Background The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program. Methods Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups. Results 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38-0.68). Conclusions Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.

AbstractBackgroundThe role of radiological staging and surveillance imaging is under debate for T1 colorectal cancer (CRC) as the risk of distant metastases is low and imaging may lead to the detection of incidental findings.ObjectiveThe aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC.MethodsIn this retrospective multicenter cohort study, all patients of 10 Dutch hospitals with histologically proven T1 CRC who underwent radiological staging in the period 2000–2014 were included. Clinical characteristics, pathological, endoscopic, surgical and imaging reports at baseline and during follow‐up were recorded and analyzed. Patients were classified as high‐risk T1 CRC if at least one of the histological risk factors (lymphovascular invasion, poor tumor differentiation, deep submucosal invasion or positive resection margins) was present and as low‐risk when all risk factors were absent.ResultsOf the 628 included patients, 3 (0.5%) had synchronous distant metastases, 13 (2.1%) malignant incidental findings and 129 (20.5%) benign incidental findings at baseline staging. Radiological surveillance was performed among 336 (53.5%) patients. The 5‐year cumulative incidence of distant recurrence, malignant and benign incidental findings were 2.4% (95% confidence interval (CI): 1.1%–5.4%), 2.5% (95% CI: 0.6%–10.4%) and 18.3% (95% CI: 13.4%–24.7%), respectively. No distant metastatic events occurred among low‐risk T1 CRC patients.ConclusionThe risk of synchronous distant metastases and distant recurrence in T1 CRC is low, while there is a substantial risk of detecting incidental findings. Radiological staging seems unnecessary prior to local excision of suspected T1 CRC and after local excision of low‐risk T1 CRC. Radiological surveillance should not be performed in patients with low‐risk T1 CRC.

OBJECTIVE:The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA:The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS:This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS:Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS:CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

INTRODUCTION: Local full-thickness resections of the scar (FTRS) after local excision of a T1 colorectal cancer (CRC) with uncertain resection margins is proposed as an alternative strategy to completion surgery (CS), provided that no local intramural residual cancer (LIRC) is found. However, a comparison on long-term oncological outcome between both strategies is missing. METHODS: A large cohort of patients with consecutive T1 CRC between 2000 and 2017 was used. Patients were selected if they underwent a macroscopically complete local excision of a T1 CRC but positive or unassessable (R1/Rx) resection margins at histology and without lymphovascular invasion or poor differentiation. Patients treated with CS or FTRS were compared on the presence of CRC recurrence, a 5-year overall survival, disease-free survival, and metastasis-free survival. RESULTS: Of 3,697 patients with a T1 CRC, 434 met the inclusion criteria (mean age 66 years, 61% men). Three hundred thirty-four patients underwent CS, and 100 patients underwent FTRS. The median follow-up period was 64 months. CRC recurrence was seen in 7 patients who underwent CS (2.2%, 95% CI 0.9%-4.6%) and in 8 patients who underwent FTRS (9.0%, 95% CI 3.9%-17.7%). Disease-free survival was lower in FTRS strategy (96.8% vs 89.9%, P=0.019), but 5 of the 8 FTRS recurrences could be treated with salvage surgery. The metastasis-free survival (CS 96.8% vs FTRS 92.1%, P=0.10) and overall survival (CS 95.6% vs FTRS 94.4%, P=0.55) did not differ significantly between both strategies. DISCUSSION: FTRS after local excision of a T1 CRC with R1/Rx resection margins as a sole risk factor, followed by surveillance and salvage surgery in case of CRC recurrence, could be a valid alternative strategy to CS.

