Publications by authors named "Manon C W Spaander"

124 Publications

Yield of Lynch Syndrome Surveillance for Patients With Pathogenic Variants in DNA Mismatch Repair Genes.

Clin Gastroenterol Hepatol 2020 May 27;18(5):1112-1120.e1. Epub 2019 Aug 27.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address:

Background & Aims: Patients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with these variants in MLH1, MSH2, MSH6, and PMS2.

Methods: We analyzed data on colonoscopy surveillance, including histopathology analysis, from all patients diagnosed with Lynch syndrome (n = 264) at a single center. We compared the development of (advanced) adenomas and CRC among patients with pathogenic variants in the DNA mismatch repair genes MLH1 (n = 55), MSH2 (n = 44), MSH6 (n = 143), or PMS2 (n = 22) over 1836 years of follow-up (median follow-up of 6 years per patient).

Results: At first colonoscopy, CRC was found in 8 patients. During 916 follow-up colonoscopies, CRC was found in 9 patients. No CRC was found in patients with variants in MSH6 or PMS2 over the entire follow-up period. There were no significant differences in the number of colonoscopies with adenomas or advanced adenomas among the groups. The median time of adenoma development was 3 years (IQR, 2-6 years). There were no significant differences in time to development of adenoma. However, patients with variants in MSH6 had a significant longer time to development of advanced neoplasia (advanced adenoma or CRC) than patients in the other groups. Six carriers died during follow up (5 from cancer, of which 3 from pancreatic cancer).

Conclusions: No CRC was found during follow-up of patients with Lynch syndrome carrying pathogenic variants in MSH6; advanced neoplasia developed over shorter follow-up time periods in patients with pathogenic variants in MLH1 or MSH2. The colonoscopy interval for patients with pathogenic variants in MSH6 might be increased to 3 years from the regular 2-year interval.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2019.08.043DOI Listing
May 2020

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age.

Clin Gastroenterol Hepatol 2020 Jun 20;18(7):1493-1500. Epub 2019 Aug 20.

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

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 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 μg Hb/g feces) and high (47 μg 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 low cutoff 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%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2019.08.021DOI Listing
June 2020

Diagnostic Yield of One-Time Colonoscopy vs One-Time Flexible Sigmoidoscopy vs Multiple Rounds of Mailed Fecal Immunohistochemical Tests in Colorectal Cancer Screening.

Clin Gastroenterol Hepatol 2020 03 13;18(3):667-675.e1. Epub 2019 Aug 13.

Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address:

Background & Aims: We compared the diagnostic yields of colonoscopy, flexible sigmoidoscopy, and fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening.

Methods: A total of 30,007 asymptomatic persons, 50-74 years old, were invited for CRC screening in the Netherlands. Participants were assigned to groups that received 4 rounds of FIT (mailed to 15,046 participants), once-only flexible sigmoidoscopy (n = 8407), or once-only colonoscopy (n = 6600). Patients with positive results from the FIT (≥10 μg Hb/g feces) were referred for colonoscopy. Patients who underwent flexible sigmoidoscopy were referred for colonoscopy if they had a polyp of ≥10 mm; adenoma with ≥25% villous histology or high-grade dysplasia; sessile serrated adenoma; ≥3 adenomas; ≥20 hyperplastic polyps; or invasive CRC. The primary outcome was number of advanced neoplasia detected (diagnostic yield) by each test. Secondary outcomes were number of colonoscopies needed to detect advanced neoplasia and number of interval CRCs found during each primary screening test. Patients with interval CRCs were found through linkage with Netherlands Cancer Registry. Advanced neoplasia were defined as CRC, adenomas ≥ 10 mm, adenomas with high-grade dysplasia, or adenomas with a villous component of at least 25%.

Results: The cumulative participation rate was significantly higher for FIT screening (73%) than for flexible sigmoidoscopy (31%; P < .001) or colonoscopy (24%; P < .001). The percentage of colonoscopies among invitees was higher for colonoscopy (24%) compared to FIT (13%; P < .001) or flexible sigmoidoscopy (3%; P < .001). In the intention to screen analysis, the cumulative diagnostic yield of advanced neoplasia was higher with FIT screening (4.5%; 95% CI 4.2-4.9) than with colonoscopy (2.2%; 95% CI, 1.8-2.6) or flexible sigmoidoscopy (2.3%; 95% CI, 2.0-2.7). In the as-screened analysis, the cumulative yield of advanced neoplasia was higher for endoscopic screening with colonoscopy (9.1%; 95% CI, 7.7-10.7) or flexible sigmoidoscopy (7.4%; 95% CI, 6.5-8.5) than with the FIT (6.1%; 95% CI, 5.7-6.6). All 3 screening strategies detected a similar proportion of patients with CRC. Follow-up times differed for each test (median 8.3 years for FIT and flexible sigmoidoscopy and 5.8 years for colonoscopy). Proportions of patients that developed interval CRC were 0.13% for persons with a negative result from FIT, 0.09% for persons with a negative result from flexible sigmoidoscopy, and 0.01% for persons with a negative result from colonoscopy.

Conclusions: Mailed multiple-round FITs detect significantly more advanced neoplasia, on a population level, compared with once-only flexible sigmoidoscopy or colonoscopy screening. Significantly fewer colonoscopies are required by individuals screened by multiple FITs. Trialregister.nl numbers: first round, NTR1096; second round and additional invitees, NTR1512; fourth round, NTR5874; COCOS trial NTR1829.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2019.08.015DOI Listing
March 2020

Olfactomedin 4 (OLFM4) expression is associated with nodal metastases in esophageal adenocarcinoma.

PLoS One 2019 8;14(7):e0219494. Epub 2019 Jul 8.

Department of Pathology, Erasmus MC University Medical Center Rotterdam, Cancer Institute, Rotterdam, The Netherlands.

