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Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Objective: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer., Background: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear., Methods: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS)., Results: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates ( P = 0.005) and nodal yield ( P < 0.001) were independently increased after TMIE, but not HMIE ( P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE., Conclusion: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer., Competing Interests: M.I.v.B.H. is a consultant for Alesi Surgical, BBraun, Johnson & Johnson, Medtronic and Viatris, and received research grants from Stryker (all fees paid to the institution). The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic oropharyngeal dysphagia (COD) and aspiration after esophageal cancer surgery may have clinical significance; however, it is a rarely studied topic. In a prospective cross-sectional observational study we comprehensively evaluated the nature, severity, and impact of COD, its predictors, and the impact of the surgical approach and site of anastomosis. Forty participants were recruited via purposive sampling from the (Irish) National Center between November 2021 and August 2022. Swallow evaluations included videofluoroscopy [Dynamic Imaging Grade of Swallowing Toxicity v2 (DIGESTv2), MBS Impairment Profile, Penetration-Aspiration Scale)]. Functional Oral Intake Scale (FOIS) identified oral intake status. The patient reported outcome measures of swallowing, and Quality of Life (QL) included EAT-10 and MD Anderson Dysphagia Inventory (MDADI). Fourteen (35%) participants presented with COD on DIGESTv2 and 10% had uncleared penetration/aspiration. Avoidance or modification of diet on FOIS was observed in 17 (42.5%). FOIS was associated with pharyngeal dysphagia (OR = 4.05, P = 0.046). Median (range) EAT-10 and MDADI Composite results were 3(0-30) and 77.9(60-92.6), respectively. Aspiration rates significantly differed across surgical groups (P = 0.029); only patients undergoing transhiatal surgery aspirated. Survivors of esophageal cancer surgery may have COD that is undiagnosed, potentially impacting swallow-related QL. Given the small number of aspirators, further research is required to determine whether aspiration risk is associated with surgical approach. A FOIS score below 7 may be a clinically useful prompt for the MDT to refer for evaluation of COD following curative intent surgery. These data present findings that may guide preventive and rehabilitative strategies toward optimizing survivorship., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Competing Interests: Conflict of interest: None declared

Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of esophageal adenocarcinoma (EAC). The most effective time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumor immunity perioperatively to help inform the optimal timing of ICIs into current standards of care for EAC patients., Methods: Systemic immunity in 11 EAC patients was phenotyped immediately prior to esophagectomy (POD-0) and post-operatively (POD)-1, 3, 7 and week 6. Longitudinal serological profiling was conducted by ELISA. The frequency of circulating lymphocytes, activation status, immune checkpoint expression and damage-associated molecular patterns was assessed by flow cytometry., Results: The frequency of naïve T-cells significantly increased in circulation post-esophagectomy from POD-0 to POD-7 (p<0.01) with a significant decrease in effector memory T-cells by POD7 followed by a subsequent increase by week 6 (p<0.05). A significant increase in activated circulating CD27 + T-cells was observed from POD-0 to POD-7 (p<0.05). The percentage of PD-1 + and CTLA-4 + T-cells peaked on POD-1 and was significantly decreased by week 6 (p<0.01). There was a significant increase in soluble PD-1, PD-L2, TIGIT and LAG-3 from POD-3 to week 6 (p<0.01). Increased checkpoint expression correlated with those who developed metastatic disease early in their postoperative course. Th1 cytokines and co-stimulatory factors decreased significantly in the immediate post-operative setting, with a reduction in IFN-γ, IL-12p40, IL-1RA, CD28, CD40L and TNF-α. A simultaneous increase was observed in Th2 cytokines in the immediate post-operative setting, with a significant increase in IL-4, IL-10, IL-16 and MCP-1 before returning to preoperative levels at week 6., Conclusion: Our study highlights the prevailing Th2-like immunophenotype post-surgery. Therefore, shifting the balance in favour of a Th1-like phenotype would offer a potent therapeutic approach to promote cancer regression and prevent recurrence in the adjuvant setting and could potentially propagate anti-tumour immune responses perioperatively if administered in the immediate neoadjuvant setting. Consequently, this body of work paves the way for further studies and appropriate trial design is needed to further interrogate and validate the use of ICI in the multimodal treatment of locally advanced disease in the neoadjuvant and adjuvant setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Donlon, Davern, Sheppard, O’Connell, Dunne, Hayes, Mylod, Ramjit, Temperley, Mac Lean, Cotter, Bhardwaj, Butler, Conroy, O’Sullivan, Ravi, Donohoe, Reynolds and Lysaght.)

