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Summary Colonic interposition is an alternative for gastric conduit reconstruction after esophagectomy. Anastomotic leakage (AL) occurs in 15–25% of patients and may be attributed to reduced blood supply after vascular ligation. Indocyanine green fluorescence angiography (ICG-FA) can visualize tissue perfusion. We aimed to give an overview of the first experiences of ICG-FA and AL rate in colonic interposition. This study included all consecutive patients who underwent a colonic interposition between January 2015 and December 2021 at a tertiary referral center. Surgery was performed for the following indications: inability to use the stomach because of previous surgery or extensive tumour involvement, cancer recurrence in the gastric conduit, or because of complications after initial esophagectomy. Since 2018 ICG-FA was performed before anastomotic reconstruction by administration of ICG injection (0.1 mg/kg/bolus), using the Spy-phi (Stryker, Kalamazoo, MI). Twenty-eight patients (9 female, mean age 62.8), underwent colonic interposition of whom 15 (54%) underwent ICG-FA-guided surgery. Within the ICG-FA group, three (20%) AL occurred, whereas in the non-ICG-FA group, three AL and one graft necrosis (31%) occurred (P=0.67). There was a change of management due to the FA assessment in three patients in the FA group (20%) which led to the choice of a different bowel segment for the anastomosis. Mean operative times in the ICG-FA and non-ICG-FA groups were 372±99 and 399±113 minutes, respectively (P=0.85). ICG-FA is a safe, easy and feasible technique to assess perfusion of colonic interpositions. ICG-FA is of added value leading to a change in management in a considerable percentage of patients. Its role in prevention of AL remains to be elucidated.

Summary Adrenal incidentalomas are regularly encountered during imaging for esophageal cancer patients, but their oncological significance remains unknown. This study aimed to describe the incidence and etiology of adrenal incidentalomas observed throughout the diagnostic workup. This retrospective cohort study included all esophageal cancer patients referred to or diagnosed in the Amsterdam UMC between January 2012 and December 2016. Radiology and multidisciplinary team meeting reports were reviewed for adrenal incidentalomas. In case of adrenal incidentaloma, the 18FDG-PET/CT was reassessed by a radiologist blinded for the original report. In case of a metachronous incidentaloma during follow-up, visibility on previous imaging was reassessed. Primary outcome was the incidence, etiology and oncological consequence of synchronous adrenal incidentalomas. This study included 1,164 esophageal cancer patients, with a median age of 66 years. Patients were predominantly male (76.1%) and the majority had an adenocarcinoma (69.0%). Adrenal incidentalomas were documented in 138 patients (11.9%) during the diagnostic workup. At primary esophageal cancer workup, 22 incidentalomas proved malignant. However, follow-up showed that four incidentalomas were inaccurately diagnosed as benign and three malignant incidentalomas were visible on staging imaging but initially missed. Stage migration occurred in 15 of 22 (68.2%), but this would have been higher if none were missed or inaccurately diagnosed. The oncological impact of adrenal incidentalomas in patients with esophageal cancer is significant as a considerable part of incidentalomas changed treatment intent from curative to palliative. As stage migration is likely, pathological examination of a synchronous adrenal incidentaloma should be weighted in mind.

Background Intraoperative perfusion assessment with indocyanine green fluorescence angiography (ICG-FA) may reduce postoperative anastomotic leakage rates after esophagectomy with gastric conduit reconstruction. This study evaluated quantitative parameters derived from fluorescence time curves to determine a threshold for adequate perfusion and predict postoperative anastomotic complications. Methods This prospective cohort study included consecutive patients who underwent FA-guided esophagectomy with gastric conduit reconstruction between August 2020 and February 2022. After intravenous bolus injection of 0.05-mg/kg ICG, fluorescence intensity was registered over time by PINPOINT camera (Stryker, USA). Fluorescent angiograms were quantitatively analyzed at a region of interest of 1 cm diameter at the anastomotic site on the conduit using tailor-made software. Extracted fluorescence parameters were both inflow (T0, Tmax, Fmax, slope, Time-to-peak) as outflow parameters (T90% and T80%). Anastomotic complications including anastomotic leakage (AL) and strictures were documented. Fluorescence parameters in patients with AL were compared to those without AL. Results One hundred and three patients (81 male, 65.7 ± 9.9 years) were included, the majority of whom (88%) underwent an Ivor Lewis procedure. AL occurred in 19% of patients (n = 20/103). Both time to peak as Tmax were significantly longer for the AL group in comparison to the non-AL group (39 s vs. 26 s, p = 0.04 and 65 vs. 51 s, p = 0.03, respectively). Slope was 1.0 (IQR 0.3–2.5) and 1.7 (IQR 1.0–3.0) for the AL and non-AL group (p = 0.11). Outflow was longer in the AL group, although not significantly, T90% 30 versus 15 s, respectively, p = 0.20). Univariate analysis indicated that Tmax might be predictive for AL, although not reaching significance (p = 0.10, area under the curve 0.71) and a cut-off value of 97 s was derived, with a specificity of 92%. Conclusion This study demonstrated quantitative parameters and identified a fluorescent threshold which could be used for intraoperative decision-making and to identify high-risk patients for anastomotic leakage during esophagectomy with gastric conduit reconstruction. A significant predictive value remains to be determined in future studies.

