Publications by authors named "Wouter L Curvers"

55 Publications

Incidence and outcomes of poor healing and poor squamous regeneration after radiofrequency ablation therapy for early Barrett's neoplasia.

Endoscopy 2021 Jun 1. Epub 2021 Jun 1.

Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Background: Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett's esophagus (BE). However, some patients experience poor healing and/or poor squamous regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration.

Methods: We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration (< 50 % squamous regeneration), and treatment success (complete eradication of BE [CE-BE]) were evaluated.

Results: 1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk [RR] 27 [95 % confidence interval [CI] 18-40]) and progression to advanced disease (15 % vs. < 1 %, RR 30 [95 %CI 12-81]). Higher body mass index, longer BE segment, reflux esophagitis, and < 50 % squamous regeneration after baseline endoscopic resection were independently associated with poor squamous regeneration in multivariable logistic regression.

Conclusions: In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased.
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http://dx.doi.org/10.1055/a-1521-6318DOI Listing
June 2021

Utility of Routine Esophageal Biopsies in Patients With Refractory Reflux Symptoms.

Am J Gastroenterol 2021 04;116(4):816-820

1Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, the Netherlands; 2Department of Gastroenterology and Hepatology, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.

Introduction: This study aimed to assess the diagnostic yield of routine esophageal biopsies in patients with refractory reflux symptoms.

Methods: We prospectively enrolled consecutive patients referred for upper endoscopy and collected histological, clinical, and endoscopic data.

Results: Of the 301 included patients, 14 (4.7%) patients met the clinicopathological diagnostic definition of eosinophilic esophagitis. Presence of dysphagia, food bolus impaction, atopic background, and typical endoscopic features were the factors with the strongest association and diagnostic accuracy for eosinophilic esophagitis. The diagnostic yield in patients lacking symptoms of dysphagia or endoscopic features was negligible (0% and 1.9%, respectively).

Discussion: Routine esophageal biopsy sampling in patients with refractory reflux symptoms has a low diagnostic yield. Esophageal biopsies should only be obtained in patients with refractory reflux symptoms who also present with dysphagia (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B792).
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http://dx.doi.org/10.14309/ajg.0000000000001064DOI Listing
April 2021

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

J Biophotonics 2021 04 31;14(4):e202000351. Epub 2021 Jan 31.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.
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http://dx.doi.org/10.1002/jbio.202000351DOI Listing
April 2021

Advanced Imaging and Sampling in Barrett's Esophagus: Artificial Intelligence to the Rescue?

Gastrointest Endosc Clin N Am 2021 Jan 26;31(1):91-103. Epub 2020 Oct 26.

Department of Gastroenterology and Hepatology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands. Electronic address:

Because the current Barrett's esophagus (BE) surveillance protocol suffers from sampling error of random biopsies and a high miss-rate of early neoplastic lesions, many new endoscopic imaging and sampling techniques have been developed. None of these techniques, however, have significantly increased the diagnostic yield of BE neoplasia. In fact, these techniques have led to an increase in the amount of visible information, yet endoscopists and pathologists inevitably suffer from variations in intra- and interobserver agreement. Artificial intelligence systems have the potential to overcome these endoscopist-dependent limitations.
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http://dx.doi.org/10.1016/j.giec.2020.08.006DOI Listing
January 2021

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study.

BMJ Open 2020 08 20;10(8):e035504. Epub 2020 Aug 20.

Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, Overijssel, The Netherlands.

Introduction: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP.

Methods And Analysis: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months.

Ethics And Dissemination: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal.

Trial Registration Number: Netherlands Trial Registry (NL7066). Prospectively registered.
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http://dx.doi.org/10.1136/bmjopen-2019-035504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440829PMC
August 2020

Prospective development and validation of a volumetric laser endomicroscopy computer algorithm for detection of Barrett's neoplasia.

Gastrointest Endosc 2021 04 29;93(4):871-879. Epub 2020 Jul 29.

Department of Gastroenterology and Hepatology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.

Background And Aims: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett's esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may help in the process of VLE image interpretation. Our aim was to train and validate a CAD algorithm for VLE-based detection of BE neoplasia.

Methods: The multicenter, VLE PREDICT study, prospectively enrolled 47 patients with BE. In total, 229 nondysplastic BE and 89 neoplastic (high-grade dysplasia/esophageal adenocarcinoma) targets were laser marked under VLE guidance and subsequently underwent a biopsy for histologic diagnosis. Deep convolutional neural networks were used to construct a CAD algorithm for differentiation between nondysplastic and neoplastic BE tissue. The CAD algorithm was trained on a set consisting of the first 22 patients (134 nondysplastic BE and 38 neoplastic targets) and validated on a separate test set from patients 23 to 47 (95 nondysplastic BE and 51 neoplastic targets). The performance of the algorithm was benchmarked against the performance of 10 VLE experts.

Results: Using the training set to construct the algorithm resulted in an accuracy of 92%, sensitivity of 95%, and specificity of 92%. When performance was assessed on the test set, accuracy, sensitivity, and specificity were 85%, 91%, and 82%, respectively. The algorithm outperformed all 10 VLE experts, who demonstrated an overall accuracy of 77%, sensitivity of 70%, and specificity of 81%.

Conclusions: We developed, validated, and benchmarked a VLE CAD algorithm for detection of BE neoplasia using prospectively collected and biopsy-correlated VLE targets. The algorithm detected neoplasia with high accuracy and outperformed 10 VLE experts. (The Netherlands National Trials Registry (NTR) number: NTR 6728.).
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http://dx.doi.org/10.1016/j.gie.2020.07.052DOI Listing
April 2021

Expert assessment on volumetric laser endomicroscopy full scans in Barrett's esophagus patients with or without high grade dysplasia or early cancer.

