Nilto C. De Oliveira

The impact of the lung allocation score on short-term transplantation outcomes: A multicenter study

OBJECTIVE The lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation. METHODS A multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005). RESULTS The study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 +/- 528.3 days to 445.6 +/- 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 +/- 6.7 days to 7.8 +/- 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6) CONCLUSIONS This multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected.

Donation after cardiac death: A 29-year experience

OBJECTIVE To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. METHODS One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). RESULTS Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. CONCLUSION This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors.

Lung transplantation with donation after cardiac death donors: Long-term follow-up in a single center

OBJECTIVE We sought to examine long-term outcomes at the University of Wisconsin for all lung transplant recipients who received lungs from donation after cardiac death donors since the initiation of this program in 1993. METHODS Eighteen (4.2%) of the 424 lung transplantations performed in 406 patients between January 1993 and April 2009 used lungs from donation after cardiac death donors. Outcomes for this recipient cohort were compared with those for recipients who received organs from brain-dead donors. RESULTS Warm ischemic time (from withdrawal of support to reperfusion of organs) was 30 +/- 17 minutes (11-93 minutes). The patient survival rates in the donation after cardiac death group (DCD group) at 1, 3, and 5 years were 88.1% +/- 7.9%, 81.9% +/- 9.5%, and 81.9% +/- 9.5%, respectively. These survival rates were not different from those of the brain-dead donor group (BDD group, P = .66). The incidence of primary graft dysfunction in the DCD group was similar to that of the BDD group (P = .59). However, the incidence of airway complications was somewhat higher in the DCD group. Freedom from bronchiolitis obliterans syndrome at 1, 3, and 5 years in the DCD group was 80.4% +/- 10.2%, 80.4% +/- 10.2%, and 72.3% +/- 11.9%, respectively, and did not differ from the incidence of bronchiolitis obliterans syndrome in the BDD group (P = .59). CONCLUSIONS Our data show that the long-term patient and graft survival rates after donation after cardiac death lung transplantation were equivalent to those after brain-dead donor lung transplantation. Our findings suggest that the use of donation after cardiac death donors can safely and substantially expand the donor pool for lung transplantation.

Lung transplantation from donation after cardiocirculatory death: A systematic review and meta-analysis

BACKGROUND Lung transplantation (LTx) can extend life expectancy and enhance the quality of life for select patients with end-stage lung disease. In the setting of donor lung shortage and waiting list mortality, the interest in donation after cardiocirculatory death (DCD) is increasing. We performed a systematic review and meta-analysis to compare outcomes between DCD and conventional donation after brain death (DBD). METHODS PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were searched. We identified original research studies with 1-year post-transplant survival data involving >5 DCD transplants. We performed meta-analyses examining 1-year survival, primary graft dysfunction, and acute rejection after LTx. RESULTS We identified 519 citations; 11 observational cohort studies met our inclusion criteria for systematic review, and 6 met our inclusion criteria for meta-analysis. There were no differences found in 1-year mortality after LTx between DCD and DBD cohorts in individual studies or in the meta-analysis (DCD [n = 271] vs DBD [n = 2,369], relative risk [RR] 0.88, 95% confidence interval [CI] 0.59-1.31, p = 0.52, I(2) = 0%). There was also no difference between DCD and DBD in a pooled analysis of 5 studies reporting on primary graft dysfunction (RR 1.09, 95% CI 0.68-1.73, p = 0.7, I(2) = 0%) and 4 studies reporting on acute rejection (RR 0.72, 95% CI 0.49-1.05, p = 0.09, I(2) = 0%). CONCLUSIONS Survival after LTx from DCD is comparable to survival after LTx from DBD in observational cohort studies. DCD appears to be a safe and effective method to expand the donor pool.

