Publications by authors named "Evelien Dekker"

313 Publications

Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis.

Cell Death Dis 2021 Oct 1;12(10):897. Epub 2021 Oct 1.

Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 69-71, Amsterdam, The Netherlands.

The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-04173-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486827PMC
October 2021

Decision-making in screening positive participants who follow up with colonoscopy in the Dutch colorectal cancer screening programme: A mixed-method study.

Psychooncology 2021 Sep 17. Epub 2021 Sep 17.

Department of General Practice, Cancer Center Amsterdam and Amsterdam Public Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Objective: To explore worry and decision-making processes used by faecal immunochemical test (FIT)-positive participants in the Dutch national screening programme for colorectal cancer.

Methods: A mixed-methods study consisting of 22 semi-structured interviews in FIT-positive participants who underwent the recommended colonoscopy within 4-6 months after the FIT result, followed by a widespread questionnaire in a larger target population (N = 1495).

Results: In the interviews, we recognised two different decision-making processes. The first is an affective heuristic decision process where the decision to participate is made instantly and is paired with high-risk perception, worry and (severe) emotional turmoil. The second is a more time-consuming analytical decision process in which participants describe discussing options with others. In the questionnaire, high levels of cancer worry (CWS > 9) were reported by 34% of respondents. Decisional difficulties were reported by 15% of respondents, and 34% of respondents reported discussing the positive FIT result with their GP. Individuals with high levels of cancer worry contacted their GP less often than those with low levels.

Conclusions: The Dutch two-step screening programme may result in high levels of cancer worry in a non-cancer population. More research is needed to monitor worry and its role in decision-making in cancer screening, as well as ways to facilitate decision-making for participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pon.5814DOI Listing
September 2021

Endoscopic full-thickness resection of T1 colorectal cancers: a retrospective analysis from a multicenter Dutch eFTR registry.

Endoscopy 2021 Sep 6. Epub 2021 Sep 6.

Gastroenterology & Hepatology, Amsterdam University Medical Centres, Amsterdam, Netherlands.

Background And Study Aims: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) is critical to determine subsequent treatment. Endoscopic Full-Thickness Resection (eFTR) is a new treatment option for T1 CRC <2cm. We aim to report clinical outcomes and short-term results.

Patients And Methods: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analysed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk-assessment, curative resections, 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% 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 for primary resected T1 CRC was 23.7% (95% CI [15.9 - 33.6%]) and 60.8% (95% CI [50.4 - 70.4%]) after excluding deep submucosal invasion as risk-factor. Risk-stratification was possible in 99.3%. Severe adverse event rates was 2.2%. Additional oncologic 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 a relatively safe and effective method to resect 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1637-9051DOI Listing
September 2021

Case-mix adjustment to compare colonoscopy performance between endoscopy centres: a nationwide registry study.

Endoscopy 2021 Sep 6. Epub 2021 Sep 6.

Scientific Bureau, Dutch Institute for Clinical Auditing, Leiden, Netherlands.

Background: Non-modifiable patient and endoscopy characteristics might influence colonoscopy performance. Differences in these so-called case-mix factors are likely to exist between endoscopy centres. This study aims to examine the importance of case-mix adjustment when comparing performance between endoscopy centres.

Methods: Prospectively collected data recorded in the Dutch national colonoscopy registry between 2016-2019 were retrospectively analyzed. Performance on cecal intubation rate (CIR) and adequate bowel preparation rate (ABPR) were studied. Additionally, polyp detection rate (PDR) was studied in fecal immunochemical test (FIT)-positive screening colonoscopies. Variation in case-mix factors between endoscopy centres and expected outcomes for each performance measure were calculated per endoscopy centre, based on their case-mix factors (sex, age, ASA score, indication), using multivariable logistic regression.

Results: In total, 363,840 colonoscopies were included from 51 endoscopy centres. The mean percentages per endoscopy centre were significantly different for age > 65 years, male patients, ASA > III and diagnostic colonoscopies (all p < 0.001). In the FIT-positive screening population, significant differences were observed per endoscopy centre for age > 65 years, male patients and ASA > III (all p value < 0.001). The expected CIR, ABPR and PDR ranged from 95.0% to 96.9%, from 93.6% to 96.4% and from 76.2% to 79.1%, respectively. Age, sex, ASA classification and indication were significant case-mix factors for CIR and ABPR. In the FIT-positive screening population, age, sex and ASA classification were significant case-mix factors for PDR.

Conclusion: Our findings emphasize that when comparing colonoscopy performance measures between endoscopy centres, case-mix adjustment should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1637-9651DOI Listing
September 2021

[Experiences with endoscopic full-thickness resection of complex colorectal lesions].

Ned Tijdschr Geneeskd 2021 05 27;165. Epub 2021 May 27.

Amsterdam UMC, afd. Maag-, Darm-, Leverziekten, Amsterdam.

Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions unsuitable to conventional endoscopic resection. With the advantage of enabling a transmural resection, eFTR offers an alternative to radical surgery. Since the introduction of the full-thickness resection device in 2015, a nationwide prospective registry of consecutive eFTR procedures for all indications was initiated in the Netherlands, aiming to monitor patient outcomes and increase further knowledge on its clinical applicability and safety. Data show that eFTR is clinically feasible and relatively safe for complex colorectal lesions. Furthermore, eFTR is gaining interest as a diagnostic and therapeutic treatment option for T1 colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2021

[Electronic chromoendoscopy: optical diagnosis strategy for colorectal polyps not yet implemented].

Ned Tijdschr Geneeskd 2021 06 3;165. Epub 2021 Jun 3.

Amsterdam UMC, locatie AMC, afd. Maag-, Darm- en Leverziekten, Amsterdam.

During colonoscopy, all detected polyps are resected and sent for histopathological assessment by the pathologist to determine the interval for a surveillance colonoscopy. Diminutive polyps (1-5 mm), which constitute up to 60% of all polyps, are rarely malignant (0-0.1%). If it would be possible to predict the histology of these diminutive polyps during colonoscopy, histopathological examination could be omitted. This 'optical diagnosis strategy' by endoscopists could lead to significant cost savings. For safe implementation of this strategy in daily practice, its accuracy must meet minimum thresholds. The development of 'electronic chromoendoscopy' has led to more accurate optical diagnosis. However, research shows that some endoscopists are yet not able to meet the required accuracy thresholds. Due to this variability in accuracy and the absence of an accreditation system implementation of the optical diagnosis strategy in daily practice is still unsuccessful.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2021

[How important is the quality of colonoscopy, considering the population screening for colorectal cancer?]

Ned Tijdschr Geneeskd 2021 05 12;164. Epub 2021 May 12.

Amsterdam UMC, afd. Maag-, Darm- en Leverziekten, Amsterdam.

Colonoscopy is the reference standard for the detection of polyps and colorectal cancer (CRC). If during colonoscopy, all colorectal lesions are detected and completely removed, this individual will be long-term protected from CRC. The quality of the colonoscopy procedure is essential for an optimal protective effect. Recently published data of negative colonoscopies within the Polish Colonoscopy Screening Program, with a maximum follow-up of 17.4 years, demonstrated that high-quality colonoscopy was associated with a lower CRC incidence and mortality compared to low-quality colonoscopy. Colonoscopy quality was defined by completeness of colonoscopy, quality of the bowel preparation and number of detected colorectal lesions. These results suggest that the interval after a negative colonoscopy for the next screening might be safely prolonged, preventing unnecessary costs and risks for the patient. The quality of the initial colonoscopy is essential and a high quality will be fundamental for surveillance guidelines in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2021

Continuous monitoring of colonoscopy performance in the Netherlands: first results of a nationwide registry.

Endoscopy 2021 Jul 22. Epub 2021 Jul 22.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Background:  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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1556-5914DOI Listing
July 2021

Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening : A Diagnostic Test Accuracy Study.

Ann Intern Med 2021 09 20;174(9):1224-1231. Epub 2021 Jul 20.

Netherlands Cancer Institute, Amsterdam, the Netherlands (L.J.B., R.J.F., B.C., M.d.W., G.A.M.).

Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement.

Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT.

Design: Diagnostic test accuracy study.

Setting: Colonoscopy-controlled series.

Participants: Persons ( = 1284) from a screening ( = 1038) and referral ( = 246) population were classified by their most advanced lesion (CRC [ = 47], advanced adenoma [ = 135], advanced serrated polyp [ = 30], nonadvanced adenoma [ = 250], and nonadvanced serrated polyp [ = 53]), along with control participants ( = 769).

Measurements: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity.

Results: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT ( = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) ( = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT.

Limitation: Study population is enriched with persons from a referral population.

Conclusion: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation.

Primary Funding Source: Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7326/M20-8270DOI Listing
September 2021

Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in FAP Patients: Post-Hoc Analysis of a Randomized Clinical Trial.

Dis Colon Rectum 2021 Jul 12. Epub 2021 Jul 12.

Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Cleveland, OH, USA Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands Division of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, AZ, USA University Hospital Gasthuisberg, Leuven, Belgium Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA Department of Internal Medicine I, University of Bonn, Bonn, Germany National Center for Hereditary Tumor Syndromes, Bonn, Germany Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, MA, USA Harvard Medical School, Boston, MA USA Cancer Prevention Pharmaceuticals, Inc., Tucson, AZ, USA Clinical Statistics Consulting, Blue Bell, PA, USA.

Background: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent progression of polyposis and surgeries in the lower gastrointestinal tract would be beneficial to patients with this disease.

Objective: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower gastrointestinal tract of patients with familial adenomatous polyposis.

Design: This is a post-hoc analysis of a randomized phase 3 trial.

Setting: Twenty-one hospitals in 7 countries treating patients with familial adenomatous polyposis.