To date no informative biomarkers exist to accurately predict presence of lymph node metastases (LNM) in esophageal adenocarcinoma (EAC). We studied the discriminative value of Olfactomedin 4 (OLFM4), an intestinal stem cell marker, in EAC. Patients who had undergone esophagectomy as single treatment modality for both advanced (pT2-4) and early (pT1b) adenocarcinoma of the esophagus or gastro-esophageal junction were selected for this study from an institutional database (Erasmus MC University Medical Center, Rotterdam, The Netherlands). Surgical resection specimens of 196 advanced and 44 early EAC were examined. OLFM4 expression was studied by immunohistochemistry and categorized as low (<30%) or high (> = 30%) expression. Low OLFM4 was associated with poor differentiation grade in both advanced (60% vs. 34.8%, p = 0.001) and early EAC (39.1% vs. 9.5%, p = 0.023). LNM were present in 161 (82.1%) of advanced and 9 (20.5%) of early EAC respectively. Low OLFM4 was independently associated with the presence of LNM in advanced EAC in multivariable analysis (OR 2.7; 95% CI, 1.16-6.41; p = 0.022), but not in early EAC (OR 2.1; 95% CI, 0.46-9.84; p = 0.338). However, the difference in association with LNM between advanced (OR 2.7; 95% CI, 1.18-6.34; p = 0.019) and early (OR 2.3; 95% CI, 0.47-11.13; p = 0.302) EAC was non-significant (p = 0.844), suggesting that the lack of significance in early EAC is due to the small number of patients in this group. OLFM4 was not of significance for the disease free and overall survival. Overall, low expression of intestinal stem cell marker OLFM4 was associated with the presence of LNM. Our study suggests that OLFM4 could be an informative marker with the potential to improve preoperative assessment in patients with EAC. Further studies are needed to confirm the value of OLFM4 as a biomarker for LNM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613772PMC
July 2020

Through-the-scope placement of a fully covered metal stent for palliation of malignant dysphagia: a prospective cohort study (with video).

Gastrointest Endosc 2019 12 29;90(6):972-979. Epub 2019 Jun 29.

Department of Gastroenterology & Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.

Background And Aims: To further optimize endoscopic stent placement, an esophageal fully covered self-expandable metal stent with a through-the-scope (TTS) delivery system was designed, providing direct endoscopic control during stent placement. The aim of the study was to assess the feasibility and safety of a TTS stent approach for palliation of malignant dysphagia.

Methods: This multicenter prospective feasibility study included patients with malignant dysphagia undergoing stent placement. The primary outcome was technical success of TTS stent placement. Secondary outcomes included functional outcome, adverse events, and survival. Patients were prospectively evaluated at days 14 and 28, and monthly thereafter, until death or stent removal.

Results: In total, 33 stents were placed in 32 patients. TTS stent placement was feasible in 30 (91%) procedures. In the other 3 procedures (9%), no large-channel endoscope could be introduced because of patient discomfort. In 10 (33%) TTS procedures, technical success was achieved because no fluoroscopy and/or guidewire was used, whereas in 20 (67%) TTS procedures, placement was supported by a guidewire (n = 9), or fluoroscopy and a guidewire (n = 11). After 2 weeks, dysphagia scores had improved in 24 (86%) patients. Median dysphagia-free time was 32 days (interquartile range [IQR], 17-76 days). In 20 (63%) patients, 29 serious adverse events (SAEs) occurred. Recurrent dysphagia occurred in 13 (41%) patients due to migration (n = 5), tissue overgrowth (n = 4), and stent deformation (n = 4). Other SAEs included significant retrosternal pain (n = 4), hemorrhage (n = 2), and esophageal perforation (n = 1). No patient died from a stent-related cause. Median survival was 42 days (IQR, 28-91 days).

Conclusion: Placement of an esophageal TTS stent was feasible in most of the patients with malignant dysphagia. However, stent placement was associated with a relatively high adverse event rate, and in more than one-third of patients, stent placement still required fluoroscopy, which limited optimal benefit of the TTS approach. (Clinical trial registration number: NCT03269903.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2019.06.030DOI Listing
December 2019

Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, NL-3000 CA Rotterdam, The Netherlands.

Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus, in addition to its anti-carcinogenic effects, 3-BP may also be effective in preventing platelet-tumor cell aggregationin cancer patients and therefore may reduce cancer mortality by limiting VTE in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8070936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678874PMC
June 2019

Multiple rounds of one sample versus two sample faecal immunochemical test-based colorectal cancer screening: a population-based study.

Lancet Gastroenterol Hepatol 2019 08 10;4(8):622-631. Epub 2019 Jun 10.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, Netherlands. Electronic address:

Background: Faecal immunochemical test (FIT)-based colorectal cancer screening requires successive rounds for maximum preventive effect. Advanced neoplasia can bleed intermittently and thus might be missed by single faecal sampling. Few studies have been done on two sample FIT (2-FIT) screening over multiple rounds. Therefore, we compared multiple rounds of one sample FIT (1-FIT) with 2-FIT screening with respect to participation, positive predictive value (PPV), diagnostic yield, and interval colorectal cancer.

Methods: In this population-based study, a random selection of asymptomatic individuals aged 50-74 years in the Rotterdam-Rijnmond region, Netherlands, were invited by post for four rounds (every 2 years) of 1-FIT or 2-FIT screening. Key exclusion criteria were a history or colorectal cancer or inflammatory bowel disease, colon imaging in the previous 2 years, and life expectancy of less than 5 years. Per round, invitees received one or two FITs to sample either one or two consecutive bowel movements. OC-Sensor Micro (Eiken Chemical Co., Ltd, Japan) FITs were used by all participants, except the fourth round of screening for the 1-FIT cohort, for which participants used either an OC-Sensor or a FOB-Gold (Sentinel Diagnostics, Milan, Italy). A faecal haemoglobin cutoff concentration of 10 μg/g of faeces in at least one test was used for referral for colonoscopy.

