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Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis
HPB
https://doi.org/10.1016/j.hpb.2019.02.020
REVIEW ARTICLE
Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis Sivesh K. Kamarajah, Nathania Sutandi, Stuart R. Robinson, Jeremy J. French & Steven A. White Department of Hepatobiliary, Pancreatic and Transplant Surgery, Academic Department of Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
Abstract Background: Robotic surgery offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes in patients undergoing distal pancreatectomy through laparoscopic (LDP) or robotic (RDP) approaches. Method: A systematic literature search was conducted for studies reporting minimally invasive surgery for distal pancreatectomy. Meta-analysis of intraoperative (blood loss, operating times, conversion and R0 resections) and postoperative outcomes (overall complications, pancreatic fistula, length of hospital stay) was performed using random effects models. Result: Twenty non-randomised studies including 3112 patients (793 robotic and 2319 laparoscopic) were considered appropriate for inclusion. LDP had significantly shorter operating time than RDP (mean: 28, p < 0.001) but no significant difference in blood loss (mean: 52 mL, p = 0.07). RDP was associated with significantly lower conversion rates than LDP (OR 0.48, p < 0.001), but no difference in spleen preservation rate and R0 resection. There were no significant differences in overall and major complications, overall and high-grade pancreatic fistula. However, RDP was associated with a shorter length of hospital stay (mean: 1, p < 0.001). Conclusion: Robotic distal pancreatectomy appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomised trial comparing both techniques are needed. Received 8 November 2018; accepted 18 February 2019
Correspondence Kathir Kamarajah, Department of Hepatobiliary, Pancreatic and Transplant Surgery, Academic Department of Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK. E-mail: siveshkk93@ gmail.com
Introduction Over the last decade, robotic surgery has emerged as a viable alternative approach to conventional laparoscopic surgery. Potential theoretical advantages of current robotic surgical systems include 3D visualisation of the surgical field and improved instrument dexterity which may facilitate complex dissection and surgical reconstruction. In addition the use of an ergonomic surgical console may reduce surgeon fatigue for long and complex procedures.1 It may also encourage more surgeons to take up complex minimally invasive approaches which they previously would not have considered doing. Furthermore, robotic
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surgery has been demonstrated to be superior to conventional laparoscopic surgery in a variety of different complex surgical procedures. For example in radical prostatectomy the robotic approach has been associated with an earlier return of sexual function as compared to conventional laparoscopic surgery, which is attributed to an increased ability to preserve the cavernous nerve.2,3 A similar reduction in impotency rates have been reported in robotic rectal surgery, presumably for similar reasons.4 Distal pancreatectomy is employed in the management of both benign (e.g. cystic lesions, chronic pancreatitis) and
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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malignant lesions (e.g. pancreatic cancer, neuroendocrine tumors) affecting the body and tail of the pancreas but again uptake has been slow.5,6 A Pan-European cohort study (DIPLOMA) comparing minimally invasive and open surgery for distal pancreatectomy in patients with pancreatic ductal adenocarcinoma demonstrated blood loss and length of hospital stay was shorter in the minimally invasive group. However, R0 resection and number of harvested lymph nodes were higher in the open group.7 A recent Cochrane review comparing laparoscopic and open distal pancreatectomy for the management of pancreatic cancer found that the use of the laparoscopic approach did not impact on short-term survival, the incidence of pancreatic fistula or other serious complications. The laparoscopic approach was however associated with a shorter duration of hospital stay.8 It is possible that the use of a robotic approach may prove superior to both conventional laparoscopic and open surgery for complex pancreatic resection although this remains to be determined. To date, evidence on the benefit RDP over LDP is limited.9 Hence, the aim of this systematic review and meta-analysis were to evaluate the current evidence regarding RDP and ascertain what advantages, if any, this has over conventional laparoscopic approaches.
Methods Search strategy A systematic search of PubMed, EMBASE and the Cochrane Library databases were conducted on the 24th October 2018 by two independent investigators (SKK, NS). The search terms used were “robotic surgery”, “laparoscopic surgery”, “open surgery”, “distal pancreatectomy”, “left pancreatectomy”, “chronic pancreatitis”, “pancreatic cancer”, “pancreatic cyst”, “MCN”, “IPMN”, and “neuroendocrine tumour”, either individually or in combination. The ‘related articles’ function was used to broaden the search, and all citations were considered for relevance. A manual search of reference lists in recent reviews and eligible studies was also undertaken. This paper is reported according to the PRISMA guidelines and flow diagram presented in Fig. 1.10 Inclusion and exclusion criteria Inclusion criteria were: (i) studies reporting the use of minimally invasive surgery (robotic and laparoscopic) for distal pancreatectomy for benign and malignant indications; (ii) published in the English language. Exclusion criteria were: (i) Conference abstracts, review articles, and case reports (<5 patients); (ii) noncomparative analysis between minimally invasive surgery. After
