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Herein, we reported the transfer of donor-derived antihuman leukocyte antigen (HLA) antibodies in 2 recipients after lung transplantation. Case 1: A 39-year-old woman with pleuroparenchymal fibroelastosis underwent a single brain-dead donor lung transplantation. Antibody screening 36 days after transplantation demonstrated high levels of de novo nondonor HLA class I-specific antibodies. The antibody screening in the donor serum revealed that the donor demonstrated a largely overlapping antibody profile. 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. Donor-derived anti-HLA antibodies were still detected in the recipient 39 months after transplantation, without causing any complications such as graft-vs-host disease. Case 2: A 47-year-old woman underwent living-donor lobar lung transplantation for pulmonary complications after bone marrow transplantation with a right lower lobe from her husband and the left lower lobe from her sister. On postoperative day 39, the recipient's anti-HLA-class I antibody profile was found to be similar to that of the highly sensitized left lung donor. These donor-derived anti-HLA antibodies remained to be produced in the recipient 66 months after transplantation, without the development of complications.

We report the first case of coronavirus disease 2019 (COVID-19)-associated respiratory failure requiring urgent living-donor lobar lung transplantation (LDLLTx). A 57-year-old woman with a positive viral status developed severe hypoxia requiring extracorporeal membrane oxygenation (ECMO). Her respiratory function deteriorated, with almost totally collapsed lungs. All of her other organs functioned well. After 104 days on ECMO, she received urgent LDLLTx under cardiopulmonary bypass. The grafts worked well, and she was weaned off cardiopulmonary bypass after reperfusion. LDLLTx is an option for selected patients with post-COVID-19 end-stage respiratory failure. Coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019 due to the unprecedented pandemic.1 Patients with end-stage COVID-19-related respiratory failure require mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). In some countries, lung transplantation (LTx) has become a treatment option for irreversible lung function deterioration.2,3 We report the first successful case of severe respiratory failure caused by COVID-19 treated with urgent living-donor lobar lung transplantation (LDLLTx).

OBJECTIVES Polyglycolic acid (PGA) sheets are difficult to adapt to the central airway because of poor durability against high air pressure. Therefore, we developed a novel layered PGA material to cover the central airway and examined its morphologic traits and functional performance as a potential tracheal replacement. METHODS A critical-size defect in rat cervical tracheas was covered with the material. Morphologic changes were bronchoscopically and pathologically evaluated. Functional performance was evaluated by regenerated ciliary area, ciliary beat frequency and ciliary transport function determined by measuring the moving distance of microspheres dropped onto the trachea (µm/s). The evaluation time points were 2 weeks, 1 month, 2 months and 6 months after surgery (n = 5, respectively). RESULTS Forty rats underwent implantation, and all survived. Histological examination confirmed ciliated epithelization on the luminal surface after 2 weeks. Neovascularization was observed after 1 month, tracheal glands after 2 months and chondrocyte regeneration after 6 months. Although the material was gradually replaced by self-organization, tracheomalacia was not bronchoscopically observed at any time point. The area of regenerated cilia significantly increased between 2 weeks and 1 month (12.0% vs 30.0%; P = 0.0216). The median ciliary beat frequency significantly improved between 2 weeks and 6 months (7.12 vs 10.04 Hz; P = 0.0122). The median ciliary transport function was significantly improved between 2 weeks and 2 months (5.16 vs 13.49 µm/s; P = 0.0216). CONCLUSIONS The novel PGA material showed excellent biocompatibility and tracheal regeneration both morphologically and functionally 6 months after tracheal implantation.

Owing to the prevalence of robot-assisted thoracoscopic surgery and the increase in the number of small lung cancer cases, robot-assisted thoracoscopic segmentectomy cases have also been increasing. For small lung cancers, such as ground-glass opacity lesions, identifying the location and securing a sufficient free margin from the main tumor can be difficult. We have already developed and reported the clinical application of a new marking system, a radiofrequency identification marker. In the current study, we applied this technique to robot-assisted thoracoscopic segmentectomies. Concomitant with other devices, we believe that robot-assisted thoracoscopic surgery has a great advantage in segmentectomy.

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.

