Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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

Extended thymectomy is a procedure to remove the thymus gland and surrounding adipose tissue, while the traditional approach via a median sternotomy, minimally invasive approaches such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) have been adopted. This report described the technique of bilateral approach for extended thymectomy in patients with myasthenia gravis (MG) by robot-assisted thoracoscopic surgery, and also showed the perioperative outcomes and postoperative exacerbation rates of 11 patients. In most patients, score of MG symptom were reduced and levels of anti-acetylcholine receptor antibodies declined postoperatively. In a small number of cases, the safety and efficacy of a RATS bilateral approach for extended thymectomy were confirmed.

PubMed

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

ABO-incompatible transplantation has been successfully performed in the kidney and liver. However, lungs are subject to strong rejection and are vulnerable to infection because they are directly exposed to air. Therefore, lung transplantation from organs with incompatible blood types has been considered a significant challenge. Due to the severe shortage of donors, ABO-incompatible lung transplantation might be a viable method to save critically ill patients with end-stage respiratory diseases. Herein, we review the worldwide published reports about both minor and major ABO-incompatible lung transplantations. In North America, major ABO-incompatible lung transplants have been performed in cases with clerical errors in blood typing. But they were successful with additional treatments following the protocol for ABO-incompatible transplants in other organs (multiple plasma exchanges and additional immunosuppressive therapy such as anti-thymocyte globulin administration). In Japan, major ABO-incompatible living-donor lobar lung transplantations have also been performed successfully when the recipient does not have an ABO antibody against the donor. This unique situation sometimes occurs when the recipient undergoes hematopoietic stem cell transplantation before lung transplantation, in which the recipient's blood type changes after hematopoietic stem cell transplantation. One infant and one adult had successful intentional major ABO-incompatible lung transplantation with both induction therapy and aggressive maintenance antibody-depletion therapy. Furthermore, an experimental antibody-depletion study has also been conducted to overcome ABO incompatibility. Even though intentional major ABO-incompatible lung transplantation has rarely been performed, several significant pieces of evidence have been accumulated to prepare for ABO-incompatible lung transplantation in selected cases. In the future, this challenge can potentially expand the donor organ pool and lead to improvements in the fairness of organ allocation.

DOI： 10.21037/jtd-23-48

Scopus

PubMed

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

BACKGROUND: Hyperparathyroidism in patients with multiple endocrine neoplasia 1 is attributed to the excessive secretion of parathyroid hormone (PTH) from multiple parathyroid glands. This can be successfully treated through complete resection of the parathyroid glands; however, subsequent surgery is often required because of the presence of supernumerary or ectopic parathyroid glands. Therefore, identifying the locations of all functional glands is crucial for precise resection. Here, we report a case of ectopic mediastinal parathyroid adenoma that was successfully resected using robot-assisted thoracoscopic surgery. CASE PRESENTATION: A 53-year-old woman underwent a total parathyroidectomy with autotransplantation for multiple endocrine neoplasia 1-associated primary hyperparathyroidism. The patient previously underwent laparoscopic distal pancreatectomy for a pancreatic neuroendocrine tumor. She also presented with a mediastinal tumor and nonfunctional pituitary adenoma that could be followed up. Blood tests before total parathyroidectomy showed high levels of intact PTH (183 pg/mL) and calcium (Ca; 10.3 mg/dL); however, postoperative blood tests still revealed high levels of intact PTH (103 pg/mL) and Ca (11.4 mg/dL). Computed tomography and magnetic resonance imaging revealed a 45-mm-sized mass in the right upper mediastinum as a well-defined solid and cystic lesion, whereas 99mTc-methoxyisobutylisonitrile scintigraphy indicated a strong accumulation of tracers, suggesting an ectopic lesion in the mediastinum. Persistent hyperparathyroidism after total parathyroidectomy via neck incision was attributed to an ectopic parathyroid tumor in the mediastinum. Thus, we decided to resect the tumor using robot-assisted thoracoscopic surgery to perform the procedure gently and carefully. During surgery, a mediastinal tumor was identified as it was detected radiographically. Because it did not invade the surrounding tissues, it could be completely resected without injuring the capsule. The patient was discharged without complications. Postoperatively, Ca and intact PTH levels decreased back to normal. The final pathological diagnosis confirmed that the mass was an ectopic mediastinal parathyroid adenoma. CONCLUSIONS: Minimally invasive surgical resection of a remnant ectopic lesion was successfully performed in a patient with multiple endocrine neoplasia 1 using robot-assisted thoracoscopic surgery.

DOI： 10.1186/s40792-023-01694-9

PubMed

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

PURPOSE: Minimally invasive surgery (MIS) using a thoraco- or laparoscope is becoming a more common surgical technique. In MIS, a magnified view from a thoracoscope helps surgeons conduct precise operations. However, there is a risk of the visible area becoming narrow. To confirm that the operation field is safe, the surgeon will draw the thoracoscope back to check the marginal area of the target and insert it again many times during MIS. To reduce the surgeon's load, we aim to visualize the entire thoracic cavity using a newly developed device called "panorama vision ring" (PVR). METHOD: The PVR is used instead of a wound retractor or a trocar. It is a ring-type socket with one big hole for the thoracoscope and four small holes for tiny cameras placed around the big hole. The views from the tiny cameras are fused into one wider view that visualizes the entire thoracic cavity. A surgeon can proceed with an operation by checking what exists outside of the thoracoscopic view. Also, she/he can check whether or not bleeding has occurred from the image of the entire cavity. RESULTS: We evaluated the view-expansion ability of the PVR by using a three-dimensional full-scale thoracic model. The experimental results showed that the entire thoracic cavity could be visible in a panoramic view generated by the PVR. We also demonstrated pulmonary lobectomy in virtual MIS using the PVR. Surgeons could perform a pulmonary lobectomy while checking the entire cavity. CONCLUSION: We developed the PVR, which uses tiny auxiliary cameras to create a panoramic view of the entire thoracic cavity during MIS. We aim to make MIS safer for patients and more comfortable for surgeons through the development of the PVR.

DOI： 10.1007/s11548-023-02859-5

Scopus

PubMed

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

Resection Process Map (RPM) is a surgical simulation system that uses preoperative three-dimensional computed tomography. Unlike the usual static simulation, this system provides surgeons an individualized dynamic deformation of the lung parenchyma and vessels. RPM was first introduced in 2020. Although the intraoperative usefulness of this system has been evaluated experimentally, there have been no reports on its clinical use. Herein, we presented in detail the first experience on RPM during robot-assisted anatomical lung resection in the real clinical setting.

DOI： 10.1093/icvts/ivad059

PubMed

Publisher：南江堂  

DOI： 10.15106/j_kyobu76_313

CiNii Research

Language：English  

Here we report the cases of five patients on continuous ambulatory peritoneal dialysis (CAPD) who developed hydrothorax because of pleuroperitoneal communication. Preoperative computed tomography (CT) peritoneography revealed penetrated sites on the diaphragm in all patients. All patients underwent video-assisted thoracoscopic surgery (VATS), and a dialysate containing indigo carmine was injected intraperitoneally through a CAPD catheter to confirm the fistula. In all patients, a thinned bleb was found at the center of the diaphragmatic tendon consistent with that noted on preoperative CT peritoneography. The bleb was resected using a surgical stapler in four patients, and the pleuroperitoneal communication did not recur. However, in one patient, the bleb was only covered with reinforcement agents and the hydrothorax recurred after CAPD. This study demonstrates that VATS treatment for pleuroperitoneal communication is safe and effective but that lesion resection would be more useful for preventing hydrothorax recurrence in patients undergoing CAPD.

DOI： 10.1111/ases.13127

Scopus

PubMed

Publisher：iScience  

The potential of extrapulmonary ventilation pathways remains largely unexplored. Here, we assessed the enteral ventilation approach in hypoxic porcine models under controlled mechanical ventilation. 20 mL/kg of oxygenated perfluorodecalin (O2-PFD) was intra-anally delivered by a rectal tube. We simultaneously monitored arterial and pulmonary arterial blood gases every 2 min up to 30 min to determine the gut-mediated systemic and venous oxygenation kinetics. Intrarectal O2-PFD administration significantly increased the partial pressure of oxygen in arterial blood from 54.5 ± 6.4 to 61.1 ± 6.2 mmHg (mean ± SD) and reduced the partial pressure of carbon dioxide from 38.0 ± 5.6 to 34.4 ± 5.9 mmHg. Early oxygen transfer dynamics inversely correlate with baseline oxygenation status. SvO2 dynamic monitoring data indicated that oxygenation likely originated from the venous outflow of the broad segment of large intestine including the inferior mesenteric vein route. Enteral ventilation pathway offers an effective means for systemic oxygenation, thus warranting further clinical development.

DOI： 10.1016/j.isci.2023.106142

Scopus

Publisher：Annals of surgical oncology  

DOI： 10.1245/s10434-022-12860-y

Scopus

Publisher：Annals of Surgical Oncology  

DOI： 10.1245/s10434-022-12844-y

Scopus

Publisher：Annals of Surgical Oncology  

Objectives: The rates of postoperative mortality and morbidity are high in patients with malignant pleural mesothelioma (MPM). Therefore, it is important to identify variables that increase the risk of postoperative complications. Pleural thickness has recently been identified as a prognostic indicator in patients with MPM. The aim of this study was to investigate clinical variables, including pleural thickness, that contribute to postoperative complications in patients with MPM. Patients and Methods: A total of 47 patients who underwent surgical excision of MPM between 2005 and 2021 were enrolled in this study. Correlations between postoperative complications within 90 days of surgery and preoperative clinical factors were investigated. Results: A total of 27 patients underwent extrapleural pneumonectomy (EPP), and the remaining 20 underwent pleurectomy/decortication (P/D). Macroscopic complete resections were obtained in all but three patients. Of the 47 patients, 23 (49%) experienced postoperative complications of grade 3 or worse. The major complication in patients with EPP was respiratory failure (n = 6), whereas the major complication in patients with P/D was prolonged air leakage (n = 7). Univariate logistic regression analysis found a correlation between postoperative complications and age, surgical side, and pleural thickness, while multivariate logistic regression analysis found surgical side (p = 0.04, 95% Cl 1.10–21.71, OR 4.90) and pleural thickness (p = 0.03, 95% Cl 1.21–23.00, OR 5.26) to significantly influence the occurrence of postoperative complications. Conclusions: Pleural thickness has a significant effect on the occurrence of postoperative complications. Patients with thick pleura on the right side are at greater risk of postoperative complications.

DOI： 10.1245/s10434-022-12790-9

Scopus

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

BACKGROUND: The COVID-19 pandemic has affected the clinical practice of lung cancer surgery in Japan, but few studies have revealed the real situation of surgical practice for lung cancer in this country. This latest information will help us to decide the future direction of lung cancer surgery under pandemic circumstances. METHODS: We collected data from patients with primary lung cancer who underwent thoracic surgery between 2018 and 2021. To investigate the impact of the COVID-19 pandemic on lung cancer surgery, we compared between 2018-2019 (prepandemic group) and 2020-2021 (pandemic group) in the respect of patient characteristics, pathological findings, and short-term outcome after lung cancer resection by Mann-Whitney and Fisher's exact tests. Moreover, the monthly number of surgeries for lung cancer in our institution during 2020-2021 was compared with the number of newly diagnosed COVID-19 patients in Japan by Spearman correlation analysis. RESULTS: From 2018 through 2021, 936 patients with primary lung cancer underwent surgical intervention in our institute and were included in this study. The number of surgeries did not decrease in the pandemic group (n=443) compared with that in the prepandemic group (n=493). Tumor and invasive size in stage I which was measured by pathologist were significantly larger in the pandemic group than in the prepandemic group (tumor size: P=0.031, invasive size: P<0.001). In terms of postoperative short-term outcome, the median hospital stay was 6 days, 30-day mortality was 2, and morbidity was around 20% in both groups. Only one patient suffered from COVID-19 infection 5 months after right upper lobectomy. An increased ratio of newly diagnosed COVID-19 cases in Japan was negatively correlated with the number of surgeries for lung cancer in our institution in the next month (r=-0.393, P=0.007), although there was no correlation in the present or the month after next. CONCLUSIONS: Even during the COVID-19 pandemic period, lung cancer surgery could be performed safely and in a sustainable manner. However, pathological findings of lung cancer tended to be progressive in early-stage lung cancer.

DOI： 10.21037/jtd-22-1289

Scopus

PubMed

Language：Japanese   Publisher：Japan Society for Laser Surgery and Medicine  

<p>As radiological imaging has progressed, smaller nodules are more frequently detected. The trend of minimal invasiveness in thoracic surgery has paved the way for video-assisted thoracic surgery. In localization for small nodules and segmentectomy for such nodules, fluorescent dyes, such as indocyanine green (ICG) have been used more often. Therefore, we herein describe the utility of fluorescent imaging in the treatment of lung cancer, which is currently the mainstream of thoracic surgery, focusing on the clinical application of ICG.</p>

DOI： 10.2530/jslsm.jslsm-43_0012

CiNii Research

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

Patients with pulmonary graft-versus-host disease (pGVHD) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, pGVHD pathogenesis is not fully elucidated in humans, and currently available immunosuppressants are inadequately effective. We performed pathologic evaluation of lung specimens from 45 allo-HSCT recipients with pGVHD who underwent lung transplantation. Patient pathology was characterized by bronchiolitis and subpleural perivascular inflammation, with B-cell, monocyte, and T-cell accumulation around bronchioles. Bronchiolitis, perivascular inflammation, and peribronchial macrophage aggregation were also identified in a murine pGVHD model after transplant of bone marrow cells and splenocytes from C57BL/6 to B10.BR mice. Among mitogen-activated protein kinase kinase (MEK) inhibitors, cobimetinib, but not trametinib, improved survival rates. Cobimetinib attenuated bronchiolitis, improved airway resistance and lung compliance in the mice, and suppressed activation of B cells and tumor necrosis factor α production by monocytes in vitro; these features were not suppressed by trametinib or tacrolimus. Furthermore, cobimetinib suppressed activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, resulting in B-cell and monocyte suppression. Dual inhibition of the MEK/extracellular signal-regulated kinase (ERK) and PI3K/AKT pathways using a combination of trametinib and the PI3K inhibitor taselisib strongly suppressed B-cell activation in vitro and improved mouse survival rates compared with vehicle or monotherapy with trametinib or taselisib. Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, whereas B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans.

DOI： 10.1182/bloodadvances.2021006678

PubMed

Publisher：JTCVS Techniques  

DOI： 10.1016/j.xjtc.2023.07.026

Scopus

Publisher：Surgery Today  

Purpose: Patients with a thymic epithelial tumor (TET), comprising thymoma, thymic carcinoma (TC), and thymic neuroendocrine neoplasm (TNEN), are rarely encountered. The present study was conducted to determine the recent outcomes of surgical treatment for TET in Japan and clarify the significance of prognostic factors by analyzing a nationwide database created by the Japanese Association for Research on the Thymus (JART). Methods: The JART database includes records of 2471 thymoma, 285 TC, and 56 TNEN cases surgically treated between 1991 and 2010. At the time of the final follow-up examination, 439 patients had died, with tumor the cause of death in 188. The disease-specific survival was examined using the Kaplan–Meier method, with Cox’s proportional hazards model utilized to determine independent prognostic factors. Results: The 10-year survival rate according to TNM-based Stage I, II, IIIA, IIIB, IVA, and IVB classification was 98.7%, 76.8%, 85.0%, 68.9%, 66.2%, and 59.8%, respectively. The T factor, M factor, and tumor size were independent prognostic factors in both thymoma and thymic carcinoma cases, while the N factor had tendency to be a prognostic factor in thymoma but not in thymic carcinoma cases. The WHO histological type was an independent factor in thymoma cases. Conclusion: The significance of pathology and TNM classification as prognostic factors was confirmed.

DOI： 10.1007/s00595-023-02705-w

Scopus

Publisher：Surgery Today  

Purpose: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. Method: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients’ airways was evaluated preoperatively and postoperatively in intensive-care units. Results: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. Conclusions: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.

DOI： 10.1007/s00595-023-02730-9

Scopus

Language：English   Publisher：The Japan Society for Transplantation  

<p><b>【Background】</b> Few studies have assessed donor-specific antibodies (DSA) and anti-human leucocyte antigen (HLA) antibodies associated with the transplantation (Tx) of organs other than kidney.</p><p><b>【Methods】</b> A total of 31 institutions participated in the current study. Patients who satisfied the study criteria were enrolled prospectively, and rituximab was used according to each institution’s clinical protocol for desensitization before Tx when patients had preexisting DSA or anti-HLA antibodies (desensitization cohort) or to treat post-Tx antibody-mediated rejection (ABMR) (ABMR treatment cohort). The desensitization cohort comprised four liver transplants, four kidney-pancreas transplants, and one heart transplant, and the ABMR treatment cohort contained two liver transplants, two heart transplants, and one lung transplant. In the desensitization cohort, organs ultimately were not allocated for the patient awaiting a heart transplant and one patient awaiting a kidney-pancreas transplant.</p><p><b>【Results】</b> In the desensitization cohort, DSA or anti-HLA antibodies decreased in the four liver Tx patients and three of the kidney-pancreas Tx patients. Although T-cell mediated rejection occurred in two patients, they did not develop ABMR. One pancreatic graft was lost due to post-transplantation thrombosis; all other grafts and all patients survived. In the ABMR treatment cohort, DSA decreased after ABMR treatment in one heart Tx patient and two liver Tx patients. Acute ABMR was eliminated completely only in the patient who developed the complication early after liver Tx.</p><p><b>【Conclusion】</b> Rituximab was well-tolerated, both during desensitization and as part of ABMR treatment for Tx of organs other than kidney.</p>

DOI： 10.11386/jst.58.1_43

CiNii Research

Language：Japanese   Publisher：Scientific Reports  

Non-invasive analysis using computed tomography (CT) data may be a promising candidate to evaluate neo-alveolarization in adult lungs following lung resection. This study evaluates and compares the validity of CT analysis with histologic morphometry for compensatory lung growth in a large animal model. We calculated the radiologic tissue volume and the radiologic lung weight from CT data taken at 1, 3, and 6 months post-surgery on 15 male beagle dogs that had a right thoractotomy, bilobectomy, or pneumonectomy (n = 5 in each group). Results were analyzed using one-way ANOVA and were subsequently compared to histologic findings of tissue samples at 6 months post-surgery using Pearson’s correlation. An increase in radiologic tissue volume and radiologic lung weight was identified, which was positively correlated with histologic lung parenchymal amounts (correlation coefficient = 0.955 and 0.934, respectively, p < 0.001). Histology of lung specimens at 6 months post-surgery revealed an increase in the tissue amount in both Bilobectomy and Peumonectomy groups, which was consistent with compensatory lung growth. Radiologic tissue volume and radiologic lung weight reflected compensatory lung growth following lung resection. Radiologic assessment using CT data can be a promising clinical modality to evaluate postoperative lung growth.

DOI： 10.1038/s41598-022-06398-y

Scopus

Publisher：Cancer Science  

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB–IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25–1.08), all-randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.

DOI： 10.1111/cas.15564

Scopus

Publisher：Journal of Cancer Research and Clinical Oncology  

Purpose: Intratumoral macrophages are reportedly involved in tumor progression in non-small cell lung cancer; however, little is known about the prognostic impact and function of alveolar macrophages (AMs). This study aims to investigate the prognostic impact of the number of peri-tumoral AMs in patients with stage I lung adenocarcinoma. Methods: We investigated 514 patients with pathological stage I lung adenocarcinoma who underwent complete resection with lobectomy or pneumonectomy. The numbers of peri-tumoral AMs were counted, and patients were classified into two groups based on the number of peri-tumoral AMs. Using the Cancer Genome Atlas (TCGA) database of stage I lung adenocarcinoma, we compared gene expression profiles of high and low peri-tumoral AM contents. Results: The median number of peri-tumoral AMs per alveolar space was 15.5. Patients with a high peri-tumoral AM content had significantly shorter disease-free survival and overall survival than patients with a low peri-tumoral AM content (both p < 0.01). In the multivariate analyses, a higher number of peri-tumoral AMs were an independent prognostic factor (p = 0.02). The analysis of TCGA database revealed that patients with a high peri-tumoral AM content had shorter disease-free survival than those with a low peri-tumoral AM content (p = 0.04). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as chemotaxis and epithelial proliferation, in patients with a high peri-tumoral AM content. Conclusion: The number of peri-tumoral AMs had a strong impact on disease-free survival in patients with stage I lung adenocarcinoma.

