Autologous pancreatic islet cell transplantation for improved glycaemic control after pancreatectomy

# Guidance
This document together with the guidance published on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus replaces previous guidance on pancreatic islet cell transplantation (interventional procedure guidance 13 issued in October 2003).
The current evidence on autologous pancreatic islet cell transplantation for improved glycaemic control after pancreatectomy shows some short term efficacy, although most patients require insulin therapy in the long term. The reported complications result mainly from the major surgery involved in pancreatectomy (rather than from the islet cell transplantation). The procedure may be used with normal arrangements for clinical governance in units with facilities for islet cell isolation (see also section 2.5.1).
During consent, clinicians should ensure that patients understand that they may require insulin therapy in the long term. They should provide them with clear written information. In addition, the use of the NICE's information for patients ('Understanding NICE guidance') is recommended.
Patient selection for this procedure should involve a multidisciplinary team with experience in the management of benign complex chronic pancreatic disease. The procedure should be carried out by surgeons with experience in complex pancreatic surgery and clinicians with experience in islet cell isolation and transplantation.
Further audit and research should address the long-term efficacy of the procedure, quality of life, insulin independence and the management of patients' diabetes (see section 3.1).# The procedure

# Indications and current treatments
Some patients with chronic pancreatitis or benign pancreatic endocrine tumours are treated by total or partial pancreatectomy, resulting in a type of insulin-dependent diabetes.
Post-pancreatectomy diabetes requires the daily injection of exogenous insulin and is relatively difficult to control.

# Outline of the procedure
This procedure is performed with pancreatectomy in a single operation, with the patient under general anaesthesia. The pancreatectomy is carried out, and islet cells are isolated and prepared for transplantation. Under continuous portal vein pressure monitoring (to help prevent portal vein thrombosis), the islet cells are infused through a catheter directly into the portal vein or a tributary, and further onto the liver parenchyma, where some will remain viable.
Sections 2.3 and 2.4 describe efficacy and safety outcomes which were available in the published literature and which the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.

# Efficacy
In four case series of 64, 45, 40 and 13 patients treated by autologous islet cell transplantation following partial or total pancreatectomy, between 24% and 85% of patients were insulin independent at follow-up periods ranging from less than 6 months to 18 months (one study did not state follow-up duration).
In a case series of 48 patients (of whom 39 were evaluated after the procedure), 15 of the 20 patients who were insulin independent at 1 month remained insulin independent at mean follow-up of 5 years, and one patient remained so at 10 years. In the case series of 13 patients, 38% (5/13) were insulin independent after 2 years.
In the case series of 40 patients, all 14 patients who were followed up at 3 years were classed as either having diabetes or impaired glucose tolerance. In a case series of 24 patients, 33% (8/24) required insulin within 8 years of the procedure.
The Specialist Advisers considered key efficacy outcomes to include quality of life, glycaemic control, glucose tolerance, avoidance of severe hypoglycaemia, long-term insulin independence and prevention of long-term diabetic complications.

# Safety
The case series of 48 patients reported that two patients who also had splenectomy at the time of transplantation had 'uncontrollable' splenic hilar bleeding due to increased portal pressure. Asymptomatic portal vein thrombosis was suspected in one patient but the vein was not thrombosed one week after the operation.
A case series of 40 patients reported that complications in the first 24 patients included one case each of portal vein thrombosis, splenic infarction and splenic thrombosis requiring splenectomy. In the last 16 patients, the series reported that complications included pancreatic fistula formation and rupture and subsequent resection of the spleen (raw data not reported; timing and cause of adverse events not adequately described).
A case report described a patient who developed heparin-induced thrombocytopenia following the procedure.
The Specialist Advisers considered theoretical and anecdotal adverse events to include portal vein thrombosis, portal hypertension, hepatic infarction, liver steatosis, liver failure, intra-abdominal haemorrhage, bile leakage, splenic rupture, disseminated intravascular coagulation, infection, intrahepatic sepsis and islet cell pulmonary emboli.

# Other comments
The Committee noted that the National Commissioning Group (NCG), which has a remit to commission highly specialised national services for very rare conditions or treatments for the population of England, has designated centres for pancreatic islet cell isolation. Scottish residents also have access to the service under an agreement between the NCG and the National Services Division, Scotland. Health Commission Wales has a separate agreement with the provider for Welsh residents. The Regional Medical Services Consortium (RMSC) commissions specialist regional services for the population of Northern Ireland. The RMSC will commission outside the region, on an individual basis, in cases for which services are not available in Northern Ireland.# Further information
This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE has identified relevant audit criteria and developed an audit tool (which is for use at local discretion).
NICE has issued a clinical guideline on type 1 diabetes, interventional procedures guidance on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus, and technology appraisals guidance on both insulin pump therapy for type 1 diabetes and long-acting insulin analogues for type 1 and 2 diabetes.

# Information for patients
NICE has produced information on this procedure for patients and carers ('Understanding NICE guidance'). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance
NICE interventional procedure guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS. It is for healthcare professionals and people using the NHS in England, Wales, Scotland and Northern Ireland, and is endorsed by Healthcare Improvement Scotland for implementation by NHSScotland.
This guidance was developed using the NICE interventional procedure guidance process.
Together with the guidance published on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus this guidance updates and replaces NICE interventional procedure guidance 13.
We have produced a summary of this guidance for patients and carers. Tools to help you put the guidance into practice and information about the evidence it is based on are also available.
Changes since publication
January 2012: minor maintenance.
Your responsibility
This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.
Copyright
 National Institute for Health and Clinical Excellence 2008. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.
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