Q1 Recommendations

The 2nd International Consensus Conference on Laparoscopic Liver Resection

Question 1 (Q1):

What are the comparative short term outcomes of LLR and OLR? (minor and major)

LLR: laparoscopic liver resectionOLR: open liver resection

Q 1 Working groupCoordinator

Daniel CherquiLiterature Review

Ruben CiriaWorking group

Mohamed Abu-Hilal Luca Adrighetti Kuo-Hsin Chen David GellerHiranori KanekoJuan Pekolj Olivier Scatton

Conference ChairmanGo Wakabayashi

Methods:

This document is based on a comprehensive review of the literature as of July 30, 2014. This review is summarized in the accompanying table. This is the largest review since the report by Nguyen and Geller published in 2009.

The MEDLINE, Ovid, Embase, PubMed, and Cochrane databases were searched. The following keywords were used: laparoscopy, hepatectomy, laparoscopic, open, liver resection, liver surgery, and minimally invasive surgery. Laparoscopic cyst unroofings were eliminated from analysis.

A Pubmed search on laparoscopic liver resection and the evolution of published articles by year as of 20 August 2014 is showed below. 2416 articles are listed under this search. Three, 6, 60, 157 and 226 articles on laparoscopic liver resection were

published in 1992, 2000, 2008 (year of the first consensus meeting in Louisville) and 2013, respectively.

1992 2002 2008 2013

No randomized trials are available. All data have been reported as case series, case–control studies, reviews and meta-analyses. Most data were obtained from prospectively maintained databases.

455 articles were found. 265 papers were not analyzed as they were either purely technical, or compared devices, or were about living donor hepatectomy. There were 23 reviews, including one Cochrane review, and 12 meta-analyses addressing short term outcomes.

155 articles were analyzed, including 81 comparative studies and 83 cases series (164 series reported in 155 articles). Among 81 comparative series, 31 addressed minor resections only, 42 a mix of minor and major, and 8 major resection only.

Data used to build these recommendations are mainly based on comparative studies and meta-analyses.

A. General features of reported cases:

1. Number of cases:

Comparative studies included 2868 LLR and 3212 OLR patients, respectively. Case series included 6300 laparoscopic liver resection patients. Efforts were made to

identify duplicated patients (i.e. same patients reported several times in sequential case series from one team or reported in case-series and comparative studies). However, it is likely that some duplicated cases were missed. Therefore, the total number of 9168 reported LLRs is probably overestimated and it seems reasonable to state that approximately 8000 LLRs have been reported.

World-wide, 93 surgical centers have published a series of LLRs including 17 centers reporting series of 100 patients or more. Geographical distribution was Asia 36 and 7, Americas 24 and 4, and Europe 33 and 6, for global reports and series>100 cases, respectively.

2. Applicability:

The proportion of open and laparoscopic resections is rarely mentioned in series. From available data and personal or congress communications, it seems that despite the increasing number of centers reporting their experience in laparoscopic liver surgery, the laparoscopic approach is still generally offered to a small percentage of liver resections (range 5–30%). However, some groups have reported higher rates, reaching 50–80%.

3. Indications:

Indications do not differ from those of open surgery. Technical feasibility has been reported as the only limiting factor.

In the case of benign tumors, these included mainly symptomatic or doubtful lesions, although occasional reports included resection of incidental asymptomatic benign lesions.

In the case of malignant lesions, colorectal metastases and hepatocellular carcinoma have been the main indications, as in open surgery.

Noncolorectal metastases are the next most commonly reported indications. Few resections for peripheral cholangiocarcinoma have been reported.

Although reported by a few authors, laparoscopic resection has been considered a contra-indication by most teams in cases of gallbladder cancer and hilar cholangiocarcinoma, because of the reported risk of the peritoneal tumor spreading and the necessary extensive resections with possible vascular reconstruction.

Similarly, bilobar colorectal liver metastases have been rarely reported, because of the need for thorough liver exploration, including palpation, and the need for complex multiple partial hepatectomies. However, the potential role and advantage of the laparoscopic approach for two stage-hepatectomies for colorectal metastases has been raisedby some authors, including for the ALPPS procedure. However, only anecdotal cases have been reported so far.

4. Types of resections and patient selection:

Despite the increasing number of centers reporting major resections, these represented less than 20% of the reported cases in the literature. Two criteria have been considered by most authors, i.e. tumor size and location

Size: Except for exophytic lesions which are easy to resect by laparoscopy, even if large in size, laparoscopy has been seldom reported for lesions exceeding 5 cm in diameter presumably because of difficult tumor mobilization and risks of rupture or inadequate margin. However, some authors have not adopted a size limitation for the laparoscopic approach and resections of intrahepatic lesions up to 10 cm or more have been reported (see below).

Location: Lesions located in the antero-lateral segments of the liver (segments 2–6) represent the majority of reported LLRs. Segments 7, 8 and 1 have been traditionally considered as non-laparoscopic segments because of difficult visualization of the surgical field. However, some teams reported successful LLR for lesions located in these segments (see below).

Extent of resections:

The vast majority of reported LLRs are minor resections. These included non-anatomic partial hepatectomies (wedge resections), segmentectomies and subsegmentectomies. The most reported and best studied laparoscopic liver resection has been left lateral sectionectomy, for which the laparoscopic approach is now used routinely by most teams.

However, the number of reported major LLR, including formal right or left hepatectomy, has increased dramatically over the past few years.

B. Comparative short term outcomes

While excellent and adequately powered RCTs on laparoscopic colon cancer resection have been published, this seems much more difficult to achieve for laparoscopic liver resection. Some of the reasons include the lower incidence of liver surgery, the variability of diseases (HCC, mets, benign etc...), the variability of the underlying liver quality (normal, steatotic, cirrhotic etc…), the variability of tumor sizes and locations, the variability of procedures (minor: wedge, segmentectomy, left lateral sectionectomy, bisegmentectomy, sectionectomy, major: right and left hepatectomy, extended hepatectomy), and the variability of techniques used (pure lap, hand-assisted, hybrid, transection techniques etc…).

In the absence of available randomized controlled trials, studies comparing LLR with open retrospective control groups were the only available data for comparative outcome analysis.

1) Mortality

37 postoperative deaths from an estimated 8000 cases, accounting for an estimated mortality rate of 0.4%. Causes of death included liver failure, sepsis, myocardial infarction, ARDS, brain death after major intraoperative hemorrhage. No intraoperative deaths were reported.

When looking at 17 comparative series that evaluated mortality, after minor and/or major resection, all showed statistically equivalent mortality after lap and open resection. Interestingly, cumulative 0.3% and 1.2% mortality rates can be counted when adding deaths from the lap and open groups, respectively. This may reflect a selection bias but, in any case, demonstrates an extremely low mortality of laparoscopic resection.

2) Morbidity

64 comparative studies analyzed morbidity rates. No study reported superior morbidity for the laparoscopic approach. Morbidity rates ranged from 5 to 20%.

17 studies reported a lower morbidity with laparoscopy and 47 found identical morbidity.

In all studies reporting lower morbidity in laparoscopic group, this included lower overall and liver-specific complications (i.e. liver failure, bile leak, collections). 11 studies analyzed bile leaks and all found equivalence.

One series reported a lower incidence of incisional hernias in the laparoscopic group and another one reported reduced surgical site infection, including wound infection and intra-abdominal abscesses.

Grading of complications, according to Clavien-Dindo or another classification, has not been possible due to heterogeneity in reporting.

3) Blood Loss and Transfusion

No comparative study reported higher blood loss or transfusions rates with laparoscopy.

Blood loss and transfusions rates were found equivalent in 29 and 34 studies, respectively. These were found lower with laparoscopy in 40 and 11 studies, respectively.

4) Specimen margins

43 studies analyzed this criterion. 37 found equivalent margins, 5 better margins and 1 worse margins, with laparoscopy

5) Duration of surgery

Of 75 comparative studies reporting operative time, 48 found identical times, 15 increased times with lap and 12 decreased times with lap.

6) Hospital stay

73 comparative studies compared hospital lengths of stay. 12 found equivalence while 66 found a shorter stay with laparoscopy.

C. Specific issues

1) HCC in cirrhotic patients

Interestingly, HCC in cirrhotic patients is one of the most commonly reported and most studied indications of laparoscopic liver resection. This specific interest for this condition was probably triggered by several reasons:

- There is a need for resection in HCC– Liver transplantation is limited by organ shortage– Percutaneous ablation is hazardous for peripheral tumors

- Early solitary tumors are diagnosed from screening patients with cirrhosis- Risk of hepatic decompensation after open resection in patients with CLD- Early observation that cirrhotics tolerated laparoscopy better than laparotomy

Nine comparative single center studies were reviewed. In addition to usual benefits that were also observed, a reduction of postoperative decompensation of liver disease with less ascites, jaundice, and encephalopathy was consistently found. These observations were confirmed in 4 meta-analyses.

Specific benefits from the laparoscopic approach have been suggested in the context of cirrhosis, such as the advantage of preserving the abdominal wall and its collateral veins, resulting in less portal hypertension, a reduced need for intraoperative fluids, reduced manipulations and improved re-absorption of ascites.

An additional benefit found in one comparative study was easier salvage transplantation when performed after primary laparoscopic vs open resection of HCC.

2) Technically challenging cases

Challenging cases, including major resections, difficult locations and large tumors. These issues were mainly studied by expert liver surgeons who are also pioneers or

early adopters. Interestingly, in those expert reports increased rates adverse events were not observed. However, these areas require specific attention.

a. Major resection

8 comparative studies specifically addressed major liver resections, accounting for over 277 lap cases and 558 open cases. Mortality rates were not statistically different but 2 and 7 deaths were reported in the lap and open groups, respectively (0.7 vs 1.2%). Morbidity rates were identical in 4 and reduced in 2. Bile leaks rates were identical in 2. Blood loss as reduced in 4, identical in 4. Transfusion was identical in 4 and reduced in 1. Margins were identical in 5. Operative time was increased in 4, identical in 2 and reduced in 2. Hospital stay was reduced in 6.

Although the international definition of major hepatectomy is the resection of 3 or more contiguous segments, several authors have classified laparoscopic right anterior and posterior sectionectomies as major resections, although they include only 2 segments. Indeed, the term “minor” hepatectomy is probably not appropriate for anatomic mono or bisegmentectomies which may prove more complex that a right or left hepatectomy.

a. Difficult locations

As mentioned above, the majority of the reports included lesions located in antero-lateral liver segment 2-6, which are more easily accessible to the laparoscope. However a few groups have reported limited resections in all liver segments including segments 7, 8 and 1 (Case series references 40, 46, 56, 60, 65). Specific technical modifications have been developed for right posterior lesions, including left lateral decubitus position and trans-thoracic port placement. No increased mortality or morbidity was found.

In one study comparing anterior and posterior locations, increased operative time and a trend towards increased conversion rates (2 vs 16%, p=0.054) was reported for lesions located in the posterior segments (Case series reference 46).

b. Large tumors

As mentioned above, most teams have limited their indications to lesions measuring 5 cm or less. However, some teams have not. One study (Abu-Hilal Ann Surg Oncol, in press) has specifically addressed the case of large tumors. In this series, 52 patients had a tumor >5cm, including 10 with a lesions > 10cm. Mortality was nil, Morbidity was 11.5% and conversion rate was 15%. R1 rate was 7.7%.

D. Meta-analyses

12 meta-analyses and one Cochrane report (Meta-analyses reference list 1-13) addressing comparative short term outcomes of laparoscopic and open liver

resection have been published. Some of these reports addressed both short term and long term issues but long term results are not analyzed in the present document (see Q2). The Cochrane study could not draw any conclusions in the absence of randomized studies.

