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Background: The FLOT4 trial demonstrated superior survival of perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) compared to anthracycline triplets for resectable gastric cancer. These results were presented at the American Society of Clinical Oncology (ASCO) congress in June 2017 and published in April 2019. However, adoption of novel treatments in clinical practice often encounters delays. This study assesses the patterns of perioperative chemotherapy utilization and FLOT uptake in clinical practice within the Netherlands., Materials and Methods: A retrospective cohort study was conducted with resectable gastric cancer patients (cT 1-4a,X cN all cM 0 ) between 2015-2020 from the Netherlands Cancer Registry. Descriptive statistics, Cochran-Armitage tests, Fisher's exact or unpaired T-tests, and Jonckheere-Terpstra tests were used to analyze chemotherapy trends and FLOT uptake across hospitals., Results: Among 3290 included patients, 42.9 % received neoadjuvant treatment. In 2015, 43.6 % of patients received perioperative chemotherapy versus 43.5 % in 2020 (p = 0.63). 40 out of 62 hospitals (64.5 %) adopted FLOT between the ASCO presentation and the full publication. FLOT increased from 42.9 % before publication to 86.8 % after publication (p < 0.0001), while anthracycline triplet use decreased to 0.9 % (p < 0.0001). Higher hospital volume was associated with fewer days to adoption (p = 0.04) but not with adoption of FLOT before publication (p = 0.14)., Conclusion: Timing of FLOT adoption varied among Dutch hospitals, leading to unequal patient access to effective treatments. Establishing (inter)national guidelines on provisional treatment adjustment pending publication is crucial to reduce variation in access. Moreover, rapid publication of final trial results is imperative to reduce variation in practice and ensure fair patient treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Grard A.P. Nieuwenhuijzen: consultant or advisory role Medtronic. Camiel Rosman: consultant DEKRA medical BV, research funding from Johnson&Johnson, Medtronic, and ZonMw. Hanneke W.M. van Laarhoven: consultant or advisory role: Amphera, AstraZeneca, Beigene, BMS, Daiichy-Sankyo, Dragonfly, Eli Lilly, MSD, Nordic Pharma, Servier, Research funding and/or medication supply: Bayer, BMS, Celgene, Janssen, Incyte, Eli Lilly, MSD, Nordic Pharma, Philips, Roche, Servier, Speaker role: Astellas, Benecke, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Travel Congress Management. B.V. Rob H.A. Verhoeven: Research grant for Bristol Myers Squib and consultant for Daiichi-Sankyo, all paid to institution. Bas P.L. Wijnhoven: research funding from BMS; consulting/advisory for BMS and Medtronic. Bianca Mostert: research funding from Sanofi, Pfizer and BMS; consulting/advisory for Lilly, Servier, BMS, Amgen and AstraZeneca. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest All authors declare that they do not have competing interest regarding this manuscript.

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival., Methods: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18 F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases., Results: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2-27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4-NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4-10.9 months)., Conclusions: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18 F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases., (© 2024. The Author(s).)

Purpose: Despite recent treatment advances, esophageal cancer still has poor survival and a high morbidity. Exploratory evidence suggests that exercise can reduce cancer-related mortality and recurrence rates. Here, we investigated the effects of an exercise intervention in the first year after esophagectomy on survival in participants of the Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT)-trial., Methods: In the PERFECT-trial, esophageal cancer patients who had undergone esophagectomy were randomized to a 12-week exercise program (EX) or the control group (CG). We assessed 2- and 5-year (progression-free) survival. (Un)adjusted Cox Proportional-Hazards models were used to calculate hazard ratios (HRs) for comparison between the trial arms. Sensitivity analyses, excluding patients with events within the exercise intervention period, were performed., Results: In total, 120 participants (EX = 61; CG = 59) were included in the PERFECT-trial. After 2-year follow-up, no significant difference in the risk of death or progression between EX and CG was found (adjusted HR = 1.65, 95% CI [0.75-3.63] and 1.38, 95% CI [0.76-2.50], respectively). After excluding patients with events during the intervention period (EX = 8; CG = 4), 2-year HRs for death (1.03, 95% CI [0.41-2.56]) and progression (1.26, 95% CI [0.64-2.48]) both decreased and remained insignificant. No significant effects were found on 5-year mortality (1.03, 95% CI [0.57-1.84]) and progression (1.21, 95% CI [0.72-2.04]) either. Sensitivity-analysis resulted in attenuated 5-year HRs for mortality (0.82, 95% CI [0.42-1.58]) and progression (1.08, 95% CI [0.61-1.92])., Conclusions: The results indicate no benefit of a 12-week exercise program in the first year post-esophagectomy on 2- and 5-year (progression-free) survival in esophageal cancer patients. The absence of beneficial effects may be explained by the relatively short exercise program, which was performed after treatment completion., Competing Interests: Conflict of Interest and Funding Source: The World Cancer Research Fund, The Netherlands (WCRF NL, project number 2013/997), financially supported this study. M. I. van Berge Henegouwen is consultant for Viatris, Johnson & Johnson, BBraun, Stryker and Medtronic. All fees paid to institution. All other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: The optimal extent of lymph node dissection (LND) and the anatomic boundaries per lymph node station (LNS) during minimally invasive esophagectomy (MIE) for esophageal cancer remain a topic of debate. This study investigated the opinion of Dutch esophageal cancer surgeons on their routine LND extent and anatomic boundaries per LNS during MIE., Methods: In April 2023, an English web-based cross-sectional survey was conducted. In each of the 15 Dutch hospitals performing MIE, two MIE surgeons were asked to participate. The routine LND extent (quantity, specific LNS) for distal esophageal adenocarcinoma, (dis)agreement with the TIGER definition, and anatomic boundaries for each LNS in six directions were queried., Results: The survey was completed by 24 Dutch MIE surgeons (80% response rate). Consensus on the routine LND extent ( ≥ 85% of the participating surgeons) included the left and right paracardial, left gastric artery, celiac trunk, proximal splenic artery, common hepatic artery, subcarinal middle mediastinal paraoesophageal, lower mediastinal paraoesophageal, pulmonary ligament, and upper mediastinal paraoesophageal LNSs. Other LNSs were not widely considered routine. Although, certain anatomic boundaries were consistent among the surgeons, the majority varied, even when they agreed on the TIGER definition., Conclusion: Significant variations in surgical practice among Dutch esophageal surgeons regarding their routine extent of LND and anatomic boundaries of LNSs during MIE were demonstrated. Variation may have an impact on clinical outcomes, hampering uniform treatment strategies and hindering comparison of performance assessments. This study highlighted the need for an international follow-up study toward one uniform defined LND during MIE for esophageal cancer., (© 2024. The Author(s).)

