Search

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.

Postoperative hemodynamic support with an Impella 5.0 was effective in a man who underwent lung lobectomy for lung cancer and cardiogenic shock. A 75-year-old man presented to hospital with an abnormal chest shadow on radiography. After thorough examination, the patient was diagnosed with lung cancer, and left lower lobectomy was performed. On the 2nd postoperative day, the patient experienced cardiac arrest because of a sudden drop in saturation of percutaneous oxygen. After a third defibrillation, his heartbeat resumed, and he was intubated and placed on a ventilator. Coronary angiography revealed acute coronary syndrome and the patient fell into a state of shock, which required venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Nevertheless, the circulatory dynamics are unstable, and Impella 5.0 was introduced. VA-ECMO and the Impella 5.0 were discontinued on the 6th and 8th postoperative days, respectively. The patient was eventually transferred to a nearby facility for further rehabilitation 109 days later.

AimsMalignant pleural mesothelioma with heterologous elements (such as osseous, cartilaginous or rhabdomyoblastic differentiation) is very rare. We tried to differentiate such mesothelioma cases from extraskeletal pleural osteosarcoma, which is very challenging.MethodsWe compared 10 malignant pleural mesotheliomas (three biphasic and seven sarcomatoid types) with two pleural osteosarcomas using clinicopathological and immunohistochemical methods, and also fluorescence in situ hybridisation (FISH) to examine for homozygous deletion of p16.ResultsThe median age was 72 years for mesotheliomas, and 69 years for osteosarcoma. For mesothelioma, eight cases were male and two were female. Growth was diffuse in all mesothelioma cases except case 10, where it was localised, as it was for the two osteosarcomas. Among mesothelioma cases, 80% displayed osteosarcomatous and 60% chondromatous elements, while 10% exhibited rhabdomyoblastic ones. Immunohistochemical labelling for calretinin and AE1/AE3 was present in 8/10 and 7/10 mesotheliomas, respectively, but in only one osteosarcoma. Loss of methylthioadenosine phosphorylase was seen in 5/7 mesotheliomas. FISH analysis revealed homozygous deletion of p16 in 5/8 mesothelioma and 2/2 osteosarcoma. Median survival was 6.5 months after biopsy or surgical operation in mesothelioma, and 12 months after operation in osteosarcoma.ConclusionsAlthough median survival was longer for osteosarcoma than for malignant mesothelioma, we could not differentiate mesothelioma from pleural osteosarcoma on the combined basis of clinicopathological and immunohistochemical data, and FISH analysis. However, diffuse growth was more frequent in mesothelioma than in osteosarcoma.

Background Pulmonary resection is occasionally performed in postpneumonectomy patients with contralateral lung lesions, such as metachronous or metastatic lung cancer. Careful intraoperative respiratory management is essential in such patients. This study evaluated the respiratory management of postpneumonectomy patients who underwent contralateral pulmonary resection with selective bronchial blockade of the lobe or segment to be resected. Methods We retrospectively analyzed the surgical findings and safety of surgery in six patients who underwent contralateral pulmonary resection with selective bronchial blockade after pneumonectomy for non‐small cell lung cancer (NSCLC). Results The percutaneous oxygen saturation did not decrease in any of the patients during bronchial blockade under high oxygen concentration. The median blockade time was 57.5 minutes. The operative field was tolerable secured under conditions of partial lung collapse, and partial pulmonary resection was performed as planned. Postoperatively, one patient developed acute respiratory distress syndrome due to acute exacerbation of interstitial pneumonia; however, no patients died within one month postoperatively. Two patients underwent pulmonary resection in order to obtain adequate tissue specimens to evaluate the biomarkers of multiple lung metastases. On histopathology, one patient tested positive for anaplastic lymphoma kinase (ALK) and was subsequently administered an ALK inhibitor, which prolonged survival. Conclusions In all patients, intraoperative respiratory condition under partial lung collapse remained stable, and all partial pulmonary resections were safely performed. However, surgical indications should be carefully reviewed preoperatively in patients with interstitial pneumonia. Key points Significant findings of the study Contralateral partial pulmonary resection was performed using selective bronchial blockade in postpneumonectomy patients.Percutaneous oxygen saturation did not decrease during the bronchial blockade under high oxygen concentration, and the operative field was tolerable secured under conditions of partial lung collapse. What this study adds Oxygen concentration can be set to the minimum level, sufficient to maintain oxygenation, during contralateral partial pulmonary resection with selective bronchial blockade., In this study, contralateral pulmonary resection was performed with selective bronchial blockade in postpneumonectomy patients, and we retrospectively analyzed the surgical findings and safety of the surgery. The patients had stable intraoperative respiratory condition under partial lung collapse, and partial pulmonary resections were safe.

