JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 00, Number 00, 2017 ª Mary Ann Liebert, Inc. DOI: 10.1089/lap.2017.0210
Full Report
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Hand-Assisted Laparoscopic Surgery Versus Conventional Laparoscopic Surgery for Colorectal Cancer: A Systematic Review and Meta-Analysis Xubing Zhang, MD,1,2,* Qingbin Wu, MD,1,2,* Tao Hu, MD,1,2 Chaoyang Gu, MM,1 Liang Bi, MD,1,2 and Ziqiang Wang, MD, PHD1
Abstract
Aim: This meta-analysis aims to compare hand-assisted laparoscopic surgery (HALS) with conventional laparoscopic surgery (LAS) for colorectal cancer (CRC) in terms of intraoperative, postoperative, and survival outcomes. Materials and Methods: A systematic literature search with no limits was performed in PubMed, Embase, and Medline. The last search was performed on March 31, 2017. The outcomes of interests included intraoperative outcomes (operative time, blood loss, length of incision, transfusion, conversion, and lymph nodes harvested), postoperative outcomes (length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, and readmission), and 5-year survival outcomes. Results: Nine articles published between 2007 and 2016 with a total of 1307 patients were enrolled in this metaanalysis. HALS was associated with longer length of incision. No differences were found for operative time, blood loss, transfusion, conversion, lymph nodes harvested, length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, readmission, or 5-year survival outcomes. Conclusion: Our meta-analysis demonstrated that HALS is similar to LAS for CRC surgery in terms of intraoperative, postoperative, and survival outcomes except for the longer length of incision. Keywords: hand-assisted laparoscopic surgery, conventional laparoscopic surgery, colorectal cancer, outcomes bowel function recovery.7–10 In addition, several studies have demonstrated that laparoscopic surgery is at least not inferior to open surgery in regard to long-term outcomes in CRC.11,12 However, laparoscopic surgery also has disadvantages and limitations in colectomy and rectectomy such as longer operative time, steep learning curve, and risk of recurrence at the port site.13 Besides, it is not easy to dissect when it comes to bulky or complex tumors especially in pelvic cavity for the lack of tactile feedback, normal stereoscopic vision, and enough exposure.13 Those conditions have promoted the proposition and development of hand-assisted laparoscopic surgery (HALS) for CRC.13
Introduction
C
olorectal cancer (CRC) is one of the most common malignant tumors worldwide.1–3 Currently, radical surgery is still the best choice for nonmetastatic disease.4 In the past decades, minimally invasive surgical techniques for CRC have been widely accepted.5 Laparoscopic surgery (LAS) has been widely used for CRC since the first report of laparoscopic colectomy in 1991.6,7 Compared to conventional open surgery, laparoscopic surgery for CRC has advantages in short outcomes such as shorter incision length, less postoperative pain, less risk of infection, less blood loss, and quicker 1
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China. West China School of Medicine, Sichuan University, Chengdu, China. *These authors contributed equally to this work.
2
1
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2
ZHANG ET AL.
HALS for CRC was first reported in 1994.14 When performing HALS for CRC, surgeons can place a hand into the abdomen through a hand access device to help visualization, retraction, and dissection without disturbing the pneumoperitoneum.7,13,15,16 It is a novel and efficient technique which combines the advantages of conventional laparoscopic and open surgery.17 Some articles revealed that HALS was superior to LAS in terms of intraoperative or postoperative outcomes of CRC,18,19 while some other studies suggested they were similar7,20,21 although HALS was safe and feasible.13 There still lacks sufficient evidence to evaluate which technique is more beneficial to patients with CRC. Therefore, we conducted a meta-analysis to compare HALS and LAS in terms of intraoperative, postoperative, and survival outcomes.
Survival outcomes: 5-year disease-free survival and 5-year overall survival.
Materials and Methods
Statistical analysis
Study selection
All data analyses were conducted using the Review Manager version 5.0 (The Cochrane Collaboration, Software Update, Oxford), and P < .05 was considered statistically significant. Weighted mean difference (WMD) was calculated for the continuous outcomes, and pooled odds ratios (ORs) or risk ratios were calculated for the dichotomous outcomes. For continuous outcomes, if the study only provided means and range values or median and range values, the means and standard deviations were calculated using methods described by Hozo et al.24 Chi-squared test and Higgins I-squared test were used for heterogeneity test. A value of P < .05 and I2 > 50% was regarded as existing heterogeneity. If I2 > 50% and P < .05, a random-effects model was applied. Correspondingly, if I2 < 50% and P > .05, a fixedeffects model was applied. Begg’s funnel plot was used to evaluate publication bias. The survival curves in articles were obtained by Engauge Digitizer version 4.1.
We performed a literature search in PubMed, Embase, and Medline for studies comparing HALS and LAS in CRC surgery. The search terms included ‘‘hand-assisted laparoscopic surgery or hand-assisted laparoscopy’’ and ‘‘laparoscopies, laparoscopic, or laparoscopy’’ and ‘‘colon cancer, rectal cancer, or colorectal cancer.’’ The last search was performed on March 31, 2017. We also performed a manual search of references of articles and reviews for additional potentially eligible studies. Inclusion and exclusion criteria
The inclusion criteria for this meta-analysis were as follows: (1) Case–control study (HALS versus LAP), (2) CRC, (3) Studies with total sample size more than 20, and (4) Intraoperative and/or postoperative outcomes were reported. The exclusion criteria studies were as follows: (1) review articles, (2) correspondences, (3) studies, including benign diseases such as colorectal polyps, (4) animal studies, (5) single-arm studies, (6) studies not in English, and (7) any study comparing hand assist for diagnosis other than CRC. Data extraction
Two authors (X.Z. and Q.W.) reviewed all the identified articles independently. They would solve the discrepancies by discussion first and a third reviewer (Z.W.) would be required if necessary. We extracted the following items from each study: correspondence author’s name, year of publication, country, publication type, study type, bowel preparation, location of disease, number of patients in each arm, gender, age, body mass index (BMI), previous abdominal surgery (PAS), and outcomes of interests. Outcomes of interests
Intraoperative outcomes: operative time, blood loss, length of incision, transfusion, conversion, and lymph nodes harvested. Postoperative outcomes: length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, and readmission.