Background Critical obstacles must be addressed before clinical application of artificial tracheas. The major complications of long tracheal replacement include anastomotic dehiscence and stenosis owing to poor vascularity and incomplete re-epithelialization. The objective of this report was to clarify whether pre-incubation of the prosthesis in the omentum could be applicable for reconstruction of a long segment of the intrathoracic trachea in a canine model. Methods The framework of an artificial trachea was fabricated from a polypropylene mesh tube and coated with 1% neutral atelocollagen inside and outside the lumen. The prosthesis was placed in the omentum of nine healthy male beagle dogs for 3 weeks. Then, the pedicled prosthesis was used to replace a 50 mm long section of intrathoracic trachea. Results were evaluated bronchoscopically, macroscopically, and histologically. Results After 3 weeks of abdominal incubation, the prostheses were incorporated into the host tissue. None of the dogs showed dehiscence of the anastomosis or infection of the prostheses during the postoperative period. Seven of the nine dogs survived for more than 1 year. One dog died of a bowel obstruction resulting from a diaphragmatic hernia 3 months after replacement, and another died due to reasons unrelated to the prosthesis at 6 months. Bronchoscopic examination revealed no stenosis or dehiscence, and microscopic examination of all dogs showed that the luminal surface was covered by newly regenerated connective tissue and respiratory epithelium. Conclusions Pedicled omentum-prosthesis complexes may allow successful reconstruction of a long segment of the intrathoracic trachea.

Objectives: To evaluate the safety and efficacy of a novel wireless localization technique that uses radiofrequency identification markers for small and deep lung lesions. Methods: Preliminary use of the device was retrospectively evaluated in 2 Japanese centers. Under general anesthesia, a marker was placed as close as possible to the tumor via computed tomography-guided bronchoscopy in a hybrid operation theater. Surgeons located the marker without lung palpation using a detection probe the tone of which changed to indicate the marker-probe distance. Efficacy was defined as functional marker placement (bronchoscopy time and marker position) and deep margin distance. Results: Twelve markers were placed for 11 lesions (mean size, 6.8±2.7mm) located at a mean depth from the pleura of 11.4±8.4mm (range=0-26.0mm). Of 12 markers, 7 markers (58.3%) were placed within 10mm from the lesion in 25.5±14.4minutes. For the 11 wedge resections, markers were placed at a mean distance of 6.7mm (range, 0-13.0mm) from the lesion and a mean distance of 14.4mm (range, 3.0-42.0mm) from the pleura. All markers were recovered without complications, and all tumors were resected with negative margins. For 5 lesions >10mm deep to the pleura (mean depth, 18.9±5.5mm; range, 11.0-26.0mm), the median depth of the surgical margin was 11.6±2.1mm (range, 9.0-14.0mm). Conclusions: Radiofrequency identification marking was safe and precisely localized small lung lesions, including their depth.

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.

OBJECTIVES Living-donor lobar lung transplantation (LDLLT) is a life-saving procedure for critically ill patients with various lung diseases, including pulmonary hypertension (PH). However, there are concerns regarding the development of heart failure with pulmonary oedema after LDLLT in which only 1 or 2 lobes are implanted. This study aimed to compare the preoperative conditions and postoperative outcomes of LDLLT with those of cadaveric lung transplantation (CLT) in PH patients. METHODS Between 2008 and 2021, 34 lung transplants for PH, including 12 LDLLTs (5 single and 7 bilateral) and 22 bilateral CLTs, were performed. Preoperative variables and postoperative outcomes were retrospectively compared between the 2 procedures. RESULTS Based on the preoperative variables of less ambulatory ability (41.7% vs 100%, P 0.99, respectively). Furthermore, the 5-year overall survival rate was similar between the 2 groups (90.0% vs 76.3%, P = 0.489). CONCLUSIONS Although LDLLT patients with PH had worse preoperative conditions and received smaller grafts than CLT patients, LDLLT patients demonstrated similar perioperative outcomes and prognoses as CLT patients. LDLLT is a viable treatment option for patients with PH.

Bronchovenous fistula (BVF) is a rare complication and can cause arterial gas embolism in vital organs, including the heart and the brain, resulting in a high mortality rate. A 51-year-old man developed a BVF during pneumonectomy for lung transplantation, which quickly was diagnosed by transesophageal echocardiography (TEE). He required highairway-pressure ventilation due to his severely restrictive ventilatory impairment and had severe left pleural adhesion due to a history of pleurodesis. Intraoperatively, he had a coronary air embolism and required temporary treatment with central venoarterial extracorporeal membrane oxygenation (VA-ECMO), but showed no postoperative cardiac or neurologic complications. BVF may be formed during lung transplantation because lung transplantation recipients often receive high-airway-pressure ventilation and are vulnerable to bronchi and pulmonary vessel injuries during surgery. Intraoperative TEE can contribute to the early detection of air bubbles in the left heart circulation and is helpful for the prevention of arterial gas embolism.

