laparoscopic vs. open liver resection for malignant liver disease. a systematic review

8
Laparoscopic vs. open liver resection for malignant liver disease. A systematic review Ahsan Rao*, Ghaus Rao a , Irfan Ahmed b Department of Surgery, Ward 31, Foresterhill, Aberdeen Royal Infirmary, Aberdeen AB25 2ZA, United Kingdom article info Article history: Received 13 May 2011 Accepted 28 June 2011 Available online 15 September 2011 Keywords: Laparoscopic Open liver resection Hepatocellular carcinoma Hepatic malignancy Meta-analysis abstract Introduction: Since the introduction of minimally invasive techniques, there is little agree- ment about use of laparoscopic surgery for malignant liver lesions as compared to open resection. We aim to analyse all available data comparing both these groups. Methods: All the studies that compared laparoscopic and open liver resections for malig- nant lesions were searched on various databases. Data were collected and analysed in Review Manager RevMan (version 5.0). Results: There were total of 10 studies (n ¼ 700) that compared laparoscopic (296/700) and open (404/700) hepatic resections for malignant lesions. Laparoscopic group was associated with reduced number of patients requiring blood transfusion [Odds ratio 0.35 CI 0.20, 0.60 P<0.001 HG 0.85], decreased number of positive resection margin [Odds ratio 0.34 CI 0.16, P0.006 HG 0.73] and decrease in overall complication rate [Odds ratio 0.43, CI 0.26, 0.73 P0.002 HG 0.22]. Laparoscopic group was associated with less operative blood loss [WMD 162.6 ml CI 261.79, 73.45 P<0.001] and reduced hospital stay [WMD 4.28 days CI 6.33, 2.23 P<0.001]; however, there was significant heterogeneity [HG <0.001] between the studies for these parameters. Conclusion: The laparoscopic group was associated with reduce overall complication rate, positive resection margins and number of patients requiring blood transfusion. There is still need for level I and II data to compare laparoscopic versus open hepatic resection in malignant lesions. Crown Copyright ª 2011 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved. Introduction Liver cancer is the fifth most common cancer in the world 1,2 and it is associated with poor prognosis. 2,3 If the tumour is not removed completely after surgical resection, the survival rate is usually between 3 and 6 months. 1,2 In 1990, it was estimated that there were more than 400,000 new cases of primary liver cancer worldwide, and a similar number of patients died as a result of this disease. 4,5 Hepatic tumours of malignant origin are commonly secondary to metastatic cancer. 1 The most common type of primary hepatic cancer is hepatocellular carcinoma. 1 The treatment options depend on the stage of liver cancer and the overall condition of the patient. * Corresponding author. Tel.: þ44 (0) 1224 323224. E-mail addresses: [email protected], [email protected] (A. Rao), [email protected] (G. Rao), [email protected] (I. Ahmed). a Tel.: þ44 (0) 1224 323224. b Tel.: þ44 (0) 1224 555056, Secretary: þ44 (0) 1224 551050; fax: þ44 (0) 1224 551236. available at www.sciencedirect.com The Surgeon, Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland www.thesurgeon.net the surgeon 10 (2012) 194 e201 1479-666X/$ e see front matter Crown Copyright ª 2011 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.surge.2011.06.007

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t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1

avai lable at www.sciencedirect .com

The Surgeon, Journal of the Royal Collegesof Surgeons of Edinburgh and Ireland

www.thesurgeon.net

Laparoscopic vs. open liver resection for malignant liverdisease. A systematic review

Ahsan Rao*, Ghaus Rao a, Irfan Ahmed b

Department of Surgery, Ward 31, Foresterhill, Aberdeen Royal Infirmary, Aberdeen AB25 2ZA, United Kingdom

a r t i c l e i n f o

Article history:

Received 13 May 2011

Accepted 28 June 2011

Available online 15 September 2011

Keywords:

Laparoscopic

Open liver resection

Hepatocellular carcinoma

Hepatic malignancy

Meta-analysis

* Corresponding author. Tel.: þ44 (0) 1224 32E-mail addresses: [email protected], a.

(I. Ahmed).a Tel.: þ44 (0) 1224 323224.b Tel.: þ44 (0) 1224 555056, Secretary: þ44 (

1479-666X/$ e see front matter Crown CopyrRoyal College of Surgeons in Ireland. Publishdoi:10.1016/j.surge.2011.06.007

a b s t r a c t

Introduction: Since the introduction of minimally invasive techniques, there is little agree-

ment about use of laparoscopic surgery for malignant liver lesions as compared to open

resection. We aim to analyse all available data comparing both these groups.

