Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction: A Multinational, High-volume Center Retrospective Cohort Analysis.

OBJECTIVE: A multi-national high-volume center study was undertaken to evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ). BACKGROUND: Optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. METHODS: Retrospective analysis of prospectively maintained databases from ten centers was performed. Between 01/2012-08/2023 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. Primary endpoint was overall survival (OS). RESULTS: In the cT2cNany cohort 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n=333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P<0.001) and had a higher ASA classification (P<0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P>0.4).Median OS was 51.0 months in the PS group (95% CI 31.6-70.4) versus 114.0 months (95% CI 53.9-174.1) in the NAT/S group (P=0.003) of cT2cNany patients. For cT2cN0 patients NAT/S was associated with longer OS (P=0.002) and disease-free survival (DFS) (P=0.001). After propensity score matching of cT2N0 patients, survival benefit for NAT/S remained (P=0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. CONCLUSIONS: Due to unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.

Radiomics in Oesogastric Cancer: Staging and Prediction of Preoperative Treatment Response: A Narrative Review and the Results of Personal Experience.

BACKGROUND: Oesophageal, gastroesophageal, and gastric malignancies are often diagnosed at locally advanced stage and multimodal therapy is recommended to increase the chances of survival. However, given the significant variation in treatment response, there is a clear imperative to refine patient stratification. The aim of this narrative review was to explore the existing evidence and the potential of radiomics to improve staging and prediction of treatment response of oesogastric cancers. METHODS: The references for this review article were identified via MEDLINE (PubMed) and Scopus searches with the terms "radiomics", "texture analysis", "oesophageal cancer", "gastroesophageal junction cancer", "oesophagogastric junction cancer", "gastric cancer", "stomach cancer", "staging", and "treatment response" until May 2024. RESULTS: Radiomics proved to be effective in improving disease staging and prediction of treatment response for both oesophageal and gastric cancer with all imaging modalities (TC, MRI, and 18F-FDG PET/CT). The literature data on the application of radiomics to gastroesophageal junction cancer are very scarce. Radiomics models perform better when integrating different imaging modalities compared to a single radiology method and when combining clinical to radiomics features compared to only a radiomics signature. CONCLUSIONS: Radiomics shows potential in noninvasive staging and predicting response to preoperative therapy among patients with locally advanced oesogastric cancer. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic features may even increase the effectiveness of these predictive and prognostic models.

Information Needs in Patients with Potentially Curable Gastroesophageal Cancer.

INTRODUCTION: Gastroesophageal cancer patients' information needs remain understudied, despite their complex treatment trajectories. METHODS: This study examined the (i) information needs of patients with or without postoperative complications, (ii) information needs of male and female patients, and (iii) the association between information needs and health-related quality of life (HR-QoL) following gastroesophageal cancer surgery. Patients completed the EORTC-QLQ-INFO25, QLQ-C30, and QLQ-OG25 questionnaires before and after curative surgery. Five information needs domains were investigated: information about the disease, about treatments, about medical tests, about things patients can do to help themselves, and overall helpfulness. Additionally, HR-QoL domains global health status, eating restrictions, and anxiety were explored. RESULTS: A total of 132 patients completed the questionnaires at baseline, 216 patients at 6-12 months, 184 patients at 18-24 months, and 163 patients at 3-5 years post-operation. There were no significant differences in information needs between patients with or without complications or between male and female patients. Patients with a higher global health status found the information more helpful at 6-12 months (p < 0.001), 18-24 months (p < 0.001), and 3-5 years (p < 0.001) postoperatively, as did patients who experienced more anxiety at 18-24 months (p = 0.009) and 3-5 years (p < 0.001). CONCLUSION: Gastroesophageal cancer patients, regardless of sex or postoperative complications, have consistent information needs, yet those with higher global health status and elevated anxiety levels find the information particularly helpful, emphasizing the importance of tailored communication strategies.

The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy: A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival. METHODS: This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. RESULTS: A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50 Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). CONCLUSIONS: MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Outcomes after gastrectomy according to the Gastrectomy Complications Consensus Group (GCCG) in the Dutch Upper GI Cancer Audit (DUCA).

