TRANSPLANTATION. See also SURGERY and CHEST
1985 (1990) Yacoub
MH, Banner NR, Khaghani A, FitzGerald M, Madden B, Tsang V, Hodson M. Heart-lung
transplantation for cystic fibrosis and subsequent domino heart transplantation.
J Heart Transplant 1990; 9:459-467. [PubMed]
A major advance, for those who had reached the end stages of their disease (an
FEV1 predicted of less than 30%), was the successful introduction of heart-lung
transplantation in 1985, pioneered by Sir Magdi Yacoub (figure 29) and his team
in London (Yacoub et al, 1990; Scott et al, 1988 below) and mr John Wallwork
and his team in Cambridge. The possibility of successful treatment in what were
previously the terminal stages of the condition had a major influence on both
prognosis and the treatment of severely affected individuals.
The first results of heart-lung transplantations were quite remarkable and were
related both to surgical skills, concentrated medical expertise in assessment
and after care and also to more successful immunosuppressive therapy to prevent
rejection of the transplanted organs. Later double lung transplants became more
popular (Pasque et al, 1990 below) and are now the most commonly performed operation.
Living donor lung transplants have proved successful in some centres and will
be an obvious choice for some families in the absence of suitable donor organs
(Cohen & Starnes, 2001 below).
1987 Penketh A,
Higenbottam T, Hakim M, Wallwork J. Heart lung transplantation in patients with
end stage lung disease. BMJ 1987; 295:311-314. [PubMed]
The cardiothoracic surgical team at Papworth, Cambridge UK under the
leadership of Mr John Wallwork (figure 41.1) report preliminary results of heart-lung
transplantation in seven patients one of whom had CF. Six of the seven patients
were well after four to 33 months. Papworth became one of the major UK transplant
centres for people with cystic fibrosis. Further experience was published in
1989 where five of 33 patients referred benefited over 18 months (Smyth RL et
al. Arch Dis Child 1989; 64: 1225-1229). The first heart lung transplants for
CF were performed by Mr. Magdi Yacoub in 1985 in London at Harefields Hospital
(Yacoub et al, 1990 below).
1988 Jones K, Higenbottam
T, Wallwork J. Successful heart-lung transplantation for cystic fibrosis. Chest
1988; 93:644-5. [PubMed]
Report of one of the first successful heart lung transplants in CF in October
1985 by Mr Wallwork’s team at Papworth Hospital, Cambridge. Sixteen months
after heart-lung transplantation, the FEV1 of a young woman, who had been in
the terminal stages of CF, has risen from 16 percent (0.6 L) to 77 percent of
her predicted value. She had returned to work.
These first reports of heart lung transplantation for a condition which was
uniformly fatal were quite dramatic and excited a great deal of hope and interest
in the CF community. John Wallwork and Magdi Yacoub were leaders in this field
in the UK for the next few years. (also Penketh et al above; Scott J et al.
Heart lung transplantation for cystic fibrosis. Lancet 1988; ii: 192-194 reporting
five of six patients with CF survived heart lung transplantation at Papworth
Hospital). Later Prof John Dark and Prof Paul Corris in Newcastle developed
a major transplant service.
1990 Pasque MK,
Cooper JD, Kaiser LR, Haydock DA, Triantafillou A, Trulock EP. Improved technique
for bilateral lung transplantation: rationale and initial clinical experience.
Ann Thorac Surg 1990; 49:785-791. [PubMed]
The first bilateral lung transplantation in CF was performed in Toronto in 1988
and 17 were carried out between 1988 and 1991 (Ramirez JC et al. J Thorac Cardiovac
Surg 1992; 103:287-293). [PubMed] This improved operation was done through a transverse thoracosternotomy and
involves sequential replacement of the two lungs. Positive features included
separate bronchial anastomoses to reduce ischemic airway complications and elimination
of the need for total cardiopulmonary bypass. Three patients were reported,
one had CF, all recovered without complications and post operative function
was excellent. The double lung transplant operation gradually replaced heart-lung
transplants for people with cystic fibrosis.