Figure 1 PRISMA Diagram
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excluding duplicates, two researchers (SKK, NS) independently reviewed the titles and abstracts of studies identified by the literature search. Where a study was considered to be potentially relevant to the research question a full copy of the publication was obtained for further review. The reference lists of all included studies were hand-searched in order to identify other potentially relevant studies. Any areas of disagreement between the two primary researchers were resolved through discussion. Quality assessment The Newcastle-Ottawa scale was used to assess the quality of included studies.11,12 This was done by two different assessors by identifying three main factors, including “the selection of study groups, comparability of the group and ascertainment of exposure/outcome”, with a number of items ranging from one to four per domain for both cohort and case-control studies. Each item was given a maximum score of one or two and the total score determines the quality of each study as summarized in the table below (Table 1). Data extraction The following data were extracted from the papers: name of first author, year of publication, country of study conducted, study
design, number of patients in robotic and laparoscopic group, patients’ characteristics (age, gender, ASA score, BMI, pathology type, size of lesion, location of lesion), intra-operative variables (operative time, total blood loss, transfusion rate, conversion rate, spleen preservation rate, R0 margin status, lymph node harvested), and post-operative variables (length of stay, 90-days readmission rate, 90-days reoperation rate, complication rate, major complication rate, pancreatic fistula rate, high-grade pancreatic fistula rate). Definitions The robot docking time was included in the measurement of the operative time in the robotic group. Grade III to V complications based on the Clavien-Dindo classification were considered as major complications.13–16 Overall pancreatic fistula and clinically-relevant fistula were defined according to the International Study Group for Pancreatic Fistula (ISGPF) classification.17,18 Statistical analysis This systematic review and meta-analysis were conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines.19,20 For categorical variables,
Table 1 Details of included studies reporting minimally invasive surgery for distal pancreatectomy
Study Demographics
Number of Patients
Age, years
Male, %
BMI, kg/m2
Malignant, %
Name
Year Country
Design All
RDP
LDP
RDP
LDP
RDP LDP RDP
LDP
RDP
LDP
Waters29
2010 USA
RCS
35
17
18
64
59
35
50
NR
NR
0
11
Kang
30
2011 Korea
RCS
45
20
25
45 (16)
57 (14)
40
44
24 (3)
23 (3)
NR
NR
Daouadi31
2013 USA
RCS
124
30
94
59 (13)
59 (16)
33
35
28 (5)
29 (7)
43
15
Benizri32
2014 France
RCS
34
11
23
50 (21)
52 (15)
27
43
26 (6)
27 (5)
NR
NR
64 (13)
NR
Adam
23
2015 USA
RCS
535
61
474
65 (14)
46
52
NR
NR
NR
Butturini5
2015 Italy
PCS
43
22
21
54 (26–77) 55 (20–71) 23
29
25
24
NR
NR
Chen33
2015 China
PCS
119
69
50
56 (13)
57 (15)
33
36
25 (3)
25 (3)
23
22
Duran34
2015 Spain
RCS
34
16
18
61 (12)
58 (10)
56
50
NR
NR
75
78
35
Lai
2015 China
RCS
35
17
18
61 (10)
63 (18)
59
22
24 (2)
26 (3)
24
11
Lee28
2015 USA
RCS
168
37
131
58 (11)
58 (15)
27
44
29
28
NR
NR
2015 USA
RCS
34
18
16
67 (13)
60 (17)
56
63
27 (6)
25 (5)
NR
NR
2016 Germany
Ryan36 Eckhardt
37
RCS
41
12
29
49 (29–76) 59 (17–85) 33
41
23 (20–34) 27 (19–36) 0
7
Goh38
2017 Singapore RCS
39
8
31
57 (21–68) 56 (25–78) 25
58
28 (22–31) 24 (19–36) 100
13
Ielpo39
2017 Spain
RCS
54
28
26
60 (35–73) 61 (41–79) 57
65
24 (19–32) 25 (18–32) 54
50
Liu
2017 China
RCS
204
102
102
48 (16)
50 (15)
33
46
NR
NR
25
25
Morelli41
2017 Italy
RCS
30
15
15
58 (14)
49 (17)
13
40
26 (3)
27 (2)
0
0
Xourafas42 2017 USA
RCS
894
200
694
62 (22–88) 62 (19–89) 42
40
29 (15–55) 28 (17–59) 54
52
Zhang43
2017 China
RCS
74
43
31
48 (11)
Qu44
2018 China
RCS
70
35
35
Raoof45
2018 USA
RCS
704
99
605
40
49 (12)
47
39
24 (3)
23 (3)
100
100
58 (11)
58 (11)
63
63
24 (3)
24 (4)
100
100
NR
NR
45
53
NR
NR
100
100
LDP: laparoscopic distal pancreatectomy, NR: not reported, PCS: prospective cohort study, RCS: retrospective cohort study, RDP: robotic distal pancreatectomy.
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analysis was performed by calculating the odds ratio (OR). For survival data, analysis was performed by calculating the logarithm of the hazard ratio (HR) with 95% confidence intervals (CI95%). HR and its variance were extracted directly from the published manuscript. Where these data were not available it was determined through additional calculations that were dependent on the data presented by the study: annual mortality rates, survival curves, number of deaths, or percentage freedom from death.20,21 The random effects, the DerSimonian-Laird method was used for the meta-analysis of outcomes. Funnel plots were used to visually assess publication bias of included studies. Heterogeneity between studies was assessed using the I2 value in order to determine the degree of variation not attributable to chance alone. I2 values were considered to represent low, moderate, and high degrees of heterogeneity where values were <25%, 25–75%, and >75%, respectively. Funnel plot asymmetry was assessed using the Egger test. Statistical significance was considered when p < 0.05. Statistical analyses were performed using the RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011).
