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.

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.

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.

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

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

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

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

The Association Between Preoperative Inspiratory Muscle Training Variables and Postoperative Pulmonary Complications in Subjects With Esophageal Cancer.

BACKGROUND: Preoperative inspiratory muscle training (IMT) is frequently used in patients waiting for major surgery to improve respiratory muscle function and to reduce the risk of postoperative pulmonary complications (PPCs). Currently, the mechanism of action of IMT in reducing PPCs is still unclear. Therefore, we investigated the associations between preoperative IMT variables and the occurrence of PPCs in patients with esophageal cancer. METHODS: A multi-center cohort study was conducted in subjects scheduled for esophagectomy, who followed IMT as part of a prehabilitation program. IMT variables included maximum inspiratory pressure (PImax) before and after IMT and IMT intensity variables including training load, frequency, and duration. Associations between PImax and IMT intensity variables and PPCs were analyzed using independent samples t tests and logistic regression analyses, corrected for age and pulmonary comorbidities and stratified for the occurrence of anastomotic leakages. RESULTS: Eighty-seven subjects were included (69 males; mean age 66.7 ± 7.3 y). A higher PImax (odds ratio 1.016, P = .07) or increase in PImax during IMT (odds ratio 1.020, P = .066) was not associated with a reduced risk of PPCs after esophagectomy. Intensity variables of IMT were also not associated (P ranging from .16 to .95) with PPCs after esophagectomy. Analyses stratified for the occurrence of anastomotic leakages showed no associations between IMT variables and PPCs. CONCLUSIONS: This study shows that an improvement in preoperative inspiratory muscle strength during IMT and training intensity of IMT were not associated with a reduced risk on PPCs after esophagectomy. Further research is needed to investigate other possible factors explaining the mechanism of action of preoperative IMT in patients undergoing major surgery, such as the awareness of patients related to respiratory muscle function and a diaphragmatic breathing pattern.

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

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

Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

BACKGROUND: Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. METHODS: All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. RESULTS: Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. CONCLUSION: For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

The Comprehensive Complication Index versus Clavien-Dindo grading after laparoscopic and open D2-gastrectomy in the multicenter randomized LOGICA-trial.

BACKGROUND: Complications can be classified using the most-severe Clavien-Dindo-Classification (CDC) per patient or the total complication burden per patient expressed in the Comprehensive Complication Index (CCI). This study determined the additional value of CCI to CDC in examining the impact of complications after gastric cancer surgery. METHODS: The CCI and CDC were determined in the multicenter randomized LOGICA-trial comparing laparoscopic versus open D2-gastrectomy for cancer (cT1-4aN0-3M0). Differences in median CCI between laparoscopic and open gastrectomy were compared for overall postoperative complications and cardiovascular, gastrointestinal, infectious, pulmonary, and other complications. CCI and CDC were correlated to hospitalization, ICU-stay and reoperations using Spearman's rho-test and compared with standard Fisher's z-transformation. RESULTS: Between 2015 and 2018, 211 patients underwent laparoscopic (n = 106) or open (n = 105) D2-gastrectomy, and 157 (74%) received neoadjuvant chemotherapy. Median CCI was comparable between laparoscopic versus open gastrectomy regarding overall complications (CCI 0 [IQR 0-23.5] versus 0 [IQR 0-22.6]; p = 0.755) and subgroups of complications (p > 0.05). Both CCI and CDC showed moderate positive correlations for hospitalization (rs = 0.646 versus rs = 0.628; p = 0.001, difference clinically irrelevant), and reoperations (rs = 0.590 versus rs = 0.599; p = 0.070), and weak correlations for ICU-stay (rs = 0.446 versus rs = 0.440; p = 0.189). CONCLUSIONS: The CCI is a composite scoring system based on the CDC and reflects a subjective interpretation of complication burden from the perspectives of both physicians and patients, following abdominal surgery other than gastrectomy. Implementing CCI showed no clinically relevant benefit and caused additional workload compared to CDC for assessing complication burden. Therefore, using the CCI alongside the CDC after gastric cancer surgery is not recommended.

Effects of exercise during chemo- or radiotherapy on immune markers - a systematic review.

Introduction Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise was shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate and high intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy, on immune markers. Methods For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the Pedro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results Methodological quality of the 15 included articles was rated fair to good. The majority of markers was unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some pro-inflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Discussion/conclusion Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.

