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Objective: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer.Summary of Background Data: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer.Methods: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods.Results: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% (P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P Conclusion: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Objective To identify risk factors for tumor positive resection margins after neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for esophageal cancer. Summary background data Esophagectomy after nCRT is associated with tumor positive resection margins in 4-9% of patients. This study evaluates potential risk factors for positive resection margins after nCRT followed by esophagectomy. Methods All patients who underwent an elective esophagectomy following nCRT in 2011-2017 in the Netherlands were included. A multivariable logistic regression was performed to assess the association between potential risk factors and tumor positive resection margins. Results In total, 3900 patients were included. Tumor positive resection margins were observed in 150 (4%) patients. Risk factors for tumor positive resection margins included tumor length (in centimeters, OR:1.1, 95% CI: 1.0-1.1), cT4-stage (OR:3.0, 95% CI: 1.2 - 6.7) and an Ivor Lewis esophagectomy (OR:1.6, 95% CI: 1.0 - 2.6). Predictors associated with a lower risk of tumor positive resection margins were; squamous cell carcinoma (OR:0.4, 95% CI: 0.2 - 0.7), distal tumors (OR:0.5, 95% CI: 0.3 - 1.0), minimally invasive surgery (OR:0.6, 95% CI: 0.4 - 0.9) and a hospital volume of >60 esophagectomies per year (OR:0.6, 95%CI: 0.4 - 1.0). Conclusions In this nationwide cohort study, tumor and surgical related factors (tumor length, histology, cT-stage, tumor location, surgical procedure, surgical approach, hospital volume) were identified as risk factors for tumor positive resection margins after nCRT for esophageal cancer. These results can be used to improve the radical resection rate by careful selection of patients and surgical approach and are a plea for centralization of esophageal cancer care.

Introduction: This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. Methods: Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. Results: A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1–4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8–7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50–0.87), trastuzumab (HR 0.41, 95% CI: 0.23–0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57–2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17–2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32–3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03–2.87, and HR 3.61, 95% CI: 2.55–5.10, respectively). Conclusion: In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years.

Introduction: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. Methods: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. Results: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans 6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. Conclusion: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.

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.

Surgical resection of the oesophagus and its surrounding lymph nodes in an en bloc manner remains the mainstay treatment in the curative management of oesophageal cancer, with or without neoadjuvant oncological treatment. Evidence in favour of the minimally invasive approach for oesophagectomy is increasing, including that for the use of robotic surgery. The past two decades have seen an increasing uptake in minimally invasive Ivor Lewis oesophagectomy (MIO)—laparoscopic mobilization of the stomach with abdominal lymph node dissection and formation of the gastric conduit, followed by the thoracoscopic resection of the oesophagus and its surrounding lymph nodes and formation of an intrathoracic anastomosis. Several multicentre randomized controlled trials and large-scale meta-analyses have shown a reduction in cardiopulmonary complications with equivalent long-term disease-free and overall survival when comparing MIO to open oesophagectomy. Robot-assisted minimally invasive oesophagectomy (RAMIO) is fast becoming a preferred approach to oesophagectomy. Its principles are similar to MIO, although the evidence available suggests that the increased dexterity, magnification, tremor reduction, and three-dimensional vision permitted by the robotic platform allows for greater lymph node yields and reduced cardiopulmonary complications. This chapter reviews the history and variety of operative approaches to the surgical resection of the oesophagus and the rationale for each approach. The steps involved and the current available evidence for both MIO and RAMIO are described.

Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery.Background: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission.Methods: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival.Results: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤ 65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6–4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4–23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65–0.84).Conclusions: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

BACKGROUND: Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD. METHODS: Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment. RESULTS: A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias. CONCLUSIONS: Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted. ispartof: Eur J Cancer vol:166 pages:254-269 ispartof: location:England status: published

Figure S3. FOXP3 evaluated on-treatment.