Results Patients’ characteristics and pre-operative variables This review included 20 studies involving 3316 patients (860 robotic and 2456 laparoscopic) undergoing distal pancreatectomy. Study-level and patient-level characteristics in RDP and LDP groups are listed in Tables 1 and 2 The age, gender, ASA score, BMI, pathology type, and size of lesion of the patients across the studies were similar between both groups. Summary of study quality and intraoperative and postoperative outcomes are presented in Tables 3 and 4 respectively. Intraoperative outcomes Eighteen studies reported operative times in both groups. Patients undergoing LDP had significantly shorter operating times than LDP (mean difference: 28 min, CI95%: 2–53 min, p < 0.001; I2 = 94%) (Fig. 2a). Fourteen studies reported blood loss in both groups. Patients undergoing RDP had less blood loss than RDP (mean difference: 52 mL, CI95%: 4–107 mL, p = 0.07; I2 = 98%) (Fig. 2b). Thirteen studies reported transfusion rates in both groups. There were no significant
Table 2 Study characteristics on pathology of distal pancreatectomy
Study Name Waters29 Kang
30
Study Year
Malignant, %
Pathology, RDP/LDP (n)
RDP
LDP
PDAC
NET
IPMN
MCN
SCN
SPN
Others
2010
0
11
0/2
5//5
6//2
3//3
1//2
NR
2/3
2011
NR
NR
1/1
3//3
2//10
5/2
4/3
4//4
1/2
Daouadi31
2013
43
15
13//14
9//21
5//11
4//30
NR
0//6
1//12
Benizri32
2014
NR
NR
0/3
2/7
1/3
2//4
2/3
3/2
1/1 NR
Adam
23
2015
NR
NR
33//234
24//197
NR
NR
NR
NR
Butturini5
2015
NR
NR
3/2
8/9
NR
6/7
0/2
3/1
2/0
Chen33
2015
23
22
15//9
3//3
6/5
26//16
NR
10//8
9//9
Duran34
2015
75
78
9/8
4/5
2/0
NR
NR
NR
NR
Lai35
2015
24
11
3/2
4//2
1/0
2//4
6//6
0/1
1/3
Lee28
2015
NR
NR
4//19
8//41
4//18
6//16
NR
2/7
13//30
Ryan36
2015
NR
NR
4//4
3//3
4//2
2//2
2/3
0/0
3/2
Eckhardt
37
2016
0
7
0/1
5//11
3/5
NR
NR
NR
0/1
Goh38
2017
100
13
NR
NR
NR
NR
NR
NR
NR
Ielpo39
50
15//13
6/7
4/3
NR
NR
NR
2/1
2017
54
40
2017
25
25
26//25
16//15
6//7
17//20
16//16
16//15
5/4
Morelli41
2017
0
0
NR
NR
NR
NR
NR
NR
NR
Xourafas42
2017
54
52
NR
NR
NR
NR
NR
NR
NR
Liu
Zhang
43
2017
100
100
0/0
43//31
0/0
0/0
0/0
0/0
0/0
Qu44
2018
100
100
35//35
0/0
0/0
0/0
0/0
0/0
0/0
Raoof45
2018
100
100
99//605
0/0
0/0
0/0
0/0
0/0
0/0
IPMN: intraductal papillary mucinous neoplasm, MCN: mucinous cystic neoplasm, LDP: laparoscopic distal pancreatectomy, NET: neuroendocrine tumour, NR: not reported, PDAC: pancreatic ductal adenocarcinoma, RDP: robotic distal pancreatectomy, SCN: serous cystic neoplasm, SPN: serous pseudopapillary neoplasm.
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Table 3 Study quality according to Newcastle Ottawa scale
Study Name
Study Year
Design
Selection
Comparability
Reliability
Total
Waters29
2010
RCS
3
2
3
8
Kang30
2011
RCS
3
1
3
7
Daouadi
31
2013
RCS
4
2
2
8
Benizri32
2014
RCS
4
2
2
8
Adam23
2015
RCS
4
2
2
8
Butturini
5
2015
PCS
4
1
2
7
Chen33
2015
PCS
4
2
3
9
Duran34
2015
RCS
3
2
2
7
Lai35
2015
RCS
4
2
3
9
Lee
2015
RCS
3
1
3
7
Ryan36
2015
RCS
3
1
2
6
Eckhardt37
2016
RCS
2
1
2
5
38
28
Goh
2017
RCS
4
2
3
9
Ielpo39
2017
RCS
3
1
2
6
Liu40
2017
RCS
4
2
3
9
Morelli
41
2017
RCS
3
1
1
5
Xourafas42
2017
RCS
4
2
3
9
Zhang43
2017
RCS
2
1
2
5
Qu44
2018
RCS
3
2
2
7
2018
RCS
4
2
3
9
Raoof
45
PCS: prospective cohort study, RCS: retrospective cohort study.
differences in transfusion rates between RDP and LDP (7% vs 7%, OR: 0.97, CI95%: 0.64–1.46, p = 0.87; I2 = 0%) (Fig. 2c). Eighteen studies reported conversion rates in both groups. Patients undergoing RDP had significantly lower conversion
rates between than LDP (8% vs 21%, OR: 0.48, CI95%: 0.35–0.67, p < 0.001; I2 = 10%) (Fig. 2d). Spleen preservation rate, lymph nodes harvested and R0 resection rates were reported in 16, 7 and 10 studies respectively.
Table 4 Summary of the meta-analysis regarding patients’ outcomes
Number of studies
OR/MD (CI95%)
p-value
I2 , %
Operative time
18
28 (2–53)
<0.001
94
Total blood loss
14
−52 (−107 - (−)4)
0.07
98
Transfusion rate
13
0.97 (0.64–1.46)
0.87
0
Conversion rate
18
0.48 (0.35–0.67)
<0.001
10
Spleen-preservation rate
16
1.38 (0.82–2.32)
0.22
58
Lymph node harvested
7
0.95 (−0.45 - 2.35)
0.18
84
R0 resection rate
10
1.01 (0.59–1.73)
0.97
0
Overall complications
14
0.87 (0.66–1.14)
0.31
0
Major complications
10
1.09 (0.60–1.95)
0.78
34
Overall pancreatic fistula
16
0.95 (0.75–1.20)
0.65
0
Clinically-relevant pancreatic fistula
13
0.78 (0.49–1.23)
0.29
0
Length of stay
20
−1.21 (−1.88 - (−)0.54)
<0.001
61
90-days readmission rate
8
1.31 (0.94–1.83)
0.11
0
90-days reoperation rate
10
0.78 (0.41–1.50)
0.46
0
Outcomes Intraoperative
Post-operative
MD: mean difference, OR: odds ratio.
