A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as a predictive marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer

A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as a predictive marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer | 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 A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as a predictive marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer Tomo Horinouchi, Naoya Yoshida, Kazuto Harada, Kojiro Eto, Hiroshi Sawayama, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1571524/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Purpose Preoperative malnutrition is a significant risk factor for post-esophagectomy morbidity. The Controlling Nutritional Status (CONUT) is an index used to assess the nutritional status, and it has been suggested to predict post-esophagectomy morbidity. However, the difference in the predictive value of CONUT in estimating morbidities between open esophagectomy (OE) and minimally invasive esophagectomy (MIE) has not yet been elucidated. Methods This study included 674 patients(OE, 295; MIE, 378) who underwent three-incision esophagectomy for esophageal cancer between April 2005 and August 2021. The patients were further divided into two groups according to their preoperative CONUT: normal and light malnutrition and moderate and severe malnutrition. Short-term outcomes between these groups were retrospectively compared in the OE and MIE groups. Results Moderate and severe malnutrition was significantly associated with a low body mass index, a poor performance status and American Society of Anesthesiologists physical status, advanced cancer stage, and frequent preoperative treatment. These patients also experienced significantly more frequent severe (p=0.016), respiratory (p=0.0013) and cardiovascular morbidities (p=0.013) after OE. Moreover, malnutrition in CONUT was an independent risk factor for severe (hazard ratio [HR]=3.38; 95%confidence interval [CI], 1.225-9.332; p=0.019), respiratory (HR=3.00; 95%CI, 1.161-7.736; p=0.023), and cardiovascular morbidities (HR=3.66; 95%CI, 1.068-12.55; p=0.039) after OE. However, it was not associated with the incidence of morbidities after MIE. Conclusion Preoperative malnutrition in CONUT reflects various disadvantageous clinical factors and could be a predictor of worse short-term outcomes after OE. Meanwhile, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes. CONUT esophagectomy morbidity short-term outcomes Figures Figure 1 Introduction Esophagectomy for esophageal cancer is a highly invasive surgery, and compared to other gastrointestinal cancer surgeries, it is associated with more postoperative morbidities [1]. Recently, minimally invasive esophagectomy (MIE) has become more widespread because compared to open esophagectomy (OE), MIE is less invasive and has fewer postoperative morbidities [2]. Several studies have suggested that MIE could alleviate the effect of disadvantageous clinical factors on the incidence of postoperative morbidities and could improve the short-term outcomes after esophagectomy [3, 4]. The nutritional status is an important factor that affects the short-term outcomes after esophagectomy. Several nutritional markers may be useful for estimating the incidence of post-esophagectomy morbidity [5, 6]. The Controlling Nutritional Status (CONUT) score is one such nutritional marker [7]. Malnutrition in CONUT has been suggested to be related to poor short-term outcomes after esophagectomy [8]. However, these studies did not analyze the use of OE versus MIE. Thus, the significance of MIE in reducing post-esophagectomy morbidity in patients with malnutrition in CONUT has not yet been established. Therefore, this study aimed to elucidate the association between preoperative malnutrition based on the CONUT score and short-term outcomes in OE and MIE, separately, as it may clarify whether the low invasiveness of MIE could contribute to alleviating the effect of preoperative malnutrition on the incidence of postoperative morbidities. Methods Patients A total of 853 Japanese patients underwent three-incision esophagectomy for esophageal cancer at Kumamoto University Hospital between April 2005 and August 2021. Among them, 179 patients with missing data were excluded. Finally, 674 patients were included in this retrospective survey. OE was performed in 296 patients, and MIE was performed in 378 patients (Figure 1). In addition, the OE and MIE groups were further divided into two groups according to the preoperative CONUT scores: normal and light malnutrition, and moderate and severe malnutrition. The short-term outcomes between the groups were retrospectively compared between the OE and MIE groups by using an institutional database. This study was conducted in accordance with the ethical standards of the Declaration of Helsinki 1975. The institutional ethics committee approved all the research procedures (Registration No. 1909) and waived the requirement for written informed consent owing to the retrospective nature of the study. Treatment strategy Patients diagnosed as not having lymph node metastasis underwent esophagectomy without preoperative treatment. Patients with non-T4 lymph node-positive tumors received either adjuvant chemotherapy (from April 2005 to July 2008) or neoadjuvant chemotherapy (from August 2008 to August 2021). For T4 tumors, neoadjuvant chemoradiotherapy (CRT) was commonly administered. If patients preferred nonsurgical treatment, definitive CRT was considered regardless of the tumor stage. If definitive CRT was performed and recurrence occurred, salvage esophagectomy was performed according to the patient’s requirement. The Union for International Cancer Control TNM staging version 8 was used to classify the pretreatment clinical staging [9]. Surgery Esophagectomy was defined as an esophagectomy requiring the placement of three incisions (on the neck, chest, and abdomen) with lymphadenectomy. The extent of lymphadenectomy was determined based on the 11th Japanese Esophageal Cancer Classification [10]. For upper or middle thoracic esophageal cancers, lymphadenectomy was performed in three regions. Cervical lymphadenectomy was not performed for clinical T1 tumors in lower thoracic esophageal cancers. MIE was defined as esophagectomy performed via thoracoscopy, regardless of the use of laparoscopy. MIE for clinical T1 and T2 tumors began in May 2011 and has been performed for clinical T3 and T4 tumors since September 2011. Perioperative management The details of perioperative management have been described previously [11]. Before the start of esophagectomy, a 24-h continuous intravenous infusion of a neutrophil elastase inhibitor and a bolus of methylprednisolone were administered. Antibiotics were administered intraoperatively every 4 h. Extubation was performed in the operating room immediately after esophagectomy. The patient was observed in the intensive care unit on postoperative day 1. Postoperative enteral nutrition was also commonly started on postoperative day 1. Definitions of morbidities The details of morbidities have been described previously [8]. A morbidity was defined as a complication ≥ grade II according to the Clavien–Dindo classification (CDc) [12]. Severe morbidity was defined as a complication ≥ grade IIIb requiring endoscopic, radiological, or surgical intervention under general anesthesia. Statistical methods All statistical analyses were performed using JMP® version 14.2 (SAS Institute, Cary, NC, USA). Statistical significance was set at p < 0.05. A chi-square test was used for comparisons between groups. The Mann-Whitney U test was used to analyze unpaired samples. A logistic regression analysis was performed to determine the hazard ratio (HR) in the 95% confidence interval (CI) of morbidities. The following data were used to analyze independent risk factors for severe, respiratory, and cardiovascular morbidities: age at esophagectomy (the cutoff value was calculated via receiver operating characteristic [ROC] analysis), sex (male vs. female), body mass index (BMI) (≥18.5 vs.