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.

Prognostic factors for lung transplant recipients focusing on age and gender: the Japanese lung transplantation report 2022.

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.

[Robot-assisted Minimally Invasive Surgery for Mediastinal Tumors].

The subxiphoid approach in thymectomy provides better visibility around the left brachiocephalic vein than the lateral thoracic approach. Robot-assisted thoracoscopic surgery is easier to parform than video- assisted thoracoscopic surgery for surgery of the upper mediastinum, because the forceps can be moved with many joints. Robot-assisted thymectomy using the subxiphoid approach may be less traumatic and less invasive than median sternotomy. We must continue to devise surgical procedures to make oncologically curative surgery more minimally invasive.

[Considerations for Perioperative Management of Patients with Complicated Respiratory Dysfunction].

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.

[Hemothorax].

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.

[Lung Transplantation at a Low Volume Center].

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.

Inflammatory Risk Factors for Early Recurrence of Non-Small Cell Lung Cancer Within One Year Following Curative Resection.

BACKGROUND: Several inflammation-based scoring systems and nutritional indicators have been shown to have relevance to survival of patients with non-small cell lung cancer (NSCLC).The present study examined preoperative and pathological factors in patients who underwent curative resection for non-small cell lung cancer, with the aim to elucidate risk factors for early recurrence within 1 year of surgery. METHODS: Patients with NSCLC who underwent surgery from January 2009 to December 2014 were retrospectively investigated. Routine laboratory measurements including carcinoembryonic antigen were performed before surgery, and pathological information was collected after surgery. Patients with recurrence within 1 year after surgery were considered as early recurrence group (ERG), those with recurrence after 1 year were as late recurrence group (LRG), and those without recurrence were as no recurrence group (NRG). RESULTS: Multivariate analysis between ERG and LRG revealed Glasgow prognostic score (GPS) and CRP-to-albumin ratio (CAR) as independent risk factors for early recurrence. Multivariate analysis between ERG and LRG + NRG confirmed CAR, vascular invasion, and pathological stage as risk factors for early recurrence. CONCLUSION: These findings indicated that CAR and GPS were confirmed to be risk factors for early recurrence, in addition to pathological factors.

[Surgical Treatment for Apical Invading Lung Cancer].

The apical invading lung cancer is the tumor infiltrating to the thoracic inlet, in other words, the 1st rib or the higher chest wall. Tumor arising in the posterior apex is invasive to the vertebral body, the sympathetic trunk, and the brachial plexus. Pancoast tumor is well known with typical triads, which is invasive to the sympathetic trunk and the brachial plexus in the posterior apex of the lung. Tumors originating in the anterior apex are called anterior apical tumors, and they often involve the subclavian vein and artery. Trimodality therapy is recommended to treat the apical invading lung cancer. Induction chemoradiotherapy followed by surgical resection lead to good local control and complete resection rate. Surgical approach should be selected based on the tumor location in the extreme apex. High posterolateral approach and hook approach are chosen for the tumor in the posterior apex. Anterior approaches developed by Masaoka, Dartevelle, Grunenwald, and Korst are suitable for the tumor in the anterior apex that are often invasive to the subclavian vessels. Surgical outcome depends on completeness of resection. Based on the preoperative evaluation of involved structures, appropriate surgical approach is important to achieve complete resection of the apical invading lung cancer.

Inflammation-Based Prognostic Score Predicts Postoperative Survival of Patients with Interstitial Pneumonia After Undergoing Lung Cancer Resection.

