Systematic review and meta-analysis of uniportal versus multiportal video-assisted thoracoscopic lobectomy for lung cancer

Introduction

Over the past two decades, surgical management of lung cancer has been characterized by the emergence of novel minimally invasive surgical techniques. Video-assisted thoracoscopic surgery (VATS) has been shown to be associated with superior perioperative outcomes when compared to open thoracotomy, with numerous meta-analyses demonstrating reduced complication rates, shorter hospital stay and improved long-term survival (1-3). In recent years, a uniportal VATS technique has emerged as an even less invasive alternative to the conventional multiportal approach (4,5). Since its adoption by thoracic surgeons, there have been numerous reports on the feasibility of this approach in the surgical management of lung and mediastinal tumors (5-7).

In addition to the reduced number of surgical incisions, institutional reports have demonstrated a number of potential advantages of the uniportal VATS technique. These included a significant reduction in postoperative pain (8,9), paresthesia (10-12) and improved patient satisfaction (11,13,14). Despite these encouraging results, comparative clinical outcomes of uniportal versus multiportal VATS remain uncertain. The present systematic review and meta-analysis aimed to compare uniportal VATS to conventional multiportal VATS in the context of lobectomy for lung cancer. Endpoints included mortality, operative time, length of hospital stay, perioperative blood loss and duration of postoperative drainage, as well as complication rates and rates of conversion to open thoracotomy.

Methods

Search strategy and selection criteria

Electronic searches were performed using Ovid Medline, Embase, PubMed, the Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club and Database of Abstracts of Reviews of Effects (DARE) from their inception date to January 2016. In order to maximize the sensitivity of the search and identify all relevant studies, we used the terms ‘uniport*’ or ‘single-port’ or ‘single port’ or ‘single-incision’ or ‘single incision’ combined with ‘VATS’ or ‘thoracosp*’ or ‘video-assisted’ or ‘video assisted’, either as key words or MeSH terms. Following initial screening based on abstracts, the full texts of potentially relevant articles were obtained. The reference lists of all retrieved articles were examined in order to identify additional potentially relevant studies.

Eligible comparative studies for the present systematic review and meta-analysis included those in which survival data was available for patients with a diagnosis of lung cancer treated by lobectomy in uniportal and multiportal VATS cohorts. Indications for surgery other than for lung malignancy, such as mediastinal tumors, primary spontaneous pneumothorax and hyperhidrosis, were excluded. In cases where institutions have published duplicated trials with accumulating patient cohorts, only the most recent and complete study was included for appraisal. All studies were limited to human subjects. Case reports, conference abstracts, editorials, expert opinions and commentaries were excluded. Review articles were also excluded due to possible duplication of results and publication bias.

Data extraction and critical appraisal

All data were extracted from article texts, tables and figures. Two investigators (C.G.H. and R.S.J.) independently reviewed each retrieved article. Any inconsistencies between the two reviewers were resolved by discussion and consensus. The final results were reviewed by the senior investigators (T.D.Y. and C.C.).

Statistical analysis

Meta-analysis was performed by combining the results of outcome variables. Data were summarized as standard mean difference, with overall weighted mean presented where appropriate. I² statistic was used to estimate the percentage of total variation across studies, due to heterogeneity rather than chance. An I² value of greater than 50% was considered substantial heterogeneity. If there was substantial heterogeneity, the possible clinical and methodological reasons for this were explored qualitatively. In the present meta-analysis, the results using the random-effects model were presented to take into account the possible clinical diversity and methodological variation amongst studies. Specific analyses considering confounding factors were not possible because raw data were not available. All P values were 2-sided. A significant difference was defined as P<0.05. Statistical analysis was conducted with Review Manager Version 5.3 (Cochrane Collaboration, Software Update, Oxford, UK).