Background and Aims: The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes., Study Design: An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology., Results: 175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%., Conclusion: FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Ninety-day mortality rates after esophagectomy are an indicator of the quality of surgical oncologic management. Accurate risk prediction based on large data sets may aid patients and surgeons in making informed decisions., Objective: To develop and validate a risk prediction model of death within 90 days after esophagectomy for cancer using the International Esodata Study Group (IESG) database, the largest existing prospective, multicenter cohort reporting standardized postoperative outcomes., Design, Setting, and Participants: In this diagnostic/prognostic study, we performed a retrospective analysis of patients from 39 institutions in 19 countries between January 1, 2015, and December 31, 2019. Patients with esophageal cancer were randomly assigned to development and validation cohorts. A scoring system that predicted death within 90 days based on logistic regression β coefficients was conducted. A final prognostic score was determined and categorized into homogeneous risk groups that predicted death within 90 days. Calibration and discrimination tests were assessed between cohorts., Exposures: Esophageal resection for cancer of the esophagus and gastroesophageal junction., Main Outcomes and Measures: All-cause postoperative 90-day mortality., Results: A total of 8403 patients (mean [SD] age, 63.6 [9.0] years; 6641 [79.0%] male) were included. The 30-day mortality rate was 2.0% (n = 164), and the 90-day mortality rate was 4.2% (n = 353). Development (n = 4172) and validation (n = 4231) cohorts were randomly assigned. The multiple logistic regression model identified 10 weighted point variables factored into the prognostic score: age, sex, body mass index, performance status, myocardial infarction, connective tissue disease, peripheral vascular disease, liver disease, neoadjuvant treatment, and hospital volume. The prognostic scores were categorized into 5 risk groups: very low risk (score, ≥1; 90-day mortality, 1.8%), low risk (score, 0; 90-day mortality, 3.0%), medium risk (score, -1 to -2; 90-day mortality, 5.8%), high risk (score, -3 to -4: 90-day mortality, 8.9%), and very high risk (score, ≤-5; 90-day mortality, 18.2%). The model was supported by nonsignificance in the Hosmer-Lemeshow test. The discrimination (area under the receiver operating characteristic curve) was 0.68 (95% CI, 0.64-0.72) in the development cohort and 0.64 (95% CI, 0.60-0.69) in the validation cohort., Conclusions and Relevance: In this study, on the basis of preoperative variables, the IESG risk prediction model allowed stratification of an individual patient's risk of death within 90 days after esophagectomy. These data suggest that this model can help in the decision-making process when esophageal cancer surgery is being considered and in informed consent.

Improved cure rates in esophageal cancer care have increased focus on health-related quality of life (HRQL) in survivorship. To optimize recovery after esophagectomy, particularly nutritional well-being, a personalized multidisciplinary survivorship clinic was established at this center. Assessments at 6 and 12 months postoperatively include validated European Organization for the Research and Treatment of Cancer (EORTC) symptom and health-related quality of life (HRQL) questionnaires, functional status review, anthropometry, and biochemical screening for micronutrient deficiencies. 75 patients, at a mean age of 63 years, 84% male, 85% with adenocarcinoma, and 73% receiving multimodal therapy were included. Mean preoperative body mass index (BMI) was 27.5 (4.3) kg m -2. 6- and 12-month assessments were completed by 66 (88%) and 37 (93%) recurrence-free patients, respectively. Mean body weight loss at 6 months was 8.5 ± 6.6% and at 12 months 8.8 ± 7.3%. Of the 12-month cohort, micronutrient deficiency was present in 27 (79.4%) preoperatively and 29 (80.6%) after 1 year (P = 0.727), most commonly iron deficiency (preoperative: 16 [43.2%] and postoperative: 17 [45.9%] patients, P = 0.100). 26 (70.3%) of these patients also had clinically significant dumping syndrome persisting to 12 months after surgery. We describe a novel follow-up support structure for esophageal cancer patients in the first year of survivorship. This may serve as an exemplar model with parallel application across oncological care., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Serum albumin perioperative decrease (∆Alb) may reflect the magnitude of the physiological stress induced by surgery. Studies highlighted its value to predict adverse postoperative outcomes, but data in esophageal surgery are scant. This study aimed to investigate the role of ∆Alb to predict major complications after esophagectomy for cancer., Methods: Multicenter retrospective study conducted in five high-volume centers, including consecutive patients undergoing an esophagectomy for cancer between 2006 and 2017. Patients were randomly assigned to a training (n = 696) and a validation (n = 350) cohort. Albumin decrease was calculated on postoperative day 1 and defined as ΔAlb. The primary endpoint was major complications according to Clavien classification., Results: In the training cohort, esophagectomy induced a rapid drop of albumin. Cut-off of ΔAlb was established at 11 g/L and allowed to distinguish patients with adverse outcomes. On multivariable analysis, ΔAlb was identified as an independent predictor of major complications (OR, 1.06; 95% CI, 1.01-1.11; p = .014). Higher BMI and laparoscopy were associated with lower ΔAlb. Analysis of the validation cohort provided consistent findings., Conclusions: ΔAlb appeared as a promising biomarker after oncological esophagectomy, allowing prediction of potential adverse outcomes., (© 2020 Wiley Periodicals LLC.)

