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RETRACTED ARTICLE: Comparison of minimally invasive Ivor Lewis esophagectomy and left transthoracic esophagectomy in esophageal squamous cell carcinoma patients: a propensity score-matched analysis

RETRACTED ARTICLE: Comparison of minimally invasive Ivor Lewis esophagectomy and left... Background: To investigate the long-term efficacy of the minimally invasive Ivor Lewis esophagectomy (MIILE) in esophageal squamous cell carcinoma (ESCC) patients, a retrospective comparison of the quality of life (QOL) and survival between patients who underwent MIILE and left transthoracic esophagectomy (Sweet approach) was conducted. Methods: A detailed database search identified 614 patients who underwent MIILE and 243 patients who underwent Sweet esophagectomy between January 2011 and December 2017. After propensity score matching, 216 paired cases were selected for statistical analysis. Survival was evaluated with Kaplan-Meier curves or Cox models. Results: MIILE was associated with a longer duration, less blood loss and more lymph node dissected than Sweet esophagectomy. MIILE patients suffered from less pain, less frequently developed pneumonia, and had fewer postoperative complications. Additionally, MIILE patients began oral intake earlier and had a shorter postoperative hospital stay, and enhanced recovery of QOL. There was no significant difference between the approaches regarding the recurrence pattern, 2-year and 5-year overall survival (OS) or disease-free survival (DFS), except that patients with tumor- node-metastasis (TNM) stage I in the MIILE group demonstrated superior OS and DFS. Pathological TNM stage and postoperative complications were determined to be independent prognostic factors based on the multivariate analysis. Conclusion: MIILE is a safe and feasible approach for treating ESCC patients. MIILE approach may provide more postoperative advantages, enhanced QOL improvement, and more favorable long-term survival in early stage patients than the Sweet procedure. Keywords: Minimally invasive surgery, Ivor Lewis esophagectomy, Left transthoracic esophagectomy, Esophageal squamous cell carcinoma * Correspondence: iwuming22@zju.edu.cn Wang Qi and Wu Zixiang are These authors contributed to the work equally and should be regarded as co-first authors Department of Thoracic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 JieFang Rd, Hangzhou 310009, China © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 2 of 13 Background and right, common hepatic artery, splenic artery, left Surgical resection with lymphadenectomy remains the gastric artery, and celiac). This procedure was followed curative choice for esophageal cancer; however, the opti- by the insertion of a jejunal feeding tube. Before closure, mal surgical approach is uncertain. Unlike in the West- the abdomen was drained. Subsequently, the patient was ern world, where the use of transthoracic and transhiatal turned to the left lateral decubitus position. After esophagectomy is debated, transthoracic esophagectomy, esophageal mobilization and lymphadenectomy (peri-e- especially the left transthoracic (Sweet) approach, has sophageal, lower posterior mediastinal, right and left re- been widely adopted in China [1]. Minimally invasive current laryngeal nerve (RLN), carina, and right Ivor Lewis esophagectomy (MIILE) is gaining popularity paratracheal), intrathoracic anastomosis was completed because of its short-term advantages over open ap- using a circular stapler or the hand-sewn method. Thor- proaches in treating esophageal adenocarcinoma [2, 3]. acic duct ligation was routinely performed. Finally, a However, the long-term outcomes of esophageal squa- nasogastric tube was placed, and the thorax was drained. mous cell carcinoma (ESCC) patients undergoing MIILE For the Sweet approach, the patient was placed in the need further investigation, as the biological and clinical right lateral decubitus position. A left posterolateral patterns of ESCC significantly differ from those of thoracotomy was performed through the sixth or sev- esophageal adenocarcinoma [4, 5]. enth intercostal space. After esophageal isolation and To investigate the long-term effects of MIILE on thoracic lymphadenectomy, the diaphragm was incised ESCC patients, a propensity score-matched study was to mobilize the stomach and dissect the abdominal conducted. We retrospectively compared clinical data lymph nodes. A gastric tube, normally 4–5 cm in width, from patients who underwent MIILE or the Sweet ap- was formed along the arcus major ventriculi. Intratho- proach and evaluated postoperative outcomes, quality of racic esophagogastric anastomosis was constructed using life (QOL), and survival. a circular stapler or the hand-sewn method. A nasoen- teric feeding tube was inserted in the jejunum, and a Methods nasogastric tube was placed. Subsequently, the thorax From January 2011 to December 2017, 1160 ESCC pa- was drained. tients who did not receive neoadjuvant therapy were ad- mitted for surgical assessment. The operability evaluation Postoperative treatment included a panel of oncological assessments (including Patients were routinely monitored in the intensive care contrast computed tomography of the chest and upper ab- unit (ICU) until their vital signs were stabilized. Enteral domen, esophageal gastroscopy, barium esophagography, nutrition was initiated on the first day after surgery. Oral endoscopic ultrasound, and positron emission tomog- intake was usually permitted after the presence of an in- raphy), and standard pulmonary and cardiac function tact anastomosis was verified by an esophagogram, the tests. The treatment regimen was decided by a multidis- implementation of which was closely related to each pa- ciplinary team and the patient based on the clinical stage tient’s recovery status. Chest drains were removed when and the National Comprehensive Cancer Network drainage volumes were less than 100 ml/24 h. The jeju- (NCCN) guidelines [6]. For patients with unresectable tu- nostomy feeding tube was retained for home enteric nutri- mors, conservative treatment was performed. For patients tion until three months after discharge. Adjuvant therapy with a cTisN0M0 or cT1aN0M0 classification, endoscopic (chemotherapy/radiotherapy/chemoradiation) was admin- mucosal resection or endoscopic submucosal dissection istered in patients with advanced stage (pathological stage was implemented. For other patients, the choice between more than T3 or N1) based on the tumor-node-metastasis MIILE and Sweet esophagectomy was made by the patient (TNM) stage and the NCCN guidelines. The clinical and after informed consent was obtained (Fig. 1). Detailed data pathological stage was determined according to the 7th were gathered from a highly maintained in-house data- edition of the American Joint Committee on Cancer [9]. base. Techniques used in the two esophagectomy proce- dures have previously been described in detail [7, 8]. Adjuvant therapy Surgical procedures Chemotherapy included four cycles of cisplatin (75– General anesthesia and double-lumen endotracheal in- 100 mg/m ) on day 1 coupled with paclitaxel (120– 2 2 tubation were routinely used, combined with epidural 175 mg/m )ortaxane(60–75 mg/m )onday 2every anesthesia or thoracic paravertebral nerve blocks. 21 days or four cycles of cisplatin or nedaplatin (75– For MIILE, the patient was initially placed in a supine 100 mg/m ) on day 1 coupled with 5-fluorouracil position. Through laparoscopy, gastric tubulization and (500–750 mg/m ) on days 1–5 every 21 days. omental flap mobilization were performed, accompanied Radiotherapy was administered with a Trilogy® (Varian by abdominal lymph node dissection (paracardiac left Medical Systems) linear accelerator. A dose of 45–50.4 RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 3 of 13 Fig. 1 Patients who underwent esophagectomy between January 2011 and December 2017. ESCC = esophageal squamous cell carcinoma; EMR = endoscopic mucosal resection; ESD = endoscopic submucosal dissection; MIILE = minimally invasive Ivor Lewis esophagectomy Gy was administered in 1.8–2.0 Gy daily fractions for 19–9, carbohydrate antigen 242, carcinoembryonic anti- 5 weeks. gen, and squamous cell carcinoma antigen levels), cer- Chemoradiotherapy included cisplatin-based chemo- vical region ultrasonography, and thorax and abdominal therapy coupled with 45–50.4 Gy of radiation at a dose computed tomography. Esophagogastroscopy was per- of 1.8–2.0 Gy per fraction for 5 weeks. formed annually after surgery. The last follow-up date was December 30, 2017. Health-related quality of life evaluation QOL parameters were measured using the European Organization for Research and Treatment of Cancer Data collection and statistical analysis (EORTC) QOL C30 questionnaire and the Supplemental A low, normal, and high body mass index (BMI) were QOL-Esophageal Module 18 questionnaire [10, 11]. The defined as a BMI of less than 18.5, between 18.5 and 25, questionnaire