Low Level of Her-2 Locus Amplification by Fluorescent In Situ Hybridization Does Not Correlate with Her-2 Protein Overexpression by Immunohistochemistry in Barrett's Esophagus

An accurate evaluation of the Her-2 status has important prognostic and therapeutic implications in many carcinomas. The aim of the study was to correlate Her-2 locus (17q11.2) amplification and chromosome 17 gains as assessed by fluorescent in situ hybridization (FISH) with Her-2 protein overexpression by immunohistochemistry (IHC) in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). We analyzed 34 patients with Her-2 amplification and/or chromosome 17gains using FISH on brush cytology specimens. Seven patients (21%) showed high Her-2 locus amplification (Her-2: Cep17 ≥ 5 : 1), 5 (15%) showed low Her-2 locus amplification (Her-2: Cep17 ≥ 2 < 5 : 1), and 22 (65%) displayed gains of chromosome 17 only. Further, we confirmed Her-2 amplification on corresponding biopsies that were taken at the same occasion as the cytologybrushings. Then, we compared the FISH results with IHC data obtained from the corresponding biopsies and showed that low level of Her-2 amplification does not correlate with Her-2 protein overexpression (score +3/+2; P = 1), in contrast to the high amplification level (P = .001). Thus, in our population of BE and EAC patients, low level of Her-2 amplification does not result in detectable level of Her-2 protein as assessed by IHC

The Duodenum harbors a Broad Untapped Therapeutic Potential

The gastroenterologist, when performing an esophagogastroduodenoscopy, is the only medical care provider with easy access to the duodenum (Figure 1A). This simple fact is pivotal in this article that discusses why the duodenum has become such an important anatomic region of interest. Recent insights have revealed the critical physiologic and pathophysiologic role of the small bowel in metabolic homeostasis and its potential role as a driver of obesity, insulin resistance, and subsequent type 2 diabetes mellitus (T2DM). Although the other parts of the small bowel cannot be ignored when describing the potential mechanisms involved in the development of metabolic diseases and T2DM, the excellent endoscopic accessibility of the duodenum makes it a prime target for disease-modifying intervention

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

A novel cryoballoon ablation system for eradication of dysplastic Barrett's esophagus:a first-in-human feasibility study

BACKGROUND:  Endoscopic cryoablation for Barrett's esophagus (BE) might offer advantages over heat-based ablation. Focal cryoballoon ablation has been promising for short-segment BE, whereas the novel 90°-swipe cryoballoon ablation system (CbSAS90) ablates larger areas in a single step (90° over 3 cm). The system allows for dose adjustment. CbSAS90 has been feasible and safe in animal and pre-esophagectomy studies. This is the first clinical study to assess feasibility, safety, and efficacy of CbSAS90 for eradication of dysplastic BE. METHODS:  In this prospective study in dysplastic BE patients, dose finding started with semi-circumferential treatment at 0.8 mm/s (dose 1). The dose was escalated by reducing speed by 0.1 mm/s in six patients until BE surface regression was ≥ 80 % without complications ("effective dose"). The effective dose was subsequently confirmed with circumferential treatment in 12 new patients. Post-procedural pain (0 - 10) and dysphagia (0 - 4) were evaluated. Outcomes were feasibility, safety, and BE surface regression. RESULTS:  25 patients were included, with technically successful treatment in 92 % (95 %CI 73 % - 99 %). Median (95 %CI) BE surface regression was 78 % (50 % - 85 %) for dose 1 and 85 % (55 % - 95 %) for dose 2 (0.7 mm/s), which was defined as the effective dose. Circumferential treatment resulted in 93 % (88 % - 96 %) regression. Two of 12 patients with circumferential treatment developed strictures that required dilation. Median pain and dysphagia scores were low (0 - 3 and 0, respectively). CONCLUSIONS: CbSAS90 was feasible and effective for ablating larger BE areas. The optimal dose for circumferential treatment that balances safety and efficacy requires further evaluation

Barrett's lesion detection using a minimal integer-based neural network for embedded systems integration

Embedded processing architectures are often integrated into devices to develop novel functions in a cost-effective medical system. In order to integrate neural networks in medical equipment, these models require specialized optimizations for preparing their integration in a high-efficiency and power-constrained environment. In this paper, we research the feasibility of quantized networks with limited memory for the detection of Barrett’s neoplasia. An Efficientnet-lite1+Deeplabv3 architecture is proposed, which is trained using a quantization-aware training scheme, in order to achieve an 8-bit integer-based model. The performance of the quantized model is comparable with float32 precision models. We show that the quantized model with only 5-MB memory is capable of reaching the same performance scores with 95% Area Under the Curve (AUC), compared to a fullprecision U-Net architecture, which is 10× larger. We have also optimized the segmentation head for efficiency and reduced the output to a resolution of 32×32 pixels. The results show that this resolution captures sufficient segmentation detail to reach a DICE score of 66.51%, which is comparable to the full floating-point model. The proposed lightweight approach also makes the model quite energy-efficient, since it can be real-time executed on a 2-Watt Coral Edge TPU. The obtained low power consumption of the lightweight Barrett’s esophagus neoplasia detection and segmentation system enables the direct integration into standard endoscopic equipment

Endoscopic submucosal dissection for early esophageal squamous cell carcinoma:long-term results from a Western cohort

Background Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data are derived from Asian studies. We aimed to evaluate the long-term outcomes of ESD for patients with early ESCC in a Western cohort. Methods In this retrospective cohort study, patients with early ESCC amenable to ESD were included from four tertiary referral hospitals in the Netherlands between 2012 and 2017. All ESD procedures were performed by experienced endoscopists, after which the decision for additional treatment was made on a per-patient basis. Outcomes were curative resection rate, ESCC-specific survival, and overall survival. Results Of 68 included patients (mean age 69 years; 34 males), ESD was technically successful in 66 (97%; 95%CI 93%-100%), with curative resection achieved in 34/66 (52%; 95%CI 39%-64%). Among patients with noncurative resection, 15/32 (47%) underwent additional treatment, mainly esophagectomy (n = 10) or definitive chemoradiation therapy (n = 4). Endoscopic surveillance was preferred in 17/32 patients (53%), based on severe comorbidities or patient choice. Overall, 31/66 patients (47%) died during a median follow-up of 66 months; 8/31 (26%) were ESCC-related deaths. The 5-year overall and ESCC-specific survival probabilities were 62% (95%CI 52%-75%) and 86% (95%CI 77%-96%), respectively. Conclusion In this Western cohort with long-term follow-up, the effectiveness and safety of ESD for early ESCC was confirmed, although the rate of noncurative resections was substantial. Irrespective of curative status, the long-term prognosis of these patients was limited mainly due to competing mortality

Spatial Predisposition of Dysplasia in Barrett’s Esophagus Segments: A Pooled Analysis of the SURF and AIM Dysplasia Trials

Surveillance endoscopy detects dysplasia within Barrett's esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly-spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens

Еволюція історичних уявлень про Україну в середньовічній Франції до середини ХVІІ ст.

У статті розглянуто стан ознайомлення французької громадськості ХІ-ХVІІ ст. з Україною, проаналізовано причини цікавості французів до цієї країни на тлі історичних взаємин України та Франції. Автор простежує еволюцію французьких історичних досліджень про Україну у Франції.The author considers the state of acquaintance of the French society of the XVII century with Ukraine, analyses the reasons of the interest the French took in this country on the phone of the historical relations between Ukraine and France and traces the evolution of the French historical studies in Ukraine

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)

Maternal risk associated with the VACTERL association:A case-control study

Background The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors. Methods A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Results Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL. Conclusion We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL