Interactive Cardiovascular and Thoracic Surgery 3:21-24(2004)
© 2004 European Association of Cardio-Thoracic Surgery
Institutional report - Transplantation |
Improved results with lung transplantation for cystic fibrosis: a 6-year experience
Federico Venuta*,
Serena Quattrucci,
Erino A. Rendina,
Tiziano De Giacomo,
Edoardo Mercadante,
Marco Moretti,
Giuseppe Cimino and
Giorgio F. Coloni
University of Rome ‘La Sapienza’, Policlinico Umberto I, Cattedra di Chirurgia Toracica, V. le del Policlinico, Rome 00161, Italy
* Corresponding author. Fax: +39-06-49970735
sofed{at}libero.it
Received September 27, 2002;
received in revised form July 6, 2003;
accepted July 17, 2003
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Abstract
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Since 1996, 102 patients with cystic fibrosis were accepted on our waiting list and 57 bilateral sequential lung transplants were performed in 56 patients. Before transplantation, the mean FEV1 was 0.64 l/s, the mean PaO2 with supplemental oxygen was 56 mmHg and the mean 6-min walking test was 320 m. Transplantation was performed through a ‘clam shell incision’ in the first 29 patients; in the rest of the patients we performed a bilateral anterolateral thoracotomy without sternal division. In 21 patients the donor lungs had to be trimmed by extra-anatomical wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Hospital mortality was 11.6%. Acute rejection occurred 1.6 times per patient/year; pulmonary infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV1 increased to 82% 1 year after the operation. The 2-year survival rate was 79%. Fifteen patients had BOS: one died 26 months after the operation with fungal sepsis after reinduction of immunosuppression, one has been successfully retransplanted, five were stabilized after modifications of immunosuppression and four are continuing to deteriorate. Lung transplantation is a concrete therapeutic option for patients with cystic fibrosis.
Key Words: Lung transplantation; Cystic fibrosis
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1. Introduction
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Cystic fibrosis (CF) is an inherited disease affecting one in every 2000 newborns; it is the most frequent genetic disease in Caucasians and one of the most common genetic killers in the United States. CF is a disease with many faces affecting many organs; however, the lung is the most seriously involved and more than 90% of the patients die of respiratory failure related to chronic obstructive lung disease and bronchiectasis. The improved therapeutic strategies currently employed had progressively increased the median survival to more than 30 years; however, it is estimated that approximately 300 CF patients die annually in the United States [1]. After the initial clinical application in the early 1980s lung transplantation has been considered with increasing enthusiasm as a concrete therapeutic option for a selected group of patients with CF-related end stage respiratory failure; at the present time CF is the most frequent indication to bilateral sequential lung transplantation (BSLT) [2] that completely replaced heart–lung and en-bloc double lung transplantation; survival rates in this specific subset of patients are reported as high as 85% [3] and the average survival after 1 and 3 years reported by the International Society of Heart and Lung Transplantation Registry is 71% and 56% [4].
We reviewed our 6-year experience with bilateral sequential lung transplantation for cystic fibrosis.
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2. Patients and methods
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Since 1996, 102 patients with CF were accepted in our waiting list for lung transplantation; we performed 57 BSLT in 56 patients (one patient was retransplanted for obliterative bronchiolitis syndrome 3 years after the first procedure). Thirty-four (33%) patients died on the waiting list and 12 (12%) are still waiting for a suitable organ. Among patients reaching the time of transplantation there were 26 females and 30 males; the mean age was 25 years (range 7–51). The mean waiting time before being transplanted was 121 days (1–281). The mean follow-up after transplantation is 28.6 months. Preoperative functional data and associated disorders are reported in Tables 1 and 2. At the time of transplantation two patients were assisted with invasive ventilation and 13 had non-invasive ventilatory support. Eight patients (14%) showed preoperatively a sputum colonization bt Burkolderia coepacia.
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Table 2 FEV1, forced expiratory volume in 1 s; 6 MWT, 6-min walking test; PAP, pulmonary artery pressure.Disorders associated with cystic fibrosis in the group of patients undergoing lung transplantation
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3. Results
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Bilateral sequential lung transplantation was performed through a ‘clam shell incision’ in the first 29 patients. Since 1999 we performed a bilateral anterolateral thoracotomy without sternal division [5]; in this group the surgical approach had to be turned into a ‘clam shell incision’ in three patients since cardio-pulmonary by pass (CPBP) was required. Overall, CPBP was required in 12 patients due to intraoperative hemodynamic instability or inadequate oxygenation. The mean ischemic time for the first lung was 259±28 min; for the second lung it was 370±31 min. In 21 (36%) patients the donor lungs had to be trimmed by extra-anatomical wedge resections with mechanical staplers and bovine pericardium buttressing (Synovis, Minneapolis, MN, USA) to fit the recipient chest size. Eleven patients (19%) were extubated in the operatory room immediately after the procedure. Intensive care unit (ICU) stay lasted between 3 and 28 days; patients were discharged from hospital after a mean of 28 days (range 14–46 days). Hospital mortality was 11.6% (seven patients) and it was related to infection [4], primary graft failure [2] and myocardial infarction [1]. Complications related to the surgical procedure are reported in Table 3. Acute rejection occurred 1.6 times per patient in the first year after transplantation. Overall, 25 patients (44%) had bacterial pneumonia, 25 (44%) had CMV infection and two (3.5%) had pulmonary Aspergillosis; one (1.7%) patient had chicken pox. B. coepacia gave infectious complications in four patients (three in the immediate postoperative period; two patients died): pneumonia in three and sternal osteomyelitis in one (requiring debridement and closure with a muscle flap). The most frequent cause of bacterial pneumonia was Pseudomonas aeruginosa: CMV infection was successfully treated in all patients. The functional improvement after lung transplantation is reported in Fig. 1. The 2-year survival rate is 79%.