5 meta-analyses included all types of indications, 4 studied LLR for HCC in cirrhotic patients and 2 focused on colorectal metastases. Another one focused on left lateral sectionectomy.

The main results of these meta-analyses are summarized in the table below.

Consistent results include reduced blood loss and transfusions requirements when studied, reduced morbidity in all but 1, identical or better margins in all but 1 and reduced hospital stay in all.

Table summarizing meta-analyses of comparative studies on laparosopic vs open liver resection

1st Author/ Year

Blood loss / Transfusion

Morbidity Op time Margin Hosp stay Number of studies

PatienstsLap / Open

All indications

Simillis 2007 Less / Equal Equal Less 8 165 / 244

Croome 2010 Less / Equal Less NA Equal Less 26 871 / 1019

Mirnezami 2011

Less / Equal Less More NA Less 26 717 / 961

Miziguchi 2011

Less / NA Less More NA Less 11 170 / 171

Rao 2012 NA / Less Less NA Better Less 32 1161 / 1305

HCC

Zhou 2011 Less / Less Less ascites NA Equal Less 10 213 / 281

Li 2012 Less / Less Less Equal Equal Less 10 244 / 383

Xiong 2012 Less / Less Equal but less liver failure and ascites

Equal EquaL Less 15 234 /316

Yin 2013 Less / Less Less Equal Equal Less 15 485 / 753

CR Mets

Zhou 2013 NA / Less Less NA Worse Less 8 268 / 427

Wei 2014 NA / Less Less NA Not clear

Less 14 376 / 599

Left Lateral

Rao 2011 Equal / NA Less More Equal Less 7 134 / 111

Recommendations

Preamble: - Specific features of liver surgery must be emphasized:

o variability of diseases, underlying liver quality, tumor sizes, numbers and locations within the liver, procedures and techniques used

- No randomized trials are available. - All data have been reported as case series, case–control studies, reviews and

meta-analyses. - Most data were obtained from prospectively maintained databases. - Best data arise from case-match studies and meta-analyses.

1. Presently, the laparoscopic approach can be reasonably considered in 25-35% of liver resections

2. A sharp increase in the number of publications has been observed since 2008 (year of the Louisville meeting). This probably heralds a rise in the proportion of laparoscopic liver surgery in the near future

3. The vast majority of data arise from minor resections but the proportion of major resections is increasing

4. Safety has been demonstrated when- Performed by trained surgeons- In patients well selected for tumor size and location

5. None of the comparative studies, including meta-analyses, showed any disadvantage of laparoscopic liver resection over open surgery

6. Comparative studies and meta-analyses strongly suggest that laparoscopic liver resection when compared with open surgery is associated with

- No increased mortality- Reduced blood loss and transfusion rates- Reduced morbidity, especially in cirrhotic patients- Identical tumor margins- Reduced hospital stay

7. New developments are a reality but require attention:- Difficult locations- Major resection- Anatomic resections- Large tumors.

REFERENCES

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CASE SERIES

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2. Hwang DW, Han H-S, Yoon Y-S, Cho JY, Kwon Y, Kim JH, et al. Laparoscopic major liver resection in Korea: a multicenter study. Journal of Hepato-Biliary-Pancreatic Sciences. 2013 Feb;20(2):125–30.

3. Zhen ZJ, Lau WY, Wang FJ, Lai ECH. Laparoscopic liver resection for hepatocellular carcinoma in the left liver: Pringle maneuver versus tourniquet method. World J Surg. 2010 Feb;34(2):314–9.

4. Lai ECH, Ngai TC, Yang GPC, Li MKW. Laparoscopic approach of surgical treatment for primary hepatolithiasis: a cohort study. Am J Surg. 2010 May;199(5):716–21.

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46. Yoon Y-S, Han H-S, Cho JY, Ahn KS. Total laparoscopic liver resection for hepatocellular carcinoma located in all segments of the liver. Surg Endosc. 2010 Jul;24(7):1630–7.

47. Bryant R, Laurent A, Tayar C, Cherqui D. Laparoscopic liver resection-understanding its role in current practice: the Henri Mondor Hospital experience. Ann Surg. 2009 Jul;250(1):103–11.

48. Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2,804 patients. Ann Surg. 2009 Nov;250(5):831–41.

49. Zhang L, Chen Y-J, Shang C-Z, Zhang H-W, Huang Z-J. Total laparoscopic liver resection in 78 patients. World J Gastroenterol. 2009 Dec 7;15(45):5727–31.

50. Nguyen KT, Laurent A, Dagher I, Geller DA, Steel J, Thomas MT, et al. Minimally Invasive Liver Resection for Metastatic Colorectal Cancer. Ann Surg. 2009 Nov;250(5):842–8.

51. Otsuka Y, Tsuchiya M, Maeda T, Katagiri T, Isii J, Tamura A, et al. Laparoscopic hepatectomy for liver tumors: proposals for standardization. J Hepatobiliary Pancreat Surg. 2009;16(6):720–5.

52. Machado MAC, Makdissi FF, Surjan RC, Herman P, Teixeira AR, C Machado MC. Laparoscopic resection of left

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54. Huang M-T, Wei P-L, Wang W, Li C-J, Lee Y-C, Wu C-H. A series of laparoscopic liver resections with or without HALS in patients with hepatic tumors. J Gastrointest Surg. 2009 May;13(5):896–906.

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56. Cho JY, Han H-S, Yoon Y-S, Shin S-H. Experiences of laparoscopic liver resection including lesions in the posterosuperior segments of the liver. Surg Endosc. 2008 Nov;22(11):2344–9.

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58. Abouljoud MS, Arenas J, Yoshida A, Kim D. New application of the bipolar vapor plasma coagulation system for laparoscopic major liver resections. Surg Endosc. 2008 Feb;22(2):426–9.

59. Alkari B, Owera A, Ammori BJ. Laparoscopic liver resection: preliminary results from a UK centre. Surg Endosc. 2008 Oct;22(10):2201–7.

60. Cho JY, Han H-S, Yoon Y-S, Shin S-H. Feasibility of laparoscopic liver resection for tumors located in the posterosuperior segments of the liver, with a special reference to overcoming current limitations on tumor location. Surgery. 2008 Jul;144(1):32–8.

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META-ANALYSES

1. Simillis C , Constantinides VA, Tekkis PP, et al. Laparoscopic versus open hepatic resection for benign and malignant neoplasms--a meta-analysis. Surgery 2007;141: 203-211.

2. Croome KP, Yamashita MH. Laparoscopic vs open hepatic resection for benign and malignant tumors: An updated meta-analysis. Arch Surg. 2010; 145:1109-18.

3. Mirnezami R, Mirnezami AH, Chandrakumaran K, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB (Oxford) 2011; 13:295-308

4. Mizuguchi T, Kawamoto M, Meguro M, Shibata T, Nakamura Y, Kimura Y, Furuhata T, Sonoda T, Hirata K. Laparoscopic hepatectomy: a systematic review, meta-analysis, and power analysis. Surg Today. 2011;41(1):39-47

5. Rao A, Rao G, Ahmed I. Laparoscopic or open liver resection? Let systematic review decide it. Am J Surg. 2012; 204:222-31.

6. Zhou YM, Shao WY, Zhao YF, et al. Meta-analysis of laparoscopic versus open resection for hepatocellular carcinoma. Dig Dis Sci 2011; 56:1937-1943

7. Li N, Wu YR, Wu B, et al. Surgical and oncologic outcomes following laparoscopic versus open liver resection for hepatocellular carcinoma: A meta-analysis. Hepatol Res 2012; 42:51-59.

8. Xiong JJ, Altaf K, Javed MA, Huang W, Mukherjee R, Mai G, Sutton R, Liu XB, Hu WM. Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma. World J Gastroenterol. 2012;18(45):6657-68

9. Yin Z, Fan X, Ye H, et al. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis. Ann Surg Oncol 2013; 20:1203-1215.

10. Zhou Y, Xiao Y, Wu L, Li B, Li H. Laparoscopic liver resection as a safe and efficacious alternative to open resection for colorectal liver metastasis: a meta-analysis. BMC Surg. 2013 Oct 1;13:44

11. Wei M, He Y, Wang J, Chen N, Zhou Z, Wang Z. Laparoscopic versus open hepatectomy with or without synchronous colectomy for colorectal liver metastasis: a meta-analysis. PLoS One. 2014;9(1):e87461.

12. Rao A, Rao G, Ahmed I. Laparoscopic left lateral liver resection should be a standard operation. Surg Endosc. 2011;25(5):1603-10.

13. Rao AM, Ahmed I. Laparoscopic versus open liver resection for benign and malignant hepatic lesions in adults. Cochrane Database Syst Rev. 2013

Q1. WHAT ARE THE COMPARATIVE SHORT TERM OUTCOMES OF LLR AND OLR? (MINOR AND MAJOR)

A. Flowchart

B. Statistics

C. Colour codes:

P values favour laparoscopic approach

P values are not significant for laparoscopic or open approach

P values favour open approach

Duplicated paper. See comment regarding considerations for final count of patients

D. Total numbers:

9168 laparoscopic patients: 2868 in comparative series / 6300 in case serieso 3440 minor resectionso 1942 major resectionso 3620 combined minor/majoro 166 unknown

3212 open patientso 1529 minoro 1256 majoro 427 unknown

E. ANALYSES (FROM COMPARATIVE SERIES ONLY).

1. Minor-only resectionsa. 7 series showed equivalent mortality between open and lap resectionsb. 20 series showed equivalent morbidity between open and lap resectionsc. 7 series showed significantly lower morbidity rates in lap vs open resectionsd. 14 series showed equivalent blood loss between open and lap resectionse. 16 series showed significantly lower blood loss rates in lap vs open resectionsf. 18 series showed equivalent transfusion rates between open and lap resectionsg. 4 series showed significantly lower transfusion rates in lap vs open resectionsh. 21 series showed equivalent operation time between open and lap resectionsi. 4 series showed significantly shorter operation time in lap vs open resectionsj. 7 series showed significantly longer operation time in lap vs open resectionsk. 3 series showed equivalent hospital stay between open and lap resectionsl. 28 series showed significantly lower hospital stay in lap vs open resections

m. 2 series showed equivalent rates of bile leak between open and lap resectionsn. 18 series showed equivalent resection margins between open and lap resectionso. 2 series showed significantly better resection margins in lap vs open resections

2. Major-only resectionsa. 5 series showed equivalent mortality between open and lap resectionsb. 4 series showed equivalent morbidity between open and lap resectionsc. 2 series showed significantly lower morbidity rates in lap vs open resectionsd. 4 series showed equivalent blood loss between open and lap resectionse. 4 series showed significantly lower blood loss rates in lap vs open resectionsf. 4 series showed equivalent transfusion rates between open and lap resectionsg. 1 series showed significantly lower transfusion rates in lap vs open resectionsh. 4 series showed equivalent operation time between open and lap resectionsi. 2 series showed significantly shorter operation time in lap vs open resectionsj. 2 series showed significantly longer operation time in lap vs open resectionsk. 2 series showed equivalent hospital stay between open and lap resectionsl. 6 series showed significantly lower hospital stay in lap vs open resectionsm. 2 series showed equivalent rates of bile leak between open and lap resectionsn. 5 series showed equivalent resection margins between open and lap resections

3. Combined minor/major resectionsa. 6 series showed equivalent mortality between open and lap resectionsb. 23 series showed equivalent morbidity between open and lap resectionsc. 9 series showed significantly lower morbidity rates in lap vs open resectionsd. 12 series showed equivalent blood loss between open and lap resectionse. 20 series showed significantly lower blood loss rates in lap vs open resectionsf. 13 series showed equivalent transfusion rates between open and lap resectionsg. 6 series showed significantly lower transfusion rates in lap vs open resectionsh. 23 series showed equivalent operation time between open and lap resectionsi. 6 series showed significantly shorter operation time in lap vs open resectionsj. 6 series showed significantly longer operation time in lap vs open resections

k. 6 series showed equivalent hospital stay between open and lap resectionsl. 33 series showed significantly lower hospital stay in lap vs open resectionsm. 7 series showed equivalent rates of bile leak between open and lap resectionsn. 14 series showed equivalent resection margins between open and lap resectionso. 4 series showed significantly better resection margins in lap vs open resectionsp. 1 series showed significantly worse resection margins in lap vs open resections

q.LAPAROSCOPIC MINOR-ONLY RESULTS RESECTIONS

Author Year

NType of lesion

MortalityConversion

rateComplications Blood loss

Blood transfusion

Operation time Hospital Stay Bile leak Resection margins Comments

LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR

LLR

-mm

-posit

-<1cm

OLR

-mm

-posit

-<1cm

COM

PARA

TIVE

STU

DIES

Memeo(1)

Creteil-France2014

45

15biS

11S

17subS

45

15biS

11S

17subS

HCC

0 2(4,5%)

0

9(20%) 20(45%) 200 (0-1500) 200 (0-2000) 0 (0-4) 0 (0-10) 140 (45-360) 180 (90-360) 7(0-69) 12 (0-34)

0 0

-10(0-50)

-5%

-/

-6(0-58)

-15%

-/Well matched study.