was completed at admission and during post- and more than 25, respectively. Tumor diameter was operative follow-up dates (3, 6, 12, and 24 months) via dir- gauged at the final pathological examination. ect or indirect communication (mail, email or telephone). The QOL score was graded following the EORTC Scor- ing Manual. Higher global health and physical function Follow-up scores indicate better QOL, while higher scores for symp- Patients had follow-up appointments every three months toms such as pain imply poorer QOL. Overall survival during the first year and every six months thereafter. (OS) was defined as the length of time from the date of Clinical examinations included a physical examination, surgery to the last known living date. Disease-free survival evaluation of tumor biomarkers (carbohydrate antigen (DFS) was defined as the length of time from the date of RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 4 of 13 surgery to the date of death from any cause or recurrence Table 1 Patient characteristics after matching verified by pathological examination or imaging features. Characteristic MIILE (n = 216) Sweet (n = 216) p value Propensity score matching was used to balance the clin- Age, year 61(56~68) 61.46 ± 8.03 0.629 ical characteristics between the two groups. To estimate Gender, n (%) 0.593 the propensity score, a multinomial logistic regression Male 181(83.8) 185(85.6) model was applied based on age, gender, BMI, Charlson Female 35(16.2) 31(14.4) comorbidity index, tumor location, tumor invasion stage, BMI (kg/m ) 21.46 21.09 0.637 lymph node stage and pathological TNM stage. A 1:1 (19.26~23.04) (18.86~23.52) match was achieved using the nearest neighbor-matching CCI, n(%) 0.808 algorithm with a caliper definition of 0.02. Finally, 216 2 9(4.2) 13(6.0) paired cases were matched. This research project was ap- proved by Ethics Committee of the 2nd Affiliated Hos- 3 46(21.3) 48(22.2) pital, School of Medicine, Zhejiang University. 4 80(37.0) 84(38.9) Variables are presented as proportions, means, or medians 5 60(27.8) 54(25.0) where appropriate. Data werecompared using Student’st 6 21(9.7) 17(7.9) test, χ test, one-way ANOVA or the Mann-Whitney U test, 7 0(0.0) 0(0.0) as appropriate. The Kaplan-Meier method or Cox propor- Tumor length (cm) 4.0(3.0~5.0) 3.5(3.0~4.5) 0.178 tional hazards method was used to analyze OS and DFS. All statistical analyses were performed using SPSS (SPSS 19.0 Tumor location , n(%) 0.974 for Windows; SPSS Inc., Chicago, IL). A p-value less than Upper and middle 11(5.1) 10(4.6) 0.05 was defined as statistically significant. junction Middle 99(45.8) 100(46.3) Results Lower 106(49.1) 106(49.1) Clinical baseline Tumor stage , n(%) 0.594 After the short acceptance phase for the MIILE early in 1 46(21.3) 42(19.4) this study, the number of patients who chose the Sweet 2 28(13.0) 34(15.8) approach decreased and eventually became significantly less than that of those who elected MIILE (Fig. 1). As 3 136(63.0) 130(60.2) shown in Table 1, the demographic and clinical charac- T4 6(2.7) 10(4.6) teristics of the MIILE and Sweet groups were well bal- b Nodal stage , n(%) 0.675 anced. There was no significant difference between 0 107(49.5) 115(53.2) patients in these groups in terms of age, gender, BMI, 1 51(23.6) 54(25.0) comorbidities, tumor location or TNM stage. 2 33(15.3) 27(12.5) Perioperative outcomes and recurrence N3 25(11.6) 20(9.3) The perioperative comparisons are presented in Table 2. Pathologic stage , n(%) 0.794 MIILE procedure took longer and resulted in less blood I 50(23.1) 53(24.5) loss than the Sweet approach (200 (150–300) ml vs 300 II 68(31.5) 72(33.3) (250–400) ml, p < 0.001), but the blood transfusion rate III 98(45.4) 91(42.2) was similar. More lymph nodes in the RLN region and Adjuvant therapy, n(%) 0.962 in the thoracic and abdominal field were retrieved dur- ing MIILE procedure, and consequently the total lymph None 118(54.6) 123(56.9) node number was higher (31(22–40) vs 18(12–28), p < Chemotherapy 26(12.0) 24(11.1) 0.001). Note that the number of patients with RLN Chemoradiotherapy 44(20.4) 41(19.0) lymph node dissection was significantly higher in the Radiaotherapy 28(13.0) 28 (13.0) MIILE (164 vs 35, p < 0.001). Intraoperative frozen sec- a,b The classification of tumor pathology and location was based on the tions were routinely obtained, and R0 resection was ob- American Joint Committee on Cancer, 7th ed. MIILE = Minimally invasive Ivor tained for all patients. Lewis esophagectomy; BMI Body mass index, CCI Charlson comorbidity index The MIILE group began oral intake earlier (6 (5–7) days vs 9 (7–11) days, p < 0.001) and left the hospital earlier (13 (11-16) days vs 18 (16–25) days, p < 0.001). MIILE, namely, six operations for chylothorax, five for More complications, especially pneumonia, occurred in wound infections, four for anastomotic leakage, two for in- the Sweet group. The reoperation rate was similar. Nine- testinal obstructions, one for intrathoracic hemorrhage, and teen reoperations were performed in patients from the one for abdominal hemorrhage. Seventeen patients in the RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 5 of 13 Table 2 Perioperative outcomes and recurrence pattern Characteristic MIILE (n = 216) Sweet (n = 216) p value Total surgical time(min) 265.5(214~330) 201.0(180~236) < 0.001 Blood loss(ml) 200(150~300) 300(250~400) < 0.001 Blood transfusion, n(%) 14(6.5) 18(8.3) 0.462 Lymphadenectomy, n RLN 7(3~10) 3(2~4) < 0.001 Thoracic 14(9~19) 10(6~14) < 0.001 Abdominal 10(6~15) 9(5~14) 0.034 Total 31(22~40) 18(12~28) < 0.001 Initiation of oral intake, d 6(5~7) 9(7~11) < 0.001 Length of stay, d Intensive care unit 4(2~6) 3(2~6) 0.629 Postoperative hospital 13(11~16) 18(16~25) < 0.001 Complications, n(%) Anastomotic leak 15/216 (6.9) 16/216(7.4) 0.852 Esophagotracheal fistula 3/216(1.4) 2/216(0.9) 0.653 Atrial fibrillation 56/216(25.9) 67/216 (31.0) 0.241 Pneumonia 80/216(37.0) 104/216(48.1) 0.020 ARDS 8/216(3.7) 11/216(5.1) 0.481 Recurrent laryngeal nerve injury 6/216(2.8) 1/216(0.5) 0.057 Chylothorax 8/216(3.7) 7/216(3.2) 0.793 Wound infection 11/216(5.1) 13/216(6.0) 0.674 Ileus 3/216(1.4) 0/216(0.0) 0.248 Volvulus 1/216(0.5) 0/216(0.0) 1.000 Total 110/216(50.9) 148/216(68.5) < 0.001 Reoperation, n(%) 19(8.8) 17(7.9) 0.728 Mortality within postoperative-30-day,n 5 6 0.760 Recurrence, n(%) Locoregional recurrence 42/89(47.2) 56/95(58.9) 0.108 Anastomosis site 4/42(9.5) 3/56(5.3) 0.703 Cervical/supraclavicular- lymph node 4/42(9.5) 9/56(16.1) 0.159 Mediastinal lymph node 18/42(42.9) 29/56(51.8) 0.089 Abdominal lymph node 16/42(38.1) 15/56(26.8) 0.852 Distance recurrence 47/89(52.8) 39/95(41.1) 0.335 Liver 15/47(31.9) 13/39(33.3) 0.696 Bone 12/47(25.6) 8/39(20.5) 0.360 Lung 11/47(23.4) 12/39(30.8) 0.830 Other sites 9/47(19.1) 6/39(15.4) 0.647 Multiple sites 9/98(9.2) 6/101(5.9) 0.430 Total 98/216(45.4) 101/216(46.7) 0.772 Data are shown as number (%) and continuous data as mean standard deviation or median (interquartile range) 81 patients in MIILE and 73 patients in Sweet had two or more than two complications MIILE Minimally invasive Ivor Lewis esophagectomy RLN Recurrent laryngeal nerves ARDS Acute respiratory distress syndrome RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 6 of 13 Sweet group required reoperation. There were four opera- Recurrence was observed in nearly half of patients tions for anastomotic leakage, four for chylothorax, five for (45.4% in the MIILE group vs 46.7% in the Sweet group, wound infections, two for intrathoracic hemorrhage, and p = 0.772). The recurrence pattern was similar between two for abdominal hemorrhage. the MIILE group and the Sweet group (locoregional, 42 There was no intraoperative mortality. The postopera- vs 56, p = 0.108; distant, 47 vs 39, p = 0.335); in half of tive 30-day mortality rate did not differ significantly be- the patients, recurrence was observed at distant sites, tween approaches. Five postoperative deaths occurred in mainly the liver, lungs, and bone. the MIILE group. One patient died from anastomotic leakage, three died from severe pneumonia, and one died Survival from sudden cardiac arrest. Six patients in the Sweet The median follow-up time was 36 months. The 2-year group died. Two patients died from anastomotic leakage, OS and DFS rates for all patients were 59.4 and 35.0%, re- three died from respiratory failure secondary to pulmon- spectively, and the 5-year OS and DFS rates were 54.8 and ary infection, and one died from congestive heart failure. 