Intensified outpatient nutrition counselling improves body weight and skeletal muscle loss after esophageal cancer surgery

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To improve nutritional status after esophagectomy, we introduced an intensified nutrition counselling (iNC) protocol. The aim of this study was to evaluate the efficacy of iNC compared with the conventional NC (cNC). Methods : We included 126 patients who underwent esophagectomy before and after NC revision, and compared nutritional status and changes in body composition after esophagectomy between the cNC and iNC groups. Nutritional parameters, including body weight, serum albumin level, and prealbumin level, were assessed. We also calculated skeletal muscle index (SMI) and visceral fat area (VFA) using computed tomography volumetry. Results : There were no significant differences in baseline characteristics or surgical outcomes between the groups. Compared with the cNC group, NC was provided more frequently (P < 0.001) in the iNC group, and compliance rate increased from 56.3% to 91.9% (P < 0.001). Body weight loss at 4 and 6 months and SMI reduction at 6 months were significantly improved in the iNC group compared with the cNC group (P < 0.001, P = 0.032, and P = 0.006, respectively). There were no significant differences in the changes in VFA, serum albumin level, and prealbumin level between the two groups. Conclusions : Outpatient iNC significantly improved body weight and SMI loss 3–6 months after esophagectomy. Therefore, iNC may improve patient quality of life and outcomes by maintaining patient nutritional status. nutritional counseling・body weight・skeletal muscle・esophagectomy Figures Figure 1 Figure 2 Figure 3 Introduction Esophagectomy is the mainstay treatment for esophageal cancer. However, most patients experience loss of appetite and reduced oral intake after esophagectomy [ 1 ]. Oral intake is often difficult to regain due to the magnitude of the surgical invasion [ 2 ], specific postoperative nutritional disturbances due to the resected organ, and reconstruction method; hence, these problems often manifest as feeding difficulties [ 3 ]. Consequently, weight loss is frequently observed in the early postoperative period after esophagectomy. The progression of malnutrition and sarcopenia after esophagectomy for esophageal cancer has a negative impact on long-term prognosis [ 1 , 4 ]. We previously reported that the massive skeletal muscle loss during the early postoperative period after esophagectomy was significantly correlated with poor prognosis in elderly patients [ 5 ]. Therefore, interventions to preserve skeletal muscle volume after esophagectomy may improve long-term outcomes. In Japan, many facilities currently provide postoperative outpatient nutritional counselling (NC) to patients who undergo esophagectomy to help maintain their postoperative nutritional status and muscle volume. However, NC management varies among facilities, and appropriate methods and timeframes are unclear. In our hospital, we routinely place a feeding enterostomy tube during esophagectomy, and experienced registered dietitians (RDs) provide NC to patients until enterostomy removal [ 6 ]. Since September 2020, we have revised the NC protocol more intensively, reinforced compliance with the protocol, and continued NC for longer until the patient’s oral intake stabilized after enterostomy removal. In this study, we aimed to compare the nutritional status and changes in body composition after esophagectomy between patients who received conventional (cNC) and intensified NC (iNC). Patients and Methods Patients We assessed 212 consecutive patients with esophageal cancer who underwent subtotal esophagectomy and gastric conduit reconstruction with cervical anastomosis at Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR) between September 2019 and December 2021. Patients who experienced disease recurrence within 1 year after surgery; underwent adjuvant chemotherapy after surgery; underwent surgery for other cancers within 1 year after surgery; were lost to follow-up within 1 year after surgery; or those who underwent incomplete resection, concurrent pharyngolaryngectomy, or salvage surgery, totaling 86, were excluded. The remaining 126 patients were then included in this study. The study protocol was approved by the Institutional Review Board of the JFCR (approval number: 2023-GB-074), and the study followed the principles of the 1964 Declaration of Helsinki and its later versions. Patients were comprehensively informed about the study without individual written forms, and were given an opportunity to opt out through public announcements, as this was an observational retrospective study. Data Collection The clinicopathological and nutritional data of the eligible patients were collected. Pathological tumor stage was classified based on the 8th edition of the Union for International Cancer Control [ 7 ], and postoperative complications were graded according to the Clavien-Dindo (CD) classification [ 8 ]. We evaluated nutritional parameters, including body weight, serum albumin, and serum prealbumin, preoperatively and at 1, 2, 3, 4, 6, and 12 months after surgery. We also calculated the skeletal muscle index (SMI) and visceral fat area (VFA) at the level of the third lumbar vertebra preoperatively [ 9 ] and at 3, 6, and 12 months after esophagectomy using computed tomography volumetry (the synapse VINCENT image analysis system; Fujifilm Medical, Tokyo, Japan). Surgery and Perioperative Nutritional Management The patients underwent subtotal esophagectomy and gastric conduit reconstruction with cervical anastomosis. Thoracic and abdominal procedures were performed using either an open or a minimally invasive approach. A feeding enterostomy tube was routinely placed during esophagectomy. Preoperatively, patients were administered a 400 kcal/day oral nutritional supplement (ONS) in addition to their usual diet for 5 days. Postoperatively, the patients were administered a polymeric formula from the first postoperative day (POD) via the feeding enterostomy, and the volume was increased by 400 kcal daily until a dose of 1600 kcal was reached. Oral intake was started on POD7, and the volume of tube feeding decreased with an increase in oral intake. After hospital discharge, the patients underwent home enteral feeding of 400 kcal for at least 2 weeks until their first visit. The RDs performed NC and evaluated the nutritional status of the patients at every visit. Postoperative Outpatient Nutritional Counselling In the cNC group, the RDs evaluated patients’ oral intake, body weight, symptoms, and nutritional parameters, including serum albumin and prealbumin levels. The RDs calculated the estimated energy requirements (EERs; 30 [kcal] × ideal body weight [kg]) for each patient, and their diet records were reviewed. When oral energy intake reached approximately 80% of the EERs, the RDs recommended that doctors remove the enterostomy tube. When the RDs did not recommend tube removal, NC was repeated and tube feeding continued. Before revising the NC protocol, NC was completed until tube removal. In September 2020, the NC protocol was revised, which included reinforced compliance with the protocol and NC continuation until the patient’s oral intake stabilized after enterostomy removal. When oral energy intake was insufficient after tube removal, the RDs recommended that the doctors provide ONSs and encourage patients to take them. No other management changes were made during the revision. Statistical Analysis Continuous variables are presented as medians and interquartile ranges and analyzed using the Mann–Whitney U test, whereas categorical variables are presented as frequencies and proportions and analyzed using the Fisher’s exact test. The Wilcoxon signed-rank test was used to compare the repeated measurements. Survival rates were estimated using the Kaplan-Meier