A recent study has found declining survival rates for pancreatic surgery patients, most of whom have opted for the operation as their only hope for a condition that can cause debilitating abdominal pain, with more than half of them also contracting insulin-dependent diabetes after 10 years.
The long-term results of this surgery, including removal of the shrimp-shaped organ behind the stomach, are not well-understood, and the study was an attempt to document these patients’ outcomes in the long run. Apart from finding diminishing survival rates over the first decade after surgery, the scientists also identified a mixed bag of post-surgical health issues, raising questions about who should undergo surgery, what support is necessary after a pancreas procedure, and whether potential harms outweigh the benefits, reports STAT.
Gregory Wilson, an assistant professor of surgery at the University of Cincinnati Pancreatic Disease Centre, had started with basic questions: he wanted to find out what had happened to his pancreatectomy and islet cell transplantation patients, and if they were recovering and getting back to their lives.
At first glance, the numbers were sobering. The Pancreatic Disease Centre’s database showed survival continued to steadily decrease over time, Wilson said. He later learned those numbers corresponded with survival rates for other pancreas procedures, too.
Pancreas removal surgeries have been performed for years, but the addition of islet cell transplants is newer. Islet cells, in a healthy pancreas, are cell clusters producing hormones needed to regulate blood sugar.
Decades ago, surgeons started transplanting islets from donor pancreases into people with compromised pancreatic function to ward off diabetes. This procedure was tried as a treatment for type 1 diabetes, but never took off. Instead, it became a companion to pancreatic surgery, mainly at two centres: the University of Cincinnati and the University of Minnesota.
Wilson and his colleagues in Cincinnati expanded their research to include other surgeries – 555 operations on 493 patients over 20 years (2000-2020). They also used the National Death Index to see which patients had died, and their cause of death. Five years after surgery, 81% of patients were alive. A decade after surgery, just 64% were still alive, and the median age at time of death was 51.
The leading causes of death were infection (16%), cardiovascular disease (13%), and diabetes-related issues (11%).
The researchers also found 59% of the patients had insulin-dependent diabetes 10 years after surgery, despite only 10% of patients going into surgery with insulin-dependent diabetes. This is not unexpected, since other research has shown people who have part or all of their pancreas removed (or diseased) have a higher risk of developing diabetes. Islet cell transplants are meant to help compensate for part of that loss.
Opioid use was the issue most strongly associated with worse overall survival. Six patients died by suicide, the earliest cause of death, and a surprisingly high number that points to a need for better interventions, Wilson said.
The findings, published in the Journal of American College of Surgeons, paint a complicated (and still incomplete) picture of the risks of these surgeries and their aftermath.
They indicate chronic pancreatitis care “needs to advance well beyond surgery,” said Timothy Gardner, professor of medicine and assistant dean for medical student research at Dartmouth’s Geisel School of Medicine. “These patients require multi-disciplinary care, both pre- and post-operatively, and no patient should undergo surgery without an effective care team in place that can manage patients closely.”
Chronic pancreatitis patients, especially those with advanced disease, are in a difficult situation. While many people don’t know what caused their disease, a sizeable slice of chronic pancreatitis cases are from alcohol use. In the group Wilson studied, tobacco use was also commonplace, with 47% being current smokers and 18% former smokers.
Many continued smoking (38%) and using opioids (30%) daily after surgery, as of their last follow-up visit. And 16% of patients continued to have alcohol problems upon their last follow-up, from two to 10 years after surgery.
Many developed diabetes, which perhaps contributed to the number of deaths from infections, like pneumonia and urosepsis, years after surgery, Wilson said.
Numerous factors could have contributed to patients’ deaths, but it’s difficult to pinpoint those details, he said, seeing his study as a starting point for more research.
Since this study is retrospective, and only includes the University of Cincinnati centre’s pancreatitis surgery patients, the results could be skewed. Ideally, the study would include a control group of patients who did not undergo surgery for their condition, and compare the two groups’ outcomes. Wilson said he and his colleagues tried “really hard” to find such data, but ultimately could not.
The paper analysed overall survival in patients who had one or more of these surgeries: total pancreatectomy with islet cell auto-transplantation (49% of patients), duodenal preserving pancreatic head resection and/or drainage procedure (22%), pancreaticoduodenectomy (16%), and distal pancreatectomy (13%).
Mixing all of the surgery outcomes together makes the paper less helpful than it could have been, said Suresh Chari, professor and deputy chair of the Department of Gastroenterology, Hepatology, and Nutrition at MD Anderson Cancer Centre.
“I want to know, when you send a 13-year-old child to a total pancreatectomy with islet cell transplantation, what can you tell the mother about how this person is going to do in the future?” Chari said.
STAT asked Wilson for survival data among patients who had total pancreatectomy with islet cell transplant. He said they did not have separate outcomes for that group. “We certainly do more total pancreatectomies and islet autotransplantation than many other centres, so our patient population is slightly different from centres that do not offer this procedure,” he said.
There were slight differences in patient outcomes based on the type of surgery, but statistical analyses of the combined data did not show a difference in overall survival by type of surgery, Wilson said.
Many patients do benefit from surgery, mostly when they have exhausted their other options, clinicians told STAT.
“Those are the patients we usually see – those who continue to struggle, have daily pain requiring narcotics, can’t live their life because they’re either in and out of bed all day or in and out of the emergency department, missing work, they can’t keep a job,” Wilson said.
He is now working with colleagues at the University of Cincinnati to build a more robust post-surgical support system for patients, one that can flex to include psychosocial care, addiction specialists and more.
Study details
Long-Term Survival Outcomes after Operative Management of Chronic Pancreatitis: Two Decades of Experience
Wilson, Gregory; Turner, Kevin; Delman, Aaron; Wahab, Shaun; Ofosu, Andrew; Smith, Milton; Choe, Kyuran; Patel, Sameer; Ahmad, Syed.
Published in the Journal of American College of Surgeons on 25 January 2023
Abstract
Background
Chronic pancreatitis is a debilitating, life altering disease; however, the long-term outcomes following operative intervention have not been established.
Study Design
Patients who underwent operative intervention at a single institution between 2000 to 2020 for chronic pancreatitis were included and survival assessed utilising the National Death Index.
Results
493 patients who underwent 555 operative interventions for chronic pancreatitis over two decades were included. 48.5% underwent total pancreatectomy ± islet auto transplantation, 21.7% underwent a duodenal preserving pancreatic head resection and/or drainage procedure, 16.2% underwent a pancreaticoduodenectomy, and 12.8% underwent a distal pancreatectomy. The most common etiology of chronic pancreatitis was idiopathic (41.8%), followed by alcohol (28.0%), and known genetic polymorphisms (9.9%). With a median follow-up of 83.9 months, median overall survival (OS) was 202.7 months, with a 5- and 10-year OS of 81.3% and 63.5%. 165 patients were deceased, and the most common causes of death included: infections (16.4%, n=27), cardiovascular disease (12.7%, n=21), and diabetes related causes (10.9%, n=18). On long-term follow-up, 73.1% (n=331) of patients remained opioid free while 58.7% (n=266) were insulin dependent diabetics. On multivariate cox-proportional hazards modelling, only persistent opioid use (HR:3.91 95%CI:2.45-6.24, p<0.01) was associated worse OS.
Conclusion
Our results represent the largest series to date evaluating long-term survival outcomes in patients with chronic pancreatitis following operative intervention. Our data give insight into the cause of death and allow for the development of mitigation strategies and long-term monitoring of co-morbid conditions.
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