BACKGROUND: In 2019, the Gastrectomy Complications Consensus Group (GCCG) published a standardized set of complications aiming toward uniform reporting of post-gastrectomy complications. This study aimed to report outcomes after gastrectomy in the Netherlands according to GCCG definitions and compare them to previously reported national results and the European database reported by the GCCG. METHODS: This nationwide, population-based cohort study included all patients undergoing gastrectomy for gastric cancer registered in the DUCA in 2020-2021. Postoperative morbidity and 30-day/in-hospital mortality were analyzed according to the GCCG definitions. For all patients, baseline characteristics and outcomes were compared with the GCCG cohort consisting of 27 European expert centers (GASTRODATA; 2017-2018). RESULTS: In 2020-2021, 782 patients underwent gastrectomy in the Netherlands. Variation was seen in baseline characteristics between the Dutch and the GCCG cohort (N = 1349), most notably in minimally invasive surgery (80.6% vs 19.6%, p < 0.001). In the Netherlands, 223 (28.5%) patients developed a total of 407 complications, the most frequent being non-surgical infections (28.5%) and anastomotic leakage (13.4%). The overall complication and 30-day mortality rates were similar between the Dutch and GCCG cohort (28.5% vs 29.8%, p = 0.563; 3.7% vs 3.6%, p = 0.953). Higher surgical and endoscopic/radiologic reintervention rates were observed in the Netherlands compared to the GCCG cohort (10.7% vs 7.8%, p = 0.025; 10.9% vs 2.9%, p < 0.001). CONCLUSION: Reporting outcomes according to the standardized GCCG definitions allows for international benchmarking. Postoperative outcomes were comparable between Dutch and GCCG cohorts, but both exceed the international benchmark for expert gastrectomy care, highlighting targets for national and international quality improvement.

Textbook Neoadjuvant Outcome-Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment.

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.

Nationwide Association of Surgical Performance of Minimally Invasive Esophagectomy With Patient Outcomes.

Importance: Suboptimal surgical performance is hypothesized to be associated with less favorable patient outcomes in minimally invasive esophagectomy (MIE). Establishing this association may lead to programs that promote better surgical performance of MIE and improve patient outcomes. Objective: To investigate associations between surgical performance and postoperative outcomes after MIE. Design, Setting, and Participants: In this nationwide cohort study of 15 Dutch hospitals that perform more than 20 MIEs per year, 7 masked expert MIE surgeons assessed surgical performance using videos and a previously developed and validated competency assessment tool (CAT). Each hospital submitted 2 representative videos of MIEs performed between November 4, 2021, and September 13, 2022. Patients registered in the Dutch Upper Gastrointestinal Cancer Audit between January 1, 2020, and December 31, 2021, were included to examine patient outcomes. Exposure: Hospitals were divided into quartiles based on their MIE-CAT performance score. Outcomes were compared between highest (top 25%) and lowest (bottom 25%) performing quartiles. Transthoracic MIE with gastric tube reconstruction. Main Outcome and Measure: The primary outcome was severe postoperative complications (Clavien-Dindo ≥3) within 30 days after surgery. Multilevel logistic regression, with clustering of patients within hospitals, was used to analyze associations between performance and outcomes. Results: In total, 30 videos and 970 patients (mean [SD] age, 66.6 [9.1] years; 719 men [74.1%]) were included. The mean (SD) MIE-CAT score was 113.6 (5.5) in the highest performance quartile vs 94.1 (5.9) in the lowest. Severe postoperative complications occurred in 18.7% (41 of 219) of patients in the highest performance quartile vs 39.2% (40 of 102) in the lowest (risk ratio [RR], 0.50; 95% CI, 0.24-0.99). The highest vs the lowest performance quartile showed lower rates of conversions (1.8% vs 8.9%; RR, 0.21; 95% CI, 0.21-0.21), intraoperative complications (2.7% vs 7.8%; RR, 0.21; 95% CI, 0.04-0.94), and overall postoperative complications (46.1% vs 65.7%; RR, 0.54; 95% CI, 0.24-0.96). The R0 resection rate (96.8% vs 94.2%; RR, 1.03; 95% CI, 0.97-1.05) and lymph node yield (mean [SD], 38.9 [14.7] vs 26.2 [9.0]; RR, 3.20; 95% CI, 0.27-3.21) increased with oncologic-specific performance (eg, hiatus dissection, lymph node dissection). In addition, a high anastomotic phase score was associated with a lower anastomotic leakage rate (4.6% vs 17.7%; RR, 0.14; 95% CI, 0.06-0.31). Conclusions and Relevance: These findings suggest that better surgical performance is associated with fewer perioperative complications for patients with esophageal cancer on a national level. If surgical performance of MIE can be improved with MIE-CAT implementation, substantially better patient outcomes may be achievable.

