Dutch-Flemish translation and validation of the gastrointestinal symptom scales from the patient­reported outcomes measurement information system (PROMIS)®.

PURPOSE: To translate the eight PROMIS® GastrointestinaI Symptom Scales into Dutch-Flemish and to evaluate their psychometric properties. METHODS: This study consisted of two parts: (1) translation according to the Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology and (2) evaluation of psychometric properties: structural validity, using confirmatory factor analysis; and construct validity using hypothesis testing. RESULTS: In the first part of the study, in 19 out of the 77 items (24.7%) translation was challenging. After discussion between the translators, consensus could be achieved. In the cognitive debriefing interview phase, ten minor changes in the wording of items were made. A universal Dutch-Flemish translation for all 77 items was obtained. In de second part of the study a good fit was found for three DF-PROMIS GI Scales: Bowel Incontinence, Gas and Bloating, and Belly Pain. Four scales (Reflux, Disrupted Swallowing, Diarrhea, and Constipation) did not show sufficient fit and fit for the Nausea and Vomiting scale could not be assessed because of skewed responses. Construct validity was considered sufficient for six out of eight DF-PROMIS GI Scales. Less than 75% of hypothesis for de Constipation and Disrupted Swallowing scales could be confirmed. CONCLUSION: The PROMIS GI Symptom Scales were successfully translated into DutchFlemish. The findings suggest a sufficient structural validity for the PROMIS GI Scales. Bowel Incontinence, Gas and Bloating and Belly Pain. Construct validity was sufficient for the Scales Gas and Bloating, Incontinence, Nausea and Vomiting, Reflux, Belly Pain, and Diarrhea.

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.

Development and External Validation of a Model to Predict Complex Treatment After Radiofrequency Ablation 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).

Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density.

BACKGROUND: The objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop an operator-independent computer-based tool to determine UC activity based on endoscopic images. METHODS: First, we built a computer algorithm using data from 29 consecutive patients with UC and 6 healthy controls (construction cohort). The algorithm (red density: RD) was based on the red channel of the red-green-blue pixel values and pattern recognition from endoscopic images. The algorithm was refined in sequential steps to optimise correlation with endoscopic and histological disease activity. In a second phase, the operating properties were tested in patients with UC flares requiring treatment escalation. To validate the algorithm, we tested the correlation between RD score and clinical, endoscopic and histological features in a validation cohort. RESULTS: We constructed the algorithm based on the integration of pixel colour data from the redness colour map along with vascular pattern detection. These data were linked with Robarts histological index (RHI) in a multiple regression analysis. In the construction cohort, RD correlated with RHI (r=0.74, p<0.0001), Mayo endoscopic subscores (r=0.76, p<0.0001) and UC Endoscopic Index of Severity scores (r=0.74, p<0.0001). The RD sensitivity to change had a standardised effect size of 1.16. In the validation set, RD correlated with RHI (r=0.65, p=0.00002). CONCLUSIONS: RD provides an objective computer-based score that accurately assesses disease activity in UC. In a validation study, RD correlated with endoscopic and histological disease activity.

Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.

BACKGROUND: To improve detection of mucosal lesions during colonoscopy a number of imaging modalities have been suggested, including high definition and virtual chromoendoscopy. Given the theoretical advantage of these new imaging techniques, we aimed to investigate their use for the detection of polyps in patients referred for colonoscopy in a large tertiary hospital. METHODS: Demographic, endoscopic, and histological data from 1855 consecutive patients undergoing colonoscopy were collected prospectively. Patients were randomly assigned to three endoscopy systems (Fujinon, Olympus, or Pentax) in combination with four modalities: conventional white-light colonoscopy (n = 505), high definition white-light colonoscopy (n = 582), virtual chromoendoscopy (n = 285) and high definition virtual chromoendoscopy (n = 483). RESULTS: The mean adenoma detection rate (ADR) was 34.9 %, and the adenoma per colonoscopy rate (APCR) was 2.1. No significant differences were noted between the three endoscopy systems. Moreover, no differences in ADR or APCR were observed between the four imaging modalities. High definition white-light colonoscopy resulted in a significantly higher detection of sessile serrated adenomas (8.2 % vs. 3.8 %; P < 0.01) and adenocarcinomas (2.6 % vs. 0.5 %; P < 0.05) compared with the conventional procedure. CONCLUSIONS: No significant differences in ADR or APCR between different endoscopy systems, high definition, and/or virtual chromoendoscopy could be observed in routine colonoscopies in the general population. High definition endoscopy was associated with a significantly higher detection rate of serrated adenomas and adenocarcinomas.

Efficacy and safety of radiofrequency ablation of Barrett's esophagus in the absence of reimbursement: a multicenter prospective Belgian registry.

BACKGROUND: Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS: Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS: 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS: Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial.

BACKGROUND: Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined. OBJECTIVE: To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC. DESIGN: A multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group. RESULTS: There was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and NBI (21.5%) (OR 1.02 (95% CI 0.44 to 2.35, p=0.964). Biopsies from the surrounding mucosa yielded no diagnosis or dysplasia. The per lesion neoplasia detection was 17.4% for CE and 16.3% for NBI (OR 1.09 (95% CI 0.59 to 1.99, p=0.793). The total procedural time was on average 7 min shorter in the NBI group. CONCLUSION: CE and NBI do not differ significantly for detection of colitis-associated neoplasia. Given the longer withdrawal time for CE and easier applicability, NBI may possibly replace classical CE. TRIAL REGISTRATION NUMBER: NCT01882205; Results.

