Laparoscopic Versus Open Liver Resection for Tumors in the Posterosuperior Segments

REVIEW ARTICLE Laparoscopic Versus Open Liver Resection for Tumors in the Posterosuperior Segments: A Systematic Review and Meta-analysis Shahab Hajibandeh, MBChB, MRCS,* Shahin Hajibandeh, MBChB, MRCS,† Madhav Dave, MBChB,‡ Munir Tarazi, MBBCh, MRCS,‡ and Thomas Satyadas, UMD, DipHPB, FRCS‡ Downloaded from http://journals.lww.com/surgical-laparoscopy by BhDMf5ePHKbH4TTImqenVDezntqwKeJGZ4+/XhAcDTlW0j2CaBkq3qofk8O3rPde on 07/05/2020 Objective: The objective of this study was to compare the outcomes of laparoscopic and open liver resection for tumors in the posterosuperior segments. Methods: We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement standards. We conducted a search of electronic information sources to identify all studies comparing outcomes of laparoscopic and open liver resection for tumors in the posterosuperior segments. We used the Risk Of Bias In Nonrandomized Studies—of Interventions (ROBINS-I) tool to assess the risk of bias of the included studies. Fixed-effect or randomeffects models were applied to calculate pooled outcome data. Results: We identified 11 observational studies, enrolling a total of 1023 patients. The included population in both groups were comparable in terms of baseline characteristics. Laparoscopic approach was associated with lower risks of total complications [odds ratio (OR): 0.45; 95% confidence interval (CI): 0.33, 0.61; P < 0.00001], major complications (Dindo-Clavien III or more) (OR: 0.52; 95% CI: 0.36, 0.73; P = 0.0002), and intraoperative blood loss [mean difference (MD): −114.71; 95% CI: −165.64, −63.79; P < 0.0001]. Laparoscopic approach was associated with longer operative time (MD: 50.28; 95% CI: 22.29, 78.27; P = 0.0004) and shorter length of hospital stay (MD: −2.01; 95% CI: −2.09, −1.92; P < 0.00001) compared with open approach. There was no difference between the 2 groups in terms of need for blood transfusion (OR: 1.23; 95% CI: 0.75, 2.02; P = 0.41), R0 resection (OR: 1.09; 95% CI: 0.66, 1.81; P = 0.72), postoperative mortality (risk difference: −0.00; 95% CI: −0.02, 0.02; P = 0.68), and need for readmission (OR: 0.70; 95% CI: 0.19, 2.60; P = 0.60). In terms of oncological outcomes, there was no difference between the groups in terms disease recurrence (OR: 1.58; 95% CI: 0.95, 2.63; P = 0.08), overall survival (OS) at maximum follow-up (OR: 1.09; 95% CI: 0.66, 1.81; P = 0.73), 1-year OS (OR: 1.53; 95% CI: 0.48, 4.92; P = 0.47), 3-year OS (OR: 1.26; 95% CI: Received for publication September 10, 2019; accepted November 7, 2019. From the *Department of General Surgery, Glan Clwyd Hospital, Rhyl, Denbighshire; †Department of General Surgery, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham; and ‡Department of Hepatobiliary and Pancreatic Surgery, Manchester Royal Infirmary Hospital, Manchester, UK. Shahab H. and Shahin H. contributed equally and joined the first authorship. The author declares no conflicts of interest. Reprints: Shahab Hajibandeh, MBChB, MRCS, Department of General Surgery, Glan Clwyd Hospital, Rhyl, Denbighshire LL18 5UJ, UK (e-mail: shahab_hajibandeh@yahoo.com). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www. surgical-laparoscopy.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  0.67, 2.37; P = 0.48), 5-year OS (OR: 0.91; 95% CI: 0.41, 1.99; P = 0.80), disease-free survival (DFS) at maximum follow-up (OR: 0.91; 95% CI: 0.65, 1.27; P = 0.56), 1-year DFS (OR: 1.04; 95% CI: 0.60, 1.81; P = 0.88), 3-year DFS (OR: 1.13; 95% CI: 0.75, 1.69; P = 0.57), and 5-year DFS (OR: 0.73; 95% CI: 0.44, 1.24; P = 0.25). Conclusions: Compared with the open approach in liver resection for tumors in the posterosuperior segments, the laparoscopic approach seems to be associated with a lower risk of postoperative morbidity, less intraoperative blood loss, and shorter length of hospital stay with comparable survival and oncological outcomes. The best available evidence is derived from observational studies with moderate quality; therefore, high-quality randomized controlled trials with adequate statistical power are required to provide a more robust basis for definite conclusions. Key Words: laparoscopy, liver cancer, posterior segment, superior segment (Surg Laparosc Endosc Percutan Tech 2020;30:93–105) aparoscopic liver resection