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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.)

The aim of this study was to evaluate the surgical treatment of esophago-tracheobronchial fistulas (ETBFs) that occurred after esophagectomy with gastric conduit reconstruction in a tertiary referral center for esophageal surgery. All patients who underwent surgical repair for an ETBF after esophagectomy with gastric conduit reconstruction were included in a tertiary referral center. The primary outcome was successful recovery after surgical treatment for ETBF, defined as a patent airway at 90 days after the surgical fistula repair. Secondary outcomes were details on the clinical presentation, diagnostics, and postoperative course after fistula repair. Between 2007 and 2022, 14 patients who underwent surgical repair for an ETBF were included. Out of 14 patients, 9 had undergone esophagectomy with cervical anastomosis and 5 esophagectomy with intrathoracic anastomosis after which 13 patients had developed anastomotic leakage. Surgical treatment consisted of thoracotomy to cover the defect with a pericardial patch and intercostal flap in 11 patients, a patch without interposition of healthy tissue in 1 patient, and fistula repair via cervical incision with only a pectoral muscle flap in 2 patients. After surgical treatment, 12 patients recovered (86%). Mortality occurred in two patients (14%) due to multiple organ failure. This study evaluated the techniques and outcomes of surgical repair of ETBFs following esophagectomy with gastric conduit reconstruction in 14 patients. Treatment was successful in 12 patients (86%) and generally consisted of thoracotomy and coverage of the defect with a bovine pericardial patch followed by interposition with an intercostal muscle., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Anastomotic leakage (AL) after esophagectomy is the most impactful complication after esophagectomy. Ischemic conditioning (ISCON) of the stomach >14 days prior to esophagectomy might reduce the incidence of AL. The current trial was conducted to prospectively investigate the safety and feasibility of laparoscopic ISCON in selected patients. This international multicenter feasibility trial included patients with esophageal cancer at high risk for AL with major calcifications of the thoracic aorta or a stenosis in the celiac trunk. Patients underwent laparoscopic ISCON by occlusion of the left gastric and the short gastric arteries followed by esophagectomy after an interval of 12-18 days. The primary endpoint was complications Clavien-Dindo ≥ grade 2 after ISCON and before esophagectomy. Between November 2019 and January 2022, 20 patients underwent laparoscopic ISCON followed by esophagectomy. Out of 20, 16 patients (80%) underwent neoadjuvant treatment. The median duration of the laparoscopic ISCON procedure was 45 minutes (range: 25-230). None of the patients developed intraoperative or postoperative complications after ISCON. Hospital stay after ISCON was median 2 days (range: 2-4 days). Esophagectomy was completed in all patients after a median of 14 days (range: 12-28). AL occurred in three patients (15%), and gastric tube necrosis occurred in one patient (5%). In hospital, the 30-day and 90-day mortalities were 0%. Laparoscopic ISCON of the gastric conduit is feasible and safe in selected esophageal cancer patients with an impaired vascular status. Further studies have to prove whether this innovative strategy aids to reduce the incidence of AL., (© The Author(s) 2023. 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.)

Esophageal resection is a high-risk and technically demanding procedure, with a long proficiency-gain curve. The European Society Diseases of the Esophagus (ESDE)-Minimally Invasive Esophagectomy (MIE) training program was launched in 2018 for European surgeons willing to train and to begin a career undertaking MIE. The aim of this study was to evaluate the first experience of the ESDE-MIE fellowship and relate this to the initially predetermined core principles and objectives of the program. Between October 2021 and May 2022, the participating fellows, in collaboration with the ESDE Educational Committee, initiated a survey to assess the outcome and experience of these fellowships. Data from each individual fellowship were analysed and reported in a descriptive manner. Between 2018 and 2022, in total, five fellows have completed the ESDE-MIE fellowship program. Despite the COVID-19 outbreak just the year after its launch, predetermined clinical and research goals were achieved in all cases. Each of the fellows were able to assist in a median of 40 (IQR 27-69) MIE and/or Robot assisted (RA)MIE procedures, of a total median of 115 (IQR 83-123) attended Upper GI cases. After the fellowship, MIE has been fully adopted by the fellows who returned to their home institutions as Upper GI surgeons. The fellowship was concluded by the European Union of Medical Specialists (UEMS) Multidisciplinary Joint Committee (MJC) certification in Upper GI Surgery, which was successfully obtained by all who took part. Based on the experience of the first five fellows, the ESDE-MIE training fellowship meets with the expected needs even despite the COVID-19 outbreak in 2019. Furthermore, these fellows have returned home and integrated MIE into their independent surgical practice, affirming the ability of this program to train the next generation of MIE surgeons, even in the most challenging of circumstances., (© The Author(s) 2023. 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.)

