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.
Currently, the most common low-thermal plasma sources used to treat external wounds are
PlasmaJets and Dielectric Barrier Discharge (DBD) plasma sources. However, the physical
dimensions of these devices limit their use in endoscopic applications. This has limited
the availability of LTP for the treatment of internal wounds and ulcers.
Argon plasma coagulation (APC) is a technology that has been used in endoscopy for more
than three decades. It has demonstrated clinical safety and efficacy in many areas,
including bleeding management (e.g., bleeding ulcers), ablation of cancerous tissue, and
precise treatment in sensitive areas. It is primarily used in endoscopic procedures with
flexible probes, but also in laparoscopic and open surgery settings. The flexible probes
are available in various diameters, 1.5 mm, 2.3 mm and 3.2 mm.
APC works by ionizing argon gas with a high-frequency alternating current passed through
an electrode. This ionized gas forms a physical plasma that is applied to tissue.
Depending on the mode and effect setting, the plasma can be adjusted in power from as low
as 1 W to as high as 120 W. At higher power settings (5 W and above), the plasma exhibits
a more pronounced thermal effect due to increased current flow through the tissue,
facilitating effective coagulation. Conversely, at lower settings below 5 W, a
low-thermal plasma effect is achieved, minimizing tissue coagulation through dynamic
application and avoiding prolonged exposure to a single spot. As with PlasmaJets and
Dielectric Barrier Discharge (DBD) plasma sources, the effectiveness of low-thermal argon
plasma is primarily due to the high energy and voltage that generate reactive oxygen and
nitrogen species (RONS).