Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer associated with poor prognosis and resistance to conventional chemotherapy. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, were found to have clinical benefits in PSC in recent studies. Nevertheless, because these studies included a small number of patients owing to disease rarity, larger studies are needed to evaluate the effectiveness and safety of ICI-based therapy for PSC. Methods: This multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan. Results: A total of 124 patients were evaluated. The overall response rate, median progression-free survival (PFS), and median overall survival (OS) were 59.0%, 10.5 months, and 32.8 months, respectively. The PFS and OS rates at 24 months were 35.3% and 51.5%, respectively. Programmed death-ligand 1 expression, concomitant chemotherapy, and the treatment line were not significantly associated with PFS or OS. Immune-related adverse events (irAEs) were observed in 70 patients (56.5%), including 30 (24.2%) with grade 3 to 5 events. Patients with mild irAEs (grades 1-2) had longer PFS and OS than did those with severe (grades 3-5) or no irAEs. In a multivariate analysis, any-grade irAEs and the absence of liver metastases were independently associated with PFS, whereas any-grade irAEs and Eastern Cooperative Oncology Group performance status less than or equal to 1 were independently associated with OS. Conclusions: ICI-based therapy was found to have promising effectiveness in patients with advanced or metastatic PSC, regardless of programmed death-ligand 1 expression, concomitant chemotherapy, or treatment line.

Acute exacerbation of idiopathic pulmonary fibrosis model by small amount of lipopolysaccharide in rats.

Idiopathic pulmonary fibrosis, a chronic and progressive lung disease with poor prognosis, presents with acute exacerbation. Pathophysiology and treatments for this acute exacerbation, and an appropriate animal model to perform such examinations, have not established yet. We presented a rat model for assessing acute exacerbation in cases of idiopathic pulmonary fibrosis. Wistar rats were intratracheally administered bleomycin (3 mg/kg) to induce pulmonary fibrosis. After 7 days, lipopolysaccharide (0, 0.05, or 0.15 mg/kg) was administered. In the bleomycin or lipopolysaccharide group, there were almost no change in the oxygen partial pressure, arterial blood gas (PaO2), plasma nitrite/nitrate, nitric oxide synthase, and lung nitrotyrosine levels. In the bleomycin (+)/lipopolysaccharide (+) groups, these three indicators deteriorated significantly. The plasma nitrite/nitrate and PaO2 levels were significantly correlated in the bleomycin (+) groups (r = 0.758). Although lung fibrosis was not different with or without lipopolysaccharide in the bleomycin (+) groups, macrophage infiltration was marked in the bleomycin (+)/lipopolysaccharide (+) group. There were many NOS2-positive macrophages, and the PaO2 levels decrease may be induced by the nitric oxide production of macrophages in the lung. This model may mimic the pathophysiological changes in cases of acute exacerbation during idiopathic pulmonary fibrosis in humans.

Pulmonary Resection for Lung Cancer Following Transcatheter Aortic Valve Implantation for Severe Aortic Valve Stenosis: A Case Report.

An 82-year-old woman was referred to our hospital because of dyspnea on effort. Echocardiography revealed severe aortic valve stenosis (AS). Simultaneously, chest computed tomography (CT) revealed a 19-mm nodule in the lower lobe of the right lung, and bronchoscopic biopsy revealed adenocarcinoma. She underwent transcatheter aortic valve implantation (TAVI) for severe AS. Three weeks later, she underwent lower lobectomy of the right lung and mediastinal dissection for the lung cancer. Her postoperative course was good, and she was discharged 8 days postoperatively. In conclusion, we encountered a patient who successfully underwent pulmonary resection for lung cancer following TAVI for severe AS. We suggest that pulmonary resection following TAVI is an acceptable choice for lung cancer in patients with severe AS because of the lack of a need for cardiopulmonary bypass, the high safety and efficacy of two-stage therapy, and the short period between the two therapies.

Right-sided Bochdalek hernia containing retroperitoneal fat in the elderly: report of a case.

BACKGROUND: Most cases of Bochdalek hernias are diagnosed during the neonatal period and arise on the left side. We report a rare case of a right-sided Bochdalek hernia in an elderly patient. CASE PRESENTATION: A 72-year-old man presented with chest tightness and nausea. He had no history of thoracic and abdominal trauma. Preoperative CT scan showed a well-circumscribed mass in the right thoracic cavity of 28-cm diameter compressing the right lower lobe. The mass was mostly fat component and seemed to connect with retroperitoneal fat. We made some diagnoses: lipoma, liposarcoma, and diaphragmatic hernia. Surgical resection was performed by thoracotomy so as to resect the mass and repair the defect of the diaphragm. The mass seemed to be retroperitoneal fat which escaped from the hernia orifice. The neck of the mass was separated by a vessel-sealing device immediately above the hernia orifice. The defect of the diaphragm was repaired by direct suturing after completion of resection. Microscopic pathologic examination showed that the mass was maturated fat tissue. Four months postoperatively, there was no evidence of recurrence of the hernia. CONCLUSIONS: The diagnosis of an adult Bochdalek hernia is often difficult, so it is important to consider the examination carefully and to determine the better surgical procedure.

