ORGAN

TRANSPLANTATION

Ana Pena
CHBPT do Hospital de Curry Cabral
Cirurgia Geral - Mestrado Integrado
Medicina FCML - UNL
Director: Prof. Dr. Hugo Pinto Marques

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 HISTORY

The actual History of Transplantation started in the

beginning of the 20th century.

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 HISTORY

• During the first half of the 20th century, several

kidney transplants were performed in animals or
in human bodies. The donors were either animals
(xenotransplants) or human cadavers. The
anatomical location varied...

• “Results depend on biological factors.” – Alexis

Carrel, 1902

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 HISTORY
1954, Boston USA – Merril and Murray performed the
first kidney transplant with long survival (9 years), in
identical twins.

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 HISTORY

Since the 1960s, there has been an increased

success rate in transplants in which the
donors and recipients were related and non-
related (cadaver donors), in parallel with the
development of immunology and consequent
immunosuppressant use.

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 HISTORY
1963 1967
ü1st liver transplant in the ü 1st heart transplant in
world – T. Starzl, Denver, the world - C. Barnard,
USA (the 1st one with 1 year Cape Town, South
survival took place in 1967) Africa

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 HISTORY
• 1968
First liver
transplant in
Europe – Prof. R.
Calne Cambridge,
UK

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 History of Transplantation in Portugal
• 20th July 1969
1st kidney
transplant in
Portugal
Linhares Furtado, HUC in
Coimbra

Living donor (sister)

Recipient †

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 History of Transplantation in Portugal

— 1976

Organ harvesting in cadavers and its use for

transplantation is approved.

Presumed consent

Media controversy in turn of the concept of brain

death

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 HISTORY

The combination azathioprine + corticosteroids

achieves satisfactory results before the 1980s.

1978 - the clinical use of ciclosporin (R. Calne)

significantly increases the graft survival, allowing the
expansion of clinical transplantation programs
worldwide.

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 History of Transplantation in Portugal

— 1993
The national registry of non-donors is created
(RENNDA)
— 1995
Linhares Furtado performs, in Coimbra, the first
sequential / domino transplant (FAP liver)

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 ORGAN TRANSPLANTATION BIOLOGY

RECIPIENT

ORGAN
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 What makes the organ recipient a
“special patient”?

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 What makes the organ recipient a
“special patient”?

§ The disease that led to the need of a

transplant
§ The transplant surgery
§ The immunosuppressant (IS) use
§ Other drugs use

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 Immunosuppression

• “NATURAL” / NON-DELIBERATE

– Malignant tumors;
– Infection;
– Myelosuppression as a side effect

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 Immunosuppression

• DELIBERATLY INDUCED IMMUNOSUPPRESSION

Immunosuppressants
– Corticosteroids
– Azathioprine
– Calcineurin inhibitors – cyclosporin A, tacrolimus (FK 506)
– Mycophenolate mofetil
– mTOR inhibitors – sirolimus and everolimus
– Antilymphocyte sera
– “MABS” (monoclonal antibodies – baziliximab, rituximab etc.)
– Irradiation
– Plasmapheresis
– Immune tolerance induction

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 Immunosuppression

Important side effects

Toxicity – regular dosage and monitoring of seric

levels

Increase in infection incidence

Increase in tumor incidence

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 MALIGNANT TUMORS

The prevalence of most malignant tumors (except for

breast and prostate) is higher than in the rest of the
population in general, especially:
• Lymphoma
• Skin tumors
• Kaposi Sarcoma
• Endocrine tumors
• Leukaemia

• And they ALL become more aggressive.

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 New Immunosuppression Techniques

• Use of monoclonal antibodies as inductors

• Previous desensitization of patients with ABO

incompatibility or anti-HLA created against the donor
(living donor) with monoclonal antibodies

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 New Immunosuppression Techniques

In search of the “Holy Grail” of transplantation:

TOLERANCE
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 ORGAN ORIGIN

– Autotransplant
– Allotransplant
• Living donor
• Cadaveric donor
– Brain death
–“Non heart beating donor”
– Xenotransplant

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 ORGAN IMPLANTATION

• Orthotopic – in its anatomical location

– Liver
– Heart
– Lung
– Etc.
• Heterotopic – out of its anatomical location
– Kidney (could be orthotopic)
– Pancreas

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 DONOR
• Living • Cadaveric
– Related – Brain death
– Non-related – Non heart beating
• Affective donor (“cardiac
relationship death”)
• Altruistic
• Paired exchange
/ chain donation