<18.5 kg/m 2 ), Brinkman index (≥800 vs.<800), CONUT (moderate and severe malnutrition vs. normal and light malnutrition), diabetes mellitus (yes vs. no), respiratory comorbidity (yes vs. no), cardiovascular comorbidity (yes vs. no), American Society of Anesthesiologists physical status (ASA-PS) (2 and 3 vs. 1), performance status (PS) (1 and 2 vs. 0), clinical stage (III and IV vs. 0, I, and II), preoperative treatment (yes vs. no), preoperative radiotherapy (yes vs. no), operative time (the cutoff values were calculated via ROC analysis), and bleeding (the cutoff values were calculated via ROC analysis). A subsequent multivariate analysis selected factors with p ≤ 0.1 and recognized variables with p < 0.05 as independent risk factors. Results Clinical features of all patients who underwent esophagectomy Table 1 shows the characteristics of all patients who underwent esophagectomy according to the CONUT scores. Of all patients, 48 (7%) were classified as having moderate and severe malnutrition. Compared to normal and light malnutrition, moderate and severe malnutrition significantly correlated with a low BMI (p < 0.001), worse PS (p < 0.001) and ASA-PS (p < 0.001), frequent respiratory comorbidities (p = 0.0023), advanced cancer stage (p < 0.001), and more frequent preoperative treatment (p < 0.001). Short-term outcomes after OE Table 2 shows the short-term outcomes after OE according to the CONUT scores. Compared to patients with normal and light malnutrition, those with moderate and severe malnutrition experienced significantly more frequent severe (p = 0.016), respiratory (p = 0.0013) and cardiovascular morbidities (p = 0.013). Short-term outcomes after MIE Table 3 shows the short-term outcomes after MIE according to the CONUT scores. Regarding short-term outcomes, malnutrition in CONUT did not increase post-MIE morbidities. Risk factors for postoperative severe, respiratory, and cardiovascular morbidities after OE Table 4 shows the results of the univariate and multivariate analyses of risk factors for severe, respiratory, and cardiovascular morbidities after OE. Moderate and severe malnutrition in CONUT was an independent risk factor for severe (HR = 3.38; 95% CI, 1.225-9.332; p = 0.019), respiratory (HR = 3.00; 95% CI, 1.161-7.736; p = 0.023), and cardiovascular morbidities (HR = 3.66%; 95% CI, 1.068-12.55; p = 0.039). Risk factor for severe morbidity included cardiovascular comorbidity (HR = 3.16; 95% CI, 1.305-7.633; p = 0.011), for respiratory morbidity included a Brinkman index ≥ 800 (HR = 2.29; 95% CI, 1.122-4.661; p = 0.023) and operation time ≥530 minutes (HR = 2.03; 95% CI, 1.006-4.098; p = 0.048), and for cardiovascular morbidity included cardiovascular comorbidity (HR = 3.38; 95% CI, 1.124-10.14; p = 0.030) and operation time ≥591 minutes (HR = 5.06; 95% CI, 1.804-14.18; p = 0.0021). Discussion This study yielded several interesting results on the association between preoperative malnutrition estimated using the CONUT scores and short-term outcomes after esophagectomy for esophageal cancer. First, moderate and severe malnutrition in CONUT was significantly associated with several disadvantageous patient characteristics, such as a low BMI, poor PS, poor ASA-PS, and frequent comorbidity. Second, it was also significantly associated with several disadvantageous cancer-related factors, such as advanced cancer stage and frequent preoperative treatment. Third, patients with moderate and severe malnutrition in CONUT who underwent OE had significantly more frequent postoperative severe, respiratory, and cardiovascular morbidities. Finally, malnutrition did not increase the incidence of postoperative morbidities after MIE. Several studies have suggested that preoperative malnutrition could cause frequent post-esophagectomy morbidities [6, 13]. However, OE and MIE were not distinctly analyzed in these studies. Thus, the effect of MIE on the incidence of post-esophagectomy morbidities in patients with a poor nutritional status has not been well established. To the best of our knowledge, this is the first study to elucidate that preoperative malnutrition in CONUT was associated with worse short-term outcomes only after OE, but not after MIE. CONUT was calculated using the serum albumin and total cholesterol levels and total lymphocyte count (TLC). Serum albumin levels reflect the nutritional status, inflammation, liver dysfunction, and kidney disease [14, 15]. Total cholesterol levels reflect the nutritional status related to lipid metabolism and inflammation [16, 17]. TLC is an indicator of nutrition and immunity [18]. Deterioration in these parameters can adversely affect tissue repair and resistance against infection, which may be a reason for the increased incidence of postoperative morbidities. Moreover, in this study, malnutrition estimated using the CONUT score was associated with disadvantageous patient characteristics and tumor-related factors for post-esophagectomy morbidity, which might result in frequent post-esophagectomy morbidity and surgery-related mortality [2]. These associations may explain why malnutrition estimated using the CONUT score could be a significant risk factor for postoperative morbidities after OE. Nevertheless, malnutrition in CONUT did not affect the incidence of postoperative morbidities after MIE. Studies have reported that MIE is less invasive than OE is and is associated with fewer postoperative morbidities [19]. Several studies have suggested that the low invasiveness of MIE could alleviate the effect of preoperative disadvantageous clinical factors on the incidence of post-esophagectomy morbidities [3, 4]. High preoperative HbA1c levels can be a risk factor for anastomotic leakage, surgical site infection, and pneumonia after esophagectomy [20]. However, it might increase morbidities only after OE, but not after MIE [3]. Moreover, we have reported that a high pretreatment red blood cell distribution width, which is a surrogate marker of the nutritional status, might be an independent risk factor for severe morbidity and reoperation only after OE [4]. These previous studies may support the current result that malnutrition in CONUT could increase the incidence of morbidities only after OE, but not after MIE. For patients assessed as being malnourished in CONUT, preoperative nutritional interventions may be effective in improving the short-term outcomes. A meta-analysis suggested that the administration of immunoenhancing enteral nutrition might reduce postoperative morbidities after gastrointestinal surgeries [21]. In contrast, a randomized controlled trial suggested that short-term nutritional intervention (7 days before esophagectomy) did not reduce post-esophagectomy morbidities. Thus, long-term nutritional intervention during preoperative treatment should be considered in malnourished patients scheduled to undergo esophagectomy [22]. Improvement in oral ingestion during preoperative treatment via stent insertion for patients with swallowing