# Freeze the Disease: Advances the Therapy for Barrett’s Esophagus and Esophageal Adenocarcinoma

## TL;DR

Cryotherapy is being explored as a safer and more effective treatment for Barrett’s Esophagus and early esophageal cancer, with potential benefits for healing and immune response.

## Contribution

This paper reviews cryotherapy’s expanding role in gastrointestinal diseases and highlights its potential in cryo-immunology and novel delivery methods.

## Key findings

- Cryotherapy preserves tissue architecture and promotes better healing compared to traditional methods.
- Cryotherapy may stimulate the immune system to attack cancer cells beyond the treated area.
- New handheld cryotherapy devices show promise as first-line treatments for Barrett’s Esophagus and esophageal cancer.

## Abstract

Cryotherapy 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, first-line 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.

Cryotherapy 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 FDA-approved 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 of cryotherapy 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 palliation for malignant esophageal strictures may become a preferred approach as more data evolves.