Uniportal versus multiportal video-assisted thoracoscopic surgery for non-small cell lung cancer: a meta-analysis


 Background Uniportal video-assisted thoracoscopic surgery (U-VATS) has recently emerged as an alternative procedure for non-small cell lung cancer (NSCLC); however, whether U-VATS has advantages over multiportal VATS (M-VATS) remains unknown. Methods We performed a systematic review of two databases (Pubmed and Web of Science) to search comparative studies of U-VATS and M-VATS anatomical pulmonary resection for NSCLC. Parameters of continuous variables (operative time, blood loss, number of resected lymph nodes, drainage duration, length of postoperative stay and pain in postoperative day 1(POD1)) or categorical variables (conversion rates) were retrieved to estimate the comparitiveoutcomes. A subgroup analysis stratified by study type (propensity-matched analysis& randomized-controlled trial versus non-propensity matched analysis) was performed. Result A total of 19 studies with 3809 patients were included in this meta-analysis. U-VATS was performed on 1747 patients, whereas the other 2062 patients underwent M-VATS. This meta-analysis showed that there was no significant difference in operative time (U-VATS: 146.48±55.07min versus M-VATS: 171.70±79.40min, P=0.81), blood loss (74.49±109.03mL versus 95.48±133.67mL, P=0.18), resected lymph nodes (17.28±9.46 versus 18.31±10.17, P=0.62), conversion rate (6.18% versus 4.34%, P=0.14), drainage duration (3.90±2.94 days versus 4.44±3.12 days, p=0.09), length of postoperative stay (6.16±4.40 days versus 6.45±4.80 days, P=0.22), and pain in POD1 (3.94±1.68 versus 3.59±2.76, p=0.07). Subgroup analysis showed the value of PSM&RCT group consistency with overall value. Conclusion This up-to-date meta-analysis shows that the perioperative outcomes of U-VATS and M-VATS anatomical pulmonary resection are equivalent. In addition to minimizing the incisions, thoracic surgeons should pay more emphasize on providing high-quality and personalized surgical care for patients, to improve the survival ultimately.

witnessed continuous evolution and progress of surgical techniques, such as the utilization of segmentectomy and the development of video-assisted thoracoscopic surgery (VATS). Compared with the traditional thoracotomy, VATS has significant advantages, such as reduced postoperative pain, less intraoperative blood loss, and better quality of life, which have been widely recognized by prospective randomized controlled trials. [2][3][4] Conventionally, the traditional VATS, known as multiportal VATS (M-VATS) was commonly performed through 3 or 4 small incisions in the thoracic wall. In recent years, uniportal VATS (U-VATS) has become a new technique in thoracic surgery.
Uniportal minimally invasive surgery has developed rapidly since Dr. Rocco first reported in 2004, expanding from the minor thoracic procedures such as wedge resection to complex operations such as lobectomy, segmentectomy, and even bronchial or pulmonary angioplasty. [5] There have already been numerous articles on the feasibility of U-VATS approach in the treatment of lung neoplasm. Quite a few studies showed no difference between the approaches in the key intraand postoperative outcome. [6][7][8][9][10]Besides, some articles have demonstrated several potential advantages of the uniportal VATS technique, such as lower mortality, shorter hospital stay, and reduced postoperative pain, [11][12][13] however, the results of these studies were highly heterogeneous.
For instance, Lin et al indicated that U-VATS significantly increased operation time compared to M-VATS approach, [14] while Bourdages-Pageau et al held the idea that operation time was significantly decreased in U-VATS group. [15] One study reported shorter average hospital stay with uniportal VATS [16], while another showed it was longer. [10] Comparative clinical outcomes of U-VATS versus M-VATS still remain uncertain.
Here in, we conducted a comprehensive meta-analysis of prospective and retrospective comparative studies, to compare the outcomes of U-VATS and M-VATS anatomical pulmonary resection (lobectomy or segmentectomy) for NSCLC.

Data Extraction And Assessment Of Methodological Quality
Two independent investigators (Y.R. Yan and Q.Y. Huang) extracted data from all included studies by Microsoft Office Excel 2010 (Microsoft, Redmond, WA). In the case of conflicts, disagreements were adjudicated by a third impartial reviewer (Y. Zhang) and resolved by combined agreement. Baseline variables retrieved included the following: study name, first author, location, publication year, study period, study design, surgical procedure, and tumor stage. The following results were retrieved as comparative outcomes: operation time, blood loss, number of resected lymph nodes, conversion rate, drainage duration, length of postoperative stay and pain in POD1. Two independent investigators (Y.R. Yan and Q.Y. Huang) assessed the methodological quality of the pertinent studies according to the Newcastle Ottawa Scale (NOS), a scale of 0 to 9. Studies scored 6 or more were included in this article.