method, and statistical differences were evaluated using the log-rank test. Statistical significance was set at a P-value less than 0.05. All statistical analyses were performed using JMP software (SAS Institute Inc., Cary, NC, USA). Results Patient Characteristics and Surgical Outcomes Patient characteristics and surgical outcomes are summarized in Table 1 . The median age was 67 years (range: 60–72 years), 97 (77%) patients were male, and 67 (53.2%) received preoperative chemotherapy. During esophagectomy, the thoracoscopic approach was used in 125 (99.2%) patients. Postoperatively, pneumonia, recurrent laryngeal nerve paralysis, and leakage occurred in 19.8%, 16.7%, and 8.7% of patients, respectively. Severe complications of CD grade III or higher were observed in 21.4% of the patients. The cNC protocol was used in 64 patients, and the iNC protocol was used in 62 patients. Table 1 Patient characteristics and surgical outcomes Variables All (n = 126) Conventional NC group (n = 64) Intensified NC group (n = 62) P value Age: years 67 (60–72) 68 (62–72) 66 (59–71) 0.163 Sex 0.4 Male 97 (77) 47 (73.4) 50 (80.6) Female 29 (23) 17 (26.6) 12 (19.4) ASA-PS 0.177 1 24 (19) 9 (14.1) 15 (24.2) 2,3 102 (81) 55 (85.9) 47 (75.8) Body weight: kg 60.2 (50.8–67.5) 57.3 (50–66) 62.7 (52.2–68.6) 0.321 BMI: kg/m 2 21.4 (19.7–24.1) 21.2 (19.3–23.6) 21.7 (20.2–25) 0.433 VFA: cm 2 73 (33.9–125) 68.6 (36.1–112) 83.1 (33.5–138) 0.303 SMI: cm 2 /m 2 43.7 (38.9–50.3) 43.1 (37.5–49.2) 44.3 (39.5–51.1) 0.262 Preoperative therapy 0.655 None 58 (46.0) 31 (48.4) 27 (43.6) Chemotherapy 67 (53.2) 33 (51.6) 34 (54.8) Chemoradiotherapy 1 (0.8) 0 (0.0) 1 (1.6) Tumor location 0.051 Upper 31 (24.6) 17 (26.5) 14 (22.6) Middle 55 (43.6) 33 (51.6) 22 (35.4) Lower 40 (31.8) 14 (21.9) 26 (42.0) Pathological stage 0.927 0-I 65 (51.6) 33 (51.6) 32 (51.6) II 30 (23.8) 16 (25) 14 (22.6) III 26 (20.6) 12 (18.8) 14 (22.6) IV 5 (4.0) 3 (4.7) 2 (3.2) Surgical approach 1 Thoracotomy 1 (0.8) 1 (1.6) 0 Thoracoscopy 125 (99.2) 63 (98.4) 62 (100) Reconstruction route 1 Retrosternal 111 (88.1) 56 (87.5) 55 (88.7) Posterior mediastinal 15 (11.9) 8 (12.5) 7 (11.3) Operative time: min 444 (372–502) 437 (364–480) 460 (376–532) 0.106 Operative blood loss: mL 100 (60–153) 105 (61–160) 80 (60–133) 0.088 Postoperative complications 64 (50.8) 36 (56.3) 28 (45.2) 0.285 Pneumonia 25 (19.8) 14 (21.9) 11 (17.7) 0.657 Recurrent laryngeal nerve paralysis 21 (16.7) 12 (18.8) 9 (14.5) 0.479 Anastomotic leakage 11 (8.7) 5 (7.8) 6 (9.7) 0.723 Surgical site infection 4 (3.2) 2 (3.1) 2 (3.2) 1 Anastomotic stenosis 15 (11.9) 10 (15.6) 5 (8.1) 0.723 Severe complications (≥ grade III) 27 (21.4) 13 (20.3) 14 (22.6) 1 Abbreviations: NC, nutrition counselling; ASA-PS, American Society of Anesthesiologists physical status; BMI, body mass index; VFA, visceral fat area; SMI, skeletal muscle index When comparing the baseline characteristics, including nutritional status and preoperative body composition, there were no significant differences between the groups. However, there were more patients with lower esophageal tumors in the iNC group. In addition, there were no significant differences in the surgical procedures or incidence of postoperative complications between the two groups. Practices of Counselling and Postoperative Course after Discharge NC was performed twice at a median of 1–3 times, and the rate of compliance in which patients and doctors followed the recommendations of the RDs and completed the protocol was 73.8% (Table 2 ). The median duration of enterostomy placement was 61 days (range: 52–83 days). Readmission within 1 year after esophagectomy due to impaired oral intake or aspiration pneumonia was observed in 3.2% (n = 4) of the patients. Table 2 Practices of counseling and postoperative course after discharge Variables All (n = 126) Conventional NC group (n = 64) Intensified NC group (n = 62) P value Frequency of postoperative outpatient NC 2 (1–3) 1 (1–2) 2 (2–4) < 0.001 * Compliance rate 98 (73.8) 36 (56.3) 57 (91.9) < 0.001 * Postoperative enterostomy duration: days 61 (52–83) 58 (51–86) 66 (52–83) 0.189 Readmission within 1 year after surgery 4 (3.2) 2 (3.1) 2 (3.2) 1 Impaired oral intake 3 (2.4) 2 (3.1) 1 (1.6) Aspiration pneumonia 1 (0.8) 0 1 (1.6) Abbreviations: NC, nutritional counselling *P < 0.05 After protocol revision, NC was provided more frequently (Table 2 , P < 0.001), and the compliance rate increased from 56.3–91.9% (P < 0.001). Before revision, 13 patients (20.3%) had never undergone NC (Supplementary Fig. 1). The enterostomy duration and readmission rates were comparable between the groups. Postoperative Nutritional Changes after Esophagectomy As shown in Fig. 1 and Supplementary Table 1, body weight, SMI, VFA, and serum prealbumin values remained significantly decreased and did not improve for 1 year after esophagectomy. Body weight decreased by 8.8% (range: 7.5–11.3%) at 3 months and by 10.9% (range: 5.3–15.6%) at 1 year postoperatively. The SMI also decreased by 1.8% (range: 5.7% decrease– 4.2% increase) at 3 months and by 3.4% (range: 7.4% decrease–1.0% increase) at 1 year after esophagectomy. In particular, the decrease in VFA was noticeable. VFA decreased by 62.8% (range: 46.9–78.6%) at 3 months and 76.3% (range: 50.4–90.6%) at 1 year postoperatively. Although serum albumin levels did not show a significant change, serum prealbumin levels decreased by 24.3% (range: 18.1–36.1%) at 3 months and 15.7% (range: 1.0–26.1%) at 1 year postoperatively (Supplementary Table 2). Body weight at 6 months (P = 0.031) and SMI at 3 and 6 months after esophagectomy (P = 0.033 and 0.049, respectively) were significantly higher in the iNC group than in the cNC group (Fig. 2 ). In addition, body weight loss at 4 and 6 months (P < 0.001 and P = 0.032, respectively) and SMI reduction at 6 months (P = 0.006) significantly improved in the iNC group compared with the cNC group (Fig. 3 ). In contrast, there were no significant differences in the changes in VFA, serum albumin level, or serum prealbumin level between the groups. None of these parameters differed between the groups at 1 year (Supplementary Table 2). Survival Analysis As shown in Supplementary Fig. 2, The median follow-up time was 39 (range: 32.4–45.1) months. There were no significant differences in overall or relapse-free survival between the groups (P = 0.140 and 0.249, respectively). When comparing survival between patients with and without major SMI reduction stratified by the quartiles of SMI reduction rate at 3 months, patients with major SMI reduction (> 5.68% decrease) showed worse relapse-free survival than did those without (P = 0.025). Discussion In the present study, we explored whether more intense NC contributes to an improved nutritional status after esophagectomy. From our results, iNC, in which NC was provided more frequently and continued after enteral feeding completion, could significantly reduce body weight loss and SMI loss 3–6 months after esophagectomy. Although the differences at 1 year were not significant, iNC may mitigate nutritional deficiency, leading to improved patient quality of life and outcomes. In general, body weight loss after esophagectomy is one of the most important postoperative sequelae, and it has been reported that more than half of patients lose more than 10% of their initial weight at 6 months postoperatively [ 1 , 10 – 12 ]. Post-esophagectomy patients often have several postoperative symptoms such as eating difficulties, pain, fatigue, nausea, and appetite loss, resulting in long-lasting weight loss after surgery [ 13 ]. Although no fundamental countermeasures for this issue have been found, enteral feeding support via enterostomy is frequently used, and ONSs and postoperative outpatient NC are provided in many facilities. Previously, it was suggested that enteral feeding immediately after esophagectomy could suppress weight loss at 14 days postoperatively [ 14 ]. However, it has also been