Paravertebral versus EPidural Analgesia in Minimally Invasive Esophageal ResectioN (PEPMEN): A Randomized Controlled Multicenter Trial.

OBJECTIVE: To compare quality of recovery in patients receiving epidural or paravertebral analgesia for minimally invasive esophagectomy (MIE). SUMMARY BACKGROUND DATA: Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery. METHODS: This randomized controlled superiority trial was conducted across four Dutch centers with esophageal cancer patients scheduled for transthoracic MIE with intrathoracic anastomosis, randomizing patients to receive either epidural or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included quality of life, postoperative pain, opioid consumption, inotropic/vasopressor medication use, hospital stay, complications, readmission, and mortality. RESULTS: From December 2019 to February 2023, 192 patients were included: 94 received epidural and 98 paravertebral analgesia. QoR-40 score on POD3 was not different between groups (mean difference 3.7, 95%CI -2.3 to 9.7; P=0.268). Epidural patients had significant higher QoR-40 scores on POD1 and 2 (mean difference 7.7, 95%CI 2.3-13.1; P=0.018 and mean difference 7.3, 95%CI 1.9-12.7; P=0.020) and lower pain scores (median 1 versus 2; P=<0.001 and median 1 versus 2; P=0.033). More epidural patients required vasopressor medication on POD1 (38.3% versus 13.3%; P<0.001). Urinary catheters were removed earlier in the paravertebral group (median POD3 versus 4; P=<0.001). No significant differences were found in postoperative complications or hospital/Intensive Care Unit stay. CONCLUSIONS: This randomized controlled trial did not demonstrate superiority of paravertebral over epidural analgesia regarding quality of recovery on POD3 after MIE. Both techniques are effective and can be offered in clinical practice.

Augmented Reality Implementation in Minimally Invasive Surgery for Future Application in Pulmonary Surgery: A Systematic Review.

OBJECTIVE: This systematic review investigates of Augmented Reality (AR) systems used in minimally invasive surgery of deformable organs, focusing on initial registration, dynamic tracking, and visualization. The objective is to acquire a comprehensive understanding of the current knowledge, applications, and challenges associated with current AR-techniques, aiming to leverage these insights for developing a dedicated AR pulmonary Video or Robotic Assisted Thoracic Surgery (VATS/RATS) workflow. METHODS: A systematic search was conducted within Embase, Medline (Ovid) and Web of Science on April 16, 2024, following the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA). The search focused on intraoperative AR applications and intraoperative navigational purposes for deformable organs. Quality assessment was performed and studies were categorized according to initial registration and dynamic tracking methods. RESULTS: 33 articles were included, of which one involved pulmonary surgery. Studies used both manual and (semi-) automatic registration methods, established through anatomical landmark-based, fiducial-based, or surface-based techniques. Diverse outcome measures were considered, including surgical outcomes and registration accuracy. The majority of studies that reached an registration accuracy below 5 mm applied surface-based registration. CONCLUSIONS: AR can potentially aid surgeons with real-time navigation and decision making during anatomically complex minimally invasive procedures. Future research for pulmonary applications should focus on exploring surface-based registration methods, considering their non-invasive, marker-less nature, and promising accuracy. Additionally, vascular-labeling-based methods are worth exploring, given the importance and relative stability of broncho-vascular anatomy in pulmonary VATS/RATS. Assessing clinical feasibility of these approaches is crucial, particularly concerning registration accuracy and potential impact on surgical outcomes.

Comparison between AJCC 8th edition gastric and esophageal ypTNM classification system in Siewert II esophagogastric junction adenocarcinomas: A retrospective study based on Eastern and Western Data.

INTRODUCTION: Multimodal therapy has become the standard treatment for curable upper gastrointestinal cancers. However, it remains unclear which 8th edition AJCC post-neoadjuvant therapy pathological classification system, esophageal (ypTNM-EC) or gastric (ypTNM-GC), can predict the overall survival (OS) of patients with Siewert II adenocarcinomas better. METHODS: Patients diagnosed with Siewert II adenocarcinomas receiving neoadjuvant therapy plus curative resection at the University Medical Center Utrecht (UMC Utrecht) and the Peking University Cancer Hospital (PUCH) between the 2001 and 2022 were included in this study. The patients from two institutions were analyzed separately. Predictive univariable and multivariable Cox models based on ypTNM-EC and ypTNM-GC were constructed. The C-index and calibration curves were used to compare the predictive abilities of ypTNM-EC and ypTNM-GC Cox models. RESULTS: A total of 125 patients from UMCU and 145 from PUCH were included. There was no significant difference in the C-index between the ypTNM-EC and the ypTNM-GC univariable and multivariable Cox models in the UMC Utrecht (p-value = 0.883; p-value=0.681) and PUCH (p-value = 0.808; p-value=0.548) cohorts, and no significant difference was observed between their calibration curves in the two cohorts. CONCLUSION: The AJCC 8th edition ypTNM prognostic classification systems for esophageal and gastric cancer demonstrated no difference in predicting OS for patients with Siewert II adenocarcinomas both in the Western and Eastern data. The ypTNM-GC, with fewer stage groups, may offer greater convenience for clinical application.

