar, Valeria Jimenez Valerio, Alejandro Diaz Giron Gidi, Regina Faes
Peterson, Dulce Momblan Garcia, Victor Turrado Rodriguez, Ainitze Ibarzabal Olano, Antonio M Lacy,
Raigam Jafet Martinez Portilla

Citation
Julio Jimenez Lillo, Eduardo Villegas Tovar, Valeria Jimenez Valerio, Alejandro Diaz Giron Gidi,
Regina Faes Peterson, Dulce Momblan Garcia, Victor Turrado Rodriguez, Ainitze Ibarzabal Olano,
Antonio M Lacy, Raigam Jafet Martinez Portilla. Indocyanine green for intraoperative sentinel
lymph node mapping in esophageal cancer: a systematic review and meta-analysis. PROSPERO
2018 CRD42018084843 Available from:
http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018084843

Review question
What is the incremental yield of Indocyanine green over other conventional imaging techniques for sentinel
lymph node mapping in oesophageal cancer?

Searches
We will search the following databases: MEDLINE, Scopus, Web of Knowledge, Cochrane database and
PROSPERO database for meta-analysis. The search strategy will include only terms relating to or describing
the intervention. The terms will be filtered for systematic reviews and meta-analysis. Search will be restricted
to articles in English and Spanish. There will not be time restrictions for this search. The searches will be re-
run just before the final analyses and further studies retrieved for inclusion.

Types of study to be included

Observational and case control studies.

Condition or domain being studied

Use of indocyanine green for the intraoperative sentinel lymph node mapping in oesophageal cancer.

Participants/population
Inclusion: Observational studies and case series of patients with oesophageal cancer undergoing surgery
with use of Indocyanine green for sentinel lymph node mapping. Exclusion: studies with less than 5 patients
undergoing indocyanine green for lymph node mapping.

Intervention(s), exposure(s)
Patients undergoing oesophageal cancer surgery undergoing indocyanine green for sentinel lymph node
mapping.

Comparator(s)/control
Patients undergoing oesophageal cancer surgery using any other imaging technique for sentinel lymph node
mapping.

Primary outcome(s)
Incremental yield of ICG over conventional imaging methods Where incremental yield in defined as: number
of additional cases diagnosed by ICG that were not detected by conventional imaging techniques, divided by
all cases detected by ICG.

Timing and effect measures

Risk difference (RD) for both fixed and random effects models (weighting by inverse of variance) will be

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used.

Secondary outcome(s)
Incremental yield of ICG over conventional imaging methods in laparoscopic surgery techniques, where
incremental yield in defined as: number of additional cases diagnosed by ICG that were not detected by
conventional imaging techniques, divided by all cases detected by ICG. Incremental yield of ICG over
conventional imaging methods in open surgery techniques, where incremental yield in defined as: number of
additional cases diagnosed by ICG that were not detected by conventional imaging techniques, divided by all
cases detected by ICG.

Timing and effect measures

Risk difference (RD) for both fixed and random effects models (weighting by inverse of variance) will be
used.

Data extraction (selection and coding)

A systematic search will be performed using MEDLINE, Scopus, Web of Knowledge, Cochrane database
and PROSPERO database for meta-analysis, to identify relevant studies published in English or Spanish,
without publication time restrictions. References of relevant publications will be manually searched for
additional potentially relevant published studies. This review will be carried out adhering to the PRISMA
guidelines for meta-analysis. Abstracts identified as relevant will be assessed by two independent evaluators
(E.V & J.J.), both blinded to the authorship, authors' institution and study results. If studies fitted the inclusion
criteria, full-text articles were reviewed. A third investigator (R.M) will independently resolved any
disagreement between evaluators. In case of relevant studies with missing information corresponding
authors will be reached by e-mail. The following data will be extracted: author, year of publication, country
where the study was conducted, study period, original inclusion criteria, total number of patients included in
the study, number of lymph nodes detected by ICG, number of lymph nodes detected by other imaging
techniques, type of imaging techniques, surgery technique performed. The incremental yield will be analyzed
according to those patients using ICG and those using other conventional imaging techniques. Also,
outcomes will be evaluated according to laparoscopic and open surgery techniques.

