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The short and long term outcomes of laparoscopic versus open surgery for colorectal cancer a meta analysis

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Nội dung

Ung thư đại trực tràng là căn bệnh phổ biến đứng hàng thứ 4 nguyên nhân dẫn đến tử vong của bệnh nhân. Kể từ ca nội soi đầu tiên phẫu thuật đại trực tràng được phẫu thuật thành công trong năm 1991, phẫu thuật nội soi hiện nay được thực hiện rộng rãi để điều trị ung thư đại trực tràng, và kỹ năng ngày càng trở nên hoàn chỉnh hơn.

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ORIGINAL ARTICLE

The short- and long-term outcomes of laparoscopic versus

open surgery for colorectal cancer: a meta-analysis

Chun-Li Wang&Gang Qu&Hong-Wei Xu

Accepted: 31 December 2013

# Springer-Verlag Berlin Heidelberg 2014

Abstract

Purpose The aim of the study was to compare short- and

long-term outcomes of laparoscopic surgery and conventional

open surgery for colorectal cancer

Methods Published randomized controlled trial (RCT) reports

of laparoscopic surgery and open surgery for colorectal cancer

were searched, and short- and long-term factors were

extract-ed to perform meta-analysis

Results A total of 15 RCT reports (6,557 colorectal cancer

patients) were included in this study Blood loss of

laparo-scopic surgery was less by 91.06 ml than open surgery

(p= 0.044) Operation time was longer by 49.34 min

(p= 0.000) The length of hospital stay was shorter by

2.64 days (p= 0.003) Incisional length was shorter by

9.23 cm (p=0.000) Fluid intake was shorter by 0.70 day

(p= 0.001) Bowel movement was earlier by 0.95 day

(p=0.000) Incidence of complications, blood transfusion,

and 30 days death were significantly lower in laparoscopic

surgery than in open surgery (p=0.011, 0.000, 0.01) But there

was no significant difference in lymph nodes (p=0.535) and

anastomotic leak (p=0.924) There was also no significant

differ-ence in 3 and 5 years overall survival (p=0.298, 0.966),

disease-free survival (p=0.487, 0.356), local recurrence (p=0.270, 0.649),

and no difference in 5 years distant recurrence (p=0.838)

Conclusions Laparoscopic surgery is a mini-injured approach

which can cure colorectal cancer safely and radically, and it is

not different from conventional open surgery in long-term

effectiveness, so laparoscopic surgery can be tried to widely

use in colorectal cancer

Keywords Colorectal cancer Laparoscopy surgery Open surgery Meta-analysis

Introduction

Colorectal cancer is a common disease which is the fourth reason resulted to patients’ death [1] Since the first laparo-scopic colorectal surgery was operated successfully in the year

1991 [2], laparoscopic surgery is widely performed in the colorectal cancer, and the skill is becoming more and more mature Its’ security, feasibility, and short-term curative effect have already been verified [3,4] Some randomized controlled trials (RCTs) have gotten the result that laparoscopic colorec-tal surgery (LCS) had the better short-term outcomes than open colorectal surgery (OCS), for example, less blood loss, better quality life, less pain, the shorter time of return to normal life and shorter length of hospital stay, and so on [5,

6] But the post-operation recurrence is the most important problem which we should consider And there are few reports about meta-analysis results of post-operation recurrence be-tween laparoscopic and open surgery, while it is essential first-class evidence of evidence-based medicine, so several RCTs comparing LCS and OCS’s short- and long-term outcomes were selected to have been done meta-analysis And the factors of 3 and 5 years following up period below were concluded to evaluate the long-term results of LCS

Materials and methods

We looked up many materials about RCTs of colorectal cancer comparing LCS and OCS which were published from January

1991 to June 2013 and searched the major medical databases such as Pubmed, Embase, Ovid, ScienceDirect, Springer, Interscience, and so on The search terms were used:

Chun-Li Wang and Gang Qu contributed equally to this work.