Methods: All the studies that compared laparoscopic and open liver resections for malig-

nant lesions were searched on various databases. Data were collected and analysed in

Review Manager RevMan (version 5.0).

Results: There were total of 10 studies (n ¼ 700) that compared laparoscopic (296/700) and

open (404/700) hepatic resections for malignant lesions. Laparoscopic group was associated

with reduced number of patients requiring blood transfusion [Odds ratio 0.35 CI 0.20, 0.60

P<0.001 HG 0.85], decreased number of positive resection margin [Odds ratio 0.34 CI 0.16,

P0.006 HG 0.73] and decrease in overall complication rate [Odds ratio 0.43, CI 0.26, 0.73

P0.002 HG 0.22]. Laparoscopic group was associated with less operative blood loss [WMD

162.6 ml CI �261.79, 73.45 P<0.001] and reduced hospital stay [WMD 4.28 days CI �6.33,

�2.23 P<0.001]; however, there was significant heterogeneity [HG <0.001] between the

studies for these parameters.

Conclusion: The laparoscopic group was associated with reduce overall complication rate,

positive resection margins and number of patients requiring blood transfusion. There is

still need for level I and II data to compare laparoscopic versus open hepatic resection in

malignant lesions.

Crown Copyright ª 2011 Royal College of Surgeons of Edinburgh (Scottish charity number

SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights

reserved.

Introduction primary liver cancer worldwide, and a similar number of

Liver cancer is the fifth most common cancer in the world1,2

and it is associated with poor prognosis.2,3 If the tumour is

not removed completely after surgical resection, the survival

rate is usually between 3 and 6 months.1,2 In 1990, it was

estimated that there were more than 400,000 new cases of

[email protected] (A

0) 1224 551050; fax: þ44ight ª 2011 Royal Collegeed by Elsevier Ltd. All rig

patients died as a result of this disease.4,5

Hepatic tumours of malignant origin are commonly

secondary to metastatic cancer.1 The most common type of

primary hepatic cancer is hepatocellular carcinoma.1 The

treatment options depend on the stage of liver cancer and the

overall condition of the patient.

. Rao), [email protected] (G. Rao), [email protected]

(0) 1224 551236.of Surgeons of Edinburgh (Scottish charity number SC005317) andhts reserved.

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1 195

First open liver resection was carried out in 1949.6 After the

explanation of functional anatomy of liver by Couinaud,7 its

progress became worldwide. The description of segmental

anatomy immensely assisted in improving surgical techniques.

The concept of minimally invasive surgery gradually crept

into liver surgery after the first laparoscopic resection of liver

was carried out in 1992.8,9 It was initially performed for benign

and cystic lesions that were located at easy accessible loca-

tions. As the surgical techniques became better defined, the

laparoscopic liver resection surgery was carried out for

malignant lesions. With on going technological advance-

ments in laparoscopic techniques, more hepatic resections of

malignant tumours are being carried out.

The evidence of comparison between laparoscopic versus

open hepatic resection of malignant tumours is still scarce.

Some observational studies have directly compared the peri-

and post-operative outcomes of laparoscopic and open liver

resection for hepatic lesions. In the recent years there have

been few comparative studies that investigated the short-

term and long-term effects of laparoscopic and open hepatic

resections for malignant lesions only. There is no level 1 or II

evidence comparing laparoscopic and open liver resection for

malignant lesions. In this study, we will analyse all the

available data of observational studies that compare laparo-

scopic and open liver resections for malignant lesions.

Methods

All the studies that compared laparoscopic vs. open liver

resections for malignant lesions were searched on various

databases that included Medline, Ovid, Embase, and Pubmed.

The following Mesh search terms were used:

“laparoscopy,” “hepatectomy,” “liver resection,” “Open liver

resection,” “Hepatic resection,” “laparoscopic liver resection,”

“segmentectomy,” “sectionectomy,” “comparative study.”

Further, the combinations of these termswere used. The term

like “vs” was used to find comparative studies in particular.

Table 1 e Demographics of the studies included.

Author Year Design No of patients

Lap Open

Mala et al. 2002 R, P(L) 13 14

Laurent et al. 2003 RM(O) 13 14

Kaneko et al. 2005 P(L), R(O) 30 28

Belli 2007 RM 23 23

Cai et al. 2008 RM 31 31

Belli et al. 2009 RM, P(L), RM 54 125

Tranchart et al. 2009 (O) 42 42

Sarpel et al. 2009 RM 20 56

Endo et al. 2009 RM 10 11

Castaing et al. 2009 RM 60 60

L, Laparoscopic; max, maximum; O, open; n/c, not commented; P, prosp

matched.

a 1 age; 2 gender; 3 American Society of Anaesthesiologists (ASA) classifi

7 resection type; 8 cirrhosis; 9 liver metastasis; 10 primary malignancy; 1

b 1 malignancy; 2 tumour location; 3 primary hepatic cancer; 4 only pat

7 resection type.

c 1 benign disease; 2 tumour location; 3 primary hepatic cancer; 4 metas

All the searched abstracts, studies, and citations were

analyzed. All the potential articles were cross-referenced.