Recurrence and Survival After Minimally Invasive and Open Esophagectomy for Esophageal Cancer: A Post Hoc Analysis of the Ensure Study.

OBJECTIVE: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. BACKGROUND: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. METHODS: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS). RESULTS: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates ( P = 0.005) and nodal yield ( P < 0.001) were independently increased after TMIE, but not HMIE ( P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE. CONCLUSION: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer.

Western European Variation in the Organization of Esophageal Cancer Surgical Care.

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

Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

BACKGROUND: This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. METHODS: This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. RESULTS: Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). CONCLUSION: Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

History and evidence for state of the art of lymphadenectomy in esophageal cancer surgery.

The current curative multimodal treatment of advanced esophageal cancers consists of neoadjuvant or perioperative chemo(radio)therapy followed by a radical surgical resection of the primary tumor and a 2- or 3-field lymphadenectomy. One of the most important predictors of long-term survival of esophageal cancer patients is lymph node involvement. The distribution pattern of lymph node metastases in esophageal cancer is unpredictable and depends on the primary tumor location, histology, T-stage and application of neoadjuvant or perioperative treatment. The optimal extent of the lymphadenectomy remains controversial; there is no global consensus on this topic yet. Some surgeons advocate an aggressive and extended lymph node dissection to remove occult metastatic disease, to optimize oncological outcomes. Others promote a more restricted lymphadenectomy, since the benefit of an extended lymphadenectomy, especially after neoadjuvant chemoradiotherapy, has not been clearly demonstrated, and morbidity may be reduced. In this review, we describe the development of lymphadenectomy, followed by a summary of current evidence for lymphadenectomy in esophageal cancer treatment.

Evolution in Laparoscopic Gastrectomy From a Randomized Controlled Trial Through National Clinical Practice.

OBJECTIVE: To examine the influence of the LOGICA RCT (randomized controlled trial) upon the practice and outcomes of laparoscopic gastrectomy within the Netherlands. BACKGROUND: Following RCTs the dissemination of complex interventions has been poorly studied. The LOGICA RCT included 10 Dutch centers and compared laparoscopic to open gastrectomy. METHODS: Data were obtained from the Dutch Upper Gastrointestinal Cancer Audit (DUCA) on all gastrectomies performed in the Netherlands (2012-2021), and the LOGICA RCT from 2015 to 2018. Multilevel multivariable logistic regression analyses were performed to assess the effect of laparoscopic versus open gastrectomy upon clinical outcomes before, during, and after the LOGICA RCT. RESULTS: Two hundred eleven patients from the LOGICA RCT (105 open vs 106 laparoscopic) and 4131 patients from the DUCA data set (1884 open vs 2247 laparoscopic) were included. In 2012, laparoscopic gastrectomy was performed in 6% of patients, increasing to 82% in 2021. No significant effect of laparoscopic gastrectomy on postoperative clinical outcomes was observed within the LOGICA RCT. Nationally within DUCA, a shift toward a beneficial effect of laparoscopic gastrectomy upon complications was observed, reaching a significant reduction in overall [adjusted odds ratio (aOR):0.62; 95% CI: 0.46-0.82], severe (aOR: 0.64; 95% CI: 0.46-0.90) and cardiac complications (aOR: 0.51; 95% CI: 0.30-0.89) after the LOGICA trial. CONCLUSIONS: The wider benefits of the LOGICA trial included the safe dissemination of laparoscopic gastrectomy across the Netherlands. The robust surgical quality assurance program in the design of the LOGICA RCT was crucial to facilitate the national dissemination of the technique following the trial and reducing potential patient harm during surgeons learning curve.

