Jurjen J. Boonstra

Background: Screening for colorectal cancer has led to large increases in the detection of large non-pedunculated rectal polyps. Local en bloc removal is increasingly seen as the optimal approach and can be performed by surgical or endoscopic local excision, via transanal minimal invasive surgery (TAMIS) or endoscopic submucosal dissection (ESD) respectively. We hypothesised that ESD would have a non-inferior recurrence rate with less serious adverse events and lower costs than TAMIS. Methods: We performed a multicentre randomised controlled non-inferiority trial in 23 hospitals in the Netherlands. Adult patients with a non-pedunculated rectal polyp larger than two centimetres without features of deep submucosal invasion, were eligible for inclusion. Patients were randomised 1:1 to receive TAMIS or ESD, stratified for the distance from the dentate line and lesion size. The primary outcome was the intention-to-treat recurrence rate at 12 months. The non-inferiority margin was six percent. Netherlands Trial Register, NL7083. Findings: 198 patients were recruited between Jan 1, 2019, and Jan 1, 2023. 98 (57 males) were assigned to TAMIS and 100 (60 males) to ESD. For the primary outcome all randomised patients were analysed. There were six recurrences in the TAMIS arm and none in the ESD arm. The difference in recurrence rate was –6·3% in favour of ESD (95% CI [ –11·2; –1·4]). ESD cost €2,636 (95% CI [2,446; 2,826]) and TAMIS €3,340 (95% CI [3,068; 3611]. There were no treatment related deaths and no significant differences in adverse events. Interpretation: ESD should be the treatment of choice for large non-pedunculated rectal polyps.

Background: There is a paucity of data on the cost‐utility of endoscopic ultrasonography‐guided gastroenterostomy (EUS‐GE) compared with surgical gastrojejunostomy (SGJ) as palliative treatment of malignant gastric outlet obstruction. Methods: In the ENDURO trial, 98 patients with malignant gastric outlet obstruction from 12 Dutch hospitals were randomized between EUS‐GE ( N = 48) and SGJ ( N = 50). Cost utility was evaluated from a healthcare perspective with a time horizon of 1 month. A bottom‐up approach was used to calculate the costs of each intervention, including the per‐minute price of the endoscopy and operating room (OR), considering personnel, construction, inventory and overhead costs. Other in‐hospital costs were calculated using insurance claim data. Effectiveness was displayed as quality‐adjusted life years (QALY). Bootstrapping was performed to estimate uncertainty. Results: The calculated per‐minute price for the endoscopy room was €8.64 (US $9.34). The per‐minute price for an OR was €11.78 (US $12.74). The mean intervention costs were estimated at €4405.40 (US $4762.68) for EUS‐GE and €3393.71 (US $3668.93) for SGJ. Mean total in‐hospital costs were lower following EUS‐GE (€5172 [US $5591]) than after SGJ (€10,458 [US $11,306]), mainly due to a shorter length of hospital stay following EUS‐GE. Bootstrapping showed that 99.9% of iterations resulted in lower costs for EUS‐GE. Mean difference in 1‐month QALY contribution was 0.004 in favor of EUS‐GE. Most iterations fall within the bottom right quadrant (95.6%) of the cost‐effectiveness plane, indicating lower costs and improved QALY contribution for EUS‐GE. Discussion: In this study, EUS‐GE was more cost effective than SGJ. The additional intervention costs were clearly outweighed by a decrease in in‐hospital costs after the procedure.

Background and need for innovation: Train-the-trainer courses for procedural teaching, including gastrointestinal endoscopy, have been shown to improve trainer performance and learner outcomes. However, maintaining these gains over time is challenging. Refresher training has been proposed as a strategy to support long-term retention of procedural teaching skills; however, such training is currently lacking and its impact remains unclear. Goal of innovation: We developed, implemented and evaluated a bespoke Training the Colonoscopy Trainers (TCT) refresher training to support sustained endoscopy teaching skills. In addition, facilitators and barriers influencing long-term retention and transfer of teaching skills were identified. Steps taken for development and implementation of innovation: Sixteen endoscopy trainers who had previously completed the original TCT course participated in a one-on-one refresher training delivered 6–9 months after the initial training. Effectiveness was evaluated using Kirkpatrick levels 1 (reaction), 3 (behaviour) and 4 (results). Course participant interviews were thematically analysed to identify factors influencing sustained skill retention and transfer to practice. Outcomes of innovation: Participants highly valued the refresher training. Although improvements in trainer performance were not statistically significant, post-refresher training video-analysis scores exceeded all previous measurements. Residents reported high satisfaction with supervision and perceived improvements in feedback quality and procedural guidance. Institutional support and opportunities to teach were identified as key facilitators, while time constraints were the primary barrier to sustained skill application. Critical reflection: This study demonstrates the feasibility and added value of refresher training as part of faculty development for procedural teaching. While challenges remain regarding optimal timing and institutional support, this proof of principle highlights the potential of longitudinally embedded refresher training to advance teaching quality across medical education contexts.

