Donor Lobar Lung Transplantation Research Articles

Postoperative Complications in Living Donors for Lung Transplantation.

Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent.

Living Donor Lobar Lung Transplant for a Patient With Lung Disease Caused by ABCA3 Gene Mutations: A Case Report

Recessive gene mutations in ABCA3 cause lethal neonatal respiratory distress, and pediatric and adult interstitial lung disease. The effectiveness of medical treatments is limited and a subset of such patients will eventually require lung transplantation. A 20 months old boy developed interstitial lung disease and was treated with hydroxychloroquine, which had a significant effect. Sequence analysis of ABCA3 gene revealed newly discovered compound heterozygous mutations. His respiratory dysfunction gradually progressed over years and he underwent living-donor lobar lung transplantation (LDLLT) at 8 years of age with his parents serving as bilateral lobar donors. The parents had been genetically examined beforehand and found to be carriers who had one allele with an ABCA3 gene mutation and the other with no mutation. The recipient has been well without chronic lung allograft dysfunction and his parents have been enjoying healthy social lives for 7 years since the operations. LDLLT appears to be a valid option for selected children with ABCA3 gene mutations who are too ill to wait for cadaveric lung transplantation. When relatives of the recipient with ABCA3 gene mutation are deemed potential donors for LDLLT, sequence analyses of the donors are indispensable to exclude the possibility that they are late-onset patients of this recessive hereditary disease.

Long-Term Persisting Donor-Derived Anti-Human Leukocyte Antigen (HLA) Antibody as a Possible Passenger Lymphocyte Syndrome Following Lung Transplantation

<h3>Introduction</h3> A routine screening for the presence of HLA-specific antibodies after solid organ transplantation, produced by recipient B cells or plasma cells, is important for the management of antibody-mediated rejection. A novel possibility has recently been suggested in a few clinical case reports, where some de novo HLA-specific antibodies could continue to be produced by donor passenger B lymphocytes/plasma cells. We herein report the transfer of donor-derived anti-HLA antibodies in two recipients following lung transplantation. <h3>Case Report</h3> Case 1: A 39‐year‐old woman with pleuroparenchymal fibroelastosis underwent single lung transplantation with a left lung from a brain-dead donor. Antibody screening 36 days after transplant showed high levels of de novo non-donor HLA class I-specific antibodies. Then antibody screening in the donor serum identified that the donor showed a largely overlapping antibody profile to that found in the recipient. Importantly, the donor serum also included high-level HLA-specific antibodies against the recipient HLA-specific antigens, which were not detected in the recipient sera after transplantation. The donor-derived anti-HLA antibodies have still been detected in the recipient at 39 months after transplantation, which have never caused any complications such as graft-versus-host disease (GVHD). Case 2: A 47‐year‐old woman underwent living donor lobar lung transplantation for pulmonary complications after bone marrow transplantation with the right lower lobe from her husband and the left lower lobe from her sister. On postoperative day 39, the recipient anti- HLA-class I antibody profile was found to be similar to that of the high-sensitized left lung donor. These donor-derived anti-HLA antibodies have remained to be produced in the recipient at 66 months after transplantation without development of complications such as GVHD. <h3>Summary</h3> This case report suggests that alloreactive passenger B cells or plasma cells located within the highly sensitized donor lungs could lead to the early production of de novo anti-HLA-specific antibodies in the lung transplant recipients. Although there have been no overt clinical manifestations in either of the patients so far, the clinical significance of transfer of donor HLA-specific allosensitization should be elucidated.