Endoscopy 2021 Mar 8;53(3):218-225. Epub 2020 Jun 8.

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

Background:  Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE).

Methods:  29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as "neoplastic" or "NDBE." If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence.

Results:  VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % - 79 %) of neoplastic VLE videos. In 54 % (range 27 % - 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % - 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %).

Conclusions:  Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.
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http://dx.doi.org/10.1055/a-1194-0397DOI Listing
March 2021

A computer-assisted algorithm for narrow-band imaging-based tissue characterization in Barrett's esophagus.

Gastrointest Endosc 2021 01 3;93(1):89-98. Epub 2020 Jun 3.

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

Background And Aims: The endoscopic evaluation of narrow-band imaging (NBI) zoom imagery in Barrett's esophagus (BE) is associated with suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CAD) systems may assist endoscopists in the characterization of Barrett's mucosa. Our aim was to demonstrate the feasibility of a deep-learning CAD system for tissue characterization of NBI zoom imagery in BE.

Methods: The CAD system was first trained using 494,364 endoscopic images of general endoscopic imagery. Next, 690 neoplastic BE and 557 nondysplastic BE (NDBE) white-light endoscopy overview images were used for refinement training. Subsequently, a third dataset of 112 neoplastic and 71 NDBE NBI zoom images with histologic correlation was used for training and internal validation. Finally, the CAD system was further trained and validated with a fourth, histologically confirmed dataset of 59 neoplastic and 98 NDBE NBI zoom videos. Performance was evaluated using fourfold cross-validation. The primary outcome was the diagnostic performance of the CAD system for classification of neoplasia in NBI zoom videos.

Results: The CAD system demonstrated accuracy, sensitivity, and specificity for detection of BE neoplasia using NBI zoom images of 84%, 88%, and 78%, respectively. In total, 30,021 individual video frames were analyzed by the CAD system. Accuracy, sensitivity, and specificity of the video-based CAD system were 83% (95% confidence interval [CI], 78%-89%), 85% (95% CI, 76%-94%), and 83% (95% CI, 76%-90%), respectively. The mean assessment speed was 38 frames per second.

Conclusion: We have demonstrated promising diagnostic accuracy of predicting the presence/absence of Barrett's neoplasia on histologically confirmed unaltered NBI zoom videos with fast corresponding assessment time.
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http://dx.doi.org/10.1016/j.gie.2020.05.050DOI Listing
January 2021

Deep learning algorithm detection of Barrett's neoplasia with high accuracy during live endoscopic procedures: a pilot study (with video).

Gastrointest Endosc 2020 06 10;91(6):1242-1250. Epub 2020 Jan 10.

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

Background And Aims: We assessed the preliminary diagnostic accuracy of a recently developed computer-aided detection (CAD) system for detection of Barrett's neoplasia during live endoscopic procedures.

Methods: The CAD system was tested during endoscopic procedures in 10 patients with nondysplastic Barrett's esophagus (NDBE) and 10 patients with confirmed Barrett's neoplasia. White-light endoscopy images were obtained at every 2-cm level of the Barrett's segment and immediately analyzed by the CAD system, providing instant feedback to the endoscopist. At every level, 3 images were evaluated by the CAD system. Outcome measures were diagnostic performance of the CAD system per level and per patient, defined as accuracy, sensitivity, and specificity (ground truth was established by expert assessment and corresponding histopathology), and concordance of 3 sequential CAD predictions per level.

Results: Accuracy, sensitivity, and specificity of the CAD system in a per-level analyses were 90%, 91%, and 89%, respectively. Nine of 10 neoplastic patients were correctly diagnosed. The single lesion not detected by CAD showed NDBE in the endoscopic resection specimen. In only 1 NDBE patient, the CAD system produced false-positive predictions. In 75% of all levels, the CAD system produced 3 concordant predictions.

Conclusions: This is one of the first studies to evaluate a CAD system for Barrett's neoplasia during live endoscopic procedures. The system detected neoplasia with high accuracy, with only a small number of false-positive predictions and with a high concordance rate between separate predictions. The CAD system is thereby ready for testing in larger, multicenter trials. (Clinical trial registration number: NL7544.).
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http://dx.doi.org/10.1016/j.gie.2019.12.048DOI Listing
June 2020

Blue-light imaging and linked-color imaging improve visualization of Barrett's neoplasia by nonexpert endoscopists.

Gastrointest Endosc 2020 05 3;91(5):1050-1057. Epub 2020 Jan 3.

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

Background And Aims: Endoscopic recognition of early Barrett's neoplasia is challenging. Blue-light imaging (BLI) and linked-color imaging (LCI) may assist endoscopists in appreciation of neoplasia. Our aim was to evaluate BLI and LCI for visualization of Barrett's neoplasia in comparison with white-light endoscopy (WLE) alone, when assessed by nonexpert endoscopists.

Methods: In this web-based assessment, corresponding WLE, BLI, and LCI images of 30 neoplastic Barrett's lesions were delineated by 3 expert endoscopists to establish ground truth. These images were then scored and delineated by 76 nonexpert endoscopists from 3 countries and with different levels of expertise, in 4 separate assessment phases with a washout period of 2 weeks. Assessments were as follows: assessment 1, WLE only; assessment 2, WLE + BLI; assessment 3, WLE + LCI; assessment 4, WLE + BLI + LCI. The outcomes were (1) appreciation of macroscopic appearance and ability to delineate lesions (visual analog scale [VAS] scores); (2) preferred technique (ordinal scores); and (3) assessors' delineation performance in terms of overlap with expert ground truth.

Results: Median VAS scores for phases 2 to 4 were significantly higher than in phase 1 (P < .001). Assessors preferred BLI and LCI over WLE for appreciation of macroscopic appearance (P < .001) and delineation (P < .001). Linear mixed-effect models showed that delineation performance increased significantly in phase 4.

