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A SYSTEMATIC REVIEW AND META-ANALYSIS OF ROBOTIC VERSUS
LAPAROSCOPIC PARTIAL HEPATECTOMYLIVER RESECTION
Loredana Kent1, Aydin Abdullatif1, Kamran Ahmed1, Tamara Gall3 , Tim Pencavel3 , Long R
Jiao3 , Saied Froghi1, 2
1 MRC Centre for Transplantation, King’s College London, King’s Health Partners, Guy’s
Hospital, St Thomas Street, London SE1 9RT, UK
2 Renal & Transplant Surgery, Hammersmith Hospital, Imperial College NHS Trust, Du Cane
Rd, London W12 0HS
3 HPB Surgery, Hammersmith Hospital Campus, Dept of Surgery and Cancer, Imperial
College London
Correspondence to:
Mr Saied Froghi BSc (Hons) MBBS MRCS
Speciality Registrar
Renal & Transplantation Services
Hammersmith Hospital
Du Cane Rd,
London W12 0HS
Email: [email protected]
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Key words: Partial liver resection, hepatectomy, laparoscopic surgery, robotic surgery, hepatocellular carcinoma, meta-analysis, meta-regression, Blant-Altman analysis
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ABSTRACT
Objective :
To conduct a systematic A review of publications to studies compare ing the short-
outcomesterm outcomes of laparoscopic vs robotic partial liver resection to robotic partial
liver resection. hepatectomy
Background :
With the advance of minimally invasive techniques, lLaparoscopic liver resection (LLR ) of
liver pathology has become the standard accepted surgical option method alternative to open
resection with its in recent years. Laparoscopic liver resection (LLR) has evident advantages
over an open surgeryapproach. However, its use for it has inherent limitations which results
in greater challenges for mmajor liver remains challenging which is limited to skilled
laparoscopic surgeons. resections. Robotic liver resection (RLR) is possibly an improved
alternative to laparoscopic techniques. It has the potential to produce favourable intra- and
postoperative surgical outcomes for its as it has a better ergonomic profile. This article
compares laparoscopic and robotic liver resection using meta-analytical techniques.
Methods :
A systematic review of literature was performed to identify studies comparing laparoscopic
partial liver resection andwith robotic partial liver resection. Using different databases ci.e.
Pubmed, comparative studies quantitatively in English between 2010 to evaluating2016
evaluating laparoscopic and robotic partial liver resections that fulfilled the inclusion criteria
were selected. P Studies in English, and between 2010 to 2016 were reviewed for primary
outcomes measuresincluded such as surgical time, estimated blood loss (EBL), length of
stay (LoS), conversion rate and complication rate. A meta-analysis using the fixed model as
well as Bland-Altman analysis was performed.
Results:
A total of 13 studies published between 2010 and 2016 matched the selection criteria and
were included in the analysis consisting of . In total 1165 patients were analysed ((LLR,
n=xx, 61% and RLR, LLR and n=xx, 31% RLR). Overall results revealed, laparoscopic
techniqueLLR has better operative time profile and wasis associated with less blood loss
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(P<0.00, respectively001). However, there There was no statistically significant difference in
terms of ce observed in length of stay, complication rate and conversion to open rate. There
was a great deal of heterogeneity observed across all studies.
Conclusion n:
Despite a demonstration of better operative profile for laparoscopic technique results must be
interpreted with care. There was is a significant level of variability between and within the
studies that ultimately have affect results. There is a need for more robust clinical trials to
demonstrate a meaningful benefit.
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INTRODUCTION
Laparoscopic liver resection (LLR) has become an accepted established surgical
optiontreatment for liver disease since its debut in 1992 [1, 2]. Whilst some areas of
laparoscopic surgery developed rapidly, a laparoscopic approach to liver resection has been
was more tentatively developed over the last 10 years due to the nature of liver anatomy and
tendency for bleeding during liver resection [1, 3]. Two recent meta-analyses have shown its
significant t to have benefitss over the open approach, including reduced estimated blood loss
(EBL), morbidity and length of stay (LoS) [4, 5]. Additionally, outcomes such as operative
time, surgical margin and mortality, results were matched with outcomes of open surgery [4,
5]. Although these outcomes are favourable in well selected patients with experienced
surgeons, known technical difficulties do exist [6]. For example, where there is extensive bile
duct or gross vasculature involvement, the approach is often unfavourable [6]. Techniques
have been improved over time, with methods of parenchymal transection and vessel stapling
aiding control of bleeding. However, limited degrees of freedom and 2D visualisation,
inherent to laparoscopic technique may proves difficult in resection of posterior liver lesions
[7, 8]. Further to this, evidence for the benefits of laparoscopic major liver resection is
perhaps lacking in strength, with some suggested publication bias [7]. Although laparoscopic
major hepatectomy is feasible, it remains challenging [9]. This has rendered its main use in
resection of small, superficial tumours, denying many patients from the benefits of minimally
invasive surgery [6]. Nevertheless, this trend is changing with the advancement of minimally
invasive techniques and technologies, permitting more complex liver resections.[10]
The da Vinci robot (Intuitive Surgical, Sunnyvale, CA, USA) was introduced for use in 2001,
and posed a promising improvement to conventional laparoscopic techniques [11]. Robotics
have the added benefit of increased freedom of instrument movement whilst maintaining the
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benefits of a minimally invasive approach. In addition to this, the surgeon has a 3-
dimensional view [7]. As a result of this, it is expected that more complex surgeries with
improved outcomes could be achieved through robotic liver resection (RLR). The question of
whether this is true is remains to be evaluated. Common themes of current reviews on RLR
are that operative times are significantly higher in RLR compared with LLR [11, 12]. In
addition to this, it is costly and has a lack of tactile feedback, with a necessity for an
experienced assistant surgeon to be present [13-15]. Therefore, as further evidence is
produced, it is important to re-evaluate role of robotics in minimally invasive liver resection.