Findings: Between 2006 and 2015, of 10 008 invited individuals for the 1-FIT cohort, 9787 were eligible for inclusion, of whom 7310 participated at least once in four successive rounds. Of 3197 invited individuals for the 2-FIT cohort, 3131 were eligible for inclusion, and 2269 participated at least once in four successive rounds. In the 1-FIT screening cohort, 74·7% (7310 of 9787) of invitees participated at least once versus 72·5% (2269 of 3131) of invitees in the 2-FIT cohort (p=0·013). Among participants who participated at least once, the cumulative positivity rate over four rounds was 19·2% (1407 of 7310) for the 1-FIT cohort versus 28·5% (647 of 2269) for the 2-FIT cohort (p<0·0001). The cumulative PPV for advanced neoplasia was 33·0% (432 of 1308 colonoscopies) for the 1-FIT cohort versus 24·2% (147 of 607 colonoscopies) for the 2-FIT cohort (p<0·0001). The cumulative diagnostic yield of advanced neoplasia among invited individuals was 4·4% (432 of 9787) for 1-FIT versus 4·7% (147 of 3131) for 2-FIT screening (p=0·46)). FIT interval colorectal cancers were detected in eight (0·1%) of 7310 participants in the 1-FIT cohort and two (0·1%) of 2269 with 2-FIT screening (p=1·00).

Interpretation: Four rounds of 2-FIT screening with a low faecal haemoglobin cutoff level did not result in a significant increase in diagnostic yield or a decrease in interval colorectal cancers compared with 1-FIT, despite higher colonoscopy demand. Therefore, 1-FIT colorectal cancer screening programmes should be preferred.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(19)30176-1DOI Listing
August 2019

Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-analysis.

Ann Surg 2020 02;271(2):245-256

Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.

Objective: The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer.

Summary Of Background Data: After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified.

Methods: Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses.

Results: Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma.

Conclusions: Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003397DOI Listing
February 2020

Endoscopic grading of gastric intestinal metaplasia: can we do it without pathologists?

Endoscopy 2019 06 28;51(6):509-510. Epub 2019 May 28.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0831-2450DOI Listing
June 2019

Reply.

Hepatology 2019 11;70(5):1875-1876

Department of Gastroenterology and Hepatology, Erasmus Medical Center University Hospital, Rotterdam, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900052PMC
November 2019

HOXA9 mediates and marks premalignant compartment size expansion in colonic adenomas.

Carcinogenesis 2019 12;40(12):1514-1524

Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.

The transformation of normal colonic epithelium to colorectal cancer (CRC) involves a relatively ordered progression, and understanding the molecular alterations involved may aid rational design of strategies aimed at preventing or counteracting disease. Homeobox A9 (HOXA9) is an oncogene in leukemia and has been implicated in CRC pathology, although its role in disease etiology remains obscure at best. We observe that HOXA9 expression is increased in colonic adenomas compared with location-matched healthy colon epithelium. Its forced expression results in dramatic genetic and signaling changes, with increased expression of growth factors IGF1 and FLT3, super-activity of the AKT survival pathway and a concomitant increase in compartment size. Furthermore, a reduced mRNA expression of the epithelial to mesenchymal transition marker N-cadherin as well as reduced activity of the actin cytoskeletal mediator PAK was seen, which is in apparent agreement with an observed reduced migratory response in HOXA9-overexpressing cells. Thus, HOXA9 appears closely linked with adenoma growth while impairing migration and metastasis and hence is both a marker and driver of premalignant polyp growth. Colonic polyps grow but remain premalignant for up to decades. Here, we show that HOXA9 drives growth in premalignant polyps, but simultaneously prevents further transformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgz038DOI Listing
December 2019

Effects of Oral Anticoagulant and Aspirin Use on Ability of Fecal Immunochemical Tests to Detect Advanced Neoplasia.

Gastroenterology 2019 05 26;156(6):1553-1555. Epub 2019 Mar 26.

Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.03.031DOI Listing
May 2019

Accuracy of F-FDG PET/CT in Predicting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.

J Nucl Med 2019 11 15;60(11):1553-1559. Epub 2019 Mar 15.

Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Our purpose was to prospectively investigate optimal evaluation of qualitative and quantitative F-FDG PET/CT in response evaluations 12-14 wk after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer patients. This was a side study of the prospective diagnostic pre-SANO trial. F-FDG PET/CT scans at baseline and at 12-14 wk after nCRT were qualitatively assessed for the presence of tumor. Maximum SUVs normalized for lean body mass (SUL) were measured in all scans. The primary endpoint was the proportion of false-negative patients with tumor regression grade (TRG) 3-4 (>10% vital residual tumor) in qualitative and quantitative analyses. Receiver-operating-characteristic curve analysis for TRG1 versus TRG3-4 using SUL, SUL tumor-to-esophagus ratio, and Δ%SUL was performed to define optimal cutoffs. Secondary endpoints were sensitivity, specificity, negative predictive value, and positive predictive value for TRG1 versus TRG2-4. In total, 129 of 219 patients were analyzed. Qualitative F-FDG PET/CT was unable to detect TRG3-4 in 15% of patients. Sensitivity, specificity, negative predictive value, and positive predictive value in qualitative analysis for detecting TRG1 versus TRG2-4 was 80%, 37%, 42%, and 77%, respectively. In 18 of 190 patients (10%) with follow-up scans after nCRT, F-FDG PET/CT identified new interval metastases. Quantitative parameters did not detect TRG3-4 tumor in 27%-61% of patients. The optimal cutoff for detecting TRG1 versus TRG2-4 was a post-nCRT SUL of 2.93 (area under receiver-operating-characteristic curve, 0.70). Qualitative and quantitative analyses of F-FDG PET/CT are unable to accurately detect TRG3-4 and to discriminate substantial residual disease from benign inflammation-induced F-FDG uptake after nCRT. However, F-FDG PET/CT is useful for the detection of interval metastases and might become useful in an active surveillance strategy with serial F-FDG PET/CT scanning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.118.224196DOI Listing
November 2019

Participation and Ease of Use in Colorectal Cancer Screening: A Comparison of 2 Fecal Immunochemical Tests.