difficulty due to advanced esophageal cancer may also reduce post-esophagectomy mortality [23]. In this study, malnutrition in CONUT was an independent risk factor for respiratory morbidity after OE. Thus, when patients with malnutrition undergo OE, measures should be taken against respiratory morbidities. Smoking and impaired respiratory function could be risk factors for respiratory morbidities after esophagectomy [24, 25]. Thus, smoking cessation [25] and preoperative respiratory rehabilitation [26] are necessary. Moreover, oral hygiene [27], enforcement of the Enhanced Recovery after Surgery Program [28], and perioperative management by a multidisciplinary perioperative care team [29] are helpful in reducing post-esophagectomy respiratory morbidities. In addition, less invasive surgeries may further reduce post-esophagectomy morbidities in patients with malnutrition undergoing OE. A meta-analysis suggested that compared to MIE, robot-assisted esophagectomy may help reduce the incidence of pneumonia [30]. Transhiatal esophagectomy and mediastinoscopic esophagectomy are also effective candidates for further reducing postoperative respiratory morbidities [31, 32]. These procedures can be treatment options for patients assessed as being malnourished according to their CONUT scores. This study had several limitations. Because this was a single-center retrospective study conducted over a long period, historical biases with regard to treatment strategy, surgery, and perioperative management existed. Notably, MIEs were more frequently performed in recent cases, and this strategy affected the current results, wherein malnutrition did not increase the incidence of morbidities after MIE. Moreover, the exclusion of patients owing to the lack of data could be a cause of a selection bias. Nevertheless, our findings revealed that moderate and severe malnutrition assessed using the preoperative CONUT score can be a predictor of severe, respiratory, and cardiovascular morbidities after OE. Moreover, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes. Declarations Funding information This manuscript did not receive sponsorship for publication. Conflict of interest All authors declare no conflict of interest for this article. Authors’ contributions Tomo Horinouchi described and designed the article. Naoya Yoshida edited the article. Hideo Baba supervised the editing of the manuscript. Material preparation, data collection and analysis were performed by Tomo Horinouchi, Naoya Yoshida, Kazuto Harada, Kojiro Eto, Masaaki Iwatsuki and Yoshifumi Baba. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements We would like to thank Editage (www.editage.com) for English language editing. Ethics statements This study was conducted in accordance with the ethical standards of the Declaration of Helsinki 1975. The institutional ethics committee approved all the research procedures (Registration No. 1909) and waived the requirement for written informed consent owing to the retrospective nature of the study. 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Preoperative malnutrition degree in CONUT p Clinical, epidemiological, and surgical feature Normal and light malnutrition (N=626) Moderate and severe malnutrition (N=48) Age, mean ± SD 66.5 ± 8.4 68.1 ± 9.2 0.20 Sex Male 546 (87%) 44 (92%) 0.37 Body mass index, mean ± SD (kg/m²) 22.1 ± 3.1 19.6 ± 3.2 <0.001 †Brinkman Index, mean ± SD 760 ± 570 720 ± 510 0.62 Performance status <0.001 0 561 (90%) 25 (52%) 1 58 (9%) 21 (44%) 2 7 (1%) 2 (4%) American Society of Anesthesiologists physical status <0.001 1 123 (20%) 5 (10%) 2 470 (75%) 29 (60%) 3 33 (5%) 14 (30%) Comorbidity Diabetes mellitus 136 (22%) 7 (15%) 0.24 Respiratory disease 215 (34%) 27 (56%) 0.0023 Cardiovascular disease 328 (52%) 24 (50%) 0.75 Clinical stage <0.001 0, I 306 (49%) 8 (17%) II 120 (19%) 5 (10%) III 141 (23%) 16 (33%) IV 59 (9%) 19 (40%) Preoperative treatment <0.001 Absent 425 (68%) 14 (29%) Neoadjuvant chemotherapy 143 (23%) 5 (10%) Neoadjuvant chemoradiotherapy 30 (5%) 17 (36%) Definitive chemoradiotherapy 28 (4%) 12 (25%) Thoracic procedure 0.0010 OE 264 (42%) 32 (67%) MIE 362 (58%) 16 (33%) Abbreviation: CONUT, Controlling Nutritional Status; SD, standard deviation ; OE, Open esophagectomy; MIE, minimally invasive esophagectomy †Brinkman index was calculated as follows: number of cigarettes/day × smoking duration (year) Table 2 Short-term outcomes after open esophagectomy Preoperative malnutrition degree in CONUT p Variables Normal and light malnutrition (N=264) Moderate and severe malnutrition (N=32) Operative time, mean ± SD (min) 540 ± 120 550 ± 150 0.54 Bleeding, mean ± SD (g) 570 ± 440 710 ± 550 0.12 Any morbidity, CDc≥ II 99 (38%) 18 (56%) 0.055 Severe morbidity, CDc≥ IIIb 20 (8%) 7 (22%) 0.016 Respiratory morbidity 35 (13%) 12 (38%) 0.0013 Surgical site infection 71 (27%) 7 (22%) 0.67 Anastomotic leakage 40 (15%) 5 (16%) 1.00 Cardiovascular morbidity 14 (5%) 6 (19%) 0.013 Abbreviation: CONUT, Controlling Nutritional Status ; SD, standard deviation; CDc, Clavien–Dindo classification; SE , standard error Table 3 Short-term outcomes after minimally invasive esophagectomy. Preoperative malnutrition degree in CONUT p Variables Normal and light malnutrition (N=362) Moderate and severe malnutrition (N=16) Operative time, mean ± SD (min) 580 ± 100 560 ± 80 0.49 Bleeding, mean ± SD (g) 300 ± 1390 480 ± 810 0.60 Any morbidity, CDc≥ II 124 (34%) 9 (56%) 0.11 Severe morbidity, CDc≥ IIIb 43 (12%) 4 (25%) 0.12 Respiratory morbidity 52 (14%) 4 (25%) 0.27 Surgical site infection 81 (22%) 3 (19%) 1.00 Anastomotic leakage 47 (13%) 3 (19%) 0.45 Cardiovascular morbidity 26 (7%) 0 (0%) 0.61 Abbreviation: CONUT, Controlling Nutritional Status ; SD, standard deviation; CDc, Clavien–Dindo classification; SE , standard error Table 4 Logistic regression analysis of postoperative morbidities in patients who underwent open esophagectomy. Univariate analysis Multivariate analysis Morbidity Characteristics HR (95%CI) p HR (95%CI) p Severe morbidity, CDc ≥IIIb CONUT score Moderate and severe malnutrition (vs. Normal and light malnutrition) 2.35 (0.869-6.342) 0.092 3.38 (1.225-9.332) 0.019 Cardiovascular comorbidity (vs. no) 3.57 (1.438-8.842) 0.0061 3.16 (1.305-7.633) 0.011 Operation time ≥514 min (vs. <514 min) 2.36 (0.981-5.654) 0.055 1.92 (0.778-4.720) 0.16 Bleeding ≥910 g (vs. <910 g) 2.36 (0.981-5.654) 0.055 1.50 (0.543-4.129) 0.43 Respiratory morbidity †Brinkman Index ≥800 (vs. <800) 2.27 (1.189-4.322) 0.013 2.29 (1.122-4.661) 0.023 Performance status 1-2 (vs. 0) 2.07 (1.036-4.132) 0.040 1.57 (0.687-3.581) 0.29 CONUT score Moderate and severe malnutrition (vs. Normal and light malnutrition) 3.93 (1.765-8.730) 0.0008 3.00 (1.161-7.736) 0.023 Respiratory comorbidity (vs. no) 2.15 (1.145-4.037) 0.017 1.46 (0.728-2.919) 0.29 Clinical stage III-IV (vs. 0-II) 2.02 (1.072-3.812) 0.023 1.31 (0.601-2.872) 0.49 Preoperative therapy (vs. no) 2.08 (1.106-3.912) 0.023 1.32 (0.606-2.890) 0.48 Operative time ≥530 min (vs. <530 min) 1.99 (1.045-3.795) 0.036 2.03 (1.006-4.098) 0.048 Cardiovascular morbidity Age ≥73 (vs. <73) 3.10 (1.238-7.778) 0.016 2.63 (0.961-7.209) 0.060 Performance status 1-2 (vs. 0) 2.81 (1.092-7.205) 0.032 1.51 (0.462-4.919) 0.50 CONUT score Moderate and severe malnutrition (vs. Normal and light malnutrition) 4.12 (1.459-11.64) 0.0075 3.66 (1.068-12.55) 0.039 Cardiovascular comorbidity (vs. no) 2.95 (1.099-7.890) 0.032 3.38 (1.124-10.14) 0.030 Operation time ≥591 min (vs. <591 min) 3.463 (1.379-8.698) 0.0082 5.06 (1.804-14.18) 0.0021 Abbreviation: CONUT, Controlling Nutritional Status; HR, hazard ratio; CI, confidence interval; CDc, Clavien–Dindo classification †Brinkman index was calculated as follows: number of cigarettes/day × smoking duration (year) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 30 May, 2022 Reviews received at journal 06 May, 2022 Reviewers agreed at journal 02 May, 2022 Reviewers agreed at journal 02 May, 2022 Reviewers invited by journal 02 May, 2022 Editor assigned by journal 21 Apr, 2022 Submission checks completed at journal 20 Apr, 2022 First submitted to journal 19 Apr, 2022 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-1571524","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":99928031,"identity":"610721c8-84b1-4b50-a125-0e07ab99d296","order_by":0,"name":"Tomo Horinouchi","email":"","orcid":"","institution":"Kumamoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tomo","middleName":"","lastName":"Horinouchi","suffix":""},{"id":99928032,"identity":"bb2afc0d-2e85-4f81-969d-bae7b7cecc4f","order_by":1,"name":"Naoya Yoshida","email":"","orcid":"","institution":"Kumamoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Naoya","middleName":"","lastName":"Yoshida","suffix":""},{"id":99928033,"identity":"a4a868e5-8dc6-41dd-ac56-f49de2b0d69a","order_by":2,"name":"Kazuto Harada","email":"","orcid":"","institution":"Kumamoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kazuto","middleName":"","lastName":"Harada","suffix":""},{"id":99928034,"identity":"e3e6e39a-c1b9-44b5-b657-2c2819138f61","order_by":3,"name":"Kojiro Eto","email":"","orcid":"","institution":"Kumamoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kojiro","middleName":"","lastName":"Eto","suffix":""},{"id":99928035,"identity":"6b7b5f05-384a-491f-851e-f9831ce4b9a4","order_by":4,"name":"Hiroshi Sawayama","email":"","orcid":"","institution":"Kumamoto 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Baba","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBACA4YENgbGBgY5CTQJNoJajCVgfKK1JM5A04IbmLMnH3vwc4dd+swZ2YmfblT8kWOQSGD88IOBLw+XFsueZ+mGvWeSc2dL5G6WzjljYAzUwizZw8BWjNNhN3LMJHjbmHPnSeRukM5tM0jcfyOBQRrol8QGPFok/7bVp8sBbfkN0tIAtOU3IS3SvG2HE6QlcrdJQ7Ww4bflzLN0Y9kzxw1n9rzdZp1zxtiYgedhm2WPAR6/HE8+9vDtjmp5ieO5m2/nVMjJMbAnH77xo+IYzhDDBoDRxGBwLIEULWBQQ7qWUTAKRsEoGK4AAJgUVIAVlRJwAAAAAElFTkSuQmCC","orcid":"","institution":"Kumamoto University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hideo","middleName":"","lastName":"Baba","suffix":""}],"badges":[],"createdAt":"2022-04-19 07:29:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1571524/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1571524/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20654964,"identity":"5c83a3e6-a15a-40a0-8654-6adbbc85c18e","added_by":"auto","created_at":"2022-04-22 14:22:59","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":186406,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart illustrating patient selection.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-1571524/v1/b2ca11c1e14262a8a23ece9a.jpeg"},{"id":20654967,"identity":"b3c1878e-64d3-44d5-baf3-52a8ca736bea","added_by":"auto","created_at":"2022-04-22 14:23:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":391376,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1571524/v1/71ac44e7-d29f-4266-ac04-0819d090aab5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as a predictive marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophagectomy for esophageal cancer is a highly invasive surgery, and compared to other gastrointestinal cancer surgeries, it is associated with more postoperative morbidities [1]. Recently, minimally invasive esophagectomy (MIE) has become more widespread because compared to open esophagectomy (OE), MIE is less invasive and has fewer postoperative morbidities [2]. Several studies have suggested that MIE could alleviate the effect of disadvantageous clinical factors on the incidence of postoperative morbidities and could improve the short-term outcomes after esophagectomy [3, 4].\u003c/p\u003e\n\u003cp\u003eThe nutritional status is an important factor that affects the short-term outcomes after esophagectomy. Several nutritional markers may be useful for estimating the incidence of post-esophagectomy morbidity [5, 6]. The Controlling Nutritional Status (CONUT) score is one such nutritional marker [7]. Malnutrition in CONUT has been suggested to be related to poor short-term outcomes after esophagectomy [8]. However, these studies did not analyze the use of OE versus MIE. Thus, the significance of MIE in reducing post-esophagectomy morbidity in patients with malnutrition in CONUT has not yet been established.\u003c/p\u003e\n\u003cp\u003eTherefore, this study aimed to elucidate the association between preoperative malnutrition based on the CONUT score and short-term outcomes in OE and MIE, separately, as it may clarify whether the low invasiveness of MIE could contribute to alleviating the effect of preoperative malnutrition on the incidence of postoperative morbidities.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 853 Japanese patients underwent three-incision esophagectomy for esophageal cancer at Kumamoto University Hospital between April 2005 and August 2021. Among them, 179 patients with missing data were excluded. Finally, 674 patients were included in this retrospective survey. OE was performed in 296 patients, and MIE was performed in 378 patients (Figure 1). In addition, the OE and MIE groups were further divided into two groups according to the preoperative CONUT scores: normal and light malnutrition, and moderate and severe malnutrition. The short-term outcomes between the groups were retrospectively compared between the OE and MIE groups by using an institutional database. This study was conducted in accordance with the ethical standards of the Declaration of Helsinki 1975. The institutional ethics committee approved all the research procedures (Registration No. 1909) and waived the requirement for written informed consent owing to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTreatment strategy\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients diagnosed as not having lymph node metastasis underwent esophagectomy without preoperative treatment. Patients with non-T4 lymph node-positive tumors received either adjuvant chemotherapy (from April 2005 to July 2008) or neoadjuvant chemotherapy (from August 2008 to August 2021). For T4 tumors, neoadjuvant chemoradiotherapy (CRT) was commonly administered. If patients preferred nonsurgical treatment, definitive CRT was considered regardless of the tumor stage. If definitive CRT was performed and recurrence occurred, salvage esophagectomy was performed according to the patient\u0026rsquo;s requirement. The Union for International Cancer Control TNM staging version 8 was used to classify the pretreatment clinical staging [9].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSurgery\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEsophagectomy was defined as an esophagectomy requiring the placement of three incisions (on the neck, chest, and abdomen) with lymphadenectomy. The extent of lymphadenectomy was determined based on the 11th Japanese Esophageal Cancer Classification [10]. For upper or middle thoracic esophageal cancers, lymphadenectomy was performed in three regions. Cervical lymphadenectomy was not performed for clinical T1 tumors in lower thoracic esophageal cancers. MIE was defined as esophagectomy performed via thoracoscopy, regardless of the use of laparoscopy. MIE for clinical T1 and T2 tumors began in May 2011 and has been performed for clinical T3 and T4 tumors since September 2011.