The aim of this study was to evaluate the current practice in surgical techniques for esophageal and gastroesophageal junction cancer surgery worldwide and to compare the results to the previous surveys in 2007 and 2014. An online survey was sent out among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association, the Association of Upper Gastrointestinal Surgery of Great Britain and Ireland and Dutch gastroesophageal surgeons via the network of the investigators. In total, 260 surgeons completed the survey representing 52 countries and 6 continents; Europe 56%, Oceania 14%, Asia 14%, South-America 9%, North-America 7%. Of the responding surgeons, 39% worked in a hospital that performed >51 esophagectomies per year. Total minimally invasive esophagectomy was the preferred technique (53%) followed by hybrid esophagectomy (26%) of which 7% consisted of a minimally invasive thoracic phase and 19% of a minimally invasive abdominal phase. Total open esophagectomy was preferred by 21% of the respondents. Total minimally invasive esophagectomy was significantly more often performed in high-volume centers compared with non-high-volume centers (P = 0.002). Robotic assistance was used in 13% during the thoracic phase and 6% during the abdominal phase. Minimally invasive transthoracic esophagectomy has become the preferred approach for esophagectomy. Although 21% of the surgeons prefer an open approach, 26% of the surgeons perform a hybrid procedure which may reflect further transition towards the use of total minimally invasive esophagectomy., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Conflicting results are reported on the association between post-esophagectomy complications and long-term survival. This multicenter study assesses the association between complications after an esophagectomy and long-term overall survival. Five Dutch high-volume centers collected data from consecutive patients undergoing esophagectomy between 2010 and 2016 and merged these with long-term survival data from the Netherlands Cancer Registry. Exclusion criteria were non-curative resections and 90-day mortality, among others. Primary outcome was overall survival related to the presence of a postoperative complication in general. Secondary outcomes analyzed the presence of anastomotic leakage and cardiopulmonary complications. Propensity score matching was performed and the outcomes were analyzed via Log-Rank test and Kaplan Meier analysis. Among the 1225 patients included, a complicated course occurred in 719 patients (59.0%). After matching for baseline characteristics, 455 pairs were successfully balanced. Patients with an uncomplicated postoperative course had a 5-year overall survival of 51.7% versus 44.4% in patients with complications (P = 0.011). Anastomotic leakage occurred in 18.4% (n = 226), and in 208 matched pairs, it was shown that the 5-year overall survival was 57.2% in patients without anastomotic leakage versus 44.0% in patients with anastomotic leakage (P = 0.005). Overall cardiopulmonary complication rate was 37.1% (n = 454), and in 363 matched pairs, the 5-year overall survival was 52.1% in patients without cardiopulmonary complications versus 45.3% in patients with cardiopulmonary complications (P = 0.019). Overall postoperative complication rate, anastomotic leakage, and cardiopulmonary complications were associated with a decreased long-term survival after an esophagectomy. Efforts to reduce complications might further improve the overall survival for patients treated for esophageal carcinoma., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Anastomotic leakage is a feared complication after esophagectomy and associated with increased post-operative morbidity and mrotality. The aim of this study was to evaluate the management of leakage after robot-assisted minimally invasive esophagectomy (RAMIE) with intrathoracic anastomosis. From a single center prospectively maintained database, all patients with anastomotic leakages defined by the Esophageal Complications Consensus Group between 2016 and 2021 were included. Contained leakage was defined as presence of air or fluid at level of the anastomosis without the involvement of the mediastinum or thorax. Non-contained leakage was defined as mediastinitis and/or mediastinal/pleural fluid collections. The primary outcome was 90-day mortality and the secondary outcome was successful recovery. In this study, 40 patients with anastomotic leakage were included. The 90-day mortality rate was 3% (n = 1). Leakage was considered contained in 29 patients (73%) and non-contained in 11 patients (27%). In the contained group, the majority of the patients were treated non-surgically (n = 27, 93%) and management was successful in 22 patients (76%). In the non-contained group, all patients required a reoperation with thoracic drainage and management was successful in seven patients (64%). Management failed in 11 patients (28%) of whom 7 developed an esophagobronchial fistula, 3 had a disconnection of the anastomosis and 1 died of a septic bleeding. In conclusion, this study demonstrates that the management anastomotic leakage in patients who underwent RAMIE with an intrathoracic anastomosis was successful in 73% of the patients with a 90-day mortality rate of 3%. A differentiated approach for the management of intrathoracic anastomotic leakage is proposed., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background: Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE)., Methods: To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-μm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks., Results: Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins., Conclusions: The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE., (© The Author(s) 2022. 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: Structured training protocols can safely improve skills prior initiating complex surgical procedures such as robotic-assisted minimally invasive esophagectomy (RAMIE). As no consensus on a training curriculum for RAMIE has been established so far it is our aim to define a protocol for RAMIE with the Delphi consensus methodology., Methods: Fourteen worldwide RAMIE experts were defined and were enrolled in this Delphi consensus project. An expert panel was created and three Delphi rounds were performed starting December 2019. Items required for RAMIE included, but were not limited to, virtual reality simulation, wet-lab training, proctoring, and continued monitoring and education. After rating performed by the experts, consensus was defined when a Cronbach alpha of ≥0.80 was reached. If ≥80% of the committee reached a consensus an item was seen as fundamental., Results: All Delphi rounds were completed by 12-14 (86-100%) participants. After three rounds analyzing our 49-item questionnaire, 40 items reached consensus for a training curriculum of RAMIE., Conclusion: The core principles for RAMIE training were defined. This curriculum may lead to a wider adoption of RAMIE and a reduction in time to reach proficiency., (© 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.)

Robot-assisted cervical esophagectomy (RACE) enables radical surgery for tumors of the middle and upper esophagus, avoiding a transthoracic approach. However, the cervical access, narrow working space, and complex topographic anatomy make this procedure particularly demanding. Our study offers a stepwise description of appropriate dissection planes and anatomical landmarks to facilitate RACE. Macroscopic dissections were performed on formaldehyde-fixed body donors (three females, three males), according to the surgical steps during RACE. The topographic anatomy and surgically relevant structures related to the cervical access route to the esophagus were described and illustrated, along with the complete mobilization of the cervical and upper thoracic segment. The carotid sheath, intercarotid fascia, and visceral fascia were identified as helpful landmarks, used as optimal dissection planes to approach the cervical esophagus and preserve the structures at risk (trachea, recurrent laryngeal nerves, thoracic duct, sympathetic trunk). While ventral dissection involved detachment of the esophagus from the tracheal cartilage and membranous part, the dorsal dissection plane comprised the prevertebral compartment harboring the thoracic duct and right intercosto-bronchial artery. On the left side, the esophagus was attached to the aortic arch by the aorto-esophageal ligament; on the right side, the esophagus was bordered by the azygos vein, right vagus nerve, and cardiac nerves. The stepwise, illustrated topographic anatomy addressed specific surgical demands and perspectives related to the left cervical approach and dissection of the esophagus, providing an anatomical basis to facilitate and safely implement the RACE procedure., (© 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.)

Although neoadjuvant chemoradiotherapy (nCRT) is frequently used in esophageal cancer patients undergoing treatment with curative intent, it can negatively impact patients' physical fitness. A decline in physical fitness during chemoradiotherapy may be an indication of vulnerability. The aim of this study was to evaluate whether changes in physical fitness, weight, and fat-free mass index (FFMI) during nCRT can predict the risk of postoperative pneumonia. A retrospective longitudinal observational cohort study was performed in patients who received curative treatment for esophageal cancer between September 2016 and September 2018 in a high-volume center for esophageal cancer surgery. Physical fitness (handgrip strength, leg extension strength, and exercise capacity), weight, and FFMI were measured before and after chemoradiotherapy. To be included in the data analyses, pre- and post-nCRT data had to be available of at least one of the outcome measures. Logistic regression analyses were performed to evaluate the predictive value of changes in physical fitness, weight, and FFMI during nCRT on postoperative pneumonia, as defined by the Uniform Pneumonia Scale. In total, 91 patients were included in the data analyses. Significant associations were found between the changes in handgrip strength (odds ratio [OR] 0.880, 95% confidence interval [CI]: 0.813-0.952) and exercise capacity (OR 0.939, 95%CI: 0.887-0.993) and the occurrence of postoperative pneumonia. All pneumonias occurred in patients with declines in handgrip strength and exercise capacity after nCRT. A decrease of handgrip strength and exercise capacity during nCRT predicts the risk of pneumonia after esophagectomy for cancer. Measuring physical fitness before and after chemoradiotherapy seems an adequate method to identify patients at risk of postoperative pneumonia., (© 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.)

