Systematic review of robotic and non-robotic esophagectomy for the treatment in esophageal cancer patients: a meta-analysis

Systematic review of robotic and non-robotic esophagectomy for the treatment in esophageal cancer patients: a meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Systematic review of robotic and non-robotic esophagectomy for the treatment in esophageal cancer patients: a meta-analysis zipu yu, Guofei Zhang, Gang Shen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6434398/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To conduct a meta-analysis to determine the relative merits between robotic-assisted minimally invasive esophagectomy (RAMIE) and conventional video-assisted minimally invasive esophagectomy (MIE) in esophageal cancer patinents. METHODS: Eligible studies or databases for articles were retrieved via systematical search to identify comparative studies reporting peri-operative outcomes for RAMIE and MIE. Pooled odds ratios (OR) and standardized mean difference (SMD) with 95% confidence interval (95% CI) were calculated using either a fixed-effects or a random-effects model. RESULTS: Thirty studies matched the selection criteria and were included for statistical analysis, which reported on 12578 subjects with 4176 in RAMIE and 8402 in MIE. Through outcomes comparison analysis between RAMIE and MIE, this meta-analysis indicated that RAMIE was associated with less estimated blood loss (EBL) (SMD = -19.25, 95% CI −34.52 to -3.99) and less pneumonia (OR = 0.81, 95% CI 0.66 to 1.00). Meanwhile, this meta-analysis indicated that MIE was associated with shorter operative time (SMD = 23.29, 95% CI 7.35 to 39.44), less recurrent laryngeal nerve paralyses (OR = 1.31, 95% CI 1.07 to 1.59) and less total complications (OR = 1.21, 95% CI 1.03 to 1.42). Furthermore, total length of stay (LOS) (SMD = -0.01, 95% CI -0.19 to 0.18) , total morbility (within 90 days after operation) (OR = 1.06, 95% CI 0.88 to 1.27) , number of resected nodes(SMD = 0.97, 95% CI -0.20 to 2.15), conversion(OR = 0.76, 95% CI 0.23 to 2.49) , anastomotic orifice fistulae(OR = 0.98, 95% CI 0.76 to 1.25), wound infection(OR = 0.83, 95% CI 0.44 to 1.56) and chylothorax(OR = 1.12, 95% CI 0.65 to 1.93) were not significantly different for both procedures. CONCLUSION: RAMIE for esophageal cancer is not superior to conventional video-assisted MIE in terms of results of related indicators. Further studies are required to confirm this result. Health sciences/Diseases Health sciences/Oncology robotic esophagectomy minimally invasive esophagectomy conventional transthoracic surgery esophageal cancer Da Vinci robotic system Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Cancer remains one of the leading death causes worldwide. Esophageal cancer is the eighth most common malignancy and the sixth most common cause of cancer-related death ( 1 ). Incidence rates vary internationally. China has the highest rate of esophageal cancer. Despite the progress of multimodal treatment for esophageal cancer, radical surgery is the cornerstone ( 2 – 5 ). The overall 5-year survival rate for esophageal cancer remains poor ( 6 ). Radical surgical resection with lymphadenectomy represents the standard treatment. Transthoracic esophagectomy, minimally invasive esophagectomy and robot-assisted thoraco-laparoscopic esophagectomy are different surgical treatments for esophageal cancer. The da Vinci robotic system has superior advantages by giving the surgeon a better enhanced dexterity and precision due to its 3D optical system and EndoWrist® Instruments. Owing to its superiorities, application of robots has successfully attracted great attention and interest ( 7 , 8 ). In this context, the robot-assisted approach has been proposed as an alternative minimally invasive modality to conventional video-assisted surgery for esophageal cancer. Meta-analysis is considered to be an important tool for illustrating confusions. By synthesizing various independent literature and systematic analysis, relatively convincing conclusions could be drawn. The purpose of the present study is to determine the relative merits of RAMIE and MIE by performing a meta-analysis of studies comparing these two techniques. METHODS Search strategy A systematical search was made by means of the Pubmed, the Cochrane Library, EMBase and the Web of Science for all articles published in English before March 2024 that compared RAMIE and MIE in the esophageal cancer patients. The following search terms were used: “Esophageal neoplasm,”“Esophagus neoplasm,” “Esophagus cancer,” “Esophagectomy,” and“Robot.” Reference lists of all retrieved articles were also manually screened. Two authors independently applied the inclusion and exclusion criteria, and any disagreement was resolved by a third reviewer. All relevant text, tables, and figures were reviewed for data extraction. Inclusion and exclusion criteria Each recruited publication in English was evaluated as according to the following criteria: 1) it compared the outcomes of RAMIE and MIE, and 2) it reported on at least one of the outcome measures mentioned below. Abstracts, letters, editorials, reviews without original data, case reports, and studies lacking outcome measures were excluded. The studies excluded in this meta-analysis had to meet all of the following criteria: 1) it was impossible to extract the appropriate data from the published results; or 2) there was overlap between authors or centers. Outcomes of interest and data extraction The following outcomes were used to compare RAMIE and MIE techniques: 1) intra-operative data: operating time (min), conversion, number of resected nodes and estimated blood loss(ml); 2) post-operative data, which included LOS (days), and mortality (within 90 days after operation); 3) complication details, which included fistulae, wound infection, pneumonia, chylothorax, recurrent laryngeal nerve paralyses and total complications. Two reviewers independently extracted the following parameters from each study: 1) first author and year of publication; 2) study population; 3) number of subjects who underwent each technique; and lastly, 4) peri-operative outcomes data. The mean and the variance for articles reporting the median, range and the size of the trial were deduced in a way as described in Stela Pudar Hozo , s article ( 9 ). The quality of each study was assessed independently by two reviewers who used the Newcastle-Ottawa Scale (NOS). The quality of randomized trials was assessed using the Jadad scale ( 10 ). The meta-analysis was performed according to the PRISMA guidelines ( 11 ). Statistical analysis The statistical analysis was conducted as described previously ( 12 ). Briefly, Review Manager 5.2 (RevMan 5.2®, Nordic Cochrane Center and Copenhagen, Denmark) was used to perform the