Postoperative Outcomes after Minimally Invasive Esophagectomy: An International Cohort Study from the Oesophagogastric Anastomosis Audit (OGAA)

Postoperative Outcomes after Minimally Invasive Esophagectomy: An International Cohort Study from the Oesophagogastric Anastomosis Audit (OGAA) | 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 Research Article Postoperative Outcomes after Minimally Invasive Esophagectomy: An International Cohort Study from the Oesophagogastric Anastomosis Audit (OGAA) Oesophago-Gastric Anastomotic, Mr Sivesh Kathir Kamarajah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5917499/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 May, 2025 Read the published version in BMC Surgery → Version 1 posted 8 You are reading this latest preprint version Abstract Objective To compare the postoperative pulmonary complications (PPC) after minimally invasive or open transthoracic esophagectomy for esophageal cancer in an international, multicenter cohort. Summary of Background Data Ongoing debate exists around the optimal surgical approach for esophageal cancer, with limited data assessing the external validity of randomised trials on outcomes of MIE Methods Patients undergoing open (OE, n=744), hybrid (HE, n=500), and totally minimally invasive esophagectomy (TMIE, n=540) for esophageal cancer were identified from the international, prospective Oesophagogastric Anastomosis Audit (OGAA). Multivariable models were used to investigate PPC (primary outcome) as well as overall complications, major complications, anastomotic leak and 90-day mortality (secondary outcomes). Results PPC rates were lower after TMIE compared to OE and HE (28% vs 37% vs 39%, p=0.002), even on adjusted analyses compared to OE (odds ratio (OR): 0.60, CI 95% : 0.45 - 0.78). TMIE was also associated with significantly lower overall complications (OR: 0.68, CI 95% : 0.52 - 0.88) compared to OE, but not for major complications (OR: 0.90, CI 95% : 0.67 - 1.21), anastomotic leak (OR: 1.39, CI 95% : 0.96 - 2.01) and 90-day mortality (OR: 0.49, CI 95% : 0.22 - 1.04). Sensitivity analyses by underlying respiratory disease, neoadjuvant chemoradiotherapy or high-volume centers confirmed above findings. Conclusion This study provides real-world data that TMIE was associated with lower 90-day PPC than OE and HE approaches, especially in patients with underlying respiratory disease or receiving neoadjuvant chemoradiotherapy. These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE is probably of major importance. The ideal surgical approach remains unclear, and ongoing trials will provide more evidence within a few years that may clarify the optimum approach to locally advanced esophageal cancers. minimally invasive esophagectomy outcomes pulmonary complications Figures Figure 1 Figure 2 Introduction Multimodality treatment with neoadjuvant therapy and esophagectomy remains the curative treatment of patients with resectable esophageal cancer.[ 1 , 2 ] Although there has been substantive improvement in postoperative mortality after esophagectomies, morbidity rates remain as high as 70%[ 3 ] and patients are associated with reduced quality of life.[ 4 , 5 ] Furthermore, the detrimental impact of perioperative complications on long-term survival is also well understood.[ 6 – 8 ] To improve perioperative morbidity, there has been a dramatic increase in the adoption of minimally invasive esophagectomy (MIE), through implementation of these programs in centers.[ 9 ] There are several approaches used for esophagectomies such as Ivor-Lewis, McKeown, and Transhiatal. Therefore, this warrants dedicated evaluation on the role of MIE techniques. However, the benefits of MIE in patients undergoing transthoracic esophagectomy remains unclear. Firstly, evidence have until recently been limited to two randomised clinical trials.[ 10 , 11 ] Both these trials only compared either totally MIE (TMIE) or hybrid MIE with open esophagectomy demonstrating significantly lower rates of postoperative pulmonary complications (PPC) compared to open esophagectomy. However, adoption of these MIE techniques into routine clinical practice were associated with higher overall and pulmonary complications and reoperation rate.[ 12 , 13 ] Secondly, present studies are limited to cohort studies either from selected high-volume centers, single center or national series. Therefore, global data, including low- and middle-income countries comparing MIE and open surgery are needed to assess its impact on both postoperative complications. The primary aim of the present study was to compare the incidence of PPC between OE, HE and TMIE using data from the Oesophago-Gastric Anastomosis Audit (OGAA). The secondary aims were to assess the rates of postoperative morbidity (i.e., overall, and major complications, anastomotic leaks, and 90-day mortality). Methods Study design and setting This study is a secondary pre-planned analysis of the OGAA cohort study. The OGAA cohort study was an international multicenter prospective study including 137 centers across 41 countries.[14-16] All hospitals performing esophagectomies for esophageal cancers were eligible to be included in this cohort study. Patient-level data were collected over a nine-month period from 1st April 2018 to 31st December 2018 with follow-up of all patients up to 90-days after surgery. This study was delivered using a collaborative model, which has been described previously. This methodology and process has been successful in delivering several international and national cohort studies.[15-17] Briefly, a consultant or attending surgeon supervised data collection at each hospital, together with a team of clinicians, ensuring that it was performed in accordance with a pre-specified protocol. The study was conducted according to STROBE guidelines for observational studies.[18] Ethics and reporting Ethical approval was dependent on local protocols, and was country-specific, as previously described.[15, 16] Ongoing study approval was maintained locally throughout the duration of the study. Inclusion and Exclusion Criteria During the pre-defined data collection period, all consecutive adult patients undergoing elective (planned) curative esophagectomy for esophageal cancers (i.e. adenocarcinoma and SCC) were included. For the present analysis, patients undergoing two-stage transthoracic esophagectomy using any combination of open, robotic or standard minimal access approaches were included. Exclusion criteria were: (i) extended total gastrectomy, transhiatal esophagectomy, three-stage (i.e. McKeown) esophagectomy or left thoracoabdominal; (ii) pharyngolaryngo-oesophagectomy; (iii) colonic interposition or small bowel jejunal interposition reconstruction; (iv) emergency resection; and (v) resection for benign disease, as previously described.[19, 20] Outcome measures The primary outcome measure was postoperative pulmonary complications, according to the Esophagectomy Complications Consensus Group.[21, 22] Postoperative pulmonary complications were defined as pneumonia, pleural effusion requiring additional drainage procedure, pneumothorax requiring treatment, atelectasis mucous plugging requiring bronchoscopy, respiratory failure requiring reintubation, acute respiratory distress syndrome, acute aspiration, tracheobronchial injury and chest tube maintenance for air leak for > 10 days postoperatively. Secondary outcome measures were overall complications, major complications, anastomotic leaks, and 90-day mortality. Major postoperative complications were defined as those of Clavien-Dindo Grade III-V.[20] Anastomotic leaks were defined full thickness GI defect involving esophagus, anastomosis, staple line, or conduit irrespective of presentation or method of identification according to the ECCG.[21] Broadly, these leaks were defined as type I, type II or type III anastomotic leaks as defined according to the ECCG guidance. Data Collection The process of data collection was based on case report forms (CRFs), which were for data recording only. Detailed reporting on data collection process has been reported elsewhere.[23-25] Definitions of variables A range of patient-, tumour- and treatment-related factors were assessed. Data for a range of center-specific variables were also collected. Country income was defined as high-income (HIC) or low- or middle-income countries (LMIC), according to the World Bank Data.[26] The center volume[27, 28] was based on the number of cases treated by each center during the study period (nine months), from which the number of cases per year was estimated. The resulting variable was then categorized for analysis, based on tertiles, such that there were approximately equal numbers of patients in each category. The resulting categories were 50 cases (n=15 centers, HIC - 13, LMIC - 2) per year. The TNM staging was based on pathology and used the 8 th edition definitions.[29] Statistical analysis Continuous variables that were normally distributed were reported as mean ± standard deviation (SD), with p-values from independent sample t-tests. For continuous, and non-normally distributed data, we reported them as medians and interquartile ranges (IQRs). Categorical ordinal variables were also assessed using Mann-Whitney U-tests, whilst nominal variables were analysed using Fisher’s exact-tests or Chi 2 -tests, for variables with two or more than two categories, respectively. Multilevel multivariable analyses were then performed, to produce adjusted odds ratio (OR) on surgical techniques on outcomes to account for the multi-level structure of the data, by adjusting for within-centre correlations of outcomes. As such, the centre was set as the subject effect, and the patient ID as the within-subject effect, with an exchangeable correlation structure assumed. For all models, a range of centre-, patient-, tumour- and treatment-related factors were assessed. Variables included in the multivariable models were selected based on clinical relevance, existing literature, and availability in the dataset. The adjusted model includes center- (center volume, country income), patient- (i.e. age, gender, ASA grade, Charlson comorbidity index, smoking status and body mass index), tumour- (i.e. tumor histology, tumor location, AJCC clinical T and N classification) and treatment-related (i.e. preoperative nutrition, neoadjuvant therapy, surgical approach, anastomosis site) factors. Although our models were not intended for prognostic prediction, we report the c-statistic (area under the curve) for each outcome model as an indicator of overall model performance. Sensitivity analyses were performed by patients with respiratory disease, neoadjuvant chemoradiotherapy and high-volume centers. A p-value of <0.05 was considered statistically significant and 2-sided 5% significance level was applied. Data analysis was performed using R Foundation Statistical software (R 3.2.2) with TableOne, ggplot2, Hmisc, and finalfit packages (R Foundation for Statistical Computing, Vienna, Austria) as previously described.