C <L Wang:G Qu:H <W Xu (*)

The First Affiliated Hospital of Dalian Medical University, Dalian,

Liaoning 116021, People’s Republic of China

e-mail: xuhongwei@ymail.com

C <L Wang

e-mail: wangchunli808@126.com

DOI 10.1007/s00384-013-1827-1

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“laparoscopy surgery,” “colorectal cancer,” “open surgery,”

“randomized controlled trial,” and so on Furthermore, we

limited our search to those studies that involved a following

up period of 3 or 5 years to evaluate the long-term outcomes of

LCS We conducted a meta-analysis for the short and long

term For the short-term analysis, we collected data of the

operation time, blood loss, number of patients requiring blood

transfusion, number of harvested lymph nodes, time of fluid

intake, bowel movement, anastomotic leak, length of hospital

stay, length of operation incision, complications, and 30 days

death For the long-term analysis, we used data of the rate of

3 years local recurrence, 3 years overall survival rate, 3 years

disease-free survival rate, 5 years overall survival rate, 5 years

disease-free survival rate, 5 years local recurrence rate, and

5 years distant recurrence

Statistical analysis

Weighted mean difference (WMD) and odds ratio (OR) were

used for the variables analysis of continuous and

dichoto-mous, respectively.χ2

test was used to evaluate heterogeneity among the studies, and I2was used to quantify the

inconsis-tency (there were two models: fixed effect model and random

effect model The fixed effect model was used when the

effects were deemed to be homogeneous (p>0.1, I2<50 %);

otherwise, the random effects model was used) And Z test

was used to compare the overall difference The confidence

interval (CI) was established at 95 %, and p values of less than

0.05 were considered to indicate statistical significance

Begg’s test and Egger’s test were performed in order to

evaluate the publication bias (in Begg’s test p>0.05 and in

Egger’s test p>0.05 and 95 % CI includes 1; it is thought that there was no publication bias) Statistical analyses were performed using the stata12.0 (meta module) software

Results

At last 15 papers of RCTs that compared LCS and OCS for colorectal cancer [5–20] were selected The characteristics of each RCT are presented in Table1 This meta-analysis

includ-ed 6,557 patients with colorectal cancer in all, of which 3,509 had performed LCS and 3,048 had OCS The results of the short and long term are shown in Figs.1,2,3,4,5,6,7,8,9,

10,11,12,13,14,15,16,17, and18, respectively, and the data are presented in Tables2,3,4,5,6,7,8,9,10,11,12,13,14,

15,16,17,18and19 Short-term outcomes

The blood loss for LCS was significantly less than for OCS,

by an average volume of 91.06 ml (WMD=−91.06; 95 % CI=

−179.66 to −2.46; p=0.044); six of the 15 RCTs included data

of blood loss Operation time for LCS was significantly longer than for OCS, by 49.34 min (WMD=49.34; 95 % CI=29.57

to−69.12; p=0.000); five of the 15 RCTs included data of operation time The length of hospital stay for LCS was significantly shorter than for OCS, by 2.64 days (WMD=

−2.64; 95 % CI=−4.41 to −0.87; p=0.003); six of the 15 RCTs included data of the length of hospital stay The incisional length for LCS was significantly shorter than

Table 1 Characteristics of the randomized control trials

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Overall (I-squared = 0.0%, p = 0.980)

Study

Lacy

ID Schwandner

Liang Fujii

-0.29 (-1.19, 0.62)

0.00 (-2.03, 2.03)

WMD (95% CI)

-0.10 (-2.43, 2.23)

-0.40 (-1.53, 0.73) -1.10 (-8.38, 6.18)

100.00

%

19.92

Weight

15.02

63.52 1.54

0

Fig 1 Lymph node results of

forest plot (fixed effect model)

NOTE: Weights are from random effects analysis

Overall (I-squared = 99.1%, p = 0.000)

ID

Fujii

Lacy Liang Study

Jing Gong

Milsom

Braga

-91.06 (-179.66, -2.46)

WMD (95% CI)

-129.00 (-251.85, -6.15)

-88.00 (-132.02, -43.98)

-186.00 (-192.10, -179.90)