meta-analysis. The I 2 statistic was used to quantify the statistical heterogeneity of the studies included, and I 2 values of 25–49, 50–74 and ≥ 75% indicate low, moderate and high heterogeneity respectively. When the I 2 value was > 50%, indicating the presence of variability among the studies, we chose a random-effects models rather than fixed-effects models to perform the meta-analysis. We analyzed dichotomous variables using estimation of odds ratios with a 95% confidence interval (95% CI) and continuous variables using standardized mean difference (SMD) with a 95% CI. Forest plots were used to present the results of the meta-analysis. A P-value < 0.05 was considered to be statistically significant. RESULTS Description of the included studies The literature search identified 2170 articles. Through our systematic search, 30 studies fulfilled the inclusion criteria and were included in our quantitative data synthesis ( 13 – 42 ). Among the 12578 patients, 4176 patients underwent RAMIE, and 8402 patients underwent MIE. The characteristics of included studies are listed in Table 1 . The study flow diagram is depicted in Fig. 1 . Table 1 Outline of Studies Included in the Meta-Analysis Study Courntry Design RAMIE MIE PSM Study Quality 1.Xiaofeng Duan,2020 China Retro 109 75 no 6/9 2.Yang Xu,2021 China Retro 292 292 yes 6/9 3. Yin-Kai Chao,2018 China Retro 34 34 yes 6/9 4. H.-Y. Deng,2018 China Pro 42 42 yes 5/9 5. Ahmed M. Ali,2021 USA Retro 1543 5118 no 6/9 6. P. P. Grimminger,2018 Germany Pro 25 25 yes 7/9 7. Gregory J. Harbison,2019 USA Retro 100 625 no 8/9 8. Haiqi He,2018 China Retro 27 27 yes 7/9 9. Kenneth Meredith,2020 USA Pro 144 95 no 6/9 10. Satoru Motoyama,2019 Japan Retro 21 38 no 6/9 11. Samina Park,2016 South korea Retro 62 43 no 7/9 12. Yasuhiro Shirakawa,2020 Japan Retro 51 51 yes 6/9 13. Koichi Suda,2012 Japan Pro 16 20 no 7/9 14. E. Tagkalos,2020 Netherlands Pro 40 40 yes 7/9 15. Shigeru Tsunoda,2021 Japan Retro 45 45 yes 8/9 16. B. Weksler,2012 USA Retro 11 16 no 7/9 17. Benny Weksler,2017 USA Retro 569 569 yes 8/9 18. Yin-Kai Chao,2020 China Retro 39 67 no 6/9 19. Yajie Zhang,2019 China Retro 66 66 yes 7/9 20. Y. Yang,2020 China Retro 271 271 yes 6/9 21. Junying Chen,2019 China Retro 54 54 yes 6/9 22. H.-Y. Deng,2019 China Retro 52 52 yes 6/9 23. Lei Gong, 2019 China Retro 91 144 yes 7/9 24. Yang Yang,2022 China Retro 188 177 no 6/9 25. Shankar Balasubramanian, 2022 India Retro 22 22 yes 7/9 26. Itasu Ninomiya, 2021 Japan Retro 30 30 yes 7/9 27. Aditya Kulkarni, 2022 India Retro 25 25 yes 7/9 28. K. Mori,2015 Japan Retro 22 139 no 6/9 29. Chikara Kunisaki,2004 Japan Retro 15 30 no 6/9 30. Babatunde A,2016 USA Retro 170 170 yes 6/9 Note: Retro = s retrospective; Pro = prospective; PSM = propensity score matching; RAMIE = robotic-assisted minimally invasive esophagectomy; MIE = minimally invasive esophagectomy. Study characteristics Of the 30 observational studies, 12 studies were propensity matched for patient characteristics and factors, such as age, sex, body mass index, comorbidities, receipt of neoadjuvant treatment, and cancer staging. The RAMIE and MIE cohorts of each study had comparable surgical results and varied in size from 15 to 5118 patients. Of the 30 observational studies, 25 studies were retrospective studies, while the other 5 studies were prospective studies. Risk of bias assessment. No randomized controlled trials (RCTs) comparing robotic and conventional transthoracic esophagectomy were published. All studies had NOS quality scores greater than 6, indicating fair methodological quality. Specifically, thirteen studies had NOS quality score 7. The NOS quality score is represented in Table 1 . Surgical outcomes 1) Operative Time The operative time was reported in 20 studies. It was significantly shorter in the MIE group compared with the RAMIE group (SMD = 23.29, 95% CI 7.35 to 39.44). (Fig. 4 A). 2) Estimated Blood Loss Estimated blood loss was reported in 21 studies and was significantly lower in the RAMIE group, compared with the MIE group (SMD = -19.25, 95% CI − 34.52 to -3.99). The statistical heterogeneity was high (I 2 = 72%). (Fig. 4 B) 3) Conversion Conversion was reported in 8 studies and was not significantly lower in the RAMIE group, compared with the MIE group (OR = 0.76, 95% CI 0.23 to 2.49). The statistical heterogeneity was high (I 2 = 69%). (Fig. 4 D). 4) Total Lymph Nodes Resected 18 studies reported LN harvested, and total lymph nodes resected was not significantly more in the RAMIE group, compared with the MIE group (SMD = 0.97, 95% CI -0.20 to 2.15). The pooled random-effects was used due to the high (I 2 = 74%). (Fig. 4 C). 5) Length of Hospital Stay The length of hospital stay was reported in 20 studies, and it was not significantly shorter in the RAMIE group, compared with the MIE group (SMD = -0.01, 95% CI -0.19 to 0.18). The statistical heterogeneity was low (I 2 = 41%). The pooled fixed-effects was used. (Fig. 2 ). Post-operative Outcomes 1) Fistulae The anastomotic leakage rate was reported in 21 studies. No statistically significant difference was found between the RAMIE group and the MIE group (OR = 0.98, 95% CI 0.76 to 1.25). The statistical heterogeneity was low (I 2 = 4.00%). (Fig. 5 A) 2) Wound infection The rate of wound infection was reported in 12 studies, it was not significantly lower in the RAMIE group compared with the MIE group (OR = 0.83, 95% CI 0.44 to 1.56). The statistical heterogeneity was low (I 2 = 0.00%). The pooled fixed-effects was used due to the low I 2 . (Fig. 5 B) 3) Pneumonia The rate of pneumonia was reported in 22 studies, it was significantly lower in the RAMIE group compared with the MIE group (OR = 0.81, 95% CI 0.66 to 1.00). The statistical heterogeneity was low (I 2 = 0.00%). The pooled fixed-effects was used due to the low I 2 . (Fig. 5 C) 4) Chylothorax The rate of chylothorax was reported in 16 studies. No statistically significant difference was found between the RAMIE group and the MIE group (OR = 1.12, 95% CI 0.65 to 1.93). The statistical heterogeneity was low (I 2 = 0.00%). The pooled fixed-effects was used due to the low I 2 . (Fig. 6 A) 5) Recurrent laryngeal nerve paralyses The rate of RLN palsy was reported in 17 studies. There is a statistically significant difference between the RAMIE group and the MIE group (OR = 1.31, 95% CI 1.07 to 1.59). The statistical heterogeneity was low (I 2 = 22%). The pooled fixed-effects was used due to the low I 2 . (Fig. 6 B) 6) Total complication 13 studies reporting total complications were included in the meta-analysis. Pooled analysis indicated evidence of a difference for MIE compared with RAMIE (OR = 1.21, 95% CI 1.03 to 1.42). The statistical heterogeneity was low (I 2 = 35%). The pooled fixed-effects was used due to the low I 2 . (Fig. 6 C) 7) Morbility 30 studies reporting