Quality assessment
The methodological quality of the enrolled retrospective studies was assessed using the revised and modified grading system of the Scottish Intercollegiate Guidelines Network.22 Articles achieving < 8 scores, 8–14 scores, and more than 14 scores (total score, 20) were defined as poor quality, fair quality, and good quality, respectively. And the methodological quality of the randomized controlled trials was assessed by modified Jadad score system (total score, 5; 1–2, low quality; 3–5, high quality).23
Results
The process and result of literature searching are shown in Figure 1. The initial search algorithm retrieved a total of 897 studies. There remained 368 studies after removing the duplications. After reviewing titles and abstracts, only 22 relevant studies were kept for further evaluation. Besides, no additional record was identified through manual search. Among these studies, 13 literatures were excluded due to following reasons: 1 study was not in English, 9 studies included benign diseases, 2 studies compared HALS and open surgery, and 1 study’s sample size was too small. Finally, 9 articles25–33 published between 2007 and 2016 were included in our meta-analysis. One of 9 articles was randomized controlled trial.28 The characteristics of the included studies are summarized in Table 1. A total of 1307 patients (672 by HALS and 635 by LAS) were enrolled. Patient demographics
There was no significant difference between two groups in age (P = .82, WMD = -0.14, 95% confidence interval [CI] [-1.30 to 1.03], I2 = 0%), male gender (P = .60, WMD = 1.13, 95% CI [0.73 to 1.75], I2 = 56%), BMI (P = .80, WMD = 0.11, 95% CI [-0.74 to 0.96], I2 = 67%), or PAS (P = .06, OR = 1.42, 95% CI [0.99 to 2.03], I2 = 0%). In addition, surgical procedures and tumor stage were similar in both groups.
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HALS VERSUS LAS FOR CRC
FIG. 1.
3
Prisma diagram. HALS, hand-assisted laparoscopic surgery.
Quality of included studies
The scores of methodological quality assessment of the enrolled retrospective studies and randomized controlled trial are shown in Tables 2 and 3. Of those 9 articles, 7 retrospective studies had fair quality (11–13 scores)25–27, 29–32 and one randomized controlled trial had low quality (2 scores).28 What’s more, Chan’s study33 was prospective but not randomized so we didn’t assess the quality. Meta-analysis of intraoperative outcomes
The analytic results demonstrated that there were no statistically significant differences between HALS and LAS in terms of operative time (P = .19, WMD = -7.90, 95% CI [-19.58 to 3.78], I2 = 77%), lymph node harvested (P = .42, WMD = 1.00, 95% CI [-1.45 to 3.45], I2 = 74%), conversion (P = .56, OR = 0.68, 95% CI [0.18 to 2.51], I2 = 59%), blood loss (P = .88, WMD = 4.82, 95% CI [-56.23 to 65.87], I2 = 83%), or blood transfusion (P = .85, OR = 0.93, 95% CI [0.44 to 1.94], I2 = 0%). However, we observed a significant longer length of incision (P < .001, WMD = 2.32, 95% CI
[1.06 to 3.58], I2 = 96%) in HALS group although there existed heterogeneity (Fig. 2). Meta-analysis of postoperative outcomes
The meta-analysis demonstrated no significant differences in terms of length of hospital stay (P = .80, WMD = -0.11, 95% CI [-0.96 to 0.73], I2 = 82%), reoperation (P = .60, OR = 1.32, 95% CI [0.47 to 3.73]), time to first flatus (P = .87, WMD = 0.10, 95% CI [-1.10 to -1.29], I2 = 91%), time to first bowel movement (P = .15, WMD = -0.12, 95% CI [-0.28 to 0.04], I2 = 68%), postoperative complication (P = .24, OR = 1.31, 95% CI [0.83 to 2.07], I2 = 0%), readmission (P = .78, OR = 1.13, 95% CI [0.49 to 2.60], I2 = 0%, I2 = 25%), or mortality (not applicable). In addition, we observed no differences for complications particularly associated with surgery, including ileus (P = .20, OR = 1.60, 95% CI [0.78 to 3.26], I2 = 0%), postoperative bleeding (P = .39, OR = 1.64, 95% CI [0.53 to 5.06], I2 = 0%), anastomotic leakage (P = .98, OR = 0.98, 95% CI [0.54 to 1.81], I2 = 0%), wound infection (P = .09, OR = 1.63, 95% CI [0.92 to 2.89], I2 = 0%), intra-abdominal abscess (P = .76, OR = 0.83, 95%
4
RCCS PRCT RCCS RCCS RCCS RCCS
Article Article
Article
