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Surgical EndoscopyAnd Other Interventional TechniquesOfficial Journal of the Society ofAmerican Gastrointestinal andEndoscopic Surgeons (SAGES) andEuropean Association for EndoscopicSurgery (EAES) ISSN 0930-2794 Surg EndoscDOI 10.1007/s00464-014-4045-1
Donor safety in live donor laparoscopicliver procurement: systematic review andmeta-analysis
Mohamed Bekheit, Philipe-AbrahimKhafagy, Petru Bucur, Khaled Katri,Ahmed Elgendi, Wael Nabil Abdel-salam, Eric Vibert, et al.
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REVIEW
Donor safety in live donor laparoscopic liver procurement:systematic review and meta-analysis
Mohamed Bekheit • Philipe-Abrahim Khafagy •
Petru Bucur • Khaled Katri • Ahmed Elgendi •
Wael Nabil Abdel-salam • Eric Vibert • El-said El-kayal
Received: 12 September 2014 / Accepted: 11 December 2014
� Springer Science+Business Media New York 2014
Abstract
Background Donor safety is a major concern in live
organ donation. Live donor laparoscopic liver procurement
is an advanced surgical procedure that is performed in
highly specialized centers. Since its first report, not much
progress has been endeavored for that procedure.
Methods We planned to include all the randomized and
comparative nonrandomized studies. Patients’ population:
live donors who are submitted to organ procurement via
laparoscopy.
Results Out of 5,636 records retrieved from the literature,
only seven nonrandomized studies were included in this
review, which encompassed 418 patients, 151 patients of
whom underwent laparoscopic procurement. The quality
scores for the included studies ranged from 66 to 76 %.
The operative time was significantly shorter in the con-
ventional open group (SD = 0.863, 95 % CI 0.107–1.819).
Blood loss in the laparoscopic group was comparable with
the conventional open approach (SD = -0.307, 95 % CI
-0.807 to 0.192). In subgroup analysis, laparoscopy was
protective against blood loss in laparoscopic parenchymal
dissection (SD = -1.168, 95 % CI -1.758 to -0.577).
The hospital stay was equal in both groups. Patients in
laparoscopic group consumed fewer analgesics compared
with conventional open group (SD = -0.33, 95 % CI
-0.63 to -0.03). Analgesics use was lower in the laparo-
scopic group compared with the conventional approach.
The rate of Clavien complications was equal in both groups
(OR 0.721, 95 % CI 0.303–1.716). No difference was
found between subgroup analysis based on the harvested
liver lobe. Funnel plot and statistical methods used
revealed low probability of publication BIAS.
Conclusions Live donor laparoscopic liver procurement
could be as safe as the conventional open approach. Lower
blood loss and lower consumtion of analgesics might be
offered in the laparoscopic approach.
Keywords Abdominal � Digestive � Hepatobiliare
(liver) � Transplantation � Surgical � Laparoscopic � Live
donor � Liver transplantation
Live organ donation is a noble human gesture that should be
rewarded with much respect. Maintaining the highest pos-
sible level of donation safety is the least that could be done in
return. Live donation is increasingly becoming a corner stone
in organ transplantation, encountering the frustrating organ
shortage from cadaveric donation [1]. Donor safety is of
great concern in living donation [2], therefore the medical
reward of this noble act is to minimize the donors‘ sacrifice.
In live liver donation, the conventional approach with large
M. Bekheit
Minimal Invasive Surgery Unit, Department of Surgery, El
Kabbary General Hospital, El Kabbary, Alexandria, Egypt
M. Bekheit (&)
CIRE Plateform, INRA Centre Val de Loire, 37380 Nouzilly,
France
e-mail: [email protected];
M. Bekheit � P. Bucur � E. Vibert
INSERM, Unit 785, Centre Hepatobiliaire, Paul Brousse
Hospital, 94804 Villejuif, France
P.-A. Khafagy
Department of Radiology, Le Raincy-Montfermeil Hospital,
93370 Monfermeil, France
K. Katri � A. Elgendi � W. N. Abdel-salam � E. El-kayal
HPB Surgery Unit, Department of Surgery, Faculty of Medicine,
Alexandria Main University Hospitals, Alexandria University,
Alexandria, Egypt
123
Surg Endosc
DOI 10.1007/s00464-014-4045-1
and Other Interventional Techniques
Author's personal copy
variable subcostal incision is considered the standard pro-
cedure [3]. Nonetheless, this approach is associated with a
relatively high morbidity rate reaching up to 40 % in some
series [4]. Noteworthy, the large wound incurred during the
procedure and its related morbidities that, despite being
usually indolent, yet are manifest and cumbersome to most of
the donors who are usually young fit adults. Even without
complications, the incision itself is sufficiently disturbing in
appearance for most of the donors [5].
Minimal invasive surgery has developed significantly
over the past few decades. Laparoscopic surgery has pro-
ven to encompass numerous privileges in terms of post-
operative recovery and wound-related complications as
well as intraoperative events such as blood loss. Laparo-
scopic liver surgery is a well-recognized and -practiced
procedure in many centers all over the world. Since its first
report in 2002 [6], laparoscopic live donor hepatectomy
had a much slower spread than other laparoscopic proce-
dures. Nonetheless, it is performed frequently in limited
practice settings among particularly specialized centers.
Indeed, from the cosmetic point of view, live laparoscopic
liver procurement is constrained by the necessity to retrieve
an intact, minimally traumatized organ. Up to this moment,
it is not known systematically whether this approach offers
advantages over the conventional open approach.
Hypothesis We hypothesize that live donor laparoscopic
liver procurement is as safe as conventional open pro-
curement (Ho).