Background: Minimally invasive transcervical oesophagectomy is a surgical technique that offers radical oesophagectomy without the need for transthoracic access. The aim of this study was to evaluate the safety and feasibility of the minimally invasive transcervical oesophagectomy procedure and to report the refinement of this technique in a Western cohort., Methods: A single-centre prospective cohort study was designed as an IDEAL stage 2A study. Patients with oesophageal cancer (cT1b-4a N0-3 M0) who were scheduled for oesophagectomy with curative intent were eligible for inclusion in the study. The main outcome parameter was the postoperative pulmonary complication rate and the secondary outcomes were the anastomotic leakage, recurrent laryngeal nerve palsy, and R0 resection rates, as well as the lymph node yield., Results: In total, 75 patients underwent minimally invasive transcervical oesophagectomy between January 2021 and November 2023. Several modifications to the surgical technique were registered, evaluated, and implemented in the context of IDEAL stage 2A. A total of 12 patients (16%) had postoperative pulmonary complications, including pneumonia (4 patients) and pleural effusion with drainage or aspiration (8 patients). Recurrent laryngeal nerve palsy was observed in 33 of 75 patients (44%), with recovery in 30 of 33 patients (91%). A total of 5 of 75 patients (7%) had anastomotic leakage. The median number of resected lymph nodes was 29 (interquartile range 22-37) and the R0 resection rate was 96% (72 patients)., Conclusion: Introducing minimally invasive transcervical oesophagectomy for oesophageal cancer in a Dutch institution is associated with a low rate of postoperative pulmonary complications and a high rate of temporary recurrent laryngeal nerve palsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Increasing evidence supports a positive relationship between the intensity of early postoperative pain, and the risk of 30-day postoperative complications. Higher pain levels may hamper recovery and contribute to immunosuppression after surgery. This leaves patients at risk of postoperative complications., Methods: One thousand patients who underwent major abdominal surgery (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, esophageal, liver, or pancreas surgery) at the Radboud university medical center were randomly selected from eligible patients between 2014 and 2020. Pain scores on day 1, the independent variable of interest, were extracted from the electronic patient files. Outcome measures were 30-day postoperative complications (infectious, non-infectious, total complications and classification according to Clavien-Dindo)., Results: Seven hundred ninety complications occurred in 572 patients within 30 days after surgery, of which 289 (36.7%) were of infectious origin, and 501 (63.4%) complications were non-infectious. The mean duration from the end of surgery to the occurrence of infectious complications was 6.5 days (SD 5.6) and 4.1 days (SD 4.7) for non-infectious complications (p<0.001). Logistic regression analysis revealed that pain scores on postoperative day 1 (POD1) were significantly positively associated with 30-day total complications after surgery (OR=1.132, 95% CI (1.076 to 1.190)), Clavien-Dindo classification (OR=1.131, 95% CI (1.071 to 1.193)), infectious complications (OR=1.126, 95% CI (1.059 to 1.196)), and non-infectious complications (OR=1.079, 95% CI (1.022 to 1.140))., Conclusions: After major abdominal surgery, higher postoperative pain scores on day 1 are associated with an increased risk of 30-day postoperative complications. Further studies should pursue whether optimization of perioperative analgesia can improve immune homeostasis, reduce complications after surgery and enhance postoperative recovery., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Importance: When considering nonoperative treatment in a patient with acute appendicitis, it is crucial to accurately rule out complicated appendicitis. The Atema score, also referred to as the Scoring System of Appendicitis Severity (SAS), has been designed to differentiate between uncomplicated and complicated appendicitis but has not been prospectively externally validated., Objective: To externally validate the SAS and, in case of failure, to develop an improved SAS (2.0) for estimating the probability of complicated appendicitis., Design, Setting, and Participants: This prospective study included adult patients who underwent operations for suspected acute appendicitis at 11 hospitals in the Netherlands between January 2020 and August 2021., Main Outcomes and Measures: Appendicitis severity was predicted according to the SAS in 795 patients and its sensitivity and negative predictive value (NPV) for complicated appendicitis were calculated. Since the predefined targets of 95% for both were not met, the SAS 2.0 was developed using the same cohort. This clinical prediction model was developed with multivariable regression using clinical, biochemical, and imaging findings. The SAS 2.0 was externally validated in a temporal validation cohort consisting of 565 patients., Results: In total, 1360 patients were included, 463 of whom (34.5%) had complicated appendicitis. Validation of the SAS resulted in a sensitivity of 83.6% (95% CI, 78.8-87.6) and an NPV of 85.0% (95% CI, 80.6-88.8), meaning that the predefined targets were not achieved. Therefore, the SAS 2.0 was developed, internally validated (C statistic, 0.87; 95% CI, 0.84-0.89), and subsequently externally validated (C statistic, 0.86; 95% CI, 0.82-0.89). The SAS 2.0 was designed to calculate a patient's individual probability of having complicated appendicitis along with a 95% CI., Conclusions and Relevance: In this study, external validation of the SAS fell short in accurately distinguishing complicated from uncomplicated appendicitis. The newly developed and externally validated SAS 2.0 was able to assess an individual patient's probability of having complicated appendicitis with high accuracy in patients with acute appendicitis. Use of this patient-specific risk assessment tool can be helpful when considering and discussing nonoperative treatment of acute appendicitis with patients.