Highlights • Inflammatory conditions cause multilocular thymic cyst. • Causes of the inflammation include autoimmune diseases or malignant tumors. • Evaluating the cause of inflammation in multilocular thymic cyst is essential. • First reported multilocular thymic cyst with preclinical rheumatoid arthritis. • Early treatment of rheumatoid arthritis prevents irreversible disability., Introduction Multilocular thymic cyst (MTC) is a rare condition of an acquired multilocular cystic lesion caused by inflammation and often associated with autoimmune diseases or malignant tumors. We present a patient with MTC and asymptomatic rheumatoid arthritis (RA), which is termed preclinical RA. Presentation of case A 60-year-old man underwent a computed tomography scan, which revealed an 8.5 cm multilocular cystic lesion in the anterior mediastinum. The tumor had a lower intensity on T1-weighted imaging and a higher intensity on T2-weighted imaging. The imaging did not only suggest an MTC, but also the possibility of a thymoma with cystic degeneration, or lymphoma. We performed an extended thymectomy via median sternotomy. The lesion was diagnosed as MTC based on histopathological findings. Laboratory tests were performed for the purpose of screening for autoimmune diseases. He was diagnosed with preclinical RA, since the anti-cyclic citrullinated peptide antibody (ACPA) was positive. Discussion Specificity of ACPA is recorded in over 90% of patients with RA; ACPA is positive in about 40% of patients with preclinical RA. As patients with preclinical RA are more likely to develop RA, careful follow-up is required. Early diagnosis and treatment of RA can prevent destruction of joints, thereby preventing irreversible disability. Conclusion In patients with MTC, evaluating the cause of the inflammation, such as autoimmune diseases, is essential. Further studies are required to investigate the relationship between MTC and preclinical RA.

The Otofuke River is a tributary of the Tokachi River, Hokkaido Japan, consisting of a channelized reach with a steep slope and a relatively large designed width. In August 2016, the river witnessed four major flooding events with a record-breaking discharge within a time span of 15 days. The Otofuke River originally had a straight channelized reach. However, because of a series of flooding events, the river promptly followed a sinusoidal path, damaging the riverbank embankments. The straight channelized reach of Otofuke River faced active erosion of both banks, leading to the formation of a meandering channel planform. This also led to levee breaches at the seven locations. In order to understand the mechanism of such a quick shift in river channel planform, we collected various field survey data and conducted computational analysis. We investigated the underlying processes by capturing the complex interactions between the rapid channel migration, unsteady discharge, and sediment transport. Field surveys including aerial photographs and images showed rapid formation of a meandering planform in the Otofuke River as a result of the typhoon on 31 August 2016. According to the maximum water level traces, bank erosion developed after the peak discharge. Numerical investigation revealed that alternate sandbars continuously developed and propagated downstream until the moment of peak discharge, and a significant accumulation of sediment subsequently started on the bars at the mid-channel during the flood falling stage. Such morphological processes led to strong flow deflections transversely toward the embankment that resulted in lateral channel shifting and levee breaches at a location where vegetation along the embankments had already disappeared.

Double aortic arch (DAA) is a rare congenital anomaly of the heart and aorta in which a vascular ring that surrounds the trachea and esophagus is formed. In most patients, respiratory distress and dysphagia develop in childhood, and asymptomatic adult patients are rarely known. Herein, we describe a patient with lung cancer and DAA. A 66‐year‐old man who had DAA underwent video‐assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection for primary lung cancer. Lymph node dissection of the right upper mediastinum revealed that the right recurrent laryngeal nerve branched from the right vagus nerve just beneath the right aortic arch. Additionally, the right aortic arch narrowed the space surrounding the trachea, superior vena cava, and arch of the azygos vein, impeding the stapling of the truncus anterior artery and right upper lobe pulmonary vein with the video‐assisted thoracoscopic approach. Key points Significant findings of the study In double aortic arch, the recurrent laryngeal nerve branches from the vagus nerve just beneath the ipsilateral aortic arch.The right aortic arch narrows the space surrounding the trachea, superior vena cava, and arch of the azygos vein. What this study adds The anatomy of a double aortic arch impedes mediastinal lymph node dissection on the ventral side of the trachea. Handling autosuture devices for stapling pulmonary arteries and veins is also difficult., Double aortic arch (DAA) is a rare congenital anomaly of the heart and aorta in which a vascular ring that surrounds the trachea and esophagus is formed. A 66‐year‐old man who had DAA underwent video‐assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection for primary lung cancer. Lymph node dissection of the right upper mediastinum revealed that the right recurrent laryngeal nerve branched from the right vagus nerve just beneath the right aortic arch.