“Hybrid Lung Transplantation” Combining Living Donor and Cadaveric Lung Transplants: Report of 2 Cases

We present 2 cases of "hybrid lung transplant," which included sequentially implanting a living lobar graft to 1 side and a cadaveric graft to the other side. This procedure was approved by the institutional review board at Okayama University Hospital. The 2 recipients were diagnosed with severe idiopathic pulmonary fibrosis, and living donor lobar lung transplant was considered; however, 2 appropriate donors were not available. Therefore, we accepted extended criteria donor lungs with a partial pressure of oxygen/fraction of inspired oxygen ratio of <251 mm Hg. However, 1 of the 2 patients developed grade 2 primary graft dysfunction. The living donor lobar lung had a low volume but was in good condition, which contributed to the patient's recovery after primary graft dysfunction during the perioperative period. The other patient's status of bronchiolitis obliterans syndrome had gradually progressed to grade 3, and only the living donor lung was functioning at that time. However, both patients are alive 5.5 and 4.2 years after lung transplant, respectively. Hybrid lung transplantation may increase patients' chances of receiving transplants because patients are not likely to survive while waiting for ideal donor lungs to become available.

Efficacy of Three-Dimensional Computed Tomography Volumetry for Recipients in Downsizing Oversized Grafts in Brain-Dead Donor Lung Transplantation

Purpose Brain-dead donor lung transplantation frequently requires reduction in the size of oversized lung grafts for patients with a small chest cavity. We focused on the role of three-dimensional computed tomography (3D-CT) volumetry for recipients on downsizing oversized lung grafts. Methods We performed 53 brain-dead donor bilateral lung transplantations, including 15 lobar lung transplants (Lobar group) and 38 standard lung transplants with full-sized grafts (Full group), between December 2010 and December 2018. Recipient chest volume before transplantation was measured using 3D-CT volumetry, and donor lung volume was evaluated by predicted total lung capacity. Post-transplant outcomes and pulmonary function were retrospectively compared between the groups. Results The ratio of the recipient chest volume to the donor lung volume was significantly lower in the Lobar group (0.42±0.15) than in the Full group (0.77±0.30, P Conclusion Brain-dead donor lobar lung transplantation showed favorable post-transplant outcomes. The assessment of recipient chest cavity volume using 3D-CT volumetry may help surgeons precisely downsize oversized lung grafts prior to transplantation.

Efficacy of three-dimensional computed tomography volumetry for recipients in downsizing oversized grafts in brain-dead donor lung transplantation.

ObjectiveBrain-dead donor lung transplantation frequently requires reduction in the size of oversized lung grafts for patients with a small chest cavity. We focused on the role of three-dimensional computed tomography (3D-CT) volumetry for recipients on downsizing oversized lung grafts.MethodsWe performed 53 brain-dead donor bilateral lung transplantations, including 15 lobar lung transplants (Lobar group) and 38 standard lung transplants with full-sized grafts (Full group), between December 2010 and December 2018. Recipient chest volume before transplantation was measured using 3D-CT volumetry, and donor lung volume was evaluated by predicted total lung capacity. Post-transplant outcomes and pulmonary function were retrospectively compared between the groups.ResultsThe ratio of the recipient chest volume to the donor lung volume was significantly lower in the Lobar group (0.42 ± 0.15) than in the Full group (0.77 ± 0.30, P < 0.01). The calculated size matching between the donor and recipient after downsizing the grafts was significantly correlated to the ratio of the recipient chest volume to the donor lung volume (Spearman r = 0.69; P < 0.01). Early post-transplant outcomes did not significantly differ between the groups. Although the Full group showed slightly better pulmonary function after transplantation, the 1-, 3-, and 5-year overall survival rates were similar to the Lobar group (100%, 93%, and 81% in the Lobar group vs. 92%, 78%, and 70% in the Full group; P = 0.50).ConclusionsBrain-dead donor lobar lung transplantation showed favorable post-transplant outcomes. The assessment of recipient chest cavity volume using 3D-CT volumetry may help surgeons precisely downsize oversized lung grafts prior to transplantation.

Current trends in thoracic surgery.