DOI： 10.1007/s00432-022-04056-4

Web of Science

Scopus

Publisher：BMJ Surgery, Interventions, and Health Technologies  

Objectives Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: visualising anatomy, assessing tissue perfusion, identifying/localising cancer and mapping lymphatic systems. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging used to visualise anatomical structures using the IDEAL framework, a framework designed to describe the stages of innovation in surgery and other interventional procedures. Design IDEAL staging based on a thorough literature review. Setting All publications on intraoperative fluorescence imaging for visualising anatomical structures reported in PubMed through 2020 were identified for five surgical procedures: cholangiography, hepatic segmentation, lung segmentation, ureterography and parathyroid identification. Main outcome measures The IDEAL stage of research evidence was determined for each of the five procedures using a previously described approach. Results 225 articles (8427 cases) were selected for analysis. Current status of research evidence on fluorescence imaging was rated IDEAL stage 2a for ureterography and lung segmentation, IDEAL 2b for hepatic segmentation and IDEAL stage 3 for cholangiography and parathyroid identification. Enhanced tissue identification rates using fluorescence imaging relative to conventional white-light imaging have been documented for all five procedures by comparative studies including randomised controlled trials for cholangiography and parathyroid identification. Advantages of anatomy visualisation with fluorescence imaging for improving short-term and long-term postoperative outcomes also were demonstrated, especially for hepatobiliary surgery and (para)thyroidectomy. No adverse reactions associated with fluorescent agents were reported. Conclusions Intraoperative fluorescence imaging can be used safely to enhance the identification of anatomical structures, which may lead to improved postoperative outcomes. Overviewing current research knowledge using the IDEAL framework aids in designing further studies to develop fluorescence imaging techniques into an essential intraoperative navigation tool in each surgical field.

DOI： 10.1136/bmjsit-2022-000156

Scopus

Publisher：Respiratory Investigation  

Respiratory muscle weakness has attracted attention because sarcopenia and respiratory muscle dysfunction may play a key role in the development of respiratory failure. To evaluate respiratory muscle strength appropriately, individual factors such as sex, age, body size, and ethnicity should be considered. This study aimed to compare equations available in Japan and other countries for predicting respiratory muscle strength. We tested 21 equations for maximal inspiratory pressure (MIP) and 17 for maximal expiratory pressure (MEP) for each sex (76 equations in total) in 159 normal, healthy subjects. We observed wide variations in the overall agreement among the MIP and MEP equations. Some equations showed a proper normal distribution, with median values of almost 100%, and the Japanese equations released in 1997 generally showed the best distributions of both %MIP and %MEP. We can conclude that it is better to use Japanese equations when evaluating respiratory muscle strength in Japanese subjects.

DOI： 10.1016/j.resinv.2022.07.003

Scopus

Publisher：Journal of Thoracic Disease  

Background: Radial endobronchial ultrasonography transbronchial biopsy with and without a guide sheath is a useful method for diagnosing peripheral pulmonary lesions (PPLs). However, the diagnostic yield and complications of radial endobronchial ultrasonography transbronchial biopsy for PPLs remains elusive in patients with interstitial lung disease (ILD). Methods: We retrospectively analysed 431 patients (69 with and 362 without ILD) who underwent radial endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) for PPLs from April 1, 2011, to March 31, 2020. We investigated the diagnostic yield and complications of the procedure for PPLs and compared them between patients with and without ILD. We also evaluated the factors contributing to successful diagnosis. Results: The diagnostic yield of radial endobronchial ultrasonography in patients with ILD was significantly lower than in those without ILD (62.3% vs. 75.4%, P=0.024). Multivariate analysis showed that the presence of ILD as background lung [odds ratio (OR) =0.517], probe position within the lesion (OR =4.654), and the presence of solid lesion (OR =1.946) significantly affected the diagnostic yield of PPLs. There was a significant difference in the rate of pneumothorax between the patients with ILD and those without ILD (4.3% vs. 0.6%, P=0.031). Conclusions: The presence of ILD as the background lung significantly affected the diagnostic yield of PPLs with radial EBUS-GS TBB. Regarding the complications, pneumothorax occurred more frequently in patients with ILD than in those without ILD.

DOI： 10.21037/jtd-22-809

Scopus

Publisher：Anticancer Research  

Background/Aim: Multidisciplinary treatment including anatomical pulmonary and chest wall resection is recommended for lung cancer complicated by chest wall invasion. The present study aimed to investigate the survival benefit and safety of preoperative therapy followed by surgery for non-small cell lung cancer with chest wall invasion. Patients and Methods: Sixty-five patients who underwent surgical excision of lung cancer complicated with chest wall invasion between 2009 and 2020 were enrolled in this study. Results: The median age was 65 (37-81) years old, with 59 males and 6 females. Histological types included squamous cell carcinoma (n=32) and adenocarcinoma (n=21). The median tumor diameter was 5.5 cm (2.3-12.5 cm). The clinical nodal status was N0 in 49 cases and N positive in 16 cases. Of the 65 eligible patients, 5- and 10-year overall survival (OS) rates were 58.4% and 46.0%, respectively, and 5- and 10-year progression-free survival (PFS) rates were 54.2% and 41.7%, respectively. For patients receiving preoperative therapy followed by surgery (Pre-Tx), 5- and 10-year OS survival rates were 69.2% and 62.9%, and among patients receiving up-front surgery (UFS) were 48.5% and 29.1%, respectively (p=0.03). The 5- and 10-year PFS rates for pre-Tx were 65.8% and 59.2%, respectively, and 44.7% and 26.8% for UFS, respectively (p=0.02). Cox regression analysis preoperative therapy was significantly associated with OS and PFS. Conclusion: We demonstrate the survival benefit of preoperative therapy followed by surgery for patients with lung cancer and chest wall invasion.

DOI： 10.21873/anticanres.16059

Scopus

Publisher：JTCVS Techniques  

Objective: Prolonged air leak is the most common complication of thoracic surgery. Intraoperative leak site detection is the first step in decreasing the risk of leak-related postoperative complications. Methods: We retrospectively reviewed the surgical videos of patients who underwent lung resection at our institution. In the training phase, deep learning-based air leak detection software was developed using leak-positive endoscopic images. In the testing phase, a different data set was used to evaluate our proposed application for each predicted box. Results: A total of 110 originally captured and labeled images obtained from 70 surgeries were preprocessed for the training data set. The testing data set contained 64 leak-positive and 45 leak-negative sites. The testing data set was obtained from 93 operations, including 58 patients in whom an air leak was present and 35 patients in whom an air leak was absent. In the testing phase, our software detected leak sites with a sensitivity and specificity of 81.3% and 68.9%, respectively. Conclusions: We have successfully developed a deep learning-based leak site detection application, which can be used in deflated lungs. Although the current version is still a prototype with a limited training data set, it is a novel concept of leak detection based entirely on visual information.

DOI： 10.1016/j.xjtc.2022.06.011

Scopus

Publisher：Journal of Thoracic Disease  

DOI： 10.21037/jtd-22-951

Scopus

Publisher：Lung Cancer  

Objective: The COVID-19 pandemic has far-reaching collateral health impacts on the ongoing delivery of surgical care worldwide. The current study was designed to analyze the impact of the COVID-19 pandemic on the number of surgeries of general thoracic surgery in Japan. Methods: Changes in the number of surgeries for total and three representative tumors were analyzed using the National Clinical Database data with reference to the pandemic infection rate and lung cancer screening. Results: In 2020, the number of surgeries in total and for primary lung cancer and mediastinal lung tumor decreased by 4.9, 5.1, and 5.0 %, respectively. Considering the five-year trend towards a 5 % annual increase, there was a potential 10 % decrease in the number of primary lung cancer surgeries. The number of primary lung cancer surgeries bottomed in July 2020 but recovered towards the end of the year. In contrast, the number of metastatic lung tumor surgeries in 2020 increased by 3.2 %, following a similar trend observed over the previous five years. The number of lung cancer screening examinees decreased markedly with the lowest number in May. Our findings indicate that surgical triage had a limited impact on the decrease in primary lung cancer surgeries during the pandemic; rather, the decrease in lung cancer screening, which was a few months preceding, is most likely responsible. Conclusions: The decrease in primary lung cancer was mainly caused by the decrease in lung cancer screening, indicating that continuing screening is vital even during a pandemic.

DOI： 10.1016/j.lungcan.2022.08.011

Scopus

Publisher：Respirology  

Background and objective: Bronchoscopy is an airborne particle-generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, we created an ‘e-mask’, which is a simple, disposable mask for patients. Our objective was to evaluate the e-mask's protective ability against airborne particles and to assess respiratory adverse events and complications. Methods: Patients with stage 2–4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e-mask. We prospectively evaluated whether wearing the e-mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end-tidal carbon dioxide (EtCO2) elevation, in addition to complications, compared to historical controls. Results: In the visualization experiment, more than ten thousand times of airborne particles were generated without the e-mask than with the e-mask. The volume of airborne particles was significantly reduced with the e-mask, compared to that without the e-mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e-mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e-mask was a significant factor in >45 mm Hg EtCO2 elevation (p = 0.026). No significant differences in complications were observed between the e-mask and control groups (5.8% vs. 2.5%, p = 0.395). Conclusion: Wearing the e-mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications.

DOI： 10.1111/resp.14321

Scopus

Publisher：Clinical Physiology and Functional Imaging  

Background: Postoperative loss of exercise capacity and pulmonary function is a major concern among lung cancer patients. In this study, the time for a stair-climbing to 12-m height was used to investigate whether preoperative chest 3D-computed tomography (CT) could be a useful tool for predicting postoperative variations in exercise capacity and pulmonary function. Methods: Seventy-eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enroled. Preoperatively, lobe volume and low attenuation volume (LAV) were evaluated using the SYNAPSE VINCENT system. Preoperative data on stair-climbing time, spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) at baseline and 6-month postoperative data were used to evaluate variations in exercise capacity and pulmonary function. Maximal oxygen uptake (VO2t) was evaluated based on the stair-climbing time. Results: Significant differences in the variation of exercise capacity at 6 months postoperatively were found between the groups categorized by target lobe volume and LAV status: The large volume/LAV (+) group had a greater decline in VO2t. Mean loss of VO2t was −6.2%, −1.4%, −1.6% and −0.1% in the large volume/LAV (+), large volume/LAV (−), small volume/LAV (+) and small volume/LAV (−) groups, respectively. The large volume/LAV (−) group had a greater decline in forced expiratory volume in 1 s. The small volume/LAV (+) group showed a reduced decline in the DLCO. Conclusions: Analysis of chest 3D-CT scans is a potential tool for predicting the loss of exercise capacity and pulmonary function after lung lobectomy.

DOI： 10.1111/cpf.12777

Scopus

Web of Science

Publisher：Journal of Thoracic Disease  

Background: Sarcopenia and its marker, the psoas muscle index (PMI), have attracted attention as prognostic factors for various types of cancers. The fragile X-related 1 (FXR1) gene is highly expressed in myocytes, and FXR1 overexpression is a candidate biomarker for poor survival in several types of cancers. Thymic squamous cell carcinoma (TSQCC) is rare, and no studies assessing its prognostic factors, particularly in terms of skeletal muscle mass and FXR1 expression, are available. Methods: We retrospectively investigated the prognostic significance of PMI in 34 patients who underwent TSQCC resection, considering the status of FXR1 and tumor programmed death-ligand 1 (PD-L1). PMI was calculated from the bilateral psoas muscle using preoperative computed tomography (CT). Patients were divided into two groups: low PMI (<58.2%, n=17) and normal PMI (≥58.2%, n=17). Immunohistochemical analysis was performed to determine the FXR1 and PD-L1 expression levels. Results: Low PMI was significantly associated with worse overall survival (OS) (5-year survival rate; 86% vs. 100%; P=0.026) and marginally associated with worse disease-free survival (DFS) (5-year survival rate; 39% vs. 66%; P=0.090) compared with normal PMI. The immunohistochemical analysis revealed that the FXR1 intensity score (0–1+: 6% vs. 0%; 2+–3+: 94% vs. 100%; P=0.31), median FXR1 distribution (95% vs. 90%; P=0.63), and PD-L1 status (high: 47% vs. 59%; P=0.49) were not significantly different between the two groups. Conclusions: Our findings suggest that PMI might be considered as a potential prognostic factor in TSQCC and that FXR1 is widely expressed regardless of the PMI status. Skeletal muscle mass may play a role in the prognosis of TSQCC.

DOI： 10.21037/jtd-22-385

Scopus

Publisher：JTCVS Open  

DOI： 10.1016/j.xjon.2022.05.016

Scopus

Publisher：European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery  

OBJECTIVES: The incidence of postoperative complications is relatively high in smokers. Although 4-week smoking cessation before surgery is generally recommended, it has not been sufficiently studied in lung cancer surgery. This study investigated whether smoking cessation for a short period of time significantly reduced complications after lung cancer surgery. METHODS: This was a retrospective, observational study that investigated the relationship between the smoking cessation period and the incidence of complications in lung cancer surgery. Patients who underwent curative-intent surgery for lung cancer at our institution between January 2014 and December 2017 were included. The smokers were classified into the following 4 categories of smoking cessation period before surgery: current (<4 weeks), recent (4 weeks to 12 months), distant (12 months to 5 years) and ex-smokers (>5 years). RESULTS: A total of 911 patients were included in this study. The incidence of pulmonary complications was 5 times higher in the smoker group than in the never smoker group (12.9% vs 2.5%, P < 0.001). On multivariable analysis in both models, the odds ratio for complications was significantly higher in distant smokers than in recent smokers and never smokers. Across all models, low lung function significantly predicted the development of postoperative complications. CONCLUSIONS: The evidence-based smoking cessation duration that reduces the incidence of complications after thoracic surgery remains unclear. The incidence of postoperative complications was more strongly affected by low pulmonary function than by the duration of preoperative smoking cessation. For patients with marginal indications for surgery, postponing surgery to accommodate a smoking cessation period seemed unnecessary.

DOI： 10.1093/ejcts/ezac163

Scopus

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

BACKGROUND: Empyema is a serious complication of lung surgery. CASE PRESENTATION: We report a case of Streptococcus anginosus empyema complicated by descending necrotizing fasciitis after surgery. Ten days after the initial surgery, the patient presented with arrhythmia and hypotension with septic shock. Pleural fluid analysis led to the diagnosis of empyema, and surgical debridement (second surgery) was performed. One week after the emergency surgery, a palpable pink erythematous skin change was observed on the ipsilateral iliac crest. Hence, the second emergency surgery (third surgery) was performed to debride the subcutaneous and intramuscular abscesses. CONCLUSIONS: The possibility of descending abscess and necrotizing fasciitis should be considered when Streptococcus anginosus is detected.

DOI： 10.1186/s40792-022-01492-9

PubMed

Publisher：Physiotherapy Research International  

Background and Purpose: Though inspiratory muscle strength is essential for patients with respiratory disease, it is unclear whether the recovery of inspiratory muscle strength contributes to an exemplary achievement of exercise tolerance after lung transplantation (LTx). We aimed to elucidate the inspiratory muscle strength affects the recovery of exercise capacity after LTx. Methods: Recipients who underwent LTx between June 2017 and September 2018 were enrolled, and 6-min walking distance (6MWD), quadriceps force, inspiratory muscle strength (maximal inspiratory pressure [MIP]), and spirometry were evaluated at 3, 6, and 12 months after LTx. The relationships between inspiratory muscle strength and changes in physical performance were analyzed. Results: Nineteen recipients (mean age: 44.8 years, male: 32%) who completed all follow-ups were analyzed. At 3 months after LTx, mean MIP (88.4% predicted) and vital capacity (60.9% predicted), quadriceps force (QF; 2.1 N*m/kg), and 6MWD (504 m) were lower than normal values. After LTx, 6MWD significantly improved up to 12 months. From 3 to 6 months after LTx, changes in MIP were significantly associated with increases in 6MWD by univariate (r = 0.55, p = 0.02) and multivariate (β = 0.59, p = 0.01) regression analyses, whereas changes of QF in place of MIP were significantly associated with the recoveries of 6MWD from 6 to 12 months. Discussion: Improvements in MIP may impact the recovery of exercise capacity in the early phase after LTx. Factors that determine the improvement in exercise capacity following LTx may vary with postoperative time.

DOI： 10.1002/pri.1951

Scopus

Language：Japanese   Publisher：Life science alliance  

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

DOI： 10.26508/lsa.202101230

Scopus

Publisher：南江堂  

DOI： 10.15106/j_kyobu75_436

CiNii Research

Publisher：JTCVS Techniques  

DOI： 10.1016/j.xjtc.2022.03.001

Scopus

Publisher：Transplant Infectious Disease  

Background: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. Methods: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. Results: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. Conclusions: This nationwide survey revealed for the first time how living donor liver and kidney: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

DOI： 10.1111/tid.13845

Scopus

Publisher：Interactive Cardiovascular and Thoracic Surgery  

OBJECTIVES: Recently, preoperative and intraoperative simulation using three-dimensional computed tomography (CT) has attracted much attention in thoracic surgery. However, because conventional three-dimensional CT only shows static images, dynamic simulation is required for a more precise operation. We previously reported on a resection process map for pulmonary resection, which we developed to generate virtual dynamic images from preoperative patient-specific CT scans. The goal of this study was to evaluate the feasibility of the clinical use of the resection process map for anatomical lung resection. METHODS: This study included 5 lobectomies for different lobes and 4 representative segmentectomies. Dissection of the pulmonary arteries, veins and bronchi were considered key parts of each procedure. To assess the description of images obtained from the resection process map, relevant clips from the actual surgical videos were collected, retrospectively replicated and superimposed on the resection process map to explain the procedures. RESULTS: In all surgical procedures, the resection process map successfully and semiautomatically generated a virtual dynamic image from the patient-specific CT data. Moreover, superimposition of the virtual images on the selected clips from the surgical videos showed no major differences. CONCLUSIONS: The resection process map could generate virtual images that corresponded to the actual surgical videos and has the potential for clinical use as preoperative and intraoperative simulation.

DOI： 10.1093/icvts/ivab379

Scopus

Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.73.112

CiNii Research

Language：Japanese   Publisher：World Journal of Surgery  

Background: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. Methods: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. Results: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27–2.92, 2.01–5.58, 3.64–23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. Conclusions: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

DOI： 10.1007/s00268-021-06427-3

Scopus

Language：English   Publisher：The Pharmaceutical Society of Japan  

<p>Invasive <i>Aspergillus</i> infection is a major factor for poor prognosis in patients receiving lung transplantation (LT). An antifungal agent, itraconazole (ITCZ), that has antimicrobial activity against <i>Aspergillus</i> species, is used as a prophylactic agent against <i>Aspergillus</i> infection after LT. ITCZ and its metabolite, hydroxyitraconazole (OH-ITCZ), potently inhibit CYP3A and P-glycoprotein that metabolize or excrete calcineurin inhibitors (CNIs), which are the first-line immunosuppressants used after LT; thus, concomitant use of ITCZ and CNIs could induce an increase in the blood concentration of CNIs. However, no criteria for dose reduction of CNIs upon concomitant use with ITCZ in LT recipients have been defined. In this study, the effect of ITCZ and OH-ITCZ on the blood concentrations of two CNIs, tacrolimus and cyclosporine, after LT were retrospectively evaluated. A total of 39 patients who received LT were evaluated. Effects of ITCZ and OH-ITCZ on the concentration/dosage (C/D) ratio of tacrolimus and cyclosporine were analyzed using linear mixed-effects models. The plasma concentrations of OH-ITCZ were about 2.5-fold higher than those of ITCZ. Moreover, there was a significant correlation between the plasma concentrations of ITCZ and OH-ITCZ. Based on parameters obtained in the linear regression analysis, the C/D ratios of cyclosporine and tacrolimus increase by an average of 2.25- and 2.70-fold, respectively, when the total plasma concentration of ITCZ plus OH-ITCZ is 1000 ng/mL. In conclusion, the plasma levels of ITCZ and OH-ITCZ could be key factors in drawing up the criterion for dose reduction of CNIs.</p>

DOI： 10.1248/bpb.b21-00738

Scopus

CiNii Research

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

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

DOI： 10.1007/s11748-022-01774-x

PubMed

Language：Japanese   Publisher：Annals of surgical oncology  

DOI： 10.1245/s10434-021-10969-0

Scopus

Language：Japanese   Publisher：Histopathology  

Aims: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. Methods and results: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Conclusions: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

DOI： 10.1111/his.14595

Scopus

Language：Japanese   Publisher：Annals of Surgical Oncology  

Background: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. Methods: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. Results: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). Conclusion: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

DOI： 10.1245/s10434-021-10888-0

Scopus

Language：Japanese   Publisher：Journal of the National Cancer Institute  

Background: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN, a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD. Methods: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. Results: SRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P <. 001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P =. 03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism. Conclusions: Our findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.