reported that weight loss following esophagectomy occurs once tube feeding is stopped, independent of the time interval after esophagectomy [ 15 ]. Moreover, the routine placement of a feeding enterostomy did not result in the improvement of weight loss 3 months after surgery [ 16 ]. In addition, Hyltander et al. suggested that artificial nutrition after major surgery including supportive enteral and parenteral nutrition, was not superior to oral nutrition only when guided by a dietitian [ 17 ]. Although few studies have demonstrated the significance of ONSs in post-esophagectomy patients, a recent small pilot study showed that additional ONS intake for 4 weeks after esophagectomy could prevent body weight loss at 3–6 months postoperatively, and have a positive impact on quality of life 1 month after surgery [ 18 ]. Meanwhile, a recent randomized controlled trial of patients with gastric cancer undergoing gastrectomy showed that administration of ONS for 12 weeks after gastrectomy could improve body weight loss at 3 months postoperatively, although it could not improve body weight loss 1 year after gastrectomy [ 19 ]. We could not evaluate the significance of ONS in the present study, due to its retrospective nature, as intake volume was not assessed. However, ONS may be effective in improving daily energy intake and mitigating mid-term body weight loss after upper gastrointestinal cancer surgery. Our study showed that iNC could improve body weight and SMI loss 3–6 months after esophagectomy. RDs can provide detailed NC on diet and food intake based on a patient’s symptoms. Therefore, patients intensively guided by RDs can consume normal food supplemented with various ONSs. In addition, RDs can flexibly modify the type of ONS and diet depending on the patient’s condition and preferences. It has been also suggested that preoperative NC could preserve body weight in patients with esophageal cancer [ 20 , 21 ]. Prolonged postoperative NC may improve energy and protein intake, and minimize weight and skeletal muscle loss. Poor nutritional status and massive reductions in postoperative body weight and SMI are significantly correlated with poor prognosis [ 5 , 10 , 13 , 22 ]. In the present study, we also confirmed that patients with major SMI reduction had a worse prognosis than those without. However, we did not observe a significant improvement in prognosis with iNC, although iNC significantly improved body weight and SMI loss 3–6 months after esophagectomy. Since we aimed to evaluate the nutritional status and changes in body composition after esophagectomy in this study, patients who experienced disease recurrence within 1 year after surgery and those who underwent adjuvant chemotherapy after surgery were excluded. This may have influenced survival analysis. This study had some limitations that should be addressed. First, this was a retrospective observational study conducted at a single center with a limited number of patients. Second, although the study period was relatively short, the treatment and management of the patients improved with each passing year, suggesting that it is not beyond historical comparison. Third, NC was conducted using several RDs, which may have led to differences in NC content. The analytical method used in this study may have resulted in some biases, as described above. Finally, we could not evaluate long-term quality of life. Further prospective studies assessing larger numbers of patients are required. In conclusion, outpatient iNC significantly improved body weight and SMI loss 3–6 months after esophagectomy. Therefore, iNC may improve patients’ quality of life and outcomes by improving their postoperative nutritional status. Declarations Conflicts of interest: The authors declare that they have no competing financial interests or personal relationships that may have influenced this work. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution All authors contributed to the conception and design of this study. Naoki Takahashi, Akihiko Okamura, and Misuzu Ishii collected and analyzed the data. The first draft of the manuscript was written by Naoki Takahashi and Akihiko Okamura, and all authors commented on previous versions of the manuscript. All the authors have read and approved the final version of the manuscript. Acknowledgement We would like to thank Editage for English language editing. Data availability statement No datasets were generated or analysed during the current study. References Baker M, Halliday V, Williams RN, Bowrey DJ (2016) A systematic review of the nutritional consequences of esophagectomy. Clin Nutr 35:987–994 Bozzetti F (2010) Nutritional support in patients with oesophageal cancer. 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Dis Esophagus 33 Hyltander A, Bosaeus I, Svedlund J, Liedman B, Hugosson I, Wallengren O et al (2005) Supportive nutrition on recovery of metabolism, nutritional state, health-related quality of life, and exercise capacity after major surgery: a randomized study. Clin Gastroenterol Hepatol 3:466–474 Xie H, Chen X, Xu L, Zhang R, Hang X, Wei X et al (2021) A randomized controlled trial of oral nutritional supplementation versus standard diet following McKeown minimally invasive esophagectomy in patients with esophageal malignancy: a pilot study. Ann Transl Med 9:1674 Miyazaki Y, Omori T, Fujitani K, Fujita J, Kawabata R, Imamura H et al (2021) Oral nutritional supplements versus a regular diet alone for body weight loss after gastrectomy: a phase 3, multicenter, open-label randomized controlled trial. Gastric Cancer 24:1150–1159 Ligthart-Melis GC, Weijs PJ, te Boveldt ND, Buskermolen S, Esrthman CP, Verheul HM et al (2013) Dietician-delivered intensive nutritional support is associated with a decrease in severe postoperative complications after surgery in patients with esophageal cancer. Dis Esophagus 26:587–593 AlleaBelle Gongola M, Reif RJ, Cosgrove PC, Sexton KW, Marino KA, Steliga MA et al (2022) Preoperative nutritional counselling in patients undergoing oesophagectomy. J Perioper Pract 32:183–189 Liu J, Xie X, Zhou C (2012) al Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma? Eur J Cardiothorac Surg 41:e7–11 Additional Declarations No competing interests reported. Supplementary Files SupplementaryFig.1.jpg Fig. 1 Frequency of postoperative outpatient NC NC, nutrition counselling SupplementaryFig.2.jpg Fig. 2 Comparison of overall survival rate (a), relapse-free survival rate (b) between cNC and iNC groups. Comparison of overall survival rate (c), relapse-free survival rate (d) between low and major SMI reduction groups *P < 0.05 cNC, conventional nutrition counselling; iNC, intensified nutrition counselling SupplementaryTable.docx Supplementary Table Table 1 Postoperative nutritional changes after esophagectomy Table 2 Comparison of postoperative nutritional changes after esophagectomy between the two groups Cite Share Download PDF Status: Published Journal Publication published 04 Nov, 2024 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editorial decision: Revision requested 08 Sep, 2024 Reviews received at journal 08 Sep, 2024 Reviewers agreed at journal 02 Sep, 2024 Reviews received at journal 17 Jul, 2024 Reviewers agreed at journal 14 Jul, 2024 Reviewers invited by journal 13 Jul, 2024 Editor assigned by journal 02 Jul, 2024 Submission checks completed at journal 28 Jun, 2024 First submitted to journal 25 Jun, 2024 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. 