Transcript Lung transplantation

Lung transplantation, hand, skin and
corneal transplantation
Prof. Ileana Constantinescu
Lung transplantation
• The influence of HLA in lung transplantation is
open to debate.
• Donated lungs are allocated on the whole
without consideration of HLA compatibility.
• Only when a potential recipient has been
found to be sensitized to predefined HLA
specificities, is the donor HLA type used to
determine suitability.
Requirements for potential donors
There are certain requirements for potential lung donors, due to the needs of the potential recipient. In the case of living donors,
this is also in consideration of how the surgery will affect the donor:
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healthy;
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size match; the donated lung or lungs must be large enough to adequately oxygenate the patient, but small enough to fit
within the recipient's chest cavity;
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age;
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blood type.
Requirements for potential recipients
While a transplant center is free to set its own criteria for transplant candidates, certain requirements are generally agreed upon:
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end-stage lung disease;
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has exhausted other available therapies without success;
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no other chronic medical conditions (e.g. heart, kidney, liver);
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no current infections or recent cancer. There are certain cases where pre-existing infection is unavoidable, as with many
patients with cystic fibrosis. In such cases, transplant centers, at their own discretion, may accept or reject patients with
current infections of B virus
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no HIV or hepatitis
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no alcohol, smoking, or drug abuse;
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within an acceptable weight range (marked undernourishment or obesity are both associated with increased mortality);
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age
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acceptable psychological profile;
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has social support system;
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financially able to pay for expenses (where medical care is paid for directly by the patient);
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able to comply with post-transplant regimen. A lung transplant is a major operation, and following the transplant, the
patient must be willing to adhere to a lifetime regimen of medications as well as continuing medical care.
Risks
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As with any surgical procedure, there are risks of bleeding and infection. The newly transplanted lung itself may fail to properly heal
and function. Because a large portion of the patient's body has been exposed to the outside air, sepsis is a possibility,
so antibiotics will be given to try to prevent that. Other complications include Post-transplant lymphoproliferative disorder, a form
of lymphoma due to the immune suppressants, and gastrointestinal inflammation and ulceration of the stomach and esophagus.
Transplant rejection is a primary concern, both immediately after the surgery and continuing throughout the patient's life. Because
the transplanted lung or lungs come from another person, the recipient's immune system will "see" it as an invader and attempt to
neutralize it. Transplant rejection is a serious condition and must be treated as soon as possible.
Signs of rejection:
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fever;
flu-like symptoms, including chills, dizziness, nausea, general feeling of illness, night sweats;
increased difficulty in breathing;
worsening pulmonary test results;
increased chest pain or tenderness;
increase or decrease in body weight of more than two kilograms in a 24-hour period.
In order to prevent transplant rejection and subsequent damage to the new lung or lungs, patients must take a regimen
of immunosuppressive drugs. Patients will normally have to take a combination of these medicines in order to combat the risk of
rejection.
This is a lifelong commitment, and must be strictly adhered to. The immunosuppressive regimen is begun just before or after surgery.
Usually the regimen includes cyclosporine, azathioprine and corticosteroids, but as episodes of rejection may reoccur throughout a
patient's life, the exact choices and dosages of immunosuppressants may have to be modified over time. Sometimes tacrolimus is
given instead of cyclosporine and mycophenolate mofetil instead of azathioprine.
The immunosuppressants that are needed to prevent organ rejection also introduce some risks. By lowering the body's ability to
mount an immune reaction, these medicines also increase the chances of infection. Antibiotics may be prescribed in order to treat or
prevent such infections. In turn, infection may increase the risk of rejection, and generally an interaction may prevail between both
risks. Certain medications may also have nephrotoxic or other potentially harmful side-effects. Other medications may also be
prescribed in order to help alleviate these side effects. There is also the risk that a patient may have an allergic reaction to the
medications. Close follow-up care is required in order to balance the benefits of these drugs versus their potential risks.
Chronic rejection, meaning repeated bouts of rejection symptoms beyond the first year after the transplant surgery, occurs in
approximately 50% of patients. Such chronic rejection presents itself as bronchiolitis obliterans, or less frequently, atherosclerosis.
• The poorer outcome of lung transplants
compared to hearts is indicative of additional
risk factors that help to mask other influences
such as HLA.
• There are cases with no HLA mismatch, but
with time, more cases where few HLA
mismatches exist are gradually added.
• HLA mismatches have an influence on acute
rejection as well as on the development of
bronchiolitis obliterans syndrome.
• HLA-DR mismatch is commonly recognized as
having the greatest influence.
Tissue typing
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ABO match
Complete viral screening
HLA A, HLA B and HLA DRB1
PRA, crossmatch
TSH, T3, T4
PTH, calcitonine osteocalcin, vit.D, biochemistry,
tumor markers: CEA, CA 19-9, CA 125, AFP,
β-HCG, α1-globulina
Prognosis
1 year survival
5 years survival
10 years survival
Lung transplant
83.6%
53.4%
28.4%
Heart-lung
transplant
73.8%
46.5%
28.3%
Skin transplantation
Skin transplantation
• The principles of managing patients with severe
burns involve the maitenance of body homeostasis,
nitrogen balance, immunocompetence and the
exclusion of microorganism until nonviable tissue is
removed and the wound safely closed.