DOI： 10.1093/jnci/djab183

Scopus

Language：Japanese   Publisher：Supportive Care in Cancer  

Purpose: Late-onset non-infectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation are fatal; however, lung transplantation might achieve good survival. Nevertheless, improving the health-related quality of life (HRQoL) is still a major concern. This study aimed to investigate, in detail, the recovery in HRQoL and social reintegration status after lung transplantation in patients with LONIPC after allo-HSCT. Methods: This prospective cohort study involving 18 patients examined changes in the health and social reintegration status after lung transplantation following LONIPC. Results: Physical function and HRQoL were lowest before lung transplantation. Two years after lung transplantation, the dyspnea scores and performance status improved. Most patients had made a successful return to society, and patients who achieved social reintegration were significantly younger and had a good performance status. However, their Physical Functioning score and Physical Component Summary did not show significant improvement after lung transplantation. Moreover, recipients who were unemployed before lung transplantation were likely to remain unemployed and continued to show poor HRQoL. Conclusions: These results showed poor recovery of HRQoL, especially in terms of physical function, and the likelihood of failure to reintegrate into society within 2 years after lung transplantation. It is necessary to consider long-term follow-up and physical training to improve social reintegration and HRQoL.

DOI： 10.1007/s00520-021-06592-0

Scopus

Language：Japanese   Publisher：Journal of Thoracic and Cardiovascular Surgery  

Background: Necroptosis plays an important role in cell death during pulmonary ischemia-reperfusion injury (IRI). We hypothesized that therapy with necrosulfonamide (NSA), a mixed-lineage kinase domain-like protein inhibitor, would attenuate lung IRI. Methods: Rats were assigned at random into the sham operation group (n = 6), vehicle group (n = 8), or NSA group (n = 8). In the NSA and vehicle groups, the animals were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes, followed by reperfusion for 120 minutes. NSA (0.5 mg/body) and a solvent were administered i.p. in the NSA group and the vehicle group, respectively. The sham group underwent 210 minutes of perfusion without ischemia. After reperfusion, arterial blood gas analysis, physiologic data, lung wet-to-dry weight ratio, histologic changes, and cytokine levels were assessed. Fluorescence double immunostaining was performed to evaluate necroptosis and apoptosis. Results: Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) was better, dynamic compliance was higher, and mean airway pressure and lung edema were lower in the NSA group compared with the vehicle group. Moreover, in the NSA group, lung injury was significantly alleviated, and the mean number of necroptotic cells (55.3 ± 4.06 vs 78.2 ± 6.87; P =.024), but not of apoptotic cells (P =.084), was significantly reduced compared with the vehicle group. Interleukin (IL)-1β and IL-6 levels were significantly lower with NSA administration. Conclusions: In a rat model, our results suggest that NSA may have a potential protective role in lung IRI through the inhibition of necroptosis.

DOI： 10.1016/j.jtcvs.2021.01.037

Scopus

Language：Japanese   Publisher：Frontiers in Cell and Developmental Biology  

Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones.

DOI： 10.3389/fcell.2021.694018

Scopus

Language：Japanese   Publisher：Cancer Science  

The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non–small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P =.0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P =.0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P =.0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).

DOI： 10.1111/cas.15171

Scopus

Publisher：Nagoya Journal of Medical Science  

We report the case of a 20-year-old woman with carinal adenoid cystic carcinoma who underwent left sleeve pneumonectomy in the left lateral decubitus position, during which severe desaturation was encountered. After transecting the left main bronchus, the left lung was selectively intubated and ventilated. However, oxygenation was inadequate. Hence, venoarterial extracorporeal membrane oxygenation (ECMO) was introduced. Initially, Barclay’s procedure was planned to preserve the left lung, but this plan was altered due to the extent of the tumor and unstable ventilation. After the lesion was removed, the trachea and right main bronchus were anastomosed end-to-end. During left pneumonectomy, the right lung was selectively ventilated, but oxygen saturation (SpO2) dropped to <70% despite ECMO. SpO2 improved on additionally ventilating the left lung using another breathing circuit. Temporary right chest closure was performed with ventilation of the left lung across the thoracotomy wound. The patient was turned to the semi-supine position, and tolerated selective right lung ventilation with ECMO. Subsequently, left thoracotomy and pneumonectomy were successfully performed. Careful management is required for desaturation in left sleeve pneumonectomy in the left lateral decubitus position.

DOI： 10.18999/nagjms.84.3.673

Scopus

Publisher：General Thoracic and Cardiovascular Surgery  

Objective: This study aimed to demonstrate to the involved departments the goal of increasing the number of robotic-assisted thoracic surgery (RATS) cases/surgeons and acceptable surgery times. Methods: This retrospective study included 1572 patients who underwent thoracic surgery from fiscal year (FY) 2018 to FY 2021. The factors evaluated included the number of surgery cases and actual and scheduled surgery times. Results: The total number of RATS and total surgery cases increased after the quality indicator (QI) setting (n = 363, 360, 417, and 432 in FY 2018, 2019, 2020, and 2021, respectively). In FY 2020, 93.3% of the QI target was achieved, while in FY 2021, 88% was achieved. The number of RATS lobectomy/segmentectomy increased as the FY progressed (n = 31, 47, 58, and 116 in FY 2018, 2019, 2020, and 2021, respectively). The mean surgical time by RATS starters decreased in FY 2020 and 2021 (171.4 min.; 74 cases; seven RATS starters) compared with those in FY 2018 and 2019 (198.0 min.; 57 cases; six RATS starters) (P = 0.002). Conclusions: The goal of increasing the number of surgery cases and RATS cases/surgeons within the given framework was achieved by setting the QI.

DOI： 10.1007/s11748-022-01903-6

Scopus

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

<p>本学会ホームページ上で提示されている脳死下肺摘出術のオリジナル版は、2011年3〜5月当時の肺移植実施7施設に対してアンケート調査を行い、慎重なメール審議とコンセンサス形成を経て、全施設の相違点を包括するものが作成された。本邦の肺摘出術の初めての標準化プロセスであった。</p><p>2021年4〜6月共同演者の芳川豊史先生（本学会脳死・心停止下リカバリー環境改善委員会委員）が中心となり、日本肺および心肺移植研究会を通じて、肺移植実施10施設に「臓器搬送における手順標準化に向けたアンケート調査」を行い、慎重なメール審議の上、改訂がなされた。特に逆行性灌流に関して、従来の摘出後バックテーブルで行うものから術野で行う形に変更した施設が増えていたため、従来法と併記する形で加筆がなされた。事前に腹部チームとコンセンサスを得ること、呼吸循環管理医・日本臓器移植ネットワークコーディネーターと情報共有することも強調されている。この他、現状に合致させるよう複数の意見が出され、この過程で多施設間相互の手技の再確認、標準化が改めてなされた。</p><p>臓器摘出・搬送の互助制度に関しては、2018年1〜2月日本肺および心肺移植研究会による肺移植実施9施設に対するアンケート調査の結果、肺移植では時期尚早と判断し、腹部臓器の状況をオブザーブする方針となっている。</p><p>脳死下肺摘出・搬送法標準化の現状を提示し、今後の課題を議論したい。</p>

DOI： 10.11386/jst.57.supplement_s145_2

CiNii Research

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

<p>【背景と目的】生体肺移植（LDLLT）は本邦を中心に行われており，生命予後は脳死肺移植（CLT）とほぼ同等とされるが，健康関連QoL（HRQoL）に関しては定かでは無い．移植後5年までのHRQoLについて検討を行った．</p><p>【方法】当院の肺移植患者を対象とし，術前，術後3ヶ月，6ヶ月，1年，以後1年毎に5年までのSF-36を調査し，3コンポーネント・サマリースコア（PCS, MCS, RCS）を算出した．CLTは術前評価の欠測値が多く，LDLLTとの術前比較にはmMRCを用いた．術後経過の比較では，術前mMRC，QoL評価時の慢性移植肺機能不全合併の有無を共変量とし，線形混合モデルを用いて解析した．なお，有意水準は5%とした．</p><p>【結果】LDLLT68例，CLT148例が解析対象となり，全体では中央値4.4年まで経過観察され，5年後観察を完遂したのは94例（44%）だった．術前のmMRCはLDLLTで有意に高値であった（p＜0.001）．PCSは術後3ヶ月でLDLLT36点 vs. CLT40点，術後5年で41点 vs. 39点と同等になった．MCSは術前からLDLLT56点と高値であり，術後はLDLLT，CLT共に50点を超えて推移した．RCSは術前LDLLT27点と低値であり，術後3ヶ月においても低値が持続したが，術後5年ではCLT46点に対し，LDLLTは50点を超えた．線形混合モデルによる評価では，LDLLTとCLTの経過に有意な差は認められなかった．</p><p>【結論】LDLLT患者はCLTと比較して，術前の呼吸器症状はより重度であったが，少なくとも術後のHRQoLは同等，もしくは一部でLDLLTが上回ると考えられた．</p>

DOI： 10.11386/jst.57.supplement_s342_1

CiNii Research

Language：Japanese   Publisher：BMJ Open  

Introduction Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. Methods and analysis This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. Ethics and dissemination This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. Trial registration number NCT04758143.

DOI： 10.1136/bmjopen-2021-052045

Scopus

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

DOI： 10.1093/icvts/ivaa194

Scopus

Language：Japanese   Publisher：BMC Cancer  

Background: The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed. Results: Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959). Conclusions: Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

DOI： 10.1186/s12885-021-08688-6

Scopus

Language：Japanese   Publisher：JTCVS Techniques  

Objectives: Virtual-assisted lung mapping (VAL-MAP) is a bronchoscopic marking method of dye application on the surface of the lungs before resecting nonpalpable nodules. However, in some cases, it can be difficult to identify the markings of VAL-MAP on computed tomography and intraoperative thoracoscopy. We developed and assessed the feasibility of indocyanine green VAL-MAP (ICG-VAL-MAP). Methods: A historical control trial was conducted to investigate the effectiveness of ICG-VAL-MAP for marking visualization compared with that of VAL-MAP. In ICG-VAL-MAP, instead of indigo carmine, ICG and computed tomography contrast agents were used for dye marking, and near-infrared fluorescence endoscopy was employed to visualize the ICG markings. The other processes in VAL-MAP were carried out. The marking visibility was assessed in 3 grades of easy, faint, or not identifiable. We compared the visibility of the markings on computed tomography images and during thoracoscopic operations between VAL-MAP (567 markings in 147 cases) and ICG-VAL-MAP (142 markings in 63 cases). Results: On the preoperative computed tomography images, ICG-VAL-MAP provided significantly better marking visualization than VAL-MAP (easy/faint/not identifiable = 142/0/0 vs 427/100/30; P <.0001). ICG-VAL-MAP provided significantly better intraoperative markings than VAL-MAP (easy/faint/not identifiable = 141/0/1, respectively, vs 475/50/42, respectively; P <.0001). Regarding complications, pneumothorax occurred in 8 (5.4%) cases of VAL-MAP and zero cases (0%) of ICG-VAL-MAP (P =.12); fever was observed in 7 (5.0%) cases of VAL-MAP and 2 (3.2%) cases of ICG-VAL-MAP (P =.72). Conclusions: ICG-VAL-MAP provided significantly better visibility of markings than VAL-MAP. It might be useful in the resection of nonpalpable small lung lesions.

DOI： 10.1016/j.xjtc.2021.07.019

Scopus

Language：Japanese   Publisher：Respiratory Research  

Background: Waitlist mortality due to donor shortage for lung transplantation is a serious problem worldwide. Currently, the selection of recipients in Japan is mainly based on the registration order. Hence, scientific evidence for risk stratification regarding waitlist mortality is urgently needed. We hypothesized that patient-reported dyspnea and health would predict mortality in patients waitlisted for lung transplantation. Methods: We analyzed factors related to waitlist mortality using data of 203 patients who were registered as candidates for lung transplantation from deceased donors. Dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, and the health status was determined with St. George’s Respiratory Questionnaire (SGRQ). Results: Among 197 patients who met the inclusion criteria, the main underlying disease was interstitial lung disease (99 patients). During the median follow-up period of 572 days, 72 patients died and 96 received lung transplantation (69 from deceased donors). Univariable competing risk analyses revealed that both mMRC dyspnea and SGRQ Total score were significantly associated with waitlist mortality (p = 0.003 and p < 0.001, respectively) as well as age, interstitial lung disease, arterial partial pressure of carbon dioxide, and forced vital capacity. Multivariable competing risk analyses revealed that the mMRC and SGRQ score were associated with waitlist mortality in addition to age and interstitial lung disease. Conclusions: Both mMRC dyspnea and SGRQ score were significantly associated with waitlist mortality, in addition to other clinical variables such as patients’ background, underlying disease, and pulmonary function. Patient-reported dyspnea and health may be measured through multi-dimensional analysis (including subjective perceptions) and for risk stratification regarding waitlist mortality.

DOI： 10.1186/s12931-021-01715-x

Scopus

Language：Japanese   Publisher：Scientific Reports  

The coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I2 index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20–0.37, P < 0.001; I2 0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.

DOI： 10.1038/s41598-021-83103-5

Scopus

Publisher：JTCVS Open  

DOI： 10.1016/j.xjon.2021.09.043

Scopus

Language：Japanese   Publisher：Expert Systems with Applications  

In video-assisted thoracoscopic surgeries, successful procedures of nodule resection are highly dependent on the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery. Lungs in the pneumothorax state during surgery have a large volume change from normal lungs, making it difficult to build a mechanical model.The purpose of this study is to develop a deformation estimation method of 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The deformation for each vertex of the entire mesh model was estimated per-vertex as a relative position from the landmarks. The landmarks were placed in the anatomical position of the lung's outer contour. The method was applied on nine datasets of the left lungs of live beagle dogs. Contrast-enhanced CT images of the lungs were acquired.The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94. Moreover, the proposed method achieved the estimation lung deformations from a small number of training cases and a small observation area.This study contributes to data-driven modeling of pneumothorax deformation of the lung.

DOI： 10.1016/j.eswa.2021.115288

Scopus

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

BACKGROUND: Massive hemoptysis is a life-threatening complication after transbronchial biopsy (TBB). Reports on massive hemoptysis occurring several days after TBB are scarce. CASE PRESENTATION: A 62-year-old man presented with massive hemoptysis and was admitted to hospital as an emergency on the eighth day after TBB. On the 12th day after TBB, computed tomography showed complete atelectasis of the right middle and lower lobes. The patient underwent emergent right upper lobectomy. The right upper lobe bronchus was separated with a scalpel, the hematoma was pulled out with forceps, and the bronchus subsequently sutured shut. The patient was discharged from the hospital uneventfully. CONCLUSIONS: We experienced a case of massive hemoptysis on the eighth day after TBB, which required emergency surgery due to persistent bleeding into the airway and airway obstruction during follow-up. Postoperative pneumonia and atelectasis could be prevented by manual removal of the residual hematoma.

DOI： 10.1186/s40792-021-01323-3

PubMed

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

DOI： 10.1016/j.jtcvs.2020.08.017

Scopus

Language：Japanese   Publisher：Transplant International  

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

DOI： 10.1111/tri.13974

Scopus

Language：Japanese   Publisher：Annals of Thoracic Surgery  

Major pulmonary resection has been successfully performed after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in a few cases. A pulmonary nodule was detected in a 68-year-old man with a diagnosis of chronic thromboembolic pulmonary hypertension. After pulmonary hypertension was resolved with pulmonary endarterectomy, left upper lobe trisegmentectomy was performed for small lung cancer. Dissection of the pulmonary artery was carefully performed with a possibility of a fragile state on the arterial wall due to previous pulmonary endarterectomy. Pathologically, the arterial media with an uneven thickness was exposed to the vascular lumen in the resected pulmonary artery.

DOI： 10.1016/j.athoracsur.2021.02.022

Scopus

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

OBJECTIVES: The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS: Of the 663 patients enrolled in the 2 studies, 559 patients' follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS: Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS: VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. SUBJ COLLECTION: 152, 1542.

DOI： 10.1093/ejcts/ezab421

PubMed

Publisher：金原出版  

DOI： 10.18888/sh.0000001943

CiNii Research

Language：Japanese   Publisher：Medical Image Analysis  

The positions of nodules can change because of intraoperative lung deflation, and the modeling of pneumothorax-associated deformation remains a challenging issue for intraoperative tumor localization. In this study, we introduce spatial and geometric analysis methods for inflated/deflated lungs and discuss heterogeneity in pneumothorax-associated lung deformation. Contrast-enhanced CT images simulating intraoperative conditions were acquired from live Beagle dogs. The images contain the overall shape of the lungs, including all lobes and internal bronchial structures, and were analyzed to provide a statistical deformation model that could be used as prior knowledge to predict pneumothorax. To address the difficulties of mapping pneumothorax CT images with topological changes and CT intensity shifts, we designed deformable mesh registration techniques for mixed data structures including the lobe surfaces and the bronchial centerlines. Three global-to-local registration steps were performed under the constraint that the deformation was spatially continuous and smooth, while matching visible bronchial tree structures as much as possible. The developed framework achieved stable registration with a Hausdorff distance of less than 1 mm and a target registration error of less than 5 mm, and visualized deformation fields that demonstrate per-lobe contractions and rotations with high variability between subjects. The deformation analysis results show that the strain of lung parenchyma was 35% higher than that of bronchi, and that deformation in the deflated lung is heterogeneous.

DOI： 10.1016/j.media.2021.102181

Scopus

Language：Japanese   Publisher：JTCVS Techniques  

DOI： 10.1016/j.xjtc.2021.06.009

Scopus

Language：Japanese   Publisher：(株)全日本病院出版会  

肺移植は、内科的治療が尽くされた末期呼吸不全患者における唯一の治療手段として世界的に確立し、本邦でも、手術手技や一般的な周術期管理以外の患者管理に、焦点が当てられるようになってきた。肺移植適応患者は、末期の慢性呼吸不全患者であり、日常生活における活動性は低い。さらに、運動機能や日常生活動作能力も極めて低下するなど、いわゆるサルコペニアの病態である患者も多い。したがって、長い待機期間だけでなく周術期を生き抜くためにも、肺移植待機患者に対する術前リハビリテーション治療や栄養療法は重要である。また、肺移植によって肺機能は劇的に改善するが、肺の機能を活かすための身体機能は何も変化しない。したがって、肺移植後のリハビリテーション治療では、低下した身体機能の向上をはかり、日常生活動作能力を高めることで、早期社会復帰を目指すことが目標となる。肺移植患者や肺移植待機患者において、サルコペニアと栄養状態の管理の観点からの多角的なリハビリテーション治療が、今後さらに重要となる。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J03505&link_issn=&doc_id=20211014130006&doc_link_id=%2Fap5meree%2F2021%2F000266%2F008%2F0036-0042%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap5meree%2F2021%2F000266%2F008%2F0036-0042%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publisher：南江堂  

DOI： 10.15106/j_kyobu74_850

CiNii Research

Language：Japanese   Publisher：General Thoracic and Cardiovascular Surgery  

Objective: The aim of this study was to investigate the effects of inflammatory respiratory complications on long-term survival in patients with resected non-small cell lung cancer. We defined inflammatory respiratory complications to include the following six conditions: pneumonia, empyema, bronchial fistula, respiratory dysfunction, acute interstitial pneumonia, and atelectasis. Methods: Part of the National Clinical Database was linked to our prospective database from 2014 to 2017. Linkage was achieved for 866 patients. The Kaplan–Meier method was used to evaluate the overall, relapse-free, and cancer-related survival. The Cox proportional hazard model was used to analyze the impact of each complication. Results: Of the 736 patients included in the study, 149 had complications. The 5-year overall and cancer-specific survival rates were significantly lower in patients with inflammatory respiratory complications. The Cox proportional hazard model showed that the inflammatory respiratory complications had a significant impact on overall survival (hazard ratio 2.48, 95% confidence interval 1.41–4.38) but not air leak (hazard ratio 1.38, 95% confidence interval 0.70–2.70). Conclusions: Our study shows the differential impact of each complication on the survival of patients with non-small cell lung cancer. The presence of inflammatory respiratory complications was the only predictor of poor overall survival.