Introduction: The extracellular matrix (ECM) supports tumor progression by influencing tumor cell migration and invasion. This study examines the link between peritumoral ECM morphology and five-year recurrence risk in TNM Stage II colon cancer, using quantitative whole-slide ECM imaging. We hypothesize that loose ECM regions are associated with increased recurrence risk due to enhanced tumor budding (TB) or poorly differentiated clusters (PDC). Methods: In a case-control study of 100 TNM Stage II colon cancer patients (25 with recurrence and 75 controls matched by lymph node sampling and tumor extent), Picrosirius red-stained sections were imaged to quantify ten ECM parameters across 798 regions of interest (ROIs). Conditional logistic regression assessed associations between ECM morphologies, TB, PDCs, and recurrence. Results: Unsupervised clustering identified three ECM morphologies: dense fibrous, loose sparse, and complex tortuous. Dense fibrous ECM correlated strongly with recurrence (aOR 9.43, 95% CI 3.29-29.30, p < 0.001), while loose sparse and complex tortuous ECMs were associated with reduced recurrence risk (aOR 0.33, 95% CI 0.11-0.91, p = 0.040, and aOR 0.14, 95% CI 0.02-0.53, p = 0.012, respectively). TB was highest in loose sparse ECM (mean 9.3), and PDCs were highest in dense fibrous ECM (mean 5.5). Discussion: Our findings suggest that ECM morphology, particularly dense fibrous ECM, predicts recurrence in Stage II colon cancer, highlighting ECM profiling as a promising tool for patient stratification beyond traditional staging.

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors ( P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women ( P = .003, .012, respectively). CONCLUSION: Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014–2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017–2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.

The increase incidence of early colorectal cancer (T1 CRC) last years is mainly due to the introduction of population-based screening for CRC. T1 CRC staging based on histological criteria remains challenging and there is high variability among pathologists in the scoring of these criteria. It is crucial to unravel the biology behind the progression of adenoma into T1 CRC. Glycomic studies have reported extensively on alterations of the N-glycomic pattern in CRC; therefore, investigating these alterations may reveal new insights into the development of T1 CRC. We used matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) to spatially profile the N-glycan species in a cohort of pT1 CRC using archival formalin-fixed and paraffin-embedded (FFPE) material. To generate structural information on the observed N-glycans, CE-ESI-MS/MS was used in conjunction with MALDI-MSI. Relative intensities and glycosylation traits were calculated based on a panel of 58 N-glycans. Our analysis showed pronounced differences between normal epithelium, dysplastic, and carcinoma regions. High-mannose-type N-glycans were higher in the dysplastic region than in carcinoma, which correlates to increased proliferation of the cells. We observed changes in the cancer invasive front, including higher expression of α2,3-linked sialic acids which followed the glycosylation pattern of the carcinoma region.

Endoscopic treatment of large laterally spreading tumors (LSTs) with a focus of submucosally invasive colorectal cancer (T1 CRC) can be challenging. We evaluated outcomes of a hybrid resection technique using piecemeal endoscopic mucosal resection (pEMR) and endoscopic full-thickness resection (eFTR) in patients with large colonic LSTs containing suspected T1 CRC. Six hybrid pEMR-eFTR procedures for T1 CRCs were registered in a nationwide eFTR registry between July 2015 and December 2019. In all cases, the invasive part of the lesion was successfully isolated with eFTR; with eFTR, histologically complete resection of the invasive part was achieved in 5 /6 patients (83.3 %). No adverse events occurred during or after the procedure. The median follow-up time was 10 months (range 6–27), with all patients having undergone ≥ 1 surveillance colonoscopy. One patient had a small adenomatous recurrence, which was removed endoscopically. In conclusion, hybrid pEMR-eFTR is a promising noninvasive treatment modality that seems feasible for a selected group of patients with large LSTs containing a small focus of T1 CRC.

Esophageal cancers confer a major health challenge and are highly aggressive malignancies with poor prognosis. Esophageal adenocarcinoma (EAC) is one of the two major histopathological subtypes of esophageal cancer. Despite advances in treatment modalities, the prognosis of patients with EAC remains poor, with a 5-year survival rate that rarely exceeds 30% in patients treated with curative intent. Chemoradiotherapy followed by resection is the treatment of choice for EAC patients, which are deemed to be curable. Current patient stratification and treatments are based on outcomes from clinical trials. Unfortunately, the molecular heterogeneity of EAC which determines the chemo- and radiosensitivity of these cancers are not taken into account. A more personalized approach in the treatment of EAC could improve patient outcomes. This review aims at summarizing literature on translational and clinical research in the field of EAC which could be of importance to develop personalized approaches. As suggested by the TCGA, expression data features molecular classifications by different platforms, including miRNA, genomic mutations and reverse-phase protein arrays. Here, we summarize literature on transcriptomic, data-driven approaches to identify distinct subtypes of EAC associated with molecular features. These novel classifications may determine the responsiveness to chemo(radio)therapy and help to identify novel molecular targets within cell signaling pathways. Moreover, we discuss the current clinical research efforts on tailored treatment regimens for patients with EAC taking into account the heterogeneous response to chemoradiotherapy. We summarize the evidence regarding active surveillance instead of immediate surgical resection after application of neoadjuvant chemo(radio)therapy in EAC. We consider that in future patients with complete response to chemo(radio)therapy, predicted by (transcriptomic) biomarkers, might benefit most from this approach. Finally, challenges to overcome for current findings to be implemented in clinical practice and move the field forward are being discussed.