34.0%, respectively. There was no significant difference in Fig. 2 Overall survival curves by MIILE and the Sweet approach for (a) the entire cohort (p = 0.503) and for patients with (b)TNM stageI(p = 0.029), (c)TNM stage II (p = 0.544), (d) TNM stage III (p = 0.468). Kaplan-Meier, Log-rank. MIILE = minimally invasive Ivor Lewis esophagectomy. TNM = tumor-node-metastasis RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 7 of 13 OS and DFS between groups (Fig. 2 and Fig. 3). Patients hazards model revealed that TNM stage and postopera- in the MIILE group classified as TNM stage I showed su- tive complications were independent prognostic factors perior OS and DFS. for survival of the whole cohort (Table 4). Table 3 shows the results of the univariate analysis of RLN lymph node metastasis was associated with poor OS clinicopathologic variables influencing OS and DFS. The and DFS in the whole cohort and in the MIILE group but factors tumor diameter (≤3 cm vs > 3 cm), depth of had no influence on survival in the Sweet group (Fig. 4). tumor invasion (T1–2vs T3–4), lymph node metastasis status (N0 vs N1–3), TNM stage (I vs II vs III), and oc- Quality of life currence of postoperative pneumonia and complications The QOL results are shown in Table 5. There was no affected the OS and DFS of the whole cohort. Further significant difference in the baseline level of QOL. MIILE analysis showed that a high BMI was associated with group scored significantly higher in the postoperative global better OS in the MIILE group, and atrial fibrillation was health and physical component and lower in symptom cat- associated with worse DFS in the Sweet group. Regres- egories than the Sweet group. Furthermore, the scores for sion analysis using a multivariable Cox proportional global health, physical function, role function, emotional Fig. 3 Disease-free survival by MIILE and the Sweet approach for (a) the entire group (p = 0.370) and patients with (b) TNM stage I (p = 0.006), (c) TNM stage II (p = 0.582), and (d) TNM stage III (p = 0.459). Kaplan-Meier, Log-rank; MIILE = minimally invasive Ivor Lewis esophagectomy. TNM = tumor-node-metastasis RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 8 of 13 Table 3 Clinicopathologic characteristics and prognostic factor for survival of 432 ESCC patients Characteristic Total (n = 432) MIILE (n = 216) Sweet (n = 216) No p value No p value No p value OS DFS OS DFS OS DFS Gender Male 366 0.505 0.393 181 0.551 0.422 185 0.748 0.679 Female 66 35 31 Age(year) < 65 267 0.902 0.943 132 0.126 0.189 135 0.158 0.179 ≥ 65 165 84 81 BMI (kg/m ) ≤ 18.5 86 33 53 * * * * * * 18.5~25 287 0.277 0.169 156 0.717 0.528 131 0.244 0.165 * * * * * * ≥ 25 59 0.182 0.082 27 0.053 0.024 32 0.789 0.696 Tumor location Upper and middle junction 21 11 10 ** ** ** ** ** ** Middle third 199 0.898 0.964 99 0.524 0.471 100 0.761 0.616 ** ** ** ** ** ** Lower third 212 0.766 0.853 106 0.350 0.331 106 0.617 0.445 Tumor length(cm) ≤ 3 139 < 0.001 < 0.001 78 0.013 0.003 61 0.005 0.016 >3 293 138 155 Depth of invasion (T) T1–2 150 < 0.001 < 0.001 74 < 0.001 < 0.001 76 0.201 0.481 T3–4 282 142 140 Lymph node metastasis (N) N0 222 < 0.001 < 0.001 107 < 0.001 < 0.001 115 < 0.001 < 0.001 N1–3 210 109 101 Pathology stage (TNM) *** *** *** *** *** *** I 103 0.050 0.053 50 0.004 0.002 53 0.091 0.876 **** **** **** **** **** **** II 140 < 0.001 < 0.001 68 < 0.001 < 0.001 72 < 0.001 < 0.001 ***** ***** ***** ***** ***** ***** III 189 < 0.001 < 0.001 98 < 0.001 < 0.001 91 < 0.001 < 0.001 Atrial fibrillation Yes 123 0.144 0.086 56 0.493 0.594 67 0.124 0.038 No 309 160 149 Pneumonia complication (including ARDS) Yes 203 < 0.001 < 0.001 88 0.008 0.010 115 < 0.001 < 0.001 No 229 128 101 Postoperative complication Yes 258 < 0.001 < 0.001 110 0.294 0.424 148 < 0.001 < 0.001 No 174 106 68 * ** *** **** ***** Compared with low BMI group (≤18.5), log-rank. Compared with upper third group, log-rank. I compared with II, log-rank; II compared with III, log-rank; I compared with III, log-rank MIILE minimally invasive Ivor Lewis esophagectomy OS overall survival DFS disease-free survival BMI body mass index TNM tumor-node-metastasis ARDS Acute respiratory distress syndrome RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 9 of 13 Table 4 Multivariate analysis by Cox proportional hazard model Characteristic Total (n = 432) MIILE (n = 216) Sweet (n = 216) p value p value p value OS DFS OS DFS OS DFS Age 0.891 0.887 0.280 0.427 0.128 0.111 Gender 0.181 0.186 0.127 0.231 0.922 0.712 TNM stage < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 Tumor location 0.641 0.476 0.945 0.775 0.863 0.502 Tumor length 0.110 0.070 0.275 0.031 0.620 0.414 BMI 0.574 0.378 0.442 0.399 0.897 0.688 Postoperative complication < 0.001 < 0.001 0.505 0.843 0.854 < 0.001 Surgical approach 0.415 0.407 –– –– MIILE minimally invasive Ivor Lewis esophagectomy OS overall survival DFS disease-free survival TNM tumor-node-metastasis BMI body mass index -=no p value function, cognitive function, social function, fatigue, and similar studies (47–54.3%) [20, 21]and maybeascribedto pain improved faster in the MIILE group. the tumor location, undetectable metastasis, depth of inva- sion and lymph node metastasis status [22, 23]. Thus, close Discussion follow-up of patients is recommended. Although left transthoracic esophagectomy is the pri- Although the OS and DFS results were similar between mary surgical approach for ESCC in China, the debate groups, superior survival of patients with TNM stage I was regarding the left and right thoracic approaches remains noted in the MIILE, which may be due to the advantage of unsettled [12, 13]. MIILE has been demonstrated to have this approach in lymph node resection (magnified views, advantages over the open Ivor Lewis approach in the better exposure, and longer instruments), especially in the treatment of esophageal adenocarcinoma patients [3, 14], RLN field. Radical lymph node resection with RLN lymph- but its effect on the long-term survival of patients with adenectomy, such as that performed during MIILE, can re- ESCC needs further investigation. There have also been move more potential cancer-positive lymph nodes, allow few detailed comparisons between MIILE and the left more accurate staging and therapy, and offer a better prog- transthoracic approach (Sweet approach) in ESCC pa- nosis in patients with early stage ESCC [24, 25]. Our results tients [15, 16]. To fill this gap in knowledge, we compared also demonstrated that the frequency of lymph node metas- the QOL and survival of patients who underwent MIILE tasis along the RLN is high, which is consistent with the as- and the Sweet procedure. sociation of lymph node status with survival benefit [26]. We found that both surgical procedures were comparable However, RLN lymph node metastasis did not influence the at the clinical baseline. The short-term advantages of survival of patients in the Sweet group, which may be ex- MIILE, such as decreased blood loss, reduced hospital stay, plained by the limited superior mediastinal lymphadenec- and decreased pain were in line with those reported previ- tomy performed during the Sweet procedure and the ously [16, 17]. Similar to previous studies [16, 18], there omission of RLN lymphadenectomy [27]. Moreover, the were significantly fewer respiratory complications in pa- lymph nodes along the common hepatic and celiac arteries tients who underwent MIILE. This finding could be as- were not routinely retrieved during the Sweet procedure, cribed to reduced pulmonary parenchymal trauma and which could misguide pathological TNM staging and treat- gentle lung retraction with the thoracoscope. In addition, ment protocols. Thus, our findings support the recommen- the minimally invasive incisions made during MIILE pro- dation that radical lymphadenectomy, including removal of cedure resulted in less intercostal nerve injury, which re- the bilateral RLN lymph nodes, should be performed dur- duced pain and allowed effective expectoration. Compared ing esophagectomy [28]. with the Sweet approach, MIILE approach accelerated the Among factors affecting survival, the influence of a recovery phase, as MIILE patients had decreased ICU stays, longer tumor diameter may be ascribed to a more ad- accelerated oral intake and shortened postoperative hospital vanced TNM stage [29], and the impact of high BMI stays. The recurrence pattern was similar between ap- may be due to its relationship to a lower pathological proaches, which needs further investigation [19]. The rela- stage [30]. The TNM stage and occurrence of postopera- tively high recurrence rate was comparable to those in tive complications were independent prognostic factors, RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 10 of 13 Fig. 4 (See legend on next page.) RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 11 of 13 (See figure on previous page.) Fig. 4 Overall survival curve and disease-free survival curves stratified by RLN lymph node metastasis status in 199 patients with RLN lymph nodes retrieved in the whole cohort (a p < 0.001 and b p < 0.001, respectively), 164 patients with RLN lymph nodes retrieved in the MIILE group (c p < 0.001 and d p < 0.001, respectively), and 35 patients with RLN lymph nodes retrieved in the Sweet group (e p = 0.776 and f p = 0.816, respectively). MIILE = minimally invasive Ivor Lewis esophagectomy. RLN = recurrent laryngeal nerve. LN = lymph node Table 5 Quality of Life After Surgery Characteristic MIILE (n = 92) Sweet (n = 