Non-small-bowel abnormalities identified during small bowel capsule endoscopy

AIM: To investigate the incidence of non-small-bowel abnormalities in patients referred for small bowel capsule endoscopy, this single center study was performed. METHODS: Small bowel capsule endoscopy is an accepted technique to investigate obscure gastrointestinal bleeding. This is defined as bleeding from the digestive tract that persists or recurs without an obvious etiology after a normal gastroduodenoscopy and colonoscopy. Nevertheless, capsule endoscopy sometimes reveals findings outside the small bowel, i. e., within reach of conventional endoscopes. In this retrospective single center study, 595 patients undergoing capsule endoscopy between 2003 and 2009 were studied. The incidence of non-small bowel abnormalities was defined as visible abnormalities detected by capsule endoscopy that are located within reach of conventional endoscopes. RESULTS: In 595 patients, referred for obscure gas-trointestinal bleeding or for suspected Crohn's disease, abnormalities were found in 306 (51.4%). Of these 306 patients, 85 (27.7%) had abnormalities within reach of conventional endoscopes; 63 had abnormalities apparently overlooked at previous conventional endoscopies, 10 patients had not undergone upper and lower endoscopy prior to capsule endoscopy and 12 had abnormalities that were already known prior to capsule endoscopy. The most common type of missed lesions were vascular lesions (n = 47). Non-small-bowel abnormalities were located in the stomach (n = 15), proximal small bowel (n = 22), terminal ileum (n = 21), colon (n = 19) or at other or multiple locations (n = 8). Ten patients with abnormal findings in the terminal ileum had not undergone examination of the ileum during colonoscopy. CONCLUSION: A significant proportion of patients undergoing small bowel capsule endoscopy had lesions within reach of conventional endoscopes, indicating that capsule endoscopy was unnecessarily performed. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies

Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a ‘red-flag’ endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett’s Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett’s neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 µg/cm BE (n=1) or 100 µg/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses o

The optimal imaging window for dysplastic colorectal polyp detection using c-Met targeted fluorescence molecular endoscopy

Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met-targeted fluorescent peptide, in a population at high risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multidiameter single-fiber reflectance/single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13 mg/kg) at a 1-, 2- or 3-h dose-to-imaging interval (n = 3 patients per cohort). Two cohorts were expanded to 6 patients on the basis of target-to-background ratios. Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly higher fluorescence in the colorectal lesions than in surrounding tissue, with a target-to-background ratio of 1.53, 1.66, and 1.74 for the 1-, 2-, and 3-h cohorts, respectively, and a mean intrinsic fluorescence of 0.035 vs. 0.023 mm-1 (P < 0.0003), 0.034 vs. 0.021 mm-1 (P < 0.0001), and 0.033 vs. 0.019 mm-1 (P < 0.0001), respectively. Fluorescence correlated with histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a 1- to 3-h dose-to-imaging interval. No clinically significant differences were observed among the cohorts, although a 1-h dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies

Development and external validation of a model to predict complex treatment after RFA for Barrett's esophagus with early neoplasia

Background & Aims: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course. Methods: We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry. Results: A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84). Conclusions: We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039)

Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation +/- endoscopic resection:results from the national Dutch database in a 10-year period

OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039

Dysplastic Recurrence After Successful Treatment for Early Barrett's Neoplasia:Development and Validation of a Prediction Model

Background & Aims: The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment. Methods: We collected data from the Dutch Barrett Expert Center Registry, a nationwide registry that captures outcomes from all patients with BE undergoing endoscopic treatment in the Netherlands in a centralized care setting. We used predictors related to demographics, severity of reflux, histologic status at baseline, and treatment characteristics. We built a Fine and Gray survival model with least absolute shrinkage and selection operator penalization to predict the incidence of visible dysplastic recurrence after initial successful treatment. The model was validated externally in patients with BE treated in Switzerland and Belgium. Results: A total of 1154 patients with complete BE eradication were included for model building. During a mean endoscopic follow-up of 4 years, 38 patients developed recurrent disease (1.0%/person-year). The following characteristics were independently associated with recurrence (strongest to weakest predictor): a new visible lesion during treatment phase, higher number of endoscopic resection treatments, male sex, increasing BE length, high-grade dysplasia or cancer at baseline, and younger age. External validation showed a C-statistic of 0.91 (95% confidence interval, 0.86–0.94) with good calibration. Conclusions: This is the first externally validated model to predict visible dysplastic recurrence after successful endoscopic eradication treatment of BE with dysplasia or early cancer. On external validation, our model has good discrimination and calibration. This model can help clinicians and patients to determine a personalized follow-up strategy