Summary A key component of the Enhanced Recovery After Surgery pathway for esophagectomy is early mobilization. Evidence on a specific protocol of early and structured mobilization is scarce, which explains variation in clinical practice. This study aims to describe and evaluate the early mobilization practice after esophagectomy for cancer in a tertiary referral center in the Netherlands. This retrospective cohort study included data from a prospectively maintained database of patients who underwent an esophagectomy between 1 January 2015 and 1 January 2020. Early mobilization entailed increase in activity with the first target of ambulating 100 meters. Primary outcomes were the number of postoperative days (PODs) until achieving this target and reasons for not achieving this target. Secondary outcomes were the relationship between preoperative factors (e.g. sex, BMI) and achieving the target on POD1, and the relationship between achieving the target on POD1 and postoperative outcomes (i.e. length of stay, readmissions). In total, 384 patients were included. The median POD of achieving the target was 2 (IQR 1–3), with 173 (45.1%) patients achieving this on POD1. Main reason for not achieving this target was due to hemodynamic instability (22.7%). Male sex was associated with achieving the target on POD1 (OR = 1.997, 95%CI 1.172–3.403, P = 0.011); achieving this target was not associated with postoperative outcomes. Ambulation up to 100 m on POD1 is achievable in patients after esophagectomy, with higher odds for men to achieve this target. ERAS pathways for post esophagectomy care are encouraged to incorporate 100 m ambulation on POD1 in their guideline as the first postoperative target.

Background Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. Methods This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. Results Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. Conclusion A long-term symptom burden is common after oesophageal cancer surgery.

Summary Background: Fluorescence angiography (FA) assesses anastomotic perfusion during esophagectomy with gastric conduit reconstruction, but its interpretation is subjective. This study evaluated time to fluorescent enhancement in the gastric conduit, with the aim to determine a threshold to predict postoperative anastomotic complications. Methods: In a prospective cohort study, all consecutive patients undergoing esophagectomy with gastric conduit reconstruction from July 2018 to October 2019 were included. FA was performed before anastomotic reconstruction following injection of indocyanine green (ICG). During FA, the following time points were recorded: ICG injection, first fluorescent enhancement in the lung, at the base of the gastric conduit, at the planned anastomotic site, and at ICG watershed or in the tip of the gastric conduit. Anastomotic complications including anastomotic leakage and clinically relevant strictures were documented. Results: Eighty-four patients were included, the majority (67 out of 84, 80%) of which underwent an Ivor Lewis procedure. After a median follow-up of 297 days, anastomotic leakage was observed in 12 out of 84 (14.3%) and anastomotic stricture in 12 out of 82 (14.6%). Time between ICG injection and enhancement in the tip was predictive for anastomotic leakage (P = 0.174, area under the curve = 0.731), and a cut-off value of 98 seconds was derived (specificity: 98%). All times to enhancement at the planned anastomotic site and ICG watershed were significantly predictive for the occurrence of a stricture, however area under the curves were Conclusions: The identified fluorescent threshold can be used for intraoperative decision making or to identify potentially high-risk patients for anastomotic leakage after esophagectomy with gastric conduit reconstruction.

Summary Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

Background Gastrectomy with lymph node dissection is the cornerstone of curative treatment of gastric cancer. Extent of lymphadenectomy may differ depending on T-stage, as the rate of lymph node metastases may differ. The objective of this systematic review is to investigate and compare the prevalence of nodal metastases in the individual lymph node stations between different T-stages. Methods Data reporting and structure of this systematic review follows the PRISMA checklist. The Medline and PubMed databases were systematically searched. The search included the following Mesh terms: "Stomach Neoplasms", "Lymphatic Metastasis" and "Lymph Node Excision". The primary outcome was the highest prevalence of nodal metastases per T-stage. Results The initial search resulted in 175 eligible articles. Five articles met the inclusion criteria and were accordingly analyzed. Concerning the lymph node stations 1 to 7, the lymph nodes along the lesser gastric curvature (station 3) show the highest metastases rate (T1: 5.5%, T2: 21.9%, T3: 41.9%, T4: 71.0%). Concerning the lymph node stations 8 to 20, the lymph nodes around the common hepatic artery (station 8) show the highest metastases rate (T1: 0.8%, T2: 7.9%, T3: 14.0%, T4: 28.2%). Conclusion An overall low prevalence of nodal metastases in the individual lymph node stations in early, T1 gastric carcinomas and an overall high prevalence in more advanced, T3 and T4 gastric carcinomas endorse a more tailored approach based on the different gastric T-stages. In addition, a less extensive lymphadenectomy seems justified in early T1 carcinoma. Synopsis This systematic review provides an overview of the prevalence of nodal metastases for the individual lymph node stations between different T-stages, showing an overall low prevalence in early, T1 gastric carcinomas and an overall high prevalence in the more advanced, T3 and T4 gastric carcinomas.

Lymph node status in patients with esophageal carcinoma is one of the most important prognostic parameters in esophageal carcinoma. The distribution pattern of lymph node metastases and the optimal extent of lymphadenectomy remains unclear. Therefore the extent of high mediastinal lymphadenectomy, including removal of the paratracheal lymph node stations, in esophageal surgery is a subject of debate. The aim of this study is to investigate the impact of paratracheal lymphadenectomy on survival. Methods For this nation-wide population-based cohort study, patients with an esophageal or gastro-esophageal junction carcinoma treated by elective transthoracic esophagectomy with two-field lymphadenectomy between 2011 and 2017 were included from the national Dutch Upper Gastro-intestinal Cancer Audit (DUCA) registry. Patients who died within 30 days after surgery or where lymphadenectomy data was missing were excluded from analyses. After propensity score matching patients with adenocarcinoma and squamous cell separately, overall survival was compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Subgroup analysis was performed in patients with cN0 disease. Results 3143 patients were included in the DUCA. A total of 512 patients with adenocarcinoma (n = 256 vs. n = 256) and 157 patients with squamous cell carcinoma (n = 62 vs. n = 62) were matched. For both patients with adenocarcinoma and squamous cell carcinoma a paratracheal lymphadenectomy was not significantly associated with longer overall survival (11 versus 10 months, p = 0.209 and 12 versus 11 months, p = 0.206, figure 1). In subgroup analysis, including patients with a squamous cell carcinoma and cN0 disease, paratracheal lymphadenectomy was associated with longer survival (13 versus 9 months, p = 0.011). This was not seen in patients with adenocarcinoma (11 versus 9 months p = 0.263). Conclusion In both patients with an esophageal adenocarcinoma as squamous cell carcinoma, the addition of paratracheal lymphadenectomy during transthoracic esophagectomy was not significantly associated with longer survival. However, a significantly longer survival was seen in cN0 patients who underwent an additional paratracheal lymphadenectomy, therefore routine removal of paratracheal lymph nodes might still be beneficial. Further studies are warranted with larger subgroups to investigate the impact of an additional (routine) paratracheal lymphadenectomy on survival.