94) Baseline 3 months 6 months 12 months 24 months Baseline 3 months 6 months 12 months 24 months EORTC C30 * ** Global health 73.53 ± 65.82 ± 69.29 ± 72.69 ± 15.98 74.02 ± 75.89 ± 16.06 49.32 ± 57.13 ± 62.63 ± 10.37 71.81 ± */** */** ** ** 11.19 11.54 12.38 16.49 10.01 14.89 15.19 Functioning scales ** Physical 84.89(73.03– 66.94 ± 73.57 ± 81.34 84.40 ± 84.00 50.20 ± 48.69 ± 72.58 ± 12.50 73.08 ± */** */** */** * ** ** ** functioning 93.24) 10.47 12.61 (70.61–89.29) 10.18 (76.12–93.64) 8.45 12.38 14.74 Role 82.31(73.63– 61.64 ± 71.18 ± 80.88 ± 8.59 81.21 ± 79.16 ± 11.16 54.56 ± 59.72 ± 75.96 ± 12.51 81.48 ± */** */** ** ** functioning 90.02) 10.80 8.08 10.02 1.38 8.67 9.22 * ** Emotional 70.06 ± 73.30 ± 11.97 77.81 ± 78.62 ± 10.46 81.58 ± 70.00 ± 8.20 63.19 ± 69.74 ± 79.98 79.38 ± */** ** ** ** ** functioning 11.78 11.18 11.3 10.76 7.29 (71.25–90.41) 9.91 Symptom scales */** */** ** Fatigue 21.46 ± 44.16 ± 9.26 36.14 ± 27.97 ± 6.47 23.15 ± 21.40 ± 11.49 59.19 ± 49.14 ± 31.78 ± 13.40 26.23 ± */** ** ** ** 11.55 18.23 12.33 10.26 12.93 14.40 */** ** Pain 19.54 ± 9.46 32.62(23.79– 30.09 ± 26.83 ± 6.31 24.58 ± 18.78 ± 7.49 56.15 ± 40.88 ± 30.29 ± 10.48 25.74 ± */** */** ** ** ** ** 39.34) 7.76 9.12 1.61 12.56 5.36 */** ** ** Dyspnea 12.47 ± 6.63 26.78 ± 9.31 22.06 ± 16.11 ± 9.65 14.10 ± 12.80 ± 7.19 32.36 ± 25.00 ± 17.63 ± 5.68 14.12 ± */** ** ** 7.64 6.50 10.91 8.33 6.52 */** ** Insomnia 22.06 ± 9.97 34.68 ± 29.77 ± 25.81 ± 10.21 21.97 ± 24.24 ± 10.61 41.88 ± 39.40 ± 29.19 ± 9.47 21.45 ± */** */** ** ** 10.55 7.99 10.97 12.90 11.96 12.74 */** ** Appetite loss 36.01 ± 22.81 ± 22.81 ± 17.91 ± 9.43 19.45 ± 31.80 ± 19.17 27.06 ± 23.99 ± 22.33 ± 11.28 21.07 ± */** ** ** ** ** ** 12.24 12.74 13.07 8.78 10.95 13.41 8.79 ** Constipation 22.11 ± 17.87 ± 16.03 17.44 ± 1.23 16.20 ± 17.40(8.39– 22.64 ± 21.46(7.65– 18.88 ± 8.06 17.94 ± */** ** ** 13.20 11.58 (9.37–28.83) 7.81 26.69) 12.1 32.99) 9.23 EORTC OES 18 ** ** ** Dysphagia 39.26 ± 26.15 ± 13.22 23.80 ± 22.66 ± 11.98 17.29 ± 39.86 ± 10.03 27.55 ± 26.43 ± 23.02 ± 12.56 18.09 ± ** ** ** ** ** 17.21 12.06 7.39 15.03 12.16 8.73 ** ** Eating 39.57 ± 36.63 32.12 ± 24.66 ± 10.70 22.81 ± 39.00 ± 11.55 34.41 ± 29.27 ± 25.69 ± 12.28 22.15 ± ** ** ** ** ** ** 11.90 (31.88–42.97) 10.29 8.38 11.57 14.67 9.75 ** ** ** Reflux 21.67 ± 37.58 ± 12.41 33.31 ± 32.05 ± 13.96 29.57 ± 22.23 ± 11.59 37.74 ± 33.16 ± 33.06 ± 13.78 31.79 ± ** ** ** ** ** 10.37 16.21 10.20 17.40 15.51 15.02 Pain 16.55 ± 25.02 ± 14.21 ± 12.56 ± 7.12 11.92 ± 18.24 ± 10.33 28.13 ± 25.49 ± 15.50 ± 9.48 12.27 ± */** * ** ** ** 11.47 10.00 7.93 6.14 10.80 11.92 7.20 ** */** ** Choking 31.97 ± 23.08 ± 10.24 22.87 ± 21.60 ± 10.92 21.17 ± 31.33 ± 12.18 20.36 ± 25.42 ± 25.11 ± 9.80 20.06 ± ** ** ** ** ** 14.17 13.60 12.78 12.74 14.50 10.48 ** ** ** Coughing 12.03 27.51 ± 11.64 25.96 ± 21.52 ± 9.58 19.93 ± 14.32 28.11 ± 24.97 ± 20.71 ± 8.37 22.19 ± ** ** ** ** ** (6.94–20.54) 8.67 8.49 (4.79–22.67) 14.80 8.07 10.64 Data are shown as number (%) and continuous data as mean standard deviation or median (interquartile range) Measures aspects of health and function; scores range from 0 to 100, with higher scores representing better well-being. Assesses aspects of oesophageal symptoms; scores range from 0 to 100, with lower scores indicating better function Every date was compared between groups and with the baseline within respective group, only p < 0.05 was notified: MIILE compared with Sweet p < 0.05 ** compared with baseline p < 0.05 EORTC European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, MIILE minimally invasive Ivor Lewis esophagectomy RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 12 of 13 which implies that early diagnosis, prompt treatment, Acknowledgments None. and cautious ward management are essential for improv- ing survival [31, 32]. Funding QOL after esophagectomy is an important factor con- This work was supported by a grant of the Zhejiang Provincial Natural Science Foundation (grant number LY16H010004, LY18H170001, sidering the high morbidity and poor prognosis of LQ17H010002) and a grant of Zhejiang Provincial Department of Education esophageal carcinoma patients. QOL was impaired after (Y201635465). The sponsors played no role in the study design, data surgery and gradually recovered within 6–12 months in collection or interpretation, or analysis, or decision to submit the article for publication. both groups. A significant difference favoring MIILE was found in the global health, physical component sum- Availability of data and materials mary, and symptom categories in postoperative patients The data that support the findings of this study are available upon request at three to six months, which is in line with observations from the corresponding author Wu Ming. The data are not publicly available as individuals were not consented for the release of their information into a made in previous studies [16, 33]. The advantage of public database. MIILE in QOL may be ascribed to decreased surgical trauma and reduced pain [33]. Authors’ contributions For propensity score matching and minimizing the WQ, WZX, ZTW, and FS collected the data, performed the statistical analysis, analyzed data, and wrote the manuscript. ZS, SG, and WM analyzed data and statistical bias, patients who received neoadjuvant ther- wrote the manuscript. All authors read and approved the final manuscript. apy were not enrolled in this study because most of them chose MIILE afterwards. Neoadjuvant therapy has Ethics approval and consent to participate been increasingly adopted in esophageal cancer patients This research project was approved by Ethics Committee of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. In this study, with conflicting results [34, 35]. In addition, the optimal written informed consent was obtained from the patients or their families, neoadjuvant protocol needs further investigation. The and patient anonymity was preserved. likelihood that the conclusions of this study would be in- Consent for publication fluenced by the downstaging effect of neoadjuvant ther- Not applicable. apy should not be disregarded. The strength of this study lies in the large sample size, Competing interests which is one of the largest for propensity score-matched The authors declare that they have no competing interests. comparisons between ESCC patients undergoing MIILE and the Sweet procedure. This study has intrinsic limita- Publisher’sNote tions regarding statistical bias because it was retrospect- Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ive and nonrandomized and was also based on the experience of a single surgeon. In addition, it is unclear Received: 28 November 2018 Accepted: 29 April 2019 whether the results of this study were influenced by the postoperative treatments, and the effect of adjuvant ther- References apy on patients was not evaluated. The indications for 1. Mao YS, He J, Xue Q, Shao K, Su K, Li N, et al. Nationwide speaking tour of postoperative therapy in ESCC are still under debate. In standardized diagnosis and treatment for esophageal cancer. Zhonghua addition, the optimal adjuvant protocol for ESCC needs Wei Chang Wai Ke Za Zhi. 2013;16(9):801–4. 2. Takeuchi H, Miyata H, Ozawa S, Udagawa H, Osugi H, Matsubara H, et al. further analysis. 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An outcome comparison of adenocarcinoma of the esophagus to squamous cell carcinoma after improve survival, radical lymph node dissection and transthoracic esophagectomy. Turkish Journal of Thoracic and regular follow-up are recommended. Cardiovascular Surgery. 2013;21(2):402–7. 6. NCCN Clinical Practice Guidelines in Oncology for Esophageal and Esophagogastric Junction Cancers. Washington, PA, USA: National Abbreviations Comprehensive Cancer Network [first cited 20 Sept 2010 and updated BMI: Body Mass Index; DFS: disease-free survival; EORTC: European online ]. Available from: https://www.nccn.org/professionals/physician_gls/ Organization for Research and Treatment of Cancer; ESCC: Esophageal pdf/esophageal.pdf/. squamous cell carcinoma; ICU: Intensive care unit; MIILE: Minimally invasive 7. Pennathur A, Awais O, Luketich JD. Technique of minimally invasive Ivor Ivor Lewis esophagectomy; NCCN: National Comprehensive Cancer Network; Lewis Esophagectomy. Ann Thorac Surg. 2010;89(6):S2159–62. OS: Overall survival; QOL: Quality of life; RLN: Recurrent laryngeal nerve; 8. Churchill ED, Sweet RH. Transthoracic resection of tumors of the esophagus TNM: Tumor-node-metastasis and stomach. Ann Surg. 1942;116:566–73. RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 13 of 13 9. Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer staging 29. Worrell SG, Alicuben ET, Oh DS, Hagen JA, DeMeester SR. Accuracy of manual: esophagus and Esophagogastric junction. Ann Surg Oncol. 2010; clinical staging and outcome with primary resection for local-regionally 17(7):1721–4. limited esophageal adenocarcinoma. Ann Surg. 2018;267(3):484–8. 10. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. 30. Miao LS, Chen HQ, Xiang JQ, Zhang YW. 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Ann Surg. 2018; term results of neoadjuvant chemoradiotherapy using cisplatin and 5- 267(5):826–32. fluorouracil followed by esophagectomy for resectable, locally advanced 14. Tapias LF, Mathisen DJ, Wright CD, Wain JC, Gaissert HA, Muniappan A, et al. esophageal squamous cell carcinoma. J Radiat Res. 2018;59:616–24. Outcomes with open and minimally invasive Ivor Lewis Esophagectomy 35. Hamai Y, Hihara J, Emi M, Furukawa T, Murakami Y, Nishibuchi I, et al. after neoadjuvant therapy. Ann Thorac Surg. 2016;101(3):1097–103. Evaluation of prognostic factors for esophageal squamous cell carcinoma 15. Li B, Xiang JQ, Zhang YW, Li HC, Zhang J, Sun YH, et al. Comparison of Ivor- treated with neoadjuvant Chemoradiotherapy followed by surgery. World J Lewis vs Sweet Esophagectomy for esophageal squamous cell carcinoma a Surg. 2018;42(5):1496–505. randomized clinical trial. Jama Surg. 2015;150(4):292–8. 16. Wang H, Shen YX, Feng MX, Zhang Y, Jiang W, Xu ST, et al. 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RETRACTED ARTICLE: Comparison of minimally invasive Ivor Lewis esophagectomy and left transthoracic esophagectomy in esophageal squamous cell carcinoma patients: a propensity score-matched analysis

