Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Although the performance lung transplantation (LTx) in the elderly (≥ 60 years) has increased globally, the situation in Japan remains quite different, because the age limit at registration for cadaveric transplantation is 60 years. We investigated the long-term outcomes of LTx in the elderly in Japan. METHODS: This was a single-center retrospective study. We divided the patients into two groups according to age: the younger group (< 60 years; Y group; n = 194) and the elderly group (≥ 60 years; E group; n = 10). We performed three-to-one propensity score matching to compare the long-term survival between the E and Y groups. RESULTS: In the E group, the survival rate was significantly worse (p = 0.003), and single-LTx was more frequent (p = 0.036). There was a significant difference in the indications for LTx between the two groups (p < 0.001). The 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.006). After propensity score matching, the 5-year survival rates of the two groups were comparable (p = 0.55). However, the 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.007). CONCLUSION: Elderly patients showed acceptable long-term survival after LTx.

DOI： 10.1007/s00595-023-02699-5

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Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. ΔeGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the ΔeGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine.

DOI： 10.1038/s41598-023-36143-y

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OBJECTIVE: The prognostic nutrition index (PNI), calculated using serum albumin and total lymphocyte count, is a recent topical index related to inflammation. Preoperative PNI is regarded as a new preoperative prognostic score in lung transplantation (LTx). This study aimed to investigate the impact of PNI at the time of registration as a prognostic parameter of mortality on the waiting list for LTx. METHODS: A retrospective review was conducted on the data of 132 adult patients registered for LTx in our department between January 2013 and June 2020. Patients who finally received LTx were analyzed as censored data. The overall survival was evaluated using the Kaplan-Meier method for pre-registered clinical factors including the PNI at the time of registration. Overall survival was calculated from the date of listing to the Japan Organ Transplant Network to the date of death. RESULTS: The low-PNI group had a significantly worse prognosis. Multivariate analysis demonstrated that age (p = 0.023), idiopathic interstitial pneumonia (p < 0.001), lung allocation score (LAS) (p < 0.001), and PNI (p < 0.001) were independent prognostic factors for waitlist mortality. CONCLUSIONS: PNI at the time of registration can be an independent prognostic parameter in registered candidates for LTx.

DOI： 10.1007/s11748-022-01895-3

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OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous surgery. In this study, we retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.

DOI： 10.1093/ejcts/ezad048

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INTRODUCTION: Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. METHODS: In our cross-sectional survey of living lung donors, we assessed health-related quality of life based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. RESULTS: We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio = 10.2; p<.001) and recipient age (<18 years; odds ratio = 2.73; p<.032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio = 3.94, p<.002) and recipient death (odds ratio = 3.64; p = .005). There were no predictors for physical component summary. Additionally, many donors did not complain of pain or dyspnea. CONCLUSIONS: Living lung donors maintained acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support. This article is protected by copyright. All rights reserved.

DOI： 10.1111/ctr.14927

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Background: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. Methods: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. Results: The post-transplant PaO2/FiO2 ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AT group. Conclusions: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure.

DOI： 10.21037/jtd-22-226

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One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

DOI： 10.1038/s41598-022-11064-4

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BACKGROUND: Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. METHODS: This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. RESULTS: Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. CONCLUSION: Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.

DOI： 10.1186/s12957-022-02552-y

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OBJECTIVES: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age. METHODS: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1-6 years old (n = 10) and 7-17 years old (n = 33). RESULTS: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group. CONCLUSION: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older.

DOI： 10.1007/s00595-022-02492-w

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Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient.

DOI： 10.18926/AMO/63217

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Lung transplant recipients are often complicated by immunosuppressant-induced nephropathy, which may require renal replacement therapy. We report a case of unilateral lung edema and pulmonary hypertension due to arteriovenous fistula placement in a patient with unilateral chronic lung allograft dysfunction after bilateral living-donor lobar lung transplantation. Lung transplant recipients with limited residual vascular beds, such as lobar graft or severe deviation in lung perfusion, are vulnerable to the acute increase in blood flow due to arteriovenous fistula placement and can easily develop pulmonary edema regardless of the left ventricular function. Hence, careful volume control is required.

DOI： 10.1016/j.athoracsur.2021.12.017

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OBJECTIVE: Although living-donor lobar lung transplantation (LDLLT) enables an intermediate survival similar to cadaveric lung transplantation, the long-term outcome remains unknown. We examined the long-term outcomes of 30 patients who received LDLLT more than 16 years previously. METHODS: We retrospectively reviewed the clinical data of 30 patients who underwent LDLLT (bilateral LDLLT, 29 patients; single LDLLT, 1 pediatric patient) between October 1998 and April 2004. RESULTS: LDLLT was performed for 25 female and 5 male patients ranging in age from 8 to 55 years. The diagnoses included pulmonary hypertension (n = 11), pulmonary fibrosis (n = 7), bronchiolitis obliterans (n = 5), and others (n = 7). At a median follow-up of 205 months, 22 patients were alive and 8 were dead. The causes of death were infection (n = 3), malignancy (n = 2), acute rejection (n = 2), and chronic lung allograft dysfunction (CLAD; n = 1). Unilateral CLAD occurred in 17 patients (56.7%), but only 1 of these patients subsequently developed bilateral CLAD. Two patients underwent bilateral cadaveric lung retransplantations. The 5-, 10-, and 15-year CLAD-free survival rates were 80.0%, 62.8%, and 44.3%, respectively. Malignancy occurred in 7 patients. Two of 5 patients with chronic kidney disease requiring hemodialysis underwent living-donor kidney transplantation. The 5-, 10-, and 15-year overall survival rates were 96.7%, 86.7%, and 73.3%, respectively. CONCLUSIONS: Although only 2 lobes are implanted, LDLLT provides encouraging long-term outcomes. In patients with unilateral CLAD, the functioning contralateral graft might contribute to a favorable long-term outcome.

DOI： 10.1016/j.jtcvs.2021.08.090

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DOI： 10.1007/s00595-021-02390-7

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Other Link： https://link.springer.com/article/10.1007/s00595-021-02390-7/fulltext.html

Language：Japanese   Publisher：(一社)日本胸部外科学会  

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DOI： 10.1016/j.bbrc.2021.08.015

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Background: Massive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH. Methods: We retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH. Results: The median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups. Conclusions: Meticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases.

DOI： 10.21037/jtd-21-1119

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease caused by the overrepresentation of interleukin-6 (IL-6). Tocilizumab (TCZ) is a humanized monoclonal antibody that binds to the IL-6 receptor and is approved for the treatment of iMCD. The efficacy and tolerability of TCZ in patients with iMCD undergoing lung transplantation (LTx) remain unknown. CASE PRESENTATION: We present the case of a 48-year-old iMCD patient with end-stage lung disease (ESLD) who was successfully treated with cadaveric single-LTx. Intravenous TCZ was used to stabilize the iMCD patient every 2 weeks, except for withdrawal immediately after LTx. At 32 month post-transplant, the patient remained asymptomatic without evidence of rejection, development of de novo donor-specific antibody (DSA), and recurrent iMCD in the native lung. CONCLUSIONS: Single-LTx can be a feasible treatment option for ESLD caused by iMCD. TCZ can be used safely and may be beneficial in recipients with iMCD, and TCZ in combination with usual immunosuppression can be helpful in stabilizing iMCD patients pre- and post-LTx.