Data analysis
This meta-analysis retrieved and analyzed data according to the preferred reporting items for systemic reviews and meta-analysis (PRISMA) statement. [16] Meta-analysis was performed using R Studio Version 3.6.1 Meta packages (version 4.9-7). The effective values of continuous variables (operation time, blood loss, number of resected lymph nodes, drainage duration, length of postoperative stay, and pain in POD1) were estimated by standard mean differences or weighted mean difference (SMD or WMD) with 95% confidence intervals (CI), while those of categorical variables (conversion rate) were estimated by odds ratio (OR) with 95% confidence intervals. We performed a subgroup analysis stratified by study type (randomized controlled trials (RCTs) & propensity matched (PSM) studies versus non-propensity matched (non-PSM) studies) in operation time, blood loss, number of resected lymph nodes, drainage duration, and length of postoperative stay. Statistical heterogeneity was evaluated by Cochrane Chi-square test, with I 2 values of 25%, 50% and 75% representing low, moderate, and high heterogeneity. A random-effect model was used if I 2 > 25%, otherwise, a fixed-effect model was adopted. Funnel plots were used to graphically assess publication bias. Meanwhile, Egger's test and Begg's test were used to quantify the publication bias. A statistical difference was taken as two-sided P value < 0.05.  Table 1 summarized basic characteristics and demographics of the included studies.

Operative Outcomes
In this meta-analysis, the comparison of perioperative outcomes between U-VATS and M-VATS was estimated by intraoperative outcomes (operation time, blood loss, number of resected lymph nodes, and conversion rate) and postoperative outcomes (drainage duration, length of postoperative stay, and pain in POD1). Table 2 summarized the overall comparative outcomes of uniportal and multiportal group.   with NSCLC by stratifying analysis. Besides that, Borro indicated that U-VATS approach was correlated with a higher risk (HR = 1.78) of death. [33] Due to the lack of studies with regard to long-term outcomes, unfortunately, we are unable to make a meta-analysis of the long-term results. As surgical oncologists, the major impetus is always focused on optimal oncologic results, [34] and a procedure should never be performed by sacrificing the long-term survival. Although it is arbitrary to conclude that U-VATS result in poorer long-term outcomes based on only one study, thoracic surgeons should be cautious to avid uptake of this novel technique without well selecting the appropriate patients with lung cancer. Further studies of the survival of U-VATS are warranted.
VATS techniques are among the major progresses in the history thoracic surgery beyond all doubt.
Innovation of surgical approach is of great importance, but minimizing the size and number of incisions is only one part of minimally invasive surgery (MIS). We believe that the utilization of MIS should lead to preserving normal organs, prolonging survival, and improving quality of life [35]. For instance, with the help of precise intraoperative frozen section diagnosis of pre-invasive lung adenocarcinoma, we are able to perform sublobar resection for these patients, to spare pulmonary function without impairing the survival. [36] There are some limitations in this meta-analysis. Firstly, only four included studies are prospective in design, and the majority is retrospective which is of lower quality and inevitably introduce potential biases to the results.. U-VATS emerges as a novel surgical technique, so investigators have a propensity to publish positive outcomes to demonstrate the superiority or, at least, feasibility of U-VATS. Besides, due to the limited operating space and the narrow surgical field, U-VATS is usually performed in experienced hands [7,18,19,21,24] Consequently, the equivalent results between two approaches reported in this meta-analysis should be quite conservative. Secondly, our meta-analysis showed a high heterogeneity in the comparative outcomes (except conversion rates and number of resected lymph nodes). We made a subgroup analysis between PSM&RCT studies and non-PSM studies, and found that the result of PSM studies was consistent with that of all included studies.

Conclusions
To conclude, our results indicate that there is no significant difference in perioperative outcomes between U-VATS and M-VATS approaches in the treatment of NSCLC, which means that U-VATS, up to now, still cannot bring extra benefits over M-VATS on the perioperative recovery of patients. In addition, the differences in long-term outcomes of these two approaches are still unclear. Hence, U-VATS should be prudently chosen in the treatment of NSCLC.

Availability of data and materials
All data generated or analysed during this study are included in this published article.

Ethics approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Competing interests
We declared that no conflicts of interest or financial ties to disclose.

Author contribution statement
YY and QH designed and collected the data for the review. YY, QH, YZ and HH assisted with the data extraction and analysis. YZ was involved as the third reviewer to solve disagreement when necessary.
YY drafted the article. HC provided general advice and assisted with the writing of the review. All authors read and approved the final manuscript Figure 1 Flow chart detailing the search strategy and process of study selection

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