DOI： 10.1007/s11748-021-01619-z

Scopus

Language：Japanese   Publisher：Supportive Care in Cancer  

Purpose: Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are fatal, and lung transplantation is the only curative treatment. Although lung transplantation for LONIPCs may confer good survival rates, it is unclear whether or how impaired physical functioning is restored. Thus, this study aimed to investigate the long-term course and associated changes in physical functions after lung transplantation in patients with LONIPCs after allo-HSCT. Methods: This prospective cohort study enrolled 15 patients who received lung transplantation for LONIPCs after allo-HSCT between 2012 and 2018. Dyspnea scores, performance status, physical function, and exercise tolerance were assessed before lung transplantation and up to 2 years after transplantation. Results: Two years after lung transplantation, the dyspnea scores and performance status improved, but did not recover completely. Physical function was assessed using the knee extensor strength (KES) and 6-min walk test (6MWT); the results were poor until 3 months after transplantation but improved over 2 years. The 6MWT distance showed improvement to a nearly healthy level (562.7 m). Recovery of exercise tolerance was associated with recovery in % vital capacity (%VC; r=0.5) and KES (r=0.4) from 3 months to 2 years after lung transplantation. Furthermore, a flat thorax, which is a characteristic of patients with LONIPCs, affected the %VC at 2 years after transplantation (r=0.8). Conclusion: Lung transplantation for LONIPCs may restore impaired physical function. A multifaceted rehabilitation program should be considered, especially to improve muscle weakness and pulmonary function.

DOI： 10.1007/s00520-021-06118-8

Scopus

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

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

Living-donor lobar lung transplantation( LDLLT) is an established therapy for patients with end-stage lung disease, but living-donor lobar lung retransplantation (re-LDLLT) is rarely reported. We previously reported a case of unilateral antibody-mediated rejection (AMR) after bilateral LDLLT in the presence of newly formed donor-specific antibodies against a right-lobe donor. The same patient developed contralateral bronchiolitis obliterans syndrome (BOS), resulting in bilateral BOS. Re-LDLLT was performed under extracorporeal membrane oxygenation. Eight and a half years after re-LDLLT, the patient is doing well without any anti-human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. Herein, we report this rare case and discuss several issues in comparison with the findings in the previously reported similar cases.

PubMed

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

BACKGROUND: The optimal management of an aberrant artery in pulmonary sequestration (PS) is controversial. Several studies have shown that hybrid surgery with preoperative coil embolization for an aberrant artery and surgical resection of the sequestrated lung is effective. However, there are no clear indications for the procedure. CASE PRESENTATION: A 68-year-old woman without any complaints was diagnosed with right intralobar PS, which was supplied by an aberrant artery from the thoracic aorta, via computed tomography performed during a medical examination. In addition, lung adenocarcinoma was detected over the border between the right upper and middle lobes. Preoperative coil embolization was performed by an interventional radiologist the day before surgery to decrease the risk of severe intraoperative hemorrhage. On the following day, bi-lobectomy of the right upper and middle lobes for lung adenocarcinoma with systemic lymph node dissection and segmentectomy of the sequestrated lung with thoracotomy was performed. Although no active hemorrhage was observed during surgery, the aberrant artery was challenging to dissect using an energy device due to the presence of an intravascular coil. Eventually, the coil stump was exposed, and it was cut with scissors. The postoperative course was uneventful. CONCLUSIONS: We reported the pitfall of the hybrid surgery for intralobar PS. Preoperative coil embolization can prevent fatal intraoperative hemorrhage. If embolization is performed using a coil for an aberrant artery supplied from the thoracic aorta, where and how to dissect the aberrant artery should be cautiously determined based on preoperative images, with consideration of the presence of an intravascular coil.

DOI： 10.1186/s40792-021-01277-6

PubMed

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

DOI： 10.1016/j.jtcvs.2020.04.136

Scopus

Language：Japanese   Publisher：Surgery Today  

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

Scopus

Language：Japanese   Publisher：The Japanese Association for Chest Surgery  

<p>A 61-year-old woman presented with a 44-mm well-circumscribed tumor in the anterior mediastinum on chest computed tomography. ¹⁸F-Fluorodeoxyglucose positron emission tomography showed a high-level accumulation of ¹⁸F-Fluorodeoxyglucose (standardized uptake value: 12.07). She underwent thymectomy with combined resection of partial pericardium. Histopathological findings showed that the tumor was a thymic mucinous adenocarcinoma (pT2N0M0 Stage II, and Masaoka stage III). After receiving adjuvant radiotherapy, she was in good health without any tumor recurrence at 6 months after surgery.</p>

DOI： 10.2995/jacsurg.35.547

CiNii Research

Language：Japanese   Publisher：The Japanese Association for Chest Surgery  

<p>Pulmonary benign metastasizing leiomyoma (BML) is a rare disease in which a benign uterine leiomyoma metastasizes to the lung. We herein report a clinicopathological study of 10 cases. The median interval between hysterectomy and lung resection for pulmonary nodules was 114 months (range: 15-240 months). The median tumor size was 11 mm (range: 5-16 mm). While nine patients with multiple nodules underwent wedge resection, one was treated with lobectomy. Hormonal treatment was administered to 3 patients with residual lesions and 1 patient as adjuvant therapy. During the follow-up periods (range: 26-192 months, median: 105 months), seven patients were alive with disease and two without evidence of disease. One patient died of systemic metastases due to atypical leiomyoma diagnosed by reviewing uterine and pulmonary specimens. Diagnostic, surgical, and therapeutic problems associated with this disease were discussed.</p>

DOI： 10.2995/jacsurg.35.537

CiNii Research

Language：Japanese   Publisher：Science Translational Medicine  

Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling. Here, we combine human iPSCs and airway-on-a-chip technology, to demonstrate the effectiveness of fluid shear stress (FSS) for regulating the global axis of multicellular planar cell polarity (PCP), as well as inducing ciliogenesis, thereby contributing to quantifiable unidirectional mucociliary flow. Furthermore, we applied the findings to disease modeling of primary ciliary dyskinesia (PCD), a genetic disease characterized by impaired mucociliary clearance. The application of an airway cell sheet derived from patient-derived iPSCs and their gene-edited counterparts, as well as genetic knockout iPSCs of PCD causative genes, made it possible to recapitulate the abnormal ciliary functions in organized PCP using the airway-on-a-chip. These findings suggest that the disease model of PCD developed here is a potential platform for making diagnoses and identifying therapeutic targets and that airway reconstruction therapy using mechanical stress to regulate PCP might have therapeutic value.

DOI： 10.1126/scitranslmed.abb1298

Scopus

Language：Japanese   Publisher：Cancer Science  

Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non–small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

DOI： 10.1111/cas.14928

Scopus

Language：Japanese   Publisher：Journal of Heart and Lung Transplantation  

Background: Despite growing interest in donor-specific antibodies (DSAs) and antibody-mediated rejection (AMR) in lung transplantation (LTx), no study evaluating the outcomes in recipients with de novo DSAs (dnDSAs) in living-donor lobar LTx (LDLLT) exists. We compared various characteristics of DSAs in LDLLT with those in cadaveric LTx (CLT) based on prospectively collected data. Methods: Between October 2009 and September 2019, 211 recipients underwent LTx (128 CLTs and 83 LDLLTs). We reviewed 108 CLTs and 74 LDLLTs to determine the characteristics and clinical impact of dnDSAs. Eighteen data-deficient cases, 7 cases with preformed DSAs, and 4 re-transplants were excluded. Results: There were significant differences between CLT and LDLLT patients in age, primary disease, ischemic time, and number of human leukocyte antigen mismatches per donor. The dnDSA incidence in LDLLT (6.8%) was significantly lower than that in CLT (19.4%, p = 0.02). The dnDSAs appeared later in LDLLT (mean 1,256 days) than in CLT (mean 196 days, p = 0.003). According to Cox models analyzed using dnDSA as a time-dependent covariate, dnDSA positivity was significantly associated with a poor overall survival (OS; hazard ratio [HR] 3.46, 95% confidence interval [CI] 1.59-7.57, p = 0.002) and poor CLAD-free survival in case of CLT (HR: 2.23, 95% CI: 1.08-4.63, p = 0.003). However, no such significant associations were noted in case of LDLLT. Conclusions: The dnDSA occurrence was significantly lower and later in LDLLT than in CLT. Furthermore, dnDSA-positivity was significantly associated with worse OS and CLAD-free survival after CLT but not after LDLLT.

DOI： 10.1016/j.healun.2021.03.019

Scopus

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

日本国内で実施された肺移植525例を対象に、肺移植後に抗体関連型拒絶反応(AMR)を発症し、rituximabを使用した症例について検討した。その結果、肺移植後のAMRに対しrituximabを使用した症例は14例(2.7%)であった。移植時年齢は10歳が1例、23〜69歳が13例であった。rituximabは延べ20回投与され、うち11例は375mg/m2の単回投与であった。rituximab治療3ヵ月で移植肺は3例(21%)で生着したが、11例(79%)で廃絶した。重篤な有害事象は11例(79%)に認められ、うち rituximabとの関連性が否定できない事象は成人3例に発現し、肺炎2例、意識変容状態が1例であった。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00083&link_issn=&doc_id=20210716280007&doc_link_id=%2Fcl8isoke%2F2021%2F005601%2F007%2F0053-0068%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl8isoke%2F2021%2F005601%2F007%2F0053-0068%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

Language：Japanese   Publisher：Med  

Background: Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus). Methods: Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat. Findings: Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications. Conclusions: EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions. Funding: This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.

DOI： 10.1016/j.medj.2021.04.004

Scopus

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

DOI： 10.1053/j.semtcvs.2020.09.003

Scopus

Language：Japanese   Publisher：General Thoracic and Cardiovascular Surgery  

Pulmonary sequestration with feeding vessels from the abdominal aorta is relatively rare. A 56-year-old woman with chronic left thoracic pain was referred to our hospital. Computed tomography showed multiple pulmonary cysts in the left lung and an aberrant artery from the abdominal aorta. She was diagnosed with pulmonary sequestration. She underwent embolization of the aberrant artery and wedge resection of the sequestrated lung under indocyanine green guidance. The surgical treatment combining preoperative embolization of the artery and intraoperative indocyanine green-guided lung resection might be safe and minimally invasive for patients with lung sequestrations accompanied by feeding vessels from the abdominal aorta.

DOI： 10.1007/s11748-021-01612-6

Scopus

Language：Japanese   Publisher：Cells  

Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.

DOI： 10.3390/cells10061333

Scopus

Language：Japanese   Publisher：Journal of Cachexia, Sarcopenia and Muscle  

Background: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. Methods: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). Results: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79–6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27–3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. Conclusions: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

DOI： 10.1002/jcsm.12691

Scopus

Language：Japanese   Publisher：Journal of Heart and Lung Transplantation  

Background: Living-donor lobar lung transplantation (LDLLT) is viable for critically ill patients in situations of donor shortage. Because it is sometimes difficult to find 2 ideal living donors with suitable graft sizes, we developed native lung-sparing procedures, including single LDLLT and native upper lobe-sparing LDLLT. This study aimed to investigate native lung complications (NLCs) in native lung-sparing LDLLT. Methods: Between April 2002 and March 2019, 92 LDLLTs and 124 cadaveric lung transplantations (CLTs) were performed at the Kyoto University Hospital. Our prospectively maintained database and clinical records were reviewed to compare NLCs among recipients who underwent native lung-sparing LDLLT (n = 21) with those among recipients who underwent single CLT (n = 61). Results: Among 21 recipients who underwent native lung-sparing LDLLT, 11 NLCs occurred in 8 recipients. No fatal NLC was noted; however, 2 required surgical intervention. Post-transplant survival was not significantly different between native lung-sparing LDLLT recipients with NLCs and those without NLCs. The incidence of NLCs was comparable between native lung-sparing LDLLT recipients and single CLT recipients (8/21 vs 26/61, p = 0.80); however, NLCs occurred significantly later in LDLLT recipients than in CLT recipients (median: 665 vs 181.5 days after transplantation, p = 0.014). Conclusions: NLCs after native lung-sparing LDLLT had favorable outcomes. Therefore, native lung-sparing LDLLT is a useful treatment option for severely ill patients who cannot wait for CLT. However, it is important to recognize that NLCs may occur later in LDLLT than in CLT.

DOI： 10.1016/j.healun.2021.01.1562

Scopus

Language：Japanese   Publisher：Interactive cardiovascular and thoracic surgery  

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

DOI： 10.1093/icvts/ivaa311

Scopus

Language：Japanese   Publisher：(一社)日本呼吸器学会  

Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/jovs-20-166

Language：Japanese  

DOI： 10.1186/s40792-021-01148-0

Web of Science

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

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

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

DOI： 10.1007/s11748-020-01458-4

Scopus

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

DOI： 10.1007/s11748-020-01475-3

Scopus

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：Annals of Thoracic Surgery  

Background: Molecular hydrogen (H2) has protective effects against ischemia-reperfusion injury in various organs. Because they are easier to transport and safer to use than inhaled H2, H2-rich solutions are suitable for organ preservation. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. Methods: Ten beagles underwent orthotopic left LTx after 23 hours of cold ischemia followed by reperfusion for 4 hours. Forty-five minutes after reperfusion, the right main pulmonary artery was clamped to evaluate the function of the implanted graft. The beagles were divided into two groups: control group (n = 5), and H2 group (n = 5). In the control group, the donor lungs were flushed and immersed during cold preservation at 4°C using ET-Kyoto solution, and in the H2 group, these were flushed and immersed using H2-rich ET-Kyoto solution. Physiologic assessments were performed during reperfusion. After reperfusion, the wet-to-dry ratios were determined, and histology examinations were performed. Results: Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the control group (P =.045 and P <.001, respectively). The wet-to-dry ratio was significantly lower in the H2 group than in the control group (P =.032). Moreover, in histology examination, less lung injury and fewer apoptotic cells were observed in the H2 group (P <.001 and P <.001, respectively). Conclusions: Our results demonstrated that the H2-rich preservation solution attenuated ischemia-reperfusion injury in a canine left LTx model.

DOI： 10.1016/j.athoracsur.2020.05.076

Scopus

Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

<p>In video-assisted thoracoscopic surgeries, the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery is expected. The purpose of this study is to develop a deformation estimation method of the 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The method was applied on nine datasets of the left lungs of live Beagle dogs. Contrast-enhanced CT images of the lungs were acquired. The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94. </p>

DOI： 10.11239/jsmbe.annual59.515

CiNii Research

Language：Japanese   Publisher：The Japan Society for Transplantation  

<p>【<b>Objective</b>】 We retrospectively surveyed the details of treatment with rituximab for antibody-mediated rejection (AMR) after lung transplantation.</p><p>【<b>Design</b>】 Case series.</p><p>【<b>Methods</b>】 This study was conducted to assess outcomes in patients who underwent lung transplantation in Japan from August 2001 to December 2016 and were treated with rituximab for AMR. A questionnaire was sent to medical institutions that had used rituximab for such treatment, and information on AMR treatment, including rituximab dosage, efficacy, and safety, was collected.</p><p>【<b>Results</b>】 Among the 525 patients undergoing lung transplantation during the study period in Japan, fourteen patients (2.7%; 1 child and 13 adults) were enrolled. Records showed definite clinical AMR in 3 patients, probable clinical AMR in 2 patients, possible clinical AMR in 8 patients and suspected AMR in 1 patient. All patients had allograft dysfunction, and 13 adult patients were positive for donor-specific antibodies (DSA). Two patients experienced rejection more than twice. Rituximab was administered to all patients. In one patient who experienced AMR twice, rituximab was administered for each AMR. The rituximab dose was 375 mg/m² in all but one patient, who received 348 mg/m². Eight patients recovered from AMR. AMR treatments, including rituximab, were well tolerated. However, 11 patients developed graft loss due to rejection, and 10 patients died from chronic lung allograft syndrome or sepsis.</p><p>【<b>Conclusion</b>】 Based on these findings, treatment containing rituximab was considered effective for AMR, but careful monitoring is needed to prevent or reduce the number of adverse events such as infection.</p>

DOI： 10.11386/jst.56.1_53

CiNii Research

Language：Japanese   Publisher：Journal of Thoracic and Cardiovascular Surgery  

DOI： 10.1016/j.jtcvs.2021.01.083

Scopus

Language：Japanese   Publisher：Nagoya Journal of Medical Science  

Video-assisted thoracic surgery (VATS) has become widespread in the last 20 years, followed by robot-assisted thoracic surgery (RATS). Few studies compared the learning curve between RATS lobectomy and conventional VATS. This study included 79 RATS lobectomy cases performed in our hospital from November 2015 to October 2019. To estimate the required number for learning, the cumulative sum method, which is to plot a value obtained by sequentially accumulating a difference from a mean value was applied. As a result, the median total operative time and the median console time for all cases were 167 minutes and 138 minutes, respectively. Firstly, for our team, 28 cases were estimated to be required for learning curve for RATS lobectomy. For individual, each surgeon might be learned in only 5 to 6 cases. By contrast, the number of cases for learning VATS lobectomy which was underwent by a ‘single' surgeon from 2009 was estimated to be 35 cases. The time to dock from start operation (median 14 minutes) reached plateau in 18 cases, but the time after rollout was median of 18 minutes and there was no significant change from the beginning. In conclusion, RATS lobectomy might be a technique that could be learned in a small number of cases compared to VATS. The results of this study might be helpful for certified surgeons who tried to get started with RATS and for establishing a learning program.

DOI： 10.18999/nagjms.83.2.227

Scopus

Language：Japanese   Publisher：Progress in Biomedical Optics and Imaging - Proceedings of SPIE  

In this study, we introduce statistical modeling methods for pneumothorax deformation using paired cone-beam computed tomography (CT) images. We designed a deformable mesh registration framework for shape changes involving non-linear deformation and rotation of the lungs. The registered meshes with local correspondences are available for both surgical guidance in thoracoscopic surgery and building statistical deformation models with inter-patient variations. In addition, a kernel-based deformation learning framework is proposed to reconstruct intraoperative dfl ated states of the lung from the preoperative CT models. This paper reports the findings of pneumothorax deformation and evaluation results of the kernel-based deformation framework.

DOI： 10.1117/12.2581388

Scopus

Language：Japanese   Publisher：Journal of Thoracic and Cardiovascular Surgery  

Objective: The study objective was to verify whether low preoperative radiographic density of erector spinae muscles is associated with poor prognosis after lung transplantation. Methods: Preoperative chest computed tomography scans for patients who underwent deceased-donor lung transplantation between 2013 and 2019 at Kyoto University Hospital were retrospectively retrieved. The radiographic density of erector spinae muscles was quantitatively evaluated as the mean attenuation of erector spinae muscles, and low mean radiographic density of the erector spinae muscles was defined as a mean radiographic density of the erector spinae muscles value below the median value for all patients. Overall survival and chronic lung allograft dysfunction-free survival with high and low mean radiographic density of the erector spinae muscles were estimated using the Kaplan–Meier method and evaluated by the log-rank test, as well as by univariate and multivariate Cox proportional hazard analyses. Results: Of the 107 adult patients who underwent primary transplantation, 96 underwent at least 1 chest computed tomography scan within 24 hours before lung transplantation. The median mean radiographic density of the erector spinae muscles in these 96 patients was 49.2 Hounsfield units. A low mean radiographic density of the erector spinae muscles value was significantly associated with decreased overall survival (hazard ratio, 4.50; P =.030) and chronic lung allograft dysfunction–free survival (hazard ratio, 3.18; P =.028) in the multivariate analysis. Additionally, patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles value had a worse overall survival (P <.001) and chronic lung allograft dysfunction–free survival (P <.001) than patients with preoperative steroid use and a high mean radiographic density of the erector spinae muscles value and those without preoperative steroid use. Conclusions: Low mean radiographic density of the erector spinae muscles was closely associated with a poor prognosis after lung transplantation. The prognosis was particularly poor in patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles. These results may be useful when considering the indications for lung transplantation or preoperative interventions. Video Abstract:[Figure presented]

DOI： 10.1016/j.jtcvs.2021.07.039

Scopus

Language：Japanese   Publisher：Surgery Today  

Purpose: To investigate if electromagnetic navigation bronchoscopy (ENB) improves the diagnostic yield for peripheral lung lesions from that achieved by virtual bronchoscopy navigation (VBN). Methods: This retrospective study compared the results of 100 ENB-transbronchial lung biopsies (TBLBs) with those of 50 VBN-TBLBs at a single institution. Results: ENB improved the diagnostic yield significantly compared with VBN (64.0% for 19.4 ± 9.0 mm tumors vs. 46.0% for 27.6 ± 8.9 mm tumors; p < 0.0001). Irrespective of the bronchus sign, ENB was more favorable than VBN, with 81.0% (47/58) achieved by ENB vs. 60.0% (21/35) achieved by VBN in the presence of the positive bronchus sign (p = 0.0283), and 40.5% (17/42) achieved by ENB vs. 13.3% (2/15) achieved by VBN in the absence of the bronchus sign (p = 0.0431). Univariate analysis identified tumor size (p = 0.0048), amount of intravenous sedation (p = 0.0182), registration time (p = 0.0111), minimum distance to target (p = 0.0244), and the bronchus sign (p < 0.0001) as factors that affected the yield significantly for ENB. Multivariate analysis identified the bronchus sign (odds ratio 6.74; 95% CI 1.84–24.7) and the registration time (OR 1.01; 95% CI 1.00–1.02) as significant factors. Conclusions: Despite the bronchus sign being a significant factor, ENB improved the diagnostic yield of smaller lesions significantly, compared with VBN, regardless of the bronchus sign.