Aim
The objective of this study is to determine the safety profile
of laparoscopic procurement compared with the conven-
tional open procurement in live liver donors.
Objective
The objective is to identify all comparative trials compar-
ing the laparoscopic liver procurement with the conven-
tional open procurement, to assess the quality of those
trials; to determine the total number of patients included in
comparative trials and their characteristics; and to identify
the reported complications and other factors representing
the safety of the procedure such as operative time, blood
loss, consumption of analgesics, and hospital stay.
Methodology
Study inclusion in the review is based on the patient,
intervention, comparison, outcome (PICO) criteria.
Study population
The study included live donors who are submitted to organ
procurement via laparoscopy.
Types of intervention and comparison
Studies comparing the laparoscopic procurement to the
conventional open procurement will be considered for
inclusion. Laparoscopic procedures will be considered if it
is one of the following types: pure laparoscopic surgery in
which the whole procedure including the parenchymal
transaction has been performed in the laparoscopic
approach; laparoscopic-assisted surgery in which laparo-
scopic approach is used for dissection of the fibrous
attachment of the liver; or hand-assisted surgery where a
hand port is used during ligament dissection phase and/or
parenchymal dissection phase.
Outcome measures
The primary outcome measure is the Clavien scores [7] for
donor complications after procedures of live donation.
Secondary outcomes included items that would repre-
sent the hospital stay and the operative time as well as the
post-operative consumtion of analgesics.
Data transformation: all reported complications will be
transformed to the corresponding grade of Clavien score.
For the studies reporting Clavien scoring, the scores will be
treated as they are.
Typs of studies
The first target is seeking for randomized controlled trials
comparing both approaches. Other types of comparative
studies will also be considered for inclusion.
Search strategy
We plan to search Pubmed, Ovid (embase, medline), web
of science, trip database, and Cochrane database. We also
plan to do cross-references checking of the included stud-
ies, looking for related citations. We plan to have no
restriction on inclusion due to language of publication,
since the authors’ team is capable of handling more than
four live languages. Furthermore, we plan to seek profes-
sional translation for other languages provided that the title
and abstract are available in one of the languages known to
the authors to identify eligibility for inclusion. The sum-
mary of search strategy and search terms is presented in
Table 1.
We do not plan to manually search the archives. We also
do not plan to seek authors for unpublished data.
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Study selection and data extraction
The first author (MB) was responsible for conducting the
databases’ search and retrieval of full text studies. The first
(MB) and the second (P-A. K) authors were responsible for
studies’ selection and to list excluded studies with reasons
for exclusion. We plan to seek a senior author’s opinion to
resolve any conflict if any regarding studies’ inclusion and
quality scoring.
MB and PA.K plan to extract the following data:
1. Inclusion and exclusion criteria
2. Year of publication
3. Sample size
4. Demographics of study population (age, gender, BMI)
5. Intervention’s description
6. Outcome data: (Analgesic use, Blood loss, hospital
stay, donor complications, and grading {Clavien I, II,
III, IV}
7. Methodological quality assessment
Assessment of methodological quality
We plan to assess the methodological quality of the trials
without masking the trial names. We plan to follow the
instructions given in the Cochrane handbook of systematic
reviews of interventions [8]. We plan to evaluate the reported
randomization and the process of reporting complications
since there is risk of bias associated with overestimation of
intervention effects [9–12] as detailed in Appendix 1.
Inclusion and exclusion after quality assessment
The purpose of the quality assessment task is to identify the
level of evidence, on which conclusions will be based.
Nonetheless, we plan to include all randomized trials as
well as all comparative nonrandomized trials.
Exclusion criteria will include
• Single-arm studies
• Studies with significantly incomplete outcome data
• Studies comparing with nonstandard open procedure or
with an outside protocol laparoscopic intervention.
Data synthesis and statistical methods
Raw data on complications will be converted to Clavien
scoring, while in the case of studies reporting the compli-
cations grading only, the grading will be extracted as it is.
Analysis of each grade complication frequency will be
conducted separately, and then a pooled frequency estimate
will be calculated. We plan to perform the meta-analyses as
close as possible to the recommendations of the Cochrane
Collaboration [8] using the software Comprehensive met
analysis (Biostat. Inc. USA) for the statistical analysis, and
QIQQA research management software (QiqqaTM, Quan-
tisle Ltd. London, UK) for the annotation report produc-
tion. For dichotomous variables, we plan to calculate odds
ratio and the log odds ratio with standard error for
dichotomous and categorical data. For continuous vari-
ables, we plan to calculate the standardized differences of
means with standard error. We elect to calculate the
‘‘Hedges’s g’’ and its standard error for both types of data
to represent the overall (pooled) effect estimate when
including all the parameters expressing donor safety. For
data describing central tendency in median and range
instead of mean and standard deviation, we intend to
convert these values into mean and standard deviation,
when necessary, using the methods suggested by Hozo
et al. [13].
Table 1 Details of the search strategy and the accessed databases based on search terms
Database Period Search terms
Pubmed March 2014/updated May
2014
Laparoscopic live donor hepatectomy
Updated-laparoscopic live donor hepatectomy, ‘‘Laparoscopy* AND liver transplantation’’,
‘‘Laparoscopy AND liver donor’’, ‘‘Laparoscopy AND liver transplantation’’
Embase April 2014 Laparoscopic live donor hepatectomy
Midline April 2014 Laparoscopic live donor hepatectomy
Ovid April 2014 Laparoscopic live donor hepatectomy
Trip database May 2014 Laparoscopic live donor hepatectomy
Web of science March 2014/updated May
2014
Laparoscopic live donor hepatectomy
Updated term: ‘‘laparoscopic live donor hepatectomy’’, ‘‘Laparoscop* AND liver
transplantation’’, ‘‘Laparoscopy AND liver donor’’, ‘‘Laparoscopy AND liver transplantation’’
‘‘Laparoscop*AND liver AND Transplant*
Cochrane
database
May 2014 Laparoscopic live donor hepatectomy
*It is used to include the different sufixes to the term root
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For outcomes such as odds ratio for death, we plan to
use generic inverse variance method for the meta-analysis.