Purpose:The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.Patients and Methods:Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1,200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score–matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.Results:We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (n = 4), patient choice (n = 2), and death (n = 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders (P = 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.Conclusions:Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.See related commentary by Catenacci, p. 3269

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Purpose: In the era of DNA-guided personalized cancer treatment, it is essential to conduct predictive analysis on the tissue that matters. Here, we analyzed genetic differences between primary colorectal adenocarcinomas (CRC) and their respective hepatic metastasis.Experimental Design: The primary CRC and the subsequent hepatic metastasis of 21 patients with CRC were analyzed using targeted deep-sequencing of DNA isolated from formalin-fixed, paraffin-embedded archived material.Results: We have interrogated the genetic constitution of a designed “Cancer Mini-Genome” consisting of all exons of 1,264 genes associated with pathways relevant to cancer. In total, 6,696 known and 1,305 novel variations were identified in 1,174 and 667 genes, respectively, including 817 variants that potentially altered protein function. On average, 83 (SD = 69) potentially function-impairing variations were gained in the metastasis and 70 (SD = 48) variations were lost, showing that the primary tumor and hepatic metastasis are genetically significantly different. Besides novel and known variations in genes such as KRAS, BRAF, KDR, FLT1, PTEN, and PI3KCA, aberrations in the up/downstream genes of EGFR/PI3K/VEGF-pathways and other pathways (mTOR, TGFβ, etc.) were also detected, potentially influencing therapeutic responsiveness. Chemotherapy between removal of the primary tumor and the metastasis (N = 11) did not further increase the amount of genetic variation.Conclusion: Our study indicates that the genetic characteristics of the hepatic metastases are different from those of the primary CRC tumor. As a consequence, the choice of treatment in studies investigating targeted therapies should ideally be based on the genetic properties of the metastasis rather than on those of the primary tumor. Clin Cancer Res; 18(3); 688–99. ©2011 AACR.

Table S1. Combined positivity score (CPS) in responders and non-responders at baseline. Table S2. Immunohistochemistry markers evaluated at baseline and on-treatment.

Introduction: The balance between potential oncological merits and surgical risks is unclear for the additional step of performing paratracheal lymphadenectomy during esophagectomy for cancer. This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients who underwent this procedure in The Netherlands. Methods: Patients who underwent neoadjuvant chemoradiotherapy followed by transthoracic esophagectomy were included from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, lymph node yield and short-term outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Results: Between 2011-2017, 2128 patients were included. Some 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 lymph node yield in Ivor Lewis (23 vs. 19 nodes, P

Background The primary goal of this study was to determine overall survival (OS) in patients who underwent local treatment (metastasectomy or stereotactic body radiotherapy [SBRT]) or systemic therapy (chemotherapy or targeted therapy) for oligometastatic esophagogastric cancer. The secondary goal was to determine prognostic factors for OS. Methods Patients with synchronous or metachronous oligometastatic esophagogastric cancer who underwent local treatment or systemic therapy were included in this single-center, retrospective cohort study. Oligometastatic disease (OMD) included 1 organ or 1 extraregional lymph node station with ≤ 3 lesions. OS was determined after OMD detection. Treatment for OMD was categorized as (1) local treatment, (2) local plus systemic, (3) systemic therapy. The primary tumor was controlled after resection or definitive chemoradiotherapy. Results In total, 85 patients were included. Treatment for OMD was local treatment (58%), local plus systemic (14%), or systemic therapy (28%). The primary tumor was controlled in 68% of patients. Most patients were diagnosed with distal esophageal cancer (61%), with adenocarcinoma histology (76%), and presented with synchronous OMD (51%). OS after local treatment was 17 months (95% confidence interval [CI] 12–40), after local plus systemic therapy 35 months (95% CI 29–NA), and after systemic therapy 16 months (95% CI 11–NA). Better OS was independently associated with local plus systemic compared with local treatment (hazard ratio [HR] 2.11, 95% CI 1.05–5.07) or systemic therapy (HR 2.28, 95% CI 1.04–6.07). Conclusions Local plus systemic therapy for oligometastatic esophagogastric cancer was independently associated with improved OS and better OS compared with either systemic therapy or local treatment.