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Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Misuzu","middleName":"","lastName":"Ishii","suffix":""},{"id":328880420,"identity":"10262bd7-7a19-4ddd-bd76-6c235b485164","order_by":3,"name":"Naoki Moriya","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Moriya","suffix":""},{"id":328880421,"identity":"8ea68c7c-0391-4333-b241-59732f8481c3","order_by":4,"name":"Aya Yamaguchi","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Aya","middleName":"","lastName":"Yamaguchi","suffix":""},{"id":328880423,"identity":"452a794b-96e2-4f22-9fb1-48afb393d926","order_by":5,"name":"Yuka Inamochi","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Yuka","middleName":"","lastName":"Inamochi","suffix":""},{"id":328880426,"identity":"d866c40d-d545-4b57-a97b-100166827969","order_by":6,"name":"Kumi Takagi","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Kumi","middleName":"","lastName":"Takagi","suffix":""},{"id":328880428,"identity":"9669c619-822e-423e-a9ef-a379ad43e13b","order_by":7,"name":"Erika Nakaya","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Erika","middleName":"","lastName":"Nakaya","suffix":""},{"id":328880430,"identity":"dcfde5a7-5da7-413f-9f38-bace3a1c9a32","order_by":8,"name":"Kengo Kuriyama","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Kengo","middleName":"","lastName":"Kuriyama","suffix":""},{"id":328880431,"identity":"607a3e44-b521-4f16-8dfa-ba07c4adf728","order_by":9,"name":"Masayoshi Terayama","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Masayoshi","middleName":"","lastName":"Terayama","suffix":""},{"id":328880432,"identity":"2d6ff8b4-f26e-4897-b49c-8a873b0d5882","order_by":10,"name":"Masahiro Tamura","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Tamura","suffix":""},{"id":328880433,"identity":"c74c6599-b50d-4a36-80ce-6b6032205ac6","order_by":11,"name":"Jun Kanamori","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Kanamori","suffix":""},{"id":328880434,"identity":"4d31a107-409f-4901-9130-6a027975f0ed","order_by":12,"name":"Yu Imamura","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Imamura","suffix":""},{"id":328880435,"identity":"2f1bc86e-a2d0-4b6c-b0cb-8963bf288108","order_by":13,"name":"Yoko Saino","email":"","orcid":"","institution":"Department of Clinical Nutrition, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan","correspondingAuthor":false,"prefix":"","firstName":"Yoko","middleName":"","lastName":"Saino","suffix":""},{"id":328880436,"identity":"1cc20444-791e-4f8b-aba6-1d7cd46fa412","order_by":14,"name":"Masayuki Watanabe","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Masayuki","middleName":"","lastName":"Watanabe","suffix":""}],"badges":[],"createdAt":"2024-06-25 05:07:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4633595/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4633595/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00423-024-03526-2","type":"published","date":"2024-11-04T15:58:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60851095,"identity":"92d66040-8201-472a-8d30-0b5829388ce5","added_by":"auto","created_at":"2024-07-22 20:57:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":163350,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative change of body weight (a), skeletal muscle index (b), visceral fat area (c), serum albumin (d), and serum prealbumin (e)\u003c/p\u003e\n\u003cp\u003e*P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/6be242ccbd2cb9cc3399869b.jpg"},{"id":60851950,"identity":"e8ca3da9-ce83-4024-9a6d-ce37f614ad83","added_by":"auto","created_at":"2024-07-22 21:05:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":203040,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of postoperative changes in body weight (a), skeletal muscle index (b), visceral fat area (c), serum albumin (d), and serum prealbumin (e) between the two groups\u003c/p\u003e\n\u003cp\u003e*P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/b6a341efb534832457568f02.jpg"},{"id":60851097,"identity":"331610ae-172d-4690-aa4e-ef4ea417c244","added_by":"auto","created_at":"2024-07-22 20:57:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":158866,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of postoperative change rate in body weight loss (a), skeletal muscle index loss (b), and visceral fat area loss (c) between the two groups\u003c/p\u003e\n\u003cp\u003e*P \u0026lt; 0.05\u003c/p\u003e","description":"","filename":"Fig.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/e8f946de58b0ad6b599f535a.jpg"},{"id":68750078,"identity":"b47be036-1ff7-449c-97e5-6313a8f11253","added_by":"auto","created_at":"2024-11-11 16:09:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1188643,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/ebb890a0-fe69-46fc-9300-568512205ec1.pdf"},{"id":60851091,"identity":"24c8831b-57ec-4cf7-9af1-cc3f4e214791","added_by":"auto","created_at":"2024-07-22 20:57:54","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":124960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. 1 \u003c/strong\u003eFrequency of postoperative outpatient NC\u003c/p\u003e\n\u003cp\u003eNC, nutrition counselling\u003c/p\u003e","description":"","filename":"SupplementaryFig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/1d604b364ab822f892548da3.jpg"},{"id":60851949,"identity":"74c676fe-851e-4dbf-8d38-e52cb5ee5d73","added_by":"auto","created_at":"2024-07-22 21:05:54","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":72246,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. 2 \u003c/strong\u003eComparison of overall survival rate (a), relapse-free survival rate (b) between cNC and iNC groups. Comparison of overall survival rate (c), relapse-free survival rate (d) between low and major SMI reduction groups\u003c/p\u003e\n\u003cp\u003e*P \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003ecNC, conventional nutrition counselling; iNC, intensified nutrition counselling\u003c/p\u003e","description":"","filename":"SupplementaryFig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/d5a725640db981056d538b6b.jpg"},{"id":60851093,"identity":"7d994417-f308-47e1-984a-2d232e900441","added_by":"auto","created_at":"2024-07-22 20:57:54","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":27780,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Postoperative nutritional changes after esophagectomy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u003c/strong\u003eComparison of postoperative nutritional changes after esophagectomy between the two groups\u003c/p\u003e","description":"","filename":"SupplementaryTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-4633595/v1/b5e6d37a035ce3406ffc8119.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intensified outpatient nutrition counselling improves body weight and skeletal muscle loss after esophageal cancer surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophagectomy is the mainstay treatment for esophageal cancer. However, most patients experience loss of appetite and reduced oral intake after esophagectomy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Oral intake is often difficult to regain due to the magnitude of the surgical invasion [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], specific postoperative nutritional disturbances due to the resected organ, and reconstruction method; hence, these problems often manifest as feeding difficulties [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, weight loss is frequently observed in the early postoperative period after esophagectomy.\u003c/p\u003e \u003cp\u003eThe progression of malnutrition and sarcopenia after esophagectomy for esophageal cancer has a negative impact on long-term prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We previously reported that the massive skeletal muscle loss during the early postoperative period after esophagectomy was significantly correlated with poor prognosis in elderly patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, interventions to preserve skeletal muscle volume after esophagectomy may improve long-term outcomes.