Am J Gastroenterol 2019 03;114(3):511-518

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Introduction: The impact of fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening on disease incidence and mortality is affected by participation, which might be influenced by ease of use of the FIT. We compared the participation rates and ease of use of 2 different FITs in a CRC screening program.

Methods: There were two study designs within the Dutch CRC screening program. In a paired cohort study, all invitees received 2 FITs (OC-Sensor, Eiken, Japan, and FOB-Gold, Sentinel, Italy) and were asked to sample both from the same stool. Ease of use of both FITs was evaluated by a questionnaire. In a randomized controlled trial, invitees were randomly allocated to receive one of the 2 FITs to compare participation and analyzability.

Results: Of 42,179 invitees in the paired cohort study, 21,078 (50%) completed 2 tests and 20,727 (98%) returned the questionnaire. FOB-Gold was reported significantly easier to use. More participants preferred FOB-Gold (36%) than OC-Sensor (5%), yet most had no preference (59%; P < 0.001). In the randomized trial, 936 of 1,923 invitees (48.7%) returned the FOB-Gold and 940 of 1,923 invitees (48.9%) returned the OC-Sensor, a difference of -0.2% (confidence interval, -3.4% to 3.0%), well within the pre-specified 5% noninferiority margin (P = 0.001). Only one FOB-Gold (0.1%) and 4 OC-Sensors (0.4%) were not analyzable (P = 0.18).

Conclusions: Although FOB-Gold was significantly but marginally considered easier to use than OC-Sensor, the number of analyzable tests and the participation rates in organized CRC screening are not affected when either of the FITs is implemented as a primary screening test.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000000148DOI Listing
March 2019

The Yield and Safety of Screening Colonoscopy in Patients Evaluated for Liver Transplantation.

Hepatology 2019 06 6;69(6):2598-2607. Epub 2019 Apr 6.

Department of Gastroenterology and Hepatology, Erasmus Medical Center University Hospital, Rotterdam, the Netherlands.

Colorectal cancer (CRC) screening with colonoscopy is commonly used in patients who are candidates for liver transplantation. We initiated this study to define the risk-benefit ratio of performing screening colonoscopy in this population. A retrospective observational study of all consecutive patients undergoing colonoscopy during pre-liver transplantation screening between 2004 and 2017 was conducted. Endoscopic and pathological findings and clinical events potentially related to the colonoscopy in the 30 days after the procedure were registered and compared with a 30-day inpatient control time frame. A total of 858 colonoscopies were performed in 808 patients (65% male; median age, 55 years [interquartile range (IQR), 47-62]; median model for end-stage liver disease (MELD) score, 15 [IQR, 11-18]). CRC was found in 2 patients (0.2%), and advanced adenomas were found in 44 patients (5.4%). The only independent risk factor for an advanced neoplasm was age (odds ratio, 1.072 per year; 95% confidence interval, 1.031-1.115; P < 0.001). During the 30-day postprocedure period, 178 clinical events occurred in 128 patients compared with 101 clinical events in 72 patients in the control time frames (P < 0.001). After colonoscopy, there was a significantly increased risk for renal failure (P = 0.001) and gastrointestinal (GI) bleeding (P = 0.023). Presence of ascites and MELD score were identified as independent risk factors for acute renal failure and GI bleeding. During the study observation period, 53.5% of the screened population actually underwent liver transplantation. Conclusion: CRC screening in pre-liver transplantation patients is associated with a relatively low prevalence of CRC and an increased risk of postcolonoscopy complications such as acute renal failure and GI bleeding, especially in patients with advanced liver disease. Because the risk-benefit ratio of standard performance of a screening colonoscopy in this population appears questionable, alternative screening strategies should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593716PMC
June 2019

Quality Monitoring of a FIT-Based Colorectal Cancer Screening Program.

Clin Chem 2019 03 16;65(3):419-426. Epub 2019 Jan 16.

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

Background: Quality assessment is crucial for consistent program performance of colorectal cancer (CRC) screening programs using fecal immunochemical test for hemoglobin (FIT). However, literature on the consistency of FIT performance in laboratory medicine was lacking. This study examined the consistency of FIT in testing positive or detecting advanced neoplasia (AN) for different specimen collection devices, lot reagents, and laboratories.

Methods: All participants with a FIT sample with a cutoff concentration of 47 μg Hb/g feces in the Dutch CRC screening program in 2014 and 2015 were included in the analyses. Multivariable logistic regression analyses were performed to estimate the odds ratios of collection devices, reagents, and laboratories on testing positive or detecting AN and positive predictive value (PPV).

Results: In total, 87519 (6.4%) of the 1371169 participants tested positive. Positivity rates and detection rates of AN differed between collection devices and reagents (all < 0.01). In contrast, PPVs were not found to vary between collection devices, reagents, or laboratories (all > 0.05). Positivity rates showed a small difference for laboratories ( = 0.004) but not for detection rates of AN. Size of the population affected by the deviating positivity rates was small (0.1% of the total tested population).

Conclusions: Variations were observed in positivity and detection rates between collection devices and reagents, but there was no detected variation in PPV. Although the overall population effect of these variations on the screened population is expected to be modest, there is room for improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2018.294041DOI Listing
March 2019

High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors.

Cancer 2019 03 18;125(6):990-999. Epub 2018 Dec 18.

