SAN FRANCISCO — A majority of patients with chronic pancreatitis experienced pain relief and many were spared a lifetime of insulin-dependent diabetes when total pancreatectomy was followed by autotransplantation of islet cells in a University of Minnesota study.
Dr. Tun Jie and Dr. David E. Sutherland, both of the University of Minnesota, Minneapolis, reported results of the dual procedure in 136 patients at the annual clinical congress of the American College of Surgeons. Their retrospective clinical review represents the largest collection of cases presented to date.
An estimated 80,000 patients per year suffer pancreatitis, at a cost of $63.8 million, Dr. Jie said.
In some patients, the disease becomes chronic, resulting in intractable pain, malabsorption, and weight loss despite interim surgical procedures such as dilation of the pancreatic duct. For these patients, pain control often is achieved only by total pancreatectomy, he explained. However, the surgery propels patients into diabetes by removing the gland that makes insulin.
Since 1977, the University of Minnesota has been using various techniques to isolate and process patients' islet of Langerhans cells from their diseased pancreases and transplant them back into the patients following pancreatectomy.
Among 105 patients who completed a pain questionnaire following the dual procedure, 68 reported complete resolution of pain and another 22 said their pain had lessened. Just 15 patients said their pain was unchanged, and none reported worsened pain following pancreatectomy.
Insulin independence was achieved in patients who received the most pancreatic islet cells, with a threshold of 2,000 islet equivalents per kilogram required to prevent the need for regular insulin injections.
Of the 51 patients who did receive 2,000 or more islet cells, 37 required only intermittent insulin or none at all during long-term follow-up.
The investigators found a clear link between previous surgery and islet cell yield. Patients with no previous pancreatic surgery had a mean yield of about 4,000 islet equivalents per kilogram, compared with about 3,700 for patients with a previous pancreatic resection. Patients with a history of a Puestow procedure (lateral pancreaticojejunostomy) had a much lower mean yield, about 1,531 islet equivalents per kilogram.
Because extensive surgery impacts islet cell yield, pancreatectomy and autotransplantation should be performed early in the course of the disease, Dr. Jie recommended.
Over the years, the surgical team refined the procedure, eventually concluding that complete pancreatectomy was preferable to near-total pancreatectomy or distal pancreatectomy, since patients undergoing the latter procedures often required reoperation.
The method of islet processing and infusion also varied, with results representing eight different distribution options. The preferred approach is always a portal infusion, said Dr. Jie, but portal pressure variability sometimes necessitates the use of a kidney capsule or peritoneal infusion.
The mean operating time of 10 hours included 2–4 hours for islet isolation in some cases. (Today, infusion of islet cells is sometimes done post operatively.) The estimated blood loss was 1,500 cc.
The mean length of hospital stay was 22 days; however, some patients remained hospitalized for an extended period only for completion of metabolic studies.
There were two deaths in the series, one due to sepsis following colon perforation and one due to pulmonary embolism on postoperative day 2.
Complications among the 136 patients included 42 infections, 12 bleeding episodes requiring reoperation, and 6 biliary complications.
Pediatric patients included in the series “are the group doing the best,” Dr. Jie said.
Patient selection reflected referral patterns to the University of Minnesota and therefore a relatively low number of patients whose chronic pancreatitis was due to alcohol abuse.
“I can tell you that alcoholic patients in our population actually have done the worst. Part of that involves lifestyle [issues] such as trauma unrelated to the surgery itself, and not taking medical advice as they should,” he continued.
Dr. Jeffrey B. Matthews, a University of Cincinnati surgeon who has performed numerous pancreatectomy/islet cell autotransplants, raised the troubling issue of patients in intractable visceral pain whose lengthy medical histories fail to document a clear history of pancreatitis.
Dr. Sutherland agreed that these patients pose a dilemma, but said that the surgery is often their only option and noted that they do well.
Another thorny issue is narcotic-induced hyperalgesia syndrome in patients treated for years with powerful painkillers prior to the surgery.
Dr. Sutherland said that although these patients get some relief from pancreatitis pain, simple intestinal gas remains very painful for them.
Malabsorption and maldigestion are common problems following the surgery, and Dr. Sutherland said he increasingly believes colectomy should be performed in conjunction with total pancreatectomy in patients who already have extreme colon dysfunction.