Conclusions: The use of BLI and LCI has significant additional value for the visualization of Barrett's neoplasia when used by nonexpert endoscopists. Assessors appreciated the addition of BLI and LCI better than the use of WLE alone. Furthermore, this addition led to improved delineation performance, thereby allowing for better acquisition of targeted biopsy samples. (The Netherlands Trial Registry number: NL7541.).
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http://dx.doi.org/10.1016/j.gie.2019.12.037DOI Listing
May 2020

Deep-Learning System Detects Neoplasia in Patients With Barrett's Esophagus With Higher Accuracy Than Endoscopists in a Multistep Training and Validation Study With Benchmarking.

Gastroenterology 2020 03 22;158(4):915-929.e4. Epub 2019 Nov 22.

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

Background & Aims: We aimed to develop and validate a deep-learning computer-aided detection (CAD) system, suitable for use in real time in clinical practice, to improve endoscopic detection of early neoplasia in patients with Barrett's esophagus (BE).

Methods: We developed a hybrid ResNet-UNet model CAD system using 5 independent endoscopy data sets. We performed pretraining using 494,364 labeled endoscopic images collected from all intestinal segments. Then, we used 1704 unique esophageal high-resolution images of rigorously confirmed early-stage neoplasia in BE and nondysplastic BE, derived from 669 patients. System performance was assessed by using data sets 4 and 5. Data set 5 was also scored by 53 general endoscopists with a wide range of experience from 4 countries to benchmark CAD system performance. Coupled with histopathology findings, scoring of images that contained early-stage neoplasia in data sets 2-5 were delineated in detail for neoplasm position and extent by multiple experts whose evaluations served as the ground truth for segmentation.

Results: The CAD system classified images as containing neoplasms or nondysplastic BE with 89% accuracy, 90% sensitivity, and 88% specificity (data set 4, 80 patients and images). In data set 5 (80 patients and images) values for the CAD system vs those of the general endoscopists were 88% vs 73% accuracy, 93% vs 72% sensitivity, and 83% vs 74% specificity. The CAD system achieved higher accuracy than any of the individual 53 nonexpert endoscopists, with comparable delineation performance. CAD delineations of the area of neoplasm overlapped with those from the BE experts in all detected neoplasia in data sets 4 and 5. The CAD system identified the optimal site for biopsy of detected neoplasia in 97% and 92% of cases (data sets 4 and 5, respectively).

Conclusions: We developed, validated, and benchmarked a deep-learning computer-aided system for primary detection of neoplasia in patients with BE. The system detected neoplasia with high accuracy and near-perfect delineation performance. The Netherlands National Trials Registry, Number: NTR7072.
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http://dx.doi.org/10.1053/j.gastro.2019.11.030DOI Listing
March 2020

Self-sizing radiofrequency ablation balloon for eradication of Barrett's esophagus: results of an international multicenter randomized trial comparing 3 different treatment regimens.

Gastrointest Endosc 2019 09 17;90(3):415-423. Epub 2019 May 17.

Department of Gastroenterology and Hepatology, UZ Gasthuisberg, Leuven, Belgium.

Background And Aims: Recently, the 360 Express radiofrequency ablation balloon catheter (360 Express, Medtronic, Minneapolis, Minn, USA) has replaced the traditional system for circumferential radiofrequency ablation (RFA) of Barrett's esophagus (BE). The aim was to compare 3 different ablation regimens for the 360 Express.

Methods: An international multicenter noninferiority randomized controlled trial was conducted in which patients with a BE (2-15 cm) with dysplasia or early cancer were randomly assigned to the standard (1 × 10 J/cm-clean-1 × 10 J/cm), simple-double (2 × 10 J/cm-no clean), or simple-single ablation regimen (1 × 10 J/cm-no clean). The primary outcome was the percentage endoscopically visual BE regression at 3 months. Secondary outcomes were procedure time, adverse events, and patient discomfort.

Results: Between September 2015 and October 2017, 104 patients were enrolled. The simple-double ablation arm was closed prematurely because of a 21% stenosis rate. The trial continued with the standard (n = 37) and simple-single arm (n = 38). Both arms were comparable at baseline. Noninferiority of the simple-single arm could not be demonstrated: BE regression was 73% in the simple-single arm versus 85% in the standard arm; the median difference was 13% (95% confidence interval, 5%-23%). The procedure time was significantly longer in the standard arm (31 vs 17 minutes, P < .001). Both groups were comparable with regard to adverse events and patient discomfort.

Conclusions: This randomized trial shows that circumferential RFA with the 360 Express using the simple-double ablation regimen results in an unacceptable high risk of stenosis. Furthermore, the results suggest that a single ablation at 10 J/cm results in inferior BE regression at 3 months. We therefore advise using the standard ablation regimen (1 × 10 J/cm-clean-1 × 10 J/cm) for treatment of BE using the 360 Express. (Clinical trial registration number: NTR5191.).
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http://dx.doi.org/10.1016/j.gie.2019.05.023DOI Listing
September 2019

Endoscopic resection for early esophageal carcinoma.

J Thorac Dis 2019 Apr;11(Suppl 5):S713-S722

Department of Gastroenterology and Hepatology, Catharina Cancer Institute, Catharina Hospital, Eindhoven, The Netherlands.