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Figure 2 Summary of intraoperative outcomes comparing robotic and laparoscopic surgery
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© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 2 (continued)
There were no significant differences in rates between RDP and LDP for spleen preservation (33% vs 21%, OR: 1.38, CI95%: 0.82–2.32, p = 0.22; I2 = 58%; Fig. 2e), lymph nodes harvested (mean difference: 0.95, CI95%: −0.45 - 2.35, p = 0.18; I2 = 84%; Fig. 2f) and R0 resection (95% vs 89%%, OR: 1.01, CI95%: 0.59–1.73, p = 0.97; I2 = 0%; Fig. 2g). Post-operative outcomes Overall and major complications were reported in 14 and 10 studies respectively. There were no significant differences in rates between RDP and LDP for overall (40% vs 49%, OR: 0.87, CI95%: 0.66–1.14, p = 0.31; I2 = 0%; Fig. 3a) and major complications (12% vs 15%, OR: 1.09, CI95%: 0.60–1.95, p = 0.78; I2 = 34%; Fig. 3b). Overall and clinically-relevant pancreatic fistula rates were reported in 16 and 13 studies respectively. All studies
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reporting pancreatic fistula were defined according to the ISGPF 2005 definitions. There were no significant differences in rates between RDP and LDP for overall pancreatic fistula (25% vs 23%, OR: 0.95, CI95%: 0.75–1.20, p = 0.65; I2 = 0%; Fig. 3c) and clinically-relevant pancreatic fistula (8% vs 8%, OR: 0.78, CI95%: 0.49–1.23, p = 0.29; I2 = 0%; Fig. 3d). Length of hospital stay was reported in all 20 studies. Patients undergoing RDP had significantly shorter hospital stay than LDP (mean difference: 1.21, CI95%: 0.54–1.88, p < 0.001; I2 = 61%; Fig. 3e). Readmission and reoperation at 90-days were reported in 8 and 10 studies respectively. There were no significant differences in rates between RDP and LDP for 90-day readmission (12% vs 12%, OR: 1.31, CI95%: 0.94–1.83, p = 0.11; I2 = 0%; Fig. 3f) and 90-day reoperation (3% vs 3%, OR: 0.78, CI95%: 0.41–1.50, p = 0.46; I2 = 0%; Fig. 3g).
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 3 Summary of postoperative outcomes comparing robotic and laparoscopic surgery HPB 2019, 21, 1107–1118
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Figure 3 (continued).
Publication biases Funnel plot analysis for the intra-operative and post-operative variables was done to assess the possibility of publication bias. All of the studies were within 95% CI and there was no evidence of publication bias in this study for all outcomes studied.
Discussion Minimally invasive surgery for pancreatic surgery remains behind other surgical specialities such as upper and lower gastrointestinal surgery as well as urology. Over the last decade,
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many centres have adapted laparoscopic and robotic approaches for various HPB procedures, specifically pancreatic resection still remains unpopular but it is increasing. There is still limited data and no general consensus regarding the translatability of MIV distal pancreatic resections for improving clinical outcomes. Although this question maybe answered by the DIPLOMA trial which is currently recruiting. This systematic review and metaanalysis highlights (i) current evidence supporting RDP is weak and limited to retrospective cohort studies (ii) RDP is safe and has comparable outcomes to LDP (iii) RDP is associated with a lower conversion rate and a marginally shorter hospital
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stay but, (iv) RDP is associated with longer operating times, likely a result of surgeons being at an earlier stage in their learning curve, which highlights the need for ongoing application in routine clinical practise. Where appropriate, splenic preservation during distal pancreatectomy offers significant advantages for patients, not only with regard to reduced peri-operative complications but also in the longer term with the avoidance of altered immune function.22 This review has demonstrated that RDP is associated with a higher rate of splenic preservation, although not reaching significance. This is thought to be due to improved instrument dexterity and 3D visualisation of the operative field that robotic surgery offers, although further studies are needed to elucidate a clear benefit of robotic surgery for spleen preservation. These technical advantages also likely account for the demonstrated reduced conversion rates and trend towards decreased blood loss. The low numbers of patients with adenocarcinoma within the included studies means that the impact of RDP on cancer related surgical margins (e.g. R0 resection rates, recurrence) was not analysed. The adoption of minimally invasive distal pancreatectomy for the treatment of adenocarcinoma has been somewhat limited, as compared to other indications, primarily due to surgeon concerns related to compromised outcomes.23–26 In a recent propensity matched cohort study of laparoscopic vs. open distal pancreatectomy for pancreatic ductal adenocarcinoma it has been demonstrated that the laparoscopic approach is associated with a reduced R0 resection rate and less radical surgery although this did not ultimately impact on long term patient survival.7 Whilst this review did not evaluate the costs associated with RDP it has been well described elsewhere that this procedure does typically incur an increased cost for the institution.27 Of the studies included in this review that of Kang et al. reported an additional cost for RDP of $4443 (US) and that of Butturini an additional cost of V1516.5,28 In contrast, Waters et al. reported a cost saving of $2398 (US) as a consequence of the reduced hospital stay associated with RDP in that study.29 Although it is perceived that over coming years the development of new robotic systems and increased competition in the marketplace will lower the cost of robotic surgery making it more accessible for institutions and making RDP more likely to achieve at least cost neutrality when compared to LDP. Furthermore, lower conversion rates and shorter hospital stays as shown in this review may translate to lower total hospital costs overall, although this is yet to be proven. Nevertheless, it is also just as likely that robotic systems will become technologically more advanced thus actually increasing cost. Our review has strengths important to note such as: (i) inclusion of more studies than any previous meta-analyses, (ii) high-quality rating of all included studies, and (iii) detailed data extraction. This review has limitations important to address. Firstly, all studies included in this review were mainly retrospective lacking any randomised controlled trials. This may
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reflect that RDP is still in the early phase of the learning curve. Secondly, none of the studies has evaluated the long-term outcomes, which limits our ability to draw useful prognostic conclusions and quality of life. Finally, all studies in this review do not stratify splenic preservation for benign and malignant indication which are useful to know as the spleen is often removed in the latter to obtain clear margins.
Conclusion In summary, this systematic review and meta-analysis comparing RDP and LDP suggests that both techniques can be used safely for both benign and malignant cases. RDP appears to offer some advantages compared to LDP although both techniques appear equivalent. Further studies in particular a RCT is badly needed to enable us to draw useful conclusions regarding patients’ survival, quality of life, and long-term oncological outcome. Funding source None declared. Conflict of interest None declared.