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 New classification of donation after circulatory
death donors definitions and terminology

Transplant International, Volume: 29, Issue: 7, Pages: 749-759, First published: 17 March 2016, DOI: (10.1111/tri.12776)
 Modified Maastricht classification for donors
after circulatory death (Detry, 2012)
• Uncontrolled DCD I Dead in the out-of-hospital setting 1A. Cardiocirculatory death outside
hospital with no witness. Totally uncontrolled
• 1B. Cardiocirculatory death outside hospital with witnesses and rapid resuscitation attempt.
Uncontrolled
• II Unsuccessful resuscitation 2A. Unexpected cardiocirculatory death in ICU. Uncontrolled
• 2B. Unexpected cardiocirculatory death in hospital (ER or ward), with witnesses and rapid
resuscitation attempt. Uncontrolled
• ControlledDCD III Awaiting cardiac arrest 3A. Expected cardiocirculatory death in ICU.
Controlled
• 3B. Expected cardiocirculatory death in OR (withdrawal phase > 30 min). Controlled
• 3C. Expected cardiocirculatory death in OR (withdrawal phase < 30 min).
• (Highly) controlled
• IV Cardiac arrest while brain death 4A. Unexpected cardio circulatory arrest in a brain dead
donor (in ICU). Uncontrolled
• 4B. Expected cardiocirculatory arrest in a brain dead donor (in OR or ICU).
• (Highly) controlled
• V Euthanasia 5A. Medically assisted cardiocirculatory death in ICU or ward.
• Controlled
• 5B. Medically assisted cardiocirculatory death in OR.
• Highly controlled

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 CADAVERIC DONOR
ORGAN HARVESTING

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 CADAVERIC DONOR EVALUATION

- Clinical and laboratory

evaluation of the donor

- Brain death proof

- Absolute
contraindications:
-Malignant disease out
of the CNS.
-AgHbs +
-Sepsis
-Active drug addiction
(e.v.)
-HIV+
-HTLV
- Consultation of the
RENNDA
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 ORGAN HARVESTING IN CADAVERIC
DONOR

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 Kravitz’s Lifeport Kidney Transporter
PPP – Pulsatile Pump Perfusion

• Donor > 50 years-old

• Expanded criteria donor
• Allows an assessment
of the quality of the
graft
• Perfuses the kidney
during the cold
ischaemia time

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• EXPANDED CRITERIA/SUBOPTIMAL DONOR

1. Non heart beating donor

2. Low weight paediatric donor (<20Kg)
3. > ou = 60 years-old
or
4. > 50 years-old and (two of the following)
• HBP
• Death caused by stroke
• Creatinine >1.5 mg/dl

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• EXPANDED CRITERIA DONOR (20%??)

– KIDNEY – If GFR < 30-40 ml/min is forseen,

consider a block transplant of two kidneys

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 Expanded criteria donor

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 Living donor
• To increase the number of organs available
• To increase organ quality
• To diminish risks and mortality of patients in the
waiting list
• To choose the right moment to perform the
transplant (elective procedure)
• To respond to the will of donating
• Concept of pre – emotional transplant (kidney)

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 Living donor

What’s the best possible donor like??

The best candidate, in a certain time, is

not always the healthiest and/or
youngest.

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 Living donor

• Evaluation of the donor-recipient

pair
• Physical evaluation of the donor

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Psychological evaluation – motivation

Consensus statement on the live organ donor

“...the person who gives consent to be a live organ
donor should be competent, willing to donate, free
from coercion, medically and psychosocially suitable,
fully informed of the risks and benefits as a donor,
and fully informed of the risks, benefits, and
alternative treatment available to the recipient.”JAMA
2000; 284:2919-26

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 Psychological evaluation - motivation

• Expectations
• Fantasies

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 “Benefits” to the donor

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 Legal Aspects

• The Portuguese law admits donations beyond

3rd degree relatives; donations between
husbands and wives; donations between non-
related individuals (benevolant)
• EVA

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 Problems professionals face

• Ethical problems: primum no nocere

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 Surgical aspects of organ
harvesting in a living donor

• The safety of the surgery performed

on the donor is priority.

• The quality of the organ harvested is

very important, but secondary

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 Main goal ...

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 MULTIPLE
TRANSPLANT

The surgical response

to failure of more than
one vital organ.

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 MULTIPLE
TRANSPLANT
It can also be.....

