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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.)

Background: Large studies comparing totally minimally invasive oesophagectomy (TMIE) with laparoscopically assisted (hybrid) oesophagectomy are lacking. Although randomized trials have compared TMIE invasive with open oesophagectomy, daily clinical practice does not always resemble the results reported in such trials. The aim of the present study was to compare complications after totally minimally invasive, hybrid and open Ivor Lewis oesophagectomy in patients with oesophageal cancer., Methods: The study was performed using data from the International Esodata Study Group registered between February 2015 and December 2019. The primary outcome was pneumonia, and secondary outcomes included the incidence and severity of anastomotic leakage, (major) complications, duration of hospital stay, escalation of care, and 90-day mortality. Data were analysed using multivariable multilevel models., Results: Some 8640 patients were included between 2015 and 2019. Patients undergoing TMIE had a lower incidence of pneumonia than those having hybrid (10.9 versus 16.3 per cent; odds ratio (OR) 0.56, 95 per cent c.i. 0.40 to 0.80) or open (10.9 versus 17.4 per cent; OR 0.60, 0.42 to 0.84) oesophagectomy, and had a shorter hospital stay (median 10 (i.q.r. 8-16) days versus 14 (11-19) days (P = 0.041) and 11 (9-16) days (P = 0.027) respectively). The rate of anastomotic leakage was higher after TMIE than hybrid (15.1 versus 10.7 per cent; OR 1.47, 1.01 to 2.13) or open (15.1 versus 7.3 per cent; OR 1.73, 1.26 to 2.38) procedures., Conclusion: Compared with hybrid and open Ivor Lewis oesophagectomy, TMIE resulted in a lower pneumonia rate, a shorter duration of hospital stay, but higher anastomotic leakage rates. Therefore, no clear advantage was seen for either TMIE, hybrid or open Ivor Lewis oesophagectomy when performed in daily clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Tumor response and lymph node involvement are the most important prognosticators in resected patients with esophageal adenocarcinoma after neoadjuvant chemoradiotherapy (nCRT). We hypothesize that lymph node response (LNR) is also a valuable prognosticator in these patients, potentially revealing the added effect of nCRT., Methods: Hematoxylin and eosin slides of 193 esophageal adenocarcinoma patients with clinical suspicion of lymph node involvement (cN+) and treated with nCRT between 2008 and 2015 were assessed. Lymph nodes containing viable tumor cells were considered ypN+, and those negative for viable tumor were ypN0. LNR was also described according to an earlier defined method. Three groups were obtained: ypN0/LNR-, ypN0/LNR+, and ypN+. They were compared with 188 cN+ patients being pN0 (n = 45) or pN+ (n = 143) after upfront esophageal resection., Results: Forty-four patients were ypN0/LNR-, 55 were ypN0/LNR+, and 94 were ypN+. Median overall survival was 96.4, 31.2, and 20.6 months, respectively, and was significantly different between ypN0/LNR- and ypN0/LNR+ groups (P = .020). Survival was comparable between ypN0/LNR- and pN0 (104.2 months) groups (P = .519) and between ypN+ and pN+ (21.6 months) groups (P = .966). In ypN0 patients, risk of death in LNR+ patients was tripled compared with LNR- patients., Conclusions: In cN+ esophageal adenocarcinoma patients treated with nCRT with postoperative final pathology being ypN0, median overall survival is tripled when no signs of LNR were found and comparable to cN+/pN0 upfront esophagectomy patients, suggesting that 23% of patients treated with nCRT were in fact true N0 and overtreated by nCRT. ypN+ patients have no survival benefit compared with pN+ patients., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity., Objective: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival., Methods: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival., Results: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found., Conclusion: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Enhanced recovery pathways (ERP) have the potential to improve clinical outcomes. Aim of this study was to determine the impact of ERP on perioperative results as compared with traditional care (TC) after esophagectomy. In this study, two cohorts were compared. Cohort 1 represented 296 patients to whom TC was provided. Cohort 2 consisted of 200 unselected ERP patients. Primary endpoints were postoperative complications. Secondary endpoints were the length of stay and 30-day readmission rates. To confirm the possible impact of ERP, a propensity matched analysis (1:1) was conducted. A significant decrease in complications was found in ERP patients, especially for pneumonia and respiratory failure requiring reintubation (39% in TC and 14% in ERP; P<0.0001 and 17% vs. 12%; P<0.0001, respectively) and postoperative blood transfusion (26.7%-11%; P<0.0001). Furthermore, median length of stay was also significantly shorter: 13 days (interquartile range [IQR] 10-23) in TC compared with 10 days (IQR 8-14) in ERP patients (P<0.0001). The 30-day readmission rate (5.4% in TC and 9% in ERP; P=0.121) and in-hospital mortality rate (4.4% in TC and 2.5% in ERP; P=0.270) were not significantly affected. A propensity score matching confirmed a significant impact on pneumonia (P=0.0001), anastomotic leak (P=0.047), several infectious complications (P=0.01-0.034), blood transfusion (P=0.001), Comprehensive Complications Index (P=0.01), and length of stay (P=0.0001). We conclude that ERP for esophagectomy is associated with significantly fewer postoperative complications and blood transfusions, which results in a significant decrease of length of stay without affecting readmission and mortality rates., (© The Author(s) 2021. 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.)

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.