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.

Background: The FLOT4-AIO trial (2019) showed improved survival with perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) compared to anthracyclin triplets in gastric cancer treatment. It is unclear whether these results extend to real-world scenarios in the Netherlands. This study aimed to compare outcomes of perioperative FLOT to anthracyclin triplets in a real-world Dutch gastric cancer population. Methods: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) gastric or gastro-esophageal junction carcinoma between 2015-2021 who received neoadjuvant FLOT or anthracyclin triplets were selected from the Netherlands Cancer Registry. The primary outcome was overall survival (OS), analyzed through multivariable Cox regression. Secondary outcomes included pathological complete response (pCR), neoadjuvant chemotherapy cycle completion, surgical resection rates, and adjuvant therapy. Results: Adjusted OS showed no significant survival benefit (HR = 0.88, 95% CI 0.77-1.01, p = 0.07), even though the median OS was numerically improved by 8 months with FLOT compared to anthracyclin triplets (48.1 vs. 39.9 months, p = 0.16). FLOT patients were more likely to undergo diagnostic staging laparoscopies (74.2% vs. 44.1%, p < 0.001), had higher rates of completing neoadjuvant chemotherapy (OR = 1.35, 95% CI 1.09-1.68, p = 0.007), receiving adjuvant therapy (OR = 1.34, 95% CI 1.08-1.66, p = 0.08), and achieving pCR (OR = 1.52, 95% CI 1.05-2.20, p = 0.03). No significant differences were observed in (radical) resection rates. Conclusion(s): Real-world data showed no significant OS improvement for FLOT-treated patients compared to anthracyclin triplets, despite more staging laparoscopies. However, FLOT patients demonstrated higher rates of neoadjuvant therapy completion, proceeding to adjuvant therapy, and increased pCR rates. Therefore, we recommend the continued use of neoadjuvant FLOT therapy in the current clinical setting.

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Robot assisted surgery (RAS) is increasingly used, and besides conventional minimally invasive surgery (cMIS) surgeons are challenged to learn an increased array of skills. This study aimed to assess the influence of both learning curves on each other. A prospective randomized crossover study was performed. Participants without cMIS or RAS experience (Groups 1 and 2), and cMIS experienced, (Group 3) were recruited. Three suturing tasks (intracorporal suturing, tilted plane and anastomosis needle transfer) were performed on the EoSim cMIS simulator or RobotiX RAS simulator up to twenty repetitions. Subsequently, Groups 1 and 2 performed the tasks on the other modality. Outcomes were simulator parameters, validated composite and pass/fail scores. In total forty-three participants were recruited. Overall RAS suturing was better in Group 1 (cMIS followed by RAS tasks) and 3 (RAS tasks) versus Group 2 (RAS followed by cMIS tasks) for time (163 s and 157 s versus 193 s p = 0.004, p = 0.001) and composite scores (92/100 and 91/100 versus 89/100 p = 0.008, p = 0.020). The cMIS suturing was better for Group 2 versus 1 (time 287 s versus 349 s p = 0.005, composite score 96/100 versus 94/100 p = 0.002). Significant differences from the RAS suturing pass/fail were reached earlier by Group 3, followed by Groups 1 and 2 (repetition six, nine and twelve). In cMIS suturing Group 2 reached significant differences from the pass/fail earlier than Group 1 (repetition four versus six). Transferability of skills was shown for cMIS and RAS, indicating that suturing experience on cMIS or RAS is beneficial in learning either approach., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Background: This study assesses the incidence of gastrointestinal symptoms in the first year after resection of esophageal or gastric cancer and its association with health-related quality of life (HRQoL), functioning, work productivity, and daily activities., Patients and Methods: Patients diagnosed with esophageal or gastric cancer between 2015 and 2021, who underwent a resection, and completed ≥ 2 questionnaires from the time intervals prior to resection and 0-3, 3-6, 6-9, and 9-12 months after resection were included. Multivariable generalized linear mixed models were used to assess changes in gastrointestinal symptoms over time and the impact of the number of gastrointestinal symptoms on HRQoL, functioning, work productivity, and daily activities for patients who underwent an esophagectomy or gastrectomy separately., Results: The study population consisted of 961 (78.8%) and 259 (21.2%) patients who underwent an esophagectomy and gastrectomy, respectively. For both groups, the majority of gastrointestinal symptoms changed significantly over time. Most clinically relevant differences were observed 0-3 after resection compared with prior to resection and included increased diarrhea, appetite loss, and eating restrictions, and specifically after esophagectomy dry mouth, trouble with coughing, and trouble talking. At 9-12 after resection one or more severe gastrointestinal symptoms were reported by 38.9% after esophagectomy and 33.7% after gastrectomy. A higher number of gastrointestinal symptoms was associated with poorer functioning, lower HRQoL, higher impairment in daily activities, and lower work productivity., Conclusions: This study shows that gastrointestinal symptoms are frequently observed and burdensome after esophagectomy or gastrectomy, highlighting the importance to address these sequelae for high quality survivorship., (© 2023. Society of Surgical Oncology.)

Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied., Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1)., Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days)., Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objective: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL)., Background: AL after RC resection often results in a permanent stoma., Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated., Results: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76)., Conclusions: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Declaration of competing interest RV received a research grant from Bristol Myers Squibb and has served as consultant for Daiichi Sankyo. HvL reports grants or advisory/speaker role from: Astellas, BMS, Daiichy, Dragonfly, Lilly, Merck, Novartis, Nordic Pharma, Servier; research funding or medical supply from: Bayer, BMS, Celgene, Janssen, Incyte, Lilly, Merck, Nordic Pharma, Philips, Roche, Servier; and has received unrestricted research funding (non-commercial) from: Dutch Cancer Society, NWO/ZonMw, European Research Council, MaagLeverDarm Stichting. GN reports grants or advisory/speaker role from: Medtronic and Lilly and has received unrestricted research funding (non-commercial) from: Dutch Cancer Society and CZ Healthcare Insurance. MS reports an advisory role for Lilly and BMS. BW reports research grant and speaker role from BMS. The other authors have nothing to declare., (© 2023 Published by Elsevier Ltd.)

