sing Option

At the 2007 Digestive Disease Week (DDW) meeting, Syed A. Ahmad, MD, presented data from 92 patients on whom TP/IAT was performed at the University of Cincinnati Medical Center between 2000, the year the center began the procedures, and 2004. Dr. Ahmad demonstrated that, postoperatively, patients often had significantly reduced insulin requirementsincluding many who were off insulin completelyand their level of pain also dropped precipitously. He also noted that there is a wide range of patients who are good candidates for these procedures, including those with either small or large duct pancreatitis. Furthermore, he conceded that some patients do fail, such as some of those with preoperative narcotic use or advanced diabetes.

But a lot of doctors dont even know this [procedure] is possible, said Dr. Ahmad, assistant professor of surgery in the Division of Surgical Oncology at the University of Cincinnati College of Medicine. Everyone takes care of chronic pancreatitis patients, and everyone has patients they dont know what to do with because theyve failed traditional surgeries or they have small duct disease and there are no other options besides a total pancreatectomy. In those situations, people should consider referring patients to centers that perform this surgery.

Truly Revolutionary

David E.R. Sutherland, MD, PhD, professor of surgery and chief in the Division of Transplantation at the University of Minnesota Medical School, agrees strongly. The group at his institution has performed 188 of these procedures from February 1977 to September 2006. The results of these procedures were presented by Dr. Sutherlands colleague, surgery resident and research fellow Annelisa Carlson, MD, at the annual meeting of the Pancreas Club, a specialized gathering that precedes the DDW meeting every year.

In the study, 55% of the adults had full islet graft function and were insulin-independent at one year; 34% were still insulin-independent at 10 years and another third had partial islet function and minimal insulin requirements. Furthermore, 94% of the adult patients stated they had less pain after the surgery, and 49% were able to completely stop using narcotics. Among the 25 pediatric patients, only 39% were on narcotics after surgery, and 67% were completely free of pain.

Patients with chronic pancreatitis really suffer, and there is nothing more gratifying than relieving pain, said Dr. Sutherland, who is also director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota and a member of the executive committee of the Collaborative Islet Transplant Registry (CITR), which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Martin L. Freeman, MD, has referred 20 of his patients to Dr. Sutherland for these operations.

He came up with the idea for this procedure and pioneered it at the University of Minnesota starting in 1977, and now his group has the most experience in the world with it, said Dr. Freeman, professor of medicine and director of the Pancreaticobiliary Endoscopy Fellowship at the University of Minnesota Medical School, and co-director of the Minnesota Pancreas and Liver Center in Minneapolis. It is truly revolutionary, and he truly deserves the credit.

Sooner Rather Than Later

In a recent review article on TP/IAT, Dr. Sutherland and his colleagues documented the high rate of independence from insulin after these procedures (Carlson AM et al. Curr Opin Organ Transplant 2007;12:82-88). But they also note that maximal islet yield and insulin independence may be more easily obtained when the autograft is performed earlier rather than later in the disease process, as fewer islets are recovered as pathologic fibrosis increases.

The bottom line is that this approach works for selected patients. When someone has chronic pancreatitis and theyre on pain medication or theyre suffering without medication, you can try endoscopic procedures like sphincterotomies, but if you dont relieve the pain by these other procedures, then you should go to pancreatectomy early rather than lateryou should do it before they become narcotic-dependent or develop narcotic-induced hyperalgesia, Dr. Sutherland said. And whenever you do pancreatectomy, you should do islet autograft because you want to minimize or prevent the otherwise inevitable development of post-pancreatitis diabetes mellitus. But the longer the delay, the lower yield youre likely to get.

The University of Cincinnati team led by Dr. Ahmad performed 22 TP/IAT surgeries in their first three years of experience, from 2000 to 2003 (Rodriguez Rilo HL. J Gastrointest Surg 2003;7:978-989). By the end of 2006, that total had jumped to 97.

The Results Are Still Good

In his DDW presentation, Dr. Ahmad reviewed the teams experience to date with TP/IAT. They treated 45 patients by the end of 2004. Two-thirds of those individuals (29) were either completely off insulin or on less than 20 U per day, and a similar number (32) were independent of narcotics after surgery. The team treated another 52 patients in 2005 and 2006, bringing the total to 97.

Dr. Ahmad noted that there had been very few major complicationsjust 14 (14.4%) out of the 97 patients treated to date. Those included three deaths, none of which were related to the operation, and one case of hepatic failure. There were also relatively few minor complicationsjust 35 (36.1%) out of the 97, including eight cases of delayed gastric emptying, four cases of pneumonia and one brachial plexus injury. The average islet-equivalent yield was 397,053, or 5,955 per kilogram of body weight.

