Nik Dekkers

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: Decision‐making after local resection of T1 colorectal cancer (T1CRC) is often complex and calls for optimal information provision as well as active patient involvement. Objective: The aim was to evaluate the perceptions of patients with T1CRC on information provision and therapeutic decision‐making. Methods: This multicenter cross‐sectional study included patients who underwent endoscopic or local surgical resection as initial treatment. Information provision was assessed using the EORTC QLQ‐INFO25 questionnaire. In patients with high‐risk T1CRC, we evaluated decisional involvement and satisfaction regarding the choice as to whether to undergo additional treatment after local resection, and the level of decisional conflict using the Decisional Conflict Scale. Results: Ninety‐eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high‐risk T1CRC). Median time since local resection was 28 months (IQR 18); none had developed recurrence. Unmet information needs were reported by 29 patients (30%; 18 low‐risk, 11 high‐risk), mostly on post‐treatment related topics (follow‐up visits, recovery time, recurrence prevention). After local resection, 24 of the 45 high‐risk patients (53%) underwent additional treatment, while others were subjected to surveillance. Higher‐educated patients were more often actively involved in decision‐making (93% vs. 43%, p = 0.002) and more frequently underwent additional treatment (79% vs. 40%, p = 0.02). Decisional conflict ( p = 0.19) and satisfaction ( p = 0.78) were comparable between higher‐ and lower‐educated high‐risk patients. Conclusion: Greater attention should be given to the post‐treatment course during consultations following local T1CRC resection. The differences in decisional involvement and selected management strategies between higher‐ and lower‐educated high‐risk patients warrant further investigation.

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.

Background: Differentiating high‐grade dysplasia (HGD) and T1 colorectal cancer (T1CRC) from low‐grade dysplasia (LGD) in colorectal polyps can be challenging. Incorrect recognition of HGD or T1CRC foci can lead to a need for additional treatment after local resection, which might not have been necessary if it was recognized correctly. Tumor‐targeted fluorescence‐guided endoscopy might help to improve recognition.Objective: Selecting the most suitable HGD and T1CRC‐specific imaging target from a panel of well‐established biomarkers: carcinoembryonic antigen (CEA), c‐mesenchymal‐epithelial transition factor (c‐MET), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FRα), and integrin alpha‐v beta‐6 (αvβ6).Methods: En bloc resection specimens of colorectal polyps harboring HGD or T1CRC were selected. Immunohistochemistry on paraffin sections was used to determine the biomarker expression in normal epithelium, LGD, HGD, and T1CRC (scores of 0–12). The differential expression in HGD‐T1CRC components compared to surrounding LGD and normal components was assessed, just as the sensitivity and specificity of each marker.Results: 60 specimens were included (21 HGD, 39 T1CRC). Positive expression (score >1) of HGD‐T1CRC components was found in 73.3%, 78.3%, and 100% of cases for CEA, c‐MET, and EpCAM, respectively, and in <40% for FRα and αvβ6. Negative expression (score 0–1) of the LGD component occurred more frequently for CEA (66.1%) than c‐MET (31.6%) and EpCAM (0%). The differential expression in the HGD‐T1CRC component compared to the surrounding LGD component was found for CEA in 66.7%, for c‐MET in 43.1%, for EpCAM in 17.2%, for FRα in 22.4%, and for αvβ6 in 15.5% of the cases. Moreover, CEA showed the highest combined sensitivity (65.0%) and specificity (75.0%) for the detection of an HGD‐T1CRC component in colorectal polyps.Conclusion: Of the tested targets, CEA appears the most suitable to specifically detect HGD and T1 cancer foci in colorectal polyps. An in vivo study using tumor‐targeted fluorescence‐guided endoscopy should confirm these findings.

Background: T1 rectal cancer (RC) patients are increasingly being treated by local resection alone but uniform surveillance strategies thereafter are lacking. To determine whether different local resection techniques influence the risk of recurrence and cancer-related mortality, a meta-analysis was performed.Methods: A systematic search was conducted for T1RC patients treated with local surgical resection. The primary outcome was the risk of RC recurrence and RC-related mortality. Pooled estimates were calculated using mixed-effect logistic regression. We also systematically searched and evaluated endoscopically treated T1RC patients in a similar manner.Results: In 2585 unique T1RC patients (86 studies) undergoing local surgical resection, the overall pooled cumulative incidence of recurrence was 9.1% (302 events, 95% CI 7.3–11.4%;I² = 68.3%). In meta-regression, the recurrence risk was associated with histological risk status (p < 0.005; low-risk 6.6%, 95% CI 4.4–9.7% vs. high-risk 28.2%, 95% CI 19–39.7%) and local surgical resection technique (p < 0.005; TEM/TAMIS 7.7%, 95% CI 5.3–11.0% vs. other local surgical excisions 10.8%, 95% CI 6.7–16.8%). In 641 unique T1RC patients treated with flexible endoscopic excision (16 studies), the risk of recurrence (7.7%, 95% CI 5.2–11.2%), cancer-related mortality (2.3%, 95% CI 1.1–4.9), and cancer-related mortality among patients with recurrence (30.0%, 95% CI 14.7–49.4%) were comparable to outcomes after TEM/TAMIS (risk of recurrence 7.7%, 95% CI 5.3–11.0%, cancer-related mortality 2.8%, 95% CI 1.2–6.2% and among patients with recurrence 35.6%, 95% CI 21.9–51.2%).Conclusions: Patients with T1 rectal cancer may have a significantly lower recurrence risk after TEM/TAMIS compared to other local surgical resection techniques. After TEM/TAMIS and endoscopic resection the recurrence risk, cancer-related mortality and cancer-related mortality among patients with recurrence were comparable. Recurrence was mainly dependent on histological risk status.Graphical