Background Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. Methods Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. Results In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82–0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59–0.94), followed by fatigue, pain, insomnia and role functioning. Conclusion In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.

Background The impact of transthoracic (TTE) and transhiatal esophagectomy (THE) on long-term health-related quality of life (HR-QoL) in patients with distal esophageal or gastro-esophageal junction (GEJ) cancer has been studied with variable results. This study investigates long-term HR-QoL in patients having undergone TTE or THE. Methods Disease-free patients after TTE or THE for distal esophageal or GEJ cancer with a follow-up > 2 years were included. Patients who visited the outpatient clinic of a tertiary referral center between 2014 and 2018 were asked to complete EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. Uni- and multivariable linear regression analysis of HR-QoL was performed in all patients and in subgroups of minimally invasive esophagectomy and neoadjuvant therapy. Results A total of 132 patients after TTE and 56 after THE were included. When compared with the general population, all patients reported worse HR-QoL in ‘role functioning’ and ‘social functioning’ and in a range of disease- and/or treatment-specific symptoms. The only significant difference between TTE and THE was a better HR-QoL score for “hair loss” following TTE (ß = 29.4,95%CI = -49.108 – −9.671, p = 0.016). Subgroup analysis of minimally invasively operated patients showed better scores in “physical functioning” following TTE (ß = 13.8,95%CI = 2.755–24.933, p = 0.030). No significant differences in HR-QoL were found between TTE and THE after neoadjuvant therapy. Conclusion Long-term HR-QoL is largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ cancer. If there were differences between the surgical groups, they were in favor of TTE. These findings may aid in preoperative counseling of patients with esophageal or GEJ cancer.

Background The aim of this systematic review was to identify all methods to quantify intraoperative fluorescence angiography (FA) of the gastrointestinal anastomosis, and to find potential thresholds to predict patient outcomes, including anastomotic leakage and necrosis. Methods This systematic review adhered to the PRISMA guidelines. A PubMed and Embase literature search was performed. Articles were included when FA with indocyanine green was performed to assess gastrointestinal perfusion in human or animals, and the fluorescence signal was analysed using quantitative parameters. A parameter was defined as quantitative when a diagnostic numeral threshold for patient outcomes could potentially be produced. Results Some 1317 articles were identified, of which 23 were included. Fourteen studies were done in patients and nine in animals. Eight studies applied FA during upper and 15 during lower gastrointestinal surgery. The quantitative parameters were divided into four categories: time to fluorescence (20 studies); contrast‐to‐background ratio (3); pixel intensity (2); and numeric classification score (2). The first category was subdivided into manually assessed time (7 studies) and software‐derived fluorescence–time curves (13). Cut‐off values were derived for manually assessed time (speed in gastric conduit wall) and derivatives of the fluorescence–time curves (Fmax, T1/2, TR and slope) to predict patient outcomes. Conclusion Time to fluorescence seems the most promising category for quantitation of FA. Future research might focus on fluorescence–time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set‐up, calibration of fluorescence imaging systems, and validation of software programs is mandatory to allow future data comparison., The purpose of this systematic review was to provide an overview of all methods used to quantify fluorescence angiography of the gastrointestinal anastomosis, and to identify a threshold that could predict patient outcomes, including anastomotic leakage and necrosis. Four categories of quantitative parameter were identified: time to fluorescence; contrast‐to‐background ratio; pixel intensity; and numeric classification score. Cut‐off values were derived only for the first category; thus, time to fluorescence seems the most promising method for quantitation of fluorescence angiography.

Summary 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.

Background Esophagectomy has major effects on health-related quality of life (HR-QoL). Postoperative complications might contribute to a decreased HR-QOL. This population-based study aimed to investigate the difference in HR-QoL between patients with and without complications after esophagectomy for cancer. Methods A prospective comparative cohort study was performed with data from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients with esophageal and gastroesophageal junction (GEJ) cancer after esophagectomy in the period 2015–2018 were enrolled. The study investigated HR-QoL at baseline, then 3, 6, 9, 12, 18, and 24 months postoperatively, comparing patients with and without complications as well as with and without anastomotic leakage. Results The 486 enrolled patients comprised 270 patients with complications and 216 patients without complications. Significantly more patients with complications had comorbidities (69.6% vs 57.3%; p = 0.001). No significant difference in HR-QoL was found over time between the patients with and without complications. In both groups, a significant decline in short-term HR-QoL was found in various HR-QoL domains, which were restored to the baseline level during the 12-month follow-up period. No significant difference was found in HR-QoL between the patients with and without anastomotic leakage. The patients with grades 2 and 3 anastomotic leakage reported significantly more “choking when swallowing” at 6 months (ß = 14.5; 95% confidence interval [CI], − 24.833 to − 4.202; p = 0.049), 9 months (ß = 22.4, 95% CI, − 34.259 to − 10.591; p = 0.007), and 24 months (ß = 24.6; 95% CI, − 39.494 to − 9.727; p = 0.007) than the patients with grade 1 or no anastomotic leakage. Conclusion In general, postoperative complications were not associated with decreased short- or long-term HR-QoL for patients after esophagectomy for esophageal or GEJ cancer. The temporary decrease in HR-QoL likely is related to the nature of esophagectomy and reconstruction itself.