-32.20 (-43.99, -20.41)

0.00 (-176.97, 176.97)

-81.00 (-130.98, -31.02)

100.00

Weight

14.06

18.40

19.26

%

19.21

10.90

18.16

0

Fig 2 Blood loss result of forest

plot

NOTE: Weights are from random effects analysis

Overall (I-squared = 83.6%, p = 0.000) Liang

Milsom Study

Fujii

ID

Schwandner Lacy

49.34 (29.57, 69.12) 40.40 (31.24, 49.56) 75.00 (57.77, 92.23)

45.00 (4.03, 85.97)

WMD (95% CI)

72.00 (36.07, 107.93) 24.00 (11.13, 36.87)

100.00 25.85

22.66

%

12.58

Weight

14.38 24.53

Fig 3 Operation time result of

forest plot

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NOTE: Weights are from random effects analysis

Overall (I-squared = 82.1%, p = 0.000)

Lacy Study

Fujii

ID

Color

Color

Liang Schwandner

-2.64 (-4.41, -0.87)

-2.70 (-4.50, -0.90)

-4.70 (-9.48, 0.08)

WMD (95% CI)

-1.10 (-1.87, -0.33)

-0.20 (-1.62, 1.22)

-5.00 (-6.58, -3.42) -6.60 (-13.48, 0.28)

100.00

19.84

%

8.86

Weight

23.80

21.49

20.79 5.24

0

Fig 4 Length of hospital stay

result of forest plot

NOTE: Weights are from random effects analysis Overall (I-squared = 99.2%, p = 0.000)

Study

Liang

LAPKON Braga Milsom ID

-9.23 (-13.77, -4.68)

-7.40 (-7.99, -6.81)

0.40 (-1.47, 2.27) -12.20 (-12.66, -11.74) -17.50 (-18.89, -16.11) WMD (95% CI)

100.00

%

25.35

24.41 25.39 24.86 Weight

0

Fig 5 Incisional length result of

forest plot

Overall (I-squared = 0.0%, p = 0.767)

Color

ID Study

Color Schwandner

-0.95 (-1.18, -0.73) -1.00 (-1.27, -0.73) WMD (95% CI)

-0.80 (-1.27, -0.33) -1.00 (-1.79, -0.21)

100.00 69.11

Weight

%

22.67 8.22

Fig 6 Bowel movement result

of forest plot (fixed effect model)

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95 % CI=−13.77 to −4.68; p=0.000); four of the 15 RCTs

included data of incisional length The bowel movement

time for LCS was significantly shorter than for OCS, by an

−0.73; p=0.000); three of the 15 RCTs included data of

bowel movement The fluid intake for LCS was significantly

shorter than for OCS, by 0.70 day (WMD=−0.70; 95 % CI=

−1.11 to −0.29; p=0.001); four of the 15 RCTs included data

of the fluid intake There were no significant differences in lymph nodes between the LCS group and the OCS group for treatment of the colorectal cancer The rate of perioperative complications for patients in the LCS group was

significant-ly lower than for those in the OCS group in this anasignificant-lysis of the pooled data for colorectal cancer treatment (OR=0.86;

95 % CI=0.77–0.97; p=0.011) Twelve of the 15 RCTs included data of perioperative complications The number

of blood transfusion in the LCS group was significantly lower than that in the OCS group in this analysis of the pooled data for colorectal cancer treatment (OR=0.46; 95 % CI=0.32–0.65; p=0.000) Three of the 15 RCTs included data of blood transfusion There were no significant differ-ences in anastomotic leak between the LCS group and the OCS group for the treatment of the colorectal cancer The rate of 30 days death in the LCS group was signifi-cantly lower than in the OCS group in this analysis of the pooled data for colorectal cancer treatment (OR=0.58; 95 % CI=0.38–0.88; p=0.01) Seven of the 15 RCTs included data

of 30 days death

NOTE: Weights are from random effects analysis

Overall (I-squared = 63.5%, p = 0.042)

Study

Lacy

color color Schwander ID

-0.70 (-1.11, -0.29)