The optimal perioperative fluid management during esophagectomy is still not clear. Liberal regimens have been associated with higher morbidity and respiratory complications. Restrictive regimens might raise concerns for kidney function and increase the need to associate vasopressors. The aim of this study was to investigate retrospectively the perioperative fluid administration during esophagectomy and to correlate this with postoperative respiratory outcome. All patients who underwent esophagectomy between January and December 2016 were retrospectively analyzed. Patient characteristics, type of surgery and postoperative course were reviewed. Fluid administration and vasopressor use were calculated intraoperatively and during the postoperative stay at the recovery unit. Fluid overload was defined as a positive fluid balance of more than 125 mL/m2/h during the first 24 hours. Patients were divided in 3 groups: GRP0 (no fluid overload/no vasopressors); GRP1 (no fluid overload/need for vasopressors); GRP2 (fluid overload with/without vasopressors). Postoperative complications were prospectively recorded according to Esophagectomy Complications Consensus Group criteria. A total of 103 patients were analyzed: 35 (34%) GRP0, 50 (49%) GRP1 and 18 (17%) GRP2. No significant differences were found for age, treatment (neoadjuvant vs. primary), type of surgery (open/minimally invasive), histology nor comorbidities. There were significant (P ≤ 0.001) differences in fluid balance/m2/h (75 ± 21 mL; 86 ± 22 mL and 144 ± 20 mL) across GRP0, GRP1 and GRP2, respectively. We found differences in respiratory complications (GRP0 (20%) versus GRP1 (42%; P = 0.034) and GRP0 (20%) versus GRP2 (61%; P = 0.002)) and "Comprehensive Complications Index" (GRP0 (20.5) versus GRP1 (34.6; P = 0.015) and GRP0 (20.5) versus GRP2 (35.1; P = 0.009)). Multivariable analysis (binary logistic regression) for "any respiratory complication" was performed. Patients who received fluid overload (GRP2) had a 10.24 times higher risk to develop postoperative respiratory complications. When patients received vasopressors alone (GRP1), the chances of developing these complications were 3.57 times higher compared to GRP0. Among patients undergoing esophagectomy, there is a wide variety in the administration of fluid during the first 24 hours. There was a higher incidence of respiratory complications when patients received higher amounts of fluid or when vasopressors were used. We believe that a personalized and protocolized fluid administration algorithm should be implemented and that individual risk factors should be identified., (© 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.)

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission., (© 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.)

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Objective: The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity., Background: ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated., Patients and Methods: Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI)., Results: Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0-36] vs 29 [IQR 0-40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE., Conclusion: Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.

Objectives: Hiatal hernias (HH) after oesophagectomy are rare, and their surgical management is not well standardized. Our goal was to report on the management of HH after oesophagectomy in high-volume tertiary European French-speaking centres., Methods: We conducted a retrospective multicentre study among 19 European French-speaking departments of upper gastrointestinal and/or thoracic surgery. All patients scheduled or operated on for the repair of an HH after oesophagectomy were collected between 2000 and 2016. Demographics, details of the initial procedure, surgical management and long-term outcome were analysed., Results: Seventy-nine of 6608 (1.2%) patients who had oesophagectomies were included in the study. The postoesophagectomy diagnostic interval of an HH after oesophagectomy was ≤90 days (n = 17; 21%), 13 were emergency cases; between 91 days and 1 year, n = 21 (27%), 13 in emergency; ≥1 year, n = 41 (52%), 17 in emergency. The time to occurrence of HH after oesophagectomy was shorter after laparoscopy (median 308 days; interquartile range 150-693) compared to that after laparotomy (median 562 days, interquartile range 138-1768; P = 0.01). The incidence of HH after oesophagectomy was 0.73% (22/3010) after open surgery and 1.4% (26/1761) after laparoscopy (P = 0.03). Among the 79 patients, 78 were operated on: 35 had laparotomies (45%), 19 had laparoscopies (24%) and 24 (31%) had transthoracic approaches. Among the 43 urgent surgeries, 35 were open (25 laparotomies and 10 transthoracic approaches) and 8 were laparoscopies (conversion rate, 25%). Nine patients required bowel resections. Morbidity occurred in 36 (46%) patients with 1 postoperative death (1.2%). During the follow-up period, recurrent HH after oesophagectomy requiring revisional surgery developed in 8 (6 days-26 months) patients., Conclusions: Surgical management of HH after oesophagectomy could be done by laparoscopy in patients with scheduled surgery but laparotomy or thoracotomy was preferred in urgent situations. The incidence of HH after oesophagectomy is higher and its onset earlier when laparoscopy is used at the initial oesophagectomy., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Neoadjuvant treatment followed by esophagectomy is standard practice in locally advanced esophageal cancer. However, not all patients who started neoadjuvant treatment will undergo esophageal resection. The purpose of our study was to investigate the group of patients, scheduled for neoadjuvant treatment followed by esophagectomy, who never made it to esophageal resection., Methods: We retrospectively analyzed patients treated between 2002 and 2015 for locally advanced esophageal cancer, who did not undergo esophagectomy after neoadjuvant treatment. Subanalysis was performed according to time period (2002-2010 versus 2011-2015) and histology (adenocarcinoma versus squamous cell carcinoma)., Results: In 114 of 679 patients (16.8%), surgery was not performed after neoadjuvant treatment. Reasons for cancelation were disease progression (50 patients, 43.9%), poor general condition (26 patients, 22.8%), irresectability (14 patients, 12.3%), patients' own decision (15 patients, 13.2%), and death during neoadjuvant treatment (9 patients, 7.9%). In the second time period, there were less irresectable tumors (17.7% versus 5.8%; p = 0.044). Median overall survival was not different over time (9.2 versus 12.5 months; p = 0.937). Irresectability (p = 0.032), patients' refusal (p = 0.012), and poor general condition (p = 0.002) were more frequent as reasons for cancelation in squamous cell carcinoma patients. Median overall survival was, respectively, 12.5 and 9.9 months for adenocarcinoma and squamous cell carcinoma patients (p = 0.441). The majority of patients refusing surgery had a clinical complete response (73.3%). They had a median overall survival of 33.2 months., Conclusions: One in six patients starting neoadjuvant treatment for locally advanced esophageal cancer never made it to esophagectomy, more than half of them for oncological reasons, but also 1.3% because of death during treatment. Over time, irresectability as reason decreased. As a result, the relative weight of medical inoperability increased, indicating the importance of upfront testing of medical operability. Cancelation of surgery was significantly more common in patients with a squamous cell carcinoma, and this histology seems to represent a more complex oncological and functional entity. Refusal of esophagectomy based on clinical complete response showed a significant survival benefit compared to those who did not undergo esophagectomy because of other reasons.

