Laparoscopic versus open resection for gastric gastrointestinal stromal tumors: an updated systematic review and meta-analysis

A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify articles published up to June 2014. The search terms included ‘gastrointestinal stromal tumor’, ‘GIST’, ‘laparoscop*’, ‘gastrectomy’ and “gastric resection’. A personal search was also performed with reference lists of the retrieved relevant articles and reviews to identify additional trials and ensure that all the potential studies were included. The language of the articles was limited to English and Chinese according to the reviewers’ language competence.

The inclusion criteria were as follows: comparative, peer-reviewed studies of LAP versus OPEN for GISTs for which the full text of the article was available. If two or more studies from the same institution, the most recent study or that including informative data was selected unless the reports were from different time periods. We excluded studies including: GISTs out of the stomach; complicated with mixed disease, such as gastric cancer; studies in which fewer than two relevant indexes were reported, or where it was difficult to calculate these from the results; and studies where the measured outcomes were not clearly presented in the literature.

Two researchers independently extracted the data and disagreement was resolved through discussion. Extracted data included author, study period, geographical region, number of patients, operation time, blood loss, time to flatus, time to oral intake, length of hospital stay, morbidity, mortality, and long-term outcomes. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used as an assessment tool. This scale varies from zero to nine stars: studies with a score equal to or higher than six were considered methodologically sound.

Postoperative complications were classified as systematic complications (cardiovascular, respiratory or metabolic events; nonsurgical infections; deep venous thrombosis; and pulmonary embolism) or surgical complications (any anastomotic leakage or fistula, any complication that required reoperation, intra-abdominal collections, wound complications, bleeding events, pancreatitis, ileus, delayed gastric emptying, and anastomotic stricture). This classification system is based on the Memorial Sloan-Kettering Cancer Center complication reporting system [10]. Continuous variables were assessed using weighted mean difference (WMD), and dichotomous variables were analyzed using the risk ratio (RR). If the study provided medians and ranges instead of means and standard deviations, we estimated the means and standard deviations as described by Hozo et al. [11]. Statistical heterogeneity was evaluated by the Higgins I² statistic [12]. Based on method reported by DerSimonian and Laird [13], substantial significance was set when P < 0.10 and a random effect model was used. We hypothesized the outcomes of the comparison may be affected by the uneven distribution of the surgical types between the LAP and OPEN groups, especially by the relatively larger proportion of extended surgeries performed in the OPEN group. Thus, we performed a subgroup analysis of patients who underwent wedge resection in the two groups to eliminate the bias from the surgical type selection. We also conducted a subgroup analysis of studies that had comparable tumor size or risk index proposed by Fletcher et al. [3], which may have an impact on the operative outcomes. The potential publication bias based on the postoperative complications was assessed Begg’s test and funnel plots. Data analyses were performed using STATA (version 12.0). P <0.05 was considered statistically significant.

By the initial search, 768 potentially relevant articles were identified. After the titles and abstracts were reviewed, papers without comparison of LAP and OPEN were excluded, which left 28 comparative studies. An additional six [14‐19] studies did not meet the inclusion criteria and were excluded. In total, 22 observational studies were obtained [20‐41], all of which were accessible in full-text format. Twenty-one studies were published in English and one in Chinese. A flow chart of the search strategies, which contains reasons for exclusion, is presented in Figure 1.

A total of 1,166 patients were included in the analysis with 574 undergoing LAP (49.2%) and 592 undergoing OPEN (50.8%). They represented an international experience, with data included from 10 different countries or regions (six Japan, four United States, four China, two Korea, one United Kingdom, one Italy, one Belgium, one Austria, one Singapore and one Taiwan). According to the NOS, one out of the 22 observational studies got six stars, six articles got seven stars, eight articles got eight stars and the remaining seven got nine stars. Overall, all studies were evaluated as being moderate to high quality. The characteristics and methodological quality assessment scores of the included studies are summarized in Table 1.

The tumor size for LAP was significantly smaller than that for OPEN (WMD = -0.98 cm; 95% CI, -1.36 to -0.60; P <0.01; Figure 2). The present analysis showed no statistically significant difference in the operation time of the two groups (WMD = -11.22 min; 95% confidence interval (CI), -28.66 to 6.23; P = 0.21; Figure 3). Intraoperative blood loss was significantly lower in the LAP compared with the OPEN group (WMD = -58.91 ml; 95% CI, -84.60 to -33.22 ml; P <0.01; Figure 4).

The outcomes also favored LAP in first flatus day (WMD = -1.31 d; 95% CI, -1.56 to -1.06; P <0.01; Figure 5) and first oral intake (WMD = -1.75 d; 95% CI, -2.12 to -1.39; P <0.01; Figure 6). Moreover, postoperative hospital day was 3.68 days shorter for LAP patients (WMD = -3.68 d; 95% CI, -4.47 to -2.88; P <0.01; Figure 7). With respect to the rate of overall postoperative complications, LAP is significantly superior to OPEN. The rate of overall postoperative complications was significantly lower for LAP (RR = 0.57; 95% CI, 0.37 to 0.89; P = 0.01; Figure 8). After further analysis, surgical complications were similar between the two groups (RR = 0.69; 95% CI, 0.37 to 1.29; P = 0.24). However, LAP was associated with a marginal reduction in systematic complications (RR = 0.57; 95% CI, 0.32 to 1.04; P = 0.07).

15 studies reported tumor recurrence [21, 22, 24, 26‐32, 34, 36, 39‐41]. The recurrence risk in LAP was 3.6% (14 out of 388) and 9.7% (38 out of 393) in OPEN, and patients who underwent LAP were less likely than the OPEN group to have recurrence (RR = 0.51; 95% CI, 0.28 to 0.93; P = 0.03; Figure 9). The available data about recurrence patterns and survival outcomes are summarized in Table 2.

Comparison data of laparoscopic wedge resection and open wedge resection was available in eight studies[20, 22, 23, 26, 28, 30, 33, 34]. The overall effects such as operation time, blood loss, time to flatus or oral intake, hospital stay, and complications remained unchanged. However, in this subgroup analysis, the recurrence risk in LAP was 5.4% (7 out of 130) and 5.5% (9 out of 165) in OPEN, and the difference was not significant (RR = 1.01; 95% CI, 0.39 to 2.63; P = 0.99). The outcomes of subgroup analysis for studies of wedge resection are summarized in Table 3.

Thirteen studies qualified for a subgroup analysis for studies with comparable tumor size or risk index [20, 21, 23, 24, 26, 29, 30, 33, 34, 37‐40]. Like the subgroup analysis for wedge resection, outcomes other than tumor recurrence remained unchanged. The recurrence risk was similar between LAP and OPEN (RR = 0.66; 95% CI, 0.31 to 1.42; P = 0.29). The outcomes of subgroup analysis for studies with comparable tumor size or risk index are summarized in Table 4.

To test for publication bias, we used funnel plots and performed an Egger’s test based on the incidence of overall postoperative complications (Figure 10). The graphical funnel plot showed that none of the studies lay outside the 95% CI boundaries, and there was no evidence of publication bias.