Sex hormones alter Th1 responses and enhance granuloma formation in the lung.

BACKGROUND: The lung is one of the sites of granulomatous responses, which are characterized by the recruitment and organization of activated macrophages and lymphocytes. There have been several reports that have shown that some pulmonary granulomatous diseases, such as sarcoidosis and nontuberculous mycobacterial disease, are likely to be characterized by a preponderance in postmenopausal females. Although sex hormones have been shown to play an important role in the regulation of the immune system, the influence of sex hormones on pulmonary granuloma formation is still unclear. OBJECTIVES: The purpose of this study was to assess whether sex hormones are involved in granulomatous inflammation and to evaluate how sex hormones modulate this response in the lung. METHODS: Ovariectomized rats were used as an experimental postmenopausal model in which chronic pulmonary granulomatous inflammation was induced by intravenous injection of complete Freund's adjuvant. RESULTS: Histological analysis of lung tissues demonstrated enhancement of granuloma formation in the ovariectomized group. Such enhanced granuloma formation was significantly associated with generalized Th1-biased cytokine production in the bronchoalveolar lavage fluid. CONCLUSION: These results indicate that sex hormones play an important role in pulmonary granuloma formation by altering the Th1 responses.

Thymic adenocarcinoma with sarcomatoid features characterized by intracaval tumor growth: report of a case.

Primary thymic adenocarcinoma is an extremely rare tumor. This report describes a case of thymic adenocarcinoma with a peculiar pathological feature and clinical course. A 54-year-old man complained of cough, dyspnea, and chest pain. Computed tomography scans revealed an anterior mediastinal mass with intracaval growth into the superior vena cava. No definitive diagnosis could be made after several examinations and palliative radiotherapy was performed. He passed away 56 days after the appearance of the initial symptoms. An autopsy revealed that the mediastinal tumor obstructed not only the superior vena cava but also the pulmonary arteries. The histological findings revealed the tumor to be an adenocarcinoma with sarcomatous features. The tumor was immunohistochemically positive for CD5 and negative for thyroid transcription factor-1. These results suggested the tumor to be a thymic adenocarcinoma with sarcomatoid features; furthermore, the tumor invaded the great vessels, thus resulting in a poor prognosis.

[Twelve cases of advanced thymic carcinoma: a clinical review].

Thymic carcinoma is comparatively rare and no standard treatment has been established for advanced stage cases. We reviewed our therapeutic experience in 12 cases of thymic carcinoma. They consisted of 9 men and 3 women, ranging from 38 to 69 years of age, with a mean age of 56.5. According to Masaoka's classification, 5 cases were stage III and 7 were preoperative stage IVb. Nine cases were squamous cell carcinoma and 3 were adenocarcinoma. Four cases of preoperative clinical stage III underwent extended thymectomy, but none were completely resected and were classified as stage IV postoperatively. Chemotherapy combined with radiation therapy was given in 1 case, chemotherapy (monotherapy) was given in 4 cases, radiation therapy was given in 1 case, and 2 cases received best supportive care. The median survival time (MST) of patients who had undergone combined modality treatments including surgery was 1971 days, which was longer than the MST of 567 days of patients who were not able to undergo surgery. The prognosis outcome of advanced thymic carcinoma is poor, but combined modality therapies such as surgery, chemotherapy and radiation can be effective for some advanced thymic carcinoma cases.

Osteopontin is involved in the formation of malignant pleural effusion in lung cancer.

Malignant pleural effusion (MPE) is associated with advanced-stage lung cancer and is a poor prognostic sign for these patients. Osteopontin (OPN) is a multifunctional cytokine that is involved in the tumor progression and angiogenesis of lung cancer cells. The purpose of this study is to investigate and provide evidence for the role of OPN in the formation of MPE associated with lung cancer. In this study, we established an OPN knockdown murine lung cancer cell line, 3LL cells, utilizing the small interfering RNA (siRNA) technique. To reveal the effect of OPN on the formation of MPE associated with lung cancer, we directly injected OPN knockdown 3LL cells, 3LL/OPN siRNA, or control cells, 3LL/control siRNA, into the pleural space of C57BL/6 mice. OPN knockdown significantly reduced the formation of MPE, but did not inhibit in vivo tumor growth of 3LL cells in mice. Vascular endothelial growth factor (VEGF) concentration in MPE was markedly decreased in the 3LL/OPN siRNA in comparison with that of the 3LL/control siRNA. In vitro, recombinant OPN protein enhanced VEGF secretion from human umbilical vein endothelial cell (HUVEC) or human mesothelial cell line, Met5A cells, in a concentration-dependent manner. These results suggest that OPN is positively involved in the formation of MPE of lung cancer presumably by promoting VEGF secretion from vascular endothelial cells or mesothelial cells. OPN could be an effective target molecule for reducing MPE in lung cancer patients.

