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Open in new tab Download slide OBJECTIVES Double-lumen endobronchial tubes (DLTs) are essential for differential lung ventilation during pulmonary lobectomy, but they are more rigid, longer, larger in diameter and irritable. Coughing at extubation sometimes causes airway and lung injury, which causes severe air leaks, prolonged cough and sore throat. We examined the prevalence of cough-associated air leaks at extubation and postoperative cough or sore throat after lobectomy and evaluated the efficacy of supraglottic airway (SGA) in preventing these complications. METHODS Patient characteristics and operative and postoperative factors data were collected from patients who underwent pulmonary lobectomy between January 2013 and March 2022. After propensity score matching, these data were compared between the SGA and DLT groups. RESULTS A total of 1069 patients with lung cancer (SGA, 641; DLTs, 428) were enrolled and coughing at extubation occurred in 100 (23.4%) patients in the DLT group, 65 (65.0%) showed increased cough-associated air leaks at extubation and 20 (30.8%) showed prolonged air leaks. Coughing at extubation occurred in 6 (0.9%) in the SGA group. In 193 patients from each group after propensity score matching, coughing at extubation and the associated air leak increase were significantly lower in the SGA group. Visual analogue scale of postoperative cough and sore throat on postoperative days 2, 7 and 30 were significantly lower in the SGA group. CONCLUSIONS SGA is effective and safe for preventing cough-associated air leaks and prolonged postoperative cough or sore throat at extubation following pulmonary lobectomy. [ABSTRACT FROM AUTHOR]

Background: The incidence of postoperative delirium after anatomical lung resection ranges from 5 to 16%. This study aimed to analyze the risk factors and prognosis of postoperative delirium in anatomical lung resection for lung cancer. Methods: This study included 1351 patients undergoing anatomical lung resection between April 2010 and October 2020. We analyzed the perioperative risk factors of postoperative delirium. We also compared postoperative complications and survival between the delirium and non-delirium groups. Results: Postoperative delirium was identified in 44 (3.3%) of 1351 patients who underwent anatomical lung resection for lung cancer. Age, peripheral vascular disease, depression, and current smoking status were independent risk factors for postoperative delirium in the multivariate analysis. The percentage of postoperative delirium was 0.6% in never smokers and 6.0% in current smokers. The delirium and non-delirium groups showed significant differences in overall survival (p = 0.0144) and non-disease-specific survival (p = 0.0080). After propensity score matching, the two groups did not significantly differ in overall survival (p = 0.9136), non-disease-specific survival (p = 0.8146), or disease-specific survival (p = 0.6804). Conclusions: Age, peripheral vascular disease, depression, and current smoking status were considered independent risk factors for postoperative delirium in anatomical lung resection for lung cancer. Smoking cessation for at least four weeks before surgery is recommended for reducing incidence of post-operative delirium. [ABSTRACT FROM AUTHOR]

Background: The incidence of postoperative atrial fibrillation (POAF) after pulmonary lobectomy ranges from 6.4 to 12.6%. This study aimed to analyze the postoperative risk factors and prognosis for POAF in lobectomy for lung cancer. Methods: Data were collected from patients undergoing pulmonary lobectomy from April 2010 to March 2019. We analyzed risk factors for POAF among perioperative factors and compared postoperative complications or overall survival between POAF and non-POAF groups. We classified POAF as either the temporary or non-temporary type and compared perioperative factors, postoperative complications, and overall survival. Results: POAF was identified in 49 (5.2%) of the 947 lobectomies. The POAF group included more males, patients with poor performance status (PS), history of paroxysmal atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), and intraoperative blood transfusions. Poor PS, COPD, previous paroxysmal AF, and intraoperative blood transfusion were independent risk factors for POAF in multivariate analysis. The POAF group had a poorer prognosis than the non-POAF group (p = 0.0045). POAF was divided into 29 temporary and 20 non-temporary types. The onset date of non-temporary-type POAF was significantly later than that of the transient type (P < 0.01), and diabetes mellitus was significantly higher in non-temporary-type POAF. Non-temporary-type POAF had a significantly poorer prognosis in terms of overall survival (p = 0.005). Conclusions: Poor PS, COPD, history of PAF, and intraoperative blood transfusion were independent risk factors for POAF. Non-temporary-type POAF occurred significantly later than transient type and caused poorer prognosis after lobectomy for lung cancer. [ABSTRACT FROM AUTHOR]

A 49-year-old woman presented with cough, and chest X-rays showed an abnormal shadow. Chest computed tomography showed an anterior mediastinal 40-mm mass with massive calcification. The patient underwent mediastinal tumor excision performed using video-assisted thoracoscopic surgery. Pathological findings revealed the tumor to be a type B3 thymoma, with massive calcification occupying almost all of the thymoma. Due to high risk of recurrence, we performed completion thymectomy. Pathological findings revealed no remaining thymoma tissue in the residual thymus. Mediastinal tumor with entire calcification could be a candidate for surgical excision. [ABSTRACT FROM AUTHOR]