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.

Despite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy., (© 2018 New York Academy of Sciences.)

Background: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated., Methods: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses., Results: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found., Conclusion: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients., Disclosure: All authors have declared no conflicts of interest.

Background: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy., Methods: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning., Results: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH 2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH 2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050)., Conclusion: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov)., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Esophageal sarcomas are rare and evidence in literature is scarce making their management difficult. The objective is to report surgical and oncological outcomes of esophageal sarcoma in a large multicenter European cohort. This is a retrospective multicenter study including all patients who underwent en-bloc esophagectomy for esophageal sarcoma in seven European tertiary referral centers between 1987 and 2016. The main outcomes and measures are pathological results, early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21 (0.2%) patients with esophageal sarcoma were identified. The majority of tumors was located in the middle (n = 7) and distal (n = 9) third of the esophagus. Neoadjuvant chemoradiotherapy was performed in five patients. All the patients underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive). Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant chemotherapy. Definitive pathological results were carcinosarcoma (n = 7), leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1 resection was present in one patient (5%) and seven patients (33%) had positive lymph nodes. Median follow-up was 16 (3-79) months in 20 of 21 patients (95%). One-, 3-, and 5-year overall survival rates were 74%, 43%, and 35%, respectively. One-, 3- and 5-years disease-free survival rates were 58%, 40%, and 33%, respectively. Median overall survival was 6 months in N+ patients vs. 37 months for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had died from cancer recurrences (43%), three patients died from other reasons (14%), one patient was still alive with recurrence (5%) and the seven remaining patients were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most common esophageal sarcoma histological subtypes. Lymph node involvement was seen in one third of cases. A transthoracic en-bloc esophagectomy with radical lymphadenectomy should be the best surgical option to achieve complete resection. Long-term survival remained poor with a high local and distant recurrence rate.

The accepted importance of a positive circumferential resection margin (CRM) (defined as R1 in the TNM classification) is based on histopathology of the resection specimen obtained after primary surgery in esophageal cancer patients. The aim of this study is to look for the prognostic value of CRM after neoadjuvant chemoradiotherapy and to compare the clinical significance of a histologically CRM < 1 mm from the cut margin (Royal College of Pathologists definition of R1) to a positive cut margin (College of American Pathologists definition of R1) and to ≥1 mm margin (R0) resections in patients with ypT3-esophageal tumors after neoadjuvant chemoradiotherapy. Between 2000 and 2014, 458 patients who received esophagectomy after neoadjuvant chemoradiation therapy were selected. Overall (OS) and disease-free survival (DFS) were calculated by means of Kaplan-Meier curves and compared by Cox regression analysis. There were 163 (35.9%) patients who had a ypT3 tumor; in 118 (72.4%) resection was complete (R0). In 37 (22.7%) patients a CRM < 1 mm was found and 8 (4.9%) had a circumferential R1-resection. CRM involvement was inversely correlated with tumor regression grading, lymph node capsular involvement, and number of positive lymph nodes. On univariate analysis, no statistically significant difference was found between R0-resection and CRM < 1 mm (P = 0.103) for OS, but DFS showed a significant difference (P = 0.025). Circumferential R1-resections showed a significant difference compared to R0-resections for OS and DFS (both P = 0.002). In multivariate analysis, extracapsular lymph node involvement and circumferential R1-resection were withheld as independent prognosticators for OS, whereas extracapsular lymph node involvement, absence of regression on the primary tumor and circumferential R1-resection were withheld for DFS. After correcting for different variables in the multivariate model, CRM < 1 mm showed no statistical difference compared to R0-resections neither for OS nor for DFS. After neoadjuvant chemoradiotherapy, CRM is correlated with biological behavior of the tumor and with therapy response. Furthermore it is an independent prognosticator for OS and DFS. However CRM < 1 mm itself is no independent prognosticator for OS nor DFS survival in multivariable analysis. These results suggest that the definition of R1-resection should be limited to true invasion of the section plane.