There were no language restrictions. The latest date for the

search was 30th January 2010. Two independent researchers,

AR and IA reviewed the selected studies separately.

Inclusion criteria

Studies meeting the following criteria were included in the

systemic review:

(1) Studies that compared peri- and post-operative outcomes

in patients undergoing laparoscopic and open hepatic

resection

(2) Studies reporting at least one of the peri-operative

parameters, post-operative outcome measures or patho-

logical measures

(3) Studies in which all resected lesions were malignant.

Exclusion criteria

Studies were excluded from the analysis if

(1) The outcomes of interest were not reported

(2) It was impossible to extract or calculate the appropriate

data from the published results;

(3) The resected lesions were benign

Outcomes of interest and definitions

The following parameters were identified and reviewed for

each study.

Basic Demographics: first author, year of publication, total

number of patients in laparoscopic and open resection group

in each study, study design, matching criteria, inclusion and

exclusion criteria, and male to female ratio.

Peri-operative parameters: operative time, operative blood

loss, number of patients requiring blood transfusion, use of

portal triad clamping and duration of portal triad clamping.

Matchinga Inclusion criteriab Exclusion criteriac

1e6, 9, 11, 12 1 1, 3

1, 2, 4e8, 10, 12, 1, 3, 4 1, 2, 4

1, 2, 13 1, 3 1, 4

1e3, 5e8 2, 4, 6 1, 5, 6

1, 2, 5, 6, 8 e 1

1e3, 5e8 3, 4e6 1, 5, 6

1e3, 5, 7, 13 1, 4, 5 1

1, 2, 5, 8 3, 5 1

1e7, 1 3, 5 1

1e6, 9, 13 1, 2, 5e7 1

ective; PM, prospective matched; R, retrospective; RM, retrospective

cation; 4 malignancy; 5 mean size of lesion; 6 location of neoplasm;

1 previous operations; 12 neoplasm histology; 13 Child-Pugh grading.

ients with chronic liver disease; 5 ASA classification; 6 tumour size;

tatic cancer, 5 ASA classification; 6 Child-Pugh grading.

Table 2 e Characteristics of the studies included.

Author Conversions Mean age (median) Female (n [%])

n (%) Lap Open Lap Open

Mala et al. 0 68 59 4 (31) 4 (29)

Laurent et al. 2 (15.4) 62.6 65.9 3 (23) 4 (24)

Kaneko et al. 1 (3.3) 59 61 12 (40) 18 (64)

Belli 1 (4.3) 59.5 62.4 10 (43.5) 9 (39.1)

Cai et al. 1 (3.2) 54.2 51.7 7 (22.5) 5 (16.1)

Belli et al. 4 (7) 63.6 61.5 23 (42.5) 47 (37.6)

Tranchart et al. 2 (4.7) 63.7 65.7 15 (35.7) 14 (33.3)

Sarpel et al. 4 (17) 63.8 58.3 5 (25) 11(20)

Endo et al. 0 72 64 2 (20) 3 (29)

Castaing et al. 6 (10) 62 62 23 (28.3) 23 (28.3)

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1196

Postoperative parameter: time to first oral Intake, duration of

post operative hospital stay and post-operative analgesia

requirement.

Early post operative adverse events: post operative complica-

tions divided into liver resectionerelated (cirrhotic decom-

pensation/ascites, hepatic hemorrhage, biliary leakage, liver

failure) and general complications (chest infection, bowel

perforation, urinary infection, wound infection, cardiac

complications, intra-abdominal abscesses, Clostridium difficile

infection, pleural effusion).

Oncological clearance: Conversion rate, pathologic resection

margin size, positive resection margins, resection margins

<1 cm, and resection margins >1 cm.

Long-term outcomes: Short-term and long-term cost effec-

tiveness, overall complication rate (includes all liver-specific

and general complications), incisional hernia, mortality rate,

5 year and 3 year survival outcome, and recurrence rate.

Statistical analysis

Statistical softwareReviewManager, version 5.0 (TheCochrane

Collaboration, Software Update, Oxford, United Kingdom) was

used toperformtheanalysis.Weightedmeandifference (WMD)

Table 3 e Pathological characteristics of laparoscopic group.