has become more popular in the past decade despite the technical challenges and a steep learning curve. Laparoscopic liver resection has been recommended for solitary tumors ( ≤ 5 cm) located in the anterolateral segments (segments 2, 3, 4b, 5, and 6).1 Laparoscopic resection of tumors located in the posterosuperior segments of the liver (segments 1, 4a, 7, 8, and superior part of segment 6) is technically challenging due to limited visualization and working space to identify safe resection margins and difficulty in controlling bleeding.2,3 Therefore, open resection technique which involves large incision and retraction of the right ribs is the conventional technique for resection of tumors located in the posterosuperior segments of the liver. Technical improvements and accumulation of laparoscopic skills and experience have made laparoscopic resection of tumors located in the posterosuperior segments of the liver feasible and safe.4 The minimally invasive nature of the laparoscopic approach may make this approach superior to the conventional open approach in terms of intraoperative and postoperative outcomes without compromising oncological outcomes. Laparoscopic resection of tumors located in the posterosuperior segments of the liver has been compared with conventional open resection technique in some studies making performing a systematic review worthwhile. In view of this, we aimed to perform a systematic review and meta-analysis to compare the outcomes of laparoscopic and open liver resection for tumors located in the posterosuperior segments. L Volume 30, Number 2, April 2020 www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 93 Surg Laparosc Endosc Percutan Tech Hajibandeh et al METHODS This systematic review was performed according to an agreed predefined protocol and was conducted and presented according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards.5 Criteria for Considering Studies for This Review Types of Studies We included all randomized controlled trials and observational studies comparing laparoscopic and open liver resection for tumors located in the posterosuperior segments. Types of Participants The study population comprised participants of any age and sex undergoing liver resection for tumors located in the posterosuperior segments of the liver. The list of liver resection procedures of interest was not exhaustive and included wedge resection, tumorectomy, sectionectomy, segmentectomy, bisegmentectomy, trisegmentectomy, lobectomy, hepatectomy, and nonanatomic resections. The posterosuperior segments of the liver were defined as segments 1, 4a, 7, 8, or superior part of segment 6.  Volume 30, Number 2, April 2020 The full texts of relevant reports were retrieved and those articles that met the eligibility criteria of our review were selected. Any discrepancies in study selection were resolved by discussion between the authors. An independent third author was consulted in the event of disagreement. Data Extraction and Management We created an electronic data extraction spreadsheet in line with Cochrane’s data collection form for intervention reviews. We pilot-tested the spreadsheet in randomly selected articles and adjusted it accordingly. Our data extraction spreadsheet included: Study-related data (first author, year of publication, country of origin of the corresponding author, journal in which the study was published, study design, study size, clinical condition of the study participants, type of intervention, and comparison), baseline demographic and clinical information of the included populations (type of liver resection, lesion location, maximum diameter of lesion, age, sex, body mass index, and previous liver resection), and primary and secondary outcome data. Two review authors independently collected and recorded data in the data extraction spreadsheet and disagreements were resolved by discussion. If no agreement could be reached, a third review author was consulted. Types of Interventions Intervention of Interest. Laparoscopic liver resection was considered as the intervention of interest. Comparison of Interest. Open liver resection was considered as comparison of interest. Types of Outcome Measures Total postoperative complications was considered as a primary outcome measure. Secondary outcome measures included intraoperative bleeding, need