Background: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology., Methods: The expert panel consisted of specialized esophageal surgeons from 8 European countries. During a two-round Delphi process, a detailed analysis and consensus on key steps of intrathoracic gastric tube reconstruction (IL esophagectomy) was performed., Results: Response rates in Delphi rounds 1 and 2 were 100% (22 of 22 experts) and 83.3% (20 of 24 experts), respectively. Three essential technical areas of intrathoracic gastric tube reconstruction were identified: first, vascularization of the gastric conduit, second, gastric mobilization, tube formation and pull-up, and third, anastomotic technique. In addition, 3 main techniques for minimally invasive intrathoracic anastomosis are currently practiced: (i) end-to-side circular stapled, (ii) end-to-side double stapling, and (iii) side-to-side linear stapled technique. The step-by-step procedural analysis unveiled common approaches but also different expert practice., Conclusion: This precise technical description may serve as a clinical guideline for intrathoracic reconstruction after esophagectomy. In addition, the results may aid to harmonize the technical evolution of this complex surgical procedure and thereby facilitate surgical training., (© 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.)

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.)

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being adopted as the preferred surgical treatment for esophageal cancer, as it is superior to open esophagectomy and a good alternative to conventional minimally invasive esophagectomy. This paper addresses the technical details of the thoracoscopic phase of RAMIE, including the operating room set-up, patient positioning, port placement, and surgical steps., (© 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.)

The circular mechanical and hand-sewn intrathoracic anastomosis are most often used in robot-assisted minimally invasive esophagectomy (RAMIE). The aim of this study was to describe the technical details of both techniques that were pioneered in two high volume centers for RAMIE. A prospectively maintained database was used to identify patients with esophageal cancer who underwent RAMIE with intrathoracic anastomosis. The primary outcome was anastomotic leakage, which was analyzed using a moving average curve. For the hand-sewn anastomosis, video recordings were reviewed to evaluate number of sutures and distances between the anastomosis and the longitudinal staple line or gastric conduit tip. Between 2016 and 2019, a total of 68 patients with a hand-sewn anastomosis and 60 patients with a circular-stapled anastomosis were included in the study. For the hand-sewn anastomosis, the moving average curve for anastomotic leakage (including grade 1-3) started at a rate of 40% (cases 1-10) and ended at 10% (cases 59-68). For the circular-stapled anastomosis, the moving average started at 10% (cases 1-10) and ended at 20% (cases 51-60). This study showed the technical details and refinements that were applied in developing two different anastomotic techniques for RAMIE. Results markedly improved during the period of development with specific changes in technique for the hand-sewn anastomosis. The circular-stapled anastomosis showed a more stable rate of performance., (© 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.)

Pulmonary complications, and especially pneumonia, remain one of the most common complications after esophagectomy for esophageal cancer. These complications are reduced by minimally invasive techniques or by avoiding thoracic access through a transhiatal approach. However, a transhiatal approach does not allow for a full mediastinal lymphadenectomy. A transcervical mediastinal esophagectomy avoids thoracic access, which may contribute to a decrease in pulmonary complications after esophagectomy. In addition, this technique allows for a full mediastinal lymphadenectomy. A number of pioneering studies have been published on this topic. Here, the initial experience is presented as well as a review of the current literature concerning transcervical esophagectomy, with a focus on the robot-assisted cervical esophagectomy procedure., (© 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.)

The full robotic-assisted minimally invasive esophagectomy (RAMIE) is an upcoming approach in the treatment of esophageal and junctional cancer. Potential benefits are seen in angulated precise maneuvers in the abdominal part as well as in the thoracic part, but due to the novelty of this approach the optimal setting of the trocars, the instruments and the operating setting is still under debate. Hereafter, we present a technical description of the 'Mainz technique' of the abdominal part of RAMIE carried out as Ivor Lewis procedure. Postoperative complication rate and duration of the abdominal part of 100 consecutive patients from University Medical Center in Mainz are illustrated. In addition, the abdominal phase of the full RAMIE is discussed in general., (© 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.)

Initial results of the ROBOT, which randomized between robot-assisted minimally invasive esophagectomy (RAMIE) and open transthoracic esophagectomy (OTE), showed significantly better short-term postoperative outcomes in favor of RAMIE. However, it is not yet clarified if RAMIE is equivalent to OTE regarding long-term outcomes. The aim of this study was to report the long-term oncological results of the ROBOT trial in terms of survival and disease-free survival. This study is a follow-up study of the ROBOT trial, which was a randomized controlled trial comparing RAMIE to OTE in 112 patients with intrathoracic esophageal cancer. Both the trial protocol and short-term results were previously published. The primary outcome of the current study was 5-year overall survival. Secondary outcomes were disease-free survival and recurrence patterns. Analysis was by intention to treat. During the recruitment period, 109 patients were included in the survival analysis (RAMIE n = 54, OTE n = 55). Majority of patients had clinical stage III or IV (RAMIE 63%, OTE 55%) and received neoadjuvant chemoradiotherapy (80%). Median follow-up was 60 months (range 31-60). The combined 5-year overall survival rates for RAMIE and OTE were 41% (95% CI 27-55) and 40% (95% CI 26-53), respectively (log rank test P = 0.827). The 5-year disease-free survival rate was 42% (95% CI 28-55) in the RAMIE group and 43% (95% CI 29-57) in the OTE group (log rank test P = 0.749). Out of 104 patients, 57 (55%) developed recurrent disease detected at a median of 10 months (range 0-56) after surgery. No statistically difference in recurrence rate nor recurrence pattern was observed between both groups. Overall survival and disease-free survival of RAMIE are comparable to OTE. These results continue to support the use of robotic surgery for esophageal cancer., (© 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.)

The role of bedside assistants in robot-assisted minimally invasive esophagectomy is important. It includes knowledge of the procedure, knowledge of the da Vinci Surgical System, skills in laparoscopy, and good communicative skills. An experienced bedside assistant will likely improve efficiency and safety of robot-assisted minimally invasive esophagectomy., (© 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.)