Correction to: Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage IIIA (N2-positive) non-small cell lung cancer patients.

In the original publication of the article, the title was incorrectly published as "Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage.

Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage IIIA (N2-positive) non-small cell lung cancer patients.

OBJECTIVE: Surgical indication in stage IIIA (N2) non-small cell lung cancer is still controversial. Hence, there is a need for the identification of predictors of the postoperative outcome in these patients. Although sarcopenia is expected to be a novel predictor of postoperative outcome in these patients, the underlying clinical features of sarcopenia have not been well investigated. Elevation of neutrophil/lymphocyte ratio indicates cancer-associated inflammation and depression of anticancer immunity. We analyzed the influence of sarcopenia on postoperative prognosis, and investigated the relationship between sarcopenia and neutrophil/lymphocyte ratio in patients with stage IIIA (N2) non-small cell lung cancer. METHODS: We retrospectively investigated 69 patients with stage IIIA (N2) non-small cell lung cancer. We used the L3 muscle index as a clinical measurement of sarcopenia, and divided patients into the sarcopenic (n = 21) and the non-sarcopenic group (n = 48). We then investigated the effect of sarcopenia on postoperative prognosis, and evaluated the correlation between sarcopenia and neutrophil/lymphocyte ratio. RESULTS: This study included 47 males and 22 females. Univariate analysis revealed that sarcopenia, performance status, and serum cytokeratin-19 fragment level were predictors of poor prognosis; multivariate analysis revealed that performance status and sarcopenia were independent predictors of poor prognosis. The presence of sarcopenia was significantly correlated with neutrophil/lymphocyte ratio elevation. CONCLUSIONS: Sarcopenia is a novel predictor of poor prognosis in patients with stage IIIA (N2) non-small cell lung cancer. Neutrophil/lymphocyte ratio elevation might be the reason for poor prognosis in sarcopenic patients.

Pirfenidone suppresses polarization to M2 phenotype macrophages and the fibrogenic activity of rat lung fibroblasts.

Pirfenidone is a representative medication to treat interstitial pulmonary fibrosis. Researchers reported pirfenidone (>100 µg/ml) significantly suppressed fibroblast growth in vitro. However, clinically, the maximum concentration of pirfenidone in the blood is approximately 10 µg/ml. We hypothesized there might be an additional mechanism of pirfenidone to fibroblasts indirectly. Macrophages are known to control the activation of fibroblasts via the regulation of inflammatory M1 and suppressive M2 polarization. The aim of this study was to investigate the effects of pirfenidone on alveolar macrophage polarization. Rat alveolar macrophages (NR8383) were stimulated in vitro with lipopolysaccharide (LPS) + interferon (IFN)-γ, or interleukin (IL)-4 + IL-13. Expression of M1 and M2 markers and supernatant's levels of TGF-ß1 were assessed after pirfenidone treatment (0-100 µg/ml). Treatment with LPS + INF-γ or IL-4 + IL-13 significantly increased the expression of M1 and M2 markers, respectively. In macrophage polarization assays, pirfenidone significantly reduced the expression of M2 markers at concentrations greater than 10 µg/ml but had no effect on the expression of M1 markers. At these concentrations, pirfenidone significantly reduced TGF-ß1 levels in NR8383 culture supernatants. In rat lung fibroblasts treated with NR8383 culture supernatants, pirfenidone significantly suppressed proliferation, and the collagen mRNA and protein levels. In conclusion, our results demonstrated that pirfenidone suppressed polarization to M2 macrophages at clinically relevant concentrations and suppressed the rat lung fibroblasts fibrogenic activity.

Loss of Muscle Mass is a Novel Predictor of Postoperative Early Recurrence in N2-Positive Non-Small-Cell Lung Cancer.