DOI： 10.1186/s40792-021-01297-2

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BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains one of the most devastating manifestations of chronic graft-versus-host disease in hematopoietic cell transplantation (HCT). Recent findings of BOS after lung transplantation indicate that donor (lung)-derived lung-resident macrophages contribute to BOS, suggesting that differences in the origin of immune cells and localized antigen-presenting cells cause the onset of BOS. METHODS: We identified the phenotype and origin of infiltrating macrophages using immunohistochemistry and fluorescence in situ hybridization in eight sex-mismatched HCT recipients who underwent lung transplantation for BOS after HCT. RESULTS: Most of the infiltrating macrophages appeared to be derived from donor (hematopoietic) cells in patients who developed BOS following HCT. Macrophages observed in the early-stage region of BOS were positive for cluster of differentiation (CD)68 and inducible nitric oxide synthase (iNOS) and negative for CD163 and CD206, suggesting an M1 phenotype. In the late-stage region, macrophages were negative for CD68 and iNOS in all patients, but also positive for CD163 and CD206 in some patients. CONCLUSIONS: Donor-derived M1-macrophages may be involved in the pathogenesis of the early-stage region of BOS. In addition, some macrophages in the late-stage region showed M2 polarization that might be involved in fibrosis.

DOI： 10.1007/s12185-021-03214-7

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Language：Japanese   Publisher：(一社)日本移植学会  

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An incomplete interlobar fissure makes thoracoscopic lobectomy difficult and is predictive of morbidity after thoracoscopic lobectomy. This report demonstrates the robot-assisted thoracoscopic (RATS) lobectomy technique for patients with severe incomplete interlobar fissures. A fissureless approach was chosen for pulmonary resection. Near-infrared fluorescence imaging with intravenous indocyanine green (ICG) was used to detect the interlobar line after transection of the bronchus, pulmonary artery and vein. Interlobar fissure was identified and divided by robotic staplers. This combined technique using ICG and fissureless lobectomy made RATS lobectomy safe for patients with severe incomplete interlobar fissures.

DOI： 10.1093/jscr/rjab336

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PURPOSE: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT). METHODS: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups. RESULTS: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group. CONCLUSION: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT.

DOI： 10.1007/s00595-021-02339-w

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Hyper-immunoglobulin E syndrome (HIES) is one of the primary immunodeficiencies characterized by recurrent staphylococcal skin and lung infections that result in lung destruction and critically diminished pulmonary function. Despite the lack of definitive treatment, there have been no reports of successful lung transplantation (LTx) for HIES patients. We report the case of a 42-year-old female HIES patient with progressive bronchiectasis whose pulmonary infection was controlled prior to transplantation and subsequent LTx was uneventful. LTx may be feasible in HIES if the patient is immunologically stable preoperatively, and peri-operative infections, especially Aspergillus infections, are well-controlled.

DOI： 10.1016/j.athoracsur.2021.05.088

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Language：Japanese   Publisher：(一社)日本移植学会  

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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.

DOI： 10.1016/j.transproceed.2021.04.019

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PURPOSE: Anti-human leukocyte antigen (HLA) immunoglobulin (Ig) M production stimulated by an alloantigen is sensitive, making IgM a novel potential marker of allorejection after organ transplantation. This study examined the relationship between the serum levels of anti-HLA IgM early after clinical lung transplantation (LTx) and the post-transplant outcomes. METHODS: Thirty-one consecutive patients who underwent deceased LTx were included. Immunoreactivity against HLA was retrospectively analyzed by measuring the anti-HLA IgM levels in the serum sampled for the first 14 days after LTx. The flow panel reactive antibody technique was used. The ratio of the anti-class I IgM level at each day to baseline was obtained, and the peak IgM level was determined for each case. The correlation between the peak IgM level and subsequent development of acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival outcomes were examined. RESULTS: The peak IgM level was a significant risk factor for AR within 90 days in univariate and multivariate analyses. In the long term, the patients with positive IgM (peak level > 1.8) tended to have a poorer CLAD-free and overall survival than those with negative IgM. CONCLUSION: Elevation of anti-HLA IgM levels early after LTx may be correlated with a higher incidence of rejection and negative clinical outcomes.

DOI： 10.1007/s00595-021-02293-7

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Severe scoliosis causes anatomical distortion of structures in the chest, which raises concerns about donor-recipient size-mismatch in lung transplantation (LT), so that severe scoliosis is considered as an absolute contraindication for LT. Also, postoperative right-side bronchial stenosis is one of the common complications in LT recipients with severe scoliosis. To date, the long-term outcomes in severe scoliosis patients with bronchial stenosis after LT have not been reported. A 14-year-old female patient with scoliosis and interstitial pneumonia underwent bilateral cadaveric LT. Although she developed bronchial stenosis post-LT, necessitating bronchoscopic intervention on three occasions, her lung function and perfusion recovered to the levels recorded prior to development of the obstruction, with the good condition maintained for more than 5 years after the LT. Therefore, while patients with severe scoliosis are at an elevated risk of postoperative transient bronchial stenosis, scoliosis should not always be considered as a contraindication to LT.

DOI： 10.1007/s11748-020-01539-4

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While technical considerations in lung transplantation for Kartagener syndrome have been discussed, little information is available about the postoperative morphological changes of the grafted lungs. Herein, we discuss both the technical aspects and postoperative morphological adaptation of the grafted lungs in a case of Kartagener syndrome. A 46-year-old male patient with Kartagener syndrome underwent bilateral cadaveric lung transplantation. The right arterial anastomosis for transplantation of the size-matched grafts required technical elaboration. After the transplantation, we found a free space in the cardiac notch of the left lung and partial collapse of the lower lobe of the right lung due to dextrocardia. Follow-up computed tomography performed on day 42 after the transplantation demonstrated resolution of the atelectasis and morphological adaptation of the grafts into the recipient's chest cavity with dextrocardia. Considering such early morphological adaptation of size-matched grafts, lobar reduction could be avoided in lung transplantation for Kartagener syndrome.

DOI： 10.1007/s11748-020-01509-w

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PURPOSE: Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in several types of cancer. In this study, we aimed to evaluate the prognostic impact of clinicopathological factors, including postoperative NLR, in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) who underwent surgery after chemoradiotherapy (CRT) with or without postoperative adjuvant chemotherapy. METHODS: The medical records of LA-NSCLC patients treated with trimodality therapy at our institution between June 1999 and May 2019 were reviewed. The association between several clinicopathological factors and overall survival (OS) was analyzed. RESULTS: A total of 168 patients were included in this study. Regarding the prognosis, the 5-year OS rate was 68.1%, and the 2-year recurrence-free survival rate was 66.1% in the entire population. In multivariate analysis, we identified that high postoperative NLR, not pretreatment or preoperative NLR, was one of the independent factors for unfavorable OS (NLR high vs NLR low; hazard ratio = 2.45, 95% confidence interval: 1.53-3.94, p < 0.001). In addition, among patients with high postoperative NLR, patients who received postoperative adjuvant chemotherapy showed significantly better 5-year OS compared with those who did not (p = 0.016). On the other hand, postoperative adjuvant chemotherapy had no impact on the prognosis in patients with low NLR (p = 0.19). CONCLUSIONS: Our results suggest that high postoperative NLR was not only an independent unfavorable prognostic factor in patients with LA-NSCLC who were treated with trimodality therapy, but also a promising indicator for postoperative treatment in this population.

DOI： 10.1245/s10434-021-09690-9

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PURPOSE: The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT. RESULTS: The PNI was correlated significantly and negatively with the LAS (r = - 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group. CONCLUSION: Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT.

DOI： 10.1007/s00595-021-02244-2

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PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

DOI： 10.1007/s00595-021-02232-6

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PURPOSE: The number of elderly patients who undergo surgery is increasing, even though they are at a high risk due to a decreased physical strength. Furthermore, sarcopenia is generally associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: This study included NSCLC patients  ≥ 65 years old who underwent pulmonary resection in our hospital between 2012 and 2015. Sarcopenia was assessed using the psoas muscle mass index based on computed tomography at the level of the third lumbar vertebra. We elucidated the impact of sarcopenia on short- and long-term outcomes after surgery. RESULTS: We enrolled 259 patients, including 179 with sarcopenia. Patients with sarcopenia before surgery tended to have postoperative complications (p = 0.0521), although they did not show a poor prognosis. In patients with sarcopenia, a multivariate analysis revealed that postoperative complications and the progression of sarcopenia 1 year after surgery were significant risk factors for a poor prognosis (p = 0.0169 and 0.00370, respectively). CONCLUSIONS: The progression of sarcopenia after surgery is associated with a poor prognosis in elderly NSCLC patients with sarcopenia. A strategy to prevent postoperative progressive sarcopenia may be necessary for improving the clinical outcome of this population.

DOI： 10.1007/s00595-020-02221-1

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Bronchopleural fistula (BPF) is a severe complication following lung resection. We present the case of a patient with a history of advanced lung cancer, who had undergone induction chemoradiotherapy followed by right middle and lower lobectomy, and who developed BPF after completion right pneumonectomy. Although we had covered the bronchial stump with an omental pedicled flap, BPF was found on postoperative day 19. We covered the fistula with n-butyl-2-cyanoacrylate (NBCA) using bronchoscopy. Although we had to repeat the NBCA treatment, we ultimately cured the patient's BPF and no recurrence was observed up to 15.2 months after surgery.

DOI： 10.18926/AMO/61440

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Although chronic kidney disease (CKD) commonly develops after lung transplantation (LT), living-donor kid-ney transplantation (LDKT) for CKD after LT is known to provide favorable outcomes. We describe the long-term follow-up findings of a patient who underwent LDKT after bilateral cadaveric LT. A 37-year-old male underwent LDKT for CKD 18 years after receiving bilateral cadaveric LT. He developed chronic lung allograft dysfunction (CLAD) 20 years after the LT; however, at 26 years after the initial LT, he is still alive with no pro-gression of CLAD or CKD. KT could be a viable option for CKD even after LT in Japan.

DOI： 10.18926/AMO/61439

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PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

DOI： 10.1007/s00595-020-02067-7

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1245/s10434-020-09272-1

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Other Link： http://link.springer.com/article/10.1245/s10434-020-09272-1/fulltext.html

Language：Japanese   Publisher：(NPO)日本肺癌学会  

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We encountered a rare case of thymic cyst accompanied by mediastinitis. A 39-year-old Japanese male presented with fever and chest pain. The chest CT revealed a mass composed of a lobular cystic lesion with inflammation, suggesting the onset of mediastinitis. A definitive histological diagnosis was not obtained, and we performed a thymectomy. Pathologically, the thymic cyst was accompanied by multiple cavities, mimicking thymic cysts, caused by the inflammatory abscess. The surrounding adipose tissue showed inflammatory cell infiltrations with chronic fibrosis. These findings indicate that clinicians should be aware that thymic cysts may cause severe mediastinitis.

DOI： 10.18926/AMO/60804

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Language：Japanese   Publisher：(一社)日本移植学会  

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PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

DOI： 10.1007/s00595-020-02093-5

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N = 27) and the non-CLAD group (N = 31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P < 0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P = 0.0037), the total lung capacity (P = 0.0028), and the forced vital capacity (P = 0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT.

DOI： 10.1038/s41598-020-67433-4

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：岡山医学会  

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Copyright © 2020. Published by Elsevier Inc. PURPOSE: The preoperative nutritional status affects the clinical outcome of surgery. To predict the clinical outcome, a prognostic nutritional index (PNI) calculated using serum albumin levels (ALB) and total lymphocyte count (TLC) has been shown to be valuable in various fields of surgery. In this study, we investigated the relationship between PNI and lung allocation score (LAS) as well as the impact of PNI on outcomes of lung transplantation (LT), including cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: Between June 2003 and August 2016, a total of 127 patients underwent LT at Okayama University Hospital, including 71 recipients of CLT and 56 recipients of LDLLT. The PNI was calculated by the following equation: PNI = (10 × ALB(g/dl)+(0.005 × TLC(/mm3)). The overall survival was evaluated by univariate analysis (the log rank test) and multivariate analysis (the Cox proportional hazard regression model) using preoperative factors, including sex, age, BMI, diagnosis, oxygen concentration, mechanical ventilation, tracheostomy, ECMO support, use of glucocorticoids, serum creatinine level, diabetes mellitus, LAS, and PNI. RESULTS: PNI was significantly negatively correlated with LAS (r=-0.3, P=0.00062) (Fig. 1A). The univariate analysis revealed that the overall survival was significantly worse in the patients with age>28 (P=0.047), BMI<24.2 (P=0.0098), LAS>58.04 (P=0.000072), PNI<46.35 (P=0.018) (Fig. 1B). The multivariate analysis demonstrated that age (P=0.00093), BMI (P=0.0024), and PNI (P=0.0047) were independent prognostic factors of worse outcome. In the subgroup analysis, low PNI is a significant prognostic factor of worse survival after CLT (P=0.015) (Fig. 1C) and LDLLT (P=0.041) (Fig. 1D). CONCLUSION: Preoperative nutritional evaluation using PNI could contribute to the assessment of LT recipient's severity and predict survival after both CLT and LDLLT.

DOI： 10.1016/j.healun.2020.01.700

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Copyright © 2020. Published by Elsevier Inc. PURPOSE: Micro-RNAs (miRNAs) regulate genes by selectively silencing their target messenger RNAs. Recently, serum levels of miRNA related to pulmonary fibrosis (miR-21 and miR-155), have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after cadaveric lung transplantation (CLT). We investigated the relationship between miRNAs levels and CLAD after bilateral living-donor lobar lung transplantation (LDLLT) and CLT. METHODS: Blood samples were collected from a total of 70 patients who underwent bilateral LDLLT (n=39) and bilateral CLT (n=31), including patients with CLAD (the CLAD group, n=25) and those without CLAD (the non-CLAD group, n=45). Plasma miRNA levels (miR-21 and miR-155) were quantified using real-time PCR and compared between the two groups. The relationship between miRNA levels and the results of pulmonary function tests at the onset of CLAD was assessed. Appropriate cut-off values of miRNA levels were set for the diagnosis of CLAD. RESULTS: The median follow-up period was 3074 (1071-7523) days. Plasma miRNA levels of the CLAD group were significantly higher than those of the non-CLAD group (miR-21, P<0.001; miR-155, P=0.013) (Fig. 1). In the CLAD group, miRNA levels after LDLLT were comparable to those after CLT. Moreover, miRNA levels were significantly negatively correlated with the baseline values of forced expiratory volume in 1 second (FEV1) (miR-21, P<0.001; miR-155, P=0.039) and those of total lung cavity (TLC) (miR-21, P<0.001; miR-155, P=0.0012) (Fig. 2). An ROC analysis of the performance of miR-21 level as a marker of CLAD yielded an AUC of 0.94 at a threshold level of 6.51. Patients with miR-21 level≥6.51 showed significantly better CLAD-free survival than those with miR-21 level<6.51 (P<0.001) (Fig. 3). CONCLUSION: Plasma miRNA levels are associated with the development of CLAD after bilateral LDLLT and CLT, and might be a potential biomarker for the diagnosis of CLAD.