Nik Dekkers: NO financial relationship with a commercial interest | Hao Dang: NO financial relationship with a commercial interest | Jolein van der Kraan: NO financial relationship with a commercial interest | Saskia Le Cessie: NO financial relationship with a commercial interest | Philip Oldenburg: NO financial relationship with a commercial interest | Jan Schoones: NO financial relationship with a commercial interest | Alexandra Langers: NO financial relationship with a commercial interest | Monique Van Leerdam: NO financial relationship with a commercial interest | Jeanin Van Hooft: YES financial relationship with a commercial interest;Abbvie:Speaking and Teaching;Cook medical:Speaking and Teaching;Olympus:Consulting | Yara Backes: NO financial relationship with a commercial interest | Katarina Levic: NO financial relationship with a commercial interest | Alexander Meining: YES financial relationship with a commercial interest;Ovesco AG:Consulting;Ambu:Consulting;Olympus:Consulting;Falk Foundation:Speaking and Teaching;Luvos:Advisory Committees or Review Panels | Giorgio Saracco: NO financial relationship with a commercial interest | Fabian Holman: NO financial relationship with a commercial interest | Koen Peeters: NO financial relationship with a commercial interest | L.M.G. Moons: NO financial relationship with a commercial interest | Pascal Doornebosch: NO financial relationship with a commercial interest | James Hardwick: NO financial relationship with a commercial interest | Jurjen Boonstra: YES financial relationship with a commercial interest;Boston Scientific:Consulting Objective This meta-analysis aims to evaluate the risk of recurrence and mortality for T1 rectal cancer (RC) patients treated with local surgical resection and to compare these to outcomes of endoscopically treated T1RC patients.

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%; I 2 = 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 abstract

AbstractBackgroundCurrent risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over‐treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour‐stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced‐stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non‐pedunculated T1 colorectal cancer.MethodsHaematoxylin and eosin (H&E)‐stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow‐up.ResultsAll 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma‐low, and 78 were scored as stroma‐high. There was moderate inter‐observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma‐high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37–1.18; p = 0.163).ConclusionsOur study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced‐stage tumours.

Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000–2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12–14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12–2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68–2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.

Background and Aims: In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs. Methods: Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed. Results: Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69). Conclusions: In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk.

BACKGROUND AND AIMS:In patients who have undergone surgery for colorectal cancer (CRC), 3% have recurrence of (metachronous) CRC. We investigated whether tumor seeding during colonoscopy (iatrogenic implantation of tumor cells in damaged mucosa) increases risk for metachronous CRC.METHODS:In a proof of principle study, we collected data from the Dutch National Pathology Registry for patients with a diagnosis of CRC from 2013 through 2015, with a second diagnosis of CRC within 6 months to 3.5 years after surgery. We reviewed pathology reports to identify likely metachronous CRC (histologically proven adenocarcinoma located elsewhere in the colon or rectum from the surgical anastomosis). For 22 patients fulfilling the inclusion criteria, we ascribed the most likely etiology to tumor seeding when endoscopic manipulations, such as biopsies or polypectomy, occurred at the location where the metachronous tumor was subsequently detected, after endoscopic manipulation of the primary tumor. We collected clinical data from patients and compared molecular profiles of the primary and metachronous colorectal tumors using next-generation sequencing. We then examined the source of seeded tumor. We tested whether tumor cells stay behind in the working channel of the endoscope after biopsies of colorectal tumors, and whether these cells maintain viability in organoid cultures.RESULTS:In total, tumor seeding was suspected as the most likely etiology of metachronous CRC in 5 patients. Tumor tissues were available from 3 patients. An identical molecular signature was observed in the primary and metachronous colorectal tumors from all 3 patients. In 5 control cases with a different etiology of metachronous CRC, the molecular signature of the primary and metachronous tumor were completely different. Based on review of 2147 patient records, we estimated the risk of tumor seeding during colonoscopy to be 0.3%-0.6%. We demonstrated that the working channel of the colonoscope becomes contaminated with viable tumor cells during biopsy collection. Subsequent instruments introduced through this working channel also became contaminated. These cells were shown to maintain their proliferative potential.CONCLUSIONS:In an analysis of primary and secondary tumors from patients with metachronous CRC, we found that primary tumor cells might be seeded in a new location after biopsy of the primary tumor. Although our study does not eliminate other possibilities of transmission, our findings and experiments support the hypothesis that tumor seeding can occur during colonoscopy via the working channel of the endoscope. The possibility of iatrogenic seeding seems low. However, our findings compel awareness on this potentially preventable cause of metachronous CRC.