Background: The COVID-19 pandemic has affected the entire global healthcare system, including oncological care. This study investigated the effects of the COVID-19 pandemic on the diagnosis, stage, and treatment of esophagogastric cancer in the Netherlands., Methods: Patients diagnosed in 2020 were divided into 5 periods, based on the severity of the COVID-19 pandemic in the Netherlands, and compared to patients diagnosed in the same period in the years 2017-2019. Patient characteristics and treatments were evaluated for esophageal cancer (EC) and gastric cancer (GC) separately., Results: The number of esophagogastric cancer diagnoses decreased prominently during the first 2 months of the COVID-19 pandemic. During this period, a significantly higher percentage of GC patients was diagnosed with incurable disease (52.5% in 2017-2019 and 67.7% in 2020, p = 0.011). We observed a significant reduction in the percentage of patients with potentially curable EC treated with resection and neoadjuvant chemoradiotherapy (from 35.0% in 2017-2019 to 27.3% in 2020, p < 0.001). Also, patients diagnosed with incurable GC were treated less frequently with a resection (from 4.6% in 2017-2019 to 1.5% in 2020, p = 0.009) in the second half of 2020., Conclusions: Compared to previous years, the number of esophagogastric cancer diagnoses decreased in the first 2 months of the COVID-19 pandemic, while an increased percentage of patients was diagnosed with incurable disease. Both in the curative and palliative setting, patients were less likely to be treated with a surgical resection., (© 2023. The Author(s).)

Background: Video-based assessment by experts may structurally measure surgical performance using procedure-specific competency assessment tools (CATs). A CAT for minimally invasive esophagectomy (MIE-CAT) was developed and validated previously. However, surgeon's time is scarce and video assessment is time-consuming and labor intensive. This study investigated non-procedure-specific assessment of MIE video clips by MIE experts and crowdsourcing, collective surgical performance evaluation by anonymous and untrained laypeople, to assist procedure-specific expert review., Methods: Two surgical performance scoring frameworks were used to assess eight MIE videos. First, global performance was assessed with the non-procedure-specific Global Operative Assessment of Laparoscopic Skills (GOALS) of 64 procedural phase-based video clips < 10 min. Each clip was assessed by two MIE experts and > 30 crowd workers. Second, the same experts assessed procedure-specific performance with the MIE-CAT of the corresponding full-length video. Reliability and convergent validity of GOALS for MIE were investigated using hypothesis testing with correlations (experience, blood loss, operative time, and MIE-CAT)., Results: Less than 75% of hypothesized correlations between GOALS scores and experience of the surgical team (r < 0.3), blood loss (r = - 0.82 to 0.02), operative time (r = - 0.42 to 0.07), and the MIE-CAT scores (r = - 0.04 to 0.76) were met for both crowd workers and experts. Interestingly, experts' GOALS and MIE-CAT scores correlated strongly (r = 0.40 to 0.79), while crowd workers' GOALS and experts' MIE-CAT scores correlations were weak (r = - 0.04 to 0.49). Expert and crowd worker GOALS scores correlated poorly (ICC ≤ 0.42)., Conclusion: GOALS assessments by crowd workers lacked convergent validity and showed poor reliability. It is likely that MIE is technically too difficult to assess for laypeople. Convergent validity of GOALS assessments by experts could also not be established. GOALS might not be comprehensive enough to assess detailed MIE performance. However, expert's GOALS and MIE-CAT scores strongly correlated indicating video clip (instead of full-length video) assessments could be useful to shorten assessment time., (© 2023. The Author(s).)

Anastomotic leak (AL) is a common and severe complication after esophagectomy. This study aimed to assess the performance of a consensus-based algorithm for diagnosing AL after minimally invasive esophagectomy. This study used data of the ICAN trial, a multicenter randomized clinical trial comparing cervical and intrathoracic anastomosis, in which a predefined diagnostic algorithm was used to guide diagnosing AL. The algorithm identified patients suspected of AL based on clinical signs, blood C-reactive protein (cut-off value 200 mg/L), and/or drain amylase (cut-off value 200 IU/L). Suspicion of AL prompted evaluation with contrast swallow computed tomography and/or endoscopy to confirm AL. Primary outcome measure was algorithm performance in terms of sensitivity, specificity, and positive and negative predictive values (PPV, NPV), respectively. AL was defined according to the definition of the Esophagectomy Complications Consensus Group. 245 patients were included, and 125 (51%) patients were suspected of AL. The algorithm had a sensitivity of 62% (95% confidence interval [CI]: 46-75), a specificity of 97% (95% CI: 89-100), and a PPV and NPV of 94% (95% CI: 79-99) and 77% (95% CI: 66-86), respectively, on initial assessment. Repeated assessment in 19 patients with persisting suspicion of AL despite negative or inconclusive initial assessment had a sensitivity of 100% (95% CI: 77-100). The algorithm showed poor performance because the low sensitivity indicates the inability of the algorithm to confirm AL on initial assessment. Repeated assessment using the algorithm was needed to confirm remaining leaks., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data., Objective: To evaluate the length of pooled learning curves of MIDP in experienced centers., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022., Exposures: The learning curve for MIDP was estimated by pooling data from all centers., Main Outcomes and Measures: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C., Results: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated., Conclusion and Relevance: In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.

