The Leicester HPB unit has a long history in the field of islet isolation, allo- and autotransplantation (TPIAT). The considerable clinical experience is supported by an established surgical team, laboratory and clinical research and extensive peer reviewed publications in high impact journals. Eight allogenic islet transplantations were completed between 1991 and 1992 and shortly following this in 1994 the clinical auto islet transplant program was established and now boasts the second longest series in the world with the largest series outside the USA. To date, seventy-two patients in Leicester have undergone total or completion pancreatectomy combined with islet autotransplantation. The data from the series has demonstrated that an islet transplantation following surgical resection is a valuable addition which significantly improves the long-term quality of life particularly in respect of hypoglycaemic unawareness and diabetic control. Professor Ashley Dennison has pioneered autotransplantation in Leicester (and nationally) and was responsible for leading on a bid with three other centres to ensure that TPIAT was recognised as a specialised procedure by NHS England.

In 2002 the University Hospitals of Leicester invested in the TPIAT programme by building a fully accredited clean room facility, dedicated to the production of islets for transplantation. This clean room facility was the first of its kind in the UK and was funded by the UK Islet Transplant Consortium and fully approved by the Department of Health. The maintenance of our islet clean room facility and the expertise gained from the islet autotransplantation program paralleled the success of the Edmonton protocol for the treatment of diabetes by islet allotransplantation. In the last 5 years, islet isolation has been undertaken at a new location (The Cellular Therapy Laboratory, Leicester Royal Infirmary) and the excellent results achieved previously continue to be maintained. The consequence was the stimulation of interest in autotransplantation internationally and especially from a number of units in the USA and several in the UK (Newcastle, Oxford and Kings College Hospital, London). Despite this there remains a paucity of data about many aspects of the procedure and investigations and clinical studies are hindered by the very small number of units able to perform the procedure. Initially this was represented by Minneapolis, Leicester and Chicago but the substantial expansion of the number of units in the USA performing TPIAT and the collaboration of the units in the UK who have formed a TPIAT clinical and research consortium, should allow many of the outstanding questions to be addressed. In addition the team in Leicester has now been recruiting patients for over 30 years and the majority of the patients who have been transplanted are available for long term studies.

Acute and chronic pancreatitis very different diseases but both are due to complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical course. A burgeoning body of evidence demonstrating the genetic component on patients with chronic pancreatitis and confounding risk factors together with evidence that in only a minority of patients is the disease related to alcohol consumption has dramatically changed our concept of and approach to these diseases.

The heredity basis of some cases of chronic pancreatitis was originally recognised in 1952 and in 1996, a breakthrough in understanding recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) came with the discovery by David Whitcomb from the University of Pittsburgh that gain-of-function mutations in the gene that encodes cationic trypsinogen (PRSS1) cause hereditary pancreatitis 2,3 a rare syndrome characterized by recurrent acute pancreatitis and/or chronic pancreatitis in at least 2 first-degree relatives, or 3 or more second-degree relatives in 2 or more generations, for which no other predisposing factors can be identified.

It is now understood that a combination of genetic, environmental, and metabolic factors contribute to the development of acute and chronic pancreatitis. Although variants in the PRSS1 gene are the primary cause of hereditary pancreatitis not all families with hereditary pancreatitis have an identifiable PRSS1 gene mutation. It’s estimated that between 60% to 85% of people with hereditary pancreatitis will have an identifiable genetic cause.

Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidaemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene/gen and gene/environmental factor interactions.

In Leicester, the HPB surgical team remain determined to continue to support patients with chronic pancreatitis, which is a disabling, progressive condition with a dramatic impact on quality of life. Clinical and basic research has been undertaken in Leicester for almost 3 decades and continues with the support of the University Hospitals of Leicester NHS Trust, the Clinical Nurse Specialist team led by Cris Pollard who runs the TPIAT programme, HPB trainees, research fellows studying for higher degrees (MD and PhD) and the Cell and Molecular Science laboratory (for islet cell isolation and preparation for transplantation). The recognition of the genetic basis for many cases of chronic pancreatitis has resulted in the recognition of a new group of much younger patients whose symptoms often start when they are young children or teenagers. In this new cohort the known association of chronic pancreatitis with an increased lifetime risk for the development of pancreatic cancer is significantly more pronounced due to the combination of the genetic mutation and the duration of the inflammatory process. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis (usually developing between the ages of 5 and 26) approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. To prevent the development of pancreatic cancer in patients with hereditary chronic pancreatitis presenting with chronic pain a number of units around the world now advocate early total pancreatectomy and islet autotransplantation.