Introduction and definitions

Advances in surgical technique and immunology have allowed organ transplantation to become routine, limited mainly by shortage of donor organs.

Rejection

The rejection phenomenon is a consequence of the requirement to distinguish between self and non-self (e.g. infecting organisms) or abnormal self (e.g. tumour cells or cells with intracellular infections). The recognition of foreign and abnormal cells by the immune system allows the elimination and removal of the infection or tumour. Transplanted tissue activates the same process, and prevention of rejection requires suppression of the immune system. Current immunosuppressive therapy is highly effective but, not surprisingly, side effects include a higher susceptibility to infections and incidence of tumours.

Matching donor to recipient

Immunosuppression

Immunosuppressive therapy prevents or reverses rejection of the transplanted organ but at the expense of increased risk of infectious and malignant disease (Box 12.2). Prophylaxis against rejection usually requires different agents to be used in combination. The main immunosuppressive agents, mechanisms of action, doses and side effects are summarised in Table 12.2. Acute rejection crises require high-dose intravenous steroids (methylprednisolone 500 mg three times a day) and occasionally monoclonal antibody therapy with basiliximab.

Organ retrieval and management of cadaveric organ donors

Most cadaveric organ donors are head injury patients who have their diagnosis of brainstem death confirmed while they are ventilated on ITU. Brain death leads to hypothermia, coagulopathy, reduced cardiac output and endocrine disturbance. Active intervention is required to ensure the organs are retrieved in as good a condition as possible. This includes the following measures:

The retrieval operation is started by the renal/liver team followed by the heart/lung team. The organs are cold-perfused before removal then transported in double plastic bags in crushed ice.

Kidney transplantation

Kidney transplantation is indicated for end-stage renal failure. The commonest causes are:

Around 1700 kidney transplants are performed each year in the UK and over 5000 patients are on the transplant waiting list.

Ischaemic time comprises warm ischaemic time (between stopping the circulation through the organ and perfusing it with cold perfusion fluid) and cold ischaemia time, from the moment of cold perfusion to re-establishing blood flow after grafting. The shorter the ischaemia time, the sooner the graft will function after transplantation (Fig 12.1).

Figure 12.1 Completed renal transplant in right iliac fossa.

Renal transplants are heterotopic. The iliac vessels are exposed via an extraperitoneal approach and the graft placed in the iliac fossa with the renal artery and vein anastomosed to the internal or external iliac artery and vein. The ureter is implanted into the bladder and may be stented. Immune suppression is started immediately together with prophylactic antibiotics. Graft function is monitored postoperatively by measurement of urine output (oliguria is common at first), urea, creatinine and creatinine clearance. Early complications are usually technical and include thrombosis of artery or vein, urinary leak and ureteric stenosis. Occlusion of either vessel usually results in graft infarction. Cadaveric graft survival rates are 90% at one year and 50% at 10 years.

Liver transplantation

Liver immunology is rather mysterious. Some patients develop spontaneous tolerance to their new liver and immune suppression may be reduced or withdrawn. One-year survival is 70–90% and most one-year survivors are still alive at 5 years.

Indications for liver transplantation are summarised in Box 12.3. Outcome after transplantation for malignant disease is unpredictable and results are poor with high recurrence rates.

Approximately 700 liver transplants are performed each year in the UK. Liver transplantation is orthotopic, and the recipient’s hepatectomy is particularly demanding since the patients are always very sick and portal hypertension makes the abdomen hostile. Complex anastomotic work is required for the transplant. Primary graft failure occurs in up to 10% and this is usually fatal.

Pancreas transplantation

Pancreatic transplantation is indicated for insulin-dependent diabetes and may either be performed alone or together with renal transplantation for diabetics with advanced nephropathy. The operation is not widely performed in the UK though it is more popular in North America. There are two techniques: whole organ or segmental graft. The whole organ method has lower complication rates (Fig. 12.2). Results are improving but in the future it is likely that grafting of the pancreas will be replaced by transplantation of islet of Langerhans cells only.

Figure 12.2 Whole organ pancreas transplant.

Small bowel transplantation

Small bowel transplantation is inherently problematic due to the high concentrations of lymphoid tissue in the transplanted bowel (graft versus host reaction) and the colonisation of the graft with intestinal flora. Only limited numbers are performed worldwide per year, with a 2-year survival of about 50%.

Heart and lung transplantation

Heart, lung and heart-lung transplantation are discussed in Chapter 14.

Cornea

The cornea was the first solid tissue successfully transplanted between humans and it is the most commonly performed transplant. Opaque or distorted cornea from any cause is an indication for grafting. A button of the recipient’s cornea is removed and replaced with a corresponding graft from the donor using microscopic sutures. The cornea is avascular and rejection is not usually a problem. In close HLA-matched cases, graft survival is 95% and is expected to last for life.

Improving donor rates

There is significant variation between countries in the numbers of organs made available for transplantation (per head of population). Utilising specialist transplant co-ordinators in each hospital helps, but there has been little appetite in the UK to adopt an opt-out (presumed consent for donation) system.