DOI： 10.1016/j.healun.2020.01.792

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BACKGROUND: Lung transplantation (LTx) is still limited by the shortage of suitable donor lungs. Developing flexible surgical procedures can help to increase the chances of LTx by unfolding recipient-to-donor matching options based on the pre-existing organ allocation concept. We report a case in which a successful left-to-right inverted LTx was completed using the interposition of a pericardial conduit for pulmonary venous anastomosis. CASE PRESENTATION: A left lung graft was offered to a 59-year-old male who had idiopathic pulmonary fibrosis with predominant damage in the right lung. He had been prescribed bed rest with constant oxygen inhalation through an oxymizer pendant and had been on the waiting list for 20 months. Considering the condition of the patient (LAS 34.3) and the scarcity of domestic organ offers, the patient was highly likely to be incapable of tolerating any additional waiting time for another donor organ if he was unable to accept the presently reported offer of a left lung. Eventually, we decided to transplant the left donor lung into the right thorax of the recipient. Because of the anterior-posterior position gap of the hilar structures, the cuff lengths of the pulmonary veins had to be adjusted. The patient did not develop any anastomotic complications after the transplantation. CONCLUSIONS: A left-to-right inverted LTx is technically feasible using an autologous pericardial conduit for pulmonary venous anastomosis in selected cases. This technique provides the potential benefit of resolving challenging situations in which surgeons must deal with a patient's urgency and the logistical limitations of organ allocation.

DOI： 10.1186/s12890-020-1075-4

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Language：Japanese   Publisher：(公社)日本医学放射線学会  

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PURPOSE: Some long-term survivors after surgery for locally advanced non-small cell lung cancer (NSCLC) treated with induction chemoradiotherapy (trimodality treatment) develop chronic pulmonary aspergillosis (CPA). The aim of our study was to assess the characteristics and outcomes of CPA that develops after trimodality treatment. METHODS: We retrospectively reviewed the data of 187 NSCLC patients who underwent trimodality treatment between 1999 and 2018. RESULTS: Six male ever-smoker patients developed CPA. All 6 patients had undergone extended resection for NSCLC and had a history of either adjuvant chemotherapy (n = 3) or radiation pneumonitis (n = 4). Among the 4 patients with CPA localized in a single lung, 3 patients were treated surgically (completion pneumonectomy or cavernostomy) and 1 patient was treated with antifungal therapy alone. Both treatments led to the improved control of CPA. In contrast, patients with CPA in both lungs were not candidates for surgery, and died of CPA. The survival rates after trimodality treatment in the CPA group and the group without CPA were comparable (10-year survival rate, 50.0% vs. 57.6%, P = 0.59). CONCLUSION: The early diagnosis of CPA localized in a single lung after NSCLC surgery is critical to improving control and survival in patients with CPA.

DOI： 10.1007/s00595-020-01960-5

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OBJECTIVE: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD. METHODS: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx. RESULTS: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001). CONCLUSIONS: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.

DOI： 10.1007/s11748-019-01181-9

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

【背景】低侵襲に血液や体液を採取し解析を行うLiquid biopsyは、癌領域では既に臨床応用され治療方針の決定に一役買っているが、移植領域ではまだ発展途上である。当科では肺移植におけるLiquid biopsyとして、ドナー由来血中遊離DNA（dd-cf-DNA）とマイクロRNA（miRNA）を標的にした研究を行ってきたため、その成果を報告する。【方法】ドナーとレシピエントの一塩基多型を比較してdd-cf-DNAを測定し、生体肺移植後の急性拒絶反応（AR）における診断的意義を検討した。次にレシピエントのみの検体で評価できるmiRNAを測定し、脳死・生体肺移植後の移植片慢性機能不全（CLAD）における診断的意義を検討した。【結果】dd-cf-DNAは、感染群（p=0.028）や安定群（p=0.001）よりAR群で有意に増加しており、生体肺移植後ARの診断に有用であった（Sci Rep 2018）。また線維化に関与するmiRNAが、非CLAD群よりCLAD群で有意に増加しており（p=0.008）、一秒量の変化率とも相関し（p=0.014）、CLAD診断に有用であった。【結論】肺移植のLiquid biopsy として、dd-cf-DNAは生体肺移植後ARの診断に、またmiRNAはCLADの診断に有用である。今後の臨床応用を目指して症例数の集積と簡便で精度の高い方法の開発が望まれる。

DOI： 10.11386/jst.55.supplement_242_2

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

【背景】日本における高齢者レシピエントの長期成績に関しての報告は少ない．今回当院における高齢者レシピエントの長期成績について後方視的に検討した.【対象と方法】1998年1月～2020年1月に施行した18歳以上の肺移植症例161例を対象とした.60歳以上の高齢群(H群：n=10)と18-59歳の非高齢群(L群:n=151)の2群に分けて,全生存期間(OS)およびCLAD発症までの期間(CFS)について解析を行った.【結果】H群ではL群と比較して片肺移植(p=0.03),間質性肺炎(p=0.02),男性(p=0.04)の割合が有意に多かった.BMI,ドナー年齢,総虚血時間,LASスコアには有意差は認めなかった.H群とL群の5年OSはそれぞれ51.9%と75.5%であり,有意差を認めた(p=0.02).H群とL群の5年CFSはそれぞれ53.3%と72.5%であった.サブグループ解析では，H群の片肺移植症例(5年:OS 25%)は両肺移植症例(5年OS:75%)と比較してOSが悪い傾向にあった(p=0.08)が，H群の両肺移植症例はL群の両肺移植症例(5年OS:74.2%)と比較しても同等の成績であった（p=0.5）.【結語】60歳以上のレシピエントの成績は60歳未満と比較し不良だが，両肺移植がより望ましい可能性が示唆された.

DOI： 10.11386/jst.55.supplement_253_1

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Ischemia-reperfusion injury (IRI) after lung transplantation mainly contributes to the development of primary graft dysfunction. The Sprouty-related EVH1-domain-containing (SPRED) protein family inhibits the mitogen activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway. Our study was aimed at examining the role of SPRED2 in IRI in mice that received orthotopic lung transplantation. Syngeneic mouse lung transplantation was performed in wild-type C57BL/6 J (WT) mice and Spred2 knockout (Spred2-/-) mice on the C57BL/6 J background from the WT donor. Four hours after reperfusion, blood gas analysis was performed, and lung grafts were sacrificed and analyzed. By using arterial oxygen tension measurements and histological evaluation using Lung Injury Score, we revealed more severe IRI in the grafts transplanted to Spred2-/- recipients, which manifested as exacerbated airway epithelial cell damage, interstitial edema with hemorrhage and neutrophil infiltration. Intragraft ERK1/2 activation and expression levels of proinflammatory cytokines and chemokines in Spred2-/- recipients were higher than those in WT recipients. SPRED2 plays an important role in protecting the lungs from IRI in lung transplantation recipients. We suggest that focused treatments suppressing the activity of the MAPK/ERK pathway in transplantation recipients could be the potential therapeutic option for the prevention of lung IRI.