mortality within 90 days were included in the meta-analysis. Pooled analysis did not indicate evidence of a difference for MIE compared with RAMIE (OR = 1.06, 95% CI 0.88 to 1.27). The statistical heterogeneity was low (I 2 = 0%). The pooled fixed-effects was used due to the low I 2 . (Fig. 3 ) DISCUSSION By comparing and integrating the results of different studies and taking into account variations in characteristics, a recapitulatory conclusion could be drawn through the existing literature evaluation by qualitative and quantitative ways. This meta-analysis summarized results of 30 studies for esophageal cancer. To the best of our knowledge, this is the most comprehensive meta-analysis comparing RAMIE versus MIE. In our analysis, no significant differences were found in LOS (days), morbility, number of resected nodes, conversion, fistulae, wound infection and chylothorax between the two techniques, which at least demonstrated that RAMIE was equivalent to MIE in terms of safety. Oncologic outcomes after surgery are affected by the extent of lymph-node dissection. In this analysis, we found no significant differences between RAMIE and MIE in the number of dissected lymph nodes. However, long-term follow-up evaluation is necessary to evaluate the exact oncologic outcomes, which is the weakness owing to lack of long-term survival analysis data. The results of the present meta-analysis suggest that there is no additional clinical benefit for RAMIE over MIE, although RAMIE offers a number of advantages over MIE, including improvements in manual dexterity, ergonomics, and visualization. There was no difference in post-operative hospital stay between the two groups, implying that the time required for patients to resume daily activities might be similar between RAMIE and MIE. In our analysis, there was significant difference in total estimated blood loss, pneumonia, operative time, recurrent laryngeal nerve paralyses and total complication between RAMIE and MIE. In the study, we found significant heterogeneity in total operating time, total estimated blood loss, number of resected nodes and conversion, which may be attributed to the differences in personnel skills, and period of the learning curve. Operating times depend mainly on the experience and skill of the surgeon. The RAMIE group was inclined to take more time, which may be attributable to the reason for the additional set-up time required. The actual time may be shorter in RAMIE as a result of increasing experience and gradually decreased set-up time. According to results, the incidences of pneumonia and EBL were significantly lower in RAMIE group than that in MIE group. The potential reasons for the superiorities of RAMIE over MIE could be partially explained as followed: RAMIE provided a three-dimensional visualization and superior imaging quality, which optimized consequences of identifying various structures and avoiding lung tissue damage during operations. In addition, the incidences of total complication and recurrent laryngeal nerve paralyses were not significantly lower in RAMIE group than that in MIE group, which may be attributed to the rich experience in the thoracoscopic surgery in MIE procedure. Radical esophagectomy is the cornerstone of the multimodality treatment with curative intent. There are several ways for surgical treatment, including transthoracic surgery, conventional minimally invasive esophagectomy and robot-assisted esophagectomy. Owing to radical resection of the tumor with the paratracheal, subcarinal and paraesophageal lymph node dissection, conventional transthoracic esophagectomy is the preferred surgical approach worldwide. Minimally invasive esophagectomy (MIE) revolutionized surgical practice. Minimally invasive esophagectomy was designed to reduce surgical trauma, resulting in lower morbidity and mortality rates. Compared with open surgery, many reports have demonstrated clinical advantages of the minimally invasive esophagectomy: a faster post-operative recovery time and a shorter hospital stay, better cosmetic results with reduced morbidity. ( 43 – 46 ). In 2003, the robot-assisted thoraco-laparoscopic approach was developed. Data regarding the safety and the oncologic efficacy of RAMIE are limited. The existing data suggest RAMIE is a safe procedure which is associated with perioperative outcomes similar to transthoracic surgery and MIE ( 47 , 48 ). Advantage for robotic oesophagectomy over other forms of oesophagectomy is not obvious ( 49 ). The cost of equipment, specialized training and prolonged set up time are barriers to more widespread application. The fact that the surgeon is separated from the patient raises potential safety concerns. Future studies are needed to prove identifiable benefit of RAMIE over other approaches. However, our study has several limitations, so the results should be interpreted with caution. First, it is possible that investigative groups might be more likely to report positive results, and that studies with significant outcomes are more likely to be published, leading to potential publication bias. Second, there was heterogeneity between the two groups because it was impossible to match the patient characteristics across all of the studies. Third, the overall level of clinical evidence was low by reason of the data sources coming from NRCTs. However, meta-analyses for well-designed NRCTs could be probably as accurate as those for RCTs ( 50 , 51 ). Fourth, our analysis was retrospective in nature and thus subject to selection bias. CONCLUSIONS RAMIE is associated with a tendency for longer operating time, reduced blood loss and pulmonary complications as compared to MIE. There are no significant differences on the incidence of anastomotic leak, RLN palsy, total complications, wound infection, conversion to open surgery, chylothorax and mortality as compared to MIE. In conclusion, the results of this meta-analysis show that RAMIE is not superior to MIE for esophageal cancer. Further studies are required to better define its role in clinical practice. Abbreviations RAMIE robotic-assisted minimally invasive esophagectomy MIE minimally invasive esophagectomy OR odds ratios SMD standardized mean difference CI confidence interval EBL estimated blood loss LOS total length of stay NOS Newcastle-Ottawa Scale LN lymph Nodes RLN recurrent laryngeal nerve RCT randomized controlled trial Declarations Competing interests The authors declare that they have no competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Data Availability Statements The data underlying this article will be shared on reasonable request to the corresponding author. Authors’ contributions ZPY and GFZ participated in all aspects of the experiment and drafted the article. ZPY and GS performed the statistical analysis. ZPY and GS conceived of the study, and participated in its design and helped to draft the manuscript. All authors read and approved the final manuscript. Acknowledgements We acknowledge all members of Department of Thoracic Surgery, 2 nd Affiliated Hospital, Zhejiang University, Hangzhou, China for their support. We thank all the group members for their helpful discussions for our paper. Funding Statements There was no Foundation for this work. Ethics approval Not applicable. AI use statement There was no AI use for this work. References Jemal, A. et al. Global cancer statistics. CA Cancer J. Clin. 61 , 69–90 (2011). Omloo, J. M. et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann. Surg. 246 , 992–1000 (2007). discussion 1000–1001. Mariette, C., Piessen, G. & Triboulet, J. P. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol. 8 , 545–553 (2007). Burmeister, B. H. et al. 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Technical aspects and early results of robotic esophagectomy with chest anastomosis. J. Thorac. Cardiovasc. Surg. 145 , 90–96 (2013). Smithers, B. M. Minimally invasive esophagectomy: an overview. Expert Rev. Gastroenterol. Hepatol. 4 , 91–99 (2010). MacLehose, R. R. et al. A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies. Health Technol. Assess. 4 , 1–154 (2000). Abraham, N. S., Byrne, C. J., Young, J. M. & Solomon, M. J. Meta-analysis of well-designed nonrandomized comparative studies of surgical procedures is as good as randomized controlled trials. J. Clin. Epidemiol. 63 , 238–245 (2010). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6434398","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":453169986,"identity":"94940635-5518-496d-9f0d-add33a0a56be","order_by":0,"name":"zipu yu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"zipu","middleName":"","lastName":"yu","suffix":""},{"id":453169987,"identity":"50ff6e66-b875-4049-acd3-3fe5d663266a","order_by":1,"name":"Guofei Zhang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Guofei","middleName":"","lastName":"Zhang","suffix":""},{"id":453169988,"identity":"633eeb1b-2deb-47bf-aeac-f3533b156098","order_by":2,"name":"Gang Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3RvQrCMBDA8SsnmU66pgj6CpFCFwVfJSLYSdBFHCuCLj5AxMFnEF+gJeBUdHVwKPgCji5+1cmpxk0w/+3gfhwkADbbD+YiJpkcNasA8XNkBsSbsY44p13fnIg9Bd5iqtvRazQhoMn3iWG4GqcCzkMN7jIqFs6EDU5ErDeOUuGonQZ+jIsJIm584tSbQCqwPNUguCwmDCGokOAhy8nVhBCWAk9JISknjgnhmD9yLOsKtv1kvguJHz6Q1l4nWft2r9WUXmeXYaPqqg/k7V78+kwy3X/mRl8s22w221/1AIeRQSH9asi4AAAAAElFTkSuQmCC","orcid":"","institution":"Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2025-04-12 11:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6434398/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6434398/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82359605,"identity":"f5edf72a-c74c-448a-bfe4-5a5577cf7937","added_by":"auto","created_at":"2025-05-09 11:30:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":19443,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart indicating the process of selecting articles for meta-analysis.\u003c/p\u003e","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/cb7c4def4c163148feae6398.png"},{"id":82357589,"identity":"feab2d8e-88e4-48dd-82bd-74f206ad0034","added_by":"auto","created_at":"2025-05-09 11:22:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1715168,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot presenting LOS (days)from the studies included. 95%CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Onlinefigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/194795b80c10d0e7352bd069.png"},{"id":82357593,"identity":"0ea5a33d-be06-416e-9052-8ce2dce0afae","added_by":"auto","created_at":"2025-05-09 11:22:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2149007,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot presenting total morbility (within 90 days after operation) from the studies included. 95%CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Onlinefigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/92baaa06f4b84e86f0eb5295.png"},{"id":82360343,"identity":"26e53225-15d1-42a2-bb05-1e96b0a63482","added_by":"auto","created_at":"2025-05-09 11:38:25","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2975814,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot presenting total operating time (A), total estimated blood loss (B), conversion(C) and number of resected nodes(D) from the studies included. 95%CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Onlinefigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/9276fbddcc27537fdc8943af.png"},{"id":82357597,"identity":"b87a05dd-fff7-48c9-8ae4-464a7e4fcfd8","added_by":"auto","created_at":"2025-05-09 11:22:25","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":4627194,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot presenting fistulae (A), wound infection (B), pneumonia (C) from the studies included. 95% CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Onlinefigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/36fdb748ffad9901648abbf8.png"},{"id":82357606,"identity":"d69c5c60-638b-452a-ae65-d360a6635179","added_by":"auto","created_at":"2025-05-09 11:22:25","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":4875325,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot presenting chylothorax(A), recurrent laryngeal nerve paralyses (B), total complication (C) from the studies included. 95% CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Onlinefigure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/e5ce6d2f91a8f0ef6ac8bc30.png"},{"id":89298909,"identity":"146586b0-977c-48ba-881e-8faf1fbe5743","added_by":"auto","created_at":"2025-08-18 14:02:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2063187,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/88022784-0eae-4c74-91e8-36cc3de7e7bd.pdf"},{"id":82359604,"identity":"a94e8d6c-9508-495d-a65c-0680f5974a9d","added_by":"auto","created_at":"2025-05-09 11:30:25","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":177095,"visible":true,"origin":"","legend":"","description":"","filename":"Centralfigure.