Risk of bias (quality) assessment

Two reviewers (E.V. and J.J.) will independently assesses the quality of the selected studies. Quality
assessment of diagnostic accuracy studies will be carried out using the QUADAS-2 scale. The following
characteristics will be evaluated: Patient selection: Could the Selection of Patients Have Introduced Bias?
Are There Concerns That the Included Patients and Setting Do Not Match the Review Question? Index Test:
Could the Conduct or Interpretation of the Index Test Have Introduced Bias? Are There Concerns That the
Index Test, Its Conduct, or Its Interpretation Differ from the Review Question? Reference standard: Could the
Reference Standard, Its Conduct, or Its Interpretation Have Introduced Bias? Are There Concerns That the
Index Test, Its Conduct, or Its Interpretation Differ from the Review Question? Flow and timing: Could the
Patient Flow Have Introduced Bias? Results from these questions will be graphed and assessed using
Review Manager 5.3.

Strategy for data synthesis

Extracted results will be pooled in a meta-analysis. Risk difference (RD) for both fixed and random effects
models (weighting by inverse of variance) will be used. A continuity correction will also be used for cells with
zero values. Between-study heterogeneity will be assessed using the ?², ?2 (Cochrane Q) and I² statistics.
According to the Cochrane handbook, the I² will be considered non-important (<30%), moderate (30%-60%)
and substantial (>60%). Results will be assessed using forest plots and presented as RDs for the main
outcome and secondary outcomes. An influence analysis will be performed to ascertain the results of the
meta-analysis by excluding each of the individual studies. Publication bias will be assessed by a funnel plot
for meta-analysis and quantified by the Egger method. Statistical analysis will be conducted using STATA
software for Mac v15.1 (Stata Corp., College Station, Texas) [module “meta”] and R studio v1.0.136 (The R
Foundation for Statistical Computing) [package “meta v4.2”]

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Analysis of subgroups or subsets

Risk difference (RD) for both fixed and random effects models (weighting by inverse of variance) will be used
for the evaluation of the incremental yield of ICG versus other conventional imaging techniques in open
oncological surgery for esophageal cancer. Also, Risk difference (RD) for both fixed and random effects
models (weighting by inverse of variance) will be used for the evaluation of the incremental yield of ICG
versus other conventional imaging techniques in laparoscopic oncological surgery for esophageal cancer

Contact details for further information

Raigam Jafet Martinez Portilla
raifet@hotmail.com

Organisational affiliation of the review

Hospital Clinic de Barcelona

Review team members and their organisational affiliations

Dr Julio Jimenez Lillo. Hospital Clinic de Barcelona
Dr Eduardo Villegas Tovar. Hospital Clinic de Barcelona
Mr Valeria Jimenez Valerio. Hospital Clinic de Barcelona
Mr Alejandro Diaz Giron Gidi. Hospital Clinic de Barcelona
Dr Regina Faes Peterson. Hospital Clinic de Barcelona
Mr Dulce Momblan Garcia. Hospital Clinic de Barcelona
Mr Victor Turrado Rodriguez. Hospital Clinic de Barcelona
Mr Ainitze Ibarzabal Olano. Hospital Clinic de Barcelona
Professor Antonio M Lacy. Hospital Clinic de Barcelona
Dr Raigam Jafet Martinez Portilla. Hospital Clinic de Barcelona

Anticipated or actual start date

21 December 2017

Anticipated completion date

01 March 2018

Funding sources/sponsors
No funding or sponsor.

Conflicts of interest
Language
(there is not an English language summary)

Country
Spain

Stage of review
Review_Ongoing

Subject index terms status

Subject indexing assigned by CRD

Subject index terms

Esophageal Neoplasms; Humans; Indocyanine Green; Lymphatic Metastasis; Sentinel Lymph Node;
Sentinel Lymph Node Biopsy

Date of registration in PROSPERO

16 January 2018

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International prospective register of systematic reviews

Date of publication of this version

16 January 2018

Details of any existing review of the same topic by the same authors
systematic review; meta-analysis; Indocyanine green; incremental yield; oesophageal cancer; laparoscopic
surgery

Stage of review at time of this submission

Stage Started Completed

Preliminary searches Yes No

Piloting of the study selection process No No

Formal screening of search results against eligibility criteria No No

Data extraction No No

Risk of bias (quality) assessment No No

Data analysis No No

Versions
16 January 2018

PROSPERO
This information has been provided by the named contact for this review. CRD has accepted this information in good
faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration
record, any associated files or external websites.

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