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Information for Patients

The UK National Adult Intestinal Transplant Program provides isolated intestine (small bowel), combined liver and intestine, and multivisceral transplantation for patients who have irreversible intestinal failure.

The three types of intestinal transplantation offered by the program:

    1. Isolated intestine (small bowel) transplantation
      Some people are born with or develop irreversible intestinal failure. They become unable to digest food well enough to eat or be fed through a tube, and as a result require permanent total parenteral nutrition (TPN). For these adults and children, isolated intestine (small bowel) transplantation can be a life-saving and life-enhancing option.
    1. Combined liver and intestine transplantation
      Combined liver and intestine transplantation is a life-saving procedure for patients with combined organ failure. It is the only available treatment for patients with liver and intestinal failure.
  1. Multivisceral transplantation 
    Multivisceral transplantation is offered for people in whom two or more intra-abdominal organs (including the intestines) are failing. Multivisceral transplantation is the only treatment available for people who have combined organ failure and/or premalignant or low-grade malignant tumours of the gastrointestinal tract. It is sometimes better to transplant several organs together than to attempt very difficult and dangerous surgery to remove and replace organs that are difficult to remove safely on their own because of their position in the body. It is therefore often very helpful to have the option of multiple organ transplantation.
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Int. Transplantation in the UK

Addenbrooke’s is the main teaching hospital for Cambridge University.   The site has been considerably extended over the last 10 years and now hosts many scientific establishments which undertake medical research in collaboration with the hospital. There are plans to extend the site even further and this will make it the largest of its kind in Europe. There are many benefits for patients as the world leading research facilities are also used to help investigate and treat patients.

Addenbrooke’s has a long experience undertaking intestinal transplantation, and it was here that the first such transplantation in the UK was performed in 1991. Since then there has been a steady increase in demand and we have one of the longest surviving multiple organ transplant patients in the world.  The transplant team at Addenbrooke’s includes surgeons, physicians, nurse coordinators, nurses, dietitians,  and scientists, but also many other medical health care personnel who all have a vital role in making the procedure run smoothly. Ward clerks, secretaries, data managers,  researchers, cleaners and managers, all have an essential input. There are also numerous other specialties involved such as Radiology, Nuclear medicine, Microbiology, Histopathology, Intensive care, Anaesthetics, Infectious disease, Psychiatry, Nutrition and Dietetics, physiotherapy and more. It is quite a feat to coordinate all these specialties and this is achieved by our transplant nurse coordinators and junior transplantation specialist registrars and junior doctors under the guidance of the lead consultants.

The concourse at the main hospital entrance is a  particular favourite with our inpatients. It was modeled on an airport departure lounge and provides a sense of normality. There are several shops where you can buy clothes and gifts, groceries and treats, and some excellent coffee bars and food outlets. There is even a hairdressers salon.

At present Addenbrooke’s is the only UK centre to transplant the liver and other organs such as the pancreas and kidneys at the same time as  the intestine. These combined procedures are much more complex than an isolated intestine but the results have nevertheless been as good.

Despite its large size Addenbrooke’s has a friendly and warm atmosphere and our transplant ward (C9) offers a particularly personal approach to patient care, whilst maintaining the highest standard of care.

Cambridge is also  a beautiful city and if you are an inpatient here your visitors will enjoy the opportunity to  have a look a the splendid university buildings and even try punting on the Cam. They may even decide to stay for a few days sight seeing!

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Indications in Adults

It is very important to consider the pros and cons of transplantation for each patient on an individual basis. Patients who are doing well on intravenous feeding (Parenteral Nutrition: PN) have a very good life expectancy (see fig 1) and can live with a very good quality of life.
One of the most important aspects of life on PN is to be trained to use it properly.

There are two main intestinal failure centres in the UK (St Mark’s and the Hope hospital, Salford) which have excellence in PN management and training. There are also several other specialist units in the UK that manage PN to a very high standard.

However, survival following intestinal transplantation is not as good, although patients are usually free from PN and for some this can improve their quality of life, those patients who are doing well on PN will not notice a great deal of improvement in QOL, they might swap PN for other problems associated with the transplantation procedure and their life expectancy is not nearly as good (fig 1). Therefore, intestinal transplantation should only be used for patients who are not doing well on PN.

