Protocol for a systematic review and meta-analysis on the clinical outcomes and cost of deep inferior epigastric perforator (DIEP) flap versus implants for breast reconstruction
Khajuria et al. Systematic Reviews
Protocol for a systematic review and meta- analysis on the clinical outcomes and cost of deep inferior epigastric perforator (DIEP) flap versus implants for breast reconstruction
Ankur Khajuria 0 1
Oliver J. Smith 0
Maxim Prokopenko 0
Maximillian Greenfield 0
Afshin Mosahebi 0
0 Department of Plastic & Reconstructive Surgery, Royal Free Hospital NHS Trust , London , UK
1 Department of Surgery and Cancer, Imperial College London , London , UK
Background: Mastectomy in the context of breast malignancy can have a profoundly negative impact on a woman's self-image, impairing personal, sexual and social relationships. The deep inferior epigastric perforator (DIEP) flap and implants are the two commonest reconstructive modalities that can potentially overcome this psychological trauma. The comparative data on clinical outcomes and costs of the two modalities is limited. We aim to synthesise the current evidence on DIEP versus implants to establish which is the superior technique for breast reconstruction, in terms of clinical outcomes and cost-effectiveness. Methods: A comprehensive search will be undertaken of EMBASE, MEDLINE, Google Scholar, CENTRAL and Science citation index databases (1994 up to August 2017) to identify studies relevant for the review. Primary human studies evaluating clinical outcomes and cost of DIEP and implant-based reconstruction in context of breast malignancy will be included. Primary outcomes will be patient satisfaction and cosmetic outcome from patientreported outcome measures (scores from validated tools, e.g. BREAST-Q tool), complications and cost-analysis. The secondary outcomes will be duration of surgery, number of surgical revisions, length of stay, availability of procedures and total number of clinic visits. Discussion: This will be the first systematic review and meta-analysis in available literature comparing the clinical outcomes and cost-effectiveness of DIEP and implants for breast reconstruction. This review is expected to guide worldwide clinical practice for breast reconstruction. Systematic review registration: PROSPERO CRD42017072557.
Breast implant; DIEP; Cost-effectiveness; Autologous flap reconstruction; Deep inferior epigastric artery perforator flap
Breast cancer is the commonest malignancy in women
and a major cause of cancer-related mortality [
mastectomy is the primary treatment modality for these
patients, it can have a profoundly negative impact on
their lives, impairing personal, sexual and social
relationships. Fifty percent of women post-mastectomy suffer
from negative self-image with negative changes in their
]. The demand for reconstructive
procedures has risen, not only as a consequence of advancing
cancer treatment but also because of the demonstrated
functional, psychological and social benefits for patients,
overcoming the psychological trauma associated with
]. The rates of post-mastectomy breast
reconstruction doubled from 13 to 26% between 1998
and 2007 [
A number of reconstructive techniques exist for breast
reconstruction. The two most frequently employed
techniques include the autologous deep inferior epigastric
perforator (DIEP) flap and implant-based reconstruction
]. The choice of treatment is determined by
combination of patient factors (individual preference, age, body
image) and surgeon factors (team experience, availability
of resources) [
]. Despite this, many plastic surgery
units worldwide regard autologous flap reconstruction
as the superior technique as it follows the paradigm of
replacing ‘like with like’ . Indeed, there is growing
evidence to support increased aesthetic patient
satisfaction with autologous flap reconstruction compared to
implants, as well as increased suppleness and resiliency,
especially in irradiated recipient beds [
On first glance, implant-based reconstruction is a
simpler technique compared to free flap reconstruction,
requires less training and time and can be performed by
many more surgeons [
]. However, implant-based
reconstruction has complications. These include
migration, implant rupture, infection, exposure/extrusion and
patient dissatisfaction with edge visibility and implant
]. Capsular contracture can result in pain,
asymmetry, increased palpability and requirement of
implant removal [
]. The placement of the implant itself
can lead to reduced or absent sensation at the nipple in
1 in 7 women [
]. Allergan’s 10-year cumulative risk
study found that 24.6% of patients who underwent
implantbased reconstruction developed capsular contracture
necessitating implant removal and/or replacement [
Conversely, DIEP flap is often now considered the
gold-standard autologous flap reconstructive technique.
This is because it results in less abdominal donor site
morbidity compared to the traditional transverse rectus
abdominus myocutaneous (TRAM) flap, by preserving
the continuity of the rectum abdominis muscles [
Compared to implant-based reconstruction, some
authors have argued that DIEP flap reconstruction is
more cost-effective and results in fewer complications
]. Modern healthcare aims to provide
costeffective treatment, and thus, discussion on
reconstructive modalities warrants scrutiny on cost associated with
autologous and implant-based reconstruction. While
some North American and European centres have
published cost-effectiveness analysis on DIEP versus
implants, the data is sparse and there is a relative scarcity
of inclusion of data from public and free universal
healthcare system settings .