We plan to use a random-effect model [14] and a fixed-
effect model [15]. In case of discrepancy between the two
models, we plan to explore heterogeneity by Chi squared
distribution test (Q test) with significance set at p value of
0.10, and to report the random-effect model in case of
significant Q test. We plan to measure the quantity of
heterogeneity by I2 [16]. We considered an I2 of 30 % or
more to represent heterogeneity.
We plan to perform the analysis on an intention-to-treat
basis [17] for patients who underwent conversion from
laparoscopic to open approach; whenever possible. For that
purpose, multiple imputation analysis will be conducted on
SPSS version 20 (IBM Inc. Chicago, IL, USA). Otherwise,
we plan to adopt the ‘available case analysis.’ In case we
found ‘zero-event’ trials in statistically significant out-
comes, we plan to perform a sensitivity analysis with and/
or without empirical continuity correction factors as sug-
gested by Sweeting et al. [18]: one-study removed tech-
nique, and both-models compared technique. We decided
to conduct sensitivity analysis for outcomes that showed
heterogeneity in the fixed-effect model. We examined the
difference in assumption based on the model between
random- and fixed-effect models, and we conducted one-
study removed technique to test the sensitivity. Whenever
the two models are in concordance, we consider the
assumption as correct.
Subgroup analysis
We plan to conduct the following subgroup comparisons:
• Studies on right lobe versus those on left lateral section
• Studies with laparoscopic parenchymal dissection ver-
sus open parenchymal dissection
Meta-regression
Exploiting the total quality score against the pooled effect
size of the complications will be conducted according to
the unrestricted maximum likelihood model. This is par-
ticularly important since we decided to include randomized
and nonrandomized studies in the review.
Bias exploration
We plan to use a funnel plot to explore bias [19, 20] based
on standard error on the vertical axis as recommended by
Sterne et al. [21]. We also plan to perform linear regression
described by Egger et al. to determine the funnel plot
asymmetry [20].
Results
The PRISMA flow chart (Fig. 1) summarizes the search
findings. No randomized controlled trials were identified in
the identified records. Out of the nine eligible comparative
studies, seven were included in the quantitative data syn-
thesis. The included studies encompassed 419 patients, of
whom 150 patients, who underwent laparoscopic procure-
ment approach, were compared with 269 patients who
underwent the conventional open approach. 42 donors
underwent open left lateral section procurement, and 41
donated laparoscopically. 79 donated the entire left lobe in
the conventional open approach, while 31 donated under
laparoscopy. For the right lobe, 148 donors donated in the
conventional open approach and 78 donors donated under
laparoscopy.
The baseline demographic criteria (age, gender distri-
bution, and BMI) were similar between the laparoscopic
and the conventional approaches. Tables 2 and 3 summa-
rize the characteristics of the included studies and the
extracted data of interest from each study.
Methodological quality of the analyzed studies
We were not able to identify any randomized trials for the
review. Furthermore, all of the included studies scored
between 60 and 76 % on the quality score adapted from
[28]. Table 4 summarizes the quality score items and the
scores of the included studies. We provide a list of
excluded studies after initial eligibility [6, 29–61].
Assessment of baseline characteristics
between the compared groups in the included studies
There was no heterogeneity among the included studies
reporting on age (Q = 8.25, df = 6, p = 0.22, I2 = 27 %).
In the fixed-effect model, the age among the laparoscopic
group was lower than that in the conventional group (SD
difference in means = -0.344, 95 % CI -0.555 to
-0.133). Unlike the reported BMI, there was no hetero-
geneity among the included studies (Q = 10.2, df = 4,
p = 0.03, I2 = 60 %). In the random-effect model, there
was no difference between the groups (SD difference in
means = -0.15, 95 % CI -0.526 to 0.224). Similarly,
there was difference in the gender distribution between the
groups [point estimate (OR) = 0.7, 95 % CI 0.42–1.2] as
was revealed by the fixed-effect model (Q = 8.5, df = 6,
p = 0.2, I2 = 29 %). These baseline characteristics are
summarized in Fig. 2. In subgroup analysis based on the
procured lobe, 82 donors were included for left lateral
section procurement (41 in laparoscopy), while 222 right
lobe donations (98 in laparoscopy) were included. The
donor’s‘ age was significantly lower in the left lateral
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section in a fixed-effect model (SD diff in means =
-0.623, p = 0.006), unlike the right lobe where there was
no age difference. BMI was as well lower in the laparo-
scopic left lateral group (SD diff in means = -0.9,
p = 0.015), while no difference in the BMI was observed
in the right lobe subgroup.
Outcome items
Operative time
There was significant heterogeneity among the included
studies regarding the operative: (Q = 48, df = 6, p \ 0.001)
for the fixed-effect model. Still applying the random-effect
model shows significantly shorter operative time for the
conventional open approach compared with laparoscopic
approaches (SD difference in means = 0.552, 95 % CI
0.011–1.084) for the pooled effect estimate from the
included studies.