Air leakage is a common complication after pulmonary resection, which is usually caused by direct lung damage during surgery. Herein, we describe a case in which a pulmonary cyst developed rapidly in the right lower lobe and ruptured 10 days after right upper lobectomy. A 49‐year‐old man, who was a heavy smoker, underwent thoracoscopic right upper lobectomy for primary lung cancer. No air leakage was observed postoperatively, and the chest drain tube was removed on postoperative day 1. Although his postoperative course was uneventful for more than a week, extensive subcutaneous emphysema developed unexpectedly on postoperative day 10. Computed tomography (CT) scan revealed a large pulmonary cyst in the right lower lobe that was not present before the right upper lobectomy. Surgery was performed on postoperative day 13, and it revealed a large thick‐walled pulmonary cyst in the right lower lobe. The cyst was filled with blood clots, and air leaks were observed inside it, suggesting that the dissection of the pulmonary parenchyma caused its development. The cyst wall was sutured together with the pulmonary parenchyma, and no air leakage was subsequently observed. Key points Significant findings of the study In patients with fragile pulmonary tissue, the pulmonary parenchyma may become dissociated after pulmonary resection and induce rapid development of a pulmonary cyst. Risk factors for pulmonary cyst development include upper lobectomy and emphysema. Pulmonary cysts are often formed in the lower lobe. What this study adds In patients with pulmonary emphysema post‐upper lobectomy, the fragility of the pulmonary parenchyma and hyperinflation of the remaining lung may cause dissection of the pulmonary parenchyma, resulting in massive air leakage.

Malignant pleural mesothelioma (MPM) is well known as a dreadful disease with very poor prognosis. The available options for the treatment of MPM include either one or a combination of chemotherapy, surgery, radiotherapy, and immune checkpoint inhibitor. Extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) is indicated for operable MPM. However, it is difficult to decide if a case is operable or inoperable. The decision may vary among thoracic surgeons and medical oncologists, and usually factors such as imaging diagnosis, blood tests, pulmonary function, cardiac function, performance status, and past medical history should be taken into consideration. Of these, imaging diagnosis is one of the most important factors.

The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II‐IIIA non‐squamous non‐small cell lung cancer (Ns‐NSCLC). This study did not meet the primary endpoint (recurrence‐free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin‐fixed, paraffin‐embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns‐NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12‐16 mut/Mb) tended to have improved survival. In patients with wild‐type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns‐NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker., Tumor mutation burden (TMB) is a predictor of immune checkpoint inhibition therapy. When combined with EGFR mutation status, TMB could be a predictive biomarker of postoperative adjuvant chemotherapy with pemetrexed plus cisplatin for patients with non‐squamous non‐small cell lung cancer. Personalized adjuvant therapy will continue to advance.

Background Tumor spread through air spaces (STAS) has recently been reported as a novel form of lung adenocarcinoma invasion that can negatively affect survival; however, its role in pleomorphic carcinoma remains unclear. The goal of this study was to characterize tumor STAS in pleomorphic carcinoma, including its association with clinicopathologic features and prognosis. Methods Tumor specimens obtained from 35 consecutive patients with pleomorphic carcinoma who underwent surgical resection between 2009 and 2015 were reviewed. Tumor STAS was defined as tumor cells spreading within the air spaces in the surrounding lung parenchyma beyond the edge of the primary tumor. Results Fourteen patients (40%) had evidence of STAS-positive pleomorphic carcinomas. Three types of morphologic findings were observed: single cells, small tumor cell clusters, and tumor nests. Tumor necrosis tended to be more prevalent in STAS-positive tumors than in STAS-negative tumors (P = .094). Patients with STAS experienced significantly worse recurrence-free survival (P = .005) and overall survival (P = .002) rates than those without STAS. Moreover, multivariate analysis revealed that tumor STAS was an independent risk factor for both recurrence (P = .014) and poor overall survival (P = .042). Conclusions In this first study of its kind, tumor STAS in patients with pleomorphic carcinoma was shown to be associated with high recurrence rates and poor survival after surgical resection. Hence, tumor STAS can serve as a predictor of postoperative survival; this information will enable better risk stratification and more effective clinical management of patients with this rare type of tumor.