Thus, an extensive search will be undertaken in the
MEDLINE (Ovid SP), EMBASE (OvidSP), Google
Scholar, Cochrane Central Register of Controlled Trials
and Scientific Citation Index databases to identify
primary studies on DIEP (intervention) and
implantbased reconstruction (comparator) in context of patients
with breast malignancy. Data extracted will be used to
evaluate which technique is superior in terms of clinical
outcomes and cost and thus inform worldwide clinical
This systematic review is intended to evaluate the
current evidence on the clinical outcomes and cost of
deep inferior epigastric perforator (DIEP) flap versus
implants for breast reconstruction post cancer-related
mastectomy, to determine which technique is more
cost-effective and clinically superior.
This protocol has been registered with the National
Institute of Health Research (NIHR) Prospective Register
of Systematic Reviews PROSPERO CRD42017072557. We
have adhered to and completed the Preferred
Reporting Items for Systematic Review and Meta-Analysis
Protocols (PRISMA-P) 2015 statement [
] (please see
Additional file 1, PRISMA-P checklist). If no randomised
controlled trials (RCT) are available, the review will be
reported according to the Meta-Analysis of Observational
Studies in Epidemiology (MOOSE) guidelines [
We will conduct a comprehensive search of the
MEDLINE (OVID SP), EMBASE (OVID SP), Google
Scholar, CENTRAL and Science citation index databases
from 1994 up to August 2017 to identify studies relevant
to the review. A combination of Medical Subject
Headings (MeSH) terms and free text will be used,
combined with Boolean logical operators to construct
the search strategy. Explode function will be used to
capture narrower terms. No language or study design
restrictions will be applied. The reference list of all
included articles will also be screened for relevance. A
sample search strategy, for EMBASE (OVID SP), is
shown below and a similar strategy will be adapted for
the other databases:
c Clinical studies (randomised controlled trials,
prospective and retrospectives cohort studies, case
– (1) exp Breast Neoplasms/ OR ((breast adj6 cancer*)
or (breast adj6 neoplasm*) or (breast adj6
carcinoma*) or (breast adj6 tumour*) or (breast adj6
tumor*) or (breast* adj4 reconstruct*))
– (2) exp deep inferior epigastric perforator flap/ OR
DIEP flap* OR DIEAP flap* OR ((Deep and inferior
and epigastric and perforator) adj2 flap*) OR Deep
and inferior and epigastric and perforator and flap*)
– (3) exp breast implant/ OR breast adj3 implant* OR
exp silicone prosthesis/
– [(1) AND (2)] OR [(1) AND (3)]; publication date:
January 1994–August 2017
Identification and selection of studies
Studies extracted following database searching will be
populated into an Endnote X7 library (Clarivate
Analytics, USA). The screening will be carried out in
two stages using pre-specified screening criteria by
two independent reviewers. Inter-rater reliability will
be calculated using Cohen’s kappa score.
Stage 1: Title and abstract screening will be carried out
by two researchers acting independently. Any
discrepancies will be resolved by consensus. If any
doubt remains, the article would usually proceed to
Stage 2: The full-text versions of the studies included in
Stage 1 will be downloaded and screened for eligibility
by two researchers independently. Discrepancies will
again be resolved by consensus. If this is not possible, a
third author will be consulted.
All primary human studies evaluating clinical outcomes
and cost of DIEP and implant-based reconstruction in
context of breast malignancy will be included. The
intervention is the DIEP flap and the comparator is
implant-based reconstruction. The inclusion and
exclusion criteria are highlighted below.
a Studies involving adult patients between 18 and
90 years old.
b Unilateral DIEP flap or implant-based breast
reconstruction due to breast cancer (bilateral
reconstruction is usually after bilateral prophylactic
a) Review articles, case reports, simulation studies,
clinical studies in non-human subjects, patients with
segmental or partial mastectomy, technical
descriptions of operative repair with no outcome
measures, breast reconstruction not related to
cancer, other autologous flap techniques.