\u003c/p\u003e \u003cp\u003eIn Japan, many facilities currently provide postoperative outpatient nutritional counselling (NC) to patients who undergo esophagectomy to help maintain their postoperative nutritional status and muscle volume. However, NC management varies among facilities, and appropriate methods and timeframes are unclear. In our hospital, we routinely place a feeding enterostomy tube during esophagectomy, and experienced registered dietitians (RDs) provide NC to patients until enterostomy removal [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Since September 2020, we have revised the NC protocol more intensively, reinforced compliance with the protocol, and continued NC for longer until the patient\u0026rsquo;s oral intake stabilized after enterostomy removal. In this study, we aimed to compare the nutritional status and changes in body composition after esophagectomy between patients who received conventional (cNC) and intensified NC (iNC).\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eWe assessed 212 consecutive patients with esophageal cancer who underwent subtotal esophagectomy and gastric conduit reconstruction with cervical anastomosis at Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR) between September 2019 and December 2021. Patients who experienced disease recurrence within 1 year after surgery; underwent adjuvant chemotherapy after surgery; underwent surgery for other cancers within 1 year after surgery; were lost to follow-up within 1 year after surgery; or those who underwent incomplete resection, concurrent pharyngolaryngectomy, or salvage surgery, totaling 86, were excluded. The remaining 126 patients were then included in this study.\u003c/p\u003e \u003cp\u003e The study protocol was approved by the Institutional Review Board of the JFCR (approval number: 2023-GB-074), and the study followed the principles of the 1964 Declaration of Helsinki and its later versions. Patients were comprehensively informed about the study without individual written forms, and were given an opportunity to opt out through public announcements, as this was an observational retrospective study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eThe clinicopathological and nutritional data of the eligible patients were collected. Pathological tumor stage was classified based on the 8th edition of the Union for International Cancer Control [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and postoperative complications were graded according to the Clavien-Dindo (CD) classification [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe evaluated nutritional parameters, including body weight, serum albumin, and serum prealbumin, preoperatively and at 1, 2, 3, 4, 6, and 12 months after surgery. We also calculated the skeletal muscle index (SMI) and visceral fat area (VFA) at the level of the third lumbar vertebra preoperatively [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and at 3, 6, and 12 months after esophagectomy using computed tomography volumetry (the synapse VINCENT image analysis system; Fujifilm Medical, Tokyo, Japan).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSurgery and Perioperative Nutritional Management\u003c/h2\u003e \u003cp\u003eThe patients underwent subtotal esophagectomy and gastric conduit reconstruction with cervical anastomosis. Thoracic and abdominal procedures were performed using either an open or a minimally invasive approach. A feeding enterostomy tube was routinely placed during esophagectomy.\u003c/p\u003e \u003cp\u003ePreoperatively, patients were administered a 400 kcal/day oral nutritional supplement (ONS) in addition to their usual diet for 5 days. Postoperatively, the patients were administered a polymeric formula from the first postoperative day (POD) via the feeding enterostomy, and the volume was increased by 400 kcal daily until a dose of 1600 kcal was reached. Oral intake was started on POD7, and the volume of tube feeding decreased with an increase in oral intake. After hospital discharge, the patients underwent home enteral feeding of 400 kcal for at least 2 weeks until their first visit. The RDs performed NC and evaluated the nutritional status of the patients at every visit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative Outpatient Nutritional Counselling\u003c/h2\u003e \u003cp\u003eIn the cNC group, the RDs evaluated patients\u0026rsquo; oral intake, body weight, symptoms, and nutritional parameters, including serum albumin and prealbumin levels. The RDs calculated the estimated energy requirements (EERs; 30 [kcal] \u0026times; ideal body weight [kg]) for each patient, and their diet records were reviewed. When oral energy intake reached approximately 80% of the EERs, the RDs recommended that doctors remove the enterostomy tube. When the RDs did not recommend tube removal, NC was repeated and tube feeding continued. Before revising the NC protocol, NC was completed until tube removal.\u003c/p\u003e \u003cp\u003eIn September 2020, the NC protocol was revised, which included reinforced compliance with the protocol and NC continuation until the patient\u0026rsquo;s oral intake stabilized after enterostomy removal. When oral energy intake was insufficient after tube removal, the RDs recommended that the doctors provide ONSs and encourage patients to take them. No other management changes were made during the revision.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are presented as medians and interquartile ranges and analyzed using the Mann\u0026ndash;Whitney U test, whereas categorical variables are presented as frequencies and proportions and analyzed using the Fisher\u0026rsquo;s exact test. The Wilcoxon signed-rank test was used to compare the repeated measurements. Survival rates were estimated using the Kaplan-Meier method, and statistical differences were evaluated using the log-rank test. Statistical significance was set at a P-value less than 0.05. All statistical analyses were performed using JMP software (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics and Surgical Outcomes\u003c/h2\u003e \u003cp\u003ePatient characteristics and surgical outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 67 years (range: 60\u0026ndash;72 years), 97 (77%) patients were male, and 67 (53.2%) received preoperative chemotherapy. During esophagectomy, the thoracoscopic approach was used in 125 (99.2%) patients. Postoperatively, pneumonia, recurrent laryngeal nerve paralysis, and leakage occurred in 19.8%, 16.7%, and 8.7% of patients, respectively. Severe complications of CD grade III or higher were observed in 21.4% of the patients. The cNC protocol was used in 64 patients, and the iNC protocol was used in 62 patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics and surgical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;126)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional NC group (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntensified NC group (n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge: years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (60\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (62\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (59\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (73.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (80.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA-PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102 (81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (85.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (75.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody weight: kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.2 (50.8\u0026ndash;67.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.3 (50\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.7 (52.2\u0026ndash;68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI: kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.4 (19.7\u0026ndash;24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.2 (19.3\u0026ndash;23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.7 (20.2\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVFA: cm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (33.9\u0026ndash;125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.6 (36.1\u0026ndash;112)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.1 (33.5\u0026ndash;138)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSMI: cm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.7 (38.9\u0026ndash;50.