P=0,15 P=0,01 P=0,11 P=0,18 P=0,02 P<0,0001

-P=0,02

-P=0,03

-/

Chan(2)

Hong Kong-China2014

17

9LLS

1S

7subS

34

16LLS

2S

16subS

Malign 0 0 5,8% 4(23,5%) 12(35,2%)

150 (0-500)330 (100-2500)

2(11,8%) 2(6,1%) 195(75-450) 210(90-362) 6(3-15) 8(5-105)

0 0

10(4-32) 10(0-20)Population: Elderly patients > 70 years

Potential duplication in Ref. 8. Excluded 29 cases in the lap(12) and open(17) groups in final count

P=0,046 P=0,878 P=0,436 P=0,005 P=0,791

Kim(3)

Seoul

2014 29

9BiS

20S

29

11BiS

18S

HCC 0 0 23,3%

4(13,8%) 11(37,9%)483.85 ± 819.9

261.15 ± 300.66

1(3,4%) 0 210.48 ± 82.07 203.48 ± 51.197.69 ± 2.94

13.38 ± 7.37

2(6,9%) 2(6,9%)

- 11.07 ± 6.76

- 3

- 9

- 10.03 ± 7.49

- 1

- 15

Propensity-score matching

P=0,118 P=0,065 P=0,317 P=0,681 P<0,001 P=1 P=0,454

Dokmak(4)

Clichy-France2014

31

31LLS

31

31LLSBenign 0 0 12,9% (to HA)

3(9,6%) 6(19,35%) 223 ± 281 455 ± 593 2(4,8%) 3(9,6%) 182 ± 71 244 ± 105 4,1±1,7 8,06±4,4

0 0 - -Includes cost analysis

P=0,27 P=0,03 P=0,64 P=0,04 P<0,001

Inoue(5)

Osaka-Japan2013

23

19SubS

4LLS

24

19SubS

5LLS

CRLM 0 0 4,3%

2(8,7%) 5(20,8%) 99207 397381 1(4,3%) 4(16,7%) 204101 2309010,811,2

13,910,3

4,3% 4,1%

- 9.0 ± 7.4

- /

- 13(56%)

- 8.9 ± 6.2

- /

- 9(37%)

Well-matched cohorts

P=0,41 P=0,0018 P=0,34 P=0,36 P=0,33 P=0,34

Abu Hilal(6)

Southampton-UK2013 46LLS 19LLS

Malign + Benign

0 0 1(2%)

4(9%) 4(21%)100(10-1200)

435(100-3000)

3(7%) 6(32%) 144(55-240) 150(110-330) 3(1-15) 7(3-20)

0 0 - -Includes cost analysis

P=0,218 P<0,0001 P=0,015 P=0,021 P<0,0001

Kanazawa(7)

Osaka-Japan2013 28 28 HCC 0 0

5/23 hybrid (21,73%)

3(15%) 20(71%) 88(0-900)505 (80–1,150)

0 4 228 (69–515) 236 (95–376) 10 (6–25) 19 (8–49) 0 1(3,5%) 5 (0-18) 3 (0-15)Well-matched cohorts

P<0,0001 P=0,0003 P=0,03 P=0,92 P<0,0001 P=0,313 P=0,53

Cheung(8)

Hong Kong-China2013

32

8LLS

1S

23subS

64

16LLS

2S

46subS

HCC

0 1(1,6%)

6 hand-assist (18,8%)

2(6,3%) 12(18,8%)150 (100-1460)

300 (50-2700)

0 3(4,7%) 232.5 (70–450) 204.5 (67–705) 4 (2-16) 7 (4–42)

0 0

9,5 (0-30) 8 (0-35)

Well-matched cohorts

P=1 P=0,184 P=0,001 P=0,534 P=0,938 P<0,0001 P=0,237

Slim(9)

Milan-Italy2012 46 46

Malign + Benign

0 1(2,2%) 3(6,5%)

8(17,4%) 18(39,1%) 100(10-800)200(50-2000)

2(4,3%) 8(17,4%) 155(45-400) 170(85-315) 5(3-22) 8(5-54)

0 3(6,5%) - -Well-matched cohorts

P=0,017 P=0,048 P=0,4 P=0,098 P<0,001

Truant(10)

Lille-France2011

36

22Atyp

14S;BS

53

26Atyp

27S;BS

HCC

0 4(7,5%)

7(19,4%)

9(25%) 19(35,8%) 452,2 442447,2 449,8

1(2,8%) 2(3,8) 193,4104 215,888,7 6,52,7 9,54,8

0 1,8%

- 9.5 ± 2.8 - 8.6 ± 1.7 Included in Xiong et al. 2012, Yin et al 2013 and Parks et al. 2014P=0,3 P=0,3 P=0,9 P=0,1 P=0,3 P=0,003 P=0,7

Lee(11)

Hong Kong-China2011

33

18LLS

15wed

50

10LLS

40wed

HCC 0 0 6(18,2%)

2(6,1%) 12(24%)150 (10-1610)

240 (50-1880)

2(6,1%) 5(10%) 225(100-420) 195 (105-325) 5(2-15) 7(4-27)

0 0

- 18(0-40) - 10(0-40) Well-matched cohorts

Included in Xiong et al. 2012, Yin et al 2013 and Parks et

P=0,033 P=0,086 P=0,697 P=0,019 P<0,0005 P=0,016

al. 2014

Aldrighetti(12)

Milan-Italy2010

16

5LLS

2S

9sS

16

5LLS

2S

9sS

HCC

0 0

1(6,25%)

4(25%) 7(43,7%) 258186 617433 4(25%) 6(37,5%) 15057 240121 6,31,7 93,8

01(6,25%)

- 11±8

- 0

- /

-7±4

- 3

- /

Included in Xiong et al. 2012 and Yin et al 2013

P=NS P=NS P=0,008 P=NS P=0,044 P=0,039 P=NS

Robles(13)

Murcia-Spain2009

18

10LLS

8S

18

10LLS

8S

Malign + Benign

0 0 0

1(5,5%) 1(5,5%)150 (100–500)

200 (100-800)

0 1152130 (90–240)

145160 (60–240)

4,9 2 7 3

0 1(5,5%)

- /

- 0

- 6(33%)

- /

- 0

- 4(22%)

Included in Rao et al. 2012

P=NS P=NS P=NS P=NS P=0,003 P=NS

Endo(14)

Oita-Japan2009

10

10LLS

11

11LLSHCC 0 0

LAP-assisted resections

3(30%) 3(27%) 555 ± 386 483 ± 479

- -

265 ±50 230 ± 65 20 ± 4 32 ± 8

0 1(9%)

- 17±15 - 17±13 Included in Rao et al. 2012, Xiong et al. 2012 and Yin et al 2013P=NS P=NS P=NS P<0,01 P=NS

Ito(15)

New York-USA2009

65

49S

16BiS

65

47S

18BiS

Malign + Benign

0 0 13(20%)

9(13,8%) 28(43,1%) 100 (0-500) 200 (0-2500) 1(1,5%) 19(29,2%) 170 (50-478) 138 (67-378) 4(1-14) 6(4-15) 0 0

- /

- /

- 0

- /

- /

- 0

Included in Rao et al. 2012 and Parks et al. 2014

P<0,0001 P<0,0001 P<0,0001 P=0,006 P<0,0001 - -

Vanounou(16)

Montreal-Canada2009

44

44LLS

29

29LLS

Malign + Benign

0 0 -

6(13%) 12(41%)

- -

11% 14% 233 249 3 5

0 1(3,4%) - -Included in Rao et al. 2012

P=0,001 P=0,28 P=0,08 P=0,001

Carswell(17)

London-UK

2009 10

10LLS

10

10LLS

Malign + Benign

0 0 1(10%) 2(20%) 2(20%) - -

10% 20% 220(116-335) 179(118-229) 6 9

0 0 -15(3-30)

- 0

- /

-14(1-20)

- 0

- /

Included in Rao et al. 2012

P=0,782 P=0,315 P=0,005 P=0,669

Tsinberg(18)

Cleveland-USA2009

31

8BiS

23S

43

15BiS

28S

Malign + Benign

0 0 0

4(13%) 7(16%) 122.5 ± 45.4 299,6 ± 33,6

- -

201 ± 15 172 ± 12 3.2 ± 1 6.8 ± 0.7

0 0

- 8,2±2

- 2(18%)

- /

- 8,5±1,3

- 1(3%)

- /Included in Rao et al. 2012

Has financial analysis

P=0,7 P=0,002 P=0,1 P=0,004

- P=0,9

- /

- /

Abu Hilal(19)

Southampton-UK2008

24

24LLS

20

20LLS

Malign + Benign

0 0 0

13% 25% 80 (25-800)470 (100-3000)

- -

180 (40-340) 155 (110-330) 3,5 (1-6) 7 (3-12)

0 0

-11(1,5-30) -12(4-40)Included in Rao et al. 2012.