b) Duplicates will be excluded and studies will be
screened for bias. The Cochrane’s risk of bias tool
will be used for randomised controlled trials [
Bias will be assessed and judged as being high, low
or unclear for individual elements from five domains
(selection, performance, attrition, reporting and
]. For non-randomised comparative
studies, ROBINS-I (Risk Of Bias In Non-randomised
Studies—of Interventions) by Cochrane will be used
]. ROBINS-I covers seven distinct domains from
which bias may be introduced, with ‘signalling
questions’ that facilitate judgements about the risk of
bias. The judgements within each domain will be
carried forward for an overall risk of bias judgement
across bias domains [
]. Studies affected by bias will
The primary outcomes will be:
1. Patient satisfaction and cosmetic outcome from
patient-reported outcome measures (PROMs, scores
from validated tools, e.g. BREAST-Q tool)
2. Complications (arterial thrombosis, fat necrosis,
venous congestion, infection, partial/full flap loss,
donor site complications, haematoma/seroma,
return to theatre, capsular contracture, scarring,
The secondary outcomes will be:
1. Duration of surgery
2. Number of surgical revisions
3. Length of stay
4. Availability of procedures
5. Total number of clinic visits
If the data is appropriate for quantitative synthesis,
then risk ratio with 95% confidence interval (CI) will be
used to determine dichotomous outcomes
(complications). Continuous outcomes (cost, PROMs [BREAST-Q],
secondary outcomes excluding availability of procedures)
will be determined by weighted or standardised mean
differences with 95% CI. Subgroup analysis may be
performed for patients with different breast cancer types and
for breast implant materials, dependent on sufficient data
sets. Where possible, we will utilise results from an
intention to treat analysis.
Data extraction, collection and management
Data, from the full-text articles, will be extracted by two
independent authors using a standardised extraction
form. Any discrepancy will be resolved by consensus or
with referral to a third author. If any data is missing or
further information is required, the primary authors of
the manuscript will be contacted directly. The following
data will be extracted:
year of publication
participant demographics (sex, mean age, BMI,
complications (arterial thrombosis, venous
congestion, infection, fat necrosis, partial/full flap
loss, haematoma/seroma, donor site complications,
return to theatre, capsular contracture, scarring,
measures of patient satisfaction (PROMs e.g.
An assessment of heterogeneity will be performed
using Review Manager 5.3 provided by The Cochrane
]; if the studies are relatively
homogenous in terms of methodology and outcomes,
meta-analyses of the data will be performed. If there is
high heterogeneity, a narrative synthesis will be
performed instead, without meta-analysis.
Statistical heterogeneity will be quantified by the I2
]. If the I2 statistic is high, indicating high
heterogeneity, a random effects model will be employed. The
Grading of Recommendations Assessment, Development
and Evaluation (GRADE) approach [
] will be utilised to
assess the methodological quality of the studies. Cochrane
has produced GRADE tables that identify the basis for
judgements about evidence quality. An overall GRADE
score (from 4 to 0) is calculated based on quality of overall
evidence. The tables specify why points may be added or
deducted to obtain the final score [
]. Sensitivity analysis
maybe performed based on the quality of the studies, with
analyses repeated after removal of poor quality studies to
evaluate any change in the overall effect estimate.
The aim of this review is to evaluate the clinical
outcomes and cost of DIEP flap versus implants for breast
reconstruction in context of breast malignancy. Despite
many centres ascribing DIEP flap as the gold-standard
reconstructive modality, data on clinical outcomes and
cost-effectiveness is limited. Therefore, it is important to
determine which of the two techniques is clinically
superior and more cost-effective as this will guide
clinical management. To our knowledge, this is the first
systematic review to compare the clinical outcomes and
cost of DIEP versus implants.
Based on the results of this systematic review,
independent recommendations will be made to plastic surgeons,
researchers, policy makers and plastic surgery societies.
The results will be disseminated at international
meetings in the fields of Plastic, Reconstructive and Aesthetic
Surgery and published in a high-impact peer-reviewed
Additional file 1: PRISMA-P checklist. (DOCX 509 kb)
CENTRAL: Cochrane Central Register of Controlled Trials; DIEP: Deep inferior
epigastric perforator; EMBASE: Excerpta Medica Database; GRADE: Grading of
Recommendations Assessment, Development and Evaluation; MeSH: Medical
Subject Headings; MOOSE: Meta-Analysis of Observational Studies in
Epidemiology; PRISMA-P: Preferred Reporting Items for Systematic Review
and Meta-Analysis Protocols; RCT: Randomised controlled trial;
TRAM: Transverse rectus abdominus myocutaneous
No funding was sought or received for this work.
Availability of data and materials
AK contributed in the conception, design of search strategy and drafting and
critical review of manuscript; OJS and AM contributed in the conception,
design of search strategy and critical review of the manuscript; MP and MG
contributed in the two-stage study selection process. All authors read and
approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interest.
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