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© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
https://doi.org/10.1016/j.hpb.2019.02.020
REVIEW ARTICLE
Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis Sivesh K. Kamarajah, Nathania Sutandi, Stuart R. Robinson, Jeremy J. French & Steven A. White Department of Hepatobiliary, Pancreatic and Transplant Surgery, Academic Department of Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
Abstract Background: Robotic surgery offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes in patients undergoing distal pancreatectomy through laparoscopic (LDP) or robotic (RDP) approaches. Method: A systematic literature search was conducted for studies reporting minimally invasive surgery for distal pancreatectomy. Meta-analysis of intraoperative (blood loss, operating times, conversion and R0 resections) and postoperative outcomes (overall complications, pancreatic fistula, length of hospital stay) was performed using random effects models. Result: Twenty non-randomised studies including 3112 patients (793 robotic and 2319 laparoscopic) were considered appropriate for inclusion. LDP had significantly shorter operating time than RDP (mean: 28, p < 0.001) but no significant difference in blood loss (mean: 52 mL, p = 0.07). RDP was associated with significantly lower conversion rates than LDP (OR 0.48, p < 0.001), but no difference in spleen preservation rate and R0 resection. There were no significant differences in overall and major complications, overall and high-grade pancreatic fistula. However, RDP was associated with a shorter length of hospital stay (mean: 1, p < 0.001). Conclusion: Robotic distal pancreatectomy appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomised trial comparing both techniques are needed. Received 8 November 2018; accepted 18 February 2019
Correspondence Kathir Kamarajah, Department of Hepatobiliary, Pancreatic and Transplant Surgery, Academic Department of Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK. E-mail: siveshkk93@ gmail.com
Introduction Over the last decade, robotic surgery has emerged as a viable alternative approach to conventional laparoscopic surgery. Potential theoretical advantages of current robotic surgical systems include 3D visualisation of the surgical field and improved instrument dexterity which may facilitate complex dissection and surgical reconstruction. In addition the use of an ergonomic surgical console may reduce surgeon fatigue for long and complex procedures.1 It may also encourage more surgeons to take up complex minimally invasive approaches which they previously would not have considered doing. Furthermore, robotic
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surgery has been demonstrated to be superior to conventional laparoscopic surgery in a variety of different complex surgical procedures. For example in radical prostatectomy the robotic approach has been associated with an earlier return of sexual function as compared to conventional laparoscopic surgery, which is attributed to an increased ability to preserve the cavernous nerve.2,3 A similar reduction in impotency rates have been reported in robotic rectal surgery, presumably for similar reasons.4 Distal pancreatectomy is employed in the management of both benign (e.g. cystic lesions, chronic pancreatitis) and
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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malignant lesions (e.g. pancreatic cancer, neuroendocrine tumors) affecting the body and tail of the pancreas but again uptake has been slow.5,6 A Pan-European cohort study (DIPLOMA) comparing minimally invasive and open surgery for distal pancreatectomy in patients with pancreatic ductal adenocarcinoma demonstrated blood loss and length of hospital stay was shorter in the minimally invasive group. However, R0 resection and number of harvested lymph nodes were higher in the open group.7 A recent Cochrane review comparing laparoscopic and open distal pancreatectomy for the management of pancreatic cancer found that the use of the laparoscopic approach did not impact on short-term survival, the incidence of pancreatic fistula or other serious complications. The laparoscopic approach was however associated with a shorter duration of hospital stay.8 It is possible that the use of a robotic approach may prove superior to both conventional laparoscopic and open surgery for complex pancreatic resection although this remains to be determined. To date, evidence on the benefit RDP over LDP is limited.9 Hence, the aim of this systematic review and meta-analysis were to evaluate the current evidence regarding RDP and ascertain what advantages, if any, this has over conventional laparoscopic approaches.
Methods Search strategy A systematic search of PubMed, EMBASE and the Cochrane Library databases were conducted on the 24th October 2018 by two independent investigators (SKK, NS). The search terms used were “robotic surgery”, “laparoscopic surgery”, “open surgery”, “distal pancreatectomy”, “left pancreatectomy”, “chronic pancreatitis”, “pancreatic cancer”, “pancreatic cyst”, “MCN”, “IPMN”, and “neuroendocrine tumour”, either individually or in combination. The ‘related articles’ function was used to broaden the search, and all citations were considered for relevance. A manual search of reference lists in recent reviews and eligible studies was also undertaken. This paper is reported according to the PRISMA guidelines and flow diagram presented in Fig. 1.10 Inclusion and exclusion criteria Inclusion criteria were: (i) studies reporting the use of minimally invasive surgery (robotic and laparoscopic) for distal pancreatectomy for benign and malignant indications; (ii) published in the English language. Exclusion criteria were: (i) Conference abstracts, review articles, and case reports (<5 patients); (ii) noncomparative analysis between minimally invasive surgery. After