Subgroup analysis based on the approaches for paren-
chymal dissection demonstrates that in case of the laparo-
scopic dissection for left lateral sectionectomy (Q = 1.7,
df = 1, p = 0.2), the operative time was significantly
shorter than that for the open approach (standardized dif-
ference of mean = 0.863, 95 % CI 0.107–1.819). For
studies using open approach for parenchymal dissection
Fig. 1 PRISMA chart
illustrating the search strategy,
excluded records, and the
records included in quantitative
analysis. a Includes case reports,
series, technical descriptions.b Excluded after discussion
between the first and second
reviewers
Table 2 Summary of characteristics of the included studies
Study (year) Hand assisted
versus only
laparoscopic
Parenchymal
dissection
(open or lap)
Lobe Incision Sampling Temporal Quality
score (%)
Zhang (2014) [3] Hand Open Right Midline Case matched Prospective 76
Kim (2011) [23] Pure Laparoscopic Left lateral Pfennenstiel Nested case
control
Retrospective 66
Baker (2009) [24] Hand Open Right Midline Case control Retrospective 75
Soubrane (2006) [25] Pure Laparoscopic Left lateral Pfennenstiel Nested case
control
Retrospective 68
Thenappan (2011) [26] Hand Open Left lateral Midline Nested case
control
Retrospective 68
Choi (2012) [27] Laparoscopic Open Right Right subcostal Nested case
control
Retrospective 67
Marubashi (2013) [28] Hand Open Left lobe?/left lateral Midline Nested case
control
Retrospective 71
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(laparoscopy was used only for dissection of attachments)
(Q = 48, df = 4, p \ 0.001, I2 = 90 %), the mixed-effect
model demonstrated that using laparoscopy only for
hepatic mobilization resulted in no difference in operative
time compared with groups having the conventional open
approach for procurement (Fig. 3).
Sensitivity analysis (comparing both models technique)
of the assumption of the model on the operative time
demonstrated that both models fixed ( p = 0.001) and
random (p = 0.046) are significant in the same direction
(shorter operative time for the conventional approach).
Subgroup analysis based on the procured lobe identified
no significant difference in operative time between the the
conventional and laparoscopic groups in both right and left
lateral subgroup resections in the random-effect model The
model was selected based on the heterogeneity test
(Q = 6.3, p = 0.04, I2 = 69 % for the left lateral and
Q = 38, p \ 0.001, I2 = 94 %).
Blood loss
There was significant heterogeneity among the included
studies (Q = 30.6, df = 6, p \ 0.001, I2 = 80.39 %). The
random-effect model showed insignificant difference in the
blood loss between the laparoscopic and the conventional
approaches (SD difference in means = -0.307, 95 % CI
-0.807 to 0.192).
Subgroup analysis
The included studies demonstrated heterogeneity of the effect
estimate of blood loss (Q = 30.6, df = 6, p\0.001,
I2 = 80.39 %). The overall mixed-effect model demonstrated
that the blood loss was significantly lower in the laparoscopic
approaches versus the conventional approach (Standardized
difference in means = -0.509, 95 % CI -0.89 to -0.13). In
subgroup analysis based on the approach of parenchymal
dissection, laparoscopic parenchymal dissection, which was
performed for left lateral section procurement, was more
protective against blood loss compared with the conventional
open approach (SD difference in means = -1.168, 95 % CI
-1.758 to -0.577). When laparoscopy was used only for
hepatic mobilization, blood loss was equal in both arms of
comparison (Fig. 4). Furthermore, there were no significant
differences in the blood loss between the conventional and
laparoscopic groups for both the left lateral section and the
right lobe (Q = 8.2, p = 0.017, I2 = 75.5 % and Q = 16.6,
p\0.001, I2 = 87.9).
Table 3 Summary of the measurements of interest in the included studies
Study (year) Gender
(male)
n/total
Age (years)
mean (SD)
BMI (kg/m2)
Mean (SD)
Blood loss (ml)
mean (SD)
Operative (min)
mean (SD)
Analgesia (days)
mean (SD)
Hospital (days)
mean (SD)
Zhang (2014) [3]
Lap 13/25 37.2 (8.7) 23.8 (2.6) 378 (112) 385.9 (47) 2.4 (1) 7 (1.4)
Open 14/25 37.4 (10.5) 22.6 (3) 423 (139) 378 (59) 3.2 (1) 8.7 (2.4)
Kim (2011) [23]
Lap 1/11 29 (6) 396 (72) 330 (68) 6.9 (0.3)
Open 6/11 35 (2) 464 (78) 306 (29) 9.8 (0.9)
Baker (2009) [24]
Lap 15/33 37 (10.3) 25.8 (4) 417 (217) 265 (48) 4.3
Open 13/33 39 (11) 25.9 (4.3) 550 (305) 316 (61) 3.9
Soubrane (2006) [25]
Lap 2/16 29 (5) 23.8 (1.6) 18.7 (44.2) 320 (67) 2 (0.9)
Open 1/14 32 (5) 24.9 (0.1) 199.2 (185.4) 244 (55) 2.2 (0.9)
Thenappan (2011) [26]
Lap 7/15 33.9 (8.9) 814 (720) 312 (67.8) 1.6 (0.97) 6 (2)
Open 6/15 35.7 (8) 733 (457) 324 (105.6) 2 (1.4) 6 (3.7)
Choi (2012) [27]
Lap 12/20 29.7 (10) 23.6 (2.8) 870 (653) 383.6 (41.7) 2.5 (1.1) 12 (2.8)
Open 58/90 36.8 (12) 23.6 (2.9) 531 (322.6) 303 (61.5) 2.55 (1.1) 12 (3.6)
Marubashi (2013) [28]
Lap 13/31 35.8 (8.4) 21.3 (3.6) 353 (396) 435 (103) 10.3 (3.3)
Open 54/79 37.8 (10) 22.6 (3) 456 (347) 383 (73) 18.3 (16.7)
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Surg Endosc
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Analgesic use
Only four studies reported information on the post-opera-
tive consumption of analgesics. There was no
heterogeneity among the included studies (Q = 3.9,
df = 3, p = 0.25, I2 = 24 %). The overall fixed-effect
model showed significantly fewer analgesics use among
patients who underwent laparoscopic approach (SD
Fig. 2 Forest plots of the base line characteristics (A age years, B BMI kg/m2, C male gender frequency) of the included studies’ population
Surg Endosc
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difference in means = -0.33, 95 % CI -0.63 to -0.03).