Patients: Adults with familial adenomatous polyposis were randomized 1:1:1 into 3 arms.

Interventions: Patients received either eflornithine (750 mg), sulindac (150 mg), or both once daily for up to 48 months.

Main Outcome Measures: Efficacy was evaluated as time from randomization to predefined primary disease progression endpoints.

Results: Results are reported for the study population excluding patients who had undergone permanent ileostomies (n = 158). Disease progression was observed in 2/54 (3.7%), 9/53 (17.0%), and 10/51 (19.6%) patients with at least partial lower gastrointestinal tract in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions of 80% (p = 0.02) and 83% (p = 0.01) between combination and sulindac or eflornithine, respectively. When endoscopic excision of adenomas ≥10 mm in size were censored, the need for major surgery was observed in 0/54, 7/53 (13.2%), and 8/51 (15.7%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions approaching 100% between combination and sulindac (p = 0.005) or combination and eflornithine (p = 0.003).

Limitations: This was a post-hoc analysis, the sample size was small, and there were fewer than expected events.

Conclusions: Eflornithine-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower gastrointestinal tract surgery in patients with familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/B658 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DCR.0000000000002095DOI Listing
July 2021

The national FIT-based colorectal cancer screening program in the Netherlands during the COVID-19 pandemic.

Prev Med 2021 10 30;151:106643. Epub 2021 Jun 30.

Department of Public Health, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

The COVID-19 pandemic has affected many healthcare services worldwide. Like many other nations, the Netherlands experienced large numbers of individuals affected by COVID-19 in 2020, leading to increased demands on hospitals and intensive care units. The Dutch Ministry of Health decided to suspend the Dutch biennial fecal immunochemical test (FIT) based colorectal cancer (CRC) screening program from March 16, 2020. FIT invitations were resumed on June 3. In this study, we describe the short-term effects of this suspension on a myriad of relevant screening outcomes. As a result of the suspension, a quarter of the individuals due for screening between March and November 2020 had not received their invitation for FIT screening by November 30, 2020. Furthermore, 57.8% of those who received a consecutive FIT between the restart and November 30, 2020, received it outside the upper limit of the standard screening interval (26 months). Median time between positive FIT and colonoscopy did not change as a result of the pandemic. Participation rates of FIT screening and follow-up colonoscopy in the months just before and during the suspension were significantly lower than expected, but returned to normal levels after the suspension. Based on the anticipated 2020 cohort size, we estimate that the number of individuals with advanced neoplasia currently detected up until November 2020 was 31.2% lower compared to what would have been expected without a pandemic. Future studies should monitor the impact on long-term screening outcomes as a result of the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ypmed.2021.106643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241645PMC
October 2021

Individualized faecal immunochemical test cut-off based on age and sex in colorectal cancer screening.

Prev Med Rep 2021 Sep 9;23:101447. Epub 2021 Jun 9.

Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

The risk of having colorectal cancer (CRC) or its precursors vary with age and sex. Yet, most CRC screening programs using the quantitative faecal immunochemical test (FIT) use a uniform FIT cut-off. We aimed to calculate individualized FIT cut-offs based on age and sex. Data from a study of 1,112 asymptomatic average-risk screening participants undergoing colonoscopy without preselection were used to build a logistic regression model to calculate the risk of having advanced neoplasia (AN) at colonoscopy using age, sex, and FIT concentration as variables. We calculated age- and sex-adjusted FIT cut-off concentrations based on a uniform risk threshold. In a total of 101 of the 1,112 participants AN was detected at colonoscopy. We selected a risk threshold that would produce a specificity of 96.9% in the study group, matching the specificity of FIT at a cut-off of 20 µg Hb/g faeces. At this threshold, age- and sex-adjusted FIT cut-off concentrations ranged from 36.9 µg Hb/g faeces for 50-year-old women to 9.5 µg Hb/g faeces for 75-year old men. At this level of specificity, the risk-based model reached a sensitivity for AN of 28.7% (95%CI: 20.8 to 38.2) versus 27.7% (95%CI: 19.9 to 37.1) for FIT only. Using a risk threshold instead of a uniform FIT-based threshold for inviting screening participants to follow-up colonoscopy ensures that everyone has a comparable risk of AN prior to colonoscopy and may improve the detection of advanced neoplasia, although the absolute magnitude of the increase is likely to be limited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pmedr.2021.101447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209662PMC
September 2021

Apc-mutant cells act as supercompetitors in intestinal tumour initiation.

Nature 2021 06 2;594(7863):436-441. Epub 2021 Jun 2.

Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

A delicate equilibrium of WNT agonists and antagonists in the intestinal stem cell (ISC) niche is critical to maintaining the ISC compartment, as it accommodates the rapid renewal of the gut lining. Disruption of this balance by mutations in the tumour suppressor gene APC, which are found in approximately 80% of all human colon cancers, leads to unrestrained activation of the WNT pathway. It has previously been established that Apc-mutant cells have a competitive advantage over wild-type ISCs. Consequently, Apc-mutant ISCs frequently outcompete all wild-type stem cells within a crypt, thereby reaching clonal fixation in the tissue and initiating cancer formation. However, whether the increased relative fitness of Apc-mutant ISCs involves only cell-intrinsic features or whether Apc mutants are actively involved in the elimination of their wild-type neighbours remains unresolved. Here we show that Apc-mutant ISCs function as bona fide supercompetitors by secreting WNT antagonists, thereby inducing differentiation of neighbouring wild-type ISCs. Lithium chloride prevented the expansion of Apc-mutant clones and the formation of adenomas by rendering wild-type ISCs insensitive to WNT antagonists through downstream activation of WNT by inhibition of GSK3β. Our work suggests that boosting the fitness of healthy cells to limit the expansion of pre-malignant clones may be a powerful strategy to limit the formation of cancers in high-risk individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03558-4DOI Listing
June 2021

Pre-Operative Decitabine in Colon Cancer Patients: Analyses on WNT Target Methylation and Expression.

Cancers (Basel) 2021 May 13;13(10). Epub 2021 May 13.

Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

DNA hypermethylation is common in colon cancer. Previously, we have shown that methylation of WNT target genes predicts poor prognosis in stage II colon cancer. The primary objective of this study was to assess whether pre-operative treatment with decitabine can decrease methylation and increase the expression of WNT target genes , and in colon cancer patients. A clinical study was conducted, investigating these potential effects of decitabine in colon cancer patients (DECO). Patients were treated two times with 25 mg/m decitabine before surgery. Methylation and expression of and WNT target genes (primary outcome) and expression of endogenous retroviral genes (secondary outcome) were analysed in pre- and post-treatment tumour samples using pyrosequencing and rt-PCR. Ten patients were treated with decitabine and eighteen patients were used as controls. Decitabine treatment only marginally decreased methylation. More importantly, no differences in methylation or expression of WNT target or endogenous retroviral genes were observed. Due to the lack of an effect on primary and secondary outcomes, the study was prematurely closed. In conclusion, pre-operative treatment with decitabine is safe, but with the current dosing, the primary objective, increased WNT target gene expression, cannot be achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13102357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153633PMC
May 2021

Dye-Based Chromoendoscopy in Patients With Lynch Syndrome: An Individual Patient Data Meta-Analysis of Randomized Trials.

Am J Gastroenterol 2021 04;116(4):825-828

1Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam Cancer Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 3Department of Internal Medicine, University of Bonn, Bonn, Germany; 4National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany; 5Department of Hematology and Oncology, Klinikum Coburg, Coburg, Germany; 6Department of Gastroenterology, Hospital Clinic of Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain; 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA; 8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; 9Division of Cancer Genetics and Prevention, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA; 10Harvard Medical School, Boston, Massachusetts, USA; 11Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 12Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Radboud University of Nijmegen, Nijmegen, the Netherlands.

Introduction: The additional diagnostic value of dye-based chromoendosocpy (CE) for surveillance of patients with Lynch syndrome is subject of debate.

Methods: To clarify this debate, we performed an individual patient data meta-analysis of randomized studies that compared CE with WLE for the detection of adenomas in patients with Lynch syndrome.

Results: Three randomized studies comprising 533 patients were included. The adenoma detection rate was 74/265 (28%) in patients randomized to WLE compared with 83/266 (31%) in patients randomized to CE (odds ratio 1.17; 95% confidence interval 0.81-1.70).

Discussion: Based on low-quality evidence, CE showed no apparent increase in adenoma detection compared to WLE during surveillance of patients with Lynch syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001138DOI Listing
April 2021

Endoplasmic reticulum stress regulates the intestinal stem cell state through CtBP2.

Sci Rep 2021 05 10;11(1):9892. Epub 2021 May 10.

Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, Amsterdam, The Netherlands.