[15, 16] Results Clinicopathologic characteristics Of the 2,247 patients identified from the OGAA study, 1,784 patients received transthoracic OE (n = 744), HE (n = 500) or TMIE (n = 540) for esophageal cancers (Fig. 1 ). Baseline characteristics of patients are presented in Tables 1 & 2 . Patients receiving TMIE were more likely to be from high volume (< 50 cases/year) (35% vs 27%, p < 0.001) and from high-income countries (96% vs 93%, p < 0.001) than patients receiving OE. Table 1 Hospital- and patient-level clinicopathologic characteristics of patients with esophageal cancers receiving open, hybrid and totally minimally invasive esophagectomy Open, n = 750 Hybrid, n = 507 Totally minimally invasive, n = 441 p-value Hospital-level factors Center volume <28 232 (30.9) 129 (25.4) 155 (35.1) < 0.001 28–50 313 (41.7) 212 (41.8) 130 (29.5) ≥51 205 (27.3) 166 (32.7) 156 (35.4) Country income High income country 696 (92.8) 498 (98.2) 424 (96.1) < 0.001 Low-Middle income country 54 (7.2) 9 (1.8) 17 (3.9) Patient-level factors Age at surgery 63.9 (10.1) 66.0 (9.6) 64.7 (9.8) 0.001 Sex Female 155 (20.7) 89 (17.6) 74 (16.8) 0.182 Male 595 (79.3) 418 (82.4) 367 (83.2) ASA Grade 1 108 (14.4) 72 (14.2) 38 (8.6) < 0.001 2 423 (56.4) 284 (56.0) 225 (51.0) 3–4 219 (29.2) 151 (29.8) 178 (40.4) Smoking status Never smoker 300 (40.0) 181 (35.7) 142 (32.2) 0.007 Ex-smoker 320 (42.7) 234 (46.2) 216 (49.0) Current smoker 100 (13.3) 79 (15.6) 77 (17.5) Unknown 30 (4.0) 13 (2.6) 6 (1.4) Respiratory Disease No 660 (88.0) 457 (90.1) 377 (85.5) 0.090 Yes 90 (12.0) 50 (9.9) 64 (14.5) Body mass index ≤18.5 32 (4.3) 13 (2.6) 8 (1.8) 0.020 18.6–24.9 272 (36.3) 187 (36.9) 157 (35.6) 25.0-29.9 253 (33.7) 206 (40.6) 173 (39.2) ≥30.0 193 (25.7) 101 (19.9) 103 (23.4) Tumor Histology Adenocarcinoma 595 (79.3) 430 (84.8) 382 (86.6) 0.002 Squamous Cell Carcinoma 155 (20.7) 77 (15.2) 59 (13.4) Tumor location Proximal/Middle 61 (8.1) 32 (6.3) 25 (5.7) 0.005 Distal 238 (31.7) 138 (27.2) 168 (38.1) Siewert 1 239 (31.9) 197 (38.9) 133 (30.2) Siewert 2–3 211 (28.1) 140 (27.6) 115 (26.1) Missing 1 (0.1) 0 (0.0) 0 (0.0) Clinical AJCC T Stage cT1 81 (10.8) 57 (11.2) 50 (11.3) 0.411 cT2 153 (20.4) 99 (19.5) 107 (24.3) cT3/T4a 516 (68.8) 351 (69.2) 284 (64.4) Clinical AJCC N Stage cN0 313 (41.7) 218 (43.0) 208 (47.2) 0.355 cN1 295 (39.3) 189 (37.3) 162 (36.7) cN2/3 142 (18.9) 100 (19.7) 71 (16.1) Preoperative nutrition No 411 (54.8) 255 (50.3) 214 (48.5) 0.080 Yes 339 (45.2) 252 (49.7) 227 (51.5) Table 2 Operative-level clinicopathologic characteristics of patients with esophageal cancers receiving open, hybrid and totally minimally invasive esophagectomy Open, n = 744 Hybrid, n = 500 Totally minimally invasive, n = 540 p-value Operative-level factors Neoadjuvant Therapy None 171 (22.8) 129 (25.4) 119 (27.0) < 0.001 Chemoradiotherapy 201 (26.8) 114 (22.5) 184 (41.7) Chemotherapy 378 (50.4) 264 (52.1) 138 (31.3) Anastomosis technique Handsewn 123 (16.4) 38 (7.5) 75 (17.0) < 0.001 Linear Stapled 111 (14.8) 99 (19.5) 122 (27.7) Circular stapled 516 (68.8) 370 (73.0) 244 (55.3) Gastric tube Thin (<5cm) 327 (43.6) 324 (63.9) 337 (76.4) 5cm) 408 (54.4) 174 (34.3) 102 (23.1) Whole Stomach 15 (2.0) 9 (1.8) 2 (0.5) Pyloric procedures Not Performed 369 (49.2) 383 (75.5) 341 (77.3) < 0.001 Botox 9 (1.2) 2 (0.4) 28 (6.3) Dilatation 56 (7.5) 63 (12.4) 33 (7.5) Pyloromyotomy 29 (3.9) 9 (1.8) 5 (1.1) Pyloroplasty 287 (38.3) 50 (9.9) 34 (7.7) Omentoplasty No 509 (67.9) 295 (58.2) 191 (43.3) < 0.001 Yes 241 (32.1) 212 (41.8) 250 (56.7) In the TMIE cohort, ASA grade III-IV patients (40% vs 30% vs 29%, p < 0.001), adenocarcinoma histology (87% vs 85% vs 79%, p = 0.002), and distal cancers (38% vs 27% v2 32%, p = 0.005) were significantly more common than in the HE and OE cohort (Table 1 ). Also, more TMIE patients, compared with HE and OE, had neoadjuvant chemoradiotherapy (42% vs 23% vs 27%, p < 0.001), a linear stapled anastomosis (28% vs 20% vs 15%, p < 0.001), thin gastric tube (< 5cm width) (76% vs 64% vs 44%, p < 0.001), and omentoplasty (57% vs 42% vs 32%, p < 0.001) (Table 2 ). There were no significant differences in the rates of clinical AJCC T3 / T4a disease (64% vs 69% vs 69%, p = 0.4) and clinical AJCC N2 / N3 (16% vs 20% vs 19%, p = 0.4) disease across patients receiving TMIE, HE and OE. Primary outcome Postoperative pulmonary complications (PPC) Patients receiving TMIE had significantly lower rates of PPC patients having HE and OE (28% vs 39% vs 37%, p = 0.002). On adjusted analyses, patients receiving TMIE had significantly lower rates of PPC than open (OR: 0.60, CI 95% : 0.45–0.78, p < 0.001) (Table 3 , Fig. 2 ). The full model is presented in Supplementary Table 1 (c-statistic 0.71). Sensitivity analyses demonstrated significantly lower rates of PPC with TMIE compared to HE (OR: 0.53, CI 95% : 0.39–0.73, p < 0.001) (Supplementary Table 2). Exploratory analyses identified TMIE patients with PPC were more likely to have higher ASA grade, respiratory disease, distal esophageal cancers, and advanced disease (Supplementary Table 3). Table 3 Univariable and multivariable analysis of postoperative (i.e., pulmonary complications, anastomotic leaks, overall & major complications, and 90-day mortality) outcomes comparing open, hybrid and totally minimally invasive esophagectomy in patients with esophageal cancer Rates, n (%) Univariable, OR (95% CI) Multivariable, OR (95% CI) Pulmonary complications* Open 276 (36.8) REF REF Hybrid 196 (38.7) 1.08 (0.86–1.37, p = 0.504) 1.07 (0.84–1.36, p = 0.6) Totally minimally invasive 125 (28.3) 0.68 (0.53–0.88, p = 0.003) 0.60 (0.45–0.78, p < 0.001) Overall complications* Open 481 (64.1) REF REF Hybrid 310 (61.1) 0.88 (0.70–1.11, p = 0.282) 0.85 (0.67–1.09, p = 0.204) Totally minimally invasive 262 (59.4) 0.82 (0.64–1.04, p = 0.104) 0.68 (0.52–0.88, p = 0.004) Major complications* Open 178 (23.7) REF REF Hybrid 130 (25.6) 1.11 (0.85–1.44, p = 0.441) 1.10 (0.83–1.43, p = 0.510) Totally minimally invasive 107 (24.3) 1.03 (0.78–1.35, p = 0.836) 0.90 (0.67–1.21, p = 0.489) Anastomotic leaks* Open 81 (10.8) REF REF Hybrid 57 (11.2) 1.05 (0.73–1.50, p = 0.806) 1.08 (0.74–1.57, p = 0.682) Totally minimally invasive 70 (15.9) 1.56 (1.10–2.20, p = 0.012) 1.40 (0.96–2.02, p = 0.076) 90-day mortality* Open 26 (3.5) REF REF Hybrid 16 (3.2) 0.91 (0.47–1.69, p = 0.764) 0.73 (0.37–1.41, p = 0.352) Totally minimally invasive 11 (2.5) 0.71 (0.33–1.42, p = 0.352) 0.50 (0.22–1.06, p = 0.079) *Adjusted for center volume, country income, age at surgery, sex, ASA grade, smoking status, respiratory disease, body mass index, tumor histology & location, clinical AJCC T stage, clinical AJCC N stage, preoperative nutrition, neoadjuvant therapy, anastomotic technique, and surgical approach Secondary outcomes Overall complications There was no significant difference in rates of overall complications between OE, HE and TMIE (64% vs 61% vs 61%, p = 0.2). However, patients receiving TMIE had significantly lower rates of overall complications than OE (OR: 0.68, CI 95% : 0.52–0.88, p = 0.004) on adjusted analyses (Table 3 , Fig. 2 ). The full model is presented in Supplementary Table 4 (c-statistic 0.69). Sensitivity analyses demonstrated no significant difference in overall complications between HE and TMIE in adjusted analyses. (Supplementary Table 1). Major complications There was no significant difference in rates of major complications between OE, HE and TMIE (24% vs 26% vs 24%, p = 0.5). On adjusted analyses, there were no significant difference in rates of major complications between patients receiving TMIE and OE (Table 3 , Fig. 2 ). The full model is presented in Supplementary Table 5 (c-statistic 0.70). Sensitivity analyses demonstrated no significant difference in overall complications between HE and TMIE in adjusted analyses (Supplementary Table 1). Anastomotic leaks Patients receiving TMIE had significantly higher rates of anastomotic leaks compared to patients having OE and HE (16% vs 11% vs 11%, p = 0.026) (Table 3 ). On adjusted analyses, there were no significant difference in rates of anastomotic leaks in patients receiving HE (OR: 1.08, CI 95% : 0.74–1.57, p = 0.7) and TMIE (OR: 1.40, CI 95% : 0.96–2.02, p = 0.1) compared to OE (Table 3 , Fig. 2 ). The full model is presented in Supplementary Table 6 (c-statistic 0.66). Sensitivity analyses between HE and TMIE demonstrated no significant difference in anastomotic leak rates between the two techniques in adjusted analyses (Supplementary Table 1). Anastomotic leaks were further classified using ECCG definitions, with no significant difference in severity grading across surgical approaches. 90-day mortality There was no significant difference in rates of 90-day mortality between OE, HE and TMIE (4% vs 3% vs 3%, p = 0.6) (Table 3 , Fig. 2 ). On adjusted analyses, there were no significant difference in rates of 90-day mortality between patients receiving TMIE and OE (Table 3 ). The full model is presented in Supplementary Table 7 (c-statistic 0.75). Sensitivity analyses demonstrated no significant difference in 90-day mortality between HE and TMIE in adjusted analyses (Supplementary Table 1). Other complications A summary of postoperative complications as defined according to ECCG by OE, HE and TMIE are presented in Supplementary Table 8. There were significant differences in operating time between patient receiving OE, HE and TMIE (median: 350 vs 355 vs 367, p < 0.001). There were no significant differences in the overall length of stay between patients receiving OE, HE and TMIE (mean: 17.8 vs 16.7 vs 16.5 days, p = 0.2). Sensitivity analysis Respiratory Disease Of 1,784 patients receiving either OE, HE or TMIE, 11% (n = 204) had underlying respiratory disease. Baseline characteristics for these patients are presented in Supplementary Table 9. Sensitivity analyses performed for PPC, overall and major complications, anastomotic leaks and 90-day mortality (Supplementary Table 10) were in line with the findings of the main analysis. On adjusted analyses, patients receiving TMIE had significantly lower rates of PPC than (OR: 0.53, CI 95% : 0.39–0.72, p < 0.001) (Supplementary Table 10). Neoadjuvant Chemoradiotherapy Sensitivity analyses were performed in patients receiving neoadjuvant chemoradiotherapy (n = 499), of which 37% (n = 184) received TMIE. Baseline characteristics for these patients are presented in Supplementary Table 11. Sensitivity analyses performed for PPC, overall and major complications, anastomotic leaks and 90-day mortality (Supplementary Table 12) were in line with the findings of the main analysis. High Volume Centers Sensitivity analyses were performed in patients receiving treatment in high volume centers (n = 527), of which 30% (n = 156) received TMIE. Baseline characteristics for these patients are presented in Supplementary Table 13. Sensitivity analyses performed for PPC, overall complications, anastomotic leaks and 90-day mortality (Supplementary Table 14) were in line with the findings of the main analysis. However, patients receiving TMIE had significantly lower rates of major complications (17% vs 26%, p = 0.001) than OE, which remained on adjusted analyses (OR: 0.48, CI 95% : 0.24–0.94, p = 0.037). Discussion Current guidelines from the European Society of Medical Oncology (ESMO)[ 30 ] and the National Comprehensive Cancer Network (NCCN)[ 31 ] recommend hybrid esophagectomies. However, evidence demonstrating any superiority or safety for TMIE over OE or HE or any other existing surgical approach is lacking. This international cohort study on patients with esophageal cancers demonstrated that TMIE was associated with lower 90-day PPC. There was however no difference in overall complications and anastomotic leak rates in the adjusted analyses. Margin-negative resection rates were significantly higher after TMIE compared to OE or HE, albeit lower than in RCTs.[ 10 , 11 ] These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE. To date, evidence surrounding impact of MIE on postoperative outcomes, especially PPC compared to OE or HE remains unclear. Evidence from previously published RCT’s comparing OE with HE (i.e MIRO[ 11 ]) or TMIE (i.e. TIME[ 10 ], ROBOT[ 32 ]) demonstrated significantly lower rates of PPC with HE and TMIE, respectively. However, a published meta-analysis[ 33 ] of non-randomized studies comparing HE and TMIE demonstrated no significant difference in rates of pneumonia between the two techniques. A recently published review also emphasises the uncertainty that exists in the current evidence on this topic.