Some will develop PN related liver disease such that they can not continue PN; others will thrombose the veins used to give PN which eventually will make it impossible to administer PN. As these complications arise in a small group of patients it is important to make the decision whether or not they should be put forward for transplantation. If put forward too late when they have multiple complications and are in poor condition they are less likely to survive the procedure. The timing of the transplantation is therefore critical and this needs to consider a host of factors which can vary widely between patients.

In order to make the best decision possible all UK patients are reviewed in a national meeting called the National Adult Small Intestinal Transplantation forum (NASIT forum). This was founded in 1990 by Drs Simon Gabe (St Mark’s hospital, London) and Stephen Middleton (Cambridge University teaching hospital).

Therefore in general, intestinal transplantation is indicated in patients with intestinal failure who are failing on parenteral nutrition. The term failing on parenteral nutrition generally implies the development of frequent, severe or life threatening complications. The following list is derived from the approved Medicare indications and has been approved by the American Gastroenterology Association (AGA).

1. Impending or overt liver failure due to PN induced liver injury
The clinical manifestations include elevated serum bilirubin and/or liver enzymes, splenomegaly, thrombocytopenia, gastro-oesophageal varices, coagulopathy, stomal bleeding or hepatic fibrosis/cirrhosis.

2. Thrombosis of 2 or more major central veins  
This is considered a life threatening complication and failure of PN therapy.

3. Frequent central venous catheter infection & sepsis
The development of two or more episodes of systemic sepsis secondary to line infection per year that requires hospitalization indicates failure of PN therapy.  A single episode of line related fungaemia, septic shock and/or acute respiratory disease syndrome (ARDS) are considered indicators of PN failure. Patients should be reviewed by one of the primary intestinal failure centres to further evaluate the reasons for recurrent sepsis before consideration for transplantation.

4. Frequent severe dehydration despite IV fluid supplement in addition to PN
The UK indication guidelines also include patients who need removal of many organs. This might be necessary in order to excise benign tumours for conditions such as desmoid disease. Widespread mesenteric vascular disease of a critical degree might also be considered as an indication especially if there has already been an ischaemic event leading to intestinal failure.

5. Quality of life.
Patients who experience very poor quality of life on PN may wish to consider transplantation. However, careful consideration is needed as transplantation may not necessarily correct the factors causing poor quality of life. Transplantation does not put patients back to normal and does give them ongoing problems to deal with including taking life long medication, being more prone to infections, the need for regular visits to hospital for check ups, often a permanent stoma (ileostomy) is required and obtaining employment is usually much more difficult after a transplantation.

Furthermore, patients on PN who have not had any major complications are likely to live a lot longer than if they had transplantation. A general comparative survival would be 90% survival at 10 years on PN compared to 45% 10 year survival after transplantation. It should also be remembered that the technique of transplantation is improving and if patients wait their chances of long term survival may improve as we get better at transplantation, assuming that their medical condition does not deteriorate, but this of course can be closely monitored.

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Publications

Delayed dynamic abdominal wall closure following multi-visceral transplantation.
Iype S, Butler A, Jamieson N, Middleton S, Jah A.  International Journal of Surgery Case Reports. 2014;5(12):988-991. doi:10.1016/j.ijscr.2014.08.006.

Ceresa, C. D. L., Ramcharan, R. N., Friend, P. J. and Vaidya, A. (2013).
Mesenchymal stromal cells promote bowel regeneration after intestinal transplantation: myth to mucosa. Transplant International, 26: e91–e93. doi: 10.1111/tri.12139

Preoperative Comorbidity Correlates Inversely with Survival after Intestinal and Multivisceral Transplantation in Adults.
Sivaprakasam, R., Hidenori, T., Pither, C., Nishida, S., Butler, A. J., Island, E. R., … Middleton, S. J. (2013). Journal of Transplantation. 2013;2013:202410. doi:10.1155/2013/202410.

Is intestinal transplantation now an alternative to home parenteral nutrition? Middleton SJ.