This systematic review aims to compare short-term outcomes perioperative, operative and
post-operative outcomes between LLR and RLR groups.
MATERIALS AND METHODS
Study selection:
A systematic review of the literature was performed using Medline (1950-present),
EMBASE, (1950-present), Pubmed (1950-present) and Cochrane database to identify
relevant studies available between 2000-2016. Qualified studies comparing laparoscopic with
to robotic technique in liver resection were identified. The following search terms were used
in combination to yield the outcomes of Boolean search on the relevant databases: ‘robotic
hepatectomy’, ‘robotic liver resection’, ‘laparoscopic hepatectomy’, ‘robotic laparoscopic
liver resection’, ‘minimally invasive hepatectomy’, ‘laparoscopic hepatectomy’. Titles and
abstracts were screened for relevance to laparoscopic or robotic liver surgery only. Studies
focussing on hepatobiliary, pancreatic and other surgeries were excluded on this basis. A full
assessment of the remaining studies was then carried out against the eligibility criteria. Last
search was performed in September 2016.
Data Extraction
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Two reviewers (L.K. & S.F.) independently have reviewed and evaluated the relevant articles
for inclusion or exclusion. The included studies were screened and the following data was
extracted: First author, year of study, publication, characteristic of study population, study
design, total number of patients in each group, tumour size, intra-operative (operative time,
estimated blood loss (EBL), conversion to open), Length of stay (LoS), post-operative
complications, pathology type and relevant patient demographics.
Inclusion criteria:
On screening the articles the following inclusion criteria had to be fulfilled for the study to
enter meta-analysis: (1) Compare the outcomes of robotic withto laparoscopic approach for
partial liver resection, (2) Provide quantitative data on the primary outcome measures, (3)
Studies reporting on human subjects, (4) English Language, (5) When two studies were
reported by the same institution, either the study with the larger sample size or the one of
higher quality was included however, this was not applicable if the outcome measures were
mutually exclusive or measured at different time intervals.
Exclusion criteria:
Additionally, studies were excluded if they were: (1) published before 2010. (2) non-were not
in English. (3) Animal studies.
Measured outcomes:
Primary outcomes measured were surgical/operative time (OPT), estimated blood loss (EBL),
length of stay (LoS), conversion rate and complication rate post operatively.
Data from participants of all ages, with any indication for partial liver resection were
included. To maximise the number of studies used in this limited area of research, all
techniques of laparoscopic and robotic partial liver resection were selected. This included
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hand-assisted and hybrid techniques in the laparoscopic approach and robotic approaches
where a laparoscopic assistant was involved.
Statistical analysis:
This meta-analysis was performed in line with recommendations from the Cochrane
Collaboration and Met-analysis of Observable Studies in Epidemiological (QUORUM)
guidelines [16]. The effect measures estimated were odds ratio (OR) for dichotomous data
and weighted mean difference (WMD) for continuous data, both reported with 95%
confidence intervals. The odds ratio represents the odds of an adverse event occurring in the
robotic compared to the laparoscopic group. An odds ratio of less than one favoured the
robotic group. The point estimate of the odds ratio was considered statistically significant at
the p <0.05 level if the 95% confidence interval did not include the value one.
For continuous variables, the odds ratio was calculated with the Mantle-Haenszel Chi square
method using a “fixed effects” meta-analytical technique. The fixed effect model is preferred
as it takes into account for the variability and the heterogeneity between the studies. For
continuous variable such as time, statistical analysis was carried out using weighted mean
difference at the summary statistic. WMD of negative value favoured robotic group. For
studies that presented continuous data as median and/or range values, the standard deviation
was calculated using statistical algorithms [17]. In reporting the results, square is indicative
of point estimates of the treatment effect (OR or MWD) with 95% CIs indicated by
horizontal bars. The diamond represents the summary estimate from the pooled studies with
95% CIs. Further, heterogeneity is calculated and presented as I2 and a value above 50% is
considered significant level of heterogeneity. To evaluate bias between the mean different
and assess for reproducibility of the proposed methods a further Blant-Altman analysis of the
studies included in meta-analysis was carried out.
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A qualitative analysis of the studies was done using the Quality Assessment Tool for
Systematic Reviews of Observational Studies [18] and the Newcastle-Ottawa Scale [19, 20]
for reporting non-randomised comparative studies. This was altered to suite the analysis and
studies included in this evaluation. The domains analysed for quality were patient selection,
comparability of the study groups, and assessment of the outcomes. In this study, studies that
achieved 5 or more stars were considered high quality.