The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data from the Irish National Center (INC) with both published benchmark studies. All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied, with data recorded prospectively and entered onto a secure online database (Esodata.org). 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%,nrespectively. Anastomotic leak rate was 5.4%, pneumonia 18.2%, respiratory failure 10%, ARDS 2.7%, atrial dysrhythmia 22.8%, recurrent nerve injury 3%, and delirium in 5% of patients. Compared with both ECCG and DUCA, where MIE constituted 47 and 86% of surgical approaches, respectively, overall complications were similar, as were severity of complications; however, anastomotic leak rate was several-fold less, and mortality was significantly lower (P < 0.001). In this consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publications, a low mortality and anastomotic leak rate were the key differential findings. Although not risk stratified, the severity of complications from this 'open' series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss., Methods: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed., Results: Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46)., Conclusion: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Reduced appetite and weight loss are common after esophagectomy (ES), and this cohort demonstrates an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate food reward, resulting in reduced energy intake., Objectives: This study aimed to determine the effect of satiety gut hormone modulation by measuring the effect of the somatostatin analog octreotide on appetitive behavior among patients after ES., Methods: In this randomized, double-blind, placebo-controlled crossover study, patients ≥1 y after ES and matched controls received either 1 mL 0.9% saline or 1 mL (100 μg) octreotide subcutaneously before completing a progressive ratio task. A measure of appetitive behavior, this task requires subjects to undertake progressively increasing amounts of work to obtain a sweet-fat reinforcer; the final completed increment (breakpoint) represents reinforcer reward value. Separate cohorts were studied in the fasted or 1-h postprandial states., Results: Thirty-six subjects (ES, n = 18; matched controls, n = 18) were studied. The ES subjects were 2.5 ± 0.3 y postoperation and had a weight loss of 14.6% ± 2.6% and elevated postprandial glucagon-like peptide 1 compared with controls (49.2 ± 13.4 compared with 20.2 ± 2.3 pM; P = 0.04). Octreotide did not alter the breakpoint among ES or control subjects when tested in a fasting condition (ES: 980 ± 371 compared with 1700 ± 584 clicks; P = 0.16; controls: 1056 ± 274 compared with 1124 ± 273 clicks; P = 0.81). When tested 1 h postprandially, octreotide was associated with an increased breakpoint compared with placebo among ES subjects (322 ± 143 compared with 246 ± 149 clicks; P = 0.04) but not controls (248 ± 119 compared with 247 ± 120 clicks; P = 0.97)., Conclusions: Attenuation of the exaggerated postprandial satiety gut hormone response is associated with increased appetitive behavior toward a sweet-fat stimulus among patients post-ES. Suppression of satiety gut hormones may be a novel target to increase appetite, food intake, and body weight among patients after ES. This study was registered at clinicaltrials.gov as NCT02381249.

Objective: Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy., Summary of Background Data: Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects., Methods: The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period., Results: Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively., Conclusion: Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.

Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors., Purpose: Improved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy., Methods: Consecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression., Results: Seventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2 years postoperatively (144.3 ± 45.8 versus 128.6 ± 46.2 and 122.7 ± 43.5 Hounsfield Units (HU), P < 0.0001), with increased osteoporosis prevalence to 38% and 44% (P = 0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P < 0.001). While female sex (P = 0.004) and ASA grade (P = 0.043) were independently associated with osteoporosis at diagnosis, age (P = 0.050), female sex (P = 0.023), smoking (P = 0.024), and pathologic T stage (P = 0.023) were independently predictive of osteoporosis at 1 year postoperatively., Conclusions: Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.

Objective: This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes., Background: Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale., Methods: This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL., Results: The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 ± 6.6 kg), BMI (-2.6 ± 2.2 kg/m), LBM (-2.5 ± 8.7 kg), and fat mass (-3.4 ± 5.8 kg) was evident from preoperatively to 6 months. The mean (±SD) loss of LBM (kg) at 1 month was -3.7 ± 8.7 in the EN-S group, compared with -5.6 ± 12.1 in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or immune parameter at any time point., Conclusions: The thesis that EPA impacts on anabolism, immune function, and clinical outcomes post-esophagectomy was not supported. Compliance with home EN was excellent, but weight, muscle, and fat loss was significant in 30% of patients, highlighting the complexity of postoperative weight loss.

Objective: 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., Summary of Background Data: Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact on modern multimodal regimens for LAEC have not been systematically studied., Methods: 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 cm/m for males and SMI < 38.5 cm/m 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., Results: 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)., Conclusions: 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: To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy., Background: 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., Methods: 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., Results: 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)., Conclusions: 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.

Background: Benign anastomotic strictures occur frequently after esophagectomy, and impact on postoperative recovery, nutritional status, and quality of life. This large cohort study explored the incidence of stricture after transthoracic (2- and 3-stage) and transhiatal resections with uniform single-layer sutured anastomotic technique, and aimed to identify independent risk factors., Methods: Patients undergoing esophagectomy with gastric conduit reconstruction between February 2001 and October 2014 were studied prospectively. Symptomatic anastomotic stricture was defined as dysphagia requiring endoscopic dilatation, and refractory strictures as those requiring >5 dilatations. Multivariable logistic regression was performed to determine factors independently associated with stricture development., Results: Five-hundred and twenty-four patients, 77 % with adenocarcinoma, underwent esophagectomy [2-stage, n = 328 (62.6 %); 3-stage, n = 129 (23.3 %); transhiatal, n = 74 (14.1 %)], with an overall inhospital mortality rate of 2.7 %. 58.5 % of patients received neoadjuvant therapy [chemotherapy only, n = 119 (22.7 %); chemoradiation, n = 188 (35.9 %)]. Anastomotic stricture developed in 125 patients (24.5 %), was refractory in 20 (3.9 %) and required a median of 2 dilatations (range 1-18). On multivariable analysis, ASA grade (P < 0.05), cervical anastomosis (P < 0.001), and a significant postoperative cardiac event (P < 0.05) were independently associated with stricture risk. Refractory strictures were independently associated with anastomotic leak (P = 0.01) and transhiatal resections (P < 0.001)., Conclusion: Benign anastomotic strictures are common, particularly with cervical reconstruction, and after transhiatal resection. Refractory strictures are rare. Where fitness and oncologic equivalence apply, a thoracic anastomosis provides significant advantages compared with a cervical anastomosis in terms of anastomotic stricture risk.