Objective The aim of this study is to identify preoperative patient-related prognostic factors for anastomotic leakage, mortality, and major complications in patients undergoing oncological esophagectomy. Background Esophagectomy is a high-risk procedure with an incidence of major complications around 25% and short-term mortality around 4%. Methods We systematically searched the Medline and Embase databases for studies investigating the associations between patient-related prognostic factors and anastomotic leakage, major postoperative complications (Clavien–Dindo ≥ IIIa), and/or 30-day/in-hospital mortality after esophagectomy for cancer. Results Thirty-nine eligible studies identifying 37 prognostic factors were included. Cardiac comorbidity was associated with anastomotic leakage, major complications, and mortality. Male sex and diabetes were prognostic factors for anastomotic leakage and major complications. Additionally, American Society of Anesthesiologists (ASA) score > III and renal disease were associated with anastomotic leakage and mortality. Pulmonary comorbidity, vascular comorbidity, hypertension, and adenocarcinoma tumor histology were identified as prognostic factors for anastomotic leakage. Age > 70 years, habitual alcohol usage, and body mass index (BMI) 18.5–25 kg/m2 were associated with increased risk for mortality. Conclusions Various patient-related prognostic factors are associated with anastomotic leakage, major postoperative complications, and postoperative mortality following oncological esophagectomy. This knowledge may define case-mix adjustment models used in benchmarking or auditing and may assist in selection of patients eligible for surgery or tailored perioperative care.

Background The thoracic lymphadenectomy during an esophagectomy for esophageal cancer includes resection of the thoracic duct (TD) compartment containing the thoracic duct lymph nodes (TDLN). However, the role of TD compartment resection is still a topic of debate since metastatic TDLNs have only been demonstrated in squamous cell carcinomas in Eastern esophageal cancer patients. Therefore, the aim of this study was to assess the presence and metastatic involvement of TDLNs in a Western population, in which adenocarcinoma is the predominant type of esophageal cancer. Methods From July 2017 to May 2020 all consecutive patients undergoing an open or robot-assisted transthoracic esophagectomy with concurrent lymphadenectomy and resection of the TD compartment in the University Medical Center Utrecht, The Netherlands and the Citta della Salute e della Scienza University Hospital in Turin, Italy were included. The TD compartment was resected en bloc and was separated in the operation room by the operating surgeon after which it was macro- and microscopically assessed for (metastatic) TDLNs by the pathologist. Results A total of 117 patients with an adenocarcinoma (73%) or squamous cell carcinoma (27%) of the esophagus were included. In 61 (52%) patients TDLNs were found, containing metastasis in 9 (15%) patients. No major complications related to TD compartment resection were observed. Conclusions This is the first study to demonstrate the presence of metastatic TDLNs in adenocarcinomas of the esophagus. This result provides a valid argument to routinely extend the thoracic lymphadenectomy with resection of the TD compartment during an esophagectomy for esophageal cancer.

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

Introduction: Failure to cure describes: (1) nonresectional (“open-close”) surgery, (2) non-radical surgery (R1-R2), and/or (3) postoperative mortality. This study aimed to investigate whether hospitals offering surgery to a large proportion of patients have higher failure-to-cure rates than hospitals operating fewer patients. Methods: From the Netherlands Cancer Registry, all cT1–cT4a/cTx-any cN–cM0 esophageal cancer patients diagnosed in 2015–2018 were included. For each center, the expected (E) proportion of patients undergoing surgery was established and divided by the observed (O) proportion. Hospitals were categorized into three groups: (1) hospitals treating relatively many patients with surgery, (2) average hospitals, and (3) hospitals treating relatively few patients with surgery. Multilevel multivariable regression investigated the association between these hospital groups and failure to cure. Results: Some 3,437 (53.2%) of 6,457 patients underwent surgery, ranging from 45 to 64% among 16 hospitals. The failure-to-cure rate was 15.0% (hospital variation [4.6–23.7%]). After categorizing, 1,003 patients underwent surgery in hospitals with low surgery rates (O/E ratio 1.01/corrected percentage >54%). Failure-to-cure rates were 16.8%, 12.2%, and 14.0%, respectively. This was nonsignificant in multilevel analyses (aOR: 0.63, 95% CI: 0.38–1.05; aOR: 0.76, 95% CI: 0.46–1.24). Discussion/Conclusion: Failure-to-cure rates were similar in hospitals with a high surgery rate and hospitals with a low rate. Increasing the proportion of patients undergoing a resection may offer more patients, a chance for cure.