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being applied as treatment for esophageal cancer. In this study, the results of 50 RAMIE procedures were compared with 50 conventional minimally invasive esophagectomy (MIE) operations, which had been the standard treatment for esophageal cancer prior to the robotic era. Between April 2016 and March 2018, data of 100 consecutive patients with esophageal carcinoma undergoing modified Ivor Lewis esophagectomy were prospectively collected. All operations were performed by the same surgeon using an identical intrathoracic anastomotic reconstruction technique with the same perioperative management and pain control regimen. Intra-operative and postoperative complications were graded according to definitions stated by the Esophagectomy Complications Consensus Group. Data analysis was carried out with and without propensity score matching. Baseline characteristics did not show significant differences between the RAMIE and MIE group. Propensity score matching of the initial group of 100 patients resulted in two equal groups of 40 patients for each surgical approach. In the RAMIE group, the median total lymph node yield was 27 (range 13-84) compared to 23 in the MIE group (range 11-48), P = 0.053. Median intensive care unit (ICU) stay was 1 day (range 1-43) in the RAMIE group compared to 2 days (range 1-17) in the MIE group (P = 0.029). The incidence of postoperative complications was not significantly different between the two groups (P = 0.581). In this propensity-matched study comparing RAMIE to MIE, ICU stay was significantly shorter in the RAMIE group. There was a trend in improved lymphadenectomy in RAMIE., (© The Author(s) 2019. 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.)

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings., (© The Author(s) 2019. 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.)

The standard of care for gastroesophageal cancer patients with hepatic or pulmonary metastases is best supportive care or palliative chemotherapy. Occasionally, patients can be selected for curative treatment instead. This study aimed to evaluate patients who underwent a resection of hepatic or pulmonary metastasis with curative intent. The Dutch national registry for histo- and cytopathology was used to identify these patients. Data were retrieved from the individual patient files. Kaplan-Meier survival analysis was performed. Between 1991 and 2016, 32,057 patients received a gastrectomy or esophagectomy for gastroesophageal cancer in the Netherlands. Of these patients, 34 selected patients received a resection of hepatic metastasis (n = 19) or pulmonary metastasis (n = 15) in 21 different hospitals. Only 4 patients received neoadjuvant therapy before metastasectomy. The majority of patients had solitary, metachronous metastases. After metastasectomy, grade 3 (Clavien-Dindo) complications occurred in 7 patients and mortality in 1 patient. After resection of hepatic metastases, the median potential follow-up time was 54 months. Median overall survival (OS) was 28 months and the 1-, 3-, and 5- year OS was 84%, 41%, and 31%, respectively. After pulmonary metastases resection, the median potential follow-up time was 80 months. The median OS was not reached and the 1-, 3-, and 5- year OS was 67%, 53%, and 53%, respectively. In selected patients with gastroesophageal cancer with hepatic or pulmonary metastases, metastasectomy was performed with limited morbidity and mortality and offered a 5-year OS of 31-53%. Further prospective studies are required., (© The Author(s) 2019. 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.)

Adequate postoperative pain management is essential to facilitate uneventful recovery after esophagectomy. Although epidural analgesia is the gold standard, it is not satisfactory in all patients. The aim of this study is to describe the efficacy and complication profile of epidural analgesia after minimally invasive esophagectomy (MIE). A total of 108 patients who underwent a robot-assisted (McKeown) MIE for esophageal cancer were included from a single center prospective database (2012-2015). The number of patients that could receive epidural analgesia, the sensory block range per day, the number of epidural top-ups, the need for escape pain mediation (i.e. intravenous opioids), the highest pain score per day (numeric rating scale: 0-10), and epidural-related complications were assessed until postoperative day (POD) 4. Epidural catheter placement was achieved in 101 patients (94%). A complete sensory block was found in 49% (POD1), 42% (POD 2), 20% (POD3), and 30% (POD4) of patients. An epidural top-up was performed in 26 patients (24%), which was successful in 22 patients. Escape pain medication in the form of intravenous opioids was given at least once in 49 out of 108 patients (45%) on POD 1, 2, 3, or 4. Overall median highest pain scores on the corresponding days were 2.0 (range: 0-10), 3.5 (range: 0-9), 3.0 (range: 0-8), and 4.0 (range: 0-9). Epidural related complications occurred in 20 patients (19%) and included catheter problems (n = 11), hypotension (n = 6), bradypnea (n = 2), and reversible tingling in the legs (n = 1). In conclusion, in this study epidural analgesia was insufficient and escape pain medication was necessary in nearly half of patients undergoing MIE., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

A reduced forced expiratory volume in one second (FEV1) is a well-recognized risk factor for complications after esophagectomy. Lung diffusing capacity for carbon monoxide (DLCO) is not routinely integrated in the risk assessment of esophagectomy. The aim of this study is to evaluate the association of preoperative pulmonary function tests with major postoperative complications after esophagectomy for cancer. In order to achieve this aim, 459 patients with newly diagnosed esophageal cancer who underwent elective transthoracic (n = 352) or transhiatal (n = 107) surgical resection of the esophagus with cervical anastomosis between 2003 and 2015 were analyzed. Multivariable logistic regression analysis was performed to assess the association of preoperative pulmonary function tests (expressed as % of predicted) with major complications after esophagectomy, adjusted for previously identified predictors. Major complications were defined as Clavien-Dindo grade IIIb or higher. Of the 459 included patients, 114 (24.8%) developed major complications. In univariable analysis FEV1, forced vital capacity (FVC), vital capacity (VC), and DLCO were associated with major complications. After adjusting each pulmonary function test for age, American Society of Anesthesiologists (ASA) score, cardiac comorbidity, diabetes mellitus, peripheral vascular disease, and surgical approach, FVC (OR: 1.24 per 10% decrease; 95% CI: 1.06-1.45; P = 0.004), VC (OR: 1.19 per 10% decrease; 95% CI: 1.02-1.39; P = 0.025) and DLCO (OR: 1.16 per 10% decrease; 95%CI: 1.02-1.33; P = 0.025) remained predictive factors for major surgical complications. In multivariable analysis in which all pulmonary functions tests were combined, DLCO was the strongest predictor of major complications (OR: 1.14 per 10% increase; 95% CI: 1.01-1.30; P = 0.046). The ideal cut-off for DLCO% of predicted was determined at <84% (OR: 1.97; 95% CI: 1.28-3.03; P = 0.002). These data indicate that DLCO is an independent predictor of major complications after esophagectomy for cancer. This pulmonary function test deserves greater consideration in prediction research of major complications after esophagectomy., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.