OBJECTIVE:This study evaluated the preresection accuracy of optical diagnosis of T1 colorectal cancer (CRC) in large non-pedunculated colorectal polyps (LNPCPs).DESIGN:In this multicentre prospective study, endoscopists predicted the histology during colonoscopy in consecutive patients with LNPCPs using a standardised procedure for optical assessment. The presence of morphological features assessed with white light, and vascular and surface pattern with narrow-band imaging (NBI) were recorded, together with the optical diagnosis, the confidence level of prediction and the recommended treatment. A risk score chart was developed and validated using a multivariable mixed effects binary logistic least absolute shrinkage and selection (LASSO) model.RESULTS:Among 343 LNPCPs, 47 cancers were found (36 T1 CRCs and 11 ≥T2 CRCs), of which 11 T1 CRCs were superficial invasive T1 CRCs (23.4% of all malignant polyps). Sensitivity and specificity for optical diagnosis of T1 CRC were 78.7% (95% CI 64.3 to 89.3) and 94.2% (95% CI 90.9 to 96.6), and 63.3% (95% CI 43.9 to 80.1) and 99.0% (95% CI 97.1 to 100.0) for optical diagnosis of endoscopically unresectable lesions (ie, ≥T1 CRC with deep invasion), respectively. A LASSO-derived model using white light and NBI features discriminated T1 CRCs from non-invasive polyps with a cross-validation area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.90). This model was validated in a temporal validation set of 100 LNPCPs (AUC of 0.81; 95% CI 0.66 to 0.96).CONCLUSION:Our study provides insights in the preresection accuracy of optical diagnosis of T1 CRC. Sensitivity is still limited, so further studies will show how the risk score chart could be improved and finally used for clinical decision making with regard to the type of endoresection to be used and whether to proceed to surgery instead of endoscopy.TRIAL REGISTRATION NUMBER:NTR5561.

BACKGROUND & AIMS Most patients with pedunculated T1 colorectal tumors referred for surgery are not found to have lymph node metastases, and were therefore unnecessarily placed at risk for surgery-associated complications. We aimed to identify histologic factors associated with need for surgery in patients with pedunculated T1 colorectal tumors. METHODS We performed a cohort-nested matched case-control study of 708 patients diagnosed with pedunculated T1 colorectal tumors at 13 hospitals in The Netherlands, from January 1, 2000 through December 31, 2014, followed for a median of 44 months (interquartile range, 20-80 months). We identified 37 patients (5.2%) who required surgery (due to lymph node, intramural, or distant metastases). These patients were matched with patients with pedunculated T1 colorectal tumors without a need for surgery (no metastases, controls, n = 111). Blinded pathologists analyzed specimens from each tumor, stained with H&E. We evaluated associations between histologic factors and patient need for surgery using univariable conditional logistic regression analysis. We used multivariable least absolute shrinkage and selection operator (LASSO; an online version of the LASSO model is available at: http://t1crc.com/calculator/) regression to develop models for identification of patients with tumors requiring surgery, and tested the accuracy of our model by projecting our case-control data toward the entire cohort (708 patients). We compared our model with previously developed strategies to identify high-risk tumors: conventional model 1 (based on poor differentiation, lymphovascular invasion, or Haggitt level 4) and conventional model 2 (based on poor differentiation, lymphovascular invasion, Haggitt level 4, or tumor budding). RESULTS We identified 5 histologic factors that differentiated cases from controls: lymphovascular invasion, Haggitt level 4 invasion, muscularis mucosae type B (incompletely or completely disrupted), poorly differentiated clusters and tumor budding, which identified patients who required surgery with an area under the curve (AUC) value of 0.83 (95% confidence interval, 0.76-0.90). When we used a clinically plausible predicted probability threshold of ≥4.0%, 67.5% (478 of 708) of patients were predicted to not need surgery. This threshold identified patients who required surgery with 83.8% sensitivity (95% confidence interval, 68.0%-93.8%) and 70.3% specificity (95% confidence interval, 60.9%-78.6%). Conventional models 1 and 2 identified patients who required surgery with lower AUC values (AUC, 0.67; 95% CI, 0.60-0.74; P = .002 and AUC, 0.64; 95% CI, 0.58-0.70; P < .001, respectively) than our LASSO model. When we applied our LASSO model with a predicted probability threshold of ≥4.0%, the percentage of missed cases (tumors mistakenly assigned as low risk) was comparable (6 of 478 [1.3%]) to that of conventional model 1 (4 of 307 [1.3%]) and conventional model 2 (3 of 244 [1.2%]). However, the percentage of patients referred for surgery based on our LASSO model was much lower (32.5%, n = 230) than that for conventional model 1 (56.6%, n = 401) or conventional model 2 (65.5%, n = 464). CONCLUSIONS In a cohort-nested matched case-control study of 708 patients with pedunculated T1 colorectal carcinomas, we developed a model based on histologic features of tumors that identifies patients who require surgery (due to high risk of metastasis) with greater accuracy than previous models. Our model might be used to identify patients most likely to benefit from adjuvant surgery.

Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases. Co-culturing macrophages with patient-derived colonospheres promoted 'budding' of small clusters of tumor cells from the bulk. Immunohistochemistry showed that budding tumor clusters in stroma-rich areas of T1 colorectal carcinomas were surrounded by macrophages. In vitro budding was accompanied by reduced levels of the tight junction protein occludin, but OCLN mRNA levels did not change, nor did markers of epithelial mesenchymal transition. Budding was accompanied by nuclear accumulation of β-catenin, which was also observed in budding tumor cell clusters in situ. The NFκB inhibitor Sanguinarine resulted in a decrease in MMP7 protein expression and both NFκB inhibitor Sanguinarine and MMP inhibitor Batimastat prevented occludin degradation and budding. We conclude that macrophages contribute to the aggressive nature of stroma-rich colon tumors by promoting an MMP-dependent pathway that operates in parallel to classical EMT and leads to tight junction disruption.

Surgical resection of upper gastrointestinal (GI) subepithelial tumors (SETs) is associated with significant morbidity and mortality. A new over-the-scope (OTS) clip can be used for endoscopic full-thickness resection (eFTR). We aimed to prospectively evaluate feasibility and safety of upper GI eFTR with a new, flat-based OTS clip. Consecutive patients with a gastric or duodenal SET < 20 mm were prospectively included. After identification of the lesion, the clip was placed and lesions were resected. Patients were followed for 1 month to assess severe adverse events (SAEs); 3-6 months after eFTR, endoscopy was performed. eFTR was performed on 13 lesions in 12 patients: 7 gastric and 6 duodenal SETs. Technical success was achieved in 11 cases (85%). In all 11 cases, R0-resection was achieved. In all 6 duodenal cases and in one gastric case, FTR was achieved (64%). One SAE (pain) was observed after eFTR of a gastric SET. After eFTR of duodenal SETs, several SAEs were observed: perforation (n = 1), microperforation (n = 3), and hemorrhage (n = 1). During follow-up endoscopy, the clip was no longer in situ in most patients (7 of 10; 70%). eFTR with this new flat-based OTS clip is feasible and effective. Although gastric eFTR was safe, eFTR in the duodenum was complicated by (micro)perforation in several patients. Therefore, the design of the clip or the technique of resection needs further refinement to improve safety of resection of SET in thin-walled areas such as the duodenum before being applied in clinical practice. Dutch trial register: NTR5023.

