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The size of the solid part of a tumor, as measured using thin-section computed tomography, can help predict disease prognosis in patients with early-stage lung cancer. Although three-dimensional volumetric analysis may be more useful than two-dimensional evaluation, measuring the solid part of some lesions is difficult using this methods. We developed an artificial intelligence-based analysis software that can distinguish the solid and non-solid parts (ground-grass opacity). This software calculates the solid part volume in a totally automated and reproducible manner. The predictive performance of the artificial intelligence software was evaluated in terms of survival or recurrence-free survival.We analyzed the high-resolution computed tomography images of the primary lesion in 772 consecutive patients with clinical stage 0-I adenocarcinoma. We performed automated measurement of the solid part volume using an artificial intelligence-based algorithm in collaboration with FUJIFILM Corporation. The solid part size, the solid part volume based on traditional three-dimensional volumetric analysis, and the solid part volume based on artificial intelligence were compared.Higher areas under the curve related to the solid part volume were provided by the artificial intelligence-based method (0.752) than by the solid part size (0.722) and traditional three-dimensional volumetric analysis-based method (0.723). Multivariate analysis demonstrated that the solid part volume based on artificial intelligence was independently correlated with overall survival (P = 0.019) and recurrence-free survival (P 0.001).The solid part volume measured by artificial intelligence was superior to conventional methods in predicting the prognosis of clinical stage 0-I adenocarcinoma.

The growth pattern of peripheral squamous cell carcinoma (SCC) of the lung is divided into two types: alveolar space-filling (ASF) growth and alveolar space-destructive (ASD) growth. The aim of this study was to investigate the clinicopathological differences between cancer cells displaying ASF and ASD growth. We analyzed 155 patients with peripheral SCC measuring 30 mm or less in diameter. The proportion of ASF in the total tumor area (%ASF) was determined using digital image analysis. We examined the clinicopathological characteristics of the cancer cells and compared the immunophenotypes of high %ASF tumors (> 30%) and low %ASF tumors (0%). Finally, we analyzed the prognostic impact of ASD area with small SCC cases (≤ 2.0 cm, n = 72). Cases of high %ASF tumors showed significantly lower frequencies of lymphovascular invasion (p = 0.008). Immunohistochemical staining revealed that the expression score of laminin-5, invasive-related molecule, in cancer cells was significantly lower in high %ASF cases than in low %ASF cases (p = 0.001). Within the same tumor, laminin-5 expression in the ASF area was significantly lower than that in the ASD area (p = 0.001). The overall 5-year survival rate of patients with a larger ASD area (> 1.0 cm2) was significantly lower than that of patients with a smaller ASD area (≤ 1.0 cm2) (p = 0.017). In this study, we clearly showed that cancer cells presenting with ASF represents a “less invasive phenotype” in peripheral SCC.

Cancer cells can invade the surrounding stroma with the aid of fibroblasts (fibroblasts-dependent invasion). The aim of this study was to explore the spatiotemporal characteristics of fibroblast-dependent invasion of cancer cells. We performed an in vitro three-dimensional collagen invasion assay using Fluorescent Ubiquitination-based Cell Cycle indicator (Fucci)-labeled A431 carcinoma cells co-cultured with fibroblasts. We used time-lapse imaging to analyze the total cell number, frequencies of small cancer cell nests and S/G2/M phase of A431 cells in the invasion area. We compared the frequencies of small cancer cell nests and geminin (+) cancer cells within fibroblast-rich areas and fibroblast-poor areas in surgically resected human invasive squamous cell carcinoma tissue. The total invasion number of A431 cells was significantly higher when cultured with fibroblasts than without. The formation of small cancer cell nests was observed within the invasion area only in the presence of fibroblasts. The frequency of S/G2/M phase cells was significantly higher in A431 cells when cultured with fibroblasts than without. Immunohistochemical analysis of surgically resected human invasive squamous cell carcinoma tissue revealed that the frequencies of small cancer cell nests and geminin-positive cancer cells were significantly higher in fibroblast-rich areas compared to those in fibroblast-poor areas within the same tumor region. Our current study clearly showed that fibroblast-dependent cancer cell invasion was characterized by the progression in cell cycle and formation of small cancer cell nests.