Restaging after neoadjuvant therapy aims to reduce the number of patients undergoing esophagectomy in case of distant (interval) metastases. The aim of this study is to systematically review and meta-analyze the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and 18F-FDG PET/CT for the detection of distant interval metastases after neoadjuvant therapy in patients with esophageal cancer. PubMed/MEDLINE, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the detection of distant interval metastases with 18F-FDG PET(/CT) in patients with esophageal cancer who received neoadjuvant therapy and both baseline staging and restaging after neoadjuvant therapy with 18F-FDG PET(/CT) imaging. The primary outcome measure was the proportion of patients in whom distant interval metastases were detected by 18F-FDG PET(/CT) as confirmed by pathology or clinical follow-up (i.e. true positives). The secondary outcome measure was the proportion of patients in whom 18F-FDG PET(/CT) restaging was false positive for distant interval metastases (i.e. false positives). Risk of bias and applicability concerns were assessed using the QUADAS-2 tool. Random-effect models were used to estimate pooled outcomes and examine potential sources of heterogeneity. Fourteen studies were included comprising a total of 1,110 patients who received baseline staging with 18F-FDG PET(/CT) imaging of whom 1,001 (90%) underwent restaging with 18F-FDG PET(/CT) imaging. Studies were generally of moderate quality. The pooled proportion of patients in whom true distant interval metastases were detected by 18F-FDG PET(/CT) restaging was 8% (95% confidence interval [CI]: 5-13%). The pooled proportion of patients in whom false positive distant findings were detected by 18F-FDG PET(/CT) restaging was 5% (95% CI: 3-9%). In conclusion,18F-FDG PET(/CT) restaging after neoadjuvant therapy for esophageal cancer detects true distant interval metastases in 8% of patients. Therefore, 18F-FDG PET(/CT) restaging can considerably impact on treatment decision-making. However, false positive distant findings occur in 5% of patients at restaging with 18F-FDG PET(/CT), underlining the need for pathological confirmation of suspected lesions.

New-onset atrial fibrillation (AF) is frequently observed following esophagectomy and may predict other complications. The aim of the current study was to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy. Consecutive patients who underwent elective esophagectomy with curative intent for esophageal cancer between 2004 and 2016 in the University Medical Center Utrecht were included from a prospective database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. The association between new-onset AF and infectious complications was studied in univariable and multivariable logistic regression analyses. A total of 455 patients were included. In 93 (20.4%) patients new-onset AF was encountered after esophagectomy. There were no significant differences in patient and treatment-related characteristics between the patients with and without AF. In 9 (9.7%) patients, AF was the only adverse event following surgery. In multivariable analyses, AF was significantly associated with infectious complications in general (OR 3.00, 95% CI: 1.73-5.21). More specifically, AF was associated with pulmonary complications (OR 2.06, 95% CI: 1.29-3.30), pneumonia (OR 2.41, 95% CI: 1.48-3.91) and anastomotic leakage (OR 3.00, 95% CI: 1.80-4.99). In patients who underwent esophagectomy, new-onset AF was highly associated with infectious complications. AF may serve as an early clinical warning sign for anastomotic leakage. Therefore, further evaluation of patients who develop new-onset AF after esophagectomy is warranted.

Surgery is a central component of multimodality therapy for esophageal and gastroesophageal junction cancer. Pneumonia is a common sequela of esophagectomy, leading to an increase in intensive care unit stay, hospital stay, readmission rates, and postoperative mortality. Developing strategies to reduce pneumonia after esophagectomy is hampered by the absence of a standardized methodology for defining pneumonia. This study aims to validate the Uniform Pneumonia Score (UPS) in a high volume center in the USA. The UPS was developed to define pneumonia after esophagectomy for cancer and is based on the assessment of temperature (°C), leukocyte count (×109/L), and pulmonary radiography. The UPS has been validated utilizing a prospective, Institutional Review Board approved database of esophageal cancer patients treated in a high volume esophagectomy center in the USA between 2010 and 2015. One hundred ninety-three consecutive patients were included and 21 (10.9%) were treated for pneumonia. The UPS was able to predict treatment for suspected pneumonia with a good sensitivity (85.7%, confidence interval (CI): 63.7%-96.7%), specificity (97.1%, CI: 93.4%-99.1%), positive predictive value (78.3%, CI: 59.9%-89.7%), and negative predictive value (98.2%, CI: 95.1%-99.4%). The diagnostic accuracy was 95.9%, CI: 92.0%-98.2%. The UPS demonstrated to be a reliable scoring system to define pneumonia after esophagectomy for cancer. Global application of this model will standardize the definition of pneumonia after esophagectomy. This will improve outcome reporting and comparisons of complications between individual institutions, clinical trials, and national audits.

Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

A nil-by-mouth regime with enteral nutrition via an artificial route is frequently applied following esophagectomy. However, early initiation of oral feeding could potentially improve recovery and has shown to be beneficial in many types of abdominal surgery. Although short-term nutritional safety of oral intake after an esophagectomy has been documented, long-term effects of this feeding regimen are unknown. In this cohort study, data from patients undergoing minimal invasive Ivor-Lewis esophagectomy between 04-2012 and 09-2015 in three centers in Netherlands were collected. Patients in the oral feeding group were retrieved from a previous prospective study and compared with a cohort of patients with early enteral jejunostomy feeding but delayed oral intake. Body mass index (BMI) measurements, complications, and nutritional re-interventions (re- or start of artificial feeding, start of total parenteral nutrition) were gathered over the course of one year after surgery. One year after surgery the median BMI was 22.8 kg/m2 and weight loss was 7.0 kg (9.5%) in 114 patients. Patients in the early oral feeding group lost more weight during the first postoperative month (P = 0.004). However, in the months thereafter this difference was not observed anymore. In the early oral feeding group, 28 patients (56%) required a nutritional re-intervention, compared to 46 patients (72%) in the delayed oral feeding group (P = 0.078). During admission, more re-interventions were performed in the delayed oral feeding group (17 vs. 46 patients P < 0.001). Esophagectomy reduces BMI in the first year after surgery regardless of the feeding regimen. Direct start of oral intake following esophagectomy has no impact on early nutritional re-interventions and long-term weight loss., (© The Authors 2017. 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.)