for blood transfusion, operative time, R0 resection, major complications (DindoClavien III or more), postoperative mortality, length of hospital stay, need for readmission, disease recurrence, overall survival (OS) at maximum follow-up, 1-, 3-, 5-year OS, disease-free survival (DFS) at maximum follow-up, 1-, 3-, and 5-year DFS. Search Methods for Identification of Studies Electronic Searches Two authors independently searched the following electronic databases: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). The last search was run on July 25, 2019. Thesaurus headings, search operators and limits in each of the above databases were adapted accordingly. The literature search strategy is outlined in Appendix I (Supplemental Digital Content 1, http://links. lww.com/SLE/A231). In addition, World Health Organization International Clinical Trials Registry (http://apps.who.int/ trialsearch/), ClinicalTrials.gov (http://clinicaltrials.gov/), and ISRCTN Register (www.isrctn.com/) were searched for details of ongoing and unpublished studies. No language restrictions were applied in our search strategies. Searching Other Resources We searched the bibliographic lists of relevant articles and reviews for further potentially eligible trials. Data Collection and Analysis Selection of Studies The title and abstract of articles identified from the literature searches were assessed independently by 2 authors. Assessment of Risk of Bias in Included Studies Two authors independently assessed the methodological quality and risk of bias of the included articles using the Risk Of Bias In Nonrandomized Studies—of Interventions (ROBINS-I) assessment tool. The ROBINS-I tool assesses methodological quality of studies in terms of the following domains: bias due to confounding, bias in selection of participants into the study, bias in classification of interventions, bias due to deviations from intended intervention, bias due to missing data, bias in measurement of outcomes, and bias in selection of the reported result. Disagreements were resolved by discussion between the reviewers. If no agreement could be reached, a third author acted as an adjudicator. Risk of bias graph was constructed to present the results. Measures of Treatment Effect For dichotomous outcome variables, we calculated the odds ratio (OR) as the summary measure. We planned to calculate the risk difference (RD) when more than a third of the studies had 0 events in both groups. For continuous parameters, we calculated the mean difference (MD) between the 2 groups Unit of Analysis We used the individual patient as the unit of analysis in our review. Assessment of Heterogeneity Heterogeneity among the studies was assessed using the Cochran Q test (χ2). We quantified inconsistency by calculating I2 and interpreted it using the following guide: 0% to 50% may represent low heterogeneity, 50% to 75% may represent moderate heterogeneity, and 75% to 100% may represent high heterogeneity. Assessment of Reporting Biases We planned to construct funnel plots and evaluate their symmetry to visually assess publication bias for outcomes reported by at least 10 studies. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 94 | www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 Liver Resection for Posterosuperior Segments Tumors Data Synthesis We used the Review Manager 5.3 software for data synthesis. The extracted data were entered into Review Manager by an independent reviewer and checked by a second independent reviewer. Random-effects or fixed-effect modeling were used as appropriate for analysis; random-effects models were used if considerable heterogeneity was found among the studies. The results were reported in a forest plot with 95% confidence intervals (CIs). Information about dropouts, withdrawals, and other missing data were recorded and, if not reported, we contacted the study authors where possible. We based our analysis on intention-to-treat data from the individual clinical studies. Sensitivity and Subgroup Analyses To explore potential sources of heterogeneity and assess the robustness of our results, additional analyses were conducted for the outcomes reported by at least 4 studies. We repeated the primary analysis using the random-effects and fixed-effect model. In addition, we calculated the risk ratio and RD for dichotomous