We present the first reported case of successful surgical management of esophageal cancer post-lung transplantation for cystic fibrosis. This case of a 42-year-old man highlights the risk factors for esophageal adenocarcinoma associated with cystic fibrosis and lung transplantation, the management options for early esophageal cancer and the surgical option chosen to minimise respiratory risks. Individualised patient care may allow for curative surgical approaches, even where complex surgery is required., (2015 BMJ Publishing Group Ltd.)

Objective: To study malabsorption and malnutrition after curative resection of esophageal and gastric cancer., Design: Prospective cohort study., Background: Improved cure rates for esophageal and gastric cancer have increased focus on health-related quality of life (HR-QL) in survivorship. Although malnutrition is well described in long-term follow-up, and gastrointestinal symptoms are common, data on gut and pancreatic-related malabsorption are scant., Methods: Disease-free patients at least 18 months after esophageal or gastric oncologic resections represented the study cohort. A modified Gastrointestinal Symptom Rating Scale questionnaire was completed, and weight, fecal elastase (FE), albumin, vitamins, and micronutrients measured preoperatively and at 1, 6, and 18 to 24 months postoperatively. Small intestinal bacterial overgrowth (SIBO) and changes in body composition were also evaluated postoperatively., Results: At a median follow-up of 23 months, 45 of 66 patients in a consecutive series were disease-free. Mean weight (78 ± 19 vs 67 ± 16 kg), body mass index (27 ± 5 vs 24 ± 5 kg/m), Vitamin A (1.7 ± 0.6 vs 1.2 ± 0.4 umol/L), and Vitamin E (28 ± 7 vs 20 ± 7 umol/L) were significantly decreased (P < 0.01) at last follow-up compared with preoperatively. Malabsorption was evident in 73% of patients, of whom 44% had FE < 200 μg/g and 38% had evidence of SIBO. Total body fat-free mass (175 ± 96 vs 84 ± 71, P < 0.001) and skeletal muscle index (44 ± 8 vs 39 ± 8, P = 0.007) were significantly decreased at 18 to 24 months., Conclusions: Malabsorption and malnutrition are prevalent in survivorship of esophageal and stomach cancer. This may be underappreciated, and both gut and pancreatic insufficiency represent modifiable targets in the interdisciplinary approach to recovery of HR-QL.

Objectives: To characterize the gut hormone profile and determine the effect of satiety gut hormone blockade on food intake in disease-free postesophagectomy patients., Background: Improved oncologic outcomes for esophageal cancer have resulted in increased survivorship and a focus on health-related quality of life. Anorexia and early satiety are common, but putative causative factors, in particular the gut-brain hormonal axis, have not been systematically studied., Methods: In a double-blind, placebo-controlled, randomized crossover study, disease-free patients at least 1 year postresection and gastric conduit reconstruction received either 1 mL 0.9% saline or 1 mL (100 μg) octreotide acetate subcutaneously followed by a standardized ad libitum meal on each of two assessments. Fasting and postprandial plasma glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin immunoreactivity were measured. Gut hormone responses and calorie intake postsaline versus octreotide were compared between experimental and control groups., Results: Eighteen subjects [esophagectomy (ES), n = 10, 2.4 ± 0.75 years postresection; and unoperated control subjects, n = 8] were studied. ES demonstrated significant weight loss at 3, 6, 12, and 24 months postoperatively (all P < 0.05). Ghrelin levels were similar (P = 0.58) for both groups, but postprandial GLP-1 and PYY responses were significantly (P < 0.001) greater among ES as compared with controls. After octreotide, ad libitum calorie intake increased among ES (1.5 ± 0.2 fold-change, P = 0.02) but not controls (1.1 ± 0.1 fold-change, P = 0.30)., Conclusions: ES demonstrated an exaggerated postprandial satiety gut hormone response that was attenuated by octreotide, thus identifying a potential therapeutic target to modulate in the ES patient with early satiety.

Introduction: Perioperative complications influence long- and short-term outcomes after esophagectomy. The absence of a standardized system for defining and recording complications and quality measures after esophageal resection has meant that there is wide variation in evaluating their impact on these outcomes., Methods: The Esophageal Complications Consensus Group comprised 21 high-volume esophageal surgeons from 14 countries, supported by all the major thoracic and upper gastrointestinal professional societies. Delphi surveys and group meetings were used to achieve a consensus on standardized methods for defining complications and quality measures that could be collected in institutional databases and national audits., Results: A standardized list of complications was created to provide a template for recording individual complications associated with esophagectomy. Where possible, these were linked to preexisting international definitions. A Delphi survey facilitated production of specific definitions for anastomotic leak, conduit necrosis, chyle leak, and recurrent nerve palsy. An additional Delphi survey documented consensus regarding critical quality parameters recommended for routine inclusion in databases. These quality parameters were documentation on mortality, comorbidities, completeness of data collection, blood transfusion, grading of complication severity, changes in level of care, discharge location, and readmission rates., Conclusions: The proposed system for defining and recording perioperative complications associated with esophagectomy provides an infrastructure to standardize international data collection and facilitate future comparative studies and quality improvement projects.