Histopathological response to chemotherapy and survival of mucinous type gastric cancer.

BACKGROUND: Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. METHODS: Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). RESULTS: In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). CONCLUSION: Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

Evaluation of Treatment Strategies and Survival of Patients with cT4bM0 Esophageal Cancer: A Nationwide Cohort Study.

INTRODUCTION: The optimal therapeutic strategy for patients with cT4bM0 esophageal cancer is controversial and varies internationally. This study aimed to describe treatment and survival of patients with cT4bM0 esophageal cancer in the Netherlands. METHODS: Patients staged with cT4bM0 esophageal cancer who were registered in the Netherlands Cancer Registry (NCR) were included. All patients were categorized by the treatment modality received. The Kaplan-Meier method was used to estimate the overall survival of them. RESULTS: Between 2015 and 2020, 286 patients with cT4bM0 esophageal cancer were included. Treatment consisted of preoperative chemoradiotherapy/chemotherapy followed by surgery (8%), chemoradiotherapy alone (35%), chemotherapy alone (6%), radiotherapy alone (19%), and best supportive care (32%). The median follow-up was 28.1 months. The 1-, 3-, and 5-year survival rates of each group were 82%, 58%, 49% for preoperative therapy plus surgery; 53%, 27%, 16% for chemoradiotherapy only; 13%, 0%, 0% for chemotherapy only; 13%, 0%, 0% for radiotherapy only; and 5%, 0%, 0% for best supportive care. CONCLUSION: In a selected group of patients, preoperative therapy followed by esophagectomy may lead to improved survival, which is comparable to patients with <cT4bM0 tumors. Therefore, reevaluation following chemo(radio)therapy is recommended in these patients to evaluate the possibility of additional surgical resection.

Impact of Preoperative Time Intervals for Neoadjuvant Chemoradiotherapy on Short-term Postoperative Outcomes of Esophageal Cancer Surgery: A Population-Based Study Using the Dutch Upper Gastrointestinal Cancer Audit (DUCA) Data.

OBJECTIVE: To clarify the impact of the preoperative time intervals on short-term postoperative and pathological outcomes in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. SUMMARY BACKGROUND DATA: The impact of preoperative intervals on esophageal cancer patients who received multimodality treatment remains unknown. METHODS: Patients(cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA-database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathological outcomes: diagnosis-to-nCRT intervals (≤5, 5-8 and 8-12 wk), nCRT-to-surgery intervals (5-11, 11-17 and >17 wk) and total preoperative intervals (≤16, 16-25 and >25 wk). RESULTS: Between 2010-2021, a total of 5052 patients were included. Compared to diagnosis-to-nCRT interval ≤5 weeks, the interval 8-12 weeks was associated with higher risk of overall complications (P=0.049). Compared to nCRT-to-surgery interval 5-11 weeks, the longer intervals (11-17 wk and >17 wk) were associated with higher risk of overall complications (P-value=0.016; P-value<0.001) and anastomotic leakage (P-value=0.004; P-value=0.030), but the interval >17 weeks was associated with lower risk of ypN+ (P-value=0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared to the interval ≤16 weeks, but the longer total preoperative interval (>25 wk) was associated with higher ypT stage (P-value=0.010) and lower pCR rate (P-value=0.013). CONCLUSION: In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation.

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

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

Electrical vagus nerve stimulation is a promising approach to reducing pulmonary complications after an esophagectomy: an experimental rodent model.

After esophagectomy, an imbalanced inflammatory response increases the risk of postoperative morbidity. The vagus nerve modulates local and systemic inflammatory responses, but its pulmonary branches are transected during esophagectomy as part of the oncological resection, which may account for the high incidence of postoperative (pulmonary) complications. This study investigated the effect of electrical vagus nerve stimulation (VNS) on lipopolysaccharide (LPS)-induced lung injury in rats. Rats (n = 60) were randomly assigned to a non-vagotomy or cervical vagotomy group, with VNS or without (NOSTIM). There were four non-vagotomy groups: NOSTIM and bilateral VNS with 100, 50, or 10 µA. The four vagotomy groups were NOSTIM and VNS with fixed amplitude (50 µA) bilaterally before (VNS-50-before) or after bilateral vagotomy (VNS-50-after), or unilaterally (left) before ipsilateral vagotomy (VNS-50-unilaterally). LPS was administered intratracheally after surgery. Pulmonary function, pro-inflammatory cytokines in serum, broncho-alveolar lavage fluid (BALF), and histopathological lung injury (LIS) were assessed 180 min post-procedure. In non-vagotomized rats, neutrophil influx in BALF following intra-tracheal LPS (mean 30 [± 23]; P = 0.075) and LIS (mean 0.342 [± 0.067]; P = 0.142) were similar after VNS-100, compared with NOSTIM. VNS-50 reduced neutrophil influx (23 [± 19]; P = 0.024) and LIS (0.316 [± 0.093]; P = 0.043). VNS-10 reduced neutrophil influx (15 [± 6]; P = 0.009), while LIS (0.331 [± 0.053]; P = 0.088) was similar. In vagotomized rats, neutrophil influx (52 [± 37]; P = 0.818) and LIS (0.407 [SD ± 0.037]; P = 0.895) in VNS-50-before were similar compared with NOSTIM, as well as in VNS-50-after (neutrophils 30 [± 26]; P = 0.090 and LIS 0.344 [± 0.053]; P = 0.073). In contrast, VNS-50-unilaterally reduced neutrophil influx (26 [± 10]; P = 0.050) and LIS (0.296 [± 0.065]; P = 0.005). Systemic levels of cytokines TNF-α and IL-6 were undetectable in all groups. Pulmonary function was not statistically significantly affected. In conclusion, VNS limited influx of neutrophils in lungs in non-vagotomized rats and may attenuate LIS. Unilateral VNS attenuated lung injury even after ipsilateral vagotomy. This effect was absent for bilateral VNS before and after bilateral vagotomy. It is suggested that the effect of VNS is dependent on (partially) intact vagus nerves and that the level of the vagotomy during esophagectomy may influence postoperative pulmonary outcomes.