ERC/mesothelin as a marker for chemotherapeutic response in patients with mesothelioma.

BACKGROUND: It has been recently reported that soluble mesothelin-related protein (SMRP), serum mesothelin, and osteopontin (OPN) are considered as relevant biomarkers for the diagnosis of mesothelioma. The aim of this study was to investigate whether serum N-ERC/mesothelin, an NH3-terminal fragment of mesothelin, and plasma OPN reflect chemotherapeutic effect in patients with mesothelioma. MATERIALS AND METHODS: Serum N-ERC/mesothelin and plasma osteopontin were determined with a sandwich enzyme-linked immunosorbent assay (ELISA) system. RESULTS: The average N-ERC ratio, determined by dividing the N-ERC levels following chemotherapy by those prior to chemotherapy, in the partial response (PR) group was significantly lower than that of the stable disease (SD)/progressive disease (PD) group. In contrast, the average OPN ratio, determined by dividing the OPN levels following chemotherapy by those prior to chemotherapy, in the PR group was not statistically different from that of the SD/PD group. CONCLUSION: N-ERC/mesothelin is considered as relevant in monitoring chemotherapeutic response in patients with mesothelioma.

[Efficacy of gefitinib according to smoking status in non-small cell lung cancer patients].

Gefitinib is a molecular targeting agent and more effective in patients with characteristics of oriental ethnicity, female gender, adenocarcinoma and non-smokers. It is sometimes effective in smokers, but few papers have focused on the association between efficacy and smoking history. The aim of this study is to evaluate the association between efficacy of gefitinib and patients' characteristics, especially smoking history. Between July 2002 and September 2006, 89 patients were diagnosed as non-small cell lung cancer and administered gefitinib. Eighty of them were assessable for efficacy and toxicity of gefitinib. Response rate was 16.2% and 39.6%(p=0.031)in smokers and non-smokers. Survival was statistically greater in non-smokers. In smokers, there are more cases which showed response to gefitinib with a lower smoking index and longer duration after smoking cessation. Smoking index and duration after smoking cessation should be considered when gefitinib is administered or EGFR mutation analysis is conducted in patients with non-small cell lung cancer.

[A case of exogenous lipoid pneumonia with marked elevation of serum KL-6 and interstitial lung shadows due to aspiration of liquid paraffin].

A 64-year-old man who ingested liquid paraffin as a laxative for over two years, was admitted to our hospital with a persistent interstitial lung shadow and marked elevation of serum KL-6. He had no overt symptoms although his chest radiograph revealed ground glass opacities in the left lower lung field and right middle and lower lung fields. We performed fiberoptic bronchoscopy. Exogenous lipoid pneumonia was diagnosed based on microscopic analysis of the bronchoalveolar lavage fluid that revealed the presence of lipid-laden alveolar macrophages. We instructed the patient to discontinue liquid paraffin ingestion and observed his clinical course. The chest radiograph and thoracic computed tomography revealed a tendency to improve and serum KL-6 decreased with time. Serum KL-6 may be an important index of the severity of exogenous lipoid pneumonia.

Effect of telling patients their "spirometric-lung-age" on smoking cessation in Japanese smokers.

