PROSPERO

International prospective register of systematic reviews

Pre-, peri- and post-operative immune-enhancing formulas for patients with cancer
undergoing oesophagectomy: a systematic review protocol
Astrid Naranjo, Elizabeth Isenring, Laisa Teleni

Citation
Astrid Naranjo, Elizabeth Isenring, Laisa Teleni. Pre-, peri- and post-operative immune-enhancing
formulas for patients with cancer undergoing oesophagectomy: a systematic review protocol.
PROSPERO 2017 CRD42017056908 Available from:
http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017056908

Review question
In cancer patients undergoing oesophageal resection and requiring postoperative nutritional support:
(1) Is there sufficient quality evidence on perioperative IEF enriched with Arginine (Arg), omega-3 and
ribonucleic acids (RNA) to recommend it as routine practice amongst clinicians?
(2) Do these IEFs confer additional clinical benefits such as reducing the risk of postoperative infectious
complications and improve patients´ healthcare outcomes compared to standard enteral formula (SEF)?
(3) Are IEFs perioperative IEF enriched with Arginine (Arg), omega 3 and ribonucleic acids (RNA) a cost-
effective practice to be considered by clinicians?

Searches
Searches for RCTs will be conducted systematically by the reviewers, with no publication year restriction.
Computerized searches will be performed for relevant published studies on the following databases from
their inception until August 2017; the Cochrane Central Register of Controlled Trials (CENTRAL-The
Cochrane Library); PubMed; EMBASE; CINAHL; LILACS; ClinicalTrials.gov and TRIP database.

Types of study to be included

RCTs

Condition or domain being studied

Adults cancer patients, undergoing esophageal resection

Participants/population
Inclusion:
All patients over 18 years undergoing surgical procedure for oesophageal cancer will be included. Also,
those included should be receiving IEF (containing a combination of Arg, omega-3 and RNA) pre-, peri- or
post-operatively for at least 5-7 days. Moreover, all inpatient and outpatient/ambulatory in the setting-linked
to the health care facility where patients are having surgery will be included.
Exclusion:
Lower GI, gastric or head cancer surgery with parenteral nutrition (PN) or non-IEF or the use of isolated
immunonutrient (Arg VS omega-3 VS RNA)

Intervention(s), exposure(s)
IEFs containing the immunonutrients Arginine, omega-3 PUFA and RNA provided either orally or via an
enteral feeding tube, given pre-, peri- and/or post-operatively.

Comparator(s)/control
Isonitrogenous-isocaloric SEF or polymeric nutritional supplements either orally or via enteral feeding tube.

Primary outcome(s)
Post-operative infectious complications (POIC): including wound infections or fistulae formation,
bacteraemia, sepsis, anastomotic leakage, abscess and pulmonary complications, especially pneumonia or

Page: 1 / 4
PROSPERO
International prospective register of systematic reviews

bronchopneumonia

Timing and effect measures

Measured within the first 2 weeks of surgery & during the whole stay in hospital
The measure will be as defined by trial authors (categorical: present/absent or yes/no or continuous as
number of cases or percentage (%) of people with POIC).

Secondary outcome(s)
- Health-related costs/cost-effectiveness/cost-benefit: defined by the authors.
- Healthcare use: LOS; Readmissions to acute care, sub-acute care or ICU; Re-operations>> all measured in
number of cases.
- Survival/mortality: Number/proportion of deaths related to treatment below 18 months (long term survival)
or up to 30-day and/or in-hospital post-operatively).
- Quality of life (QoL) within the first 3, 6 and 24 weeks postoperatively. Including symptoms such as eating
difficulties, reflux, dysphagia, and trouble with coughing
- Nutritional status: well-nourished or malnourished. Measured by validated nutrition assessment tool within 2
weeks pre-operatively.
- Percentage of weight loss: more than (>) 5% weight loss in past month (1/12) and 1 week and/or 3 weeks
post-operatively.
- Biochemical changes: as per trial authors,C-reactive protein (CRP) levels (from up to 7 days prior surgery
and first 2 weeks post-operatively)

Data extraction (selection and coding)

- Data such as study’s design and setting, number of participants, outcome measure and timing of IN
initiation, route feeding and total duration of IN will be autonomously extracted and organized on the matrix
table.
- If further information is needed from an RCT, will contact the nominated trial investigator/author.