-1.20 (-1.83, -0.57)

-0.20 (-0.70, 0.30) -0.90 (-1.21, -0.59) -0.50 (-1.14, 0.14) WMD (95% CI)

100.00

%

20.92

25.50 33.09 20.49 Weight

0

Fig 7 Fluid intake result of

forest plot

Overall (I-squared = 41.2%, p = 0.067)

ID

Liang

JingGong

Lacy

Leung

color

color

LAPKON

CLASICC

SChwandner

Braga

Study

Milsom

cost

0.86 (0.77, 0.97)

ratio (95% CI)

0.68 (0.41, 1.15)

0.61 (0.18, 2.05)

0.37 (0.21, 0.64) 0.88 (0.60, 1.28)

0.82 (0.59, 1.14)

1.00 (0.79, 1.27)

1.03 (0.75, 1.42) 0.67 (0.43, 1.05) 1.00 (0.48, 2.07)

0.61 (0.37, 1.00)

odds

0.98 (0.40, 2.43)

1.06 (0.82, 1.39)

100.00

Weight

5.51

1.19

7.10 8.58

12.40

20.93

10.75 7.65 1.89

6.25

%

1.53

16.22

1

Fig 8 Complication result of forest plot

Overall (I-squared = 72.7%, p = 0.026)

ID LAPKON Braga Study

Fujii

0.46 (0.32, 0.65)

ratio (95% CI) 0.66 (0.42, 1.03) 0.55 (0.27, 1.10) odds

0.02 (0.00, 0.38)

100.00

Weight 48.51 23.48

%

28.01

Fig 9 Blood transfusion result

of forest plot

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Overall (I-squared = 0.0%, p = 0.996)

color cost Milsom

color

Lacy

Braga Schwandner

Study ID

0.58 (0.38, 0.88)

0.59 (0.22, 1.63) 0.49 (0.09, 2.67) 0.98 (0.06, 15.30)

0.66 (0.23, 1.89)

0.32 (0.03, 3.07)

0.59 (0.34, 1.05) 0.33 (0.01, 7.89)

odds ratio (95% CI)

100.00

18.38 7.38 1.85

14.68

5.56

49.40 2.74

% Weight

1

Fig 10 Thirty-day death result

of forest plot

Overall (I-squared = 0.0%, p = 0.543)

Leung

Jing Gong

LAPKON

Fujii

color

Braga Park

ID Study

0.99 (0.72, 1.34)

0.25 (0.03, 2.18)

1.06 (0.07, 16.60)

1.42 (0.47, 4.28)

0.59 (0.31, 1.14)

1.15 (0.73, 1.80)

0.80 (0.22, 2.91) 1.17 (0.51, 2.71)

ratio (95% CI) odds

100.00

5.54

1.33

7.28

20.17

45.93

6.87 12.88

Weight

%

1

Fig 11 Anastomotic leak result

of forest plot

Overall (I-squared = 0.0%, p = 0.856) Braga

Study ID

CLASICC

Schwandner Leung

1.03 (0.97, 1.10) 1.09 (0.93, 1.28)

odds ratio (95% CI)

1.02 (0.92, 1.14)

1.00 (0.88, 1.13) 1.02 (0.93, 1.12)

100.00 17.01

% Weight

45.84

5.80 31.35

1

Fig 12 Three-year overall

survival result of forest plot

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Overall (I-squared = 3.0%, p = 0.356)

ID Study

CLASICC

Schwandner Park

1.30 (0.82, 2.07)

ratio (95% CI) odds

1.10 (0.65, 1.86)

3.00 (0.13, 71.00) 2.64 (0.82, 8.53)

100.00

Weight

%

87.41

1.74 10.85

1

Fig 14 Three-year local

recurrence result of forest plot

Overall (I-squared = 76.5%, p = 0.014)

Study

CLASICC ID

Park cost

1.03 (0.95, 1.10)

odds

0.98 (0.89, 1.09) ratio (95% CI)

0.94 (0.86, 1.03) 1.29 (1.04, 1.59)