[ 34 ] These findings were aligned with a recent population-based cohort study from Sweden.[ 13 ] Reducing rates of anastomotic leaks remain a major topic of discussion amongst esophageal surgeons and efforts to reduce them remain a priority. However, adoption of TMIE has been associated with significantly higher rates of anastomotic leaks compared to OE. Firstly, a recently published cohort study from the ESOData demonstrated higher anastomotic leaks rate with TMIE than HE.[ 35 ] However, the ESOData included patients from high volume, high income countries compared to the present study. Therefore, the present study allowed the true impact of adoption of TMIE from global real-world data. Secondly, a meta-analysis[ 33 ] that compared TMIE with HE reported significantly higher rates of anastomotic leaks with transthoracic TMIE compared with HE. In addition, these anastomotic leaks following esophagectomy is linked to reduced long-term overall survival from a recent meta-analysis.[ 7 , 8 ] However, in the present study, there was a trend towards higher anastomotic leak rates with TMIE compared to OE and HE, as high as 40%. Although the relative risks are higher, the absolute rates of anastomotic leak rates are lower than previously published randomised and non-randomised trials. Several reasons may explain, the numerically higher rate of anastomotic leaks observed with TMIE, although not statistically significant in adjusted models. Firstly, TMIE involves a technically complex, intracorporeal anastomosis that can be affected by reduced tactile feedback and visualization limitations. Moreover, conduit perfusion can be more difficult to assess accurately in minimally invasive approaches, especially without adjuncts such as ICG fluorescence angiography. Second, stapling techniques and conduit preparation also vary—thin gastric tubes, more commonly used in TMIE, may be more vulnerable to ischemia. Third, learning curve effects cannot be excluded, particularly as TMIE adoption is increasing globally and standardisation of technique remains heterogeneous. Our analysis did not directly measure surgeon experience, but future studies should address this as a modifiable factor. The present study has some limitations. Firstly, the present study does not capture proficiency gains or learning curves of individual surgeons performing TMIE to assess impact of this on complications. Although interhospital variation has been included into the adjusted model, unknown confounders such as these may also affect postoperative complications. Secondly, impact of surgical approaches on long-term survival data and health-related quality of life were not available in this cohort study. Important endpoints such as dysphagia, reflux, nutritional status, and patient-reported quality of life were not collected. These outcomes are essential to understanding the true burden of surgery from the patient’s perspective, particularly when comparing different minimally invasive approaches. Future collaborative efforts should prioritize the inclusion of longitudinal follow-up with validated quality of life instruments to better inform surgical decision-making. Thirdly, there are potentially unmeasured confounders that were not included in the adjusted models. These include surgeon experience (e.g., learning curves) and hospital-level services such as prehabilitation and enhanced recovery after surgery protocols which may exists in some centers. Variation in some of these measures may affect outcomes in patients undergoing esophagectomy around the world. Conclusion This study provides real-world data that TMIE was associated with lower 90-day PPC than OE and HE approaches, especially in patients with underlying respiratory disease or receiving neoadjuvant chemoradiotherapy. These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE is probably of major importance. The ideal surgical approach remains unclear, and ongoing trials will provide more evidence within a few years that may clarify the optimum approach to locally advanced esophageal cancers. Declarations Human ethics and consent to participate: Ethical approval was not applicable for this study, as this was a secondary analysis of cohort study with existing approval. This study was reviewed by the University Hospital Birmingham NHS Trust ethics committee and the need for full ethics review was waived since the study is an observation study of routinely collected data. Informed consent was not needed for all participants in the main study by the ethics committee. This study adhered to the Helsinki declaration. Consent for publication: Not applicable Availability of data and material: The data and statistical codes can be made available on request from corresponding author. Competing interests: None declared Clinical trial number: Not applicable Funding: No funding to report for this study Authors' contributions: The following are the writing group: Kamarajah SK, Darling G, Duong C, Evans R, Gockel I, Gossage J, Hedberg J, Kauppila JH, Maynard N, Monig S, Hsu PK, Reynolds J, Singh P, So JBY, Wijnhoven BPL, Griffiths EA The role of all coauthors is shown in appendix. SKK and EAG were involved in study design, coordination of the study, manuscript concept, and editing. SKK and EAG conducted the data analysis. SKK and EAG accessed and verified the data. The writing group and the statistical analysis group contributed to data interpretation and critical revision of the manuscript. The writing committee was responsible for the decision to submit. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Conflict of Interest: All authors have no conflict of interest to declare Financial disclosures: All authors have financial disclosure to make Acknowledgements : We are grateful to the Birmingham Surgical Trials Consortium at the University of Birmingham for the use of their servers for secure online data collection. References Shapiro J, van Lanschot JJB, Hulshof M, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–8. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. Navidi M, Phillips AW, Griffin SM, Duffield KE, Greystoke A, Sumpter K, Sinclair RCF. Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer. Br J Surg. 2018;105(7):900–6. Noordman BJ, Wijnhoven BPL, Lagarde SM, Boonstra JJ, Coene P, Dekker JWT, Doukas M, van der Gaast A, Heisterkamp J, Kouwenhoven EA, et al. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer. 2018;18(1):142. Markar SR, Zaninotto G, Castoro C, Johar A, Lagergren P, Elliott JA, Gisbertz SS, Mariette C, Alfieri R, Huddy J et al. Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study. Ann Surg 2020. Markar S, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, Lefevre JH, Brigand C, Vaillant JC, Adham M, et al. The Impact of Severe Anastomotic Leak on Long-term Survival and Cancer Recurrence After Surgical Resection for Esophageal Malignancy. Ann Surg. 2015;262(6):972–80. Booka E, Takeuchi H, Suda K, Fukuda K, Nakamura R, Wada N, Kawakubo H, Kitagawa Y. Meta-analysis of the impact of postoperative complications on survival after oesophagectomy for cancer. BJS Open. 2018;2(5):276–84. Gujjuri RR, Kamarajah SK, Markar SR. Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis. Dis Esophagus 2021, 34(3). Siaw-Acheampong K, Kamarajah SK, Gujjuri R, Bundred JR, Singh P, Griffiths EA. Minimally invasive techniques for transthoracic oesophagectomy for oesophageal cancer: systematic review and network meta-analysis. BJS Open. 2020;4(5):787–803. Biere SS, van Berge Henegouwen MI, Maas KW, Bonavina L, Rosman C, Garcia JR, Gisbertz SS, Klinkenbijl JH, Hollmann MW, de Lange ES, et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet. 2012;379(9829):1887–92. Mariette C, Markar SR, Dabakuyo-Yonli TS, Meunier B, Pezet D, Collet D, D'Journo XB, Brigand C, Perniceni T, Carrere N, et al. Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer. N Engl J Med. 2019;380(2):152–62. Markar SR, Ni M, Gisbertz SS, van der Werf L, Straatman J, van der Peet D, Cuesta MA, Hanna GB, van Berge Henegouwen MI, Dutch Upper GICA, et al. Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice. J Clin Oncol. 2020;38(19):2130–9. Hayami M, Ndegwa N, Lindblad M, Linder G, Hedberg J, Edholm D, Johansson J, Lagergren J, Lundell L, Nilsson M et al. Population-Based Cohort Study from a Prospective National Registry: Better Long-Term Survival in Esophageal Cancer After Minimally Invasive Compared with Open Transthoracic Esophagectomy. Ann Surg Oncol 2022. Evans RPT, Singh P, Nepogodiev D, Bundred J, Kamarajah S, Jefferies B, Siaw-Acheampong K, Wanigasooriya K, McKay S, Mohamed I et al. Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA). Dis Esophagus 2020, 33(1). Oesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. Rates of Anastomotic Complications and their Management following Esophagectomy: Results of the Oesophago-Gastric Anastomosis Audit (OGAA). Ann Surg 2021. Oesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study. Eur J Surg Oncol 2021. Collaborative ST, Writing/Steering C, Data Management G, External Advisory G. REspiratory COmplications after abdomiNal surgery (RECON): study protocol for a multi-centre, observational, prospective, international audit of postoperative pulmonary complications after major abdominal surgery. Br J Anaesth. 2020;124(1):e13–6. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96. Dindo D, Muller MK, Weber M, Clavien PA. Obesity in general elective surgery. Lancet. 2003;361(9374):2032–5. Low DE, Alderson D, Cecconello I, Chang AC, Darling GE, D'Journo XB, Griffin SM, Holscher AH, Hofstetter WL, Jobe BA, et al. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015;262(2):286–94. Low DE, Kuppusamy MK, Alderson D, Cecconello I, Chang AC, Darling G, Davies A, D'Journo XB, Gisbertz SS, Griffin SM et al. Benchmarking Complications Associated with Esophagectomy. Ann Surg 2017. Collaborative S. Impact of postoperative non-steroidal anti-inflammatory drugs on adverse events after gastrointestinal surgery. Br J Surg. 2014;101(11):1413–23. Collaborative S. Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study. BJS Open 2018. CholeS Study Group WMRC. Population-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases. Br J Surg. 2016;103(12):1704–15. Oesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. International Variation in Surgical Practices in Units Performing Oesophagectomy for Oesophageal Cancer: A Unit Survey from the Oesophago-Gastric Anastomosis Audit (OGAA). World J Surg. 2019;43(11):2874–84. Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, Welch HG, Wennberg DE. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128–37. Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL. Surgeon volume and operative mortality in the United States. N Engl J Med. 2003;349(22):2117–27. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin. 2017;67:7. Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50–7. Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Besh S, Chao J, Das P, Denlinger C, Fanta P, Fuchs CS, et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw. 2015;13(2):194–227. van der Sluis PC, van der Horst S, May AM, Schippers C, Brosens LAA, Joore HCA, Kroese CC, Haj Mohammad N, Mook S, Vleggaar FP, et al. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg. 2019;269(4):621–30. van Workum F, Klarenbeek BR, Baranov N, Rovers MM, Rosman C. Totally minimally invasive esophagectomy versus hybrid minimally invasive esophagectomy: systematic review and meta-analysis. Dis Esophagus 2020, 33(8). Vashist Y, Goyal A, Shetty P, Girnyi S, Cwalinski T, Skokowski J, Malerba S, Prete FP, Mocarski P, Kania MK et al. Evaluating Postoperative Morbidity and Outcomes of Robotic-Assisted Esophagectomy in Esophageal Cancer Treatment-A Comprehensive Review on Behalf of TROGSS (The Robotic Global Surgical Society) and EFISDS (European Federation International Society for Digestive Surgery) Joint Working Group. Curr Oncol 2025, 32(2). van der Wilk BJ, Hagens ERC, Eyck BM, Gisbertz SS, van Hillegersberg R, Nafteux P, Schroder W, Nilsson M, Wijnhoven BPL, Lagarde SM, et al. Outcomes after totally minimally invasive versus hybrid and open Ivor Lewis oesophagectomy: results from the International Esodata Study Group. Br J Surg. 2022;109(3):283–90. Additional Declarations No competing interests reported. Supplementary Files r0MIEPPCv14250207supplement.docx Cite Share Download PDF Status: Published Journal Publication published 22 May, 2025 Read the published version in BMC Surgery → Version 1 posted Editorial decision: Accepted 29 Apr, 2025 Reviews received at journal 25 Apr, 2025 Reviewers agreed at journal 13 Apr, 2025 Reviews received at journal 13 Apr, 2025 Reviewers agreed at journal 13 Apr, 2025 Reviewers invited by journal 12 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 09 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-5917499","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442270999,"identity":"0174ece1-2ea4-4e13-b69a-8ee3ab1b1382","order_by":0,"name":"Oesophago-Gastric Anastomotic","email":"","orcid":"","institution":"University of Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Oesophago-Gastric","middleName":"","lastName":"Anastomotic","suffix":""},{"id":442271000,"identity":"c2bd65bf-fa5f-42e1-9202-c733eec417a6","order_by":1,"name":"Mr Sivesh Kathir Kamarajah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYFACNgbGBggrgZmh4kACTNyASC1nSNTCwMzYRoQW+Qa2BMYZNdvkzdsPPPxcOO9OHv+0A4wffjAcNsalxeAA2wHGDcduG845k5AsPXPbs2KJ2wnMkj0Mh81wamFgb2B8wHabcQZDQoI077bDiQ23ExikGRgO2+B2GEjLv9v2M/gfJP/mnXM4cT7Qlt/4tDCAHLax7XbiDImENGnehsOJG24nsIFswe2ww2wJB2f23U6eIfEgzZrn2LPEjbcT2yx7DNJxel++vc3wYc+327Yz+HOSb/PU3Emcdzv58I0fFdaGDbj0MAPdBmHxJECFQPGEJyKRAPsBopSNglEwCkbByAMAZvpe2Ptjb/kAAAAASUVORK5CYII=","orcid":"","institution":"University of Birmingham","correspondingAuthor":true,"prefix":"Mr","firstName":"Sivesh","middleName":"Kathir","lastName":"Kamarajah","suffix":""}],"badges":[],"createdAt":"2025-01-28 09:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5917499/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5917499/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12893-025-02941-6","type":"published","date":"2025-05-22T15:57:40+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80792138,"identity":"8e587f3f-550e-4bd6-9174-dc5f81d68dfc","added_by":"auto","created_at":"2025-04-17 06:53:53","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":541595,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart on inclusion of patients with esophageal cancers (i.e. adenocarcinoma and squamous cell carcinoma) from the Oesophagogastric Anastomosis Audit\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5917499/v1/170f73e0a7f7ea52df1ebe4c.jpeg"},{"id":80791092,"identity":"4bf17136-02c2-45a6-8dd3-2bed8b4dfb5a","added_by":"auto","created_at":"2025-04-17 06:45:53","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":286038,"visible":true,"origin":"","legend":"\u003cp\u003eSummary Forest plot of primary (i.e. pulmonary complications) and secondary (i.e overall \u0026amp; major complications, anastomotic leaks, 90-day mortality) outcomes surgical approaches in patients with transthoracic esophageal cancers\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e*Postoperative outcomes (i.e. pulmonary complications, overall \u0026amp; major complications, anastomotic leaks, and 90-day mortality) were adjusted for center volume, country income, age at surgery, sex, ASA grade, smoking status, respiratory disease, body mass index, tumor histology \u0026amp; location, clinical AJCC T stage, clinical AJCC N stage, preoperative nutrition, neoadjuvant therapy, anastomotic technique, and surgical approach\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5917499/v1/627630ac4c63d46a0c531cd9.jpeg"},{"id":83460007,"identity":"2a4580bf-7cc3-467a-a1fd-7444c376c1ea","added_by":"auto","created_at":"2025-05-26 16:08:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1902331,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5917499/v1/c2b7d109-2a59-4a1e-a093-c82322ed6435.pdf"},{"id":80789917,"identity":"a64f952d-85ef-4d8f-8d3e-1600ae0ff5b5","added_by":"auto","created_at":"2025-04-17 06:37:53","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":141209,"visible":true,"origin":"","legend":"","description":"","filename":"r0MIEPPCv14250207supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-5917499/v1/b20f28a3c0010459f9ecdf30.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postoperative Outcomes after Minimally Invasive Esophagectomy: An International Cohort Study from the Oesophagogastric Anastomosis Audit (OGAA)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultimodality treatment with neoadjuvant therapy and esophagectomy remains the curative treatment of patients with resectable esophageal cancer.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Although there has been substantive improvement in postoperative mortality after esophagectomies, morbidity rates remain as high as 70%[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and patients are associated with reduced quality of life.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Furthermore, the detrimental impact of perioperative complications on long-term survival is also well understood.[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] To improve perioperative morbidity, there has been a dramatic increase in the adoption of minimally invasive esophagectomy (MIE), through implementation of these programs in centers.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThere are several approaches used for esophagectomies such as Ivor-Lewis, McKeown, and Transhiatal. Therefore, this warrants dedicated evaluation on the role of MIE techniques. However, the benefits of MIE in patients undergoing transthoracic esophagectomy remains unclear. Firstly, evidence have until recently been limited to two randomised clinical trials.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Both these trials only compared either totally MIE (TMIE) or hybrid MIE with open esophagectomy demonstrating significantly lower rates of postoperative pulmonary complications (PPC) compared to open esophagectomy. However, adoption of these MIE techniques into routine clinical practice were associated with higher overall and pulmonary complications and reoperation rate.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Secondly, present studies are limited to cohort studies either from selected high-volume centers, single center or national series. Therefore, global data, including low- and middle-income countries comparing MIE and open surgery are needed to assess its impact on both postoperative complications.\u003c/p\u003e \u003cp\u003eThe primary aim of the present study was to compare the incidence of PPC between OE, HE and TMIE using data from the Oesophago-Gastric Anastomosis Audit (OGAA). The secondary aims were to assess the rates of postoperative morbidity (i.e., overall, and major complications, anastomotic leaks, and 90-day mortality).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy design and setting\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a secondary pre-planned analysis of the OGAA cohort study. The OGAA cohort study was an international multicenter prospective study including 137 centers across 41 countries.[14-16] All hospitals performing esophagectomies for esophageal cancers were eligible to be included in this cohort study. Patient-level data were collected over a nine-month period from 1st April 2018 to 31st December 2018 with follow-up of all patients up to 90-days after surgery. This study was delivered using a collaborative model, which has been described previously. This methodology and process has been successful in delivering several international and national cohort studies.[15-17] Briefly, a consultant or attending surgeon supervised data collection at each hospital, together with a team of clinicians, ensuring that it was performed in accordance with a pre-specified protocol. The study was conducted according to STROBE guidelines for observational studies.[18]\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics and reporting\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was dependent on local protocols, and was country-specific, as previously described.[15, 16] Ongoing study approval was maintained locally throughout the duration of the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInclusion and Exclusion Criteria\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDuring the pre-defined data collection period, all consecutive adult patients undergoing elective (planned) curative esophagectomy for esophageal cancers (i.e. adenocarcinoma and SCC) were included. For the present analysis, patients undergoing two-stage transthoracic esophagectomy using any combination of open, robotic or standard minimal access approaches were included. Exclusion criteria were: (i) extended total gastrectomy, transhiatal esophagectomy, three-stage (i.e. McKeown) esophagectomy or left thoracoabdominal; (ii) pharyngolaryngo-oesophagectomy; (iii) colonic interposition or small bowel jejunal interposition reconstruction; (iv) emergency resection; and (v) resection for benign disease, as previously described.[19, 20]\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcome measures\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was postoperative pulmonary complications, according to the Esophagectomy Complications Consensus Group.[21, 22] Postoperative pulmonary complications were defined as pneumonia, pleural effusion requiring additional drainage procedure, pneumothorax requiring treatment, atelectasis mucous plugging requiring bronchoscopy, respiratory failure requiring reintubation, acute respiratory distress syndrome, acute aspiration, tracheobronchial injury and chest tube maintenance for air leak for \u0026gt; 10 days postoperatively. Secondary outcome measures were overall complications, major complications, anastomotic leaks, and 90-day mortality. Major postoperative complications were defined as those of Clavien-Dindo Grade III-V.[20] Anastomotic leaks were defined full thickness GI defect involving esophagus, anastomosis, staple line, or conduit irrespective of presentation or method of identification according to the ECCG.[21] Broadly, these leaks were defined as type I, type II or type III anastomotic leaks as defined according to the ECCG guidance.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData Collection\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe process of data collection was based on case report forms (CRFs), which were for data recording only. Detailed reporting on data collection process has been reported elsewhere.[23-25]\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDefinitions of variables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA range of patient-, tumour- and treatment-related factors were assessed. Data for a range of center-specific variables were also collected. Country income was defined as high-income (HIC) or low- or middle-income countries (LMIC), according to the World Bank Data.