Figure 1 PRISMA Diagram
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excluding duplicates, two researchers (SKK, NS) independently reviewed the titles and abstracts of studies identified by the literature search. Where a study was considered to be potentially relevant to the research question a full copy of the publication was obtained for further review. The reference lists of all included studies were hand-searched in order to identify other potentially relevant studies. Any areas of disagreement between the two primary researchers were resolved through discussion. Quality assessment The Newcastle-Ottawa scale was used to assess the quality of included studies.11,12 This was done by two different assessors by identifying three main factors, including “the selection of study groups, comparability of the group and ascertainment of exposure/outcome”, with a number of items ranging from one to four per domain for both cohort and case-control studies. Each item was given a maximum score of one or two and the total score determines the quality of each study as summarized in the table below (Table 1). Data extraction The following data were extracted from the papers: name of first author, year of publication, country of study conducted, study
design, number of patients in robotic and laparoscopic group, patients’ characteristics (age, gender, ASA score, BMI, pathology type, size of lesion, location of lesion), intra-operative variables (operative time, total blood loss, transfusion rate, conversion rate, spleen preservation rate, R0 margin status, lymph node harvested), and post-operative variables (length of stay, 90-days readmission rate, 90-days reoperation rate, complication rate, major complication rate, pancreatic fistula rate, high-grade pancreatic fistula rate). Definitions The robot docking time was included in the measurement of the operative time in the robotic group. Grade III to V complications based on the Clavien-Dindo classification were considered as major complications.13–16 Overall pancreatic fistula and clinically-relevant fistula were defined according to the International Study Group for Pancreatic Fistula (ISGPF) classification.17,18 Statistical analysis This systematic review and meta-analysis were conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines.19,20 For categorical variables,
Table 1 Details of included studies reporting minimally invasive surgery for distal pancreatectomy
Study Demographics
Number of Patients
Age, years
Male, %
BMI, kg/m2
Malignant, %
Name
Year Country
Design All
RDP
LDP
RDP
LDP
RDP LDP RDP
LDP
RDP
LDP
Waters29
2010 USA
RCS
35
17
18
64
59
35
50
NR
NR
0
11
Kang
30
2011 Korea
RCS
45
20
25
45 (16)
57 (14)
40
44
24 (3)
23 (3)
NR
NR
Daouadi31
2013 USA
RCS
124
30
94
59 (13)
59 (16)
33
35
28 (5)
29 (7)
43
15
Benizri32
2014 France
RCS
34
11
23
50 (21)
52 (15)
27
43
26 (6)
27 (5)
NR
NR
64 (13)
NR
Adam
23
2015 USA
RCS
535
61
474
65 (14)
46
52
NR
NR
NR
Butturini5
2015 Italy
PCS
43
22
21
54 (26–77) 55 (20–71) 23
29
25
24
NR
NR
Chen33
2015 China
PCS
119
69
50
56 (13)
57 (15)
33
36
25 (3)
25 (3)
23
22
Duran34
2015 Spain
RCS
34
16
18
61 (12)
58 (10)
56
50
NR
NR
75
78
35
Lai
2015 China
RCS
35
17
18
61 (10)
63 (18)
59
22
24 (2)
26 (3)
24
11
Lee28
2015 USA
RCS
168
37
131
58 (11)
58 (15)
27
44
29
28
NR
NR
2015 USA
RCS
34
18
16
67 (13)
60 (17)
56
63
27 (6)
25 (5)
NR
NR
2016 Germany
Ryan36 Eckhardt
37
RCS
41
12
29
49 (29–76) 59 (17–85) 33
41
23 (20–34) 27 (19–36) 0
7
Goh38
2017 Singapore RCS
39
8
31
57 (21–68) 56 (25–78) 25
58
28 (22–31) 24 (19–36) 100
13
Ielpo39
2017 Spain
RCS
54
28
26
60 (35–73) 61 (41–79) 57
65
24 (19–32) 25 (18–32) 54
50
Liu
2017 China
RCS
204
102
102
48 (16)
50 (15)
33
46
NR
NR
25
25
Morelli41
2017 Italy
RCS
30
15
15
58 (14)
49 (17)
13
40
26 (3)
27 (2)
0
0
Xourafas42 2017 USA
RCS
894
200
694
62 (22–88) 62 (19–89) 42
40
29 (15–55) 28 (17–59) 54
52
Zhang43
2017 China
RCS
74
43
31
48 (11)
Qu44
2018 China
RCS
70
35
35
Raoof45
2018 USA
RCS
704
99
605
40
49 (12)
47
39
24 (3)
23 (3)
100
100
58 (11)
58 (11)
63
63
24 (3)
24 (4)
100
100
NR
NR
45
53
NR
NR
100
100
LDP: laparoscopic distal pancreatectomy, NR: not reported, PCS: prospective cohort study, RCS: retrospective cohort study, RDP: robotic distal pancreatectomy.
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analysis was performed by calculating the odds ratio (OR). For survival data, analysis was performed by calculating the logarithm of the hazard ratio (HR) with 95% confidence intervals (CI95%). HR and its variance were extracted directly from the published manuscript. Where these data were not available it was determined through additional calculations that were dependent on the data presented by the study: annual mortality rates, survival curves, number of deaths, or percentage freedom from death.20,21 The random effects, the DerSimonian-Laird method was used for the meta-analysis of outcomes. Funnel plots were used to visually assess publication bias of included studies. Heterogeneity between studies was assessed using the I2 value in order to determine the degree of variation not attributable to chance alone. I2 values were considered to represent low, moderate, and high degrees of heterogeneity where values were <25%, 25–75%, and >75%, respectively. Funnel plot asymmetry was assessed using the Egger test. Statistical significance was considered when p < 0.05. Statistical analyses were performed using the RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011).