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePerioperative management\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe details of perioperative management have been described previously [11]. Before the start of esophagectomy, a 24-h continuous intravenous infusion of a neutrophil elastase inhibitor and a bolus of methylprednisolone were administered. Antibiotics were administered intraoperatively every 4 h. Extubation was performed in the operating room immediately after esophagectomy. The patient was observed in the intensive care unit on postoperative day 1. Postoperative enteral nutrition was also commonly started on postoperative day 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDefinitions of morbidities\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe details of morbidities have been described previously [8]. A morbidity was defined as a complication \u0026ge; grade II according to the Clavien\u0026ndash;Dindo classification (CDc) [12]. Severe morbidity was defined as a complication \u0026ge; grade IIIb requiring endoscopic, radiological, or surgical intervention under general anesthesia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical methods\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using JMP\u0026reg; version 14.2 (SAS Institute, Cary, NC, USA). Statistical significance was set at p \u0026lt; 0.05. A chi-square test was used for comparisons between groups. The Mann-Whitney U test was used to analyze unpaired samples. A logistic regression analysis was performed to determine the hazard ratio (HR) in the 95% confidence interval (CI) of morbidities. The following data were used to analyze independent risk factors for severe, respiratory, and cardiovascular morbidities: age at esophagectomy (the cutoff value was calculated via receiver operating characteristic [ROC] analysis), sex (male vs. female), body mass index (BMI) (\u0026ge;18.5 vs.\u0026lt;18.5 kg/m\u003csup\u003e2\u003c/sup\u003e), Brinkman index (\u0026ge;800 vs.\u0026lt;800), CONUT (moderate and severe malnutrition vs. normal and light malnutrition), diabetes mellitus (yes vs. no), respiratory comorbidity (yes vs. no), cardiovascular comorbidity (yes vs. no), American Society of Anesthesiologists physical status (ASA-PS) (2 and 3 vs. 1), performance status (PS) (1 and 2 vs. 0), clinical stage (III and IV vs. 0, I, and II), preoperative treatment (yes vs. no), preoperative radiotherapy (yes vs. no), operative time (the cutoff values were calculated via ROC analysis), and bleeding (the cutoff values were calculated via ROC analysis). A subsequent multivariate analysis selected factors with p \u0026le; 0.1 and recognized variables with p \u0026lt; 0.05 as independent risk factors.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical features of all patients who underwent esophagectomy\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 shows the characteristics of all patients who underwent esophagectomy according to the CONUT scores. Of all patients, 48 (7%) were classified as having moderate and severe malnutrition. Compared to normal and light malnutrition, moderate and severe malnutrition significantly correlated with a low BMI (p \u0026lt; 0.001), worse PS (p \u0026lt; 0.001) and ASA-PS (p \u0026lt; 0.001), frequent respiratory comorbidities (p = 0.0023), advanced cancer stage (p \u0026lt; 0.001), and more frequent preoperative treatment (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eShort-term outcomes after OE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows the short-term outcomes after OE according to the CONUT scores. Compared to patients with normal and light malnutrition, those with moderate and severe malnutrition experienced significantly more frequent severe (p = 0.016), respiratory (p = 0.0013) and cardiovascular morbidities (p = 0.013).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eShort-term outcomes after MIE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 shows the short-term outcomes after MIE according to the CONUT scores. Regarding short-term outcomes, malnutrition in CONUT did not increase post-MIE morbidities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eRisk factors for postoperative severe, respiratory, and cardiovascular morbidities after OE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 shows the results of the univariate and multivariate analyses of risk factors for severe, respiratory, and cardiovascular morbidities after OE. Moderate and severe malnutrition in CONUT was an independent risk factor for severe (HR = 3.38; 95% CI, 1.225-9.332; p = 0.019), respiratory (HR = 3.00; 95% CI, 1.161-7.736; p = 0.023), and cardiovascular morbidities (HR = 3.66%; 95% CI, 1.068-12.55; p = 0.039). Risk factor for severe morbidity included cardiovascular comorbidity (HR = 3.16; 95% CI, 1.305-7.633; p = 0.011), for respiratory morbidity included a Brinkman index \u0026ge; 800 (HR = 2.29; 95% CI, 1.122-4.661; p = 0.023) and operation time \u0026ge;530 minutes (HR = 2.03; 95% CI, 1.006-4.098; p = 0.048), and for cardiovascular morbidity included cardiovascular comorbidity (HR = 3.38; 95% CI, 1.124-10.14; p = 0.030) and operation time \u0026ge;591 minutes (HR = 5.06; 95% CI, 1.804-14.18; p = 0.0021).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study yielded several interesting results on the association between preoperative malnutrition estimated using the CONUT scores and short-term outcomes after esophagectomy for esophageal cancer. First, moderate and severe malnutrition in CONUT was significantly associated with several disadvantageous patient characteristics, such as a low BMI, poor PS, poor ASA-PS, and frequent comorbidity. Second, it was also significantly associated with several disadvantageous cancer-related factors, such as advanced cancer stage and frequent preoperative treatment. Third, patients with moderate and severe malnutrition in CONUT who underwent OE had significantly more frequent postoperative severe, respiratory, and cardiovascular morbidities. Finally, malnutrition did not increase the incidence of postoperative morbidities after MIE.\u003c/p\u003e\n\u003cp\u003eSeveral studies have suggested that preoperative malnutrition could cause frequent post-esophagectomy morbidities [6, 13]. However, OE and MIE were not distinctly analyzed in these studies. Thus, the effect of MIE on the incidence of post-esophagectomy morbidities in patients with a poor nutritional status has not been well established. To the best of our knowledge, this is the first study to elucidate that preoperative malnutrition in CONUT was associated with worse short-term outcomes only after OE, but not after MIE.\u003c/p\u003e\n\u003cp\u003eCONUT was calculated using the serum albumin and total cholesterol levels and total lymphocyte count (TLC). Serum albumin levels reflect the nutritional status, inflammation, liver dysfunction, and kidney disease [14, 15]. Total cholesterol levels reflect the nutritional status related to lipid metabolism and inflammation [16, 17]. TLC is an indicator of nutrition and immunity [18]. Deterioration in these parameters can adversely affect tissue repair and resistance against infection, which may be a reason for the increased incidence of postoperative morbidities. Moreover, in this study, malnutrition estimated using the CONUT score was associated with disadvantageous patient characteristics and tumor-related factors for post-esophagectomy morbidity, which might result in frequent post-esophagectomy morbidity and surgery-related mortality [2]. These associations may explain why malnutrition estimated using the CONUT score could be a significant risk factor for postoperative morbidities after OE.