[26] The center volume[27, 28] was based on the number of cases treated by each center during the study period (nine months), from which the number of cases per year was estimated. The resulting variable was then categorized for analysis, based on tertiles, such that there were approximately equal numbers of patients in each category. \u0026nbsp;The resulting categories were \u0026lt;28 (n=94 centers; HIC - 68, LMIC - 26), 28-50 (n=28 centers; HIC - 25, LMIC - 3) and \u0026gt;50 cases (n=15 centers, HIC - 13, LMIC - 2) per year. The TNM staging was based on pathology and used the 8\u003csup\u003eth\u003c/sup\u003e edition definitions.[29]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables that were normally distributed were reported as mean \u0026plusmn; standard deviation (SD), with p-values from independent sample t-tests. For continuous, and non-normally distributed data, we reported them as medians and interquartile ranges (IQRs). Categorical ordinal variables were also assessed using Mann-Whitney U-tests, whilst nominal variables were analysed using Fisher\u0026rsquo;s exact-tests or Chi\u003csup\u003e2\u003c/sup\u003e-tests, for variables with two or more than two categories, respectively. Multilevel multivariable analyses were then performed, to produce adjusted odds ratio (OR) on surgical techniques on outcomes to account for the multi-level structure of the data, by adjusting for within-centre correlations of outcomes. As such, the centre was set as the subject effect, and the patient ID as the within-subject effect, with an exchangeable correlation structure assumed. For all models, a range of centre-, patient-, tumour- and treatment-related factors were assessed. Variables included in the multivariable models were selected based on clinical relevance, existing literature, and availability in the dataset. The adjusted model includes center- (center volume, country income), patient- (i.e. age, gender, ASA grade, Charlson comorbidity index, smoking status and body mass index), tumour- (i.e. tumor histology, tumor location, AJCC clinical T and N classification) and treatment-related (i.e. preoperative nutrition, neoadjuvant therapy, surgical approach, anastomosis site) factors. Although our models were not intended for prognostic prediction, we report the c-statistic (area under the curve) for each outcome model as an indicator of overall model performance. Sensitivity analyses were performed by patients with respiratory disease, neoadjuvant chemoradiotherapy and high-volume centers. A p-value of \u0026lt;0.05 was considered statistically significant and 2-sided 5% significance level was applied. Data analysis was performed using R Foundation Statistical software (R 3.2.2) with TableOne, ggplot2, Hmisc, and finalfit packages (R Foundation for Statistical Computing, Vienna, Austria) as previously described.[15, 16]\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathologic characteristics\u003c/h2\u003e \u003cp\u003eOf the 2,247 patients identified from the OGAA study, 1,784 patients received transthoracic OE (n\u0026thinsp;=\u0026thinsp;744), HE (n\u0026thinsp;=\u0026thinsp;500) or TMIE (n\u0026thinsp;=\u0026thinsp;540) for esophageal cancers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline characteristics of patients are presented in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u0026amp; \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Patients receiving TMIE were more likely to be from high volume (\u0026lt;\u0026thinsp;50 cases/year) (35% vs 27%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and from high-income countries (96% vs 93%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than patients receiving OE.\u003c/p\u003e \u003cp\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\u003eHospital- and patient-level clinicopathologic characteristics of patients with esophageal cancers receiving open, hybrid and totally minimally invasive esophagectomy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOpen,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;750\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHybrid,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;507\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotally minimally invasive,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;441\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital-level factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCenter volume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e232 (30.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e129 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e155 (35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e313 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e212 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e130 (29.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e205 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e166 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e156 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCountry income\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh income country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e696 (92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e498 (98.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e424 (96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow-Middle income country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatient-level factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e63.9 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66.0 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64.7 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e155 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e89 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e74 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e595 (79.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e418 (82.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e367 (83.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA Grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e38 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e423 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e284 (56.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e225 (51.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e219 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e151 (29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e178 (40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNever smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e300 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e181 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e142 (32.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEx-smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e320 (42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e234 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e216 (49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e79 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e77 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e660 (88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e457 (90.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e377 (85.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.6\u0026ndash;24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e272 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e187 (36.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e157 (35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0-29.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e253 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e206 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e173 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;30.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e193 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e101 (19.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e103 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor Histology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e595 (79.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e430 (84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e382 (86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSquamous Cell Carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e155 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e59 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProximal/Middle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDistal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e238 (31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e138 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e168 (38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSiewert 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e239 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e197 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e133 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSiewert 2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e211 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e140 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e115 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical AJCC T Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e50 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e153 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e99 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e107 (24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecT3/T4a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e516 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e351 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e284 (64.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical AJCC N Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e313 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e218 (43.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e208 (47.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.355\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e295 (39.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e189 (37.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e162 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecN2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e142 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100 (19.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e71 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative nutrition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e411 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e255 (50.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e214 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e339 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e252 (49.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e227 (51.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOperative-level clinicopathologic characteristics of patients with esophageal cancers receiving open, hybrid and totally minimally invasive esophagectomy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOpen,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;744\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHybrid,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;500\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotally minimally invasive,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;540\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative-level factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e171 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e129 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e119 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChemoradiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e201 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e114 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e184 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e378 (50.