outcomes. We assessed the effect of each study on the overall effect size and heterogeneity by repeating the analysis after removing one study at a time. We also planned to perform separate analyses for studies with a low risk of bias to assess the change in direction of the effect size. Where possible, we aimed to perform subgroup analyses based on the location of lesion and type of liver resection. RESULTS Results of the Search Searches of electronic databases identified 238 articles of which 11 retrospective observational studies,6–16 enrolling a total of 1023 patients, were eligible for inclusion in this study. Overall, 424 patients were included in the laparoscopic group and 599 patients were included in the open group. The included patients in both groups were comparable in terms of age (60.4 vs. 61.6; MD: −0.94; 95% CI: −2.31, 0.43; P = 0.18), male sex (65% vs. 73%; OR: 0.76; 95% CI: 0.57, 1.00; P = 0.05), and female sex (35% vs. 27%; OR: 1.32; 95% CI: 1.00, 1.75; P = 0.05). Both groups were comparable in terms of maximum diameter of lesion (2.80 vs. 3.3 cm; MD: −0.06; 95% CI: −0.19, 0.06; P = 0.33). The conversion to open surgery rate was 7.8% in the laparoscopic group. The literature search flow chart, baseline characteristics of the included studies, and baseline characteristics of the included population are demonstrated in Figure 1 and Tables 1, 2, respectively. Risk of Bias in Included Studies The summary and results of the methodological quality assessment of the 11 observational studies6–16 are demonstrated graphically in Figure 2. Outcome Synthesis Total Postoperative Complications. Total postoperative complications was reported in 11 studies,6–16 enrolling 1023 patients (Fig. 3). Laparoscopic resection was associated with a lower risk of total postoperative complications compared with open resection (OR: 0.45; 95% CI: 0.33, 0.61; P < 0.00001). A low level of heterogeneity among the studies existed (I2 = 18%; P = 0.27). The likelihood of publication bias was low based on the funnel plot (Fig. 4). Intraoperative Blood Loss. Intraoperative blood loss was reported in 8 studies,6,8,9,11–15 enrolling 795 patients (Fig. 3). There was no difference in intraoperative blood loss between FIGURE 1. Study flow diagram. the 2 groups (MD: −57.24; 95% CI: −247.12, 132.63; P = 0.55). A high level of heterogeneity among the studies existed (I2 = 96%; P < 0.00001). Considering that the study by Aghayan et al6 was the source of significant heterogeneity in this outcome, the analyses were repeated after the exclusion of Aghayan et al. After removing Aghayan et al, laparoscopic resection was associated with lower intraoperative blood loss compared with open resection (MD: −114.71; 95% CI: −165.64, −63.79; P < 0.0001) and a low level of heterogeneity among the studies existed (I2 = 0%; P = 0.58). Need for Transfusion. Need for transfusion was reported in 7 studies,6,8–10,12,13,15 enrolling 709 patients (Fig. 3). There was no difference in the achievement of R0 resection between the 2 groups (OR: 1.23; 95% CI: 0.75, 2.02; P = 0.41). A low level of heterogeneity among the studies existed (I2 = 34%; P = 0.17). Operative Time. Operative time was reported in 11 studies,6–16 enrolling 1023 patients (Fig. 3). A laparoscopic approach was associated with longer operative time (MD: 50.28; 95% CI: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 95 Surg Laparosc Endosc Percutan Tech Hajibandeh et al  Volume 30, Number 2, April 2020 TABLE 1. Baseline Characteristics of the Included Studies Sample Size References Country Journal Design Aghayan et al6 Norway HPB Retrospective observational Del Pino et al7 Germany Digestive Surgery Retrospective observational Morikawa et al8 Japan Surgery Today Retrospective observational Okuno et al9 USA Surgical Endoscopy Retrospective observational Rhu et al10 Korea World Journal of Surgery Retrospective observational Belgium British Journal of Surgery Retrospective observational D’Hondt et al12 Belgium Surgical Endoscopy Retrospective observational Guro et al13 Korea Surgical Endoscopy Retrospective observational Tarantino et al14 Italy Retrospective observational Xiao et al15 China Journal of Laparoendoscopic and Advanced Surgical Techniques Surgical Endoscopy Cho et al16 Korea Surgery Scuderi et al11 Retrospective observational Retrospective observational 22.29, 78.27; P = 0.0004). A high level of heterogeneity among the studies existed (I2 = 90%; P < 0.00001). The likelihood of publication bias was low based on the funnel plot (Fig. 4). R0 Resection. R0 resection was reported in 10 studies,6–15 enrolling 967 patients (Fig. 3). There was no difference in the achievement of R0 resection between the 2 groups (OR: 1.09; 95% CI: 0.66, 1.81; P = 0.72). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.84). The likelihood of publication bias was low based on the funnel plot (Fig. 4). Description of the Included Population Patients undergoing liver resection for tumors located in posterosuperior segments Patients undergoing liver resection for tumors located in posterior segments Patients undergoing liver resection for tumors located in posterosuperior segments Patients undergoing liver resection for colorectal liver metastases in the posterosuperior segments Patients undergoing liver resection for hepatocellular carcinoma in the right posterior section Patients undergoing liver resection for tumors located in posterosuperior segments Patients undergoing liver resection for tumors located in posterosuperior segments Patients undergoing liver resection for hepatocellular carcinoma in segments 7 or 8 Patients undergoing liver resection for hepatocellular carcinoma in the right posterior section Patients undergoing liver resection for hepatocellular carcinoma in posterosuperior segments Patients undergoing liver resection for hepatocellular carcinoma in the right posterior section Total Laparoscopic Open Group Group 136 62 74 35 15 20 64 20 44 58 29 29 150 53 97 172 86 86 70 35 35 104 46 58 64 13 51 127 41 86 43 24 19 Length of Hospital Stay. Length of hospital stay was reported in 11 studies,6–16 enrolling 1023 patients (Fig. 3). A laparoscopic approach was associated with a shorter length of hospital stay (MD: −2.01; 95% CI: −2.09, −1.92; P < 0.00001). A moderate level of heterogeneity among the studies existed (I2 = 66%; P = 0.001). The likelihood of publication bias was low based on the funnel plot (Fig. 4). Need for Readmission. The need for readmission was reported in 3 studies,7–9 enrolling 157 patients (Fig. 3). There was no difference in the need for reoperation between the 2 groups (OR: 0.70; 95% CI: 0.19, 2.60; P = 0.60). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.83). Major Complications (Dindo-Clavien III or More). Major complications was reported in 10 studies,6–15 enrolling 980 patients (Fig. 3). Laparoscopic resection was associated with a lower risk of major complications compared with open resection (OR: 0.52; 95% CI: 0.36, 0.73; P = 0.0002). A low level of heterogeneity among the studies existed (I2 = 18%; P = 0.57). The likelihood of publication bias was low based on the funnel plot (Fig. 4). Disease Recurrence. Disease recurrence was reported in 3 studies,10,11,14 enrolling 386 patients (Fig. 3). There was no difference in the risk of disease recurrence between the 2 groups (OR: 1.58; 95% CI: 0.95, 2.63; P = 0.08). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.71). Postoperative Mortality. Postoperative mortality was reported in 5 studies,6,11,15–17 enrolling 513 patients (Fig. 3). There was no difference in the risk of postoperative mortality between the 2 groups (RD: −0.00; 95% CI: −0.02, 0.02; P = 0.68). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.99). OS (at Maximum Follow-up). OS was reported in 6 studies,8–10,13,15,16 enrolling 546 patients (Fig. 3). There was no difference in OS between the 2 groups (OR: 1.09; 95% CI: 0.66, 1.81; P = 0.73). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.85). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 96 | www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 Liver Resection for Posterosuperior Segments Tumors TABLE 2. Baseline Characteristics of the Included Population References Aghayan et al6 Del Pino et al7 Morikawa et al8 Okuno et al9 Rhu et al10 Scuderi et al11 D’Hondt et al12 Guro et al13 Tarantino et al14 Xiao et al15 Cho et al16 Type of Liver Resection Lesion Location Maximum Diameter of Lesion (cm) Average Age Segmentectomy Segments 1, 4a, 7, 8 Segments 6, 7 2.3 (0.5) vs. 2.2 (0.5) 3.1 (1.4) vs. 4.7 (2.4) 66 (10) vs. 67 (9) 59.9 (11.7) vs. 65.4 (10.2) 31/62 vs. 48/74 31/62 vs. 26/74 9/15 vs. 13/20 6/15 vs. 7/20 2.3 (1.6) vs. 2.0 (1.6) 1.66 (1.5) vs. 