Risk of bias (quality) assessment

The risk of bias will be independently assessed by the reviewers
- Every RCT will be appraised according to the quality of 6 domains: random sequence generation and
allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of
outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting
bias) and any other potential concerns to validity.
- Blinding, in particular, will be assessed separately for subjective (for example, nutritional status, LOS, QoL)
and objective (for instance, percentage of weight loss, biochemical/immunological changes, mortality)
outcome measures as the latter are less likely to be affected by knowledge of the treatment allocation group.
Publication bias will be visually assessed by funnel plots as indicated by PRISMA.
Based on study reports, preliminary information will be collected in the matrix tables to inform the risk of bias
assessments. Trial authors shall be contacted to provide a study protocol or to clarify uncertainties where
inconsistencies or unclear methodology were present during the risk of bias assessment.

Strategy for data synthesis

- The meta-analysis (MA) data will be pooled and organized on the matrix table.
- Categorical data will be presented as risk ratio (RR) and risk difference or odds ratio (OR) including their
95% confidence intervals (CI), excluding health care use (LOS) and biochemical/immunological changes that
are exclusively represented as continuous variables.
- Numbers needed to treat (NNT) for benefit or harm, could be calculated as needed.
- Continuous data will be presented as mean, mean difference (MD) or standardised mean difference (SMD)
with 95% CI, as applicable, excluding the nutritional status outcome measure (exclusively as dichotomous
variable).
- If a specific study does not report standard deviations (SD), these will be calculated from the standard error
(SE) and the sample size or the 95% CI.
- A p value of <0.05 for both continuous and dichotomous variables, will be considered statistically significant

Page: 2 / 4
PROSPERO
International prospective register of systematic reviews

Analysis of subgroups or subsets

- Clinical heterogeneity will be reported using subgroup (pre, peri and postoperative subgroups using IEF;
well-nourished vs malnourished patient’s subgroups).
- Sensitivity analysis (SA) might be also calculated by restricting the analysis to trials classified as having an
overall low risk of bias, which will assist in determining whether excluding studies at high risk of bias affects
the results of the MA.
- Statistical heterogeneity, will be calculated I-squared test.

Contact details for further information

astrid naranjo
a.naranjomartinez@student.bond.edu.au

Organisational affiliation of the review

Bond University
www.bond.edu.au

Review team members and their organisational affiliations

Miss Astrid Naranjo. faculty of health sciences and medicine, Bond University, Gold Coast, Queensland
Professor Elizabeth Isenring. faculty of health sciences and medicine, Bond University, Gold Coast,
Queensland
Ms Laisa Teleni. Faculty of health sciences and medicine, Bond university, Gold Coast, Queensland

Anticipated or actual start date

01 August 2017

Anticipated completion date

01 March 2018

Funding sources/sponsors
none

Conflicts of interest
None known

Language
English

Country
Australia

Stage of review
Review_Ongoing

Subject index terms status

Subject indexing assigned by CRD

Subject index terms

Esophagectomy; Food, Formulated; Humans; Neoplasms; Postoperative Period

Date of registration in PROSPERO

20 March 2017

Date of publication of this version

20 March 2017

Page: 3 / 4
 PROSPERO
International prospective register of systematic reviews

Revision note for this version

Action by administrator

Details of any existing review of the same topic by the same authors
Mudge, L., Isenring, E., & Jamieson, G. G. (2011). Immunonutrition in patients undergoing esophageal
cancer resection. Dis Esophagus, 24(3), 160-165. doi:10.1111/j.1442-2050.2010.01117.x

Stage of review at time of this submission

The review has not started

Stage Started Completed

Preliminary searches No 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

Revision note
Action by administrator

Versions
20 March 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.

Page: 4 / 4

Powered by TCPDF (www.tcpdf.org)