Background Pleomorphic carcinoma (PC) of the lung is a rare histological type of lung carcinoma. The association between computed tomography (CT) findings and histology with outcome remains unclear. We examined the relationships between CT features and histopathologic findings, and evaluated the impact of CT features and other clinicopathologic factors on survival. Methods Thirty-five consecutive patients with PC of the lung who underwent surgery between October 2010 and December 2015 were enrolled in this study. The 35 tumors were classified with or without air bronchogram in the tumors, and with or without intratumoral ground glass opacity (GGO) on CT. Results Air bronchogram and GGO were detected in 12 (34.3%) and 5 (14.3%) tumors, respectively. Multivariate analysis revealed that air bronchogram was significantly associated with the presence of adenocarcinoma components with lepidic growth patterns (P = 0.005), and predominance of adenocarcinomas (P = 0.026). GGO was significantly associated with the presence of adenocarcinoma component with lepidic growth pattern (P = 0.010). Air bronchogram was an independent favorable prognostic factor for overall survival, whereas GGO did not have a significant effect on survival. Conclusion Air bronchogram observed in PCs of the lung is strongly related with histological components of the tumor and favorable outcome.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with an unfavorable prognosis. The standard therapeutic approaches are limited to surgery, chemotherapy, and radiotherapy. Because the consequent clinical outcome is often unsatisfactory, a different approach in MPM treatment is required. S100A11, a Ca2+-binding small protein with two EF-hands, is frequently upregulated in various human cancers. Interestingly, it has been found that intracellular and extracellular S100A11 have different functions in cell viability. In this study, we focused on the impact of extracellular S100A11 in MPM and explored the therapeutic potential of an S100A11-targeting strategy. We examined the secretion level of S100A11 in various kinds of cell lines by enzyme-linked immunosorbent assay. Among them, six out of seven MPM cell lines actively secreted S100A11, whereas normal mesothelial cell lines did not secrete it. To investigate the role of secreted S100A11 in MPM, we inhibited its function by neutralizing S100A11 with an anti-S100A11 antibody. Interestingly, the antibody significantly inhibited the proliferation of S100A11-secreting MPM cells in vitro and in vivo. Microarray analysis revealed that several pathways including genes involved in cell proliferation were negatively enriched in the antibody-treated cell lines. In addition, we examined the secretion level of S100A11 in various types of pleural effusions. We found that the secretion of S100A11 was significantly higher in MPM pleural effusions, compared to others, suggesting the possibility for the use of S100A11 as a biomarker. In conclusion, our results indicate that extracellular S100A11 plays important roles in MPM and may be a therapeutic target in S100A11-secreting MPM.

OBJECTIVES Although some retrospective studies have reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. METHODS The Japanese Association for Chest Surgery (JACS) conducted a nationwide multicentre prospective cohort and enrolled a total of 1019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications. RESULTS Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had Grade 3-4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. Five predictive factors, gender, comprehensive geriatric assessment75: memory and Simplified Comorbidity Score (SCS): diabetes mellitus, albumin and percentage vital capacity, were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66 and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross-validation was performed as an internal validation to reconfirm these 5 predictive factors (average area under the curve 0.70). We developed a simplified RS system as follows: RS = 3 (gender: male) + 2 (comprehensive geriatric assessment 75: memory: yes) + 2 (albumin

The diaphragm dissection should be started from anterior, because the portion is just under the thoracotomy incision. The diaphragmatic muscle was cut by an electric knife along the line of 1 to 2 cm from the chest wall from anterior and lateral to posterior. The diaphragm including the tendon center is dissected from the peritoneum. The peritoneum should be preserved. If the peritoneum is opened, it should be repaired by sutures. The pericardium is opened at the apex. The pericardium incision is extended from the apex to cranial side. And then, it is cut from the apex to posterior with the diaphragm. And next, the incision of the cranial side edge is extended to posterior. The lower pulmonary vein, upper pulmonary vein, and pulmonary artery are exposed. They are encircled and divided in the pericardium by autosutures. A Goretex sheet with 1 mm thickness is used to reconstruct the diaphragm. Nine sutures were placed in advance for the Goretex, and pulled out from the chest cavity through upper and lower sides of the 10th or 9th rib. The sutures were tied outside the rib cage. For mediastinal side, the Goretex was sutured to the residual diaphragm. A Goretex sheet with 0.1 mm thickness is used to reconstruct the pericardium by interrupted sutures. Because the contralateral lung is overinflated, the reconstruction should not be tight. Slits for the Goretex are made to prevent regional tamponade.