\u003c/p\u003e\n\u003cp\u003eNevertheless, malnutrition in CONUT did not affect the incidence of postoperative morbidities after MIE. Studies have reported that MIE is less invasive than OE is and is associated with fewer postoperative morbidities [19]. Several studies have suggested that the low invasiveness of MIE could alleviate the effect of preoperative disadvantageous clinical factors on the incidence of post-esophagectomy morbidities [3, 4]. High preoperative HbA1c levels can be a risk factor for anastomotic leakage, surgical site infection, and pneumonia after esophagectomy [20]. However, it might increase morbidities only after OE, but not after MIE [3]. Moreover, we have reported that a high pretreatment red blood cell distribution width, which is a surrogate marker of the nutritional status, might be an independent risk factor for severe morbidity and reoperation only after OE [4]. These previous studies may support the current result that malnutrition in CONUT could increase the incidence of morbidities only after OE, but not after MIE.\u003c/p\u003e\n\u003cp\u003eFor patients assessed as being malnourished in CONUT, preoperative nutritional interventions may be effective in improving the short-term outcomes. A meta-analysis suggested that the administration of immunoenhancing enteral nutrition might reduce postoperative morbidities after gastrointestinal surgeries [21]. In contrast, a randomized controlled trial suggested that short-term nutritional intervention (7 days before esophagectomy) did not reduce post-esophagectomy morbidities. Thus, long-term nutritional intervention during preoperative treatment should be considered in malnourished patients scheduled to undergo esophagectomy [22]. Improvement in oral ingestion during preoperative treatment via stent insertion for patients with swallowing difficulty due to advanced esophageal cancer may also reduce post-esophagectomy mortality [23].\u003c/p\u003e\n\u003cp\u003eIn this study, malnutrition in CONUT was an independent risk factor for respiratory morbidity after OE. Thus, when patients with malnutrition undergo OE, measures should be taken against respiratory morbidities. Smoking and impaired respiratory function could be risk factors for respiratory morbidities after esophagectomy [24, 25]. Thus, smoking cessation [25] and preoperative respiratory rehabilitation [26] are necessary. Moreover, oral hygiene [27], enforcement of the Enhanced Recovery after Surgery Program [28], and perioperative management by a multidisciplinary perioperative care team [29] are helpful in reducing post-esophagectomy respiratory morbidities. In addition, less invasive surgeries may further reduce post-esophagectomy morbidities in patients with malnutrition undergoing OE. A meta-analysis suggested that compared to MIE, robot-assisted esophagectomy may help reduce the incidence of pneumonia [30]. Transhiatal esophagectomy and mediastinoscopic esophagectomy are also effective candidates for further reducing postoperative respiratory morbidities [31, 32]. These procedures can be treatment options for patients assessed as being malnourished according to their CONUT scores.\u003c/p\u003e\n\u003cp\u003eThis study had several limitations. Because this was a single-center retrospective study conducted over a long period, historical biases with regard to treatment strategy, surgery, and perioperative management existed. Notably, MIEs were more frequently performed in recent cases, and this strategy affected the current results, wherein malnutrition did not increase the incidence of morbidities after MIE. Moreover, the exclusion of patients owing to the lack of data could be a cause of a selection bias.\u003c/p\u003e\n\u003cp\u003eNevertheless, our findings revealed that moderate and severe malnutrition assessed using the preoperative CONUT score can be a predictor of severe, respiratory, and cardiovascular morbidities after OE. Moreover, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript did not receive sponsorship for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no conflict of interest for this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTomo Horinouchi described and designed the article. Naoya Yoshida edited the article. Hideo Baba supervised the editing of the manuscript. Material preparation, data collection and analysis were performed by Tomo Horinouchi, Naoya Yoshida, Kazuto Harada, Kojiro Eto, Masaaki Iwatsuki and Yoshifumi Baba. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.com) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical standards of the Declaration of Helsinki 1975. The institutional ethics committee approved all the research procedures (Registration No. 1909) and waived the requirement for written informed consent owing to the retrospective nature of the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMarubashi S, Takahashi A, Kakeji Y, Hasegawa H, Ueno H, Eguchi S, Endo I, Goi T, Saiura A, Sasaki A, Takiguchi S, Takeuchi H, Tanaka C, Hashimoto M, Hiki N, Horiguchi A, Masaki T, Yoshida K, Gotoh M, Konno H, Yamamoto H, Miyata H, Seto Y, Kitagawa Y; National Clinical Database (2021) National Clinical Database. Surgical outcomes in gastroenterological surgery in Japan: Report of the National Clinical Database 2011\u0026ndash;2019. Ann Gastroenterol Surg. 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Jan; 29 (1): 33\u0026ndash;37. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/0218492320963976\u003c/span\u003e\u003cspan address=\"10.1177/0218492320963976\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eAssociation between malnutrition according to the CONUT and patient characteristics.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003ePreoperative malnutrition degree in CONUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eClinical, epidemiological, and surgical feature\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNormal and light malnutrition\u003c/p\u003e\n \u003cp\u003e(N=626)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eModerate and severe malnutrition\u003c/p\u003e\n \u003cp\u003e(N=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66.5 \u0026plusmn; 8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68.1 \u0026plusmn; 9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSex Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e546 (87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44 (92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBody mass index, mean \u0026plusmn; SD (kg/m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.1 \u0026plusmn; 3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19.6 \u0026plusmn; 3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026dagger;Brinkman Index, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e760 \u0026plusmn; 570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e720 \u0026plusmn; 510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerformance status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e561 (90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25 (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e58 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21 (44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAmerican Society of Anesthesiologists physical