OBJECTIVES: Idiopathic interstitial pneumonias (IIPs) are associated with an increased risk of lung cancer. Glasgow prognostic score (GPS), which uses serum C-reactive protein (CRP) and albumin levels to indicate systemic inflammatory response and nutrition level, has been reported to be a predictor of overall survival in patients with various types of cancer. We evaluated the usefulness of GPS for prediction of survival of patients with both lung cancer and IIPs following a lung resection procedure. METHODS: Patients with IIPs who underwent lung cancer resection from January 2006 through December 2015 were investigated. Routine laboratory measurements, including serum CRP and albumin for determining GPS, were performed before the operation. Univariate and multivariate analyses with a COX proportional hazards regression model were used to identify independent risk factors for overall survival (OS), relapse-free survival (RFS), cancer-specific survival (CSS), and other disease-specific survival (ODSS). RESULTS: A total of 135 patients underwent lung resection during the study period. Multivariate analysis selected sublobar resection (p = 0.035), UIP pattern (p = 0.025), and GPS of 1-2 (p = 0.042) as predictive factors associated with OS, while GPS of 1-2 (p = 0.039) was shown to be a predictive factor associated with RFS. Multivariate analysis also revealed pTNM (p < 0.001), usual interstitial pneumonia pattern (p = 0.006), and GPS of 2 (p = 0.003) as predictive factors associated with CSS, while univariate analysis indicated pTNM (p = 0.042), GPS of 1 (p = 0.044), and %DLCO (p = 0.038) as predictive factors associated with ODSS. CONCLUSION: GPS is an independent prognostic factor of OS and RFS in lung cancer patients with IIPs undergoing a lung resection procedure. Furthermore, a GPS of 2 was found to be associated with CSS following lung cancer resection, while a score of 1 was associated with ODSS.

Mitosis count and number of cancer cells in cases of primary pulmonary adenocarcinoma: Correlations among phosphorylated histone 3, number of cancer cells, nuclear grade, pathologic features and prognosis.

Immunohistochemistry findings for the phosphorylated form of histone 3 (pHH3) have been shown to be a reliable mitosis-specific marker. We evaluated the correlation between pHH3-stained mitotic figures (PHMFs) and clinical outcome, and compared the results with findings for numbers of PHMFs and cancer cells. The primary tumor was obtained from 113 patients with pulmonary adenocarcinomas (≤2 cm maximum dimension). All specimens were stained with pHH3, then the number of cancer cells in each was determined. Cases with a cancer-cell index ≥1000 showed worse recurrence-free survival as compared to those with a value <1000 (P < 0.001). Also, cases with a pHH3 index ≥0.27 showed worse recurrence-free survival as compared to <0.27 (P = 0.001) and cases with a pHH3/cancer-cell index ≥0.001 showed worse recurrence-free survival as compared to <0.001 (P = 0.002). Multivariate analysis demonstrated that pHH3/cancer-cell index was significantly correlated with prognosis, but not Ki-67 index. The number of cancer cells was also strongly correlated with progression of Noguchi's classification and WHO pathologic type. pHH3/cancer-cell index was correlated with prognosis, and those were useful for prognostic evaluation of pulmonary adenocarcinoma patients. Furthermore, cancer cell number was correlated with Noguchi's classification and WHO pathologic type.

L-Type Amino Acid Transporter 1 Immunoreactivity as a Possible Diagnostic and Prognostic Marker of Thymic Carcinoma.

L-type amino acid transporter 1 (LAT1) functions to transport large neutral amino acids, such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine. These amino acids are essential for cell growth and proliferation. Many studies have demonstrated LAT1 expression in various types of cancer, and its high expression level was associated with poor prognosis. However, the significance of LAT1 expression in thymic epithelial tumors is controversial. We conducted this retrospective study to investigate the LAT1 immunoreactivity in thymic epithelial tumors and its impact on prognosis. We analyzed 32 patients with thymoma and 14 patients with thymic carcinoma who underwent surgery at our institute. Immunohistochemical analysis was performed using formalin-fixed paraffin-embedded surgical tissues and an anti-LAT1 polyclonal antibody. We thus found that LAT1 immunoreactivity was undetectable in all of the thymoma specimens, regardless of the subtypes of thymoma. By contrast, LAT1 immunoreactivity was consistently detected in the cytosol of thymic carcinoma cells; namely, all 14 thymic carcinoma specimens demonstrated LAT1 immunoreactivity in the cytosol. Among these 14 thymic carcinoma specimens, four carcinoma specimens also showed LAT1 immunoreactivity in the cell membrane. Survival analysis indicated that the thymic carcinoma with the LAT1 membrane signal was associated with poor prognosis, compared with the specimens with the LAT1 cytosol signal. We therefore propose that LAT1 is expressed in the cytosol of thymic carcinoma cells, which could be a diagnostic marker of thymic carcinoma. Moreover, LAT1 expression in the cell membrane is a prognostic marker of thymic carcinoma.