1990 Yacoub M, Banner
NR, Khaghani A, Fitzgerald M, Madden B, Tsang V, Smyth R, Hodson ME. Heart lung
transplantation for CF and subsequent domino cardiac transplantation. J Heart
Transplantation 1990; 9:459-67. [PubMed]
Between September 1984 and October 1988, 27 patients underwent combined heart-lung
transplantation for treatment of end-stage respiratory disease caused by CF:
survival was 78% at 1 year and 72% at 2 years. Lung function was greatly improved
after transplantation, and long-term survivors achieved an excellent quality
of life. Lymphoproliferative disorders developed in two patients; these disorders
regressed after a reduction in immunosuppression. Two patients required retransplantation:
one because of obliterative bronchiolitis and the other because of recurrent
respiratory infections associated with a moderate tracheal stenosis and severe
deterioration in lung function. A modification of the technique used for heart-lung
transplantation allowed 20 hearts from cystic fibrosis patients to be used for
subsequent heart transplantation.
This report by Mr Yacoub and his team, who performed the first heart lung transplantations
in people with CF at Harefields Hospital, London in 1984. There were also reports
from Mr Wallwork’s unit at Papworth, Cambridge (Penketh et al, 1987 above;
Jones et al, 1988 above and later from Professors Dark and Paul Corrie from
Newcastle)
2001 Cohen RG, Starnes
VA. Living donor lung transplantation. World J Surg 2001; 25: 244-250. [PubMed]
Since 1993 a total of 101 living-donor bilateral lung transplants had
been performed with acceptable results. Though most recipients were patients
with CF who were rapidly deteriorating, the indications for live-donor lung
transplantation had been expanded to include some CF patients in a more elective
setting, as well as select patients with other end-stage pulmonary diseases.
One-year Kaplan-Meier recipient survival is 72%. Seventy-six percent of deaths
occur within the first 2 months after transplantation. There has been no donor
mortality and 83% had no problems.
This is a remarkable series which does not appear to have been replicated anywhere else, although there are further publications on the subject from Starnes group reporting further experience (Backhus LM. Et al. J Heart Lung Transpl 2005; 24:2086-90) [PubMed] Eighty-seven transplants were performed on 84 adult recipients from 1993 through 2003 - 76 had cystic fibrosis. Starnes had been publishing on the subject of living donor lung transplants since 1996. The technique has not become popular in the UK.
2003 Date H. Aoe
M. Nagahiro I. Sano Y. Andou A. Matsubara H. Goto K. Tedoriya T. Shimizu N.
Living-donor lobar lung transplantation for various lung diseases. J Thorac
Cardiov Sur 2003; 126:476-481. [PubMed]
This papaer from Okayama Japan reports experience in living-donor
lobar lung transplantation for patients with various lung diseases including
restrictive, obstructive, septic, and hypertensive lung diseases. From October
1998 to March 2002, living-donor lobar lung transplantation was performed in
14 patients with end-stage lung diseases. Diagnoses included primary pulmonary
hypertension (n = 6), idiopathic interstitial pneumonia (n = 2), bronchiolitis
obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1),
and cystic fibrosis (n = 1). Bilateral living-donor lobar lung transplantation
was performed in 13 patients and right single living-donor lobar lung transplantation
was performed for a 10-year-old boy with primary pulmonary hypertension. All
the 14 patients are currently alive with a follow-up period of 4 to 45 months.
Although their forced vital capacity (1327 +/- 78 mL, 50.2% of predicted) was
limited at discharge, arterial oxygen tension on room air (98.5 +/- 1.8 mm Hg)
and systolic pulmonary artery pressure (24.8 +/- 1.6 mm Hg) were excellent.
Forced vital capacity improved gradually and reached 1894 +/- 99 mL, 67.4% of
predicted, at 1 year. All donors have returned to their previous lifestyles.