BACKGROUND: We often experienced early recurrence in patients with completely resected N2-positive non-small-cell lung cancer (NSCLC). Loss of muscle mass is a poor prognostic factor in patients with several stages of NSCLC. This study aimed to investigate the relationship between preoperative loss of muscle mass and postoperative early recurrence in patients with N2-positive NSCLC. METHODS: We retrospectively analyzed 47 male patients with completely resected pathological N2-positive NSCLC. Early recurrence was defined as that diagnosed within 1 year after the operation. We used the L3 muscle index (cross-sectional area of muscle at the L3 level, normalized for height) as a clinical measurement of loss of muscle mass (cutoff value, 52.4 cm2/m2). RESULTS: In all, 18 patients with early recurrence had significantly poorer outcomes compared with those without (P <0.01). In univariate analysis, loss of muscle mass (P = 0.023), carcinoembryonic antigen (CEA) level >5.0 ng/mL (P = 0.002), and absence of postoperative chemotherapy (P = 0.042) were predictors of postoperative early recurrence. In multivariate analysis, loss of muscle mass (P = 0.004) and CEA level >5.0 ng/mL (P = 0.001) were independent predictors. CONCLUSIONS: Loss of muscle mass is an independent predictor of postoperative early recurrence in pathological N2-positive NSCLC patients.

Impact of multiple malignancies on surgical outcomes in patients with 1 cm or smaller non-small cell lung cancer.

BACKGROUND: Because most patients with small-sized non-small cell lung cancer (NSCLC) are asymptomatic, their lesions are detected by cancer screenings or routine checkups for other diseases. Incidences of multiple malignancies have been reported to be 27% in patients with stage I-III NSCLC. Some patients have treatment histories for other malignancies, and their small-sized NSCLC was incidentally detected during follow-up. There is no established report regarding the influence of multiple malignancies on small-sized NSCLC prognosis. Therefore, we investigated the correlation between multiple malignancies and surgical outcomes in patients with small-sized NSCLC. METHODS: In total, 44 patients underwent definitive pulmonary resection for NSCLC of 1 cm or smaller between January 2003 and December 2012. Tumor size was measured by macroscopic findings of the resected specimens, and we then retrospectively investigated their clinical courses. RESULTS: One patient had hemoptysis symptoms, whereas 43 patients were asymptomatic; among them, NSCLC was detected by examinations for other diseases in 31 patients and by cancer screening in 12 patients. In total, 20 patients (45%) had multiple malignancies. The median follow-up period was 68 months. One patient had a recurrence from current NSCLC. No patients died of current NSCLC. The overall 5-year survival rate was 90% for all patients. Patients with multiple malignancies had significantly poorer prognoses compared with those without multiple malignancies (P = 0.016). However, patients with treatment intervals of more than 5 years had prognoses equivalent to those of patients without multiple malignancies (P = 0.829). Only the presence of multiple malignancies was a significantly poor prognostic factor in univariate and multivariate analyses. CONCLUSION: NSCLC of 1 cm or smaller showed good prognoses. The presence of multiple malignancies was a significantly poor prognostic factor, and short treatment intervals also correlated with poor prognosis.

Platelet-to-lymphocyte ratio predicts the prognosis of patients with non-small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy.

BACKGROUND: Markers of preoperative tumor immunity, such as platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors for patients with various cancers. However, the relationship between PLR and the prognosis of non-small cell lung cancer (NSCLC) patients treated with surgery and adjuvant chemotherapy as a multidisciplinary treatment is unknown. METHODS: We enrolled 327 NSCLC patients treated surgically with or without adjuvant chemotherapy (78 and 249 patients, respectively) at our hospital from 2008 to 2012. Patients had no preoperative hematological disease or infection. Preoperative PLR and clinicopathologic characteristics were recorded and their potential associations and prognostic values were assessed by Kaplan-Meier and multivariate Cox regression. The optimal cut-off value for high and low PLR was calculated from receiver operating characteristic curves. RESULTS: The five-year overall survival rates for patients with low and high PLR were 78% and 57% (P < 0.01) for all patients, and 69% and 37% (P < 0.01) for patients who received adjuvant chemotherapy, respectively. Similarly, the five-year disease-free survival rates for patients with low and high PLR were 66% and 62% (P = 0.03) for all patients, and 47% and 14% (P < 0.01) for patients who received adjuvant chemotherapy, respectively. Cox proportional hazard regression indicated that high PLR was an independent prognostic factor for both overall and disease-free survival in the adjuvant chemotherapy group. CONCLUSION: Elevated PLR predicts poor prognosis in surgically treated NSCLC patients, especially those who receive adjuvant chemotherapy.

Elevation of Serum Carcinoembryonic Antigen Concentration Caused by Everolimus-Induced Lung Injury: A Case Report.

