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BACKGROUND: The usefulness of autologous blood pleurodesis for air leak after pulmonary resection is well known; however, factors predicting the therapeutic efficacy are poorly understood. Herein, we aimed to examine the predictors of early autologous blood pleurodesis for air leak following pulmonary resection. METHODS: Patients who underwent pulmonary resection and autologous blood pleurodesis with thrombin for postoperative air leak between January 2016 and October 2022 were retrospectively analyzed. Patients received 50-100 mL of autologous blood and 20,000 units of thrombin on postoperative days 1-4. If necessary, the same procedure or pleurodesis with other chemical agents was repeated until the air leak stopped. Patients were divided into single-dose and multiple-dose groups based on the number of times pleurodesis had occurred before the air leak stopped and were statistically analyzed. Logistic regression analysis was performed to identify predictors of treatment efficacy. RESULTS: Of the 922 patients who underwent pulmonary resection, 57 patients (6.2%) were included and divided into single-dose (n = 38) and multiple-dose (n = 19) groups. The amount of air leaks was identified as a significant predictor of multiple dosing, with a cutoff of 60 mL/min, in multivariate logistic regression analyses (odds ratio 1.13, 95% CI 1.03-1.24, p = 0.0065). The multiple-dose group showed a significantly higher recurrence of air leak (p = 0.0417). CONCLUSIONS: The amount of air leaks after pulmonary resection is the only significant factor predicting whether multiple autologous blood pleurodesis is required, and the recurrence rate of pneumothorax is significantly higher in such cases.

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BACKGROUND: This study analyzed the preventive effect of 50 mg/day pregabalin on postoperative neuropathic pain, and any additional benefits related to sleep and respiratory function. METHODS: This prospective randomized controlled study included lung resection patients 20-89 years of age. Patients were randomly assigned to the treatment (pregabalin; initial dose, 50 mg/day) or control (non-steroidal anti-inflammatory drugs) group. Pregabalin patients received non-steroidal anti-inflammatory drugs and pregabalin (25 mg, twice daily) from the second postoperative day. Pain scores, neuropathic pain, analgesic use, respiratory function, and insomnia scale scores for 3 months after surgery were evaluated. RESULTS: This study included 46 patients who received pregabalin and 46 control patients. Pregabalin patients had significantly less postoperative neuropathic pain than control patients (19.6% vs. 41.3%; P=0.0404), and their duration of neuropathic pain was significantly shorter (30 vs. 90 days; P=0.024). The onset of postoperative neuropathic pain, insomnia scale scores, and respiratory function were similar between groups. No pregabalin-related adverse events were reported. CONCLUSIONS: Pregabalin (50 mg/day) had a significant preventive effect on postoperative neuropathic pain after thoracic surgery, without side effects. Early postoperative administration of pregabalin would help prevent neuropathic pain and provide better pain control after thoracic surgery.

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An increasing number of patients with lung cancer are undergoing outpatient chemotherapy, and thus, it is very important to maintain the quality of life(QOL)of these patients. Ninjin-Youei-To(TJ-108), a Japanese traditional medicine, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-108 in patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate factors influencing the QOL of these patients, we administered a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 15 patients with non-small cell lung cancer. Factors related to the overall QOL scores and other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale" were analyzed. No significant decrease in each of the evaluated factors was observed in this study.

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BACKGROUND: This study aimed to clarify the incidence and risk factors of neuropathic pain after thoracic surgery, focusing especially on patients who underwent complete video-assisted thoracoscopic surgery (VATS). METHODS: We retrospectively identified 185 patients who underwent thoracic surgery at our hospital over a 2-year period. Logistic regression analysis was used to analyze the association of various factors with postoperative neuropathic pain. RESULTS: Forty-eight (25.9%) patients developed postoperative neuropathic pain, and 9 (18.8%) of these patients reported persistent pain 1 year postoperatively. The median interval from surgical treatment to the onset of neuropathic pain was 7 days, and the duration was 50 days. Multivariate logistic regression analysis revealed a significant positive correlation between postoperative neuropathic pain and preoperative use of hypnotic medication [odds ratio (OR), 5.45; 95% confidence interval (CI); 2.52-12.17] and duration of surgery ≥2.5 hours (OR, 2.72; 95% CI, 1.27-6.09), and a significant negative association with the complete VATS approach (OR, 0.18; 95% CI, 0.073-0.42). CONCLUSIONS: Preoperative use of hypnotic medication, the thoracotomy approach, and duration of surgery ≥2.5 hours are associated with increased risk of neuropathic pain after thoracic surgery. The complete VATS approach could decrease the incidence of postoperative neuropathic pain, regardless of the duration of surgery.