Surgical quality and prospective quality control of the D2-gastrectomy for gastric cancer in the multicenter randomized LOGICA-trial.

BACKGROUND: Quality of gastric cancer surgery is crucial for favorable prognosis. Generally, prospective trials lack quality control measures. This study assessed surgical quality and a novel D2-lymphadenectomy photo-scoring in the LOGICA-trial. METHODS: The multicenter LOGICA-trial randomized laparoscopic versus open total/distal D2-gastrectomy for resectable gastric cancer (cT1-4aN0-3M0) in 10 Dutch hospitals. During the trial, two reviewers prospectively analyzed intraoperative photographs of dissected nodal stations for quality control, and provided centers weekly feedback on their D2-lymphadenectomy, as continuous quality-enhancing incentive. After the trial, these photographs were reanalyzed to develop a photo-scoring for future trials, rating the D2-lymphadenectomy dissection quality (optimal-good-suboptimal-unevaluable). Interobserver variability was calculated (weighted kappa). Regression analyses related the photo-scoring to nodal yield, recurrence and 5-years survival. RESULTS: Between 2015 and 2018, 212 patients underwent total/distal D2-gastrectomy (n = 122/n = 90), and 158 (75%) received neoadjuvant chemotherapy. R0-resection rate was 95%. Rate of ≥15 retrieved lymph nodes was 95%. Moderate agreement was obtained in stations 8 + 9 (κ = 0.522), 11p/11d (κ = 0.446) and 12a (κ = 0.441). Consensus was reached for discordant cases (30%). Stations 8 + 9, 11p/11d and 12a were rated 'optimal' in 76%, 63% and 68%. Laparoscopic photographs could be rated better than open (2% versus 12% 'unevaluable'; 73% versus 50% 'optimal'; p = 0.042). The photo-scoring did not show associations with nodal yield (p = 0.214), recurrence (p = 0.406) and survival (p = 0.988). CONCLUSIONS: High radicality and nodal yield demonstrated good quality of D2-gastrectomy. The prospective quality control probably contributed to this. The photo-scoring did not show good performance, but can be refined. Laparoscopic D2-gastrectomy was better suited for standardized surgical photo-evaluation than open surgery.

Incidence, Stage, Treatment, and Survival of Noncardia Gastric Cancer.

Importance: Gastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions. Objective: To analyze the trends in incidence, staging, and treatment of gastric cancer. Design, Setting, and Participants: This nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands. Main Outcomes and Measures: Differences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021). Results: In total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%). Conclusions and Relevance: In this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival.

Cost analysis of robot-assisted versus open transthoracic esophagectomy for resectable esophageal cancer. Results of the ROBOT randomized clinical trial.

BACKGROUND: The previously published ROBOT trial demonstrated that robot assisted minimally invasive esophagectomy (RAMIE) is associated with a lower percentage of postoperative complications compared to open esophagectomy (OTE) for patients with esophageal cancer. The implications of these results on healthcare costs are important given the increased attention for cost-reduction in healthcare. Therefore the aim of this study was to report the hospital costs of RAMIE compared to OTE as treatment for esophageal cancer. METHODS: The ROBOT trial randomized 112 patients with esophageal cancer between RAMIE and OTE through January 2012 and August 2016 in a single tertiary care academic centre in the Netherlands. The primary outcome of the current study was hospital costs from the day of esophagectomy until 90 days after discharge based on Time-Driven Activity-Based Costing methodology. Secondary outcomes included the incremental cost-effectiveness ratio per complication prevented and risk factors for increased hospital costs. RESULTS: Of the 112 included patients, 109 patients underwent an esophagectomy, of whom 54 RAMIE and 55 OTE. The mean total hospital costs were comparable between RAMIE €40211 and OTE €39495 (mean difference €-715; bias-corrected and accelerated confidence interval € -14831 to 14783, p = 0.932). At a willingness-to-pay threshold of €20.000 to €25.000 (i.e. estimated additional costs to the hospital to treat patients with a complication) RAMIE had a probability 62%-70% of being cost effective to prevent postoperative complications. In multivariable regression analysis, major postoperative complications were the main driver of hospital costs after esophagectomy (€31839, p = 0.009). CONCLUSION: In this randomized trial RAMIE resulted in fewer postoperative complications compared to OTE without increasing total hospital costs.

Pain and Opioid Consumption After Laparoscopic Versus Open Gastrectomy for Gastric Cancer: A Secondary Analysis of a Multicenter Randomized Clinical Trial (LOGICA-Trial).

