Impact of ≥ 0.1-mm free resection margins on local intramural residual cancer after local excision of T1 colorectal cancer

Background and study aims  A free resection margin (FRM) > 1 mm after local excision of a T1 colorectal cancer (CRC) is known to be associated with a low risk of local intramural residual cancer (LIRC). The risk is unclear, however, for FRMs between 0.1 to 1 mm. This study evaluated the risk of LIRC after local excision of T1 CRC with FRMs between 0.1 and 1 mm in the absence of lymphovascular invasion (LVI), poor differentiation and high-grade tumor budding (Bd2-3). Patients and methods  Data from all consecutive patients with local excision of T1 CRC between 2014 and 2017 were collected from 11 hospitals. Patients with a FRM ≥ 0.1 mm without LVI and poor differentiation were included. The main outcome was risk of LIRC (composite of residual cancer in the local excision scar in adjuvant resection specimens or local recurrence during follow-up). Tumor budding was also assessed for cases with a FRM between 0.1 and 1mm. Results  A total of 171 patients with a FRM between 0.1 and 1 mm and 351 patients with a FRM > 1 mm were included. LIRC occurred in five patients (2.9 %; 95 % confidence interval [CI] 1.0-6.7 %) and two patients (0.6 %; 95 % CI 0.1-2.1 %), respectively. Assessment of tumor budding showed Bd2-3 in 80 % of cases with LIRC and in 16 % of control cases. Accordingly, in patients with a FRM between 0.1 and 1 mm without Bd2-3, LIRC was detected in one patient (0.8%; 95 % CI 0.1-4.4 %). Conclusions  In this study, risks of LIRC were comparable for FRMs between 0.1 and 1 mm and > 1 mm in the absence of other histological risk factors

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Background: Endoscopic 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 ≥ 2 cm 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. Methods: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) 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 < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion: The 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 ≥ 2 cm 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 registration: ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Background: Endoscopic 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 ≥ 2 cm 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. Methods: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) 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 < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion: The 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 ≥ 2 cm 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 registration: ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021

Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022)

Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis

Introduction  Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis. Methods  Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I–III colon (CC), stage I–III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I–III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population. Results  In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6. Conclusions  Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system

Efficacy and safety of cap-assisted endoscopic mucosal resection for treatment of nonlifting colorectal polyps

BACKGROUND : Suboptimal lifting increases complexity of endoscopic mucosal resection (EMR) for benign colorectal polyps. Cap-assisted EMR (EMR-C) may allow fibrotic polyp tissue to be captured in the snare. This study evaluated the efficacy and safety of EMR-C for benign nonlifting colorectal polyps. METHODS : This was a multicenter study, which prospectively registered all EMR-C procedures (2016-2018) for presumed benign nonlifting colorectal polyps. RESULTS : 70 nonlifting polyps with a median size of 25 mm (interquartile range [IQR] 15-40) were treated with EMR-C. Complete polyp removal was achieved in 68 (97.1 %), including 47 (67.1 %) with EMR-C alone. Overall, 66 polyps showed benign histology, and endoscopic follow-up after a median of 6 months (IQR 6-10) showed recurrence in 19.7 %. First (n = 10) and second (n = 2) benign recurrences were all treated endoscopically. Deep mural injury type III-V occurred in 7.4 % and was treated successfully with clips. CONCLUSION : EMR-C may be an alternative therapeutic option for removal of benign nonlifting polyp tissue. Although recurrence still occurs, repeat endoscopic therapy usually leads to complete polyp clearance

Impact of multidisciplinary tumor board discussion on palliation of patients with esophageal or gastro-esophageal junction cancer: a population-based study

Background: The Dutch guidelines for esophageal and gastro-esophageal junction (GEJ) cancer recommend discussion of patients by a multidisciplinary tumor board (MDT). Despite this recommendation, one previous study in the Netherlands suggested that therapeutic guidance was missing for palliative care of patients with esophageal cancer. The aim of the current study was therefore to assess the impact of an MDT discussion on initial palliative treatment and outcome of patients with esophageal or GEJ cancer. Material and methods: The population-based Netherlands Cancer Registry was used to identify patients treated for esophageal or GEJ cancer with palliative intent between 2010 and 2017 in 7 hospitals. We compared patients discussed by the MDT with patients not discussed by the MDT in a multivariate analysis. Primary outcome was type of initial palliative treatment. Secondary outcome was overall survival. Results: A total of 389/948 (41%) patients with esophageal or GEJ cancer were discussed by the MDT before initial palliative treatment. MDT discussion compared to non-MDT discussion was associated with more patients treated with palliative intent external beam radiotherapy (38% vs. 21%, OR 2.7 [95% CI 1.8–3.9]) and systemic therapy (30% vs. 23%, OR 1.6 [95% CI 1.0–2.5]), and fewer patients treated with stent placement (4% vs. 12%, OR 0.3 [95% CI 0.1–0.6]) and best supportive care alone (12% vs. 33%, OR 0.2 [95% CI 0.1–0.3]). MDT discussion was also associated with improved survival (169 days vs. 107 days, HR 1.3 [95% CI 1.1–1.6]). Conclusion: Our study shows that MDT discussion of patients with esophageal or GEJ cancer resulted in more patients treated with initial palliative radiotherapy and chemotherapy compared with patients not discussed by the MDT. Moreover, MDT discussion may have a positive effect on survival, highlighting the importance of MDT meetings at all stages of treatment

Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: A new endoscopic approach

Background The risk of lymph node metastasis associated with deep submucosal invasion should be balanced against the mortality and morbidity of total mesorectal excision (TME). Dissection through the submucosa hinders radical deep resection, and full-thickness resection may influence the outcome of completion TME. Endoscopic intermuscular dissection (EID) in between the circular and longitudinal part of the muscularis propria could potentially provide an R0 resection while leaving the rectal wall intact. Methods In this prospective cohort study, the data of patients treated with EID for suspected deep submucosal invasive rectal cancer between 2018 and 2020 were analyzed. Study outcomes were the percentages of technical success, R0 resection, curative resection, and adverse events. Results 67 patients (median age 67 years; 73% men) were included. The median lesion size was 25mm (interquartile range 20-33mm). The rates of overall technical success, R0 resection, and curative resection were 96% (95%CI 89%-99%), 81% (95%CI 70%-89%), and 45% (95%CI 33%-57%). Only minor adverse events occurred in eight patients (12%). Conclusion EID for deep invasive T1 rectal cancer appears to be feasible and safe, and the high R0 resection rate creates the potential of rectal preserving therapy in 45% of patients