Proc Nutr Soc. 2007 Aug;66(3):316-20

Patients with irreversible intestinal failure and complications of parenteral nutrition should now be routinely considered for small intestine transplantation. Despite attempts for >40 years immunological graft intolerance presented an impenetrable barrier to successful engraftment until the development in the late 1970s of the powerful calcineurin-inhibitor immunosuppressive agents. Their use over the last 17 years has led to small intestinal transplantation being generally considered as a routine option for patients with irreversible intestinal failure and failing parenteral nutrition. The 1-year patient survival rates (%) are now excellent for renal (95), liver (78), heart (82) and lung (75) transplantation. In contrast, survival rates for small intestinal transplantation have been slow to improve, although they are now approaching those for lung and liver transplantation (intestine 78%, intestine and liver 60%, multivisceral 66%), and well-performing centres report recent 1-year graft survival rates as high as 92%. Patient 5-year survival (%) has also improved (intestine alone 50, intestine and liver 50 and multivisceral 62) and compares increasingly favourably with renal (85), liver (67), heart (67) and lung (46). Currently, small intestinal transplantation is reserved for patients with irreversible small intestinal failure who have a poor prognosis on parenteral nutrition. However, as 5-year patient survival following intestinal transplantation approaches that for parenteral nutrition there will be increasing pressure to offer this modality of treatment as an alternative to parenteral nutrition, especially for those patients who have a poor quality of life as a result of parenteral nutrition.
Small bowel transplantation in the UK. Middleton SJ, Jamieson NV

Gut. 2006 Jul;55(7):1047

The current status of small bowel transplantation in the UK and internationally. Middleton SJ, Jamieson NV

Gut. 2005 Nov;54(11):1650-7

Adult small intestinal transplantation in England and Wales. Middleton SJ, Pollard S, Friend PJ, Watson C, Calne RY, Davies M, Cameron EA, Gimson AE, Bradley JA, Shaffer J, Jamieson NV.

Br J Surg. 2003 Jun;90(6):723-7

In 1996 two transplantation centres in the UK were commissioned by the National Specialist Commissioning Advisory Group for England and Wales to assess small intestinal transplantation in adults. The joint experience of the two centres is presented. METHODS: Patients with irreversible small intestinal failure and complications of parenteral nutrition, and those with abdominal disease requiring extensive visceral resection, were assessed as candidates and where appropriate listed for surgery. RESULTS: Thirty-six patients were assessed for small intestinal transplantation and, of these, 14 underwent surgery. Twelve patients survived the transplantation procedure. Of these, seven patients were alive at 1 year, five at 3 years and three at 5 years. Three patients remain alive. Patient and graft survival improved with experience; the 1-year survival rate improved in the last 4 years of this experience from 43 to 57 per cent, and the 3-year survival rate from 29 to 43 per cent.

CONCLUSION: Small intestinal transplantation is associated with a high mortality rate but may benefit carefully selected patients in whom conservative management is likely to carry a greater mortality rate.

Quality of life in adults following small bowel transplantation. Cameron EA, Binnie JA, Jamieson NV, Pollard S, Middleton SJ.

Transplant Proc. 2002 May;34(3):965-6

Retrieval of abdominal organs for transplantation. Brockmann JG, Vaidya A, Reddy S, Friend PJ.

Br J Surg. 2006 Feb;93(2):133-46

Organ retrieval and donor management are not yet standardized. Different transplant centres apply various techniques, such as single or dual organ perfusion, dissection in the cold or warm, and single or en bloc organ removal. These different approaches may cause inconvenience, especially when more than one organ retrieval team is involved. METHODS: Cochrane Library, Medline and PubMed were searched for publications on multiorgan donor/donation, retrieval technique and procurement. Levels of evidence and grades of recommendation were evaluated based on current advice from the Oxford Centre for Evidence-Based Medicine. RESULTS: Multiorgan donation itself does not compromise the outcome of individual organ transplants. Dissection of abdominal organs for transplantation is best performed after cold perfusion. Abdominal organs should be removed rapidly, en bloc, and separated during back-table dissection in the cold, particularly if pancreas or intestine is included. Perfusion itself should be carried out after single cannulation of the aorta with an increased pressure.
CONCLUSION: Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. Nevertheless, optimized donor treatment and organ retrieval should increase the number and quality of cadaveric donor organs and improve graft function and survival.

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How to Refer a Patient

Patients can be referred directly to an intestinal transplant centre, or to an Intestinal Failure Unit.  In addition, patients can be presented for consideration at the NASIT Forum meetings by any centre.