Endoscopic resection for early esophageal cancer is a very precise endoscopic surgical technique and having experience in endoscopic resection is mandatory to perform these kinds of procedures safely. In case of adequate resection and favorable histological outcome, long-term prognosis of the patient is excellent. The basic principle for endoscopic treatment of early adenocarcinoma is based on the fact that the risk of lymph node metastasis gradually increases with the depth of invasion. Inspection and evaluation of all mucosal and submucosal lesions need to be done carefully before endoscopic resection. Endoscopic resection of mucosal (T1m1-3) and superficial submucosal (T1sm1) adenocarcinoma can be curative as well as for superficial mucosal (T1m1-m2) squamous cell carcinoma. In Paris type I lesions in Barrett's esophagus and for early squamous cell carcinoma endoscopic submucosal dissection (ESD) is the preferred option. The risk of severe adverse events associated with endoscopic resection are low. Most adverse events are managed endoscopically and can be treated conservatively. Endoscopic radiofrequency ablation is the most widely used ablation technique for Barrett's epithelium and highly effective to achieve full remission of dysplasia and intestinal metaplasia. The role of radiofrequency ablation in the treatment armamentarium in squamous cell carcinoma of the esophagus has still to be determined.
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http://dx.doi.org/10.21037/jtd.2019.03.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503291PMC
April 2019

The Argos project: The development of a computer-aided detection system to improve detection of Barrett's neoplasia on white light endoscopy.

United European Gastroenterol J 2019 05 6;7(4):538-547. Epub 2019 Mar 6.

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

Background: Computer-aided detection (CAD) systems might assist endoscopists in the recognition of Barrett's neoplasia.

Aim: To develop a CAD system using endoscopic images of Barrett's neoplasia.

Methods: White light endoscopy (WLE) overview images of 40 neoplastic Barrett's lesions and 20 non-dysplastic Barret's oesophagus (NDBO) patients were prospectively collected. Experts delineated all neoplastic images.The overlap area of at least four delineations was labelled as the 'sweet spot'. The area with at least one delineation was labelled as the 'soft spot'. The CAD system was trained on colour and texture features. Positive features were taken from the sweet spot and negative features from NDBO images. Performance was evaluated using leave-one-out cross-validation. Outcome parameters were diagnostic accuracy of the CAD system per image, and localization of the expert soft spot by CAD delineation (localization score) and its indication of preferred biopsy location (red-flag indication score).

Results: Accuracy, sensitivity and specificity for detection were 92, 95 and 85%, respectively. The system localized and red-flagged the soft spot in 100 and 90%, respectively.

Conclusion: This uniquely trained and validated CAD system detected and localized early Barrett's neoplasia on WLE images with high accuracy. This is an important step towards real-time automated detection of Barrett's neoplasia.
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http://dx.doi.org/10.1177/2050640619837443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488793PMC
May 2019

Blue-light imaging has an additional value to white-light endoscopy in visualization of early Barrett's neoplasia: an international multicenter cohort study.

Gastrointest Endosc 2019 04 9;89(4):749-758. Epub 2018 Nov 9.

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

Background And Aims: Endoscopic features of early neoplasia in Barrett's esophagus (BE) are subtle. Blue-light imaging (BLI) may improve visualization of neoplastic lesions. The aim of this study was to evaluate BLI in visualization of Barrett's neoplasia.

Methods: Corresponding white-light endoscopy (WLE) and BLI images of 40 BE lesions were obtained prospectively and assessed by 6 international experts in 3 assessments. Each assessment consisted of overview and magnification images. Assessments were as follows: assessment 1, WLE only; assessment 2, BLI only; and assessment 3, corresponding WLE and BLI images. Outcome parameters were as follows: (1) appreciation of macroscopic appearance and surface relief (visual analog scale scores); (2) ability to delineate lesions (visual analog scale scores); (3) preferred technique for delineation (ordinal scores); and (4) quantitative agreement on delineations (AND/OR scores).

Results: Experts appreciated BLI significantly better than WLE for visualization of macroscopic appearance (median 8.0 vs 7.0, P < .001) and surface relief (8.0 vs 6.0, P < .001). For both overview and magnification images, experts appreciated BLI significantly better than WLE for ability to delineate lesions (8.0 vs 6.0, P < .001 and 8.0 vs 5.0, P < .001). There was no overall significant difference in AND/OR scores of WLE + BLI when compared with WLE, yet agreement increased significantly with WLE + BLI for cases with a low baseline AND/OR score on WLE, both in overview (mean difference, 0.15; P = .015) and magnification (mean difference, 0.10; P = .01).

Conclusions: BLI has additional value for visualization of BE neoplasia. Experts appreciated BLI better than WLE for visualization and delineation of BE neoplasia. Quantitative agreement increased significantly when BLI was offered next to WLE for lesions that were hard to delineate with WLE alone. (ISRCTN registry study ID: ISRCTN15916689.).
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http://dx.doi.org/10.1016/j.gie.2018.10.046DOI Listing
April 2019

Cancer risk perception in relation to associated symptoms in Barrett's patients: A cross sectional study on quality of life.

United European Gastroenterol J 2018 Nov 7;6(9):1316-1322. Epub 2018 Sep 7.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands.

Background: Barrett's oesophagus affects patients' quality of life and may be a psychological burden due to the threat of developing an oesophageal adenocarcinoma.

Objective: Assessing the oesophageal adenocarcinoma risk perceived by non-dysplastic Barrett's oesophagus patients and its association with quality of life, illness perception and reflux symptoms.

Methods: This cross-sectional questionnaire study included 158 Barrett's oesophagus non-dysplastic patients aged 18-75 years. Based on their annual and lifetime oesophageal adenocarcinoma risk estimations measured with the Magnifier Scale, patients were classified as overestimating or underestimating. Associations between the groups where assed on demographics, reflux symptoms and results of the Outcomes Study Short-Form-36 (SF-36) and the Brief Illness Perception Questionnaire (B-IPQ).

Results: The annual oesophageal adenocarcinoma risk was overestimated by 41%. Overestimating patients had lower means on the SF-36 domains: bodily pain (annual  = 0.007 and lifetime  = 0.014), general health (annual 0.011 and lifetime  = 0.014), vitality (annual  = 0.030), physical functioning (lifetime  = 0.028), worse illness perception (total score  = 0.001) and significantly more reflux symptoms.