Colon cancer in lung transplant recipients with CF: Increased risk and results of screening

OBJECTIVE To determine the incidence of colon cancer in lung transplant recipients with cystic fibrosis (CF) and review screening colonoscopic findings in other recipients with CF. METHODS A retrospective chart review was performed for all patients with CF transplanted at the University of Wisconsin Hospital and Clinics (January 1994 through December 2010). RESULTS Four of 70 transplant recipients with CF developed fatal colon carcinoma following transplantation, and the cancer was advanced in all 4 recipients (age 31, 44, 44, 64) at the time of diagnosis. In contrast, only one of 287 recipients transplanted for non-CF indications developed colon cancer. Of all recipients with CF who did not develop colon cancer, 20 recipients underwent screening colonoscopy at 1 to 12 years following transplantation. Seven (35%) of the screened transplant recipients (ages 36, 38, 40, 41, 43, 49, 51) had colonic polyps in locations ranging from cecum to sigmoid colon and up to 3 cm in diameter. CONCLUSIONS In contrast to non-CF recipients, patients with CF displayed a significant incidence of colon cancer (4 of 70 recipients; 5.7%) with onset ranging from 246 days to 9.3 years post-transplant, which may be due to a combination of their underlying genetic disorder plus intense, sustained immunosuppression following lung transplantation. Colonoscopic screening may identify patients with pre-malignant colonic lesions and prevent progression to colonic malignancy.

Reflux-Induced Collagen Type V Sensitization: Potential Mediator of Bronchiolitis Obliterans Syndrome

BACKGROUND Lung transplantation continues to have poor long-term survival partly because of the high incidence of bronchiolitis obliterans syndrome (BOS). Gastroesophageal reflux disease (GERD) has been implicated in BOS pathogenesis. We investigated the role of collagen type V [col(V)] sensitization in this process. METHODS Only primary lung transplant recipients were included. Reflux status was assessed with pH monitoring, impedance plethysmography, and esophagogastroduodenoscopy. Sensitivity to col(V) was determined with trans vivo delayed-type hypersensitivity reaction (DTH). Kaplan-Meier analyses were performed. RESULTS Of the 54 recipients, 26 had proven GERD. There were no significant between-group differences in diagnosis; donor and recipient age; sex; ischemic time; single vs bilateral; human leukocyte antigen A, B, and DR matching cytomegalovirus status; acute rejections; or mean follow-up period. The mean DTH response in the GERD group was 25.7 x 10(-4) inches vs 18.3 x 10(-4) inches in the non-GERD group (P = .023). There was a significant reduction in BOS-free survival in the GERD group for both BOS-I (GERD+, 28.3%; GERD-, 86.6%; P = .0001) and BOS-II/III (GERD+, 66.2%; GERD-, 91.7%; P = .0374). A second cohort of 53 patients awaiting lung transplantation also was assayed. The mean DTH response in the GERD group was 24.0 x 10(-4) inches vs 13.1 x 10(-4) inches in the non-GERD group (P = .003). There were no differences in age or sex. CONCLUSIONS GERD is strongly associated with the development of BOS after primary lung transplantation. Col(V) sensitization is associated with reflux and BOS and may play an intermediary role in the pathogenesis of BOS. Trials using col(V) reactivity to assess the impact of antireflux procedures in patients with lung transplantation and idiopathic pulmonary fibrosis are warranted.

Redo lung transplantation for acute and chronic lung allograft failure: long-term follow-up in a single center

OBJECTIVE This study was undertaken to evaluate outcomes of redo lung transplantation (LT) for acute and chronic graft failure. METHODS Between 1988 and 2007, 388 LT procedures were performed on 369 patients. From those, 17 (4.6%) patients had redo LT once and 2 patients had redo LT twice. Patient survival and recurrence of bronchiolitis obliterans syndrome (BOS) after redo LT were reviewed. RESULTS The overall survival rates of the 17 redo LT recipients at 1, 2 and 5 years were 59+/-23%, 59+/-23% and 42+/-25%, respectively. For the chronic graft failure group (n=12), survival rates at 1, 2 and 5 years were 67+/-26%, 67+/-26% and 44+/-30%, respectively. These survival rates were significantly lower than the survival rates observed in our experience after primary LT (n=352, 1-, 2- and 5-year survival rates of 88+/-4%, 80+/-4% and 65+/-5%, respectively. For the acute graft failure group (n=5), the 1-year survival rate was 40%; two patients remain free from BOS. Two patients had a second redo LT, one died from multi-organ failure on postoperative day 86 and the other died from pulmonary aspergillosis on postoperative day 214. CONCLUSIONS Redo LT is a valid therapeutic option for selected patients with BOS and might be an option for highly selected patients with acute lung graft failure. Outcomes from a second redo LT are poor, and a second lung retransplantation must be used very cautiously, if at all.

