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Objective: Solid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown., Methods: We performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination., Results: There were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9-10.2) vs 2.8 (1.9-4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250-500) vs 1000 (1000-1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients., Conclusions: The antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objectives: Lung transplantation (LT) is an effective treatment for patients with interstitial lung disease (ILD) refractory to medical treatment. Although the cases of cadaveric LT (CLT) have increased, the donor shortage in Japan has remained severe. This study aimed to evaluate the International Society of Heart and Lung Transplantation (ISHLT) listing criteria for LT in patients with ILD by predicting outcomes during the waiting time for CLT., Methods: We retrospectively identified 166 patients with fibrotic ILDs who were evaluated and registered for CLT at Kyoto Universal Hospital from April 1, 2008, to December 31, 2017. We examined the correlation between individual parameters of the ISHLT listing criteria and patient outcomes., Results: Among 166 patients, 57 (34.3%) underwent CLT, whereas 83 (50.0%) died before CLT. The median survival time from the date of registration was 22.5 months. The 2-year survival rate was 47.8%. On multivariate Cox proportional hazards analysis, relative decline of percent predicted forced vital capacity (%FVC) in 6 months ≥ 10% (hazard ratio [HR]: 1.72; 95% confidence interval [95%CI]: 1.03-2.87, p = 0.04) and 6-min walking distance (6MWD) < 250 m (HR: 2.77; 95%CI: 1.64-4.69, p < 0.001) were independently associated with worse outcome (i.e., death or living-donor lobar LT)., Conclusions: The 2014 ISHLT criteria could appropriately identify patients with ILD who have a potentially poor prognosis. In particular, 6-month decline in %FVC and shorter 6 min walk distance may be useful for selecting patients with higher risks of mortality., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

The fissure-last technique is used to minimize postoperative air leak after anatomical lung resection when the interlobar pulmonary artery is inaccessible through the fused fissure. After first dividing the hilar bronchovascular structures, the incomplete fissure is divided using staplers. This technique can be applied for lobectomy combined with segmentectomy in lung cancer with interlobar invasion. We performed this thoracoscopic fissure-last technique in a lung cancer patient in the left upper lobe with invasion to the superior segment (S6) in the left lower lobe., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Despite the use of near-infrared thoracoscopy with intravenous indocyanine green, intraoperative assessment of the surgical margin for the resection of non-palpable tumors located near the intersegmental plane requires highly advanced surgical skill for the prevention of local recurrence. Because the demarcation line is limited to the pleural surface, to overcome uncertainty in tumor palpation for deeply located small-sized lesions, other supplemental localization techniques have been proposed. Here, we present a novel surgical technique using radiofrequency identification markers for intraoperative assessment of the lateral surgical margin in segmentectomy., (© 2021. The Author(s).)

Objective: The perioperative outcome of lung transplantation (LTx) for patients with severe pulmonary hypertension (PH) remains poor due to the occurrence of primary graft dysfunction (PGD) from left ventricular failure. We hypothesized that tapering pretransplant use of epoprostenol rather than abrupt discontinuation after transplantation might improve perioperative outcomes., Methods: We performed 23 LTxs for patients with severe PH who received epoprostenol therapy from 2008 until 2021. In the discontinued group (n = 6), epoprostenol was discontinued after the establishment of extracorporeal circulation. In the tapered group (n = 17), epoprostenol was discontinued and resumed after reperfusion, and then gradually tapered over the following 2 weeks. We assessed survival, bleeding, blood transfusion, re-opening of the chest, oxygenation, PGD score, extracorporeal membrane oxygenation (ECMO) requirement for recovery after transplantation, and duration of mechanical ventilation., Results: The PGD score was significantly lower in the tapered group than in the discontinued group at 0 h, 24 h, and 48 h after LTx. In addition, the discontinued group required longer mechanical ventilation than the tapered group. Delayed chest closure and post-transplant ECMO use for recovery occurred significantly more frequently in the discontinued group., Conclusions: To resume and taper epoprostenol administration after reperfusion in patients with severe PH may be a valuable new strategy associated with better perioperative outcomes., (© 2021. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