The authors suggest that living-donor lobar lung transplantation can be applied
to restrictive, obstructive, septic, and hypertensive lung diseases. This type
of procedure can be an alternative to conventional cadaveric lung transplantation
for both pediatric and adult patients who would die soon otherwise.
This is an interesting paper for Japan with obvious success with this procedure of which there are few reports other than the work from Starnes group in 2001 from San Diego.
2003 Gilljam M.
Chaparro C. Tullis E. Chan C. Keshavjee S. Hutcheon M. GI complications after
lung transplantation in patients with cystic fibrosis. Chest. 2003; 123:37-41. [PubMed]
Lung transplantation is now available for patients with
cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function
is often considered the major priority following transplantation, the non pulmonary
complications of this systemic disease also continue. GI complications after
lung transplantation were common in patients with CF, and the authors advised
that attention should be paid to the risk for DIOS in the early postoperative
period. Prevention and early medical treatment are important in order to avoid
acute surgery. Close collaboration with the CF clinic, in order to diagnose
and treat CF-related complications, is recommended.
The gastrointestinal aspects of treatment may receive insufficient attention if there are serious respiratory problems. This report of extensive experience from Toronto of patient after lung transplantations documents this advice and records experience of 27 of 75 patients. The present writer is aware of an instance where failure to give enzymes in the post operative period resulted in intestinal obstruction then complications with resulting fluid and parenteral nutrition eventually leading to fatal systemic candida infection.
2004 Bech B. Pressler
T. Iversen M. Carlsen J. Milman N. Eliasen K. Perko M. Arendrup H. Long-term
outcome of lung transplantation for cystic fibrosis--Danish results. Eur J Cardio-Thor
Surg 2004; 26:1180-1186. [PubMed]
In
a 10-year period, 47 patients with CF were listed for lung transplantation;
29 patients underwent transplantation and 18 patients died while waiting for
donor organs. Eleven patients received en block double lung transplantation
with direct bronchial artery revascularization and 18 patients received bilateral
sequential lung transplantation. Median age at transplantation was 29 years
(range 11-50). The perioperative mortality (< or =30 days) was 3.5% (1/29
patients). Actuarial survival of transplanted patients at 1, 3, 5 and 8 years
was 89, 80, 80 and 70%, respectively. Actuarial survival of non-transplanted
patients on the waiting list at 1 and 2 years was 28 and 11% (P<0.0001).
Impressive results from the Danish CF centre
2004 Starnes VA.
Bowdish ME. Woo MS. Barbers RG. Schenkel FA. Horn MV. Pessotto R. Sievers EM.
Baker CJ. Cohen RG. Bremner RM. Wells WJ. Barr ML. A decade of living lobar
lung transplantation: recipient outcomes. J Thorac Cardiov Surg 2004; 27:114-122. [PubMed]
One hundred twenty-eight living lobar lung transplantations were performed in
123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27
+/- 7.7 years), and 39 were pediatric patients (age, 13.9 +/- 2.9 years). The
primary indication for transplantation was cystic fibrosis (84%). At the time
of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated.
One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%,
54%, and 45%, respectively. There was no difference in actuarial survival between
adult and pediatric living lobar recipients (P =.65). There were 63 deaths among
living lobar recipients, with infection being the predominant cause (53.4%),
followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction
(7.9%). The overall incidence of acute rejection was 0.8 episodes per patient.
Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication,
donor relationship, preoperative hospitalization status, use of preoperative
steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However,
patients on ventilators preoperatively had significantly worse outcomes and
those undergoing retransplantation had an increased risk of death. These results
support the continued use of living lobar lung transplantation in patients deemed
unable to await a cadaveric transplantation. We consider patients undergoing
retransplantation and intubated patients to be at significantly high risk because
of the poor outcomes in these populations.