Discontinuation of neoadjuvant therapy does not influence postoperative short-term outcomes in elderly patients (≥ 70 years) with resectable gastric cancer: a population-based study from the dutch upper gastrointestinal cancer audit (DUCA) data.

BACKGROUND: For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. METHODS: Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. RESULTS: Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012). CONCLUSION: A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.

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

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

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

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

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

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

Identification of subgroups of patients with oesophageal cancer based on exercise intensity during prehabilitation.

PURPOSE: To identify subgroups of patients with oesophageal cancer based on exercise intensity during prehabilitation, and to investigate whether training outcomes varied between subgroups. MATERIALS AND METHODS: Data from a multicentre cohort study were used, involving participants following prehabilitation before oesophagectomy. Hierarchical cluster analysis was performed using four cluster variables (intensity of aerobic exercise, the Borg score during resistance exercise, intensity of physical activity, and degree of fatigue). Aerobic capacity and muscle strength were estimated before and after prehabilitation. RESULTS: In 64 participants, three clusters were identified based on exercise intensity. Cluster 1 (n = 23) was characterised by fatigue and physical inactivity, cluster 2 (n = 9) by a low training capacity, despite high physical activity levels, and cluster 3 (n = 32) by a high training capacity. Cluster 1 showed the greatest improvement in aerobic capacity (p = 0.37) and hand grip strength (p = 0.03) during prehabilitation compared with other clusters. CONCLUSIONS: This cluster analysis identified three subgroups with distinct patterns in exercise intensity during prehabilitation. Participants who were physically fit were able to train at high intensity. Fatigued participants trained at lower intensity but showed the greatest improvement. A small group of participants, despite being physically active, had a low training capacity and could be considered frail.

Implications for rehabilitationPatients with oesophageal cancer show different patterns of exercise intensity during prehabilitation, resulting in three distinct subgroups.Patients with a good level of physical fitness are able to train at high intensity and may require less intensive supervision during the programme.Fatigued patients are able to perform the training programme, having more room for improvement.A small group of frail patients seem to be at risk for overtraining and may require an adjusted training intensity.

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

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

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

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

Staging laparoscopy in gastric cancer patients: From a Dutch nationwide Delphi consensus towards a standardized protocol.

BACKGROUND: Staging laparoscopy is a common diagnostic tool in gastric cancer, but its performance varies widely. The aim of this study was to gain Dutch nationwide consensus regarding the indications for and execution of staging laparoscopy in patients with gastric cancer. METHODS: All surgeons in the Netherlands specialized in gastric cancer surgery (n = 52) were asked to participate in a Delphi consensus study. The study involved an initial questionnaire with a 3-point Likert scale, an online consensus meeting, and a second questionnaire using a 2-point Likert scale (agree/disagree). Consensus was defined as 70% or more agreement among participants. RESULTS: In total, 45 experts completed both questionnaires (87% response rate). Consensus was reached on the indication to perform staging laparoscopy in cT3-4 or cN + or diffuse-type gastric cancer, including Siewert type III oesophagogastric junctional cancer. The experts agreed that if preoperative scans suggest infiltration of surrounding organs (cT4), the tumour's resectability should explicitly be investigated. Consensus was also reached for a systematic peritoneal cavity inspection according to Sugarbaker's Peritoneal Cancer Index (PCI) score. All regions should be inspected routinely, although the omental bursa may be inspected on indication. Aspiration of ascites or peritoneal washing should be performed for cytology. The experts agreed that restaging laparoscopy should be performed before resection in case of progressive disease on preoperative imaging. Without progression, global inspection was considered sufficient. CONCLUSIONS: The results of this Dutch nationwide Delphi consensus study exposed the variability of performing staging laparoscopy in patients with gastric cancer and provided the concept for a standardized protocol.

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

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