The impact of the lung allocation scoring system at the single national Veterans Affairs Hospital lung transplantation program

OBJECTIVE The lung allocation score (LAS) has changed the distribution of donor lungs for transplantation. This study was undertaken to evaluate the impact of the LAS on a unique patient population undergoing lung transplantation (LTX) at the single national Veterans Affairs (VA) LT center. METHODS One hundred and ten consecutive VA patients underwent LTX between 1994 and 2007. Patients transplanted using the LAS (LAS, n=26) were compared to patients transplanted prior to introduction of the LAS (pre-LAS, n=84). RESULTS Waiting time decreased from 353.8+/-254.7 (pre-LAS) to 238.0+/-306.6 (LAS) days (p<0.01). Recipient diagnoses have changed with an increase in idiopathic pulmonary fibrosis [11% (9/84) pre-LAS vs 46% (12/26) LAS, p<0.01] and a decrease in emphysema [57% (48/84) pre-LAS vs 35% (9/26) LAS, p<0.01]. Mean LAS calculation was 33.1+/-2.9 for pre-LAS versus 41.9+/-9.8 for the LAS (p<0.01). Postoperative complications did not differ between the groups. Length of hospital stay decreased from 44.3+/-42.9 (pre-LAS) to 18.1+/-12.3 (LAS) days (p<0.01). Hospital mortality and 1-year survival did not differ between the pre-LAS and LAS groups (7% vs 8%; p=0.72 and 92% [95% confidence interval (CI) 86-98] vs 92% [CI 82-100]; p=0.23, respectively). CONCLUSIONS The LAS appears to be achieving its objectives by reducing waitlist time and altering the distribution of lung disease being transplanted on the basis of medical necessity in the U.S. VA population. In addition, the LAS does not appear to have adversely affected short-term post-transplant outcomes in our recipient cohort.

The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation

Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH.

Lung transplant for interstitial lung disease: outcomes before and after implementation of the united network for organ sharing lung allocation scoring system.

OBJECTIVES This study was undertaken to evaluate whether the adoption of the united network for organ sharing lung allocation score (LAS) was associated with significant changes in lung transplantation (LTX) outcomes for patients with interstitial lung disease (ILD) who underwent LTX at the University of Wisconsin Hospital and Clinics. METHODS Outcomes for 107 consecutive patients with various forms of ILD who underwent LTX between January 1993 and March 2009 were examined. Patients transplanted following the implementation of the LAS system (LAS, n = 56) were compared with those transplanted prior to LAS implementation (pre-LAS, n = 51) for whom LAS scores were calculated. RESULTS Patients with idiopathic pulmonary fibrosis (IPF) comprised the majority of patients with ILD. Recipients transplanted after the implementation of the LAS were significantly older (pre-LAS: 50.4 vs. LAS: 56.7 years, P < 0.01), required more supplemental oxygen (3 vs. 5 l/min, P < 0.01) and displayed lower cardiac index values (3.1 vs. 2.6 l/m(2), P < 0.01). The estimated LAS was significantly increased from 38.3 (pre-LAS) to 43.3 (LAS), P < 0.01. However, waiting time decreased from 266 to 78 days (P < 0.01). The rate of bilateral vs. single LTX was lower (35 vs. 16%, P = 0.02) for the post-LAS group. Cold ischaemic time was shorter in the post-LAS group (434 vs. 299 min, P < 0.01), and the length of hospital stay decreased from 24 to 11 days (P < 0.01). Hospital mortality (11 vs. 7%, P = 0.51) and post-transplant survival did not differ between the groups. CONCLUSIONS Post-transplant outcomes for patients with ILD or the subset of recipients with IPF were not adversely affected by the implementation of the LAS.