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e264 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e138 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomosis technique\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHandsewn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e123 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e38 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e75 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLinear Stapled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e111 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e99 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e122 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCircular stapled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e516 (68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e370 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e244 (55.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric tube\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThin (\u0026lt;5cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e327 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e324 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e337 (76.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWide (\u0026gt;5cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e408 (54.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e174 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e102 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhole Stomach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePyloric procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot Performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e369 (49.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e383 (75.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e341 (77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBotox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e28 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDilatation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e33 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePyloromyotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePyloroplasty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e287 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e34 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmentoplasty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e509 (67.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e295 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e191 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e241 (32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e212 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e250 (56.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the TMIE cohort, ASA grade III-IV patients (40% vs 30% vs 29%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), adenocarcinoma histology (87% vs 85% vs 79%, p\u0026thinsp;=\u0026thinsp;0.002), and distal cancers (38% vs 27% v2 32%, p\u0026thinsp;=\u0026thinsp;0.005) were significantly more common than in the HE and OE cohort (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Also, more TMIE patients, compared with HE and OE, had neoadjuvant chemoradiotherapy (42% vs 23% vs 27%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), a linear stapled anastomosis (28% vs 20% vs 15%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), thin gastric tube (\u0026lt;\u0026thinsp;5cm width) (76% vs 64% vs 44%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and omentoplasty (57% vs 42% vs 32%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were no significant differences in the rates of clinical AJCC T3 / T4a disease (64% vs 69% vs 69%, p\u0026thinsp;=\u0026thinsp;0.4) and clinical AJCC N2 / N3 (16% vs 20% vs 19%, p\u0026thinsp;=\u0026thinsp;0.4) disease across patients receiving TMIE, HE and OE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003ePostoperative pulmonary complications (PPC)\u003c/h2\u003e \u003cp\u003ePatients receiving TMIE had significantly lower rates of PPC patients having HE and OE (28% vs 39% vs 37%, p\u0026thinsp;=\u0026thinsp;0.002). On adjusted analyses, patients receiving TMIE had significantly lower rates of PPC than open (OR: 0.60, CI\u003csub\u003e95%\u003c/sub\u003e: 0.45\u0026ndash;0.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The full model is presented in Supplementary Table\u0026nbsp;1 (c-statistic 0.71). Sensitivity analyses demonstrated significantly lower rates of PPC with TMIE compared to HE (OR: 0.53, CI\u003csub\u003e95%\u003c/sub\u003e: 0.39\u0026ndash;0.73, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Supplementary Table\u0026nbsp;2). Exploratory analyses identified TMIE patients with PPC were more likely to have higher ASA grade, respiratory disease, distal esophageal cancers, and advanced disease (Supplementary Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable and multivariable analysis of postoperative (i.e., pulmonary complications, anastomotic leaks, overall \u0026amp; major complications, and 90-day mortality) outcomes comparing open, hybrid and totally minimally invasive esophagectomy in patients with esophageal cancer\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRates, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariable, OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariable, OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary complications*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e276 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHybrid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e196 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.08 (0.86\u0026ndash;1.37, p\u0026thinsp;=\u0026thinsp;0.504)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.07 (0.84\u0026ndash;1.36, p\u0026thinsp;=\u0026thinsp;0.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotally minimally invasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e125 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.68 (0.53\u0026ndash;0.88, p\u0026thinsp;=\u0026thinsp;0.003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60 (0.45\u0026ndash;0.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall complications*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e481 (64.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHybrid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e310 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.88 (0.70\u0026ndash;1.11, p\u0026thinsp;=\u0026thinsp;0.282)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.85 (0.67\u0026ndash;1.09, p\u0026thinsp;=\u0026thinsp;0.204)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotally minimally invasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e262 (59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.82 (0.64\u0026ndash;1.04, p\u0026thinsp;=\u0026thinsp;0.104)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.68 (0.52\u0026ndash;0.88, p\u0026thinsp;=\u0026thinsp;0.004)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMajor complications*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e178 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHybrid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e130 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11 (0.85\u0026ndash;1.44, p\u0026thinsp;=\u0026thinsp;0.441)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.10 (0.83\u0026ndash;1.43, p\u0026thinsp;=\u0026thinsp;0.510)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotally minimally invasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e107 (24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03 (0.78\u0026ndash;1.35, p\u0026thinsp;=\u0026thinsp;0.836)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.90 (0.67\u0026ndash;1.21, p\u0026thinsp;=\u0026thinsp;0.489)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnastomotic leaks*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHybrid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05 (0.73\u0026ndash;1.50, p\u0026thinsp;=\u0026thinsp;0.806)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.08 (0.74\u0026ndash;1.57, p\u0026thinsp;=\u0026thinsp;0.682)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotally minimally invasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.56 (1.10\u0026ndash;2.20, p\u0026thinsp;=\u0026thinsp;0.012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.40 (0.96\u0026ndash;2.02, p\u0026thinsp;=\u0026thinsp;0.076)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90-day mortality*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eREF\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHybrid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.91 (0.47\u0026ndash;1.69, p\u0026thinsp;=\u0026thinsp;0.764)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.73 (0.37\u0026ndash;1.41, p\u0026thinsp;=\u0026thinsp;0.352)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotally minimally invasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.71 (0.33\u0026ndash;1.42, p\u0026thinsp;=\u0026thinsp;0.352)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.50 (0.22\u0026ndash;1.06, p\u0026thinsp;=\u0026thinsp;0.079)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e*Adjusted for center volume, country income, age at surgery, sex, ASA grade, smoking status, respiratory disease, body mass index, tumor histology \u0026amp; location, clinical AJCC T stage, clinical AJCC N stage, preoperative nutrition, neoadjuvant therapy, anastomotic technique, and surgical approach\u003c/em\u003e\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 \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSecondary outcomes\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003eOverall complications\u003c/h2\u003e \u003cp\u003eThere was no significant difference in rates of overall complications between OE, HE and TMIE (64% vs 61% vs 61%, p\u0026thinsp;=\u0026thinsp;0.2). However, patients receiving TMIE had significantly lower rates of overall complications than OE (OR: 0.68, CI\u003csub\u003e95%\u003c/sub\u003e: 0.52\u0026ndash;0.88, p\u0026thinsp;=\u0026thinsp;0.004) on adjusted analyses (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The full model is presented in Supplementary Table\u0026nbsp;4 (c-statistic 0.69). Sensitivity analyses demonstrated no significant difference in overall complications between HE and TMIE in adjusted analyses. (Supplementary Table\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMajor complications\u003c/h2\u003e \u003cp\u003eThere was no significant difference in rates of major complications between OE, HE and TMIE (24% vs 26% vs 24%, p\u0026thinsp;=\u0026thinsp;0.5). On adjusted analyses, there were no significant difference in rates of major complications between patients receiving TMIE and OE (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The full model is presented in Supplementary Table\u0026nbsp;5 (c-statistic 0.70). Sensitivity analyses demonstrated no significant difference in overall complications between HE and TMIE in adjusted analyses (Supplementary Table\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eAnastomotic leaks\u003c/h2\u003e \u003cp\u003ePatients receiving TMIE had significantly higher rates of anastomotic leaks compared to patients having OE and HE (16% vs 11% vs 11%, p\u0026thinsp;=\u0026thinsp;0.026) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). On adjusted analyses, there were no significant difference in rates of anastomotic leaks in patients receiving HE (OR: 1.08, CI\u003csub\u003e95%\u003c/sub\u003e: 0.74\u0026ndash;1.57, p\u0026thinsp;=\u0026thinsp;0.7) and TMIE (OR: 1.40, CI\u003csub\u003e95%\u003c/sub\u003e: 0.96\u0026ndash;2.02, p\u0026thinsp;=\u0026thinsp;0.1) compared to OE (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The full model is presented in Supplementary Table\u0026nbsp;6 (c-statistic 0.66). Sensitivity analyses between HE and TMIE demonstrated no significant difference in anastomotic leak rates between the two techniques in adjusted analyses (Supplementary Table\u0026nbsp;1). Anastomotic leaks were further classified using ECCG definitions, with no significant difference in severity grading across surgical approaches.