PROSPERO

International prospective register of systematic reviews

Minimally invasive versus open esophagectomy in patients with esophageal cancer: a

systematic review and meta-analysis
Pascal Probst, Eva Kalkum, Patrick Heger, Henrik Nienhüser, Jonas Senft, Shila Fazeli, Thomas Schmidt,
Markus K. Diener, Beat Müller

Citation
Pascal Probst, Eva Kalkum, Patrick Heger, Henrik Nienhüser, Jonas Senft, Shila Fazeli, Thomas
Schmidt, Markus K. Diener, Beat Müller. Minimally invasive versus open esophagectomy in
patients with esophageal cancer: a systematic review and meta-analysis. PROSPERO 2017
CRD42017073147 Available from:
http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017073147

Review question
The objective of this review is to evaluate the potential benefits of minimally invasive esophagectomy
compared to open surgery in the treatment of esophageal cancer.

Searches
The review authors will search the following electronic bibliographic databases: MEDLINE, The Central
Library and Web of Science.
The search strategy will be built using a combination of the following key search terms:
esophagectomy, oesophagectomy, esophageal resection, esophagus resection, transhiatal resection,
minimally, thoracoscopic, laparoscopic, laparoscopical, laparoscopically, cancer, carcinoma , malignancy
and malignancies
All articles in English or German will be applied. There will be no other restrictions.

Types of study to be included

Exclusively randomized controlled trials (RCT) and prospective comparative cohort studies will be used for
the qualitative and quantitative synthesis of the systematic review.All other studies such as animal studies,
retrospective studies, meeting abstracts, letters/comments/editorials and publications, for which the full text
is irretrievable will be excluded.To determine the publications to be included, two researchers will scan the
titles and abstracts of all studies retrieved according to the inclusion criteria. Full texts of all relevant articles
will then be further reviewed. Any disagreement will be resolved by consensus, or by consultation of a third
reviewer.

Condition or domain being studied

Esophagectomy for esophageal cancer.

Participants/population
Inclusion: Adult patients with esophageal cancer
Exclusion: Patients with esophagectomy due to other pathologies than esophageal cancer.

Intervention(s), exposure(s)
Inclusion: Minimally invasive esophagectomy at least in one phase (abdominal or thoracic)
Exclusion: n (group size) <10, retrospective studies.

Comparator(s)/control
Inclusion: Open esophagectomy: transhiatal or transthoracic
Exclusion: n<10, retrospective studies.

Primary outcome(s)
Overall morbidity.

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Secondary outcome(s)
Short and long-term mortality, major complications according to the Clavien-Dindo classification (III-V),
reoperations, anastomotic leakages, overall pulmonary complications, pneumonia, operative time, blood
loss, length of hospital stay, length of intensive care unit stay, 1-year-survival-rate, positive resection margin
(R1/R2 status), number of harvested lymph nodes.

Data extraction (selection and coding)

Data will be extracted from the studies that meet our final inclusion criteria using a standardized form. The
form will be piloted in the first three trials and revised accordingly. Two authors will independently extract
data using the standardized form, and any queries/discrepancies will be resolved by a third party.

Risk of bias (quality) assessment

Risk of bias in RCTs included will be analyzed independently by two review authors using the Cochrane
Collaboration tool for assessing the risk of bias in randomized trials (Higgins 2011). Each of the following
domains will be evaluated and graded as high, low or unclear risk of bias: Random sequence generation,
allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete
outcome data, selective outcome reporting, other bias (e.g. baseline imbalance, surgical experience, early
termination of the trial, funding bias, etc.).
For non-randomized studies risk of bias assessment will be conducted in accordance to ACROBAT-NRSI
tool (Sterne JAC, Higgins JPT, Reeves BC on behalf of the development group for ACROBAT-NRSI. A
Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions (ACROBAT-NRSI),
Version 1.0.0, 24 September 2014). Each of the following domains will be evaluated and graded as low,
moderate, high or unclear risk of bias: Bias due to confounding, bias in selection of participants into the
study, bias in classification of intervention, bias due to departures from intended interventions, bias due to
missing data, bias in measurement of outcomes, bias in selection of the reported results.
The quality of the body of evidence will be addressed using the GRADE system. The following issues will be
considered: limitations in the design, indirectness of evidence, unexplained heterogeneity or inconsistency of
results, imprecision of results, and high probability of publication bias.