BACKGROUND & AIMS:Risk stratification for adverse events, such as metastasis to lymph nodes, is based only on histologic features of tumors. We aimed to compare adverse outcomes of pedunculated vs nonpedunculated T1 colorectal cancers (CRC). METHODS:We performed a retrospective study of 1656 patients diagnosed with T1CRC from 2000 through 2014 at 14 hospitals in The Netherlands. The median follow-up time of patients was 42.5 months (interquartile range, 18.5-77.5 mo). We evaluated the association between tumor morphology and the primary composite end point, adverse outcome, adjusted for clinical variables, histologic variables, resection margins, and treatment approach. Adverse outcome was defined as metastasis to lymph nodes, distant metastases, local recurrence, or residual tissue. Secondary end points were tumor metastasis, recurrence, and incomplete resection. RESULTS:Adverse outcome occurred in 67 of 723 patients (9.3%) with pedunculated T1CRCs vs 155 of 933 patients (16.6%) with nonpedunculated T1CRCs. Pedunculated morphology was independently associated with decreased risk of adverse outcome (adjusted odds ratio [OR], 0.59; 95% CI, 0.42-0.83; P = .003). Metastasis, incomplete resection, and recurrence were observed in 5.8%, 4.6%, and 3.9% of pedunculated T1CRCs vs 10.6%, 8.0%, and 6.6% of nonpedunculated T1CRCs, respectively. Pedunculated morphology was independently associated with a reduced risk of metastasis (adjusted OR, 0.62; 95% CI, 0.41-0.94; P = .03), incomplete resection (adjusted OR, 0.57; 95% CI, 0.36-0.91; P = .02), and recurrence (adjusted hazard ratio, 0.52; 95% CI, 0.32-0.85; P = .009). Metastasis, incomplete resection, and recurrence did not differ significantly between low-risk pedunculated vs nonpedunculated T1CRCs (0.8% vs 2.9%, P = .38; 1.5% vs 0%, P = .99; 1.5% vs 0%; P = .99). However, incomplete resection and recurrence were significantly lower for high-risk pedunculated vs nonpedunculated T1CRCs (6.5% vs 12.5%; P = .007; 4.4% vs 8.6%; P = .03). CONCLUSIONS:In a retrospective study of patients with T1CRC, we found pedunculated morphology to be associated independently with a decreased risk of adverse outcome in a T1CRC population at high risk of adverse outcome. Incorporating morphologic features of tumors in risk assessment could help predict outcomes of patients with T1CRC and help identify the best candidates for surgery.

BACKGROUND AND AIMS:To optimize therapeutic decision-making in early invasive colorectal cancer (T1 CRC) patients, it is important to elicit the patient's perspective next to considering medical outcome. Because empirical data on patient-reported impact of different treatment options are lacking, we evaluated patients' quality of life, perceived time to recovery, and fear of cancer recurrence after endoscopic or surgical treatment for T1 CRC. METHODS:In this cross-sectional study, we selected patients with histologically confirmed T1 CRC who participated in the Dutch Bowel Cancer Screening Programme and received endoscopic or surgical treatment between January 2014 and July 2017. Quality of life was measured using the European Organization for Research and Treatment 30-item Core Quality of Life Questionnaire and the 5-level EuroQoL 5-dimension questionnaire. We used the Cancer Worry Scale (CWS) to evaluate patients' fear of cancer recurrence. A question on perceived time to recovery after treatment was also included in the set of questionnaires sent to patients. RESULTS:Of all 119 eligible patients, 92.4% responded to the questionnaire (endoscopy group, 55/62; surgery group, 55/57). Compared with the surgery group, perceived time to recovery was on average 3 months shorter in endoscopically treated patients after adjustment for confounders (19.9 days vs 111.3 days; P = .001). The 2 treatment groups were comparable with regard to global quality of life, functioning domains, and symptom severity scores. Moreover, patients in the endoscopy group did not report more fear of cancer recurrence than those in the surgery group (CWS score, 0-40; endoscopy 7.6 vs surgery 9.7; P = .140). CONCLUSIONS:From the patient's perspective, endoscopic treatment provides a quicker recovery than surgery, without provoking more fear of cancer recurrence or any deterioration in quality of life. These results contribute to the shared therapeutic decision-making process of clinicians and T1 CRC patients.