Summary The 11th edition of the “Japanese Classification of Esophageal Cancer” by the Japan Esophageal Society (JES) and the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) “Cancer Staging Manual” are two separate classification systems both widely used for the clinical and pathological staging of esophageal cancer. Furthermore, the lymph node stations from these classification systems are combined for research purposes in the multinational TIGER study, which investigates the distribution pattern of lymph node metastases. The existing classification systems greatly differ with regard to number, location and anatomical boundaries of locoregional lymph node stations. The differences in these classifications cause significant heterogeneity in studies on lymph node metastases in esophageal cancer. This makes data interpretation difficult and comparison of studies challenging. In this article, we propose a match for these two commonly used classification systems and additionally for the TIGER study classification, in order to be able to compare results of studies and exchange knowledge and to make steps towards one global uniform classification system for all patients with esophageal cancer.

Both a transthoracic (TTE) and a transhiatal (THE) esophagectomy may be possible in patients with a distal esophageal or gastroesophageal junction (GEJ) cancer. A number of studies report conflicting results in long-term health-related quality of life (HR-QoL) following these operations. This study investigates long-term HR-QoL in TTE and THE in a tertiary referral center. Methods Disease-free patients after a TTE or THE for distal esophageal or GEJ carcinoma with a follow-up >2 years were included. Patients who visited the outpatient clinic of a tertiary referral center in the Netherlands between 2014–2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. Outcome measures were all 31 HR-QoL domains. Results During the study period, 132 patients underwent a TTE and 56 a THE. A better HR-QoL score was found for “problems with hair loss” (mean score 85.0 vs 114.4, p = 0.016) following TTE. Patients after minimally invasive TTE had better scores in ´physical functioning´ compared to minimally invasive THE (mean score 103.2 vs 88.6, p = 0.020). Patients following neoadjuvant therapy and TTE reported better “social functioning” compared to patients after neoadjuvant therapy and THE (mean scores 76.1 vs 59.9, p = 0.040). Conclusion Long-term HR-QoL results are largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ carcinoma. Some domains in the whole cohort and in subgroups differed at the advantage of a TTE. These findings may aid in providing information to esophageal or GEJ cancer patients on what can be expected following treatment.

Both a total gastrectomy and an esophagectomy may be technically possible in a patient with a gastroesophageal (GEJ) carcinoma. The aim of this study was to investigate the morbidity, mortality, pathology results and long-term survival in patients following an esophagectomy or a total gastrectomy for GEJ cancer. Methods A retrospective comparative cohort study of prospectively collected data from the Dutch Upper-GI Cancer Audit combined with survival data of the medical insurance database of the Netherlands was performed. Patients with a GEJ carcinoma in whom a total gastrectomy or an esophagectomy was performed, between 2011–2016 were included. Primary outcome was 3-year overall survival. Postoperative morbidity, mortality, 3-year conditional survival, reinterventions, radicality of surgery, (y)pTNM stage and lymph node yield were secondary endpoints. Results A total of 999 patients were included: 918 underwent an esophagectomy and 81 underwent a gastrectomy. Postoperative morbidity (54.9% vs 49.4%, p = 0.336), mortality (30-day; 2.3% vs 3.7%, p = 0.436; 90-day: 1.9% vs 2.5%, p = 0.662) and 3-year conditional survival (38.3% vs 30.3%, p = 0.553) did not differ significantly between groups. A longer ICU-stay (median 2 [IQR1–4] vs 1 days [IQR0–2], p Conclusion Patients with GEJ tumors after an esophagectomy required longer ICU-stay and had comparable short-term morbidity and mortality when compared to a total gastrectomy. Long-term overall and conditional survival was not significantly different between groups. The two procedures are therefore largely comparable from an oncological viewpoint, and the choice for either procedure might also be based on other outcomes such as quality of life.

Despite the attempts to reduce postoperative complication incidence after esophageal cancer surgery, up to 60% of patients endure postoperative complications. These patients often have a reduced health related quality of life (HR-QoL) and it may also have a negative effect on long-term survival. The aim of this study is to investigate the difference in short- and long-term HR-QoL in patients with and without a complicated postoperative course. Methods A retrospective comparative cohort study was performed with data from the Dutch Cancer Registry (IKNL) and QoL questionnaires from POCOP, a longitudinal patient reported outcomes study. All patients with esophageal and gastroesophageal junction (GEJ) cancer after an esophagectomy with or without neoadjuvant chemo(radio) therapy in the period of 2015–2018 were included. Exclusion criteria were palliative surgery, patients with a recurrence, reconstruction with a colonic or jejunal interposition, no reconstruction and emergency surgery. HR-QoL was investigated at baseline and at 3, 6, 9, 12, 18 and 24 months postoperatively between patients with and without complications following an esophagectomy. Results A total of 486 patients were included: 270 with and 216 without postoperative complications. The majority of patients were male (79.8%) with a median age of 66 years (IQR 60–70.25). Significantly more patients had comorbidities in the group with postoperative complications (69.6% vs 57.3%, p = 0.001). A significant difference in HR-QoL over time was found between the two groups in “choked when swallowing” score (p = 0.028). Patients that endured postoperative complications reported more problems with choking when swallowing at 9 months follow-up (mean score 12.9 vs 8.4, p = 0.047). This difference was not clinically relevant with a mean score difference of 4.6 points. Conclusion Postoperative complications do not significantly influence the short- and long-term HR-QoL in patients following an esophagectomy. Only one HR-QoL domain showed difference over time, however, this was not clinically relevant.

