Association between socioeconomic status and net survival after primary lung cancer surgery: a tertiary university hospital retrospective observational study in Japan.

BACKGROUND: Inequalities in opportunities for primary lung cancer surgery due to socioeconomic status exist. We investigated whether socioeconomic inequalities exist in net survival after curative intent surgery at a tertiary university hospital, in Japan. METHODS: Data from the hospital-based cancer registry on primary lung cancer patients who received lung resection between 2010 and 2018 were linked to the surgical dataset. An area deprivation index, calculated from small area statistics and ranked into tertiles based on Japan-wide distribution, was linked with the patient's address as a proxy measure for individual socioeconomic status. We estimated net survival of up to 5 years by deprivation tertiles. Socioeconomic inequalities in cancer survival were analyzed using an excess hazard model. RESULTS: Of the 1039 patient-sample, advanced stage (Stage IIIA+) was more prevalent in the most deprived group (28.1%) than the least deprived group (18.0%). The 5-year net survival rates (95% confidence interval) from the least to the most deprived tertiles were 82.1% (76.2-86.6), 77.6% (70.8-83.0) and 71.4% (62.7-78.4), respectively. The sex- and age-adjusted excess hazard ratio of 5-year death was significantly higher in the most deprived group than the least deprived (excess hazard ratio = 1.64, 95% confidence interval: 1.09-2.47). The hazard ratio reduced toward null after additionally accounting for disease stage, suggesting that the advanced stage may explain the poor prognosis among the deprived group. CONCLUSION: There was socioeconomic inequality in the net survival of patients who received curative intent surgery for primary lung cancer. The lower socioeconomic status group might be less likely to receive early curative surgery.

[Minimally Invasive Surgery for Mediastinal Tumor].

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

Postoperative Delirium in Lung Cancer Anatomical Resection-Analysis of Risk Factors and Prognosis.

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.

Endovascular Treatment for Acute Ischemic Stroke After Video-Assisted Thoracoscopic Pulmonary Lobectomy in Patients With Lung Cancer: A Report of Four Cases and Literature Review.

BACKGROUND: Postoperative cerebral embolic stroke is a serious complication of pulmonary lobectomy, occurring in 1.1% of patients undergoing lobectomy through video-assisted thoracoscopic surgery (VATS). The mechanism of this complication is thought to be embolic stroke caused by thrombus formed due to stagnation in the pulmonary vein stump after VATS lobectomy. There have been few reports demonstrating the utility of endovascular treatment (EVT) for cerebral embolic stroke after VATS lobectomy. CASE DESCRIPTION: In our case series, cerebral embolic stroke occurred after VATS pulmonary lobectomy for lung cancer, including the left upper lobe in three cases and the right lobe in one. The median duration of ischemic stroke after VATS was 4.5 days (interquartile range, 2-9 days). The median time from stroke onset to puncture was 130 min. Successful recanalization was achieved in all cases, and two patients achieved favorable clinical outcomes (modified Rankin scale, 0-2). CONCLUSION: We report a case series of four patients who underwent EVT for acute embolic stroke after VATS lobectomy for lung cancer. EVT is considered a reasonable and feasible therapeutic option for this condition.

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma.

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.

Postoperative Atrial Fibrillation in Lung Cancer Lobectomy-Analysis of Risk Factors and Prognosis.

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.

Cortical Actin Alteration at the Matrix-Side Cytoplasm in Lung Adenocarcinoma Cells and Its Significance in Invasion.

OBJECTIVES: Cortical actin is a thin layer of filamentous (F-)actin that lies beneath the plasma membrane, and its role in pathophysiology remains unclear. We investigated the subcellular localization of cortical actin by the histopathological and experimental studies of lung adenocarcinomas. MATERIALS AND METHODS: The subcellular localization of cortical actin was studied in surgically resected lung adenocarcinomas tissues and in 3-dimensionally cultured lung adenocarcinoma A549 cells. RESULTS: In normal type II alveolar cells and the bronchiolar epithelium, cortical actin was localized to the apical-side cytoplasm. In invasive adenocarcinoma cells, cortical actin was frequently localized to the matrix side. The degree of cortical actin localized to the matrix side was associated with the loss of basement membrane and a poor prognosis. In A549 cell spheroids cultured in a type I collagen and basement membrane extract Matrigel™ mixed gel, cortical F-actin was localized to the matrix side with phosphorylated myosin light chain. Super-resolution and electron microscopy results suggest that compact wrinkling of the plasma membrane by myosin-mediated F-actin contraction is an explanation for cortical actin accumulation at the matrix side. The myosin II inhibitor blebbistatin suppressed the 3-dimensional collective migration of A549 cells induced by constitutively active Cdc42 and MT1-MMP. CONCLUSION: Cortical actin accumulation at the matrix-side cytoplasm of cancer cells occurs in invasive lung adenocarcinomas and it possibly participates in the migration of cancer cells through myosin-mediated contraction.