Virtual chromoendoscopy (I-SCAN) detects more polyps in patients with Lynch syndrome: a randomized controlled crossover trial.

Background and study aims (Virtual) chromoendoscopy detects more polyps than standard white-light endoscopy in patients with Lynch syndrome. Previous back-to-back trials did not randomize for the examination order, creating a possible bias in favor of chromoendoscopy. We aimed to assess the difference in polyp detection between high definition white-light endoscopy (HD-WLE) and virtual chromoendoscopy with I-SCAN in patients with Lynch syndrome. Patients and methods In this prospective, controlled trial, patients were randomized to either HD-WLE followed by I-SCAN (Group 1; n = 31) or I-SCAN followed by HD-WLE (Group 2; n = 30). Polyps found during the first pass were removed. The primary end point of the study was the difference in adenoma detection between HD-WLE and I-SCAN, expressed as the miss rate for adenomas for each technique. Results In Group 1, I-SCAN detected four additional patients with at least one adenoma, whereas HD-WLE did not increase the adenoma detection rate in Group 2 (relative risk [RR] 0.4; P = 0.08). In Group 1, five adenomas were detected and removed with HD-WLE and a second pass with I-SCAN detected a further eight adenomas. In Group 2, I-SCAN detected 15 adenomas and subsequent HD-WLE detected 2 additional adenomas. The adenoma miss rate was significantly higher for HD-WLE (62 %) compared with I-SCAN (12 %; RR 0.44, 95 % confidence interval [CI] 0.21 to 0.87; P = 0.007). The miss rate for lesions was 57 % and 24 %, respectively, and was significantly different in favor of I-SCAN (RR 0.54, 95 %CI 0.3 to 0.85; P = 0.005). The mean inspection time in both groups was not significantly different during first (485 vs. 536 seconds; 95 %CI - 139.91 to 33.34) or second pass (421 vs. 387 seconds; 95 %CI - 32.24 to 104.89). Conclusion Our data suggest that virtual chromoendoscopy with I-SCAN reduces the adenoma and polyp miss rate in patients with Lynch syndrome, independently of inspection time. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01823471).

A tiered system for assessing the risk of genetically modified plants to non-target organisms.

Representatives of the developers of modern agricultural biotechnology are proposing a tiered approach for conducting non-target organism risk assessment for genetically modified (GM) plants in Europe. The approach was developed by the Technical Advisory Group of the EuropaBio Plant Biotechnology Unit (http://www.europabio.org/TAG.htm) and complements other international activities to harmonize risk assessment. In the European Union (EU), the principles and methods to be followed in an environmental risk assessment for the placing on the market of GM plants are laid out in Annex II of Directive 2001/18/EC on the deliberate release into the environment of GMOs, Commission Decision 2002/623/EC and Regulation (EC) No. 1829/2003. Additional information is provided in the European Food Safety Authority guidance document of 2004. However, risk assessment for effects to non-target organisms could benefit from further clarification and remains the subject of much discussion in Europe. The industry-wide approach developed by EuropaBio is based on the fundamental steps of risk evaluation, namely hazard and exposure assessment. It follows a structured scheme including assessment planning, product characterization and assessment of hazard/exposure (Tier 0), single high dose and dose response testing (Tier 1), refined hazard characterization and exposure assessment (Tier 2) and further refined risk assessment experiments (Tier 3). An additional tier (Tier 4) was included to reflect the fact that post-market activities such as monitoring are required under Directive 2001/18/EC. The approach is compatible with conditions of commercial release in the EU and around the world.

Different responses of tobacco antioxidant enzymes to light and chilling stress.

The effect of elevated light treatment (25 degrees C, PPFD 360 mumol m-2 sec-1) or chilling temperatures combined with elevated light (5 degrees C, PPFD 360 mumol m-2 sec-1) on the activity of six antioxidant enzymes, guaiacol peroxidases, and glutathione peroxidase (GPx, EC 1.11.1.9) protein accumulation were studied in tobacco Nicotiana tabacum cv. Petit Havana SR1. Both treatments caused no photooxidative damage, but chilling caused a transient wilting. The light treatment increased the activities of ascorbate peroxidase (APx, EC 1.11.1.11) and guaiacol peroxidases while catalase (EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1), monodehydroascorbate reductase (MDHAR, EC 1.6.5.4), dehydroascorbate reductase (DHAR, EC 1.8.5.1), and glutathione reductase (EC 1.6.4.2) were unchanged. In contrast, chilling treatment did not increase any of the antioxidant enzyme activities, but decreased catalase and to a lesser extent DHAR activities. Glutathione peroxidase protein levels increased sporadically under light treatment and constantly under chilling. Both chilling and light stress caused induction of glutathione synthesis and accumulation of oxidised glutathione, although the predominant part of the glutathione pool remained in the reduced form. Antioxidant enzymes from the chilling treated plants were measured at both 25 degrees C and 5 degrees C. Measurements at 5 degrees C revealed a 3-fold reduction in catalase activity, compared with that measured at 25 degrees C, indicating that the overall reduction in catalase after four days of chilling was approximately 10-fold. The overall reduction in activity for the other antioxidant enzymes after four days of chilling was 2-fold for GR and APx, 1.5-fold for MDHAR, 3.5-fold for DHAR. The activity of SOD was the same at 25 and 5 degrees C. These results indicate that catalase and DHAR are most strongly affected by the chilling treatment and may be the rate-limiting factor of the antioxidant system at low temperatures.