Author No. of procedures n (%) Pathology ofresecte

Mala et al. 15 (52) C ¼ 13

Laurent et al. 13 (48) E ¼ 13

Kaneko et al. 30 (52) E ¼ 30

Belli et al. 23 (50) E ¼ 23

Cai et al. 31 (50) E ¼ 24, G ¼ 4

Belli et al. 54 (30) E ¼ 54

Tranchart et al. 42 (50) E ¼ 42

Sarpel et al. 20 (24) E ¼ 20

Endo et al. 10 (49) E ¼ 10

Castaing et al. 60 (50) C ¼ 60

L, Laparoscopic; n/c, not commented; O, open.

T, three segments resection; LLS, left lateral segmentectomy; RHL, right he

n/c not commented.

a C, malignant metastatic; E, hepatocellular carcinoma; G, gallbladder ca

b W, Wedge resections; S, segmentectomies; B, bisegmentectomies; T, t

hepatic lobectomy; LH, Left hemihepatectomy; PH, partial hepatectomy;

was used to analyse difference among continuous variables.

Odds Ratio (OR) was used to analyse difference in dichotomous

variables. 95% confidence interval (CI) was reported for each

analysed value. To standardize the data on continuous vari-

ables standard deviation (SD) were included. For the studies

that provided the range values for each variable, their range

values were converted to SD and analysed. Continuous vari-

ableswithoutSDwerenot included in theanalysis.Studieswith

no events in a particular outcome for laparoscopic and open

groupswere not included. To assess publication bias, graphical

Exploration with funnel plots were used.

Results

There were total of 10 studies10e19 (n ¼ 700) that compared

laparoscopic (296/700) and open (404/700) hepatic resections

for malignant lesions.

Basic demographics

Tables 1 and 2: The average age for laparoscopic and open liver

resection was 62.84 and 61.15 respectively. The proportion of

lesionsda

Mean size(mm)

Procedures performedb

26 S ¼ 6, B ¼ 7, T ¼ 2

33.5 W ¼ 3, S ¼ 7, B ¼ 3

30 LLS ¼ 10, PH ¼ 20

31 W ¼ 15, S ¼ 3, LLS ¼ 5

, C ¼ 3 39.9 PH ¼ 17, S ¼ 8, LLS ¼ 3, LH ¼ 3

36 W ¼ 21, S ¼ 16, LLS ¼ 14

35.8 RHL ¼ 3, LH ¼ 2, LLS ¼ 9, B ¼ 3,

S ¼ 15, W ¼ 10

43 n/c

30 LLS ¼ 10

33 RHL ¼ 20, S ¼ 5, B ¼ 5, W ¼ 30

patic lobectomy; LH, Left hemihepatectomy; PH, partial hepatectomy;

ncer.

hree segments resection; LLS, left lateral segmentectomy; RHL, right

n/c not commented.

Table 4 e Pathological characteristics of open group.

Author Number of procedures n (%) Pathology of lesionsresecteda

Mean size(mm)

Procedures performedb

Mala et al. 14 (48) C ¼ 14 30 S ¼ 9, B ¼ 3, T ¼ 2

Laurent et al. 14 (52) E ¼ 14 31 W ¼ 4, S ¼ 7, B ¼ 3

Kaneko et al. 28 (48) E ¼ 28 31 LLS ¼ 8, PH ¼ 20

Belli et al. 23 (50) E ¼ 23 32.4 W ¼ 12, S ¼ 5, LLS ¼ 6

Cai et al. 31 (50) E ¼ 26, G ¼ 3, C ¼ 2 36.2 PH ¼ 17, S ¼ 8, LLS ¼ 3, LH ¼ 3

Belli et al. 125 (70) E ¼ 125 60 T ¼ 39

Tranchart et al. 42 (50) E ¼ 42 36.8 RHL ¼ 3, LH ¼ 2, LLS ¼ 7, B ¼ 7,

S ¼ 13, W ¼ 10

Sarpel et al. 5 (76) E ¼ 56 43 n/c

Endo et al. 11 (51) E ¼ 11 41 LLS ¼ 11

Castaing et al. 60 (50) C ¼ 60 44 RHL ¼ 7, S ¼ 10, B ¼ 8 W ¼ 35

L, Laparoscopic; n/c, not commented; O, open.