DOI： 10.1016/j.trim.2019.101242

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DOI： 10.1007/s11748-019-01273-6

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DOI： 10.1111/crj.13108

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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DOI： 10.1007/s11748-019-01245-w

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：岡山医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. METHODS: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT. RESULTS: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083). CONCLUSION: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT.

DOI： 10.1007/s00595-019-01782-0

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Intrapulmonary solitary fibrous tumors (SFTs) are extremely rare neoplasms. We report a case of an intrapulmonary SFT and describe the findings of computed tomography (CT) and F-18 fluorodeoxyglucose positron emission tomography. The case indicates that a benign intrapulmonary SFT can present as a ground-glass nodule in the early stages of disease and may appear as a well-defined, lobular, homogeneously enhanced mass with slow growth on chest CT images. To our knowledge, this is the first report describing the natural course of an intrapulmonary SFT over 16 years based on the findings of chest CT and F-18 fluorodeoxyglucose positron emission tomography/CT.

DOI： 10.1016/j.radcr.2019.03.023

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PURPOSE: Suppressor of cytokine signaling-3 (SOCS3) is a negative feedback inhibitor of cytokine signaling with T-cell-mediated immunosuppressive effects on obliterative bronchiolitis (OB). In this study, we aimed to investigate the impact of T-cell-specific overexpression of SOCS3 using a murine heterotopic tracheal transplantation (HTT) model. METHODS: Tracheal allografts from BALB/c mice were subcutaneously transplanted into wild-type C57BL/6J (B6; WT) mice and SOCS3 transgenic B6 (SOCS3TG) mice. Tracheal allografts were analyzed by immunohistochemistry and quantitative polymerase chain reaction assays at days 7 and 21. RESULTS: At day 21, allografts in SOCS3TG mice showed significant amelioration of airway obstruction and epithelial loss compared with allografts in WT mice. The intragraft expression of IFN-γ and CXCL10 was suppressed, while that of IL-4 was enhanced in SOCS3TG mice at day 7. The T-bet levels were lower in SOCS3TG allografts than in WT allografts at day 7. CONCLUSION: We revealed that the overexpression of SOCS3 in T cells effectively ameliorates OB development in a murine HTT model by inhibiting the Th1 phenotype in the early phase. Our results suggest that the regulation of the T-cell response, through the modulation of SOCS expression, has potential as a new therapeutic strategy for chronic lung allograft dysfunction.

DOI： 10.1007/s00595-018-1753-5

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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive lung disease with exceptionally poor prognosis. While lung transplantation (LTx) is considered the last-resort therapeutic option, dismal waitlist mortality still hampers the salvage of patients with IPF. Pirfenidone, originally designed for IPF treatment, has increasingly been utilized. This study aimed to evaluate whether Pirfenidone could influence outcomes of patients with IPF on the Japanese LTx waitlist. METHODS: This retrospective single-center cohort study included 25 consecutive patients with IPF who were registered as LTx candidates at our institution between July 1999 and August 2016. Patients with a history of pretransplant Pirfenidone therapy (Pirfenidone group) were compared with those with no history (non-Pirfenidone group). RESULTS: In total, 6 (24%) patients received Pirfenidone as pretransplant therapy for 45.2 (range, 18.6-66.8) months. During the treatment period, the Pirfenidone group achieved a significant reduction in the decline rate of the forced vital capacity (-6.2% vs. -0.3%, p = 0.04) and a lower lung allocation score (31 vs. 41, p = 0.013) compared with the non-Pirfenidone group. The Pirfenidone group exhibited 100% waitlist survival three years after registration that was comparable to other indications, and 66% of the patients were still alive at the time of organ availability. No patient in the Pirfenidone group developed Pirfenidone-related surgical complications postoperatively. CONCLUSIONS: Patients with IPF successfully managed with long-term Pirfenidone therapy achieved favorable outcomes after LTx registration, comparable to other patients with LTx indications. The tolerability to antifibrotic therapy can be a predictor of waitlist survival.

DOI： 10.1016/j.resinv.2018.12.002

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PURPOSE: When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for < 5 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥ 5 days (long-term group). RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%). CONCLUSION: The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage.

DOI： 10.1007/s00595-018-1730-z

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PURPOSE: Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT. METHODS: A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values. RESULTS: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

DOI： 10.1007/s00595-018-1717-9

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PURPOSE: Inflammatory changes during lung ischemia-reperfusion injury (IRI) are related to the activation of the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (SPREDs) are known inhibitors of ERK1/2 signaling. The role of SPRED2 in lung IRI was examined in a left hilar clamp mouse model. METHODS: C57BL/6 wild-type (WT) and Spred2-/- mice were used in the left hilar clamp model. Experimental groups underwent 30 min of left hilar clamping followed by 1 h of reperfusion. U0126, an ERK1/2 inhibitor, was administered to Spred2-/- mice with reperfused lungs. RESULTS: The partial pressures of oxygen of the Spred2-/- mice after reperfusion were significantly worse than those of WT mice (p < 0.01). Spred2-/- mice displayed more severe injuries than WT mice with increased neutrophil infiltration observed by a histological evaluation and flow cytometry (p < 0.001). This severe inflammation was inhibited by U0126. In addition, the rate of ERK1 activation was significantly higher in the lungs of Spred2-/- mice after reperfusion than in WT mice according to a Western blot analysis (p < 0.05). CONCLUSION: The activation of the ERK1/2 signaling pathway influences the severity of lung IRI, causing inflammation with neutrophil infiltration. SPRED2 may be a promising target for the suppression of lung IRI.

DOI： 10.1007/s00595-018-1696-x

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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.

DOI： 10.1038/s41598-018-33848-3

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PURPOSE: The lung allocation score (LAS) has been generally recognized as a contributor to the overall survival in lung transplant candidates. However, donor-related risks have never been taken into consideration in previous research that validated the LAS. This study aimed to determine whether or not the role of the LAS as a predictor of the posttransplant outcome is influenced by the quality of the donor lungs. METHODS: We retrospectively reviewed 108 patients who underwent lung transplantation at Okayama University Hospital since 1998. The cohort was divided into two groups based on the lung donor score (DS; ≤ 4/> 4). Correlations between the LAS and posttransplant outcomes were investigated in both groups. RESULTS: In the high-DS group, an elevated LAS was strongly associated with posttransplant PaO2/FiO2 (p = 0.018). However, in the low-DS group, no correlation was found between them. There was no significant difference in the long-term survival according to the LAS in the low-DS group. The LAS effectively predicted the posttransplant outcome only when lungs with DS > 4 were transplanted; the LAS was not reliable if high-quality lungs were transplanted. CONCLUSION: Lung transplantation can be feasible and provides a survival benefit even for high-LAS patients if lungs from a low-risk donor are transplanted.