A 66-year-old woman underwent right nephrectomy for treatment of renal cell carcinoma (RCC). Two years later, she underwent wedge resection of the right lung for treatment of metastatic RCC and primary adenocarcinoma of the lung. She began oral sorafenib for the remaining nodules of the left lung, which were suspected to be metastatic RCC. Two years later, the sorafenib was changed to everolimus because of slight enlargement of the left pulmonary nodules. The carcinoembryonic antigen (CEA) concentration then increased to 25.7 ng/mL, and chest computed tomography (CT) revealed ground-glass opacities (GGO) in the bilateral lungs. Everolimus-induced lung injury was suspected, and she discontinued the everolimus. Two months later, the serum CEA concentration decreased to almost within the reference range at 5.9 ng/mL, and the GGO disappeared on chest CT. In conclusion, we encountered a patient who developed an elevated serum CEA concentration caused by everolimus-induced lung injury.

Carbon monoxide-releasing molecule, CORM-3, modulates alveolar macrophage M1/M2 phenotype in vitro.

Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess the modulation of M1/M2 phenotype in alveolar macrophages by water-soluble carbon monoxide-releasing molecule-3 (CORM-3). Rat alveolar macrophages (AM) (NR8383) in culture were stimulated with LPS (5 ng/ml)/IFN-γ (10 U/ml) or IL-4 (10 ng/ml)/IL-13 (10 ng/ml) to induce M1 and M2 phenotypes, respectively. Expression of M1 phenotype markers, iNOS and TNF-α, and M2 phenotype markers, CD206 and Ym-1, was assessed by western blotting after 1, 3, 6, or 24 h in the absence or presence of CORM-3 (0.15 mM) treatment. Inactive CORM-3 (iCORM-3) was used as a control. Treatment of naïve (unstimulated) AM with CORM-3 promoted progression of the M2 phenotype as evidenced by the increased expression of CD206 (at 1 h; 1.8-fold) and Ym-1 (at 3 h; 1.9-fold), respectively. Surprisingly, CORM-3 treatment also upregulated the expression of iNOS protein as assessed 6 h following stimulation of AM with CORM-3 (2.6-fold). On the contrary, CORM-3 effectively reduced LPS/IFN-γ-induced expression of iNOS protein (0.6-fold); however, it had no effect on TNF-α expression. Finally, CORM-3 acutely (1-3 h) upregulated CD206 (1.4-fold) and Ym-1 (1.6-fold) levels in IL-4-/IL-13-treated (M2-stimulus) macrophages. These findings indicate that CORM-3 modulates macrophage M1 and M2 phenotypes in vitro with respect to continuous suppression of iNOS expression in M1-polarized macrophages and transient (early-phase) upregulation of CD206 and Ym-1 proteins in M2-polarized macrophages.

Solitary splenic metastasis from lung adenocarcinoma: A case report.

Solitary splenic metastasis is extremely rare, with only 27 reported cases in the literature. An 81-year-old woman was referred to our hospital for treatment of pulmonary and splenic lesions. Chest computed tomography showed a small lung nodule in the right upper lobe, abdominal computed tomography showed an 8 cm splenic mass with abnormal accumulation, and positron emission tomography revealed a maximum standardized uptake value of 7.9. She had elevated serum cancer antigen 19-9 (1847 U/mL) and carcinoembryonic antigen concentrations (17.9 ng/mL). She underwent laparoscopic splenectomy. Pathological examination revealed poorly differentiated adenocarcinoma. We performed partial lung resection and diagnosed the small lung lesion as lung adenocarcinoma. Both lesions were positive for thyroid transcription factor 1. Thus, primary lung adenocarcinoma and solitary splenic metastasis were diagnosed. The patient was still alive without recurrence four years postoperatively. Herein, we report a rare case of lung adenocarcinoma with solitary splenic metastasis and review the literature.

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine.

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 µg/mg and 28.2 ± 2.1 µg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats' lungs, SAC also attenuated the increased expression of transforming growth factor-ß1 (TGF-ß1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-ß1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis.

Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

OBJECTIVES: Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. METHODS: We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. RESULTS: Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. CONCLUSION: Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease.

Huge mediastinal liposarcoma resected by clamshell thoracotomy: a case report.