This was particularly pronounced among the subgroups
who had open parenchymal dissection through midline
incision (SD difference in means = -0.618, 95 % CI
-1.068 to -0.168) (Fig. 5).
Hospital stay
There was significant heterogeneity among the included
studies (Q = 38.7, df = 6, p \ 0.001, I2 = 84.5 %). In the
random-effect model: the hospital stay was equal in the
laparoscopic group compared with the conventional one
(SD difference in means = -0.577, 95 % CI -1.158 to
0.004). Nonetheless, for the fixed-effect model, the hospital
stay was shorter in the laparoscopic group (p = 0.003). In
sensitivity analysis, we removed one study (the lowest
quality score), but both models retained their values. So we
resort to subgroup analysis.
For the subgroup analysis, in the overall mixed-effect
model (SDM = -0.272, 95 % CI -0.674 to 0.130), the
hospital stay was equal for both the laparoscopic and the
conventional groups. In the subgroup analysis based on the
approach of parenchymal dissection, both subgroups (open
parenchymal dissection and laparoscopic parenchymal
dissection) of the laparoscopic approaches resulted in equal
hospital stay compared with the conventional approach
(Fig. 6). Subgroup analysis based on the procured lobe
demonstrated no significant difference in hospital stay
between the laparoscopic and the conventional groups in
the left lateral section and right lobe subgroups in the
Fig. 3 Forest plot for the estimate of the operative time comparing the laparoscopic approaches versus conventional. The operative time was
shorter in the open group. It also demonstrated the longer operative time in the subgroup where laparoscopy was used for parenchymal dissection
Fig. 4 Forest plot with group analysis demonstrating the lower
estimate of blood loss in the subgroup where laparoscopy was used
for parenchymal dissection in left lateral section procurement and the
no difference in the subgroup where laparoscopy was used only for
hepatic mobilization
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random-effect model (Q = 25.5, p \ 0.001, I2 = 92 %
and Q = 8.9, p = 0.01, I2 = 77.7 % for left and right,
respectively).
Complications
Clavien grade I complication There was no significant
heterogeneity among the included studies (Q = 5.856,
df = 6, p = 0.4). In the fixed-effect model (OR 0.837,
95 % CI 0.431–1.628), both the conventional and the lap-
aroscopic approaches had the same risk factor for grade
Clavien I complication. The frequency of grade one com-
plication among the laparoscopic group was 16 events for
the 151 patients included in this review compared with 32
events among the 267 patients who underwent the con-
ventional open approach. There was no difference in the
estimate in the subgroup analysis based on the approach for
parenchymal dissection (Fig. 7A). No difference was seen
in Clavien grade I complications in subgroup analysis
based on procured lobe (OR 0.4, p = 0.2 and OR 1.2,
p = 0.7) for left lateral and right lobes.
Clavien grade II complications: Only six studies reported
on Clavien II complications. There was no heterogeneity
among the included studies (Q = 1.1, df = 5, p = 0.9,
I2 = 0 %). In the fixed-effect model, the rate of Clavien II
grade complication was similar in the laparoscopic 6/151
versus 22/267 to that in the conventional open approach
group (OR 0.505, 95 % CI 0.190–1.343). This was also
similar when the laparoscopy was used only for hepatic
mobilization or for parenchymal dissection as well
(Fig. 7B). Also, the rate of this grade was similar between the
Fig. 5 Forest plot for subgroup analysis based on the incision site showing the lower estimate of consumption of analgesics among subgroup of
patients who underwent laparoscopic hepatic mobilization and open parenchymal dissection through midline incision
Fig. 6 Forest plot for group comparison, showing no difference in the overall estimates of hospital stay in both groups
Surg Endosc
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conventional and the laparoscopic groups in a subgroup
analysis of the procured lobe (OR 0.45, p = 0.3 and OR 0.49,
p = 0.27 for left lateral section and right lobe, respectively).
Clavien grade III complications Two studies reported on
Clavien III complications. There was significant hetero-
geneity between the included studies in terms of
(Q = 3.13, df = 1, p = 0.007, I2 = 68 %). In the mixed-
effect model, the incidence rates of grade III complications
were equal when compared: 3/151 in the laparoscopic
group versus 9/267 in the conventional approach group
(OR 1.989, 95 % CI 0.087–45.49). The subgroup analysis
demonstrated that all Clavien III occurred when the lapa-
roscopy is used only for hepatic mobilization. In one-study
removed sensitivity analysis technique, the model
assumption was retained (Fig. 7C). Only one study was
included in the subgroup analysis based on the procured
lobe which demonstrated insignificant difference in the
rates of Clavien III (OR 13.9, p = 0.1).
Clavien IV No clavien VI complications were reported in
any of the included studies.
