Background: The 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... Show moreBackground: The 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. Objective: The aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC. Methods: In 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. Results: Of 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. Conclusion: The 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. Show less
BackgroundThe 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... Show moreBackgroundThe 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. Show less
Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are... Show moreIntroduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. 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
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
Nass, K.J.; Schaar, P.J. van der; Vlugt, M. van der; Ledeboer, M.; Esch, A.A.J. van; Beek, S. van der; ... ; Dekker, E. 2021
Background To optimize colonoscopy quality, several performance measures have been developed. These are usually assessed without distinction between the indications for colonoscopy. This study... Show moreBackground To optimize colonoscopy quality, several performance measures have been developed. These are usually assessed without distinction between the indications for colonoscopy. This study aimed to assess the feasibility of linking two national registries (one for colonoscopy and one for adverse events of gastrointestinal endoscopies in the Netherlands), and to describe the results of colonoscopy quality per indication.Methods This retrospective study was conducted with prospectively collected data of the Dutch Gastrointestinal Endoscopy Audit (DGEA) and the Dutch Registration of Complications in Endoscopy (DRCE). Data between 01-01-2016 and 01-01-2019 were analyzed. To calculate adverse event rates, data were linked at the level of endoscopy service.Results During the 3-year study period, 266 981 colonoscopies were recorded in DGEA. Of all indications, cecal intubation rate was highest in fecal immunochemical test (FIT)-positive screening colonoscopies (97.1 %), followed by surveillance (93.2 %), diagnostic (90.7 %), and therapeutic colonoscopies (83.1 %). The highest rate of adequate bowel preparation was observed in FIT-positive screening colonoscopies (97.1 %). A total of 1540 colonoscopy-related adverse events occurred (0.58 % of all colonoscopies). Bleeding and perforation and rates were highest for therapeutic (1.56 % and 0.51 %, respectively) and FIT-positive screening (0.72 % and 0.06 %, respectively) colonoscopies. The colonoscopy-related mortality was 0.006 %.Conclusion This study describes the first results of the Dutch national colonoscopy registry, which was successfully linked to data from the national registry for adverse events of gastrointestinal endoscopies. In this large dataset, performance varied between indications. Our results emphasize the importance of defining benchmarks per indication in future guidelines. Show less
Background Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in... Show moreBackground Current 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.Methods Haematoxylin 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.Results All 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 kappa = 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).Conclusions Our 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. Show less
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 ... Show moreAdvanced 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. Show less
Barrett's oesophagus (BE) has been associated with an increased risk of both colorectal adenomas and colorectal cancer. A recent investigation reported a high frequency of BE in patients with... Show moreBarrett's oesophagus (BE) has been associated with an increased risk of both colorectal adenomas and colorectal cancer. A recent investigation reported a high frequency of BE in patients with adenomatous polyposis coli (APC)-associated polyposis (FAP). The aim of the present study is to evaluate the prevalence of BE in a large cohort of patients with MUTYH-associated polyposis (MAP) and APC-associated adenomatous polyposis. Patients with a genetically confirmed diagnosis of familial adenomatous polyposis (FAP) or MAP were selected and upper gastrointestinal (GI) endoscopy reports, pathology reports of upper GI biopsies were reviewed to determine the prevalence of BE in these patients. Histologically confirmed BE was found in 7 (9.7%) of 72 patients with MAP. The mean age of diagnosis was 60.2 years (range 54.1-72.4 years). Two patients initially diagnosed with low grade dysplasia showed fast progression into high grade dysplasia and esophageal cancer, respectively. Only 4 (1.4%) of 365 patients with FAP were found to have pathologically confirmed BE. The prevalence of BE in patients with MAP is much higher than reported in the general population. We recommend that upper GI surveillance of patients with MAP should not only focus on the detection of gastric and duodenal adenomas but also on the presence of BE. 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
Patients with refractory inflammatory bowel disease (IBD) might require a subtotal colectomy with construction of an ileostomy. Due to the risk of nerve damage and pelvic sepsis, the diverted... Show morePatients with refractory inflammatory bowel disease (IBD) might require a subtotal colectomy with construction of an ileostomy. Due to the risk of nerve damage and pelvic sepsis, the diverted rectum is often left in situ. Evidence on long-term complications of this rectal stump is limited, particularly in patients with Crohns disease (CD). In addition to the risk of development of neoplasia, diversion proctitis is a frequently reported rectal stump associated complication. Surprisingly, clear recommendations concerning rectal stump surveillance and timing of proctectomy are lacking.Through the use of a pathology database and a review of medical records, we established a cohort of IBD patients with a diverted rectum. Among these patients, long-term complications of the rectal stump were identified. Main endpoint was advanced neoplasia (carcinoma or high-grade dysplasia [HGD]) in the rectal stump. Risk factors for advanced neoplasia were identified using Cox regression modeling. In the second, prospective part of the study, a questionnaire was sent out to 165 patients with either a rectal stump in situ or who had undergone a proctectomy, in order to identify differences in patient-reported outcome measures associated with the excision of the rectal stump.From 530 patients with IBD and a (temporal) diversion of the rectum, we included 250 patients in whom the rectal stump was left in situ for more than 12 months. The majority of patients was female (61%) and had Crohns disease (67%). On follow-up (median 8 years), 8 carcinomas, 2 cases of high-grade dysplasia, and 7 cases of low-grade dysplasia were found with incidence rates of 3.9 and 8.5 per 1000 patient-years of follow-up for cancer and all neoplasia, respectively. The 8 cases of rectal stump cancer (RSC) were diagnosed after a median of 15 years after colectomy. A history of colorectal neoplasia was associated with advanced rectal stump neoplasia. Out of 191 patients with endoscopic follow-up, rectal stump inflammation occurred in 161 (88.5%) patients. Results of the questionnaire did not show a significant difference in quality of life between patients with and patients without a rectal stump, although the latter group reported significantly more sexual and urinary symptoms than patients with a rectal stump in situ. The majority of rectal stump patients reported rectal blood loss, but 65.5% of them were not or barely limited in daily life by their rectal stumprelated problems.Rectal stump cancer has a low incidence rate, with patients with a history of colonic neoplasia carrying the highest risk of developing this severe complication. We observed no significant differences in quality of life between rectal stump and postproctectomy patients, but proctectomy surgery is associated with sexual and urinary complications. Show less