Addenbrooke’s Hospital, Cambridge

Isolated small intestine, Liver and Intestine, multivisceral transplants (NCG approved)

Consultant Gastroenterologist

Consultant Gastroenterologist

Consultant Transplant Surgeon

Consultant Transplant Surgeon

Cambridge University Hospital

John Radcliffe Hospital, Oxford

Isolated small intestine, (NCG approved)

Consultant Transplant Surgeon
Consultant Transplant Surgeon

John Radcliffe Hospital

St Mark’s Hospital, Lennard Jones IF Unit, London

Intestinal failure unit (NCG approved)

Consultant Gastroenterologist & Co-Chair Lennard Jones IF Unit

St Mark’s Hospital

Salford Royal NHS Foundation Trust Hospital, Manchester.

Intestinal failure unit (NCG approved)

Consultant Gastroenterologist

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Indication for Intestinal Transplantation in Adults

It is very important to consider the pros and cons of transplantation for each patient on an individual basis. Patients who are doing well on intravenous feeding (Parenteral Nutrition: PN) have a very good life expectancy (see fig 1) and can live with a very good quality of life.
One of the most important aspects of life on PN is to be trained to use it properly.

There are two main intestinal failure centres in the UK (St Mark’s and the Hope hospital, Salford) which have excellence in PN management and training. There are also several other specialist units in the UK that manage PN to a very high standard.

However, survival following intestinal transplantation is not as good, although patients are usually free from PN and for some this can improve their quality of life, those patients who are doing well on PN will not notice a great deal of improvement in QOL, they might swap PN for other problems associated with the transplantation procedure and their life expectancy is not nearly as good (fig 1). Therefore, intestinal transplantation should only be used for patients who are not doing well on PN.

Some will develop PN related liver disease such that they can not continue PN; others will thrombose the veins used to give PN which eventually will make it impossible to administer PN. As these complications arise in a small group of patients it is important to make the decision whether or not they should be put forward for transplantation. If put forward too late when they have multiple complications and are in poor condition they are less likely to survive the procedure. The timing of the transplantation is therefore critical and this needs to consider a host of factors which can vary widely between patients.

In order to make the best decision possible all UK patients are reviewed in a national meeting called the National Adult Small Intestinal Transplantation forum (NASIT forum). This was founded in 1990 by Drs Simon Gabe (St Mark’s hospital, London) and Stephen Middleton (Cambridge University teaching hospital).

Therefore in general, intestinal transplantation is indicated in patients with intestinal failure who are failing on parenteral nutrition. The term failing on parenteral nutrition generally implies the development of frequent, severe or life threatening complications. The following list is derived from the approved Medicare indications and has been approved by the American Gastroenterology Association (AGA).

1. Impending or overt liver failure due to PN induced liver injury
The clinical manifestations include elevated serum bilirubin and/or liver enzymes, splenomegaly, thrombocytopenia, gastro-oesophageal varices, coagulopathy, stomal bleeding or hepatic fibrosis/cirrhosis.

2. Thrombosis of 2 or more major central veins  
This is considered a life threatening complication and failure of PN therapy.

3. Frequent central venous catheter infection & sepsis
The development of two or more episodes of systemic sepsis secondary to line infection per year that requires hospitalization indicates failure of PN therapy.  A single episode of line related fungaemia, septic shock and/or acute respiratory disease syndrome (ARDS) are considered indicators of PN failure. Patients should be reviewed by one of the primary intestinal failure centres to further evaluate the reasons for recurrent sepsis before consideration for transplantation.

4. Frequent severe dehydration despite IV fluid supplement in addition to PN
The UK indication guidelines also include patients who need removal of many organs. This might be necessary in order to excise benign tumours for conditions such as desmoid disease. Widespread mesenteric vascular disease of a critical degree might also be considered as an indication especially if there has already been an ischaemic event leading to intestinal failure.

5. Quality of life.
Patients who experience very poor quality of life on PN may wish to consider transplantation. However, careful consideration is needed as transplantation may not necessarily correct the factors causing poor quality of life. Transplantation does not put patients back to normal and does give them ongoing problems to deal with including taking life long medication, being more prone to infections, the need for regular visits to hospital for check ups, often a permanent stoma (ileostomy) is required and obtaining employment is usually much more difficult after a transplantation.

Furthermore, patients on PN who have not had any major complications are likely to live a lot longer than if they had transplantation. A general comparative survival would be 90% survival at 10 years on PN compared to 45% 10 year survival after transplantation. It should also be remembered that the technique of transplantation is improving and if patients wait their chances of long term survival may improve as we get better at transplantation, assuming that their medical condition does not deteriorate, but this of course can be closely monitored.