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Autologous Islet Cell Transplantation

Improved Quality of Life for Select Patients with Chronic Pancreatitis after Pancreatectomy with Autologous Islet Cell Transplantation

Pain isolates. If severe, it can lay waste to a life. Yet it often yields little outward sign of its presence, sometimes leading others to underestimate its burden, doubt its existence or even judge the person in pain.

The debilitating pain associated with chronic pancreatitis (CP) can trap patients in their homes, often leaving them unable to work, socialize or even maintain relationships.

When a severe bout of pancreatitis sends such patients to an emergency department, their requests for pain relief may be mistaken for attempts to obtain narcotics for resale since no biomarker assay exists to “prove” that they have advanced CP.

Devastated by pain and stigmatized by society, these patients can at last gain a new lease on life with complete pancreatectomy followed by autologous transplantation of islet cells, the insulin-producing cells in the pancreas. MUSC’s Digestive Disease Center, long a center of excellence in the treatment of pancreatic disease, has performed almost 90 of these procedures since 2009 and is one of the busiest such centers, second only to the University of Minnesota, which pioneered the procedure

According to Katherine A. Morgan, M.D., Associate Professor of Surgery and Medical Director of the Islet Auto-Transplantation  Program at MUSC, offering these patients a new lease on life is “what makes this surgery so gratifying. You put someone so sick and unable to function in life because they’re stuck on chronic narcotics and unable to hold a job or interact with community and then you do this major procedure…and you see them go back to work and have their relationships reestablished. It’s very gratifying to see patients come back and say the pain is gone.”

Selecting the patients who would most benefit from this procedure and helping them to reassemble their shattered lives require the efforts of a multidisciplinary team. At MUSC, this team comprises surgeons, anesthesiologists, endocrinologists,  interventional  radiologists, nurse pain specialists, physician assistants, research scientists and technicians, psychologists and social workers, who provide patients the support they need before, during and after surgery.

Complete pancreatectomy has long been known to provide pain relief in patients who have not  received  substantial  relief from or are not suitable candidates for lesser therapies (ie, medical management with supplemental digestive enzymes, endoscopic techniques, partial resections of the pancreas—all also available at MUSC’s Digestive Disease Center). However, it was rarely performed because the removal of the pancreas resulted in brittle diabetes, marked by dramatic, recurrent swings in glucose levels that were very difficult to control. With the advent of autologous islet cell transplantation, in which islet cells (ie, insulin-producing cells) are isolated from the patient’s excised pancreas and, a few hours later, infused back into the patient’s liver via the portal vein, complete pancreatectomy has become a viable treatment option for the control of pain in select CP patients. There is no threat of rejection because the islet cells are derived from the same patient into whom they are later infused.

Patients in whom complete pancreatectomy with islet cell transplantation should be considered include those with diffuse small-duct CP, which does not benefit  from  typical  procedures such as unblocking of the pancreatic duct or partial resection of the pancreas, and those with hereditary CP, who likely develop the disease when young and are at increased risk of pancreatic cancer. In all patients, but particularly in children with hereditary pancreatitis, it is important to intervene early (after every attempt to save the organ has been made) to remove the pain stimulus so as to prevent remodeling of central pain pathways. Once those central pain pathways are established, they are much harder to break and freeing the patient of pain becomes much more challenging. MUSC has performed this procedure in two children with hereditary pancreatitis, one within the last month, to mitigate pain, improve quality of life and lessen the risk for cancer.

Islet cell transplantation is currently done at only a handful of centers because it requires a clean cell facility capable of operating in accordance with good manufacturing practice (GMP) to ensure the high degree of sterility needed in cells to be infused back into patients. Drawing on funds donated by the Abney Foundation, MUSC invested in such a clean cell facility in 2007. This state-of-the-art facility, capable of handling at least twice the current volume of cases, positions MUSC as a national referral center for the treatment of this complicated and devastating disease, offering patients a chance at a renewed quality of life.

Improved quality of life after complete pancreatectomy with autologous islet cell transplantation was reported in a recent article by David Adams, M.D., Professor of Surgery and Head of the Division of Gastrointestinal and Laparoscopic Surgery at MUSC, and Dr. Morgan, among others. Study patients showed  significant improvement in both the physical component score  (PCS) and mental component score (MCS) of the SF-12 quality of life (QOL) questionnaire.1 Of the 33 patients (25 women; average age, 42 years) undergoing the procedure between March 2009 and April 2010, 74% and 61% of patients showed improvement in PCS and MCS at 6 months, respectively, with both percentages increasing to 86% at 1 year. For a healthy individual, the average QOL is about 50. Patients with chronic pancreatitis have PCS and MCS scores much lower than for patients of other chronic disease (PCS: 25 vs 37 for chronic renal failure and 38 for congestive heart failure; MCS: 32 vs 44 for chronic renal failure and 48 for congestive heart failure), with average PCS increasing to 33 at 6 months and 36 at 1 year and average MCS increasing to 43 at 6 months and 44 at 1 year.

Such marked and early improvement in QOL scores are especially notable, according to Dr. Morgan, because “it is hard to demonstrate changes in quality of life based on any medical intervention … so it is impressive to see such a clear QOL improvement in these patients.”

Other end points considered in the study included narcotics use and insulin dependence. Narcotics use increased in the months after surgery to treat surgery-induced pain but had tapered to less than preoperative rates in half of patients at 6 months and in two-thirds by one year, with continued though slow tapering seen. At 6 months after surgery, 7 of the 33 patients were insulin free and 7 were taking fewer than 10 units per day. At 1 year, 8 were insulin free and 5 required fewer than 10 units. Although the remaining patients required higher doses of insulin, the diabetes was well controlled with the insulin and not subject to the radical swings associated with brittle diabetes. Even patients taking more than 10 units daily of insulin or whose narcotic use was not drastically reduced reported substantial gains in both the mental and physical components of QOL.

The autologous islet cell transplantation program at MUSC dramatically illustrates how close collaboration between clinicians and research scientists and a commitment to the translation of research findings into clinical practice can change patients’ lives for the better. If pain isolates, a community of caring health care professionals dedicated to relieving the pain of CP can help these patients as they take the first steps toward resuming a normal life.

Reference

1 Morgan K, Owczarski S, Borckardt J, et al. Pain control and quality of life after pancreatectomy with islet autotransplantation for chronic pancreatitis. J Gastrointest Surg. 2012;16(1):129-134. DOI:10.1007/s11605-011-1744-y.

*Data on location of centers from Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J. 2011;35:199-206

This article originally appeared in the July/August 2012 issue of Progressnotes.