This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II–IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m2/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m2/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4–71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

Objectives Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy. Methods Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function. Results The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips. Conclusions Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes.

A 62-year-old man with a history of long-term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography. The computed tomography also revealed multiple plaques in the pleura. Malignant pleural mesothelioma was suspected, and thoracoscopic surgery was performed. Thoracoscopy revealed that the tumor location was extrapleural. Thus, excisional biopsy was performed. The tumor was histologically diagnosed as chondrosarcoma. Additional wide resection of the chest wall, including the fifth, sixth, and seventh ribs, was performed. Chest wall reconstruction was performed with a polypropylene mesh.

Accidents while using lawn mowers are often reported, but chest injuries are rare. We report a case of a penetrating pulmonary injury due to a rusty nail thrown by a lawn mower. A 63-year-old man injured his left precordium by a thrown object while using a lawn mower; he thereafter visited a nearby hospital. A computed tomography image showed a left-sided pneumothorax and a penetrating pulmonary injury of the left upper lobe due to a foreign body. Pneumothorax was treated with thoracic drainage and resolved. He was transferred to our hospital on the second day after the injury, and video-assisted thoracoscopic surgery was performed to remove the foreign body. Surgical findings showed a penetrating wound in the left upper lobe and leakage of pus from its margin. The foreign body was a rusty nail. The penetrating wound was treated by partial pulmonary resection to control the infection. Histopathological findings revealed the formation of a lung abscess. Penetrating pulmonary injuries do not require surgical treatment for most patients. However, residual foreign bodies can cause lung abscesses. The removal of foreign bodies depends on the type of injury as well as the type and location of the foreign body. Theoretically, the foreign body should be removed and the penetrating pulmonary injury should be treated, if possible, to control infection.

Chylothorax after lung cancer surgery is relatively rare but must be considered as a complication of thoracic surgery.Between January 2012 and June 2017, 818 patients underwent lung cancer surgery at our hospital. Among them, 14 (1.7%) patients with chylothorax were retrospectively reviewed. Three patients were treated with oral intake cessation except water and total parental nutrition( TPN)[TPN group], 11 patients were treated with a fat-free diet( fat-free diet group).The drainage period was similar in both group [group TPN;13 (12~14) days and group fat-free diet;15.7 (6~42) days]. In the TPN group, 3 patients underwent pleurodesis and no patient needed surgical intervention. In the fat-free diet group, 5 patients improved only with diet management. Pleurodesis was necessary in 5 of which 3 underwent surgical intervention.A fat-free diet is useful in treating chylothorax after lung cancer surgery.

Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the pleura that is difficult to diagnose, contributing to its dismal prognosis. Previously, we reported that the degree of microRNA (miR)‑34b/c methylation in circulating DNA is associated with the development of MPM. Herein, we present a newly developed droplet digital PCR (ddPCR)‑based assay for the detection of miR‑34b/c methylation in circulating DNA in patients with MPM. We originally prepared two probes within a short amplicon of 60 bp, designing one from the positive strand and the other from the complementary strand. The two probes functioned cooperatively, and our established assay detected DNA methylation accurately in the preliminary validation. We subsequently verified this assay using clinical samples. Serum samples from 35 cases of MPM, 29 cases of pleural plaque and 10 healthy volunteers were collected from 3 different institutions and used in this study. We divided the samples into 2 groups (group A, n=33; group B, n=41). A receiver‑operating characteristic curve analysis using the samples in group A determined the optimal cut‑off value for the diagnosis of MPM, with a sensitivity of 76.9% and a specificity of 90%. On the other hand, the use of the same criterion yielded a sensitivity of 59.1% and a specificity of 100% in group B, and corresponding values of 65.7 and 94.9% for the entire cohort, indicating a moderate sensitivity and a high specificity. In addition, when the analysis was focused on stage II or more advanced MPM, the sensitivity improved to 81.8%, suggesting the possibility that the methylated allele frequency in MPM may be associated with the stage of disease progression. On the whole, the findings of this study indicate that miR‑34b/c methylation in circulating DNA is a promising biomarker for the prediction of disease progression in patients with MPM.