ABSTRACTThoracic surgery has evolved drastically in recent years. Although thoracic surgeons mainly deal with tumorous lesion in the lungs, mediastinum, and pleura, they also perform lung transplantation surgery in patients with end-stage lung disease. Herein, we introduce various major current topics in thoracic surgery. Minimally invasive surgical procedures include robot-assisted thoracic surgery and uniportal video-assisted thoracic surgery. Novel techniques for sublobar resection include virtual-assisted lung mapping, image-guided video-assisted thoracic surgery, and segmentectomy using indocyanine green. Three-dimensional (3D) computed tomography (CT) simulation consists of surgeon-friendly 3D-CT image analysis systems and new-generation, dynamic 3D-CT imaging systems. Updates in cadaveric lung transplantation include use of marginal donors, including donation after circulatory death, and ex vivo lung perfusion for such donors. Topics in living donor lobar lung transplantation include size matching, donor issues, and new surgical techniques. During routine clinical practice, thoracic surgeons encounter various pivotal topics related to thoracic surgery, which are described in this report.

Malignancy after Lung Transplantation in Japan

Malignancy is one of the leading causes of death after organ transplantation. We conducted a national survey of malignancy after lung transplantation among all lung transplant centers in Japan. All recipients who underwent lung transplantation since October 1998 until December 2017 in Japan were retrospectively reviewed. Malignant diseases developed in 41 (6.9%) of 596 lung transplant recipients in 388 brain-dead donor lung transplantation and 208 living donor lobar lung transplantation. Except recurrence of the original malignant diseases (n=4/596, 0.7%) and possible progression after transplantation in cancer-baring recipients (n=5/596, 0.8%), de novo malignancy occurred in 33 patients (5.5%). The most common de novo malignancy was lymphoproliferative disorder (n=16/34, 46%). Compared with the ISHLT registry, we observed far fewer skin cancer (n=1). In terms of the underlying disease for lung transplantation, interstitial pneumonitis (n=13/33, 39%) and lung complication after hematopoietic stem cell transplantation (n=10/33, 30%) were common, suggesting that long-term immunosuppression before and after transplantation has a negative impact on occurrence of de novo malignancy. The average time of occurrence after transplantation was 39 (±38) months. Death due to malignancy occurred in 11/33 (33%). The overall 5-year survival of patients with malignancies after lung transplantation was 49%. In Japan, the most common malignancy after lung transplantation was posttransplant lymphoproliferative disorder. Long-term immunosuppression before and after transplantation can have a negative impact on occurrence of de novo malignancy after lung transplantation.

Comparison of Outcomes of Living-Donor Lobar and Cadaveric Lung Transplantation in Patients with Pulmonary Arterial Hypertension