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Springer Journals
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Copyright © The Author(s). 2019
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Biomedicine; Cancer Research; Oncology; Surgical Oncology; Health Promotion and Disease Prevention; Biomedicine, general; Medicine/Public Health, general
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Abstract

Background: To investigate the long-term efficacy of the minimally invasive Ivor Lewis esophagectomy (MIILE) in esophageal squamous cell carcinoma (ESCC) patients, a retrospective comparison of the quality of life (QOL) and survival between patients who underwent MIILE and left transthoracic esophagectomy (Sweet approach) was conducted. Methods: A detailed database search identified 614 patients who underwent MIILE and 243 patients who underwent Sweet esophagectomy between January 2011 and December 2017. After propensity score matching, 216 paired cases were selected for statistical analysis. Survival was evaluated with Kaplan-Meier curves or Cox models. Results: MIILE was associated with a longer duration, less blood loss and more lymph node dissected than Sweet esophagectomy. MIILE patients suffered from less pain, less frequently developed pneumonia, and had fewer postoperative complications. Additionally, MIILE patients began oral intake earlier and had a shorter postoperative hospital stay, and enhanced recovery of QOL. There was no significant difference between the approaches regarding the recurrence pattern, 2-year and 5-year overall survival (OS) or disease-free survival (DFS), except that patients with tumor- node-metastasis (TNM) stage I in the MIILE group demonstrated superior OS and DFS. Pathological TNM stage and postoperative complications were determined to be independent prognostic factors based on the multivariate analysis. Conclusion: MIILE is a safe and feasible approach for treating ESCC patients. MIILE approach may provide more postoperative advantages, enhanced QOL improvement, and more favorable long-term survival in early stage patients than the Sweet procedure. Keywords: Minimally invasive surgery, Ivor Lewis esophagectomy, Left transthoracic esophagectomy, Esophageal squamous cell carcinoma * Correspondence: iwuming22@zju.edu.cn Wang Qi and Wu Zixiang are These authors contributed to the work equally and should be regarded as co-first authors Department of Thoracic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 JieFang Rd, Hangzhou 310009, China © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 2 of 13 Background and right, common hepatic artery, splenic artery, left Surgical resection with lymphadenectomy remains the gastric artery, and celiac). This procedure was followed curative choice for esophageal cancer; however, the opti- by the insertion of a jejunal feeding tube. Before closure, mal surgical approach is uncertain. Unlike in the West- the abdomen was drained. Subsequently, the patient was ern world, where the use of transthoracic and transhiatal turned to the left lateral decubitus position. After esophagectomy is debated, transthoracic esophagectomy, esophageal mobilization and lymphadenectomy (peri-e- especially the left transthoracic (Sweet) approach, has sophageal, lower posterior mediastinal, right and left re- been widely adopted in China [1]. Minimally invasive current laryngeal nerve (RLN), carina, and right Ivor Lewis esophagectomy (MIILE) is gaining popularity paratracheal), intrathoracic anastomosis was completed because of its short-term advantages over open ap- using a circular stapler or the hand-sewn method. Thor- proaches in treating esophageal adenocarcinoma [2, 3]. acic duct ligation was routinely performed. Finally, a However, the long-term outcomes of esophageal squa- nasogastric tube was placed, and the thorax was drained. mous cell carcinoma (ESCC) patients undergoing MIILE For the Sweet approach, the patient was placed in the need further investigation, as the biological and clinical right lateral decubitus position. A left posterolateral patterns of ESCC significantly differ from those of thoracotomy was performed through the sixth or sev- esophageal adenocarcinoma [4, 5]. enth intercostal space. After esophageal isolation and To investigate the long-term effects of MIILE on thoracic lymphadenectomy, the diaphragm was incised ESCC patients, a propensity score-matched study was to mobilize the stomach and dissect the abdominal conducted. We retrospectively compared clinical data lymph nodes. A gastric tube, normally 4–5 cm in width, from patients who underwent MIILE or the Sweet ap- was formed along the arcus major ventriculi. Intratho- proach and evaluated postoperative outcomes, quality of racic esophagogastric anastomosis was constructed using life (QOL), and survival. a circular stapler or the hand-sewn method. A nasoen- teric feeding tube was inserted in the jejunum, and a Methods nasogastric tube was placed. Subsequently, the thorax From January 2011 to December 2017, 1160 ESCC pa- was drained. tients who did not receive neoadjuvant therapy were ad- mitted for surgical assessment. The operability evaluation Postoperative treatment included a panel of oncological assessments (including Patients were routinely monitored in the intensive care contrast computed tomography of the chest and upper ab- unit (ICU) until their vital signs were stabilized. Enteral domen, esophageal gastroscopy, barium esophagography, nutrition was initiated on the first day after surgery. Oral endoscopic ultrasound, and positron emission tomog- intake was usually permitted after the presence of an in- raphy), and standard pulmonary and cardiac function tact anastomosis was verified by an esophagogram, the tests. The treatment regimen was decided by a multidis- implementation of which was closely related to each pa- ciplinary team and the patient based on the clinical stage tient’s recovery status. Chest drains were removed when and the National Comprehensive Cancer Network drainage volumes were less than 100 ml/24 h. The jeju- (NCCN) guidelines [6]. For patients with unresectable tu- nostomy feeding tube was retained for home enteric nutri- mors, conservative treatment was performed. For patients tion until three months after discharge. Adjuvant therapy with a cTisN0M0 or cT1aN0M0 classification, endoscopic (chemotherapy/radiotherapy/chemoradiation) was admin- mucosal resection or endoscopic submucosal dissection istered in patients with advanced stage (pathological stage was implemented. For other patients, the choice between more than T3 or N1) based on the tumor-node-metastasis MIILE and Sweet esophagectomy was made by the patient (TNM) stage and the NCCN guidelines. The clinical and after informed consent was obtained (Fig. 1). Detailed data pathological stage was determined according to the 7th were gathered from a highly maintained in-house data- edition of the American Joint Committee on Cancer [9]. base. Techniques used in the two esophagectomy proce- dures have previously been described in detail [7, 8]. Adjuvant therapy Surgical procedures Chemotherapy included four cycles of cisplatin (75– General anesthesia and double-lumen endotracheal in- 100 mg/m ) on day 1 coupled with paclitaxel (120– 2 2 tubation were routinely used, combined with epidural 175 mg/m )ortaxane(60–75 mg/m )onday 2every anesthesia or thoracic paravertebral nerve blocks. 