CD163-positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma.

CD163 is one of the scavenger receptors expressed on macrophages. However, several immunohistochemical studies have demonstrated that CD163 is also detected on cancer cells, and is associated with a poor prognosis. In the present study, we detected CD163 staining on cancer cells in lung adenocarcinoma and squamous cell carcinoma (SCC), and investigated the relationship between CD163 on cancer cells and the clinical prognosis. CD163 staining was seen in 128 of 342 adenocarcinoma cases and 35 of 103 SCC cases. Among the lung adenocarcinoma cases, the progression-free survival and overall survival were significantly shorter in the CD163 high group than the CD163 low group. A similar trend was observed among the SCC cases, but the difference was not statistically significant. Additionally, a higher number of macrophages was detected in areas with CD163-positive cancer cells when compared to areas with CD163-negative cancer cells. In summary, we found that CD163-positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma and SCC.

Infiltration of tumor-associated macrophages is involved in tumor programmed death-ligand 1 expression in early lung adenocarcinoma.

Programmed death-ligand 1 (PD-L1) is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Although tumor cell PD-L1 expression has been shown to be associated with the clinical response to anti-PD-L1 antibodies, its concise regulatory mechanisms remain elusive. In this study, we evaluated the associations of tumor PD-L1 expression and immune cell infiltrating patterns in 146 cases of early lung adenocarcinoma (AC) to investigate the possible extrinsic regulation of tumor PD-L1 by immune cells. Using immunohistochemistry, cell surface PD-L1 expression in tumor cells was observed in 18.5% of stage 0-IA lung AC patients. Tumor PD-L1 positivity was significantly associated with stromal invasion, which was accompanied by increased tumor-associated macrophages (TAM), CD8+ cytotoxic T cells and FoxP3+ regulatory T cells. Among these immune cells, TAM and CD8+ T cells significantly accumulated in PD-L1-positive carcinoma cell areas, which showed a tumor cell nest-infiltrating pattern. Although CD8+ T cells are known to induce tumor PD-L1 expression via interferon-É£ production, the increased TAM within tumors were also associated with tumor cell PD-L1 positivity, independently of CD8+ T cell infiltration. Our in vitro experiments revealed that PD-L1 expression in lung cancer cell lines was significantly upregulated by co-culture with M2-differentiated macrophages; expression of PD-L1 was reduced to baseline levels following treatment with a transforming growth factor-ß inhibitor. These results demonstrated that tumor-infiltrating TAM are extrinsic regulators of tumor PD-L1 expression, indicating that combination therapy targeting both tumor PD-L1 and stromal TAM might be a possible strategy for effective treatment of lung cancer.

[Role of Surgery in Multimodality Treatment for Non-small Cell Lung Cancer;Current Status and Future Perspectives].

Recent improvement of outcomes for resected non-small cell lung cancer (NSCLC) has been contributed not only by increased detection of early-stage disease and improvement of preoperative diagnosis/perioperative management but also by improvement of multimodality treatment. The introduction of newly developed systemic therapies including molecular targeted agents and immune checkpoint inhibitors dramatically changed clinical outcomes of advanced NSCLC. Accordingly, the role of surgery during the multimodality treatment will be changed more than ever. In this article, we overviewed the current status of the multimodality treatment for clinical stageⅢ (N2)disease and postoperative adjuvant therapy and discussed the role of surgery during these situations. We also discussed the future perspectives of the role of surgery during the multimodality treatment for advanced NSCLC.

Multifocal Cholesterol Granulomas of the Thymus: A Case Report of Positron Emission Tomography- Positive Benign Tumor of the Anterior Mediastinum.

Cholesterol granulomas of the thymus are extremely rare benign entities. Herein, we describe a case of cholesterol granuloma in a 45-year-old man who presented with multifocal anterior mediastinal lesions on computed tomography (CT). Positron emission tomography (PET)-CT revealed increased fluorodeoxyglucose uptake, with a maximum standardized uptake value of 8.3. Diffusion-weighted magnetic resonance imaging (MRI) revealed extreme hypointensity. He underwent total thymectomy by median sternotomy for presumed multiple thymoma. On histopathological analysis, cholesterol granuloma of the thymus was confirmed, and the patient had an uneventful postoperative course without recurrence for 28 months. Cholesterol granuloma of the thymus is a PET-CT-positive benign tumor with unique histological findings. The MRI findings were indicative of hypocellularity associated with a benign entity, whereas the PET-CT findings corresponded to granulomatous inflammation. Therefore, concurrent use of PET-CT and MRI can be helpful in distinguishing between benign cholesterol granulomas and malignant anterior mediastinal tumors.