Purpose Lung transplantation is indicated in patients with severe pulmonary arterial hypertension (PAH). Living donor lobar lung transplantation (LDLLT) may be considered in patients who might not survive the longer waiting duration for cadaveric lung transplantation (CLT). This study compared the outcomes of LDLLT and CLT in patients with PAH. Methods Retrospective review of medical records from our institutional database between April 2008 and August 2018 revealed 191 lung transplants, of which 6 LDLLTs and 10 CLTs were performed for PAH patients, defined based on the criteria for group 1 of the Nice classification. Results Preoperatively, LDLLT and CLT groups showed no significant differences in age (median 14 vs. 29.5 years, p=0.08), height (median 155 vs. 160 cm, p=0.91), mean pulmonary arterial pressure (PAP) (median 60.5 vs. 57.0 mmHg, p=0.96), brain natriuretic peptide (median 153 vs. 89.0 pg/mL, p=0.36), and dose of intravenous epoprostenol (median 29.7 vs. 65.2 ng/kg/min, p=0.55). All cases of LDLLT were bilateral, except one performed in a pediatric patient. In 2 cases, bilateral LDLLTs were performed by preserving the upper lobes for size mismatch. After surgery, extracorporeal cardiopulmonary support was required in 5 LDLLT cases and 4 CLT cases (p= 0.384). One hospital death occured on day 192 due to sepsis in the CLT group. The median postoperative PAP was 16.5 mmHg and 14.0 mmHg (p=0.213) and the ratio between the pre- and postoperative mean PAP were 26.6% and 26.4% (p=0.456) in the LDLLT and CLT groups, respectively. The median follow-up period was 57.5 and 22.5 months and the five-year survival was 100% and 88.9% (p=0.41) in LDLLT and CLT groups, respectively. Conclusion LDLLTs were associated with acceptable outcomes in patients with PAH and were not inferior to CLTs. Thus, for patients with severe progressive PAH, LDLLTs may be a lifesaving procedure. Lung transplantation is indicated in patients with severe pulmonary arterial hypertension (PAH). Living donor lobar lung transplantation (LDLLT) may be considered in patients who might not survive the longer waiting duration for cadaveric lung transplantation (CLT). This study compared the outcomes of LDLLT and CLT in patients with PAH. Retrospective review of medical records from our institutional database between April 2008 and August 2018 revealed 191 lung transplants, of which 6 LDLLTs and 10 CLTs were performed for PAH patients, defined based on the criteria for group 1 of the Nice classification. Preoperatively, LDLLT and CLT groups showed no significant differences in age (median 14 vs. 29.5 years, p=0.08), height (median 155 vs. 160 cm, p=0.91), mean pulmonary arterial pressure (PAP) (median 60.5 vs. 57.0 mmHg, p=0.96), brain natriuretic peptide (median 153 vs. 89.0 pg/mL, p=0.36), and dose of intravenous epoprostenol (median 29.7 vs. 65.2 ng/kg/min, p=0.55). All cases of LDLLT were bilateral, except one performed in a pediatric patient. In 2 cases, bilateral LDLLTs were performed by preserving the upper lobes for size mismatch. After surgery, extracorporeal cardiopulmonary support was required in 5 LDLLT cases and 4 CLT cases (p= 0.384). One hospital death occured on day 192 due to sepsis in the CLT group. The median postoperative PAP was 16.5 mmHg and 14.0 mmHg (p=0.213) and the ratio between the pre- and postoperative mean PAP were 26.6% and 26.4% (p=0.456) in the LDLLT and CLT groups, respectively. The median follow-up period was 57.5 and 22.5 months and the five-year survival was 100% and 88.9% (p=0.41) in LDLLT and CLT groups, respectively. LDLLTs were associated with acceptable outcomes in patients with PAH and were not inferior to CLTs. Thus, for patients with severe progressive PAH, LDLLTs may be a lifesaving procedure.

New Technique Which Was Combined Living Donor Lower Lobe with Cadaveric Marginal Lung as Called “Hybrid Lung Transplant”

Purpose When extended criteria donor was transplanted to reduce on waitlist time and mortality for severe donor shortage, it had a potential risk to cause worse outcome. Furthermore, using marginal donor for single lung transplant (LT) was more difficult than double LT. In case of adult male recipients, living donor lobar lung transplant (LDLLT) might not be established due to the lung volume and function after LT. We reported good outcome due to new technique which was combined merits of LDLLT with cadaveric LT as called “hybrid LT”. Methods The relatively high-quality cadaveric single lung was choose and transplanted to unilateral chest, living donor lower lobe was transplanted to the other when extended criteria donor lung was allocated for severe illness recipient. Results Both of recipients were diagnosed idiopathic pulmonary fibrosis . They were registered on waiting list. However, they were considered no survive on the list for their severe illness, because long waiting time, approximately 3 years, was needed in Japan for severe donor shortage. On the other hand, donors were rejected by all other transplant centers because of the lungs on the basis of the initial conventional assessments. PaO2/FiO2 ratio of case 1 was at less than 250 and case 2 was at less than 188. Left cadaveric and right living donor lower robe was transplanted on case 1. The recipient experienced grade 2 primary graft dysfunction (PGD) but rapidly recovered. The other was transplanted right cadaveric and left living donor lower robe on case 2 and had no severe PGD. Both of them returned to their normal daily life and is doing well for 2 years after lung transplantation. Conclusion Hybrid LT using unilateral cadaveric lung and living donor lower lobe is feasible and reasonable option for a high-risk recipient when using marginal lung grafts. Hybrid LT reduce perioperative risk due to overcome lung volume, function and quality at the same time and have merit of bilateral LT at the long term outcome.

Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donor-lobar lung transplantation

Donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation (LT) from deceased donors. However, in living-donor lobar LT, because small grafts from blood relatives are implanted with short ischemic times, the detection of dd-cf-DNA might be challenging. Our study was aimed at examining the role of dd-cf-DNA measurement in the diagnosis of primary graft dysfunction and acute rejection early after living-donor lobar LT. Immediately after LT, marked increase of the plasma dd-cf-DNA levels was noted, with the levels subsequently reaching a plateau with the resolution of primary graft dysfunction. Increased plasma levels of dd-cf-DNA were significantly correlated with decreased oxygenation immediately (p = 0.022) and at 72 hours (p = 0.046) after LT. Significantly higher plasma dd-cf-DNA levels were observed in patients with acute rejection (median, 12.0%) than in those with infection (median, 4.2%) (p = 0.028) or in a stable condition (median, 1.1%) (p = 0.001). Thus, measurement of the plasma levels of dd-cf-DNA might be useful to monitor the severity of primary graft dysfunction, and plasma dd-cf-DNA could be a potential biomarker for the diagnosis of acute rejection after LT.

Early Detection of Chronic Lung Allograft Dysfunction After Bilateral Living Donor Lobar Lung Transplantation by Computed Tomographic Scanning Scoring Method

In common bilateral living-donor lobar lung transplantation (LDLLT), two allografts with different antigenicity are transplanted simultaneously. As a result, different immune reactions occur in each side of the allograft that would degrade individually. Therefore, the accuracy of conventional spirometry based detection for chronic lung allograft dysfunction (CLAD) is limited. The purpose of this study was to examine whether computed tomographic scanning (CT) evaluation on an allograft basis enable earlier diagnosis of CLAD than conventional spirometry in this kind of population.

Increased Plasma Levels of Donor-derived Cell-free DNA Correlate With Acute Rejection in the Recipients of Living Donor-lobar Lung Transplantation

Circulating donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation from deceased donors. However, in living-donor lobar lung transplantation (LDLLT), because small grafts are implanted with short ischemic time from blood-relatives, the detection of dd-cf-DNA might be challenging, and the role of dd-cf-DNA in the LDLLT recipients remains unknown. Our study was aimed at examining the role of the dd-cf-DNA in the diagnosis of acute rejection after LDLLT.

(861) - Intermediate-Term Change of Pulmonary Function and Lung Volume after Bilateral Living Donor Lobar Lung Transplantation

(861) - Intermediate-Term Change of Pulmonary Function and Lung Volume after Bilateral Living Donor Lobar Lung Transplantation

(350) - Importance of Thoracic Shape for Postoperative Pulmonary Function in Living Donor Lobar Lung Transplantation

(350) - Importance of Thoracic Shape for Postoperative Pulmonary Function in Living Donor Lobar Lung Transplantation

Outcomes after pregnancy in living lobar lung transplantation.

Pregnancy after lung transplantation has been described, but pregnancy after living donor lobar lung transplantation (LDLT) has not been reported. The aim of this study was to evaluate outcomes after pregnancy with LDLT and discuss current recommendations regarding pregnancy and lung transplantation. A total of four LDLT patients and five pregnancies were identified, all from our institution. No patient has developed worsening pulmonary function or acute or chronic rejection. The complications of pulmonary hypertension and rejection may be overestimated in this population, and recommendations for preventive sterilization at transplantation or abortion at the time of conception are likely unwarranted and unnecessary.