OBJECTIVES We developed a novel wireless localization technique after electromagnetic navigation bronchoscopy-guided radiofrequency identification marker placement for fluoroscopically invisible small lung lesions. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared 2 marking approaches with or without cone-beam computed tomography (CBCT). METHODS Consecutive patients from January 2021 to March 2022 in our institution were enrolled. Markers were placed central to the lesions either in a bronchoscopic suite under intravenous anaesthesia or a hybrid operation theatre with CBCT under general anaesthesia. The efficacy of the 2 marking methods was compared using an inverse probability of treatment weighting adjusted analysis. RESULTS Totally 80 markers were placed (45 under CBCT and 35 under fluoroscopy) for 74 patients with 80 lesions [mean size: 6.9 mm (interquartile range: 5.1–8.4) at a median depth from the pleura of 14.0 mm (interquartile range: 8.5–19.5)]. The median distance from marker to lesion was 9.1 mm, with a pleural depth of 15.5 mm. The tumour resection rate was 97.5% (78/80) with the median surgical margin of 10.0 mm (interquartile range: 8.0–11.0). Although the bronchoscopy time was longer using CBCT because of the need for 2.8 scans per lesion, the distance from the marker to the lesion was shorter for marking using CBCT than marking using fluoroscopy (adjusted difference: −4.56, 95% confidence interval: −6.51 to −2.61, P CONCLUSIONS Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking provided a high tumour resection rate with sufficient surgical margins.

Small, non-palpable, parasternal lymph nodes can be difficult to locate during minimally invasive thoracoscopy. We here present a simple technique for thoracoscopic localization of small parasternal lymph nodes using echo-guided injection of indocyanine green. This technique rapidly marks the whole chain of enhanced lymph nodes for radical resection, enabling accurate endoscopic resection of small parasternal lymph nodes.

This study aimed to analyze the influences of single nucleotide polymorphisms (SNPs) in Fc gamma receptor IIA (FCGR2A) on postoperative outcomes after lung transplantation (LTx). We enrolled 191 lung transplant recipients [80 undergoing living-donor lobar lung transplants (LDLLTs) and 111 undergoing deceased-donor lung transplants (DDLTs)] in this study. We identified SNPs in FCGR2A (131 histidine [H] or arginine [R]; rs1801274) and reviewed the infectious complication-free survival after ICU discharge. The SNPs in FCGR2A comprised H/H (n = 53), H/R (n = 24), and R/R (n = 3) in LDLLT and H/H (n = 67), H/R (n = 42), and R/R (n = 2) in DDLT. Recipients with H/H (H/H group) and those with H/R or R/R (R group) were compared in the analyses of infectious complications. In multivariate analyses, the R group of SNPs in FCGR2A was associated with pneumonia-free survival {HR: 2.52 [95% confidence interval (CI): 1.35-4.71], P = 0.004}, fungal infection-free survival [HR: 2.50 (95% CI: 1.07-5.84), P = 0.035], and cytomegalovirus infection-free survival [HR: 2.24 (95% CI: 1.07-4.69), P = 0.032] in LDLLT, but it was not associated with infectious complication-free survival in DDLT. Therefore, in LDLLT, more attention to infectious complications might need to be paid for LTx recipients with H/R or R/R than for those with H/H.

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the

Lung cancer with distant metastases is associated with a very poor prognosis, and epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Therefore, elucidation and inhibition of EMT signaling in lung cancer may be a new therapeutic strategy for improving the prognosis of patients. We constructed a high-throughput screening system for EMT inhibitors. Using this system, we aimed to identify compounds that indeed inhibit EMT.We generated a luciferase reporter cell line using A549 human lung cancer cells and E-cadherin or vimentin as EMT markers. EMT was induced by transforming growth factor β1 (TGF-β1), and candidate EMT inhibitors were screened from a library of 2,350 compounds. The selected compounds were further tested using secondary assays to verify the inhibition of EMT and invasive capacity of cells.Values obtained by the assay were adjusted for the number of viable cells and scored by determining the difference between mean values of the positive and negative control groups. Four compounds were identified as novel candidate drugs. Among those, one (avagacestat) and two compounds (GDC-0879 and levothyroxine) improved the expression of E-cadherin and vimentin, respectively, in epithelial cells. GDC-0879 and levothyroxine also significantly inhibited the invasive capacity of cells.We systematically screened approved, investigational, and druggable compounds with inhibitory effects using a reporter assay, and identified candidate drugs for EMT inhibition.