100.00

%

44.77 Weight

36.05 19.18

1

Fig 13 Three-year disease-free

survival result of forest plot

Overall (I-squared = 0.0%, p = 0.595) Fujii

cost

Braga

ID Study

Leung

CLASICC

1.00 (0.95, 1.05) 1.02 (0.89, 1.16)

0.96 (0.90, 1.03)

1.09 (0.93, 1.28)

ratio (95% CI) odds

1.04 (0.93, 1.17)

1.00 (0.88, 1.13)

100.00 3.41

43.22

10.63

Weight

%

17.77

24.97

1

Fig 15 Five-year overall

survival result of forest plot

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Long-term outcomes

We found no significant differences in the rate of 3 years local

recurrence between the surgery groups when we pooled data

for the treatment of the colorectal cancer Our analysis of the

5 years of local and distant recurrence between the LCS group

and the OCS group for the treatment of the colorectal cancer

indicated no significant difference There were also no

signif-icant differences between the surgery groups for the overall

survival in the 3 and 5 years We also found no significant

differences in the 3- and 5-year disease-free survival rates between patients who underwent LCS and OCS

Heterogeneity

In the short-term period, significant heterogeneity was

detect-ed among studies with respect to the following six factors: blood loss, the length of hospital stay, operation time, time of fluid intake, the rate of perioperative complications, and the number of blood transfusion In the long-term period,

Overall (I-squared = 0.0%, p = 0.649)

Study

CLASICC

Fujii Braga Leung ID

0.97 (0.90, 1.04)

odds

0.94 (0.83, 1.07)

1.06 (0.91, 1.24) 1.00 (0.83, 1.20) 0.96 (0.86, 1.07) ratio (95% CI)

100.00

%

43.58

5.68 17.60 33.14 Weight

1

Fig 16 Five-year disease-free

survival result of forest plot

Overall (I-squared = 53.1%, p = 0.119) Leung

Study

CLASICC

Lacy ID

1.09 (0.76, 1.57) 1.55 (0.61, 3.91) odds

1.26 (0.80, 2.00)

0.49 (0.20, 1.16) ratio (95% CI)

100.00 13.64

%

58.92

27.44 Weight

1

Fig 17 Five-year local

recurrence result of forest plot

Overall (I-squared = 0.0%, p = 0.754)

ID

CLASICC

Study

Lacy Leung

1.03 (0.81, 1.30)

ratio (95% CI)

1.02 (0.76, 1.36)

odds

0.76 (0.29, 1.96) 1.14 (0.70, 1.85)

100.00

Weight

67.36

%

8.43 24.21

Fig 18 Five-year distant

recurrence result of forest plot

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Table 2 Number of lymph nodes compared LCS and OCS ( p=0.535)

among four studies (n)

studies (in milliliters)

Table 4 Operation time compared LCS and OCS (p=0.000) among five

studies (in minutes)

Table 5 Hospital length of stay compared LCS and OCS ( p=0.003)

among six studies (in days)

Table 6 Incisional length compared LCS and OCS ( p=0.000) among four studies (in centimeters)

three studies (in days)

Table 8 Fluid intake compared LCS and OCS (p=0.001) during four studies (in days)

Table 9 Number of complication compared LCS and OCS (p=0.011) among 12 studies (n)

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Table 10 Number of blood transfusion compared LCS and OCS

(p=0.000) among three studies (n)

Table 11 Number of 30-day death compared LCS and OCS ( p=0.011)

among seven studies (n)

Table 12 Number of anastomotic leak compared LCS and OCS

(p=0.924) among seven studies (n)

Table 13 Three-year overall survival compared LCS and OCS

(p= 0.298) among five studies (n)

Table 14 Three-year disease-free survival compared LCS and OCS (p=0.487) among five studies (n)

Table 15 Three-year local recurrence compared LCS and OCS (p=0.270) among five studies (n)

Table 16 Five-year overall survival compared LCS and OCS (p=0.966) among five studies (n)

Table 17 Five-year disease-free survival compared LCS and OCS (p=0.356) among five studies (n)

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