Article
Article Article
I 5, II 11, III 14 0, I, II 30, III, IV 17 I 11, II 7, III 7 0 2, I 5, II 28, III 18 I 14, II 12, III 37, IV 4 —
Ng et al.28 Orcutt et al.29 Gezen et al.30 Bae et al.31 Larson et al.32 Tjandra et al.33
Stage
NR
NR NR
NR
NR
NR Yes
Yes
Yes Malignant
22
18
8
79 18
65 69 (44–84)
57.4 – 10.3
HALS
LAS
Malignant
I 3, II 12, III 15 0, I, II 30, III, IV 17 I 11, II 7, III 7 0 11, I 15, II 9, III 10 I 7, II 5, III 19, IV 2 —
0, I 62, II 27, III 39 0 5, I 5, II 3, III 3 —
Rectum
Sigmoid, Malignant Rectum Right colon Malignant Rectum Malignant
Colorectum Malignant
32
53 67
25
47
65 (22–86)
57.8 – 10.4
LAS
59 (33–83) 70.8 (34–89)
Age
23.8 – 2.94 21 (15.3–26.6)
30.5 (19–39)
24.1 – 2.8
HALS
BMI
23.8 – 2.88 21 (15.3–34.7)
28 (21–38)
23.8 – 3.7
LAS
14
19 19
15
65 – 13
28 – 5
28 – 5
28.8 – 3
14 8 — 17 37 10
19 3 —
HALS
PAS
6 7 — 14 12 9
20 1 —
LAS
28.3 – 1.8
22.9 (16.2–32.9) 23.6 (18.7–32.3) 26.9 25.9
— RC 11, LC 7 LAR 259, AR 4, HO 3, IR 8, APR 4 — — AR 7, LAR 18 — APR 19, LAR 14 —
LAS
62.4 – 10.4
63 (36–90) 61.9
Surgical procedures
61.7 – 10.8
68 (30–85) 61.0
67 – 11
46 62.8 (45.5–95.0) 62.6 (38.5–88.8) 28.4 (18.3–45.2) 29.2 (19.5–59.4)
HALS
14
34 42
11
46
— RC 11, LC 11 LAR 258, AR 12, HO 1, IR 5, APR 2 — — AR 7, LAR 18 — APR 9, LAR 58 —
31
45 33
25
47
Rectum Malignant 278 278 182 177 58 (27–88) Right colon Malignant 30 30 9 10 73.5 (34–85)
Colon
Left colon Malignant 118 128
Disease HALS LAS HALS LAS
Gender (male)
APR, abdominoperineal resection; AR, anterior resection; BMI, body mass index; HALS, hand-assisted laparoscopic surgery; HO, Hartmann’s operation; IR, intersphincteric resection; LAR, low anterior resection; LAS, laparoscopic surgery; LC, left colectomy; NR, not reported; PAS, previous abdominal surgery; PNCT, prospective nonrandomized controlled trials; PRCT, prospective randomized controlled trials; RC, right colectomy; RCCS, retrospective case–control study.
0, I 45, II 27, III 46 0 3, I 7, II 3, III 9 —
HALS
PNCT
RCCS
Article
Article
RCCS
Article
Yun et al.25 Ringley et al.26 Pyo et al.27
Authors
Yun et al.25 2010 South Korea Ringley 2007 United et al.26 States Pyo et al.27 2016 Korea Ng et al.28 2012 Hong Kong Orcutt 2012 United et al.29 States Gezen 2015 United et al.30 States Bae et al.31 2014 Korea Larson 2010 United et al.32 States Tjandra 2008 Hong et al.33 Kong
Authors
Publication Study Bowel Year Country type type preparation Location
No. of patients
Table 1. The Characteristics of the Included Studies
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HALS VERSUS LAS FOR CRC
5
Table 2. Methodological Qualities of Included Retrospective Studies Were Assessed Using the Revised and Modified Grading System of the Scottish Intercollegiate Guideline Network Yun Ringley Pyo Orcutt Gezen Bae Larson et al.25 et al.26 et al.27 et al.29 et al.30 et al.31 et al.32
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Items/Authors Inclusion criteria Exclusion criteria Comparable demographics? Could the number of participating centers be determined? Could the number of surgeons who participated be determined? Could the reader determine whether the authors were the learning curve for the reported procedure? Were diagnostic criteria clearly stated for clinical outcomes if required? Was the surgical technique adequately described? Did they try to standardize the surgical technique? Did they try to standardize perioperative care? Was the age and range given for patients in the HALS group? Did the authors address whether there were any missing data? Was the age and range given for patients in the comparative group? Were patients in each group treated along similar timelines? The patients asking to enter the study, did they actually take part in it? Were dropout rates stated? Were outcomes clearly defined? Were there blind assessors? Were there standardized assessment tools? Was the analysis by intention to treat? Total scores
1 1 1 1 0
1 1 1 1 0
0 1 1 1 0
0 0 1 1 0
0 1 1 1 0
0 1 1 1 0
0 0 1 1 0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0 1 0 0 1 13
0 1 0 0 1 13
0 1 0 0 1 12
0 1 0 0 1 11
0 1 0 0 1 12
0 1 0 0 1 12
0 1 0 0 1 11
Total scores, 20; 14, good quality. HALS, hand-assisted laparoscopic surgery.