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BACKGROUND: While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported. OBJECTIVE: We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy. METHODS: Clinical data were retrospectively analyzed and survival duration was compared using the logrank test. RESULTS: A total of 22 patients were included. Median progression-free survival in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies was 15.1 months, 6.3 months, and 13 months, respectively. Two patients receiving treatment with EGFR-TKI did not show disease progression at 41.3 months and 45.8 months(p=0.265). Median overall survivals in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies were 26.5 months, 20 months, and 37.9 months, respectively(p=0.510). After the treatment, 6 patients showed regrowth of the recurrent lesion, 8 patients showed remote metastases, and 2 patients showed both regrowth of the recurrent lesion and remote metastases. CONCLUSION: Patients who received treatment including local therapy showed longer survival duration, but statistical significance was not detected. Our study suggested that regrowth of the recurrent lesion and remote metastases can be equally observed after treatment.

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A ciliated muconodular papillary tumor (CMPT) has been reported to be a low-grade malignant tumor or benign tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation, occur in the peripheral lung. We present a case of CMPT in this report. A 42-year-old male was referred to our department due to a nodule detected in the peripheral left lower lobe of lung. The nodule was resected via wedge resection based on a suspected diagnosis of carcinoma. Intraoperative analysis of the frozen sections was suggestive of mucinous adenocarcinoma. A left lower lobectomy and mediastinal lymph node dissection were performed. The resected specimen was characterized as a papillary tumor with central fibrosis, proliferating along the alveolar walls, surrounded by mucous lakes, and consisting of ciliated columnar cells and goblet cells. Nuclear atypia was mild, and no mitotic activity was observed. Based on these findings, the tumor was finally diagnosed as CMPT. No recurrence has been noted for 24 months after surgery.

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The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I-IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival. The difference in survival of the clusters was confirmed separately for pStage I and pStage II-IIIA patients. Cluster A patients who also had CD4 and CD8 T-cell infiltration showed even better survival, as expected. The findings were confirmed by examining an independent validation cohort of 68 pStage I lung adenocarcinoma patients. Our data showed that PD-L1 expression was a positive indicator, whereas Galectin-9 and XAGE1 expression was negative. In vitro analyses suggested that PD-L1 expression was upregulated by IFNγ secreted from activated T cells in the tumor and Galectin-9 expression was counteracting those T cells. Thus, use of these immune markers enables the creation of a discriminant function with which to classify tumors and predict survival. Cancer Immunol Res; 4(12); 1049-60. ©2016 AACR.

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In this review article, we describe several topics, including the sandwich technique, the transatrial re-endocardialization technique, the limited apical left ventriculotomy approach and device closure. The sandwich technique was introduced for the closure of muscular ventricular septal defects (VSD) by sandwiching the septum between two felt patches placed in the left and right ventricle. This technique requires neither the transection of muscular trabeculae nor ventriculotomy. Although the sandwich technique has resulted in the improvement of surgical outcomes, cases of postoperative cardiac dysfunction have been reported. Multiple smaller VSDs have been closed with transatrial re-endocardialization. Septal dysfunction may be avoided through this technique, in which the septal trabeculae are approximated in two layers of superficial, endocardial running sutures. Recently, a number of reports have recommended a limited apical left ventriculotomy approach. With this technique, a much shorter incision of around 1 cm at the apex of the left ventricle may be sufficient for achieving the complete closure of apical muscular VSDs. The transcatheter or perventricular device closure of muscular VSDs has increasingly been performed with good results. Although favorable early and mid-term results of device closure have been reported, this method is not always safer or less invasive than surgical closure. Long-term evaluations should be performed to determine whether the right and left ventricular functions are affected by treatment with relatively large devices in the heart.