1.7 (1.2) 3.1 vs. 3.1 2.6 (1) vs. 3 (1.1) 65 (10.3) vs. 63.5 (17.3) 54 (12.3) vs. 54 (9.3) 58 (8.8) vs. 58.2 (9.4) 64 (13.3) vs. 63.9 (12.3) 14/20 vs. 30/44 6/20 vs. 14/44 2.4 (1.95) vs. 2.0 (1) Bisegmentectomy, segmentectomy, nonanatomic resections Segmentectomy Segments 7, 8 Segmentectomy Segments 4a, 7, 8 Sectionectomy Segments 6, 7 Wedge resection, Segments segmentectomy, 1, 4a, 7, 8 bisegmentectomy Segments Sectionectomy, 6, 7, 8 segmentectomy, bisegmentectomy, trisegmentectomy, nonanatomic resections Segments Tumorectomy, 7, 8 segmentectomy, bisegmentectomy, sectionectomy, hepatectomy, bisectionectomy Wedge resection, Segments 6, 7 segmentectomy, sectionectomy Segmentectomy, Segments bisegmentectomy, 1, 4a, 7, 8 lobectomy, nonanatomic resection Sectionectomy Superior part of segments 6, 7 Male Sex Female Sex BMI 24.7 (4) vs. 25.2 (6) 28.2 (3.6) vs. 24.7 (4.2) Intraoperative Blood Loss (mL) 500 (64.5) vs. 250 (59) NR 23.5 (2.5) vs. 22.6 (4.8) 14/29 vs. 15/29 15/29 vs. 14/29 27.6 (5.1) vs. 29.0 (3.8) 43/53 vs. 81/97 10/53 vs. 16/97 23.8 (2.9) vs. 24.6 (3.2) 54/86 vs. 50/86 32/86 vs. 36/86 25.5 (3.7) vs. 25.4 (3.5) 318 (548.8) vs. 535 (1037.5) 100 (197.5) vs. 150 (317.5) NR 64 (15.8) vs. 64 (8.8) 18/35 vs. 23/35 17/35 vs. 12/35 NR 150 (362.5) vs. 300 (317.5) 2.8 (1.4) vs. 4.7 (5.3) 62 (9.3) vs. 66 (11) 35/46 vs. 47/58 11/46 vs. 11/58 23.3 (2.8) vs. 23.2 (3.3) 550 (1425) vs. 700 (1700) 2.6 (0.9) vs. 3.7 (2.3) 65 (13) vs. 65.5 (9) 7/13 vs. 37/51 6/13 vs. 14/51 25.7 ± 2 vs. 25.5 ± 3 125 ± 80 vs. 208 ± 263 4.22 (2.05) vs. 4.30 (1.49) 52.07 (11.62) vs. 50.28 (11.89) 34/41 vs. 77/86 7/41 vs. 9/86 NR 272.20 ± 170.86 vs. 450.12 ± 344.70 3.7 (1.8) vs. 4.8 (2.5) 53.9 (12.6) vs. 60 (8.9) 17/24 vs. 16/19 7/24 vs. 3/19 NR NR 200 (500) vs. 200 (1000) BMI indicates body mass index; NR, not reported. 1-Year OS. One-year OS was reported in 3 studies,9,10,15 enrolling 335 patients (Fig. 3). There was no difference in 1-year OS between the 2 groups (OR: 1.53; 95% CI: 0.48, 4.92; P = 0.47). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.72). 3-Year OS. Three-year OS was reported in 3 studies,10,13,15 enrolling 381 patients (Fig. 3). There was no difference in 3-year OS between the 2 groups (OR: 1.26; 95% CI: 0.67, 2.37; P = 0.48). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.66). 5-Year OS. Five-year OS was reported in 4 studies,8,10,16 enrolling 257 patients (Fig. 3). There was no difference in 5-year OS between the 2 groups (OR: 0.91; 95% CI: 0.41, 1.99; P = 0.80). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.83). DFS (at Maximum Follow-up). DFS was reported in 7 studies,8–11,13,15,16 enrolling 681 patients (Fig. 3). There was no difference in DFS between the 2 groups (OR: 0.91; 95% CI: 0.65, 1.27; P = 0.56). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.82). 1-Year DFS. One-year DFS was reported in 3 studies,9,10,15 enrolling 335 patients (Fig. 3). There was no difference in 1-year DFS between the 2 groups (OR: 1.04; 95% CI: 0.60, 1.81; P = 0.88). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.72). 3-Year DFS. Three-year DFS was reported in 4 studies,10,11,13,15 enrolling 516 patients (Fig. 3). There was no difference in 3-year DFS between the 2 groups (OR: 1.13; 95% CI: 0.75, 1.69; P = 0.57). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.92). 5-Year DFS. Five-year DFS was reported in 3 studies,11,12,14 enrolling 257 patients (Fig. 3). There was no difference in 5-year DFS between the 2 groups (OR: 0.73; 95% CI: 0.44, 1.24; P = 0.25). A low level of heterogeneity among the studies existed (I2 = 0%; P = 0.44). Sensitivity Analyses We performed sensitivity analyses for the outcomes reported by at least 4 studies. Removing one study at a time did not change the direction of the effect sizes and the overall heterogeneity for any of the outcomes except intraoperative blood loss where removal of Aghayan et al changed the direction of the effect size in favor of laparoscopic approach. The direction of the effect sizes remained unchanged when ORs, risk ratios or RDs were calculated separately. The use of random-effects or fixed-effect models did not affect the Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 97 Hajibandeh et al Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 FIGURE 2. Risk of bias summary and graph showing the authors’ judgments about each