Pooled estimate of combined Clavien complica-
tions There was no heterogeneity among the included
studies when estimating the combined Clavien rates
(Q = 1.799, df = 6, p = 0.9, I2 = 0). The overall fixed-
effect model showed no difference in the incidence rates of
complications between laparoscopic group and the con-
ventional approach group (OR 0.721, 95 % CI
0.303–1.716). Similarly in analysis of the subgroups, there
was no difference in rates between open or laparoscopic
groups whether laparoscopy was used only for hepatic
mobilization or for parenchymal dissection as well
(Fig. 7D). No difference was calculated for the pooled
complication rates based on the procured lobe subgroup
analysis (OR 0.53, p = 0.44 and OR 0.89, p = 0.85 for left
lateral section and right lobe, respectively).
Pooled effect size of the outcomes representing the donor
safety
There was no heterogeneity among the included studies
when assessing the pooled effect estimate for criteria cor-
responding to donor safety (Q = 5.52, df = 6, p = 0.47,
I2 = 0). In the fixed-effect model, the different approaches
had the nearly the same outcome (Hedges’s g = -0.236,
95 % CI -0.578 to 0.107). The result was also the same for
the subgroup analysis based on the approach used for
parenchymal dissection (Fig. 8). No difference was
observed for a subgroup analysis based on the procured lobe
(Hedges’ g = -0.43, p = 0.17 and Hedges’ g = -0.13,
p = 0.55 for left lateral section and right lobe, respectively).
BIAS exploration was conducted for selected outcome
variables using funnel plots with regression intercept test,
trim and fill method, and Kendall‘s rank correction. For the
operative time, studies showed symmetric distribution
around the common standardized difference in means (Fig.
9A). This was confirmed by the Egger’s regression inter-
cept [Intercept = 0.55, 95 % CI -12.6 to 13.7, p (1-
tail) = 0.4, (2-tail) = 0.9]. Kendall’s Tau without conti-
nuity correction was s = 0.04, p = 0.8, while with conti-
nuity correction was s = 0, p = 1.
Similarly, the Egger’s regression intercept for blood loss
demonstrated statistical symmetry [intercept = -3.47,
95 % CI -12.4 to 5.5, p (1-tail) = 0.18, (2-tail) = 0.36].
The Kendall’s Tau without continuity correction was
s = -0.3, p = 0.2, while with continuity, the correction
was s = -0.2, p = 0.36. In trim and fill methods, only two
studies were required to nullify the effect (Fig. 9B).
The Egger’s regression intercept test demonstrated sym-
metry of the plots for the pooled estimates of combined Clavien
complications [intercept = -0.59, 95 % CI -3.45 to 2.27,
p (2-tail) = 0.6, (1-tail) = 0.3]. The Kendall’s Tau without
continuity correction was s = -0.14, p = 0.6, and with con-
tinuity, correction was s = -0.09, p = 0.7 (Fig. 9C).
Meta-regression was performed using the total quality
score as a predictor variable for the pooled effect estimate
of the donor safety criteria considered in this review
(Fig. 10). For the unrestricted maximum likelihood model:
Q = 0.34, df = 1, p = 0.56, s2 = 0.
Discussion
Live donor laparoscopic liver procurement seems to be as
safe as open approach, even when laparoscopy is only used
for hepatic mobilization. It seems that the effect modifi-
cation imposed by the use of laparoscopy in liver pro-
curement demonstrated potential benefits related to the
lower blood loss, particularly in the subgroup where
parenchymal dissection was performed in laparoscopy. The
two studies reported on laparoscopic parenchymal dissec-
tion were for left lateral sectionectomy [22, 24]. The
potential for lower blood loss in pure laparoscopic liver
procurement is similar to what is reported as a difference
between laparoscopic and open liver resection [62]. Per-
haps, the fact that there is a difference in blood loss in left
lateral section harvesting while there is no such difference
in right lobe is related to two important reasons: the first
one is that the left lateral section resection is generally
easier compared with other lobes. The second reason could
be that the parenchymal thickness in the dissection plane is
relatively thinner than any other dissection plane. Fur-
thermore, patients who underwent laparoscopic approaches
generally consumed lower amounts of analgesics than
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those who underwent the conventional approach. This
difference was more significant for patients who underwent
laparoscopic hepatic mobilization and midline incision for
parenchymal dissection.
The hospital stay was similar between the comparison
groups, and the rate of complications was similar as well in
both the groups. In the subgroup analysis, all events for
Clavien III grade complications were recorded among the
subgroups, where laparoscopy was used only for liver
mobilization. There was, nevertheless, a tendency of Cla-
vien I complication grade to have lower incidence, but not
significant, in the left lateral section donation under pure
laparoscopic approach. The operative time was generally
longer for the laparoscopic approaches, and this was more
evident in studies that performed the parenchymal dissec-
tion under laparoscopy.
There was no difference in outcome measures in sub-
group analysis based on the procured lobe. Despite this, the
included number of laparoscopic right lobe donations was
higher than that in the left lateral section donations; no
comparative study reported a pure laparoscopic right lobe
donation, and laparoscopy was only used for mobilization
or for hand-assisted surgery. This would highlight that live
donor laparoscopic right liver lobe procurement is still
beyond the core scope of this report.
None among the included studies reported conversion
from laparoscopy to open except the which reported an
intention-to-treat analysis. Complications were reported
among the included studies; therefore, we did not perform
multiple imputations for the intention-to-treat analysis.
None of the included studies reported donor mortality.
In general, donor liver donation is not associated with high
rate of mortality. Trotter et al. reported a donor mortality
rate of 0.15 % after open donation from all the reported
cases in the literature [63]. To our knowledge, the only
confirmed donor death after laparoscopic live donor liver
procurement was the famous Lahey’s clinic case [64].
