BackgroundNeoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer.MethodsThis is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy.DiscussionIf active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

BACKGROUND The oncological efficacy and safety of laparoscopic gastrectomy are under debate for the Western population with predominantly advanced gastric cancer undergoing multimodality treatment. METHODS In 10 experienced upper GI centers in the Netherlands, patients with resectable (cT1-4aN0-3bM0) gastric adenocarcinoma were randomly assigned to either laparoscopic or open gastrectomy. No masking was performed. The primary outcome was hospital stay. Analyses were performed by intention to treat. It was hypothesized that laparoscopic gastrectomy leads to shorter hospital stay, less postoperative complications, and equal oncological outcomes. RESULTS Between 2015 and 2018, a total of 227 patients were randomly assigned to laparoscopic (n = 115) or open gastrectomy (n = 112). Preoperative chemotherapy was administered to 77 patients (67%) in the laparoscopic group and 87 patients (78%) in the open group. Median hospital stay was 7 days (interquartile range, 5-9) in both groups ( P = .34). Median blood loss was less in the laparoscopic group (150 v 300 mL, P < .001), whereas mean operating time was longer (216 v 182 minutes, P < .001). Both groups did not differ regarding postoperative complications (44% v 42%, P = .91), in-hospital mortality (4% v 7%, P = .40), 30-day readmission rate (9.6% v 9.1%, P = 1.00), R0 resection rate (95% v 95%, P = 1.00), median lymph node yield (29 v 29 nodes, P = .49), 1-year overall survival (76% v 78%, P = .74), and global health-related quality of life up to 1 year postoperatively (mean differences between + 1.5 and + 3.6 on a 1-100 scale; 95% CIs include zero). CONCLUSION Laparoscopic gastrectomy did not lead to a shorter hospital stay in this Western multicenter randomized trial of patients with predominantly advanced gastric cancer. Postoperative complications and oncological efficacy did not differ between laparoscopic gastrectomy and open gastrectomy.

Background Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. Methods Patients with oesophageal cancer were randomized to a home‐based IMT programme before surgery or usual care. IMT included the use of a flow‐resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. Results Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). Conclusion Despite an increase in preoperative inspiratory muscle function, home‐based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

BackgroundFor 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.MethodsThe 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.DiscussionIn 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

Immediate start of oral nutrition following esophagectomy seems to be feasible and does not increase complications compared to a retrospective cohort and literature. However, if complications arise an alternative nutritional route is required. This explorative study shows that a randomized controlled trial is needed.