Background: Esophageal resection is associated with a high incidence of postoperative pneumonia. Respiratory complications account for almost half of the readmissions to the critical care unit. Postoperative complications can result in prolonged hospital stay and consequently increase healthcare costs. In cardiac surgery a preoperative inspiratory muscle training program has shown to prevent postoperative pneumonia and reduce length of hospital stay. While in some surgical centers inspiratory muscle training is already used in the preoperative phase in patients undergoing esophageal resection, the added value of this intervention on the reduction of pulmonary complications has not yet been investigated in large surgical populations other than cardiac surgery in a randomized and controlled study design., Methods/design: The effect of a preoperative inspiratory muscle training program on the incidence of postoperative pneumonia in patients undergoing esophageal resection will be studied in a single blind multicenter randomized controlled trial (the PREPARE study). In total 248 patients (age >18 years) undergoing esophageal resection for esophageal cancer will be included in this study. They are randomized to either usual care or usual care with an additional inspiratory muscle training intervention according to a high-intensity protocol which is performed with a tapered flow resistive inspiratory loading device. Patients have to complete 30 dynamic inspiratory efforts twice daily for 7 days a week until surgery with a minimum of 2 weeks. The starting training load will be aimed to be 60% of maximal inspiratory pressure and will be increased based on the rate of perceived exertion.The main study endpoint is the incidence of postoperative pneumonia. Secondary objectives are to evaluate the effect of preoperative inspiratory muscle training on length of hospital stay, duration of mechanical ventilation, incidence of other postoperative (pulmonary) complications, quality of life, and on postoperative respiratory muscle function and lung function., Discussion: The PREPARE study is the first multicenter randomized controlled trial to evaluate the hypothesis that preoperative inspiratory muscle training leads to decreased pulmonary complications in patients undergoing esophageal resection., Trial Registration: NCT01893008.

Introduction: We report a case of a 37-year-old man, with a background of a rare polyglandular autoimmune syndrome and achalasia, who developed an oesophageal tumour. Both autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or type I polyglandular syndrome and achalasia confer increased risk of development of oesophageal squamous cell carcinoma., Methods: Despite having had multiple endoscopic examinations and dilatations in the recent past, this patient presented with dysphagia, and on endoscopy, he was found to have a mid-oesophageal tumour. A multidisciplinary team approach was vital in his management as careful monitoring of underlying disorders including Addison's disease and hypoparathyroidism were challenging during neoadjuvant chemoradiotherapy and in the perioperative period., Results: He made an uneventful recovery after a three-stage oesophagectomy, and histologically, he had a complete pathological response., Conclusion: To our knowledge, this is the first successful outcome of a patient with APECED and oesophageal carcinoma in the literature.

Objective: Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed., Methods: Three time periods were studied, 1990 to 1998 (period 1), 1999 to 2003 (period 2), and 2004 to 2008 (period 3), in which 471, 254, and 342 patients, respectively, with esophageal cancer were treated with curative intent. All data were prospectively recorded, and staging, pathology, treatment, operative, and oncologic outcomes were compared., Results: Five-year disease-specific survival was 28%, 35%, and 44%, and in-hospital postoperative mortality was 6.7%, 4.4%, and 1.7% for periods 1 to 3, respectively (P < .001). Period 3, compared with periods 1 and 2, respectively, was associated with significantly (P < .001) more early tumors (17% vs 4% and 6%), higher nodal yields (median 22 vs 11 and 18), and a higher R0 rate in surgically treated patients (81% vs 73% and 75%). The use of multimodal therapy increased (P < .05) across time periods. By multivariate analysis, age, T stage, N stage, vascular invasion, R status, and time period were significantly (P < .0001) associated with outcome., Conclusions: Improved survival with localized esophageal cancer in the modern era may reflect an increase of early tumors and optimized staging. Important surgical and pathologic standards, including a higher R0 resection rate and nodal yields, and lower postoperative mortality, were also observed., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Transthoracic esophagectomy (TTE) with lymphadenectomy represents the gold standard of operative approaches to esophageal cancer. The TTE procedure carries significant operative risk, particularly in patients with co-morbidities, and the possible oncologic benefit of a mediastinal lymph node dissection in certain subgroups of patients with esophageal cancer is controversial. Transhiatal esophagectomy (THE), which avoids a thoracotomy, may reduce morbidity and mortality below levels seen with TTE, and there is no proof from randomized studies of any oncologic inferiority to TTE in patients with early tumors. Accordingly, the selective use of THE has increased in our high-volume center in recent years, and this study audits that experience over the last decade, Methods: Between 2000 and 2009 inclusive, 584 patients were treated surgically with curative intent. The standard operative approach in our unit is en bloc TTE, and THE represents 5.5% overall, and 11.1% in the second 5-year period (2004-2009), compared with 2% previously. The present study details the selection of these cases (n = 32) treated with THE and their outcomes, as well as the outcomes in the TTE (n = 438) group, Result: Transhiatal esophagectomy was used for early stage carcinoma (n = 18) and for patients of advanced age who also had co-morbidities (n = 14). Patients undergoing THE were significantly older (68.46 versus 63.07 years of age; p = 0.002), and were at higher operative risk based on ASA grade (grade 3: 53.1% versus 17.3%; p < 0.001), compared with TTE patients. The THE cohort also included more patients with early cancers compared with the TTE cohort (56.3% versus 17.6%; p < 0.001). There were no differences in R0 resection rates for patients with early tumors or advanced co-morbidity. Nodal yields were lower in THE patients (p = 0.005). The overall complication rate was lower in the THE group (31.6% versus 44.2%; p = 0.021), and there were no postoperative deaths in the transhiatal group, whereas the in-hospital mortality rate for the TTE group was 3% (p < 0.001). Disease-specific survival was equivalent with each approach., Conclusions: Transhiatal esophagectomy has a role in a pragmatic individualized approach to esophageal cancer. As an alternative to a standardized en bloc transthoracic esophagectomy, the transhiatal approach may be suitable for patients with predicted node-negative cancers or those with resectable disease who are not candidates for TTE because of co-morbidity.

