External validation of ¹⁸F-FDG PET-based radiomic models on identification of residual oesophageal cancer after neoadjuvant chemoradiotherapy

Objectives Detection of residual oesophageal cancer after neoadjuvant chemoradiotherapy (nCRT) is important to guide treatment decisions regarding standard oesophagectomy or active surveillance. The aim was to validate previously developed 18F-FDG PET-based radiomic models to detect residual local tumour and to repeat model development (i.e. 'model extension') in case of poor generalisability. Methods This was a retrospective cohort study in patients collected from a prospective multicentre study in four Dutch institutes. Patients underwent nCRT followed by oesophagectomy between 2013 and 2019. Outcome was tumour regression grade (TRG) 1 (0% tumour) versus TRG 2-3-4 (≥1% tumour). Scans were acquired according to standardised protocols. Discrimination and calibration were assessed for the published models with optimism-corrected AUCs &gt;0.77. For model extension, the development and external validation cohorts were combined. Results Baseline characteristics of the 189 patients included [median age 66 years (interquartile range 60-71), 158/189 male (84%), 40/189 TRG 1 (21%) and 149/189 (79%) TRG 2-3-4] were comparable to the development cohort. The model including cT stage plus the feature 'sum entropy' had best discriminative performance in external validation (AUC 0.64, 95% confidence interval 0.55-0.73), with a calibration slope and intercept of 0.16 and 0.48 respectively. An extended bootstrapped LASSO model yielded an AUC of 0.65 for TRG 2-3-4 detection. Conclusion The high predictive performance of the published radiomic models could not be replicated. The extended model had moderate discriminative ability. The investigated radiomic models appeared inaccurate to detect local residual oesophageal tumour and cannot be used as an adjunct tool for clinical decision-making in patients.</p

Body Composition Is a Predictor for Postoperative Complications After Gastrectomy for Gastric Cancer:a Prospective Side Study of the LOGICA Trial

PURPOSE: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. METHODS: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). RESULTS: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. CONCLUSION: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11605-022-05321-0

2 days versus 5 days of postoperative antibiotics for complex appendicitis:a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.</p

Hereditary Factors in Esophageal Adenocarcinoma

BACKGROUND: The vast majority of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of EAC. Here, we review data from the published literature in order to address the current knowledge on familial EAC. SUMMARY: Although familial EAC comprises a relatively small group of patients, it is a clinically relevant category due to the poor prognosis of this type of cancer. Efforts should be made to identify specific genetic risk factors for familial EAC to enable identification of relatives at risk, since endoscopic surveillance can diagnose preneoplastic or early neoplastic lesions leading to early treatment, with improved outcome. KEY MESSAGE: Although familial EAC comprises a relatively small group of patients, this is a clinically relevant category due to the poor prognosis. Efforts should be made to identify specific genetic risk factors for familial EAC in order to facilitate the identification of other family members with a predisposition for this type of cancer. PRACTICAL IMPLICATIONS: Approximately 7% of BE and EAC cases are considered familial. Age at diagnosis is generally lower for patients with familial EAC as compared to sporadic cases, while other known risk factors for EAC, such as male gender and Caucasian ethnicity, do not differ between the two groups. In several described families with clustering of EAC the pattern of inheritance seems to be consistent with a rare autosomal dominant genetic trait. However, some association has been found with (attenuated) familial adenomatous polyposis, mismatch repair deficiency and recently with the genes MSR1, ASCC1 and CTHRC1. Nevertheless, no specific genetic predisposition has yet been identified

Lasting symptoms and long-term health-related quality of life after totally minimally invasive, hybrid and open Ivor Lewis esophagectomy

Aim: Compared to open esophagectomy (OE), both totally minimally invasive (TMIE) and laparoscopy-assisted hybrid minimally invasive (HMIE) reduce postoperative morbidity and improve short-term health-related quality of life (HRQoL). We aimed to compare lasting symptoms and long-term HRQoL in an international population-based setting between patients who underwent Ivor Lewis TMIE, HMIE or OE.  Methods: Patients who were relapse-free at least one year after TMIE, HMIE or OE for esophageal or junctional carcinoma between January 2010 and June 2016 were included. Patients completed the LASER questionnaire to assess lasting symptoms after esophagectomy and the EORTC QLQ-C30 and QLQ-OG25 questionnaires to assess HRQoL. Primary endpoint was chest pain and secondary endpoints were pain from chest scars or abdominal scars, abdominal pain, fatigue and physical functioning. Differences in lasting symptoms and HRQoL were assessed with multivariable logistic and ANCOVA regression, respectively.  Results: A total of 362 patients were included (TMIE n = 91, HMIE n = 85, OE n = 186). Median follow-up was 3.9 years (IQR 2.8–5.4). Chest pain was reported less after TMIE compared with HMIE (adjusted OR 0.21, 95% CI 0.05–0.84), but was comparable between TMIE and OE (adjusted OR 0.41, 95% CI 0.12–1.41) and between HMIE and OE (adjusted OR 1.85, 95% CI 0.71–4.81). All secondary endpoints were comparable between TMIE, HMIE and OE. The impact of symptoms on taking medication, return to work, and performance status were comparable between groups.  Conclusion: Surgical technique seems to have little effect on lasting symptoms and long-term HRQoL after a median of four years after Ivor Lewis esophagectomy