Chronic Pancreatitis
Jada Fabrizio
Beth Schrope, MD, PhD, Assistant Professor of Surgery, and Mark A. Hardy, MD, Director Emeritus and Founder, Renal & Islet Transplantation, look on as Joseph Dinordo III, MD, Surgical Resident, uses a Ricordi chamber to harvest and purify pancreatic islet cells.
Chronic pancreatitis is a relatively rare condition characterized by progressive, irreversible damage to the pancreas. It may be caused by gallstones, alcoholism, or hypertriglyceridemia (high concentrations of fatty molecules called triglycerides), or it may develop after an episode of acute (short-term) pancreatitis. In at least half of patients, the cause remains unknown. Over time, chronic pancreatitis leads to inability to properly digest food due to lack of digestive enzymes (pancreatic exocrine insufficiency), which can cause indigestion, bloating, diarrhea, and even malnutrition.
But the most devastating feature of chronic pancreatitis is pain, which frequently becomes severe enough to require daily narcotic medications. For those whose lives have deteriorated because of unrelenting pain, relief—and return to normal life—is possible only when the pancreas is removed.
The singular goal of total pancreatectomy (removal of the pancreas) for patients with chronic pancreatitis is to relieve pain. Because the pancreas produces digestive enzymes and hormones including insulin, this surgery is reserved only for those in whom pain is so severe and unremitting that it has led to dependence on narcotic medications. After pancreatectomy, pain is relieved in 93% of cases, but the absence of insulin production leaves patients fully diabetic.
For people whose lives had been transformed by unbearable pain and narcotic dependence, the benefits of living pain-free far outweigh the tradeoff of managing surgically-induced diabetes. Diabetes is largely manageable today with advances in medications and insulin delivery devices such as continual pumps. Nevertheless, even when diabetes is well controlled, it still requires significant lifestyle changes, and it presents many risks to patients' long-term health.
At NewYork-Presbyterian/Columbia, a new therapeutic option now enables some patients to undergo pancreatectomy without becoming diabetic. This alternative, called autologous islet transplantation, involves infusion of the patient's own pancreatic islet cells into his or her liver, where they may act like a backup pancreas, independently producing insulin.
It works like this: First, the patient's pancreas is surgically removed. Islet of Langerhans cells (the cells in the pancreas that produce insulin), are isolated from the pancreas and made into a solution. The solution is then infused into the patient's liver, through the hepatic vein. Once in the liver, the islet cells may begin to produce insulin that functions just as it did when produced in the pancreas.
When autologous islet transplantation is successful, the procedure results in patients maintaining normal blood sugar levels without needing insulin. According to Beth Schrope, MD, PhD, Assistant Professor of Surgery, Columbia University College of Physicians and Surgeons, the procedure is fully successful in one third of patients. "In this group, the cells maintain their natural function, insulin continues to be produced, and patients live both pain free and diabetes free." The durability of success varies, with patients remaining insulin independent for as little as one year up to 11 years.
In another third of patients, success is moderate. These patients require small amounts of insulin to maintain relatively normal glucose management.
In the last third of patients, the islet cells do not function as hoped, and patients become fully diabetic. In some cases, failure may occur if the pancreas was so diseased at the time of surgery that the islets are just too unhealthy. In other patients, the islet cells may be destroyed by high blood sugar from inadequately controlled diabetes.
"It is important to remember that most patients are pain free after pancreatectomy, which is the primary goal of surgery," says Dr. Schrope. "Patients may become partially or fully diabetic, but they have their lives back. They can return to work and normal life, which is tremendous. If islet cell transplantation is successful, the ability to avoid diabetes is an added bonus."
The Department of Surgery at Columbia is one of only a few U.S. centers to offer autologous cell transplantation, which is a highly specialized and complex procedure. It has been made possible by years of groundwork laid by Mark Hardy, MD, Director Emeritus and Founder, Renal & Islet Transplantation, a pioneer of the development of allogeneic islet cell transplantation and transplant immunology (involving transplantation from a separate donor to a recipient). During his 40year career in kidney and pancreas transplantation at NewYork-Presbyterian/Columbia, Dr. Hardy's team had amassed not only a laboratory full of specialized equipment, but years of invaluable expertise. His research led to the first successful transplant of islet cells from pancreatic donors to recipients in 2004.
When Dr. Schrope realized that the unique needs of patients with chronic pancreatitis could potentially be met by the resources already in place from Dr. Hardy's work, she introduced the concept of doing autologous procedures (use of the patient's own cells) in this population. Because autologous transplants do not involve transplantation from one person to another, they do not pose the risk of rejection or require that patients take immunosuppressant medication after transplantation.
"Patients with chronic pancreatitis have no good treatments for their pain other than narcotics. We are very pleased that we can offer autologous islet transplantation so that they can be free from pain, while having a chance at retaining the endocrine function of the pancreas," says Dr. Schrope.