Effective pain management after esophagectomy is essential for patient comfort, early recovery, low surgical morbidity, and short hospitalization. This systematic review and meta-analysis aims to determine the best pain management modality focusing on the balance between benefits and risks. Medline, Embase, and the Cochrane library were systematically searched to identify all studies investigating different pain management modalities after esophagectomy in relation to primary outcomes (postoperative pain scores at 24 and 48 hours, technical failure, and opioid consumption), and secondary outcomes (pulmonary complications, nausea and vomiting, hypotension, urinary retention, and length of hospital stay). Ten studies investigating systemic, epidural, intrathecal, intrapleural and paravertebral analgesia involving 891 patients following esophagectomy were included. No significant differences were found in postoperative pain scores between systemic and epidural analgesia at 24 (mean difference (MD) 0.89; 95% confidence interval (CI) -0.47-2.24) and 48 hours (MD 0.15; 95%CI -0.60-0.91), nor described for systemic and other regional analgesia. Also, no significant differences in pulmonary complication rates were identified between systemic and epidural analgesia (relative risk (RR) 1.69; 95%CI 0.86-3.29), or between systemic and paravertebral analgesia (RR 1.49; 95%CI 0.31-7.12). Technical failure ranged from 17% to 22% for epidural analgesia. Sample sizes were too small to draw inferences on opioid consumption, the risk of nausea and vomiting, hypotension, urinary retention, and length of hospital stay when comparing the different pain management modalities including systemic, epidural, intrathecal, intrapleural, and paravertebral analgesia. This systematic review and meta-analysis shows no differences in postoperative pain scores or pulmonary complications after esophagectomy between systemic and epidural analgesia, and between systemic and paravertebral analgesia. Further randomized controlled trails are warranted to determine the optimal pain management modality after esophagectomy., (© The Authors 2017. 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.)

Survival of patients with esophageal adenocarcinoma remains poor and individual differences in prognosis remain unexplained. This study investigated whether gene mutations can explain why patients with high-risk (pT3-4, pN+) esophageal adenocarcinoma survive past 5 years after esophagectomy. Six long-term survivors (LTS) (≥5 years survival without recurrence) and six short-term survivors (STS) (<2 years survival due to recurrence) who underwent resection without neoadjuvant therapy for high-risk esophageal adenocarcinoma were included. Targeted next-generation sequencing of 16 genes related to esophageal adenocarcinoma was performed. Mutations were compared between the LTS and STS and described in comparison with literature. A total of 48 mutations in 10 genes were identified. In the LTS, the median number of mutated genes per sample was 5 (range: 0-5) and the samples together harbored 22 mutations in 8 genes: APC (n = 1), CDH11 (n = 2), CDKN2A (n = 2), FAT4 (n = 5), KRAS (n = 1), PTPRD (n = 1), TLR4 (n = 8), and TP53 (n = 2). The median number of mutated genes per sample in the STS was 4 (range: 1-8) and in total 26 mutations were found in six genes: CDH11 (n = 5), FAT4 (n = 7), SMAD4 (n = 1), SMARCA4 (n = 1), TLR4 (n = 7), and TP53 (n = 5). CDH11, CDKN2A, FAT4, TLR4, and TP53 were mutated in at least 2 LTS or STS, exceeding mutation rates in literature. Mutations across the LTS and STS were found in 10 of the 16 genes. The results warrant future studies to investigate a larger range of genes in a larger sample size. This may result in a panel with prognostic genes, to predict individual prognosis and to select effective individualized therapy for patients with esophageal adenocarcinoma., (© The Authors 2017. 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.)

Morbidity and mortality after esophagectomy are often related to anastomotic leakage or pneumonia. This study aimed to assess the relationship of intraoperative and postoperative vital parameters with anastomotic leakage and pneumonia after esophagectomy. Consecutive patients who underwent transthoracic esophagectomy with cervical anastomosis for esophageal cancer from January 2012 to December 2013 were analyzed. Univariable and multivariable logistic regression analyses were used to determine potential associations of hemodynamic and respiratory parameters with anastomotic leakage or pneumonia. From a total of 82 included patients, 19 (23%) developed anastomotic leakage and 31 (38%) experienced pneumonia. The single independent factor associated with an increased risk of anastomotic leakage in multivariable analysis included a lower minimum intraoperative pH (OR 0.85, 95% CI 0.77-0.94). An increased risk of pneumonia was associated with a lower mean arterial pressure (MAP) in the first 12 hours after surgery (OR 0.93, 95% CI 0.86-0.99) and a higher maximum intraoperative pH (OR 1.14, 95% CI 1.02-1.27). Interestingly, no differences were noted for the MAP and inotrope requirement between patients with and without anastomotic leakage. A lower minimum intraoperative pH (below 7.25) is associated with an increased risk of anastomotic leakage after esophagectomy, whereas a lower postoperative average MAP (below 83 mmHg) and a higher intraoperative pH (above 7.34) increase the risk of postoperative pneumonia. These parameters indicate the importance of setting strict perioperative goals to be protected intensively., (© International Society for Diseases of the Esophagus 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to evaluate management strategies and related outcomes for cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer with gastric conduit reconstruction. Patients with esophageal cancer undergoing transthoracic esophagectomy with cervical anastomosis from October 2003 to December 2014 were identified from a prospectively acquired database. Management strategies and related outcomes among patients with anastomotic leakage confined to the neck were compared to patients with intrathoracic manifestation of anastomotic leakage. From a total of 286 patients, leakage of the cervical anastomosis occurred in 60 patients (21%) at a median time of 7 days after esophagectomy. Leakage was confined to the neck in 23 of 60 patients (38%), whereas 37 of 60 patients (62%) presented with intrathoracic spread. Leakages with intrathoracic manifestation were more frequently accompanied by a positive SIRS score compared to leakages confined to the neck (73% vs. 35%, respectively; P = 0.004). Drainage of the anastomotic leakage through the neck wound was effective in all of 23 patients (100%) with cervical manifestation. In patients with intrathoracic manifestation, mediastinal drainage through the neck was successful in 15 of 37 patients (41%), whereas 22 patients (59%) required an intervention through the thoracic cavity. Compared to patients with leakage confined to the neck, patients with intrathoracic manifestation showed prolonged intensive care unit (ICU) stay (median 6 vs. 2 days, respectively; P = 0.001), hospital stay (median 34 vs. 19 days, respectively; P < 0.001), and time to oral intake (32 vs. 23 days, respectively; P = 0.018). Intrathoracic manifestation of cervical anastomotic leakage occurs in more than half of patients with anastomotic leakage after transthoracic esophagectomy for cancer. A SIRS reaction should raise the suspicion of intrathoracic spread of leakage. Intrathoracic manifestation can be managed effectively by mediastinal drainage through the neck in 41% of patients, but a reintervention through the thoracic cavity is required in 59%. Intrathoracic manifestation of leakage results in prolonged ICU/hospital stay and delays time to oral intake compared with leakage confined to the neck., (© 2016 International Society for Diseases of the Esophagus.)