• If the function of skin is not restored in a few weeks,
the patient will die as a result of complex sequence
of metabolic abnormalities and septic
complications.
Skin transplantation
• In the absence of autologous skin, allograft skin
(fresh human cadaveric skin) is the best biological
membrane for burn wound coverage.
• Xenograft (porcine skin) – strong antigenity that
leads to rapid rejection
xenograft has to be
removed on the third day after application.
• Human placental membranes – accelerate the
healing process by exerting an angiogenic effect
and increasing capillary density of the underlying
wound bed.
Allograft skin
• Used for temporary coverage of burn wounds.
• Rejection of the grafts inevitably occurs after 2
weeks, despite of depressed immunity.
• Prolongation of the allograft skin survival to
about 6 weeks could be achieved by pretreating with steroids and UV light.
• The best match between donor and recipient is
identity for HLA-A, B and DRB1.
• The use of cyclosporine prolongs the skin graft
survival, but the rejection occurs within 2 weeks
after treatment is stopped.
Hand transplantation
(composite tissue allotransplatation)
Hand transplantation
(composite tissue allotransplatation)
• A hand transplant, unlike a solid organ transplant,
involves multiple tissues (skin, muscle, tendon,
bone, cartilage, fat, nerves and blood vessels) and
can be considered the “gold standard” in CTA.
• The world experience in human hand
transplantation to date includes 50 transplants
performed in 36 recipients.
(www.handregistry.com)
Hand transplantation
• The procedure is for individuals who have experienced
the difficult loss of a hand or forearm due to: (1)
trauma; (2) life saving interventions that caused
permanent injury to the hand or forearm.
• Hand transplant procedure is not being considered for:
congenital anomalies
loss of a limb due to cancer
leg amputations
individuals whose injury is limited to fingers
Donated limbs would come from brain dead living
donors.
Hand transplantation
• The majority of patients demonstrated at least one
episode of acute rejection in the first year, and the skin
was the primary target of the immune response.
• The high antigenicity of the skin can, in part, be related to
the high proportion of potent antigen-presenting cells
(Langerhans cells) and keratinocytes that express major
histocompatibility complex (MHC) I constitutively, and
MHC II, intercellular adhesion molecule 1 (ICAM)-I and
proinflammatory cytokines upon stimulation.
• Viral infections, in particular cytomegalovirus (CMV), have
been postulated to trigger the episodes of acute rejection
Hand transplantation is a surgical procedure to transplant a hand from one human to another.
The "donor" hand usually comes from a brain-dead donor and is transplanted to a recipient who
has lost one or both hands/arms. Most hand transplants to date have been performed on below
elbow amputees, although above elbow transplants are gaining popularity. Hand transplants were
the first of a new category of transplants where multiple organs are transplanted as a single
functional unit, now termed "Vascularized Composite Allotransplantation" or VCA.
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The operation is quite extensive and typically lasts from 8–12 hours. By comparison, a typical head
transplantoperation lasts 6 to 8 hours. Surgeons usually connect the bones first, followed by
tendons, arteries, nerves, veins, and skin.
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The recipient of a hand transplant needs to take immunosuppressive drugs similar to other
transplants such as kidneys or livers, as the body's natural immune system will try to reject, or
destroy, the hand. These drugs cause the recipient to have a weaker immune system which may
lead to an increased risk of infections and some cancers. There have been many advances in solid
organ transplantation over the years that have made these medications quite tolerable.
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After the transplant, there is a period of extensive hand therapy/rehabilitation which helps the
recipients regain function of the transplanted hand. Those patients who are dedicated to taking
the medications and performing the physical therapy following a hand transplant have had
remarkable success in regaining function of the new hands/arms.
Corneal transplantation
Types of Cornea Transplants
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The cornea contains five layers. Cornea transplants don't always transfer all the
layers.
Types of cornea transplants include:
• Penetrating (full thickness) cornea transplant. This involves transplanting all the
layers of the cornea from the donor.
• Lamellar cornea transplant. During this procedure, the surgeon only replaces
some of the layers of the cornea with the transplant.
• In a lamellar cornea transplant, selected layers are transplanted, which can include
the deepest layer, called the endothelium (posterior lamellar cornea transplant).
Commonly performed versions of this procedure include Descemet's Stripping
Automated Endothelial Keratoplasty (DSAEK) or Descemet's Membrane
Endothelial Keratoplasty (DMEK).
• Or it can include layers closer to the surface (anterior lamellar cornea transplant).
• Lamellar transplants may be more appropriate than full penetrating transplants
when the disease process is limited to only a portion of the cornea.
Corneal transplantation
• It is estimated that 10.000.000 people are
affected by various disorders that would benefit
from corneal transplantation.
• 100.000 procedures are performed worldwide
each year.
