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Background The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports. Methods A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens). Results The pooled SN identification rate was 90.7 % (95 % CI 88.2–93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6 % (95 % CI 64.7–74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2 % (95 % CI 4.7–10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3 %, p  = 0.003), colon versus rectal cancer (77.6 vs. 65.7 %, p  = 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8 %, p  = 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9 % (range 0–50 %). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7 %. Conclusions The SN procedure in colorectal cancer has an overall sensitivity of 70 %, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.

ObjectiveEvaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.DesignA multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.ResultsIn total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.ConclusionLaparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.Clinical trial registration numberDutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).

Background Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival. Methods Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18 F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases. Results Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2–27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4–NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4–10.9 months). Conclusions Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18 F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases.

A substantial proportion of individuals with oesophageal cancer have a pathological complete response after neoadjuvant chemoradiotherapy and oesophagectomy. We aimed to investigate whether active surveillance could be an alternative for individuals with a clinical complete response after neoadjuvant chemoradiotherapy. We performed a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial in 12 Dutch hospitals. Individuals with locally advanced oesophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy (ie, no tumour detected with endoscopic biopsies, ultrasound, and PET-CT) underwent active surveillance or standard surgery (ie, oesophagectomy within 2 weeks after reaching clinical complete response). There were no inclusion restrictions regarding comorbidities or performance status, but participants had carcinoma, were age 18 years or older, and were treated with curative intent. Randomisation of hospitals was performed using computer-generated sequences without stratification methods, after an initial phase of all hospitals performing standard surgery. The primary endpoint was overall survival, analysed according to a modified intention-to-treat principle (allowing crossover at time of clinical complete response) and an intention-to-treat principle. Non-inferiority was defined as 2-year survival rate for active surveillance of 15% or less below that for standard surgery. The trial was registered within the Netherlands Trial Register, NTR-6803, and the inclusion phase has been completed. Between Nov 8, 2017, and Jan 17, 2021, 1115 individuals were screened, of whom 309 were included. 198 underwent active surveillance and 111 underwent standard surgery. 242 (78%) participants were male and 67 (22%) were female. Median follow-up was 38 months (IQR 32–48). 2-year overall survival for active surveillance (74% [95% CI 69–78]) was non-inferior to standard surgery (71% [62–78]) after modified intention-to-treat analysis (one-sided 95% boundary: 7% lower). It remained non-inferior in the intention-to-treat analysis (75% [68–80] vs 70% [63–77], one-sided 95% boundary: 6% lower). There were no significant differences in overall survival according to modified intention-to-treat analysis (hazard ratio 1·14, two-sided 95% CI 0·74–1·78) or intention-to-treat analysis (0·83, 0·53–1·31). The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was similar between groups. Overall survival after active surveillance for oesophageal cancer was non-inferior compared with standard surgery after 2 years. For the long-term efficacy of active surveillance, extended follow-up is required. The results of the present trial could be used for patient counselling and shared decision making. Dutch Cancer Society (KWF) and Netherlands Organisation for Health Research and Development (ZonMw).

Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.

Salvage esophagectomy is more complex and associated with higher postoperative morbidity and mortality than standard resection. This study aimed to investigate short-term outcomes and the influence of hospital volume on these outcomes of salvage surgery for esophageal cancer. The study enrolled all patients undergoing esophagectomy for esophageal cancer registered in the Dutch Upper Gastrointestinal Cancer Audit (DUCA) between 2012 and 2022. The patients were classified as salvage or non-salvage by registering surgeons. Salvage surgery is defined in the DUCA as surgery after definitive chemoradiotherapy. Postoperative mortality (30-day/in-hospital) and morbidity were compared between the salvage and non-salvage patients using multilevel logistic regression analyses. Hospital variation in the use of salvage esophagectomy was investigated using funnel plots. The influence of hospital volume (≤ 40 to > 40 cases) and salvage volume (< 6 to ≥ 6 cases) on outcomes for salvage patients were investigated. Using backward elimination, relevant baseline characteristics influencing salvage outcomes were identified. Between 2012 and 2022, 7749 patients underwent esophagectomy, 251 (3%) of whom underwent salvage resection, varying from 0 to 8% between centers. Severe complications (43% vs 28%; odds ratio [OR], 1.81; 95 % confidence interval [CI], 1.40-2.34) and 30-day/in-hospital mortality (11% vs 3%; OR, 3.65; 95% CI, 2.38-5.61) were higher after salvage surgery than after non-salvage surgery. Salvage patients treated in high-volume centers had a lower risk of 30-day/in-hospital mortality than those treated in low-volume centers (9% vs 19%; OR, 0.42; 95% CI, 0.18-0.99), with no relation between salvage volume and outcome. Male sex, older age (> 75 years), and squamous cell carcinoma were associated with worse short-term outcomes of salvage surgery. Salvage surgery is associated with worse short-term outcomes than non-salvage esophagectomy. Outcomes after salvage surgery were favorable in high-volume esophagectomy centers.

Background Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial. Methods This nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret. Discussion Active surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available. Trial registration The SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) – Retrospectively registered.

Background The optimal extent of lymph node dissection (LND) and the anatomic boundaries per lymph node station (LNS) during minimally invasive esophagectomy (MIE) for esophageal cancer remain a topic of debate. This study investigated the opinion of Dutch esophageal cancer surgeons on their routine LND extent and anatomic boundaries per LNS during MIE. Methods In April 2023, an English web-based cross-sectional survey was conducted. In each of the 15 Dutch hospitals performing MIE, two MIE surgeons were asked to participate. The routine LND extent (quantity, specific LNS) for distal esophageal adenocarcinoma, (dis)agreement with the TIGER definition, and anatomic boundaries for each LNS in six directions were queried. Results The survey was completed by 24 Dutch MIE surgeons (80% response rate). Consensus on the routine LND extent ( ≥ 85% of the participating surgeons) included the left and right paracardial, left gastric artery, celiac trunk, proximal splenic artery, common hepatic artery, subcarinal middle mediastinal paraoesophageal, lower mediastinal paraoesophageal, pulmonary ligament, and upper mediastinal paraoesophageal LNSs. Other LNSs were not widely considered routine. Although, certain anatomic boundaries were consistent among the surgeons, the majority varied, even when they agreed on the TIGER definition. Conclusion Significant variations in surgical practice among Dutch esophageal surgeons regarding their routine extent of LND and anatomic boundaries of LNSs during MIE were demonstrated. Variation may have an impact on clinical outcomes, hampering uniform treatment strategies and hindering comparison of performance assessments. This study highlighted the need for an international follow-up study toward one uniform defined LND during MIE for esophageal cancer.

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.