All analysis was conducted using Review Manager Version 5 (The Cochrane Collaboration,
Software Update, Oxford). Where suitable Meta-regression analysis was conducted using
Comprehensive Meta-Analysis Software Version 3.3 (CMA group) and for parametric/non-
parametric analysis Minitab software version 16 (LEAD Technologies Inc) was used.
RESULTS
Study selection:
Initial search revealed a total of 620 (Figure 1) potential articles published between 2010 and
2016 fulfilling our search terms. Subsequent screening of titles and abstracts for their
relevance to the review topic resulted in excluding 497 articles. Studies that did not satisfy
the inclusion criteria were excluded leaving 99 studies for further review. Out of this, a total
of 13 studies satisfied the inclusion criteria and were suitable for the meta-analysis [8, 13, 21-
31]. There was some minor overlap between Troisi et al.[28] and Montalti et al[8], but both
studies were included to maximise sample size.
Study characteristics:
The characteristics of the studies are summarised in table 1two. There were no randomised
control trials comparing the two procedures. Each study had a laparoscopic group as control
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and a robotic group as the interventional arm of the study. Most the studies had a recent year
of publication (2010 or later) and they contained at least 9 patients in both the laparoscopic
and the robotic groups. All studies were case series, ranging from 32 people included in
Berber et al. to 263 participants in Troisi et al[28]. Four studies matched patients before
analysis [8, 23, 24, 27]. On review of data extraction there was 100% agreement between the
two reviewers (LK & SF).
A total of 1165 subjects were analysed, of which 714 underwent LLR laparoscopic partial
hepatectomy (61%) and 451 RLR were treated by robotic (31%) means. All patients included
in the studies had a tumour size of less than 6cm with majority of them being male (54%)
subjects (t. Tables 2 and 3). Need a breakdown here what type of liver resection, minor,
definition for this, less than 2 segements, left lateral , left or right etc… ( two and three
summarise the parameters extracted from each study. fFigure 2-4) two along with tables four
and five provide a summary of the pathologies encountered in the studies.
Results of meta-analysis:
Data utilised from all 13 studies were used in meta-analysis to compare surgical outcomes
(summarised in figures 3-5): operative time, estimated blood loss, and length of stay.
Surgical outcomes
Surgical Time
All studies found surgical time to be longer in RLR with a MWD of 52.41min and 95% CI:
44.38min to 60.45min (Figure 3). Although results were significantly in favour of
laparoscopic group (P < 0.00001), there was a substantial degree of heterogeneity (Chi2 =
57.88; df = 12; I2 = 79%) displayed between studies.
Estimated Blood Loss
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Eleven studies reported on estimated blood loss and were subsequently used in the analysis
(Figure 4). There was less intra-operative bleeding in the laparoscopic group (P < 0.00001)
compared to robotic with a MWD of 73.29ml and 95% CI ranging from -7.67 to 99.47mls.
Analogous to operative time, considerable heterogeneity (Chi2 = 28.15; df = 10; I2 = 64%) is
noted.
Length of Stay
There were no significant differences in LoS between each group (Figure 5) (P = 40).
Conversion Rate
No significant differences were found in conversion rate between the groups (P = 0.63).
Reasons for conversion are summarised for 7 of the studies in Table 6 [8, 13, 21, 24, 26-28].
Tsung et al,[23] stated reasons for conversion in RLR group occurred due to bleeding and
technical difficulties. The laparoscopic conversions had the same reasons in addition to a left
hepatic vein injury and concerns over resection margin. Wu et al..[22], performed 2
conversions in RLR due to bleeding and malignant hyperthermia. 4 studies did not state
reasons for conversion[25, 29-31].
Complication Rate
Complication rate, where stated, was not significantly different between groups (P = 0.35).
Table 7 provides a summary of the complications across studies. 7 studies used a
classification system to report types of complication.[8, 22, 24, 25, 27, 28, 31]. Troisi et
al[28]., grouped differently, reporting grade 1 Clavien-Dindo complications in 2.5% of RLR
and 3.6% of LLR. Grade 2-4 complications existed in 10% of RLR and 9% LLR.
Further analysis
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To further evaluate role of robotics in liver resection we have performed a meta-regression
analysis to delineate the true effect of co-variates on the effect size. In addition, to assess bias
and compare methods of robotic with laparoscopic technique we have performed a Bland-
Altman Analysis.
Meta regression analysis
Amongst covariates analysed, malignant tumour (including HCC & colorectal metastasis) of
any type displayed a significant correlation (p-value = 0.0026, Q = 18.27, df = 5) (Table 8).
In the same analysis model, male sex (p = 0.1132), and minor resections (p = 0.5821) showed
no significant correlation. The only important correlation with regards to regression analysis
of resection type was left sided hepatectomies (P = 0.0436, Q = 13.83, df = 7) (Table 9).
Bland-Altman Analysis
All thirteen studies were used to construct Bland-Altman plots. Data with regards to OPT &
EBL were used to compare correlation between robotic and laparoscopic group. Results are
detailed in figures 7 and 8.