We were conscious about the liability of sources of
reporting BIAS in this report; that is why we had several
preemptive measures to detect them. We explored publi-
cation BIAS for positive effects (operative time, blood loss,
and hospital stay) as well as for the pooled estimate of the
complications. From the visual inspection of funnel plot,
the distribution of studies around the pooled estimate was
not inhomogeneous. This was confirmed by the statistical
tests used to explore BIAS. Unfortunately, this does not
seem to protect against BIAS, particularly since we just
mentioned none reported donor mortality.
A priori we decided to include non-English language
studies in the review. This decision was less important in
this particular case since we assume the low probability
that such type of studies will be published in other lan-
guage without being published in English. Furthermore,
during our search, we did not come across except one case
report [57]. Despite this, language BIAS is one of the
potential sources of reporting BIAS in this report. This is
still possible as studies from certain locations, even if we
do not have restriction on location, have less access to
publications. We think that this particular sort of BIAS is
less likely for this particular sort of intervention. We did
run cross-references checking of the included studies,
which did not turn out larger number of records.
The other important potential source of BIAS is the
moderate quality of the included studies. Besides that, none
b Fig. 7 A Forest plot for Clavien grade I complication. The frequency
estimates are similar in both groups as well as in subgroup analysis.
B Forest plot for Clavien grade II complication with similar frequency
estimates among the comparisons. C Forest plot for Clavien grade III
comolication with similar frequency estimates among the compari-
sons. D Forest plot for the pooled estimate of combined frequency of
Clavien grades I, II, and III complications, where there is no
difference between the groups
Fig. 8 Forest plot for the pooled estimate from the measured donor safety criteria considered in this review. The model estimates showed similar
safety profiles in both groups as well as in the subgroups
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of the included studies is randomized controlled: all of the
included trials scored between 66 and 76 % on the adapted
quality assessment score for nonrandomized trials. This
highlights the important possibility for sampling BIAS
within the studies. This is particularly a convincing argu-
ment since sampling methodology was one of the low
scored items among the included studies; despite this, there
was no difference in the baseline criteria of the included
Fig. 9 Funnel plot for BIAS
exploration with trim and fill
method for correction.
A Operative time, B blood loss,
C pooled estimate of combined
Clavien grade I, II, and III
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participants except for the age that was lower in the lapa-
roscopic group.
We had some modifications on the initially planned
protocol. We updated the search to May–June 2014 in
order not to miss any possible events of the newly pub-
lished trials. This was particularly motivated by the lack of
any randomized trial in the included studies. We also added
one item to the criteria adapted for quality assessment of
nonrandomized trials (intention-to-treat analysis). We jus-
tify this addition to enable us have stratification of the
quality scores that could be reflected as a positive differ-
entiation value in the regression analysis. The one last
modification on the protocol was in the subgroup analysis
based on the incision site, which was not anticipated to be
more suitable for consumption of analgesics.
The beforehand study is the first on the topic it
addresses. Despite the nonexistence of randomized con-
trolled trials on the review topic, we still conducted the
analysis since we decided a priori to synthesize a meta-
analysis from the existing data. This was motivated by our
desire to provide an insight ointon the potential benefits or
harms of the technique, which could be a stepping stone for
further propagation of the technique or a future randomized
trial to be conducted as suggested by Steeves [8]. It is yet
unconceivable that the technique is technically demanding
and it requires highly equipped and experienced facility
and special skill sets that are not currently available for a
large sector of liver surgeons who would require significant
training before embarking on such complex surgery;
therefore, encouragement for further studies to be con-
ducted should be initially restricted to these expert centers.
Conclusions and recommendations
With caution, we accept the null hypothesis, and we would
conclude that the laparoscopic approaches for live donor
liver procurement could be as safe as the conventional open
approach with similar complication rates. Lower blood loss
might be offered in full laparoscopic procurement of left
lateral sectionectomy. Lower consumption of analgesics
was shown among the laparoscopic group. Obviously, the
procedure is still in its infancy, particularly the right lobe
harvesting; despite more than a decade since its first report
has lapsed. There are no robust conclusions that could be
made based on the available data in the literature.
Acknowledgments On the other hand, the authors would like to
acknowledge that access to full text manuscripts was provided via
institutional access of the INSERM; U785, Centre Hepatobiliare, Paul
Brousse Hospital, Villejuif, France.
Disclosures Mohamed Bekheit, Philipe-Abrahim Khafagy, Petru
Bucur, Khaled Katri, Ahmed Elgendi, Wael Nabil Abdel-salam, Eric
Vibert, and El-said El-kayal have no conflict of interest or financial
ties to disclose.
Appendix 1: Methodological assessment of quality
of potential studies to be included in the review
Sequence generation
• Adequate, if the allocation sequence was generated by a
computer or random-number table. Drawing of lots,
tossing of a coin, shuffling of cards, or throwing dice
was considered as adequate if a person who was not
otherwise involved in the recruitment of participants
performed the procedure.
• Unclear, if the trial was described as randomized, but
the method used for the allocation sequence generation
was not described.
• Inadequate, if a system involving dates, names, or
admittance numbers were used for the allocation of
patients.
Allocation concealment
• Adequate, if the allocation of patients involved a cen-
tral independent unit, on-site locked computer, or
sealed envelopes.
• Unclear, if the trial was described as randomized, but
the method used to conceal the allocation was not
described.