Background: Health-related quality of life (HRQL) has been studied extensively during the first year following esophagectomy, but little is known about HRQL in long-term survivors. The aim of this study was to investigate HRQL in patients alive at least 1 year after surgical resection for esophageal cancer using validated European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaires (QLQ)., Methods: Eligible patients, without known disease recurrence and at least 1 year after esophagectomy, were identified from a prospectively maintained database. Patients completed general (QLQ-C30) and esophageal cancer-specific (QLQ-OES18, OG25) questionnaires. A numeric score (0-100) was computed in each conceptual area and compared with validated cancer (n = 1031) and age-matched (n = 7802) healthy populations using two-tailed unpaired t-tests. A cohort of 80 patients had pretreatment scores recorded., Results: Altogether, 132 of 156 eligible patients (84%) completed the self-rated questionnaire, 105 (67.3%) were men, and the mean age was 62 years (range 29-84 years). The mean time since esophagectomy was 70.3 months (12-299 months). Global health status was significantly reduced at least 1 year after esophagectomy (mean ± SD score 48.4 ± 18.6) when compared with patients with esophageal cancer prior to treatment (55.6 ± 24.1) and the general population (71.2 ± 22.4) (p < 0.0001). In a prospective cohort of eighty patients, symptoms related to swallowing difficulty, reflux, pain, and coughing significantly decreased in the long term (p < 0.0001). The degree of subjective swallowing dysfunction was highly correlated with a poor QOL (Spearman's ρ = 0.508, p < 0.01)., Conclusions: Global health status remains significantly reduced in long-term survivors after esophagectomy compared with population controls, and swallowing dysfunction is highly associated with this compromised QOL.

Achalasia is an oesophageal motility disorder characterised by aperistalsis and failure of relaxation of a hypertensive lower oesophageal sphincter. Treatment intent targets the sphincter, and either Heller's myotomy or pneumatic dilatation successfully relieves dysphagia in the majority of cases. End-stage achalasia, typified by a massively dilated and tortuous oesophagus, may occur in patients previously treated but where further dilatation or myotomy fails to relieve dysphagia or prevent nutritional deterioration, and oesophagectomy may be the only option. We describe two patients with end-stage achalasia and nutritional failure despite exhaustive conventional therapy including pneumatic dilatation and surgical myotomy. Both patients were successfully managed with transhiatal oesophagectomy and cervical gastro-esophageal anastomosis, with excellent symptomatic control and improved quality of life. These cases are discussed and the literature reviewed., (Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear., Objectives: To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications., Methods: In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines., Results: Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group., Conclusions: EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.

Objective: Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications., Methods: A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20-25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level., Results: Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83-0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU., Conclusion: Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes.

Objective: To examine the association of single nucleotide polymorphisms (SNPs) in inflammation-related genes in the development of infections following esophagectomy., Summary Background Data: Genetic polymorphisms for immunoregulatory cytokines may explain individual variation in response to trauma. Esophagectomy is associated with a high risk of postoperative infection and sepsis, and this study explored a number of SNPs in cytokine genes and their relationship to postoperative infection., Methods: : In a prospective analysis of 197 patients with esophageal cancer undergoing resection, 55 developed postoperative infections. DNA was extracted and genotyping was performed for polymorphisms in genes encoding TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-10, and Toll-like receptor 4 (TLR-4) using Taqman chemistry and PCR/RFLP. In a blinded analysis, the cohort with infections was compared with the no complication cohort (n = 114) and a cohort that had noninfective complications (n = 28)., Results: No differences in polymorphisms for IL-1beta, IL-1 RN, IL-10, and TLR-4 genes were observed across groups. The frequency of TNF-alpha -308 GG homozygotes was significantly (P = 0.021) higher in the postoperative infection group. The G allele was significantly higher in the postoperative infection group compared with the no complication group (P = 0.017) and other complication group (P = 0.013). By multivariate analysis, this polymorphism as well as age and body mass index were predictors of infection., Conclusion: The TNF-alpha -308A allele has been shown to be associated with higher circulating levels of TNF-alpha and the -308 G allele is a comparative low secretor allele. We propose that the polymorphism in the promotor region of TNF-alpha gene may lead to altered expression and a possible suboptimal activity of TNF-alpha in persons with GG genotypes, and these data suggest a link with infection following major surgery.

Background: The role of neoadjuvant chemotherapy and radiation therapy before resection in esophageal cancer remains controversial. Operative risks may be increased, but this has not been systematically addressed in published trials or reports., Methods: This was a prospective, nonrandomized, restricted cohort design of patients (n = 200) from 1997 to 2003 with resectable cancer of the esophagus or esophagogastric junction. A total of 102 patients underwent multimodal therapy with 5-fluorouracil, cisplatin, and radiation therapy before surgery, and 98 patients opted for surgery alone. In-hospital mortality and morbidity were the primary end points, and cancer survival was a secondary end point., Results: In patient cohorts matched for operative risk factors, the odds ratio for postoperative sepsis (P = .007), respiratory failure (P = .009), and acute respiratory distress syndrome (P = .02) was increased in the multimodal group. There was no significant difference between groups comparing median and 1-, 2-, and 3-year survivals., Conclusions: Multimodal therapy was associated with increased respiratory and septic complications compared with a surgery-only cohort undergoing the equivalent surgery. Respiratory failure was in most cases idiopathic. The data suggest that efforts should be made to limit radiation lung exposure in multimodal regimens, and to understand and modulate the local and systemic effects of preoperative chemoradiation.

