Objective The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. Methods We performed a ...retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or heart transplant, were colonized with Burkholderia cenocepacia , or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Results Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass ( P = .32). Conclusions Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.
The evaluation of donor lungs by normothermic ex vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used ...to assess lungs during ex vivo perfusion compared with those traditionally used to evaluate the donor lung in vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical ex vivo evaluation.
Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO2, compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in vivo blood perfusion and ex vivo acellular perfusion.
During 12 hours of ex vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but ex vivo PO2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO2. A reduced effect of shunt on ex vivo lung perfusion PO2 was found to be attributable to the linearization of the relationship between oxygen content and PO2, which occurs with acellular perfusate.
Ex vivo PO2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the ex vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance.
Experience with the first 50 ex vivo lung perfusions in clinical transplantation Cypel, Marcelo, MD, MSc; Yeung, Jonathan C., MD, PhD; Machuca, Tiago, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
11/2012, Letnik:
144, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Objective Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo ...lung perfusion. Methods A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pa o2 /F io2 <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pa o2 /F io2 greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). Results A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pa o2 /F io2 was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group ( P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group ( P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction ( P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group ( P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Conclusions Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity.
Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung ...transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated.
Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used.
Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07).
RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients.
Localization of small, nonvisible and nonpalpable nodules is challenging during video-assisted thoracoscopic surgery. We evaluated the feasibility of using a new ultrasound thoracoscope to localize ...nodules in resected ex vivo human lungs.
The tumor was localized and measured in its greatest dimension with a prototype ultrasound thoracoscope (XLTF-UC180; Olympus Corporation, Tokyo, Japan) at different frequencies (5.0 to 12.0 MHz) and different lung specimen states (deflated, semiinflated). Measured tumor size and depth from lung surface were compared and correlated to the true diameter and depth from lung surface acquired from pathologic morphology.
Ex vivo evaluation was performed on 16 solid nodules and nine part solid ground-glass nodules. All tumors were successfully localized in the deflated lung specimens (average size, 13.7 ± 5.2 mm). The tumor boundaries were best evaluated with an ultrasound frequency of 10 MHz. Solid nodules were more easily visualized than ground-glass nodules. Part solid ground-glass nodules were not easily detected in the semiinflated specimen owing to peritumoral air surrounding the tumor. Tumor boundaries were also difficult to identify in deeply situated tumors and in lungs with underlying disease. A strong positive correlation existed between the ultrasound measurement and true measurement of tumor size (R
= 0.89, p < 0.001).
The ultrasound thoracoscope can be used to localize nodules in resected human lungs. The clarity of the tumor boundaries is influenced by the tumor type and depth and the underlying pulmonary disease. Complete lung deflation and the use of 10 MHz ultrasound frequency optimize the visualization of target tumors.
The timing of disease onset may affect the prognosis in chronic lung allograft dysfunction (CLAD). The relationship between the timing of disease onset and the prognosis of CLAD and its sub-types, ...bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), was examined.
Clinical records and pulmonary function data of 597 patients who underwent bilateral lung transplantation from 1996 to 2010 and survived for >3 months were examined.
Among 155 patients with a final diagnosis of BOS, patient survival after disease onset was significantly different according to disease-onset timing (BOS onset/post-BOS median survival: overall/1,438 days; <1 year/511 days; 1-2 years/1,199 days; 2-3 years/1,403 days; >3 years/did not reach median survival; p < 0.0001). The prognosis of RAS was generally poorer than that of BOS (overall post-RAS median survival, 377 days). Treating non-CLAD, CLAD, BOS, and RAS as time-dependent covariates, recipient sex-adjusted and age-adjusted Cox regression analysis demonstrated an overall mortality risk of BOS (reference: no CLAD) of 6.7 (95% confidence interval, 4.6-9.9). However, when patients survived 3 years without CLAD, the mortality risk of subsequent BOS was only 1.9 (95% confidence interval, 0.8-4.4) compared with no CLAD. The number of RAS patients was too small to obtain sufficient power to estimate time-dependent mortality risk.
Late-onset BOS showed a better prognosis than early-onset BOS. Studies that do not distinguish BOS from RAS may overestimate the mortality risk of BOS. Multicenter studies will be required to further elucidate risk factors toward the development of better management strategies for CLAD.
Abstract Objective To evaluate a new protocol of accelerated hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for patients with resectable ...malignant pleural mesothelioma (MPM). Methods A total of 25 Gy of radiation was delivered in 5 daily fractions over 1 week to the entire ipsilateral hemithorax with concomitant boost of 5 Gy to volumes at high risk based on computed tomography and positron emission tomography scan findings. EPP was performed at 6 ± 2 days after the end of radiation therapy. Adjuvant chemotherapy was offered to patients with ypN2 disease. Results A total of 62 patients were included between November 2008 and October 2014. One patient died in the hospital 2 months after EPP, for an operative mortality of 1.6%, and 2 died after discharged from the hospital for an overall treatment-related mortality (grade 5 toxicity) of 4.8%. Twenty-four patients (39%) developed grade 3 to 5 (grade 3+) complications. On final pathology, 94% of the patients were stage III or IV, and 52% had ypN2 disease. The median survival for all patients as an intention-to-treat analysis was 36 months. The median overall survival and disease-free survival was 51 and 47 months, respectively, in epithelial subtypes, compared with 10 and 8 months in biphasic subtypes ( P = .001). Ipsilateral chest recurrence occurred in 8 patients. Conclusions Accelerated hemithoracic IMRT followed by EPP has become our preferred approach for resectable MPM. The results have been encouraging in patients with epithelial subtype.
Abstract Objective We hypothesized that administration of a homodimer of recombinant annexin V, diannexin, could shield phosphatidylserine on the endothelium, and inhibit leukocyte and platelet ...adhesion, thereby potentially reducing ischemia reperfusion injury (IRI) in lung transplantation. This hypothesis was tested using a rat syngeneic single left-lung transplant model. Methods Rats were randomly assigned to receive diannexin (DN group; n = 10) or normal saline (control group; n = 10). Diannexin (1000 μg/kg) was administered to the donor lung in the pulmonary flush solution, and to the recipient intravenously, 5 minutes after initiation of reperfusion. Grafts were reperfused for 2 hours. Results The transplanted grafts in the DN group performed significantly better in gas exchange with higher partial pressure of oxygen (control group: 179 ± 121 vs DN group: 330 ± 54 mm Hg; P = .007) and lower partial pressure of carbon dioxide (control: 55.1 ± 26 vs DN: 34.2 ± 11 mm Hg; P = .04), as well as lower peak airway pressure (control: 20.5 ± 8.5 vs DN: 12.0 ± 7.9 cm H2 O; P = .035) after 2 hours of reperfusion. Wet-to-dry lung weight ratio ( P = .054), and alveolar fibrin deposition score ( P = .04), were reduced in the DN group. Caspase-cleaved cytokeratin 18 in plasma (a marker of epithelial apoptosis) was significantly reduced in the DN group ( P = .013). Furthermore, gene-expression levels of proinflammatory cytokines in the transplanted graft, including interleukin-6 ( P = .04) and macrophage inflammatory protein 2 ( P = .03) were significantly decreased in the DN group. Conclusions A homodimer of recombinant annexin V reduced ischemia reperfusion injury in a lung transplant animal model, by reducing cell death and tissue inflammation.
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