DOI： 10.1007/s00595-021-02398-z

Scopus

Language：Japanese   Publisher：Journal of Thoracic and Cardiovascular Surgery  

DOI： 10.1016/j.jtcvs.2021.01.030

Scopus

Language：Japanese   Publisher：Seminars in Thoracic and Cardiovascular Surgery  

DOI： 10.1053/j.semtcvs.2021.06.018

Scopus

Language：Japanese   Publisher：Annals of Thoracic Surgery  

Background: In this study we evaluated the R(un) category proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the medical records of patients with NSCLC who underwent segmentectomy or lobectomy between 2014 and 2015 at our institution. Residual tumor (R) status was reclassified from the Union for International Cancer Control designation to the IASLC-proposed R classification of R0 and R(un). The underlying reasons for the R(un) reclassification were analyzed according to pathologic stage, lymph node status, and resected lobe. A Cox proportional hazard model was used to evaluate the impacts of R(un) categorization on overall survival. Results: Of 355 patients, 44.5% were reclassified as R(un). The most common reason for the reclassification was insufficient number of harvested lymph nodes or no station 7 lymph nodes. When stratified by tumor location, the absence of station 7 lymph nodes was especially prominent in both the right and left upper lung resections. In the multivariate Cox regression model, the IASLC R classification was associated with poor overall survival in node-positive patients (hazard ratio, 2.657; P =.016). Conclusions: Various factors resulted in reclassification to R(un) because the R(un) group was highly heterogeneous. Careful consideration is required to determine whether the R(un) classification can be used as an indicator of lymph node dissection quality. For advanced cases, the R(un) definition may be useful in predicting poor prognosis.

DOI： 10.1016/j.athoracsur.2021.07.087

Scopus

Publisher：ERJ Open Research  

Background Bronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO. Methods This retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation. Results Of a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <−950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology. Conclusions In patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO.

DOI： 10.1183/23120541.00123-2021

Scopus

Language：Japanese   Publisher：一般社団法人 日本呼吸理学療法学会  

DOI： 10.51116/kokyurigakuryohogaku.7th.meeting.0_sj-2

CiNii Research

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

<p>背景：肺移植後の栄養管理では, 体外循環使用に伴う腸管浮腫, 誤嚥, 肺水腫に注意が必要で, 既存のプロトコルは無い. 今回プロトコルを作成, 導入したので, その成果を報告する.</p><p>対象と方法：2019年1月から2020年12月に当院で実施した18歳以上の肺移植43例を対象とした. プロトコルは, 術後2-3日に経腸栄養または中心静脈栄養を開始し, 術後7日目の目標エネルギーを標準体重×25 kcal, 蛋白量を標準体重×1 gとし, 極端なやせは現体重を用いた. プロトコル開始前28例（前群）と開始後15例（後群）で, 栄養開始日, 術後7日目の栄養充足率, 体重・体組成の変化, 脊柱起立筋の筋量（CT断面積）を比較した.</p><p>結果：経腸栄養は中央値で前群71%, 後群100%, 中心静脈栄養は前群79%, 後群100%に実施された. 栄養開始は後群で早かった（前群4日, 後群3日, p=0.004）. 術後7日目のエネルギー充足率は前群69%, 後群83%（p=0.010）, 蛋白充足率は前群74%, 後群95%（p=0.008）であった. 術後1か月, 3か月の体重減少は後群で有意に抑制された（-3.7 kg vs -1.4 kg, p=0.031; -4.4 kg vs -0.1 kg, p=0.013）. 術後2か月で細胞外水分率に差はなく, 体重に対する浮腫の影響は否定的であった. ICU退室時に見られた筋量減少（前群-16%, 後群-12%）は, 術後3か月で後群において有意に回復していた（前群-14%, 後群-4%, p=0.009）.</p><p>結語：早期栄養介入により, 術後早期の体重減少, 筋量減少が抑制された可能性がある.</p>

DOI： 10.11386/jst.56.supplement_s104

CiNii Research

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

<p>脳死関連肺傷害を受けているマージナルドナー肺の使用には、移植前にその傷害を的確に評価することにより、移植後の虚血再灌流傷害を予防しうる、より優れた臓器保存法が必要である。Ex Vivo Lung Perfusion（EVLP）は、正常体温（37℃）下に換気と灌流が維持された状態で臓器を保存することにより、移植前の体外での的確な肺機能評価と臓器保存時間の延長を可能にした。2000年に初めて、スウェーデングループが心停止ドナー肺の評価のために、EVLPを臨床の現場に導入して以降、世界各国においてEVLPを用いた臨床試験が行われている。EVLP評価により、移植適応ありと判断されたマージナルドナー肺を用いた肺移植は、良好な移植後成績を示しただけでなく、ドナー肺の使用率を倍増させることに成功している。本邦では2015年に初めて、EVLPを用いた肺移植が１例のみ単発で行われ、その有用性が報告された。京都大学では、2018年よりEVLPの臨床導入の準備を進め、2020年に実症例を経験した。他施設にて移植が断念されたマージナル肺を、EVLPにより的確に評価することで救い上げ、移植に成功することができた。EVLPによる的確な移植前機能評価は、マージナルドナー肺の使用拡大による移植待機患者の予後改善だけでなく、移植後患者の移植後成績改善のために、本邦においても重要になってくると考えられる。</p>

DOI： 10.11386/jst.56.supplement_s556

CiNii Research

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

<p>【背景】脳死ドナー臓器摘出では、外科医だけでなく臨床工学技士（ME）・看護師・コーディネーター等多職種が関わる医療で、実際の手技を知っていればよりよい連携が可能かもしれない。献体されたご遺体の固定方法は進化しており、特殊な保存液で固定された状態は生体と類似しているため、手術トレーニングに用いることが可能となった。肺移植実施施設でない当院での実施施設へのとり組みの一貫として、心臓外科医・ME・医学生と合同で臓器摘出トレーニングを実行したので報告する。</p><p>【トレーニング概要】開胸・心嚢切開し臓器評価方法を全員で確認した後、心灌流液注入用と肺灌流液ドレナージ用のカテーテルを各留置し、大血管を遮断し心臓摘出、続いて肺摘出を行った。続いてバックテーブルにて肺の植え込みができる状態にまで処理を行いトレーニング終了とした。心肺摘出に際して重要となる左房の処理については、操作を止め指導医にポイントを解説してもらいつつ、心臓外科・呼吸器外科の双方の考えを伝え、解剖を確認しながら行った。また、MEと肺灌流液ドレナージ経路の方法や肺灌流のタイミングなど細やかな部分まで共有できた。</p><p>【結語】本トレーニングは多職種での手技と順序の確認に有用で、臓器摘出の際互いに心がけているポイントや考えも共有・理解できた。今後はプログラムを定型化し、実践に対応できるレベルに質を高めつつ、看護師やコーディネーターも含めて行う予定である。</p>

DOI： 10.11386/jst.56.supplement_s105

CiNii Research

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

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

DOI： 10.1007/s11748-020-01305-6

PubMed

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

DOI： 10.1371/journal.pone.0241422

Scopus

Language：Japanese  

DOI： 10.1183/13993003.congress-2020.1943

Web of Science

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

DOI： 10.1093/ejcts/ezaa091

Scopus

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

PURPOSE: We investigated the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to evaluate programmed cell death ligand-1 (PD-L1) expression in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective chart review of patients who underwent EBUS-TBNA between April 2017 and April 2019 was conducted. Among patients diagnosed with NSCLC, we investigated the rate of successful evaluation of tumor PD-L1 expression, compared the relevant factors between patients with evaluable and those with unevaluable PD-L1 expression, and examined the response to immune checkpoint inhibitors (ICIs) after EBUS-TBNA. RESULTS: Of the 40 patients assessed, 32 (80%) had evaluable PD-L1 expression. Patients with evaluable PD-L1 expression were older than those with unevaluable PD-L1 expression (p = 0.017), and we noted a tendency for a larger diameter of the biopsied lymph node (p = 0.12). The response rate to ICIs was 100% in patients with a tumor proportion score (TPS) ≥ 50%, 33% in those with a TPS 1-49%, and 0% in those with a TPS < 1%. CONCLUSION: The diagnostic yield of EBUS-TBNA to evaluate PD-L1 expression in advanced NSCLC appeared acceptable in association with relevant clinical outcomes after treatment with ICIs. A further prospective study with a larger sample size is required to confirm our findings.

DOI： 10.1007/s00595-020-01989-6

PubMed

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

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

DOI： 10.1007/s11748-020-01289-3

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Association for Chest Surgery  

<p>A 76-year-old man presented with an abnormal shadow on a chest roentgenogram. After a comprehensive radiographic examination and transbronchial lung biopsy, the preoperative diagnosis was lung adenocarcinoma Stage IA2 (cT1bN0M0).</p><p>Chest computed tomography showed a partial anomalous pulmonary venous connection from the right upper and middle lobe and a right B1 bronchus branching from the trachea simultaneously. We attempted to perform complete video-assisted thoracic surgery (VATS) for right upper lobectomy. However, we required a small window incision to complete VATS lobectomy to improve our understanding of the intraoperative anatomy. In cases with uncommon anomalies such as the present patient, enlargement of the port incision to improve intraoperative understanding of the anatomy is important to perform a safe and minimally invasive procedure.</p>

DOI： 10.2995/jacsurg.34.321

CiNii Research

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

Because the lung deforms during surgery because of pneumothorax, it is important to be able to track the location of a tumor. Deformation of the whole lung can be estimated using intraoperative cone-beam CT (CBCT) images. In this study, we used deformable mesh registration methods for paired CBCT images in the inflated and deflated states, and analyzed their deformation. We proposed a deformable mesh registration framework for deformations of partial organ shapes involving large deformation and rotation. Experimental results showed that the proposed methods reduced errors in point-to-point correspondence. As a result of registration using surgical clips placed on the lung surface during imaging, it was confirmed that an average error of 3.9 mm occurred in eight cases. The result of analysis showed that both tissue rotation and contraction had large effects on displacement.

DOI： 10.1109/EMBC44109.2020.9176729

PubMed

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

BACKGROUND: Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare disease that resembles fetal lung tubules. Most of previous reports concerning WDFA have focused on histological features, while there are few reports describing radiological features. In addition, there are no reports evaluating the difficulty of intraoperative diagnosis of WDFA with frozen section. We report a case of WDFA and review the radiological features of WDFA including the findings of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and assess the difficulty of intraoperative diagnosis with frozen section. CASE PRESENTATION: A chest radiography performed in a 20-year-old female revealed a mass in the hilum of the right lung. Computed tomography revealed a well-defined mass measuring 3.5 × 3.0 cm in diameter in the right upper lobe, whereas PET showed a high accumulation of FDG. The most likely diagnosis was clinical T2aN0M0 stage 1B non-small cell lung cancer. A right S3 segmentectomy was performed via thoracotomy, and a benign tumor that was possibly an adenoma was intraoperatively diagnosed based on frozen section analysis. The mass was a solid tumor measuring 2.9 × 2.5 cm in diameter. Microscopically, the tumor comprised abundant glands with single or double layers of nonciliated cells and bronchial structures resembling a fetal lung. Rounded morules of polygonal cells were frequently observed. Immunohistochemistry revealed that nuclei and cytoplasm of the tumor cell were positive for β-catenin. Finally, the postoperative pathological diagnosis was well-differentiated fetal adenocarcinoma of the lung, and completion right upper lobectomy and mediastinal lymph node dissection were conducted 1 month after the initial segmentectomy. No residual tumor or lymph node metastasis was identified, and the final pathological stage was pT1cN0M0 stage 1A3. The patient did not wish to receive any adjuvant therapy. At the 1-year follow-up, no evidence of recurrence was noted. CONCLUSIONS: Here, we report a rare case of well-differentiated fetal adenocarcinoma of the lung that was difficult to diagnose based on radiological evaluations including FDG-PET and intraoperative diagnosis using frozen section analysis.

DOI： 10.1186/s40792-020-00910-0

PubMed

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

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

DOI： 10.2196/10.21873/anticanres.14311

Scopus

Language：English  

This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

DOI： 10.1111/ajt.15762

PubMed

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

BACKGROUND: Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS. METHODS: Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale. RESULTS: The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura. CONCLUSIONS: Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.

DOI： 10.1097/TP.0000000000003097

PubMed

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

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

DOI： 10.21873/anticanres.14311

PubMed

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

DOI： 10.1007/s10147-020-01624-x

Scopus

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

DOI： 10.18999/nagjms.82.2.161

Scopus

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

BACKGROUND: Molecular hydrogen can reduce the oxidative stress of ischemia-reperfusion injury in various organs for transplantation and potentially improve survival rates in recipients. This study aimed to evaluate the protective effects of a hydrogen-rich preservation solution against ischemia-reperfusion injury after cold ischemia in rat lung transplantation. METHODS: Lewis rats were divided into a nontransplant group (n = 3), minimum-ischemia group (n = 3), cold ischemia group (n = 6), and cold ischemia with hydrogen-rich (more than 1.0 ppm) preservation solution group (n = 6). The rats in the nontransplant group underwent simple thoracotomy, and the rats in the remaining 3 groups underwent orthotopic left lung transplantation. The ischemic time was <30 minutes in the minimum-ischemia group and 6 hours in the cold ischemia groups. After 2-hour reperfusion, we evaluated arterial blood gas levels, pulmonary function, lung wet-to-dry weight ratio, and histologic features of the lung tissue. The expression of proinflammatory cytokines was measured using quantitative polymerase chain reaction assays, and 8-hydroxydeoxyguanosine levels were evaluated using enzyme-linked immunosorbent assays. RESULTS: When compared with the nontransplant and minimum-ischemia groups, the cold ischemia group had lower dynamic compliance, lower oxygenation levels, and higher wet-to-dry weight ratios. However, these variables were significantly improved in the cold ischemia with hydrogen-rich preservation solution group. This group also had fewer signs of perivascular edema, lower interleukin-1β messenger RNA expression, and lower 8-hydroxydeoxyguanosine levels than the cold ischemia group. CONCLUSIONS: The use of a hydrogen-rich preservation solution attenuates ischemia-reperfusion injury in rat lungs during cold ischemia through antioxidant and anti-inflammatory effects.

DOI： 10.1016/j.jtcvs.2019.09.175

PubMed

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

Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody-photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.

DOI： 10.3390/cells9041019

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：THE INSTITUTE OF SYSTEMS, CONTROL AND INFORMATION ENGINEERS (ISCIE)  

<p>It is expected to grasp how the lung deform by the deaeration during surgery compared to the inflated lung. In this study we propose a method to estimate deformation of the deflated lung from the inflated one based on the relative position of some landmarks using dog lungs. The kernel method was employed for the estimation as a machine learning technique. We achieved mean local positional error of 2.96 mm for test data where the volume reduction by the deaeration was 40 %.</p>

DOI： 10.5687/iscie.33.123

CiNii Research

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

DOI： 10.1016/j.healun.2020.01.515

Scopus

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

DOI： 10.1016/j.healun.2020.01.1269

Scopus

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

DOI： 10.1016/j.healun.2020.01.690

Scopus

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

Copyright © 2020. Published by Elsevier Inc. PURPOSE: Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P < 0.01) and to have a significantly lower body mass index (BMI) (17.6±3.6 vs 22.6±4.2 kg/m2; P < 0.01) than those in the IPF group. Kaplan-Meier survival curves showed no significant difference in overall survival between groups (P = 0.66; Figure 1A). The stay in the intensive care unit (ICU) was significantly longer in the IPPFE group (22.8±19.15 vs 13.2±11.2 days; P < 0.01). In the IPPFE group, BMI did not improve even 1 year after transplant (pre-; 16.5±3.2 kg/m2 vs 2 years later; 15.6±2.5 kg/m2; P = 0.08). By two years after transplantation, percent predicted forced vital capacity in IPPFE group significantly improved (pre-; 36.9±17.2 vs 2 years later; 52.0±20.0 %; P = 0.03; Figure 1B). However, compared with the IPF group, the value was still significantly lower (52.0±20.0 vs 70.8±18.7 %; P < 0.01). CONCLUSION: The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.

DOI： 10.1016/j.healun.2020.01.706

Scopus

PubMed

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

DOI： 10.1016/j.healun.2020.01.414

Scopus

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

OBJECTIVES: T4 lung cancer has become a more heterogeneous group since the 8th edition of tumour, node, metastasis classification. The aim of this study was to identify predictive factors related to post-surgical survival in patients with clinical T4 non-small-cell lung cancer (NSCLC), based on the 8th edition of the classification. METHODS: We retrospectively reviewed consecutive patients with clinical T4 NSCLC who underwent resection between January 2006 and December 2016, to identify factors associated with overall survival. RESULTS: Ninety-three patients were identified. The criteria for clinical T4 disease included tumours larger than 7 cm (n = 54), great vessels or left atrial invasion (n = 22), mediastinal invasion (n = 11), vertebral invasion (n = 3), tracheal or carina invasion (n = 3), diaphragm invasion (n = 1) and ipsilateral different lobe pulmonary metastasis (n = 2). The postoperative nodal status was 0, 1, 2 and 3 in 59, 18, 15 and 1 patient, respectively. R0 resection was achieved in 80 patients, and the 30-day mortality was 0%. The median follow-up time was 37.6 months, and the 5-year overall survival rate was 56.3%. The multivariable analysis revealed that nodal status and R-status were significant prognostic factors for postoperative survival [hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.20-5.72, P = 0.016 and HR 3.29, 95% CI 1.45-7.44, P = 0.004]. CONCLUSIONS: Surgery provided encouraging survival outcomes for clinical T4 NSCLC based on the 8th edition of classification. The nodal status and R-status were significant prognostic factors for postoperative survival.

DOI： 10.1093/ejcts/ezz288

PubMed

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

DOI： 10.1016/j.jtcvs.2019.09.109

Scopus

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

BACKGROUND: Skeletal muscle dysfunction is a common feature in patients with severe lung diseases. Although lung transplantation aims to save these patients, the surgical procedure and disuse may cause additional deterioration and prolonged functional disability. We investigated the postoperative course of antigravity muscle condition in terms of quantity and quality using chest computed tomography. METHODS: 35 consecutive patients were investigated for 12 months after living-donor lobar lung transplantation (LDLLT). The erector spinae muscles (ESMs), which are antigravity muscles, were evaluated, and the cross-sectional area (ESMCSA) and mean attenuation (ESMCT) were analysed to determine the quantity and quality of ESMs. Functional capacity was evaluated by the 6-min walk distance (6MWD). Age-matched living donors with lower lobectomy were evaluated as controls. RESULTS: Recipient and donor ESMCSA values temporarily decreased at 3 months and recovered by 12 months post-operatively. The ESMCSA of recipients, but not that of donors, surpassed baseline values by 12 months post-operatively. Increased ESMCSA (ratio to baseline ≥1) may occur at 12 months in patients with a high baseline ESMCT. Although the recipient ESMCT may continuously decrease for 12 months, the ESMCT is a major determinant, in addition to lung function, of the postoperative 6MWD at both 3 and 12 months. CONCLUSION: The quantity of ESMs may increase within 12 months after LDLLT in recipients with better muscle quality at baseline. The quality of ESMs is also important for physical performance; therefore, further approaches to prevent deterioration in muscle quality are required.