Objective: The aim of this study was to determine if prophylactic mesh placement is an effective, safe, and cost-effective procedure to prevent parastomal hernia (PSH) formation in the long term., Background: A PSH is the most frequent complication after stoma formation. Prophylactic placement of a mesh has been suggested to prevent PSH, but long-term evidence to support this approach is scarce., Methods: In this multicentre superiority trial patients undergoing the formation of a permanent colostomy were randomly assigned to either retromuscular polypropylene mesh reinforcement or conventional colostomy formation. Primary endpoint was the incidence of a PSH after 5 years. Secondary endpoints were morbidity, mortality, quality of life, and cost-effectiveness., Results: A total of 150 patients were randomly assigned to the mesh group (n = 72) or nonmesh group (n = 78). For the long-term follow-up, 113 patients were analyzed, and 37 patients were lost to follow-up. After a median follow-up of 60 months (interquartile range: 48.6-64.4), 49 patients developed a PSH, 20 (27.8%) in the mesh group and 29 (37.2%) in the nonmesh group ( P = 0.22; RD: -9.4%; 95% CI: -24, 5.5). The cost related to the meshing strategy was € 2.239 lower than the nonmesh strategy (95% CI: 491.18, 3985.49), and quality-adjusted life years did not differ significantly between groups ( P = 0.959; 95% CI: -0.066, 0.070)., Conclusions: Prophylactic mesh placement during the formation of an end-colostomy is a safe procedure but does not reduce the incidence of PSH after 5 years of follow-up. It does, however, delay the onset of PSH without a significant difference in morbidity, mortality, or quality of life, and seems to be cost-effective., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study explores patients' need for information and support in deciding on esophageal cancer treatment, when experimental active surveillance and standard surgery are both feasible., Methods: This psychological companion study was conducted alongside the Dutch SANO-trial (Surgery As Needed for Oesophageal cancer). In-depth interviews and questionnaires were used to collect data from patients who declined participation in the trial because they had a strong preference for either active surveillance (n = 20) or standard surgery (n = 20). Data were analyzed using both qualitative and quantitative techniques., Results: Patients prefer to receive information directly from their doctors and predominantly rely on this information to make a treatment decision. Other information resources are largely used to confirm their treatment decision. Patients highly value support from their loved ones and appreciate emphatic doctors to actively involve them in the decision-making process. Overall, patients' needs for information and support during decision-making were met., Conclusions: The importance of shared decision-making and the role doctors have in this process is underlined. The role of doctors is essential at the initial phase of decision-making: Once patients seem to have formed their treatment preference for either active surveillance or surgery, the influence of external resources (including doctors) may be limited., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy., Methods: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders., Results: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary treatment strategies., Conclusion: Less extensive primary treatment of anastomotic leak was associated with less morbidity. A less extensive primary treatment approach may potentially be considered for anastomotic leak. Future studies are needed to confirm current findings and guide optimal treatment of anastomotic leak after oesophagectomy., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