CI [0.25 to 2.75], I2 = 20%), urinary complication (P = .77, OR = 1.09, 95% CI [0.61 to 1.96], I2 = 0%), or cardiopulmonary complication (P = .11, OR = 0.44, 95% CI [0.16 to 1.19], I2 = 0%) (Fig. 3). Meta-analysis of survival outcomes
The results showed that there were no significant differences on 5-year disease-free survival (P = .77, hazard ratio [HR] = 0.95, 95% CI [0.66 to 1.36], I2 = 0%) and overall survival (P = .81, HR = 1.10, 95% CI [0.50 to 2.39], I2 = 0%) (Table 4).
were enrolled (223 HALS and 221 LAS). We observed that HALS group had a longer length of incision (P = .02, WMD = 2.14, 95% CI [0.28 to 4.00], I2 = 98%) (Table 5). Besides, we also designed a subgroup analysis to compare the results of HALS and LAS for patients with rectal cancer. Three studies were enrolled (310 HALS and 309 LAS), and no significant differences were observed (Table 6). Publication bias
A funnel plot of the studies reporting on wound infection shows that there was no obvious publication bias among the studies (Fig. 4).
Subgroup analysis of HALS and LAS for colon cancer and rectal cancer
Discussion
We conducted subgroup analysis to compare the result of HALS and LAS for patients with colon cancer. Four studies
Since the first report of hand-assisted laparoscopic technique for colorectal surgery, a large number of studies have
Table 3. Modified Jadad Score of the Included Trials
Authors Ng et al.28
Described as randomized
Appropriate randomization method described
Subject blinded to intervention
Evaluator blinded to intervention
Description of withdrawals and dropouts
Total score
1
1
0
0
0
2
A total modified Jadad score of 1–2, low quality trial; 3–5, high quality trial. 1, reported; 0, not reported.
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FIG. 2. Meta-analysis of intraoperative outcomes. CI, confidence interval; HALS, hand-assisted laparoscopic surgery; IV, inverse-variance; LAS, conventional laparoscopic surgery; M-H, Mantel-Haenszel; SD, standard deviation. 6
7
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HALS VERSUS LAS FOR CRC
FIG. 3. Meta-analysis of postoperative outcomes. CI, confidence interval; HALS, hand-assisted laparoscopic surgery; IV, inverse-variance; LAS, conventional laparoscopic surgery; M-H, Mantel-Haenszel; SD, standard deviation. been conducted to compare the benefits of HALS and LAS, including short-term and long-term outcomes.14,18,20,34 However, this is still a controversial issue especially for CRC because different studies may have different outcomes.13 So it is difficult to tell which of those two surgical techniques is
better. Thus, we performed this meta-analysis to compare HALS with LAS for CRC. In our meta-analysis, we included nine studies with 1307 patients; HALS group showed a significant longer length of incision, which is controversial in previous reviews.35 The
ZHANG ET AL.
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8
FIG. 3. possible reason is that a 7- to 8-cm incision is needed for hand-access device and specimen extraction in HALS.35 This incision is generally longer compared with LAS although the length of incision may also depend on the size of surgeon’s hand and location of specimen extraction.36
(Continued). As for operative time, it is generally thought that HALS should have a shorter operative time with the help of handaccess device.17,37 However, our results suggested that there was no significant difference between the two groups. Our explanation is that both groups need to create an additional
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HALS VERSUS LAS FOR CRC
9
FIG. 3.
incision for specimen extraction although that is at the beginning part of HALS and final part of LAS. Surgeon’s learning curve and experience also play an important role in the surgery.17 Besides, the condition of abdominal adhesions should be taken into account and our result revealed that there was no significant difference in PAS (P = .06). Additional
(Continued).
advantages of HALS in operative time may be more obvious for bulky and complex tumors which are just very few parts in this meta-analysis.13,18 Thus, the total operative time had no difference between two groups. Although HALS has a superior intra-abdominal visualization and exposure which may reduce the risk of vascular
Table 4. Five-Year Survival Outcomes for Overall Survival and Disease-Free Survival
OS DFS
5-year survival rate
Model
No. of studies
HR
95% CI
P
HALS (%)
LAS (%)
Fixed Fixed
2 3
1.10 0.95
0.50–2.39 0.66–1.36
.81 .77
87.3–88.4 75.2–78.9
86.4–92.6 75.4–78.0
CI, confidence interval; DFS, disease-free survival; HALS, hand-assisted laparoscopic surgery; HR, hazard ratio; LAS, laparoscopic surgery; OS, overall survival.
10
ZHANG ET AL.