Department of Gastroenterology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Background: Hodgkin lymphoma (HL) survivors treated with abdominal radiotherapy and/or alkylating chemotherapy have an increased risk of colorectal cancer (CRC). This study was aimed at evaluating the prevalence of colorectal neoplasia in HL survivors.

Methods: This multicenter cohort study assessed the diagnostic yield of advanced colorectal neoplasia detected by a first surveillance colonoscopy among HL survivors treated with abdominal radiotherapy and/or procarbazine. Advanced colorectal neoplasia included advanced adenomas (high-grade dysplasia, ≥25% villous component, or ≥10-mm diameter), advanced serrated lesions (dysplasia or ≥10-mm diameter), and CRC. The results were compared with those for a Dutch general population cohort that underwent a primary screening colonoscopy (1426 asymptomatic individuals 50-75 years old). This study demonstrated the results of a predefined interim analysis.

Results: A colonoscopy was performed in 101 HL survivors, who were significantly younger (median, 51 years; interquartile range [IQR], 45-57 years) than the general population controls (median, 60 years; IQR, 55-65 years; P < .001). The prevalence of advanced neoplasia was higher in HL survivors than controls (25 of 101 [25%] vs 171 of 1426 [12%]; P < .001). Advanced adenomas were detected in 14 of 101 HL survivors (14%) and in 124 of 1426 controls (9%; P = .08). The prevalence of advanced serrated lesions was higher in HL survivors than controls (12 of 101 [12%] vs 55 of 1426 [4%]; P < .001). Serrated polyposis syndrome was present in 6% of HL survivors and absent in controls (P < .001).

Conclusions: HL survivors treated with abdominal radiotherapy and/or procarbazine have a high prevalence of advanced colorectal neoplasia. The implementation of a colonoscopy surveillance program should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.31903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590398PMC
March 2019

Endoscopic ultrasound measurements for detection of residual disease after neoadjuvant chemoradiotherapy for esophageal cancer.

Endoscopy 2019 04 29;51(4):326-332. Epub 2018 Nov 29.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Background: Endoscopic ultrasound (EUS) measurements of residual thickness and residual area have been suggested to correlate with histopathological residual tumor after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study assessed the predictive value of EUS-based measurements using tumor thickness and tumor area before nCRT, and residual thickness and residual area 6 and 12 weeks after completion of nCRT for detection of residual disease.

Methods: This was a substudy of the diagnostic multicenter preSANO trial. The primary end point of the current study was the percentage of tumor regression grade (TRG) 3 - 4 (> 10 % vital tumor cells) residual disease that was detected using EUS-based measurements. Associations of absolute measurements of residual thickness/area and proportional change compared with baseline were evaluated. In the case of a statistically significant association, optimal cut-offs to distinguish TRG3 - 4 residual disease from TRG1 (no vital tumor cells) were determined using Youden's J index.

Results: 138 patients were included. Residual thickness and residual area were statistically significantly associated with TRG3 - 4 residual disease 12 weeks after completion of nCRT (odds ratio 1.36,  < 0.01 and 1.64,  = 0.02, respectively). The cut-off for residual thickness was 4.5 mm, which correctly detected 87 % of TRG3 - 4 residual disease and 52 % of TRG1. The cut-off for residual area was 0.92 cm, which detected 89 % of TRG3 - 4 residual disease and 40 % of TRG1.

Conclusions: EUS measurements of residual thickness and residual area adequately detected TRG3 - 4 residual disease with a sensitivity of almost 90 % 12 weeks after completion of nCRT. Hence, residual thickness and residual area may aid in the restaging of esophageal cancer after nCRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0795-3220DOI Listing
April 2019

Quality assurance of colonoscopy within the Dutch national colorectal cancer screening program.

Gastrointest Endosc 2019 01 18;89(1):1-13. Epub 2018 Sep 18.

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

Colorectal cancer (CRC) screening is capable of reducing CRC-related morbidity and mortality. Colonoscopy is the reference standard to detect CRC, also providing the opportunity to detect and resect its precursor lesions: colorectal polyps. Therefore, colonoscopy is either used as a primary screening tool or as a subsequent procedure after a positive triage test in screening programs based on non-invasive stool testing or sigmoidoscopy. However, in both settings, colonoscopy is not fully protective for the occurrence of post-colonoscopy CRCs (PCCRCs). Because most PCCRCs are the result of colonoscopy-related factors, a high-quality procedure is of paramount importance to assure optimal effectiveness of CRC screening programs. For this reason, at the start of the Dutch fecal immunochemical test (FIT)-based screening program, quality criteria for endoscopists performing colonoscopies in FIT-positive screenees, as well as for endoscopy centers, were defined. In conjunction, an accreditation and auditing system was designed and implemented. In this report, we describe the quality assurance process for endoscopists participating in the Dutch national CRC screening program, including a detailed description of the evidence-based quality criteria. We believe that our experience might serve as an example for colonoscopy quality assurance programs in other CRC screening programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2018.09.011DOI Listing
January 2019

Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer.

Dig Surg 2019 18;36(6):462-469. Epub 2018 Sep 18.

Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Background: Active surveillance after neoadjuvant therapies has emerged among several malignancies. During active surveillance, frequent assessments are performed to detect residual disease and surgery is only reserved for those patients in whom residual disease is proven or highly suspected without distant metastases. After neoadjuvant chemoradiotherapy (nCRT), nearly one-third of esophageal cancer patients achieve a pathologically complete response (pCR). Both patients that achieve a pCR and patients that harbor subclinical disseminated disease after nCRT could benefit from an active surveillance strategy.