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/7defd1619a8d305e70dd044c.jpg"},{"id":82357591,"identity":"0a82548b-342f-4176-a7af-48e6dc21c2f2","added_by":"auto","created_at":"2025-05-09 11:22:25","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":32181,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMA2020checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-6434398/v1/e332d35099ae3ded514130a5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Systematic review of robotic and non-robotic esophagectomy for the treatment in esophageal cancer patients: a meta-analysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCancer remains one of the leading death causes worldwide. Esophageal cancer is the eighth most common malignancy and the sixth most common cause of cancer-related death (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Incidence rates vary internationally. China has the highest rate of esophageal cancer. Despite the progress of multimodal treatment for esophageal cancer, radical surgery is the cornerstone (\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The overall 5-year survival rate for esophageal cancer remains poor (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRadical surgical resection with lymphadenectomy represents the standard treatment. Transthoracic esophagectomy, minimally invasive esophagectomy and robot-assisted thoraco-laparoscopic esophagectomy are different surgical treatments for esophageal cancer. The da Vinci robotic system has superior advantages by giving the surgeon a better enhanced dexterity and precision due to its 3D optical system and EndoWrist\u0026reg; Instruments. Owing to its superiorities, application of robots has successfully attracted great attention and interest (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In this context, the robot-assisted approach has been proposed as an alternative minimally invasive modality to conventional video-assisted surgery for esophageal cancer.\u003c/p\u003e \u003cp\u003eMeta-analysis is considered to be an important tool for illustrating confusions. By synthesizing various independent literature and systematic analysis, relatively convincing conclusions could be drawn. The purpose of the present study is to determine the relative merits of RAMIE and MIE by performing a meta-analysis of studies comparing these two techniques.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy\u003c/h2\u003e \u003cp\u003eA systematical search was made by means of the Pubmed, the Cochrane Library, EMBase and the Web of Science for all articles published in English before March 2024 that compared RAMIE and MIE in the esophageal cancer patients. The following search terms were used: \u0026ldquo;Esophageal neoplasm,\u0026rdquo;\u0026ldquo;Esophagus neoplasm,\u0026rdquo; \u0026ldquo;Esophagus cancer,\u0026rdquo; \u0026ldquo;Esophagectomy,\u0026rdquo; and\u0026ldquo;Robot.\u0026rdquo;\u003c/p\u003e \u003cp\u003eReference lists of all retrieved articles were also manually screened. Two authors independently applied the inclusion and exclusion criteria, and any disagreement was resolved by a third reviewer. All relevant text, tables, and figures were reviewed for data extraction.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003eEach recruited publication in English was evaluated as according to the following criteria: 1) it compared the outcomes of RAMIE and MIE, and 2) it reported on at least one of the outcome measures mentioned below.\u003c/p\u003e \u003cp\u003eAbstracts, letters, editorials, reviews without original data, case reports, and studies lacking outcome measures were excluded. The studies excluded in this meta-analysis had to meet all of the following criteria: 1) it was impossible to extract the appropriate data from the published results; or 2) there was overlap between authors or centers.\u003c/p\u003e\n\u003ch3\u003eOutcomes of interest and data extraction\u003c/h3\u003e\n\u003cp\u003eThe following outcomes were used to compare RAMIE and MIE techniques: 1) intra-operative data: operating time (min), conversion, number of resected nodes and estimated blood loss(ml); 2) post-operative data, which included LOS (days), and mortality (within 90 days after operation); 3) complication details, which included fistulae, wound infection, pneumonia, chylothorax, recurrent laryngeal nerve paralyses and total complications.\u003c/p\u003e \u003cp\u003eTwo reviewers independently extracted the following parameters from each study: 1) first author and year of publication; 2) study population; 3) number of subjects who underwent each technique; and lastly, 4) peri-operative outcomes data.\u003c/p\u003e \u003cp\u003eThe mean and the variance for articles reporting the median, range and the size of the trial were deduced in a way as described in Stela Pudar Hozo\u003csup\u003e,\u003c/sup\u003es article (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The quality of each study was assessed independently by two reviewers who used the Newcastle-Ottawa Scale (NOS). The quality of randomized trials was assessed using the Jadad scale (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The meta-analysis was performed according to the PRISMA guidelines (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe statistical analysis was conducted as described previously (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Briefly, Review Manager 5.2 (RevMan 5.2\u0026reg;, Nordic Cochrane Center and Copenhagen, Denmark) was used to perform the meta-analysis. The \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e statistic was used to quantify the statistical heterogeneity of the studies included, and \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e values of 25\u0026ndash;49, 50\u0026ndash;74 and \u0026ge;\u0026thinsp;75% indicate low, moderate and high heterogeneity respectively. When the \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e value was \u0026gt;\u0026thinsp;50%, indicating the presence of variability among the studies, we chose a random-effects models rather than fixed-effects models to perform the meta-analysis.\u003c/p\u003e \u003cp\u003eWe analyzed dichotomous variables using estimation of odds ratios with a 95% confidence interval (95% CI) and continuous variables using standardized mean difference (SMD) with a 95% CI. Forest plots were used to present the results of the meta-analysis. A P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDescription of the included studies\u003c/h2\u003e \u003cp\u003eThe literature search identified 2170 articles. Through our systematic search, 30 studies fulfilled the inclusion criteria and were included in our quantitative data synthesis (\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Among the 12578 patients, 4176 patients underwent RAMIE, and 8402 patients underwent MIE. The characteristics of included studies are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The study flow diagram is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutline of Studies Included in the Meta-Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCourntry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDesign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRAMIE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMIE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eStudy Quality\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.Xiaofeng\u0026nbsp;Duan,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.Yang Xu,2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3. Yin-Kai Chao,2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4. H.