Table 5. Subgroup Analysis of Hand-Assisted Laparoscopic Surgery Versus Laparoscopic Surgery for Colon Cancer No. of studies
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Outcomes of interests Operative time LN harvested Hospital day Blood loss Conversion Incision length Ileus Leakage Wound infection Postoperative complication
4 4 4 2 3 2 2 3 3 2
No. of patients HALS 223 223 223 52 201 75 171 201 201 171
LAS 221 221 221 48 203 63 163 203 203 173
I 2 (%) 83 80 75 87 0 98 0 0 0 0
Analysis model Random Random Random Random Fixed Random Fixed Fixed Fixed Fixed
OR/WMD b
-11.13 1.46b -0.15b -40.88b 1.37a 2.14b 1.29a 0.93a 0.98a 1.43a
95% CI -32.03 -2.75 -1.61 -123.26 0.47 0.28 0.40 0.16 0.35 0.64
to to to to to to to to to to
9.77 5.67 1.30 41.51 4.04 4.00 4.18 5.61 2.78 3.22
P .30 .50 .84 .33 .56 .02 .67 .94 .97 .39
a
OR. WMD. Bold values signify when P value
Full Report
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Hand-Assisted Laparoscopic Surgery Versus Conventional Laparoscopic Surgery for Colorectal Cancer: A Systematic Review and Meta-Analysis Xubing Zhang, MD,1,2,* Qingbin Wu, MD,1,2,* Tao Hu, MD,1,2 Chaoyang Gu, MM,1 Liang Bi, MD,1,2 and Ziqiang Wang, MD, PHD1
Abstract
Aim: This meta-analysis aims to compare hand-assisted laparoscopic surgery (HALS) with conventional laparoscopic surgery (LAS) for colorectal cancer (CRC) in terms of intraoperative, postoperative, and survival outcomes. Materials and Methods: A systematic literature search with no limits was performed in PubMed, Embase, and Medline. The last search was performed on March 31, 2017. The outcomes of interests included intraoperative outcomes (operative time, blood loss, length of incision, transfusion, conversion, and lymph nodes harvested), postoperative outcomes (length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, and readmission), and 5-year survival outcomes. Results: Nine articles published between 2007 and 2016 with a total of 1307 patients were enrolled in this metaanalysis. HALS was associated with longer length of incision. No differences were found for operative time, blood loss, transfusion, conversion, lymph nodes harvested, length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, readmission, or 5-year survival outcomes. Conclusion: Our meta-analysis demonstrated that HALS is similar to LAS for CRC surgery in terms of intraoperative, postoperative, and survival outcomes except for the longer length of incision. Keywords: hand-assisted laparoscopic surgery, conventional laparoscopic surgery, colorectal cancer, outcomes bowel function recovery.7–10 In addition, several studies have demonstrated that laparoscopic surgery is at least not inferior to open surgery in regard to long-term outcomes in CRC.11,12 However, laparoscopic surgery also has disadvantages and limitations in colectomy and rectectomy such as longer operative time, steep learning curve, and risk of recurrence at the port site.13 Besides, it is not easy to dissect when it comes to bulky or complex tumors especially in pelvic cavity for the lack of tactile feedback, normal stereoscopic vision, and enough exposure.13 Those conditions have promoted the proposition and development of hand-assisted laparoscopic surgery (HALS) for CRC.13
Introduction
C
olorectal cancer (CRC) is one of the most common malignant tumors worldwide.1–3 Currently, radical surgery is still the best choice for nonmetastatic disease.4 In the past decades, minimally invasive surgical techniques for CRC have been widely accepted.5 Laparoscopic surgery (LAS) has been widely used for CRC since the first report of laparoscopic colectomy in 1991.6,7 Compared to conventional open surgery, laparoscopic surgery for CRC has advantages in short outcomes such as shorter incision length, less postoperative pain, less risk of infection, less blood loss, and quicker 1
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China. West China School of Medicine, Sichuan University, Chengdu, China. *These authors contributed equally to this work.
2
1
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2
ZHANG ET AL.
HALS for CRC was first reported in 1994.14 When performing HALS for CRC, surgeons can place a hand into the abdomen through a hand access device to help visualization, retraction, and dissection without disturbing the pneumoperitoneum.7,13,15,16 It is a novel and efficient technique which combines the advantages of conventional laparoscopic and open surgery.17 Some articles revealed that HALS was superior to LAS in terms of intraoperative or postoperative outcomes of CRC,18,19 while some other studies suggested they were similar7,20,21 although HALS was safe and feasible.13 There still lacks sufficient evidence to evaluate which technique is more beneficial to patients with CRC. Therefore, we conducted a meta-analysis to compare HALS and LAS in terms of intraoperative, postoperative, and survival outcomes.
Survival outcomes: 5-year disease-free survival and 5-year overall survival.
Materials and Methods
Statistical analysis
Study selection
All data analyses were conducted using the Review Manager version 5.0 (The Cochrane Collaboration, Software Update, Oxford), and P < .05 was considered statistically significant. Weighted mean difference (WMD) was calculated for the continuous outcomes, and pooled odds ratios (ORs) or risk ratios were calculated for the dichotomous outcomes. For continuous outcomes, if the study only provided means and range values or median and range values, the means and standard deviations were calculated using methods described by Hozo et al.24 Chi-squared test and Higgins I-squared test were used for heterogeneity test. A value of P < .05 and I2 > 50% was regarded as existing heterogeneity. If I2 > 50% and P < .05, a random-effects model was applied. Correspondingly, if I2 < 50% and P > .05, a fixedeffects model was applied. Begg’s funnel plot was used to evaluate publication bias. The survival curves in articles were obtained by Engauge Digitizer version 4.1.
We performed a literature search in PubMed, Embase, and Medline for studies comparing HALS and LAS in CRC surgery. The search terms included ‘‘hand-assisted laparoscopic surgery or hand-assisted laparoscopy’’ and ‘‘laparoscopies, laparoscopic, or laparoscopy’’ and ‘‘colon cancer, rectal cancer, or colorectal cancer.’’ The last search was performed on March 31, 2017. We also performed a manual search of references of articles and reviews for additional potentially eligible studies. Inclusion and exclusion criteria
The inclusion criteria for this meta-analysis were as follows: (1) Case–control study (HALS versus LAP), (2) CRC, (3) Studies with total sample size more than 20, and (4) Intraoperative and/or postoperative outcomes were reported. The exclusion criteria studies were as follows: (1) review articles, (2) correspondences, (3) studies, including benign diseases such as colorectal polyps, (4) animal studies, (5) single-arm studies, (6) studies not in English, and (7) any study comparing hand assist for diagnosis other than CRC. Data extraction
Two authors (X.Z. and Q.W.) reviewed all the identified articles independently. They would solve the discrepancies by discussion first and a third reviewer (Z.W.) would be required if necessary. We extracted the following items from each study: correspondence author’s name, year of publication, country, publication type, study type, bowel preparation, location of disease, number of patients in each arm, gender, age, body mass index (BMI), previous abdominal surgery (PAS), and outcomes of interests. Outcomes of interests
Intraoperative outcomes: operative time, blood loss, length of incision, transfusion, conversion, and lymph nodes harvested. Postoperative outcomes: length of hospital stay, time to first flatus, time to first bowel movement, postoperative complications, mortality, reoperation, ileus, anastomotic leakage, postoperative bleeding, wound infection, intra-abdominal abscess, urinary complication, cardiopulmonary complication, and readmission.