Summary: Esophagectomy is still the cornerstone of treatment in patients with esophageal cancer. Non-surgical treatment via definitive chemoradiotherapy (dCRT) is currently reserved only for patients not eligible for esophagectomy. Since salvage esophagectomy after dCRT (50-60 Gy) results in increased complications, morbidity and mortality compared to surgery after nCRT (41.4 Gy), the latter seems preferable in the setting of active surveillance. Clinical response evaluations can detect substantial (i.e., tumor regression grade [TRG] 3-4) tumors after nCRT with a sensitivity of 90%, minimizing the risk of development of non-resectable recurrences. Current scarce and retrospective literature suggests that active surveillance following nCRT might not jeopardize overall survival and postponed surgery could be performed safely. Key Message: Before an active surveillance approach could be considered standard treatment, results of phase III randomized trials should be awaited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878756PMC
March 2020

Routine Molecular Analysis for Lynch Syndrome Among Adenomas or Colorectal Cancer Within a National Screening Program.

Gastroenterology 2018 11 29;155(5):1410-1415. Epub 2018 Jul 29.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, the Netherlands. Electronic address:

Background & Aims: It is important to identify individuals with Lynch syndrome because surveillance programs can reduce their morbidity and mortality from colorectal cancer (CRC). We assessed the diagnostic yield of immunohistochemistry to detect Lynch syndrome in patients with advanced and multiple adenomas within our national CRC screening program.

Methods: We performed a prospective study of all participants (n = 1101; 55% male; median age, 66 years; interquartile range, 61-70 years) referred to the Erasmus MC in The Netherlands after a positive result from a fecal immunohistochemical test, from December 2013 to December 2016. Colon tissues were collected from patients with advanced adenomas, ≥4 nonadvanced adenomas, or CRC, and analyzed by immunohistochemistry to identify patients with loss of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, or PMS2): a marker of Lynch syndrome. Specimens from patients with loss of MLH1 were analyzed for MLH1 promoter hypermethylation. Patients with an MMR-deficient tumor or adenoma without MLH1 promoter hypermethylation were referred for genetic analysis.

Results: At colonoscopy, 456 patients (41%) (65% male; mean age, 67 years; interquartile range, 63-71 years) were found to have CRC and/or an adenoma eligible for analysis by immunohistochemistry. Of 56 CRCs, 7 (13%) had lost an MMR protein and 5 had hypermethylation of the MLH1 promoter. Analyses of tumor DNA revealed that 2 patients without MLH1 promoter hypermethylation had developed sporadic tumors. In total, 400 patients with adenomas were analyzed. Of the examined adenomas, 208 (52%) had a villous component and/or high-grade dysplasia: 186 (47%) had a villous component and 41 (10%) had high-grade dysplasia. Only 1 adenoma had lost an MMR protein. This adenoma was found to have 2 somatic mutations in MSH6.

Conclusions: In a CRC screening program in The Netherlands for individuals aged 55 to 75 years, routine screening for Lynch syndrome by immunohistochemistry analysis of colon tissues from patients with advanced and multiple adenomas identified no individuals with this genetic disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2018.07.029DOI Listing
November 2018

Equivalent Accuracy of 2 Quantitative Fecal Immunochemical Tests in Detecting Advanced Neoplasia in an Organized Colorectal Cancer Screening Program.

Gastroenterology 2018 11 25;155(5):1392-1399.e5. Epub 2018 Jul 25.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address:

Background & Aims: Although different brands of fecal immunochemical tests (FITs) are used for colorectal cancer (CRC) screening, few studies have compared their accuracy in detecting advanced neoplasia.

Methods: We performed a large prospective cohort study within the Dutch national CRC screening program to evaluate 2 quantitative FITs: FOB-Gold (Sentinel, Milan, Italy) and OC-Sensor (Eiken Chemical, Tokyo Japan), from May 2016 through March 2017. We randomly selected 42,179 screening-naïve individuals (55-75 years old), who were asked to perform both FITs themselves using the same bowel movement. Participants with positive results from 1 or both FITs (≥15 μg hemoglobin/gram feces) were invited for colonoscopy examination (reference standard). Equivalence in detection of advanced neoplasia was evaluated with a predefined margin of 0.15%.

Results: Of 42,179 invitees, 22,064 (52%) participated and FITs were completed for 21,078 participants. Of 2112 participants (9.6%) with 1 or 2 positive results from FITs, 1778 (84%) underwent a colonoscopy. Of all invitees, the FOB-Gold test detected advanced neoplasia (confirmed by colonoscopy) in 610 participants (1.45%) and the OC-Sensor detected advanced neoplasia (confirmed by colonoscopy) in 606 participants (1.44%)-an absolute difference of 0.01% (95% confidence interval [CI], -0.06% to 0.08%). Of the 21,078 participants who completed both FITs, 1582 (7.5%) had a positive result from the FOB-Gold test and 1627 (7.7%) a positive result from the OC-Sensor test (P = .140). The relative true-positive rate of FOB-Gold vs OC-Sensor in detecting advanced neoplasia was 0.97 (95% CI, 0.92-1.01) and 0.95 (95% CI, 0.87-1.03) for CRC. The relative false-positive rate of the FOB-Gold test vs the OC-Sensor test in detecting advanced neoplasia was 0.99 (95% CI, 0.93-1.05).

Conclusions: In a large prospective study of individuals invited for CRC screening in The Netherlands, we found equivalent accuracy of the FOB-Gold FIT vs the OC-Sensor FIT in detecting advanced neoplasia. These results are relevant for selecting FITs for CRC screening programs worldwide. Dutch National Trial Registry: NTR5874.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2018.07.021DOI Listing
November 2018

Lower Annual Rate of Progression of Short-Segment vs Long-Segment Barrett's Esophagus to Esophageal Adenocarcinoma.

Clin Gastroenterol Hepatol 2019 04 8;17(5):864-868. Epub 2018 Aug 8.

Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, Kansas; Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri. Electronic address:

Background & Aims: European guidelines recommend different surveillance intervals of non-dysplastic Barrett's esophagus (NDBE) based on segment length, as opposed to guidelines in the United States, which do recommend surveillance intervals based on BE length. We studied rates of progression of NDBE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with short-segment BE using the definition of BE in the latest guidelines (length ≥1 cm).