status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e123 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e470 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e29 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e33 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e Diabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e136 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e Respiratory disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e215 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e27 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e Cardiovascular disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e328 (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eClinical stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 0, I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e306 (49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e120 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e141 (23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e59 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePreoperative treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Absent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e425 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Neoadjuvant chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143 (23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Neoadjuvant chemoradiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17 (36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Definitive chemoradiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e28 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eThoracic procedure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; OE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e264 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e32 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; MIE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e362 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003eAbbreviation:\u003cem\u003e\u0026nbsp;CONUT,\u0026nbsp;\u003c/em\u003eControlling Nutritional Status; \u003cem\u003eSD,\u003c/em\u003e standard deviation\u003cem\u003e; OE,\u003c/em\u003e Open esophagectomy; \u003cem\u003eMIE,\u003c/em\u003e minimally invasive esophagectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003e\u0026dagger;Brinkman index was calculated as follows: number of cigarettes/day \u0026times; smoking duration (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eShort-term outcomes after open esophagectomy\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003ePreoperative malnutrition degree in CONUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNormal and light malnutrition\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(N=264)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eModerate and severe malnutrition\u003c/p\u003e\n \u003cp\u003e(N=32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOperative time, mean \u0026plusmn; SD (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e540 \u0026plusmn; 120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e550 \u0026plusmn; 150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBleeding, mean \u0026plusmn; SD (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e570 \u0026plusmn; 440\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e710 \u0026plusmn; 550\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAny morbidity, CDc\u0026ge; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e99 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSevere morbidity, CDc\u0026ge; IIIb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRespiratory morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSurgical site infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e71 (27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnastomotic leakage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCardiovascular morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003eAbbreviation:\u003cem\u003e\u0026nbsp;CONUT,\u0026nbsp;\u003c/em\u003eControlling Nutritional Status\u003cem\u003e; SD,\u003c/em\u003e standard deviation; \u003cem\u003eCDc,\u003c/em\u003e Clavien\u0026ndash;Dindo classification; \u003cem\u003eSE\u003c/em\u003e, standard error\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eShort-term outcomes after minimally invasive esophagectomy.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003ePreoperative malnutrition degree in CONUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.63049853372434%\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.205278592375368%\"\u003e\n \u003cp\u003eNormal and light malnutrition\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(N=362)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.16422287390029%\"\u003e\n \u003cp\u003eModerate and severe malnutrition\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(N=16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOperative time, mean \u0026plusmn; SD (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e580 \u0026plusmn; 100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e560 \u0026plusmn; 80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBleeding, mean \u0026plusmn; SD (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e300 \u0026plusmn; 1390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e480 \u0026plusmn; 810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAny morbidity, CDc\u0026ge; II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e124 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSevere morbidity, CDc\u0026ge; IIIb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRespiratory morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSurgical site infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnastomotic leakage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e47 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCardiovascular morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e26 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003eAbbreviation:\u003cem\u003eCONUT,\u0026nbsp;\u003c/em\u003eControlling Nutritional Status\u003cem\u003e; SD,\u003c/em\u003e standard deviation; \u003cem\u003eCDc,\u003c/em\u003e Clavien\u0026ndash;Dindo classification; \u003cem\u003eSE\u003c/em\u003e, standard error\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eLogistic regression analysis of postoperative morbidities in patients who underwent open esophagectomy.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.602836879432624%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"38.43971631205674%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"23.26241134751773%\"\u003e\n \u003cp\u003eUnivariate analysis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"22.69503546099291%\"\u003e\n \u003cp\u003eMultivariate analysis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003eSevere morbidity,\u0026nbsp; CDc \u0026ge;IIIb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCONUT score Moderate and severe malnutrition\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(vs. Normal and light malnutrition)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.35 (0.869-6.342)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.38 (1.225-9.332)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCardiovascular comorbidity (vs. no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.57 (1.438-8.842)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.16 (1.305-7.633)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOperation time \u0026ge;514 min (vs. \u0026lt;514 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.36 (0.981-5.654)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.92 (0.778-4.720)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBleeding \u0026ge;910 g (vs. \u0026lt;910 g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.36 (0.981-5.654)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.50 (0.543-4.129)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\"\u003e\n \u003cp\u003eRespiratory morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026dagger;Brinkman Index \u0026ge;800 (vs. \u0026lt;800)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.27 (1.189-4.322)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.29 (1.122-4.661)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerformance status 1-2 (vs. 