The aim of this study was to evaluate the worldwide trends in surgical techniques for esophageal cancer surgery by comparing it to our survey from 2007. In addition, new questions were added for gastroesophageal junction (GEJ) cancer. An international survey on surgery of esophageal and GEJ cancer was performed among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association. Also, surgeons from personal networks were contacted. The participants filled out a web based questionnaire about surgical strategies for esophageal and gastroesophageal cancer. The overall response rate was 478/1147 (42%). The respondents represented 49 different countries and 6 different continents. The annual cumulative number of esophageal and gastric resections per surgeon was low (≤11) in 11%, medium (11-21) in 17%, and high (≥21) in 72% of respondents. In a subgroup analysis of esophageal surgeons the number of high volume surgeons increased from 45 to 54% over the past 7 years. The preferred lymph node dissection was two-field in 86%. A gastric conduit was the preferred method of reconstruction in 95%. In 2014, the preferred approach to esophagectomy was minimally invasive transthoracic in 43%, compared with 14% in 2007. In minimally invasive transthoracic esophagectomy the cervical anastomosis was favored in 54% of respondents in 2014 compared with 87% in 2007. The preferred technique of construction of the cervical anastomosis was hand-sewn in 64% and stapled in 36%, whereas the thoracic anastomosis was stapled in 77% and hand-sewn in 23%. The preferred surgical approach for Siewert type 1 tumors (5-1 cm proximal of the GEJ) was esophagectomy in 93% of respondents, whereas 6% favored gastrectomy and 3% combined a distal esophagectomy with a proximal gastrectomy. For Siewert type 2 tumors (1-2 cm from the GEJ) an extended gastrectomy was favored by 66% of respondents, followed by esophagectomy in 27% and total gastrectomy in 7%. Siewert type 3 tumors (2-5 cm distal of the GEJ) were preferably treated with gastrectomy in 90% of respondents, esophagectomy in 6%, and extended gastrectomy in 4%. The preferred curative surgical treatment of esophageal cancer is minimally invasive transthoracic esophagectomy with a two-field lymph node dissection and gastric conduit reconstruction. A strong worldwide trend toward minimally invasive surgery is observed. The preferred surgical treatment of GEJ tumors is esophagectomy for Siewert type 1 tumors and gastrectomy for Siewert type 3 tumors. The majority of surgeons favor an extended gastrectomy for Siewert type 2 tumors., (© 2016 International Society for Diseases of the Esophagus.)

Minimally invasive techniques in transhiatal esophagectomy (THE) were introduced to reduce morbidity and enhance postoperative recovery. Aim of this study was to systematically review the current status and possible beneficial effects of the minimally invasive approach in THE. A systematic search was performed in PubMed, the Cochrane Library, and Embase to identify English articles published on laparoscopic THE. Comparative cohort studies were included for critical appraisal. Data describing perioperative and oncological outcomes were analyzed. A total of four comparative cohort studies that compared laparoscopic THE (n = 122) with open THE (n = 144) and four noncomparative cohort studies reporting on laparoscopic THE (n = 212) were included in this review. Median blood loss was significantly lower in the laparoscopic group in all studies (100-500 vs. 526-900 mL). Length of hospital stay was also significantly shorter for the laparoscopic approach in all studies (9-13 vs. 12-16 days). One study reported less major postoperative complications after laparoscopic THE (12 vs. 23%), in the other studies no differences were found. Also no differences were found with regard to operating time, postoperative morbidity, radicality, and lymph node retrieval. Based on these pioneer studies, laparoscopic THE was demonstrated to be safe and feasible with evidence of reduced blood loss and shorter hospital stays. However, level 1 evidence is lacking and further research is warranted to confirm these findings and also to evaluate long-term oncologic outcomes., (© 2016 International Society for Diseases of the Esophagus.)

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection., (© 2016 International Society for Diseases of the Esophagus.)

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection., (© 2016 International Society for Diseases of the Esophagus.)

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning., (© 2016 International Society for Diseases of the Esophagus.)

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer., (© 2015 International Society for Diseases of the Esophagus.)

Neoadjuvant chemotherapy may improve the outcome of esophageal cancer after esophagectomy, but is accompanied by considerable toxicity by collateral destruction of normal cells. Such side effects may be avoided by developing therapies that specifically target molecular characteristics of tumors. The aim of the present study was to determine the proportion of esophageal squamous cell carcinoma (ESCC) patients that could possibly benefit from (a combination of) currently available targeted therapies, by assessing the frequency of immunohistochemical expression of their target molecular markers in ESCC tissues. Sections from a validated tissue microarray comprising 108 ESCCs were immunohistochemically stained for Bcl-2, c-KIT, cyclo-oxygenase-2 (COX-2), cyclin D1, estrogen receptor (ER), epidermal growth factor receptor (EGFR), Her-2/neu, progesterone receptor (PR), and vascular endothelial growth factor (VEGF). VEGF, cyclin D1, EGFR, and COX-2 could be detected in 55, 42, 40, and 40%, respectively. Her-2/neu, Bcl-2, and c-KIT were detected in 12, 11, and 10% of the tumors, respectively. No nuclear expression of ER or PR was noticed. Concurrent expression of two markers was noticed in 28% of ESCCs, whereas 25% of ESCCs showed concurrent expression of three markers. The concurrent expression of two of the most frequently expressed markers (VEGF, cyclin D1, EGFR, and COX-2) ranged from 11 (COX-2 and EGFR) to 26% (cyclin D1 and VEGF). The expression of all of these four markers was seen in 5% of ESCCs. Promising targets for molecular therapy in ESCC appear to be COX-2, VEGF, EGFR, and cyclin D1, as they are frequently overexpressed. Phase II clinical studies on these molecular markers may therefore be warranted. The role for targeted therapy against ER, PR, Her-2/neu, c-KIT, or Bcl-2 in ESCC seems limited.

