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To date no informative biomarkers exist to accurately predict presence of lymph node metastases (LNM) in esophageal adenocarcinoma (EAC). We studied the discriminative value of Olfactomedin 4 (OLFM4), an intestinal stem cell marker, in EAC. Patients who had undergone esophagectomy as single treatment modality for both advanced (pT2-4) and early (pT1b) adenocarcinoma of the esophagus or gastro-esophageal junction were selected for this study from an institutional database (Erasmus MC University Medical Center, Rotterdam, The Netherlands). Surgical resection specimens of 196 advanced and 44 early EAC were examined. OLFM4 expression was studied by immunohistochemistry and categorized as low (<30%) or high (> = 30%) expression. Low OLFM4 was associated with poor differentiation grade in both advanced (60% vs. 34.8%, p = 0.001) and early EAC (39.1% vs. 9.5%, p = 0.023). LNM were present in 161 (82.1%) of advanced and 9 (20.5%) of early EAC respectively. Low OLFM4 was independently associated with the presence of LNM in advanced EAC in multivariable analysis (OR 2.7; 95% CI, 1.16–6.41; p = 0.022), but not in early EAC (OR 2.1; 95% CI, 0.46–9.84; p = 0.338). However, the difference in association with LNM between advanced (OR 2.7; 95% CI, 1.18–6.34; p = 0.019) and early (OR 2.3; 95% CI, 0.47–11.13; p = 0.302) EAC was non-significant (p = 0.844), suggesting that the lack of significance in early EAC is due to the small number of patients in this group. OLFM4 was not of significance for the disease free and overall survival. Overall, low expression of intestinal stem cell marker OLFM4 was associated with the presence of LNM. Our study suggests that OLFM4 could be an informative marker with the potential to improve preoperative assessment in patients with EAC. Further studies are needed to confirm the value of OLFM4 as a biomarker for LNM. [ABSTRACT FROM AUTHOR]

Importance: The optimal staging for gastric cancer remains a matter of debate., Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer., Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020., Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging., Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay., Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days., Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.

Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE., Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial., Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020., Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis., Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life., Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7])., Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer., Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333).

Background: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy., Methods: The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness., Discussion: In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient., Trial Registration: NCT02248519.