Enforcing differentiation of cancer stem cells is considered as a potential strategy to sensitize colorectal cancer cells to irradiation and chemotherapy. Activation of the unfolded protein response, due to endoplasmic reticulum (ER) stress, causes rapid stem cell differentiation in normal intestinal and colon cancer cells. We previously found that stem cell differentiation was mediated by a Protein kinase R-like ER kinase (PERK) dependent arrest of mRNA translation, resulting in rapid protein depletion of WNT-dependent transcription factor c-MYC. We hypothesize that ER stress dependent stem cell differentiation may rely on the depletion of additional transcriptional regulators with a short protein half-life that are rapidly depleted due to a PERK-dependent translational pause. Using a novel screening method, we identify novel transcription factors that regulate the intestinal stem cell fate upon ER stress. ER stress was induced in LS174T cells with thapsigargin or subtilase cytotoxin (SubAB) and immediate alterations in nuclear transcription factor activity were assessed by the CatTFRE assay in which transcription factors present in nuclear lysate are bound to plasmid DNA, co-extracted and quantified using mass-spectrometry. The role of altered activity of transcription factor CtBP2 was further examined by modification of its expression levels using CAG-rtTA3-CtBP2 overexpression in small intestinal organoids, shCtBP2 knockdown in LS174T cells, and familial adenomatous polyposis patient-derived organoids. CtBP2 overexpression organoids were challenged by ER stress and ionizing irradiation. We identified a unique set of transcription factors with altered activation upon ER stress. Gene ontology analysis showed that transcription factors with diminished binding were involved in cellular differentiation processes. ER stress decreased CtBP2 protein expression in mouse small intestine. ER stress induced loss of CtBP2 expression which was rescued by inhibition of PERK signaling. CtBP2 was overexpressed in mouse and human colorectal adenomas. Inducible CtBP2 overexpression in organoids conferred higher clonogenic potential, resilience to irradiation-induced damage and a partial rescue of ER stress-induced loss of stemness. Using an unbiased proteomics approach, we identified a unique set of transcription factors for which DNA-binding activity is lost directly upon ER stress. We continued investigating the function of co-regulator CtBP2, and show that CtBP2 mediates ER stress-induced loss of stemness which supports the intestinal stem cell state in homeostatic stem cells and colorectal cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-89326-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111031PMC
May 2021

Clinicopathological features and risk factors for developing colorectal neoplasia in Hodgkin's lymphoma survivors.

Dig Endosc 2021 Apr 30. Epub 2021 Apr 30.

Departments of, Department of, Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.

Aims: We evaluated the clinicopathological characteristics and risk factors for developing (advanced) neoplasia (AN) in HL survivors.

Methods: In all, 101 HL survivors (median age 51 years, median age of HL diagnosis 25 years) underwent colonoscopy and 350 neoplasia and 44 AN (classified as advanced adenomas/serrated lesions or colorectal cancer), mostly right-sided, were detected, as published previously. An average-risk asymptomatic cohort who underwent screening colonoscopy were controls (median age 60 years). Clinicopathological characteristics of AN were evaluated in both groups. Mismatch repair (MMR) status was assessed using immunohistochemistry (MLH1/MSH2/MSH6/PMS2). Logistic regression analysis was performed to evaluate the risk factors for AN in HL survivors, including age at HL diagnosis and interval between HL and colonoscopy.

Results: In 101 colonoscopies in HL survivors, AN was primarily classified based on polyp size ≥10 mm, whereas (high-grade)dysplasia was more often seen in AN in controls. An interval between HL diagnosis and colonoscopy >26 years was associated with more AN compared with an interval of <26 years, with an odds ratio for AN of 3.8 (95% confidence interval 1.4-9.1) (p < 0.01). All 39 AN that were assessed were MMR proficient.

Conclusions: Colorectal neoplasia in HL survivors differ from average-risk controls; classification AN was primarily based on polyp size (≥10 mm) in HL survivors. Longer follow-up between HL diagnosis and colonoscopy was associated with a higher prevalence of AN in HL survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.14004DOI Listing
April 2021

Guidance for setting easy-to-adopt competence criteria for optical diagnosis of diminutive colorectal polyps: a simulation approach.

Gastrointest Endosc 2021 Oct 19;94(4):812-822.e43. Epub 2021 Apr 19.

Department of Epidemiology and Data Science, Amsterdam University Medical Centers, location VU Medical Center, VU University of Amsterdam, Amsterdam, the Netherlands.

Background And Aims: One reason the optical diagnosis strategy for diminutive colorectal polyps has not yet been implemented is that the current competence criteria (Preservation and Incorporation of Valuable Endoscopic Innovation [PIVI] initiative) are difficult to use in daily practice. To provide guidance for setting alternative easy-to-adopt competence criteria, we determined the lowest proportion of diminutive polyps that should have a correct optical diagnosis to meet the PIVI.

Methods: For this simulation study, we used datasets from 2 prospectively collected cohorts of patients who underwent colonoscopy in either a primary colonoscopy or fecal immunochemical test (FIT) screening setting. In the simulation approach, virtual endoscopists or computer-aided diagnosis systems performed optical diagnosis of diminutive polyps with a fixed diagnostic performance level (strategy) on all individuals in the cohort who had ≥1 diminutive polyp. Strategies were defined by systematically varying the proportion of correct optical diagnoses for each polyp subtype (ie, adenomas, hyperplastic polyps, sessile serrated lesions). For each strategy, we determined whether PIVI-1 (≥90% agreement with U.S. or European Society for Gastrointestinal Endoscopy [ESGE] surveillance guidelines) and PIVI-2 (≥90% negative predictive value [NPV] for neoplastic lesions in the rectosigmoid) were met using Monte Carlo sampling with 1000 repetitions, with histology as reference.

