Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity.

Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell-specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets.

Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer.

Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.

Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project-14.

PURPOSE: Various studies have demonstrated the causal relationship between gut microbiota and efficacy of chemotherapy; however, the impact of gut microbiota on breast cancer has not been fully elucidated. This study aimed to evaluate the associations between the gut microbiota before neoadjuvant chemotherapy and its consequent efficacy in breast cancer. METHODS: This prospective observational study included patients who received neoadjuvant chemotherapy for primary early breast cancer at eight institutions between October 1, 2019, and March 31, 2022. We performed 16S rRNA analysis of fecal samples and α and ß diversity analyses of the gut microbiota. The primary endpoint was the association between the gut microbiota and pathological complete response (pCR) to neoadjuvant chemotherapy. RESULTS: Among the 183 patients, the pCR rate after neoadjuvant chemotherapy was 36.1% in all patients and 12.9% (9/70), 69.5% (41/59), and 29.6% (16/54) in those with the luminal, human epidermal growth factor receptor 2, and triple-negative types, respectively. The α diversity of the gut microbiota did not significantly differ between patients with pCR and those without pCR. Among the gut microbiota, two species (Victivallales, P = 0.001 and Anaerolineales, P = 0.001) were associated with pCR, and one (Gemellales, P = 0.002) was associated with non-pCR. CONCLUSION: Three species in the gut microbiota had potential associations with neoadjuvant chemotherapy efficacy, but the diversity of the gut microbiota was not associated with response to chemotherapy. Further research is needed to validate our findings.

Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010.

BACKGROUND: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung. METHODS: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model. RESULTS: Patients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II-III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group's overall and recurrence-free survival. CONCLUSIONS: Surgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II-III of the disease, could be considered for treating patients with pathological stage II-III sarcomatoid carcinoma of the lung.

Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation.

INTRODUCTION: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT. METHODS: This study included individuals who underwent LT from brain-dead donors. Skeletal muscle mass (cm2 /m2 ) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6-minute walk distance at discharge, and 5-year survival after LT. RESULTS: This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0-913.0). The median changes in skeletal muscle mass and quality were -4.4% (IQR, -13.3-3.1) and -2.9% (IQR, -16.0-4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51-16.42) and hospital LOS (B = 36.00, 95% CI: 3.23-68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89-14.81) and ICU LOS (B = 7.97, 95% CI: .83-15.10). CONCLUSION: Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT.

Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism. METHODS: This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30 days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points. RESULTS: The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P = 0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P = 0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P = 0.005). CONCLUSION: NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC.

Effective division of the intersegmental plane using a robotic stapler in robotic pulmonary segmentectomy.

PURPOSES: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. METHODS: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. RESULTS: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. CONCLUSIONS: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective.

Restrictive allograft dysfunction rather than bronchiolitis obliterans syndrome had a major impact on the overall survival after living-donor lobar lung transplantation.

PURPOSE: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). METHODS: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. RESULTS: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). CONCLUSIONS: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.

Prophylactic effect of tissue flap in the prevention of bronchopleural fistula after surgery for lung cancer.

PURPOSE: Bronchopleural fistula (BPF) is a serious complication of lung resection. To avoid BPF, the bronchial stump/anastomotic site is often covered with a flap of surrounding tissue. One risk factor for BPF is radical lung resection after induction chemoradiotherapy for lung cancer. We retrospectively reviewed our database to elucidate the characteristics of tissue flaps that prevent BPF. METHODS: This retrospective study included 152 patients treated between 1999 and 2019. We examined the clinicopathological characteristics, including the type and thickness of the tissue flap used to cover the bronchial stump/anastomotic site, and postoperative complications, including BPF. RESULTS: BPF occurred in 5 patients (3.3%). All 5 patients had complications that could have affected delayed wound healing, such as pneumonia. The covering tissue flap thickness was significantly greater in patients without BPF than in those who developed BPF (p = 0.0290). Additionally, the tissue flap thickness was significantly greater than in those with BPF (p = 0.0077), even in high-risk patients who developed pneumonia or radiation pneumonitis on the operative side within 6 months postoperatively. CONCLUSION: Perioperative management is crucial to avoid complications affecting the healing of the bronchial stump/anastomotic site, and the covering tissue flap thickness may be an important factor in avoiding or minimizing BPF.

Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.

Impact of the neutrophil-to-lymphocyte ratio on patients with locally advanced non-small cell lung cancer who suffer radiation pneumonitis during the course of induction chemoradiotherapy followed by surgery.

PURPOSE: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. METHODS: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. RESULTS: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. CONCLUSION: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.

Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients.

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma.

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers. METHODS: We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis. RESULTS: As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively. CONCLUSIONS: CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.

EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation.

INTRODUCTION: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). METHODS: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. RESULTS: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = -.36, P = .0031), the forced vital capacity (r = -.27, P = .027), and the total lung capacity (r = -.40, P < .001) were seen at the time of CLAD diagnosis. CONCLUSION: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT.

Donor's long-term quality of life following living-donor lobar lung transplantation.

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

S100A8/A9 as a prognostic biomarker in lung transplantation.

OBJECTIVES: S100A8/A9 is a damage-associated molecule that augments systemic inflammation. However, its role in the acute phase after lung transplantation (LTx) remains elusive. This study aimed to determine S100A8/A9 levels after lung transplantation (LTx) and evaluate their impact on overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. METHODS: Sixty patients were enrolled in this study, and their plasma S100A8/A9 levels were measured on days 0, 1, 2, and 3 after LTx. The association of S100A8/A9 levels with OS and CLAD-free survival was assessed using univariate and multivariate Cox regression analyses. RESULTS: S100A8/A9 levels were elevated in a time-dependent manner until 3 days after LTx. Ischemic time was significantly longer in the high S100A8/9 group than in the low S100A8/A9 group (p = .017). Patients with high S100A8/A9 levels (> 2844 ng/mL) had worse prognosis (p = .031) and shorter CLAD-free survival (p = .045) in the Kaplan-Meier survival analysis than those with low levels. Furthermore, multivariate Cox regression analysis showed that high S100A8/A9 levels were a determinant of poor OS (hazard ratio [HR]: 3.7; 95% confidence interval [CI]: 1.2-12; p = .028) and poor CLAD-free survival (HR: 4.1; 95% CI: 1.1-15; p = .03). In patients with a low primary graft dysfunction grade (0-2), a high level of S100A8/A9 was also a poor prognostic factor. CONCLUSIONS: Our study provided novel insights into the role of S100A8/A9 as a prognostic biomarker and a potential therapeutic target for LTx.

Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma.

Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well.

Elderly lung transplant recipients show acceptable long-term outcomes for lung transplantation: A propensity score-matched analysis.

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