Objective: Preoperative weight loss might increase the risk of postoperative morbidity and mortality after esophagectomy for cancer. We hypothesized that patients with esophageal cancer with >10% weight loss during the 3 months before their diagnosis would be at an increased risk of postoperative complications, have a longer length of stay, and have worse overall survival., Methods: In the present hospital-based cohort study, all patients who had undergone surgery for esophageal cancer in 1990 to 2010 at the Erasmus University Medical Center Rotterdam were included. Weight loss was defined as "no, or limited" (≤10%) or "severe" (>10%). Logistic regression analysis was used to estimate the relative risk of complications, expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Hazard ratios were calculated to assess the length of hospital stay and survival. The risk estimates were adjusted for potential confounding factors., Results: Of 922 included patients, 155 (17%) had experienced severe weight loss. These patients had no increased risk of early surgical, early nonsurgical, or late surgical complications (OR, 0.83 and 95% CI, 0.54-1.24; OR, 0.90 and 95% CI, 0.63-1.30; OR, 1.14 and 95% CI, 0.79-1.66, respectively) and had no increased length of stay (hazard ratio, 1.09; 95% CI, 0.89-1.35). Preoperative weight loss was followed by increased 5-year mortality (hazard ratio, 1.34; 95% CI, 1.02-1.74)., Conclusions: A >10% preoperative weight loss was followed by decreased 5-year survival after esophageal cancer surgery but no increased risk of postoperative complications., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Currently, most surgical training programs are focused on the development and evaluation of professional competencies. Also in the Netherlands, competency-based training and assessment programs were introduced to restructure postgraduate medical training. The current surgical residency program is based on the Canadian Medical Education Directives for Specialists (CanMEDS) competencies and uses assessment tools to evaluate residents' competence progression. In this study, we examined the attitude of surgical residents and attending surgeons toward a competency-based training and assessment program used to restructure general surgical training in the Netherlands in 2009., Methods: In 2011, all residents (n = 51) and attending surgeons (n = 108) in 1 training region, consisting of 7 hospitals, were surveyed. Participants were asked to rate the importance of the CanMEDS competencies and the suitability of the adopted assessment tools. Items were rated on a 5-point Likert scale and considered relevant when at least 80% of the respondents rated an item with a score of 4 or 5 (indicating a positive attitude). Reliability was evaluated by calculating the Cronbach's α, and the Mann-Whitney test was applied to assess differences between groups., Results: The response rate was 88% (n = 140). The CanMEDS framework demonstrated good reliability (Cronbach's α = 0.87). However, the importance of the competencies 'Manager' (78%) and 'Health Advocate' (70%) was undervalued. The assessment tools failed to achieve an acceptable reliability (Cronbach's α = 0.55), and individual tools were predominantly considered unsuitable for assessment. Exceptions were the tools 'in-training evaluation report' (91%) and 'objective structured assessment of technical skill' (82%). No significant differences were found between the residents and the attending surgeons., Conclusion: This study has demonstrated that, 2 years after the reform of the general surgical residency program, residents and attending surgeons in a large training region in the Netherlands do not acknowledge the importance of all CanMEDS competencies and consider the assessment tools generally unsuitable for competence evaluation., (Copyright © 2013 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Standardised uptake values (SUVs) depend on acquisition, reconstruction and region of interest (ROI) parameters. SUV quantification in multi-centre trials therefore requires standardisation of acquisition and analysis protocols. However, standardisation is difficult owing to the use of different scanners, image reconstruction and data analysis software. In this study we evaluated whether SUVs, obtained at three different institutes, may be directly compared after calibration and correction for inter-institute differences., Methods: First, an anthropomorphic thorax phantom containing variously sized spheres and activities, simulating tumours, was scanned and processed in each institute to evaluate differences in scanner calibration. Secondly, effects of image reconstruction and ROI method on recovery coefficients were studied. Next, SUVs were derived for tumours in 23 subjects. Of these 23 patients, four and ten were scanned in two institutes on an HR+ PET scanner and nine were scanned in one institute on an ECAT EXACT PET scanner. All phantom and clinical data were reconstructed using iterative reconstruction with various iterations, with both measured (MAC) and segmented attenuation correction (SAC) and at various image resolutions. Activity concentrations (AC) or SUVs were derived using various ROI isocontours., Results: Phantom data revealed differences in SUV quantification of up to 30%. After application-specific calibration, recovery coefficients obtained in each institute were equal to within 15%. Varying the ROI isocontour value resulted in a predictable change in SUV (or AC) for both phantom and clinical data. Variation of image resolution resulted in a predictable change in SUV quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2 cc), differences of up to 40% were found between high (7 mm) and low (10 mm) resolution images. Similar differences occurred when data were reconstructed with a small number of iterations. Finally, no significant differences between MAC and SAC reconstructed data were observed, except for tumours near the diaphragm., Conclusion: Standardisation of acquisition, reconstruction and ROI methods is preferred for SUV quantification in multi-centre trials. Small unavoidable differences in methodology can be accommodated by performing a phantom study to assess inter-institute correction factors.

Objectives: The convergent validity between utility assessment methods was assessed., Methods: Investigated were patients with esophageal cancer treated surgically with curative intent. Patients were interviewed in a period from 3 to 12 months after surgical resection. Patients evaluated their actual health and seven other states. Visual analogue scale (VAS) and standard gamble (SG) utilities were obtained for the health states in an interview. Patients also indicated whether or not they preferred death to living in a health state (worse than dead [WTD] preferences)., Results: Fifty patients completed the interview. Convergent validity was excellent at the aggregate and individual level. However, the relation between VAS and SG differed strongly across individuals. On a scale from 0 (dead) to 100 (perfect health), SG scores were lower for patients with WTD preferences (mean difference d = 35; p = .002); however, VAS scores did not vary by WTD preferences., Conclusions: In general, there is good agreement between VAS and SG measures, although patients disagree about how the VAS and SG are related. The standard gamble varied by WTD preferences, however, the VAS did not.