Quality assessment
The methodological quality of the enrolled retrospective studies was assessed using the revised and modified grading system of the Scottish Intercollegiate Guidelines Network.22 Articles achieving < 8 scores, 8–14 scores, and more than 14 scores (total score, 20) were defined as poor quality, fair quality, and good quality, respectively. And the methodological quality of the randomized controlled trials was assessed by modified Jadad score system (total score, 5; 1–2, low quality; 3–5, high quality).23
Results
The process and result of literature searching are shown in Figure 1. The initial search algorithm retrieved a total of 897 studies. There remained 368 studies after removing the duplications. After reviewing titles and abstracts, only 22 relevant studies were kept for further evaluation. Besides, no additional record was identified through manual search. Among these studies, 13 literatures were excluded due to following reasons: 1 study was not in English, 9 studies included benign diseases, 2 studies compared HALS and open surgery, and 1 study’s sample size was too small. Finally, 9 articles25–33 published between 2007 and 2016 were included in our meta-analysis. One of 9 articles was randomized controlled trial.28 The characteristics of the included studies are summarized in Table 1. A total of 1307 patients (672 by HALS and 635 by LAS) were enrolled. Patient demographics
There was no significant difference between two groups in age (P = .82, WMD = -0.14, 95% confidence interval [CI] [-1.30 to 1.03], I2 = 0%), male gender (P = .60, WMD = 1.13, 95% CI [0.73 to 1.75], I2 = 56%), BMI (P = .80, WMD = 0.11, 95% CI [-0.74 to 0.96], I2 = 67%), or PAS (P = .06, OR = 1.42, 95% CI [0.99 to 2.03], I2 = 0%). In addition, surgical procedures and tumor stage were similar in both groups.
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HALS VERSUS LAS FOR CRC
FIG. 1.
3
Prisma diagram. HALS, hand-assisted laparoscopic surgery.
Quality of included studies
The scores of methodological quality assessment of the enrolled retrospective studies and randomized controlled trial are shown in Tables 2 and 3. Of those 9 articles, 7 retrospective studies had fair quality (11–13 scores)25–27, 29–32 and one randomized controlled trial had low quality (2 scores).28 What’s more, Chan’s study33 was prospective but not randomized so we didn’t assess the quality. Meta-analysis of intraoperative outcomes
The analytic results demonstrated that there were no statistically significant differences between HALS and LAS in terms of operative time (P = .19, WMD = -7.90, 95% CI [-19.58 to 3.78], I2 = 77%), lymph node harvested (P = .42, WMD = 1.00, 95% CI [-1.45 to 3.45], I2 = 74%), conversion (P = .56, OR = 0.68, 95% CI [0.18 to 2.51], I2 = 59%), blood loss (P = .88, WMD = 4.82, 95% CI [-56.23 to 65.87], I2 = 83%), or blood transfusion (P = .85, OR = 0.93, 95% CI [0.44 to 1.94], I2 = 0%). However, we observed a significant longer length of incision (P < .001, WMD = 2.32, 95% CI
[1.06 to 3.58], I2 = 96%) in HALS group although there existed heterogeneity (Fig. 2). Meta-analysis of postoperative outcomes
The meta-analysis demonstrated no significant differences in terms of length of hospital stay (P = .80, WMD = -0.11, 95% CI [-0.96 to 0.73], I2 = 82%), reoperation (P = .60, OR = 1.32, 95% CI [0.47 to 3.73]), time to first flatus (P = .87, WMD = 0.10, 95% CI [-1.10 to -1.29], I2 = 91%), time to first bowel movement (P = .15, WMD = -0.12, 95% CI [-0.28 to 0.04], I2 = 68%), postoperative complication (P = .24, OR = 1.31, 95% CI [0.83 to 2.07], I2 = 0%), readmission (P = .78, OR = 1.13, 95% CI [0.49 to 2.60], I2 = 0%, I2 = 25%), or mortality (not applicable). In addition, we observed no differences for complications particularly associated with surgery, including ileus (P = .20, OR = 1.60, 95% CI [0.78 to 3.26], I2 = 0%), postoperative bleeding (P = .39, OR = 1.64, 95% CI [0.53 to 5.06], I2 = 0%), anastomotic leakage (P = .98, OR = 0.98, 95% CI [0.54 to 1.81], I2 = 0%), wound infection (P = .09, OR = 1.63, 95% CI [0.92 to 2.89], I2 = 0%), intra-abdominal abscess (P = .76, OR = 0.83, 95%
4
RCCS PRCT RCCS RCCS RCCS RCCS
Article Article
Article
