Sharara, Ala I.

Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge, being the sixth leading cause of cancer mortality with pronounced geographic variability. The incidence rates range from 125 per 100,000 in northern China to 1–1.5 per 100,000 in the United States, driven by environmental and lifestyle factors such as tobacco and alcohol use, dietary habits, and pollution. Major modifiable risk factors include tobacco and alcohol consumption, with a synergistic risk increase when combined. Nonmodifiable risk factors include previous diagnoses of head and neck squamous cell carcinoma (H&N SCC), achalasia, and prior radiotherapy. Prevention strategies must be tailored to specific regional burdens to efficiently allocate medical and financial resources. Gastrointestinal endoscopy is crucial in reducing ESCC burden through early detection and characterization of neoplastic changes, such as high‐grade dysplasia. Early diagnosis significantly improves survival rates, while endoscopic resection of noninvasive dysplasia can prevent ESCC onset, reducing treatment burden for advanced disease. Postresection surveillance can detect high‐risk metachronous lesions. Despite these benefits, endoscopic prevention faces challenges, including the lack of high‐level evidence supporting its efficacy, opportunity costs, the need for specialized training and techniques, and the requirement for advanced technology investments. This Position Statement from the World Endoscopy Organization (WEO) aims to address these challenges, supplying recommendations for the exploitation of endoscopic resources regarding the possible role of screening, quality, and training for the detection, characterization, resection, and surveillance of ESCC.

To evaluate whether ATP in bile serves as a signaling factor regulating ductular secretion, voltage-clamp studies were performed using a novel normal rat cholangiocyte (NRC) model. In the presence of amiloride (100 μM) to block Na+channels, exposure of the apical membrane to ATP significantly increased the short-circuit current ( Isc) from 18.2 ± 5.9 to 52.8 ± 12.7 μA ( n = 18). The response to ATP is mediated by basolateral-to-apical Cl−transport because it is inhibited by 1) the Cl−channel blockers 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (1 mM), diphenylanthranilic acid (1.5 mM), or 5-nitro-2-(3-phenylpropylamino)benzoic acid (50 or 100 μM) in the apical chamber, 2) the K+channel blocker Ba2+(5 mM), or 3) the Na+-K+-2Cl−cotransport inhibitor bumetanide (200 μM) in the basolateral chamber. Other nucleotides stimulated an increase in Iscwith a rank order potency of UTP = ATP = adenosine 5′-O-(3)-thiotriphosphate, consistent with P2upurinergic receptors. ADP, AMP, 2-methylthioadenosine 5′-triphosphate, and adenosine had no effect. A cDNA encoding a rat P2ureceptor (rP2uR) was isolated from a liver cDNA library, and functional expression of the corresponding mRNA in Xenopus laevis oocytes resulted in the appearance of ATP-stimulated currents with a similar pharmacological profile. Northern analysis identified hybridizing mRNA transcripts in NRC as well as other cell types in rat liver. These findings indicate that exposure of polarized cholangiocytes to ATP results in luminal Cl−secretion through activation of P2ureceptors in the apical membrane. Release of ATP into bile may serve as an autocrine or paracrine signal regulating cholangiocyte secretory function.