Results: The level of overall diagnostic accuracy to achieve the PIVI differed significantly depending on the clinical setting and guidelines used. In the colonoscopy screening setting, all diagnostic strategies in which 92% of all diminutive polyps (regardless of histology) were diagnosed correctly led to 90% or more agreement with U.S. surveillance intervals (ie, PIVI-1). For all diagnostic strategies in which ≥89% of all diminutive polyps were correctly diagnosed, at least 90% NPV was achieved (ie, PIVI-2). For the FIT screening setting, values were respectively ≥77% and ≥94%. When using ESGE guidelines, PIVI-1 was in both settings already met when 40% of all diminutive polyps were diagnosed correctly.

Conclusions: In contrast to the fixed PIVI criteria, our simulation study shows that different thresholds for the proportion of correctly diagnosed diminutive polyps lead to different clinical consequences depending on guidelines and clinical setting. However, this target proportion of diminutive colorectal polyps correctly diagnosed with optical diagnosis represents easier-to-adopt competence criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2021.04.008DOI Listing
October 2021

Response.

Gastrointest Endosc 2021 05;93(5):1202-1203

Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam, Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2021.02.025DOI Listing
May 2021

Prophylactic clipping for delayed postpolypectomy bleeding: Moderately effective, but is it feasible in daily practice?

Gastrointest Endosc 2021 04;93(4):816-817

Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2020.12.028DOI Listing
April 2021

When and How To Use Endoscopic Tattooing in the Colon: An International Delphi Agreement.

Clin Gastroenterol Hepatol 2021 05 22;19(5):1038-1050. Epub 2021 Jan 22.

Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Instituto de Investigación Biomédica Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. Electronic address:

Background & Aims: There is a lack of clinical studies to establish indications and methodology for tattooing, therefore technique and practice of tattooing is very variable. We aimed to establish a consensus on the indications and appropriate techniques for colonic tattoo through a modified Delphi process.

Methods: The baseline questionnaire was classified into 3 areas: where tattooing should not be used (1 domain, 6 questions), where tattooing should be used (4 domains, 20 questions), and how to perform tattooing (1 domain 20 questions). A total of 29 experts participated in the 3 rounds of the Delphi process.

Results: A total of 15 statements were approved. The statements that achieved the highest agreement were as follows: tattooing should always be used after endoscopic resection of a lesion with suspicion of submucosal invasion (agreement score, 4.59; degree of consensus, 97%). For a colorectal lesion that is left in situ but considered suitable for endoscopic resection, tattooing may be used if the lesion is considered difficult to detect at a subsequent endoscopy (agreement score, 4.62; degree of consensus, 100%). A tattoo should never be injected directly into or underneath a lesion that might be removed endoscopically at a later point in time (agreement score, 4.79; degree of consensus, 97%). Details of the tattoo injection should be stated clearly in the endoscopy report (agreement score, 4.76; degree of consensus, 100%).

Conclusions: This expert consensus has developed different statements about where tattooing should not be used, when it should be used, and how that should be done.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.01.024DOI Listing
May 2021

Evaluation of a panel of tumor-specific differentially-methylated DNA regions in IRF4, IKZF1 and BCAT1 for blood-based detection of colorectal cancer.

Clin Epigenetics 2021 01 21;13(1):14. Epub 2021 Jan 21.

Clinical Genomics Pty Ltd, North Ryde, NSW, Australia.

Background: Differentially-methylated regions (DMRs) are characteristic of colorectal cancer (CRC) and some occur more frequently than common mutations. This study aimed to evaluate the clinical utility of assaying circulating cell-free DNA for methylation in BCAT1, IKZF1 and IRF4 for detection of CRC.

Methods: A multiplexed real-time PCR assay targeting DMRs in each of the three genes was developed. Assay accuracy was explored in plasma specimens banked from observational cross-sectional trials or from volunteers scheduled for colonoscopy or prior to CRC surgery.

Results: 1620 specimens were suitable for study inclusion including 184 and 616 cases with CRC and adenomas, respectively, and 820 cases without neoplasia (overall median age, 63.0 years; 56% males). Combining the PCR signals for all targeted DMRs returned the best sensitivity for CRC (136/184, 73.9%, 95% CI 67.1-79.7), advanced adenomas (53/337, 15.7%, 95% CI 12.0-20.1) and high-grade dysplastic (HGD) adenomas (9/35, 25.7%, 95% CI 14.0-42.3) with a 90.1%, specificity for neoplasia (739/820, 95% CI 87.9-92.0, p < 0.01). Detection of methylation in all three genes were more likely in CRC cases than those without it (OR 28.5, 95% CI 7.3-121.2, p < 0.0001). Of the 81 positive cases without neoplasia, 62 (76.5%) were positive by a single PCR replicate only and predominantly due to detection of methylated BCAT1 (53.2%). Single replicate positivity was significantly higher than that in CRC (26/136, 19.1%, p < 0.0001), and single BCAT1 replicate positivity was more likely in cases without neoplasia than in CRC (OR 17.7, 95% CI 6.6-43.3, p < 0.0001). When a positive result was limited to those with ≥ 1 PCR replicate positive for either IKZF1 or IRF4, or at least two replicates positive for BCAT1, the multi-panel test maintained a high sensitivity for CRC (131/184, 71.2%, 95% CI 64.3-77.3) and HGD adenomas (8/35, 22.9%, 95% CI 11.8-39.3, p = 0.029) but improved specificity significantly (772/820, 94.1%, 95% CI 92.3-95.6, p < 0.0001 vs. any PCR replicate positive).