Article
Article Article
I 5, II 11, III 14 0, I, II 30, III, IV 17 I 11, II 7, III 7 0 2, I 5, II 28, III 18 I 14, II 12, III 37, IV 4 —
Ng et al.28 Orcutt et al.29 Gezen et al.30 Bae et al.31 Larson et al.32 Tjandra et al.33
Stage
NR
NR NR
NR
NR
NR Yes
Yes
Yes Malignant
22
18
8
79 18
65 69 (44–84)
57.4 – 10.3
HALS
LAS
Malignant
I 3, II 12, III 15 0, I, II 30, III, IV 17 I 11, II 7, III 7 0 11, I 15, II 9, III 10 I 7, II 5, III 19, IV 2 —
0, I 62, II 27, III 39 0 5, I 5, II 3, III 3 —
Rectum
Sigmoid, Malignant Rectum Right colon Malignant Rectum Malignant
Colorectum Malignant
32
53 67
25
47
65 (22–86)
57.8 – 10.4
LAS
59 (33–83) 70.8 (34–89)
Age
23.8 – 2.94 21 (15.3–26.6)
30.5 (19–39)
24.1 – 2.8
HALS
BMI
23.8 – 2.88 21 (15.3–34.7)
28 (21–38)
23.8 – 3.7
LAS
14
19 19
15
65 – 13
28 – 5
28 – 5
28.8 – 3
14 8 — 17 37 10
19 3 —
HALS
PAS
6 7 — 14 12 9
20 1 —
LAS
28.3 – 1.8
22.9 (16.2–32.9) 23.6 (18.7–32.3) 26.9 25.9
— RC 11, LC 7 LAR 259, AR 4, HO 3, IR 8, APR 4 — — AR 7, LAR 18 — APR 19, LAR 14 —
LAS
62.4 – 10.4
63 (36–90) 61.9
Surgical procedures
61.7 – 10.8
68 (30–85) 61.0
67 – 11
46 62.8 (45.5–95.0) 62.6 (38.5–88.8) 28.4 (18.3–45.2) 29.2 (19.5–59.4)
HALS
14
34 42
11
46
— RC 11, LC 11 LAR 258, AR 12, HO 1, IR 5, APR 2 — — AR 7, LAR 18 — APR 9, LAR 58 —
31
45 33
25
47
Rectum Malignant 278 278 182 177 58 (27–88) Right colon Malignant 30 30 9 10 73.5 (34–85)
Colon
Left colon Malignant 118 128
Disease HALS LAS HALS LAS
Gender (male)
APR, abdominoperineal resection; AR, anterior resection; BMI, body mass index; HALS, hand-assisted laparoscopic surgery; HO, Hartmann’s operation; IR, intersphincteric resection; LAR, low anterior resection; LAS, laparoscopic surgery; LC, left colectomy; NR, not reported; PAS, previous abdominal surgery; PNCT, prospective nonrandomized controlled trials; PRCT, prospective randomized controlled trials; RC, right colectomy; RCCS, retrospective case–control study.
0, I 45, II 27, III 46 0 3, I 7, II 3, III 9 —
HALS
PNCT
RCCS
Article
Article
RCCS
Article
Yun et al.25 Ringley et al.26 Pyo et al.27
Authors
Yun et al.25 2010 South Korea Ringley 2007 United et al.26 States Pyo et al.27 2016 Korea Ng et al.28 2012 Hong Kong Orcutt 2012 United et al.29 States Gezen 2015 United et al.30 States Bae et al.31 2014 Korea Larson 2010 United et al.32 States Tjandra 2008 Hong et al.33 Kong
Authors
Publication Study Bowel Year Country type type preparation Location
No. of patients
Table 1. The Characteristics of the Included Studies
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HALS VERSUS LAS FOR CRC
5
Table 2. Methodological Qualities of Included Retrospective Studies Were Assessed Using the Revised and Modified Grading System of the Scottish Intercollegiate Guideline Network Yun Ringley Pyo Orcutt Gezen Bae Larson et al.25 et al.26 et al.27 et al.29 et al.30 et al.31 et al.32
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Items/Authors Inclusion criteria Exclusion criteria Comparable demographics? Could the number of participating centers be determined? Could the number of surgeons who participated be determined? Could the reader determine whether the authors were the learning curve for the reported procedure? Were diagnostic criteria clearly stated for clinical outcomes if required? Was the surgical technique adequately described? Did they try to standardize the surgical technique? Did they try to standardize perioperative care? Was the age and range given for patients in the HALS group? Did the authors address whether there were any missing data? Was the age and range given for patients in the comparative group? Were patients in each group treated along similar timelines? The patients asking to enter the study, did they actually take part in it? Were dropout rates stated? Were outcomes clearly defined? Were there blind assessors? Were there standardized assessment tools? Was the analysis by intention to treat? Total scores
1 1 1 1 0
1 1 1 1 0
0 1 1 1 0
0 0 1 1 0
0 1 1 1 0
0 1 1 1 0
0 0 1 1 0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0 1 0 0 1 13
0 1 0 0 1 13
0 1 0 0 1 12
0 1 0 0 1 11
0 1 0 0 1 12
0 1 0 0 1 12
0 1 0 0 1 11
Total scores, 20; 14, good quality. HALS, hand-assisted laparoscopic surgery.