Results

Quantity and quality of trials

A total of 1,051 references were identified by the electronic search strategy. After excluding duplicate or irrelevant articles, 38 references were retrieved for further evaluation. Manual searching of the reference lists of these retrieved articles did not identify any additional relevant studies. After applying the selection criteria and excluding studies that compared uniportal and multiportal VATS for indications other than lung cancer, eight studies remained for assessment. All of these studies were observational studies and deemed suitable for quantitative meta-analysis. The study selection process is summarized in Figure 1 according to the PRISMA statement (15). A summary of the study characteristics is presented in Table 1. Overall, a total of 1,850 patients were compared, including 627 patients who underwent uniportal VATS and 1,223 patients who underwent multiportal VATS. Three studies reported propensity-matched data (20-22). Two of these studies presented data from both unmatched and propensity-matched cohorts (20,22) and unmatched data from these studies is presented in Tables 1-3.

Figure 1 PRISMA flow chart for literature search.

Table 1 Summary of all studies comparing uniportal and conventional multiportal lobectomy in for management of lung cancer
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Table 2 Summary of baseline patient operative characteristics in all studies comparing uniportal and conventional multiportal lobectomy in lung cancer treatment
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Table 3 Summary of patient histopathological characteristics in all studies comparing uniportal and conventional multiportal lobectomy in lung cancer treatment.
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Patient operative and histopathological details

A summary of the patient operative details is presented in Table 2 and a summary of patient histopathological details is summarized in Table 3. See Table S1 for a summary of patient comorbidities in all included studies.

Table S1 Summary of patient comorbidities in all studies comparing uniportal and conventional multiportal lobectomy in lung cancer treatment
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Assessment of operative outcomes

There was a statistically significant reduction in the length of hospital stay for patients who underwent uniportal VATS lobectomy compared to the multiportal approach (6.2±2.6 vs. 6.7±3.4 days, P<0.0001, Figure 2). There was also a statistically significant reduction in the duration of postoperative drainage for the uniportal group (4.5±2.2 vs. 5.4±2.9 days, P=0.0006, Figure 3). In regard to overall morbidity as reported by the included studies, there was a statistically significant reduction in the incidence of overall morbidities for patients undergoing uniportal VATS lobectomy compared to the multiportal approach (12.0% vs. 13.7%, P=0.009, Figure 4).

Figure 2 Forest plot of length of stay for uniportal and multiportal groups. The estimate of the mean difference of each study corresponds to the middle of the squares and the horizontal line shows the 95% confidence interval (CI). On each line, the mean and standard deviations are shown for both treatment groups. The sum of the statistics, along with the summary standardized mean difference, is represented by the middle of the solid diamonds. A test of heterogeneity between the trials within a subgroup is given below the summary statistics.

Figure 3 Forest plot of duration of postoperative drainage for uniportal and multiportal groups. The estimate of the mean difference of each study corresponds to the middle of the squares and the horizontal line shows the 95% confidence interval (CI). On each line, the mean and standard deviations are shown for both treatment groups. The sum of the statistics, along with the summary standardized mean difference, is represented by the middle of the solid diamonds. A test of heterogeneity between the trials within a subgroup is given below the summary statistics.

Figure 4 Forest plot of overall morbidity for uniportal and multiportal groups. The estimate of the mean difference of each study corresponds to the middle of the squares and the horizontal line shows the 95% confidence interval (CI). On each line, the mean and standard deviations are shown for both treatment groups. The sum of the statistics, along with the summary standardized mean difference, is represented by the middle of the solid diamonds. A test of heterogeneity between the trials within a subgroup is given below the summary statistics.

There were no significant differences between uniportal versus multiportal VATS in regard to operative time (155.8±53.8 vs. 167±64.6 minutes, P=0.69), perioperative blood loss (86.3±76.2 vs. 82.4±74 mL, P=0.63) or rate of conversion to open thoracotomy (3.6% vs. 2.6%, P=0.83). It should be noted that there were no perioperative mortalities in any patients who underwent uniportal VATS and only one patient who underwent the multiportal approach (16). Long-term clinical outcomes were not reported in any of the studies.