Methods: We collected demographic, clinical, endoscopy, and histopathology data from 1883 patients with endoscopic evidence of NDBE (mean age, 57.3 years; 83.5% male; 88.1% Caucasians) seen at 7 tertiary referral centers. Patients were followed for a median 6.4 years. Cases of dysplasia or EAC detected within 1 year of index endoscopy were considered prevalent and were excluded. Unadjusted rates of progression to HGD or EAC were compared between patients with short (≥1 and <3) and long (≥3) BE lengths using log-rank tests. A subgroup analysis was performed on patients with a documented Prague C&M classification. We used a multivariable proportional hazards model to evaluate the association between BE length and progression. Adjusted hazards ratios were calculated after adjusting for variables associated with progression.

Results: We found 822 patients to have a short-segment BE (SSBE) and 1061 to have long segment BE (LSBE). We found patients with SSBE to have a significantly lower annual rate of progression to EAC (0.07%) than of patients with LSBE (0.25%) (P = .001). For the combined endpoint of HGD or EAC, annual progression rates were significantly lower among patients with SSBE (0.29%) compared to compared to LSBE (0.91%) (P < .001). This effect persisted in multivariable analysis (hazard ratio, 0.32; 95% CI, 0.18-0.57; P < .001).

Conclusion: We analyzed progression of BE (length ≥1 cm) to HGD or EAC in a large cohort of patients seen at multiple centers and followed for a median 6.4 years. We found a lower annual rate of progression of SSBE to EAC (0.07%/year) than of LSBE (0.25%/year). We propose lengthening current surveillance intervals for patients with SSBE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050470PMC
April 2019

Risk factors for refractory anastomotic strictures after oesophageal atresia repair: a multicentre study.

Arch Dis Child 2019 02 14;104(2):152-157. Epub 2018 Jul 14.

Department of Paediatric Surgery and Intensive Care Children, Erasmus MC University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.

Objective: To determine the incidence of refractory anastomotic strictures after oesophageal atresia (OA) repair and to identify risk factors associated with refractory strictures.

Methods: Retrospective national multicentre study in patients with OA born between 1999 and 2013. Exclusion criteria were isolated fistula, inability to obtain oesophageal continuity, death prior to discharge and follow-up <6 months. A refractory oesophageal stricture was defined as an anastomotic stricture requiring ≥5 dilations at maximally 4-week intervals. Risk factors for development of refractory anastomotic strictures after OA repair were identified with multivariable logistic regression analysis.

Results: We included 454 children (61% male, 7% isolated OA (Gross type A)). End-to-end anastomosis was performed in 436 (96%) children. Anastomotic leakage occurred in 13%. Fifty-eight per cent of children with an end-to-end anastomosis developed an anastomotic stricture, requiring a median of 3 (range 1-34) dilations. Refractory strictures were found in 32/436 (7%) children and required a median of 10 (range 5-34) dilations. Isolated OA (OR 5.7; p=0.012), anastomotic leakage (OR 5.0; p=0.001) and the need for oesophageal dilation ≤28 days after anastomosis (OR 15.9; p<0.001) were risk factors for development of a refractory stricture.

Conclusions: The incidence of refractory strictures of the end-to-end anastomosis in children treated for OA was 7%. Risk factors were isolated OA, anastomotic leakage and the need for oesophageal dilation less than 1 month after OA repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2017-314710DOI Listing
February 2019

A novel device for intracolonoscopy cleansing of inadequately prepared colonoscopy patients: a feasibility study.

Endoscopy 2019 01 11;51(1):85-92. Epub 2018 Jul 11.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: The importance of high quality preprocedural bowel preparation is widely acknowledged, but suboptimal bowel cleansing still occurs in up to 20 % of all colonoscopy patients. The aim of this study was to evaluate the performance of a novel intraprocedural cleaning device for cleaning poorly prepared colons.

Methods: This multicenter feasibility study included patients aged 18 - 75 years who were referred for colonoscopy. Intraprocedural cleaning was performed in patients after a limited preprocedural bowel preparation regimen (2 days of dietary restrictions and 2 × 10 mg bisacodyl). The primary outcome was the proportion of adequately prepared patients (Boston Bowel Preparation scale [BBPS] ≥ 2 in each segment) before and after segmental washing with the new device. Secondary outcomes included: cecal intubation rate, procedure time, system usability, patient satisfaction, and safety.

Results: 47 patients (42.6 % male), with a median age of 61 years (interquartile range [IQR] 46 - 67 years), were included at three clinical sites. Cecal intubation was achieved in 46/47 patients (97.9 %). The cleaning device significantly improved the proportion of patients with adequate bowel cleansing (from 19.1 % to 97.9 %;  < 0.001) and median BBPS score (from 3.0 [IQR 0.0 - 5.0] to 9.0 [IQR 8.0 - 9.0]). Median cecal intubation time and total procedure time were 16.5 minutes (IQR 9.0-28.3) and 34.0 minutes (IQR 25.0 - 42.8), respectively. Physicians were satisfied with the ease of use of the device and it was well tolerated by patients. No severe adverse events occurred during the study period.

Conclusions: This feasibility study suggests that the intraprocedural cleaning device appears to be safe and effective in cleaning poorly prepared colons to an adequate level, allowing a thorough colorectal examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0632-1927DOI Listing
January 2019

Self-expandable metal stent placement for malignant esophageal strictures - changes in clinical outcomes over time.

Endoscopy 2019 01 10;51(1):18-29. Epub 2018 Jul 10.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Background: Self-expandable metal stents (SEMSs) are effective for improving dysphagia in patients with incurable esophageal cancer but are also associated with recurrent dysphagia and adverse events. In the past decades, new SEMSs have been introduced, but also patients' risk profiles have altered. It is unknown if these changes have affected SEMS outcomes.