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Various etiologies of spontaneous hemothorax have been reported, though the cause remains unidentified in some patients despite an exploratory thoracotomy. We report on an 89-year-old man with spontaneous hemothorax resolved by partial resection of the lung using complete video-assisted thoracoscopic surgery. The histopathologic findings revealed a ruptured micro-venous hemangioma located just below the bleeding visceral pleura. To the best of our knowledge, this is the first report of spontaneous hemothorax caused by a pulmonary micro-venous hemangioma.

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Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-ß-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.

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Diaphragm plication has become the accepted treatment for major respiratory impairment caused by diaphragmatic eventration and paralysis. Various open and minimally invasive plication techniques have been described and while video-assisted thoracoscopic diaphragm plication appears to be a safe and effective alternative to open surgery, the workspace is limited. We describe how we performed complete thoracoscopic diaphragm plication using carbon dioxide (CO2) insufflation for a patient with unilateral diaphragmatic eventration. Using CO2 insufflation seems to dramatically improve the workspace.

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Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20%. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10%, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.

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Activation of numerous pathways has been documented in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) has emerged as a common therapeutic target. The mitogen-activated protein kinase (MAPK) and AKT signaling pathways are downstream of EGFR and deregulated via genetic and epigenetic mechanisms in many human cancers. We evaluated selected markers in the EGFR pathway with reference to outcome. Tissues from 220 cases of NSCLC patients presented in a tissue microarray were assayed with immunohistochemistry for phosphorylated AKT, phosphorylated MAPK, phosphorylated mTOR, and EGFR and then quantified by automated image analysis. Individually, the biomarkers did not predict. Combined as ratios, p-mTOR/p-AKT, and p-MAPK/EGFR function as prognostic markers of survival (p=0.008 and p=0.029, respectively), however, no significance was found after adjustment (p=0.221, p=0.103). The sum of these ratios demonstrates a stronger correlation with survival (p<0.001) and remained statistically significant after adjustment (p=0.026). The algebraic combination of biomarkers offer the capacity to understand factors that predict outcome better than current approaches of evaluating biomarkers individually or in pairs. Our results show the sum of p-mTOR/p-AKT and p-MAPK/EGFR is a potential predictive marker of survival in NSCLC patients.

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The mediastinum is a unique anatomic area containing various structures and pluripotent cells, which allow for the development of a range of tumors. We report two pediatric cases of a lipomatous tumor of the posterior mediastinum. Complete surgical excision of the mass in each was achieved through a lateral thoracotomy. Histopathologic findings showed a lipoma in one case and a lipoblastoma in the other. A lipomatous tumor in the posterior mediastinum is extremely rare and preoperative diagnosis is difficult. When an operative plan is being considered, the presence of a potentially malignant tumor should be kept in mind.

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A 52-year-old man with fever and dyspnea was admitted to our hospital. Chest computed tomography showed a mass measuring 3.5×3.0 cm in the S(1+2) segment of the left lung with involvement of the aorta. Although cytological examination using broncho fiberscopy did not show any malignancy, we suspected the mass to be T4N0M0 lung cancer. The tumor was diagnosed as having invaded the aorta using intravascular ultrasound. First, an endovascular graft was inserted, and then, a left upper lobectomy with resection of the infiltrated aortic wall was performed without cardiopulmonary bypass. The patient had an uneventful recovery without any complications. Pathological examination revealed the tumor to be a large-cell carcinoma. We think that an aortic endograft can be useful for resection of an infiltrated aortic wall, although further studies are necessary.

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BACKGROUND AND OBJECTIVE: Many lung diseases arise as the consequence of inhalational injury. When pathogenic materials are inhaled, it is possible that their clearance routes become the main focus of injury in the lung. Lymphatic clearance is important in the removal from the lung of small inhaled particles. The leak of toxic agents from the lymphatic flow potentially explains the topographic distribution of diffuse lung diseases triggered by inhaled materials, for example asbestosis. The aim of this study was to evaluate the differences in lymphatic distribution across various craniocaudal levels of the lung by using carbon dust deposition (CDD) as a tracing marker. METHODS: We evaluated 61 HE-stained slides of the normal lung area from 61 lobectomy specimens. The intensity of CDD was scored into five degrees (0-4) in bronchiolovascular (BV) areas and subpleural/septal (SP) areas per slide. The distribution was highlighted by subtraction scores of SP areas from those of bronchiolovascular areas. RESULTS: The subtraction scores of the upper lung area were significantly greater than those in the lower area, whereas there was no significant difference in scores by pulmonary lobes. CONCLUSIONS: Our results indicated that the main lymphatic clearance routes vary according to the craniocaudal levels, and are predominant in BV areas of the upper areas and in SP areas of the lower areas of the lung. This may explain the histological variations in anatomical distribution observed in the biopsy specimens of some diffuse lung diseases.

