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Tissue injury is driven by rapid multiple freeze–thaw cycles that rupture cell membranes, supporting favorable wound healing. The approach has drawn growing attention for upper gastrointestinal diseases, including Barrett’s esophagus and early cancer. The review discusses FDA-approved delivery options (Cryoballoon and spray cryotherapy), their roles in eradicating dysplasia, and comparisons in efficacy and safety with radiofrequency ablation and esophageal stent placement, while emphasizing emerging cryo-immunology and handheld delivery platforms.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/freeze-the-disease-advances-the-therapy-for-barretts-esophagus-and-esophageal-adenocarcinoma/469137/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/freeze-the-disease-advances-the-therapy-for-barretts-esophagus-and-esophageal-adenocarcinoma/469137.png","ImageObject",300,407,{"name":92,"@type":93},"Grenda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What mechanism of action does cryotherapy use to treat upper GI tissue?","Question",{"text":112,"@type":113},"Cryotherapy works through flash freezing and rapid multiple freeze–thaw cycles that cause cell membrane rupture, while preserving the tissue architecture and collagen matrix to support favorable wound healing.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which FDA-approved cryotherapy delivery methods are discussed for the GI tract?",{"text":117,"@type":113},"The review discusses Cryoballoon and spray cryotherapy as the two FDA-approved delivery methods available in the GI tract.",{"name":119,"@type":110,"acceptedAnswer":120},"How does cryotherapy relate to Barrett’s esophagus treatment and dysplasia eradication?",{"text":121,"@type":113},"It highlights cryotherapy’s established role in eradicating Barrett’s esophagus with low and high-grade dysplasia, and compares outcomes and safety with radiofrequency ablation (RFA).",{"name":123,"@type":110,"acceptedAnswer":124},"What additional research directions are emphasized beyond esophageal disease?",{"text":125,"@type":113},"The text emphasizes cryo-immunology potential, ongoing research into shrinking primary and metastatic disease, and increasing use of cryotherapy in other upper gastrointestinal precancerous conditions.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},469137,1792164352,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149,"preview_page_count":4},7971474921005,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review  \nFreeze the Disease: Advances the Therapy for Barrett’s Esophagus and Esophageal Adenocarcinoma  \nTed G. Xiao 1,2, Shree Atul Patel 2, Nishita Sunkara 2 and Virendra Joshi 1, *  \nAcademic Editor: Hidekazu Suzuki  \nReceived: 24 November 2025  \nRevised: 19 December 2025  \nAccepted: 19 December 2025  \nPublished: 24 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Digestive Diseases, Emory University, Atlanta, GA 30322, USA; [ted.xiao@emory.edu](ted.xiao@emory.edu)  \n2 Department of Internal Medicine, Emory University, Atlanta, GA 30322, USA; [shree.patel@emory.edu](shree.patel@emory.edu) (S.A.P.); [nishita.sunkara@emory.edu](nishita.sunkara@emory.edu) (N.S.)  \n* [Correspondence: virendra.joshi@emory.edu](Correspondence: virendra.joshi@emory.edu)  \nSimple Summary  \nCryotherapy is a medical technique that uses extreme cold to “flash freeze” and remove unhealthy tissue in the digestive tract. Research is being suggested to prove it is a safer, more effective alternative for treating early-stage cancers and Barrett’s Esophagus compared to traditional “burning” methods. By destroying bad cells while keeping the body’s natural structural “scaffolding” intact, it promotes better healing. For the research community, the most exciting impact is Cryo-immunology, where freezing a tumor may “wake up” the immune system to recognize and attack cancer cells throughout the body. Additionally, studying new handheld delivery devices aims to establish cryotherapy as a standard, firstline treatment. By proving it can effectively clear blockages and improve a patient’s ability to swallow, this research could shift medical practice toward simpler freezing methods that significantly improve quality of life.  \nAbstract  \nCryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing attention as a treatment option for upper gastrointestinal diseases (Barrett’s Esophagus and early cancer) . Currently, two FDAapproved delivery methods are available in the GI tract: Cryoballoon and spray cryotherapy, which will be discussed. In this review, we also propose to examine the expanding role ofcryotherapy in gastrointestinal practice, drawing from both clinical studies and illustrative vignettes. In addition, we will highlight its established role in eradicating Barrett’s with low and high-grade dysplasia and compare its outcomes and safety profile with radiofrequency ablation (RFA) . We will also discuss the application and safety of spray cryotherapy in the palliation of malignant esophageal strictures when compared with Esophageal stent placement. Cryotherapy may have immunological potential, and it may shrink both primary and metastatic diseases. Ongoing research in this field of Cryo-immunology will be highlighted. Beyond esophageal neoplasia, cryotherapy is increasingly utilized in other upper gastrointestinal precancerous conditions. Through this synthesis, our goal is to provide a timely and comprehensive overview of advancements in cryotherapy and its potential to reshape novel therapeutic approaches in upper gastrointestinal cancers. Finally, we highlight the evolution of a novel platform using nitrous oxide delivered by a handheld device, a contact balloon, and a small replaceable cartridge. This approach may make delivery of cryogen application favorable and a first-line approach in the management of Barrett’s esophagus and early cancer. In addition, Cryoballoon therapy for dysphagia  \npalliation for malignant esophageal strictures may become a preferred approach as more data evolves.  \nKeywords: cryotherapy; Barret","cbCaif6eTAtNCdUL","https://ap.wps.com/l/cbCaif6eTAtNCdUL","pdf",8011439,17,"English","# Introduction\n## Barrett’s esophagus, reflux, and esophageal adenocarcinoma\n## Current endoscopic therapies and limitations\n## Rationale for cryotherapy in upper GI conditions\n## Purpose and scope of the review","[{\"question\":\"What mechanism of action does cryotherapy use to treat upper GI tissue?\",\"answer\":\"Cryotherapy works through flash freezing and rapid multiple freeze–thaw cycles that cause cell membrane rupture, while preserving the tissue architecture and collagen matrix to support favorable wound healing.\"},{\"question\":\"Which FDA-approved cryotherapy delivery methods are discussed for the GI tract?\",\"answer\":\"The review discusses Cryoballoon and spray cryotherapy as the two FDA-approved delivery methods available in the GI tract.\"},{\"question\":\"How does cryotherapy relate to Barrett’s esophagus treatment and dysplasia eradication?\",\"answer\":\"It highlights cryotherapy’s established role in eradicating Barrett’s esophagus with low and high-grade dysplasia, and compares outcomes and safety with radiofrequency ablation (RFA).\"},{\"question\":\"What additional research directions are emphasized beyond esophageal disease?\",\"answer\":\"The text emphasizes cryo-immunology potential, ongoing research into shrinking primary and metastatic disease, and increasing use of cryotherapy in other upper gastrointestinal precancerous conditions.\"}]","Freeze the Disease - Advances the Therapy for Barrett’s Esophagus and Esophageal Adenocarcinoma | PDF",1790775145,43]