CI [0.25 to 2.75], I2 = 20%), urinary complication (P = .77, OR = 1.09, 95% CI [0.61 to 1.96], I2 = 0%), or cardiopulmonary complication (P = .11, OR = 0.44, 95% CI [0.16 to 1.19], I2 = 0%) (Fig. 3). Meta-analysis of survival outcomes
The results showed that there were no significant differences on 5-year disease-free survival (P = .77, hazard ratio [HR] = 0.95, 95% CI [0.66 to 1.36], I2 = 0%) and overall survival (P = .81, HR = 1.10, 95% CI [0.50 to 2.39], I2 = 0%) (Table 4).
were enrolled (223 HALS and 221 LAS). We observed that HALS group had a longer length of incision (P = .02, WMD = 2.14, 95% CI [0.28 to 4.00], I2 = 98%) (Table 5). Besides, we also designed a subgroup analysis to compare the results of HALS and LAS for patients with rectal cancer. Three studies were enrolled (310 HALS and 309 LAS), and no significant differences were observed (Table 6). Publication bias
A funnel plot of the studies reporting on wound infection shows that there was no obvious publication bias among the studies (Fig. 4).
Subgroup analysis of HALS and LAS for colon cancer and rectal cancer
Discussion
We conducted subgroup analysis to compare the result of HALS and LAS for patients with colon cancer. Four studies
Since the first report of hand-assisted laparoscopic technique for colorectal surgery, a large number of studies have
Table 3. Modified Jadad Score of the Included Trials
Authors Ng et al.28
Described as randomized
Appropriate randomization method described
Subject blinded to intervention
Evaluator blinded to intervention
Description of withdrawals and dropouts
Total score
1
1
0
0
0
2
A total modified Jadad score of 1–2, low quality trial; 3–5, high quality trial. 1, reported; 0, not reported.
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FIG. 2. Meta-analysis of intraoperative outcomes. CI, confidence interval; HALS, hand-assisted laparoscopic surgery; IV, inverse-variance; LAS, conventional laparoscopic surgery; M-H, Mantel-Haenszel; SD, standard deviation. 6
7
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HALS VERSUS LAS FOR CRC
FIG. 3. Meta-analysis of postoperative outcomes. CI, confidence interval; HALS, hand-assisted laparoscopic surgery; IV, inverse-variance; LAS, conventional laparoscopic surgery; M-H, Mantel-Haenszel; SD, standard deviation. been conducted to compare the benefits of HALS and LAS, including short-term and long-term outcomes.14,18,20,34 However, this is still a controversial issue especially for CRC because different studies may have different outcomes.13 So it is difficult to tell which of those two surgical techniques is
better. Thus, we performed this meta-analysis to compare HALS with LAS for CRC. In our meta-analysis, we included nine studies with 1307 patients; HALS group showed a significant longer length of incision, which is controversial in previous reviews.35 The
ZHANG ET AL.
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8
FIG. 3. possible reason is that a 7- to 8-cm incision is needed for hand-access device and specimen extraction in HALS.35 This incision is generally longer compared with LAS although the length of incision may also depend on the size of surgeon’s hand and location of specimen extraction.36
(Continued). As for operative time, it is generally thought that HALS should have a shorter operative time with the help of handaccess device.17,37 However, our results suggested that there was no significant difference between the two groups. Our explanation is that both groups need to create an additional
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HALS VERSUS LAS FOR CRC
9
FIG. 3.
incision for specimen extraction although that is at the beginning part of HALS and final part of LAS. Surgeon’s learning curve and experience also play an important role in the surgery.17 Besides, the condition of abdominal adhesions should be taken into account and our result revealed that there was no significant difference in PAS (P = .06). Additional
(Continued).
advantages of HALS in operative time may be more obvious for bulky and complex tumors which are just very few parts in this meta-analysis.13,18 Thus, the total operative time had no difference between two groups. Although HALS has a superior intra-abdominal visualization and exposure which may reduce the risk of vascular
Table 4. Five-Year Survival Outcomes for Overall Survival and Disease-Free Survival
OS DFS
5-year survival rate
Model
No. of studies
HR
95% CI
P
HALS (%)
LAS (%)
Fixed Fixed
2 3
1.10 0.95
0.50–2.39 0.66–1.36
.81 .77
87.3–88.4 75.2–78.9
86.4–92.6 75.4–78.0
CI, confidence interval; DFS, disease-free survival; HALS, hand-assisted laparoscopic surgery; HR, hazard ratio; LAS, laparoscopic surgery; OS, overall survival.
10
ZHANG ET AL.
Table 5. Subgroup Analysis of Hand-Assisted Laparoscopic Surgery Versus Laparoscopic Surgery for Colon Cancer No. of studies
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Outcomes of interests Operative time LN harvested Hospital day Blood loss Conversion Incision length Ileus Leakage Wound infection Postoperative complication
4 4 4 2 3 2 2 3 3 2
No. of patients HALS 223 223 223 52 201 75 171 201 201 171
LAS 221 221 221 48 203 63 163 203 203 173
I 2 (%) 83 80 75 87 0 98 0 0 0 0
Analysis model Random Random Random Random Fixed Random Fixed Fixed Fixed Fixed
OR/WMD b
-11.13 1.46b -0.15b -40.88b 1.37a 2.14b 1.29a 0.93a 0.98a 1.43a
95% CI -32.03 -2.75 -1.61 -123.26 0.47 0.28 0.40 0.16 0.35 0.64
to to to to to to to to to to
9.77 5.67 1.30 41.51 4.04 4.00 4.18 5.61 2.78 3.22
P .30 .50 .84 .33 .56 .02 .67 .94 .97 .39
a
OR. WMD. Bold values signify when P value