Background: The use of double-lumen endobronchial tubes (DLTs) is necessary for differential lung ventilation during pulmonary lobectomy. However, when used with conventional extubation procedures, coughing is more likely and is associated with an increased risk for parenchymal air leak along the staple line and possible subsequent lung injury. We examined the prevalence of coughing-associated air leaks at extubation and the efficacy of using supraglottic airways (SGAs) to prevent air leaks with post-lobectomy extubation. Methods: This study included 150 patients with pulmonary emphysema diagnosed using preoperative computed tomography, who underwent pulmonary lobectomy between April 2010 and March 2015. The patients were chronologically enrolled in two groups: the DLT group (60 patients) from April 2010 to August 2012, and the SGA group (90 patients) from September 2012 to March 2015. (Note: the DLT group only included cases without air leak present just prior to extubation). Data were collected on specific patient characteristics and operative and postoperative factors. Results: Coughing at extubation occurred in 15 (25.0 %) of 60 DLT patients, and parenchymal air leaks developed in 10 (66.7 %) of these 15. Comparison of groups revealed the SGA group was significantly lower for the following: patients with coughing at extubation ( P < 0.001), coughing-associated air leaks at extubation ( P < 0.001), air leaks >7 days ( P = 0.006), reoperation due to air leaks ( P = 0.013), and duration of chest tube drainage ( P < 0.001). Conclusions: The SGA is effective for preventing air leaks associated with coughing during conventional DLT extubation in post-lobectomy patients. [ABSTRACT FROM AUTHOR]

A 62-year-old female with myasthenia gravis and a mediastinal tumor underwent extended thymothymectomy by video-assisted thoracoscopic surgery (VATS). The tumor was diagnosed as a stage I type B2 thymoma. Eight years after the initial surgery, an abnormal shadow was detected on the annual follow-up chest radiograph, and computed tomography showed a homogeneous 35 × 15 mm hemispherical mass under a port-site scar in the right anterior chest wall. The mass was between the second and third ribs and was found to be adherent to the lung during surgery, and was excised via lung and chest wall resection. The pathological examination confirmed that it was a type B2 thymoma invading the third rib, and the tumor was considered to be a port-site recurrence. Care should be taken during VATS to avoid contact between the tumor surface and the port tracts to prevent tumor cell implantation. [ABSTRACT FROM AUTHOR]

Abstract: Blunt tracheobronchial injuries are rare, but can be life-threatening. A precise preoperative diagnosis and a well-recognised plan of surgical treatment, which may be unique for each patient, are needed to restore the continuity of tracheobronchial tree in a one-stage intervention. We encountered a patient with complete tracheal transection and 15cm tear in the posterior membranous trachea and right bronchus, and whose tracheal injury was difficult to repair using direct intubation of distal airway by bronchoscopy. We achieved a good result of one-stage repair using a percutaneous cardiopulmonary support (PCPS). [Copyright &y& Elsevier]

Simple Summary: Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer. The expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression. The correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells was also examined. A quantitative analysis of protein expression in macrophages and cancer cells revealed that PD-L1-positive cells expressed higher levels of B7-H3 than that of PD-L1-negative cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies. Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1− cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies. [ABSTRACT FROM AUTHOR]

Background: The recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. Materials and Methods: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). Results: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10). Conclusion: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

Background: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. Methods: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD‐L1 positive cells, cell density, and cell‐to‐cell distance were analyzed by multiplex immunofluorescence. Results: PD‐L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. Conclusions: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LSCC) exhibits poor response to treatment compared with other lung cancer subtypes, resulting in worse prognosis. Therefore, new therapeutic strategies are required for advanced LSCC. Ferroptosis is a recently discovered nonapoptotic cell death caused by intracellular lipid peroxidation that can bring about effective cell death in cancer cells resistant to apoptosis. Hence, ferroptosis is a potential therapeutic strategy for refractory cancer. In this study, we performed clinicopathological and molecular analyses on tumor specimens from 270 patients with squamous cell lung cancer, focusing on the expression of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1), which are known to be key regulators of ferroptosis, and the accumulation of 4-hydroxynoneral (4-HNE), a lipid peroxidation marker. Immunohistochemistry revealed that patients with low 4-HNE accumulation and low levels of GPX4 or FSP1 had significantly worse prognoses than other patients (P = 0.001). This stratification was an independent prognostic predictor (P = 0.003). A dramatic cell death synergistic effect was observed on LSCC-derived LK-2 and EBC1 cells treated with GPX4 and FSP1 inhibitors. This effect was completely inhibited by treatment with the ferroptosis inhibitor. Notably, this was not the case in LK-2 cells treated with the apoptosis inhibitor, and in these cells, ferroptosis was induced. Ferroptosis regulators GPX4 and FSP1 are associated with lung squamous cell cancer cancer's prognosis. We present the clinicopathological and molecular basis of novel therapeutic strategies for refractory LSCC. [ABSTRACT FROM AUTHOR]