Summary Anastomotic leakage is one of the most severe complications after esophagectomy and is associated with increased postoperative morbidity and mortality. Several projects ranging from small retrospective studies to large collaborations have aimed to identify potential pre- and perioperative risk factors and to improve the diagnostic processes and management. Despite the increase in available literature, many aspects of anastomotic leakage are still debated, without the existence of widely accepted guidelines. The purpose of this review is to provide a cutting edge overview of the recent literature regarding the definition and classification of anastomotic leakage, risk factors, novel diagnostic modalities, and emerging therapeutic options for treatment and prevention of anastomotic leakage following esophagectomy.

Summary Introduction Both cervical (McKeown) and intrathoracic (Ivor Lewis) anastomosis of transthoracic esophagectomy are surgical procedures that can be performed for distal esophageal or gastro-esophageal junction (GEJ) cancer. The purpose of this study was to investigate the long-term health-related quality of life (HR-QoL) after McKeown and Ivor Lewis esophagectomy in a tertiary referral center. Methods Disease-free patients >1 year following a McKeown or an Ivor Lewis esophagectomy with a two-field lymphadenectomy for a distal or GEJ carcinoma visiting the outpatient clinic between 2014 and 2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. HR-QoL was investigated in both groups. Results A total of 89 patients were included after McKeown and 115 after Ivor Lewis esophagectomy. Median follow-up was 2.4 years (IQR 1.7–3.6). Patients after McKeown esophagectomy reported more problems with ‘eating with others’ compared to patients after Ivor Lewis esophagectomy (mean scores: 49.9 vs. 38.8). This difference was both clinically relevant and significant after correction for multiple testing (β = 11.1, 95% CI 3.105–19.127, P = 0.042). Patients in both groups reported a poorer HR-QoL (≥10 points) than the general population with respect to nausea and vomiting, dyspnea, appetite loss, financial difficulties, problems with eating, reflux, eating with others, choked when swallowing, trouble with coughing, and weight loss. Conclusion Long-term HR-QoL of disease-free patients following a McKeown or Ivor Lewis esophagectomy for a distal or GEJ carcinoma is largely comparable. Irrespective of the surgical technique, patients’ HR-QoL following esophagectomy is compromised. When given the choice, patients should be informed that after a McKeown esophagectomy more problems while eating with others can occur.

Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.

Aim To assess conditional survival and design a nomogram predicting the conditional probability of survival for esophageal cancer patients after surgery. Background and methods Conditional survival accounts for the time already survived after surgery and may be informative in addition to conventional static survival estimates during follow-up. Consecutive patients with esophageal cancer who received neoadjuvant chemoradiation followed by an esophagectomy between January 2004 and 2019 in the Amsterdam UMC, The Netherlands were included. Conditional survival was defined as the probability of surviving “y” years after already surviving for “x” years. Cox proportional hazard models were used to evaluate predictors for overall survival. A nomogram was constructed to predict 5-year survival correcting for time already survived. Results 660 patients were included in this study. The median overall survival was 46.4 months (95%CI 39.1–53.8). The probability to achieve 5-year overall survival after resection increased from 46% directly after surgery to 55%, 67%, 79% and 88% per additional year survived. ypN-stage was the strongest predictor for overall survival (HR6.50, p Conclusion The proposed nomogram showed an accurate prediction of survival in patients after esophageal cancer surgery, taking the years already survived after surgery into account. This nomogram can be helpful in counselling patients in the follow-up after esophageal cancer surgery.

Aim In this study we correlated time to fluorescent enhancement as a quantitative value of intraoperative fluorescence angiography (IFA) to anastomotic leakage (AL) after esophagectomy with gastric conduit reconstruction. Background & Methods IFA seems a helpful technique to visualize anastomotic perfusion after esophagectomy. However, IFA is interpreted subjectively. To evaluate fluorescence objectively and find a threshold to predict AL, we evaluated time to fluorescence enhancement. All consecutive patients undergoing elective esophagectomy with gastric conduit reconstruction for a one-year period since the introduction of IFA in June 2018 were prospectively recorded. IFA was performed after injection of indocyanine green (ICG) before and/or after anastomotic reconstruction. During IFA, time to fluorescent enhancement was recorded (time points: ICG injection, enhancement in lung, base of gastric conduit, planned anastomotic site, tip of gastric conduit). The anastomotic site was changed according to subjective interpretation of IFA. AL was classified according to the ECCG classification. Results Sixty-five patients underwent esophagectomy with gastric conduit reconstruction for esophageal cancer. The anastomosis was either constructed in the cervical (13/65, 20%) or intrathoracic (52/65, 80%) region. The anastomotic site was adjusted due to IFA in 3/65 (4.6%) cases. AL occurred in 7/65 (10.8%) patients and in 1/3 (33.3%) after change of anastomotic site. Before anastomotic reconstruction, time between ICG injection and enhancement of the tip (injection-tip) and time between enhancement in the lung and base of the conduit (lung-conduit) were significantly correlated with AL (p=0.027 and p=0.042, respectively). ROC curve analysis revealed a cut-off value of 61 seconds for injection-tip with an area under the curve (AUC) of 0.91 and corresponding sensitivity 82.9% and specificity 100%. For lung-conduit a cut-off value of 11 seconds was found with an AUC of 0.71 and corresponding sensitivity 63% and specificity 83%. Conclusion In this study cut-off values for the time between injection-tip and lung-conduit were derived to predict AL after esophagectomy. Time to fluorescent enhancement is a quantitative fluorescent parameter, which is easy to implement, as no software is required. However, a larger cohort needs to be observed for potential significance of the difference between other time points and to confirm these thresholds.

