Accelerated Marginal Ulcer Healing With Low-Thermal Argon Plasma Endoscopic Treatment

Gastric bypass surgery, specifically Roux-en-Y gastric bypass (RYGB), is the second most common bariatric procedure performed worldwide (29.3%) after sleeve gastrectomy (55.4%). Despite its success in reducing obesity-related conditions, RYGB is associated with the development of marginal ulcers (MUs)-internal wounds at the gastrojejunal anastomosis prone to poor healing. The incidence of MUs in patients post-RYGB ranges widely, reported at 0.6% to 25% in the U.S., with some estimates as high as 34% worldwide due to asymptomatic cases that go undetected unless investigated endoscopically. These ulcers can become chronic and persisting over time, significantly complicating post-surgical outcomes and increasing the risk of severe complications like perforation, which necessitates urgent surgical intervention in approximately 1-2% of cases.

The current standard of care for MUs involves prolonged use of proton pump inhibitors (PPIs), which reduce gastric acidity to promote ulcer healing. However, this approach addresses only one aspect of MU pathophysiology and is limited by several shortcomings. It is often insufficient in preventing recurrence and carries risks of significant side effects, including increased risk of infection, electrolyte imbalances, and potential kidney disease, particularly with long-term use. Standard therapy is 8 weeks high-dose treatment, and a lifelong PPI therapy is considered if success is seen with medical management. For those not responding to 8 weeks of therapy, most advocate for continued PPI treatment with serial endoscopic evaluation, even up to 2 years out from initial diagnosis. Given these challenges, there is an evident need for alternative treatments that can more effectively target the underlying causes of MUs and reduce the reliance on PPIs.

Low-thermal or low-temperature plasma (LTP) represents a significant advance in accelerated wound healing technologies. As the fourth state of matter, physical plasma is used in the field of plasma medicine to treat a variety of medical conditions at atmospheric pressure and temperatures close to body temperature (typically between 20°C and 50°C). Over the past 10 to 15 years, wound healing has been a primary clinical application for LTP, with extensive use demonstrating its clinical efficacy in the treatment of chronic and poorly healing wounds.

The mechanisms by which LTP facilitates wound healing include oxygenation of tissues, activation of growth factors, improvement of microcirculation, reduction of bacterial load in wounds, and devitalization of senescent cells. These effects are primarily achieved by the ionization of argon gas and the generation of reactive oxygen and nitrogen species (RONS) in the gas phase. Clinically, LTP has been applied to a variety of wound types, including pressure ulcers, chronic wounds, and acute wounds, and has demonstrated effectiveness across a range of wound sizes and stages. LTP treatments are particularly noted for their ability to transform chronic wounds into actively healing wounds, thereby altering the physiological state of the wound.

Several studies have rigorously evaluated the safety profile of LTP and confirmed that it does not pose mutagenic or carcinogenic risks. Long-term evaluations have shown no evidence of tumor formation or abnormal tissue architecture in gas plasma-treated animal models, even after extended periods corresponding to 60 human-equivalent years. Patient follow-up studies using advanced imaging techniques have further confirmed the absence of abnormal healing responses, supporting the absence of adverse long-term effects.