There was poor correlation demonstrated between robotic and laparoscopic group: EBL
(Bias: -203.48, 95% CI: -307.3 to -99.6) and OPT (Bias: 76.45, 95% CI: 32.34 to 120.56).
Mortality
Six studies reported no mortality [13, 22, 26, 28-30]. Four? studies reported 1 death within 30
days in the LLR group: [25] due to portal vein thrombosis, [24] and [23] due to sepsis, [31]
due to duodenal perforation and peritonitis. [8] had one death in the RLR group due to a
myocardial infarction. 1 died from portal vein thrombosis in LRL, 90 days [25]
Cost
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A direct comparison of cost was included in three studies. Yu et al., [13], found the RLR
group costed significantly more than the LLR group ($11,475 mean vs. $6,762 P=0.001).
Kim et al.,[30] found total costs for patients undergoing laparoscopic surgery were 5190.9 ±
3148 versus 8183.3 ± 3343.2 in the robotic group (P=0.009). Croner et al [31] estimated a
perioperative cost of €3,437 for laparoscopic procedures versus €8,765 for robotic. Berber et
al,[21] suggested that cost of robotic equipment is an extra $500 per case compared with
laparoscopic cost .
Surgical technique
Details of surgical techniques can be found in table 10 and 11. Of those studies that stated
numbers of each resection type, the greatest proportion of operations in both groups were left
lateral sectionectomies, followed by wedge resections then monosegmentectomies. All
robotic surgeries were carried out with either 1 or 2 ports utilised by an assistant at the table.
3 reported the use of Kelly clamp crushing technique in RLR using robotic forceps [8, 21,
24]. 5 reported use harmonic scalpels for parenchymal transection [8, 13, 24, 26]. In LLR
there were 2 reported uses of Cavitron ultrasonic surgical aspirator (CUSA; ValleyLab,
Boulder, CO, USA) [13, 26], 3 used harmonic scalpels [8, 13, 21], 1 used tissue link (Medical
Inc, Dover DE, USA) and 1 used thermofusion techniques [24]. 2 studies did not provide
details of techniques used [22, 23].
Use of the pringle manoeuvre was not mentioned in all studies however, it was reported as
being practised in six studies [8, 24, 25, 27-29]. In Montalti et al., [8] a significantly greater
proportion of the RLR had the pringle manoeuvre (55% Vs. 22.2% P=0.001) and for a
significantly longer time when used (76.7 Vs. 24.6 minutes (mean) P= < 0.001). Similarly in
Tranchart et al. [24], where 12 people required the procedure in the RLR compared with 0 in
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the LLR group (P=0.0001) and in Troisi et al.,[28] where 45% of RLR used it compared to
2.7% LLR. In Spampinato et al.[25] however, there was significantly more use of the pringle
manoeuvre in the LLR than the RLR group, where it was not used (32% Vs. 0% P=0.004)
[25]. In Lee et al.[26], the RLR group underwent significantly more major hepatectomies
than the LLR group (P=0.002) [26]. Wu et al.,[22] was similar in this respect with 78% major
resections in RLR vs 37% in the LLR group (P value not stated). In Tranchart et al.[24], the
RLR group had significantly more associated procedures (10 vs 2 respectively, P=0.02) [14].
In an outcomes analysis of those without associated procedures, the groups had similar
results.
Tsung et al.,[23] and Lai et al., 2016 [29] were the only two studies to include hand-assisted
and hybrid techniques in the LLR group. Taking into account conversions in [23], the RLR
group had a significantly higher number of purely minimally invasive surgeries compared
with LLR group (93% vs 55% P=<0.001) [23].
Tumour size
The only significant finding was between tumour size in Wu et al (P=0.02)[22].
DISCUSSION
Tranchart et al., displayed that five significant factors linked to complications were BMI
≥Kg/m2 (P=0.037) ASA score ≥ 3 (P=0.047), operative time (P=0.001), EBL (P=0.05) and
transfusion (P=0.049).
Liver surgery has unique challenges, due to the possibility of bile leakage and risk of
excessive blood loss [5]. LLR has made steps to overcoming these challenges; as suggested
in literature it can achieve reduced blood loss, as well as decreased LoS and morbidity when
compared to an open approach [4-6]. Yet some types of LLR remain challenging, for
example removal of lesions located in segments VII and VIII [32]. Theoretically, the da Vinci
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robot should overcome the limitations of laparoscopic surgery in its design. New wristed
instruments instead of straight instruments, providing the seven degrees of freedom, tremor
filtration and a more life-like visualisation of the surgery [33, 34].
Currently, literature suggests that RLR is safe and largely able to match pure laparoscopic
outcomes [35, 36]. Its possible drawbacks are in increased surgical time, as found in this
review [37]. Two of the studies which had significantly longer surgical times in the RLR
group also were the only two with significantly more major hepatectomies in this group. Lee
et al., [26] had 3% major hepatectomies in the LLR compared with 20% in the RLR
(P=0.002) and Wu et al., [22] had 78% vs 37% in addition to a greater tumour size on average
in the RLR group. These are possible explanations for the increased surgical time. However,
this was not the case in Tsung et al[23]., where there were no significant differences between
resection type, BMI, tumour size and other possible factors affecting surgical time [23].