T, three segments resection; LLS, left lateral segmentectomy; RHL, right hepatic lobectomy; LH, Left hemihepatectomy; PH, partial hepatectomy;

n/c not commented.

a C, malignant metastatic; E, hepatocellular carcinoma; G, gallbladder cancer.

b W, Wedge resections; S, segmentectomies; B, bisegmentectomies; T, three segments resection; LLS, left lateral segmentectomy; RHL, right

hepatic lobectomy; LH, Left hemihepatectomy; PH, partial hepatectomy; n/c not commented.

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1 197

females in the laparoscopic and open groups was 31.15% and

32.04% respectively.

Six studies10e14,18 were retrospectively matched and one

study17 was retrospectively unmatched. Two studies16,19

included prospective selection of laparoscopic group, which

wasmatchedwithretrospectivedata foropengroup.Twentyone

patients from laparoscopic group were converted to open (7%).

Tables 3 and 4: Seven studies10,11,14e16,18,19 included only

metastatic malignant lesions, 2 studies13,17 only included

hepatocellular carcinoma (HCC) lesions and one study12

included a combination of metastatic malignant lesion, HCC

and gallbladder cancer.

Peri-operative parameters

Eight studies10e12,14e17,19 reported that laparoscopic groupwas

associated with less operative blood loss by 162.6 ml [CI

�261.79, 73.45] than open group ( p < 0.001) but there was

significant heterogeneity between the studies ( p < 0.001).

Six studies10,11,13,16,17,19 reported that laparoscopic group

was associated with reduced number of patients requiring

blood transfusion by 0.35 [CI 0.20, 0.60] than open group

( p < 0.001) and it was not associated with heterogeneity

between studies (p0.85) (Figs. 1 and 2).

Five studies10,11,13,16,19 reported that laparoscopic group

was associated with less use of portal triad clamping by 0.08

Study or Subgroup

Mala et alLaurent et alBelli et alBelli et al.Castaing et alTranchart et al

Total (95% CI)

Total eventsHeterogeneity: Tau² = 0.00; Chi² = 2.03, df = 5 (P = 0.85); I² = 0%Test for overall effect: Z = 3.81 (P = 0.0001)

Events

110694

21

Total

131323546042

205

Events

144

3222

7

70

Total

141423

1256042

278

Weight

3.5%5.3%3.3%

33.2%37.6%17.0%

100.0%

M

Laparoscopic Open

Fig. 1 e Laparoscopic vs open resection: Number

[CI 0.01, 0.46] than open group (p0.005) but it was associated

with significant heterogeneity between the studies (p0.01).

There was no significant difference between the two groups

for operative time (p0.71). Although laparoscopic group was

associated with reduced duration of portal triad clamping

( p < 0.001) but it was only reported by one study.16

Post operative parameters

Eight studies10e12,14e17,19 reported that laparoscopic groupwas

associated with reduced hospital stay by 4.28 days [CI �6.33,

�2.23] than open group ( p < 0.001) but there was significant

heterogeneity between the studies ( p < 0.001).

Three studies12,14,15 reported that laparoscopic group

was associated with reduced time to oral intake by 1.29

days [CI �2.23, �0.35] than open group (p0.007) but there

was significant heterogeneity between the studies (p0.007).

Early post-operative adverse outcomes

� Liver related adverse outcomes:There was no significant

difference between the two groups for cirrhotic decom-

pression/ascites (p 0.39), hepatic haemorrhage (p 0.08),

biliary leakage (p 0.25), and liver failure (p 0.07).

� General complications: There was no significant difference

between the two groups for chest infection (p 0.56), wound

infection (p 0.79) and mortality (p 0.58).

-H, Random, 95% CI

1.08 [0.06, 19.31]0.21 [0.02, 2.18]0.09 [0.00, 1.82]0.36 [0.14, 0.93]0.30 [0.13, 0.74]0.53 [0.14, 1.95]

0.35 [0.20, 0.60]

Year

200220032007200920092009

Odds Ratio Odds Ratio

M-H, Random, 95% CI

0.01 0.1 1 10 100Laparoscopic Open

of patients requiring blood transfusion (n).

0.01 0.1 1 10 100

0

0.5

1

1.5

2OR

SE(log[OR])

Fig. 2 e Laparoscopic vs open resection: Funnel plot of number of patients requiring blood transfusion (n).

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1198

� Oncological clearance: Three studies11,13,18 reported that

laparoscopic group was associated with reduced number of

positive resection margin by 0.34 [CI 0.16, 0.73] than open

group (p0.006) and it was not associated with heterogeneity

between studies (p0.75) (Fig. 3). There was no significant

difference between the two groups for size of pathological

resection margin (p0.84).

