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... Show moreBackground 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. Show less
Zwager, L.W.; Moons, L.M.G.; Sarasqueta, A.F.; Lacle, M.M.; Albers, S.C.; Hompes, R.; ... ; Dutch eFTR Working Group 2022
Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with... Show moreBackground: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
BackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly... Show moreBackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization.Methods/designIn this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate.DiscussionSince the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
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... Show moreObjective: 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 R-0 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. Show less
Background: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC Methods: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. Results: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %-90.3 %), 85.6 % (95 %CI 81.2 %-89.2 %), and 60.3 % (95 %CI 54.7 %-65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection. Conclusions: eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes. Show less
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... Show moreINTRODUCTION: 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. Show less
Background Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC < 2 cm. We aimed to report clinical outcomes and short-term results.Methods Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes.Results We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %–90.3 %), 85.6 % (95 %CI 81.2 %–89.2 %), and 60.3 % (95 %CI 54.7 %–65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %–33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %–70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection.Conclusions eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes. Show less
BackgroundEndoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after... Show moreBackgroundEndoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps >= 2cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk.MethodsThe CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (>= 2cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of <1cm between the clips. Primary outcome is delayed bleeding within 30days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding.DiscussionThe CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps 2cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice.Trial registrationClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021. Show less
Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions <= 30mm unsuitable... Show moreBackground Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions <= 30mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry.Methods Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events.Results Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), reresection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9%). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4%) and full-thickness resection in 288 (83.2%). The median diameter of resected specimens was 23mm. Overall adverse event rate was 9.3% (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis.Conclusion eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed. Show less
Ven, S.E.M. van de; Backes, Y.; Hilbink, M.; Seerden, T.C.J.; Kessels, K.; Cappel, W.H.D.T.N.; ... ; Dutch T1 CRC Working Grp 2020