Aim The aim of this study was to investigate the difference in long-term health-related quality of life in patients undergoing total gastrectomy versus Ivor Lewis esophagectomy in a tertiary referral center. Background & Methods Surgical treatment for gastroesophageal junction (GEJ) cancers is challenging. Both a total gastrectomy and an esophagectomy can be performed. Which of the two should be preferred is unknown given the scarce evidence regarding effects on surgical morbidity, pathology, long-term survival and health-related quality of life (HR-QoL). From 2014 to 2018, patients with a follow-up of > 1 year after either a total gastrectomy or an Ivor Lewis esophagectomy for GEJ or cardia carcinoma completed the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. Problems with eating, reflux and nausea and vomiting were chosen as the primary HR-QoL endpoints. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. Multivariable linear regression was applied taking confounders age, gender, ASA classification and neoadjuvant therapy into account. Results 30 patients after gastrectomy and 71 after Ivor Lewis esophagectomy with a mean age of 63 years were included. Median follow-up was two years (range 12-84 months). Patients after total gastrectomy reported significantly less choking when swallowing and coughing (β=-5.952, 95% CI -9.437 – -2.466; β=-13.084, 95% CI -18.525 – -7.643). Problems with eating, reflux and nausea and vomiting were not significantly different between the two groups. No significant difference was found in postoperative complications or Clavien-Dindo grade. Significantly more lymph nodes were resected in esophagectomy group (p=0.008). No difference in number of positive lymph nodes or R0 resection was found. Conclusion After a follow-up of > 1 year choking when swallowing and coughing were less common after total gastrectomy. No significant difference was found in problems with eating, reflux or nausea and vomiting nor in postoperative complications or radicality of surgery. Based on this study no general preference can be given to either of the procedures for GEJ cancer. Patients may be informed about the HR-QoL domains that are likely to be affected by the different surgical procedures, which in turn may support shared decision making when a choice between the two treatment options is possible.

Aim Long-term functional outcomes and the associations to health-related quality of life (HRQOL) after esophagectomy is largely unknown. LASER is a multi-center European study aimed to identify the most prevalent symptoms, and those with the greatest impact upon HRQOL among patients surviving more than one-year after esophagectomy for cancer, and to develop a clinically relevant symptom-based tool to measure HRQOL. Background & Methods Between 2010 and 2016, patients from 20 European Centers who underwent esophagectomy for esophageal cancer, and were disease-free at least one year postoperatively were invited to complete the LASER questionnaire, EORTC-QLQ30 and OG25. Specific symptom questionnaire items that were associated with a poor HRQOL as identified by EORTC-QLQC30 and OG25 were identified by multivariable linear and logistic regression analysis and combined to form a tool, which was tested using receiver operating characteristics curve analysis. Results A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had had symptoms associated with their esophagectomy and 52.4% of patients had sought medical treatment for their symptoms. Ongoing weight loss was reported by 10.4% of patients while 32.4% were struggling to maintain their body weight, and 18.8% of patients required supplemental oral nutrition. Only 13.8% of patients had returned to work with the same activities as before. Three LASER symptoms in multivariate analysis were correlated with poor HRQOL; pain on scars on chest (Odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81±0.02 and 0.82±0.09 respectively. Conclusions Two-thirds of patients experience symptoms related to their esophagectomy more than one year after surgery. The three key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased long-term term support.

Aim In this systematic review we aimed to identify all quantitative fluorescent parameters of intraoperative fluorescence angiography (IFA) during gastrointestinal surgery to pave way for a threshold that could predict anastomotic leakage (AL). Background &Methods In the last decade quantification of IFA using indocyanine green is attempted to objectively evaluate anastomotic perfusion during gastrointestinal surgery. In this systematic review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of PubMed and Embase was performed. Articles were included when IFA was performed to assess gastrointestinal perfusion in both animal and human and analysed the fluorescence signal using quantitative fluorescent parameters. A fluorescent parameter was defined as ‘quantitative’ when a diagnostic numeral threshold for AL could potentially be produced. Results Some 1317 articles were identified, of which 23 were included in this review. Eight applied IFA during upper and fifteen during lower gastrointestinal surgery. The quantitative fluorescent parameters were divided into four categories: (1) time to fluorescence (n=19), (2) contrast-to-background ratio (n=3), (3) pixel intensity (n=3), and (4) numeral classification score (n=2). The first category was subdivided into (a) time to fluorescent enhancement (n=7) and (b) fluorescent-time curves (n=12). Thirteen studies correlated the fluorescent parameters to the occurrence of AL. Cut-off values for AL were derived for time to fluorescent enhancement (speed in gastric conduit wall) and derivatives of the fluorescent-time curves (Fmax, T1/2, TR, and slope). Conclusion Of the four categories, time to fluorescent enhancement seems the most promising quantitative parameter for clinical usage, as development of a cut-off value is possible on a large scale in the near future and no software is required. Future research might want to focus on fluorescent-time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set-up, and calibration of the different fluorescent imaging systems and software programs is mandatory to allow future data aggregation.

Aim The aim of this study was to evaluate long-term HR-QoL in patients undergoing transhiatal versus transthoracic esophagectomy in a tertiary referral center. Background & Methods Treatment of esophageal cancers is challenging. Besides (neo)adjuvant chemo(radio)therapy different surgical approaches are possible such as transhiatal (THE) or transthoracic esophagectomy (TTE) with a cervical or intrathoracic anastomosis. Studies have been performed to establish evidence which is the preferred procedure in terms of postoperative morbidity, survival and short- and long-term health-related quality of life (HR-QoL). All patients after THE or TTE for distal esophageal or gastroesophageal junction carcinoma performed between 2003 and 2016 received EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. All questionnaires with a follow-up of more than two years after surgery were analysed. Three HR-QoL domains were chosen as primary endpoints: problems with eating, reflux and nausea and vomiting. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. The results were corrected for possible confounders such as age and gender. Results The questionnaire response rate was 47.6%, with 56 patients in the THE group and 134 in the TTE group. The mean age was 63.5 years and a median follow-up of 3.7 years (range 24-137 months) was reached. No significant difference was found in any of the HR-QoL domains or postoperative complications between the two groups. Significantly more lymph nodes were resected in the TTE group (p Conclusion After a long follow-up of more than two years no differences in HR-QoL or postoperative complications were found between patients with distal esophageal or gastroesophageal junction carcinoma undergoing THE or TTE esophagectomy. Based on this study we conclude that long-term quality of life should not influence the decision making for surgical approach between THE and TTE esophagectomy.