DOI： 10.1007/s00595-018-1670-7

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PURPOSE: Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. METHODS: We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. RESULTS: The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). CONCLUSION: ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

DOI： 10.1007/s00595-018-1663-6

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DOI： 10.1016/j.jtcvs.2018.03.003

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Language：Japanese   Publisher：日本がん免疫学会  

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Although the number of patients developing pulmonary complications after hematopoietic stem cell transplantation (HSCT) necessitating lung transplantation (LT) is increasing, a little information is available about factors influencing the prognosis after LT in these patients. Corticosteroids represent the first-line therapy for pulmonary complications after HSCT; however, prolonged corticosteroid treatment prior to LT increases the potential risks of LT. In this study, we assessed the effect of preoperative corticosteroid therapy on long-term survival in patients undergoing LT after HSCT. We retrospectively investigated data from 13 patients who had received high-dose corticosteroid therapy and nine who had received low-dose corticosteroid therapy prior to LT for pulmonary complications after HSCT. Other than the preoperative corticosteroid dose, patient clinical characteristics did not differ. The incidence of postoperative complications within the first year after LT was significantly lower in the low-dose corticosteroid group (p = 0.026). Survival after LT was also significantly better in the low-dose corticosteroid group than in the high-dose corticosteroid group (p = 0.034). In recipients of LT after HSCT, preoperative low-dose corticosteroid use, as compared to preoperative high-dose corticosteroid use, could limit the risks of postoperative complications developing within the first year after the LT, leading to improved long-term survival after LT.

DOI： 10.1007/s12185-018-2417-3

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Pneumatosis intestinalis, which could complicate a spectrum of clinical conditions ranging from benign to life-threatening, is a rarely encountered complication after lung transplantation (LT). We describe two cases in which PI developed as a complication following LT for pulmonary graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In addition to the long-term immunosuppression administered for pulmonary GVHD, the intense immunosuppression needed after LT might increase the risk of PI in lung transplant recipients after HSCT. Conservative therapy should be considered for the treatment of PI developing after LT.

DOI： 10.21037/jtd.2017.11.121

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Language：English   Publisher：OXFORD UNIV PRESS  

DOI： 10.1093/jjco/hyx121

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Single living-donor lobar lung transplantation provides acceptable results for critically ill children; however, an additional lung transplantation may be required in the future as the recipient grows. We describe a case of successful lung retransplantation in a grown-up patient after single lobar lung transplantation in childhood. A 23-year-old man underwent bilateral cadaveric lung retransplantation for chronic lung allograft dysfunction 13 years after right single living-donor lobar transplantation for idiopathic pulmonary arterial hypertension performed at the age of 10 years. The postoperative course was uneventful. The patient had received growth hormone therapy at a local hospital for 3 years until the development of chronic lung allograft dysfunction after the initial transplantation. Pediatric recipients undergoing single living-donor lobar lung transplantation should be cautiously followed for potential retransplantation.

DOI： 10.1007/s11748-016-0732-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT SCIENTIFIC LITERATURE, INC  

Background: Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation.
Material/Methods: We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015.
Results: The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the followup period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively.
Conclusions: These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

DOI： 10.12659/AOT.904225

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Language：English   Publisher：ELSEVIER SCIENCE INC  

A 53-year-old man with pulmonary fibrosis associated with Erdheim-Chester disease achieved long-term survival after lung transplantation. Major clinical manifestations included lung and bone injuries, and other vital organs were functionally unaffected by the disease. After a careful observation for the disease progression, he underwent bilateral deceased-donor lung transplantation. He has returned to his normal social life and is doing well without recurrence of Erdheim-Chester disease in the lung allograft or progression in other organs 5 years after transplant. Lung transplantation is a potentially reasonable treatment option for Erdheim-Chester disease involving the lungs if the functions of other vital organs remain stable. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.02.020

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BACKGROUND: Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. METHODS: We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. RESULTS: Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. CONCLUSIONS: Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list.

DOI： 10.1016/j.resinv.2017.03.002

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Language：English   Publisher：SPRINGER  

In cadaveric lung transplantation (LTx), a donor lung with an inadequate donor left atrial cuff is considered a "surgically marginal donor lung". The donor pericardium is commonly applied to reconstruct the inadequate donor left atrial cuff; however, in some cases, the donor pericardium is inadvertently removed during the lung procurement. We devised an alternative technique for reconstruction to overcome the absence of pericardium in a donor lung with an inadequate atrial cuff, using a patch of the donor pulmonary artery (PA) in single lung transplantation. In a recent case of lung transplantation in which the donor pericardium had been removed, we harvested a segment of the right PA distal to the main PA of the donor and used a PA patch to repair the inadequate donor left atrial cuff. No vascular complications were encountered in the recipient, who remains in good health after the transplantation.

DOI： 10.1007/s00595-016-1370-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Successful bronchial healing after a bronchoplastic procedure mainly depends on bronchial circulation at the anastomostic site. We developed a bronchial fluorescein angiography (B-FAG) technique for visualizing circulation on the bronchial surface. The technique was evaluated in animals.
Fluorescein was used as a contrast agent and an autofluorescence imaging (AFI) bronchoscope as a detector. The left main pulmonary artery (PA) and main bronchus of 10 pigs were isolated. After transection of the left main bronchus and bronchial arteries and re-anastomosis of the bronchus, the pigs were randomly divided into two groups: the PA- group (n = 5), in which the pulmonary artery was transected; and the PA+ group (n = 5), in which the pulmonary artery was preserved. Following intravenous injection of fluorescein, the distal anastomotic site was observed for 30 min with autofluorescence imaging bronchoscopy. Bronchial specimens sampled 2 days after the surgical intervention were histologically evaluated.
In the PA- group, there was no fluorescein enhancement in the distal bronchus throughout the observation time. However, enhancement, which turned the bronchial surface from magenta to bright green, was clearly observed in less than 207 +/- 102.5 s in the PA+ group. The enhancement status detected by bronchial fluorescein angiography was related to the extent of tissue damage, as was proven histologically in the acute healing stage.
Bronchial fluorescein angiography clearly visualized the circulatory status promptly after the anastomosis procedure at the central bronchus. This technique is a potentially practical approach to predict ischaemic airway complications following bronchial anastomosis.

DOI： 10.1093/icvts/ivw210

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Stent placement is an essential treatment for airway diseases. Although self-expandable metallic stents and silicone stents are commonly applied for the treatment of airway diseases, these stents are unsuitable for the treatment of small airway diseases encountered in pediatric patients and lung transplant recipients with airway complications. Currently, only vascular balloon-expandable metallic stents are available for the treatment of small airway diseases; however, little research has been conducted on the use of these stents in this field. We have launched a prospective feasibility study to clarify the safety and efficacy of balloon-expandable metallic stents for the treatment of airway diseases.