Conclusions: Overestimation of the oesophageal adenocarcinoma risk by Barrett's oesophagus patients was associated with decreased quality of life and worse illness perceptions, which is most likely caused by symptoms of dyspepsia and reflux. These symptoms should be adequately treated, and patients may be in need of extra support and specific information about their oesophageal adenocarcinoma risk.
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http://dx.doi.org/10.1177/2050640618798508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206536PMC
November 2018

Salvage endoscopic resection in patients with esophageal adenocarcinoma after chemoradiotherapy.

Endosc Int Open 2018 Sep 11;6(9):E1126-E1129. Epub 2018 Sep 11.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands.

 For early esophageal adenocarcinoma, endoscopic resection is an accepted curative treatment with an excellent long-term prognosis. Case series from Japan have reported endoscopic resection of residual esophageal squamous cell carcinoma after chemoradiotherapy. This is the first report describing endoscopic resection of residual esophageal adenocarcinoma after chemoradiotherapy. Two patients with advanced esophageal adenocarcinoma had been treated with chemoradiotherapy because comorbidity precluded esophageal resection. When residual tumor was observed endoscopically, complete remission was achieved by salvage endoscopic therapy alone or in combination with argon plasma coagulation (APC). Both patients achieved long-term sustained remission and died of non-tumor-related causes.
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http://dx.doi.org/10.1055/a-0599-6008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133672PMC
September 2018

Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett's oesophagus: a multicentre randomised controlled trial.

Lancet Gastroenterol Hepatol 2018 08 20;3(8):566-574. Epub 2018 Jun 20.

Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands. Electronic address:

Background: For focal radiofrequency ablation of Barrett's oesophagus, a simplified regimen (3 × 15 J/cm, without cleaning) has proven to be as effective as the standard regimen (2 × 15 J/cm, followed by cleaning, followed by 2 × 15 J/cm). However, this simplified regimen seemed to be associated with a higher stenosis rate. Therefore, we lowered the radiofrequency energy and hypothesised that this new simplified regimen would be as effective and safe as the standard regimen.

Methods: This randomised non-inferiority trial included patients with dysplastic Barrett's oesophagus or residual Barrett's oesophagus after endoscopic resection or circumferential radiofrequency ablation, in five European tertiary referral centres. Patients were randomly assigned (1:1) to the new simplified regimen (3 × 12 J/cm, without cleaning) or the standard regimen, with variable block sizes of four, six, and eight patients, stratified by participating hospital. Focal radiofrequency ablation was done every 3 months, up to a maximum of three treatments, until all Barrett's oesophagus was eradicated. The primary outcome was complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments, assessed in the intention-to-treat population. Non-inferiority was assessed on the basis of the difference between groups in the median percentage of Barrett's oesophagus surface regression, with a non-inferiority margin of -15%. This study is registered with www.trialregister.nl, number NTR4994, and is completed.

Findings: Between March 25, 2015, and July 25, 2016, 84 patients were randomly assigned to treatment: 44 to receive the simplified regimen and 40 to receive the standard regimen. One patient assigned to the simplified regimen and four assigned to the standard regimen were excluded because they weree found not to be eligible; therefore the final intention-to-treat population consisted of 43 patients in the simplified ablation group and 36 in the standard ablation group. Complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments was achieved in 32 (74%, 95% CI 59-87) patients treated with the simplified protocol, versus 30 (83%, 95% CI 67-94) patients treated with the standard protocol (p=0·34). Median Barrett's oesophagus surface regression after two focal radiofrequency ablation sessions was 98% (IQR 95-100) in the simplified regimen group and 100% (97-100) in the standard regimen group. The difference between medians was 2% (95% CI -0·562 to 3·162); thus the simplified regimen was deemed non-inferior to the standard regimen. Stenoses requiring dilatation were observed in four (9%) of 43 patients in the simplified regimen group and four (11%) of 36 in the standard regimen group. Post-procedural bleeding requiring repeat endoscopy occurred in one (2%) patient in the simplified ablation group and three (8%) patients in the standard ablation group. One patient (2%) in the simplified treatment group died 36 days after the second radiofrequency ablation procedure, due to an unknown cause.

Interpretation: Based on the results of this study, we conclude that the simplified regimen is the preferred regimen for focal radiofrequency ablation of Barrett's oesophagus.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(18)30157-2DOI Listing
August 2018

Predictive features for early cancer detection in Barrett's esophagus using Volumetric Laser Endomicroscopy.

Comput Med Imaging Graph 2018 07 13;67:9-20. Epub 2018 Apr 13.

Department of Electrical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address:

The incidence of Barrett cancer is increasing rapidly and current screening protocols often miss the disease at an early, treatable stage. Volumetric Laser Endomicroscopy (VLE) is a promising new tool for finding this type of cancer early, capturing a full circumferential scan of Barrett's Esophagus (BE), up to 3-mm depth. However, the interpretation of these VLE scans can be complicated, due to the large amount of cross-sectional images and the subtle grayscale variations. Therefore, algorithms for automated analysis of VLE data can offer a valuable contribution to its overall interpretation. In this study, we broadly investigate the potential of Computer-Aided Detection (CADe) for the identification of early Barrett's cancer using VLE. We employ a histopathologically validated set of ex-vivo VLE images for evaluating and comparing a considerable set of widely-used image features and machine learning algorithms. In addition, we show that incorporating clinical knowledge in feature design, leads to a superior classification performance and additional benefits, such as low complexity and fast computation time. Furthermore, we identify an optimal tissue depth for classification of 0.5-1.0 mm, and propose an extension to the evaluated features that exploits this phenomenon, improving their predictive properties for cancer detection in VLE data. Finally, we compare the performance of the CADe methods with the classification accuracy of two VLE experts. With a maximum Area Under the Curve (AUC) in the range of 0.90-0.93 for the evaluated features and machine learning methods versus an AUC of 0.81 for the medical experts, our experiments show that computer-aided methods can achieve a considerably better performance than trained human observers in the analysis of VLE data.
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http://dx.doi.org/10.1016/j.compmedimag.2018.02.007DOI Listing
July 2018

Novel Developments in Endoscopic Mucosal Imaging.