21 days or four cycles of cisplatin or nedaplatin (75– For MIILE, the patient was initially placed in a supine 100 mg/m ) on day 1 coupled with 5-fluorouracil position. Through laparoscopy, gastric tubulization and (500–750 mg/m ) on days 1–5 every 21 days. omental flap mobilization were performed, accompanied Radiotherapy was administered with a Trilogy® (Varian by abdominal lymph node dissection (paracardiac left Medical Systems) linear accelerator. A dose of 45–50.4 RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 3 of 13 Fig. 1 Patients who underwent esophagectomy between January 2011 and December 2017. ESCC = esophageal squamous cell carcinoma; EMR = endoscopic mucosal resection; ESD = endoscopic submucosal dissection; MIILE = minimally invasive Ivor Lewis esophagectomy Gy was administered in 1.8–2.0 Gy daily fractions for 19–9, carbohydrate antigen 242, carcinoembryonic anti- 5 weeks. gen, and squamous cell carcinoma antigen levels), cer- Chemoradiotherapy included cisplatin-based chemo- vical region ultrasonography, and thorax and abdominal therapy coupled with 45–50.4 Gy of radiation at a dose computed tomography. Esophagogastroscopy was per- of 1.8–2.0 Gy per fraction for 5 weeks. formed annually after surgery. The last follow-up date was December 30, 2017. Health-related quality of life evaluation QOL parameters were measured using the European Organization for Research and Treatment of Cancer Data collection and statistical analysis (EORTC) QOL C30 questionnaire and the Supplemental A low, normal, and high body mass index (BMI) were QOL-Esophageal Module 18 questionnaire [10, 11]. The defined as a BMI of less than 18.5, between 18.5 and 25, questionnaire was completed at admission and during post- and more than 25, respectively. Tumor diameter was operative follow-up dates (3, 6, 12, and 24 months) via dir- gauged at the final pathological examination. ect or indirect communication (mail, email or telephone). The QOL score was graded following the EORTC Scor- ing Manual. Higher global health and physical function Follow-up scores indicate better QOL, while higher scores for symp- Patients had follow-up appointments every three months toms such as pain imply poorer QOL. Overall survival during the first year and every six months thereafter. (OS) was defined as the length of time from the date of Clinical examinations included a physical examination, surgery to the last known living date. Disease-free survival evaluation of tumor biomarkers (carbohydrate antigen (DFS) was defined as the length of time from the date of RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 4 of 13 surgery to the date of death from any cause or recurrence Table 1 Patient characteristics after matching verified by pathological examination or imaging features. Characteristic MIILE (n = 216) Sweet (n = 216) p value Propensity score matching was used to balance the clin- Age, year 61(56~68) 61.46 ± 8.03 0.629 ical characteristics between the two groups. To estimate Gender, n (%) 0.593 the propensity score, a multinomial logistic regression Male 181(83.8) 185(85.6) model was applied based on age, gender, BMI, Charlson Female 35(16.2) 31(14.4) comorbidity index, tumor location, tumor invasion stage, BMI (kg/m ) 21.46 21.09 0.637 lymph node stage and pathological TNM stage. A 1:1 (19.26~23.04) (18.86~23.52) match was achieved using the nearest neighbor-matching CCI, n(%) 0.808 algorithm with a caliper definition of 0.02. Finally, 216 2 9(4.2) 13(6.0) paired cases were matched. This research project was ap- proved by Ethics Committee of the 2nd Affiliated Hos- 3 46(21.3) 48(22.2) pital, School of Medicine, Zhejiang University. 4 80(37.0) 84(38.9) Variables are presented as proportions, means, or medians 5 60(27.8) 54(25.0) where appropriate. Data werecompared using Student’st 6 21(9.7) 17(7.9) test, χ test, one-way ANOVA or the Mann-Whitney U test, 7 0(0.0) 0(0.0) as appropriate. The Kaplan-Meier method or Cox propor- Tumor length (cm) 4.0(3.0~5.0) 3.5(3.0~4.5) 0.178 tional hazards method was used to analyze OS and DFS. All statistical analyses were performed using SPSS (SPSS 19.0 Tumor location , n(%) 0.974 for Windows; SPSS Inc., Chicago, IL). A p-value less than Upper and middle 11(5.1) 10(4.6) 0.05 was defined as statistically significant. junction Middle 99(45.8) 100(46.3) Results Lower 106(49.1) 106(49.1) Clinical baseline Tumor stage , n(%) 0.594 After the short acceptance phase for the MIILE early in 1 46(21.3) 42(19.4) this study, the number of patients who chose the Sweet 2 28(13.0) 34(15.8) approach decreased and eventually became significantly less than that of those who elected MIILE (Fig. 1). As 3 136(63.0) 130(60.2) shown in Table 1, the demographic and clinical charac- T4 6(2.7) 10(4.6) teristics of the MIILE and Sweet groups were well bal- b Nodal stage , n(%) 0.675 anced. There was no significant difference between 0 107(49.5) 115(53.2) patients in these groups in terms of age, gender, BMI, 1 51(23.6) 54(25.0) comorbidities, tumor location or TNM stage. 2 33(15.3) 27(12.5) Perioperative outcomes and recurrence N3 25(11.6) 20(9.3) The perioperative comparisons are presented in Table 2. Pathologic stage , n(%) 0.794 MIILE procedure took longer and resulted in less blood I 50(23.1) 53(24.5) loss than the Sweet approach (200 (150–300) ml vs 300 II 68(31.5) 72(33.3) (250–400) ml, p < 0.001), but the blood transfusion rate III 98(45.4) 91(42.2) was similar. More lymph nodes in the RLN region and Adjuvant therapy, n(%) 0.962 in the thoracic and abdominal field were retrieved dur- ing MIILE procedure, and consequently the total lymph None 118(54.6) 123(56.9) node number was higher (31(22–40) vs 18(12–28), p < Chemotherapy 26(12.0) 24(11.1) 0.001). Note that the number of patients with RLN Chemoradiotherapy 44(20.4) 41(19.0) lymph node dissection was significantly higher in the Radiaotherapy 28(13.0) 28 (13.0) MIILE (164 vs 35, p < 0.001). Intraoperative frozen sec- a,b The classification of tumor pathology and location was based on the tions were routinely obtained, and R0 resection was ob- American Joint Committee on Cancer, 7th ed. MIILE = Minimally invasive Ivor tained for all patients. Lewis esophagectomy; BMI Body mass index, CCI Charlson comorbidity index The MIILE group began oral intake earlier (6 (5–7) days vs 9 (7–11) days, p < 0.001) and left the hospital earlier (13 (11-16) days vs 18 (16–25) days, p < 0.001). MIILE, namely, six operations for chylothorax, five for More complications, especially pneumonia, occurred in wound infections, four for anastomotic leakage, two for in- the Sweet group. The reoperation rate was similar. Nine- testinal obstructions, one for intrathoracic hemorrhage, and teen reoperations were performed in patients from the one for abdominal hemorrhage. Seventeen patients in the RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 5 of 13 Table 2 Perioperative outcomes and recurrence pattern Characteristic MIILE (n = 216) Sweet (n = 216) p value Total surgical time(min) 265.5(214~330) 201.0(180~236) < 0.001 Blood loss(ml) 200(150~300) 300(250~400) < 0.001 Blood transfusion, n(%) 14(6.5) 18(8.3) 0.462 Lymphadenectomy, n RLN 7(3~10) 3(2~4) < 0.001 Thoracic 14(9~19) 10(6~14) < 0.001 Abdominal 10(6~15) 9(5~14) 0.034 Total 31(22~40) 18(12~28) < 0.001 Initiation of oral intake, d 6(5~7) 9(7~11) < 0.001 Length of stay, d Intensive care unit 4(2~6) 3(2~6) 0.629 Postoperative hospital 13(11~16) 18(16~25) < 0.001 Complications, n(%) Anastomotic leak 15/216 (6.9) 16/216(7.4) 0.852 Esophagotracheal fistula 3/216(1.4) 2/216(0.9) 0.653 Atrial fibrillation 56/216(25.9) 67/216 (31.0) 0.241 Pneumonia 80/216(37.0) 104/216(48.1) 0.020 ARDS 8/216(3.7) 11/216(5.1) 0.481 Recurrent laryngeal nerve injury 6/216(2.8) 1/216(0.5) 0.057 Chylothorax 8/216(3.7) 7/216(3.2) 0.793 Wound infection 11/216(5.1) 13/216(6.0) 0.674 Ileus 3/216(1.4) 0/216(0.0) 0.248 Volvulus 1/216(0.5) 0/216(0.0) 1.000 Total 110/216(50.9) 148/216(68.5) < 0.001 Reoperation, n(%) 19(8.8) 17(7.9) 0.728 Mortality within postoperative-30-day,n 5 6 0.760 Recurrence, n(%) Locoregional recurrence 42/89(47.2) 56/95(58.9) 0.108 Anastomosis site 4/42(9.5) 3/56(5.3) 0.703 Cervical/supraclavicular- lymph node 4/42(9.5) 9/56(16.1) 0.159 Mediastinal lymph node 18/42(42.9) 29/56(51.8) 0.089 Abdominal lymph node 16/42(38.1) 15/56(26.8) 0.852 Distance recurrence 47/89(52.8) 39/95(41.1) 0.335 Liver 15/47(31.9) 13/39(33.3) 0.696 Bone 12/47(25.6) 8/39(20.5) 0.360 Lung 11/47(23.4) 12/39(30.8) 0.830 Other sites 9/47(19.1) 6/39(15.4) 0.647 Multiple sites 9/98(9.2) 6/101(5.9) 0.430 Total 98/216(45.4) 101/216(46.7) 0.772 Data are shown as number (%) and continuous data as mean standard deviation or median (interquartile range) 81 patients in MIILE and 73 patients in Sweet had two or more than two complications MIILE Minimally invasive Ivor Lewis esophagectomy RLN Recurrent laryngeal nerves ARDS Acute respiratory distress syndrome RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 6 of 13 Sweet group required reoperation. There were four opera- Recurrence was observed in nearly half of patients tions for anastomotic leakage, four for chylothorax, five for (45.4% in the MIILE group vs 46.7% in the Sweet group, wound infections, two for intrathoracic hemorrhage, and p = 0.772). The recurrence pattern was similar between two for abdominal hemorrhage. the MIILE group and the Sweet group (locoregional, 42 There was no intraoperative mortality. The postopera- vs 56, p = 0.108; distant, 47 vs 39, p = 0.335); in half of tive 30-day mortality rate did not differ significantly be- the patients, recurrence was observed at distant sites, tween approaches. Five postoperative deaths occurred in mainly the liver, lungs, and bone. the MIILE group. One patient died from anastomotic leakage, three died from severe pneumonia, and one died Survival from sudden cardiac arrest. Six patients in the Sweet The median follow-up time was 36 months. The 2-year group died. Two patients died from anastomotic leakage, OS and DFS rates for all patients were 59.4 and 35.0%, re- three died from respiratory failure secondary to pulmon- spectively, and the 5-year OS and DFS rates were 54.8 and ary infection, and one died from congestive heart failure. 