BACKGROUND: Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail. METHODS: This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1-5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0-10) at POD 1-10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia. RESULTS: Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1-3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p < 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1-2 (47 mg OME, p = 0.002 and 69 mg OME, p < 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, < 2 at discharge, and did not relevantly differ between treatment arms. CONCLUSION: In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. TRIAL REGISTRATION: NCT02248519.

A novel anatomical description of the esophagus: the supracarinal mesoesophagus.

BACKGROUND: During thoracoscopic esophageal resection, while performing the supracarinal lymphadenectomy along the left recurrent laryngeal nerve (LRLN) from the aortic arch to the thoracic apex, we observed a not previously described bilayered fascia-like structure, serving as prolongation of the already known mesoesophagus. METHODS: We retrospectively evaluated 70 consecutively unedited videos of thoracoscopic interventions on esophageal resections for cancer, in order to determine the validity of this finding and to describe its utility for performing a systematic and more accurate dissection of the LRLN and its adequate lymphadenectomy. RESULTS: After mobilization of the upper esophagus from the trachea and tilting the esophagus by means of two ribbons, a bilayered fascia was observed between the esophagus and the left subclavian artery in 63 of the 70 patients included in this study. By opening the right layer, the left recurrent nerve became visualized and could be dissected free in its whole trajectory. Vessels and branches of the LRLN were divided between miniclips. Mobilizing the esophagus to the right, the base of this fascia could be found at the left subclavian artery. After dissecting and clipping the thoracic duct, complete lymphadenectomy of 2 and 4L stations could be performed. Mobilizing the esophagus in distal direction, the fascia continued at the level of the aortic arch, where it had to be divided in order to mobilize the esophagus from the left bronchus. Here, a lymphadenectomy of the aorta-pulmonary window lymph nodes (station 8) can be performed. It seems that from there the fascia continued without interruption with the previously described mesoesophagus between the thoracic aorta and the esophagus. CONCLUSIONS: Here we described the concept of the supracarinal mesoesophagus on the left side. Applying the description of the mesoesophagus will create a better understanding of the supracarinal anatomy, leading to a more adequate and reproducible surgery.

Distal Versus Total D2-Gastrectomy for Gastric Cancer: a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial.

BACKGROUND: Distal gastrectomy (DG) for gastric cancer can cause less morbidity than total gastrectomy (TG), but may compromise radicality. No prospective studies administered neoadjuvant chemotherapy, and few assessed quality of life (QoL). METHODS: The multicenter LOGICA-trial randomized laparoscopic versus open D2-gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0) in 10 Dutch hospitals. This secondary LOGICA-analysis compared surgical and oncological outcomes after DG versus TG. DG was performed for non-proximal tumors if R0-resection was deemed achievable, TG for other tumors. Postoperative complications, mortality, hospitalization, radicality, nodal yield, 1-year survival, and EORTC-QoL-questionnaires were analyzed using Χ2-/Fisher's exact tests and regression analyses. RESULTS: Between 2015 and 2018, 211 patients underwent DG (n = 122) or TG (n = 89), and 75% of patients underwent neoadjuvant chemotherapy. DG-patients were older, had more comorbidities, less diffuse type tumors, and lower cT-stage than TG-patients (p < 0.05). DG-patients experienced fewer overall complications (34% versus 57%; p < 0.001), also after correcting for baseline differences, lower anastomotic leakage (3% versus 19%), pneumonia (4% versus 22%), atrial fibrillation (3% versus 14%), and Clavien-Dindo grading compared to TG-patients (p < 0.05), and demonstrated shorter median hospital stay (6 versus 8 days; p < 0.001). QoL was better after DG (statistically significant and clinically relevant) in most 1-year postoperative time points. DG-patients showed 98% R0-resections, and similar 30-/90-day mortality, nodal yield (28 versus 30 nodes; p = 0.490), and 1-year survival after correcting for baseline differences (p = 0.084) compared to TG-patients. CONCLUSIONS: If oncologically feasible, DG should be preferred over TG due to less complications, faster postoperative recovery, and better QoL while achieving equivalent oncological effectiveness. Distal D2-gastrectomy for gastric cancer resulted in less complications, shorter hospitalization, quicker recovery and better quality of life compared to total D2-gastrectomy, whereas radicality, nodal yield and survival were similar.