Background Waitlist mortality due to donor shortage for lung transplantation is a serious problem worldwide. Currently, the selection of recipients in Japan is mainly based on the registration order. Hence, scientific evidence for risk stratification regarding waitlist mortality is urgently needed. We hypothesized that patient-reported dyspnea and health would predict mortality in patients waitlisted for lung transplantation. Methods We analyzed factors related to waitlist mortality using data of 203 patients who were registered as candidates for lung transplantation from deceased donors. Dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, and the health status was determined with St. George’s Respiratory Questionnaire (SGRQ). Results Among 197 patients who met the inclusion criteria, the main underlying disease was interstitial lung disease (99 patients). During the median follow-up period of 572 days, 72 patients died and 96 received lung transplantation (69 from deceased donors). Univariable competing risk analyses revealed that both mMRC dyspnea and SGRQ Total score were significantly associated with waitlist mortality (p = 0.003 and p Conclusions Both mMRC dyspnea and SGRQ score were significantly associated with waitlist mortality, in addition to other clinical variables such as patients’ background, underlying disease, and pulmonary function. Patient-reported dyspnea and health may be measured through multi-dimensional analysis (including subjective perceptions) and for risk stratification regarding waitlist mortality.

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

OBJECTIVES Identifying the risks for chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) is beneficial to the patient. We hypothesized that diabetes mellitus (DM) is relevant to CLAD development. Our study aimed to clarify if DM is a risk for poor post-LTx outcomes. METHODS The records of patients first undergoing LTx in our institution between 2010 and 2018 were reviewed retrospectively. Patient characteristics and postoperative outcomes were analysed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and CLAD development. To identify perioperative DM, we evaluated the patient for DM at 6 months post-LTx. RESULTS A total of 172 patients were investigated. DM and CLAD occurred in 76 and 39 patients, respectively, and 40 died. At 6 months post-LTx, the unadjusted and adjusted hazard ratios of DM for OS were 3.36 [95% confidence interval (CI) = 1.67–6.73] and 2.78 (95% CI = 1.35–5.75), respectively. The unadjusted and adjusted hazard ratios of DM for CLAD-free survival were 2.20 (95% CI = 1.27–3.80) and 2.15 (95% CI = 1.24–3.74). The patients with DM were older and had a higher body mass index and more incidents of post-LTx malignant disease than the non-DM patients. The 5-year OS and CLAD-free survival rates of the patients with or without DM were 57.2% vs 86.5% and 50.1% vs 72.9%, respectively. CONCLUSIONS Perioperative DM was identified as an independent adverse factor for OS and CLAD-free survival. Perioperative management of DM should be emphasized in the clinical setting of LTx.

Adjuvant cisplatin‑vinorelbine is a standard therapy for stage II/III lung cancer. However, a poor survival rate of patients with lung cancer is attributed to vinorelbine resistance arising from ATP‑binding cassette (ABC) sub‑family B member 1 (ABCB1) and phosphorylated Fyn (p‑Fyn) overexpression. However, the underlying mechanisms remain unclear. NF‑E2‑related factor 2 (Nrf2) regulates the ABC family and activates the nuclear transport of Fyn. The present study evaluated the roles of the Nrf2/p‑Fyn/ABCB1 axis in vinorelbine‑resistant (VR) cells and clinical samples. To establish VR cells, H1299 cells were exposed to vinorelbine, and the intracellular reactive oxygen species (ROS) level in the H1299 cells was determined using a DCFH‑DA assay. The total and subcellular expression of Nrf2, ABCB1 and p‑Fyn in VR cells was evaluated. Immunofluorescence was used to detect the subcellular localization of p‑Fyn in VR cells. A cell viability assay was used to examine whether the sensitivity of VR cells to vinorelbine is dependent on Nrf2 activity. Immunohistochemistry was performed on 104 tissue samples from patients with lung cancer who underwent surgery followed by cisplatin‑vinorelbine treatment. The results revealed that persistent exposure to vinorelbine induced intracellular ROS formation in H1299 cells. p‑Fyn was localized in the nucleus, and ABCB1 and Nrf2 were overexpressed in VR cells. ABCB1 expression was dependent on Nrf2 downstream activation. The decreased expression of Nrf2 restored the sensitivity of VR cells to vinorelbine. In the surgical samples, Nrf2 and ABCB1 were associated with disease‑free survival, and p‑Fyn was associated with overall survival (P0.05). On the whole, the present study demonstrates that Nrf2 upregulates ABCB1 and, accompanied by the nuclear accumulation of p‑Fyn, induces vinorelbine resistance. These findings may facilitate the development of drug resistance prevention strategies or new drug targets against non‑small cell lung cancer.