Aim The objectives of this study were to confirm the association of textbook outcome (TO) and overall long-term survival after esophagectomy for esophageal cancer, to investigate the relationship of TO and recurrence rates and to identify clinicopathological predictors for not achieving TO. Background & Methods Despite current improvements in the multimodal treatment of esophageal cancer, surgery remains the key component. Therefore, it is essential to optimize the surgical procedure and to pursue the highest surgical quality. TO is a composite measure of ten perioperative parameters reflecting the quality of surgical care concerning esophagectomy. All patients with esophageal cancer who underwent a transthoracic or transhiatal esophagectomy with curative intent in two tertiary referral centers in The Netherlands between 2007-2016 were included. Patients with a carcinoma in situ, patients undergoing salvage or emergency procedure and patients that applied for opt-out were excluded. Clinicopathological predictors for not achieving TO were identified using univariate and multivariate logistic regression. Survival was compared using Kaplan-Meier life-table estimates and cox regression. Results In total, 1057 patients were included. Over time, the percentage of patients who achieved TO increased from 28.9% in 2007 to 37.5% in 2016. BMI under 18.5, ASA score above one and age above 65 years were associated with a worse TO rate (OR 2.72 [1.02-7.24], ASA 2 OR 1.57 [1.13-2.17] and ASA 3+4 OR 2.33 [1.56-3.48], OR 1.387 [1.06-1.81], respectively), whereas neoadjuvant treatment predicted a better TO rate (OR 0.58 [0.41-0.81]). The median overall survival was 53 months (95% CI 42 – 63) for patients with TO and 35 months (95% CI 29 – 41) for patients without TO; resulting in an overall survival benefit of 18 months (HR 0.759, 95% CI 0.636 – 0.906, P = 0.002). The recurrence rates between TO and no-TO differed, but was not statistically significant (47.1% vs 42.8%, P = 0.177). Conclusion BMI less than 18.5, ASA-score higher than one and age older than 65 were characteristics associated with not achieving TO. Neoadjuvant therapy was associated with a better TO rate. Achieved TO resulted in a better overall five-year survival indicating the importance of pursuing TO.

Aim The aim this study was to investigate possible differences in outcomes between Ivor-Lewis (IL) versus McKeown esophagectomy (MK) in a population based cohort. Background It is unknown whether IL or MK should be preferred in patients with potentially curable locoregionally oesophageal or gastro-oesophageal junction (GEJ) cancer. Methods Oesophageal and GEJ cancer patients without distant metastases who underwent a transthoracic oesophagectomy between 2015 and 2017 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, and treatment outcomes were analysed and compared between IL and MK after propensity score matching (PSM). Patients were matched based on sex, age, tumour morphology and topography, comorbidities, neoadjuvant treatment, cT and cN stage, ASA-score and hospital volume. Postoperative complications and survival were compared between both groups using Chi-Square and multivariable Cox regression analyses. In the multivariable Cox regression analyses we corrected for infectious complications (wound complications and pneumonia) and anastomotic leakage to investigate its effect on survival. Results Off all 1764 included patients (1201 IL patients and 563 MK patients), 948 patients remained after matching. Significantly more lymph nodes were yielded after IL compared to MK (P=0.02). Surgical radicality did not differ between both groups (P=0.25). The complication rate was significantly lower in the IL group regarding anastomotic leakage (17% vs. 28%, P Conclusion Patients who underwent an IL have better outcomes in terms of anastomotic leakage and recurrent laryngeal nerve palsy rate and overall survival compared to MK. The difference in survival appears not to be related to the differences in infectious complications. Based on these results, IL appears to be the treatment of choice in patients in whom both oncological resections are appropriate.

Aim The current study aims to compare transthoracic and transhiatal esophagectomy in a propensity score matched nation-wide cohort study. Background & Methods Chemoradiotherapy followed by resection is the standard therapy for resectable esophageal carcinoma in the Netherlands. The optimal surgical approach remains a matter of debate. Data was acquired from the Dutch Upper-GI Cancer Audit. Patients who underwent esophagectomy with curative intent and gastric tube reconstruction for mid/distal esophageal or esophagogastric junction carcinoma from 2011-2016 were included. Patients with missing baseline data and patients undergoing emergency or hybrid surgery were excluded. Patients who underwent a transthoracic (TTE) or transhiatal (THE) esophagectomy were compared after propensity score matching. Results After propensity score matching, 1532 patients were included for analysis. The transthoracic approach yielded more lymph nodes (median 19 vs 14; p Conclusion TTE provided a more extensive lymph node dissection which resulted in a higher N-stage, at the cost of increased morbidity and short-term mortality. Although results in high-volume centers are often superior, these data reflect nationwide results. Future research should investigate if a more extensive lymph node dissection leads to an improved long-term survival.

