Background: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations.

This article translates the guidelines for the treatment of empyema established by the Japanese Association of Chest Surgery in 2023 from Japanese to English. These guidelines were developed by the Working Group on Guidelines for the Treatment of Empyema of our society, involving the establishment of clinical questions, conducting systematic reviews in accordance with the MINDS (Medical Information Distribution Service) Manual for Guideline Development 2020 version 3.0 and the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system, and determining the levels of recommendations. Furthermore, external evaluators provided assessments. Subsequently, the guidelines were finalized after receiving public comments from the members of the society. Even in the current era of advanced antibiotic therapy, empyema remains difficult to treat. However, the specific guideline for the treatment of empyema lacks in our country. Each institution is conducting clinical practices in its own way. Therefore, aiming to standardize the treatment of empyema, we have developed a practice guideline of empyema treatment. The pathophysiology of empyema is diverse, so empyema is classified into acute, chronic, and postoperative empyema. The recommended surgical treatment for each type of empyema is described, being categorized by the strength of recommendation, strength of evidence, and consensus rate.

Bronchoscopic lung volume reduction( BLVR) has a history of over 10 years and has been performed in more than 25,000 cases worldwide. It is recommended with an evidence A rating in the Global Initiative for Chronic Obstructive Lung Disease( GOLD) guidelines. However, in Japan, it was only approved for insurance coverage in December 2023, and treatment has just begun at designated facilities. BLVR serves as a treatment option that bridges the gap between medical and surgical treatments for severe chronic obstructive pulmonary disease (COPD) cases. In Japan, where homogeneous emphysema is more prevalent, BLVR offers a promising new treatment option for severe COPD patients who continue to experience dyspnea despite receiving maximal medical therapy. The success of BLVR depends on proper patient selection based on appropriate evaluation, including the assessment of collateral ventilation using the Chartis system. Patients undergoing BLVR can expect improvements in FEV1.0 and the six-minute walk distance, ultimately leading to better survival rates. It is hoped that BLVR will help severe COPD patients break free from the negative spiral of COPD, maintain their quality of life, and ultimately contribute to reducing COPD-related mortality.

INTRODUCTION:Approximately 20% of patients who contract coronavirus disease (COVID-19) pneumonia require oxygen therapy; of these patients, approximately 5% progress to acute respiratory distress syndrome, necessitating mechanical ventilation. The incidence of secondary infections among patients with COVID-19 is relatively low (16% for bacterial infections and 6.3% for fungal infections), but is predominantly observed in those with severe respiratory failure. Microvascular damage in COVID-19 can also lead to thrombus formation, causing infarctions, and in some cases, necrotizing pneumonia with cavity formation. Pulmonary resection may be necessary in patients who develop pneumothorax or empyema. Management options in complicated COVID-19 continue to evolve and should be individualized. Here, we present a case of Aspergillus empyema with refractory pleural fistula following COVID-19 pneumonia. CASE PRESENTATION:The patient was hospitalized in the intensive care unit for respiratory failure caused by COVID-19 pneumonia and developed a right pneumothorax 1 month after admission, with a halo sign in the middle lobe on computed tomography. Persistent massive air leakage and hypoxia developed, even with mechanical ventilation. Initially, to reduce the massive air leakage, endobronchial silicone spigot (endobronchial Watanabe spigot: EWS) were placed in the right B2 and middle lobe bronchi to stabilize the severe respiratory failure and septic shock. After EWS placement, the air leak decreased, with gradual improvement in the patient's multi-organ failure status. Subsequently, the patient underwent a right middle lobectomy and upper lobe wedge resection. Histopathology confirmed an active Aspergillus infection in the resected lung, and voriconazole was administered postoperatively. Air leakage persisted postoperatively, necessitating repeat surgery and, finally, thoracoplasty and negative pressure wound therapy. The patient was eventually discharged with home oxygen therapy. CONCLUSIONS:This case illustrates the successful treatment of invasive pulmonary aspergillosis with refractory pulmonary fistula and empyema following COVID-19 pneumonia using a combination of endoscopic and surgical interventions. In cases of severe COVID-19 pneumonia, clinicians must remain vigilant for secondary infections, including aspergillosis. EWS placement can be effective in reducing significant air leakage and stabilizing patients' condition.