Gastroenterology 2018 05 17;154(7):1876-1886. Epub 2018 Feb 17.

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

Endoscopic techniques such as high-definition and optical-chromoendoscopy have had enormous impact on endoscopy practice. Since these techniques allow assessment of most subtle morphological mucosal abnormalities, further improvements in endoscopic practice lay in increasing the detection efficacy of endoscopists. Several new developments could assist in this. First, web based training tools could improve the skills of the endoscopist for enhancing the detection and classification of lesions. Secondly, incorporation of computer aided detection will be the next step to raise endoscopic quality of the captured data. These systems will aid the endoscopist in interpreting the increasing amount of visual information in endoscopic images providing real-time objective second reading. In addition, developments in the field of molecular imaging open opportunities to add functional imaging data, visualizing biological parameters, of the gastrointestinal tract to white-light morphology imaging. For the successful implementation of abovementioned techniques, a true multi-disciplinary approach is of vital importance.
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http://dx.doi.org/10.1053/j.gastro.2018.01.070DOI Listing
May 2018

Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy.

J Biomed Opt 2017 08;22(8):86001

, Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam.

Early neoplasia in Barrett’s esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm−1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.
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http://dx.doi.org/10.1117/1.JBO.22.8.086001DOI Listing
August 2017

Computer-aided detection of early Barrett's neoplasia using volumetric laser endomicroscopy.

Gastrointest Endosc 2017 Nov 16;86(5):839-846. Epub 2017 Mar 16.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands.

Background And Aims: Volumetric laser endomicroscopy (VLE) is an advanced imaging system that provides a near-microscopic resolution scan of the esophageal wall layers up to 3-mm deep. VLE has the potential to improve detection of early neoplasia in Barrett's esophagus (BE). However, interpretation of VLE images is complex because of the large amount of data that need to be interpreted in real time. The aim of this study was to investigate the feasibility of a computer algorithm to identify early BE neoplasia on ex vivo VLE images.

Methods: We used 60 VLE images from a database of high-quality ex vivo VLE-histology correlations, obtained from BE patients ± neoplasia (30 nondysplastic BE [NDBE] and 30 high-grade dysplasia/early adenocarcinoma images). VLE features from a recently developed clinical VLE prediction score for BE neoplasia served as input for the algorithm: (1) higher VLE surface than subsurface signal and (2) lack of layering. With this input, novel clinically inspired algorithm features were developed, based on signal intensity statistics and grayscale correlations. For comparison, generic image analysis methods were examined for their performance to detect neoplasia. For classification of the images in the NDBE or neoplastic group, several machine learning methods were evaluated. Leave-1-out cross-validation was used for algorithm validation.

Results: Three novel clinically inspired algorithm features were developed. The feature "layering and signal decay statistics" showed the optimal performance compared with the other clinically features ("layering" and "signal intensity distribution") and generic image analyses methods, with an area under the receiver operating characteristic curve (AUC) of .95. Corresponding sensitivity and specificity were 90% and 93%, respectively. In addition, the algorithm showed a better performance than the clinical VLE prediction score (AUC .81).

Conclusions: This is the first study in which a computer algorithm for BE neoplasia was developed based on VLE images with direct histologic correlates. The algorithm showed good performance to detect BE neoplasia in ex vivo VLE images compared with the performance of a recently developed clinical VLE prediction score. This study suggests that an automatic detection algorithm has the potential to assist endoscopists in detecting early neoplasia on VLE. Future studies on in vivo VLE scans are needed to further validate the algorithm.
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http://dx.doi.org/10.1016/j.gie.2017.03.011DOI Listing
November 2017

Feasibility of laser marking in Barrett's esophagus with volumetric laser endomicroscopy: first-in-man pilot study.

Gastrointest Endosc 2017 Sep 2;86(3):464-472. Epub 2017 Feb 2.

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

Background And Aim: Volumetric laser endomicroscopy (VLE) provides a circumferential scan of the esophageal wall layers and has potential to improve detection of neoplasia in Barrett's esophagus (BE). The novel VLE laser marking system enables direct in vivo marking of suspicious areas as identified on VLE. These laser marked areas can subsequently be targeted for biopsies. The aim was to evaluate the visibility and positional accuracy of laser marks (LMs) in different esophageal tissue types on white light endoscopy (WLE) and VLE.

Methods: Patients with BE with or without neoplasia underwent imaging with VLE. Protocol refinements were practiced in a learning phase. In the second phase, visibility of LMs was assessed by random marking in squamous, BE, and gastric tissue. In phase 3, positional accuracy of the LMs was tested by identifying and laser marking surrogate targets (endoscopically placed cautery marks). In the final phase, the most suspicious areas for neoplasia were identified in each patient using VLE, targeted by LMs, and biopsy samples subsequently obtained.

Results: Sixteen patients with BE were included (14 men; median age, 68 years), 1 of whom was included twice in different study phases. Worst histologic diagnoses were 9 non-dysplastic Barrett's esophagus (NDBE), 3 low-grade dysplasia (LGD), 4 high-grade dysplasia (HGD), and 1 early adenocarcinoma (EAC). In total, 222 LMs were placed, of which 97% was visible on WLE. All LMs were visible on VLE directly after marking, and 86% could be confirmed during post hoc analysis. LM targeting was successful with positional accuracy in 85% of cautery marks. Inaccurate targeting was caused by system errors or difficult cautery mark visualization on VLE. In the final phase (5 patients), 18 areas suspicious on VLE were identified, which were all successfully targeted by LMs (3 EAC, 3 HGD, 1 LGD, and 11 NDBE). Mean VLE procedure time was 22 minutes (±6 minutes standard deviation); mean endoscopy time was 56 minutes (±17 minutes). No adverse events were reported.