Aim This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients undergoing esophagectomy for cancer. Background & Methods Although the addition of paratracheal lymphadenectomy to a standard two-field lymphadenectomy possibly may provide survival benefits for patients undergoing esophagectomy for esophageal cancer, the required dissection along the recurrent laryngeal nerves might be associated with increased morbidity. To investigate the impact of paratracheal lymphadenectomy on short-term oncological outcomes and postoperative complications, this nation-wide population-based cohort study included esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by elective transthoracic esophagectomy with at least subcarinal and para-esophageal lymphadenectomy from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, the lymph node yield and clinical outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Results Between 2011-2017, a total of 2128 patients were included. A total of 770 patients (n=385 vs. n=385) and 516 patients (n=258 vs. n=258) were matched for the Ivor Lewis and McKeown approaches, respectively. Paratracheal lymphadenectomy was associated with a higher total lymph node yield in both Ivor Lewis (23 vs. 19 nodes, P Conclusion In patients undergoing transthoracic esophagectomy for cancer, the addition of paratracheal lymphadenectomy results in a higher lymph node yield with comparable complication and mortality rates.

Aim The purpose of this study was to investigate the difference in long-term health-related quality of life (HR-QoL) between McKeown and Ivor Lewis esophagectomy in a tertiary referral center. Background & Methods The therapy of esophageal cancers consist of (neo)adjuvant chemo(radio)therapy and surgery. Often different surgical approaches are possible such as transthoracic esophagectomy with a cervical anastomosis (McKeown) or an intrathoracic anastomosis (Ivor Lewis). Evidence is scarce on whether either of these approaches is better in terms of survival, perioperative morbidity, pathology results and quality of life. Patients with mid-, distal esophageal, gastroesophageal (GEJ) or cardia carcinoma who have undergone a McKeown or an Ivor lewis esophagectomy in the period of 2003 – 2018 were included in this study. EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires were handed out during the outpatient clinic visits and a follow-up of at least one year was ensured. Problems with eating, reflux and nausea and vomiting were chosen as primary HR-QoL domain endpoints while the remaining HR-QoL domains, postoperative complications and pathology results were observed as secondary endpoints. Correction for confounders age and gender was performed. Results 147 patients were included in the McKeown group and 120 in the Ivor Lewis group. Mean age was 63.5 years and median follow-up was three years (range 12-137 months). No significant difference was found in problems with eating, reflux and nausea and vomiting. Significantly more problems with eating with others were found in McKeown group (β=10.435, 95% CI 4.474 – 16.395) and anastomotic leakage was significantly more common after McKeown esophagectomy (p=0.004). No significant difference was found in Clavien Dindo classification. During Ivor Lewis esophagectomy significantly more lymph nodes were resected (p Conclusion No major differences in long-term HR-QoL were found in patients with mid-, distal esophageal, GEJ or cardia carcinoma following McKeown or Ivor Lewis esophagectomy. Problems with eating with others and anastomotic leakages were more common after McKeown esophagectomy, however, Clavien Dindo classification and radicality of surgery were similar between the two groups. Results of this study could assist the patient during the decision-making process prior to the surgery.

Background Total minimally-invasive transthoracic esophagectomy (ttMIE) faces increasing application in surgical treatment of esophageal cancer. For esophago-gastric reconstruction, different anastomotic techniques are currently used, but their impact on postoperative anastomotic leakage and morbidity has not been investigated. The aim of this retrospective multicenter analysis was to describe anastomotic techniques used for ttMIE and to analyze the associated morbidity. Patients and Methods Patients were selected from a basic dataset, collected over 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 CD 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 (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 esophago-gastrostomies (11.8%) (P 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.

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 = 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 = 23 for lymph node yield. Benchmarks at 30 and 90 days were

Background & Aims Immune checkpoint inhibition may affect growth or progression of highly aggressive cancers, such as esophageal adenocarcinoma (EAC). We investigated the regulation of expression of major histocompatibility complex, class 1 (MHC-I) proteins (encoded by HLA-A, HLA-B, and HLA-C) and the immune response to EACs in patient samples. Methods We performed quantitative polymerase chain reaction array analyses of OE33 cells and OE19 cells, which express different levels of the ATP binding cassette subfamily B member 1 (TAP1) and TAP2, required for antigen presentation by MHC-I, to identify microRNAs (miRNAs) that regulate their expression. We performed luciferase assays to validate interactions between miRNAs and potential targets. We overexpressed candidate miRNAs in OE33, FLO-1, and OACP4 C cell lines and performed quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses to identify changes in messenger RNA (mRNA) and protein expression; we studied the effects of cytotoxic T cells. We performed miRNA in situ hybridization, RNA-sequencing, and immunohistochemical analyses of tumor tissues from 51 untreated patients with EAC in the Netherlands. Clinical and survival data were collected for patients, and EAC subtypes were determined. Results We found OE19 cells to have increased levels of 7 miRNAs. Of these, we found binding sites for miRNA 125a (MIR125a)-5p in the 3′ untranslated region of the TAP2 mRNA and binding sites for MIR148a-3p in 3′ untranslated regions of HLA-A, HLA-B, and HLA-C mRNAs. Overexpression of these miRNAs reduced expression of TAP2 in OE33, FLO-1, and OACP4 C cells, and reduced cell-surface levels of MHC-I. OE33 cells that expressed the viral peptide BZLF1 were killed by cytotoxic T cells, whereas OE33 that overexpressed MIR125a-5p or MIR 148a along with BZLF1 were not. In EAC and nontumor tissues, levels of MIR125a-5p correlated inversely with levels of TAP2 protein. High expression of TAP1 by EAC correlated with significantly shorter overall survival times of patients. EACs that expressed high levels of TAP1 and genes involved in antigen presentation also expressed high levels of genes that regulate the adaptive immune response, PD-L1, PD-L2, and IDO1; these EACs had a poor response to neoadjuvant chemoradiotherapy and associated with shorter overall survival times of patients. Conclusions In studies of EAC cell lines and tumor tissues, we found increased levels of MIR125a-5p and MIR148a-3p to reduce levels of TAP2 and MHC-I, required for antigen presentation. High expression of MHC-I molecules by EAC correlated with markers of an adaptive immune response and significantly shorter overall survival times of patients.