[Perioperative Management of Patients with Pulmonary Comorbidities Undergoing Lung Resection].

Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) are 2 major pulmonary comorbidities of primary lung cancer patients. The COPD patients are at risk for respiratory failure after a major lung resection when lung resection exceeds the patient's pulmonary reserve. It is important to assess a postoperative risk based on the patient's cardiopulmonary function. Cardiac risks are initially evaluated for all the candidates for lung resection, then, ppoFEV1% and ppoDLco% are calculated. If these 2 parameters are not satisfactory, cardiopulmonary exercise test is required to assess the risk. Adequate treatment for COPD should be given to the patients through the perioperative period. ILD is another major comorbidity of lung cancer patients, and its acute exacerbation (AE) is the leading cause of postoperative death. The Japanese Association of Chest Surgery proposed a risk scoring system for predicting postoperative AE. Currently there is no reliable management to prevent or ameliorate postoperative AE. Methylprednisolone pulse therapy is empirically performed as a treatment for AE with controversial evaluation. Pirfenidone and some other drugs are expected to reduce the occurrence of postoperative AE, however, further studies will be needed to confirm the efficacy and the safety.

[Salvage Surgery Following Chemoradiotherapy for Thymic Basaloid Cell Carcinoma].

We performed salvage surgery after chemoradiotherapy(CRT) in a patient with thymic basaloid cell carcinoma. A 46-year-old man with an abnormal chest shadow on X-ray findings was referred to our hospital. Computed tomography revealed a partially solid tumor along with a multilocular cyst in the anterior mediastinum with mediastinal lymph node swelling infiltrating to the superior vena cava(SVC). Positron emission tomography revealed FDG accumulation (SUVmax 7.94)in the tumor. Pathological findings of a tumor biopsy specimen obtained by thoracoscopy led to a diagnosis of thymic basaloid cell carcinoma. Following CRT (ADOC+RT:60 Gy), a complete resection (R0)with replacement of the SVC was performed. The postoperative course was uneventful, and the patient was alive at 20 months after surgery with metastasis to the cervical lymph nodes and bone.

LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells.

L-type amino acid transporter 1 (LAT1, SLC7A5) incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

[Minimally Invasive Thoracoscopic Surgery for Mediastinal Lesions].

This review article describes minimally invasive thoracoscopic surgery for anterior mediastinal lesions. The operative procedures for anterior mediastinal lesions have been changed in a couple of decades from open surgery under median sternotomy to complete thoracoscopic mediastinal surgery with sternal lifting or carbon dioxide insufflation. Carbon dioxide insufflation of the thoracic cavity or the mediastinum is now prevailing to improve the surgical field and facilitate the operative procedures. Surgical indications for complete thoracoscopic mediastinal surgery include benign cystic lesions generally regardless of their size and non-invasive anterior mediastinal tumors usually less than 50~60 mm in the greatest dimension. There are currently three surgical approaches in the complete thoracoscopic surgery for the anterior mediastinal lesions. One is the unilateral or bilateral transthoracic approach. The second is the combination of the subxiphoid and the transthoracic approach. The last is the subxiphoid approach. The selection of the surgical approach depends on the surgeon's preference and experiences. When carbon dioxide insufflation is applied during the operation, following complications may occur;hypercapnia, gas embolism, subcutaneous emphysema, endotracheal tube dislocation due to the mediastinal sift, and hypotention. Special safety considerations are necessary during the complete thoracoscopic mediastinal surgery with carbon dioxide insufflation.

[Anti-thymocyte Globulin Therapy for Cases of Acute Rejection Following Lung Transplantation].

A 58-year-old male underwent right lung transplantation from a brain-dead donor, after which acute rejection developed that was resistant to steroid pulse therapy. Rabbit-derived anti-thymocyte globulin (rATG) therapy was successful for controlling the rejection. However, following that therapy, the patient was affected by an opportunistic infection and suffered from repeated empyema. It is important to pay attention to immunosuppressive agent levels in blood following treatment, because ATG is a potent immunosuppressive drug and its effects can continue for more than 6 months after administration.

[Spindle Cell Sarcoma Originated in the Anterior Mediastinum;Report of a Case].