Duplicated in Ref. 6. All cases excluded form the count

P=0,541 P=0,002 P=0,885 P<0,001 P=1

Aldrighetti(20)

Milan-Italy2008

20

20LLS

20

20LLS

Malign + Benign

0 0 0

2(10%) 5(25%) 165 ± 43 214 ± 47

0 0

260±50 220±30 4.5 ± 0.6 5.8 ± 1.6

0 0

-11±3 -13±5 Well-matched cohorts

Included in Rao et al. 2012

Duplicated paper in Ref 12. Excluded 16 cases from open(8) and lap(8)

P=NS P=0,001 P=NS P=0,003 P=NS

Polignano(21)

Dundee-UK2008

25

16BiS

4S

5At

25

14BiS

5S

6At

Malign + Benign

0 0 2(8%)

12% 40% 135 ± 84 420 ± 225

- -

362 ± 113 366±73 7,4 13,1

0 1(4%) - -

Well-matched cohorts

Financial analysis

Included in Rao et al. 2012

P=0,002 P<0,0001 P=NS P=0,003

Lee(22)

Hong Kong-China

2007 25

11LLS

14oth

25

11LLS

14oth

Malign + Benign

0 08%

1(4%) 1(4%)100 (20-1500)

250 (50-900)1 (4%) 0

220 (100-420) 195 (135-285) 4 (2-8) 7 (3-15)0 0

-14(0-30) -13(1-30)Included in Rao et al. 2012

Duplicated in Ref 11. Excluded 32 HCC from count in open(16) and lap(16)

P=1 P=1 P=0,012 P=0,118 P<0,001 P=0,803

Belli(23)

Naples-Italy2007

23

15sS

3S

5LLS

23

12sS

5S

6LLS

HCC 1(4,3%) 0 1(4,3%)

5(21,7%) 17(74%) 260 ± 127376.95 ± 114.32

0 4(17,3%) 148 ± 29.73 125.21 ± 17.48 8.2 ± 2.612,04 ± 3.93

0 0

- /

- 0

- 2(8,6%)

- /

- 0

- 0

Included in Rao et al. 2012, Xiong et al. 2012 and Parks et al. 2014

P=0,01 P=0,652 P=0,036 P=0,016 P=0,048 P=0,148

Soubrane(24)

Paris-France2006

16

16LLS

14

14LLSLDLT 0 0 1(6,25%)

3(18,7%) 5(35,7%) 18.7 ± 44.2199.2 ± 185.4

0 0

320 ± 67 244 ± 55 7,5 ± 2,3 8,1 ± 3

1(6,25%) 0 - -Included in Rao et al. 2012

P=NS P<0,005 P<0,005 P=NS

Tang(25)

Hong Kong-China2005

10

10LLS

7

7LLSBenign 0 0 1(10%)

2(20%) 4(57%)350 (100-1000)

400 (300-500)

- -232.5 (175–290)

150 (80–225) 8 (5-60) 14 (8-28)

1(10%) 1(14%) - -Included in Rao et al. 2012

P=NS P=NS P=- P=0,007 P=0,019

Kaneko(26)

Tokyo-Japan2005

30

10LLS

20nAR

28

8LLS

20nAR

HCC 0 0 3,3% 10% 18%

350210 505185

- -

18238 21040 14,97,1 21,68,8

1(3,3%)2(7,14%)

- -

Well-matched

Included in Rao et al. 2012, Xiong et al. 2012, Yin et al 2013 and Parks et al. 2014

P=NS P=NS P<0,005

Morino(27)

Turin-Italy2003

30

5w

12S

13BiS

30

5w

12S

13BiS

Malign + Benign

0 0 0

2(6,6%) 2(6,6%) 320 479 4(13%) 2(6,6%) 148 142 6,4 8,7

0 0

- /

- 0

- 43%

- /

- 4%

- 40%

Matched-pair analysis

Included in Rao et al. 2012

P=NS P=NS P=NS P=NS P<0,05 P=NS

Laurent(28)

Creteli-France2003

13

3At

7S

3LLS

14

4At

7S

3LLS

HCC

0 2(14%)

2(15%) 4(31%) 13(93%)

620 ± 130 720 ± 240 1(7%) 4(28%) 267 ± 79 182 ± 57

15,3 ± 8,6 17,3 ± 18,9 0 0

-9±2,5 (1-35)

- /

-2

-8,8±1,3 (1-15)

- /

-2

Included in Rao et al. 2012 and Yin et al 2013.

P=0,2 P=0,45 P=0,49 P=0,006 P=0,77

Lesurtel(29) 2003 18 20 Malign + 0 0 2(11%) 11% 15% 236 ± 155 429 ± 286 0 3(15%) 202 ± 48 145 ± 31 8 ± 3 10 ± 6 0 0 - / - / Matched-pair analysis

Creteil-France 18LLS 20LLS Benign- 0

- 1

- 0

- 0

Included in Rao et al. 2012

Duplication in Ref. 28. Excluded 6 cases: in open(3) and lap(3) groups from final count.

P=NS P=NS P<0,05 P=NS P<0,01 P=NS

Farges(30)

Clichy-France2002

21

9w

4S

8BiS

21

9w

4S

8BiS

Benign 0 0 0

2(9,5%) 2(9,5%) 218 ± 173 285 ± 178

1(4,76%) 0

177 ± 57 156 ± 42 5,1 ± 1,3 6,5 ± 1

1(4,76%) 0 - -

Matched-pair analysis

Included in Rao et al. 2012

P=NS P=NS P=NS P=0,0002

Mala(31)

Oslo-Norway2002 13 14 CRLM 0 0 0

13% 29%600 (100-3300)

500 (100-3500)

1(0-6) 1,5(0-9) 187(80-334) 185(100-335) 4(1-6) 8,5(5-23)

0 2(14%)

- /

- 1

- 5

- /

- 2

- 5

Included in Rao et al. 2012, Zhou et al. 2013 and Parks et al. 2014

P=NS P=NS P=NS P=NS P<0,001 P=0,57

Shimada(32)

Fukuoka-Japan2001

17

7LLS

10subS

38 HCC 0 0 0

1(5,9%) 4(10,5%)400 (188, 1050)

800 (500, 1125)

5,9% 10,5% 325 (214, 430) 280 (215, 318) 12 ± 5 22 ± 8

0 0

- 8±7

- /

- 41,2%

- 7±6

- /

- 50%

Well-matched

Included in Xiong et al. 2012, Yin et al 2013 and Parks et al. 2014

P=0,99 P=0,08 P=0,99 P=0,18 P<0,001P=0,65

P=0,54

CLIN

ICAL

SER

IES

Long(33)

Ho Chi Minh-Vietnam

2014 173 - HCC 0 0 4(2,3%) 4(2,4%) -100 (20–1200)

- - 112 ± 56 . 6.5 ± 2.0 - 2(1,2%) -

Hwang(34)

Multic-Korea

2013 744 - Malign + Benign

2(0,27%) - 34(4,6%) 52(7%) - 410.0 ± 451.4

- 67(9%) - 214.9 ± 114.1 - 8.6 ± 5.0 - - -

Zhen(35)

Guang Dong-China2010

29

3S

17BiS

9LLS

- HCC 0 - 3(10,3%)9(31,03%)

- 164 - 0 - 120 - 7,08 - 0 -

Lai(36)

Hong Kong-China2010

19

19LLS-

Hepato-lithiasis

Salit(37)

Haifa-Israel2010 9 - Malign Hand-assisted

Santambrogio(38)

Milan-Italy2009

22

5BiS

9S

2SubS

3nAR

- HCC 0 - 13,6% 2(9%) - 18372 - 1(4,5%) - 19969 - 5,41 - 0 -

Vigano(39)

Creteil-France2009

60

60LLS-

Malign + Benign

0 -

A. 1(5%)

B. 0

A. 1(5%)

A.4(20%)

B.1(5%)

0

-

A.200

B.200

C.100

-

A.0

B.0

C1(5%)

-

A.180

B.170

C.140

-

A.7

B.5

C.5

- 0 -

A. first 20

B. second 20

C. last 20

Sasaki(40)

Morioka-Japan2009

82

71w

11LLS

-Malign + Benign

0 - 1(1,2%) 3(4%) - 64 (1-917) - 4(4,8%) - 177 (70-430) - 9 (3-37) - 1(1,2%) -

Chen(41)

Kaohsiung-Taiwan2008 97 - HCC 0 - 0 6,2% -

101.6 ± 324.4

- 5(5,1%) - 152.4 ± 336.3 - 6,4(2-16) - 0 -

Pai(42)

London-UK

2008 28 - Malign + Benign

Nissen(43)

Los Angeles-USA2007

15

15nAn-

Malign + Benign

0 - 1(7%) to HA 2(13,3%) . - - 0 - - - 4,1(1-5) - 0 -

Chang(44)

Creteil-France2007

36

36LLS-

Malign + Benign

0 - 1 (2,7%) 2(5,5%) -208 (50–600)

- 0 - 171,5 (90–240) - 7,8 (2–52) - 0 -

Duplicated paper on Ref. 39. All cases excluded from the final count

Poultsides(45)

Hartford-USA2007 28 -

Malign + Benign

Hand-assisted

Bachelier(46)

London-UK2007 18 -

Malign + Benign

Toyama(47)

Chiba-Japan2006 9 - Malign 0 - 0 2(22,2%) - 77.4 ｱ 37.2 - 0 - 113.6 ｱ 41.3 - 11.3 ｱ 3.9 - 0 -

3-ports lap resections

Belli(48)

Naples-Italy2006

8

8LLS-

Malign + Benign

0 - 0 0 -170 (100-300)

- 0 - 142 (120-180) - 5,7 - 0 -

Kamiyama(49)

Sapporo-Japan2005

8

7LLS

1nAR

- HCC 0 - 0 2(25%) -177.6 ｱ129.1

- - - 181.1 ｱ 44.6 -9.88 ｱ4.36

- 0 -

Croce(50)

Monza-Italy2003 7 -

Malign + Benign

0 - 0 0 - 120 (80-200) - 0 - 90 (80-110) - 4 - 0 -

Huang(51)

Taipei-Taiwan2003 7

Malign + Benign

Hand-assisted

Teramoto(52)

Tokyo-Japan

2003 11 HCC

CN Tang(53)

Hong Kong-China2003

6

6LLSBenign

Hand-assisted

Duplicated paper in Ref. 36. All cases excluded from the final count

Cherqui(54)

Creteil-France2002

2

2LLSLDLT

Antonetti(55)

Hartford-USA2002 11 -

Malign + Benign

0 - 0 2(18%) - 150 (50-400) - 0 - 197±62 - 4,5 - 0 -

Hand-assisted

Duplicated paper in Ref. 45. All cases excluded from the final count

Ker(56)

Kaohsiung-Taiwan2000

9

9subS- HCC 0 - 0 1(11%) - - - 0 - - - 4-7 - 0 -

Duplicated paper on Ref. 41. All cases excluded from the final count

Fong(57)

New York-USA2000 11 - Malign 0 - 6(54%) 2/5 - - - - - 248 (143-358) - 5 - 1(20%) .

Hand-assisted

Data of 5 patients

Katkhouda(58)

Los Angeles-USA1999 43 - Benign 0 - 3(7%) 6(14,1%) - 156 (90-980) - 3(7%) - 179 (45-325) - 4,7(1-17) - 0 -

Samama(59)

Caen-France1998

4

4LLS

Malign + Benign

Azagra(60)

Montigny-Belgium1996

1

1LLSBenign 0 - 0 0 -

LAPAROSCOPIC MINOR/MAJOR COMBINED-RESULTS RESECTIONS

Author Year

NType of lesion

MortalityConvers.

rateComplications Blood loss Blood transfusion Operation time Hospital Stay Bile leak Resection margins Comments

LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR

LLR

-mm

-posit

-<1cm

OLR

-mm

-posit

-<1cm

COM

PARA

TIVE

STU

DIES

Franken(61)

Los Angeles-USA2014

52

7maj

45min

52

7maj

45min

Malign + Benign

1(2%) 2(4%)

7(13%)

22(42%) 19(37%) 237(10-1200)387(25-3000)

1(2%) 5(10%) 219 (84-449)198 (107-347)

5(1-17) 6(3-23) 0 2(4%)

- /

- 2(4%)

- /

- /

- 1(2%)

- /

Matched-pair analysis

P=0,99 P=0,7 P=0,049 P=0,2 P=0,16 P=0,13 P=0,49 P=0,99

Iwahashi(62)

Tokushima-Japan2014

21

4maj

17min

21

4maj

17min

CRLM - - -

2(9,5%) 5(23,8%) 198 ± 39 326 ± 50

- -

377 ± 29 369 ± 31 18,3 27

0 4,76% - -Includes long-term results

P=0,21 P<0,05 P=NS P=0,14

Montalti(63)