risk of bias item for the included studies. direction of the effect sizes for any of the outcomes except intraoperative blood loss where use of fixed-effect model changed the direction of the effect size in favor of open approach; nevertheless, considering the level of heterogeneity for this outcome, the results of random-effects model should be considered for final conclusion. The separate analyses for studies with a low or moderate risk of bias did not affect the direction of the effect sizes. The available data did not allow for performing subgroup analyses based on the location of lesion and type of liver resection. DISCUSSION We performed systematic review literature and metaanalysis to compare the outcomes of laparoscopic and open liver resection for tumors located in the posterosuperior segments. We identified 11 retrospective observational studies,6–16 enrolling a total of 1023 patients. The results of the analyses showed that the laparoscopic approach was associated with lower risks of total complications, major complications (Dindo-Clavien III or more) and intraoperative blood loss, longer operative time, and shorter length of hospital stay Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 98 | www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 Liver Resection for Posterosuperior Segments Tumors FIGURE 3. Forest plots of the comparison of outcomes between laparoscopic and open liver resection for tumors located in the posterosuperior segments. A, Total complications. B, Major complications (Dindo-Clavien III or more). C, Intraoperative blood loss. D, Need for transfusion. E, Operative time. F, R0 resection. G, Postoperative mortality. H, Length of hospital stay. I, Need for readmission. J, Disease recurrence. K, Overall survival (at maximum follow-up). L, One-year overall survival. M, Three-year overall survival. N, Five-year overall survival. O, Disease-free survival (at maximum follow-up). P, One-year disease-free survival. Q, Three-year disease-free survival. R, Five-year disease-free survival. CI indicates confidence interval. compared with an open approach. There was no difference between the 2 groups in terms of the need for blood transfusion, R0 resection, postoperative mortality, and the need for readmission. In terms of oncological outcomes, there was no difference between the 2 groups in terms of disease recurrence, OS at maximum follow-up, 1-, 3-, 5-year OS, DFS at maximum follow-up, 1-, 3-, and 5-year DFS. The results remained consistent through sensitivity analyses. The between-study heterogeneity was low for total complications, major complications, need for transfusion, R0 resection, postoperative Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 99 Hajibandeh et al Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 FIGURE 3. (Continued). mortality, need for readmission, disease recurrence, OS and DFS; moderate for the length of hospital stay; and high for intraoperative blood loss and operative time. The quality of the available evidence was moderate. Previous studies have shown that laparoscopic liver resection is associated with less intraoperative blood loss, less postoperative morbidity, and shorter length of stay compared with open liver resections.17,18 They have also demonstrated that laparoscopic liver resection is comparable with open liver resection in terms of OS and DFS. Previous studies did not provide any evidence on outcomes of laparoscopic versus open liver resection of tumors located in the posterosuperior segments of the liver. Unlike resection of tumors located in the anterolateral segments, laparoscopic resection of tumors located in the posterosuperior segments of the liver is technically challenging due to limited visualization and working space to identify safe resection margins and difficulty in controlling bleeding. Interestingly, our results demonstrated that the laparoscopic approach is still superior to the open approach for resection of tumors Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 100 | www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 Liver Resection for Posterosuperior Segments Tumors FIGURE 3. (Continued). located in the posterosuperior segments. Technical improvements and accumulation of laparoscopic skills and experience may explain our findings. Performing postural changes, positioning the