Conclusions: This first-in-human study of VLE-guided laser marking was found to be feasible and safe in 17 procedures. Most LMs were visible on WLE and VLE. Targeting VLE areas of interest proved to be highly successful. VLE-guided laser marking may improve the detection and delineation of Barrett's neoplasia in the future.
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http://dx.doi.org/10.1016/j.gie.2017.01.030DOI Listing
September 2017

Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett's esophagus using high-quality histological correlation.

Gastrointest Endosc 2017 May 19;85(5):918-926.e7. Epub 2016 Sep 19.

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

Background And Aims: Volumetric laser endomicroscopy (VLE) provides a circumferential scan that enables visualization of the subsurface layers of the esophageal wall at 7 μm resolution. The aims of this study were to identify VLE features of Barrett's esophagus (BE) neoplasia and to develop a VLE prediction score.

Methods: A database of VLE images from endoscopic resection specimens, precisely correlated with histology, from patients with BE with and without neoplasia was used. Features potentially predictive for early BE neoplasia were identified by unblinded evaluation of 25 VLE-histology images. In a learning phase, 20 VLE images with or without BE neoplasia were scored by 2 VLE experts, blinded to histology. A prediction score was created by using multivariable logistic regression analyses and validated by scoring 40 VLE images (50% neoplastic) by using area under receiver operating characteristic (ROC) curve (AUC) analysis.

Results: Three VLE features independently predictive for BE neoplasia were identified: (1) lack of layering; (2) higher surface than subsurface signal; (3) presence of irregular, dilated glands/ducts. A VLE neoplasia prediction score was developed with the following: (1) 6 points; (2) 6 or 8 points for equal or higher surface signal; and (3) 5 points. The ROC curve of this prediction score showed an AUC of 0.81 (95% confidence interval, 0.71-0.90). A cut-off value of ≥8 was associated with sensitivity and specificity of 83% and 71%, respectively.

Conclusions: When high-quality ex vivo VLE-histology correlation was used, the VLE features of layering, surface signal, and irregular glands/ducts were independently and significantly associated with BE neoplasia. A VLE prediction score for BE neoplasia was developed and validated, with promising accuracy. (Clinical trial registration number: NCT01862666.).
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http://dx.doi.org/10.1016/j.gie.2016.09.012DOI Listing
May 2017

Diagnosis by Endoscopy and Advanced Imaging of Barrett's Neoplasia.

Adv Exp Med Biol 2016;908:81-98

Department of Gastroenterology and Hepatology, Academic Medical Center, Room B1-245, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.

Evaluation of patients with Barrett's esophagus (BE) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BE because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia. The evaluation and treatment of patients with BE and early stage neoplasia should be centralized in tertiary referral centers, where procedures are performed under optimal conditions, by expert endoscopists. Lesions that require resection are almost always detected by HD-WLE, although advanced imaging techniques can detect additional flat lesions. However, these are of limited clinical significance because they are effectively eradicated by ablation therapy. No endoscopic imaging technique can reliably assess submucosal or lymphangio invasion. Endoscopic resection of early stage neoplasia in patients with BE is important for staging and management. Optical chromoendoscopy can also be used to evaluate lesions before endoscopic resection and in follow-up after successful ablation therapy.
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http://dx.doi.org/10.1007/978-3-319-41388-4_5DOI Listing
January 2017

Computer-aided detection of early neoplastic lesions in Barrett's esophagus.

Endoscopy 2016 Jul 21;48(7):617-24. Epub 2016 Apr 21.

Department of Gastroenterology, Catharina Hospital, Eindhoven, the Netherlands.

Background And Study Aims: Early neoplasia in Barrett's esophagus is difficult to detect and often overlooked during Barrett's surveillance. An automatic detection system could be beneficial, by assisting endoscopists with detection of early neoplastic lesions. The aim of this study was to assess the feasibility of a computer system to detect early neoplasia in Barrett's esophagus.

Patients And Methods: Based on 100 images from 44 patients with Barrett's esophagus, a computer algorithm, which employed specific texture, color filters, and machine learning, was developed for the detection of early neoplastic lesions in Barrett's esophagus. The evaluation by one endoscopist, who extensively imaged and endoscopically removed all early neoplastic lesions and was not blinded to the histological outcome, was considered the gold standard. For external validation, four international experts in Barrett's neoplasia, who were blinded to the pathology results, reviewed all images.

Results: The system identified early neoplastic lesions on a per-image analysis with a sensitivity and specificity of 0.83. At the patient level, the system achieved a sensitivity and specificity of 0.86 and 0.87, respectively. A trade-off between the two performance metrics could be made by varying the percentage of training samples that showed neoplastic tissue.

Conclusion: The automated computer algorithm developed in this study was able to identify early neoplastic lesions with reasonable accuracy, suggesting that automated detection of early neoplasia in Barrett's esophagus is feasible. Further research is required to improve the accuracy of the system and prepare it for real-time operation, before it can be applied in clinical practice.
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http://dx.doi.org/10.1055/s-0042-105284DOI Listing
July 2016

A new paradigm shift in endoscopy: From interpretation to automated image analysis?

Gastrointest Endosc 2016 Jan;83(1):115-6

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

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http://dx.doi.org/10.1016/j.gie.2015.08.057DOI Listing
January 2016

Detection of buried Barrett's glands after radiofrequency ablation with volumetric laser endomicroscopy.