Background and Aims: The purpose of this study was to prospectively evaluate post-operative jejunostomy feeding in terms of nutritional, biochemical, gastrointestinal and mechanical complications in patients undergoing upper gastrointestinal surgery for oesophageal malignancy., Methods: The study included 205 consecutive patients who underwent oesophagectomy for malignancy. All patients had a needle catheter jejunostomy (NCJ) inserted at the conclusion of laparotomy. Patients were followed prospectively to record nutritional intake, type of feed administered, rate progression, tolerance, weight changes and complications either mechanical, biochemical or gastrointestinal., Results: Ninety-two per cent of patients were successfully fed exclusively by NCJ post-oesophagectomy, and 94% of patients were tolerating a maintenance regimen of 2000 ml feed over 20 h by day 2 post-operatively. Patients spent a median of 15 days on jejunostomy feeding post-surgery (range 2-112 days); however, 26% required prolonged jejunostomy feeding (>20 days). Minor gastrointestinal complications were effectively managed by slowing the rate of infusion, or administering medication. Three (1.4%) serious complications of jejunostomy feeding occurred, all requiring re-laparotomy, one resulting in death. NCJ feeding was extremely effective in preventing severe post-operative weight loss in the majority of oesophagectomy patients post-op. However, oral intake was generally poor at discharge with only 65% of requirements being met orally. Sixteen patients (8%) patients required home jejunostomy feeding. By the first post-operative month, a further 6% (12) patients were recommenced on jejunostomy feeding., Conclusion: NCJ feeding is an effective method of providing nutritional support post-oesophagectomy, and allows home support for the subset that fail to thrive. Serious complications, most usually intestinal ischaemia or intractable diarrhoea, are rare.

Esophagectomy is an exemplar of complex oncological surgery and is associated with a relatively high risk of major morbidity and mortality. In the modern era, where specific complications are targeted in prevention and treatment pathways, and where the principles of enhanced recovery after surgery are espoused, optimum outcomes are targeted via a number of approaches. These include comprehensive clinical and physiological risk assessment, specialist perioperative care by a high-volume team, and multimodal inputs throughout the patient journey that aim to preserve or restore nutritional deficits, muscle mass and function. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. Summary Background Data: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. Methods: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009–2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. Results: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12–0.25]) and increased tumor-directed therapy (OR 2.09 [1.58–2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89–1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47–0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58–0.89]). IS was associated with greater anxiety (P =0.016), but similar overall HRQL. Conclusions: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding. [ABSTRACT FROM AUTHOR]

Esophageal cancer has a notably high recurrence rate with a paucity of robust evidence in defining the optimal surveillance strategy. The surveillance protocol at our institution comprises of annual esophagogastroduodenoscopy (OGD) from years 1 to 5 postoperatively. This study aims to evaluate the implementation of the endoscopic surveillance at our center and ascertain the value of endoscopy in detecting local recurrence after esophagectomy. A retrospective cohort review of all patients (320 patients) who underwent esophagectomy between 2013 and 2018 was conducted. The local esophageal cancer database and corresponding OGD reports were accessed to obtain data on demographics, operation details, local recurrence, and endoscopy performed. 1086 OGDs were performed between 2014 and 2020, broadly categorized to surveillance and symptomatic OGDs; 555 and 531, respectively. Surveillance OGDs detected four asymptomatic local recurrences, of which only one was treated with curative intent. Symptomatic OGDs resulted in a higher yield for the detection of local recurrence compared with surveillance endoscopy; 5% versus 0.7%, with overall median time-to-recurrence of 11.5 months (95% confidence interval 9–17). Of local recurrences, 85.7% occurred within the first 2 years postoperatively. The proportion of endoscopic findings differed between intensive and ad hoc surveillance cohorts for strictures, esophagitis, Barrett's esophagus, and sloughing. Thirteen patients were diagnosed with histologically confirmed Barrett's with no subsequent local recurrences. Surveillance endoscopy had a low positive yield rate with subsequent minimal survival benefits. Therefore, it is prudent to consider an alternative protocol that focuses on the period with the highest risk of recurrence and symptom presentation. [ABSTRACT FROM AUTHOR]