In patients with esophageal cancer, radical surgical resection of the esophagus and surrounding lymph nodes is the only curative treatment option. Nevertheless, no standard surgical procedure exists. The aims of the present study were to gain insight into the frequencies of the various surgical techniques in esophageal cancer surgery as applied by surgeons throughout the world and to identify intercontinental differences regarding surgical techniques. Surgeons with particular interest in esophageal surgery, including members of the International Society for Diseases of the Esophagus, the European Society of Esophagology Group d'Etude Européen des Maladies de l'Oesophage and the OESO, were invited to participate in an online questionnaire. Questions were asked regarding approach to esophagectomy, extent of lymphadenectomy (LND), type of reconstruction, and anastomotic techniques. Subanalyses were performed for the surgeons' case volume per year, years of experience in esophageal cancer surgery, and continent. Of 567 invited surgeons, 269 participated, resulting in an overall response rate of 47%. The responders currently performing esophagectomies (n= 250; 44%), represented 41 countries across the six continents. Fifty-two percent of responders favor open transthoracic esophagectomy (TTE) over transhiatal esophagectomy (THE) or minimally invasive esophagectomy (MIE). THE is preferred by 26%, whereas MIE is favored by 14%. Eight percent have no preference for one approach to esophagectomy over the other. The extent of LND is most frequently the 2-field, routinely performed by 73% of surgeons. The continuity of the digestive tract is most frequently restored with a gastric conduit (85%). In open TTE, the anastomosis is routinely created in the neck by 56% of responders and in the chest by 40%. Cervical anastomoses are routinely fashioned by means of a handsewn technique by 65% of responders, while 35% favor the stapled technique. The cervical incision is predominantly performed vertically on the left side of the neck (routinely by 66%). A horizontal neck incision is routinely carried out by 19% of responders and a vertical right-sided incision by 11%. Significant differences in surgical techniques could be detected between low- and high-volume surgeons, between surgeons with or=21 years of experience, and between surgeons from different continents. In conclusion, currently the most commonly applied surgical procedure is the open right-sided transthoracic approach with a two-field lymphadenectomy, using a gastric tube anastomosed at the left side of the neck by means of a handsewn, end-to-side technique. The results of this survey provide baseline data for future research and for the development of international guidelines.

The outcome of esophagectomy could be improved by optimal diagnostic strategies leading to adequate preoperative patient selection. Neoadjuvant therapy could improve outcome by increasing the number of radical resections and by controlling metastatic disease. The purposes of this study were to gain insight into the current worldwide practice of staging modalities and neoadjuvant therapy in esophageal cancer, and to detect intercontinental differences. Surgeons with particular interest in esophageal surgery, including members of the International Society for Diseases of the Esophagus, the European Society of Esophagology - Group d'Etude Européen des Maladies de l'Oesophage, and the OESO, were invited to participate in an online questionnaire. Questions were asked regarding staging modalities, neoadjuvant therapy, and response evaluation applied in esophageal cancer patients. Of 567 invited surgeons, 269 participated resulting in a response rate of 47%. The responders currently performing esophagectomies (n= 250; 44%) represented 41 countries across the six continents. Esophagogastroscopy with biopsy and computed tomography (CT) scanning were routinely performed by 98% of responders for diagnosing and staging esophageal cancer, while endoscopic ultrasound (EUS) and barium esophagography were routinely applied by 58% and 51%, respectively. Neoadjuvant therapy is routinely administered by 33% and occasionally by 63% of responders. Of the responders that administer identical neoadjuvant regimens to esophageal adenocarcinoma (AC) and squamous cell carcinoma, 54% favor chemoradiotherapy. For AC, chemotherapy is preferred by 31% of the responders that administer neoadjuvant therapy, whereas for squamous cell carcinoma, the majority of responders (38%) prefer chemoradiotherapy. Response to neoadjuvant therapy is predominantly assessed by CT scanning of the chest and abdomen (86%). Barium esophagography, EUS, and combined CT/PET scan are requested for response monitoring in equal frequency (25%). Substantial differences in applied staging modalities and neoadjuvant regimens were detected between surgeons from different continents. In conclusion, currently the most commonly applied diagnostic modalities for staging and restaging esophageal cancer are CT scanning of the chest and abdomen, gastroscopy, barium esophagography and EUS. Neoadjuvant therapy is routinely applied by one third of the responders. Intercontinental differences have been detected in the diagnostic modalities applied in esophageal cancer staging and in the administration of neoadjuvant therapy. The results of this survey provide baseline data for future research and for the development of international guidelines.

The standard surgical procedure for esophageal cancer is transthoracic esophagectomy with en bloc resection of the azygos vein, thoracic duct and mediastinal lymph nodes. To reduce morbidity of esophago-lymphadenectomy, minimally invasive techniques are increasingly being applied. In (robot-assisted) thoracoscopic esophagolymphadenectomy, the azygos vein is generally left in place, as the scopic ligation of the numerous intercostal veins is technically difficult and time-consuming. This could affect the extent of mediastinal lymph node dissection. Therefore, in this study, the effect of azygos vein preservation during thoracic esophagectomy on mediastinal lymph node harvesting was assessed. In 15 human cadavers, a right-sided thoracotomy was performed, followed by esophagectomy with mediastinal lymph node dissection after ligation of the azygos arch (representing the situation in robot-assisted thoracoscopic esophagolymphadenectomy). Subsequently, the remaining azygos vein with surrounding tissue was resected. The number of lymph nodes in both specimens was determined. A mean of 17.3 (95% Poisson CI 15.3-19.6) lymph nodes was dissected en bloc with the esophagus, and 0.67 (95% Poisson CI 0.32-1.23) around the separately resected azygos vein. The additional azygos vein resection did not add to the number of lymph nodes dissected in 60% (9/15) of cadavers. In conclusion, the extent of mediastinal lymph node dissection was not substantially affected by leaving the azygos vein in situ . Time-sparing azygos vein preservation in (robot-assisted) thoracoscopic esophagolymphadenectomy may therefore be considered justified.

This is the first report of a thoracoscopic esophagectomy for a giant leiomyoma of the upper esophagus aided by a robotic system. A 37-year-old man presented with progressive dysphagia and nocturnal aspiration. Endoscopic ultrasound and CT scan of the chest revealed an upper esophageal tumor of 9 x 4 cm arising from the muscularis mucosae. A fine needle aspiration showed clustering of mesenchymal cells, confirming the diagnosis of a stromal cell tumor. A mesenchymal malignancy was suspected because the tumor was located in the upper esophagus and was arising from the muscularis mucosae, both uncommon for a leiomyoma. Moreover, tumor size, an indicator of potential malignancy if >3 cm, was 9 cm. Therefore, an esophagectomy was performed thoracoscopically with the formation of a gastric conduit via laparotomy and a hand-sewn end-to-side cervical anastomosis. The thoracoscopic phase was performed with support of the da Vincitrade mark robotic system, which allowed for an excellent 3-dimensional view and a precise dissection of the esophagus along the vital mediastinal structures. The duration of the thoracoscopic part was 115 min and that of the total procedure was 270 min. Blood loss during the thoracoscopic phase was 50 mL; total blood loss was 200 mL. The patient was ventilated for 1 day; his total intensive care stay was 2 days. He left the hospital in good condition on the 11th postoperative day. Histopathological examination combined with immunohistochemistry revealed a leiomyoma of 9.0 x 5.0 x 2.5 cm. After 3 years of follow-up, the patient is in good health.