This team who pioneered this technique have impressive results. The operation does not seem to have been developed in the UK transplant centres.
2005 Young AL. Peters CJ. Toogood GJ. Davies MH. Millson CE. Lodge JP. Pollard SG. Prasad KR. A combined liver-pancreas en-bloc transplant in a patient with cystic fibrosis. Transplantation 2005; 80:605-607. [PubMed]
2005 Fridell JA.
Vianna R. Kwo PY. Howenstine M. Sannuti A. Molleston JP. Pescovitz MD. Tector
AJ. Simultaneous liver and pancreas transplantation in patients with cystic
fibrosis. Transplant Proc 2005; 37:3567-9.[PubMed]
Improved
survival in patients with cystic fibrosis (CF) has led to an increased incidence
of extrapulmonary complications of this disease. Of these, cirrhosis and pancreatic
insufficiency, including CF-related diabetes (CFRD) and exocrine insufficiency,
are significant causes of morbidity and mortality. Liver transplantation is
the treatment of choice for cirrhosis in this setting, but the addition of an
isolated simultaneous pancreas transplant in patients with CFRD has not been
reported. METHODS: Two female patients with CF underwent simultaneous pancreas
and liver transplantation. Both had pancreatic insufficiency, CFRD, cirrhosis,
and preserved renal function. In each case, the liver and pancreas were procured
from a single cadaveric donor. The liver transplant was performed first. A lower
midline extension was added for improved exposure of the iliac vessels. The
donor pancreas transplant was performed with systemic venous drainage and enteric
exocrine drainage. Immunosuppression included rabbit anti-thymocyte globulin,
tacrolimus, mycophenolate mofetil, and early steroid withdrawal. RESULTS: Both
patients recovered well with normal liver function, resolution of portal hypertension,
and normal blood glucoses independent of insulin. As a result of the enteric
exocrine drainage of the pancreas, they are now independent of supplemental
pancreatic enzymes. CONCLUSIONS: Simultaneous liver and pancreas transplantation
in CF patients provides the advantages of normalization of glucose and improved
nutrition for patients requiring liver transplantation and should be considered
in CF patients with CFRD who require liver transplants.
2008 Meachery G.
De Soyza A. Nicholson A. Parry G. Hasan A. Tocewicz K. Pillay T. Clark S. Lordan
JL. Schueler S. Fisher AJ. Dark JH. Gould FK. Corris PA. Outcomes of lung transplantation
for cystic fibrosis in a large UK cohort. Thorax 2008; 63:725-731.
[PubMed]
176
patients with CF underwent lung transplantation at the Freeman Hospital Newcastle
UK. The majority (168) had bilateral sequential lung transplantation. Median
age at transplantation was 26 years. Diabetes was common pretransplantation
(40%). Polymicrobial infection was common in individual recipients. A diverse
range of pathogens were encountered, including the Burkholderia cepacia complex
(BCC). The bronchial anastomotic complication rate was 2%. Pulmonary function
(FEV1 % predicted) improved from a pretransplantation median of 0.8 l (21% predicted)
to 2.95 l (78% predicted) at 1 year following transplantation. We noted an acute
rejection rate of 41% within the first month. Our survival values were 82% survival
at 1 year, 70% at 3 years, 62% at 5 years and 51% at 10 years. Patients with
BCC infection had poorer outcomes and represented the majority of those who
had a septic death. Data are presented on those free from these infections.
Bronchiolitis obliterans syndrome (BOS) and sepsis were common causes of death.
Freedom from BOS was 74% at 5 years and 38% at 10 years. Biochemical evidence
of renal dysfunction was common although renal replacement was infrequently
required (<5%). The authors concluded that lung transplantation is an important
therapeutic option in patients with CF even in those with more complex microbiology.
Good functional outcomes are noted although transplantation associated morbidities
accrue with time.
These excellent results are from the UKs largest transplant centre and the summary is reproduced in full.