DOI： 10.1183/23120541.00205-2019

PubMed

Language：Japanese   Publisher：Journal of Thoracic Disease  

Backgrounds: The number of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) cases is increasing due to its less-invasiveness and usefulness. However, there are several unresolved issues, including the existence of incomplete cases and complications. This study aimed to investigate the frequency and diagnostic management of incomplete EBUS-TBNA cases. Methods: Between July 2009 and December 2017, 424 patients underwent EBUS-TBNA for the diagnosis of suspected malignancy. Among them, we retrospectively reviewed the frequency, characteristics and diagnostic managements of incomplete cases of EBUS-TBNA. Results: EBUS-TBNA was not completed in 16 patients (3.8%), all of whom underwent EBUS-TBNA cases under conscious sedation. The factors for incompleteness of EBUS-TBNA under conscious sedation were divided into two groups: impossibility to perform EBUS-TBNA under conscious sedation (n=8) and impossibility to perform safe needle biopsy (n=8). The former factor consisted of strong coughing reflex and insufficient sedation (n=5), frequent desaturation during EBUS-TBNA (n=2), and allergy to lidocaine (n=1), while the latter factor consisted of anatomical reasons (n=4), abundant blood flow in the target lesion (n=3), and invisibility of the target lesion due to airway deformation (n=1). Eventually, 10 out of 16 cases were histologically diagnosed as having malignancy by a surgical approach (n=5) and EBUS-TBNA under general anesthesia (n=5). Conclusions: Although the number was small, we did note some incomplete cases of EBUS-TBNA under conscious sedation. In incomplete cases under conscious sedation, EBUS-TBNA under general anesthesia and other surgical approaches can be considered as additional options.

DOI： 10.21037/jtd.2019.12.133

Scopus

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

© 2020 The Authors Background: Small cell lung cancer (SCLC) has a poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is expressed specifically in SCLC and is considered a promising therapeutic target for patients with this disease. Rovalpituzumab tesirine (Rova-T) was the first antibody-drug conjugate targeting DLL3. Although Rova-T development was unfortunately terminated, DLL3 remains an ideal target for SCLC. Near infrared photoimmunotherapy (NIR-PIT) is a new form of cancer treatment that employs an antibody-photosensitiser conjugate followed by NIR light exposure and damage target cells specifically. In this study, we demonstrate DLL3-targeted NIR-PIT to develop a novel molecularly targeted treatment for SCLC. Methods: The anti-DLL3 monoclonal antibody rovalpituzumab was conjugated to an IR700 photosensitiser (termed ‘rova-IR700’). SCLC cells overexpressing DLL3 as well as non-DLL3-expressing controls were incubated with rova-IR700 and then exposed to NIR-light. Next, mice with SCLC xenografts were injected with rova-IR700 and irradiated with NIR-light. Findings: DLL3-overexpressing cells underwent immediate destruction upon NIR-light exposure, whereas the control cells remained intact. The xenograft in mice treated with rova-IR700 and NIR-light shrank markedly, whereas neither rova-IR700 injection nor NIR-light irradiation alone affected tumour size. Interpretation: Our data suggest that targeting of DLL3 using NIR-PIT could be a novel and promising treatment for SCLC. Funding: Research supported by grants from the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, JSPS), Medical Research Encouragement Prize of The Japan Medical Association, The Nitto Foundation, Kanae Foundation for the Promotion of Medical Science.

DOI： 10.1016/j.ebiom.2020.102632

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PubMed

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

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

DOI： 10.1007/s11748-019-01189-1

PubMed

Language：Japanese  

CiNii Research

Language：English  

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

DOI： 10.3748/wjg.v26.i3.366

PubMed

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

OBJECTIVES: In a living-donor lobectomy, the donor undergoes a right or left lower lobectomy. The surgical procedures for living-donor lobectomy are sometimes influenced by the anatomical variations of the pulmonary vein (PV). The goal of this study was to analyse the PV variations in living donors and to review the influence of these variations on the surgical procedures used. METHODS: Between June 2008 and September 2018, 154 living donors underwent right or left lower lobectomy. The PV variations were analysed using 3-dimensional computed tomography (3D-CT), and the surgical management of these variations was reviewed. RESULTS: Among 154 donors, 21 PV variations that could influence the surgical procedure for a right lower lobectomy were found in 19 (12.3%) donors, whereas no such variations for a left lower lobectomy were found. Detected PV variations were dorsal branch of the right upper PV (n = 12), middle PV draining into the right lower PV (n = 6) and the superior segment branch of the right lower PV draining into the right upper PV (n = 3). Among 96 donors undergoing right lower lobectomy, 9 (9.4%) donors had PV variations that could influence the surgical procedure. In 2 donors, sparing of PV branches with multiple vascular clamps was required. Pulmonary venoplasty was not required in any donor, whereas pulmonary venoplasty in recipient surgery was required in 4 recipients. There were no complications related to the surgical procedures performed on the PV. CONCLUSIONS: Living-donor lobectomy was performed safely owing to the preoperative evaluation of PV on 3D-CT and the use of appropriate surgical approaches to PV.

DOI： 10.1093/icvts/ivz238

PubMed

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

<p>We retrospectively surveyed the status of rituximab use in treatment for antibody-mediated rejection (AMR) in Japan between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.</p><p>Two hundred twenty-seven institutions responded. AMR developed in 493 patients who underwent kidney transplantation; 288 of those patients were treated with rituximab. AMR developed in 81 patients for liver transplantation, 4 patients for pancreas transplantation, 16 patients for heart transplantation, 22 patients for lung transplantation, and 2 patients for small intestine transplantation; rituximab was used in 18, 4, 4, 14, and 1 of those patients, respectively.</p><p>We also report on treatment details and rituximab dosage.</p>

DOI： 10.11386/jst.55.1_51

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

<p>A retrospective survey was conducted to assess the status of organ transplantation in patients with pre-formed donor-specific anti-HLA antibodies and the implementation of desensitization with rituximab in Japan. We obtained the data from 227 institutions for procedures performed between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.</p><p>Results showed pre-formed donor-specific antibodies (DSA) in recipients of 529 transplanted kidneys; rituximab was used in 462 of those transplantations. Rituximab was used in 48 of 135 liver transplantations in recipients with pre-formed DSA and in 1 of 1 small intestine transplantation involving pre-formed DSA. Such DSA was also reported in 5 heart transplants and 4 lung transplants. However, rituximab was not used for desensitization in any of those procedures.</p><p>We also report on detection and assay of anti-HLA antibodies and DSA, criteria for transplantation, dosage of rituximab, and concomitant immunosuppressive drugs used at the institutions.</p>

DOI： 10.11386/jst.55.1_39

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

DOI： 10.1053/j.semtcvs.2020.06.004

Scopus

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

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

DOI： 10.1007/s11748-020-01382-7

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PubMed

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

DOI： 10.1016/j.jtcvs.2019.12.089

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PubMed

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

DOI： 10.1155/2020/4912920

Scopus

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

Objective: According to the tumor-node-metastasis classification for thymic malignancies, the proportion of patients diagnosed with stage I is expected to increase significantly. However, whether those patients have homogenous clinicopathological features and survival has not been fully evaluated. Methods: We reviewed 153 consecutive patients with stage I thymic epithelial tumors (133 thymomas, 15 thymic carcinomas, and 5 neuroendocrine tumors) who underwent complete resection at our institution between 2001 and 2016 and evaluated the prognostic significance of their clinicopathological factors. Results: The stage I patients accounted for 78% of all thymic epithelial tumors. The 5-year overall survival and recurrence-free survival rates of the 153 patients were 94% and 80%, respectively. The patients with the histology of thymic carcinoma or neuroendocrine tumor and with a tumor larger than 5.0 cm showed significantly worse recurrence-free survival in multivariate analysis (p = 0.027 and 0.038, respectively). Only the tumor size was revealed as a significant prognostic factor for recurrence-free survival when limited in the 133 cases of thymoma (p = 0.048). Conclusions: Patients with large tumors showed significantly worse recurrence-free survival than those with small tumors both in stage I thymic epithelial tumors and thymomas.

DOI： 10.1007/s11748-020-01427-x

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PubMed

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

DOI： 10.1007/s11325-020-02092-3

Scopus

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

OBJECTIVES: This study investigated survival outcomes of resection for pulmonary malignancies after esophagectomy for esophageal carcinoma, comparing non-small cell lung cancer and pulmonary metastases. METHODS: We retrospectively reviewed consecutive patients who underwent resection for pulmonary malignancies after esophagectomy for esophageal carcinoma between 2009 and 2018. The overall survival and relapse-free survival rate were assessed using Kaplan-Meier analysis. RESULTS: Eleven patients had non-small cell lung cancer and eight patients had pulmonary metastases from esophageal carcinoma. The 5-year overall survival rate was 92.9% in all patients with a median follow-up period of 50.4 (range: 9.1-130.2) months. While the 5-year overall survival rate was 100.0% in patients with non-small cell lung cancer, it was 85.7% in patients with pulmonary metastases from esophageal carcinoma. The 5-year relapse-free survival rate was 85.7% in patients with non-small cell lung cancer. CONCLUSIONS: Our data suggest that resection for pulmonary malignancies after esophagectomy for esophageal carcinoma is associated with favorable survival outcomes and should be considered in selected patients.

DOI： 10.1007/s11748-020-01373-8

Scopus

PubMed

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

DOI： 10.1016/j.jtcvs.2020.09.110

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：一般社団法人 日本移植学会  

DOI： 10.11386/jst.55.3_145

CiNii Research

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

DOI： 10.1016/j.jtcvs.2020.10.065

Scopus

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

<p>2019年末からの中国武漢での報告後、瞬く間に世界中に拡散した新型コロナウイルス感染症 (COVID-19)は、現在も収束することなく、2020年8月31日時点で全世界で2500万人以上が感染していると報告されている。COVID-19は、移植医療の在り方に大きな影響をもたらし、世界中の多くの移植施設で、生命に関わる臓器の移植を除き、生体移植を中心とした待機可能な移植は一時停止を余儀なくされた。ドナーからの伝播の可能性、院内感染の可能性、移植患者への感染対応など、様々な状況を想定し、院内のコンセンサスを得ることで、現状では多くの施設が移植医療の提供を再開した。しかし、安心安全な移植医療を提供するためには、COVID-19以前とは異なる、新しい移植医療の様式を実践していく必要がある。また、移植患者は免疫抑制剤を服用しており、ウイルス感染症に脆弱である一方、COVID-19は、感染後期での免疫抑制剤使用による重症化抑制も知られている。相反する病態を理解し、免疫抑制剤調整を含めた移植患者の管理を適切に行うことも重要である。これまでに得られたCOVID-19と移植医療に関する文献的報告をレビューし、新しい移植医療の様式について提言したい。</p>

DOI： 10.11386/jst.55.supplement_194_1

CiNii Research

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

<p>【背景】固形臓器移植後の術後成績にFcγ受容体の一塩基多型（SNP）が与えうる影響についての研究はいくつかあるが、肺移植に関する研究はほとんどない。本研究の目的はFcγ受容体IIA（FCGR2A）のSNPが肺移植後の術後成績に与える影響を検討することである。【対象と方法】2008年から2018年までに201例の肺移植が施行された。この中から再肺移植症例、残余DNAサンプルがない症例、ICU退室不可症例を除いた191例を対象とした。この191例に関してFCGR2AのSNP（131 histidine [H] or arginine [R]）を解析し、術後成績とSNPとの関連について検討した。【結果】FCGR2AのSNPの内訳は、H/H（n=120）、H/R（n=66）、R/R（n=5）であった。H/H群（H/H）とR群（H/R or R/R）の2群で解析を行ったところ、ICU退室から術後1年以内の肺炎の頻度および真菌感染症の頻度は、R群で有意に高かった（p=0.004およびp=0.012）。全生存率に関しては2群間に有意差を認めなかった（p=0.67）。【結語】FCGR2AのSNPに関して、予後には2群間で有意な差を認めなかったが、R群では1年以内の肺炎および真菌感染症の頻度が有意に高かった。</p>

DOI： 10.11386/jst.55.supplement_354_1

CiNii Research

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

OBJECTIVES: Studies showing that individuals with non-small cell lung cancer (NSCLC) and diabetes mellitus (DM) have reported poor outcomes after pulmonary resection with varying results. Therefore, we investigated the clinical impact of preoperative DM on postoperative morbidity and survival in individuals with resectable NSCLC. PATIENTS AND METHODS: Data of individuals who underwent pulmonary resection for NSCLC from 2000 to 2015 were extracted from the database of Kyoto University Hospital. The primary endpoint was the incidence of postoperative complications, and secondary endpoints were postoperative length of hospital stay and overall survival. The survival rate was analyzed using the Kaplan-Meier method. RESULTS: A total of 2,219 patients were eligible for the study. The median age of participants was 67 years. Among them, 39.5% were women, and 259 (11.7%) presented with DM. The effect of DM on the incidence of postoperative complications and postoperative length of hospital stay was not significant. Although the 5-year survival rates were similar in both patients with and without DM (80.2% versus 79.4%; p = 0.158), those with DM who had a hemoglobin A1c level ≥ 8.0% had the worst survival. CONCLUSIONS: In individuals with resectable NSCLC, preoperative DM does not influence the acute phase postoperative recovery. However, poorly controlled preoperative DM could lead to low postoperative survival rates.

DOI： 10.1371/journal.pone.0241930

PubMed

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

BACKGROUND: Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated. METHOD: Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated. RESULTS: Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index. CONCLUSION: Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients.

DOI： 10.1371/journal.pone.0227775

PubMed

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

BACKGROUND: Primary peritoneal carcinoma (PPC) is a very rare and aggressive type of malignancy with a poor prognosis. CASE PRESENTATION: A 66-year-old woman was referred to our hospital with two pulmonary nodules that developed after PPC resection and postoperative adjuvant chemotherapy administered 5 years earlier. Computed tomography revealed a 1.3-cm-sized nodule in the left lung with a small airspace in the posterior basal segment and a 0.9-cm-sized solid nodule in the apico-posterior segment that grew slightly within a 2-month period. 18F-Fluorodeoxyglucose-positron emission tomography of these lesions revealed respective maximum standardized uptake values of 7.11 and 2.46. Her serum cancer antigen-125 level remained within the normal range, despite elevation before the first surgery. The posterior basal segment and superior division were subjected to anatomical segmentectomy. An intraoperative frozen section examination could not distinguish metastatic PPC from primary lung cancer. Immunopathologically, the two nodules were identified as metastatic PPC. CONCLUSIONS: Our findings suggest that PPC patients may develop late-phase thoracic recurrence that is difficult to diagnose clinically after initial treatment in a potentially resectable setting.

DOI： 10.1186/s40792-019-0752-0

PubMed

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

OBJECTIVES: Owing to the severe donor shortage in Japan, living-donor lobar lung transplantation (LDLLT) remains a valuable option. As only lobes are implanted in LDLLT, grafts may be too small, especially for adult recipients. To overcome this obstacle, we developed right-to-left inverted LDLLT. In this procedure, the right lower lobe, which is 25% bigger than the left lower lobe, is used as the left-side graft instead of the left lower lobe. This study aimed to investigate the characteristics and intermediate outcomes of right-to-left inverted LDLLT. METHODS: Since the first right-to-left inverted LDLLT performed in 2014, 48 LDLLTs have been performed in our institution, of which 15 were right-to-left inverted LDLLTs. We reviewed their characteristics and intermediate outcomes. RESULTS: The reasons for choosing an inverted procedure instead of the standard LDLLT were small-for-size graft in 11 cases and anatomical variation of donor vessels in 4 cases. The first patient underwent left single LDLLT using a right lower lobe graft, and the following 14 patients underwent bilateral LDLLT using 2 right lower lobe grafts. A native upper lobe-sparing procedure was additionally applied in 2 patients. No complications occurred in the bronchial and vascular anastomoses. No operative mortality occurred, and all the patients were discharged home after LDLLT. The 3-year survival was 92.3%, with a median follow-up time of 40 months. The donor postoperative course was uneventful, and all the donors returned to their regular routine postoperatively. CONCLUSION: Right-to-left inverted LDLLT is a safe and useful option with encouraging intermediate outcome.

DOI： 10.1093/ejcts/ezz244

PubMed

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

PURPOSE: The pulmonary artery (PA) in patients with pulmonary hypertension (PH) becomes dilated. We analyzed the postoperative changes of the main PA after lung transplantation (LuTx). METHODS: The subjects of this retrospective study were 68 LuTx recipients, divided into a PH group (n = 36) and a non-PH group (n = 32), based on preoperative right heart catheterization findings. The PA diameter was measured on chest computed tomography. We evaluated the correlation between the mean pulmonary arterial pressure (mPAP) and the main PA diameter and compared the main PA diameters before and 3 months after LuTx. RESULTS: The main PA diameter was significantly correlated with the mPAP (r = 0.423, P < 0.001). Preoperatively, the mean main PA diameter in the PH group was significantly greater than that in the non-PH group. However, by 3 months after LuTx, the main PA diameter in the PH group had decreased significantly from 32.4 ± 6.7 to 26.9 ± 4.8 mm (P < 0.001), while that in the non-PH group had decreased minimally from 28.3 ± 4.9 to 26.4 ± 4.6 mm (P < 0.001), resulting in no significant difference in postoperative main PA diameters between the two groups. CONCLUSIONS: The main PA diameter in recipients with PH was enlarged and correlated with the mPAP. The dilated main PA diameter in PH patients decreased shortly after LuTx.

DOI： 10.1007/s00595-019-01887-6

PubMed

Language：English  

DOI： 10.1016/j.jtcvs.2019.07.136

PubMed

Language：English  

DOI： 10.1093/icvts/ivz110

PubMed

Language：English  

DOI： 10.1016/j.jtcvs.2019.04.093

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Thoracic Society  

DOI： 10.1165/rcmb.2018-0188OC

PubMed

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

Language：English  

DOI： 10.1016/j.jtcvs.2019.07.099

PubMed

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

Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article.

DOI： 10.1016/j.athoracsur.2019.06.092

PubMed

Language：English  

DOI： 10.1016/j.athoracsur.2019.06.087

PubMed

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

Observational or randomized studies on survival outcome following surgery versus stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) demonstrated various results, and several meta-analyses on this topic have been published. The PubMed database was queried for meta-analyses comparing surgery and SBRT for early stage NSCLC. Six meta-analyses on this comparison were identified and 4 (66.7%) suggested that surgery be associated with significantly more favorable overall survival than SBRT, using odds ratio or hazard ratio (HR) as measures of effect. Most of the included studies in the meta-analyses were observational studies and those meta-analyses should be interpreted with caution.

DOI： 10.21037/jtd.2018.10.35

PubMed

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

OBJECTIVE: In standard bilateral living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted in the recipient in place of whole right and left lungs. In other words, total 10 lobes (5 lobes in each donor) are shared by the 2 donors (4 lobes in each donor) and the recipient (2 lobes) in this transplant procedure. This study aimed to compare pulmonary function between donors and recipients before and after LDLLT. METHODS: We performed 76 LDLLT procedures between June 2008 and March 2017. After excluding 12 single LDLLT and 11 native-lung-sparing LDLLT procedures, we identified 38 recipients of bilateral LDLLT who survived >1 year and underwent routine pulmonary function testing. Acquired recipient pulmonary function was compared with lost donor pulmonary function at 1 year post-LDLLT. RESULTS: The median age of the 38 recipients was 44 years (range, 8-62 years); 14 were men. The median age of the 76 donors was 41.5 years (range, 20-60 years); 50 were men. One year post-LDLLT, acquired recipient forced vital capacity was significantly greater than lost donor forced vital capacity (1889.5 ± 581.3 mL vs 1073.9 ± 661.6 mL; P < .001). Similarly, acquired recipient forced expiratory volume in 1 second at 1 year post-LDLLT was significantly greater than lost donor forced expiratory volume in 1 second (1646.8 ± 483.0 mL vs 1064.2 ± 534.5 mL; P < .001). CONCLUSIONS: These results indicated that acquired recipient pulmonary function was better than lost donor pulmonary function in bilateral LDLLT.

DOI： 10.1016/j.jtcvs.2019.06.058

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DOI： 10.1016/j.stemcr.2019.05.022

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DOI： 10.1007/s11748-018-1006-y

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DOI： 10.1016/j.jtcvs.2018.08.098

PubMed

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

DOI： 10.1007/s11548-019-02013-0

PubMed

Other Link： https://dblp.uni-trier.de/db/journals/cars/cars14.html#NakaoTCDM19

Language：English  

Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition-related factors associated with waiting list mortality. Seventy-six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2 ; 6-minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C-reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97-1015) days, and median survival time was 550 (95% CI 414-686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person-years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633-0.988) and 6MWD (HR 0.795, 95% CI 0.674-0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes.

DOI： 10.1111/ctr.13566

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DOI： 10.1016/j.jtcvs.2018.12.064

PubMed

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DOI： 10.1016/j.athoracsur.2018.09.013

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DOI： 10.1007/s11748-018-1038-3

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DOI： 10.1007/s00595-018-1740-x

PubMed

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

It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases.