Long term outcomes

Nine studies10e15,17e19 reported that laparoscopic group was

associated with reduced overall complication rate by 0.43 [CI

0.26, 0.73] than open group (p0.002) and it was not associated

with heterogeneity between studies (p0.22) (Figs. 4 and 5).

There was no significant difference between two groups for

recurrence rate (p0.17), 5-year survival (p 0.10 and 0.07) and 3-

year survival (p 0.17 and 0.26).

Discussion

Overall, laparoscopic group has been favoured over open

group for a few post-operative parameters in our analysis

(Table 5). The laparoscopic group was associated with less

number of patients requiring blood transfusion and reduce

Study or Subgroup

Castaing et alBelli et al.Sarpel et al

Total (95% CI)

Total eventsHeterogeneity: Tau² = 0.00; Chi² = 0.58, df = 2 (P = 0.75); I² = 0%Test for overall effect: Z = 2.75 (P = 0.006)

Events

802

10

Total

605420

134

Events

178

15

40

Total

60125

56

241

Weight

68.7%7.3%

24.0%

100.0%

M

Laparoscopic Open

Fig. 3 e Laparoscopic vs open resection: Nu

positive resection margins. Similarly, laparoscopic group had

decreased overall complication rate than open group. All

these results were significant and not associated with

heterogeneity between the studies. Although, laparoscopic

group was also associated with reduced operative blood loss,

use of portal triad clamping, duration of hospital stay and time

to oral intake, however, this was linked to significant hetero-

geneity between the studies. There was no significant differ-

ence between the two groups for other peri- and post-

operative parameters.

This study is the one of the first meta-analysis to be con-

ducted that compared laparoscopic and open hepatic resec-

tion for malignant lesions. To our knowledge, there has been

no randomised controlled trial or systemic review evaluating

this topic before. The study included 10 observational studies

with a good participants’ size (n ¼ 700). It investigated most of

the peri- and post-operative parameters along with short and

long term adverse outcomes.

The inclusion and exclusion criteria of majority of the

studies were clearly indicated to delineate any discrepancies

in the results and its analysis. Most studies had laparoscopic

and open groups matched for demographics and character-

istics of the patients. It included the patients with cirrhosis

and moderate to severe co-morbidity (ASA grade II and above)

to take into account common factors associated with

-H, Random, 95% CI

0.39 [0.15, 0.99]0.13 [0.01, 2.24]0.30 [0.06, 1.47]

0.34 [0.16, 0.73]

Year

200920092009

Odds Ratio Odds Ratio

M-H, Random, 95% CI

0.01 0.1 1 10 100Laparoscopic Open

mber of positive resection margins (n).

Study or Subgroup

Mala et alKaneko et alBelli et alCai et alBelli et al.Sarpel et alTranchart et alCastaing et alEndo et al

Total (95% CI)

Total eventsHeterogeneity: Tau² = 0.15; Chi² = 10.71, df = 8 (P = 0.22); I² = 25%Test for overall effect: Z = 3.15 (P = 0.002)

Events

2350

1015

163

45

Total

133023315420426010

283

Events

45

175

454

1217

3

112

Total

14282331

12556426011

390

Weight

6.4%9.2%

11.1%2.9%

22.8%4.8%

14.2%22.1%6.5%

100.0%

M-H, Random, 95% CI

0.45 [0.07, 3.04]0.51 [0.11, 2.37]0.10 [0.03, 0.38]0.08 [0.00, 1.45]0.40 [0.19, 0.88]0.68 [0.07, 6.51]0.34 [0.11, 1.07]0.92 [0.41, 2.05]1.14 [0.17, 7.60]

0.43 [0.26, 0.73]

Year

200220052007200820092009200920092009

Laparoscopic Open Odds Ratio Odds Ratio

M-H, Random, 95% CI

0.01 0.1 1 10 100Laparoscopic Open

Fig. 4 e Laparoscopic vs open resection: Overall complication rate (n).

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1 199

resection of malignant lesions. Most of the studies included in

the analysis were conducted within the last 5 years. It means

that most of the operative measures for laparoscopic tech-

nique indicate advancement in the technique and takes into

account surgical experience with the technology. There was

previous meta-analysis conducted in 2006, which included 6

studies.20 It was performed on the studies whose pathological

resections were both malignant and benign.

The individual studies15,16 have shown reduced operative

time for open group as compared to laparoscopic group but

the analysis of all the studies showed no difference between

the groups. The analyses have taken into account sample size

and standard deviation. With the advent of minimally inva-

sive surgery, it was hoped that the blood loss would be

reduced. Our compiled data suggested less blood loss with

laparoscopic technique but it was associated with heteroge-

neity between the studies. On the other hand, number of

patients requiring blood transfusion was reduced in laparo-

scopic technique without heterogeneity between the studies.