34.0%, respectively. There was no significant difference in Fig. 2 Overall survival curves by MIILE and the Sweet approach for (a) the entire cohort (p = 0.503) and for patients with (b)TNM stageI(p = 0.029), (c)TNM stage II (p = 0.544), (d) TNM stage III (p = 0.468). Kaplan-Meier, Log-rank. MIILE = minimally invasive Ivor Lewis esophagectomy. TNM = tumor-node-metastasis RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 7 of 13 OS and DFS between groups (Fig. 2 and Fig. 3). Patients hazards model revealed that TNM stage and postopera- in the MIILE group classified as TNM stage I showed su- tive complications were independent prognostic factors perior OS and DFS. for survival of the whole cohort (Table 4). Table 3 shows the results of the univariate analysis of RLN lymph node metastasis was associated with poor OS clinicopathologic variables influencing OS and DFS. The and DFS in the whole cohort and in the MIILE group but factors tumor diameter (≤3 cm vs > 3 cm), depth of had no influence on survival in the Sweet group (Fig. 4). tumor invasion (T1–2vs T3–4), lymph node metastasis status (N0 vs N1–3), TNM stage (I vs II vs III), and oc- Quality of life currence of postoperative pneumonia and complications The QOL results are shown in Table 5. There was no affected the OS and DFS of the whole cohort. Further significant difference in the baseline level of QOL. MIILE analysis showed that a high BMI was associated with group scored significantly higher in the postoperative global better OS in the MIILE group, and atrial fibrillation was health and physical component and lower in symptom cat- associated with worse DFS in the Sweet group. Regres- egories than the Sweet group. Furthermore, the scores for sion analysis using a multivariable Cox proportional global health, physical function, role function, emotional Fig. 3 Disease-free survival by MIILE and the Sweet approach for (a) the entire group (p = 0.370) and patients with (b) TNM stage I (p = 0.006), (c) TNM stage II (p = 0.582), and (d) TNM stage III (p = 0.459). Kaplan-Meier, Log-rank; MIILE = minimally invasive Ivor Lewis esophagectomy. TNM = tumor-node-metastasis RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 8 of 13 Table 3 Clinicopathologic characteristics and prognostic factor for survival of 432 ESCC patients Characteristic Total (n = 432) MIILE (n = 216) Sweet (n = 216) No p value No p value No p value OS DFS OS DFS OS DFS Gender Male 366 0.505 0.393 181 0.551 0.422 185 0.748 0.679 Female 66 35 31 Age(year) < 65 267 0.902 0.943 132 0.126 0.189 135 0.158 0.179 ≥ 65 165 84 81 BMI (kg/m ) ≤ 18.5 86 33 53 * * * * * * 18.5~25 287 0.277 0.169 156 0.717 0.528 131 0.244 0.165 * * * * * * ≥ 25 59 0.182 0.082 27 0.053 0.024 32 0.789 0.696 Tumor location Upper and middle junction 21 11 10 ** ** ** ** ** ** Middle third 199 0.898 0.964 99 0.524 0.471 100 0.761 0.616 ** ** ** ** ** ** Lower third 212 0.766 0.853 106 0.350 0.331 106 0.617 0.445 Tumor length(cm) ≤ 3 139 < 0.001 < 0.001 78 0.013 0.003 61 0.005 0.016 >3 293 138 155 Depth of invasion (T) T1–2 150 < 0.001 < 0.001 74 < 0.001 < 0.001 76 0.201 0.481 T3–4 282 142 140 Lymph node metastasis (N) N0 222 < 0.001 < 0.001 107 < 0.001 < 0.001 115 < 0.001 < 0.001 N1–3 210 109 101 Pathology stage (TNM) *** *** *** *** *** *** I 103 0.050 0.053 50 0.004 0.002 53 0.091 0.876 **** **** **** **** **** **** II 140 < 0.001 < 0.001 68 < 0.001 < 0.001 72 < 0.001 < 0.001 ***** ***** ***** ***** ***** ***** III 189 < 0.001 < 0.001 98 < 0.001 < 0.001 91 < 0.001 < 0.001 Atrial fibrillation Yes 123 0.144 0.086 56 0.493 0.594 67 0.124 0.038 No 309 160 149 Pneumonia complication (including ARDS) Yes 203 < 0.001 < 0.001 88 0.008 0.010 115 < 0.001 < 0.001 No 229 128 101 Postoperative complication Yes 258 < 0.001 < 0.001 110 0.294 0.424 148 < 0.001 < 0.001 No 174 106 68 * ** *** **** ***** Compared with low BMI group (≤18.5), log-rank. Compared with upper third group, log-rank. I compared with II, log-rank; II compared with III, log-rank; I compared with III, log-rank MIILE minimally invasive Ivor Lewis esophagectomy OS overall survival DFS disease-free survival BMI body mass index TNM tumor-node-metastasis ARDS Acute respiratory distress syndrome RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 9 of 13 Table 4 Multivariate analysis by Cox proportional hazard model Characteristic Total (n = 432) MIILE (n = 216) Sweet (n = 216) p value p value p value OS DFS OS DFS OS DFS Age 0.891 0.887 0.280 0.427 0.128 0.111 Gender 0.181 0.186 0.127 0.231 0.922 0.712 TNM stage < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 Tumor location 0.641 0.476 0.945 0.775 0.863 0.502 Tumor length 0.110 0.070 0.275 0.031 0.620 0.414 BMI 0.574 0.378 0.442 0.399 0.897 0.688 Postoperative complication < 0.001 < 0.001 0.505 0.843 0.854 < 0.001 Surgical approach 0.415 0.407 –– –– MIILE minimally invasive Ivor Lewis esophagectomy OS overall survival DFS disease-free survival TNM tumor-node-metastasis BMI body mass index -=no p value function, cognitive function, social function, fatigue, and similar studies (47–54.3%) [20, 21]and maybeascribedto pain improved faster in the MIILE group. the tumor location, undetectable metastasis, depth of inva- sion and lymph node metastasis status [22, 23]. Thus, close Discussion follow-up of patients is recommended. Although left transthoracic esophagectomy is the pri- Although the OS and DFS results were similar between mary surgical approach for ESCC in China, the debate groups, superior survival of patients with TNM stage I was regarding the left and right thoracic approaches remains noted in the MIILE, which may be due to the advantage of unsettled [12, 13]. MIILE has been demonstrated to have this approach in lymph node resection (magnified views, advantages over the open Ivor Lewis approach in the better exposure, and longer instruments), especially in the treatment of esophageal adenocarcinoma patients [3, 14], RLN field. Radical lymph node resection with RLN lymph- but its effect on the long-term survival of patients with adenectomy, such as that performed during MIILE, can re- ESCC needs further investigation. There have also been move more potential cancer-positive lymph nodes, allow few detailed comparisons between MIILE and the left more accurate staging and therapy, and offer a better prog- transthoracic approach (Sweet approach) in ESCC pa- nosis in patients with early stage ESCC [24, 25]. Our results tients [15, 16]. To fill this gap in knowledge, we compared also demonstrated that the frequency of lymph node metas- the QOL and survival of patients who underwent MIILE tasis along the RLN is high, which is consistent with the as- and the Sweet procedure. sociation of lymph node status with survival benefit [26]. We found that both surgical procedures were comparable However, RLN lymph node metastasis did not influence the at the clinical baseline. The short-term advantages of survival of patients in the Sweet group, which may be ex- MIILE, such as decreased blood loss, reduced hospital stay, plained by the limited superior mediastinal lymphadenec- and decreased pain were in line with those reported previ- tomy performed during the Sweet procedure and the ously [16, 17]. Similar to previous studies [16, 18], there omission of RLN lymphadenectomy [27]. Moreover, the were significantly fewer respiratory complications in pa- lymph nodes along the common hepatic and celiac arteries tients who underwent MIILE. This finding could be as- were not routinely retrieved during the Sweet procedure, cribed to reduced pulmonary parenchymal trauma and which could misguide pathological TNM staging and treat- gentle lung retraction with the thoracoscope. In addition, ment protocols. Thus, our findings support the recommen- the minimally invasive incisions made during MIILE pro- dation that radical lymphadenectomy, including removal of cedure resulted in less intercostal nerve injury, which re- the bilateral RLN lymph nodes, should be performed dur- duced pain and allowed effective expectoration. Compared ing esophagectomy [28]. with the Sweet approach, MIILE approach accelerated the Among factors affecting