Lecture Notes: General Surgery

Harold Ellis, Sir Roy Calne, Christopher Watson

Self-assessment Questions

47 Transplantation surgery

  • 1. When was the first ever successful organ transplant?

    Correct answer:

    It was not until the mid-1950s that successful replacement of a diseased organ with a transplanted organ occurred, when the immune response was bypassed by performing renal transplants between identical twins.

  • 2. What is the historical background of transplantation surgery?

    Correct answer:

    Early attempts at organ transplantation were fraught with failure owing to a lack of appreciation of the immune response that resulted in rapid destruction of the transplanted organ. It was not until the mid-1950s that successful replacement of a diseased organ with a transplanted organ occurred, when the immune response was bypassed by performing renal transplants between identical twins. In 1960, the first immunosuppressive drugs appeared with which the immune response could be partly controlled, permitting longer useful function of organs from unrelated donors. In the subsequent decade regular haemodialysis, and later peritoneal dialysis, also became increasingly available, able to support patients with renal failure while awaiting transplantation. In the 1980s the more powerful immunosuppressant ciclosporin permitted transplantation of the liver, heart, lungs and pancreas, and afforded better results of kidney transplantation. With the advances in immunosuppression, better techniques of organ preservation and improved anaesthetic and intensive care management, organ transplantation to replace diseased organs is now an accepted treatment offering transplant recipients the possibility of long-term survival.

  • 3. What is a structural graft?

    Correct answer:

    A structural graft acts as a non-living scaffold. It can be of biological origin, e.g. arterial and heart valve grafts, or synthetic, e.g. Dacron vascular prosthesis.

  • 4. What is an orthotopic graft?

    Correct answer:

    The diseased organ is removed and replaced by the transplanted organ lying in the normal anatomical position, e.g. heart, lung and liver transplants are usually orthotopic.

  • 5. What is a heterotopic graft?

    Correct answer:

    The transplanted organ is placed in a different position from the normal anatomical position, e.g. kidney and pancreas transplants. The diseased organ is not usually removed.

  • 6. What are the two potential sources of donor organs?

    Correct answer:

    (1) Living donors. (2) Deceased donors.

  • 7. What is a living organ donation? Which organs are most commonly donated?

    Correct answer:

    Living donation is possible when removal of either a paired organ (e.g. the kidney) or part of an unpaired organ (e.g. the liver or lung) leaves the donor with sufficient residual organ function, and provides an organ or part of an organ for a recipient. Live donation is most common in kidney transplantation, in which the donor can maintain adequate renal function with only one kidney and donate the other to a relative, partner or, less commonly, a friend. As with any operation, there are risks to the donor, especially of postoperative events such as chest and wound infection, deep vein thrombosis and pulmonary embolism; the risk of death following kidney donation is estimated to be between 1 in 1600 and 1 in 3200. In the UK, there are now more living kidney donors than deceased kidney donors. Donation of a portion of the liver, either to a child or to another adult, involves a major operation and runs the risk of leaving the donor with borderline liver function from the remaining liver lobe; the risk of death following donation of a liver lobe is estimated at between 1 in 100 and 1 in 200. Live donation of a lung lobe is also possible, the recipients usually being children.

  • 8. What are the main principles behind deceased organ donation?

    Correct answer:

    There are two types of organ donation from deceased donors: (1) donations after brain stem death and (2) donation after cardiac death (non-heart-beating donation). Most organs for transplantation come from donors who have sustained a lethal brain injury following a head injury, intracranial haemorrhage or primary brain tumour, and who have been certified dead by ‘brain stem’ criteria. The organs are removed from the donor in the operating theatre after isolating their vascular pedicles and while the heart is still beating; when circulation ceases the organs are rapidly cooled by perfusion in situ with an ice-cold organ-preservation solution. When patients have sustained a catastrophic brain injury, but do not fulfil the criteria for the diagnosis of death by brain stem criteria, the supervising doctors may nevertheless decide that future treatment is futile. In such circumstances life-supporting treatment is withdrawn and the patient dies, death being certified by the absence of a circulation. Following cardiac arrest the donor is transferred to the operating theatre, where the organs are rapidly cooled, perfused with preservation solution and removed. Unlike organs from brain dead donors, organs removed from donors after cardiac death suffer a period of warm ischaemia prior to cooling. During this period, the organs switch from aerobic to anaerobic metabolism, which depletes intracellular energy stores and causes the accumulation of lactic acid. Unchecked, this process rapidly results in cell death. Organs vary in their tolerance of warm ischaemia, with kidneys remaining viable for about 60 minutes whereas the liver tolerates less than 30 minutes. In such cases, the initial function of the organs is inferior to those removed following brain stem death, but the ultimate function is satisfactory.