0.01 0.1 1

0

0.5

1

1.5

2

SE(log[OR])

Fig. 5 e Laparoscopic vs open resection: Fun

More evidence is required to justify blood loss associated with

each technique.

Similarly, previous studies indicated reduction in hospital

stay and time to oral intake.12,14,15 Our analysis showed

similar results, but there was marked heterogeneity between

studies when standard deviation for each parameter was

taken into consideration. There was no significant difference

between two groups for early post-operative adverse

outcomes. As there were few studies that reported early

adverse outcomes for each group, the results of these

parameters are not fully justified. For that reason,when all the

complications were taken into account, which increased the

sample size, the laparoscopic group was associated with

reduced overall complication rate.

Because of the limited access through laparoscopic tech-

nique, it was assumed that this technique was prone to

reduced resection margin size and increased positive resec-

tion sampling. However, our analysis showed reduced

positive resection associated with laparoscopic group and no

10 100OR

nel plot of overall complication rate (n).

Table 5 e Overall summary of analysis of outcomes.

Outcome of interest No of studies No of resections OR/WMD 95% CI P value HG P value

Peri-operative parameters

Operative time (min) 10 700 3.31 [�14.05, 20.66] 0.71 <0.001

Operative blood loss (mls) 8 504 �162.62 [-251.79, �73.45] <0.001 <0.001

No of Patients requiring blood transfusion 6 91 0.35 [0.20, 0.60] <0.001 0.85

Use of portal triad clamping 5 140 0.08 [0.01, 0.46] 0.005 0.01

Duration of portal triad clamping (min) 1 27 43 [26.59, 59.41] <0.001 Not estimated

Post operative parameter

Duration of hospital stay (days) 8 504 �4.28 [�6.33, �2.33] <0.001 <0.001

Time to first oral intake (days) 3 141 �1.29 �2.23, �0.35] 0.007 0.007

Early post operative adverse outcomes

Liver resection related

Cirrhotic decompression/ascites 5 43 0.46 [0.08, 2.73] 0.39 0.004

hepatic haemorrhage 3 4 5.31 [0.84, 33.55] 0.08 0.81

biliary leakage 4 8 0.43 [0.10, 1.82] 0.25 0.88

Liver failure 3 8 0.22 [0.04, 1.11] 0.07 0.91

General complications

Chest infection 5 13 0.7 [0.21, 2.32] 0.56 0.7

Wound infection 3 4 0.74 [0.08, 6.87] 0.79 0.24

Mortality 5 13 0.71 [0.21, 2.41] 0.58 0.77

Oncological clearance

Pathological resection margin size (mm) 4 152 0.13 [�1.13, 1.40] 0.84 1

Positive resection margins 3 50 0.34 [0.16, 0.73] 0.006 0.75

Long term outcomes

Overall complications 9 157 0.43 [0.26, 0.73] 0.002 0.22

3 year survival rate 3 166 3.21 [0.61, 16.90] 0.17 0.005

3 year survival without recurrence 3 89 2.38 [0.52, 10.91] 0.26 0.007

5 year survival rate 6 215 2.33 [0.85, 6.42] 0.1 <0.001

5 year survival without recurrence 6 112 1.97 [0.93, 4.16] 0.07 0.04

Recurrence rate 4 202 0.75 [0.50, 1.13] 0.17 0.75

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1200

difference in the size of margin size between the two groups.

The possible reason being the camera used with laparoscopy,

which magnifies area of resection and provides detailed visi-

bility. In the long-term post-operative outcome, however,

there was no difference between the recurrence and 5 and 3

year survival rate between the two groups.

Since the analysis was carried out on the observational

studies, there was an inherent selection bias as the analysis

was unable to assess the differences between open and

laparoscopic groups within each study. For example, the rate

of major hepatectomies was higher in open group than lapa-

roscopic group in the study conducted by Belli et al.11 Like-

wise, the open group included resection of larger tumours in

the study by Castaing et al.13

We aimed to analyse all the parameters asmentioned in the

methodology but there were not enough studies to document

all the parameters, for example, cost effectiveness and post op

analgesia. There is still a need for level I and II data to compare

laparoscopic versus open hepatic resection in malignant

lesions. With more data available, the results will be reliable,

promising and significant with reduced heterogeneity between

the studies.Althoughwe feel that itwill bedifficult toplanRCTs

and recruit patients as minimally invasive techniques are now

well established in most institutions that will make it difficult

for researchers to recruit patients in the open surgery arm.