Conclusion: The multi-panel methylation assay differentiates cases with CRC from those without it and does so with high specificity when criteria for BCAT1 detection are applied. The marker panel is flexible and studies in those at average risk for CRC are now warranted to determine which panel configuration best suits screening goals.

Trial Registration: ACTRN12611000318987. Registered 25 March 2011, https://www.anzctr.org.au/ ACTRN12611000318987.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-020-00999-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818774PMC
January 2021

Colon Capsule Endoscopy: An Alternative for Conventional Colonoscopy?

Clin Endosc 2021 Jan 21;54(1):4-6. Epub 2021 Jan 21.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5946/ce.2021.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939767PMC
January 2021

Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study.

BMJ Open Gastroenterol 2020 12;7(1)

Department of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The Netherlands

Objective: After prophylactic colectomy, adenomas continue to develop in the remaining intestine of patients with familial adenomatous polyposis (FAP). There is a lack of standard clinical recommendation for chemoprevention in patients with FAP. Because of promising in vivo studies, the aim of this pilot study was to investigate the safety of sirolimus and its effect on progression of intestinal adenomas.

Design: Patients with FAP with InSiGHT Polyposis Staging System 3 of the retained rectum or pouch received sirolimus for 6 months, dosed at plasma concentration levels of 5-8 µg/L. Primary outcomes were safety and change in marked polyp size. Secondary outcomes were change in number of polyps and effect on proliferation and apoptosis assessed by immunohistochemistry.

Results: Each of the included four patients reported 4 to 18 adverse events (toxicity grades 1-3). One patient prematurely terminated the study because of adverse events. Marked polyp size decreased in 16 (80%)/20 and remained the same in 4 (20%)/20 patients. The number of polyps decreased in all patients (MD -25.75, p=0.13). Three out of four patients showed substantial induction of apoptosis or inhibition of proliferation.

Conclusion: Six months of sirolimus treatment in four patients with FAP showed promising effects especially on the number of polyps in the rectal remnant and ileal pouch, although at the cost of numerous adverse events.

Trial Registration Number: ClinicalTrials.gov ID NCT03095703.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjgast-2020-000497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778746PMC
December 2020

Motives for non-adherence to colonoscopy advice after a positive colorectal cancer screening test result: a qualitative study.

Scand J Prim Health Care 2020 Dec 13;38(4):487-498. Epub 2020 Nov 13.

Department of General Practice, Cancer Center Amsterdam, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Setting: Participants with a positive faecal immunochemical test (FIT) in screening programs for colorectal cancer (CRC) have a high risk for colorectal cancer and advanced adenomas. They are therefore recommended follow-up by colonoscopy. However, more than ten percent of positively screened persons do not adhere to this advice.

Objective: To investigate FIT-positive individuals' motives for non-adherence to colonoscopy advice in the Dutch CRC screening program.

Subjects: Non-adherent FIT-positive participants of the Dutch CRC screening program.

Design: We conducted semi structured in-depth interviews with 17 persons who did not undergo colonoscopy within 6 months after a positive FIT. Interviews were undertaken face-to-face and data were analysed thematically with open coding and constant comparison.

Results: All participants had multifactorial motives for non-adherence. A preference for more personalised care was described with the following themes: aversion against the design of the screening program, expectations of personalised care, emotions associated with experiences of impersonal care and a desire for counselling where options other than colonoscopy could be discussed. Furthermore, intrinsic motives were: having a perception of low risk for CRC (described by all participants), aversion and fear of colonoscopy, distrust, reluctant attitude to the treatment of cancer and cancer fatalism. Extrinsic motives were: having other health issues or priorities, practical barriers, advice from a general practitioner (GP) and financial reasons.

Conclusion: Personalised screening counselling might have helped to improve the interviewees' experiences with the screening program as well as their knowledge on CRC and CRC screening. Future studies should explore whether personalised screening counselling also has potential to increase adherence rates. Key points Participants with a positive FIT in two-step colorectal cancer (CRC) screening programs are at high risk for colorectal cancer and advanced adenomas. Non-adherence after an unfavourable screening result happens in all CRC programs worldwide with the consequence that many of the participants do not undergo colonoscopy for the definitive assessment of the presence of colorectal cancer. Little qualitative research has been done to study the reasons why individuals participate in the first step of the screening but not in the second step. We found a preference for more personalised care, which was not reported in previous literature on this subject. Furthermore, intrinsic factors, such as a low risk perception and distrust, and extrinsic factors, such as the presence of other health issues and GP advice, may also play a role in non-adherence. A person-centred approach in the form of a screening counselling session may be beneficial for this group of CRC screening participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02813432.2020.1844391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781896PMC
December 2020

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

Clin Gastroenterol Hepatol 2020 Nov 3. Epub 2020 Nov 3.