Successful Video-Assisted Thoracoscopic Removal of a Chest Tube Protruding Deep Into the Pulmonary Hilum.

Tube thoracostomy is an invasive procedure frequently used to drain pleural fluid collections or to manage pneumothorax, wherein the lungs commonly sustain trauma. In some cases, deep pulmonary hilar injuries are managed by anatomical lung resections. A deep hilar injury with the chest tube protruding into the lung parenchyma is a rare complication of tube thoracostomy. We report the case of a patient with tube thoracostomy-related deep pulmonary laceration treated using video-assisted thoracic surgery (VATS). A 74-year-old man with a left-sided pneumonia-associated empyema underwent tube thoracostomy for drainage of intrathoracic purulent collection at another hospital; however, chest radiography and computed tomography (CT) revealed intrusion of the 22 Fr chest tube into the left lower lobe parenchyma for approximately 10 cm toward the pulmonary hilum, with the chest tube tip located near the left main bronchus and pulmonary artery. Although no massive intrapulmonary hemorrhage, pneumothorax, or pneumomediastinum was observed, multiple pyothoracic cavities were present. He was transferred to our hospital the following day in a hemodynamically stable condition. The next day, he underwent both surgical chest tube removal and decortication for empyema. Owing to the worsening of his physical condition and due to prolonged severe inflammation and lack of appetite, without any sign of bleeding or chest tube air leak, a two-port VATS with sparing of the lung parenchyma was attempted. After decortication, the penetrating chest tube was slowly removed. No hemorrhage or air leaks were observed at the site of penetration, requiring no sutures or dressing. Following his uneventful postoperative course, he was discharged on day 9. In selected cases, anatomic lung resection can be avoided, even for deep hilar injuries, depending upon the degree of intrapulmonary hemorrhage and the presence of air leak from the chest tube, and the CT scan findings.

Pulmonary metastasis of matrix-producing carcinoma mimicking small cell lung cancer.

Matrix-producing carcinoma (MPC) of the breast is an extremely rare subtype of invasive breast cancer. MPC is characterized by the production of a cartilaginous or osseous matrix without spindle cells. It is an aggressive carcinoma, often presenting as triple-negative breast cancer. MPC frequently metastasizes to the lungs; however, it rarely reoccurs as a solitary pulmonary metastasis. We report a case of a 77-year-old non-smoking woman with a solitary pulmonary metastasis of MPC, which mimicked small cell lung cancer (SCLC). Initially, the pulmonary metastasis was misdiagnosed as SCLC based on its morphological and immunochemical features, including focal positivity for CD56 and thyroid transcription factor-1. Although the portion of the chondromyxoid matrix of the primary site was not small, that of the metastatic site was small. A focal cartilaginous matrix deposition of pulmonary metastasis from MPC could make it difficult to differentiate from SCLC. We should acknowledge that the portion of chondromyxoid matrix may differ between primary and distant metastatic sites in MPC.

Thymoma exhibiting spontaneous regression with developing myasthenia gravis: A case report.

Spontaneous regression (SR) of thymoma is rare. A 44-year-old man with right chest pain underwent computed tomography (CT), which showed an 11.0 cm mass in the anterior mediastinum and right pleural effusion. He refused surgery and was sent home without medication and additional treatment. One year later, the mass had regressed to 5.5 cm, and the right pleural effusion had disappeared. He was then lost to follow-up. Four years after the initial visit, he presented with diplopia and fatigue. A significant increase in his anti-acetylcholine receptor antibody levels led to myasthenia gravis (MG) diagnosis. CT revealed a regressed mediastinal mass (3.0 cm). After extended thymectomy, histologic analysis confirmed a thymoma type B2, Masaoka stage IIa. The SR was due to intratumoral infarction. This report is the first to describe MG developing during SR. Anterior mediastinal tumors undergoing SR should be differentiated from thymomas and MG perioperative development should be considered.