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

Background: Guidelines do not provide clear recommendations with regard to the use of low intra-abdominal pressure (IAP) during laparoscopic surgery. The aim of this meta-analysis is to assess the influence of low versus standard IAP during laparoscopic surgery on the key-outcomes in perioperative medicine as defined by the StEP-COMPAC consensus group., Materials and Methods: We searched the Cochrane Library, PubMed, and EMBASE for randomized controlled trials comparing low IAP (<10 mmHg) with standard IAP (10 mmHg or higher) during laparoscopic surgery without time, language, or blinding restrictions. According to the PRISMA guidelines, two review authors independently identified trials and extracted data. Risk ratio (RR), and mean difference (MD), with 95% CIs were calculated using random-effects models with RevMan5. Main outcomes were based on StEP-COMPAC recommendations, and included postoperative complications, postoperative pain, postoperative nausea and vomiting (PONV) scores, and length of hospital stay., Results: Eighty-five studies in a wide range of laparoscopic procedures (7349 patients) were included in this meta-analysis. The available evidence indicates that the use of low IAP (<10 mmHg) leads to a lower incidence of mild (Clavien-Dindo grade 1-2) postoperative complications (RR=0.68, 95% CI: 0.53-0.86), lower pain scores (MD=-0.68, 95% CI: -0.82 to 0.54) and PONV incidence (RR=0.67, 95% CI: 0.51-0.88), and a reduced length of hospital stay (MD=-0.29, 95% CI: -0.46 to 0.11). Low IAP did not increase the risk of intraoperative complications (RR=1.15, 95% CI: 0.77-1.73)., Conclusions: Given the established safety and the reduced incidence of mild postoperative complications, lower pain scores, reduced incidence of PONV, and shorter length of stay, the available evidence supports a moderate to strong recommendation (1a level of evidence) in favor of low IAP during laparoscopic surgery., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Anastomotic leak (AL) is a common but severe complication after esophagectomy, and over 10% of patients with AL suffer mortality. Different prognostic factors in patients with AL are known, but a tool to predict mortality after AL is lacking. This study aimed to develop a prediction model for postoperative mortality in patients with AL after esophagectomy. TENTACLE-Esophagus is an international retrospective cohort study, which included 1509 patients with AL after esophagectomy. The primary outcome was 90-day postoperative mortality. Previously identified prognostic factors for mortality were selected as predictors: patient-related (e.g. comorbidity, performance status) and leak-related predictors (e.g. leucocyte count, overall gastric conduit condition). The prediction model was developed using multivariable logistic regression and validated internally using bootstrapping. Among the 1509 patients with AL, 90-day mortality was 11.7%. Sixteen predictors were included in the prediction model. The model showed good performance after internal validation: the c-index was 0.79 (95% confidence interval 0.75-0.83). Predictions for mortality by the internally validated model aligned well with observed 90-day mortality rates. The prediction model was incorporated in an online tool for individual use and can be found at: https://www.tentaclestudy.com/prediction-model. The developed prediction model combines patient-related and leak-related factors to accurately predict postoperative mortality in patients with AL after esophagectomy. The model is useful for clinicians during counselling of patients and their families and may aid identification of high-risk patients at diagnosis of AL. In the future, the tool may guide clinical decision-making; however, external validation of the tool is warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the learning curve of laparoscopic gastrectomy (LG) after an implementation program., Background: Although LG is increasingly being performed worldwide, little is known about the learning curve., Methods: Consecutive patients who underwent elective LG for gastric adenocarcinoma with curative intent in each of the 5 highest-volume centers in the Netherlands were enrolled. Generalized additive models and a 2-piece model with a break point were used to determine the learning curve length. Analyses were corrected for casemix and were performed for LG and for the subgroups distal gastrectomy (LDG) and total gastrectomy (LTG). The learning curve effect was assessed for (1) anastomotic leakage; and (2) the occurrence of postoperative complications, conversions to open surgery, and short-term oncological parameters., Results: In total 540 patients were included for analysis, 108 patients from each center; 268 patients underwent LDG and 272 underwent LTG. First, for LG, no learning effect regarding anastomotic leakage could be identified: the rate of anastomotic leakage initially increased, then reached a plateau after 36 cases at 10% anastomotic leakage. Second, the level of overall complications reached a plateau after 20 cases, at 38% overall complications, and at 5% conversions. For both LDG and LTG, each considered separately, fluctuations in secondary outcomes and anastomotic leakage followed fluctuations in casemix., Conclusion: On the basis of our study of the first 108 procedures of LG in 5 high-volume centers with well-trained surgeons, no learning curve effect could be identified regarding anastomotic leakage. A learning curve effect was found with respect to overall complications and conversion rate., Competing Interests: M.I.v.B.H. is consultant for Mylan, Johnson & Johnson, Alesi Surgical, BBraun and Medtronic, and received unrestricted research grants from Olympus and Stryker (all fees paid to institution). J.H.M.B.S. has served as faculty in an online training course for inguinal hernia repair from Medtronic. M.D.P.L. has a consulting and advisory role at Galvani and Medtronic, and received research funding from the Dutch Cancer Foundation. G.A.P.N. has received research funding from Medtronic. J.P.H.R. and R.v.H. have a consulting and advisory role at Intuitive Surgical. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027)., 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., Competing Interests: Luyer received research grants from Galvani and Medtronic. Nieuwenhuijzen reports consulting fees and research grants from Medtronic. Rosman has received research grants from Johnson&Johnson and Medtronic. van Berge Henegouwen reports research grants from Olympus and Stryker, in addition to consulting fees from Medtronic, Alesi Surgical, Johnson&Johnson and Mylan. van Oijen has received unrestricted research grants from Bayer, Lilly, Merck Serono, Nordic, Servier, and Roche. The remaining authors have no conflict of interest to report. No funding was received for this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Active surveillance may be a safe and effective treatment in oesophageal cancer patients with a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). In the NOSANO-study we gained insight in patients' motive to opt for either an experimental treatment called active surveillance or for standard immediate surgery. Both qualitative and quantitative analyses methods were used. Forty patients were interviewed about their treatment preference, 3 months after completion of nCRT (T1). Data were recorded, transcribed verbatim and analysed according to the principles of grounded theory. In addition, at T1 and T2 (12 months after completion of nCRT) questionnaires on health-related quality of life, coping, anxiety and decisional regret (only T2) were administered. Interview data analyses resulted in a conceptual model with 'dealing with threat of cancer' as the central theme. Patients preferring active surveillance tend to cope with this threat by confiding in their bodies and good outcomes. Their mind-set is one of 'enjoy life now'. Patients preferring surgery tend to cope by minimizing uncertainty and eliminating the source of cancer. Their mind-set is one of 'don't give up, act now'. Furthermore, questionnaire results showed that patients with a preference for standard surgery had a lower quality of life. Patient preferences are individualized and thus difficult to predict. Our model can help healthcare professionals to determine patient preferences for treatment. Coping style and mind-set seem to be determining factors here., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

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., Competing Interests: M.D.P.L. received research grants from Galvani and Medtronic. G.A.P.N. reports consulting fees and research grants from Medtronic. C.R. has received research grants from Johnson&Johnson and Medtronic. M.I.v.B.H. reports research grants from Olympus and Stryker, in addition to consulting fees from Medtronic, Alesi Surgical, Johnson&Johnson, and Mylan. M.G.H.v.O. has received unrestricted research grants from Bayer, Lilly, Merck Serono, Nordic, Servier, and Roche. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The probability of undergoing treatment with curative intent for esophagogastric cancer has been shown to vary considerately between hospitals of diagnosis. Little is known about the factors that attribute to this variation. Since clinical decision making (CDM) partially takes place during an MDTM, the aim of this qualitative study was to assess clinician's perspectives regarding facilitators and barriers associated with CDM during MDTM, and second, to identify factors associated with CDM during an MDTM that may potentially explain differences in hospital practice., Methods: A multiple case study design was conducted. The thematic content analysis of this qualitative study, focused on 16 MDTM observations, 30 semi-structured interviews with clinicians and seven focus groups with clinicians to complement the collected data. Interviews were transcribed ad verbatim and coded., Results: Factors regarding team dynamics that were raised as aspects attributing to CDM were clinician's personal characteristics such as ambition and the intention to be innovative. Clinician's convictions regarding a certain treatment and its outcomes and previous experiences with treatment outcomes, and team dynamics within the MDTM influenced CDM. In addition, a continuum was illustrated. At one end of the continuum, teams tended to be more conservative, following the guidelines more strictly, versus the opposite in which hospitals tended towards a more invasive approach maximizing the probability of curation., Conclusion: This study contributes to the awareness that variation in team dynamics influences CDM during an MDTM., Competing Interests: Author PS received research support or funding from EndoStim, Pentax, Norgine, Motus GI and The Enose company and is a member of the Advisory Board of Motus GIE. Author HL is a consultant or adviser in BMS, Lilly, MSD, Nordic Pharma, Servier, and received research funding and/or medication supply from Bayer, BMS, Celgene, Janssen, Lilly, Nordic Pharma, Philips, Roche, Servier. Author RV: received research grants from Roche and Bristol-Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luijten, Westerman, Nieuwenhuijzen, Walraven, Sosef, Beerepoot, van Hillegersberg, Muller, Hoekstra, Bergman, Siersema, van Laarhoven, Rosman, Brom, Vissers and Verhoeven.)

Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with esophageal cancer receiving neoadjuvant chemoradiotherapy and surgery were analyzed for tumor-specific mutations. These tumor-informed mutations were used to measure the presence of ctDNA in serially collected plasma samples using hybrid capture-based sequencing. Plasma samples were obtained before chemoradiotherapy, and prior to surgery. The association between ctDNA detection and progression-free and overall survival was measured. Before chemoradiotherapy, ctDNA was detected in 56% (44/78) of patients and detection was associated with tumor stage and volume ( p = 0.05, Fisher exact and p = 0.02, Mann-Whitney, respectively). After chemoradiotherapy, ctDNA was detected in 10% (8/78) of patients. This preoperative detection of ctDNA was independently associated with recurrent disease (hazard ratio 2.8, 95% confidence interval 1.1-6.8, p = 0.03, multivariable Cox-regression) and worse overall survival (hazard ratio 2.9, 95% confidence interval 1.2-7.1, p = 0.02, multivariable Cox-regression).Ultradeep sequencing-based detection of ctDNA in preoperative plasma of patients with locally advanced esophageal cancer may help to assess which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery.

Purpose: Little is known about the optimal treatment of anastomotic leakage after low anterior resection (LAR) for rectal cancer and whether treatment strategy depends on leakage features and patient characteristics. The objective of this study was to determine which treatment principles are used by expert colorectal surgeons worldwide., Methods: In this international case-vignette study, participants completed a survey on their preferred treatment for 11 clinical cases with varying leakage features and two patient scenarios depending on surgical risk (a total of 22 cases)., Results: In total, 42 of 64 invited surgeons completed the survey from 18 countries worldwide. The majority worked at a university training hospital (62%) and had more than 15 years of experience performing LAR for rectal cancer (52%). Early leaks in septic patients were preferably treated by major salvage surgery, to some extent depending on the patient scenario. In early leaks in non-septic patients, drainage and faecal diversion were the cornerstones of the proposed treatment. Endoscopic vacuum therapy was more often proposed than percutaneous drainage. A minority proposed anastomotic reconstruction, more often for larger defects. Treatment of late leaks ranged from watchful waiting, drainage, or transanal repair to major (non-)restorative salvage surgery, with minimal influence of the degree of symptoms on the proposed strategy. Leaks of the blind loop and rectovaginal fistulae showed high variability in the proposed treatment strategy., Conclusion: This TENTACLE-Rectum case-vignette study demonstrates tailored treatment strategies depending on the clinical type of leak and patient characteristics, with variable degrees of consensus and knowledge gaps which should be addressed in future studies., (© 2022. The Author(s).)

Background: Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score., Methods: This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally., Results: Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification., Conclusion: The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: The number of older patients undergoing curative esophagectomy for esophageal cancer is increasing, and minimally invasive techniques are being increasingly used. The aim of this study is to compare postoperative outcomes after curative esophagectomy between older and younger patients., Methods: Data was retrieved from the Dutch Upper Gastrointestinal Cancer Audit (DUCA), a national surgical outcome registry. The primary outcome was severe complications, defined as complications graded Clavien-Dindo ≥ 3. The secondary outcomes were postoperative complications, reintervention rates, length of hospital stays, and mortality. Outcomes were compared between patients aged ≥75 and < 75 years. We performed additional subgroup analyses between these age groups after totally minimally invasive esophagectomy (TMIE) and in patients with severe complications. We adjusted for the following parameters: gender, BMI, Charlson Comorbidity Index score (CCI), ASA score, histology, type of neoadjuvant therapy, and surgical technique., Results: Of all 3775 included patients, 455 (12.1%) were aged ≥75 years and 3302 (87.9%) were aged <75 years. Overall, severe complications occurred in 184 (40.4%) older and in 1140 (34.5%) younger patients (CI = 1.009-1.080). After TMIE, severe complications occurred in 150 (42.1%) older and in 891 (35.8%) younger patients (CI = 1.007-1.088). In patients with severe complications, rates of complications, reinterventions, mortality, and ICU stays were comparable between older and younger patients. After adjustment for casemix, age and CCI score were not independent risk factors for (severe) complications and mortality., Conclusions: Age and Charlson Comorbidity Index are not adequate predictors of postoperative morbidity and mortality after curative esophagectomy for esophageal cancer., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Robotic surgery may improve surgical performance during minimally invasive pancreatoduodenectomy as compared to 3D- and 2D-laparoscopy but comparative studies are lacking. This study assessed the impact of robotic surgery versus 3D- and 2D-laparoscopy on surgical performance and operative time using a standardized biotissue model for pancreatico- and hepatico-jejunostomy using pooled data from two randomized controlled crossover trials (RCTs)., Methods: Pooled analysis of data from two RCTs with 60 participants (36 surgeons, 24 residents) from 11 countries (December 2017-July 2019) was conducted. Each included participant completed two pancreatico- and two hepatico-jejunostomies in biotissue using 3D-robotic surgery, 3D-laparoscopy, or 2D-laparoscopy. Primary outcomes were the objective structured assessment of technical skills (OSATS: 12-60) rating, scored by observers blinded for 3D/2D and the operative time required to complete both anastomoses. Sensitivity analysis excluded participants with excess experience compared to others., Results: A total of 220 anastomoses were completed (robotic 80, 3D-laparoscopy 70, 2D-laparoscopy 70). Participants in the robotic group had less surgical experience [median 1 (0-2) versus 6 years (4-12), p < 0.001], as compared to the laparoscopic group. Robotic surgery resulted in higher OSATS ratings (50, 43, 39 points, p = .021 and p < .001) and shorter operative time (56.5, 65.0, 81.5 min, p = .055 and p < .001), as compared to 3D- and 2D-laparoscopy, respectively, which remained in the sensitivity analysis., Conclusion: In a pooled analysis of two RCTs in a biotissue model, robotic surgery resulted in better surgical performance scores and shorter operative time for biotissue pancreatic and biliary anastomoses, as compared to 3D- and 2D-laparoscopy., (© 2021. The Author(s).)