patient in a left lateral decubitus and adjusting the table’s inclination on-demand to semiprone have allowed surgeons to improve the poor visibility and restriction of instrumental movement associated with resection of posterosuperior segments in the supine position. Moreover, minimally invasiveness of the laparoscopic approach for the resection of the posterior lesions might be a relevant factor that positively affects the postoperative clinical outcome.7 Laparoscopic liver resection was associated with longer operative time compared with open liver resection. The Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 101 Hajibandeh et al Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 FIGURE 3. (Continued). learning curve for laparoscopic liver resections is long and demanding compared with open liver resection. In contrast, resection of tumors located in the posterosuperior segments is classed as “technically major” resection by the expert panel at European Guidelines Meeting on Laparoscopic Liver Surgery.6 All of these may explain the longer operative time associated with the laparoscopic approach. The use of intercostal trocars and placing the patient in a semiprone position have been suggested as solutions for shortening the operation time for laparoscopic resection of tumors located in the posterosuperior segments.19,20 A laparoscopic approach was associated with a shorter length of hospital stay in this study. This can be explained by the fact that less invasiveness of laparoscopic liver resection compared with open liver resection helps to reduce postoperative demands of analgesia, delayed mobilization, and the patient’s related pulmonary complications, hence better postoperative recovery and shorter length of hospital stay. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. 102 | www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. Surg Laparosc Endosc Percutan Tech  Volume 30, Number 2, April 2020 Liver Resection for Posterosuperior Segments Tumors FIGURE 3. (Continued). In this review, we used a systematic approach to provide a summary of the best available evidence and to assess the risk of bias of relevant studies. The included studies were homogenous in terms of design and included population. Moreover, the included population in both groups were comparable in terms of baseline characteristics. Also, our results remained consistent through additional analyses. All of these would make our conclusions robust from the best available evidence. However, the reported outcomes of our review should be viewed and interpreted in the context of inherent limitations. The included studies had retrospective nonrandomized design subjecting them to inevitable selection bias. Moreover, most of the included studies had a sample size of <100; therefore, the possibility of type 2 error cannot be excluded. Although between-study heterogeneity was low for most of the outcomes, it was high for Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. www.surgical-laparoscopy.com Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved. | 103 Surg Laparosc Endosc Percutan Tech Hajibandeh et al  Volume 30, Number 2, April 2020 FIGURE 4. Funnel plots of the comparison of outcomes between laparoscopic and open liver resection for tumors located in the posterosuperior segments. A, Total complications. B, Major complications (Dindo-Clavien III or more). C, Operative time. D, R0 resection. E, Length of hospital stay. MD indicates mean difference; OR, odds ratio. intraoperative blood loss and operative time. Finally, the available data did not allow for performing subgroup analyses based on the location of lesion and type of liver resection. CONCLUSIONS Compared with the open approach in liver resection for tumors in the posterosuperior segments, the laparoscopic approach seems to be associated with a lower risk of postoperative morbidity, less intraoperative blood loss, and shorter length of hospital stay with comparable survival and oncological outcomes. The best available evidence is derived from observational studies with moderate quality; therefore, high-quality randomized controlled trials with adequate statistical power are required to provide a more robust basis for definite conclusions. REFERENCES 1. Buell JF, Cherqui D, Geller DA, et al. 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