Strategy for data synthesis

A quantitative analysis is planned, and the data synthesis will be presented in tables or written in text in the
result section. If RCT and non-RCT are available, the study types will always be pooled separately and
together.
For all outcomes, a random-effect model will be applied to account for methodological and clinical
differences. Statistical heterogeneity among the effect estimates of the included trials will be evaluated using
the I-squared statistic. We will consider an I-squared less than 25% to indicate low heterogeneity and an I-
squared > 75% to indicate high heterogeneity.
Odds ratios (OR) and 95%-CI will be pooled for dichotomous outcomes using the Mantel–Haenszel (M-H)
method. Continuous outcomes will be pooled as mean difference and 95%-CI with the inverse variance
method. If trials only report medians or ranges, the methods described by Hozo, 2005 [1] will be applied to
calculate means and standard deviations (SD) from the values reported.
Publication bias will be explored by funnel plotting.
Primary statistical analysis and meta-analysis will be performed with program R [2] and Revman 5.3.5 [3],
respectively. Forest plots will be used for graphical presentation of (overall) effect estimates.
[1] Hozo SP1, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the
size of a sample. BMC Med Res Methodol. 2005 Apr 20;5:13.
[2] R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical
Computing. Vienna, Austria, 2013. http://www.R-project.org. (Accessed 01 Nov 2015).
[3] Cochrane collaboration. http://tech.cochrane.org/revman/download (Accessed 01 Nov 2015).

Analysis of subgroups or subsets

If possible, subgroup analysis of totally or partially minimally invasive esophagectomy will be performed. If
possible, subgroup analysis of transhiatal and thoracic esophagectomy will be performed. Sensitivity

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analyses will be performed for study quality according to the risk of bias assessment.

Contact details for further information

Eva Kalkum
Eva.Kalkum@med.uni-heidelberg.de

Organisational affiliation of the review

Study Center of the German Surgical Society, University Hospital of Heidelberg.
https://www.klinikum.uni-heidelberg.de/Home.6187.0.html

Review team members and their organisational affiliations

Dr Pascal Probst. Study Center of the German Surgical Society, University of Heidelberg, Germany.
Dr Eva Kalkum. Study Center of the German Surgical Society, University of Heidelberg, Germany.
Dr Patrick Heger. Study Center of the German Surgical Society, University of Heidelberg, Germany.
Dr Henrik Nienhüser. Department of General, Visceral and Transplantation Surgery, University of
Heidelberg, Germany.
Dr Jonas Senft. Department of General, Visceral and Transplantation Surgery, University of Heidelberg,
Germany.
Ms Shila Fazeli. Department of General, Visceral and Transplantation Surgery, University of Heidelberg,
Germany.
Dr Thomas Schmidt. Department of General, Visceral and Transplantation Surgery, University of Heidelberg,
Germany.
Professor Markus K. Diener. Study Center of the German Surgical Society, University of Heidelberg,
Germany.
Professor Beat Müller. Department of General, Visceral and Transplantation Surgery, University of
Heidelberg, Germany.

Anticipated or actual start date

01 January 2017

Anticipated completion date

31 December 2017

Funding sources/sponsors
None

Conflicts of interest
None known

Language
English

Country
Germany

Stage of review
Review_Ongoing

Subject index terms status

Subject indexing assigned by CRD

Subject index terms

Esophageal Neoplasms; Esophagectomy; Humans

Date of registration in PROSPERO

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International prospective register of systematic reviews

27 July 2017

Date of publication of this version

27 July 2017

Details of any existing review of the same topic by the same authors
Stage of review at time of this submission

Stage Started Completed

Preliminary searches Yes Yes
Piloting of the study selection process Yes Yes

Formal screening of search results against eligibility criteria Yes No

Data extraction No No
Risk of bias (quality) assessment No No

Data analysis No No

Versions
27 July 2017

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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