We examined the immunohistochemical distribution of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the enzyme responsible for the conversion of bioactive glucocorticoids to their receptor-inactive forms, in lung tissue obtained at autopsy from 14 patients who had died due to acute respiratory distress syndrome (ARDS). We found positive immunoreactivity for 11β-HSD2 in 13 cases. The cells expressing 11β-HSD2 in the alveolar wall were positive for surfactant apoprotein-A as well as cytokeratin. Immunoreactivity for 11β-HSD2 was also detected in the CD68+ cells, which were found in the alveolar spaces. All patients had been treated with glucocorticoids for ARDS and/or the underlying diseases. There was no statistically significant correlation between the use of glucocorticoids and 11β-HSD2 immunoreactivity in the alveolar wall ( P = 0.0729). However, expression of grade + + was found in three out of five patients who received dexamethasone pulse therapy at relatively large doses, as well as in three other patients treated with prednisolone for a long period of time for the underlying disease. An increase in the expression of 11β-HSD2 may result in faster glucocorticoid breakdown in lung cells in patients with ARDS. Impaired glucocorticoid availability in the lungs of such patients may explain, in part, the fact that glucocorticoid therapy does not always rescue patients with ARDS. [ABSTRACT FROM AUTHOR]

Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30–100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40–100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial–myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1–30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut‐off value of the percentage of En1‐expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1‐positive and the others were En1‐negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms. [ABSTRACT FROM AUTHOR]

Objectives Placental (P)-cadherin expression is associated with malignant phenotype of cancer cell. The loss of E-cadherin has been thought to play a key role in tumor progression in several cancers. In this study, we aimed to clarify the role of P-cadherin expression in non-small-cell lung cancer (NSCLC). Materials and methods NSCLC patients ( n  = 172) were enrolled in this study; among them, 107 harbored adenocarcinomas, and 65 had squamous cell carcinomas. We examined P-cadherin and E-cadherin expression by immunohistochemical analysis and assessed the associations between each cadherin expression and both cadherin expression patterns with clinicopathological factors and prognosis. To investigate the pathway to acquire tumor progression associated with P-cadherin and E-cadherin, we examined p120 catenin localization by immunohistochemical analysis. Results High P-cadherin expression was significantly associated with lymphatic metastasis, pathological stage, and Ki-67 proliferation index ( P <  .05, respectively). Low E-cadherin expression was significantly associated with maximum standardized uptake value, lymphatic metastasis, and pathological stage ( P <  .05, respectively). The cytoplasmic p120 catenin localization was associated with the low E-cadherin and high P-cadherin expression group ( P <  .001). High P-cadherin expression was associated with shorter disease-free survival ( P  = .044) and shorter overall survival (OS; P  = .044). The low E-cadherin and high P-cadherin expression group was associated with shorter OS ( P  = .024). Conclusions High P-cadherin expression was associated with tumor progression and poor patient survival in NSCLC. In these patients, the low E-cadherin expression might be associated with tumor progression involving cytoplasmic p120 catenin. [ABSTRACT FROM AUTHOR]

Objectives: 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which requires oxidized nicotinamide adenine dinucleotide as a cofactor, metabolizes endogenous glucocorticoids. Since 11beta-HSD2 has been detected in lung epithelial cells, we examined whether carbenoxolone, a potent inhibitor of 11beta-HSD, would enhance endogenous glucocorticoid action on lung fluid balance and inflammation.Design: Controlled laboratory study.Setting: University research laboratory.Subjects: Adult Sprague-Dawley rats (n = 66).Interventions: Rats were intraperitoneally injected with carbenoxolone (2 x 10 mg.kg(-1).day(-1) for 3 days) and allowed free access to water and food. Rats were further challenged with endotoxin instillation (1 mg/kg).Measurements and Main Results: We discovered that carbenoxolone significantly increased messenger RNA expression of all three epithelial sodium channel subunits in distal lung tissues (two-fold increase of alpha-subunit, four-fold increase of beta-subunit, and two-fold increase of gamma-subunit) as well as in trachea. Carbenoxolone increased the amiloride-sensitive alveolar fluid clearance significantly. When rats were further challenged by endotoxin instillation (1 mg/kg), pretreatment with carbenoxolone significantly inhibited endotoxin-induced increase in lung neutrophils as well as tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1 concentrations in serum and bronchoalveolar lavage fluid.Conclusions: These beneficial effects of carbenoxolone on lung fluid balance and inflammation are very similar to those expected when glucocorticoids are introduced exogenously. We conclude that carbenoxolone increased the actions of endogenous bioactive glucocorticoids on lung cells by reducing local steroid breakdown. [ABSTRACT FROM AUTHOR]