Gastrointest Endosc 2016 Jan 26;83(1):80-8. Epub 2015 Jun 26.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands.

Background And Aims: The prevalence and clinical relevance of buried Barrett's glands (BB) after radiofrequency ablation (RFA) in Barrett's esophagus (BE) are debated. Recent optical coherence tomography studies demonstrated a high prevalence of BBs. Direct histological correlation, however, has been lacking. Volumetric laser endomicroscopy (VLE) is a second-generation optical coherence tomography system capable of scanning a large surface of the esophageal wall layers with low-power microscopy resolution. The aim was to evaluate whether post-RFA subsquamous glandular structures (SGSs), detected with VLE, actually correspond to BBs by pursuing direct histological correlation with VLE images.

Methods: In vivo VLE was performed to detect SGSs in patients with endoscopic regression of BE post-RFA. A second in vivo VLE scan was performed to confirm correct delineation of the SGSs. After endoscopic resection, the specimens were imaged ex vivo with VLE. Extensive histological sectioning of SGS areas was performed, and all histology slides were evaluated by an expert BE pathologist.

Results: Seventeen patients underwent successful in vivo VLE (histological diagnosis before endoscopic treatment: early adenocarcinoma in 8 patients and high-grade dysplasia in 9). In 4 of 17 patients, no SGSs were identified during VLE, and a random resection was performed. In the remaining 13 patients (76%), VLE detected SGS areas, which were all confirmed on a second in vivo VLE scan and subsequently resected. Most SGSs identified by VLE corresponded to normal histological structures (eg, dilated glands and blood vessels). However, 1 area containing BBs was found on histology. No specific VLE features to distinguish between BBs and normal SGSs were identified.

Conclusions: VLE is able to detect subsquamous esophageal structures. One area showed BBs beneath endoscopically normal-appearing neosquamous epithelium; however, most post-RFA SGSs identified by VLE correspond to normal histological structures. (

Clinical Trial Registration Number: NTR4056.).
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http://dx.doi.org/10.1016/j.gie.2015.05.028DOI Listing
January 2016

PPI-responsive esophageal eosinophilia cannot be distinguished from eosinophilic esophagitis by endoscopic signs.

Eur J Gastroenterol Hepatol 2015 May;27(5):506-11

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

Background: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated disease histologically characterized by eosinophil-predominant inflammation. One-third of patients respond to proton pump inhibitor (PPI) treatment; this group is identified as having PPI-responsive esophageal eosinophilia (PPI-REE). If we could predict the response to PPIs on the basis of endoscopic signs, futile treatment efforts and additional endoscopies to assess treatment response can be prevented.

Objective: To determine whether endoscopic signs can distinguish PPI-REE from EoE.

Methods: Endoscopic images of 30 EoE and 30 PPI-REE patients were included. Baseline characteristics were compared between groups. Complete clinical remission after a PPI trial for at least 8 weeks was classified as PPI-REE. Per patient, at least three depersonalized images were incorporated into a slideshow. These images were scored by two experienced endoscopists according to a validated classification system.

Results: Characteristics were highly comparable between EoE and PPI-REE patients. Endoscopic signs were similar and did not enable differentiation between EoE and PPI-REE [presence of: rings (P=0.893), white exudates (P=0.209), furrows (P=0.371), edema (P=0.554), crepe paper esophagus (P=1.000), and strictures (P=0.071)].

Conclusion: Endoscopic signs at baseline endoscopy cannot distinguish EoE from PPI-REE before a PPI trial; the demographic and clinical characteristics in both groups are similar. Endoscopic features do not enable differentiation between PPI-REE and EoE.
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http://dx.doi.org/10.1097/MEG.0000000000000331DOI Listing
May 2015

Evaluating the endoscopic reference score for eosinophilic esophagitis: moderate to substantial intra- and interobserver reliability.

Endoscopy 2014 Dec 10;46(12):1049-55. Epub 2014 Sep 10.

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

Background And Study Aims: Recently the Endoscopic Reference Score (EREFS) for endoscopic assessment of eosinophilic esophagitis was introduced, with good interobserver agreement for most signs. The EREFS has not yet been evaluated by other investigators and intraobserver agreement has not been assessed. The aim of this study was to further validate the EREFS by assessing interobserver and intraobserver agreement of endoscopic signs in patients with eosinophilic esophagitis.

Patients And Methods: High-quality endoscopic images were made of the esophagus of 30 patients with eosinophilic esophagitis (age 36 years, range 23 - 46 years; 5 female), 6 of whom were in remission. At least three depersonalized images per patient were incorporated into a slideshow. Images were scored by four expert and four trainee endoscopists who were blinded to the patients' conditions. Interobserver agreement was assessed. After 4 weeks, the images were rescored in a different order to assess intraobserver agreement.

Results: Interobserver agreement was substantial for rings (κ 0.70), white exudates (κ 0.63), and crepe paper esophagus (κ 0.62), moderate for furrows (κ 0.49) and strictures (κ 0.54), and slight for edema (κ 0.12). Intraobserver agreement was substantial for rings (median κ 0.64, IQR 0.46 - 0.70), furrows (median κ 0.69, IQR 0.50 - 0.89), and crepe paper esophagus (median κ 0.69, IQR 0.62 - 0.83), moderate for white exudates (median κ 0.58, IQR 0.54 - 0.71) and strictures (median κ 0.54, IQR 0.33 - 0.70), and less than chance for edema (median κ 0.00, IQR 0.00 - 0.29). Inter- and intraobserver agreement was not substantially different between expert and trainee endoscopists.

Conclusions: Using the EREFS, endoscopic signs of eosinophilic esophagitis were scored consistently by expert and trainee endoscopists.
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http://dx.doi.org/10.1055/s-0034-1377781DOI Listing
December 2014
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