Ghent-Belgium2014

57

44min

13maj

57

44min

13maj

CRLM 0 0 15,8%

9% 24%

- - - -

28282 284112 6,55 9,24 1,8% 5,3%

-5.2 ± 6

-13%

-/

-4.5 ± 5

-9%

- / Matched-pair analysis

P=0,03 P=0,81 P=0,005 P=0,67P=0,51

P=0,54

Lopez-Ben(64) 2014 50

8maj

100

16maj

Malign + Benign

1(2%) 1(1%) 6(12%) 18(36%) 36(36%) 401(18-2192) 475(20-2000)

8(16%) 20(20%) 295(120-600)

200(70-450) 4(1-60) 7(3-44) 0 3% - 6(0-50) -6,5(0-50) Matched-pair analysis 1:2

Gerona-Spain 42min 84min P=0,65 P=1 P=0,89 P=0,65 P=0,0001 P=0,0001 P=0,29 P=0,94

Jung(65)

Seoul-Korea2014

24

6maj

18min

24

6maj

18min

CRLM 0 0 0 4(17%) 10(42%)

325 (50-900)250 (50-850)

- -

290 (183-551)

244 (149-375)

8 (5-23) 10,5 (8-23)

4,1% 4,1% - -Combined liver + colon resections

P=0,35 P=0,008 P=0,001

Fallahzadeh(66)

Louisiana-USA2013

54

19maj

35min

54

19maj

35min

Malign + Benign

2(4%) 2(4%) -

38(70%) 33(61%)

- -

6(11%) 9(17%) 17464 18961 5,934,43 8,986,93

- -

-/

- 1(3%)

-/

-/

- 4(11%)

- /

Matched-pair analysis

P=0,69 P=0,28 P=0,24 P=0,006 P=0,36

Cheung(67)

Hong Kong-China2013

20

1maj

19min

40

2maj

38min

CRLM 0 02(10%) hand-port

2(10%) 2(5%) 200 (10-1300)310 (0-1150)

0 0 180(58–460) 210(60–634) 4.5(3–56) 7(2-96) 0 0 -5(1-25) -6(1-20) Matched-pair analysis

Included in Zhou et al. 2013P=0,85 P=0,043 - P=0,059 P=0,021 P=- P=0,979

Ai(68)

Putian-China2013

97

15maj

82min

178

59maj

119min

HCC 0 0 9,3%

11% 28% 460±426 454±365 4,6% 2,8% 245105 226112 8.23.6 13.53.8

0 2,8%

- 15,3±5,9

- 21%

- /

- 13,6±6

- 23%

- /

P=0,01 P=0,913 P=0,480 P=0,469 P=0,028- P=0,818

- P=0,936

Yoon(69)

Seoul-Korea2013

13

4min

9maj

23

4min

19maj

Malign + Benign

0 0 0

3(23%) 11(47%)

- - 5(38,5%) -

381,5 319,5 10,1 23,9

0 0

- 4

-5(38,5%)

-/

- 10

-0(0%)

-/

Matched-pair analysis

Tumors close to major vessels only

Duplicated in Ref. 65. Excluded 1 lap case from the final count

P=0,143 P=0,179 P=0,022- P=0,008

- P=0,009

Guerron(70) 2013 40 40 CRLM 0 0 5% 15% 20% 376±122 753±120 2(5%) 8(20%) 239±17 219±16 3.7±0.5 6.5±0.5 0 2,5% -10±2 -11±2 Matched-pair analysis

Cleveland-USA35min

5maj

31min

9maj

Included in Zhou et al. 2013

P=0,591 P=0,041 P=0,040 P=0,307 P<0,001 P=0,713

Tranchart(71)

Paris-France2013

52

28maj

24min

52

28maj

24min

Malign + Benign

0 1(1,9%) 1(1,9%)

8(15%) 13(25%) 367,3±484,3589,8 ± 428,1

2(3,8%) 9(17,3%) 309.2±114,3 295,5±87,2 7,45,9 118,9 1,9% 0-14.3 ± 12.1

- 14,8 ± 16

Matched-pair analysis

P=NS P=0,001 P=0,05 P=0,75 P=0,001 P=1 P=0,8

Tian(72)

Chongqing-China2013

116

76 maj

40min

78

43maj

25min

Benign

(Hepato-lithiasis)

0 0 13(11,2%)

23(19,8%) 17(21,8%) 479.2±402.1505.8 ± 396.9

21(18,1%) 14(17,9%) 323.3 ± 103 272.8±66.8 13.1 ±5.6 16.5 ±8.3

2(1,7%) 2(2,5%) - -

P=0,740 P=0,650 P=0,978 P<0,001 P=0,001

Doughtie(73)

Louisville-USA2013

8

7maj

1min

76

56maj

20min

CRLM 0 4(8,9%) 0

12,5% 60,5% 225 400 14,3% 30,9%

- -

3,5 7

- - - -

CRLM > 5cm

Duplicated series in Ref. 79. All patients excluded from the final count

P=0,0192 0,0427 0,6660 P=0,0005

Qiu(74)

Sichuan-China2013

30

2maj

28min

30

5min

25maj

CRLM 0 0 2(6,66%)

10(33%) 20(66%) 215±170 385±260

- -

235±70 255±80 7,5±1,5 11,5±3

- -

9±5 10±5 Matched-pair analysis

Included in Zhou et al. 2013

P=0,01 P<0,001 P=0,30 P<0,001 P=0,44

Slakey(75)

New Orleans-USA2013

45

3maj

42min

17

3maj

14min

Malign + Benign

0 1(5,8%) 5(11,1%)

7(15,5%) 9(53%) 95±115 988± 1050

1(2,2%) 5(29%) - -

3(2,1) 6(6)

1(2,2%) 0 - -Focused on complications

P=0,007 P=0,0001 P=0,01

Zhou(76)

Nanchang-China2013

44

28min

16maj

44

28min

16maj

Benign (Hepato-lithiasis)

1(2,3%) 0 3(6,8%)

10(22,7%) 14(31,8%)367.5 (150–1200)

392.5 (200–1400)

6(13,6%) 8(18,2%)277.5 (190–410)

212.5 (140–315)

9.5 (7–50) 13.5 (8–61)

1(2,3%) 0 - -Matched-pair analysis

P=0,338 P=0,152 P=0,560 P=0,001 P=0,001

Kandil(77) 2012 15

2maj

21

9maj

NET Mets 0 0 2(13,3%) 3(20%) 7(33,3%) 158,3 (104,2) 538,9 (442,8)

0 8(38,1%) 162±78 324±42 3,2±1,7 7,5±1,7 - - - 6(4) - 9(4) Focused on prognosis of NET

New Orleans-USA 13min 12min mtxP=0,38 P=0,004 P=0,01 P<0,001 P<0,001 P=0,9

Johnson(78)

Washington-USA2012

88

34min

54Maj

*8LDLT

124

40min

84Maj

*20LDLT

Malign + Benign +

LDLT

1(1,1%) 1(0,8%) 6,8%

6,8% 10,4% 697±739 833±1008 17,2% 19,8% 238 234 6,3±3,82 7,59±4,76 1,1% 0,8%

- -LAP-ASSISTED VS OPEN

P=0,59 P=0,3 P=0,71 P=0,75 P=0,036 P=NS

Cannon(79)

Louisville-USA2012

35

19maj

16min

140

68maj

72min

CRLM 0 2(1,4%) -

23% 50% 202 ± 180 392 ± 322 5(17%) 30(25%)

- -

4,8 8,3

0 5 (3,5%)

-/

-3%

-/

-/

21%

-/

Matched-pair analysis

Included in Zhou et al. 2013

P=0,004 P<0,001 P=0,334 P<0,001 P=0,020

Hu(80)

Beijing-China2012

13

11min

2maj

13

11min

2maj

CRLM 0 0 0

1(7,6%) 0 258 ± 111 273 ± 95 2(15,3%) 3(23%) 313 ± 44 350 ± 46 8.5 ± 1.9 11.2 ± 1.8

1(7,6%) 0 - -Matched-pair analysis

P=NS P=NS P=NS P<0,05 P<0,05

Gustafson(81)

Dayton-USA2012

27

6maj

21min

49

18maj

31min

Malign 0 2(4,1%) 4(14,8%) 6(22,2) 20(48,8)

311 1086

- - - -

5 8

0 4(8,1%) - -

P=0,0031 P=0,045

Nguyen(82)

Pittsburgh-USA

2011 17

6maj

11min

20

6maj

14min

HCC - - -

6% 5% 101 164

- -

235 247 4,1 5,7

0 0 -11,2

-0%

-/

-6,9

-15%

-/

Included in Xiong et al. 2012 and Yin et al 2013

P=0,21 P=0,13 P=0,63 P=0,002 -P=0,04

-P=0,25

-/

Nguyen(82)

Pittsburgh-USA2011

24

7maj

17min

25

8maj

17min

CRLM - - -

4% 12% 67 92

- -

256 303 3,1 6,3

0 4%

-15

-4%

-/

-15

-4%

-/Matched-pair analysis

P=0,21 P=0,04 P=0,04 P=0,001

-P=0,92

-P=0,75

-/

Huh(83)

Jeonnam-Korea2011

20

19min

1maj

20

15min

5maj

CRLM 0 0

10(50%) 8(40%)350 (120–950)

500 (100-1200)

- -

358 (215–595)

278 (140–465)

10 (7-30) 10 (7-31)

1(5%) 0 - -Simultaneous colon and liver resections

P=0,525 P=0,048 P=0,004 P=0,831

Hu(84)

Jiangsu-China2011

30

¿

30

¿HCC 0 0 0

4(13,3%) 3(10%) 520±30 480±46

- -

180±45 170±32 13±2,1 20±3,2

3(10%) 0 - -

Included in Xiong et al. 2012, Yin et al 2013 and Parks et al. 2014

P=NS P=NS P=NS P<0,01

Kim(85)

Gwangju-Korea2011

26

5maj

21min

29

7maj

22min

HCC 0 0 3(10,3%)

1(3,8%) 7(24,1%)

- -

5(19,2) 7(24,1%)147,5(45-500)

220(65-445)11.08 ± 4.96

16.07 ± 10.697

0 0

-/

-1(3,8%)

-/

-/

-1(3,4%)

-/

Included in Xiong et al. 2012 and Yin et al 2013

P=0,054 P=0,660 P=0,031 P=0,034 P=1

Ker(86)

Kaohsiung-China2011

116

¿

208

¿HCC

0 6(2,8%)

6(5,2%)

7(6%) 63(30%) 138.9 ± 3361147.4 ± 1649.4

8(6,8%) 106(51%)156.3 ± 308.2

190.9 ± 79.2 6.2 ± 3 12.4 ± 6.8

0 4(1,9%) - -

Included in Xiong et al. 2012 and Yin et al 2013P=0,092 P<0,001 P<0,001 P<0,001 P=0,126 P=0,001

Tu(87)

Zheijang-China2010

28

3maj

25min

33

5maj

28min

Benign (Hepato-lithiasis)

0 0 0

4(14,2%) 5(15,2%) 180±56 184±50 0 1(3%) 158±43 132±39 6,8±2,8 10,2±3,4

2(7,1%) 0 - -

P=NS P=NS P=NS P<0,05 P<0,01

Tranchart(88)2010 42

5maj

42

5maj

HCC 1(2,4%) 1(2,4%) 2(4,7%) 9(21,4%) 17(40,4%) 364.3 ± 435.7723.7 ± 559.5

4(9,5%) 7(16,7%) 233.1 ± 92.7 221.8 ± 46.3 6.7 ± 5.9 9.6 ± 3.4 1(2,4%) 1(2,4%) 10.4 ± 8.0 10.6 ± 9.0 Included in Rao et al. 2012, Xiong et al.