BACKGROUND: Cigarette smoking remains a significant public health problem. However, current treatment programs have not yet succeeded in sufficiently reducing smoking rates. The study aimed to examine whether patients' recognition of "spirometric-lung-age (SLA)" estimated from spirometry data prompts smoking cessation. METHODS: From December 2010 to September 2011, participating smokers were prospectively enrolled into the standardized smoking cessation program (Visits 1-5 for 12 weeks) and assigned single-blindly to either SLA assessment or control groups. The SLA group was informed of the estimated age of their lungs from spirometry analysis and given an opportunity to recognize the difference from their actual chronological age, whereas the control group was not. The primary calculation of outcome was the smoking quit rate on Visit 5, whereas the secondary end-point was the proportion of patients who remained abstinent 1 year later. RESULTS: One hundred and twenty-six Japanese smokers (88 males) participated and were randomly assigned to the SLA group (n=52) or the control group (n=74). The smoking quit rate on Visit 5 was similar in the SLA assessment group and control group (59.6% vs. 41.9%; P=0.0700). However, the proportion of patients who remained abstinent 1 year later was similar in both groups (78.6% vs. 69.0%; P=0.5497). Multivariate logistic regression analysis after adjusting baseline characteristics demonstrated that telling patients their SLA, the use of varenicline, and age were significantly associated with smoking quit rate on Visit 5 whereas only age was associated with remaining abstinent 1 year later. CONCLUSIONS: Telling patients their SLA can become a useful tool prompting smoking cessation among Japanese smokers although other factors such as pharmacotherapy and age also influence the cessation of smoking.

Prognostic factors in patients with inoperable non-small cell lung cancer--an analysis of long-term survival patients.

A survival benefit of patients with inoperable non-small cell lung cancer has been reported since a development of new therapeutic agents in the 1990's. However, multivariate analyses of patients have not been evaluated. The aim of this study is to identify prognostic factors in the long-term survivors who had been treated with chemotherapy using these new agents and/or radiotherapy. A retrospective study and clinical analysis of 121 inoperable nonsmall cell lung cancer patients were conducted. Fifteen cases (male: 9, female: 6) with a survival of more than 2 years were revealed. Regarding clinical variables between the 15 cases and others, an early nodal (N) status, a high serum protein level, a good performance status (PS) and those having first-line chemotherapy or radiotherapy were all identified as significant prognostic factors for the long-term survivors. Multivariate analyses also revealed that an early N status, a good PS, female gender and chemotherapy and/or radiotherapy were associated with the long-term survivors. These results suggest that patients with inoperable non-small cell lung cancer should be considered for appropriate treatments including new chemotherapeutic agents.

[Case of Heerfordt's syndrome with prolonged peripheral nerve involvement].

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.

Serum tenascin-C as a potential predictive marker of angiogenesis in non-small cell lung cancer.

BACKGROUND: Tenascin (Tn)-C is an extracellular matrix protein that is involved in tissue interactions during fetal development and oncogenesis. However, the role of serum Tn-C in non-small cell lung cancer (NSCLC) has not been clarified. PATIENTS AND METHODS: In this study, we determined the serum levels of Tn-C among NSCLC patients who underwent surgery, as well as other factors implicated for angiogenesis, to address the clinical implications in NSCLC. RESULTS AND CONCLUSION: The median concentration of serum Tn-C in NSCLC patients was slightly higher than that of normal controls, but this difference was not statistically significant. There was a positive correlation between serum Tn-C levels and microvessel density (MVD), serum osteopontin (OPN) and vascular endothelial growth factor (VEGF). In contrast, there was no correlation between serum Tn-C levels and serum carcinoembryonic antigen (CEA) and sialyl lewis-X (SLX) levels. The overall survival of patients with low Tn-C levels (<96 ng/ml) was significantly greater than that of patients with high Tn-C levels (> or =96 ng/ml). Intratumoral Tn-C expression was co-localized with expression of microvessels in the stroma of the cancer cells by immunohistochemical analysis. Moreover, enhanced in vitro migration of human umbilical vascular endothelial cells (HUVEC) was induced by recombinant Tn-C. Collectively, Tn-C may play an important role in angiogenesis of patients with NSCLC, and the determination of serum Tn-C may be useful in predicting intratumoral vasculature and patients' prognosis.

Small-cell lung cancer exhibiting spontaneous regression.

A 56-year-old woman was admitted to our hospital because a chest X-ray and thoracic computed tomography (CT) scan revealed a heterogeneous tumor in the middle mediastinum during a visit to a nearby clinic for a consultation regarding a persistent cough and body weight loss. However, the tumor spontaneously decreased on thoracic CT performed on admission. Subsequently, a biopsy of the tumor using video-assisted thoracoscopy was performed. The pathological findings disclosed the tumor to be small-cell lung cancer with infiltration of CD8-positive T-cells exhibiting spontaneous regression. Cell-mediated immunity, including CD8-positive T-cells, may have relevance to the spontaneous regression of malignant tumors.

Factors influencing weaning from mechanical ventilation in elderly patients with severe pneumonia.