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

BACKGROUND: Although endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most Barrett's Esophagus (BE) patients, some might experience poor healing (PH) and/or poor squamous regeneration (PSR). We aimed to evaluate PH/PSR incidence and treatment outcomes. METHODS: We included all patients treated with RFA for early BE neoplasia, from a nationwide Dutch registry based on a joint treatment protocol. PH was defined as active inflammatory changes or visible ulcerations ≥3 months post-RFA, PSR as <50% squamous regeneration, and treatment success as complete eradication of BE (CE-BE). Results 1,386 patients (median BE C2M5) underwent RFA with baseline low-grade dysplasia (27%), high-grade dysplasia (30%), or early cancer (43%). In all 134 patients with PH (10%), additional time and acid suppression resulted in complete esophageal healing. 67/134 (50%) had normal regeneration with 97% CE-BE. In total, 74 patients had PSR (5%). As compared to patients with normal squamous regeneration, PSR patients had a higher risk for treatment failure (64% versus 2%, RR 27 [95% CI 18-40]) and progression to advanced disease (15% versus <1%, RR 30 [95% CI 12-81]). Higher BMI, longer BE, reflux esophagitis, and <50% squamous regeneration after baseline endoscopic resection were independently associated with PSR in multivariable logistic regression. Conclusions In half of the patients with PH, additional time and acid suppression may lead to normal squamous regeneration and excellent treatment outcomes. However, if patients experience PSR, the risk for treatment failure and progression to advanced disease is significantly increased with a relative risk of 27 and 30, respectively

Analysis of metastases rates during follow-up after endoscopic resection of early "high-risk" esophageal adenocarcinoma

BACKGROUND AND AIMS: After endoscopic resection (ER) of early esophageal adenocarcinoma (EAC), the optimal management of patients with high-risk histological features for lymph node metastases (LNM) (i.e., submucosal invasion, poor differentiation grade, or lymphovascular invasion (LVI)), remains unclear. We aimed to evaluate outcomes of endoscopic follow-up after ER for high-risk EAC. METHODS: For this retrospective cohort study, data was collected from all Dutch patients managed with endoscopic follow-up (endoscopy, endoscopic ultrasound) after ER for high-risk EAC between 2008 and 2019. We distinguished 3 groups: intramucosal cancers with high-risk features, submucosal cancers with low-risk features, and submucosal cancers with high-risk features. Primary outcome was the annual risk for metastases during follow-up, stratified for baseline histology. RESULTS: A total of 120 patients met the selection criteria. Median FU was 29 months (IQR 15-48). Metastases were observed in 5/25 (annual risk 6.9%; 95% CI 3.0-15), 1/55 (annual risk 0.7%; 95% CI 0-4.0) and 3/40 (annual risk 3.0%; 95% CI 0-7.0) in high-risk intramucosal, low-risk submucosal, and high-risk submucosal cancers, respectively. CONCLUSIONS: Whereas the annual metastasis rate for high-risk submucosal EAC (3.0%) was somewhat lower than expected in comparison with previous reported percentages, the annual metastasis rate of 6.9% for high-risk intramucosal EAC is new and worrisome. This calls for further prospective studies and suggests that strict follow-up of this small subgroup is warranted until prospective data are available

Video capsule enteroscopy : technical and clinical aspects

In this thesis we aimed to answer several questions in capsule endoscopy (CE). In chapter one. the introduction and outline of the thesis, the concept and technical aspects of CE are discussed. Chapter two provides an overview of CE.lt explains the technique of capsule endoscopies and how to optimally watch and interpret the images. Several clinical topics in the field of CE are addressed such as the importance of bowel preparation and the use of prokinetic agents to improve visualization. Indications and contra-indications for CE are discussed. In addition, the role of capsule endoscopy in the workup of small bowel pathology and its place among other small bowel diagnostic modalities such as balloon-assisted enteroscopy is addressed. The first clinical problem we addressed is the fact that analyzing CE is very timeconsuming, since over 50.000 images have to be reviewed. In chapter tree of this thesis we examined whether we could reduce the reading time by reducing the number of analyzed images without missing small bowel lesions. In this single centre prospective study two techniques aimed at reducing the number of images to be viewed were studied. The number of images was reduced by (A) neglecting 50 % of the number of images or by (B) the Quickview~ method. The Quickview mode is a computational tool in which only images suspected for pathology are displayed, thereby discarding most of the available images. I n both studies, one endoscopist viewed the images in the conventional way while another viewed the reduced number of images. Reading times for small bowel images were recorded. K-values were used to calculate inter-observer agreement between viewing techniques. Also diagnostic miss rates were calculated. In total 200 CE procedures were analyzed. We found that median procedure reading times were substantially reduced by viewing half the number of images (10.2 min) and the Quickview technique (4.4 min) compared to conventional viewing (17.0 min). However the diagnostic miss rate was 2 % when half the number of images was viewed and 8 % when the Quickview technique was used. Mainly polyps and tumors were missed while viewing less images. Techniques which reduce the number of images appear to be safe only for some indications, especially in those patients in who a suspected disorder is usually characterized by multiple lesions, diffusely spread throughout the small bowel, such as inflammatory bowel disease.