George D. Nossent

Lung Transplantation for Cystic Fibrosis

Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patients quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.

The use of non-heart-beating lung donors category III can increase the donor pool

OBJECTIVE The use of non-heart-beating (NHB) lung donors has been propagated as an alternative besides heart-beating (HB) lung donors to overcome organ shortage. We evaluated the effectiveness of NHB lung transplantation. METHODS The donor and recipient data of all 35 NHB category III lung transplantations (LTx) between January 2005 and December 2009 were reviewed. For comparison, we collected recipient and donor data of a cohort of 77 HB lung transplantations. In both groups, we assessed survival, primary graft dysfunction (PGD), forced expiratory volume in 1s (FEV(1)), acute rejection, and bronchiolitis obliterans syndrome (BOS). RESULTS Thirty-five NHB lung transplantations were performed, five single LTx and 30 bilateral LTx in 12 male and 23 female patients. The donor oxygenation capacity was 61 kPa (interquartile range (IQR), 56-64). Warm ischemia time in the donor was 29 min (IQR, 24-30). Cold ischemic time of the last implanted lung was 458 min (IQR, 392-522). Cardiopulmonary bypass was used 13 times. PGD (1-3) was observed in 45% of the patients at T0, in 42% at T24, in 53% at T48, and in 50% at T72. PGD 3 decreased from 24% at T0 to 6% at T72. The use of nitric oxide (NO) within 24h after transplantation was necessary in three patients with successful weaning in all. There was no significant difference for donor and recipient characteristics between NHB and HB lung transplantations. Survival, occurrence of PGD, and acute rejection was equal to the HB cohort. The incidence of BOS was lower in the NHB group. The measured FEV(1) tended to be better in the NHB group. CONCLUSION Lungs from nonheparinized category III NHB donors are well suited for transplantation and can safely increase the donor pool.

Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant

BACKGROUND The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). METHODS All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components. RESULTS Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005). CONCLUSION LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality.

A staged approach for a lung-liver transplant patient using ex vivo reconditioned lungs first followed by an urgent liver transplantation

Combined lung–liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end‐stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung–liver transplantation. The long waiting for this caused an interesting clinical dilemma. We decided to change our policy in this situation by listing him only for the lung transplantation and to apply for a high urgent liver transplantation if the liver failed after the lung transplantation. This strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP, the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an acute‐on‐chronic liver failure for which he received a successful liver transplantation 19 days after the lung transplantation.

Transmission of breast cancer by a single multiorgan donor to 4 transplant recipients

We report 4 cases of breast cancer transmission to transplant recipients from a single organ donor that occurred years after donation. The diagnosis of breast cancer was occult at the time of donation. All of the recipients developed a histologically similar type of breast cancer within 16 months to 6 years after transplantation. Three out of 4 recipients died as a result of widely metastasized disease. One of the recipients survived after transplant nephrectomy followed by cessation of immunosuppression and chemotherapy. This extraordinary case points out the often fatal consequences of donor‐derived breast cancer and suggests that removal of the donor organ and restoration of immunity can induce complete remission.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine‐tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty‐three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Somatostatin receptor based hybrid imaging in sarcoidosis

Several diagnostic imaging methodologies are available for the clinical evaluation of sarcoidosis, but all have their limitations. FDG PET/CT is frequently used, but this technique does not provide optimal results in all cases. Novel radiopharmaceuticals aimed at other disease targets may be helpful, particularly in cardiac sarcoidosis when FDG PET/CT has a low diagnostic accuracy, due to difficulties in preparing the patients who should use a specific diet combined with prolonged fasting. 68Ga-labeled somatostatin based receptor hybrid imaging is a potential alternative to FDG PET/CT.This short communication provides a rapid overview of initial findings concerning the application of 68Ga-labeled somatostatin based receptor hybrid imaging in the diagnosis of (cardiac) sarcoidosis activity.