To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. 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. The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8

This single-arm multi-institutional prospective study aimed to evaluate the 10-year outcomes of sublobar resection for small-sized ground-glass opacity-dominant lung cancer. Among 73 patients prospectively enrolled from 13 institutions between November 2006 and April 2012, 53 ground-glass opacity-dominant lung cancer patients underwent sublobar resection with wedge resection as the first choice. The inclusion criteria were maximum tumor size of 8-20 mm; ≥ 80% ground-glass opacity ratio on high-resolution computed tomography; lower 18F-fluorodeoxyglucose accumulation than the mediastinum; intraoperative pathological diagnosis of adenocarcinoma in situ; and no cancer cells on intraoperative cut margins. The primary endpoint was a 10-year disease-specific survival. The 53 eligible patients had a mean tumor size of 14 ± 3.4 mm and a mean ground-glass opacity ratio of 95.9 ± 7.2%. Wedge resection and segmentectomy were performed in 39 and 14 patients, respectively. The final pathological diagnoses were adenocarcinoma in situ in 47 patients (88.7%) and adenocarcinoma with mixed subtype in 6 patients (11.3%). The 10-year disease-specific survival and overall survival were 100% and 96.2%, respectively, during a median follow-up period of 120 months (range, 37-162 months). Ground-glass opacity-dominant small lung cancer is cured by sublobar resection when patients are strictly selected by the inclusion criteria of this study.

Acknowledgments The authors sincerely appreciate the helpful assistance provided by the Miki Akiba of Tohoku University Hospital, the JSLHT database manager. Funding: None.

Purpose To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. Methods Patients’ data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. Results Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient’s age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. Conclusion The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.

We have been performing multiport thoracoscopic surgery as a minimally invasive procedure for mediastinal tumors. The criteria for thoracoscopic surgery are as follow;tumor under 6 cm without invasion of great vessels, chest wall, or lung. We started one port surgery since 2017 and robot-assisted thoracoscopic surgery since 2018. We retrospectively reviewed these three approaches for mediastinal tumor for 12 years. 269 patients underwent surgery for mediastinal tumor, 141 patients by multiport surgery, 21 patients by one port surgery, and 38 patients by robot-assisted thoracoscopic surgery. Of 203 patients with anterior mediastinal tumors, 141 patients underwent thymectomy for thymic tumors (72 patients by multiport surgery, 9 patients by one port surgery, 17 patients by robot-assisted thoracoscopic surgery, and 43 patients by open surgery). There was no difference in tumor size, but the operating time and blood loss were significantly less in one port surgery than in multiport surgery or robot-assisted thoracoscopic surgery. The approaches have become more diverse, with a wider choice of surgical techniques, allowing us to offer more radical minimally invasive surgeries.

This article describes the perioperative complications, perioperative risk assessment, and perioperative management of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease, especially idiopathic pulmonary fibrosis( IPF), which are the leading diseases in respiratory dysfunction. In COPD, testing for forced expiratory volume during the first second and pulmonary diffusing capacity is important and an algorithm for testing has been presented by the Japanese Association for Chest Surgery. Acute exacerbation of IPF is the leading cause of postoperative mortality in Japan, and risk factors are being analyzed. To reduce the occurrence of postoperative complications, it is important to carry out a risk assessment, select appropriate surgical strategy, and implement a well-planned perioperative management.

Abstract Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive NSCLC treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of micro-T790M-positive patients in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.

Hemothorax is defined as blood accumulation in the pleural cavity with a hematocrit value of the effusion exceeding 50%. Symptoms and severity vary, ranging from asymptomatic to an imminent state of threatened cardiac arrest. This paper presents the etiology, initial work-up, and treatment of hemothorax, with an emphasis on massive hemothorax requiring an emergent thoracotomy for hemostasis. The etiology of hemothorax can be traumatic, iatrogenic, and non-traumatic/non-iatrogenic. Regardless of the etiology, the initial medical examination should be performed as in the initial trauma examination to evaluate the urgency, the amount of bleeding in the chest cavity, and the coexistence of pneumothorax. If massive hemothorax or tension pneumothorax is present, thoracic tube drainage should be started immediately. Contrast-enhanced computed tomography (CT) should be performed to identify the source of bleeding. Treatment includes fluid and blood transfusions to stabilize the circulation. Anticoagulants and antiplatelet agents should be neutralized, reduced, or withdrawn. Emergent thoracotomy for hemostasis is indicated for massive hemothorax with unstable circulation. Anterior-parasternal thoracotomy performed in the supine position has the advantage of rapid thoracotomy and good visualization. Endovascular therapy is effective when contrast-enhanced CT identifies the source of bleeding.