BACKGROUND: Liposarcoma is the single most common soft tissue sarcoma. Because mediastinal liposarcomas often grow rapidly and frequently recur locally despite adjuvant chemotherapy and radiotherapy, they require complete excision. Therefore, the feasibility of achieving complete surgical excision must be carefully considered. We here report a case of a huge mediastinal liposarcoma resected via clamshell thoracotomy. CASE PRESENTATION: A 64-year-old man presented with dyspnea on effort. Cardiomegaly had been diagnosed 6 years previously, but had been left untreated. A computed tomography scan showed a huge (36 cm diameter) anterior mediastinal tumor expanding into the pleural cavities bilaterally. The tumor comprised mostly fatty tissue but contained two solid areas. Echo-guided needle biopsies were performed and a diagnosis of an atypical lipomatous tumor was established by pathological examination of the biopsy samples. Surgical resection was performed via a clamshell incision, enabling en bloc resection of this huge tumor. Although there was no invasion of surrounding organs, the left brachiocephalic vein was resected because it was circumferentially surrounded by tumor and could not be preserved. The tumor weighed 3500 g. Pathologic examination of the resected tumor resulted in a diagnosis of a biphasic tumor comprising dedifferentiated liposarcoma and non-adipocytic sarcoma with necrotic areas. The patient remains free of recurrent tumor 20 months postoperatively. CONCLUSIONS: Clamshell incision provides an excellent surgical field and can be performed safely in patients with huge mediastinal liposarcomas.

Prognostic value of the frequency of vascular invasion in stage I non-small cell lung cancer.

OBJECTIVES: There is no standard pathological method for determining vessel invasion in lung cancer. Herein, we examine whether vessel invasion can be accurately assessed using hematoxylin-eosin staining alone, and investigate the prognostic impact of the presence and frequency of vessel invasion in lung cancer. METHODS: Vessel invasion was assessed by hematoxylin-eosin, Victoria blue, and D2-40 in 251 completely resected stage I non-small cell lung cancer patients. Vessel invasion was classified into 3 grades according to the number of invaded vessels. RESULTS: Using hematoxylin-eosin and Victoria blue, vascular invasion was detected in 27 (10.8 %) and 75 (29.9 %) of patients, respectively. Lymphatic permeation was detected in 126 (50.2 %) and 70 (27.9 %) of patients using hematoxylin-eosin and D2-40 staining. Hematoxylin-eosin staining did not accurately detect a high frequency of vessel invasion; only 5 and 21.7 % of high-frequency vascular invasion and lymphatic permeation cases diagnosed with Victoria blue and D2-40 were detected. Multivariate analysis based on elastic stain and immunostaining indicated that plural invasion, a high frequency of vascular invasion (hazard ratio 4.00), and a high frequency of lymphatic permeation (hazard ratio 2.30) were independent predictors of cancer recurrence within 3 years. Likewise, an age ≥70 years, male, and a high frequency of vascular invasion (hazard ratio 3.41) were independent predictors of overall survival. CONCLUSIONS: Vascular invasion should be confirmed by elastic stains, and the frequency, not but the presence, of vascular invasion is a powerful independent prognostic factor in completely resected stage I non-small cell lung cancer patients.

[Multiple Pulmonary Sclerosing Pneumocytoma with Abnormal Accumulation of Fluorodeoxyglucose-positron Emission Tomography Diagnosed by Surgical Treatment;Report of a Case].

A 36-year-old Chinese woman was referred to our hospital for further examination of an abnormal shadow on chest X-ray. Chest computed tomography(CT) revealed a 5 mm circular nodule in diameter in right lung S3 and a 32 mm mass in diameter in right lung S7. The S7 mass showed an abnormal accumulation of SUVmax=4.0 on positron emission tomography( PET)-CT. Transbronchial biopsy was performed, but failed to rule out possible malignancy. Differential diagnoses were multiple lung benign tumor, multiple lung metastases from unknown primary cancer, malignant lymphoma or primary lung cancer, and so on. We performed surgical resection for diagnosis. She underwent lung partial resection of S3 at 1st, and the intraoperative diagnosis of carcinosarcoma was made. Therefore, we performed additional lobectomy of the right lower lobe and mediastinum lymph node dissection. The postoperative course was uneventful. Pathological diagnosis was both pulmonary sclerosing pneumocytoma. No findings of recurrence have been detected at 1-year postoperatively.

[Papillary fibroelastoma derived from the left ventricular wall just under the mitral leaflet; report of a case].

A 74-year-old male was referred to our department due to a mobile solid mass of 10 mm in diameter on the left ventricular interior wall just below the posterior leaflet of the mitral valve. Mild mitral regurgitation and moderate tricuspid regurgitation were also detected. A high serum level of IL-6 was detected(33.0 pg/ml), and myxoma was suspected. The tumor, which was bright yellowish brown with a partly jelly-like surface, was successfully removed surgically through the mitral valve under cardiopulmonary bypass. Pathological findings of the mass was papillary fibroelastoma. Papillary fibroelastoma derived from the left ventricular wall is very rare.