Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis

Abstract

Background: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. Methods: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. Results: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. Conclusion:The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

The clinical and genetic features of hereditary pancreatitis in South Australia

“…Further, 12% of adults admitted to hospital because of chronic pancreatitis were Indigenous people, some of whom may have had undiagnosed hereditary pancreatitis. A 2004 case report 25 described an Indigenous family with several members who had hereditary pancreatitis; in our reports on total pancreatectomy and islet auto‐transplantation (TP‐IAT), most patients with hereditary pancreatitis were also Indigenous people 5,16 . The prevalence of exocrine pancreas disorders is generally higher in indigenous than European origin populations 24 .…”

“…Diabetes secondary to chronic pancreatic inflammation might be averted by TP‐IAT, a new treatment in which the pancreas is removed, and its islet cells are isolated and infused into the liver. Our experience with this procedure is that, if undertaken early, it can greatly improve the quality of life of people with hereditary pancreatitis in terms of pain relief and prevention of type 3c diabetes 5,6,16 . Twenty‐nine people in our study (66%) fulfilled the Minnesota criteria for the appropriateness of TP‐IAT for patients with chronic pancreatitis, taking history of recurrent acute pancreatitis, medical imaging and biochemistry findings, lifestyle, and need for narcotic medications into account 5,6,16 …”

“…We found the prevalence of hereditary pancreatitis in South Australia to be higher than reported in Europe, and it was markedly higher among Indigenous people than other South Australians. Building on our earlier reports, 5,16 we have identified the number of South Australians with hereditary pancreatitis eligible for newer therapies, including TP‐IAT. Hereditary pancreatitis is an important but inadequately recognised cause of early onset pancreatitis in South Australia, particularly in young Indigenous people.…”

“…In hereditary pancreatitis, inflammation is initially restricted to the acinar and ductal cells, leading to exocrine insufficiency; the pancreatic islets are affected only late in the disease process, 1,15 and patients require pancreatic enzyme replacement long before diabetes develops 15,16 . As many as 60% of people with symptomatic pancreatitis will ultimately require surgical interventions (including endoscopic procedures) because of severe abdominal pain, with unavoidable loss of pancreatic function 1,2,6,16 …”

Current status of total pancreatectomy with islet autotransplantation for chronic and recurrent acute pancreatitis

“…28 Table 2 and Figure 2 show the demographic characteristics of studies on TPIAT for CP and RAP at institutions in the United States, United Kingdom, and Australia. 22,[29][30][31][32][33] The optimal timing of TPIAT is a sensitive issue. In recent years, previous studies have reported the superiority of early surgical intervention to nonsurgical treatment for CP.…”