Purpose Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this... Show morePurpose Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this is also safe for NETs up to 20 mm is unclear. We performed a nationwide study to determine the risk of lymph node and distant metastases in endoscopically removed NETs. Methods All endoscopically removed rectal NETs between 1990 and 2010 were identified using the national pathology database (PALGA). Each NET was stratified according to size, grade and resection margin. Follow-up was until February 2016. Results Between 1990 and 2010, a total of 310 NETs smaller than 20 mm were endoscopically removed. Mean size of NETs was 7.4 mm (SD 3.5). In 49% of NETs (n = 153), no grade (G) could be assessed from the pathology report, 1% was G2 (n = 3), and the remaining NETs were G1. Median follow up was 11.6 years (range 4.9-26.0). During follow-up, 30 patients underwent surgical resection. Lymph node or distant metastasis was seen in 3 patients (1%) which all had a grade 2 NET. Mean time from endoscopic resection to diagnosis of metastases was 6.1 years (95% CI 2.9-9.2). Conclusion No lymph node or distant metastases were seen in endoscopically removed G1 NETs up to 20 mm during the long follow-up of this nationwide study. This adds evidence to the ENET guideline that endoscopic resection of G1 NETs up to 20 mm appears to be safe. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less
BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and... Show moreBACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age.METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 mu g Hb/g feces) and high (47 mu g Hb/g feces) cutoff value.RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the lowcutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001).CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%. Show less
Purpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy... Show morePurpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations.Results: Fifty-six patients with tumors located in the proximal (n=1), mid (n=7), or distal esophagus (n=25) or at the gastroesophageal junction (n=23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins.Conclusions: Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy. (C) 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Show less
Kooyker, A.I.; Toes-Zoutendijk, E.; Opstal-van Winden, A.W.J.; Spaander, M.C.W.; Buskermolen, M.; Vuuren, H.J. van; ... ; Lansdorp-Vogelaar, I. 2020
The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data... Show moreThe Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 mu g Hb/g feces on outcomes in the second round. Second round screening was done with a 47 mu g Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round. Show less
Bleijenberg, A.G.C.; IJspeert, J.E.G.; Herwaarden, Y.J. van; Carballal, S.; Pellise, M.; Jung, G.; ... ; Dekker, E. 2020
Background and aims Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC). International guidelines recommend surveillance intervals of 1-2 years.... Show moreBackground and aims Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC). International guidelines recommend surveillance intervals of 1-2 years. However, yearly surveillance likely leads to overtreatment for many. We prospectively assessed a surveillance protocol aiming to safely reduce the burden of colonoscopies.Methods Between 2013 and 2018, we enrolled SPS patients from nine Dutch and Spanish hospitals. Patients were surveilled using a protocol appointing either a 1-year or 2-year interval after each surveillance colonoscopy, based on polyp burden. Primary endpoint was the 5-year cumulative incidence of CRC and advanced neoplasia (AN) during surveillance.Results We followed 271 SPS patients for a median of 3.6 years. During surveillance, two patients developed CRC (cumulative 5-year incidence 1.3%[95% CI 0% to 3.2%]). The 5-year AN incidence was 44% (95% CI 37% to 52%), and was lower for patients with SPS type III (26%) than for patients diagnosed with type I (53%) or type I and III (59%, p<0.001). Most patients were recommended a 2-year interval, and those recommended a 2-year interval were not at increased risk of AN: AN incidence after a 2-year recommendation was 15.6% compared with 24.4% after a 1-year recommendation (OR 0.57, p=0.08).Conclusion Risk stratification substantially reduced colonoscopy burden while achieving CRC incidence similar to previous studies. AN incidence is considerable in SPS patients, but extension of surveillance intervals was not associated with increased AN in those identified as low-risk by the protocol. We identified SPS type III patients as low-risk group that might benefit from even less frequent surveillance. Show less
Roos, V.H.; Mangas-Sanjuan, C.; Rodriguez-Girondo, M.; Medina-Prado, L.; Steyerberg, E.W.; Bossuyt, P.M.M.; ... ; Leerdam, M.E. van 2019
Main Recommendations ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures. Strong... Show moreMain Recommendations ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures. Strong recommendation, low quality evidence, level of agreement 100 %. ESGE recommends starting colonoscopy surveillance at the age of 25 years for MLH1 and MSH2 mutation carriers and at the age of 35 years for MSH6 and PMS2 mutation carriers. Strong recommendation, moderate quality evidence, level of agreement 100 %. ESGE recommends the routine use of high-definition endoscopy systems in individuals with Lynch syndrome. Strong recommendation, high quality evidence, level of agreement 100 %. ESGE suggests the use of chromoendoscopy may be of benefit in individuals with Lynch syndrome undergoing colonoscopy; however routine use must be balanced against costs, training, and practical considerations. Weak recommendation, moderate quality evidence, level of agreement 89 %. ESGE recommends definition of familial risk of colorectal cancer as the presence of at least two first-degree relatives with colorectal cancer or at least one first-degree relative with colorectal cancer before the age of 50 years. Strong recommendation, moderate quality evidence, level of agreement 92 %. ESGE recommends colonoscopy surveillance in first-degree relatives of colorectal cancer patients in families that fulfill the definition of familial risk of colorectal cancer. Strong recommendation, moderate quality evidence, level of agreement 100 %. Show less
Background Neuroendocrine tumours (NETs) are rare. However, a rising incidence has been reported over the past decades. For colorectal NETs, this is presumably caused by an increased awareness of... Show moreBackground Neuroendocrine tumours (NETs) are rare. However, a rising incidence has been reported over the past decades. For colorectal NETs, this is presumably caused by an increased awareness of colorectal diseases and colonoscopic procedures. This study aims to analyse the change in incidence of colorectal NETs, characteristics and management and evaluate the proportion of colorectal NETs detected in a national colorectal cancer (CRC) screening programme. Methods Histopathological reports on colorectal well-differentiated NETs detected between 2006 and 2016 were collected from the Dutch pathology database (PALGA) containing nationwide histo- and cytopathology reports of all pathology laboratories in the Netherlands. Results Colorectal NETs were detected in 1055 individuals. Increasing incidence rates were observed from 0.36 per 100,000 inhabitants in 2006 to 0.75 per 100,000 inhabitants in 2011 (p value < 0.001), remaining stable afterward. Most NETs were grade I (73.5%) and detected in the rectum (76.4%). The majority (88.2%) were detected by colonoscopy, and the final intervention depended significantly on primary location of the tumour; 94.6% of rectal NETs were endoscopically removed, whereas 61.0% of colonic NETs were removed by surgery. There was an increase in local excision both of rectal and colonic NETs over the years instead of radical resection. Screening for CRC started in 2014 and contributed by detecting 32% of the diagnosed colorectal NETs within the invited age group, of which 94.6% were detected at an early stage. Conclusion The incidence of reported colorectal NETs in the Netherlands doubled over the last decade. The Dutch CRC screening programme had a clear contribution to colorectal NETs incidence among its target population. A shift to more local management of detected lesions was observed over time. Show less
Ende, R.P.J. van den; Rigter, L.S.; Kerkhof, E.M.; Meerten, E.L.V. van; Rijkmans, E.C.; Lambregts, D.M.J.; ... ; Heide, U.A. van der 2019