DOI： 10.1016/j.stemcr.2019.01.014

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DOI： 10.1093/icvts/ivy260

PubMed

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

BACKGROUND: Selecting the proper surgical approach for mediastinal tumors in the thoracic outlet is difficult. Video-assisted thoracoscopic surgery is ideal because of the less invasiveness; however, it is often difficult to resect tumors only by video-assisted thoracoscopic surgery due to the poor visualization of the cranial side of tumors. We report two successfully treated cases by using a dual approach consisting of the transmanubrial osteomuscular sparing technique and video-assisted thoracoscopic surgery for aiming both the less invasiveness and the good visualization of the cranial side of tumors. CASE PRESENTATIONS: We present two resected cases of the mediastinal tumor in the thoracic outlet. The first case was a 28-year-old woman and the second case was a 37-year-old man. They had a mediastinal tumor in the thoracic outlet which was detected on the roentgenogram. A definitive preoperative diagnosis was unavailable. The surgical resection was started with video-assisted thoracoscopic surgery in the both cases. After the dissection of the caudal side of the tumor, the dissection of the cranial side was judged to be difficult and risky because the tumor was located adjacent to major vessels and the good visualization of this side couldn't be acquired. Therefore, the transmanubrial approach was sequentially performed and complete resection was safely achieved. Postoperatively, although transient Horner syndrome appeared in both cases, they recovered from this syndrome and were discharged. The final diagnosis was schwannoma for both cases. Neither of the cases had any functional restriction of the upper extremity. CONCLUSIONS: This dual approach for mediastinal tumors in the thoracic outlet is useful in terms of safety and lower invasiveness.

DOI： 10.1186/s13019-019-0863-5

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Language：English  

DOI： 10.1093/ejcts/ezy248

PubMed

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

OBJECTIVES: Microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor. MATERIALS AND METHODS: From 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining. RESULTS: Among the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/-; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p =  0.016). CONCLUSION: MVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.

DOI： 10.1016/j.lungcan.2018.12.001

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DOI： 10.1016/j.healun.2018.09.012

PubMed

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DOI： 10.1016/j.jtcvs.2018.09.062

PubMed

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

Purpose: The epithelial to mesenchymal transition (EMT) is pivotal for driving metastasis and recurrence in lung cancer. Some in vitro reports have shown that statins suppress EMT by inactivating mutant p53 functions. Several clinical trials of conventional treatments with statins have been performed, but the effect of these drugs on prognosis is still uncertain. The purpose of this study is to examine the impact of statins on EMT and the prognosis of patients with lung adenocarcinoma. Materials and methods: Morphological changes were evaluated and EMT markers (E-cadherin, vimentin) were analyzed by Western blotting in p53-overexpressing H1650 and mutant p53-harboring H1975 lung adenocarcinoma cells, with and without simvastatin administration. The invasive ability of these cells was analyzed in a Matrigel chemoinvasion assay. A total of 250 lung adenocarcinoma specimens were also collected from patients who underwent surgery in our institute. EMT markers in these tumor specimens were evaluated by immunostaining and p53 mutation status was determined by direct sequencing. Associations among EMT status, p53 mutation status, and statin use were evaluated, and prognosis was analyzed using a marginal structural model. Results: Mutant p53 induced EMT and increased the invasive ability of H1650 cells. Simvastatin restored the epithelial phenotype and decreased the invasive ability of both H1650 and H1975 cells. Statin administration was associated with inactivation of EMT only in patients with mutant p53, which was consistent with the in vitro results. Moreover, in patients with mutant p53, statin users had significantly better survival than non-statin users. In contrast, statins significantly worsened the prognosis of patients with wild type p53 (HR 2.10, 95% CI 1.14-3.85). Conclusion: Statins suppress EMT and change the prognosis of patients with lung adenocarcinoma in a p53 mutation-dependent manner.

DOI： 10.2147/CMAR.S200819

PubMed

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DOI： 10.1055/s-0038-1675346

PubMed

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DOI： 10.1016/j.lungcan.2018.09.023

PubMed

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

Background: Early diagnosis of unilateral chronic lung allograft dysfunction (CLAD) is difficult because the unaffected contralateral lung functions as a reservoir in bilateral living-donor lobar lung transplantation (LDLLT). We previously reported the usefulness of 133Xe ventilation scintigraphy for detection of unilateral change, but the supply of 133Xe has been stopped globally. The present study aimed to examine the usefulness of inspiratory and expiratory computed tomography (I/E CT) volumetry for detection of unilateral change in CLAD patients. Methods: This was a retrospective single-center, observational study using prospectively collected data. A total of 58 patients who underwent bilateral LDLLT from August 2008 to February 2017 were analyzed. Respiratory function tests, I/E CT were prospectively conducted. ΔLung volume was defined as the value obtained by subtracting expiratory lung volume from inspiratory lung volume. Results: Fourteen (24%) cases were clinically diagnosed with CLAD, of which 10 (71%) were diagnosed as unilateral CLAD. ΔLung volume of bilateral lungs strongly correlated with forced vital capacity (r = 0.92, P < 0.01) and forced expiratory volume in 1 second (r = 0.80, P < 0.01). Regardless the phenotypes (bronchiolitis obliterans syndrome or restrictive allograft syndrome) of CLAD, Δlung volume onset/baseline significantly decreased compared with that in the non-CLAD group. Among the 10 unilateral CLAD patients, 3 with clinically suspected unilateral rejection yet did not show a 20% decline in forced expiratory volume in 1 second. In 2 of these, Δlung volume of unilateral lungs on the rejection side decreased by 20% or more. Conclusions: Our findings suggest that I/E CT volumetry may be useful for assessment and early diagnosis of unilateral CLAD after bilateral LDLLT.

DOI： 10.1097/TXD.0000000000000839

PubMed

DOI： 10.1093/icvts/ivy107

PubMed

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

PURPOSE: Gastrointestinal complications after lung transplantation (LTx) are an important postoperative morbidity associated with malnutrition and the malabsorption of drugs. We reviewed our experience of managing gastrointestinal complications after LTx. METHODS: Between June, 2008 and April, 2017, 160 lung transplants were performed at our institution, as living-donor lobar lung transplants in 77 patients, and as deceased-donor lung transplants in 83. We reviewed, retrospectively, the incidence, type and management of gastrointestinal complications. RESULTS: Among the 160 LTx recipients, 58 (36.3%) suffered a collective 70 gastrointestinal complications, the most frequent being gastroparesis, followed by gastroesophageal reflux disease. Two complications were managed surgically, by Nissen fundoplication for gastroesophageal reflux disease in one recipient and Hartmann's operation for sigmoid colon perforation in one. The other 68 complications were managed medically. Two patients died of complications: one, of aspiration pneumonia caused by gastroparesis; and one, of panperitonitis caused by a gastric ulcer. There were no significant differences in overall survival or chronic lung allograft dysfunction-free survival between the patients with and those without gastrointestinal complications. CONCLUSIONS: Gastrointestinal complications are not uncommon in LTx recipients and may be serious; therefore, early detection and appropriate treatment are imperative. Surgical management is required for some complications, but most can be managed medically.

DOI： 10.1007/s00595-018-1666-3

PubMed

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

BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

DOI： 10.1186/s12931-018-0860-6

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Purpose: We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC
UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects. Methods: Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen. Results: After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies. Conclusion: Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.

DOI： 10.1007/s00595-018-1646-7

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

Aims: GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry (IHC) in order to define its association with clinicopathological characteristics. Methods and results: IHC analysis of GATA6 was performed with tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumours other than lung cancer was also evaluated. GATA6 expression was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P = 0.005), and was associated with the absence of lymph node metastasis (P =0.024), well-differentiated to moderately differentiated tumours (P &lt
0.001), the absence of lymphatic invasion (P = 0.020), and the absence of vascular invasion (P = 0.011). GATA6 expression was associated with mucin production (P &lt
0.001), the invasive mucinous adenocarcinoma subtype (P &lt
0.001), KRAS mutations (P = 0.026), expression of MUC2 (P &lt
0.001), CDX2 (P = 0.049), and MUC5AC (P &lt
0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also associated with hepatocyte nuclear factor 4α (HNF4α) expression (P &lt
0.001). GATA6 expression tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (P = 0.033). Of 270 tumours other than lung cancer, 110 expressed GATA6. Conclusions: These findings suggest that GATA6 might interact with HNF4α and contribute to the development of mucinous-type LAs.

DOI： 10.1111/his.13500

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Background: The validity of lobar lung transplantation (LT) has been established in both living-donor lobar lung transplantation (LDLLT) and cadaveric-donor lung transplantation (CLT). However, bronchial stump management in lobar LT has not been precisely documented. Thus, we retrospectively analyzed our strategies for bronchial stump management in lobar LT. Methods: Between June 2008 and August 2016, 145 LTs (72 LDLLTs and 73 CLTs) were performed at our institution. Bronchial stumps were left in 14 LDLLTs. Eight patients underwent bilateral CLTs with downsizing lobectomy. We avoided leaving donor bronchial stumps by lobar-to-lobar bronchial anastomosis, and left recipient bronchial stumps if necessary. We retrospectively reviewed the bronchial stump management methods and outcomes in these 22 patients. Results: Among the 14 LDLLTs, right-to-left inverted lobar LT and right single-lobe LT with left pneumonectomy were performed in 12 and 2 patients, respectively. Among the 8 CLTs, 11 lobectomies were performed because of oversized grafts and/or localized pneumonia. Twenty-three lobar-to-lobar bronchial anastomoses were performed, and there were 21 recipient bronchial stumps in total. Three bronchial stumps were left in the donor graft, the middle bronchus in all cases. No complications related to lobar-to-lobar bronchial anastomoses were observed. All bronchial stumps healed well without developing a bronchopleural fistula. The 3-year overall survival rate was 88.1% (95% confidence interval, 58.8%-97.0%). Conclusions: We successfully avoided leaving bronchial stumps in the donor graft, except in the middle bronchus, by performing lobar-to-lobar bronchial anastomoses in lobar LTs. Excellent healing of lobar-to-lobar bronchial anastomoses and bronchial stumps was observed.

DOI： 10.1016/j.jtcvs.2017.10.150

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Objectives: Extended thymectomy is a treatment option for myasthenia gravis (MG), but the surgical indications are controversial. Pathologic features of the thymus can be used to predict surgical outcomes, but there is no reliable method for evaluating these characteristics preoperatively. The purpose of this study was to determine whether anterior mediastinal tissue volume, as measured via 3-dimensional computed tomography (3DCT) volumetry, correlates with serum anti-acetylcholine receptor antibody (AChRAb) levels in patients undergoing thymectomy for myasthenia gravis. Therefore, we investigated the relationships among anterior mediastinal tissue volume determined by 3DCT volumetry and AChRAb levels. Methods: The subjects were 28 patients who underwent extended thymectomy and were enrolled retrospectively. We measured volume of the anterior mediastinum and calculated the volumes of more than −30 Hounsfield units (V−30) by using 3DCT volumetry and compared them with perioperative AChRAb levels. The significance of their volumes in MG was examined by comparison with 53 patients without MG. Results: V−30 values were related to age and were significantly greater in patients with MG than in patients without MG (P &lt
.001). V−30 values were correlated positively with preoperative AChRAb levels (ρ = 0.505, P =.006) and inversely with the post/preoperative AChRAb ratio (ρ = −0.453, P =.018). The histologic nonadipose tissue ratio was correlated with the V−30/volume of the anterior mediastinum (ρ = 0.700, P &lt
.001). Conclusions: This method for evaluation of the anterior mediastinal tissue volume and AChRAb production may be helpful in establishing a treatment plan for MG.

DOI： 10.1016/j.jtcvs.2017.10.082

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

Background: Electromagnetic navigational bronchoscopy (ENB) is a new bronchoscopic technique for navigational transbronchial lung biopsy (TBLB) that guides the sheath to the target lesion in real time. Herein, we report our experience with this navigational system, its diagnostic yields, and associated complications. Methods: A single-center, single-operator retrospective chart review was performed. We included 35 consecutive patients who underwent ENB with superDimension™ (Medtronic, MN, USA) for the diagnosis of pulmonary lesions from February 2016 to May 2017 in Kyoto University Hospital. The size of the target lesion varied from 8 to 25 mm (median, 15.28±5.48 mm). All ENB procedures were performed under conscious sedation using 2 to 10 mg midazolam and 1 to 10 mg morphine hydrochloride. No fluoroscopic guide was employed except in three cases. Results: A total of 25 patients were diagnosed via ENB, yielding a diagnostic rate of 71.4% (25/35). The average lesion size of the diagnosed group was 16.44±5.44 mm (range, 8-25 mm). Eighteen cases were diagnosed as primary lung cancer, 3 were metastatic lung cancer, and 4 were inflammatory diseases. The average lesion size of the 10 undiagnosed cases was 12.40±5.21 mm (range, 8-24 mm). The lesion size of the undiagnosed group was significantly smaller than that of the diagnosed group (P=0.02). The average time required for the procedure was 16.78±9.57 minutes (range, 3-46 minutes), independent of the diagnosis, the lesion size, and the tumor location. We encountered one pneumothorax which required chest drainage and one hemopneumothorax which required non-elective thoracotomy and wedge resection. One patient developed high fever over 38 ° for one day following the procedure. Conclusions: In our initial series of 35 cases, ENB-guided TBLB showed an acceptable diagnostic yield.

DOI： 10.21037/jtd.2018.04.123

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Association for Cardio-Thoracic Surgery  

The authors report the first case involving a patient with Wiskott-Aldrich syndrome who underwent single living-donor lobar lung transplantation after haematopoietic stem cell transplantation. Haematopoietic stem cell transplantation was performed at 1 year of age
however, he developed severe pulmonary complications. Although lung transplantation is generally contraindicated in patients with immunodeficiency disease, the patient was able to undergo living-donor lobar lung transplantation because his immunodeficiency and thrombocytopenia were well controlled as a result of haematopoietic stem cell transplantation. Currently, the patient is doing well and is free from oxygen supplementation.

DOI： 10.1093/ejcts/ezx461

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

There is a dearth of data on management of anastomotic airway dehiscence following lung transplantation. Herein we report a case of successful conservative management of an anastomotic airway dehiscence after cadaveric donor lung transplantation. A 41-year-old woman with primary ciliary dyskinesia underwent cadaveric bilateral lung transplantation without cardiopulmonary bypass. On the postoperative day 25, left pneumothorax developed and bronchoscopy demonstrated a localized anastomotic dehiscence at the left main bronchus. The dehiscence was managed with 2 weeks of pleural drainage and was completely covered with regenerated bronchial epithelium at 4 months after transplantation. There is no finding suggestive of significant stenosis at 4 years of follow-up. Our case suggested asymptomatic and localized anastomotic dehiscence does not always require endobronchial stent placement or re-operation. Multiple factors that may contribute to the successful conservative management were discussed in this article.

DOI： 10.1007/s11748-017-0826-5

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Language：English  

DOI： 10.1002/jso.25045

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Objectives: The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes. Methods: We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: “early” if less than 3 days or “late” if 3 or more days after lung transplantation. Results: Forty-nine patients (51%) underwent tracheostomy 3.2 ± 1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p = 0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p = 0.003) and oral feeding (p = 0.0006) earlier and had a shorter duration of mechanical ventilation (p = 0.04) and shorter length of intensive care unit (p = 0.01) and hospital stay (p = 0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p = 0.06), oral feeding (p = 0.17), or length of hospital stay (p = 0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy. Conclusions: Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.

DOI： 10.1007/s11748-018-0949-3

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Background: Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. Methods: To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. Results: Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. Conclusions: Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.

DOI： 10.1016/j.resinv.2017.12.010

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PubMed

DOI： 10.1177/0218492318765872

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier USA  

Background: To overcome the problem of small-for-size grafts in standard living-donor lobar lung transplantation (LDLLT), we developed inverted LDLLT, in which a right lower lobe from 1 donor is implanted as a right graft and another right lower lobe from another donor is implanted as a left graft. We retrospectively analyzed the functions of inverted grafts vs noninverted grafts. Methods: Between 2008 and 2015, 64 LDLLTs were performed. Included were 35 LDLLTs whose recipients were adults and monitored for more than 6 months without developing chronic lung allograft dysfunction. Among them, 65 implanted lobes were eligible for this analysis. There were 31 right lower lobes implanted as right grafts (right-to-right group), 7 right lower lobes as inverted left grafts (right-to-left group), and 27 left lower lobes as left grafts (left-to-left group). We evaluated the graft forced vital capacity (G-FVC) and graft volume of the 65 lobes before and 6 months after LDLLT and compared them among the three groups. Results: Preoperatively, G-FVC in the right-to-left group (1,050 mL) was comparable to that in the right-to-right group (1,177 mL) and better than that in the left-to-left group (791 mL, p &lt
0.01). Six months after LDLLT, G-FVC in the right-to-left group (1,015 mL) remained comparable to that in the right-to-right group (1,001 mL) and better than that in the left-to-left group (713 mL, p = 0.047). The ratio of graft volume 6 months after LDLLT to the preoperative value was comparable. Conclusions: The functions of inverted grafts in inverted LDLLTs were satisfactory compared with those of noninverted grafts.

DOI： 10.1016/j.athoracsur.2017.11.034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

OBJECTIVES: Surgical treatments for metachronous second primary lung cancer (MSPLC) may be increasing. It was thought that surgery for MSPLC is associated with high mortality and morbidity. However, recent diffusion of minimally invasive surgical procedures may improve the safety of surgery for MSPLC. The aim of this study was to clarify the safety and prognosis of surgery for MSPLC compared with that for primary lung cancer (PLC). METHODS: We reviewed medical records of 1340 patients who underwent pulmonary resection for non-small-cell lung cancer between 2006 and 2013. We identified patients with PLC and those with MSPLC, and surgical parameters and survival outcome were compared. To eliminate selection bias between the MSPLC group and the PLC group, propensity score-matched analysis on the basis of clinicopathological factors was performed. RESULTS: Fifty-three patients underwent resection for MSPLC. Propensity score matching identified 50 patients from each treatment group. Of the 50 MSPLC patients, 41 (82.0%) underwent segmentectomy or wedge resection, 44 (82.0%) had clinical Stage I tumour and 36 (72.0%) received resection via video-assisted thoracoscopic surgery approach. Postoperative complications with a severity of Grade II or more occurred in 11 (22.0%) patients. The incidence of postoperative complications in the MSPLC group was not different from that of the PLC group (P = 0.4894). The 5-year overall survival rates were 68.7% and 83.0% in the PLC and the MSPLC groups, respectively. There was no significant difference between the PLC and the MSPLC groups in terms of overall survival (P = 0.2018, log-rank test). CONCLUSIONS: Pulmonary resection for MSPLC was safely performed with low short-term morbidity similar to that of PLC, and its longterm overall survival was acceptable.

DOI： 10.1093/icvts/ivx389

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DOI： 10.1016/j.athoracsur.2017.11.003

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

A 55-year-old man with end-stage emphysema underwent a right single-lung transplantation through a posterolateral thoracotomy. The fifth rib was divided and fused back using a biodegradable pin made of polylactide acid and hydroxyapatite. Two weeks postoperatively, he suffered from central vein catheter-related sepsis due to methicillin-sensitive Staphylococcus aureus. After being successfully treated for sepsis, he was discharged. However, 3 months later, computed tomography revealed multiple loculated abscesses in the chest wall and the right pleural space. Reoperative thoracotomy revealed abscesses mainly located around the fifth rib, where the pin was inserted. Both cultures of the abscess and the fifth rib were positive for methicillin-sensitive S. aureus, which suggested that the rib pin was the cause of the secondary infection. This case suggests the rib pins, even if they are biodegradable, could have a risk of infections side effect especially for the immunosuppressed patients.

DOI： 10.1007/s11748-017-0768-y

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

BACKGROUND: Whether compensatory lung growth occurs in adult humans is controversial. The aim of this study was to confirm compensatory lung growth by analyzing ipsilateral residual lung after lower lobectomy in living lung transplant donors with quantitative and qualitative computed tomography assessments. METHODS: Chest computed tomography and pulmonary function tests were performed in 31 eligible donors before and 1 year after donor lobectomy. Ipsilateral residual lung volume was measured with three-dimensional computed tomography volumetry. The computed tomography-estimated volumes of low, middle, and high attenuations in the lung were calculated. Assessment of the D value, a coefficient of the cumulative size distribution of low-density area clusters, was performed to evaluate the structural quality of the residual lung. RESULTS: Postoperative pulmonary function test values were significantly larger than preoperative estimated values. Although postoperative total volume, low attenuation volume, middle attenuation volume, and high attenuation volume of the ipsilateral residual lung were significantly larger than the preoperative volumes, with 50.2%, 50.0%, 41.5%, and 43.1% increase in the median values, respectively (all p < 0.0001), the differences in D values before and after donor lobectomy were not significant (p = 0.848). The total volume of ipsilateral residual lung was increased by more than 600 mL (50%). CONCLUSIONS: The volume of ipsilateral residual lung increased, but its structural quality did not change before and after donor lobectomy. The existence of compensatory lung growth in adult humans was suggested by quantitative and qualitative computed tomography assessments.