The answer to surpass the

deterioration of other
graft, when isolated (reno-
pancreatic), or to make a
vital transplant possible
(hepatorenal)

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 Block transplant
Toracic:
Heart - Lung
Abdominal cluster:
Liver - Intestine

Combined / simultaneous transplant (same donor)

Pancreas + Kidney
Liver + Kidney
Heart + Liver
Heart + Liver + Kidney
Lung + Kidney ✿

Deffered (different donors and timing)

Kidney after Liver
Pancreas after Kidney
etc.

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 Multiple transplant: Heart/Lung
(block)

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 LIVER-KIDNEY COMBINED/SIMULTANEOUS
TRANSPLANT

1º
2º

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 COMBINED TRANSPLANT

RENO-PANCREATIC

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 Multiple Transplant – Abdomen
block

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Multiple Transplant
Combined Transplant of Separate Organs
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 Case, published in May 2003, of a heart, liver
and kidney multiple transplant performed in
the University of Chicago Hospitals, on a
patient suffering from Glycogen storage
disease type III (Forbes Disease) :

The multiple transplant started at 7:30 am.

Firstly, the thoracic surgeons performed the
heart transplant. The liver transplant was
performed in second place, after which the
thoracic surgeons came back to close the
sternal incision. The abdominal incision was
posteriorly closed by general surgeons. A third
team performed, in last place, the kidney
transplant, which was finished around 9:30
pm.

The next day, the patient was awake and was

breathing spontaneously.
The patient left the ICU 7 days later, and was
27/12/19 discharged from hospital 15 days p.o. 53
 Lung Transplantation
• 1963 – 18 days of survival

• > 1981 (CyA) 1st successful lung transplants:

heart-lung; single lung; double lung

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 Lung Transplantation

1. Chronic Obstructive
Pulmonary Disease (COPD)
Indications
2. Idiopathic pulmonary fibrosis
3. Cystic fibrosis
4. Alpha1-antitrypsin deficiency
5. Idiopathic pulmonary
hypertension

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 Adult and Pediatric Lung Transplants
Number of Transplants by Year and Location
5000
Other
4500
North America
4000 Europe
Number of transplants

3500

3000

2500

2000

1500

1000

500

2018
JHLT. 2018 Oct; 37(10): 1155-1206
NOTE: This figure includes only the lung transplants that are
reported to the ISHLT Transplant Registry. As such, this should
not be construed as representing changes in the number of lung
transplants performed worldwide.
 Adult and Pediatric Lung Transplants
Number of Transplants by Year and Procedure Type
5000 4661

4500 Bilateral/Double Lung 4177

4261
4098
3852
Number of Transplants

4000 Single Lung

3869
3587
3500 3313

29503025
3000 2811
2583
2500 2228
19792018
2000 17081785
1512 1568
1392
1500 1213 1391
1550
1105
923
1000 709
408
500 167
5 7 35 74
0

NOTE: This figure includes only the lung transplants that are
reported to the ISHLT Transplant Registry. As such, this should
2018 not be construed as representing changes in the number of lung
transplants performed worldwide.
JHLT. 2018 Oct; 37(10): 1155-1206
 Adult and Pediatric Lung Transplants
Kaplan-Meier Survival by Age Group
(Transplants: January 1990 – June 2016)
100
Adult (N = 59,993)
Pediatric (N = 2,205)

75
p = 0.1672
Survival (%)

50

25

Median survival (years): Adult

= 6.0; Pediatric = 5.5
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Years
2018
JHLT. 2018 Oct; 37(10): 1155-1206
 Lung Transplantation
• Average survival of 5.5 years
• > survival in double transplants (6.8 to 4.7)

• Cadaveric donor – only 15% are suitable

• Living donor – lobes (more than 1 donor...)
– Children
– Very urgent transplant with a long waiting list and
other priority patients

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 HEART TRANSPLANTATION
• Cardiac transplantation has evolved into the
treatment of choice for many patients with end-
stage heart failure (HF) with severely impaired
functional capacity despite optimal medical
therapy. Although barriers to long-term survival
remain, the outcome among transplant recipients
has improved over the past 30 years as a result of
careful recipient and donor selection, advances in
imunossuppression, and the prevention and
treatment of infection.