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.07 (1.036-4.132)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.57 (0.687-3.581)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCONUT score Moderate and severe malnutrition\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(vs. Normal and light malnutrition)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.93 (1.765-8.730)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.00 (1.161-7.736)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRespiratory comorbidity (vs. no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.15 (1.145-4.037)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.46 (0.728-2.919)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eClinical stage III-IV (vs. 0-II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.02 (1.072-3.812)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.31 (0.601-2.872)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePreoperative therapy (vs. no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.08 (1.106-3.912)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.32 (0.606-2.890)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOperative time \u0026ge;530 min (vs. \u0026lt;530 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.99 (1.045-3.795)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.03 (1.006-4.098)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\"\u003e\n \u003cp\u003eCardiovascular morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAge \u0026ge;73 (vs. \u0026lt;73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.10 (1.238-7.778)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.63 (0.961-7.209)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerformance status 1-2 (vs. 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.81 (1.092-7.205)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.51 (0.462-4.919)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCONUT score Moderate and severe malnutrition\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(vs. Normal and light malnutrition)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.12 (1.459-11.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.66 (1.068-12.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCardiovascular comorbidity (vs. no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.95 (1.099-7.890)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.38 (1.124-10.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOperation time \u0026ge;591 min (vs. \u0026lt;591 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.463 (1.379-8.698)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.06 (1.804-14.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003eAbbreviation:\u003cem\u003eCONUT,\u0026nbsp;\u003c/em\u003eControlling Nutritional Status; \u003cem\u003eHR,\u0026nbsp;\u003c/em\u003ehazard ratio; \u003cem\u003eCI,\u0026nbsp;\u003c/em\u003econfidence interval; \u003cem\u003eCDc,\u003c/em\u003e Clavien\u0026ndash;Dindo classification\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003e\u0026dagger;Brinkman index was calculated as follows: number of cigarettes/day \u0026times; smoking duration (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"CONUT, esophagectomy, morbidity, short-term outcomes","lastPublishedDoi":"10.21203/rs.3.rs-1571524/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1571524/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePreoperative malnutrition is a significant risk factor for post-esophagectomy morbidity. The Controlling Nutritional Status (CONUT) is an index used to assess the nutritional status, and it has been suggested to predict post-esophagectomy morbidity. However, the difference in the predictive value of CONUT in estimating morbidities between open esophagectomy (OE) and minimally invasive esophagectomy (MIE) has not yet been elucidated.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis study included 674 patients(OE, 295; MIE, 378) who underwent three-incision esophagectomy for esophageal cancer between April 2005 and August 2021. The patients were further divided into two groups according to their preoperative CONUT: normal and light malnutrition and moderate and severe malnutrition. Short-term outcomes between these groups were retrospectively compared in the OE and MIE groups.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eModerate and severe malnutrition was significantly associated with a low body mass index, a poor performance status and American Society of Anesthesiologists physical status, advanced cancer stage, and frequent preoperative treatment. These patients also experienced significantly more frequent severe (p=0.016), respiratory (p=0.0013) and cardiovascular morbidities (p=0.013) after OE. Moreover, malnutrition in CONUT was an independent risk factor for severe (hazard ratio [HR]=3.38; 95%confidence interval [CI], 1.225-9.332; p=0.019), respiratory (HR=3.00; 95%CI, 1.161-7.736; p=0.023), and cardiovascular morbidities (HR=3.66; 95%CI, 1.068-12.55; p=0.039) after OE. However, it was not associated with the incidence of morbidities after MIE.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePreoperative malnutrition in CONUT reflects various disadvantageous clinical factors and could be a predictor of worse short-term outcomes after OE. Meanwhile, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.\u003c/p\u003e","manuscriptTitle":"A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as a predictive marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-22 14:22:57","doi":"10.21203/rs.3.rs-1571524/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-05-30T16:51:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-05-06T13:36:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"ae7a1c3f-64ca-4185-acd9-1c6f09b1aff9","date":"2022-05-02T15:39:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"086a7fee-9eb4-4deb-a3f6-2b7867c2a091","date":"2022-05-02T15:34:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-05-02T15:23:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-04-21T12:30:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-04-20T06:17:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2022-04-19T07:21:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"cc16caef-fc23-47b5-a100-9f62722f098f","owner":[],"postedDate":"April 22nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-08-13T20:14:13+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-22 14:22:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1571524","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1571524","identity":"rs-1571524","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}