Objective: To analyze the spectrum of Centers for Disease Control and Prevention (CDC)-defined pneumonia after esophageal cancer surgery. Summary Background Data: Pneumonia is commonly documented after esophageal cancer surgery, and reducing its incidence is central to both ERAS development and to the evidence-base for minimally invasive approaches. The existing definitions of pneumonia based on hospital acquired pneumonia classifications may be suboptimal in this context and merits strict academic scrutiny. Methods: Patients (2013-2018) treated with curative intent by open surgery were studied. Pneumonia was defined per the CDC definition. Risk factors and associations were analyzed, as was the implications of positive cultures. Multivariable logistic regression examined independently predictive factors of pneumonia and oncologic outcomes. Results: Of 343 patients, 56 (16%) had defined pneumonia, 22 (39%) with positive cultures. Preoperative respiratory disease predicted pneumonia (P = 0.043). Neoadjuvant therapy was significantly (P = 0.004) associated with culture negative pneumonia, and age (P = 0.001) with culture positive pneumonia. In multivariable analysis, pneumonia was associated (P < 0.05) with respiratory comorbidity, tumor site, and neoadjuvant chemoradiation. Pneumonia did not impact on overall survival (P = 0.807). Discussion: CDC-defined pneumonia occurred in 16% of cases. Culture-negative pneumonia accounted for 61% of cases and was significantly associated with neoadjuvant chemoradiation. Pneumonia as currently defined seems to represent a spectrum of etiology and severity in the post-esoph-agectomy patient, with infection per se rarely proven, suggesting a need to reevaluate its definition, severity classification, and preventive and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, risk factors, and consequences of AKI in patients undergoing surgery for esophageal cancer Summary of Background Data: Esophageal cancer surgery is an exemplar of major operative trauma, with well-defined risks of respiratory, cardiac, anastomotic, and septic complications. However, there is a paucity of literature regarding AKI. Methods: consecutive patients undergoing curative-intent surgery for esophageal cancer from 2011 to 2017 in 3 high-volume centers were studied. AKI was defined according to the AKI Network criteria. AKI occurred if, within 48 hours postoperatively, serum creatinine rose by 50% or by 0.3 mg/dL (26.5 μmol/L) from preoperative baseline. Complications were recorded prospectively. Multivariable logistic regression determined factors independently predictive of AKI. Results: A total of 1135 patients (24.7%:75.3% female:male, with a mean age of 64, a baseline BMI of 27 kg m−2, and dyslipidemia in 10.2%), underwent esophageal cancer surgery, 85% having an open thoracotomy. Overall in-hospital mortality was 2.1%. Postoperative AKI was observed in 208 (18.3%) patients, with AKI Network 1, 2, and 3 in 173 (15.2%), 28 (2.5%), and 7 (0.6%), respectively. Of these, 70.3% experienced improved renal function within 48 hours. Preoperative factors independently predictive of AKI were age [ P = 0.027, odds ratio (OR) 1.02 (1.00–1.04)], male sex [ P = 0.015, OR 1.77 (1.10–2.81)], BMI at diagnosis [ P < 0.001, OR 1.10 (1.07–1.14)], and dyslipidemia [ P = 0.002, OR 2.14 (1.34–3.44)]. Postoperatively, AKI was associated with atrial fibrillation (P = 0.013) and pneumonia (P = 0.005). Postoperative AKI did not impact survival outcomes. Conclusion: AKI is common but mostly self-limiting after esophageal cancer surgery. It is associated with age, male sex, increased BMI, dyslipidemia, and postoperative morbidity. [ABSTRACT FROM AUTHOR]

Background Hiatus hernia after oesophagectomy is an uncommon but serious complication of oesophageal cancer surgery. With improving long-term oncologic outcomes, post oesophagectomy hiatus hernia is an increasingly recognised entity in oesophageal cancer survivorship. The aim of this study was to assess the incidence of and risk factors for paraconduit hiatus hernia (PHH), and to describe management approaches in a tertiary referral centre. Methods All patients undergoing oesophagectomy for cancer from 2008 to 2022 were included. Early PHH was defined as occurring within 3 months of index surgery, with all other PHH defined as late PHH. Surveillance computed tomography scans were undertaken among all disease-free patients to 5-years postoperatively. Kaplan Meier and Cox proportional hazards regression models were used to determine independent risk factors for PHH. Results 897 patients were studied. Early PHH occurred in 1.2%, and late PHH in 5.7% of patients. There was no late recurrence after early PHH. PHH was an asymptomatic radiologic finding in 45.5% of early and 84.3% of late cases. Median time to PHH was 15.7 months postoperatively. Nausea, abdominal pain and vomiting were the most common symptoms associated with PHH. Surgical intervention was required in 25.8% of cases, more commonly following early PHH (63.6%) as compared with late PHH (17.6%, P < 0.01). Operative approach (P < 0.001), extended resection of crura or diaphragm (P < 0.001) and male sex (P = 0.037) were associated with increased risk of hiatus hernia. Conclusion Paraconduit hiatus hernia is an uncommon complication after oncologic oesophagectomy. Surgical intervention is often required for patients with PHH presenting in the first three months after surgery, but a majority of patients with asymptomatic late PHH may be managed expectantly. [ABSTRACT FROM AUTHOR]

Introduction: With the increasing prevalence of obesity and its associated comorbidities, strides to improve treatment strategies have enhanced our understanding of the function of the gut in the regulation of food intake. The most successful intervention for obesity to date, bariatric surgery effectively manipulates enteroendocrine physiology to enhance satiety and reduce hunger. Areascovered: In the present article, we provide a detailed overview of the physiology of enteroendocrine control of food intake, and discuss its pathophysiologic correlates and therapeutic implications in both obesity and gastrointestinal disease. Expertcommentary: Ongoing research in the field of nutrient sensing by L-cells, as well as understanding the role of the microbiome and bile acid signaling may facilitate the development of novel strategies to combat the rising population health threat associated with obesity. Further refinement of post-prandial satiety gut hormone based therapies, including the development of chimeric peptides exploiting the pleiotropic nature of the gut hormone response, and identification of novel methods of delivery may hold the key to optimization of therapeutic modulation of gut hormone physiology in obesity. [ABSTRACT FROM PUBLISHER]

Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from 1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n=84) who had one node positive had a median survival of 16 months (p=0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p=0.01). The survival of patients with one node positive [number of nodes (N)=1] was also significantly greater than the survival of patients with 2-3 nodes positive (N=2-3) (p=0.049) and greater than three nodes positive (p<0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups. [ABSTRACT FROM AUTHOR]