We previously reported that the use of a stapler to divide intersegmental planes did not decrease preserved pulmonary volume or function relative to electrocautery. However, preservation of pulmonary volume or function can be compromised when a stapler is used with larger intersegmental planes. Here, we assessed the correlations between preserved lung volume and pulmonary function after segmentectomy and the size of the intersegmental planes, based on the division method. Intersegmental plane sizes in 56 patients were semi-automatically calculated using image analysis software on computed tomography images. The ratios of the remnant segment and ipsilateral lung volumes to their preoperative values (R-seg and R-ips) and the ratio of the postoperative pulmonary function relative to the predicted value were calculated based on three-dimensional volumetry. Correlations between preserved lung volume and pulmonary function and the intersegmental plane sizes were analyzed according to the division method. Intersegmental planes were divided by either electrocautery or with a stapler (EC/Mixed) in 21 patients and by stapler alone (ST) in 35 patients. There was no difference in the average size of the intersegmental planes between the two groups. The intersegmental plane size negatively correlated with R-seg in the ST group. Using the stapler method, as the size of the intersegmental planes increased, the preserved remnant segmental volume decreased; however, relation between the plane size and preserved pulmonary function was unclear. These findings indicate that stapler use is acceptable even for large intersegmental planes.

Malignant pleural mesothelioma (MPM) is an aggressive disease that is resistant to conventional therapies. Cell lines are useful models for studying the biological characteristics of tumors; therefore, the establishment of MPM cell lines is valuable for exploring novel therapeutic strategies for MPM. In the present study, 4 MPM cell lines (YUMC8, YUMC44, YUMC63, and YUMC64) were established, which consisted of 2 epithelioid and 2 sarcomatoid mesothelioma histological subtypes, from Japanese patients with MPM. The DNA methylation status, mutations, copy number gains, protein expression of representative genes, and the sensitivity to several drugs were examined in these 4 cell lines. Methylation of P16 was demonstrated in 3/4 cell lines, in which the protein expression of p16 was lost. Methylation of RASSF1A was observed in 3/4 cell lines. Copy number gains of EGFR, HER2 or MET were not detected in the 4 cell lines. Mutations in various genes, including EGFR, KRAS, HER2, BRAF, and PIK3CA, which are frequently detected in non-small cell lung cancer, were not detected in the 4 cell lines. microRNA-34b/c is a direct transcriptional target of p53 and is often silenced in MPM by promoter methylation. In the present study, miR-34b/c was heavily methylated in 2/4 established MPM cell lines. For cell adhesion molecules, E-cadherin expression was detected in the 2 epithelioid MPM cell lines, whereas N-cadherin expression was detected in all 4 established cell lines by western blotting. Vimentin was strongly expressed in the 2 sarcomatoid MPM cell lines. None of the established MPM cell lines demonstrated significant responses to the drugs tested, including NVP-AUY922, 17-DMAG, Trichostatin A, and Vorinostat. Although novel molecular findings were not observed in the current characterization of these MPM cell lines, these lines will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies.

Background: Patients with squamous cell carcinoma (SqCC) of the lung sometimes have a comorbid pulmonary disease such as pulmonary emphysema or an interstitial lung disease (ILD), both of which negatively affect patient outcome. The aim of this study was to determine the outcome of patients in a multicenter database who underwent surgery for cT1aN0M0 peripheral SqCC lung cancer. Methods: The medical records of a total of 228 eligible patients from seven institutions were reviewed to evaluate the impact of concomitant impaired pulmonary function and other clinicopathological factors on overall survival (OS) and relapse-free survival (RFS). Results: Six patients with positive or unclear tumor margins were excluded. Of the 222 remaining study patients, 42 (18.9%) and 97 (43.7%) patients were found to have coexisting restrictive or obstructive ventilatory impairment, respectively. Over a median follow-up period of 30.6 months, the 5-year OS and RFS were 69.0% and 62.6%, respectively. By multivariate analysis, ILDs identified on high-resolution computed tomography (HRCT), pulmonary function test results indicating a restrictive ventilatory impairment, and wedge resection were found to be independent risk factors for poor OS. An increased level of serum squamous cell carcinoma antigen (SCC-Ag) (>1.5 ng/mL) and the same risk factors for poor OS were independent risk factors for recurrence. Among patients who underwent anatomical lung resection (lobectomy and segmentectomy, n=173), a restrictive ventilatory impairment was an independent risk factor for poor OS, and increased serum SCC-Ag level, ILDs on HRCT, and restrictive ventilatory impairment were independent risk factors for poor RFS by multivariate analysis. Factors such as visceral pleural invasion, and lymphatic or vascular invasion were not significantly associated with outcome. Conclusions: A restrictive ventilatory impairment negatively affects the outcome of patients with cT1aN0M0 peripheral SqCC lung cancer.