The number of lung transplantation performed in Japan is extremely low compared to other countries, whereas we have 10 facilities certified as cadaveric lung transplantation in Japan, meaning that there are low volume centers. By August 2021, we performed lung transplantation in 21 cases for 12 years, therefore, our facility should be considered as low volume center. Surgical outcomes at low volume centers are generally considered poor. However, the overall five-year survival rate of total cases was 84.8%, and that of cadaveric cases was 94.4% in our hospital. It was better than the average of about 73% of all facilities in Japan. These data suggested that the accreditation system in Japan is functioning well. On the other hand, there may be a disparity between facilities. At our facility, we are actively performing inverted lung transplantation so as not to lose the opportunity for transplantation, and we have performed it in three cases so far and have achieved good results.

We successfully performed left-to-right rotated single lung transplants in 2 patients. For this procedure, the left pulmonary artery of the donor undergoes a U-shaped turn with A3 at the bottom to anastomose with the recipient's right pulmonary artery in front of the bronchus. It is extremely important to avoid kinking the pulmonary artery at the site of the U-shaped turn.

e21177 Background: The significance of micro-pretreatment EGFR T790M mutation on EGFR-tyrosine kinase inhibitor (TKI) efficacy in patients with non-small cell lung cancer (NSCLC) remains uncertain. In addition, there has been no method to examine the micro-T790M mutation after excluding formalin-fixed and paraffin-embedded (FFPE)-derived artificial mutations. Therefore, we used a novel method to examine the variant allele frequency (VAF) of T790M mutation in the FFPE samples after excluding the artificial mutations. Subsequently, we retrospectively investigated the association between micro-T790M mutations and time to treatment failure (TTF) in patients treated with 1st, 2nd, or 3rd generation (1G, 2G, 3G) EGFR-TKIs. Methods: We enrolled patients with NSCLC who harbored EGFR exon 19 deletion (Del19) or L858R without T790M mutation using conventional methods. Patients who received 1G or 2G EGFR-TKIs until June 2018 or 3G EGFR-TKI until June 2019 from 31 institutions were included. Droplet digital PCR was performed using pretreatment FFPE tumor samples. We defined cases as micro-T790M positive when the VAF of T790M was higher than that of F795F, owing to the FFPE-derived artificial mutations. The ratio of micro-T790M mutation was calculated as follows: {(VAF of T790M) – (VAF of F795F)} /VAF of (Del19 or L858R). The lowest value was set as 0. Results: A total of 110, 102, and 103 patients received 1G, 2G, and 3G EGFR-TKIs, respectively. Of these patients, 48.1%, 47.0%, and 47.6% were classified as micro-T790M positive, respectively. The ratios of micro-T790M mutation, represented as median (%) (interquartile range), in 1G, 2G, and 3G EGFR-TKI groups were 0.27 (0.12-0.87), 0.28 (0.13-0.47), and 0.42 (0.20-0.68), respectively. The VAF of T790M or F795F in all patients, represented as median (%) (interquartile range), was 0.26 (0.19-0.35) or 0.25 (0.19-0.33), respectively. The TTF was not significantly different between the T790M-positive and negative groups in analysis based on each generation TKIs. In the Del19 group, the TTF of the 1G EGFR-TKI was significantly shorter, while that of the 3G EGFR-TKI was significantly longer in the T790M-positive group than in the negative group ( p= 0.02, 0.04, respectively). In the T790M-positive group, the TTF of the 2G or 3G EGFR-TKI group was significantly longer than that of the 1G EGFR-TKI group ( p= 0.04, 0.01, respectively). This result was observed in the Del19 group but not in the L858 group. Furthermore, TTF did not significantly differ between the 1G, 2G, and 3G EGFR-TKIs in the T790M-negative group. Conclusions: This study showed that micro- EGFR T790M mutations influence the EGFR-TKI efficacy. Detection of micro-T790M mutations will facilitate selection of the optimal EGFR-TKI for patients with EGFR mutated NSCLC.

日本肺癌学会肺がん検診委員会は，2022年に「肺がん検診ガイドライン」の改訂を行った．本稿では改訂に至った経過とその概要について解説する．「現行検診」に対する「推奨」は2010年ガイドラインから変化はなかった．全国的な精度管理の徹底や，国全体の死亡率減少効果への寄与度や感度・特異度の測定などに関する評価が必要である．「重喫煙者に対する低線量CT検診」は，欧米において肺癌死亡率減少効果のエビデンスが得られたが，過剰診断，偽陽性，放射線被ばくなどの不利益は無視できない．安易な導入を行って混乱する事態を避けるためには，まずは適切な「実装研究」を行うことにより，日本の社会にどのように導入することが望ましいのかを検討することが重要である．一方，「非/軽喫煙者に対する低線量CT検診」は，現在のところ有効性のエビデンスは十分でないため，それを集積することが第一に重要である．

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