Summary 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.

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.

Background: Multidisciplinary team meetings (MDTM) and especially MDTMs in which expert centres are involved (expert MDTMs) are a key element in adequate cancer care. However, variation among hospitals in the proportion of patients presented during an expert MDTM has been described. This study aims to investigate national practice variation in the proportion of patients with oesophageal or gastric cancer being discussed during an expert MDTM. Methods: Patients diagnosed with oesophageal or gastric cancer in 2018–2019 were selected from the Netherlands Cancer Registry (n = 6,921). Multilevel logistic regression analyses were used to analyse the association between patient, and tumour characteristics, and the probability to be discussed in an expert MDTM. Variation was analysed according to the hospital and region of diagnosis for: all patients, patients with a potentially curable (cT1-4A cTX, any cN, cM0) or incurable tumour stage (cT4b and/or cM1). Results: In total, 79% of patients were discussed during an expert MDTM, of whom 84% (n = 3,424) and 71% (n = 2,018) with potentially curable, or incurable oesophageal or gastric cancer, respectively. The proportion of patients discussed during an expert MDTM ranged from 54% to 98%, and 17% to 100% between hospitals for potentially curable and incurable patients, respectively (all p < 0.0001). Adjusted analyses showed significant hospital (all p < 0.0001), but no regional variation regarding the patients discussed during an expert MDTM. Conclusion: For patients with oesophageal or gastric cancer the probability of being discussed during an expert MDTM varies considerably according to the hospital of diagnosis.

Gastric cancer; Metastasectomy; Oligometastasis Cáncer gástrico; Metastasectomía; Oligometástasis Càncer gàstric; Metastasectomia; Oligometàstasi Background Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. Methods In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). Conclusion The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

Summary 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.

Purpose Participation in a post-treatment exercise program improves cardiorespiratory fitness and aspects of quality of life for esophageal cancer survivors. For optimal effects, high adherence to the exercise intervention is important. We assessed which facilitators and barriers to exercise adherence are perceived by esophageal cancer survivors, who participate in a post-treatment exercise program. Methods The current qualitative study was performed within the randomized controlled PERFECT trial, in which we investigated effects of a 12-week supervised exercise program with moderate-to-high intensity and daily physical activity advice. Semi-structured interviews were conducted with patients randomized to the exercise group. A thematic content approach was used to derive perceived facilitators and barriers. Results Thematic saturation was reached after inclusion of sixteen patients. Median session attendance was 97.9% (IQR 91.7–100%), and relative dose intensity (compliance) to all exercises was ≥90.0%. Adherence to the activity advice was 50.0% (16.7–60.4%). Facilitators and barriers were captured in seven themes. The most important facilitators were patients’ own intention to engage in exercise and supervision by a physiotherapist. Barriers were mainly experienced in completion of the activity advice, and included logistic factors and physical complaints. Conclusions Esophageal cancer survivors are well capable to attend a moderate-to-high intensity post-treatment exercise program, and to fulfill the exercises according to protocol. This is facilitated by patients’ own intention to engage in exercise and supervision of the physiotherapist, and only minimally affected by barriers as logistic factors and physical complaints. Implications for cancer survivors When implementing postoperative exercise programs in clinical care, it can be useful to be aware of perceived facilitators and barriers of cancer survivors in order to achieve optimal exercise adherence and maximize beneficial exercise effects. Trial registration Dutch Trial Register NTR 5045