Background and study aims We aimed to evaluate the feasibility and safety of a new, flat-based over-the-scope clip (Padlock Clip) for colorectal endoscopic full-thickness resection (eFTR). Patients and methods We prospectively included 26 patients with lesions < 20mm. Indications for eFTR were re-resection of the scar of a low risk malignant polyp (n = 11), recurrent adenoma in a non-lifting scar (n = 10), non-lifting polyp (n = 4), and an adenoma located in a diverticulum (n = 1). Results Technical success rate and full-thickness resection rate were 100% (26/26) and 92% (24/26), respectively. Median procedure time was 43 minutes (IQR 27 - 56). No complications occurred during the procedure; 3 complications (12%) occurred within 48 hours, of which one was a perforation requiring laparoscopic suturing. Specimen volumes from eFTR of scar tissue where the original polyp had been = 20mm (n = 13) were smaller compared with those from non-scar resections or scars where the original polyps had been < 20 mm (n=13) (median 0.8 vs. 1.5 cm(3), P = 0.03). Conclusions In this first series of colorectal eFTR using the Padlock Clip, feasibility was demonstrated. It was relatively safe in view of surgery as the alternative treatment, but could still benefit from technical refinement. Future studies should explore for which indication this technique is most suitable.

A shift is seen towards more endoscopic resections of T1 colorectal cancer (CRC) as compared to surgical resections, making it even more important to determine the optimal surveillance strategy after endoscopic resection. Current guidelines conclude that no evidence-based recommendation for appropriate surveillance intervals can be given, due to a limited number of studies reporting on long-term outcomes, low number of local recurrences, and missing data on the completeness of follow-up.

Background: Detection of circulating methylated septin 9 (mSEPT9) DNA in blood has been recently approved by the FDA as a non-invasive screening test for colorectal cancer (CRC) and is commercially available.As yet, whether mSEPT9 can be used in the postoperative monitoring of CRC patients remains unknown.Aim: To determine the performance of the second generation mSEPT9 assay in the post-operative monitoring of CRC patients and compare its performance with carcinoembryonic antigen (CEA).Methods: We enrolled consecutive CRC patients who were scheduled for surgical resection of CRC.Blood samples were prospectively collected from these patients immediately before surgery and postoperatively at 3-monthly intervals for determination of mSEPT9 and CEA.mSEPT9 was determined by commercially available assay (Epi proColon 2.0; Epigenomics AG, Germany) in an independent laboratory, which was blinded to the patient's diagnosis and timing of blood samples.All samples were analyzed by real time PCR in triplicate and the mSEPT9 assay was considered as positive when more than one PCR reactions was positive.Abnormal CEA was defined as value above 3 ng/ml as recommended by our hospital central laboratory.Results: A total of 90 CRC patients were enrolled in this study (60 men; mean age 67.6 years).The overall sensitivity of plasma mSEPT9 for the detection of CRC before surgery was 75.6% (95% CI, 64.0%-85.2%)and increased from stage I to IV cancers (I: 52.6%, II: 87.5%, III: 84.6%, IV: 100%).There was however no association between positive mSEPT9 with patient's gender, age and location of CRC at baseline.The positive rate of mSEPT9 was significantly higher than elevated CEA for the detection of CRC in the pre-operative blood samples (75.6% vs 47.7%; P<0.001).For patients with a positive mSEPT9 or CEA at baseline, 57.9% and 40.7% turned negative at 3-month (P = 0.37), respectively.Among the 7 patients with tumor recurrence, 5 (71.4%) of them had persistently positive mSEPT9 or elevated CEA on follow-up.For patients with no clinical evidence of recurrence, mSEPT9 or CEA was negative in the following proportions of patients at 3 months (56.5% vs 67.9%; P =0.44), 6 months (55.8% vs 67.4%; P = 0.30) and 12 months (65.4% vs 73.0%; P = 0.58), respectively.Conclusion: The second generation plasma mSEPT9 was more sensitive than CEA for the diagnosis of CRC patients, but may not be as specific as CEA for monitoring after curative resection.

Up to 4% of patients with non-invasive polyps attending the colorectal cancer (CRC) screening program are referred for surgical resection. Endoscopic full-thickness resection (eFTR) using over-the-scope clips is a new, promising, minimally invasive technique when standard polypectomy techniques are unsuccessful or inadequate.