However, they highlighted in their comparison between early and late RLR groups that
surgical time was significantly shorter in later surgeries (253 LLR vs. 198.5 P=0.001). This
indicates the effects of the learning curve and the need for studies to report findings over
longer periods of time.
Robotics have demonstrated the potential to carry out major hepatectomies with greater ease
and safety than LLR. Three studies demonstrated greater numbers of major hepatectomies
carried out in the RLR group [26, 27, 29]. One study, [25] included only major hepatecomies,
including 4 extended right hepatectomies in the RLR group, and found outcomes to be
similar in each group. Although it is to be noted that ASA grade was lower in the LLR group
(not significant). Despite promising results, it must be remembered that these results have
been achieved in small samples of cautiously selected patients in specialised centres.
Nevertheless, it is hopeful from this that RLR has the potential to achieve what it was
designed to.
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Literature has highlighted varied results in EBL. Two recent meta-analyses disagreed, one
finding increased EBL in RLR [37] and another suggesting no significant difference between
the groups [11]. This review found only one study with significantly higher EBL in the RLR
group [22], otherwise no significant differences were found. It is possible the variations in
EBL are accountable for by the diversity in technique and instrument use. For example, the
pringle manoeuvre was used significantly more in one group during four studies [8, 24, 25,
28]. This potentially could have an effect on surgical outcomes. A randomised controlled trial
(RCT) showed that intermittent use of the pringle manoeuvre resulted in a significantly
higher morbidity rate compared with no use. However, no significant difference was seen in
any other outcomes, including EBL [38] In contrast, another RCT found transection time to
be significantly higher when PM was used, but no difference when comparing complications
[39]. The studies included in this review did not specify whether the PM was used
continuously or not, but use of the pringle manoeuvre in general could potentially affect EBL.
It is possible that differences in parenchymal transection techniques also have an effect on
outcomes.
Limitations
A key limitation of this review is that the data had numerous gaps due to variations in
reporting methods and extent of information provided in the studies. This was particularly
noticeable in the complications section. Therefore, comparisons were limited and a clear
conclusion could not be made on differences in complication type between groups. Details
such as surgical techniques, BMI, ASA grade were also not reported consistently throughout
the studies, despite them having possible influences on results. In addition to this, a
comparison of cost between the two techniques was only made in three studies. This should
be considered an important factor in future studies to determine if RLR is justifiable.
16
Once more studies have been carried out prospectively with larger cohorts, longer follow-up
times and consistent methods of data presentation, conclusions can be made with greater
conviction. As suggested from this review and other meta-analyses [37], randomised
controlled trials comparing RLR to LLR could then be carried out, knowing the two
techniques have similar safety. These trials would provide the rigorous evidence required to
determine whether RLR has an advantageous edge compared to LLR and therefore should or
should not be standardised.
CONCLUSION
Overall, research to date is yet to provide a definitive answer of whether RLR has better
outcomes than LLR due to small sample sizes and heterogeneity of studies being compared.
The data included in this review suggests RLR is capable of at least matching LRR. No
significant differences were seen between groups in LoS, conversion and complication rate.
Current differences in surgical time may reflect a learning curve in use of the technology. The
varied findings between studies in EBL could be due to differences in surgical techniques or
also be part of the learning curve. One promising finding from this review is that major RLR
can be carried out safely, and potentially as a better alternative to major LLR. The
improvements that robotic systems bring to minimally invasive surgery give a convincing
argument to invest more research into this growing area.
17
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29. Lai ECH, T.C., Robotic versus laparoscopic approach for hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech, 2016. 26(2): p. 162-166.
30. Kim JK, P.J., Han DH, Choi GH, Robotic versus laparoscopic left lateral sectionectomy of liver. Surgical endoscopy, 2016. 30(11): p. 4756-4764.
31. Croner RS, P.A., Hohenberger W, Brunner M, Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures. Langenbecks Arch Surg, 2016. 401: p. 707-714.
32. Lin, N.C., H. Nitta, and G. Wakabayashi, Laparoscopic major hepatectomy: a systematic literature review and comparison of 3 techniques. Ann Surg, 2013. 257(2): p. 205-13.
33. Boggi, U., F. Caniglia, and G. Amorese, Laparoscopic robot-assisted major hepatectomy. J Hepatobiliary Pancreat Sci, 2014. 21(1): p. 3-10.
34. Hockstein NG, G.C., Faust RA, Terris DJ, A history of robots: from science fiction to surgical robotics. Journal of Robotic Surgery, 2007. 1: p. 113-118.
35. Ho, C.M., et al., Systematic review of robotic liver resection. Surg Endosc, 2013. 27(3): p. 732-9.
36. Qiu, J., S. Chen, and D. Chengyou, A systematic review of robotic-assisted liver resection and meta-analysis of robotic versus laparoscopic hepatectomy for hepatic neoplasms. Surg Endosc, 2015.
37. Montalti, R., et al., Outcomes of robotic vs laparoscopic hepatectomy: A systematic review and meta-analysis. World J Gastroenterol, 2015. 21(27): p. 8441-51.