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Fig. 1 Functional results: improvement of FEV1, FVC, PaO2 and PaCO2 measured 6 months after bilateral sequential lung transplantation. FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity.
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A Cyclosporine-based immunosuppressive regimen was initially employed in all patients (blood through level >400 ng/dl in the immediate postoperative period; >300 ng/dl after 3 months); azathioprine and steroids were always administered; 23 were subsequently switched to FK 506 because of CNS toxicity [3], myopathy [1], renal failure [3], gingival hyperplasia [1], Bronchiolitis Obliterans Syndrome (BOS) [13] and hypertricosis [2]. Ten patients were subsequently switched to Rapamicin for renal failure (dose adjustments made according to blood through levels: 4–12 ng/ml for combined therapy with CNI and 12–20 ng/ml without CNI). Overall, 15 (27%) patients had BOS: one was retransplanted, five were stabilized with FK 506, five died with respiratory failure and four are continuing to deteriorate notwithstanding changes in the immunosuppressive regimen.
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4. Discussion
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During the last decade lung transplantation has become a concrete therapeutic option for patients with CF related end stage lung disease. During this time, double lung and more recently BSLT have replaced heart–lung transplantation as the procedure of choice and outcomes continue to improve as surgical procedures are refined and more experience is acquired with these challenging patients [3]. Also, living related donation [6], split lung and reduced lung techniques [7] are now part of the surgical armamentarium useful to approach these patients and contribute to widen the suitable donor population.
One of the most important key factor for success is certainly the accurate selection of patients. It is crucial to ascertain that the patient's illness is such that extended life without the transplant would not be possible, that the risks related to factors other than pulmonary disease are not inordinately high, that renal and hepatic function will allow the administration of proper immunosuppression, and that the patient will properly comply with the complex post transplant medical regimen. The drive and determination of these patients, along with their network of support, plays an extremely important role, allowing to achieve results that are similar, if not better, to those undergoing lung transplantation for diseases that are limited to the chest.
Timing of referral is also crucial to reduce mortality on the waiting list and improve results; unfortunately, actual predictors of death for patients with CF are difficult to quantitate [8,9] and slightly predict the ‘transplant window’ [10]. A number of variables are currently evaluated to attempt to stage the clinical course of the disease and new variables are continuously proposed [11,12]; careful evaluation of this new information is obviously required but it is clear that any useful parameter able to stage the disease may be helpful to improve timing and results.
The encouraging results obtained have contributed to reconsider some of the previous absolute and relative contraindications to lung transplantation. Previous thoracic operations like pleurodesis for pneumothorax or pulmonary resections are no longer considered an obstacle to the transplant [13] as demonstrated also in our series; B. cepacia colonization still remains a controversial issue [14] and it is considered on a case-by-case basis by each center, since panresistant strains can certainly contribute to raise morbidity. The need of non-invasive and invasive mechanical ventilation, given a well preserved kidney and liver function, are not considered a contraindication to transplantation any more. In particular, nasal mask positive pressure ventilation and even an invasive support are increasingly considered as a bridge to pulmonary transplantation, since patients have been maintained this way for weeks to months; however, this approach is advisable only if patients have already undergone the evaluation process and have been accepted on the waiting list. The successful use of non-invasive techniques as a bridge to transplantation is influenced by the patient's tolerance and motivation, as well as by the judicious alternation of positive pressure ventilation, spontaneous breathing and secretion clearance by physiotherapy or tracheobronchial suction. For all these reasons pre and post-transplant care requires strict cooperation with the CF team; in fact, complications occurring during the clinical course are usually specific for this group of patients.
Pulmonary function and quality of life improve dramatically after successful bilateral sequential lung transplantation, as well as the nutritional status that reaches the normal standards within a few weeks after surgery. The routine use of bilateral anterolateral thoracotomy without sternal division contributes to achieve an earlier improvement of functional parameters; in the future, other minimally invasive approaches [15] could gain more acceptance and further reduce surgical morbidity and mortality.
Overall, lung transplantation offers a unique opportunity to improve the quality and length of life in patients with cystic fibrosis, with outcomes comparable to those requiring transplantation for disorders limited to the lung.
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Footnotes
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Presented at the 16th Annual Meeting of the European Association for Cardio-thoracic Surgery, Monte Carlo, Monaco, September 22–25, 2002.
doi:10.1016/S1569-9293(03)00147-6
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Abstract
1. Introduction