An anterior mediastinal sarcoma is a very rare type of mediastinal tumor. A 45-year-old female visited our hospital with swelling in the right anterior chest wall. Radiographically, the tumor was found to originate from the thymus and to infiltrate to the major pectoral muscle through the 1st intercostal space. Positron emission tomography revealed fluorodeoxyglucose accumulation at a standardized uptake maximum value of 16.1. Percutaneous needle biopsy showed the pathological findings of sarcoma. The tumor was resected along with the thymus and chest wall tissues including the right hemi-manubrium of the sternum, clavicle head, 1st and second ribs, and major pectoral muscle. After 4 months, tumor relapse occurred at the site of needle biopsy and additional resection was performed. At 10 months after the 2nd surgery, the patient was free from disease. From histologic and immunohistochemical findings, the tumor was diagnosed as spindle cell sarcoma.

A survey about further work-up for cases with positive sputum cytology during lung cancer mass screening in Ishikawa Prefecture, Japan: a retrospective analysis about quality assurance of lung cancer screening.

OBJECTIVE: In cancer screening programs, performing appropriate further work-up is essential. In order to elucidate whether the further work-up for the subjects with positive screening results by sputum cytology was performed appropriately, the present study was conducted as the first large-scale thorough survey in Japan. METHODS: All of the lung cancer screening records from 2007 to 2012 in Ishikawa Prefecture were reviewed. Additional investigations about the further work-up were performed. RESULTS: In total, 2 234 984 people were invited to undergo lung cancer screening, and 494 424 people participated in the screening. Of these, 25 264 people underwent sputum cytology, and 68 positive cases were identified. Three of these 68 cases did not undergo further work-up, and another three cases had already been diagnosed to have lung cancer. Forty-five of the remaining 62 cases did not have suspicious chest shadows, and bronchoscopic examinations were performed in 36 cases. Seventeen of these 36 cases were diagnosed as having cancer, whereas none of the nine cases who did not receive the examination was diagnosed (P = 0.038). A bronchoscopic examination was not performed due to other medical conditions in three cases, due to the patient's refusal in another three cases and in the remaining three cases, the reasons were unknown. CONCLUSION: The participation rate for further work-up was very high. However, there are some issues to be resolved regarding the transmission of information. With our new registered hospital system, the quality assurance of our screening program will be improved.

Successful bilateral lung transplantation after 16 h of lung preservation with EP-TU solution: report of a case.

We report a case of bilateral lung transplantation (BLT) after preservation of the donor graft for 16 h 5 min with EP-TU, an extracellular phosphate-buffered lung preservation solution. The recipient was a 26-year-old woman with idiopathic pulmonary arterial hypertension and the graft ischemic time was prolonged significantly because of the time required to induce peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) under local anesthesia, and address the severe intrathoracic and pericardial adhesions from past surgery for partial anomalous pulmonary venous return, with concurrent annular plication of the tricuspid valve. After the operation, ECMO and continuous hemodiafiltration were started preemptively to protect the grafts against excessive edema. Postoperative chest X-ray showed diffuse bilateral infiltrates, which improved within a few days and she was weaned off ECMO on day 9. Successful BLT after a graft ischemic time of over 16 h has rarely been described in clinical lung transplantation.

[Perioperative management of lung cancer patients with cardiovascular complications].

Lung cancer patients with cardiovascular complications often require antithrombotic therapy. In this study, we discuss the present conditions and future problems associated with the perioperative management of such patients. We examined 36 lung cancer patients undergoing surgery who received antithrombotic therapy for cardiovascular complications. Twenty-one patients were administered unfractionated heparin in the perioperative period (heparin group). Fifteen patients were not administered unfractionated heparin in the perioperative period (no-heparin group). No significant intergroup differences were observed in operating time, intraoperative blood loss, duration of chest tube placement, and the number of hospitalization days. However, 2 serious cases of thromboembolism developed after surgery. One was a case of pulmonary thromboembolism and the other was one of superior mesenteric artery thromboembolism. These results suggest that the appropriate perioperative usage of heparin enables the standard surgical treatment of lung cancer patients with cardiovascular complications. We recommend the use of low-molecular-weight heparin or low-dose unfractionated heparin as the antithrombotic agent after lung cancer surgery.