• Inadequate, if the allocation sequence was known to the
investigators who assigned participants or if the study
was quasi-randomized. In addition, if there was no
blinding in the trials, the allocation concealment was
considered inadequate if it was possible to predict
future assignments of participants based on previous
assignments such as when fixed size blocks were used
in a single centre trial.
Regression of Quality Score % on Hedges's g
Quality Score %
Hed
ges'
s g
65.00 66.20 67.40 68.60 69.80 71.00 72.20 73.40 74.60 75.80 77.00
0.60
0.34
0.08
-0.18
-0.44
-0.70
-0.96
-1.22
-1.48
-1.74
-2.00
Fig. 10 Meta-regression using the unrestricted maximum likelihood
model using the total quality scores as a predictor variable for pooled
effect estimate of donor safety criteria included in this review
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Blinding
It is not possible to blind the health-care provider (surgeon)
to the group. However, it is possible to blind assessors of
certain outcomes as well as patients to the group. So,
blinding was considered adequate if patients and the out-
come assessors were blinded.
• Adequate, if patients and the outcome assessors were
blinded and the method of blinding was described
provided that the outcome could be blinded from
assessor. However, it is not necessary that for the
patients to be blinded for the outcome to be assessed
without bias (except for one noncrucial outcome;
analgesic use)
• Unclear, if patients and/or the outcome assessors were
blinded and the method of blinding was not described.
• Inadequate, if no attempts were made to blind the
outcome assessors or if the outcome assessors could
easily identify the group to which the patient belongs.
Outcomes assessed with possible blinded assessors
All outcomes considered in the study could be blinded
from assessors except for wound complications.
Incomplete data outcomes
• Adequate, if there were no post-randomization dropouts
or withdrawals or if the post-randomization dropouts
were balanced in both groups or reasons for missing
data unlikely to be related to true outcome(e.g., patients
did not undergo surgery after randomization).
• Unclear, if it is not clear whether there are any dropouts
or withdrawals or if the reasons for these dropouts are
not clear.
• Inadequate, if the reasons for missing data are likely to
be related to true outcomes, ‘‘as-treated’’ analysis was
performed, potentially inappropriate application of
simple imputation, potential for patients with missing
outcomes to induce clinically relevant bias in effect
estimate or effect size.
Selective outcome reporting
• Adequate, if complications were reported or if the trial
protocol was available and the outcome of interest to
this review was reported in the trial protocol.
• Unclear, if there is insufficient information to assess
whether the risk of selective outcome reporting is present.
• Inadequate, if not all the pre-specified outcomes were
reported or if the primary outcomes were changed or if
some of the important outcomes were incompletely
reported.
Other biases: baseline imbalance
• Adequate, if there was no baseline imbalance in
important characteristics.
• Unclear, if the baseline characteristics were not reported.
• Inadequate, if there was a baseline imbalance due to
chance or due to imbalanced exclusion after
randomization.
Each item is given score of 0 (inadequate), 1 (unclear), or 2
(adequate). A maximum score of 12 indicates flawless trial
and a minimum score of 0 indicates inappropriate trial.
We considered any trial classified as adequate sequence
generation, allocation concealment, blinding, incomplete data
outcomes, and selective reporting as trials of low bias-risk.
However, if Clavien IV complications are reported, a trial will
be considered as low bias risk for complications even if
blinding was not performed as long as the trial is classified as
adequate in adequate sequence generation, allocation con-
cealment, incomplete data outcomes, and selective reporting.
Quality assessment of nonrandomized trials
Assessment of quality of nonrandomized trials will be
adapted based on ‘‘systems to rate the strength of scientific
evidence’’ using an adaptation of a subset of the U.S.
preventive task force criteria noted below:
II-2A well-designed prospective cohort with concurrent
control
II-2B well-designed prospective cohort with historic
control
II-2C well-designed retrospective cohort with concurrent
control
II-3 well-designed retrospective case controlled study
Studies will obtain a score based on the sum of point
scoring according to the following criteria, and each cri-
terion will be scored either on a SCALE from 0 (poorest) to
5 (highest) or DICHOTOMOUS (0/1):
A. Clearly focused study question.
B. Clear definition of intervention.
C. Clear definition of primary and secondary outcomes.
D. Sampling of the study population (for nonrandomized
studies):
• 5 = prospective cohort with concurrent control.
• 4 = prospective cohort with historic control.
• 3 = retrospective cohort with concurrent control.
• 2 = retrospective case controlled study.
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• 1 = not specified (N.B: this item takes one since
we will be able to detect the presence of control
group which in any case will rank higher than
single arm studies).
• 0 = case series (will be excluded from the review).
E. Confounders are considered during interpretation of
results through (from 0 to 4 for the method and 1/3 for
each category of confounders)
i. 4 = Restriction in selection.
ii. 3 = Matching on the confounders.
iii. 2 = Demonstrated balanced distribution among
both groups.
iv. 1 = Controlled for in the statistical analysis.
v. 0 = Not done
• List of anticipated potential confounders
(three categories; 1/3 for each):
• Base line and characteristics: age, gender,
BMI
• Anatomical characteristics: lobe
• Experience and learning curve:
F. Statistical methods used to take into account the effect
of multiple variables on the outcome such as regression
analysis, multivariate models.
G. Statistical analysis considered intention to treat princi-
ple for dropouts and switch over (DICHOTOMOUS).
H. Measure of effect of outcome and appropriate measure of
precision (SE, CI) (central tendency and dispersion
measures will be accounted for as sufficient if appropriate).
I. Conclusions supported by results with possible bias
and limitations taken into consideration: i.e.: clinical
significance of effect size provided.
Total score will be provided to the each individual study
with a maximum possible score 41.
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