OBJECTIVES Patients with lung cancer and interstitial lung disease (ILD), usual interstitial pneumonia in particular, are known to have a poor outcome. The aim of this study was to evaluate the prognostic impact of ILD in patients with non-small-cell lung cancer. METHODS A total of 2054 consecutive patients underwent complete resection of Stage IA-IIIA non-small-cell lung cancer in our institution between January 2002 and March 2013. The presence of ILD was diagnosed and categorized based on high-resolution computed tomography images. Multivariate analysis was performed to identify the prognostic factors. RESULTS There were 106 (5%) patients with ILD. There were significantly more patients who developed severe complications (P

Objectives Since survival after postoperative non-small-cell lung cancer (NSCLC) recurrence is extremely poor, the long-term post-recurrence outcomes are not well understood. The purpose of this study was to evaluate the long-term post-recurrence outcomes and clarify who are possibly 'cured' in recent clinical practice. Methods We reviewed the medical records of 635 patients who developed postoperative recurrence until 2012 after R0 resection for pathological Stage IA-IIIA NSCLC between 1993 and 2006. Factors associated with post-recurrence survival (PRS) and the characteristics of the long-term (≥5 years) survivors were analysed retrospectively. Results The 5-year PRS rate of all 635 patients was 13%. Multivariable analysis revealed that female [hazard ratio (HR) = 0.78], adenocarcinoma (HR = 0.77), locoregional (only) recurrence (HR = 0.59) and longer recurrence-free survival (HR = 0.99) were favourably associated with PRS. A total of 51 patients achieved 5-year PRS; however, 32 (63%) were cancer-bearing patients in their fifth post-recurrent year who were mainly treated by epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Subsequent PRS curves for cancer-controlled and cancer-bearing groups were different (8-year PRS: 94% vs 31%, P = 0.003). Among 19 cancer-controlled patients in their fifth post-recurrent year, 17 (89%) patients initially received radical local therapy for their recurrence. Conclusions Two-thirds of 5-year survivors after postoperative NSCLC recurrence had a cancer-bearing status and showed deteriorated subsequent survival. Curability of postoperative NSCLC recurrence should be evaluated in terms of the 'cancer-controlled' status, and 'cured' population is included in the patients who are 'cancer controlled' at the fifth post-recurrent year.

Introduction: Meningioma is mostly a benign tumor, but sometimes it is malignant, and there have been reports of distant metastases. Patient concerns: The patient, a woman in her 40s, was under follow-up after resection of an ectopic malignant meningioma originating in the left axilla. She was referred to our department because of a nodule shadow in the right lung on chest computed tomography (CT) 3 years and 5 months postoperatively. Diagnosis: Chest CT showed a 1.0 cm nodule shadow in the right S4, which was positive on positron emission tomography-CT; no abnormality was found in any other organ. Therefore, it was considered to be a metastatic lung tumor. Interventions: Right middle lobe partial resection was performed using thoracoscopic surgery, and a diagnosis of pulmonary metastasis of ectopic malignant meningioma was made by histopathology and immunohistochemistry. Outcomes: In this case, complete resection was possible. Conclusion: Meningioma occurs mainly in the cranium, and occurrence in the soft tissue of the extremities is extremely rare. To our knowledge, ours is the first report of a histologically malignant ectopic meningioma with metastasis to the thoracic cavity.

The hydrogenase reaction in Hydrogenobacter thermophilus strain TK-6, an obligately autotrophic, thermophilic, aerobic hydrogen-oxidizing bacterium, was studied in the membrane fraction, methionaquinone-depleted membrane, and purified membrane-bound hydrogenase. Both b and c type cytochromes were involved in the hydrogen oxidation. Methionaquinone mediated an electron transport between membrane-bound hydrogenase and cytochrome b560. Methionaquinone was reduced directly by purified hydrogenase. From these results, we conclude that methionaquinone is a direct natural electron acceptor for the membrane-bound hydrogenase in the strain.