Conflicts of interest

None declared.

r e f e r e n c e s

1. Bosch FX, Ribes J. Epidemiology of liver cancer in Europe. Can JGastroenterol 2000 Jul-Aug;14(7):621e30.

2. Srivatanakul P, Sriplung H, Deerasamee S. Epidemiology ofliver cancer: an overview. Asian Pac J Cancer Prev Apjcp 2004Apr-Jun;5(2):118e25.

3. Llovet JM, Wurmbach E. Gene expression profiles inhepatocellular carcinoma: not yet there. J. Hepatol 2004 Aug;41(2):336e9.

4. Bosch FX, Ribes J, Borras J. Epidemiology of primary livercancer. Semin Liver Dis 1999;19(3):271e85.

5. Bosch FX, Ribes J, Cleries R, Dıaz M. Epidemiology ofhepatocellular carcinoma. Clin Liver Dis 2005 May;9(2):191e211.

6. Tsuchiya R. A tribute to Dr. Ischio Honjo. Surg Today 1989;19(1):1.

7. Couinaud C. Contribution of anatomical research to liversurgery. France Medecine 1956 May;19(5):5e12.

8. Gagner M, Rogula T, Selzer D. Laparoscopic liver resection:benefits and controversies. Surg.Clin North Am 2004 Apr;84(2):451e62.

9. Topal B, Fieuws S, Aerts R, Vandeweyer H, Penninckx F.Laparoscopic versus open liver resection of hepaticneoplasms: comparative analysis of short-term results. Surg.Endosc 2008 Oct;22(10):2208e13.

10. Belli G, Fantini C, D’Agostino A, Cioffi L, Langella S,Russolillo N, et al. Laparoscopic versus open liver resectionfor hepatocellular carcinoma in patients with histologicallyproven cirrhosis: short- and middle-term results. Surg Endosc2007;21(11):2004e11.

11. Belli G, Limongelli P, Fantini C, D’Agostino A, Cioffi L, Belli A,et al. Laparoscopic and open treatment of hepatocellular

t h e s u r g e on 1 0 ( 2 0 1 2 ) 1 9 4e2 0 1 201

carcinoma in patients with cirrhosis. Br.J.Surg 2009 Sep;96(9):1041e8.

12. Cai XJ, Yang J, Yu H, Liang X, Wang YF, Zhu ZY, et al. Clinicalstudy of laparoscopic versus open hepatectomy for malignantliver tumors. Surg.Endosc 2008 Nov;22(11):2350e6.

13. Castaing D, Vibert E, Ricca L, Azoulay D, Adam R, Gayet B.Oncologic results of laparoscopic versus open hepatectomyfor colorectal liver metastases in two specialized centers.Ann.Surg 2009 Nov;250(5):849e55.

14. Endo Y, Ohta M, Sasaki A, Kai S, Eguchi H, Iwaki K, et al. Acomparative study of the long-term outcomes afterlaparoscopy-assisted and open left lateral hepatectomy forhepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech2009;19(5):171e4.

15. Kaneko H, Takagi S, Otsuka Y, Tsuchiya M, Tamura A,Katagiri T, et al. Laparoscopic liver resection of hepatocellularcarcinoma. Am.J.Surg 2005 Feb;189(2):190e4.

16. Laurent A, Cherqui D, Lesurtel M, Brunetti F, Tayar C,Fagniez PL. Laparoscopic liver resection for subcapsular

hepatocellular carcinoma complicating chronic liver disease.Arch Surg 2003;138(7):763e9. discussion 769; Jul.

17. Mala T, Edwin B, Gladhaug I, Fosse E, Soreide O, Bergan A,et al. A comparative study of the short-term outcomefollowing open and laparoscopic liver resection of colorectalmetastases. Surg.Endosc 2002 Jul;16(7):1059e63.

18. Sarpel U, Hefti MM, Wisnievsky JP, Roayaie S,Schwartz ME, Labow DM. Outcome for patients treatedwith laparoscopic versus open resection of hepatocellularcarcinoma: case-matched analysis. Ann Surg Oncol 2009Jun;16(6):1572e7.

19. Tranchart H, Di Giuro G, Lainas P, Roudie J, Agostini H,Franco D, et al. Laparoscopic resection for hepatocellularcarcinoma: a matched-pair comparative study. J Surg Endosc;2009. doi:10.1007/s00464-009-0745-3 (epub).

20. Simillis C, Constantinides VA, Tekkis PP, Darzi A,Lovegrove R, Jiao L, et al. Laparoscopic versus open hepaticresections for benign and malignant neoplasmsea meta-analysis. Surgery 2007 Feb;141(2):203e11.