Paris-France 37min 37min2012, Yin et al 2013 and Parks et al. 2014

P=1 P=1 P<0,0001 P=0,51 P=0,90 P<0,0001 P=1 P=0,82

Alemi(89)

San Francisco-USA2010

28

23min

5maj

25

10min

15maj

HCC 0 0 0 12(42%) 12(48%)

200 825 4 9 317 379 7 9

1(3,5%) 3(12%) - -

Clear selection bias

Included in Parks et al. 2014

P=0,003 - P=0,33 P=0,71

Abu Hilal(90)

Southampton-UK2010

50(55)

36min

19maj

85(119)

63min

56maj

CRLM 0 2(2,3%) 6(12%) 8(16%) 24(28%) 363 (500) 500 (600) 2(4%) 0 220 (145) 192 (87,5) 4(2,5) 10(9) 1(2%) 3(2,5%) 15(12,5) -

No P values as no comparisons

Included in Zhou et al. 2013

Potential duplication in Ref. 153. 19 major resections excluded from analysis

Belli(91)

Naples-Italy2009

54

3maj

51min

125

39maj

86min

HCC

1(2%) 5(4%)

7%

10(19%) 45(36%)297 (100 – 750)

580 (200 – 1300)

6(11%) 32(25,6%) 167 (80–240)185 (90–255)

8,4 (3–15) 9,2 (7–12)

0 0

-/

-0(0%)

-9(17%)

-/

-8(6,4%)

-51(41%)

Better margins but smaller tumors

Included in Rao et al. 2012 and Yin et al 2013.P=0,615 P=0,020 P<0,001 P=0,030 P=0,012 P=0,113

-/

-P=0,057

-P<0,001

Rowe(92)

Vancouver-Canada2009

18

17min

1maj

12

12min

Malign + Benign

0 0 1(5,5%)

5,5% 41,66 287 ± 109 473 ± 286

0 0

214 ± 30 224 ± 45 4.3 ± 2.3 5.8 ± 1.7

0 0 - -

Matched-pair analysis

Included in Rao et al. 2012,

P<0,05 P=0,03 P=0,5 P=0,01

Sarpel(93) 2009 20 56 HCC - - 0 1(5%) 4(7%) - - - - 161 ± 37 165 ± 53 - - - - -/ -/ Matched-pair analysis

New York-USA ¿ ¿-2(10%)

-/

-15(26%)

-/

Included in Rao et al. 2012, Yin et al 2013 and Parks et al. 2014

P=0,80

Lai(94)

Hong Kong-China2009

25

24min

1maj

33

¿HCC

0 1(3%)

1 (4%)

4(16%) 5(15%)

200 (5-2000) - 2(8%) -

150 (75-210) 135 (50-120) 7(4-11) 9(5-37)

0 -

-/

-3(12%)

- 6(24%)

-

Included in Xiong et al. 2012, Yin et al 2013 and Parks et al. 2014

P=0,25 P=0,83 P=0,34 P=0,008

Castaing(95)

Paris-France2009

60

26maj

34min

60

23maj

37min

CRLM 1,7% 1,7% 6(10%) 38(63%) 38(63%) - -

15% 36% 278 ± 123 294 ± 89 10 (5-50) 11 (7-36)

- -

-5.3 ± 7.5

-13%

-/

-5,2 ± 9,2

-28%

-/

Matched-pair analysis

Included in Rao et al. 2012, Zhou et al. 2013 and Parks et al. 2014P=0,007 P=0,41 P=0,76

-P=NS

-P=0,04

-P=-

Topal(96)

Leuven-Belgium2008

76

21maj

55min

76

21maj

55min

Malign 1(1,3%) 0 7(9,2%)

6(7,8%) 22(28,9%) 150 (5-4000) 300 (10-7000)

- - 95 (30-385) 179 (35-415)

6 (0-41) 8 (4-73)

- -

10(0-30) 7,5(0-45) Propensity-matched score

Included in Rao et al. 2012P=0,0008 P=0,013 P<0,0001 P=0,237

Cai(97)

Hangzhou-China2008

31

28min

3maj

31

28min

3maj

Malign 0 0 1(3,2%) 0 16,12%

502.9 (50–2000)

588.1 (80–2500)

- -

140.1 (60–380)

152,7(70-280)

7.5 (5–15) 12.2 (7–20)

0 0

-/

-0

-0

-/

-0

-0

Matched-pair analysis

Included in Rao et al. 2012 and Parks et al. 2014

P=0,51 P=0,41 P=0,001

Troisi(98)

Ghent-Belgium2008

20

1maj

19min

20

2maj

18min

Benign 0 0 2(10%)

4(20%) 9(45%)

- - 2(10%) 5(25%)

220.25 ± 122.28 (130–140)

241.8 ± 97.7 (150–530)

7.1 ± 4.4 (3–25)

10.45 ± 3.92 (6–21)

0 1(5%)

- -Included in Rao et al. 2012

P=0,176 P=0,673 P=0,008 P=NS

Cai(99) 2007 29 22 Benign (Hepato-

0 0 1(3,3%) 2(6,8%) 4(18,2%) 603 ± 525 655 ± 569 - - 236 ± 135 220 ± 61 8.8 ± 4.4 13 ± 9.2 1(3,4%) 1(3,4%) - -

Hangzhou-China26min

3maj

20min

2majlithiasis) P=0,424 P=0,737 P=0,589 P=0,045

Koffron(100)

Illinois-USA

2007 241

175min

66maj

100

49min

51maj

Malign + Benign

0 0

20(6%) to H-assisted

9,3% 22% 100 325 0 8% 95 182 1,7 5,4 2(0,8%) 4(4%) - - No P values as no comparisons

Included in Rao et al. 2012

Buell(101)

Ohio-USA2004

17

5maj

16min

100

¿

Malign + Benign

1(5,8%) - - 4(23%) -

288(50-150) 485

- -

2,8 4,5 2,9 (1-14) 6,5

1(5,8%) - - -Included in Rao et al. 2012

P<0,05 P<0,05 P<0,05

CLIN

ICAL

SER

IES

Shelat(102)

Southampton-UK2014

19

17min

2maj

-Malign + Benign

0 - 0 1(5,2%) - 100 (50-275) - - - 165 (90-203) - 4(1-8) - 0 -

-/

-1(5,2%)

-/

-

Primary liver resection

Potential duplication in Ref. 153. 2 major resections excluded from analysis

Shelat(102)

Southampton-UK2014

20

14min

6maj

-Malign + Benign

0 - 3 (15%) 2(10%) -400 (150-2000)

- - -285 (195-360)

- 4(1-57) - 1(5%) -

-/

-2(10%)

-/

-

Repeat lap liver resection on same population as before

Potential duplication in Ref. 153. 6 major resections excluded from analysis

Shelat(103)

Southampton-UK2014

52

32maj

20min

- Malign 0 - 8(15,4%) 6(11,5%) -500 (200-1373)

- - -240 (150-330)

- 5(1-21) - 1(1,9%) -

-/

-4(7,7%)

-/

-

Large tumors only. Mean tumor diameter = 83 mm (range 50-180)

Potential duplication in Ref. 153. 32 major resections excluded from analysis

Honda(104)

Tokyo-Japan2014 29 - Malign 0 - 1(3,4%) 20,7% - 141 (5-430) - - -

329 (147–519)

- 9(4-21) - 1(3,4%) -

-/

-1

-/

Cannon(105)

Louisville-USA2014

52

47min

5maj

-Malign + Benign

5(9,6%) - - 13(25%) - 100 (50-1500) - 8(15,4%) - 120 (60-360) - 3(0-16) - - -Only cirrhotic patients

Soyama(106)

Nagasaki-Japan2014

102

62maj

40min

-Malign + Benign

Hand-assisted

Cai(107)

Hangzhou-China2014

365

80LH

112LLS

68nAR

35S

11;Oth

-Malign + Benign

0 - 63(17,2%) 12,24% - 370.6±404.0 - - -150.8±73.0

- 9.2 ± 5.3 - 1,32% -

Laparoscopic Peng’s multifunction operative disector (LPMOD)

Troisi(108)

Ghent-Belgium

2014 265

46maj

219min

- Malign + Benign

0 . 17(6,4%) 38(11,3%) - 172±150 - - - 254±111 - 5,5±3,6 - 4(1,5%) -

Soubrane(109)

Paris-France2014

351

36maj

315min

- HCC 7(2%) - 45(13%) 80(23%) - - - 12(3%) - 180 (15-655) - 7(1-90) - 7(2%) -

Potential duplication with papers 119, 39, 138, 140, 142. All cases excluded from final count

Choi(110)

Gwangju-Korea2013

57

43min

14maj

- HCC

Honda(111)

Tokyo-Japan2013

41

7maj

34min

- Malign 0 - 2(4,9%) 9,8% - 216 (0-1600) - 0 -361 (176–605)

8 (5-28) - 0 - Only

Ikeda(112)

Fukuoka-Japan2013

30

7RH

4RPS

- Malign 0 - 0 2(6,6%) - 91 (0–330) - 1(3,3%) - 301 (79–697) - 9 (5-15) - 0 -Semiprone position

Casaccia(113)

Genoa-Italy2012

22

1maj

21min

- HCC

Park(114)

Multic-Korea2012

416

105maj

311min

-Malign + Benign

2001-2008

Gumbs(115)

Philapdelphia-USA

2012 53

28min

25maj

- Malign + Benign

Costi(116)

Paris-France2012

100

52maj

48min

-Malign + Benign + LDLT

0 - 17% 29% - 120±127.6 - 1% - 253±91.6 - 8.9 ± 9 - 4% -39 LLS LDLT included as major

Ramos-Fdez(117)

Alcorcon-Spain2011

11

4maj

7min

- Malign

Shafaee(118)

Paris / Oslo / Los Angeles2011

76

16maj

60min

.Malign + Benign

Dagher(119)

Clamart-France2010

163

16maj

147min

- HCC 2(1,2%) - 15(9,2%) 36(22%) - 250 (30-2000) - 16 (9,8%) - 180 (60-655) - 7(2-76) - 1(0,6%) -

Dagher(119)

Clamart-France2010

88

10maj

78min

- HCC 0 - 6(6,8%) 18(20,4%) - 200(30-2000) - 8 (9,1%) - 175 (60-450) - 7(2-20) - - -

Subgroup analysis: Recent experience

Duplicated paper (before). All cases excluded from final count

Cugat(120)

Multic-Spain2010 182 -

Malign + Benign

0 - 16(8,8%) 27 (14,8%) - - - 10(5,5%) - 150 (20-390) - 6 (1-20) - 4(2,2%) -

Kazaryan(121)

Oslo-Norway2010 121 - Malign 1(0,8%) - 5(4,1%) 8(8,6%) - 400 (50-4000) - 23(20%) - 180 (50-488) - 3 (1-42) - 3(2,4%) -

Kazaryan(121)

Oslo-Norway2010 28 - Benign 0 - 0 2(7,1%) - 200 (50-1800) - 3(10,7%) - 148 (80-325) - 2 (1-25) - 0 -

Yoon(122) 2010 69 - HCC 0 - 5(7,2%) 15 (21,7%) . 808,3 ± - 23 (33,3%) . 280.9 ± - 9.9 ± 5.6 - 2(2,8%) - Duplicated paper in Ref.