Methods: This retrospective cohort study was conducted in a tertiary referral center in the Netherlands. Patients who underwent palliative esophageal SEMS placement for malignant dysphagia between 1994 and 2017 were included. The primary outcome was to assess shifts over time with respect to recurrent dysphagia and adverse events after SEMS placement.

Results: 997 patients who underwent SEMS placement were included. Recurrent dysphagia occurred in 309 patients (31 %) and remained stable, although with a trend towards an increase over time (hazard ratio [HR] 1.02 per 1-year increase;  = 0.05). Migration rate significantly increased over time (HR 1.04 per 1-year increase;  = 0.01). SEMS-related complications occurred in 461 patients (46.2 %), with 207 (20.7 %) major and 336 (33.7 %) minor complications. Prior chemoradiotherapy was significantly associated with major complications (HR 1.69;  < 0.001). Pain was the most common adverse event and showed a significant increase over time ( < 0.01). Factors associated with pain were prior chemoradiotherapy, absence of a fistula, axial and radial forces, and squamous cell carcinoma.

Conclusions: Despite the introduction of novel esophageal SEMS designs, recurrent dysphagia has not declined over the years. Stent-related complications have increased in recent years, which seems to be mainly associated with more frequent use of chemoradiotherapy prior to SEMS placement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0644-2495DOI Listing
January 2019

Incidence of faecal occult blood test interval cancers in population-based colorectal cancer screening: a systematic review and meta-analysis.

Gut 2019 05 22;68(5):873-881. Epub 2018 Jun 22.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Objective: Faecal immunochemical tests (FITs) are replacing guaiac faecal occult blood tests (gFOBTs) for colorectal cancer (CRC) screening. Incidence of interval colorectal cancer (iCRC) following a negative stool test result is not yet known. We aimed to compare incidence of iCRC following a negative FIT or gFOBT.

Design: We searched Ovid Medline, Embase, Cochrane Library, Science Citation Index, PubMed and Google Scholar from inception to 12 December 2017 for citations related to CRC screening based on stool tests. We included studies on FIT or gFOBT iCRC in average-risk screening populations. Main outcome was pooled incidence rate of iCRCs per 100 000 person-years (p-y). Pooled incidence rates were obtained by fitting random-effect Poisson regression models.

Results: We identified 7 426 records and included 29 studies. Meta-analyses comprised data of 6 987 825 subjects with a negative test result, in whom 11 932 screen-detected CRCs and 5 548 gFOBT or FIT iCRCs were documented. Median faecal haemoglobin (Hb) positivity cut-off used was 20 (range 10-200) µg Hb/g faeces in the 17 studies that provided FIT results. Pooled incidence rates of iCRC following FIT and gFOBT were 20 (95% CI 14 to 29; I=99%) and 34 (95% CI 20 to 57; I=99%) per 100 000 p-y, respectively. Pooled incidence rate ratio of FIT versus gFOBT iCRC was 0.58 (95% CI 0.32 to 1.07; I=99%) and 0.36 (95% CI 0.17 to 0.75; I=10%) in sensitivity analysis. For every FIT iCRC, 2.6 screen-detected CRCs were found (ratio 1:2.6); for gFOBT, the ratio between iCRC and screen-detected CRC was 1:1.2. Age below 60 years and the third screening round were significantly associated with a lower iCRC rate.

Conclusion: A negative gFOBT result is associated with a higher iCRC incidence than a negative FIT. This supports the use of FIT over gFOBT as CRC screening tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2017-315340DOI Listing
May 2019

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

Endoscopy 2018 10 12;50(10):961-971. Epub 2018 Jun 12.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis.

Methods: In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first.

Results: Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs ( = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively ( = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events.

Conclusions: Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0620-8135DOI Listing
October 2018

Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions.

Gut 2019 04 6;68(4):585-593. Epub 2018 Jun 6.

Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Objective: International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression.

Design: Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17.

Results: 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02).

Conclusion: In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2017-314498DOI Listing
April 2019

Effect of anticoagulants and NSAIDs on accuracy of faecal immunochemical tests (FITs) in colorectal cancer screening: a systematic review and meta-analysis.

Gut 2019 05 5;68(5):866-872. Epub 2018 Jun 5.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Objective: Most colorectal cancer (CRC) screening programmes are nowadays based on faecal immunochemical testing (FIT). Eligible subjects often use oral anticoagulants (OACs) or non-steroidal anti-inflammatory drugs (NSAIDs), which could possibly stimulate bleeding from both benign and premalignant lesions in the colon. The aim of this meta-analysis was to study the effect of OACs and NSAIDs use on FIT performance.

Design: A systematic search was conducted until June 2017 to retrieve studies from PubMed, Embase, MEDLINE, Web of science, Cochrane Central and Google Scholar. Studies were included when reporting on FIT results in users versus non-users of OACs and/or NSAIDs in average risk CRC screening populations. Primary outcome was positive predictive value for advanced neoplasia (PPV) of FIT in relation to OACs/NSAIDs use. Values were obtained by conducting random-effect forest plots.

Results: Our literature search identified 2022 records, of which 8 studies were included. A total of 3563 participants with a positive FIT were included. Use of OACs was associated with a PPV of 37.6% (95% CI 33.9 to 41.4) compared with 40.3% (95% CI 38.5 to 42.1) for non-users (p=0.75). Pooled PPV in aspirin/NSAID users was 38.2% (95% CI 33.8 to 42.9) compared with 39.4% (95% CI 37.5 to 41.3) for non-users (p=0.59).

Conclusion: FIT accuracy is not affected by OACs and aspirin/NSAIDs use. Based on the current literature, withdrawal of OACs or NSAIDs before FIT screening is not recommended. Future studies should focus on duration of use, dosage and classes of drugs in association with accuracy of FIT to conduct more specific guideline recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2018-316344DOI Listing
May 2019