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e90-day mortality\u003c/h2\u003e \u003cp\u003eThere was no significant difference in rates of 90-day mortality between OE, HE and TMIE (4% vs 3% vs 3%, p\u0026thinsp;=\u0026thinsp;0.6) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). On adjusted analyses, there were no significant difference in rates of 90-day mortality between patients receiving TMIE and OE (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The full model is presented in Supplementary Table\u0026nbsp;7 (c-statistic 0.75). Sensitivity analyses demonstrated no significant difference in 90-day mortality between HE and TMIE in adjusted analyses (Supplementary Table\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eOther complications\u003c/h2\u003e \u003cp\u003eA summary of postoperative complications as defined according to ECCG by OE, HE and TMIE are presented in Supplementary Table\u0026nbsp;8. There were significant differences in operating time between patient receiving OE, HE and TMIE (median: 350 vs 355 vs 367, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no significant differences in the overall length of stay between patients receiving OE, HE and TMIE (mean: 17.8 vs 16.7 vs 16.5 days, p\u0026thinsp;=\u0026thinsp;0.2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003eRespiratory Disease\u003c/h2\u003e \u003cp\u003eOf 1,784 patients receiving either OE, HE or TMIE, 11% (n\u0026thinsp;=\u0026thinsp;204) had underlying respiratory disease. Baseline characteristics for these patients are presented in Supplementary Table\u0026nbsp;9. Sensitivity analyses performed for PPC, overall and major complications, anastomotic leaks and 90-day mortality (Supplementary Table\u0026nbsp;10) were in line with the findings of the main analysis. On adjusted analyses, patients receiving TMIE had significantly lower rates of PPC than (OR: 0.53, CI\u003csub\u003e95%\u003c/sub\u003e: 0.39\u0026ndash;0.72, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Supplementary Table\u0026nbsp;10).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eNeoadjuvant Chemoradiotherapy\u003c/h2\u003e \u003cp\u003eSensitivity analyses were performed in patients receiving neoadjuvant chemoradiotherapy (n\u0026thinsp;=\u0026thinsp;499), of which 37% (n\u0026thinsp;=\u0026thinsp;184) received TMIE. Baseline characteristics for these patients are presented in Supplementary Table\u0026nbsp;11. Sensitivity analyses performed for PPC, overall and major complications, anastomotic leaks and 90-day mortality (Supplementary Table\u0026nbsp;12) were in line with the findings of the main analysis.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eHigh Volume Centers\u003c/h2\u003e \u003cp\u003eSensitivity analyses were performed in patients receiving treatment in high volume centers (n\u0026thinsp;=\u0026thinsp;527), of which 30% (n\u0026thinsp;=\u0026thinsp;156) received TMIE. Baseline characteristics for these patients are presented in Supplementary Table\u0026nbsp;13. Sensitivity analyses performed for PPC, overall complications, anastomotic leaks and 90-day mortality (Supplementary Table\u0026nbsp;14) were in line with the findings of the main analysis. However, patients receiving TMIE had significantly lower rates of major complications (17% vs 26%, p\u0026thinsp;=\u0026thinsp;0.001) than OE, which remained on adjusted analyses (OR: 0.48, CI\u003csub\u003e95%\u003c/sub\u003e: 0.24\u0026ndash;0.94, p\u0026thinsp;=\u0026thinsp;0.037).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrent guidelines from the European Society of Medical Oncology (ESMO)[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and the National Comprehensive Cancer Network (NCCN)[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] recommend hybrid esophagectomies. However, evidence demonstrating any superiority or safety for TMIE over OE or HE or any other existing surgical approach is lacking. This international cohort study on patients with esophageal cancers demonstrated that TMIE was associated with lower 90-day PPC. There was however no difference in overall complications and anastomotic leak rates in the adjusted analyses. Margin-negative resection rates were significantly higher after TMIE compared to OE or HE, albeit lower than in RCTs.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE.\u003c/p\u003e \u003cp\u003eTo date, evidence surrounding impact of MIE on postoperative outcomes, especially PPC compared to OE or HE remains unclear. Evidence from previously published RCT\u0026rsquo;s comparing OE with HE (i.e MIRO[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]) or TMIE (i.e. TIME[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], ROBOT[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]) demonstrated significantly lower rates of PPC with HE and TMIE, respectively. However, a published meta-analysis[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] of non-randomized studies comparing HE and TMIE demonstrated no significant difference in rates of pneumonia between the two techniques. A recently published review also emphasises the uncertainty that exists in the current evidence on this topic.[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] These findings were aligned with a recent population-based cohort study from Sweden.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eReducing rates of anastomotic leaks remain a major topic of discussion amongst esophageal surgeons and efforts to reduce them remain a priority. However, adoption of TMIE has been associated with significantly higher rates of anastomotic leaks compared to OE. Firstly, a recently published cohort study from the ESOData demonstrated higher anastomotic leaks rate with TMIE than HE.[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] However, the ESOData included patients from high volume, high income countries compared to the present study. Therefore, the present study allowed the true impact of adoption of TMIE from global real-world data. Secondly, a meta-analysis[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] that compared TMIE with HE reported significantly higher rates of anastomotic leaks with transthoracic TMIE compared with HE. In addition, these anastomotic leaks following esophagectomy is linked to reduced long-term overall survival from a recent meta-analysis.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, in the present study, there was a trend towards higher anastomotic leak rates with TMIE compared to OE and HE, as high as 40%. Although the relative risks are higher, the absolute rates of anastomotic leak rates are lower than previously published randomised and non-randomised trials.\u003c/p\u003e \u003cp\u003eSeveral reasons may explain, the numerically higher rate of anastomotic leaks observed with TMIE, although not statistically significant in adjusted models. Firstly, TMIE involves a technically complex, intracorporeal anastomosis that can be affected by reduced tactile feedback and visualization limitations. Moreover, conduit perfusion can be more difficult to assess accurately in minimally invasive approaches, especially without adjuncts such as ICG fluorescence angiography. Second, stapling techniques and conduit preparation also vary\u0026mdash;thin gastric tubes, more commonly used in TMIE, may be more vulnerable to ischemia. Third, learning curve effects cannot be excluded, particularly as TMIE adoption is increasing globally and standardisation of technique remains heterogeneous. Our analysis did not directly measure surgeon experience, but future studies should address this as a modifiable factor.\u003c/p\u003e \u003cp\u003eThe present study has some limitations. Firstly, the present study does not capture proficiency gains or learning curves of individual surgeons performing TMIE to assess impact of this on complications. Although interhospital variation has been included into the adjusted model, unknown confounders such as these may also affect postoperative complications. Secondly, impact of surgical approaches on long-term survival data and health-related quality of life were not available in this cohort study. Important endpoints such as dysphagia, reflux, nutritional status, and patient-reported quality of life were not collected. These outcomes are essential to understanding the true burden of surgery from the patient\u0026rsquo;s perspective, particularly when comparing different minimally invasive approaches. Future collaborative efforts should prioritize the inclusion of longitudinal follow-up with validated quality of life instruments to better inform surgical decision-making. Thirdly, there are potentially unmeasured confounders that were not included in the adjusted models. These include surgeon experience (e.g., learning curves) and hospital-level services such as prehabilitation and enhanced recovery after surgery protocols which may exists in some centers. Variation in some of these measures may affect outcomes in patients undergoing esophagectomy around the world.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides real-world data that TMIE was associated with lower 90-day PPC than OE and HE approaches, especially in patients with underlying respiratory disease or receiving neoadjuvant chemoradiotherapy. These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE is probably of major importance. The ideal surgical approach remains unclear, and ongoing trials will provide more evidence within a few years that may clarify the optimum approach to locally advanced esophageal cancers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eHuman ethics and consent to participate:\u003c/em\u003e Ethical approval was not applicable for this study, as this was a secondary analysis of cohort study with existing approval. This study was reviewed by the University Hospital Birmingham NHS Trust ethics committee and the need for full ethics review was waived since the study is an observation study of routinely collected data. Informed consent was not needed for all participants in the main study by the ethics committee. This study adhered to the Helsinki declaration.