Results Patients’ characteristics and pre-operative variables This review included 20 studies involving 3316 patients (860 robotic and 2456 laparoscopic) undergoing distal pancreatectomy. Study-level and patient-level characteristics in RDP and LDP groups are listed in Tables 1 and 2 The age, gender, ASA score, BMI, pathology type, and size of lesion of the patients across the studies were similar between both groups. Summary of study quality and intraoperative and postoperative outcomes are presented in Tables 3 and 4 respectively. Intraoperative outcomes Eighteen studies reported operative times in both groups. Patients undergoing LDP had significantly shorter operating times than LDP (mean difference: 28 min, CI95%: 2–53 min, p < 0.001; I2 = 94%) (Fig. 2a). Fourteen studies reported blood loss in both groups. Patients undergoing RDP had less blood loss than RDP (mean difference: 52 mL, CI95%: 4–107 mL, p = 0.07; I2 = 98%) (Fig. 2b). Thirteen studies reported transfusion rates in both groups. There were no significant
Table 2 Study characteristics on pathology of distal pancreatectomy
Study Name Waters29 Kang
30
Study Year
Malignant, %
Pathology, RDP/LDP (n)
RDP
LDP
PDAC
NET
IPMN
MCN
SCN
SPN
Others
2010
0
11
0/2
5//5
6//2
3//3
1//2
NR
2/3
2011
NR
NR
1/1
3//3
2//10
5/2
4/3
4//4
1/2
Daouadi31
2013
43
15
13//14
9//21
5//11
4//30
NR
0//6
1//12
Benizri32
2014
NR
NR
0/3
2/7
1/3
2//4
2/3
3/2
1/1 NR
Adam
23
2015
NR
NR
33//234
24//197
NR
NR
NR
NR
Butturini5
2015
NR
NR
3/2
8/9
NR
6/7
0/2
3/1
2/0
Chen33
2015
23
22
15//9
3//3
6/5
26//16
NR
10//8
9//9
Duran34
2015
75
78
9/8
4/5
2/0
NR
NR
NR
NR
Lai35
2015
24
11
3/2
4//2
1/0
2//4
6//6
0/1
1/3
Lee28
2015
NR
NR
4//19
8//41
4//18
6//16
NR
2/7
13//30
Ryan36
2015
NR
NR
4//4
3//3
4//2
2//2
2/3
0/0
3/2
Eckhardt
37
2016
0
7
0/1
5//11
3/5
NR
NR
NR
0/1
Goh38
2017
100
13
NR
NR
NR
NR
NR
NR
NR
Ielpo39
50
15//13
6/7
4/3
NR
NR
NR
2/1
2017
54
40
2017
25
25
26//25
16//15
6//7
17//20
16//16
16//15
5/4
Morelli41
2017
0
0
NR
NR
NR
NR
NR
NR
NR
Xourafas42
2017
54
52
NR
NR
NR
NR
NR
NR
NR
Liu
Zhang
43
2017
100
100
0/0
43//31
0/0
0/0
0/0
0/0
0/0
Qu44
2018
100
100
35//35
0/0
0/0
0/0
0/0
0/0
0/0
Raoof45
2018
100
100
99//605
0/0
0/0
0/0
0/0
0/0
0/0
IPMN: intraductal papillary mucinous neoplasm, MCN: mucinous cystic neoplasm, LDP: laparoscopic distal pancreatectomy, NET: neuroendocrine tumour, NR: not reported, PDAC: pancreatic ductal adenocarcinoma, RDP: robotic distal pancreatectomy, SCN: serous cystic neoplasm, SPN: serous pseudopapillary neoplasm.
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Table 3 Study quality according to Newcastle Ottawa scale
Study Name
Study Year
Design
Selection
Comparability
Reliability
Total
Waters29
2010
RCS
3
2
3
8
Kang30
2011
RCS
3
1
3
7
Daouadi
31
2013
RCS
4
2
2
8
Benizri32
2014
RCS
4
2
2
8
Adam23
2015
RCS
4
2
2
8
Butturini
5
2015
PCS
4
1
2
7
Chen33
2015
PCS
4
2
3
9
Duran34
2015
RCS
3
2
2
7
Lai35
2015
RCS
4
2
3
9
Lee
2015
RCS
3
1
3
7
Ryan36
2015
RCS
3
1
2
6
Eckhardt37
2016
RCS
2
1
2
5
38
28
Goh
2017
RCS
4
2
3
9
Ielpo39
2017
RCS
3
1
2
6
Liu40
2017
RCS
4
2
3
9
Morelli
41
2017
RCS
3
1
1
5
Xourafas42
2017
RCS
4
2
3
9
Zhang43
2017
RCS
2
1
2
5
Qu44
2018
RCS
3
2
2
7
2018
RCS
4
2
3
9
Raoof
45
PCS: prospective cohort study, RCS: retrospective cohort study.
differences in transfusion rates between RDP and LDP (7% vs 7%, OR: 0.97, CI95%: 0.64–1.46, p = 0.87; I2 = 0%) (Fig. 2c). Eighteen studies reported conversion rates in both groups. Patients undergoing RDP had significantly lower conversion
rates between than LDP (8% vs 21%, OR: 0.48, CI95%: 0.35–0.67, p < 0.001; I2 = 10%) (Fig. 2d). Spleen preservation rate, lymph nodes harvested and R0 resection rates were reported in 16, 7 and 10 studies respectively.
Table 4 Summary of the meta-analysis regarding patients’ outcomes
Number of studies
OR/MD (CI95%)
p-value
I2 , %
Operative time
18
28 (2–53)
<0.001
94
Total blood loss
14
−52 (−107 - (−)4)
0.07
98
Transfusion rate
13
0.97 (0.64–1.46)
0.87
0
Conversion rate
18
0.48 (0.35–0.67)
<0.001
10
Spleen-preservation rate
16
1.38 (0.82–2.32)
0.22
58
Lymph node harvested
7
0.95 (−0.45 - 2.35)
0.18
84
R0 resection rate
10
1.01 (0.59–1.73)
0.97
0
Overall complications
14
0.87 (0.66–1.14)
0.31
0
Major complications
10
1.09 (0.60–1.95)
0.78
34
Overall pancreatic fistula
16
0.95 (0.75–1.20)
0.65
0
Clinically-relevant pancreatic fistula
13
0.78 (0.49–1.23)
0.29
0
Length of stay
20
−1.21 (−1.88 - (−)0.54)
<0.001
61
90-days readmission rate
8
1.31 (0.94–1.83)
0.11
0
90-days reoperation rate
10
0.78 (0.41–1.50)
0.46
0
Outcomes Intraoperative
Post-operative
MD: mean difference, OR: odds ratio.