Objective: To define "best possible" outcomes in total minimally invasive transthoracic esophagectomy (ttMIE)., Background: TtMIE, performed by experts in patients with low comorbidity, may serve as a benchmark procedure for esophagectomy., Patients and Methods: From a cohort of 1057 ttMIE, performed over a 5-year period in 13 high-volume centers for esophageal surgery, we selected a study group of 334 patients (31.6%) that fulfilled criteria of low comorbidity (American Society of Anesthesiologists score ≤2, WHO/ECOG score ≤1, age ≤65 years, body mass index 19-29 kg/m). Endpoints included postoperative morbidity measured by the Clavien-Dindo classification and the comprehensive complication index. Benchmark values were defined as the 75th percentile of the median outcome parameters of the participating centers to represent best achievable results., Results: Benchmark patients were predominantly male (82.9%) with a median age of 58 years (53-62). High intrathoracic (Ivor Lewis) and cervical esophagogastrostomy (McKeown) were performed in 188 (56.3%) and 146 (43.7%) patients, respectively. Median (IQR) ICU and hospital stay was 0 (0-2) and 12 (9-18) days, respectively. 56.0% of patients developed at least 1 complication, and 26.9% experienced major morbidity (≥grade III), mostly related to pulmonary complications (25.7%), anastomotic leakage (15.9%), and cardiac events (13.5%). Benchmark values at 30 days after hospital discharge were ≤55.7% and ≤30.8% for overall and major complications, ≤18.0% for readmission, ≤3.1% for positive resection margins, and ≥23 for lymph node yield. Benchmarks at 30 and 90 days were ≤1.0% and ≤4.6% for mortality, and ≤40.8 and ≤42.8 for the comprehensive complication index, respectively., Conclusion: This outcome analysis of patients with low comorbidity undergoing ttMIE may serve as a reference to evaluate surgical performance in major esophageal resection.

Objectives: We developed a new algorithm to identify high-risk patients for underweight after oesophagectomy for cancer. Patients were assigned to an age-gender-specific body mass index percentile (AG-BMI) which is then used in a survival analysis. This model was able to identify patients more at risk for being underweight in comparison with the classically used BMI. It shows a worse overall survival (OS) in patients with a preoperative AG-BMI < 10th percentile. The aim of this study is to validate this new model based on a cohort of patients from an external high-volume institution specialized in oesophageal cancer surgery., Methods: The validation cohort consists of 407 patients operated on between 1999 and 2012 with the prerequisite data to calculate AG-BMI and OS. The base cohort consisted of 642 consecutive patients, operated on in our institution between 2005 and 2010. Age, gender, height and weight on the day before surgery were used to calculate the BMI and the AG-BMI. OS was analysed and a multivariate analysis was performed., Results: Incidence rates of the AG-BMI < 10th percentile risk-patients in the validation cohort showed similar results to our original results (17.8 vs 17.2% for the base cohort) with a similar significant OS difference between at-risk patients and not-at-risk patients (P < 0.001). Multivariate analysis found the same five independent prognosticators for OS in both datasets: age, early versus advanced disease, resection status, number of positive lymph nodes and the AG-BMI 10th percentile, but not BMI itself. In the validation cohort, gender was identified as an additional independent prognosticator. The worse OS survival in AG-BMI < 10th percentile in both patient populations was related to a significantly higher number of deaths without oesophageal cancer recurrence., Conclusions: This study validates the newly developed AG-BMI model to predict more accurately a subgroup of patients at risk for worse survival after oesophagectomy. Improved perioperative identification of risk factors for poorer OS could help to develop perioperative strategies to reduce these risks., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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.

Objectives: To evaluate baseline health-related quality of life (HRQL) factors that influence short-term outcome after oesophagectomy for cancer of the oesophagus and gastro-oesophageal junction and the effects of postoperative length of hospital stay on postoperative HRQL, as perceived by the patients themselves., Methods: Four hundred and fifty-five patients operated on with curative intent between January 2005 and December 2009 were analysed. HRQL scores were obtained by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and oesophageal-specific symptoms (OES-18) questionnaires at baseline (=day before surgery) and 3-monthly post-surgery for the first year., Results: There were 372 males and 83 females, with a mean age of 63.1 years. Hospital mortality was 3.7% (17 patients). When analysing postoperative length of stay (LOS), a median of 10 days was found. In a multivariable analysis, using a binary logistic regression model, independent prognosticators for a longer LOS (>10 days) were: medical [hazard ratio, HR, 6.2 (3.62-10.56); P < 0.0001] and surgical [HR 2.79 (1.70-4.59); P < 0.0001] morbidity, readmittance to intensive care unit [HR 33.82 (4.55-251.21); P = 0.001] and poor physical functioning [HR 1.89 (1.14-3.14); P = 0.014]. Postoperatively, patients with early discharge (LOS <10 days) indicated, at 3 and 12 months postoperatively, significant better HRQL scores in the functional scales (physical, emotional, social and role functioning) and in symptoms scales (fatigue, nausea, dyspnoea appetite loss and dry mouth) when compared with LOS >10 days. Return to the level of the reference population scores was achieved at 1 year in the LOS ≤10 days for almost all the scales, but not in the LOS >10 days group., Conclusions: A better perception of preoperative physical functioning might have a beneficial effect on LOS. Our data, furthermore, suggest that early discharge correlates with improved postoperative HRQL outcomes. A clear decrease of the HRQL is seen at 3 months after the surgery, particularly in the LOS >10 days group. Generally, return to the level of the reference population scores is achieved at 1 year in the LOS ≤10 days, but not in the LOS >10 days group.