Efficacy of Supraglottic Airway for Preventing Lung Injury Associated with Coughing at Extubation after Pulmonary Lobectomy.

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.

Port-site recurrence after complete resection of stage I thymoma by video-assisted thoracoscopic surgery: report of a case.

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.

[Management of Patients with Preexisting Cardiac Complications during Thoracic Surgery for Lung Cancer].

UNLABELLED: In patients with preoperative cardiac complications such as myocardial ischemia, arrhythmia, or congestive heart failure, it is important to offer any necessary medical treatments, such as anticoagulation therapy, prior to surgery. This study investigated the perioperative results of surgical treatment for primary lung cancer in patients with cardiac complications. Data relating to 467 patients who underwent lung resection for lung cancer between April 2010 and March 2014 were collected. Perioperative factors for patients with preoperative cardiac complications and patients without preoperative cardiac complications were compared. Perioperative factors were also compared for a heparin bridging group and non-heparin bridging group in 53 anti-coagulation therapy patients. RESULTS: Fifty-three (11.3%) patients had preoperative cardiac complications;the majority of these had ischemic heart disease( n=31, 58.5%), while a significant minority had atrial fibrillation( n=14, 33.3 %). Of these, 42 patients(79.2%)were receiving anti-coagulation therapy;pre-operative bridging anti-coagulation using heparin was performed in 19 patients(45.2%). There were significant differences between those patients with preoperative cardiac complications, and those without preoperative cardiac complications, in terms of sex( male;81.1% vs 65.7%, p=0.024), mean age(73.1±1.0 year vs 68.4±0.7 year, p=0.001), and duration (days) of hospitalization after surgery(10.1±2.4 vs 7.8±2.0, p=0.023). There were significant differences between patients who received pre-operative heparin bridging anticoagulation, compared with those who did not, in terms of age(70.8±1.2 year vs 76.8±0.9 year, p=0.001)and duration (days) of hospitalization after surgery(10.5±2.1 vs 7.5±1.3, p=0.005). CONCLUSION: Fifty-three(11.3%)patients had preoperative cardiac complications. Recent changes in the demographics of surgical candidates, in terms of age, have increased the number of patients with surgical risk factors. Perioperative patient management has become more important than before.

Usefulness of the Global Leadership Initiative on malnutrition (GLIM) criteria in preoperative nutritional assessment of patients with primary lung cancer.

BACKGROUND AND AIMS: The Global Leadership Initiative on Malnutrition (GLIM) developed a new method for evaluating malnutrition; however, no consensus has been reached regarding the use of these criteria. Therefore, this study aimed to investigate the association between nutritional status assessed using the GLIM criteria and outcomes of lung cancer after surgery. METHODS: Patients with non-small cell lung cancer who underwent lung resection and bioelectrical impedance analysis to estimate muscle mass before surgery were included. Their background, pathological stage, recurrence, and prognosis were investigated. Patients were divided into two groups according to the GLIM criteria: normal nutrition and malnutrition groups. RESULTS: The normal and malnutrition groups comprised 110 and 88 patients, respectively. Malnutrition was significantly associated with poor overall survival after surgery (P = 0.025) but not with disease-free survival. Multivariate analysis showed that malnutrition (hazard ratio [HR]:2.374, P = 0.020), advanced pathological stage of lung cancer (HR: 1.919, P = 0.002), and the presence of postoperative complications (HR: 2.035, P = 0.047) were significantly associated with poor overall survival. CONCLUSION: Malnutrition assessed using the GLIM criteria was associated with the prognosis of patients with postoperative non-small cell lung cancer. Preoperative assessment using the GLIM criteria would allow for effective nutritional and rehabilitative interventions to improve prognosis.

Pulmonary Artery Aneurysm in a Patient with Nontuberculous Mycobacteria Infection.