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© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 2 Summary of intraoperative outcomes comparing robotic and laparoscopic surgery
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© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 2 (continued)
There were no significant differences in rates between RDP and LDP for spleen preservation (33% vs 21%, OR: 1.38, CI95%: 0.82–2.32, p = 0.22; I2 = 58%; Fig. 2e), lymph nodes harvested (mean difference: 0.95, CI95%: −0.45 - 2.35, p = 0.18; I2 = 84%; Fig. 2f) and R0 resection (95% vs 89%%, OR: 1.01, CI95%: 0.59–1.73, p = 0.97; I2 = 0%; Fig. 2g). Post-operative outcomes Overall and major complications were reported in 14 and 10 studies respectively. There were no significant differences in rates between RDP and LDP for overall (40% vs 49%, OR: 0.87, CI95%: 0.66–1.14, p = 0.31; I2 = 0%; Fig. 3a) and major complications (12% vs 15%, OR: 1.09, CI95%: 0.60–1.95, p = 0.78; I2 = 34%; Fig. 3b). Overall and clinically-relevant pancreatic fistula rates were reported in 16 and 13 studies respectively. All studies
HPB 2019, 21, 1107–1118
reporting pancreatic fistula were defined according to the ISGPF 2005 definitions. There were no significant differences in rates between RDP and LDP for overall pancreatic fistula (25% vs 23%, OR: 0.95, CI95%: 0.75–1.20, p = 0.65; I2 = 0%; Fig. 3c) and clinically-relevant pancreatic fistula (8% vs 8%, OR: 0.78, CI95%: 0.49–1.23, p = 0.29; I2 = 0%; Fig. 3d). Length of hospital stay was reported in all 20 studies. Patients undergoing RDP had significantly shorter hospital stay than LDP (mean difference: 1.21, CI95%: 0.54–1.88, p < 0.001; I2 = 61%; Fig. 3e). Readmission and reoperation at 90-days were reported in 8 and 10 studies respectively. There were no significant differences in rates between RDP and LDP for 90-day readmission (12% vs 12%, OR: 1.31, CI95%: 0.94–1.83, p = 0.11; I2 = 0%; Fig. 3f) and 90-day reoperation (3% vs 3%, OR: 0.78, CI95%: 0.41–1.50, p = 0.46; I2 = 0%; Fig. 3g).
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 3 Summary of postoperative outcomes comparing robotic and laparoscopic surgery HPB 2019, 21, 1107–1118
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 3 (continued).
Publication biases Funnel plot analysis for the intra-operative and post-operative variables was done to assess the possibility of publication bias. All of the studies were within 95% CI and there was no evidence of publication bias in this study for all outcomes studied.
Discussion Minimally invasive surgery for pancreatic surgery remains behind other surgical specialities such as upper and lower gastrointestinal surgery as well as urology. Over the last decade,
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many centres have adapted laparoscopic and robotic approaches for various HPB procedures, specifically pancreatic resection still remains unpopular but it is increasing. There is still limited data and no general consensus regarding the translatability of MIV distal pancreatic resections for improving clinical outcomes. Although this question maybe answered by the DIPLOMA trial which is currently recruiting. This systematic review and metaanalysis highlights (i) current evidence supporting RDP is weak and limited to retrospective cohort studies (ii) RDP is safe and has comparable outcomes to LDP (iii) RDP is associated with a lower conversion rate and a marginally shorter hospital
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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stay but, (iv) RDP is associated with longer operating times, likely a result of surgeons being at an earlier stage in their learning curve, which highlights the need for ongoing application in routine clinical practise. Where appropriate, splenic preservation during distal pancreatectomy offers significant advantages for patients, not only with regard to reduced peri-operative complications but also in the longer term with the avoidance of altered immune function.22 This review has demonstrated that RDP is associated with a higher rate of splenic preservation, although not reaching significance. This is thought to be due to improved instrument dexterity and 3D visualisation of the operative field that robotic surgery offers, although further studies are needed to elucidate a clear benefit of robotic surgery for spleen preservation. These technical advantages also likely account for the demonstrated reduced conversion rates and trend towards decreased blood loss. The low numbers of patients with adenocarcinoma within the included studies means that the impact of RDP on cancer related surgical margins (e.g. R0 resection rates, recurrence) was not analysed. The adoption of minimally invasive distal pancreatectomy for the treatment of adenocarcinoma has been somewhat limited, as compared to other indications, primarily due to surgeon concerns related to compromised outcomes.23–26 In a recent propensity matched cohort study of laparoscopic vs. open distal pancreatectomy for pancreatic ductal adenocarcinoma it has been demonstrated that the laparoscopic approach is associated with a reduced R0 resection rate and less radical surgery although this did not ultimately impact on long term patient survival.7 Whilst this review did not evaluate the costs associated with RDP it has been well described elsewhere that this procedure does typically incur an increased cost for the institution.27 Of the studies included in this review that of Kang et al. reported an additional cost for RDP of $4443 (US) and that of Butturini an additional cost of V1516.5,28 In contrast, Waters et al. reported a cost saving of $2398 (US) as a consequence of the reduced hospital stay associated with RDP in that study.29 Although it is perceived that over coming years the development of new robotic systems and increased competition in the marketplace will lower the cost of robotic surgery making it more accessible for institutions and making RDP more likely to achieve at least cost neutrality when compared to LDP. Furthermore, lower conversion rates and shorter hospital stays as shown in this review may translate to lower total hospital costs overall, although this is yet to be proven. Nevertheless, it is also just as likely that robotic systems will become technologically more advanced thus actually increasing cost. Our review has strengths important to note such as: (i) inclusion of more studies than any previous meta-analyses, (ii) high-quality rating of all included studies, and (iii) detailed data extraction. This review has limitations important to address. Firstly, all studies included in this review were mainly retrospective lacking any randomised controlled trials. This may
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reflect that RDP is still in the early phase of the learning curve. Secondly, none of the studies has evaluated the long-term outcomes, which limits our ability to draw useful prognostic conclusions and quality of life. Finally, all studies in this review do not stratify splenic preservation for benign and malignant indication which are useful to know as the spleen is often removed in the latter to obtain clear margins.
Conclusion In summary, this systematic review and meta-analysis comparing RDP and LDP suggests that both techniques can be used safely for both benign and malignant cases. RDP appears to offer some advantages compared to LDP although both techniques appear equivalent. Further studies in particular a RCT is badly needed to enable us to draw useful conclusions regarding patients’ survival, quality of life, and long-term oncological outcome. Funding source None declared. Conflict of interest None declared.
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© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.