The aim of this article was to study the prevalence and significance of sarcopenia in the multimodal management of locally advanced esophageal cancer (LAEC), and to assess its independent impact on operative and oncologic outcomes. Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact on modern multimodal regimens for LAEC have not been systematically studied. Two hundred fifty-two consecutive patients were studied. Lean body mass (LBM), skeletal muscle index (SMI), and fat mass (FM) were determined pre-treatment, preoperatively, and 1 year postoperatively. Sarcopenia was defined by computed tomography (CT) at L3 as SMI < 52.4 cm2/m2 for males and SMI < 38.5 cm2/m2 for females. All complications were recorded prospectively, including comprehensive complications index (CCI), Clavien-Dindo complication (CDC), and pulmonary complications (PPCs). Multivariable linear, logistic, and Cox regression analysis was performed. In-hospital mortality was 1%, and CCI was 21 ± 19. Sarcopenia increased (P = 0.02) from 16% at diagnosis to 31% post-neoadjuvant therapy, with loss of LBM (-3.0 ± 5.4 kg, P < 0.0001), but not FM (-0.3 ± 2.7 kg, P= 0.31) during treatment. On multivariable analysis, preoperative sarcopenia was associated with CCI (P = 0.043), and CDC ≥IIIb (P = 0.003). PPCs occurred in 36% nonsarcopenic versus 55% sarcopenic patients (P = 0.01). Sarcopenia did not impact disease-specific (P = 0.14) or overall survival (P = 0.11) after resection. At 1 year, 35% had sarcopenia, significantly associated with pre-treatment BMI (P = 0.013) but not complications (P = 0.20). Sarcopenia increases through multimodal therapy, is associated with an increased risk of major postoperative complications, and is prevalent in survivorship. These data highlight a potentially modifiable marker of risk that should be assessed and targeted in modern multimodal care pathways.

Objective: The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life (HRQOL) of esophagogastric cancer survivors. Background: Patients following treatment for esophagogastric cancer are at risk of physical deconditioning, nutritional compromise, and sarcopenia. Accordingly, compelling rationale exists to target these impairments in recovery. Methods: Disease-free patients treated for esophagogastric cancer were randomized to either usual care or the 12-week RESTORE program (exercise training, dietary counseling, and multidisciplinary education). The primary outcome was cardiopulmonary exercise testing (VO₂peak). Secondary outcomes included body composition (bioimpedance analysis), and HRQOL (EORTC-QLQ-C30). Outcomes were assessed at baseline (T0), postintervention (T1), and at 3-month follow-up (T2). Results: Twenty-two participants were randomized to the control group [mean (standard deviation) age 64.14 (10.46) yr, body mass index 25.67 (4.83) kg/m², time postsurgery 33.68 (19.56) mo], and 21 to the intervention group [age 67.19(7.49) yr, body mass index 25.69(4.02) kg/m², time postsurgery 23.52(15.23) mo]. Mean adherence to prescribed exercise sessions were 94(12)% (supervised) and 78(27)% (unsupervised). Correcting for baseline VO₂peak, the intervention arm had significantly higher VO₂peak at both T1, 22.20 (4.35) versus 21.41 (4.49) mL · min⁻¹ · kg⁻¹, P < 0.001, and T2, 21.75 (4.27) versus 20.74 (4.65) mL · min⁻¹ · kg⁻¹, P = 0.001, compared with the control group. Correcting for baseline values, no changes in body composition or HRQOL were observed. Conclusions: The RESTORE program significantly improved cardiorespiratory fitness of disease-free patients after esophagogastric cancer surgery, without compromise to body composition. This randomized controlled trial provides proof of principle for rehabilitation programs in esophagogastric cancer. Clinical Trial Registration Number: NCT03314311.

The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiore

Objective: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. Background: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. Patients and Methods: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. Results: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities. Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97–1.65), low mood (OR 1.42; 95% CI 1.15–1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18–1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively. Conclusion: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy. With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood. In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires. Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ± 2.3% (P < 0.001) and 16.3 ± 2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ± 0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ± 0.6-, 4.7 ± 0.8-, and 4.4 ± 0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73). After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.