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.1 (37.5\u0026ndash;49.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.3 (39.5\u0026ndash;51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (46.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemoradiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0-I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (20.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical approach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThoracotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThoracoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125 (99.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (98.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReconstruction route\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetrosternal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111 (88.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior mediastinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time: min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e444 (372\u0026ndash;502)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e437 (364\u0026ndash;480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e460 (376\u0026ndash;532)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative blood loss: mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (60\u0026ndash;153)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (61\u0026ndash;160)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (60\u0026ndash;133)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.657\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrent laryngeal nerve paralysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.479\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical site infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic stenosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere complications (\u0026ge;\u0026thinsp;grade III)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: NC, nutrition counselling; ASA-PS, American Society of Anesthesiologists physical status; BMI, body mass index; VFA, visceral fat area; SMI, skeletal muscle index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen comparing the baseline characteristics, including nutritional status and preoperative body composition, there were no significant differences between the groups. However, there were more patients with lower esophageal tumors in the iNC group. In addition, there were no significant differences in the surgical procedures or incidence of postoperative complications between the two groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePractices of Counselling and Postoperative Course after Discharge\u003c/h2\u003e \u003cp\u003eNC was performed twice at a median of 1\u0026ndash;3 times, and the rate of compliance in which patients and doctors followed the recommendations of the RDs and completed the protocol was 73.8% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median duration of enterostomy placement was 61 days (range: 52\u0026ndash;83 days). Readmission within 1 year after esophagectomy due to impaired oral intake or aspiration pneumonia was observed in 3.2% (n\u0026thinsp;=\u0026thinsp;4) of the patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePractices of counseling and postoperative course after discharge\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;126)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConventional NC group (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntensified NC group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency of postoperative outpatient NC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompliance rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98 (73.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative enterostomy duration: days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (52\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (51\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (52\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReadmission within 1 year after surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImpaired oral intake\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspiration pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: NC, nutritional counselling\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*P\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter protocol revision, NC was provided more frequently (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the compliance rate increased from 56.3\u0026ndash;91.9% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Before revision, 13 patients (20.3%) had never undergone NC (Supplementary Fig.\u0026nbsp;1). The enterostomy duration and readmission rates were comparable between the groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative Nutritional Changes after Esophagectomy\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Supplementary Table\u0026nbsp;1, body weight, SMI, VFA, and serum prealbumin values remained significantly decreased and did not improve for 1 year after esophagectomy. Body weight decreased by 8.8% (range: 7.5\u0026ndash;11.3%) at 3 months and by 10.9% (range: 5.3\u0026ndash;15.6%) at 1 year postoperatively. The SMI also decreased by 1.8% (range: 5.7% decrease\u0026ndash; 4.2% increase) at 3 months and by 3.4% (range: 7.4% decrease\u0026ndash;1.0% increase) at 1 year after esophagectomy. In particular, the decrease in VFA was noticeable. VFA decreased by 62.8% (range: 46.9\u0026ndash;78.6%) at 3 months and 76.3% (range: 50.4\u0026ndash;90.6%) at 1 year postoperatively. Although serum albumin levels did not show a significant change, serum prealbumin levels decreased by 24.3% (range: 18.1\u0026ndash;36.1%) at 3 months and 15.7% (range: 1.0\u0026ndash;26.1%) at 1 year postoperatively (Supplementary Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBody weight at 6 months (P\u0026thinsp;=\u0026thinsp;0.031) and SMI at 3 and 6 months after esophagectomy (P\u0026thinsp;=\u0026thinsp;0.033 and 0.049, respectively) were significantly higher in the iNC group than in the cNC group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, body weight loss at 4 and 6 months (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and P\u0026thinsp;=\u0026thinsp;0.032, respectively) and SMI reduction at 6 months (P\u0026thinsp;=\u0026thinsp;0.006) significantly improved in the iNC group compared with the cNC group (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In contrast, there were no significant differences in the changes in VFA, serum albumin level, or serum prealbumin level between the groups. None of these parameters differed between the groups at 1 year (Supplementary Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSurvival Analysis\u003c/h2\u003e \u003cp\u003eAs shown in Supplementary Fig.\u0026nbsp;2, The median follow-up time was 39 (range: 32.4\u0026ndash;45.1) months. There were no significant differences in overall or relapse-free survival between the groups (P\u0026thinsp;=\u0026thinsp;0.140 and 0.249, respectively). When comparing survival between patients with and without major SMI reduction stratified by the quartiles of SMI reduction rate at 3 months, patients with major SMI reduction (\u0026gt;\u0026thinsp;5.68% decrease) showed worse relapse-free survival than did those without (P\u0026thinsp;=\u0026thinsp;0.025).