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.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.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).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.

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.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.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.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.

OBJECTIVES Few studies have evaluated the outcomes of lung transplantation (LTx) in recipients with preformed donor-specific antibodies (DSAs). This study investigated the postoperative changes in preformed DSAs based on prospectively collected data of DSAs, and the influences of preformed DSAs on postoperative outcomes among LTx recipients. METHODS Between July 2010 and December 2019, 216 recipients underwent LTx (81 living-donor lobar lung transplants and 135 deceased-donor lung transplants). We reviewed 8 cases with preformed DSAs to determine postoperative changes in DSAs and compared postoperative outcomes between recipients with and without DSAs. RESULTS The preoperative mean fluorescence intensity of preformed DSAs ranged from 1141 to 14 695. Two recipients experienced antibody-mediated rejection within 2 weeks after LTx. DSAs disappeared in 7 recipients; however, 1 recipient experienced the relapse of DSAs and died from chronic lung allograft syndrome (CLAD), whereas 1 recipient had persisting DSAs within the study period and died from CLAD. Neither overall survival (OS) nor CLAD-free survival was significantly different between recipients with and without DSAs (P = 0.26 and P = 0.17, respectively). However, both OS and CLAD-free survival were significantly lower in recipients with DSAs against HLA class II than in those without these antibodies {5-year OS: 25.0% [95% confidence interval (CI): 0.9–66.5%] vs 72.1% (95% CI: 63.8–78.9%), P = 0.030 and 5-year CLAD-free survival: 26.7% (95% CI: 1.0–68.6%) vs 73.7% (95% CI: 66.5–79.5%), P = 0.002}. CONCLUSIONS Prognosis in recipients experiencing the relapse of preformed DSAs and those with persisting DSAs may be poor. The recipients with anti-HLA class II preformed DSAs had a significantly worse prognosis.

Objectives Precise small lung nodule resection is challenging in minimally invasive thoracoscopic surgery. Various methods that help surgeons to locate the target nodule have been devised; however, the ideal way that satisfies the demand has not yet been realized. We have developed and applied a novel marking system to localize small lung nodules for the first time in humans. Methods A radiofrequency identification tag (1.8 mm in diameter and 7 mm in length) that can communicate with a wand-shaped antenna (10 mm in diameter) from the distance of 3 cm was prepared. The tag was delivered adjacent to a 7-mm subsolid nodule in the right lower lobe of a patient under cone beam computed tomography guidance and video-assisted thoracoscopic surgery wedge resection was subsequently performed. Results The delivery of the tag was smooth, and the tag was almost immediately detected by the antenna. Wedge resection was successfully performed with the guiding signal from the tag. Conclusions We have so far demonstrated that this technology could be applicable for small lung nodule detection in preclinical studies. In this first clinical experience, this system proved to provide accurate positional information of small lung nodules with depth.

Indocyanine green (ICG) is widely used during thoracic surgery to enhance visualization, allowing assessment of the intersegmental plane based on intrapulmonary blood flow (Travis et al. in Ann Thorac Surg 108(2):363-369, 2019; Seshiru et al. in Gen Thorac Cardiovasc Surg 66(2):81-90, 2018). Using ICG to detect blood flow disruption after lung resection, however, has not been addressed. We therefore report a case in which the left lingular pulmonary vein was incidentally divided during left lower lobectomy in a living-lung donor. Intraoperative ICG-enhanced near-infrared fluoroscopic imaging to assess intrapulmonary blood flow detected the problem. We thus avoided potential postoperative residual lung complications in this patient.

Background/aim Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an anti-allergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. Materials and methods We examined the effects of tranilast treatment on EMT markers, TGF-β1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. Results Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-β1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. Conclusion Tranilast inhibited TGF-β1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.