Gyeonggi-Korea21maj

48min1011,7 128.2

114. All cases excluded from final count

Bryant(123)

Creteil-France2009

166

31maj

135min

-Malign + Benign

0 - 16 (9,6%) 25(15,1%) - 200 (0-2000) - 9 (5,4%) - 6 (2-76) -180 (30-480)

- 1(0,6%) -

Duplicated paper in Ref. 39. All cases excluded from final count

Zhang(124)

Guangzhou-China2009

78

7maj

71min

-Malign + Benign

0 - 0 0 - 288 (101000) - 4 (5,12%) . 165 (60-390) - 5,6 (2-10) - 0 -

Vigano(39)

Creteil-France2009 174 -

Malign + Benign

0 -

A. 9(15,5%)

B. 6(10,3%)

C. 2(3,4%)

A.17,2%

B.22,4%

C.3,4%

-

A. 300

B. 200

C. 200

-

A. 6,9%

B. 5,2%

C. 3,4%

-

A. 210

B. 180

C. 150

-

A. 7

B. 7

C. 6

-

A. 0

B. 1

C. 1

-

A. first 58

B. second 58

C. last 58

Nguyen(125)

Pittsburgh-USA2009

109

37S

29LLS

31RH

10LH

1ERH

1Caud

- CRLM 0 - 4(3,6%) 13(11,9%) - 200 (20-2500) - 11(10,1%) - 234 (60-555) - 4(1-22) - 3(2,75%) -

Otsuka(126)

Tokyo-Japan2009 90 -

Malign + Benign

0 - 2(2,2%) 11(12,2%) - 262.9 ± 344.8 - - -268.0 ± 123.1

- 11.8 ± 7.3 - 1(1,1%) -

Machado(127)

Sao Paulo-Brasil2009

9

8min

1maj

-Malign + Benign

0 - 0 0 - - - 1(11%) -180 (120-300)

- 3 (1-5) - 0 -All left liver resections

Inagaki(128) 2009 68 - Malign + 0 - 2(2,9%) 18(26,4%) - 393 ± 564 - - - 214 ± 93 - 15,12 - 1(1,4%) -

Nagoya-Japan4 maj

64minBenign

Huang(129)

Taipei-Taiwan

2009 45

3maj

42min

-

Malign + Benign

Itano(130)

Tokyo-Japan2009

19

¿-

Malign + Benign

Cho(131)

Gyeonggi-do-Korea

2008 128

47maj

81min

-

Malign + Benign

Machado(132)

Sao Paulo-Brasil

2008 7

3min

4maj

- Malign

Abouljoud(133)

Detroit-USA

2008 11

7maj

4min

- Benign

Alkari(134)

Manchester-UK

2008 24

20 min

4maj

-

Malign + Benign

0 - 0 4% - 100 (25-1100) - 1(4,1%) - 155(50-300) - 3(1-14) - - -

Cho(135)

Seoul-Korea

2008 82

26maj

56min

-

Malign + Benign

0 - 4(5%) 12(15%) . 425 (20-900) - 21 (26%) - 240 (30-540) - 9(4-21) - 1(1,2%) -

Buell(136) 2008 253 - Malign + Benign

4(1,6%) - 6(2,4%) 41(16%) - 222 - 7% - 162 - 2,9 - 4% -

Louisville-USA70maj

183min

Chen(41)

Kaohsiung-Taiwan2008 19 - HCC 0 - 0 1(5,2%) - 329.2 ± 338.0 - 3(15,7%) - 175.8 ± 57.4 - 6,4 - 0 -

Dagher(137)

Clamart-France2008

32

3maj

29min

- HCC 1(3,1%) - 3(9%) 8(25%) - 461 ± 498 - 5(15,6%) - 231 ± 101 - 7.1 ± 7 - 1(3,1%) -

Duplicated paper in Ref. 119. All cases excluded form final count

Dagher(138)

Clamart-France2007

70

19maj

51min

-Malign + Benign

1(1,4%) - 7(10%) 11(16%) - 397 ± 356 - 9(13%) - 227 ± 109 - 5.9 ± 5.6 - 1(1,4%) -

Hompes(46)

Leuven-Belgium2007

45

9maj

36min

-Malign + Benign

0 - 3(6,6%) 11(24%) - 200 (5-4000) - - 115 (45-360) - 7(3-41) - 1(2,2%) -

Min(139)

Seoul-Korea2006

10

4min

6maj

-Malign + Benign

Pure laparoscopic

Min(139)

Seoul-Korea2006

9

2maj

7min

-Malign + Benign

Hand.assisted

Vibert(140)

Paris-France2004

46

20min

26 maj

-Malign + Benign

1(2,1%) - 7(15%) 34% - - - 5(10%) -Maj: 360

Min: 190 - 10 (3-36) - 3(6,5%) -

Belli(141) 2004 16 - HCC 1(6,25%) - 1(6,25%) 2(13,3%) - 280 (100–550)

- 0 - 152 (80–180 - 8.8 (5–15) - 0 -

Naples-Italy1LH

15min

Descottes(142)

Limoges-France2003

87

3maj

84min

- Benign 0 - 9(10%) 5% - - - 5(6%) - - - 5(2-13) - 0 -

Gigot(143)

Brussels-Belgium2002

37

2maj

35min

-

Malign

10HCC

27CRLM

0 - 13,5% 8(22%) - - - 6(16%) - - - 7(2-16) - 0 -

Cherqui(144)

Creteil-France2000

30

1maj

29min

-Malign + Benign

0 - 2(6,6%) 6(20%) - 300(0-1500) - 10% - 214 ± 87 - 9,6(3-40) - 0 -

Duplicated in Ref. 39. All cases excluded from final count.

Hüscher(145)

Esine-Italy1997

20

14maj

6min

- Malign 1(5%) - 0 45% -397,5 (100-1200)

- 7(35%) -193 (120-270)

- 11(5-25) - 1(5%) -

LAPAROSCOPIC MAJOR-ONLY RESECTIONS

Author Year

NType of lesion

MortalityConvers.

rateComplications Blood loss

Blood transfusion

Operation time Hospital Stay Bile leak Resection margins Comments

LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR LLR OLR

LLR

-mm

-posit

-<1cm

OLR

-mm

-posit

-<1cm

COM

PARA

TIVE

STU

DIES

Medbery(146)

Atlanta-USA2014

46

46RH

57

57RH

Malign + Benign

2(4,2%) 2(3,5%)

5(10,4%)

13(27,1%) 25(43,9%) 281±306 737±947

- -

233±32 285±85 5(3-31) 7(4-35)

0 3,5%

-/

-4(8,3%)

-/

-/

-4(7%)

-/Includes cost analysis

P=1 P=0,075 P=0,002 P<0,001 P<0,001 P=1

Abu Hilal(6)

Southampton-UK

201338

38RH

46

46RH

Malign + Benign

0 2(4%) 4LA (11%)

4 open (11%)

5(13%) 7(15%) 650(50-3000) 500(50-5200) 8(21%) 15(33%) 310(177-480) 190(90–440) 5(2-20) 9(3-50)

2,6% 0 - -Cost analysis. Neutrality for lap/open

P=0,499 P=0,788 P=0,397 P=0,237 P<0,001 P<0,001

Topal(147)

Leuven-Belgium2012

20

13RH

4LH

3nAr

20

7RH

6LH

7nAr

CRLM 0 0 0

7(35%) 7(35%)550 (100-4000)

550 (100-2500)

- -

257.5 (75–360)

232.5 (120–400)

8 (5-51) 8 (5-19)

0 0

-7,5(0-20)

-1(5%)

-/

-5,5(0-30)

-1(5%)

-/Matched-pair analysis

Included in Zhou et al. 2013

P=1 P=0,884 P=0,228 P=0,848-P=0,651

-P=1

Abu Hilal(148)

Southampton-UK

201136

36RH

34

34RH

Malign + Benign

0 2(6)

4LA (11%)

4 open (11%)

5(14%) 5(15%) 700 (75-3000) 500(50-5200) 8(22%) 7(21%) 300 (180-465) 180 (90-360) 5(3-20) 9(4-48) 1(2,7%) 0

-/

-1(5%)

-/

-/

-5(20%)

-/

Included in Parks et al. 2014

Duplicated in Ref 6. Excluded all cases from

countP=0,232 P=0,922 P=0,156 P=0,868 P<0,0001 P<0,0001 P=0,198

Martin(149)

Louisville-USA2010

90

39RH

51LH

360

201RH

159LH

Malign + Benign

1 3

4(4%)

23% 52% 150(20-1000) 400(65-5000) Unclear unclear 140 (50–240) 160 (30–432) 3(1-13) 7(2-57) 7% 8%

-/

-3%

-/

-/

-4%

-/

P=NS P<0,0001 P<0,0001 P<0,001 P=0,009 P<0,0001 P=0,2 P=0,3

Dagher(150)

Paris-France2009

22

22RH

50

50RH

Malign + Benign

0 1(2%)

2(9%)

3(13,6%) 23(48%) 519,5±93,4 735,2±74,4 3(14%) 9(18%) 360±20,3 328±10,6 8,2±1,1 12,5±1,5 1(4,5%) 2(4%)-20.1 ± 4.3

-16,6±2,6

Included in Rao et al. 2012,

P=1P=0,427 (specific)

P=0,04 (general)P=0,038 P=0,744 P=0,069 P=0,009 P=1 P=0,348

Cai(151)

Hangzhou-China2009

19

19LH

19

19LH

Malign + Benign

0 0 2(11%) 2(10,5%) 4(21%)

462 ± 372 895 ± 704 2(10,5%) 8(42%) 222 ± 104 204 ± 59 9 ± 5 13 ± 7

0 1(5,2%) - -

P=0,03 P=0,062 P=NS P=0,086

Saint-Marc(152)

France+Italy2008

6

4RH

2LH

6

4RH

2LH

Benign 0 0 0 1(16,6%) 0

205 ± 156.7 341.7 ± 28.1

- -

201.7 ± 64.01 180.0 ± 38.9 5.5 ± 1 10.8 ± 2.6

1(16,6%) 0 - -

P=0,129 P=0,4 P=0,001

Di Fabio(153)

Southampton-UK

2014 127 -Malign + Benign

2(1,6%) - 11(9%) 28(22%) . 500 (950-275) - - - 330 (270-400) - 5(4-7) - 3(2,3%) -

-/

-12(10%)

-/

-

Some cases may be potentially duplicated in Ref. 154, but impossible to know.

CLIN

ICAL

SER

IES

Hwang(34)

Multic-Korea2013 265 -

Malign + Benign

2(0,75%) - 17(6,4%) 53(20%) -836.0 ± 1223.7

- 65 (24,5%) - 399.3 ± 169.8 -12.3 ± 7.9

- - -

Nitta(154)

Morioka-Japan2013 106 - - - -

8 full-lap

4 hand-assist

84 lap-assist

No convers.

18(17%) - - - - - - - - - 6(5,6%) -

Tzanis(155)

Multic-Europe2013

495

348RH

108LH

5CH

34Tri

-Malign + Benign

- - 49(10,8%) - -437-RH

275-LH- - -

301-RH

250-LH- - - - -

Pearce(156)

Southampton-UK

201135

35RH-

Malign + Benign

0 - 7(19,6%) 4 (11,4%) -650 (75–3,000)

- - -295 (180–465)

- 5 (3-20) - 1(2,8%) -Duplication in Ref. 155. All cases excluded from final count

Pearce(157)

Southampton-UK

201120

20LH-

Malign + Benign

Duplication in Ref. 155. All cases excluded from final count

Nitta(158)

Morioka-Japan2010

42

2RTri

14RH

16LH

10Oth

-Malign + Benign

0 - - 5(11,9%) - 631 6(14,2%) 317 - 13 - 2(4,8%) - LAP-ASSISTED + HANGING

Dagher(159)

Clamart-France2009

210

136RH

74LH

-Malign + Benign

2(0,9%) - 26(12,4%) 46(21,9%) - 300(20-2500) - 30(14,3%) - 250±103,8 - 6±4,5 - 13(6,2%) - MULTICENTER

Cho(160)

Seoul-Korea2007

6

4LH

2RH

-Malign + Benign

0 - 0 0 - 370 (80-1250) - 0 - 175 (95-330) - 9 (4-14) - 0 -

Hand-assisted

Duplication in Ref. 34. All cases excluded from final count

DISTRIBUTION BY NUMBERS, HOSPITALS AND COUNTRIES

100 cases published

50 and <100 cases published

25 and <50 cases published

<25 cases published

REGION HOSPITAL YEAR NUMBER REGION HOSPITAL YEAR NUMBER REGION HOSPITAL YEAR

NUMBER

ASIA Division of Hepatobiliary and Pancreatic Surgery, and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong.