(806) - Outcomes Following Pregnancy in Living Lobar Lung Transplantation

Pregnancy following lung transplantation has been described, but pregnancy following living donor lobar lung transplantation (LDLT) has not been reported. LDLT was originally developed to decrease transplant waiting list mortality due to a lack of available organs. As female patients with LDLT matured, physicians were faced with advising patients on family planning. Generally, most physicians recommend abstaining from pregnancy after lung transplantation due to the required alterations in immunosuppressive therapy that could increase the risk of rejection.

(814) - The Impact of Incomplete Pulmonary Fissures of Living Lobar Lung Transplant Donors on Bronchial Stenosis of Lung Recipients

Bronchial complications are among the most challenging problems after living-donor lobar lung transplantation (LDLLT), although the ischemic time of living-donor lungs can be minimized compared to cadaveric lung transplantation. To prevent bronchial complications, maintaining the pulmonary blood flow is critical for the bronchial healing. However, in the donor lobectomy of LDLLT, the inadequate dissection of interlobar fissures could cause unexpected obstruction of the pulmonary vessels and decreased blood flow to the bronchial anastomosis. The purpose of this study was to examine the relationships between incomplete pulmonary fissures of living-donor lungs and bronchial stenosis of LDLLT recipients. We retrospectively analyzed 127 donors and 69 recipients of bilateral and unilateral LDLLT at our institution between October 1998 and October 2013. According to Craig’s classification of pulmonary fissures, interlobar fissures of donor lungs were Grade 1 in 43, Grade 2 in 73, Grade 3 in 11 and Grade 4 in no donor. Postoperative lung perfusion scintigraphy was available in 119 of 127 transplanted lungs after LDLLT. Lung perfusion scintigraphy showed segmental defect or reduced blood flow in the lobar apex in 12 transplanted lungs (Group A), and homogenous distribution of blood flow in 107 transplanted lungs (Group B). Grade of interlobar fissures in Group A was significantly higher than that in Group B (2.1 ± 0.15 v.s. 1.7 ± 0.059; p < 0.05). While 3 of 12 (25 %) transplanted lungs in Group A revealed bronchial stenosis after LDLLT, no bronchial stenosis was encountered in 107 transplanted lungs of Group B. Our experience suggests that the incomplete pulmonary fissure of living-donors is a possible risk factor for bronchial stenosis of lung recipients in LDLLT. Careful dissection of incomplete pulmonary fissures should be required to maintain the pulmonary blood flow in the living-donor lobectomy.

Living Donor Lobar Lung Transplantation: A Longstanding Concept Being Revisited with the Same Old Nemesis

Living donor lobar lung transplantation (LDLLT) has been successfully used in select patient populations. A 29-year-old male, who underwent bilateral LDLLT 12 years earlier with allografts donated by father and paternal uncle, developed bronchiolitis obliterans syndrome at distinctly different rates. LDLLT can be done successfully with unique management issues.

Postoperative respiratory management in living donor lobar lung transplantation

We evaluated postoperative respiratory management of living donor lobar lung transplantation (LDLLT). Perioperative variables were reviewed in 21 patients who underwent LDLLT at our institution. Recipients were kept intubated for at least two d after LDLLT to maintain optimal expansion of the implanted lobes. Subsequently, if weaning from artificial ventilation could be tolerated, extubation was considered with the assistance of non-invasive ventilation (NIV). If this could not be tolerated, early tracheostomy was considered. All 21 recipients were weaned from artificial ventilation. Twelve patients underwent tracheotomy 4.4 ± 1.8 d after LDLLT and were weaned from artificial ventilation 24.3 ± 17.0 d after LDLLT. Eleven patients were extubated 3.6 ± 1.7 d after LDLLT with NIV, but two of them were reintubated, and finally weaned from artificial ventilation via tracheostomy. Excluding these two patients, NIV was required for 3.8 ± 3.9 d after extubation. The early postoperative course was significantly eventful in patients with tracheostomies, and artificial ventilation, ventilatory support, and intensive care unit stays were longer. Twenty patients (95%) showed survival at 24.4 ± 13.4 months of follow-up. Postoperative respiratory management with NIV and early tracheostomy were useful after LDLLT.