DOI： 10.1016/j.athoracsur.2017.09.060

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DOI： 10.1016/j.jtcvs.2017.11.047

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non–small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP-binding Cassette Sub-family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins β1 and β3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB-resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.

DOI： 10.1002/cam4.1282

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Background Lung transplantation is the final lifesaving option for patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT for hematologic diseases are thought to be high-risk candidates for lung transplantation
therefore, few lung transplants are performed for these patients, and few studies have been reported. This study aimed to describe the characteristics and outcomes of lung transplantation in patients with pulmonary complications after HSCT. Methods We retrospectively investigated 62 patients who underwent lung transplantation after HSCT. All data were collected from 6 lung transplant centers in Japan. Results Seventeen patients underwent cadaveric lung transplantation, whereas 45 underwent living-donor lobar lung transplantation (LDLLT). In the LDLLT group, 18 patients underwent LDLLT after HSCT in which one of the donors had also served as a donor for HSCT. Seven patients underwent single LDLLT for which the donor was the same as the patient from whom stem cells were obtained for HSCT. Preoperative hypercapnia was observed in 52 patients (84%). Thirteen patients (21%) required mechanical ventilation preoperatively. Fifty-five patients underwent HSCT for hematologic malignancies, and 4 (7%) relapsed after lung transplantation. The 5-year survival rate was 64.2%. In a multivariable analysis, patients younger than 45 years and those with the same donor for both procedures exhibited significantly better survival (P = 0.012 and 0.041, respectively). Conclusions Lung transplantation for pulmonary complications after HSCT was performed safely and yielded better survival, especially in younger recipients for whom both lung transplantation and HSCT involved the same donor.

DOI： 10.1097/TP.0000000000001886

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Language：English   Publisher：Springer Tokyo  

Three-dimensional computed tomography (3D-CT) technologies have been developed and, recently, high-speed and high-quality 3D-CT technologies have been introduced to the field of thoracic surgery. The purpose of this manuscript is to demonstrate the clinical application of 3D-CT technologies in lung transplantation. In Japan, because of the severe donor shortage, living-donor lobar lung transplantation (LDLLT) is essential, in addition to cadaveric lung transplantation. In LDLLT, size matching is a grave issue, since ideal size matching between donor and recipient is usually difficult because of the limited population of potential donor. Size matching using pulmonary function test results has been widely used as a gold standard, but anatomical size matching using 3D-CT volumetry data has also been utilized in LDLLT. In donor lobectomy, 3D-CT images provided a variety of information regarding anatomical variation of pulmonary vessels and bronchial trees preoperatively. These images ensure surgical quality and safety, and they also affect surgical procedures for the recipient. 3D-CT images are also utilized in various aspects of postoperative care, such as detection of chronic lung allograft dysfunction and clarification of its subtypes. Furthermore, preoperative 3D-CT simulation is useful in developing and performing a special surgical procedure, such as right-to-left inverted LDLLT. In conclusion, following the introduction of 3D-CT to the field of thoracic surgery, various 3D-CT images and their application to preoperative simulations have been introduced in lung transplantation. In the near future, this technique will become more prevalent, and frequent use by thoracic surgeons will be seen worldwide in daily practice.

DOI： 10.1007/s11748-017-0849-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Purpose: Few studies have investigated pulmonary endothelial chimerism after hematopoietic stem cell transplantation. In the present study, we investigated pulmonary endothelial chimerism using the ABH histo-blood group antigen as an identifying marker in cases of ABO-incompatible hematopoietic stem cell transplantation. Methods: Sixteen lung samples were analyzed. Of these, seven were explanted lungs from lung transplant recipients with severe pulmonary chronic graft-versus-host disease (GVHD). The remaining nine were autopsy samples from patients who died from various causes, and six of these nine cases had a diagnosis of pulmonary chronic GVHD. The ABH histo-blood group antigen was used to differentiate donor cells from recipient cells immunohistochemically. We estimated the percentage of vessels positive for donor blood group antigens in comparison with the total number of vessels. Results: Donor blood group antigens were expressed in the endothelium of 13 samples, all of which were pathologically diagnosed with pulmonary chronic GVHD. The proportion of vessels with donor group antigens ranged from 0.1 to 17.5%. In contrast, no chimeric vessels were observed in the three samples without pulmonary chronic GVHD. Conclusions: Our results demonstrate that circulating stem cells engraft into the endothelium to a considerable extent in pulmonary chronic GVHD.

DOI： 10.1007/s00595-017-1562-2

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Language：English   Publisher：OXFORD UNIV PRESS  

Indocyanine green fluorescent image-guided surgery was developed to identify primary and metastatic nodules of various malignancies. However, currently, surgeons need to identify the fluorescent image on a monitor, which impedes surgical procedures. Herein, we developed a novel projection mapping device that can cast the real-time fluorescent image onto the surface of the targeted organ. We performed surgical resection of a lung metastasis of hepatoblastoma using this technique. The projection mapping technique clearly detected the pulmonary lesion, and no other lesions were identified in the ipsilateral thorax. The patient is well and free of recurrence 2 years after surgery.

DOI： 10.1093/icvts/ivx247

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

Purpose Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level.
Methods The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models.
Results A physical activity level of &lt;= 1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival.
Conclusions Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

DOI： 10.1007/s00595-017-1542-6

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.jtcvs.2017.07.041

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered useful for the staging and diagnosis of lung cancer or thoracic lymph node enlargement; however, little is known about its complications. Between July 2009 and November 2016, 413 patients underwent EBUS-TBNA, and four complications (0.97%) occurred. Here we report four cases involving complications of EBUS-TBNA, including mediastinitis (n = 2), obstructive pneumonia (n = 1), and airway obstruction requiring admission to the intensive care unit (n = 1). All patients recovered with appropriate medical treatment. Despite their low incidence, the complications associated with EBUS-TBNA can be serious. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.06.015

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

OBJECTIVES: Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT.
METHODS: The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed.
RESULTS: Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D-recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P &lt; 0.001). Twenty-eight patients (25.5%) had early cessation of anti-CMV prophylaxis due to toxicity; however, the extended prophylaxis duration did not increase the incidence of early cessation (P = 0.88). These trends were seen in both LDLLT and CLT.
CONCLUSIONS: We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT.

DOI： 10.1093/icvts/ivx226

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

Background. Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation.& para;& para;Methods. Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less.& para;& para;Results. The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02).& para;& para;Conclusions. Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating post operative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.06.023

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

In living-donor lobar lung transplantation, donor lobectomies must be performed carefully for both donors and recipients. Furthermore, the recipients undergo pneumonectomies rather than lobectomies. Occasionally, anastomosis of the pulmonary vessels is difficult in living-donor lobar lung transplantation because of the limited length of the pulmonary vessels in the graft. This report describes a successful case of pulmonary venoplasty using an autologous pericardial conduit, which was interposed between the superior pulmonary vein of the recipient and the inferior pulmonary vein of the donor in living-donor lobar lung retransplantation. This technique may be required for the success of living-donor lobar lung retransplantation.

DOI： 10.1093/icvts/ivx122

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

Gastrointestinal complications sometimes occur after lung transplantation and remain a cause of postoperative morbidity. Superior mesenteric artery syndrome is caused by the compression of the duodenum by the superior mesenteric artery, but few reports have described superior mesenteric artery syndrome after lung transplantation. We herein report two cases of superior mesenteric artery syndrome as an early complication after lung transplantation. Both patients were emaciated and had lost weight before transplantation. They also lost an additional 2-4 kg early after transplantation. They were medically treated with enteral nutrition and recovered without recurrence of the syndrome. Since critically ill patients with pulmonary disease usually lose weight both before and early after lung transplantation, superior mesenteric artery syndrome is important to consider in the differential diagnosis of gastrointestinal complications after transplantation.

DOI： 10.1007/s00595-017-1513-y

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Language：English   Publisher：OXFORD UNIV PRESS INC  

Posterior reversible encephalopathy syndrome is a neurological complication associated with calcineurin inhibitors. There is no consensus regarding the continuation of calcineurin inhibitors in the event of posterior reversible encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor trough level exceeded the therapeutic range in only 1 case. Our findings demonstrate that temporary cessation of calcineurin inhibitors and administration of basiliximab may be effective strategies for managing posterior reversible encephalopathy syndrome.

DOI： 10.1093/ejcts/ezx151

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

The body mass index (BMI) before lung transplantation (LT) is a benchmark of the post-LT survival. The aim of the study is to determine the BMI inadequate for the post-LT survival.
We examined the survival after LT in patients grouped into the following BMI categories: &lt; 18.5 kg/m(2) (underweight), 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and 30.0 kg/m(2) (obese) according to the World Health Organization (WHO) criteria. A more detailed categorization was made for further evaluation of the underweight group: mild (17.0 BMI &lt; 18.5 kg/m(2)) and severely underweight (BMI &lt; 17.0 kg/m(2)).
There was no statistically significant difference in the post-LT survival between underweight and normal-weight patients (5-year survival: 78.7 vs. 76.1%). Patients with BMI &lt; 17.0 kg/m(2) had a worse prognosis than those with 17.0 BMI &lt; 18.5 kg/m(2) (5-year survival: 70.3 vs. 90.0%).
Standard BMI categorization per the WHO criteria is inadequate for determining the post-LT survival, especially in underweight patients. For the nutritional evaluation of underweight pre-LT patients, BMI &lt; 17.0 kg/m(2) should be used instead of BMI &lt; 18.5 kg/m(2).

DOI： 10.1007/s00595-017-1508-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Objective
Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation.
Methods
We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014.
Results
Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an inconsistent with usual interstitial pneumonia pattern on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99, p &lt; 0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72-0.95, p &lt; 0.01) independently contributed to mortality in patients with IPF.
Conclusions
Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality.

DOI： 10.1371/journal.pone.0183171

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

Purpose The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants.
Methods We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months.
Results Time trends of IK values in stable recipients peaked 1 week after DDLT (477 +/- 247 ATP ng/ml), and 1 month after LDLLT (433 +/- 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002).
Conclusions IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

DOI： 10.1007/s00595-016-1440-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA.
Methods Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically.
Results By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63.
Conclusions DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

DOI： 10.1097/TP.0000000000001665

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.healun.2016.12.003

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

Purpose: Gastroparesis is a frequent gastrointestinal complication after lung transplantation. Although gastric emptying scintigraphy (GES) is the standard technique to evaluate gastroparesis, magnetic resonance imaging (MRI) can also assess gastric motility and emptying. This study compared the results obtained by these two modalities.
Methods: Twenty-two lung transplant recipients underwent MRI and GES after ingesting a small pancake as a test meal. Parameters assessed on MRI included antral peristaltic wave velocity and frequency, and the ratios of gastric content volume at 15 and 35 min. GES parameters included retention rates (RR) in the stomach at 30, 60, and 120 min (RR30, RR60, and RR120) and half-time of emptying (T1/2) calculated by exponential curve fitting. Correlations between MRI and GES results were evaluated.
Results: Peristaltic wave velocity showed significant moderate negative correlations with RR120 (r = - 0.58, p &lt; 0.05) and T1/2 (r = - 0.60, p &lt; 0.05), indicating an association between reduced velocity and prolonged gastric emptying. Gastric content volume ratios on MRI showed significant moderate positive correlations with RR30 (r = 0.46, p &lt; 0.05), RR60 (r = 0.60, p &lt; 0.01), and T1/2 (r = 0.60, p &lt; 0.01). There were no significant correlations between peristaltic wave frequency and GES parameters. MRI and GES parameters did not differ significantly between the six patients with and the 16 without upper gastrointestinal symptoms.
Conclusions: MRI-based determinations of gastric motility and gastric emptying correlate with GES-based gastric emptying in lung transplant recipients, suggesting that MRI is useful for evaluating patients with gastroparesis.

DOI： 10.1007/s00261-016-0959-5

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

OBJECTIVES: Anti-oxidant effects of hydrogen have been reported in studies examining ischaemia-reperfusion injury (IRI). In this study, we evaluated the therapeutic efficacy of immersing lungs in hydrogen-rich saline on lung IRI.
METHODS: Lewis rats were divided into three groups: (i) sham, (ii) normal saline and (iii) hydrogen-rich saline. In the first experiment, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline for 1 h. Then, we measured the hydrogen concentration in the left lung using a sensor gas chromatograph (N = 3 per group). In the second experiment, lung IRI was induced by occlusion of the left pulmonary hilum for 1 h, followed by reperfusion for 3 h. During the ischaemic period, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline. After reperfusion, we assessed lung function, histological changes and cytokine production (N = 5-7 per group).
RESULTS: Immersing lungs in hydrogen-rich saline resulted in an elevated hydrogen concentration in the lung (6.9 +/- 2.9 mu mol/1 g lung). After IRI, pulmonary function (pulmonary compliance and oxygenation levels) was significantly higher in the hydrogen-rich saline group than in the normal saline group (P &lt; 0.05). Similarly, pro-inflammatory cytokine levels (interleukin-1 beta and interleukin-6) in the left lung were significantly lower in the hydrogen-rich saline group than in the normal saline group (P &lt; 0.05).
CONCLUSIONS: Immersing lungs in hydrogen-rich saline delivered hydrogen into the lung and consequently attenuated lung IRI. Hydrogen-rich solution appears to be a promising approach to managing lung IRI.

DOI： 10.1093/ejcts/ezw342

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

An 8-year-old girl with Chediak-Higashi syndrome (CHS) had pulmonary complications after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) and eventually underwent single living-donor lobar lung transplantation (LDLLT). Electron micrographic findings showed vagus nerve tissue in extracted lung having granular inclusions, which are pathognomonic for CHS. Because her mother was the donor for both hematopoietic stem cell and lung transplantations, she was weaned from immunosuppression and is doing well 3 years after lung transplantation. Furthermore, an induced pluripotent stem (iPS) cell line was established from her skin fibroblasts for investigation and potential future treatment for CHS. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.08.049

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

Background. We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with highdose short-acting beta(2)-adrenergic receptor agonists.
Methods. Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 mu g of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5 '-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation.
Results. Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5 '-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation.
Conclusions. High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.07.066

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PubMed

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

OBJECTIVES: Donor lobectomies in living-donor lobar lung transplantation sometimes require additional surgical procedures on the interlobar pulmonary artery. We retrospectively reviewed the surgical techniques and outcomes of living-donor lobectomy.
METHODS: Between 2008 and 2015, 116 living-donor lobectomies were performed in 64 consecutive living-donor lobar lung transplantations (52 bilateral, 12 single). The surgical techniques and outcomes were reviewed retrospectively.
RESULTS: Right lower lobectomies were performed in 69 donors, left lower lobectomies in 45 and middle lobectomies in 2. In 61 living donors (52.6%), small branches of the pulmonary artery were sacrificed for anatomical reasons. Pulmonary arterioplasties to preserve the pulmonary artery branches were performed in 13 donors (11.2%). Thirteen left lower lobectomies with pulmonary arterioplasty were performed to preserve lingular branches, as the lingular branch originated far distal to the superior segmental branch of the left lower lobe. Pulmonary arterioplasty with an autologous pericardial patch in 10 donors and with an end-to-end anastomosis in three donors was performed. All surgical procedures had no complications. Three months after lobectomy, the ratio of the pulmonary function test results to the preoperative values and the complication rate showed no significant differences between donors with and without pulmonary arterioplasties, and donors with and without sacrifice of small branches. All living donors resumed their previous lifestyles without restriction.
CONCLUSIONS: Although additional surgical procedures were often required in living-donor lobectomies, the donor outcomes were satisfactory. Arterioplasty to close the interlobar artery in the donor was needed in left-sided cases only.

DOI： 10.1093/ejcts/ezw298

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1(+) myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.
Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1(+) myeloid cells using several cell-type-specific markers.
Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1(+) cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1(+) cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1(+) cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.
Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a bio-marker indicating poor prognosis of colorectal cancer patients with lung metastases. (C) 2016 AACR.

DOI： 10.1158/1078-0432.CCR-16-0520

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PubMed

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

Background. Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI.
Methods. The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each). The lungs were exposed to 60 minutes of warm ischemia by perfusion cessation. At the onset of ischemia, nebulized fasudil, a novel Rho-kinase inhibitor, and saline were inhaled in the Rho-kinase inhibitor and warm ischemia groups, respectively. Perfusion was restarted after the ischemic period, and physiologic data were collected for 90 minutes. Lungs in the sham group were continuously perfused without ischemia or drug administrations. Protein expression in tissue specimens related to the Rho-kinase pathway was evaluated by Western blotting.
Results. Warm ischemia and subsequent reperfusion enhanced Rho-kinase activity, and this was suppressed by fasudil inhalation. Fasudil inhalation significantly attenuated IRI pathophysiology, including pulmonary vascular contraction, dynamic compliance, lung edema, and oxygenation. Molecular analysis showed that Rho-kinase suppressed myosin phosphatase and endothelial nitric oxide synthase activities, suggesting these are downstream targets of Rho-kinase during lung IRI pathogenesis.
Conclusions. The present study suggests that Rho-kinase activation is involved in lung IRI pathogenesis and that inhaled Rho-kinase inhibitors may attenuate this pathogenesis. (Ann Thorac Surg 2017; 103: 476-83) (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.07.067

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor's measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor's right lower lobe was inverted and implanted into the recipient's left chest cavity.
Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing + inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three-and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P = .712).
Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT.

DOI： 10.1016/j.jtcvs.2016.10.017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1 and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1 expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1 in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.

DOI： 10.1002/cam4.991

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DOI： 10.7889/hct.6.120

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

J-GLOBAL

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DOI： 10.1093/ejcts/ezz288

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DOI： 10.1093/icvts/ivz238

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DOI： 10.1007/s00595-019-01887-6

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DOI： 10.1016/j.jtcvs.2019.09.040

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DOI： 10.1016/j.jtcvs.2019.07.136

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DOI： 10.1093/icvts/ivz110

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DOI： 10.1016/j.jtcvs.2019.04.093

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DOI： 10.1165/rcmb.2018-0188OC

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

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DOI： 10.1016/j.jtcvs.2019.07.099

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DOI： 10.1016/j.athoracsur.2019.06.092

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DOI： 10.1016/j.athoracsur.2019.06.087

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DOI： 10.1007/s11748-019-01189-1

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DOI： 10.21037/jtd.2018.10.35

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DOI： 10.1016/j.jtcvs.2019.06.058

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DOI： 10.1016/j.stemcr.2019.05.022

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DOI： 10.1016/j.jtcvs.2018.08.098

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DOI： 10.1007/s11748-018-1006-y

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DOI： 10.1007/s11548-019-02013-0

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DOI： 10.1111/ctr.13566

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DOI： 10.1016/j.jtcvs.2018.12.064

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DOI： 10.1007/s11748-018-1038-3

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DOI： 10.1016/j.athoracsur.2018.09.013

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DOI： 10.1007/s00595-018-1740-x

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DOI： 10.1016/j.stemcr.2019.01.014

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DOI： 10.1093/icvts/ivy260

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DOI： 10.1186/s13019-019-0863-5

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DOI： 10.1093/ejcts/ezy248

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DOI： 10.1016/j.lungcan.2018.12.001

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DOI： 10.1016/j.healun.2018.09.012

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DOI： 10.1016/j.jtcvs.2018.09.062

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DOI： 10.2147/CMAR.S200819

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DOI： 10.1055/s-0038-1675346

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DOI： 10.1097/TXD.0000000000000839

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DOI： 10.1016/j.lungcan.2018.09.023

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DOI： 10.1007/s11748-018-0949-3

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DOI： 10.1007/s00595-018-1666-3

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DOI： 10.1186/s12931-018-0860-6

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DOI： 10.1111/his.13500

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DOI： 10.1007/s00595-018-1646-7

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DOI： 10.1016/j.jtcvs.2017.10.150

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DOI： 10.1093/ejcts/ezx461

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DOI： 10.1002/jso.25045

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DOI： 10.21037/jtd.2018.04.123

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DOI： 10.1016/j.jtcvs.2017.10.082

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DOI： 10.1007/s11748-017-0826-5

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DOI： 10.1016/j.resinv.2017.12.010

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DOI： 10.1093/icvts/ivx389

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DOI： 10.1016/j.athoracsur.2017.11.034

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DOI： 10.1016/j.athoracsur.2017.09.060

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DOI： 10.1007/s11748-017-0768-y

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DOI： 10.1016/j.jtcvs.2017.11.047

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DOI： 10.1002/cam4.1282

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DOI： 10.1007/s11748-017-0849-y