-Y. Deng,2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5. Ahmed\u0026nbsp;M.\u0026nbsp;Ali,2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6. P. P. Grimminger,2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7. Gregory J. Harbison,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8. Haiqi He,2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9. Kenneth\u0026nbsp;Meredith,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10. Satoru Motoyama,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11. Samina Park,2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSouth korea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12. Yasuhiro\u0026nbsp;Shirakawa,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13. Koichi Suda,2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14. E. Tagkalos,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNetherlands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15. Shigeru Tsunoda,2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16. B. Weksler,2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17. Benny Weksler,2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18. Yin-Kai Chao,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19. Yajie Zhang,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20. Y. Yang,2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21. Junying Chen,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22. H.-Y. Deng,2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23. Lei Gong, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24. Yang Yang,2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25. Shankar\u0026nbsp;Balasubramanian, 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26. Itasu\u0026nbsp;Ninomiya, 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27. Aditya\u0026nbsp;Kulkarni, 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28. K. Mori,2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29. Chikara Kunisaki,2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30. Babatunde A,2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: Retro\u0026thinsp;=\u0026thinsp;s retrospective; Pro\u0026thinsp;=\u0026thinsp;prospective; PSM\u0026thinsp;=\u0026thinsp;propensity score matching; RAMIE\u0026thinsp;=\u0026thinsp;robotic-assisted minimally invasive esophagectomy; MIE\u0026thinsp;=\u0026thinsp;minimally invasive esophagectomy.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy characteristics\u003c/h3\u003e\n\u003cp\u003eOf the 30 observational studies, 12 studies were propensity matched for patient characteristics and factors, such as age, sex, body mass index, comorbidities, receipt of neoadjuvant treatment, and cancer staging. The RAMIE and MIE cohorts of each study had comparable surgical results and varied in size from 15 to 5118 patients. Of the 30 observational studies, 25 studies were retrospective studies, while the other 5 studies were prospective studies.\u003c/p\u003e \u003cp\u003e \u003cb\u003eRisk of bias assessment.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eNo randomized controlled trials (RCTs) comparing robotic and conventional transthoracic esophagectomy were published. All studies had NOS quality scores greater than 6, indicating fair methodological quality. Specifically, thirteen studies had NOS quality score 7. The NOS quality score is represented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSurgical outcomes\u003c/b\u003e \u003c/p\u003e\n\u003ch3\u003e1) Operative Time\u003c/h3\u003e\n\u003cp\u003eThe operative time was reported in 20 studies. It was significantly shorter in the MIE group compared with the RAMIE group (SMD\u0026thinsp;=\u0026thinsp;23.29, 95% CI 7.35 to 39.44). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2) Estimated Blood Loss\u003c/h2\u003e \u003cp\u003eEstimated blood loss was reported in 21 studies and was significantly lower in the RAMIE group, compared with the MIE group (SMD = -19.25, 95% CI \u0026minus;\u0026thinsp;34.52 to -3.99). The statistical heterogeneity was high (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;72%). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eB)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3) Conversion\u003c/h2\u003e \u003cp\u003eConversion was reported in 8 studies and was not significantly lower in the RAMIE group, compared with the MIE group (OR\u0026thinsp;=\u0026thinsp;0.76, 95% CI 0.23 to 2.49). The statistical heterogeneity was high (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;69%). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4) Total Lymph Nodes Resected\u003c/h2\u003e \u003cp\u003e18 studies reported LN harvested, and total lymph nodes resected was not significantly more in the RAMIE group, compared with the MIE group (SMD\u0026thinsp;=\u0026thinsp;0.97, 95% CI -0.20 to 2.15). The pooled random-effects was used due to the high (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;74%). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003eC).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e5) Length of Hospital Stay\u003c/h2\u003e \u003cp\u003eThe length of hospital stay was reported in 20 studies, and it was not significantly shorter in the RAMIE group, compared with the MIE group (SMD = -0.01, 95% CI -0.19 to 0.18). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;41%). The pooled fixed-effects was used. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePost-operative Outcomes\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e1) Fistulae\u003c/h2\u003e \u003cp\u003eThe anastomotic leakage rate was reported in 21 studies. No statistically significant difference was found between the RAMIE group and the MIE group (OR\u0026thinsp;=\u0026thinsp;0.98, 95% CI 0.76 to 1.25). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;4.00%). (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003eA)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e2) Wound infection\u003c/h2\u003e \u003cp\u003eThe rate of wound infection was reported in 12 studies, it was not significantly lower in the RAMIE group compared with the MIE group (OR\u0026thinsp;=\u0026thinsp;0.83, 95% CI 0.44 to 1.56). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.00%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003eB)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3) Pneumonia\u003c/h2\u003e \u003cp\u003eThe rate of pneumonia was reported in 22 studies, it was significantly lower in the RAMIE group compared with the MIE group (OR\u0026thinsp;=\u0026thinsp;0.81, 95% CI 0.66 to 1.00). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.00%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003eC)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4) Chylothorax\u003c/h2\u003e \u003cp\u003eThe rate of chylothorax was reported in 16 studies. No statistically significant difference was found between the RAMIE group and the MIE group (OR\u0026thinsp;=\u0026thinsp;1.12, 95% CI 0.65 to 1.93). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.00%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003eA)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e5) Recurrent laryngeal nerve paralyses\u003c/h2\u003e \u003cp\u003eThe rate of RLN palsy was reported in 17 studies. There is a statistically significant difference between the RAMIE group and the MIE group (OR\u0026thinsp;=\u0026thinsp;1.31, 95% CI 1.07 to 1.59). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;22%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003eB)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e6) Total complication\u003c/h2\u003e \u003cp\u003e13 studies reporting total complications were included in the meta-analysis. Pooled analysis indicated evidence of a difference for MIE compared with RAMIE (OR\u0026thinsp;=\u0026thinsp;1.21, 95% CI 1.03 to 1.42). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;35%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003eC)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e7) Morbility\u003c/h2\u003e \u003cp\u003e30 studies reporting mortality within 90 days were included in the meta-analysis. Pooled analysis did not indicate evidence of a difference for MIE compared with RAMIE (OR\u0026thinsp;=\u0026thinsp;1.06, 95% CI 0.88 to 1.27). The statistical heterogeneity was low (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%). The pooled fixed-effects was used due to the low I\u003csup\u003e2\u003c/sup\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eBy comparing and integrating the results of different studies and taking into account variations in characteristics, a recapitulatory conclusion could be drawn through the existing literature evaluation by qualitative and quantitative ways. This meta-analysis summarized results of 30 studies for esophageal cancer. To the best of our knowledge, this is the most comprehensive meta-analysis comparing RAMIE versus MIE.\u003c/p\u003e \u003cp\u003eIn our analysis, no significant differences were found in LOS (days), morbility, number of resected nodes, conversion, fistulae, wound infection and chylothorax between the two techniques, which at least demonstrated that RAMIE was equivalent to MIE in terms of safety. Oncologic outcomes after surgery are affected by the extent of lymph-node dissection. In this analysis, we found no significant differences between RAMIE and MIE in the number of dissected lymph nodes. However, long-term follow-up evaluation is necessary to evaluate the exact oncologic outcomes, which is the weakness owing to lack of long-term survival analysis data. The results of the present meta-analysis suggest that there is no additional clinical benefit for RAMIE over MIE, although RAMIE offers a number of advantages over MIE, including improvements in manual dexterity, ergonomics, and visualization. There was no difference in post-operative hospital stay between the two groups, implying that the time required for patients to resume daily activities might be similar between RAMIE and MIE.\u003c/p\u003e \u003cp\u003eIn our analysis, there was significant difference in total estimated blood loss, pneumonia, operative time, recurrent laryngeal nerve paralyses and total complication between RAMIE and MIE. In the study, we found significant heterogeneity in total operating time, total estimated blood loss, number of resected nodes and conversion, which may be attributed to the differences in personnel skills, and period of the learning curve.\u003c/p\u003e \u003cp\u003eOperating times depend mainly on the experience and skill of the surgeon. The RAMIE group was inclined to take more time, which may be attributable to the reason for the additional set-up time required. The actual time may be shorter in RAMIE as a result of increasing experience and gradually decreased set-up time.\u003c/p\u003e \u003cp\u003eAccording to results, the incidences of pneumonia and EBL were significantly lower in RAMIE group than that in MIE group. The potential reasons for the superiorities of RAMIE over MIE could be partially explained as followed: RAMIE provided a three-dimensional visualization and superior imaging quality, which optimized consequences of identifying various structures and avoiding lung tissue damage during operations. In addition, the incidences of total complication and recurrent laryngeal nerve paralyses were not significantly lower in RAMIE group than that in MIE group, which may be attributed to the rich experience in the thoracoscopic surgery in MIE procedure.\u003c/p\u003e \u003cp\u003eRadical esophagectomy is the cornerstone of the multimodality treatment with curative intent. There are several ways for surgical treatment, including transthoracic surgery, conventional minimally invasive esophagectomy and robot-assisted esophagectomy. Owing to radical resection of the tumor with the paratracheal, subcarinal and paraesophageal lymph node dissection, conventional transthoracic esophagectomy is the preferred surgical approach worldwide. Minimally invasive esophagectomy (MIE) revolutionized surgical practice. Minimally invasive esophagectomy was designed to reduce surgical trauma, resulting in lower morbidity and mortality rates. Compared with open surgery, many reports have demonstrated clinical advantages of the minimally invasive esophagectomy: a faster post-operative recovery time and a shorter hospital stay, better cosmetic results with reduced morbidity. (\u003cspan additionalcitationids=\"CR44 CR45\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). In 2003, the robot-assisted thoraco-laparoscopic approach was developed. Data regarding the safety and the oncologic efficacy of RAMIE are limited. The existing data suggest RAMIE is a safe procedure which is associated with perioperative outcomes similar to transthoracic surgery and MIE (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). Advantage for robotic oesophagectomy over other forms of oesophagectomy is not obvious (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). The cost of equipment, specialized training and prolonged set up time are barriers to more widespread application. The fact that the surgeon is separated from the patient raises potential safety concerns. Future studies are needed to prove identifiable benefit of RAMIE over other approaches.