Malignant pleural mesothelioma (MPM) is a dreadful disease with a poor prognosis. Multimodality therapy including surgical macroscopic complete resection is performed to treat operable MPM. Intraoperative intracavitary hyperthermic chemotherapy for MPM was reviewed. Appropriate papers published between 2006 and present were extracted by the PubMed advanced search by MPM (Title/Abstract), chemotherapy (Title/Abstract), and hyperthermia (All fields). Among the selected papers, those written in English, and treated more than ten MPM patients were reviewed. The intraoperative intracavitary hyperthermic chemotherapy has been performed following extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) for MPM. Cisplatin was mainly used for perfusion, and the morbidity and mortality was acceptable. In conclusion, the intraoperative intracavitary hyperthermic chemotherapy following EPP or P/D for MPM might enhance local control in the chest cavity.

Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. This study revealed eight risk factors for fatal AEIP.

PURPOSE To examine the relationship between the density of tumor-infiltrating T cell subpopulations and the pathological response to induction chemoradiotherapy (CRT) in patients with locally advanced NSCLC, and to assess the impact of T cell density on patient prognosis. METHODS A total of 64 patients with c-stages IIA-IIIB NSCLC who underwent induction CRT followed by R0 surgery were enrolled. Tumor-infiltrating T cells expressing either FOXP3 or CD8 were detected by immunohistochemical staining. RESULTS Mean numbers of tumor-infiltrating FOXP3+ T cells were 39.9 for patients with minor pathological responses (n = 9), 18.4 for those with major pathological responses (n = 25), and 12.9 for those with complete pathological responses (n = 30; P

Background: Malignant pleural mesothelioma (MPM) is a refractory disease with poor prognosis despite multimodality therapy. Because standard therapy is unsatisfactory, it is expected to establish a novel strategy such as molecular-targeting therapy for MPM. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein, is one of the tumor-specific stem cell marker and is revealed that the cell survival is reduced by inhibiting this protein in pancreatic and colorectal cancers. DCLK1 is known to have several isoforms named as isoform #1-#4, although the significance of them in MPM has not been clarified. We hypothesized that DCLK1 was a potential therapeutic target for MPM. Methods: Immunohistochemical staining was performed using surgically resected formalin-fixed paraffin-embedded tissue of MPM to evaluate the expression of DCLK1. Additionally, MPM cell lines were analyzed to characterize the protein and mRNA expression of DCLK1 by western blotting and RT-PCR. The expression of DCLK1 isoforms were selectively knocked down by small interfering RNA (siRNA) and cell viability was analyzed by colony formation and cell count assays. Results: Immunohistochemical staining demonstrated that the expression of DCLK1 in MPM specimens was positive in 24 out of 27 samples (89%). Western blotting and RT-PCR revealed that DCLK1 was expressed in seven out of nine MPM cell lines. The results of RT-PCR revealed that isoform #2 and isoform #4 of DCLK1 were expressed in H2052, isoform #4 was expressed in H28, and isoform #2 was expressed in YUMC44 cell lines. Expressions of DCLK1 isoforms were selectively suppressed by isoform-specific siRNAs. Colony formation and cell count assays revealed that siRNA-mediated knockdown of both isoforms #2 and #4 suppressed cell growth compared to knockdown by negative control siRNA and knockdown of only isoform #2 or #4. Conclusion: Our results demonstrate that simultaneous knockdown of both isoforms #2 and #4of DCLK1 results in the inhibition of cell growth and suggest its potential as a therapeutic target in MPM. Citation Format: Akihiro Miura, Hiromasa Yamamoto, Hiroyuki Tao, Ken Suzawa, Syunsaku Miyauchi, Kota Araki, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kazuhiko Shien, Junichi Soh, Kazunori Okabe, Shuta Tomida, Masakiyo Sakaguchi, Shinichi Toyooka. Doublecortin-like Kinase 1 (DCLK1) correlates with the cell proliferation in malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2136.

