Novel cryoballoon 180° ablation system for treatment of Barrett's esophagus-related neoplasia:a first-in-human study

Background The novel 180 degrees cryoballoon (CbAS (180) ) enables semicircumferential treatment over a length of 3cm per application. This first-in-human study evaluates its feasibility, efficacy, and safety for the treatment of Barrett's esophagus (BE) neoplasia. Methods This multicenter study consisted of dose-finding and extension phases. Dose-finding started with the lowest dose possible (1.0mm/s). For each dose, six patients were treated circumferentially over a 3-cm length. The dose was increased until the median BE regression was >= 60% without serious adverse events (SAEs). In the extension phase, the dose was confirmed in 19 new patients. The outcomes were technical success, BE regression after one treatment, and SAEs. Results 25 patients (median Prague C0M3) were included (6 dose-finding/19 extension). In two patients, the CbAS (180) could not be applied because of unstable balloon positioning. The technical success rate was 96% (22/23). In the six dose-finding patients, the starting dose resulted in median BE regression of 94% (95% confidence interval [CI] 60%-97%) without SAEs and was thus considered effective. Overall median BE regression was 80% (95%CI 60%-90%). Conclusion Single-session CbAS (180) seems feasible, safe, and effective, and is a promising technique for the treatment of patients with BE neoplasia

Disease burden in primary sclerosing cholangitis in the Netherlands: A long-term follow-up study

Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss. Methods: All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time. Results: A total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%. Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time

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

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

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

Background & 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 <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

Goals of endoscopic eradication therapy in Barrett’s esophagus: a narrative review

Barrett’s esophagus is a premalignant condition, and endoscopic eradication therapy is indicated upon development of early neoplasia. Therapy consists of endoscopic resection for visible lesions, if present, followed by endoscopic ablation for remaining flat Barrett’s epithelium. Since Barrett’s esophagus with early neoplasia in itself is asymptomatic disease, the ultimate goal of endoscopic eradication therapy is to prevent progression to advanced cancer: a disease stage with limited treatment options and a poor prognosis. The preventive nature of endoscopic treatment may give rise to debate about the preferred endpoint to pursue. Establishment of a careful balance between the benefits of endoscopic eradication therapy against its risks, such as complications and other adverse events, may help to define the optimum endpoint for each individual patient. To date, various endpoints have been used in regular practice and different endpoints are used in clinical studies. The most important differences between these endpoints are whether all visible Barrett’s epithelium is eradicated or all dysplasia and cancer; and whether the endpoint is assessed on endoscopic examination only or with histologic confirmation. In this narrative review, we aim to evaluate these different endpoints of endoscopic eradication therapy with potential advantages and limitations, and present three clinical vignettes each with a different suggestion for an appropriate treatment endpoint

Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett's esophagus: impact on treatment response and postprocedural pain

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) but is associated with significant postprocedural pain. Alternatively, balloon-based focal cryoablation (CRYO) has recently been developed, which preserves the extracellular matrix and might therefore be less painful. Although data for CRYO are still limited, uncontrolled studies suggest comparable safety and efficacy to RFA in eradicating limited BE areas. Therefore, secondary endpoints such as pain might become decisive for treatment selection. We aimed to compare efficacy and tolerability between focal CRYO and RFA. METHODS: We identified BE patients undergoing focal ablation (either RFA or CRYO) of all visible BE from our prospective cohort in 2 Dutch referral centers. After ablation, patients completed a 14-day digital diary to assess chest pain (0-10), dysphagia (0-4), and analgesics use. A follow-up endoscopy was scheduled after 3 months to assess the BE surface regression (blindly scored by 2 independent BE expert endoscopists). Outcomes were BE surface regression; 14-day cumulative scores (area under the curves [AUCs]) for pain, dysphagia, analgesics, and peak pain. RESULTS: We identified 46 patients (20 CRYO, 26 RFA) with similar baseline characteristics. The BE regression was comparable (88% vs 90%, P = .62). AUCs for pain, dysphagia, and analgesics were significantly smaller after CRYO versus RFA (all P < .01). Peak pain was lower after CRYO (visual analog scale 2 vs 4, P < .01), and the duration of pain was also shorter after CRYO (2 vs 4 days, P < .01). CRYO patients used analgesics for 2 days versus 4 days for RFA (P < .01). CONCLUSIONS: In this multicenter, nonrandomized cohort study, we found no differences in efficacy after a single treatment with CRYO and RFA for short-segment BE. Patients reported less pain after CRYO as compared with RFA. Moreover, CRYO patients used fewer analgesics. Our results suggest a different pain course favoring CRYO over RFA, but a randomized trial is needed for definitive conclusions. (Clinical trial registration number: NCT02249975.).status: publishe