Background: Little is known about recurrence patterns in patients with a pathologically complete response (pCR) or an incomplete response after neoadjuvant chemoradiotherapy (CRT) followed by resection for oesophageal cancer. This study was performed to determine the pattern of recurrence in patients with a pCR after neoadjuvant CRT followed by surgery., Methods: All patients who received neoadjuvant CRT followed by oesophagectomy between 1993 and 2009 were identified from a database, and categorized according to pathological tumour response. Recurrences were classified as locoregional or distant., Results: One hundred and eighty-eight patients were included. Median potential follow-up was 71·6 months. A pCR was achieved in 62 (33·0 per cent) of 188 patients. Recurrence developed in 24 (39 per cent) of 62 patients with a pCR and 70 (55·6 per cent) of 126 without a pCR (P = 0·044). Locoregional recurrence with or without synchronous distant metastases occurred in eight patients (13 per cent) in the pCR group and 31 (24·6 per cent) in the non-pCR group (P = 0·095). Locoregional recurrences without synchronous distant metastases occurred four (6 per cent) and ten (7·9 per cent) patients respectively (P = 0·945). The overall 5-year survival rate was significantly higher in the pCR group than in the non-pCR group (52 versus 33·9 per cent respectively; P = 0·019)., Conclusion: Of patients with a pCR, 13 per cent still developed a locoregional recurrence. Although pCR is more favourable for survival, it is not synonymous with cure or complete locoregional disease control., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: The aim was to conduct a comparative analysis of outcome after minimally invasive oesophagectomy (MIO) versus open oesophagectomy (OO) for early oesophageal and gastro-oesophageal junction (GOJ) carcinoma., Methods: Inclusion criteria for MIO and a matched group of OO were pT<2 and N0. Surgical outcome, complications, survival and health-related quality of life (HRQL) were assessed., Results: Between January 2005 and January 2010, 175 patients (101 OOs, 65 MIOs and nine MIOs converted to OO) fulfilled the abovementioned criteria. Histology was predominantly adenocarcinoma (75%), equally distributed between both groups as were preoperative co-morbidities (p = 0.43), pathologic staging (pT: p = 0.56) and mean number of resected lymph nodes in pTIS/1a (p = 0.23) and pT1b (p = 0.13). Blood loss was less (p = 0.01) and duration of operation longer (p = 0.001) in MIO. Hospital mortality (p = 0.66) and postoperative complications (p = 0.34) were comparable. However, respiratory complications (p = 0.008) and intensive care unit (ICU) admission (p = 0.02) were higher in OO. Gastrointestinal complications (p = 0.005), that is, gastroparesis (p = 0.004) were more frequent in MIO. At 3 months, postoperative fatigue, pain (general) and gastrointestinal pain were less in MIO (p = 0.09, 0.05 and 0.01, respectively). Five-year cancer-specific and recurrence-free survival stratified to the pathologic T-stage were not statistically different between MIO and OO., Conclusion: MIO is a valuable alternative to OO for the treatment of early oesophageal and GOJ carcinoma. This study underscores the need for large-scale, preferably multicentric studies to assess the real value of MIO versus OO., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the impact of postoperative complications after transthoracic esophagectomy, using the modified Clavien classification, on recurrence and on its timing in patients with cancer of the esophagus or gastroesophageal junction., Background Data: It is hypothesized that complications after esophagectomy for cancer may have a negative effect on recurrence and its timing because of negative interference with the immune system., Methods: Out of 150 consecutive patients operated with curative intent between January 2005 and May 2006, the data of 138 patients with macroscopically complete resection and no synchronous other malignancy were graded according to the modified Clavien classification. Uni- and multivariable analyses were performed to study the impact of postoperative complications on tumor recurrence and its timing., Results: Mean age was 63.1 years, male-female ratio was 4:1; 76.1% of the patients underwent primary surgery, 23.9% received induction therapy, R0-resection rate was 92.8%. Adenocarcinoma was found in 75%. Complication rates according to the modified Clavien classification were grade 0: 29.7%, grade 2: 35.5%, grade 3: 17.4%, grade 4: 15.9%, and grade 5 (postoperative mortality): 1.4%. Ten patients developed recurrence within 6 months, 29 within 12 months, 39 within 18 months, 42 within 24 months, totaling up to 47 at 3 years. Univariable analysis retained complications, LN-status, number of positive nodes, extracapsular lymph node involvement (EC LNI), pStage, pT, and R1-status as factors significantly influencing occurrence of recurrence. In the multivariable model, presence of complications, EC LNI, and R1-status were independent negative factors. Cox-regression analysis also identified these same 3 factors as significant determinators for the timing of recurrence., Conclusions: This study indicates a correlation between complications and early recurrence and its timing. Modified Clavien classification, beside R1-status and EC LNI, appears to be a useful prognostic indicator of early recurrence and its timing. Achieving esophagectomy without postoperative complications is of utmost importance also for oncologic reasons given its negative potential on early oncologic outcome.