Doublecortin and CaM kinase-like-1 (DCLK1) regulates microtubule polymerization in migrating neurons. Recently, DCLK1 has been reported to act as an intestinal tumor stem cell marker and has been shown to be expressed in cancer cells and in the stroma of breast, colon, pancreatic, and prostate cancers. Here, we studied DCLK1 expression in non-small cell lung cancer (NSCLC) by immunohistochemistry in association with clinicopathological factors and patient prognosis. DCLK1 expression was analyzed by immunohistochemical staining of surgical specimens from 232 patients with pathological stage I NSCLC, including 187 adenocarcinomas. Relationships between the expression status of DCLK1 and clinicopathological factors were examined. The impact of DCLK1 expression status and other clinicopathological factors on survival was evaluated by univariate and multivariate analyses. Thirty-three (14.2%) of 232 patients had DCLK1-positive cancer cells. DCLK1 was also expressed in the tumor stroma in most of the specimens and was significantly associated with DCLK1 expression in cancer cells. DCLK1-positive cancer cells were more common in non-adenocarcinoma tissues (44.4%) than in adenocarcinoma tissues (7.0%). Moreover, positive DCLK1 expression in cancer cells and stromal cells was correlated with a worse prognosis. Histological analyses revealed that the presence of DCLK1-positive cancer cells was an independent risk factor for poor prognosis in adenocarcinoma, but was not significantly associated with prognosis in non-adenocarcinoma. DCLK1 expression was observed in tumor cells in patients with pathological stage I NSCLC and was correlated with adverse prognosis, especially in patients with adenocarcinoma. DCLK1 may be a potential new therapeutic target.

Background Chylothorax is a relatively rare but well-known complication of thoracic surgery. Case Presentation A 70-year-old man underwent right upper and middle bilobectomy and systematic lymph node dissection through a posterolateral thoracotomy for lung cancer. On the second postoperative day, he developed chylothorax that was treated with dietary management and pleurodesis. The discharge diminished and his chest tube was removed on the ninth postoperative day. On the 14th postoperative day, the patient complained of dyspnea and dysphagia, and imaging studies revealed mediastinal chyloma. Thoracoscopic surgical drainage was performed and the site of chyle leakage was sutured. Conclusions This report presents an unexpected complication of chemical pleurodesis and reviews the indications for surgical intervention in cases of postoperative chylothorax.

There is no recommended standard follow-up program after resection for lung cancer. Under these circumstances, each doctor establishes his or her own follow-up protocol. This questionnaire survey was conducted to grasp the current status of postoperative follow-up in Japan. The questionnaire survey was aimed at determining what examinations were performed and at what frequencies in the setting of postoperative follow-up. Based on these results, examinations performed at a frequency of >50% and the time points after resection at which they were performed were selected and presented as components of an average follow-up program. Questionnaires were sent to 44 institutions, and 26 doctors responded to the questionnaire. All 26 of the doctors performed physical examinations, blood examinations, chest radiography, and computed tomography (CT) routinely, but their frequencies varied widely among the doctors. The average frequencies of the follow-up examinations as judged from this survey are as follows: Physical and blood examinations are performed three to four times a year for the first 3 years and twice a year during the next 2 years. CT is scheduled at 6 and 12 months after resection and is repeated annually thereafter. Chest radiography is performed three to four times a year for the first 3 years and once a year thereafter, between the CT examinations. The follow-up programs used in clinical practice vary widely among institutions and doctors in terms of the types of examination performed and the frequencies at which they are performed.

Expression of the transcription factor FOXP3 characterizes regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Intra-tumoral accumulation of Tregs is associated with unfavorable prognosis in several kinds of cancers. Recently, expression of FOXP3 and its association with prognosis have also been shown in some cancer cells in clinical studies. For non-small cell lung cancer (NSCLC), however, prognostic significance of tumor FOXP3 expression and its relationship with Tregs remain unknown. FOXP3 expression in cancer cells and tumor-infiltrating lymphocytes was examined by immunohistochemical staining of surgical specimens from 87 patients with NSCLC. Prognostic values of the tumor-infiltrating Treg count and tumor FOXP3 expression status were evaluated retrospectively. FOXP3-positive cancer cells were observed in 27 of 87 (31.0%) patients. There was no significant relationship between Treg count and tumor FOXP3 status. Increased Treg counts were associated with worse overall and relapse-free survival whereas the influence of tumor FOXP3 status on survival was not significant. However, when FOXP3-positive cancer cells were present, the relationship between Treg accumulation and worse prognosis was attenuated. In contrast, patients without tumor FOXP3 expression and high Treg count had significantly worse overall and relapse-free survival (hazard ratio: 3.118 and 3.325, p=0.028 and 0.024, respectively) than other groups. These results suggest that tumor FOXP3 expression has a better prognostic potential in NSCLC and that in combination with tumor-infiltrating Treg count the absence of tumor FOXP3 allows the selection of high-risk patients.