Poor quality of sleep is a common feature in patients with various lung diseases and affects their health-related quality of life (HRQL). We evaluated sleep quality and HRQL in patients on the waitlist for lung transplantation in Japan. In this prospective study, patient-reported and physiological data were collected from patients newly registered on the waitlist for lung transplantation in Japan. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) and HRQL using the St. George’s Respiratory Questionnaire (SGRQ). The frequency of poor sleep quality, correlations between sleep quality and various clinical parameters, and predictive factors of sleep quality were examined. Of 193 patients, the three most-frequent indications for lung transplantation were interstitial pneumonia (n = 96), pulmonary complications of hematopoietic stem cell transplantation (n = 25), and pulmonary hypertension (n = 17). Poor sleep quality (PSQI > 5) was observed in 102 patients (53%) and was significantly associated with worse Hospital Anxiety and Depression Score (HADS), worse SGRQ score, worse modified Medical Research Council Dyspnea score, and shorter 6-min walk distance. However, it was not associated with sex, pulmonary function, interstitial pneumonia, or arterial blood gas. Stepwise multiple regression analysis indicated that poor sleep quality was explained significantly by HADS anxiety (23%) and SGRQ Symptoms (10%). Poor sleep quality was found to be common among patients on the lung transplantation waitlist in Japan. The two most significant factors responsible for impaired sleep quality were anxiety and respiratory symptoms. Additional care should be taken to ensuring a better quality of sleep for such patients.

Background Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain. Case summary A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer. Conclusion This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

The union rate of wire fixation after median sternotomy remains unsatisfactory. We developed a novel osteoconductive sheet composed of hydrophilized hydroxyapatite and evaluated its osteogenetic effect when interposed between sternal halves in a canine model. Eighteen canines were divided equally into groups based on the hemostatic agent used: osteoconductive sheet (S), none (C), and bone wax (BW). After median sternotomy, the sternal halves were closed by wire fixation. In each group, 3 canines were euthanized at 1 month, while 3 were euthanized at 2 months. Resected sternums were mechanically assessed by the 3-point bending test, radiographically assessed by micro-CT, and pathologically assessed to quantify the osteogenesis between sternal halves. Compared with the BW group, the S group had a greater maximum stress at 1 month (S: 322.9 ± 107.7 N, C: 233.0 ± 62.7 N, BW: 124.9 ± 88.4 N; P = 0.025), and greater maximum shear force at 1 month (S: 1.92 ± 0.67 N/m2; C: 1.23 ± 0.28 N/m2; BW: 0.68 ± 0.41 N/m2; P = 0.025). Micro-CT revealed that the S group had more osteogenesis than the BW group at 1 month (25.7% ± 9.8% vs 6.9% ± 9.2%), and 2 months (34.0% ± 15.1% vs 14.8% ± 9.4%); the respective values in the C group were 17.1% ± 7.2% and 29.7% ± 9.3%. Pathologic examination revealed that the S group had the greatest osteogenetic area at 2 months (S: 38.8% ± 18.8%; C: 24.5% ± 6.9%; BW: 24.7% ± 18.6%). Adjuvant osteoconductive therapy using a cotton-like hydroxyapatite sheet in addition to wire fixation significantly improved sternal healing compared with BW. This new material also showed relatively better outcome than the C group.

Background Part-solid lung adenocarcinoma appears as a heterogeneous subgroup, and its surgical management is controversial. This study aimed to elucidate whether preoperative carcinoembryonic antigen, a time-honored tumor marker, can be used as a prognostic factor that contributes to its management. Methods We retrospectively reviewed consecutive patients with clinical-T1a-cN0M0 part-solid adenocarcinoma who underwent surgical resection between January 2011 and December 2015 at two institutions. Results Overall, 288 patients were identified. The median age was 69 years with 176 patients (61%) being female. The median follow-up time was 5.6 years. Lymph node metastases were found in 6 (15%) of 41 patients with elevated carcinoembryonic antigen levels, while 10 (4.0%) of 247 patients had normal carcinoembryonic antigen levels ( P = 0.016). The 5-year overall survival rates in patients with normal and elevated carcinoembryonic antigen levels were 96.9% and 87.2%, respectively ( P = 0.006), and the 5-year relapse-free survival rates were 91.8% and 62.8%, respectively ( P Conclusions Our data suggest that preoperative carcinoembryonic antigen level appears to be an important predictor of postoperative survival outcomes in early-stage part-solid adenocarcinoma. Further studies are required to optimize management of patients with elevated preoperative carcinoembryonic antigen levels, although segmentectomy appeared acceptable in those patients.