Since 1992, various combinations of thoracoscopy (VATS), laparoscopy or hand-assisted thoracolaparoscopy have been used for 'minimally invasive' cancer esophagectomy (MIE). Despite widespread current use, indications and potential benefits of the many technical approaches remain controversial. A systematic literature search was conducted until June 2007. Out of 128 publications, 46 original series (1932 patients) met the inclusion criteria and were analyzed for surgical and oncological outcome. No prospective controlled study has compared any MIE technique to another or to open surgery. Most publications are retrospective series of highly selected patients, mostly excluding high-risk patients and locally advanced (T3) tumors. Altogether, the overall conversion rate was 5.9%, mortality 2.9% and morbidity 46%, many papers reporting only major complications. Overall, rates for pulmonary complications were 22%, leakage 8.8% and vocal cord palsy 7.1%. Fifteen tracheo-bronchial injuries or fistulas (1% of all VATS cases) were reported. Laparoscopy and VATS were combined in 11 series (609 patients, 4.7% conversions, 2.4% mortality). VATS combined with (mini)-laparotomy was reported in 14 papers (743 patients, 6.3% conversions, 2.4% mortality). Laparoscopy combined with right thoracotomy was reported in four papers (147 patients, 5.4% conversions, 2% mortality). Laparoscopic transhiatal resections were reported in 17 papers (433 patients, 7% conversions, 4.6% mortality). Overall morbidity rates for these four approaches were 43%, 47.6%, 51.6% and 46%, respectively. Data on oncological outcome are scarce. Lymph node retrieval (median of all series: 14 nodes, range 5-62) was mostly inferior to open surgery standards and follow-up too short to draw definitive conclusions regarding long-term survival. Based on the available literature, the morbidity and mortality of MIE is substantial and not inferior to radical open esophagectomy in experienced centers. Many different operative techniques for MIE have been reported without obvious superiority for any of them. The term 'minimally invasive' is not supported by hitherto reported results. Selection bias and huge variability in extent of resection and lymphadenectomy impair comparisons of different MIE techniques. Oncological outcome of MIE remains largely unknown by lack of good quality data and selection bias. MIE remains an investigational and still evolving treatment for invasive cancer.

Objective: Though the surgical treatment of esophageal cancer is increasingly accepted for elderly people defined as aged over 70 years, less is reported about the results in patients over 75. This study is a single institution retrospective analysis of outcome after esophagectomy for cancer of the esophagus and GEJ in patients aged over 75 years., Methods: All consecutive patients 76 years old and over undergoing curative esophagectomy for cancer in the period 1991-2006 were analyzed as to comorbidities, outcome and long-term survival. All the data had been prospectively collected in a database. Postoperative mortality risk was assessed by P-POSSUM and O-POSSUM score for in-hospital mortality and by the recently published Steyerberg's score system [Steyerberg EW, Neville BA, Koppert LB, Lemmens VEPP, Tilanus HW, Coebergh JWW, Weeks JC, Earle CC. Surgical mortality in patients with esophageal cancer: development and validation of a simple risk score. J Clin Oncol 2006;24:4277-84.] for 30-day mortality. Five-year survival was compared to the standardized survival in the general population., Results: One hundred and eight patients fulfilling the abovementioned criteria were found (76 males and 32 females, mean age 79.5 years, mean standardized life-expectancy: 7.36 years). Among them, 69% had esophageal tumors and 31% GEJ tumors. The predominant histology was adenocarcinoma (74%). Eighty-six (79.6%) presented with one or more major comorbidities or a history of previous major upper-GI surgery, potentially affecting the surgical outcome. All underwent resection with curative intent (R(0) 83.3%, R(1) 12%, R(2) 4.6%). The overall postoperative morbidity rate was 51.9%, pulmonary complications (37%) being the most frequent. Postoperative mortality, mainly due to cardiopulmonary complications, was 7.4%, which was consistent with that predicted by P-POSSUM score (7.2%) and lower than that predicted by O-POSSUM score (15.1%). Thirty-day mortality was 5.5%, being consistent with that predicted by the Steyerberg's score (6.8%). Overall 5-year survival was 35.7%, while R(0) overall survival 42% and cancer specific R(0) survival 51.7%., Conclusions: Patients 76 years old and over with esophageal or GEJ cancer should not be denied surgery solely on the basis of age. Outcome and long-term results in the selected elderly are not differing from those reported for younger patients. However, despite thorough preoperative assessment being applied in the selection of the candidates for surgery, a practical and reliable individual risk-analysis stratification is still lacking.

Adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) has shown a remarkable increase during recent decades. Most patients are present with advanced stage disease, reflecting transmural growth and metastasis to lymph nodes at the time of diagnosis. Moreover, the pattern of lymph node dissemination is chaotic and difficult to predict, and despite the use of modern technology (e.g., spiral CT, EUS, FDG-PET), clinical staging remains suboptimal. These shortcomings in staging, as well as in different attitudes toward extent of resection and lymphadenectomy, are reflected by a great variation in surgical techniques, which are discussed in this review. As to the results, primary surgery can currently be performed with low mortality, below 5% in high volume centers. Hospital mortality and morbidity are mainly related to pulmonary complications and anastomotic leaks, the latter mostly resolving under conservative treatment. Overall 5-year survival varies between 10% and 59%. As expected the most important prognostic determinants are completeness of resection (R0 vs. R1-R2) and lymph node status (N0, N1). R0 resection currently offers 5-year survival rates of over 40%. Five-year survival figures for node-negative (N0) patients exceed 70%, and even for node-positive (N1), patients reach 25%. It is not known whether performing a three-field lymph node dissection is beneficial for patients with adenocarcinoma of the distal esophagus. With overall 5-year survival currently exceeding 30%-40%, these figures should be the gold standard against which all other therapeutic modalities are compared., ((c) 2005 Wiley-Liss, Inc.)