Lymphatic permeation and vascular invasion should not be integrated as lymphovascular invasion in lung adenocarcinoma.

OBJECTIVE: Lymphatic permeation (LY) and vascular invasion (VI) are well-known as postoperative prognostic factors in non-small cell lung cancer (NSCLC). Some reports use the term "lymphovascular invasion (LVI)" in reference to the integration of LY and VI. The purpose in this study is to elucidate whether NSCLC with LY or VI can be labeled as LVI-positive NSCLC or it should be treated as an LY- or VI-positive tumor, respectively. METHODS: We reviewed 601 completely resected lung adenocarcinomas and squamous cell carcinomas, and examined the respective prognostic and biological significance of LY and VI. RESULTS: Among 454 adenocarcinomas, multivariate survival analyses showed that LY and VI were unfavorable prognostic factors in stages II and III and stages I and II, respectively. Conversely, this relationship was not found among 147 squamous cell carcinomas. Patients with adenocarcinomas with LY and VI had a significantly worse prognosis than those with adenocarcinomas with LY or VI in stage II, but not in stage I. Among 149 recurrent adenocarcinomas, only VI had a strong effect on early recurrence and shorter post-recurrence survival. LY and VI were predictors for multiple organ recurrence of adenocarcinoma. The recurrence of adenocarcinoma with LY was high in the ipsilateral mediastinal lymph nodes, whereas VI was significantly correlated with distant metastasis to organs, such as the brain, liver, and adrenal gland. CONCLUSIONS: LY and VI have differing effects postoperative prognosis and recurrence-relevant events, suggesting that these pathological findings should not be integrated as LVI.

Feasibility of intraoperative diagnosis of lung adenocarcinoma in situ to avoid excessive resection.

BACKGROUND: Limited lung resection is generally believed to be available for lung adenocarcinoma in situ (AIS). At our institute, intraoperative hematoxylin-eosin staining of frozen-section slides is routinely performed for evaluating tumor invasiveness after partial resection to avoid excessive lung resection. This study aimed to evaluate the feasibility and usefulness of intraoperative frozen-section diagnosis of AIS. METHODS: We retrospectively reviewed 143 patients with 151 AISs diagnosed by intraoperative frozen sections between 2012 and 2019 at our institute. All patients underwent limited resection because of the result of intraoperative frozen-section diagnosis. RESULTS: The total concordance rate between the diagnoses of AIS by intraoperative frozen sections and postoperative paraffin-embedded sections was 82.7% for 151 nodules. Although 21 minimally invasive adenocarcinomas (MIA) and 5 invasive adenocarcinomas were diagnosed as AIS intraoperatively, no patient had tumor recurrence after resection. Among 125 pathologically proven cases of AIS postoperatively, there were 67 (53.6%) radiologically invasive tumors including ground-glass nodules (GGNs) with part-solid component or pure-solid nodules. CONCLUSIONS: This intraoperative evaluation of frozen-section slides will help surgeons avoid excessive lung resection for AIS that was radiologically diagnosed as invasive adenocarcinoma. Intraoperative frozen-section diagnosis will provide to be clinically useful and lead to less invasive surgical treatment for lung nodules.

Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer.

Even after complete resection, non-small cell lung cancer (NSCLC) shows preferential recurrence in the mediastinal lymph nodes, lungs, brain, bone, liver, and adrenal gland. However, the relationship between clinicopathological factors and recurrence patterns after resection has not been well-evaluated. Among 688 NSCLC cases with complete resection between 2004 and 2016, 233 cases recurred at our institute. On multivariate analyses, NSCLCs with lymph node metastasis and pulmonary metastasis at surgery commonly recurred in the mediastinal lymph nodes and lungs, respectively. Young age, adenocarcinoma, and vascular invasion were correlated with brain metastasis. Although no variable was associated with bone metastasis, vascular invasion was correlated with postoperative liver and adrenal gland metastasis. Pathologically proven stage II or III NSCLC, adenocarcinoma, and the presence of lymphatic permeation would result in multiple metastases. Vascular invasion, larger invasive size, and advanced stage were independent risk factors of early recurrence. Considering survival, vascular invasion, elderly age, and non-adenocarcinoma were unfavorable prognostic factors after recurrence. Some clinicopathological variables were correlated with organ-specific metastasis and post-recurrence survival. Particularly, vascular invasion was a biomarker of brain, liver, and adrenal gland metastases and a prognostic marker after recurrence among completely resected NSCLC. This information is useful for more frequent patient follow-up and identifying organ-specific distant metastasis.