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e Not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material:\u0026nbsp;\u003c/em\u003eThe data and statistical codes can be made available on request from corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests:\u0026nbsp;\u003c/em\u003eNone declared\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical trial number:\u0026nbsp;\u003c/em\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e No funding to report for this study\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/em\u003eThe following are the writing group: Kamarajah SK, Darling G, Duong C, Evans R, Gockel I, Gossage J, Hedberg J, Kauppila JH, Maynard N, Monig S, Hsu PK, Reynolds J, Singh P, So JBY, Wijnhoven BPL, Griffiths EA\u003c/p\u003e\n\u003cp\u003eThe role of all coauthors is shown in appendix. SKK and EAG were involved in study design, coordination of the study, manuscript concept, and editing. SKK and EAG conducted the data analysis. SKK and EAG accessed and verified the data. The writing group and the statistical analysis group contributed to data interpretation and critical revision of the manuscript. The writing committee was responsible for the decision to submit. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eAll authors have no conflict of interest to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures:\u0026nbsp;\u003c/strong\u003eAll authors have financial disclosure to make\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: We are grateful to the Birmingham Surgical Trials Consortium at the University of Birmingham for the use of their servers for secure online data collection.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShapiro J, van Lanschot JJB, Hulshof M, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, et al. 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The Impact of Severe Anastomotic Leak on Long-term Survival and Cancer Recurrence After Surgical Resection for Esophageal Malignancy. Ann Surg. 2015;262(6):972\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBooka E, Takeuchi H, Suda K, Fukuda K, Nakamura R, Wada N, Kawakubo H, Kitagawa Y. Meta-analysis of the impact of postoperative complications on survival after oesophagectomy for cancer. BJS Open. 2018;2(5):276\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGujjuri RR, Kamarajah SK, Markar SR. Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis. Dis Esophagus 2021, 34(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiaw-Acheampong K, Kamarajah SK, Gujjuri R, Bundred JR, Singh P, Griffiths EA. Minimally invasive techniques for transthoracic oesophagectomy for oesophageal cancer: systematic review and network meta-analysis. BJS Open. 2020;4(5):787\u0026ndash;803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiere SS, van Berge Henegouwen MI, Maas KW, Bonavina L, Rosman C, Garcia JR, Gisbertz SS, Klinkenbijl JH, Hollmann MW, de Lange ES, et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet. 2012;379(9829):1887\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMariette C, Markar SR, Dabakuyo-Yonli TS, Meunier B, Pezet D, Collet D, D'Journo XB, Brigand C, Perniceni T, Carrere N, et al. Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer. N Engl J Med. 2019;380(2):152\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkar SR, Ni M, Gisbertz SS, van der Werf L, Straatman J, van der Peet D, Cuesta MA, Hanna GB, van Berge Henegouwen MI, Dutch Upper GICA, et al. Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice. J Clin Oncol. 2020;38(19):2130\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayami M, Ndegwa N, Lindblad M, Linder G, Hedberg J, Edholm D, Johansson J, Lagergren J, Lundell L, Nilsson M et al. Population-Based Cohort Study from a Prospective National Registry: Better Long-Term Survival in Esophageal Cancer After Minimally Invasive Compared with Open Transthoracic Esophagectomy. Ann Surg Oncol 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvans RPT, Singh P, Nepogodiev D, Bundred J, Kamarajah S, Jefferies B, Siaw-Acheampong K, Wanigasooriya K, McKay S, Mohamed I et al. Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA). Dis Esophagus 2020, 33(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. Rates of Anastomotic Complications and their Management following Esophagectomy: Results of the Oesophago-Gastric Anastomosis Audit (OGAA). \u003cem\u003eAnn Surg\u003c/em\u003e 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study. Eur J Surg Oncol 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaborative ST, Writing/Steering C, Data Management G, External Advisory G. REspiratory COmplications after abdomiNal surgery (RECON): study protocol for a multi-centre, observational, prospective, international audit of postoperative pulmonary complications after major abdominal surgery. Br J Anaesth. 2020;124(1):e13\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindo D, Muller MK, Weber M, Clavien PA. Obesity in general elective surgery. Lancet. 2003;361(9374):2032\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLow DE, Alderson D, Cecconello I, Chang AC, Darling GE, D'Journo XB, Griffin SM, Holscher AH, Hofstetter WL, Jobe BA, et al. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015;262(2):286\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLow DE, Kuppusamy MK, Alderson D, Cecconello I, Chang AC, Darling G, Davies A, D'Journo XB, Gisbertz SS, Griffin SM et al. Benchmarking Complications Associated with Esophagectomy. Ann Surg 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaborative S. Impact of postoperative non-steroidal anti-inflammatory drugs on adverse events after gastrointestinal surgery. Br J Surg. 2014;101(11):1413\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaborative S. Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study. BJS Open 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCholeS Study Group WMRC. Population-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases. Br J Surg. 2016;103(12):1704\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOesophago-Gastric Anastomosis Study Group on behalf of the West Midlands Research C. International Variation in Surgical Practices in Units Performing Oesophagectomy for Oesophageal Cancer: A Unit Survey from the Oesophago-Gastric Anastomosis Audit (OGAA). 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CA Cancer J Clin. 2017;67:7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjani JA, D'Amico TA, Almhanna K, Bentrem DJ, Besh S, Chao J, Das P, Denlinger C, Fanta P, Fuchs CS, et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw. 2015;13(2):194\u0026ndash;227.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Sluis PC, van der Horst S, May AM, Schippers C, Brosens LAA, Joore HCA, Kroese CC, Haj Mohammad N, Mook S, Vleggaar FP, et al. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg. 2019;269(4):621\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Workum F, Klarenbeek BR, Baranov N, Rovers MM, Rosman C. Totally minimally invasive esophagectomy versus hybrid minimally invasive esophagectomy: systematic review and meta-analysis. Dis Esophagus 2020, 33(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVashist Y, Goyal A, Shetty P, Girnyi S, Cwalinski T, Skokowski J, Malerba S, Prete FP, Mocarski P, Kania MK et al. Evaluating Postoperative Morbidity and Outcomes of Robotic-Assisted Esophagectomy in Esophageal Cancer Treatment-A Comprehensive Review on Behalf of TROGSS (The Robotic Global Surgical Society) and EFISDS (European Federation International Society for Digestive Surgery) Joint Working Group. Curr Oncol 2025, 32(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Wilk BJ, Hagens ERC, Eyck BM, Gisbertz SS, van Hillegersberg R, Nafteux P, Schroder W, Nilsson M, Wijnhoven BPL, Lagarde SM, et al. Outcomes after totally minimally invasive versus hybrid and open Ivor Lewis oesophagectomy: results from the International Esodata Study Group. Br J Surg. 2022;109(3):283\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"minimally invasive, esophagectomy, outcomes, pulmonary complications","lastPublishedDoi":"10.21203/rs.3.rs-5917499/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5917499/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo compare the postoperative pulmonary complications (PPC) after minimally invasive or open transthoracic esophagectomy for esophageal cancer in an international, multicenter cohort.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSummary of Background Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOngoing debate exists around the optimal surgical approach for esophageal cancer, with limited data assessing the external validity of randomised trials on outcomes of MIE\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients undergoing open (OE, n=744), hybrid (HE, n=500), and totally minimally invasive esophagectomy (TMIE, n=540) for esophageal cancer were identified from the international, prospective Oesophagogastric Anastomosis Audit (OGAA). Multivariable models were used to investigate PPC (primary outcome) as well as overall complications, major complications, anastomotic leak and 90-day mortality (secondary outcomes).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePPC rates were lower after TMIE compared to OE and HE (28% vs 37% vs 39%, p=0.002), even on adjusted analyses compared to OE (odds ratio (OR): 0.60, CI\u003csub\u003e95%\u003c/sub\u003e: 0.45 - 0.78). TMIE was also associated with significantly lower overall complications (OR: 0.68, CI\u003csub\u003e95%\u003c/sub\u003e: 0.52 - 0.88) compared to OE, but not for major complications (OR: 0.90, CI\u003csub\u003e95%\u003c/sub\u003e: 0.67 - 1.21), anastomotic leak (OR: 1.39, CI\u003csub\u003e95%\u003c/sub\u003e: 0.96 - 2.01) and 90-day mortality (OR: 0.49, CI\u003csub\u003e95%\u003c/sub\u003e: 0.22 - 1.04). Sensitivity analyses by underlying respiratory disease, neoadjuvant chemoradiotherapy or high-volume centers confirmed above findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study provides real-world data that TMIE was associated with lower 90-day PPC than OE and HE approaches, especially in patients with underlying respiratory disease or receiving neoadjuvant chemoradiotherapy. These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE is probably of major importance. The ideal surgical approach remains unclear, and ongoing trials will provide more evidence within a few years that may clarify the optimum approach to locally advanced esophageal cancers.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Postoperative Outcomes after Minimally Invasive Esophagectomy: An International Cohort Study from the Oesophagogastric Anastomosis Audit (OGAA)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 06:37:48","doi":"10.21203/rs.3.rs-5917499/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-04-29T09:51:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-25T06:54:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89191122656847129689022299663023247112","date":"2025-04-13T13:32:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-13T07:32:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324541303914066615487340152185417015176","date":"2025-04-13T07:28:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-12T16:56:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-11T06:15:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2025-04-09T09:15:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e16a47a-126f-43af-82a4-facf811dbfe1","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T16:01:13+00:00","versionOfRecord":{"articleIdentity":"rs-5917499","link":"https://doi.org/10.1186/s12893-025-02941-6","journal":{"identity":"bmc-surgery","isVorOnly":false,"title":"BMC Surgery"},"publishedOn":"2025-05-22 15:57:40","publishedOnDateReadable":"May 22nd, 2025"},"versionCreatedAt":"2025-04-17 06:37:48","video":"","vorDoi":"10.1186/s12893-025-02941-6","vorDoiUrl":"https://doi.org/10.1186/s12893-025-02941-6","workflowStages":[]},"version":"v1","identity":"rs-5917499","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5917499","identity":"rs-5917499","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}