38. Lee KF, C.Y., Chong CCN, Wong JS, Lai PB, Randomized clinical trial of open hepatectomy with or without intermittent Pringle manoeuvre. British journal of surgery, 2012. 99(9): p. 1203-1209.
39. Capussotti L, M.A., Ferrero A, Massucco P, Ribero D, Polastri R, Randomized clinical trial of liver resection with and without hepatic pedicle clamping. British journal of surgery, 2006. 93(6): p. 685-689.
40. Moher D, L.A., Tetlaff J, Altman DG. The PRISMA Group, Preferred reporting items for systematic reviews and meta analyses: The PRISMA statement. PLoS Med 2009. 6(6): p. e1000097.
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Figure 1 : PRISMA fFlow diagram of selection. Adapted from Moher D et al., 2009.[40]
21
Table 1 – Study Characteristics
Study Study Type
Cases, number
Type of Resection
Matching Study Quality (Newcastle-Ottawa scale)
LLR n=714
RLR n=451
Selection (max 4 stars)
Comparability (max 2 stars)
Outcome (max 3 stars)
Croner et al., 2016
Prospective
19 10 minor 1,2,3,4,5,6,9,10
**** * *
Kim et al., 2016
Prospective
31 12 minor 1,2,5,6,7,9,10 **** ** **
Lai et al., 2016
Prospective
35 100 major and minor
1,2,6,7,9,10 **** * **
Lee et al., 2015
Prospective
66 70 major and minor
1,2,4,6,7,9,10 **** - *
Montalti et al., 2015
Matched prospective
72 36 minor 1,2,4,5,6,8,9,10
**** ** **
Spampinato et al., 2014
Prospective
25 25 major 1,2,3,4,5,6,7,8,9,10
*** ** *
Tranchart et al., 2014
Matched prospective
28 28 minor 1,2,3,4,5,6,7,9,10
*** ** *
Tsung et al., 2014
Matched retrospective
114 57 major and minor
1,2,3,4,6,7,9,10
**** ** *
Wu et al., 2014
Retrospective
41 38 major and minor
1,2,6,9,10 **** - **
Yu et al., 2014
Retrospective
17 13 major and minor
1,2,6,7,9,10 **** - *
Troisi et al., 2013
Prospective
223 40 major and minor
1,2,5,6,8,9,10 *** * **
Ji et al., 2011
Matched unclear
20 13 major and minor
1,2,5,6,7,9,10 **** ** *
Berber et al., 2010
Prospective
23 9 minor 1,2,6,9,10 **** ** **
22
P: Prospective, MP: Matched Prospective, MR: Matched retrospective, R: retrospective, Matching: Age=1, M:F=2, BMI=3, ASA=4, Previous abdominal surgery=5, Indication for surgery=6, liver disease = 7, neoadjuvant chemotherapy=8, laparoscopic resection=9, robotic resection=10
Pls define minor and major liver resection…
Table 2 – Parameters for laparoscopic liver resection
Study Mean/median surgical time (mins)
Mean/median EBL (ml)
Mean/median LoS (d)
Complications, num (%)
Conversion to open, num (%)
Croner et al., 2016 242 (80-478) 356† 8 (4.0-33.0) 3 (16) -Kim et al., 2016 245.9 ±100.7 150 (50-425) 7 (5.0-8.0) 6 (19.4) -Lai et al., 2016 134.2 ±41.7 336 5.0-2000 7.1 ±2.6 7 (20) 2 (5.7)Lee et al., 2015 215 90-420 100 (5-1610) 5 (2.0-15.0) 3 (4.5) 8 (12.1)Montalti et al., 2015
295 ± 107 473 ±523 4.9 ±2.95 14 (19.4) 7 (9.7)
Spampinato et al., 2014
360 (180-600)
400 (50-1200)
7 (5.0-22.0) 9 (36) 1 (4)
Tranchart et al., 2014
176 (30-420) 150 (0-1000) 5.5 (1.0-50.0) 5 (17.9) 2 (7.1)
Tsung et al., 2014 198.5 (137.75-261.5)
100 (50-350) 4 (3.0-5.0) 29 (26) 10 (8.8)
Wu et al., 2014 227 ±80 173 ±165 7.2 ±4.4 4(10) 5 (12.2)Yu et al., 2014 240.9 ±68.6 342.6 ±84.7 9.5 ±3.0 2 (11.7) 0Troisi et al., 2013 262 ±111 174 ±133 5.9 ±3.8 28 (12.6) 17 ( 7.6 )Ji et al., 2011 130† 350† 5.2† 2 (10) 2(10)Berber et al., 2010 233.6 ±68.6 155 ±54 - 4 (17) 0
†Mean only provided, EBL=estimated blood loss, LoS=Length of stay
Table 3 – Parameters for robotic liver resection
Study Mean/median surgical time (mins)
Mean/median EBL (ml)
Mean/median LoS (d)
Complication, num (%)
Conversion, num (%)
Croner et al., 2016 321 (138-458)
306† 7 (5.0-13.0) 1 (10) -
Kim et al., 2016 403.8 ±139 225 (125-275)