  • 9. What are the three main exclusions to organ donation?

    Correct answer:

    There are three main reasons why a potential donor may be unsuitable. (1) Potential transmission of infection. The transplanted organ could carry with it viral infections such as hepatitis B and C and human immunodeficiency virus, and bacterial infection that was disseminated in the donor. Likewise, donors in whom there is risk of prion infection such as new variant Creutzfeld–Jakob disease are unsuitable. (2) Malignancy. Malignant disease in the donor can be transplanted into the recipient, where it may become established in the immunosuppressed environment. Therefore, with the exception of low-grade primary brain tumours (which do not spread outside the central nervous system) and superficial non-melanoma skin tumours, active malignancy is a contraindication for organ donation. (3) Impaired function of donor organ. If the function of the organ is impaired in the donor it is unsuitable for transplantation. For example, a heart with severe coronary artery disease is unsuitable, and a donor with polycystic kidneys is an unsuitable kidney donor but may be a suitable heart donor.

  • 10. How are organs preserved once removed from the donor?

    Correct answer:

    Once removed from the donor the organs must be maintained in their optimum state prior to transplant. This is achieved by a combination of (1) cooling the organ to approximately 4°C to reduce metabolic activity and (2) perfusing it with, and storing it in, a preservation solution that a pH buffer to counter the lactic acid accumulation and a compound to prevent cell swelling by osmosis. One such solution is the University of Wisconsin (UW) solution. In this solution a kidney can be preserved for 36–40 hours, and a liver for up to 20 hours, although in both cases the shortest possible preservation period, or cold ischaemia time (the time between cessation of circulation in the donor and implantation in the recipient), is desirable. No comparable preservation solution exists for the heart and lungs, and implantation must occur within 4–6 hours, to ensure immediate life-sustaining function of these organs. An alternative for kidney preservation is to place the organ on a machine that continuously pumps ice-cold preservation through it.

  • 11. Can you name an organ preservation solution?

    Correct answer:

    University of Wisconsin solution.

  • 12. What are the main indications for renal or liver organ transplantation?

    Correct answer:

    Patients are considered for transplantation when they are in chronic organ failure without hope of recovery, but still fit enough to withstand the operative procedure. For kidney transplantation, potential transplant recipients should be on or about to start dialysis. Patients with chronic liver disease are placed on the transplant waiting list when their liver disease warrants, such that their risk of death without a transplant is greater than the risk of death following transplantation. For example, in patients with primary biliary cirrhosis, an elevation of serum bilirubin concentration over 100 μmol/L is an indication for transplantation. In acute liver failure, transplantation is indicated if the synthetic function of the liver is severely impaired, as best reflected by the degree of elevation of prothrombin time.

  • 13. What is the major histocompatibility complex? What is its relevance to organ transplantation?

    Correct answer:

    When an organ is transplanted it is recognized as foreign by the host’s immune system and the rejection response is initiated. The recognition is mediated by an interaction between host T lymphocytes (T cells) and histocompatibility antigens on the surface of the allograft (the foreign organ). The major histocompatibility complex (MHC) is a group of genes that encode molecules (antigens) expressed on the surface of cells. The MHC molecules are of two principal sorts. MHC class I antigens are present on all nucleated cells. MHC class II antigens are present on certain cells (e.g. macrophages, monocytes and dendritic cells), and can be induced to appear on others by the presence of cytokines such as interferon γ(IFN- γ).

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