Nontuberculous mycobacterial (NTM) infection sometimes leads to the development of pulmonary artery aneurysm (PAA), a rare but life-threatening complication. We herein report a 64-year-old woman with a history of NTM infection who presented with severe hemoptysis. Computed tomography revealed a ruptured PAA, which was treated successfully with pulmonary artery embolization. Subsequent right total pneumonectomy was performed to control infection. This case emphasizes the need to consider PAA in patients with NTM infection who present with hemoptysis. Early detection and appropriate management are critical for preventing this fatal complication.

The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.

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.

Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).

[Surgical treatment of oral cancer pulmonary metastases].

We examined the efficacy of surgical resection of oral cancer pulmonary metastases. Between April 2001 and October 2010, 12 patients with pulmonary metastases underwent thoracic operations. There were 8 men and 4 women with a median age of 66.5 years (range, 27~76). All tumors were squamous cell carcinomas and the most common primary site was tongue (7 patients). Overall survival rate after metastasectomy was 50% at 3 years. Overall survival rate at 2 years by lobectomy was greater than by partial resection. For patients with oral cancer pulmonary metastasis, surgical resection is the effective treatment option.

Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma.

Objective: To evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin for malignant pleural mesothelioma (MPM), we investigated the pharmacokinetics of platinum, adverse events after HIOC, and survival outcome. Methods: Fifty-three patients with pathologically diagnosed MPM (cT1-3N0-1M0, excluding sarcomatoid) underwent an extended P/D and HIOC (cisplatin 80 mg/m2 in saline 2 L, 42°C, 60 minutes) since 2011. The protocol includes postoperative 4 cycles of cisplatin and pemetrexed. Platinum concentrations in the perfusate (before and after) and the serum (1, 2, 4, 8, 24, 48, 72 hours after perfusion) were measured in 10 patients. Mortality and morbidity, especially adverse events of renal function, were investigated, and survival and affecting factors were examined. Results: All patients obtained macroscopic complete resection and pathologic staging revealed as follows: T1/2/3/4: 12/8/23/10, N0/1: 36/17, stage 1A/1B-3A/3B: 12/31/10, respectively. Platinum concentrations in the perfusate indicated that 28% of the dose remained in the pleural cavity, and the maximum concentration in the serum was 0.91 µg/mL. Six patients (11%) showed elevated max-creatinine (>2 mg/dL) postoperatively. Two patients (4%) received renal-replacement therapy, and one was weaned before discharge. There was no 30-day mortality and one in-hospital death (1.9%). Forty-six patients (87%) received multiple cycles of perioperative systemic chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 52.4 months and 18.7 months. Patents with stage 1A demonstrated a 5-year OS of 67.3% and a median DFS of 67.1 months, and patients with stage 1B-3A demonstrated a 5-year OS of 50.1% and a median DFS of 20.4 months. Univariate analysis showed histological subtype, p-T, p-stage, and multimodality treatment as significant factors affecting OS. Multivariate analysis revealed histology, p-stage, and multimodality as independent. Conclusions: Extended P/D and HIOC with cisplatin for MPM is acceptable with limited acute kidney injury. This multimodality protocol provides promising favorable survival for stage 1A-3A disease.

Extubation by supraglottic airway after lobectomy prevents cough-associated air leaks and prolonged coughing or sore throat.

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.

The possibility of mutations of RAS signaling genes and/or TP53 in combination as a negative prognostic impact on pathological stage I non-small cell lung cancer.

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.

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.

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.

[Surgery for mediastinal tumor; by video-assisted thoracoscopic thymo-thymomectomy with sternal lifting].

The successful key of video-assisted thoracoscopic surgery (VATS) for mediastinal tumor should be appropriate surgical approach according to the site of tumor and relationship between large vessels and tumor. We retrospectively reviewed VATS for mediastinal tumor for 2 years. Thirty-three patients underwent surgery for mediastinal tumor, 19 patients by VATS;12 thymo-thymomectomies (2 myastenia gravis with thymoma), 4 neurinomas, 3 cystic tumors. Thymoma is the most frequent mediastinal tumor and thymo-thymomectomy for thymoma and extended thymectomy for myasthenia gravis is usually recommended. Thymus is located in the narrow anterior mediastinum between sternum and heart. So that we use sternal lifting devices to get working space for video-assisted thoracoscopic thymo-thymomectomy. Our indication is thymic cyst, thymoma (noninvasive to surrounding organs, without dissemination, diameter less than 6 cm, and tolerable for one-lung ventilation), and myasthenia gravis. Video-assisted thoracoscopic thymo-thymomectomy using sternal lifting was performed for 12 patients among 19 thymic tumor patients and is considered to be a minimally invasive and safe operative procedure for selected thymoma patients.