A Video-Based Procedure-Specific Competency Assessment Tool for Minimally Invasive Esophagectomy.

Importance: Minimally invasive esophagectomy (MIE) is a complex procedure with substantial learning curves. In other complex minimally invasive procedures, suboptimal surgical performance has convincingly been associated with less favorable patient outcomes as assessed by peer review of the surgical procedure. Objective: To develop and validate a procedure-specific competency assessment tool (CAT) for MIE. Design, Setting, and Participants: In this international quality improvement study, a procedure-specific MIE-CAT was developed and validated. The MIE-CAT contains 8 procedural phases, and 4 quality components per phase are scored with a Likert scale ranging from 1 to 4. For evaluation of the MIE-CAT, intraoperative MIE videos performed by a single surgical team in the Esophageal Center East Netherlands were peer reviewed by 18 independent international MIE experts (with more than 120 MIEs performed). Each video was assessed by 2 or 3 blinded experts to evaluate feasibility, content validity, reliability, and construct validity. MIE-CAT version 2 was composed with refined content aimed at improving interrater reliability. A total of 32 full-length MIE videos from patients who underwent MIE between 2011 and 2020 were analyzed. Data were analyzed from January 2021 to January 2023. Exposure: Performance assessment of transthoracic MIE with an intrathoracic anastomosis. Main Outcomes and Measures: Feasibility, content validity, interrater and intrarater reliability, and construct validity, including correlations with both experience of the surgical team and clinical parameters, of the developed MIE-CAT. Results: Experts found the MIE-CAT easy to understand and easy to use to grade surgical performance. The MIE-CAT demonstrated good intrarater reliability (range of intraclass correlation coefficients [ICCs], 0.807 [95% CI, 0.656 to 0.892] for quality component score to 0.898 [95% CI, 0.846 to 0.932] for phase score). Interrater reliability was moderate (range of ICCs, 0.536 [95% CI, -0.220 to 0.994] for total MIE-CAT score to 0.705 [95% CI, 0.473 to 0.846] for quality component score), and most discrepancies originated in the lymphadenectomy phases. Hypothesis testing for construct validity showed more than 75% of hypotheses correct: MIE-CAT performance scores correlated with experience of the surgical team (r = 0.288 to 0.622), blood loss (r = -0.034 to -0.545), operative time (r = -0.309 to -0.611), intraoperative complications (r = -0.052 to -0.319), and severe postoperative complications (r = -0.207 to -0.395). MIE-CAT version 2 increased usability. Interrater reliability improved but remained moderate (range of ICCs, 0.666 to 0.743), and most discrepancies between raters remained in the lymphadenectomy phases. Conclusions and Relevance: The MIE-CAT was developed and its feasibility, content validity, reliability, and construct validity were demonstrated. By providing insight into surgical performance of MIE, the MIE-CAT might be used for clinical, training, and research purposes.

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Thyroid Incidentalomas: Incidence and Oncological Implication in Patients with Esophageal Cancer.