AIMS: The purpose of this study was to determine the factors that adversely affect the weaning of elderly patients with community-acquired pneumonia from mechanical ventilation. METHODS: This study retrospectively investigated the medical records of 71 elderly patients (65 years or older) who were admitted to the hospital because of community-acquired pneumonia and required mechanical ventilation between January 2003 and December 2007. The patients were divided into two groups: group A, which included 33 patients who were successfully weaned from mechanical ventilation, and group B, which included 38 patients who could not be weaned from mechanical ventilation. The study compared the patients' background, vital signs, and laboratory and bacteriological examinations at the beginning of mechanical ventilation. A multiple logistic regression analysis was performed to identify the factors associated with difficulties in weaning patients from mechanical ventilation. RESULTS: In group B, there were significantly more smokers (P < 0.05) and more patients with emphysematous changes on thoracic CT (P < 0.05). In group A, the concentrations of total serum protein (P < 0.05) and albumin (P < 0.05) were significantly higher. A multiple logistic regression analysis revealed that patients with community-acquired pneumonia who showed emphysematous changes on thoracic CT (OR = 4.92, 95%CI 1.08-22.46) and/or a low concentration of serum albumin <3.0 g/dL (OR = 4.25, 95%CI 1.17-15.45) had difficulty being weaned from mechanical ventilation. CONCLUSION: Our study suggests that elderly patients with community-acquired pneumonia with emphysematous changes on thoracic CT and/or a low concentration of serum albumin level have difficulty being weaned from mechanical ventilation.

Malignant lymphoma with diffuse cardiac involvement detected by multiple imaging examinations: a case report.

INTRODUCTION: In malignant lymphoma, cardiac involvement, which usually forms pathologically focal and firm nodules in the cardiac walls, is considered to be a late manifestation of the disease. CASE PRESENTATION: We describe the case of a 71-year-old Asian Japanese woman whose first presentation of lymphoma was congestive heart failure. Multiple imaging examinations and laboratory findings led to a presumed diagnosis of a malignant lymphoma. A tissue diagnosis of the mediastinal mass could not be performed due to our patient's generally poor condition. Our patient received corticosteroid therapy, but died 42 days after her admission. An autopsy revealed lymphoid cells encircling her ventricular wall and infiltrating her endocardium. A histological examination confirmed the diagnosis of diffuse large B-cell lymphoma. CONCLUSION: Imaging examinations such as echocardiography, computed tomography with three-dimensional reconstruction, and gallium-67-citrate scintigraphy could clearly detect the diffuse cardiac involvement antemortem. A combination of these imaging techniques could provide a working diagnosis and allow empirical initiation of treatment in patients with poor general condition.

A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus paclitaxel in patients with non-small cell lung cancer with bone metastases.

AIMS AND BACKGROUND: Although zoledronic acid (ZOL) has been reported to inhibit bone metastasis from lung cancer, the optimum chemotherapy regimen in combination with ZOL has not yet been determined. METHODS AND STUDY DESIGN: Eighteen patients having non-small cell lung cancer (NSCLC) with bone metastasis who received carboplatin/nedaplatin plus paclitaxel combined with ZOL (4 mg every 28 days) were enrolled to investigate the feasibility of this treatment. The efficacy was evaluated by the percentage of patients at 9 months who were receiving radiation therapy, the time to first radiation treatment, and quality of life. Adverse effects were also evaluated. RESULTS: Only 3 among 18 patients received radiation therapy for bone metastases during the 9 months of the study. ZOL seems to prolong the median time to the first radiation treatment and maintain the quality of life regarding pain and activity status. No patients discontinued the treatment, although grade 3 or 4 treatment-related adverse effects occurred in 8 patients. CONCLUSIONS: ZOL combined with carboplatin/nedaplatin plus paclitaxel is an effective and tolerable treatment for NSCLC with bone metastases.

Malignant pleurisy associated with primary lung cancer well controlled by pleurodesis using distilled water.

The patient was an 84-year-old man patient diagnosed as malignant pleurisy associated with lung cancer. After drainage of the right pleural effusion, pleurodesis with distilled water was performed. Despite the enlargement of the primary lesion of the lung cancer during the follow-up period, the amount of pleural effusion did not increase for more than one year. No adverse effects associated with pleurodesis were noted. Pleurodesis with distilled water should be considered as one of the choices for treatment in the management of malignant pleurisy especially in elderly.