Background: The probability of undergoing treatment with curative intent according to the hospital of diagnosis varies for esophagogastric cancer in the Netherlands. Little is known about the factors contributing to this variation. This study aimed to improve the understanding of the differences between the multidisciplinary team meeting treatment proposal and the treatment that was actually carried out and to qualitatively investigate the differences in treatment decision-making after the multidisciplinary team meeting treatment proposal between hospitals., Methods: To gain an in-depth understanding of treatment decision-making, quantitative data (i.e., multidisciplinary team meeting proposal and treatment that was carried out) were collected from the Netherlands Cancer Registry. Changes in the multidisciplinary team meeting proposal and applied treatment comprised changes in the type of treatment option (i.e., curative or palliative, or no change) and were calculated according to the multivariable multilevel probability of undergoing treatment with curative intent (low, middle, and high). Qualitative data were collected from eight hospitals, including observations of 26 outpatient clinic consultations, 30 in-depth interviews with clinicians, seven focus groups with clinicians, and three focus groups with patients. Clinicians and patients' perspectives were assessed using thematic content analysis., Results: The multidisciplinary team meeting proposal and applied treatment were concordant in 97% of the cases. Clinicians' implementation of treatment decision-making in clinical practice varied, which was mentioned by the clinicians to be due to the clinician's personality and values. Differences between clinicians consisted of discussing all treatment options versus only the best fitting treatment option and the extent of discussing the benefits and harms. Most patients aimed to undergo curative treatment regardless of the consequences, since they believed this could prolong their life., Conclusion: Since changes in the multidisciplinary team meeting-proposed treatment and actual treatment were rarely observed, this study emphasizes the importance of an adequately formulated multidisciplinary team meeting proposal., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival., Methods and Results: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001)., Conclusions: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: Data on the age-specific incidence of esophageal cancer are lacking. Our aim was to investigate the age-stratified incidence, treatment, and survival trends of esophageal cancer in the Netherlands, with a focus on adults <50 years., Material and Methods: Patients diagnosed with esophageal cancer were included from the nationwide Netherlands Cancer Registry (1989-2018). Follow-up data were available until 31 December 2018. Annual percentage changes of incidence were analyzed according to age group (<50, 50-74, and ≥75 years) and histology type: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). Treatment trends and relative survival rates (RSR) were estimated by age and stage grouping., Results: A total 59,584 patients were included. In adults <50 years, EAC incidence tripled (mean increase per year: males 1.5%, females 3%), while the incidence of ESCC decreased (mean decrease per year: males -5.3%, females -4.3%). Patients <50 years more often presented with advanced disease stages compared to older patients and were more likely to receive multimodality treatments. Most patients <50 years with potentially curable disease were treated with neoadjuvant chemoradiotherapy followed by surgery compared to patients 50-74 and ≥75 years (74% vs. 55% vs. 15%, respectively; p  < .001), and received more frequent systemic therapy once staged with palliative disease (72% vs. 54% vs. 19%, respectively; p  < .001). The largest RSR improvement was seen in patients <50 years with early-stage (five years: +47%), potentially curable (five years: +22%), and palliative disease (one year: +11%). Over time, a trend of increasing survival difference was seen between patients <50 and ≥75 years with potentially curable (five-year difference: 17% to 27%) and palliative disease (one-year difference: 11% to 20%)., Conclusion: The incidence of EAC is increasing in adults <50 years in the Netherlands. Differences in the use of multimodality treatments with curative or life-prolonging intent in different age categories may account for increasing survival gaps.

Objective: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors., Background: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning., Methods: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision., Results: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume <50. Analysis with an annual volume cut-off of 30 cases showed similar but less pronounced results. No outcomes suggesting more efficient learning were found for longer experience as consultant, visiting an expert clinic, completing a minimally invasive esophagectomy fellowship or implementation under proctor supervision., Conclusions: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Among esophagogastric cancer patients, the probability of having undergone treatment with curative intent has been shown to vary, depending on the hospital of diagnosis. However, little is known about the factors that contribute to this variation. In this study, we sought to understand the organization of clinical pathways and their association with variation in practice., Methods: A mixed-method study using quantitative and qualitative data was conducted. Quantitative data were obtained from the Netherlands Cancer Registry (e.g., outpatient clinic consultations and diagnostic procedures). For qualitative data, thematic content analysis was performed using semi-structured interviews (n = 30), observations of outpatient clinic consultations (n = 26), and multidisciplinary team meetings (MDTM, n = 16) in eight hospitals, to assess clinicians' perspectives regarding the clinical pathways., Results: Quantitative analyses showed that patients more often underwent surgical consultation prior to the MDTM in hospitals associated with a high probability of receiving treatment with curative intent, but more often consulted with a geriatrician in hospitals associated with a low probability of such treatment. The organization of clinical pathways was analyzed quantitatively at three levels: regional, local, and patient levels. At a regional level, hospitals differed in terms of the number of patients discussed during the MDTM. At the local level, the revision of radiological images and restaging after neoadjuvant treatment varied. At the patient level, some hospitals routinely conduct fitness tests, whereas others estimated the patient's physical fitness during an outpatient clinic consultation. Few clinicians performed a standard geriatric consultation in older patients to assess their mental fitness and frailty., Conclusion: Surgical consultation prior to MDTM was more often conducted in hospitals associated with a high probability of receiving treatment with curative intent, whereas a geriatrician was consulted more often in hospitals associated with a low probability of receiving such treatment., (© 2022. The Author(s).)

Background: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase., Materials and Methods: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance., Results: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged ≤70 years., Conclusion: With nationwide centralization, travel distance increased for patients undergoing oesophageal, gastric, and pancreatic cancer surgery. Younger patients travelled longer distances and experienced a lower travel burden, as compared to elderly patients. Nevertheless, on a global scale, travel distances in the Netherlands remain limited., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)