INTRODUCTION: Thyroid incidentalomas are often encountered during imaging performed for the workup of esophageal cancer. Their oncological significance is unknown. This study aimed to establish incidence and etiology of thyroid incidentalomas found during the diagnostic workup of esophageal cancer. METHODS: All esophageal cancer patients referred to or diagnosed at the Amsterdam UMC between January 2012 and December 2016 were included. Radiology and multidisciplinary team meeting reports were reviewed for presence of thyroid incidentalomas. When present, the fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) or CT was reassessed by a radiologist. Primary outcome was the incidence and etiology of thyroid incidentalomas. RESULTS: In total, 1,110 esophageal cancer patients were included. Median age was 66 years, most were male (77.2%) and had an adenocarcinoma (69.4%). For 115 patients (10.4%), a thyroid incidentaloma was reported. Two thyroidal lesions proved malignant. One was an esophageal cancer metastasis (0.9%) and one was a primary thyroid carcinoma (0.9%). Only the primary thyroid carcinoma resulted in treatment alteration. The other malignant thyroid incidentaloma was in the context of disseminated esophageal disease and ineligible for curative treatment. CONCLUSION: In this study, thyroid incidentalomas were only very rarely oncologically significant. Further etiological examination should only be considered in accordance with the TI-RADS classification system and when clinical consequences are to be expected.

The association between hospital variation in curative treatment for esophagogastric cancer and health-related quality of life and survival.

BACKGROUND: As previous studies showed significant hospital variation in curative treatment of esophagogastric cancer, this study assesses the association between this variation and overall, cancer-specific and recurrence-free survival, and Health-Related Quality of Life (HRQoL). METHODS: Patients diagnosed with potentially curable esophageal or gastric cancer between 2015 and 2018 as registered in the Netherlands Cancer Registry were included. Data on overall survival was available for all patients, data on cancer-specific and recurrence-free survival and HRQoL was available for subgroups. Patients were classified according to diagnosis in hospitals with low, medium or high probability of treatment with curative intent (LP, MP or HP). Multivariable models were used to assess the association between LP, MP and HP hospitals and HRQoL and survival. RESULTS: This study includes 7,199 patients with esophageal, and 2,407 with gastric cancer. Overall and cancer-specific survival was better for patients diagnosed in HP versus LP hospitals for both esophageal (HR = 0.82, 95%CI:0.77-0.88 and HR = 0.82, 95%CI:0.75-0.91, respectively), and gastric cancer (HR = 0.82, 95%CI:0.73-0.92 and HR = 0.74, 95%CI:0.64-0.87, respectively). These differences disappeared after adjustments for treatment. Recurrence-free survival was worse for gastric cancer patients diagnosed in HP hospitals (HR = 1.50, 95%CI:1.14-1.96), which disappeared after adjustment for radicality of surgery. Minor, but no clinically relevant, differences in HRQoL were observed. CONCLUSIONS: Patients diagnosed in hospitals with a high probability of treatment with curative intent have a better overall and cancer-specific but not recurrence-free survival, while minor differences in HRQoL were observed.

External validation of a nomogram predicting conditional survival after tri-modality treatment of esophageal cancer.

BACKGROUND: A conditional survival nomogram was developed at a single high-volume center to predict 5-year overall survival for esophageal cancer patients after neoadjuvant chemoradiation and esophagectomy. The aim of this study was to externally validate the nomogram in a cohort of patients with esophageal adeno- or squamous cell carcinoma from another high-volume center. METHODS: Consecutive patients with an esophageal adeno- or squamous cell carcinoma who had undergone esophagectomy after being treated with preoperative chemoradiation between 2004 and 2016 were selected from a prospectively maintained institutional database. The level of discrimination for prediction of 5-year overall survival was quantified by Harrell's C statistic. Calibration of the conditional survival nomogram was visualized by plotting predicted 5-year survival and observed 5-year survival for comparison. RESULTS: Of the 296 patients examined, the probability of 5-year overall survival directly after surgery was 45% and increased to 51%, 68%, 78%, and 89% for each additional year survived. The predicted 5-year overall survival differed from the observed survival, with a calibration slope of 0.54, 0.55, 0.59, 0.73, and 1.09 directly after surgery and 1, 2, 3, and 4 years of survival after surgery, respectively. The nomogram's discrimination level for 5-year survival was moderate, with a C statistic of 0.65 compared to the 0.70 reported in the original study. CONCLUSION: The nomogram model has moderate predictive discrimination and accuracy, supporting its applicability to external cohorts to predict conditional survival. Further validation studies should empirically assess the model for predictive performance.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.