More patients accepted into Mayo's islet cell autotransplant program

Intractable pain from pancreatitis is profoundly debilitating for patients and challenging for clinicians. Historically associated with ductal hypertension, it is now known to result from complex mechanisms involving altered pain perceptions at the peripheral level as well as alterations in central pain processing of nociceptive information. Although increased understanding of the neurobiological basis of pain explains the limitations of current therapies, it has not made treatment less problematic.

For example, patients with pain from chronic, hereditary or recurrent acute pancreatitis that is not successfully controlled by conservative medical management may be candidates for total pancreatectomy with islet cell autotransplantation. But the procedure won't benefit those whose pain is due to neuroplastic changes.

For that reason, Mayo Clinic has always been extremely selective in the patients offered autologous islet cell transplantation, says Santhi Swaroop Vege, M.D., director of the multidisciplinary pancreas disease group at Mayo Clinic in Rochester, Minn. "We are very careful with chronic pancreatitis patients who experience continual pain with little fluctuation or are on high doses of narcotics. That is a sign of central neuroplasticity," he explains. "We send those patients to our pain rehabilitation program for one to three weeks to wean them from drugs. If their pain is a little better at that point, they may be more suitable candidates for islet cell autotransplantation."

Conservative approach reconsidered

As yet, there are no validated tools for assessing the pathogenesis of pancreatic pain, but some are likely to become available in the near future, including advanced neuroimaging techniques and a nerve excitability test currently under investigation in Scandinavia. In the meantime, Dr. Vege says Mayo pancreas specialists are rethinking their cautious approach to pancreatitis patients.

"We wanted to be very sure, very conservative," he explains, "but we began to realize that we were denying the procedure to patients who might benefit, especially those taking large doses of narcotics. After intense discussions, we decided to begin offering islet cell transplantation to more patients because we are developing a clinical feel for those most likely to be helped by it."

Yogish C. Kudva, MBBS, also of Mayo Clinic in Minnesota, notes that a more liberal islet cell transplantation policy still requires expert patient evaluation. "You must take into account patient age and how severely affected the pancreas is," he says. "It is not easy to get islet cells from a pancreas that's deeply scarred. So the question becomes, 'When do you decide to remove it?' You don't want to perform the procedure so early that it isn't appropriate or so late that the pancreas is too scarred to be of use."

More young patients

Dr. Kudva notes that the clinic is now seeing more young patients with hereditary pancreatitis whose path to surgery and transplantation is generally smoother. "We don't hesitate to offer islet cell transplantation to these patients at a young age because they have a relatively high risk of pancreatic cancer in the third, fourth and fifth decades of life. In patients younger than 25, the pancreas is still undamaged and the chance of having a good islet yield and insulin independence is higher," he explains.

Infusion of the sterile islet cells into a patient's portal vein takes place in the surgical ICU and lasts approximately 90 minutes. "Initially, we used ultrasound and fluoroscopy to access the portal vein, but now we cannulate or leave a catheter in the vein during surgery," Dr. Kudva says.

Patients remain on an insulin drip for three days and receive insulin injections for several weeks, after which glucose control is assessed. Ten years post-surgery, about 30 percent of patients are insulin independent, and Dr. Kudva says he expects the results to improve as the program expands.

Dr. Vege adds that given successful outcomes with the first 25 patients, a new islet isolation lab, and highly experienced surgeons and clinicians, the time is right to offer the procedure to more pancreatitis patients. "We are fortunate to have an extremely reputable, cohesive, high-quality, multidisciplinary pancreas disease group that includes five pancreatic surgeons, pancreatic radiologists, interventional radiologists, pathologists and researchers all dedicated to this area. Historically, we are one of the best pancreatic disease centers in the world with a high volume of patients, and we can now broaden that to include more of those with intractable pancreatitis pain."