survival, the influence of a recovery phase, as MIILE patients had decreased ICU stays, longer tumor diameter may be ascribed to a more ad- accelerated oral intake and shortened postoperative hospital vanced TNM stage [29], and the impact of high BMI stays. The recurrence pattern was similar between ap- may be due to its relationship to a lower pathological proaches, which needs further investigation [19]. The rela- stage [30]. The TNM stage and occurrence of postopera- tively high recurrence rate was comparable to those in tive complications were independent prognostic factors, RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 10 of 13 Fig. 4 (See legend on next page.) RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 11 of 13 (See figure on previous page.) Fig. 4 Overall survival curve and disease-free survival curves stratified by RLN lymph node metastasis status in 199 patients with RLN lymph nodes retrieved in the whole cohort (a p < 0.001 and b p < 0.001, respectively), 164 patients with RLN lymph nodes retrieved in the MIILE group (c p < 0.001 and d p < 0.001, respectively), and 35 patients with RLN lymph nodes retrieved in the Sweet group (e p = 0.776 and f p = 0.816, respectively). MIILE = minimally invasive Ivor Lewis esophagectomy. RLN = recurrent laryngeal nerve. LN = lymph node Table 5 Quality of Life After Surgery Characteristic MIILE (n = 92) Sweet (n = 94) Baseline 3 months 6 months 12 months 24 months Baseline 3 months 6 months 12 months 24 months EORTC C30 * ** Global health 73.53 ± 65.82 ± 69.29 ± 72.69 ± 15.98 74.02 ± 75.89 ± 16.06 49.32 ± 57.13 ± 62.63 ± 10.37 71.81 ± */** */** ** ** 11.19 11.54 12.38 16.49 10.01 14.89 15.19 Functioning scales ** Physical 84.89(73.03– 66.94 ± 73.57 ± 81.34 84.40 ± 84.00 50.20 ± 48.69 ± 72.58 ± 12.50 73.08 ± */** */** */** * ** ** ** functioning 93.24) 10.47 12.61 (70.61–89.29) 10.18 (76.12–93.64) 8.45 12.38 14.74 Role 82.31(73.63– 61.64 ± 71.18 ± 80.88 ± 8.59 81.21 ± 79.16 ± 11.16 54.56 ± 59.72 ± 75.96 ± 12.51 81.48 ± */** */** ** ** functioning 90.02) 10.80 8.08 10.02 1.38 8.67 9.22 * ** Emotional 70.06 ± 73.30 ± 11.97 77.81 ± 78.62 ± 10.46 81.58 ± 70.00 ± 8.20 63.19 ± 69.74 ± 79.98 79.38 ± */** ** ** ** ** functioning 11.78 11.18 11.3 10.76 7.29 (71.25–90.41) 9.91 Symptom scales */** */** ** Fatigue 21.46 ± 44.16 ± 9.26 36.14 ± 27.97 ± 6.47 23.15 ± 21.40 ± 11.49 59.19 ± 49.14 ± 31.78 ± 13.40 26.23 ± */** ** ** ** 11.55 18.23 12.33 10.26 12.93 14.40 */** ** Pain 19.54 ± 9.46 32.62(23.79– 30.09 ± 26.83 ± 6.31 24.58 ± 18.78 ± 7.49 56.15 ± 40.88 ± 30.29 ± 10.48 25.74 ± */** */** ** ** ** ** 39.34) 7.76 9.12 1.61 12.56 5.36 */** ** ** Dyspnea 12.47 ± 6.63 26.78 ± 9.31 22.06 ± 16.11 ± 9.65 14.10 ± 12.80 ± 7.19 32.36 ± 25.00 ± 17.63 ± 5.68 14.12 ± */** ** ** 7.64 6.50 10.91 8.33 6.52 */** ** Insomnia 22.06 ± 9.97 34.68 ± 29.77 ± 25.81 ± 10.21 21.97 ± 24.24 ± 10.61 41.88 ± 39.40 ± 29.19 ± 9.47 21.45 ± */** */** ** ** 10.55 7.99 10.97 12.90 11.96 12.74 */** ** Appetite loss 36.01 ± 22.81 ± 22.81 ± 17.91 ± 9.43 19.45 ± 31.80 ± 19.17 27.06 ± 23.99 ± 22.33 ± 11.28 21.07 ± */** ** ** ** ** ** 12.24 12.74 13.07 8.78 10.95 13.41 8.79 ** Constipation 22.11 ± 17.87 ± 16.03 17.44 ± 1.23 16.20 ± 17.40(8.39– 22.64 ± 21.46(7.65– 18.88 ± 8.06 17.94 ± */** ** ** 13.20 11.58 (9.37–28.83) 7.81 26.69) 12.1 32.99) 9.23 EORTC OES 18 ** ** ** Dysphagia 39.26 ± 26.15 ± 13.22 23.80 ± 22.66 ± 11.98 17.29 ± 39.86 ± 10.03 27.55 ± 26.43 ± 23.02 ± 12.56 18.09 ± ** ** ** ** ** 17.21 12.06 7.39 15.03 12.16 8.73 ** ** Eating 39.57 ± 36.63 32.12 ± 24.66 ± 10.70 22.81 ± 39.00 ± 11.55 34.41 ± 29.27 ± 25.69 ± 12.28 22.15 ± ** ** ** ** ** ** 11.90 (31.88–42.97) 10.29 8.38 11.57 14.67 9.75 ** ** ** Reflux 21.67 ± 37.58 ± 12.41 33.31 ± 32.05 ± 13.96 29.57 ± 22.23 ± 11.59 37.74 ± 33.16 ± 33.06 ± 13.78 31.79 ± ** ** ** ** ** 10.37 16.21 10.20 17.40 15.51 15.02 Pain 16.55 ± 25.02 ± 14.21 ± 12.56 ± 7.12 11.92 ± 18.24 ± 10.33 28.13 ± 25.49 ± 15.50 ± 9.48 12.27 ± */** * ** ** ** 11.47 10.00 7.93 6.14 10.80 11.92 7.20 ** */** ** Choking 31.97 ± 23.08 ± 10.24 22.87 ± 21.60 ± 10.92 21.17 ± 31.33 ± 12.18 20.36 ± 25.42 ± 25.11 ± 9.80 20.06 ± ** ** ** ** ** 14.17 13.60 12.78 12.74 14.50 10.48 ** ** ** Coughing 12.03 27.51 ± 11.64 25.96 ± 21.52 ± 9.58 19.93 ± 14.32 28.11 ± 24.97 ± 20.71 ± 8.37 22.19 ± ** ** ** ** ** (6.94–20.54) 8.67 8.49 (4.79–22.67) 14.80 8.07 10.64 Data are shown as number (%) and continuous data as mean standard deviation or median (interquartile range) Measures aspects of health and function; scores range from 0 to 100, with higher scores representing better well-being. Assesses aspects of oesophageal symptoms; scores range from 0 to 100, with lower scores indicating better function Every date was compared between groups and with the baseline within respective group, only p < 0.05 was notified: MIILE compared with Sweet p < 0.05 ** compared with baseline p < 0.05 EORTC European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, MIILE minimally invasive Ivor Lewis esophagectomy RETRACTED ARTICLE Wang et al. BMC Cancer (2019) 19:500 Page 12 of 13 which implies that early diagnosis, prompt treatment, Acknowledgments None. and cautious ward management are essential for improv- ing survival [31, 32]. Funding QOL after esophagectomy is an important factor con- This work was supported by a grant of the Zhejiang Provincial Natural Science Foundation (grant number LY16H010004, LY18H170001, sidering the high morbidity and poor prognosis of LQ17H010002) and a grant of Zhejiang Provincial Department of Education esophageal carcinoma patients. QOL was impaired after (Y201635465). The sponsors played no role in the study design, data surgery and gradually recovered within 6–12 months in collection or interpretation, or analysis, or decision to submit the article for publication. both groups. A significant difference favoring MIILE was found in the global health, physical component sum- Availability of data and materials mary, and symptom categories in postoperative patients The data that support the findings of this study are available upon request at three to six months, which is in line with observations from the corresponding author Wu Ming. The data are not publicly available as individuals were not consented for the release of their information into a made in previous studies [16, 33]. The advantage of public database. MIILE in QOL may be ascribed to decreased surgical trauma and reduced pain [33]. Authors’ contributions For propensity score matching and minimizing the WQ, WZX, ZTW, and FS collected the data, performed the statistical analysis, analyzed data, and wrote the manuscript. ZS, SG, and WM analyzed data and statistical bias, patients who received neoadjuvant ther- wrote the manuscript. All authors read and approved the final manuscript. apy were not enrolled in this study because most of them chose MIILE afterwards. Neoadjuvant therapy has Ethics approval and consent to participate been increasingly adopted in esophageal cancer patients This research project was approved by Ethics Committee of the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. In this study, with conflicting results [34, 35]. In addition, the optimal written informed consent was obtained from the patients or their families, neoadjuvant protocol needs further investigation. The and patient anonymity was preserved. likelihood that the conclusions of this study would be in- Consent for publication fluenced by the downstaging effect of neoadjuvant ther- Not applicable. apy should not be disregarded. The strength of this study lies in the large sample size, Competing interests which is one of the largest for propensity score-matched The authors declare that they have no competing interests. comparisons between ESCC patients undergoing MIILE and the Sweet procedure. This study has intrinsic limita- Publisher’sNote tions regarding statistical bias because it was retrospect- Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ive and nonrandomized and was also based on the experience of a single surgeon. In addition, it is unclear Received: 28 November 2018 Accepted: 29 April 2019 whether the results of this study were influenced by the postoperative treatments, and the effect of adjuvant ther- References apy on patients was not evaluated. The indications for 1. Mao YS, He J, Xue Q, Shao K, Su K, Li N, et al. Nationwide speaking tour of postoperative therapy in ESCC are still under debate. In standardized diagnosis and treatment for esophageal cancer. Zhonghua addition, the optimal adjuvant protocol for ESCC needs Wei Chang Wai Ke Za Zhi. 2013;16(9):801–4. 2. Takeuchi H, Miyata H, Ozawa S, Udagawa H, Osugi H, Matsubara H, et al. further analysis. 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J Gastrointest Surg. 2014;18(1):187–93. RETRACTED ARTICLE

Journal

BMC CancerSpringer Journals

Published: May 27, 2019

Keywords: Minimally invasive surgery; Ivor Lewis esophagectomy; Left transthoracic esophagectomy; Esophageal squamous cell carcinoma

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