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Although improved surgical techniques have led to significantly better outcomes of surgery for total anomalous pulmonary venous connection, the risk of progressive pulmonary venous obstruction continues to be a clinical problem. Both obstructed total anomalous pulmonary venous connection and post-repair pulmonary venous obstruction are associated with a significant risk of recurrent obstruction or death, requiring reoperation for stenosis. In general, side to side anastomosis of the pulmonary venous confluence to the functional left atrium has been performed for supracardiac and infracardiac total anomalous pulmonary venous connection. Repair of total anomalous pulmonary venous connection to the coronary sinus invariably involved unroofing the coronary sinus, followed by pericardial patch closure of the atrial septal defect. Recently, sutureless technique has been adopted as the primary operation for the subgroups of patients that are thought to be at high risk for post-repair pulmonary venous obstruction, such as those with total anomalous pulmonary venous connection associated with right isomerism, infracardiac total anomalous pulmonary venous connection with small individual pulmonary veins, or mixed-type total anomalous pulmonary venous connection. Because the sutureless technique does not require direct anastomosis to the confluence, aggressive resection of the obstructed pulmonary venous tissue can be achieved, and surgically induced distortion of the suture line can be avoided, which may help to prevent subsequent pulmonary venous obstruction. Conventional management strategies for recurrent pulmonary venous obstruction have typically been associated with poor outcomes. Recent reports have supported the use of the sutureless technique to treat post-repair pulmonary venous obstruction.

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A 61-year-old man was pointed out a solitary nodule located in the left lung (S9) measuring 18 × 29 mm in size along with lymphadenopathy by chest computed tomography (CT). Positron emission tomography( PET) scan showed a positive sign corresponding to the nodule[ standardized uptake value (SUV) max 5.8]. No diagnostic material was obtained from the transbronchial tumor biopsy, since it was difficult to rule out malignancy, surgical biopsy was performed with sampling of mediastinal lymph nodes. Histopathological examination showed marked infiltration of inflammatory cells, many of which were demonstrated to be immunoglobulin (Ig) G4-positive plasma cells by immunohistochemical staining. Hence, IgG4-related inflammatory pseudotumor of the lung was diagnosed.

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Calpains are a family of calcium-dependent proteases. Two isoforms, calpain 1 and 2, have been implicated in angiogenesis and endothelial cell adhesion and migration. Calpains regulate the function of eNOS;however, the relation of calpains and eNOS to lymphangiogenesisis still unclear. In the present study, we evaluated the role of calpain and eNOS in the formation of cords by lymphatic endothelial cells on Matrigel. Human lymphatic microvascular dermal-derived endothelial cells were transfected with siRNA against calpain 1 or 2. Calpain 2 knockdown, but not calpain 1 knockdown, significantly reduced cord formation, adhesion, and migration on Matrigel. These decreases correlated with a reduction in eNOS, and phosphorylated eNOS and Hsp90 levels, as assayed by immunoprecipitation and western blotting. In contrast, the knockdown of calpain 1, but not calpain 2,increased cell adhesion, enhanced migration, and stabilized late-stage cord formation by increasing cord length compared to the control. These differences correlated with an increase in the level of phosphorylated eNOS. The results indicated that the functions of calpains and eNOS are important for cord formation by lymphatic endothelial cells. For the first time, we have found different functions of calpain 1 and 2. Calpain 1 is involved in the degradation of eNOS and Hsp90 and the phosphorylation of eNOS,while calpain 2 regulates eNOS phosphorylation during cord formation by lymphatic endothelial cells on Matrigel.

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A 78-year-old man referred to our hospital with the chief complaints of anorexia, general malaise, rash, and weight loss. Laboratory examination revealed pancytopenia, hyperglobulinemia, generalized adenopathy, and multiple pulmonary nodules. Video-assisted thoracic surgery (VATS) was performed to diagnose pulmonary nodules. After operation, it was difficult to achieve hemostasis for a while. Finally, the patient was diagnosed as pulmonary cryptococcosis and Evans syndrome.

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