The purpose of this study was to investigate hospital variation in the placement, surgical techniques, and safety of feeding jejunostomies (FJ) during minimally invasive esophagectomy (MIE) in the Netherlands. This nationwide cohort study analyzed patients registered in the Dutch Upper Gastrointestinal Cancer Audit (DUCA) that underwent MIE for cancer. Hospital variation in FJ placement rates were investigated using case-mix corrected funnel plots. Short-term outcomes were compared between patients with and without FJ using multilevel multivariable logistic regression analysis. The incidence of FJ-related complications was described and compared between hospitals performing routine and non-routine placement (≥90%&ndash

OBJECTIVE: To evaluate changes in treatment and outcomes of esophagogastric cancer surgery after introduction of the DUCA. In addition, the presence of risk-averse behavior was assessed. SUMMARY OF BACKGROUND DATA: Clinical auditing is seen as an important quality improvement tool; however, its long-term efficacy remains largely unknown. In addition, critics claim that enhancements result from risk-averse behavior rather than positive effects of auditing. METHODS: DUCA data were used from registration start (1-1-2011) until 31-12-2018. Trends in patient, tumor, hospital and treatment characteristics were univariably assessed. Trends in short-term outcomes were investigated using multilevel multivariable logistic regression. Presence of risk aversion was described by the corrected proportion of patients undergoing surgery, using data from the Netherlands Cancer Registry. To evaluate the impact of centralization on time trends identified, the association between hospital volume and outcomes was investigated. RESULTS: This study included 6172 patients with esophageal and 3,690 with gastric cancer who underwent surgery. Pathological outcomes (lymph node yield, radicality) improved and futile surgery decreased over the years. In-hospital/30-day mortality decreased for esophagectomy (4.2% to 2.5%) and for gastrectomy (7.1% to 4.3%). Reinterventions, (minor) complications and readmissions increased. Risk aversion appeared absent. Between 2011-2018, annual median hospital volumes increased from 38 to 53 for esophagectomy and from 14 to 29 for gastrectomy. Higher hospital volumes were associated with several improved outcomes measures. CONCLUSIONS: During 8 years of auditing, outcomes improved, with no signs of risk-averse behavior. These improvements occurred in parallel with centralization. Feedback on postoperative complications remains the focus of the DUCA.

Purpose Emerging evidence suggests a detrimental prognostic association between radiation-induced lymphopenia (RIL) and pathologic response, progression-free survival, and overall survival (OS) in patients who undergo radiation therapy for cancer. The aim of this study was to systematically review and meta-analyze the prognostic impact of RIL on OS in patients with solid tumors. Methods and Materials PubMed/MEDLINE and Embase were systematically searched. The analysis included intervention and prognostic studies that reported on the prognostic relationship between RIL and survival in patients with solid tumors. An overall pooled adjusted hazard ratio (aHR) was calculated using a random-effects model. Subgroup analyses for different patient-, tumor-, treatment-, and study-related characteristics were performed using meta-regression. Results Pooling of 21 cohorts within 20 eligible studies demonstrated a statistically significant association between OS and grade ≥3 versus grade 0-2 RIL (n = 16; pooled aHR, 1.65; 95% confidence interval [CI], 1.43-1.90) and grade 4 RIL versus grade 0-3 (n = 5; aHR, 1.53; 95% CI, 1.24-1.90). Moderate heterogeneity among aHRs was observed, mostly attributable to overestimated aHRs in 7 studies likely subject to model-overfitting. Subgroup analysis showed significant prognostic impact of grade ≥3 RIL in 4 brain tumor (aHR, 1.63; 95% CI, 1.06-2.51), 4 lung cancer (aHR, 1.52; 95% CI, 1.01-2.29), and 3 pancreatic cancer (aHR, 1.92; 95% CI, 1.10-3.36) cohorts. Conclusions This meta-analysis demonstrates a significant detrimental prognostic association between grade ≥3 lymphopenia and OS in patients receiving radiation therapy for solid tumors. This finding appears consistent for tumors of the brain, thorax, and upper abdomen and provides an imperative to further elucidate the potential survival benefit of lymphopenia-mitigating strategies.