We report our successful experience in two lung transplant cases in which ex vivo lung perfusion (EVLP) was used to evaluate the function of injured brain-dead donor lungs that were otherwise initially unacceptable. After the donor's lungs were declined for transplantation by all other transplant centers, the lungs were offered to the patients listed for lung transplantation in our hospital. The donor lung function was considered acceptable for transplantation after the 3-h EVLP assessment. In the first case, a 32-year-old man with bronchiolitis obliterans after hematopoietic stem cell transplantation underwent hybrid lung transplantation, that was right brain-dead donor lung transplantation, combined with native-upper lobe sparing living-donor lobar lung transplantation on the left side. In the second case, a 61-year-old woman received the right single lung transplantation for idiopathic pulmonary fibrosis. Both patients are doing well at one and a half years after lung transplantation., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objectives: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation., Methods: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan., Results: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years., Conclusions: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended., (© 2021. The Japanese Association for Thoracic Surgery.)

Objective: 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 < 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)., Conclusions: 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.

Lung transplantation is an established life-saving intervention for patients with end-stage lung diseases. The success of lung transplantation mainly depends on the quality and function of the implanted donor lungs, which are frequently subject to brain-death-induced lung injuries and intensive care unit (ICU)-related complications before transplantation. Recent innovations, particularly the development of ex vivo lung perfusion (EVLP), in which donor lungs are ventilated and perfused under normothermic conditions outside the body, have allowed clinicians to more accurately assess the donor lung function prior to transplantation. Therefore, EVLP has been successfully translated into clinical practice with the expansion of the donor lung pool, leading to favorable post-transplant outcomes in a growing number of transplant centers worldwide. The EVLP system and techniques, following the Toronto protocol, have recently been applied for the assessment of extended criteria brain-death donors in clinical lung transplantation in Japan. The advancement of EVLP from organ assessment to organ treatment will be the next challenging stage not only to expand donor lung pool, but also to improve graft survival and long-term outcomes after transplantation.

The management of a tracheal bronchus in lung transplantation is poorly studied and ill-defined. We report a case of lung transplantation performed using a donor right lung graft with an apical tracheal bronchus and propose a novel anastomosis technique for this procedure. The neo-upper lobe bronchus created by suturing the apical tracheal bronchus and the upper lobe bronchus of the donor was anastomosed to the upper lobe bronchus of the recipient in a double-barrel fashion. A follow-up at 19 months demonstrated no stenosis of the anastomosis. The advantages and potential disadvantages of this procedure are discussed.

Objective: Among the standard techniques for anatomical lung cancer resection, left upper lobectomy has been regarded as challenging by thoracic surgeons. Thus, this study aimed to examine whether laterality of robot-assisted thoracoscopic procedures has any influence on the incidence of conversion to thoracotomy, operation time, amount of bleeding, and postoperative complications in the introduction phase of this procedure., Methods: The first consecutive 65 patients (right upper/middle/lower lobe with 31/3/15 cases, left upper/lower lobe with 10/6 cases) who underwent robot-assisted thoracoscopic lobectomy from December 2011 to April 2019 in Kyoto University were retrospectively reviewed., Results: Five cases were converted to open thoracotomy, including four for the left upper lobectomy and one for the right lower lobectomy (p = 0.011). The mean operation time was 229.9 ± 53.9 min (n = 12) and 192.8 ± 53.1 min (n = 48) for the left-sided and right-sided procedures, respectively (p = 0.043, conversion cases were not included). The mean bleeding amount was 29.1 ± 75.7 g (n = 49) and 136.8 ± 330.9 g (n = 16) for the right side and left side, respectively (p = 0.036). The mean operation time (min) for each lobe was as follows: 253.5 ± 73.9 for the left upper lobe (n = 6), 206.3 ± 41.3 for the left lower lobe (n = 6), 189.7 ± 51.3 for the right upper lobe (n = 31), 192.3 ± 57.5 for the right middle lobe (n = 3), and 199.9 ± 61.8 for the right lower lobe (n = 14)., Conclusion: Robot-assisted thoracoscopic surgery on the left side was associated with higher conversion rate, longer operation time, and more blood loss than that on the right side.