DOI： 10.18926/AMO/54606

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DOI： 10.1016/j.transproceed.2015.12.021

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OBJECTIVE: Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. METHODS: EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. RESULTS: During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. CONCLUSIONS: A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

DOI： 10.1007/s11748-015-0585-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. Renal dysfunction is common after lung and heart-lung transplantation (Tx), and it limits the recipient's survival and quality of life. This study analyzed the outcomes of simultaneous and late kidney Tx following lung and heart-lung Tx.
Methods. From a single-center retrospective chart review of 1031 lung and heart-lung Tx recipients, we identified 13 simultaneous or late kidney Tx cases in 12 patients.
Results. Three patients underwent simultaneous deceased donor lung and kidney Tx. Eight patients underwent lung and heart-lung Tx, followed by nine living donor kidney Tx (including one ABO-incompatible Tx). One additional patient underwent a late deceased donor kidney Tx following heart-lung Tx. The median time from lung and heart-lung Tx to later kidney Tx was 127 (interquartile range [IQR], 23 to 263) months. Three patients died, 1 of sepsis, 1 of multiple organ failure, and 1 of transplant coronary disease. At a median follow-up of 33 (IQR, 10 to 51) months, 9 patients are alive and well. Eight patients required dialysis before kidney Tx for a median time of 14 months (IQR, 5 to 49). Kidney graft loss occurred in 1 patient at 51 months. After kidney Tx, dialysis was necessary in association with acute allograft dysfunction in 2 patients. No acute kidney rejection has been detected in any patient. Treatable acute lung rejection was seen in 1 patient. Well-preserved pulmonary function was noted in recipients of late kidney Tx.
Conclusions. Simultaneous kidney Tx and late deceased donor kidney Tx have challenges in the setting of lung Tx. By contrast, late living related kidney Tx after lung Tx is associated with excellent long-term survival and acceptable kidney and lung allograft function. (C) 2015 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2014.11.023

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Background: The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the pen-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation.
Methods: This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies.
Results: We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well.
Conclusions: Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients. (C) 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jcf.2014.08.003

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Language：Japanese   Publisher：(株)南江堂  

症例1:32歳女。特発性肺線維症に対し両側脳死肺移植を行った。なお、移植肺は患者の胸郭よりやや大きめであった。術後、移植肺に虚血再灌流障害による肺水腫が生じ、柔軟性を失い胸腔内に納まらなくなったため、Esmarch駆血帯を用いて仮閉胸した。移植肺の浮腫が改善して肺が柔軟性を取り戻すのを待ち、術後3日に閉胸した。症例2:40歳女。原発性肺高血圧症に対し両側生体肺移植を行った。術後、左心不全のため大動脈送血、右房脱血によるextracorporeal membrane oxygenation(ECMO)を導入し、Esmarch駆血帯で仮閉創した。心不全は軽快し、術後2週にECMOを離脱し閉胸した。症例3:38歳男。強皮症に伴う間質性肺炎に対し脳死右片肺移植を行った。虚血再灌流障害のため右鼠径部からVA ECMOを導入した。全身heparin化に起因する血腫、high PEEPによる続発性気胸のためEsmarch駆血帯で仮閉胸した。経過中13回の再開胸を要したが、移植肺の状態改善を待ち、術後27日にECMOを離脱し閉胸した。

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Language：Japanese   Publishing type：Research paper (scientific journal)  

There are patients in whom management in an open-chest state after lung transplantation is necessary due to over-sized grafts, heart failure, use of extracorporeal membrane oxygenation (ECMO), or bleeding. In such patients, we suture Esmarch bandages, which are used for orthopedic surgery, to the open chest wound and perform wound management. We report 3 patients in whom wound management using this method was performed due to postoperative cardiac failure, primary graft dysfunction, and a postoperative pulmonary edema, respectively. Due to improvement in the wound management method and use of appropriate antibiotics, each patient could be managed without developing wound infection. This method was also useful for the management of bleeding.

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Background: The importance of antibody-mediated rejection (AMR) following lung transplantation remains contentious. In particular, the diagnostic criteria suggested to define AMR, namely the presence of donor-specific antibodies (DSA), C4d immunoreactivity, histological features and allograft dysfunction are not always readily applicable or confirmatory in lung transplantation.
Methods: In a retrospective single-center study of 255 lung transplant recipients (LTR), we identified 9 patients in whom a clinical diagnosis of AMR was made within 12 months of transplant, and define the immunological, histological, clinical features, as well as the therapeutic response of this cohort.
Results: Nine LTR with AMR underwent combination therapy with high-dose intravenous corticosteroid, intravenous immunoglobulin, plasmapheresis and rituximab. Following therapy, while the total number of the original DSA dropped by 17%, and the median value of the mean fluorescence intensity (mfi) of the originally observed DSA decreased from 5292 (IQR 1319-12,754) to 2409 (IQR 920-6825) (p &lt; 0.001), clinical outcomes were variable with a number of patients progressing to either chronic lung allograft dysfunction or death within 12 month.
Conclusion: AMR in lung transplantation remains both a diagnostic and therapeutic challenge, but when clinically suspected is associated with a variable response to therapy and poor long-term outcomes. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.trim.2014.06.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

OBJECTIVES: Airway complications related to ischaemia are a major cause of morbidity after lung transplantation. Early detection of airway ischaemia and optimal management of the anastomotic site could reduce the risk of airway complications. Autofluorescence imaging (AFI) bronchoscopy has been increasingly recognized as an effective technique for detecting abnormal mucosal thickening. The aim of this study was to investigate whether AFI bronchoscopy can facilitate the detection of airway ischaemic damage in lung transplant patients.
METHODS: Twenty Landrace pigs were used to create a tracheal autotransplantation model. A four-ring length of trachea was excised and implanted orthotopically. The tracheal autograft was observed on postoperative days 0, 2, 4 and 7 with AFI bronchoscopy. The extent and origin of graft autofluorescence were examined using histology and measured according to fluorescence intensity.
RESULTS: The lesions on the tracheal autografts appeared as bright green fluorescence on AFI bronchoscopy. On confocal fluorescence microscopy, high-intensity green fluorescence was observed in the elastin fibre layer of the submucosa. The fluorescence intensity of elastin was significantly higher in the graft showing fluorescence than the graft that did not show fluorescence and that at the control site.
CONCLUSIONS: Bright green fluorescence was seen in an elastin fibre layer in the submucosa, which was likely a result of epithelial sloughing. There is a close relationship between the bright green fluorescence pattern observed using AFI bronchoscopy and airway ischaemic damage. We conclude that AFI bronchoscopy may detect airway ischaemic damage after lung transplantation.

DOI： 10.1093/ejcts/ezt437

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Objective The shortage of organ donors is a serious problem in Japan. The right and left upper lobes of rejected extended-criteria lungs have the potential to be used for downsized lung transplantation
however, the 2 upper lobes are too small for a size-matched recipient. The present study investigated the feasibility of unilateral transplantation using the right and left upper lobes. Methods After harvesting the heart-lung block from donor swine, a left lung graft was created using the right and left upper lobes and transplanted into the left thoracic space of the recipient swine (group A, n = 5). We then evaluated graft function for 6 hours and compared these results with those of a control group (group B, n = 5), in which orthotopic left lung transplantation had been performed. Results The mean partial pressure of oxygen in the arterial blood gas after reperfusion was 507 mm Hg in group A and 463 mm Hg in group B (P =.2). The mean pulmonary arterial pressure was 30.3 mm Hg in group A and 27.5 mm Hg in group B (P =.4). The mean airway pressure was 6.4 mm Hg in group A and 6.2 mm Hg in group B (P =.7). Conclusions Our results suggest that unilateral left lung transplantation using the right and left upper lobes is technically and functionally feasible for size-matched recipients. In addition, this technique enables the use of rejected lungs if the upper lobes are still intact. Copyright © 2013 by The American Association for Thoracic Surgery.