How long is cessation of preoperative smoking required to improve postoperative survival of patients with pathological stage I non-small cell lung cancer?

BACKGROUND: Smoking can cause non-small cell lung cancer (NSCLC). However, the effects of preoperative smoking on tumor progression are not well-known. In addition, the duration of smoking cessation that can provide NSCLC patients with smoking history similar postoperative prognosis as that of nonsmokers remains unknown. This study aimed to investigate the period of smoking cessation that may "compensate" for past smoking history regarding postoperative survival in cases of resected pathological stage I NSCLC by examining the relationship between clinicopathological factors and preoperative smoking. METHODS: We retrospectively examined clinicopathological factors including preoperative smoking status and postoperative survival in 453 patients with pathologically proven stage I NSCLC at our Institute. Smoking status was evaluated using the following four parameters: cigarettes per day, number of years of smoking, pack-years, and number of years since smoking cessation. RESULTS: Pathological factors that reflect tumor invasiveness including vascular invasion (VI) and pleural invasion (PL) were associated with the degree of preoperative smoking in adenocarcinomas, particularly invasive diameters of 2-3 cm. Such a relationship was not identified for non-adenocarcinomas. Heavy smoking status was significantly related to PL in lepidic or papillary predominant adenocarcinomas and to VI in acinar or solid predominant adenocarcinomas. Former smokers who quit smoking for ≥10 years had similar postoperative survival as non-smokers for adenocarcinoma ≤3 cm. CONCLUSIONS: Accumulative smoking habit correlated with VI and PL, particularly in 2-3 cm adenocarcinoma, whereas larger adenocarcinomas and non-adenocarcinomas of any size appear to grow and become invasive independent of preoperative smoking status. Longer smoking cessation ≥10 years can result in postoperative survival similar to that of non-smokers with adenocarcinomas ≤3 cm. Current smokers should quit smoking immediately to ensure longer survival even though they suffer from small-sized lung adenocarcinomas in the future.

Thoracoscopic enucleation for intrapulmonary lipoma: case report.

A 67-year-old woman with a history of uterine body cancer was admitted because of a nodular shadow in the right lower lobe on chest computed tomography. We planned thoracoscopic resection for diagnosis. Thoracoscopically, the tumor was seen through the visceral pleura as a round yellow nodule close to the inferior pulmonary vein, and it was soft on palpation with surgical forceps, which was consistent with intrapulmonary lipoma. We therefore performed thoracoscopic enucleation. Histological examination confirmed an intrapulmonary lipoma. We report the first case of intrapulmonary lipoma which was enucleated thoracoscopically.

Nonlinear acoustic response through minute surface cracks: FEM simulation and experimentation.

The second harmonic of a Rayleigh wave passing through a minute surface crack has been numerically analyzed by semi-explicit FEM including special elements which account for a nonlinear stress-strain relation at crack surfaces. Minute cracks perpendicular to a free, flat surface close under compressive stress when width of the crack opening is less than the longitudinal amplitude of the Rayleigh wave. Thereafter, compressive and shear stresses are partially transmitted through the closed cracks, whereas tensile and shear stresses are not transmitted through cracks that remain open. This leads to marked nonlinear ultrasonic response. Calculation was performed for an aluminum block having a surface crack. The transverse component of the Rayleigh wave propagating through the cracks shows distorted waveforms, making the second harmonic amplitude clearly noticeable. In an experiment, the second harmonic component of the leaky Rayleigh wave was detected for a simple crack model consisting of two aluminum blocks, by use of a PVDF line-focused transducer. The results of the experiment show that the second harmonic amplitude is a second-order function of the fundamental wave amplitude, and is more pronounced for low compressive stress applied to close the crack surfaces.