Objective: Lung autotransplantation was originally developed to avoid pneumonectomy for centrally located lung cancer. We herein report our experience with lung autotransplantation for the treatment of various types of lung diseases., Methods: This is a single-center case series of lung autotransplantation with ex vivo bench surgery. Five patients underwent lung autotransplantation between September 2014 and October 2018. A common surgical technique was as follows: pneumonectomy was first completed. The intact lobes were then separated ex vivo, flushed using cold ET-Kyoto solution on a back table, and reimplanted., Results: The indications for lung autotransplantation were postpneumonectomy-like syndrome, locally advanced lung cancer, pulmonary artery sarcoma, central lung cancer, and bronchopleural fistula after right upper bronchial sleeve lobectomy. No major post-transplant complications were observed except for mild stenosis of bronchial anastomosis in one case that required bronchial intervention. One patient died of recurrence of pulmonary artery sarcoma 14 months after surgery. The other patients are alive without any recurrence of the native respiratory diseases or symptoms., Conclusions: Lung autotransplantation following ex vivo bench surgery was found to be technically feasible for various lung diseases, showing a favorable early post-transplant outcome.

Objectives: This study assessed the outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation., Methods: Retrospective chart reviews were performed for all patients who received combination therapy including rituximab for post-lung transplantation antibody-mediated rejection between June 2008 and October 2018., Results: Among the 196 consecutive patients undergoing lung transplantation during the study period, eight (4.1%) were eligible for this study. Two patients (25.0%) were classified as having clinically definite antibody-mediated rejection and six (75.0%) as having possible antibody-mediated rejection. Prior to treatment, four patients (50.0%) met the definition of chronic lung allograft dysfunction; seven of the eight patients (87.5%) remained alive at 6 months and four (50.0%) at 12 months after antibody-mediated rejection. All patients identified as having chronic lung allograft dysfunction, prior to the treatment, died of allograft failure, or underwent re-transplantation. Decreases in the mean fluorescence intensities of the major donor-specific antibodies were observed in three patients. One patient, diagnosed with clinical antibody-mediated rejection but without pre-treatment chronic lung allograft dysfunction, began treatment relatively soon after lung transplantation, and demonstrated improved respiratory function at the 3-year follow-up., Conclusions: Our experience suggests that multimodality therapy that includes rituximab is feasible and may prevent progression of antibody-mediated rejection after lung transplantation in selected patients.

Purpose: We investigated the impact of the duration of agonal period on donor lung function after reperfusion in an ex vivo rat lung perfusion model., Methods: Three mechanical hypoventilation conditions were used for three agonal periods, which were defined as the interval between the start of hypoventilation and the time when systolic arterial blood pressure reached < 50 mmHg, i.e., < 10, 30-60, and 150-200 min for very short (VS), short (S), and long (L) groups (n = 5 rats/group). After flushing the lung, heart-lung blocks were reperfused ex vivo for 120 min; physiological data were obtained throughout the reperfusion process., Results: Pulmonary vascular resistance was significantly higher throughout reperfusion in group L than in the other two groups (p < 0.05). After reperfusion, oxygenation was worse and pulmonary edema was more severe in group L than in group S (p < 0.05). Potassium concentrations in the perfusates were significantly higher in group L than in group VS. Histological analysis revealed more severe injury in group L than in the other two groups., Conclusions: Long agonal periods may lead to deterioration of donor lung function; short intervals may not significantly affect donor lung function.