DOI： 10.1016/j.jtcvs.2013.08.042

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DOI： 10.1016/j.healun.2012.12.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Although lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia-reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI.
Methods: Cold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion.
Results: Only the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group.
Conclusions: This study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.trim.2011.11.002

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DOI： 10.4044/joma.123.191

CiNii Books

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Other Link： http://ousar.lib.okayama-u.ac.jp/47082

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Objectives: Ex vivo lung evaluation (ex vivo) has been developed as a useful method by which to assess lungs from donation-after-cardiac death (DCD) donors prior to transplant. However, the safety of the ex vivo circulation itself with respect to grafts has not been fully investigated. The aim of this study is to evaluate the effects of the ex vivo circuit using a swine lung transplant model. Methods: Lungs with or without 2-h warm ischemia were used. To assess post-transplant graft function, the left lung was transplanted after 2-h ex vivo or cold preservation; blood gas analysis of the left pulmonary vein (partial pressure of oxygen, PO(2)) was performed during the 6-h post-transplant follow-up period. Data were compared between the ex vivo (+) and ex vivo (-) groups. Results: Partial pressure of oxygen/inspired oxygen fraction (PO(2)/FiO(2)) in the ex vivo (-) group was significantly greater than that in the ex vivo (+) group until 3 h after transplant. The PO(2)/FiO(2) levels in both groups then increased and became similar at 6 h after transplant, regardless of whether ischemic or non-ischemic lungs (p &lt; 0.001 and p = 0.004, respectively) were used. Conclusions: Negative effects of the ex vivo system were limited and seen only in the immediate post-transplant period. Therefore, in DCD swine lung transplantation, the ex vivo system appears to be safe. (C) 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ejcts.2010.12.071

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BACKGROUND: The start of warm ischemic time -(WIT) of donor lungs in donation after cardiac death (DCD) is not clearly defined. We investigated the effect of donor pre-mortem hypotension and hypoxia to determine which physiologic factor is the determinant of WIT onset in controlled DCD lung transplantation.
METHODS: Twenty mechanically-ventilated donor pigs were placed in 4 groups (n = 5 each) and exposed to each of the pseudo-agonal conditions for 60 minutes: (I) control group, no intervention and optimum ventilation, followed by cardiac arrest; (2) hypotension (HT) group, controlled cardiac tamponade reducing systolic blood pressure to &lt;50 mm Hg, followed by cardiac arrest; (3) hypoventilation (HV) group, ventilation with room air at 5 breaths/min, followed by cardiac arrest; (4) non-circulation (NC) group, initial cardiac arrest, followed by a 60-minute standoff time. The lung graft was retrieved and the left lung was transplanted to the recipient. Graft function was evaluated for 4 hours after contralateral pulmonary artery ligation. The reperfusion injury was evaluated based on tissue cytokine expression, wet weight-to-dry weight ratio, and histology at the end of the reperfusion period.
RESULTS: Impaired post-transplant graft function was seen in the HV group, which had significantly poorer oxygenation during the reperfusion period than the other groups (p &lt;0.001). The HV group also had higher tissue levels of interleukin-8 (p &lt;0.05), a higher wet weight-to-dry weight ratio (p &lt; 0.05), and histologic findings of graft tissue injury than the control group. The difference in these parameters among the control, HT, and NC groups was not significant.
CONCLUSIONS: Only pre-mortem hypoxia provoked by hypoventilation significantly impaired lung graft function in DCD lung transplantation. Ventilatory rather than circulatory deterioration can trigger the onset of warm ischemia. J Heart Lung Transplant 2011;30:445-51 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

DOI： 10.1016/j.healun.2010.11.010

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Language：Japanese   Publisher：岡山医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. Lung grafts can be perfused ex vivo for 2 hours without edema formation; however, prolonged ex vivo lung perfusion (EVLP) eventually induces lung injury. This study evaluated the change in proinflammatory cytokines of the perfusate during EVLP and investigated the effect of cytokine removal using an adsorbent membrane.
Methods. Porcine heart-lung blocks were harvested after electrically induced cardiac arrest and underwent 12-hour EVLP with an adsorbent membrane (membrane group: n = 5) and without an adsorbent membrane (control group: n = 6).
Results. In the control group, both tumor necrosis factor-alpha and interleukin 8 levels were elevated in the perfusate 2 hours after perfusion. Although tumor necrosis factor-alpha and interleukin 8 levels were significantly lower in the membrane group than in the control group during the EVLP period, there was no significant difference in oxygenation, pulmonary vascular resistance, edema formation, or myeloperoxidase activity between the two groups.
Conclusions. Tumor necrosis factor-alpha and interleukin 8 levels of the perfusate were elevated during EVLP. Although adverse effects of these inflammatory cytokines were anticipated, removal of inflammatory cytokines by the adsorbent membrane did not improve lung function during prolonged EVLP. Factors other than the cytokines may play a major role in causing lung injury during EVLP. Further research is needed to investigate the real mechanism of lung graft injury during prolonged EVLP and to establish longer EVLP duration for graft treatment. This strategy could contribute to the salvage of potentially damaged lungs, especially from cardiac death donors, and to expansion of the donor pool. (Ann Thorac Surg 2010; 89: 1773-81) (C) 2010 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2010.02.077

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2008&ichushi_jid=J00298&link_issn=&doc_id=20080521390055&doc_link_id=10.18907%2Fjjsre.30.Special_S98_3&url=https%3A%2F%2Fdoi.org%2F10.18907%2Fjjsre.30.Special_S98_3&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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DOI： 10.18907/jjsre.30.Special_S98_3

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DOI： 10.2995/jacsurg.21.361_1

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DOI： 10.2995/jacsurg.20.768_2

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DOI： 10.1016/j.healun.2021.01.995

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DOI： 10.1016/j.jtho.2019.08.1994

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DOI： 10.1016/j.healun.2019.01.1036

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DOI： 10.1016/j.healun.2019.01.077

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DOI： 10.1016/j.healun.2019.01.853

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DOI： 10.1016/j.healun.2018.01.1186

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DOI： 10.1016/j.healun.2018.01.509

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DOI： 10.1016/j.healun.2018.01.570

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DOI： 10.1016/j.healun.2018.01.520

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＜Point＞COPDの肺移植適応基準には,1秒量に加え,全身機能や栄養状態も含まれる.肺移植医への紹介は,肺移植適応となる前段階(55歳未満,HOT導入時)が望ましい.日本のCOPDに対する肺移植はほとんどが脳死片肺移植で,その成績は良好である.(著者抄録)

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DOI： 10.1016/j.healun.2016.01.1052

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DOI： 10.1016/j.healun.2016.01.676

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

researchmap

Language：English   Publisher：Elsevier {BV}  

DOI： 10.1016/j.healun.2016.01.880

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Language：English   Publisher：Elsevier {BV}  

DOI： 10.1016/j.healun.2016.01.1064

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Language：English   Publisher：Elsevier {BV}  

DOI： 10.1016/j.healun.2016.01.396

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Language：English   Publisher：Elsevier {BV}  

DOI： 10.1016/j.healun.2016.01.037

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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