Department of Gastroenterology, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.

Background & Aims: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS.

Methods: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model.

Results: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33).

Conclusions: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2020.11.002DOI Listing
November 2020

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

Endoscopy 2020 12 26;52(12):1127-1141. Epub 2020 Oct 26.

Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

1: ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.Strong recommendation, high quality evidence.ESGE/ESGAR do not recommend barium enema in this setting.Strong recommendation, high quality evidence. 2: ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors.Strong recommendation, low quality evidence.ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete.Weak recommendation, low quality evidence. 3: When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms.Strong recommendation, high quality evidence.Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation.Very low quality evidence.ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms.Strong recommendation, high quality evidence.In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms.Weak recommendation, low quality evidence. 4: Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors.Strong recommendation, high quality evidence.ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer.Weak recommendation, low quality evidence. 5: ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs.Strong recommendation, moderate quality evidence.ESGE/ESGAR also suggest the use of CCE in this setting based on availability.Weak recommendation, moderate quality evidence. 6: ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasibleWeak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in this setting.Very low quality evidence. 7: ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible.Weak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in post-polypectomy surveillance.Very low quality evidence. 8: ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation.Strong recommendation, low quality evidence. 9: ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥ 6 mm detected at CTC or CCE.Follow-up CTC may be clinically considered for 6 - 9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia.Strong recommendation, moderate quality evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1258-4819DOI Listing
December 2020

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

Eur Radiol 2021 May;31(5):2967-2982

Radiology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

Main Recommendations: 1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence. ESGE/ESGAR do not recommend barium enema in this setting. Strong recommendation, high quality evidence.2. ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors. Strong recommendation, low quality evidence. ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete. Weak recommendation, low quality evidence.3. When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms. Strong recommendation, high quality evidence. Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation. Very low quality evidence. ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms. Strong recommendation, high quality evidence. In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms. Weak recommendation, low quality evidence.4. Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors. Strong recommendation, high quality evidence. ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer. Weak recommendation, low quality evidence.5. ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs. Strong recommendation, moderate quality evidence. ESGE/ESGAR also suggest the use of CCE in this setting based on availability. Weak recommendation, moderate quality evidence.6. ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in this setting. Very low quality evidence.7. ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in post-polypectomy surveillance. Very low quality evidence.8. ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation. Strong recommendation, low quality evidence.9. ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥6 mm detected at CTC or CCE. Follow-up CTC may be clinically considered for 6-9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia. Strong recommendation, moderate quality evidence. Source and scope This is an update of the 2014-15 Guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of imaging alternatives to standard colonoscopy. A targeted literature search was performed to evaluate the evidence supporting the use of computed tomographic colonography (CTC) or colon capsule endoscopy (CCE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07413-4DOI Listing
May 2021

Interpretation and adherence to the updated risk-stratified guideline for colonoscopy surveillance after polypectomy - a nationwide survey.

Endosc Int Open 2020 Oct 22;8(10):E1405-E1413. Epub 2020 Sep 22.

Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.

Low adherence to the Dutch guideline for colonoscopy surveillance after polypectomy led to release of a new guideline in 2013. This new guideline was risk-stratified at a more detailed level than the previous one to achieve more efficient use of colonoscopy resources. This study assessed the feasibility of the risk-stratified guideline by evaluating correct interpretation of and adherence to this guideline. Based on semi-structured interviews with 10 gastroenterologists, we developed an online survey to evaluate gastroenterologists' recommendations for surveillance in 15 example cases of patients with polyps. If recommended intervals differed from the new guideline, respondents were asked to indicate their motives for doing so. Ninety-one of 592 (15.4 %) invited gastroenterologists responded to at least one case, of whom 84 (14.2 %) completed the survey. Gastroenterologists gave a correct recommendation in a median of 10 of 15 cases and adherence per case ranged from 14 % to 95 % (median case 76 %). The two cases that addressed management of serrated polyps were least often answered correctly (14 % and 28 % correct answers). Discrepancies were mainly due to misinterpretation of the guideline with respect to serrated polyps (48 %) or misreading of the questions (30 %). Median adherence to the updated colonoscopy surveillance guideline of 76 % seems reasonable, and is higher than adherence to the previous guideline (range: 22 %-80 %, median 59 %). This shows that detailed (more complex) risk stratification for designation of a surveillance interval is feasible. Adherence could potentially be improved by clarifying correct interpretation of serrated polyps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1190-3656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508656PMC
October 2020
-->