\u003c/p\u003e \u003cp\u003eHowever, our study has several limitations, so the results should be interpreted with caution. First, it is possible that investigative groups might be more likely to report positive results, and that studies with significant outcomes are more likely to be published, leading to potential publication bias. Second, there was heterogeneity between the two groups because it was impossible to match the patient characteristics across all of the studies. Third, the overall level of clinical evidence was low by reason of the data sources coming from NRCTs. However, meta-analyses for well-designed NRCTs could be probably as accurate as those for RCTs (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). Fourth, our analysis was retrospective in nature and thus subject to selection bias.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eRAMIE is associated with a tendency for longer operating time, reduced blood loss and pulmonary complications as compared to MIE. There are no significant differences on the incidence of anastomotic leak, RLN palsy, total complications, wound infection, conversion to open surgery, chylothorax and mortality as compared to MIE.\u003c/p\u003e \u003cp\u003eIn conclusion, the results of this meta-analysis show that RAMIE is not superior to MIE for esophageal cancer. Further studies are required to better define its role in clinical practice.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRAMIE \u0026nbsp; \u0026nbsp; \u0026nbsp; robotic-assisted minimally invasive esophagectomy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMIE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; minimally invasive esophagectomy\u003c/p\u003e\n\u003cp\u003eOR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;odds ratios\u003c/p\u003e\n\u003cp\u003eSMD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;standardized mean difference\u003c/p\u003e\n\u003cp\u003eCI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;confidence interval\u003c/p\u003e\n\u003cp\u003eEBL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;estimated blood loss\u003c/p\u003e\n\u003cp\u003eLOS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;total length of stay\u003c/p\u003e\n\u003cp\u003eNOS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Newcastle-Ottawa Scale\u003c/p\u003e\n\u003cp\u003eLN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;lymph Nodes\u003c/p\u003e\n\u003cp\u003eRLN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; recurrent laryngeal nerve\u003c/p\u003e\n\u003cp\u003eRCT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; randomized controlled trial\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZPY and GFZ participated in all aspects of the experiment and drafted the article. ZPY and GS performed the statistical analysis. ZPY and GS conceived of the study, and participated in its design and helped to draft the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge all members of Department of Thoracic Surgery, 2\u003csup\u003end\u003c/sup\u003e Affiliated Hospital, Zhejiang University, Hangzhou, China for their support. We thank all the group members for their helpful discussions for our paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no Foundation for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAI use statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no AI use for this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJemal, A. et al. Global cancer statistics. \u003cem\u003eCA Cancer J. Clin.\u003c/em\u003e \u003cb\u003e61\u003c/b\u003e, 69\u0026ndash;90 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmloo, J. M. et al. 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Epidemiol.\u003c/em\u003e \u003cb\u003e63\u003c/b\u003e, 238\u0026ndash;245 (2010).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"robotic esophagectomy, minimally invasive esophagectomy, conventional transthoracic surgery, esophageal cancer, Da Vinci robotic system","lastPublishedDoi":"10.21203/rs.3.rs-6434398/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6434398/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo conduct a meta-analysis to determine the relative merits between robotic-assisted minimally invasive esophagectomy (RAMIE) and conventional video-assisted minimally invasive esophagectomy (MIE) in esophageal cancer patinents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS: \u003c/strong\u003eEligible studies or databases for articles were retrieved via systematical search to identify comparative studies reporting peri-operative outcomes for RAMIE and MIE. Pooled odds ratios (OR) and standardized mean difference (SMD) with 95% confidence interval (95% CI) were calculated using either a fixed-effects or a random-effects model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS:\u003c/strong\u003e Thirty studies matched the selection criteria and were included for statistical analysis, which reported on 12578 subjects with 4176 in RAMIE and 8402 in MIE. Through outcomes comparison analysis between RAMIE and MIE, this meta-analysis indicated that RAMIE was associated with less estimated blood loss (EBL) (SMD = -19.25, 95% CI −34.52 to -3.99) and less pneumonia (OR = 0.81, 95% CI 0.66 to 1.00). Meanwhile, this meta-analysis indicated that MIE was associated with shorter operative time (SMD = 23.29, 95% CI 7.35 to 39.44), less recurrent laryngeal nerve paralyses (OR = 1.31, 95% CI 1.07 to 1.59) and less total complications (OR = 1.21, 95% CI 1.03 to 1.42).\u003c/p\u003e\n\u003cp\u003eFurthermore, total length of stay (LOS) (SMD = -0.01, 95% CI -0.19 to 0.18) , total morbility (within 90 days after operation) (OR = 1.06, 95% CI 0.88 to 1.27) , number of resected nodes(SMD = 0.97, 95% CI -0.20 to 2.15), conversion(OR = 0.76, 95% CI 0.23 to 2.49) , anastomotic orifice fistulae(OR = 0.98, 95% CI 0.76 to 1.25), wound infection(OR = 0.83, 95% CI 0.44 to 1.56) \u0026nbsp;and chylothorax(OR = 1.12, 95% CI 0.65 to 1.93) were not significantly different for both procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSION: \u003c/strong\u003eRAMIE for esophageal cancer is not superior to conventional video-assisted MIE in terms of results of related indicators. Further studies are required to confirm this result.\u003c/p\u003e","manuscriptTitle":"Systematic review of robotic and non-robotic esophagectomy for the treatment in esophageal cancer patients: a meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 11:22:20","doi":"10.21203/rs.3.rs-6434398/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb8e1b05-b17f-4a56-9a1c-8b2e7a863e40","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48190920,"name":"Health sciences/Diseases"},{"id":48190921,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-08-18T13:53:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 11:22:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6434398","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6434398","identity":"rs-6434398","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}