And the results are still good, in terms of insulin and narcotic independence, just as they were in our earlier experience, Dr. Ahmad told Gastroenterology & Endoscopy News. Approximately 40% of patients remain insulin-independent, and our narcotic independence rate is 63%, which is modestly lower than in our initial experience from 2000 to 2003, but we are also now operating on patients with a more diseased pancreas and/or who have been on narcotics for a long time.

Most Patients Would Recommend TP/IAT

The 188 pancreatitis patients treated at the University of Minnesota from February 1977 to September 2006, as presented at the 2007 Pancreas Club meeting, is the largest such population at a single institution anywhere in the world. The patients had a range of etiologies for their pancreatitis60% (113) of cases were idiopathic, 17% (32) were alcohol related, 12% (22) were due to pancreas divisum, 7% (13) were biliary related and 5% (9) were hereditary. Altogether, 85% (160) of the patients underwent total (128) or completion (32) pancreatectomy with IAT, while 11% (21) had partial or distal pancreatectomy procedures. The volume of islet yield was significantly lower in individuals who had undergone a previous pancreatic resection.

Of the 163 adult patients, 74% (121) experienced full or partial graft function at one year, and in an actuarial analysis this declined slightly thereafter to 70% (114) at five years. The actuarial patient survival rate for all the patients in the study after surgery was 98% (184) at one year, 82% after three years, 87% after five years and 73% after 10 years.

Furthermore, among the 83 adult patients contacted by telephone at a median of 42 months postoperatively, all of them stated that prior to surgery, they had pancreatitis-related pain and 93% (77) said they were on daily narcotics for the pain. Discussing their experience after their surgery, the vast majority of patients reported relief of pain, 86% (71) said their quality of life significantly improved and 96% (80) said they would recommend the procedures to others who could benefit from them.

Similarly, among the 25 pediatric patients (age range, 5-18 years) who underwent TP/IAT at the University of Minnesota, narcotic use was significantly lower postoperatively and at one year, 80% (20) had full or partial islet function and 56% (14) were independent from insulin therapy. Furthermore, Dr. Sutherland and his colleagues found that among those pediatric patients without previous direct surgery on the pancreas (15), 67% (10) were insulin-independent after surgery, while among those with such previous surgery (9), only 33% (3) enjoyed this status.

Patients with chronic pancreatitis who have persistent pain after standard interventions should be considered for TP/IAT, and ideally should not be on narcotic analgesics for more than six months without being referred, Dr. Sutherland concluded.


Series Editor

Tarun Mullick, MD,
Clinical Faculty, RushCopley Medical Center
Clinical Staff, Delnor and ProvenaMercy Hospitals
Gastrointestinal Health Specialists LLC
Chicago, Illinois

Commentary by Dr. Mullick

Ever wonder what else to do with your chronic pancreatitis patients? Tired of just prescribing narcotics? In this months Found In Translation, we explore the option of a new operation that may change the algorithm for the treatment of patients with chronic pancreatitis.

For years, the management of patients with chronic pancreatitis has not changed much. First, there are the medications required for relief of symptoms. These include medications for pain like narcotics and pancreatic enzymes, medications for pancreatic insufficiency like pancreatic enzyme supplements, and medications for insulin requirements. Other options include interventions via endoscopic retrograde cholangiopancreatography (ERCP) for stenting of strictures or surgical bypass of the affected pancreas. And then there are nutritional interventions that provide significant rest that allows the pancreas to heal in a minimally stimulated environment with percutaneous endoscopic jejunostomy (PEJ) tubes or total parenteral nutrition (TPN).

But when all of the above measures stop working, you are then often left with a patient with a large pain management issue. Furthermore, these patients may require insulin. But more importantly for the patient, there are a lot of lifestyle changes and limitationshe or she may be the patient with recurrent admissions to the hospital for management of pain or other pancreatitis symptoms. So what next?

Pioneers in Cincinnati and Minnesota have performed total pancreatectomy with islet cell transplantation with dramatic improvements in quality of life, pain control/relief and insulin requirements. This new surgery has provided a sense of promise to patients with refractory symptoms who otherwise felt they had no other choice but to live with the symptoms.

My recommendation is that we follow the Dr. Sutherlands suggestion to refer patients with six months or more of sustained symptoms to centers that may be able to perform that surgery. With careful and prudent selection, these patients are likely to achieve better symptom control and a better life.
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