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)

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia:Endoscopic Findings and Long-Term Mortality

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation

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

Klinische chemie voor iedereen: het Wikipedia-project

Public relations (PR) and information to patients are key goals of the Dutch Society of Clinical Chemistry (NVKC). In this paper several initiatives will be discussed that have been undertaken to meet this statement. The Wikipedia project is one of those initiatives in which information concerning clinical chemistry is added or revised to the Dutch version of the online encyclopaedia Wikipedia. Over 100 tests and items of clinical chemistry have been added or revised and are recognized as a separate category within this online encyclopaedia. Statistical analysis showed an increase in the number of visitors to these articles of Wikipedia. Furthermore, by adding and improving the available information, the quality of the information provided online is enhanced. In conclusion: the attribution of health care professionals to this public domain leads to enhanced access of high quality information for the main public to clinical chemistry in general and to specific laboratory blood tests

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia

Background &amp; Aims: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. Methods: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. Results: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25–p75 37–91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5–28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1–1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age &lt;71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72–0.84) and fair calibration. Conclusion: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15–99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing.</p