When propensity-matched data were analyzed, there were no statistically significant differences in operation time, length of hospital stay, perioperative blood loss, duration of postoperative drainage, rate of conversion to thoracotomy or overall morbidity. A summary of these findings is presented in Table 4 for all included studies and Table 5 for the studies with propensity-matched data.

Table 4 Summary of perioperative outcomes in all studies comparing uniportal and do not delete multiportal. Leave heading as is lobectomy in lung cancer treatment
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Table 5 Summary of perioperative outcomes in studies with propensity-matched patient cohorts comparing uniportal and do not delete multiportal. Leave heading as is lobectomy in lung cancer treatment
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Discussion

The present systematic review demonstrated that uniportal VATS was associated with a statistically significant shorter duration of chest tube drainage (4.5±2.2 vs. 5.3±2.9 days), shorter hospital stay (6.2±2.6 vs. 6.7±3.4 days) and lower overall morbidity (12.0% vs. 13.7%) compared to multiportal VATS. However, these findings must be considered in the context of their clinical relevance, as the improvements were only minor. Furthermore, the benefits of uniportal VATS were even less significant when propensity-matched data were meta-analyzed. Results also demonstrated that there were no significant differences between the two treatment modalities in regard to the number of lymph nodes dissected, operative time or rates of conversion to open thoracotomy. Overall, these findings suggested that uniportal VATS can be performed with relatively similar or improved perioperative outcomes without compromising safety or oncologic principles. However, there was a paucity of long-term clinical data and equivalent oncologic efficacy cannot be ascertained based on the existing literature.

Improved pain management has been a frequently claimed benefit to the uniportal VATS approach. However, the evidence for this was limited, with only one study in the present review reporting patient pain outcomes (23). Although this study demonstrated a reduction in pain scores, as measured by Visual Analogue Score (VAS) of 1–10 on day 1 postoperatively, a recent Best Evidence Topic review of uniportal and multiport VATS surgery concluded that the single port approach made little difference in pain outcomes for patients undergoing minor thoracic surgeries (24). Based on these findings, it is clear that further studies with standardized pain management protocols are required to determine benefits of the uniportal approach for pain management. Opponents of uniportal VATS have voiced concerns that this approach may be associated with longer operative duration, worse safety outcomes and higher likelihood of conversion to open thoracotomy. However, results of the present meta-analysis have refuted these concerns, at least in the context of selected patients treated in specialized centers.

It is important to acknowledge a number of limitations when considering the results of the present systematic review. Of the eight observational studies included for meta-analysis, one was prospective (20) and all others were retrospective in design. Wang and colleagues noted that a randomized control trial could not be easily performed in this setting, but suggested further prospective studies in the future (22). In order to minimize patient selection bias due to the non-random allocation of treatment, three studies performed propensity-matched analyses to improve the matching of patients according to relevant prognostic factors (20-22). Other limitations of the systematic review included the variable reporting of conversions in different studies and variable grading of postoperative morbidities. Whilst most studies included conversion rates (from single port to multiportal VATS or from VATS to open thoracotomy) in their analysis of surgical outcomes, Wang and colleagues used conversion as one of their exclusion criteria for statistical analysis (22). Furthermore, some studies accounted for a learning curve period by excluding the initial patients who underwent uniportal VATS from analysis in order to exclude the learning curve (21). These arbitrary exclusions may have had an impact on the surgical outcomes of the uniportal VATS treatment arm.

In conclusion, the present study was the first to meta-analyze clinical outcomes of uniportal VATS versus multiportal VATS in the treatment of lung cancer. Results suggested that uniportal VATS was associated with a statistically significant reduction in the duration of chest tube drainage, in-hospital stay and overall morbidity, but these improvements may only be minor in the clinical setting. Future studies should aim to standardize clinical outcomes with longer follow-up to assess the oncologic efficacy of the uniportal approach.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

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