OBJECTIVES This study aimed to compare long-term survival following minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) for esophageal cancer using a nationwide propensity-score matched cohort. SUMMARY BACKGROUND DATA MIE provides lower postoperative morbidity and mortality, and similar short-term oncological quality compared to OE. METHODS Data was acquired from the Dutch Upper Gastrointestinal Cancer Audit. Patients undergoing minimally invasive or open, transthoracic or transhiatal esophagectomy for primary esophageal cancer between 2011-2015 were included. A propensity-score matching analysis for MIE versus OE was performed separately for transthoracic and transhiatal esophagectomies. RESULTS A total of 1036 transthoracic MIE and OE patients, and 582 transhiatal MIE and OE patients were matched. Long-term survival was comparable for MIE and OE for both transthoracic and transhiatal procedures (5-year overall survival: transthoracic MIE 49.2% vs. OE 51.1%, p 0.695; transhiatal MIE 48.4% vs. OE 50.7%, p 0.832). For both procedures, MIE yielded more lymph nodes (transthoracic median 21 vs. 18, p < 0.001; transhiatal 15 vs. 13, p 0.007). Post-operative morbidity was comparable after transthoracic MIE and OE (60.8% vs. 64.9%, p 0.177), with a reduced length of stay after transthoracic MIE (median 12 vs. 15 days, p < 0.001). After transhiatal MIE, more postoperative complications (64.9% vs. 56.4%, p 0.034) were observed, without subsequent difference in length of stay. CONCLUSION Long-term survival after minimally invasive esophagectomy was equivalent to open in both propensity-score matched cohorts of patients undergoing transthoracic or transhiatal esophageal resections. Transhiatal minimally invasive esophagectomy was accompanied with more post-operative morbidity. Both transthoracic and transhiatal minimally invasive esophagectomy resulted in a more extended lymphadenectomy.

OBJECTIVE: This international multicenter study by the Upper GI International Robotic Association aimed to gain insight in current techniques and outcomes of RAMIE worldwide.BACKGROUND: Current evidence for RAMIE originates from single-center studies, which may not be generalizable to the international multicenter experience.METHODS: Twenty centers from Europe, Asia, North-America, and South-America participated from 2016 to 2019. Main endpoints included the surgical techniques, clinical outcomes, and early oncological results of ramie.RESULTS: A total of 856 patients undergoing transthoracic RAMIE were included. Robotic surgery was applied for both the thoracic and abdominal phase (45%), only the thoracic phase (49%), or only the abdominal phase (6%). In most cases, the mediastinal lymphadenectomy included the low paraesophageal nodes (n=815, 95%), subcarinal nodes (n = 774, 90%), and paratracheal nodes (n = 537, 63%). When paratracheal lymphadenectomy was performed during an Ivor Lewis or a McKeown RAMIE procedure, recurrent laryngeal nerve injury occurred in 3% and 11% of patients, respectively. Circular stapled (52%), hand-sewn (30%), and linear stapled (18%) anastomotic techniques were used. In Ivor Lewis RAMIE, robot-assisted hand-sewing showed the highest anastomotic leakage rate (33%), while lower rates were observed with circular stapling (17%) and linear stapling (15%). In McKeown RAMIE, a hand-sewn anastomotic technique showed the highest leakage rate (27%), followed by linear stapling (18%) and circular stapling (6%).CONCLUSION: This study is the first to provide an overview of the current techniques and outcomes of transthoracic RAMIE worldwide. Although these results indicate high quality of the procedure, the optimal approach should be further defined.