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 Adult and Pediatric Heart Transplants
Number of Transplants by Year and Location
6000
Other
5500
North America
5000
Europe
Number of transplants

4500
4000
3500
3000
2500
2000
1500
1000
500
0

2018
JHLT. 2018 Oct; 37(10): 1155-1206
NOTE: This figure includes only the heart transplants that are
reported to the ISHLT Transplant Registry. As such, the
presented data may not mirror the changes in the number of
heart transplants performed worldwide.
 Adult and Pediatric Heart Transplants
Kaplan-Meier Survival by Age Group
(Transplants: January 1982 – June 2016)
100
Adult (N=118,449)
Pediatric (N=13,698)
75

p<0.0001
Survival (%)

50

25
Median survival (years): Adult=10.8;
Conditional=13.4; Pediatric=16.5;
Conditional=21.4
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Years

2018
JHLT. 2018 Oct; 37(10): 1155-1206
 Adult and Pediatric Heart-Lung Transplants
Number of Transplants Reported by Location and Year
300
Other
250 North America
Number of Transplants

Europe
200

150

100

50

NOTE: This figure includes only the heart-lung transplants

2018
JHLT. 2018 Oct; 37(10): 1155-1206
that are reported to the ISHLT Transplant Registry. As such,
this should not be construed as evidence that the number of
heart-lung transplants worldwide has declined in recent
years.
 Adult and Pediatric Heart-Lung Transplants
Kaplan-Meier Survival by Age Group
(Transplants: 1982 - June 2016)
100
Median survival (years): Adult = 3.4, Pediatric = 3.0
Conditional median survival (years): Adult = 10.3, Pediatric = 7.8

75

p = 0.6779
Survival (%)

50

25

Adult (N=3,998)
Pediatric (N=726)
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Years
2018
JHLT. 2018 Oct; 37(10): 1155-1206
 Intestinal and Multivisceral
Transplantation

• Intestinal transplants are mostly targeted

towards patients suffering from “intestinal
failure”
• Most patients have developed serious
complications due to TPN (Total Parenteral
Nutrition), by short bowel syndrome (SBS).

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 Intestinal and Multivisceral
Transplantation

• Serious complications of TPN

– Central venous access catheters failure

– Recurrent infections originated in the catheter
– Cholestatic hepatitis

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 Intestinal and Multivisceral
Transplantation

• Results have improved. However, they are

worse than the ones registered in transplants
involving other organs.
– 62% at 3 years -> Intestinal transplant
– 68% at 3 years -> Combined liver-intestin
transplant and multivisceral transplant

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 Multivisceral and Intestinal
Transplantation

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• Survival rate of the graft, 5 years after the
transplant

– Living donor – 91%

– Cadaveric donor – 83%

– Expanded criteria donor – 70%

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• Kidney transplants are the best therapeutical
approach to ALMOST every patient suffering
from end-stage kidney failure.

• Global survival after 5 years in hemodialysis

35%

• Global survival 3 years after the transplant

>90%
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 Kidney Heterotopic Implant in the
Iliac Fossa (extraperitoneal)

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 LIVER TRANSPLANT

Recipient Disease 281

484 360

12 92

CIR (39,4%) DHM (22,8%) PAF (29,3%)

FHF (7,4%) DIV (0,9%)

 LIVER TRANSPLANT
• The European Liver Transplant Registry (ELTR)
– 44,286 liver transplantations (LTs ) performed on 39,196
patients in a 13-year period
– lack of organs => split LT, domino LT, or living-related LT (LRLT)
are being used increasingly 11% of all procedures; older donors
>80Years
– improvement of results along time with, for the mean time, a
one-year survival of 83%, all indications confounded
– retransplantation is associated with much less optimal results
than first LT
– LRLT is now performed by almost half of the European centers
=> special attention is paid to reducing the risk for the donor -
0.5% mortality and 21% postoperative morbidity

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 Model for End-stage Liver Disease
(MELD)
• INR (prothrombin time)
• Total bilirubin
• Serum creatinine
• Serum sodium
• Hemodialysis

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LIVER TRANSPLANT –
SEQUENTIAL
 LIVER TRANSPLANT - SPLIT

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1. Simultaneous Kidney + Pancreas transplant,
same cadaveric donor (SPK)
2. Simultaneous Kidney (living donor) +
Pancreas (cadaveric donor) transplant (SPK-
LD)
3. Kidney transplant (living or cadaveric donor)
followed by pancreas transplant (PAK ou KA-
LD+PAK)
4. Isolated pancreas transplant (PTA)
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End-stage kidney
disease (while on
hemodialysis)
/pre-terminal
+
DM1 with
complications

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 – Serious hypoglycemia episodes, not “recognised”
by the patient
– Insulin resistance/allergy
– Hard metabollic control of the disease as well as
its fast progression

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 THE “FUTURE”... IS THE PRESENT!!

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