–UK: >2300 grafts/yr
–Australia: 1500 grafts/yr
–USA: > 40.000 people are corneal
transplanted
Corneal transplantation
Indications:
• Bullous keratopathy
• Corneal degeneration
• Corneal perforation
• Keratoglobus and dystrophy
• Scarring due to keratitis and trauma
• Inflamed corneal tissue unresponsive to
antibiotics or anti-viral treatment
Indications
Indications for include the following:
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Optical: To improve visual acuity by replacing the opaque or distorted host tissue by clear healthy donor
tissue. The most common indication in this category is pseudophakic bullous keratopathy, followed
by keratoconus, corneal degeneration, keratoglobus and dystrophy, as well as scarring due
to keratitis and trauma.
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Tectonic/reconstructive: To preserve corneal anatomy and integrity in patients with stromal thinning
and descemetoceles, or to reconstruct the anatomy of the eye, e.g. after corneal perforation.
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Therapeutic: To remove inflamed corneal tissue unresponsive to treatment by antibiotics or anti-virals.
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Cosmetic: To improve the appearance of patients with corneal scars that have given a whitish or opaque hue
to the cornea.
Pre-operative examination
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In most instances, the patient will meet with their ophthalmologist for an examination in the weeks or
months preceding the surgery. During the exam, the ophthalmologist will examine the eye and diagnose the
condition. The doctor will then discuss the condition with the patient, including the different treatment
options available. The doctor will also discuss the risks and benefits of the various options. If the patient
elects to proceed with the surgery, the doctor will have the patient sign an informed consent form. The
doctor might also perform a physical examination and order lab tests, such as blood work, X-rays, or an EKG.
The surgery date and time will also be set, and the patient will be told where the surgery will take place.
Within the United States, the supply of corneas is sufficient to meet the demand for surgery and research
purposes. Therefore, unlike other tissues for transplantation, delays and shortages are not an issue.
Corneal transplantation
• HLA-A and HLA-B antigens have been identified on
corneal epithelium, stromal cells, corneal endothelial
cells and are targets for CD8+ cytotoxic T cells.
• HLA-A and HLA-B matching was associated with
improved outcome of corneal graft survival in high risk
recipients.
• HLA-DR antigens are carried on Langerhans cells.
• The role of HLA-DR matching in corneal transplantation
remains controversial.
• ABO incompatibility would lead to late corneal clouding
Corneal transplantation
Risks:
• Infection – the cornea has no blood vessels and
it heals much more slowly.
• Graft failure – can occur at any time, even years
or decades later.
The role of HLA matching in reducing corneal graft
failure could not be confirmed by all studies.
< 10% of primary grafts undergo immune rejection
despite no routine HLA matching.
Risks
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The risks are similar to other intraocular procedures, detachment or displacement of lamellar
transplants.
There is also a risk of infection. Since the cornea has no blood vessels (it takes its nutrients
from the aqueous humor) it heals much more slowly than a cut on the skin. While the wound
is healing, it is possible that it might become infected by various microorganisms.This risk is
minimized by antibiotic prophylaxis (using antibiotic eyedrops, even when no infection
exists).
There is a risk of cornea rejection, which occurs in about 20% of cases.
Prognosis
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The prognosis for visual restoration and maintenance of ocular health with corneal
transplants is generally very good. Risks for failure or guarded prognoses are multifactorial.
The type of transplant, the disease state requiring the procedure, the health of the other
parts of the recipient eye and even the health of the donor tissue may all confer a more or
less favorable prognosis.
The majority of corneal transplants result in significant improvement in visual function for
many years or a lifetime. In cases of rejection or transplant failure, the surgery generally can
be repeated.
Recovery From a Cornea Transplant
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The risks of complications vary depending on how many layers of the cornea are transplanted. The cornea
is “immunologically privileged” so that no matching of donor to recipient is required. Additionally, steroid
eye drops afford protection against rejection so that pills and systemic medications are not required to
prevent rejection. Y our body is even less likely to reject the transplant if only the outer layers are used,
compared to using all the layers or the deepest layer. Rejection happens in less than 20% of cases overall.
Other problems can include:
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Bleeding (rare)
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Scarring
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Cataract formation, retinal detachment, and damage to other parts of the eye
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Leakage of fluid from the transplant incision
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Infection (rare)
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Vision problems. Full thickness transplants can heal with large amounts
of astigmatism, nearsightedness and farsightedness, requiring thick lenses on eyeglasses or contact
lenses.
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In addition, some ailments that damage people's original cornea can also harm the new cornea. For
example, there is the possibility of recurrence of herpes simplex infection in the transplant.
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Rejection may even occur years after the surgery. If you notice any of these signs that last for more than
six hours, call your eye doctor promptly. The doctor can give you medicine that can help prevent as well as
treat rejection.
Success Rates of Cornea Transplants
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Experts know more about the long-term success rates of penetrating cornea
transplants, which use all the layers of the cornea.
Success rates are also affected by the problem that needed to be fixed with the
transplant.
For example, research has found that the new cornea lasts for at least 10 years in:
• 89% of people with keratoconus
• 73% of people with Fuchs' dystrophy
• 60% to 70% of people with corneal scarring