7 (7.0-8.0) 3 (25) -
Lai et al., 2016 207.4 ±77.1 334.6 (5.0-3500)
7.3 ±5.3 14 (14) 4 (4)
Lee et al., 2015 251.5 (97- 100 (2.0- 5 (2.0-22.0) 8 (11.4) 4 (5.7)
23
620) 2500.0)Montalti et al., 2015 306 ±182 415 ±414 6 ±2.9 7 (19.4) 5 (13.9)Spampinato et al., 2014
430 (240-725)
250 (100-1900)
8 (4.0-22) 5(20) 1 (4)
Tranchart et al., 2014
210 (45-480) 200 (0-1800) 6 (1.0-15.0) 5 (17.9) 4 (14.3)
Tsung et al., 2014 253 (180-355)
200 (50-337.5)
4 (3-5.5) 11 (19.3) 4(7)
Wu et al., 2014 380 ±166 325 ± 480 7.9 ±4.7 3 (8) 2(5)Yu et al., 2014 291.5 ±85.1 388.5 ±65.0 7.8 ±2.3 0 (0) 0Troisi et al., 2013 271 ±100 330 ±303 6.1 ±2.6 5 (12.5) 8 ( 20 )Ji et al., 2011 338† 280† 6.7† 1(7.8) 0Berber et al., 2010 258.5 ±27.9 136 ±61 - 1 (11) 1 (11.1)
†Mean only provided, EBL=estimated blood loss, LoS=Length of stay
Pls combine take 2 and 3 lap vs robotic
Table 4 – Tumour characteristics for laparoscopic liver resection
Study Total HCC
CRM other malignant†
IHD stone
hepatic cyst
hepatic adenoma
FNH abscess
hemangioma other benign
Croner et al., 2016
19 5 5 5 1 2 1 0
Kim et al., 2016
31 18 6 0 5 0 0 0 1 1
Lai et al., 2016
35 35 0 3‡ 0 0 0 0 0
Lee et al., 2015
66 41 13 3 0 - 0 4 - 3 2
Montalti et al., 2015
72 6 44 0 0 4 9 4 0 4 -
Spampinato et al., 2014
25 1 16 4 - - 1 - - 0 -
Tsung et al., 2014
114 18 36 - - - - - - 36
Wu et al., 2014
41 41 0 0 0 0 0 0 0 0 0
Yu et al., 2014
17 3 1 1 8 1 1 1 0 0 1
Troisi et al., 2013
223 9 108 2 - 4 38 32 - 9 17
Berber et al., 2010
23 7 14 - - - - - - - -
24
†includes other metastases and cholangiocarcinoma. ‡3 within HCC group. HCC=hepatocellular carcinoma, CRM=colorectal metastases, IHD=intrahepatic duct, FNH=focal nodular hyperplasia. No data provided in two studies.
Table 5 – Tumour characteristics for robotic liver resection
Study Total HCC CRM other malignancy†
IHD stone
hepatic cyst
hepatic adenoma
FNH
abscess hemangioma
Croner et al., 2016
10 4 5 1 0 0 0 0 0
Kim et al., 2016
12 6 1 0 4 1 0 0 0 0
Lai et al., 2016
100 100 0 2 ‡ 0 0 0 0
Lee et al., 2015
70 40 8 4 - - 1 1 - 1
Montalti et al., 2015
36 3 21 1 0 4 1 - 4
Spampinato et al., 2014
25 2 11 3 - - 1 - - 5
Tsung et al., 2014
57 7 21 - - - - - -
Wu et al., 2014
38 38 0 0 0 0 0 0 0 0
Yu et al., 2014
13 10 0 0 1 0 0 1 - -
Troisi et al., 2013
40 3 24 1 - 4 0 0 - 6
Ji et al., 2011
13 6 0 2 1 0 0 1 0 3
Berber et al., 2010
9 3 4 - - - - - - -
†includes other metastases and cholangiocarcinoma. ‡3 within HCC group. HCC=hepatocellular carcinoma, CRM=colorectal metastases, IHD=intrahepatic duct, FNH=focal nodular hyperplasia. No data provided in one study
Please combine table 4 and 5, lap vs robotic
25
Figure x – Distribution of pathologies treated in the laparoscopic & robotic group (the difference in the distribution of pathologies is not significant (p = 0.235).
26
FIGURE 3 – OPERATIVE TIME
FIGURE 4 – ESTIMATED BLOOD LOSS
FIGURE 5- LENGTH OF STAY
27
Table 6 – Summary of reasons for conversion
Number of CasesLLR RLR
Bleeding 23 11Oncological 5 4Lack of progress 1 1Adhesions 4 2Technical 3 3
Data only provided from 7 papers: [8, 13, 21, 24, 26-28]
Table 7 – Summary of complications
Clavien-Dindo Classification of Complications
Minor Complication (grades 1-2), number (% of total people)
Major Complication (grades 3-5)
LLR RLR LLR RLRCroner et al., 2016 10 10 1 0Kim et al., 2016 12.9 8.3 9.6 16.6Montalti et al., 2015 15.3 25 6.9 11.1Spampinato et al., 2014
24 16 12 4
Tranchart et al., 2014 10.7 7.1 10.7 10.7Wu et al., 2014 ? 8 ? 0Ji et al., 2011 10 7.8 0 0
Table 8 – Meta-regression results for relation between malignant tumours, Male sex, and resection type. HCC: Hepatocellular carcinoma.