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we explored whether more intense NC contributes to an improved nutritional status after esophagectomy. From our results, iNC, in which NC was provided more frequently and continued after enteral feeding completion, could significantly reduce body weight loss and SMI loss 3\u0026ndash;6 months after esophagectomy. Although the differences at 1 year were not significant, iNC may mitigate nutritional deficiency, leading to improved patient quality of life and outcomes.\u003c/p\u003e \u003cp\u003eIn general, body weight loss after esophagectomy is one of the most important postoperative sequelae, and it has been reported that more than half of patients lose more than 10% of their initial weight at 6 months postoperatively [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Post-esophagectomy patients often have several postoperative symptoms such as eating difficulties, pain, fatigue, nausea, and appetite loss, resulting in long-lasting weight loss after surgery [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although no fundamental countermeasures for this issue have been found, enteral feeding support via enterostomy is frequently used, and ONSs and postoperative outpatient NC are provided in many facilities.\u003c/p\u003e \u003cp\u003ePreviously, it was suggested that enteral feeding immediately after esophagectomy could suppress weight loss at 14 days postoperatively [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, it has also been reported that weight loss following esophagectomy occurs once tube feeding is stopped, independent of the time interval after esophagectomy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Moreover, the routine placement of a feeding enterostomy did not result in the improvement of weight loss 3 months after surgery [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition, Hyltander et al. suggested that artificial nutrition after major surgery including supportive enteral and parenteral nutrition, was not superior to oral nutrition only when guided by a dietitian [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough few studies have demonstrated the significance of ONSs in post-esophagectomy patients, a recent small pilot study showed that additional ONS intake for 4 weeks after esophagectomy could prevent body weight loss at 3\u0026ndash;6 months postoperatively, and have a positive impact on quality of life 1 month after surgery [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Meanwhile, a recent randomized controlled trial of patients with gastric cancer undergoing gastrectomy showed that administration of ONS for 12 weeks after gastrectomy could improve body weight loss at 3 months postoperatively, although it could not improve body weight loss 1 year after gastrectomy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. We could not evaluate the significance of ONS in the present study, due to its retrospective nature, as intake volume was not assessed. However, ONS may be effective in improving daily energy intake and mitigating mid-term body weight loss after upper gastrointestinal cancer surgery.\u003c/p\u003e \u003cp\u003eOur study showed that iNC could improve body weight and SMI loss 3\u0026ndash;6 months after esophagectomy. RDs can provide detailed NC on diet and food intake based on a patient\u0026rsquo;s symptoms. Therefore, patients intensively guided by RDs can consume normal food supplemented with various ONSs. In addition, RDs can flexibly modify the type of ONS and diet depending on the patient\u0026rsquo;s condition and preferences. It has been also suggested that preoperative NC could preserve body weight in patients with esophageal cancer [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Prolonged postoperative NC may improve energy and protein intake, and minimize weight and skeletal muscle loss.\u003c/p\u003e \u003cp\u003ePoor nutritional status and massive reductions in postoperative body weight and SMI are significantly correlated with poor prognosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In the present study, we also confirmed that patients with major SMI reduction had a worse prognosis than those without. However, we did not observe a significant improvement in prognosis with iNC, although iNC significantly improved body weight and SMI loss 3\u0026ndash;6 months after esophagectomy. Since we aimed to evaluate the nutritional status and changes in body composition after esophagectomy in this study, patients who experienced disease recurrence within 1 year after surgery and those who underwent adjuvant chemotherapy after surgery were excluded. This may have influenced survival analysis.\u003c/p\u003e \u003cp\u003eThis study had some limitations that should be addressed. First, this was a retrospective observational study conducted at a single center with a limited number of patients. Second, although the study period was relatively short, the treatment and management of the patients improved with each passing year, suggesting that it is not beyond historical comparison. Third, NC was conducted using several RDs, which may have led to differences in NC content. The analytical method used in this study may have resulted in some biases, as described above. Finally, we could not evaluate long-term quality of life. Further prospective studies assessing larger numbers of patients are required.\u003c/p\u003e \u003cp\u003eIn conclusion, outpatient iNC significantly improved body weight and SMI loss 3\u0026ndash;6 months after esophagectomy. Therefore, iNC may improve patients\u0026rsquo; quality of life and outcomes by improving their postoperative nutritional status.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eConflicts of interest:\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no competing financial interests or personal relationships that may have influenced this work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the conception and design of this study. Naoki Takahashi, Akihiko Okamura, and Misuzu Ishii collected and analyzed the data. The first draft of the manuscript was written by Naoki Takahashi and Akihiko Okamura, and all authors commented on previous versions of the manuscript. All the authors have read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Editage for English language editing.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eBaker M, Halliday V, Williams RN, Bowrey DJ (2016) A systematic review of the nutritional consequences of esophagectomy. Clin Nutr 35:987\u0026ndash;994\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBozzetti F (2010) Nutritional support in patients with oesophageal cancer. Support Care Cancer 18:S41\u0026ndash;50\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRiccardi D, Allen K (1999) Nutritional management of patients with esophageal and esophagogastric junction cancer. Cancer Control 6:64\u0026ndash;72\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKubo Y, Miyata H, Sugimura K, Shinno N, Asukai K, Hasegawa S et al (2021) Prognostic implication of postoperative weight loss after esophagectomy for esophageal squamous cell cancer. Ann Surg Oncol 28:184\u0026ndash;193\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eTakahashi K, Watanabe M, Kozuki R, Toihata T, Okamura A, Imamura Y et al (2019) Prognostic significance of skeletal muscle loss during early postoperative period in elderly patients with esophageal cancer. Ann Surg Oncol 26:3727\u0026ndash;3735\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKanie Y, Okamura A, Fujihara A, Matsuo H, Maruyama S, Sakamoto K et al (2022) Long-term insufficiency of oral intake after esophagectomy: who needs intense nutritional support after esophagectomy? Ann Nutr Metab 78:106\u0026ndash;113\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRice TW, Patil DT, Blackstone EH (2017) 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg 6:119\u0026ndash;130\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eClavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD et al (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250:187\u0026ndash;196\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNakashima Y, Saeki H, Nakanishi R, Sugiyama M, Kurashige J, Oki E et al (2018) Assessment of sarcopenia as a predictor of poor outcomes after esophagectomy in elderly patients with esophageal cancer. Ann Surg 267:1100\u0026ndash;1104\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eD\u0026rsquo;Journo XB, Ouattara M, Loundou A, Trousse D, Dahan L, Nathalie T et al (2012) Prognostic impact of weight loss in 1-year survivors after transthoracic esophagectomy for cancer. Dis Esophagus 25:527\u0026ndash;534\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHaverkort EB, Binnekade JM, Busch OR, van Berge Henegouwen MI, de Haan RJ, Gouma DJ (2010) Presence and persistence of nutrition-related symptoms during the first year following esophagectomy with gastric tube reconstruction in clinically disease-free patients. World J Surg 34:2844\u0026ndash;2852\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLudwig DJ, Thirlby RC, Low DE (2001) A prospective evaluation of dietary status and symptoms after near-total esophagectomy without gastric emptying procedure. Am J Surg 181:454\u0026ndash;458\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMartin L, Lagergren P (2015) Risk factors for weight loss among patients surviving 5 years after esophageal cancer surgery. Ann Surg Oncol 22:610\u0026ndash;616\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eTakesue T, Takeuchi H, Ogura M, Fukuda K, Nakamura R, Takahashi T et al (2015) A prospective randomized trial of enteral nutrition after thoracoscopic esophagectomy for esophageal cancer. Ann Surg Oncol 22:S802\u0026ndash;809\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWeijs TJ, van Eden HWJ, Ruurda JP, Luyer MDP, Steenhagen E, Nieuwenhuijzen GAP et al (2017) Routine jejunostomy tube feeding following esophagectomy. J Thorac Dis 9:S851\u0026ndash;860\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKoterazawa Y, Oshikiri T, Hasegawa H, Yamamoto M, Kanaji S, Yamashita K et al (2020) Routine placement of feeding jejunostomy tube during esophagectomy increases postoperative complications and does not improve postoperative malnutrition. Dis Esophagus 33\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHyltander A, Bosaeus I, Svedlund J, Liedman B, Hugosson I, Wallengren O et al (2005) Supportive nutrition on recovery of metabolism, nutritional state, health-related quality of life, and exercise capacity after major surgery: a randomized study. Clin Gastroenterol Hepatol 3:466\u0026ndash;474\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eXie H, Chen X, Xu L, Zhang R, Hang X, Wei X et al (2021) A randomized controlled trial of oral nutritional supplementation versus standard diet following McKeown minimally invasive esophagectomy in patients with esophageal malignancy: a pilot study. Ann Transl Med 9:1674\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMiyazaki Y, Omori T, Fujitani K, Fujita J, Kawabata R, Imamura H et al (2021) Oral nutritional supplements versus a regular diet alone for body weight loss after gastrectomy: a phase 3, multicenter, open-label randomized controlled trial. Gastric Cancer 24:1150\u0026ndash;1159\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLigthart-Melis GC, Weijs PJ, te Boveldt ND, Buskermolen S, Esrthman CP, Verheul HM et al (2013) Dietician-delivered intensive nutritional support is associated with a decrease in severe postoperative complications after surgery in patients with esophageal cancer. Dis Esophagus 26:587\u0026ndash;593\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAlleaBelle Gongola M, Reif RJ, Cosgrove PC, Sexton KW, Marino KA, Steliga MA et al (2022) Preoperative nutritional counselling in patients undergoing oesophagectomy. J Perioper Pract 32:183\u0026ndash;189\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLiu J, Xie X, Zhou C (2012) al Which factors are associated with\u0026nbsp;\u003cspan\u003eactual 5-year survival of oesophageal squamous cell carcinoma? Eur J Cardiothorac Surg 41:e7\u0026ndash;11\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"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":"nutritional counseling・body weight・skeletal muscle・esophagectomy","lastPublishedDoi":"10.21203/rs.3.rs-4633595/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4633595/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eThe progression of malnutrition and sarcopenia after esophagectomy for esophageal cancer negatively influences long-term prognosis. To improve nutritional status after esophagectomy, we introduced an intensified nutrition counselling (iNC) protocol. The aim of this study was to evaluate the efficacy of iNC compared with the conventional NC (cNC).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eWe included 126 patients who underwent esophagectomy before and after NC revision, and compared nutritional status and changes in body composition after esophagectomy between the cNC and iNC groups. Nutritional parameters, including body weight, serum albumin level, and prealbumin level, were assessed. We also calculated skeletal muscle index (SMI) and visceral fat area (VFA) using computed tomography volumetry.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eThere were no significant differences in baseline characteristics or surgical outcomes between the groups. Compared with the cNC group, NC was provided more frequently (P\u003cem\u003e \u003c/em\u003e\u0026lt; 0.001) in the iNC group, and compliance rate increased from 56.3% to 91.9% (P\u003cem\u003e \u003c/em\u003e\u0026lt; 0.001). Body weight loss at 4 and 6 months and SMI reduction at 6 months were significantly improved in the iNC group compared with the cNC group (P \u0026lt; 0.001, P = 0.032, and P = 0.006, respectively). There were no significant differences in the changes in VFA, serum albumin level, and prealbumin level between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eOutpatient iNC significantly improved body weight and SMI loss 3–6 months after esophagectomy. Therefore, iNC may improve patient quality of life and outcomes by maintaining patient nutritional status.\u003c/p\u003e","manuscriptTitle":"Intensified outpatient nutrition counselling improves body weight and skeletal muscle loss after esophageal cancer surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-22 20:57:49","doi":"10.21203/rs.3.rs-4633595/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-08T14:08:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-08T11:19:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"86028360348107485160798393413197559480","date":"2024-09-02T07:26:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-18T02:23:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"193002907575335355004888868014015185666","date":"2024-07-15T02:00:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-13T19:47:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-02T04:17:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-28T10:13:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2024-06-25T05:05:51+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":"a8fde0ca-259f-4674-8eb9-b15c345f971d","owner":[],"postedDate":"July 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-11T16:04:18+00:00","versionOfRecord":{"articleIdentity":"rs-4633595","link":"https://doi.org/10.1007/s00423-024-03526-2","journal":{"identity":"langenbecks-archives-of-surgery","isVorOnly":false,"title":"Langenbeck's Archives of Surgery"},"publishedOn":"2024-11-04 15:58:21","publishedOnDateReadable":"November 4th, 2024"},"versionCreatedAt":"2024-07-22 20:57:49","video":"","vorDoi":"10.1007/s00423-024-03526-2","vorDoiUrl":"https://doi.org/10.1007/s00423-024-03526-2","workflowStages":[]},"version":"v1","identity":"rs-4633595","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4633595","identity":"rs-4633595","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}