Surgical treatment of cancer of the esophagus and gastroesophageal junction (GEJ) remains a complex and challenging task. Quality of care may be improved by concentrating these patients in high volume centres in order to decrease post-operative mortality. However, it appears that hospital mortality is a poor tool to measure the quality. More likely specialisation as well as appropriate hospital environment supporting a dedicated multidisciplinary team are key elements in improving both the short term and long term results. The dedicated specialist surgeon has a key role in improving these results through surgical quality. The most important goal in the surgical treatment of these cancers is to perform a complete resection (R0). Data from literature seem to indicate that R0 resection combined with extensive lymphadenectomy are resulting in improved disease free survival and possibly in improved 5 year survival, often reported to exceed 35% after such interventions. These results suggest that there is a great need for standardisation of surgery. Such a standardisation and the resulting improved quality most likely will result in a significant improvement of outcome of esophagectomy for cancer of the esophagus and GEJ. These improvements in outcome should become the gold standard to which all other therapeutic regimens should be compared. Poor surgical quality and related poor results should not be a justification for multimodality regimen.

The overall prognosis of patients with carcinoma of the esophagus and gastroesophageal junction (GEJ) remains poor mainly because of the advanced stage of the disease at the time of presentation. As a result, controversy persists over the appropriate extent of surgery. This article reviews the impact of aggressive surgery on staging, disease-free survival, and cure rate. Despite recent advances in staging including positron emission tomography (PET), the findings after aggressive surgery indicate that the overall accuracy, sensitivity, and specificity of clinical staging are still too low. These shortcomings in clinical staging therefore question the value of the indications, results, and interpretation of outcomes in multimodality treatment regimens. Extended surgery increases the R(0) resection rate, which seems to have an undeniable beneficial effect on the incidence of locoregional recurrence and which should be considered as a parameter of surgical quality, especially within the context of multimodality trials. As to the effect on cure rate, the only randomized trial with published results did not indicate a significant difference between extended and more limited resections for adenocarcinoma of the esophagus and GEJ, albeit that a subsequent subanalysis did show a significant survival benefit favoring more extended surgery in distal third adenocarcinomas. However, the bulk of current literature suggests that better survival is achieved by more aggressive surgery. For three-field lymphadenectomy the available data suggest a potential survival benefit. It appears that positive cervical lymph nodes in patients with middle or proximal third carcinoma should no longer be considered as M(1a/b) distant lymph node metastasis but rather as N(1) regional disease.

Anastomotic complications after esophagectomy continue to be a burden jeopardizing the quality of life and of swallowing. However, incidence, mortality and morbidity of anastomotic complications have substantially decreased in recent years. It seems that this is not so much related to the use of a particular conduit, approach or route for reconstruction, but rather related to refinement in anastomotic techniques and perhaps even more to progress in modern perioperative management. Knowledge of surgical anatomy and meticulous technique are of paramount importance and obviously related to individual expertise. As to the management, most leaks can be treated by conservative measures and reintervention surgery today is rather exceptional. Early endoscopy and dilatation seem to decrease the incidence and severity of anastomotic stenosis., (Copyright 2002 S. Karger AG, Basel)

Abstract Background An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. Methods The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. Discussion The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. Trial registration NCT03222895, date of registration: July 19th, 2017.

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]

Background: Minimally invasive esophagectomy (MIE) is a complex and technically demanding procedure with a long learning curve, which is associated with increased morbidity and mortality. To master MIE, training in essential steps is crucial. Yet, no consensus on essential steps of MIE is available. The aim of this study was to achieve expert consensus on essential steps in Ivor Lewis and McKeown MIE through Delphi methodology. Methods: Based on expert opinion and peer-reviewed literature, essential steps were defined for Ivor Lewis (IL) and McKeown (McK) MIE. In a round table discussion, experts finalized the lists of steps and an online Delphi questionnaire was sent to an international expert panel (7 European countries) of minimally invasive upper GI surgeons. Based on replies and comments, steps were adjusted and rephrased and sent in iterative fashion until consensus was achieved. Results: Two Delphi rounds were conducted and response rates were 74% (23 out of 31 experts) for the first and 81% (27 out of 33 experts) for the second round. Consensus was achieved on 106 essential steps for both the IL and McK approach. Cronbach's alpha in the first round was 0.78 (IL) and 0.78 (McK) and in the second round 0.92 (IL) and 0.88 (McK). Conclusions: Consensus among European experts was achieved on essential surgical steps for both Ivor Lewis and McKeown minimally invasive esophagectomy. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objectives: The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. Background: Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. Methods: From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. Results: In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52–3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. Conclusions: Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC. [ABSTRACT FROM AUTHOR]