28
Table 9– Meta-regression results of resection type
LH: Left hepatectomy, RH: Right hepatectomy, LLS: Left lateral sectionectomy, MS: Monosectionectomy, BS: Bisectionectomy, WR: Wedge resection
29
Figure 6 – Meta-regression plot for (A) Malignant tumours, (B) Males sex, and (C) Left hepatectomy
Regression of Std diff in means on Malignant
Malignant
0.0 20.0 40.0 60.0 80.0 100.0 120.0 140.0 160.0
Std
diff
in m
eans
12.50
10.00
7.50
5.00
2.50
0.00
-2.50
-5.00
-7.50
-10.00
-12.50
30
Regression of Std diff in means on Male
Male
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 110.0
Std
diff
in m
eans
8.00
6.00
4.00
2.00
0.00
-2.00
-4.00
-6.00
-8.00
-10.00
-12.00
Regression of Std diff in means on LH
LH
-20.0 -10.0 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0
Std
diff
in m
eans
20.00
15.00
10.00
5.00
0.00
-5.00
-10.00
-15.00
-20.00
-25.00
-30.00
-35.00
31
Figure 7– Bland-Altman Plot for operative time between robotic and laparoscopic mean operative time (OPT)
32
Figure 8 – Bland-Altman plot for estimated blood loss (EBL) for robotic vs laparoscopic technique
33
Table 10 – Surgical techniques for laparoscopic liver resection.
Study: Resection Type†
Surgical procedure, % of patients
Pure LLR
Pringle Manoeuvre, number (%)
LH RH LLS MS BS WR other Croner et al., 2016
minor - - - - - - - yes -
Kim et al., 2016
minor 0 0 100 0 0 0 0 yes 0
Lai et al., 2016
major and minor
0 2.9 26 26 0 45.7 0 no - pure 12, HA 23
20 (57.1)
Lee et al., 2015
major and minor
3 0 43.9 0 0 51.5 1.5 LLS+WR Yes 0
Montalti et al., 2015
minor 0 0 0 20.8 13.9 48.6 16.7 Yes 16 (22.2)
Spampinato et al., 2014
major 32 60 0 0 0 0 4 ELH, 4 LLS + MS
yes 8 (32)
Tranchart et al., 2014
minor 0 0 17.9 25 3.6 46.4 7.1 F Yes 0
Tsung et al., 2014
major and minor
- - - - - - - no - pure 49.1, HA 31, H 16
-
Wu et al., 2014
major and minor
- - - - - - - yes -
Yu et al., 2014
major and minor
65 - 35 - - - - yes 0
Troisi et al., 2013
major and minor
7.2 7.6 17.5 24.2 14.8 16.1 0.9 ERH, 11.7 non-adjacent BS
yes 6 (2.7)
Ji et al., 2011
major and minor
15 5 35 20 0 25 0 yes 3 (15)
Berber et al., 2010
minor 0 0 47.8 52.2 0 0 0 yes -
LH - left hepatectomy, RH - right hepatectomy, LLS - left lateral sectionectomy, MS - monosegmentectomy, BS - bisegmentectomy, WR - wedge resection, ERH - extended right hepatectomy , ELH - extended left hepatectomy, F - fenestration, HA - hand assisted, H – hybrid. †A major liver resection was defined as three or more segments resected.
34
Study: Resection Type†
Surgical procedure, % of patients
Pringle Manoeuvre, number ( %)
LH RH LLS MS BS WR other Croner et al., 2016
minor - - - - - - - -
Kim et al., 2016
minor 0 0 100 0 0 0 0
Lai et al., 2016
major and minor
6 20 29 10 9 23 1 ELH, 3 caudectomy
53 (53)
Lee et al., 2015
major and minor
14.3
5.7
54.3
0 0 24.3
1.4 LLS+WR 0
Montalti et al., 2015
minor 0 0 0 16.7
16.7
41.7
25 20 (55.6)
Spampinato et al., 2014
major 28 68 0 0 0 0 4 ERH, 4 LLS + MS
0
Tranchart et al., 2014
minor 0 0 17.9
25 3.6 46.4
7.1 F 12 portal triad clamping
Tsung et al., 2014
major and minor
- - - - - - - -
Wu et al., 2014
major and minor
- - - - - - - -
Yu et al., 2014
major and minor
23 0 77 0 0 0 0 0
Troisi et al., 2013
major and minor
0 0 5 17.5
20 37 20 non-adjacent BS
18 (45)
Ji et al., 2011 major and minor
46 15 31 0 0 0 8 LH+caudate segmentectomy, + 1
0
Berber et al., 2010
minor 0 0 33.3
66.7
0 0 0 -
Table 11 – Surgical techniques for robotic liver resection
LH - left hepatectomy, RH - right hepatectomy, LLS - left lateral sectionectomy, MS - monosegmentectomy, BS - bisegmentectomy, TS - trisegmentectomy WR - wedge resection, ERH - extended right hepatectomy , ELH - extended left hepatectomy, F - fenestration. †A major liver resection was defined as three or more segments resected.
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