2014

2013

2013

17

32

20

EUROPE Department of Hepatopancreatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France.

2014

2002

31

21

USA Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California.

2014 52

ASIA Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

2014 29 EUROPE Dept. of General & Hepato-Biliary Surgery, Liver Transplantation Service, Ghent University Hospital and Medical School, De Pintelaan, Ghent, Belgium.

2014

2014

2008

57

265

20

USA Division of General and Gastrointestinal Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA.

2014 46

ASIA Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan,

2014 21 EUROPE Hepato-biliary and Pancreatic Surgery Unit, Department of Surgery, "Doctor Josep Trueta" Hospital, Biomedical Institute of Research, IdIBGi, Girona, Spain,

2014 50 USA Deparment of Surgery, University of Louisville, Louisville, KY, USA.

2014

2013

2012

2010

2008

52

8

35

90

253

ASIA Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul, Republic of Korea.

2014 24 EUROPE Department of Hepatobiliary Surgery and Liver Transplant, St Antoine Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), University of Pierre and Marie Curie (UPMC), Paris, France.

2014 351 USA John C. McDonald Regional Transplant and Hepatopancreatobiliary Surgery Center , Willis-Knighton Health System, Shreveport, Louisiana.

2013 54

ASIA Department of General Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam

2014 173 EUROPE Department of Hepato-Biliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, UK.

2014

2014

2013

2011

127

91

46

36

USA Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA.

2013 40

2011

2010

2008

55

50

24

ASIA Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

2014

2013

29

41

EUROPE Department of Minimally Invasive Digestive Surgery, Antoine-Béclère Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Clamart, France.

2013

2010

2010

2010

2009

2008

2007

52

163

88

42

22

32

70

USA Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.

2013

2012

45

15

ASIA Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan,

2014 102 EUROPE MULTICENTER EUROPE 2013 495 USA Department of Surgery, Georgetown University Hospital, Washington, DC, USA

2012 88

ASIA Key Laboratory of Laparoscopic Technique of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Institute of Minimally Invasive Surgery of Zhejiang University, Qingchun Road East, Hangzhou, China,

2014

2010

2009

2008

2007

365

28

19

31

29

EUROPE Liver-Pancreas-Kidney Transplantation Surgical Unit, Department of General, HPB Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy.

2012 46 USA Division of Surgical Oncology, Department of Surgery, Wright State University Boonshoft School of Medicine, Dayton, OH, USA.

2012 27

ASIA Departments of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan.

2013 23 EUROPE Abdominal Surgery, University Hospital Gasthuisberg, Herestraat 49, Leuven, 3000, Belgium.

2012

2008

2007

20

76

45

USA University of Pittsburgh Medical Center Liver Cancer Center, University of Pittsburgh, Starzl Transplant Institute, 3459 Fifth Avenue, Pittsburgh, PA

2011

2011

2009

17

24

109

ASIA Department of Hepato-Biliary-Pancreatic Surgery, Osaka City General Hospital, Miyakojima-Hondori, Miyakojima-ku, Osaka, Japan.

2013 28 EUROPE Department of Digestive Surgery and Transplantation, Hôpital HURIEZ, Lille, France 2011 36 USA Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY

2009

2000

65

11

ASIA Department of General Surgery, Chinese People's Armed Police Force 8710 Hospital, Putian, PR China.

2013 97 EUROPE Hospital Universitario Fundacion Alcorcon, Alcorcon, Madrid, Spain. 2011 11 CANADA Department of Surgery, Jewish General Hospital, McGill University, Montreal, Canada.

2009 44

ASIA Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

2013

2010

13

69

EUROPE

USA

Institut Mutualiste Montsouris, University Paris V, Paris, France; Oslo University Hospital – Rikshospitalet), Oslo, Norway; and the Departments of Surgery, University of Louisville, Louisville, KY, and Tulane Abdominal Transplant Institute, New Orleans, LA.

2011 76 USA Department of General Surgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue/A 80, Cleveland, OH

2009 31

2008

2008

2007

2006

128

82

6

19

ASIA Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Shapingba District, Chongqing, People's Republic of China.

2013 116 EUROPE Department of Surgery, Liver Unit, Scientific Institute H San Raffaele, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy.

2010

2008

16

20

CANADA Department of Surgery, Diamond Health Care Centre, University of British Columbia, 2775 Laurel Street, 5th Floor, Vancouver, V5Z 1M9, BC, Canada.

2009 18

ASIA Department of Hepatobiliary Pancreatic Surgery, West China Hospital, Sichuan University, Cheng du, Sichuan Province, China.

2013 30 EUROPE Department of Surgery A, Carmel Medical Center, affiliated with Rappaport Faculty of Medicine, Technion-lsrael Institute of Technology, Haifa, Israel.

2010 9 USA Department of Surgery, New York University Medical Center, New York, USA.

2009 20

ASIA Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, , China,

2013 44 EUROPE Hepato-Bilio-Pancreatic Unit of Hospital Mutua de Terrassa, C/Plaza Dr Robert no 5, 08221, Terrassa, Barcelona, Spain

2010 182 USA Department of Surgery, University of California, San Francisco, USA.

2010 28

ASIA Department of Surgery, Chosun University Hospital, Gwangju, Korea. 2013

2011

57

26

EUROPE Interventional Centre, Rikshospitalet University Hospital, Oslo, Norway. 2010

2002

149

13

SOUTH AMERICA

Department of Gastroenterology, University of São Paulo, Rua Evangelista Rodrigues 407, 05463-000 São Paulo, Brazil.

2009

2008

9

7

ASIA Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

2013

2001

30

17

EUROPE Servicio de Cirugía, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, España.

2009 18 USA Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, 2799 W. Grand Boulevard, CFP2, Detroit, MI 48202, USA.

2008 11

ASIA MULTICENTER KOREA 2013 265 EUROPE Institute of Liver Studies, King's College Hospital, London, UK 2009 10 USA Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.

2007 15

ASIA Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan.

2013

2010

2009

106

42

82

EUROPE Bilio-Pancreatic Surgery Unit, Università degli Studi di Milano, Ospedale San Paolo, Milan, Italy.

2009 22 USA Division of Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

2007 241

ASIA Department of Surgical Oncology, The General Hospital of Chinese People's Liberation Army, Beijing, China.

2012 13 EUROPE Service de Chirurgie Digestive et Hépatobiliaire, Hôpital Henri Mondor-Université Paris 12, Créteil, France.

2014

2009

2009

2009

2007

2003

2003

45

166

174

60

36

13

18

USA Connecticut Surgical Group, Hartford Hospital Transplant Program, Department of Surgery, Hartford Hospital, CT, USA.

2007

2002

28

11

2002

2000

2

30

ASIA Department of Surgery, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong

2011

2007

33

25

EUROPE Department of General and Hepato-Pancreato-Biliary Surgery, S. M. Loreto Nuovo Hospital Via A. Vespucci, 80142 Naples, Italy.

2009

2007

2006

2004

54

23

8

16

USA Division of Transplantation, University of Cincinnati, OH 45267-0558, USA.

2004 17

ASIA Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeonnam, 519-809, Korea

2011 20 EUROPE AP-HP Hopital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94804, France. 2009 60 USA Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033, USA.

1999 43

ASIA Hepato-bilio-pancreatic Surgery Department, Northern Jiangsu People's Hospital, Yangzhou 225001, Jiangsu Province, China.

2011 30 MULTIC EUROPE / USA / AUSTRALIA

Dagher(159)

Clamart-France

2009 210

ASIA Division of HBP Surgery, Chung-Ho Memorial Hospital, Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

2011 116 EUROPE Unit of HPB and Advanced Laparoscopic Surgery, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.

2008 25

ASIA Department of Hepatobiliary Surgery, First People's Hospital of Foshan, Foshan, Guang Dong, China.

2010 29 EUROPE HPB unit, Division of Surgery, Hammersmith Hospital, Imperial College London, Oncology, Reproductive Biology and Anaesthesia, London, UK

2008

2007

28

18

ASIA Department of Surgery, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Rd., Chai Wan, Hong Kong SAR, China. ericlai@alumni.cuhk.edu.hk

2010

2009

2005

2003

19

25

10

6

EUROPE Department of Surgery, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.

2008 24

ASIA Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan. 2009 10 EUROPE Service de Chirurgie Digestive Endocrinienne et Thoracique, Centre Hospitalier Regional d'Orleans, France; and Department of General Surgery, University of Messina, Italy.

2008 6

ASIA Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.

2009 78 EUROPE Service de chirurgie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, France. Paris-France

2006 16

ASIA Division of General and Gastroenterological Surgery, Department of Surgery (Omori), Toho University School of Medicine, 6-11-1 Omorinishi, Otaku, Tokyo,

2009

2005

90

30

EUROPE II Department of Surgery Center of Laparoscopic and Minimally-invasive Surgery, S. Gerardo Hospital, via Donizetti 106, Monza, Italy.

2003 7

ASIA Department of Surgery, Yokoyama Hospital for Gastroenterological Diseases, Nagoya, Aichi, Japan.

2009 68 EUROPE Department of Digestive Diseases, Montsouris Institute, Paris, France. 2004 46

ASIA Department of Surgery, Taipei Medical University Hospital, 252, Wu-Hsing 2009 45 EUROPE Second Department of General Surgery, University of Turin, C.so A.M. Dogliotti 14, 2003 30

Street, 110, Taipei, Taiwan. 2003 7 10126 Turin, Italy.

ASIA Endoscopic Surgery Center, Eiju General Hospital, Tokyo, Japan. 2009 19 MULTIC

EUROPEAN

Hopital Universitaire Dupuyten, Limoges, France. 2003 87

ASIA Department of Surgery, Gastrointestinal Center, Yuan General Hospital, Kaohsiung, Taiwan.

2008

2008

2000

97

19

9

EUROPE Saint-Luc University Hospital, Brussels, Belgium. 2002 37

ASIA Department of Surgery, Kashiwa Hospital, Jikei University School of Medicine, 163-1 Kashiwashita, Kashiwa, Chiba 277-8567, Japan.

2006 9 EUROPE Department of General and Digestive Surgery, CHU, Caen, France. 1998 4

ASIA General Surgery, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.

2005 8 EUROPE Department of General Surgery, Ospedale Vallecamonica, Esine, Italy. 1997 20

ASIA Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan

2003 11 EUROPE Department of Digestive and Laparoscopic Surgery, CHU-André Vesale, 706, route de Gozée, 6110 Montigny-le-Tilleul, Belgium.

1996 1

REFERENCES

1. Memeo R, de'Angelis N, Compagnon P, Salloum C, Cherqui D, Laurent A, et al. Laparoscopic vs. Open Liver Resection for Hepatocellular Carcinoma of Cirrhotic Liver: A Case–Control Study. World J Surg. 2014 Jun 7;:InPress.

2. Chan ACY, Poon RTP, Cheung TT, Chok KSH, Dai WC, Chan SC, et al. Laparoscopic versus open liver resection for elderly patients with malignant liver tumors: a single-center experience. J Gastroenterol Hepatol [Internet]. 2014 May 15;29(6):1279–83. Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24517319&retmode=ref&cmd=prlinks

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