Brain metastases after esophagectomy are rare. Moreover, a diagnostic uncertainty remains as pathology is rarely obtained and radiological features can show similarities to primary brain tumors. Our aim was to demonstrate the diagnostic uncertainty and identify risk factors associated with brain tumors (BT) after esophagectomy with curative intent. All patients who underwent an esophagectomy with curative intent from 2000 to 2019 were reviewed. Diagnostics and characteristics of BT were analyzed. Multivariable logistic and cox regression were performed to determine factors associated with development of BT and survival, respectively. In total, 2131 patients underwent esophagectomy with curative intent, of which 72 patients (3.4%) developed BT. Pathological diagnosis was obtained in 26 patients (1.2%), of which 2 patients were diagnosed with glioblastoma. On multivariate analysis, radiotherapy (OR, 7.71; 95%CI: 2.66–22.34, p < 0.001) was associated with an increased risk of BT and early-stage tumors (OR, 0.29; 95%CI: 0.10–0.90, p = 0.004) with a decreased risk of BT. Median overall survival was 7.4 months (95%CI: 4.80–9.96). BT treated with curative intent (surgery or stereotactic radiation) had a significantly better median overall survival (16 months; 95%CI: 11.3–20.7) compared to those without (3.7 months; 95%CI: 0.9–6.6, p < 0.001) Advanced stage tumors and radiotherapy seem related to the development of brain tumors after esophagectomy with curative intent. However, an important diagnostic uncertainty remains in these patients as pathological diagnosis is only obtained in a minority of cases. Tissue confirmation can be useful to inform a patient-tailored multimodality treatment strategy in select patient. • One of the first series to include data on histology. • 8% of histologically confirmed suspected brain tumors are glioblastomas. • Radiotherapy is risk factor for developing BT (OR,7.71, 95%CI: 2.66–22.34). • Consider biopsy in oligometastatic setting. [ABSTRACT FROM AUTHOR]

Recurrent disease after esophagectomy bears an infaust prognosis, especially when multiple recurrences are present. But little is known about survival in patients with limited recurrence (solitary locoregional recurrence or solid organ metastasis). Herein, we report our experience with these subgroups. We analyzed 1754 consecutive patients surgically treated with curative resection for esophageal cancer and cancer of the gastroesophageal junction between 1990 and 2012. Seven subgroups were defined according to the recurrence type (locoregional vs. organ metastasis), the site of recurrence (abdominal, thoracic, cervical for lymph nodes and lung, liver, adrenals and others for organ metastasis) and also the number of lesions (one vs. multiple lymph node stations or organ metastasis) Of these groups; clinical isolated locoregional recurrence (ciLR) was defined as solitary lymph-node recurrence confined to one compartment (cervical, thoracic or abdominal, within or outside surgical dissection-field) at clinical staging. Clinical solitary solid organ metastasis (csSOM) was defined as metastasis in a resectable solid organ, i.e. liver, lung, brain or adrenal. Salvage therapies were grouped in five categories. Kaplan-Meier curves were used to calculate survival. Recurrent disease was observed in 766 patients (43.7%) with overall 5-year survival of 4.5% after diagnosis of recurrence. Fifty-seven patients (7.4%) showed ciLR and 110 (14.4%) csSOM. Median timeto-recurrence was 16.8 months in ciLR and 9.9 months in csSOM (P=0.0074). Survival is significantly improved compared to supportive therapy when local therapy is possible (P<0.0001). In 25 (15%) of ciLR or csSOM patients, surgical therapy with or without systemic therapy, yielded a 5-year survival of 49.9% (median 54.8 months) after diagnosis of recurrence. When surgery was impossible or contraindicated, the combination of chemoradiotherapy appeared to be superior to chemotherapy alone (respectively 27.0% vs. 4.6% 5-year survival) or radiotherapy alone (no 5-year survival). Recurrent disease after esophagectomy is a common problem with poor overall survival. However prolonged survival could be obtained in selected patients if the recurrent disease is limited to ciLR or csSOM, if surgery (+/- systemic therapy) can be performed. If not a combination of chemoradiotherapy seems to offer the second best option. Patients presenting with a ciLR or csSOM should be discussed in a dedicated multidisciplinary team meeting as to evaluate and define the place of salvage treatment which in well selected cases could offer a perspective of prolonged survival. [ABSTRACT FROM AUTHOR]

Objective: The current pathological lymph node (pN) staging is based on the number of positive lymph nodes but does not take into consideration characteristics of the involved lymph nodes itself. The current study aims to examine the prognostic value of extracapsular lymph node involvement (EC-LNI) and intracapsular lymph node involvement (IC-LNI) for esophageal adenocarcinoma treated by primary surgery. Methods: From the databases of five European high volume centers, 1639 adenocarcinoma patients with primary R0-resection were withheld after excluding 90-day mortality. Oncologic variables, including number of resected lymph nodes, number of resected positive lymph nodes, and ECLNI/ IC-LNI were examined. The Union Internationale contre le Cancer (UICC) 7th edition prognostic staging was used as baseline staging system. Statistical analysis was performed by Cox proportional hazards modeling and verified using the Random Survival Forest technique. Results: EC-LNI showed significantly worse overall 5-year survival compared with IC-LNI overall (13.4% vs 37.2%, P<0.0001), including in each pN-catergory [16.4% vs 45.6% in pN1 (P<0.0001), 16.1% vs 23.8% (P=0.047) in pN2 (P=0.065), and 8.7% vs 26.3% in pN3 categories, respectively]. pN1 IC-LNI patients show a 5-year overall survival comparable (P=0.92) with stage IIB (ie, pT3N0). Reclassifying the UICC prognostic stages according to these findings into an adapted staging model showed a significant (P<0.0001) increase in homogeneity, discriminatory ability, and monotonicity compared with the original UICC TNM 7th edition prognostic staging. Conclusions: These data suggest that lymph node capsular status is an important prognostic factor and should be considered for the future edition of the TNM staging system for esophageal cancer. [ABSTRACT FROM AUTHOR]