Transgastric Local Pancreatic Hypothermia: A Novel, Rapid Multimodal Therapy for Acute Pancreatitis

Background: Acute pancreatitis is a painful potentially life-threatening condition of the pancreas with a typically abrupt and unexpected onset. There is no specific treatment for acute pancreatitis apart from supportive care, and management of its complications as they occur. Recent data show that pancreatitis was responsible for 3,510 deaths, and 245,000 hospitalizations in the United States. Annual costs of pancreatitis were estimated at $3.7 billion.

Whereas acute pancreatitis accounts for less than 0.6% of the diagnosis codes in the general population, it comprises up to 3% of these in the Department of Veterans Affairs system. This suggests that acute pancreatitis is more common among veterans. Veterans who had amputations of their proximal limbs due to service-related trauma, when followed for 30 years, had a 3.8-fold increased risk of developing acute pancreatitis compared to distal amputees. Additionally, these veterans had a higher chance of dying from acute pancreatitis.

Current State of Treatment: There are several clinical studies showing a failure of drug therapies that target a single mechanism in acute pancreatitis. Basic science studies show that numerous signaling pathways are activated simultaneously in acute pancreatitis. These observations made us contemplate an alternate approach to this devastating disease.

The Proposal: An in-depth review of the role of cooling published in other systems revealed that cooling slows several of the deleterious signaling pathways operant in acute pancreatitis. This is like storing foods in a refrigerator to slow or prevent their spoiling (which may occur due to various bacteria or the food just decaying). Our studies in pancreatic acinar cells, i.e., the cells in which pancreatitis is initiated and which are damaged in pancreatitis support the ability of cooling to slow several deleterious pathways in pancreatitis.

When we lie down, the stomach covers most of the pancreas on the front. Noting this, we went on further to design a cooling balloon that was placed in the stomach of rats while pancreatic temperatures were monitored and verified that this cooled the pancreas. This finding supports the hypothesis that cooling of the pancreas in a patient with pancreatitis (in whom multiple deleterious signaling pathways are progressing) can be done easily and rapidly in the emergency room and may slow several of these deleterious pathways. However, it is to be noted that we would want to avoid cooling of the vital organs such as the heart and lungs since slowing down their function in acute pancreatitis -- when these organs are already at risk of damage -- would not be beneficial.

The Research: To safely cool the pancreas, we will first have to experimentally decide the ideal temperature range that stops acinar cells from dying or getting inflamed. Once this is decided, we will optimize the conditions in the stomach balloon by which this happens in the pancreas in a live animal. We will also look out to make sure that other important systems (e.g., whole body temperature, heart, lungs, and kidneys) are not affected. Once optimized, we will test the therapeutic effect of the device in animal models of pancreatitis that simulate human disease.

The Benefits: This study will usher in a rapid onset, multimodal, safe, low-cost device. This will avoid drugs, their complications and side effects. Additionally, use of temperatures up to -80C and gastric balloons up to 700 cc for 6 months in humans support this. This will benefit our veterans who are at increased risk of developing acute pancreatitis and succumbing to this catastrophic illness.