2006 Dellon ES.
Morgan DR. Mohanty SP. Davis K. Aris RM. High incidence of gastric bezoars in
cystic fibrosis patients after lung transplantation. Transplantation 2006; 81:1141-6. [PubMed]
We
performed a retrospective analysis of patients who underwent lung transplantation
from December, 1992 through July, 2005 at our tertiary care medical center.
Of the 215 patients who received lung transplantation, 17 (7.9%) developed gastric
bezoars confirmed by upper endoscopy. Cystic fibrosis was the leading indication
for lung transplantation (n=145), and 11% of cystic fibrosis patients (16 of
145) formed gastric bezoars after transplant. Additionally, 94% of patients
with bezoars (16 of 17) had cystic fibrosis (P=0.02), with the exception being
a subject with primary ciliary dyskinesia. No patient who underwent lung transplant
for another indication was found to have a bezoar. The mean time to diagnosis
was 34 days, with two-thirds of bezoars diagnosed within one month after transplant.
The annual incidence was unchanged during the study period. Gastric bezoars
are common in cystic fibrosis patients after lung transplantation. The etiology
is likely multifactorial, related to gastric motility, respiratory secretions,
and medications. Further investigation is needed to understand the pathogenesis
of bezoar formation in this selected population, and strategies for primary
prevention may be beneficial.
This complication seems
to be relatively common after transplants in people with CF.
2007 Liou TG. Adler
FR. Cox DR. Cahill BC. Lung transplantation and survival in children with cystic
fibrosis.[Erratum appears in N Engl J Med. 2008; Jul 31;359(5):e6]. N Eng J
Med 2007; 357:2143-2152. [PubMed] These conclusions were refuted
by Paul Aurora transplant paediatrican at Great Ormond Street Hospital London
where all the heart and lung transplants in children in the UK were performed. [PubMed]
The
effects of lung transplantation on the survival and quality of life in children
with cystic fibrosis are uncertain. The authors used data from the U.S. Cystic
Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation
Network to identify children with cystic fibrosis who were on the waiting list
for lung transplantation during the period from 1992 through 2002. After detailed
analysis (described in the fulll summary) a total of 248 of the 514 children
on the waiting list underwent lung transplantation in the United States during
the period from 1992 through 2002. They concluded that only 5 patients had a
significant estimated benefit, 283 patients had a significant risk of harm,
102 patients had an insignificant benefit, and 124 patients had an insignificant
risk of harm associated with lung transplantation [corrected]. Our analyses
estimated clearly improved survival for only 5 of 514 patients on the waiting
list for lung transplantation. Prolongation of life by means of lung transplantation
should not be expected in children with cystic fibrosis. They concluded a prospective,
randomized trial is needed to clarify whether and when patients derive a survival
and quality-of-life benefit from lung transplantation.
2007 Fischer S.
Bohn D. Rycus P. Pierre AF. de Perrot M. Waddell TK. Keshavjee S. Extracorporeal
membrane oxygenation for primary graft dysfunction after lung transplantation:
analysis of the Extracorporeal Life Support Organization (ELSO) registry. J
Heart & Lung Transplantation 2007; 26:472-477. [PubMed]
Some patients with severe primary graft dysfunction (PGD) after lung
transplantation (LTx) require gas exchange support using an extracorporeal membrane
oxygenator (ECMO) as a life-saving therapy.The ELSO registry currently includes
31,340 ECMO cases, of which 151 were post-LTx patients with primary graft dysfunction
(PGD) 15 had cystic fibrosis. ECMO was discontinued in 93 patients owing to
lung recovery. In total, 63 (42%) patients survived the hospital stay. Although
the ELSO registry was not primarily established to study ECMO in LTx, it provides
valuable insights and evidence that there is indeed an appreciable salvage rate
with the use of ECMO for PGD after LTx.
Clearly, this is a very high-risk patient population, and no single center can accumulate a large experience of ECMO for primary graft dysfunction after lung transplantation.
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