[FREQUENCY OF IMAGING FINDINGS RESEMBLING MYCOBACTERIOSIS AND CHARACTERISTICS OF COMORBID PULMONARY NON-TUBERCULOSIS MYCOBACTERIOSIS IN THE PATIENTS WITH ALLERGIC BRONCHOPULMONARY MYCOSIS].

OBJECTIVE: To clarify the frequency of imaging findings similar to mycobacterial infection and the characteristics of comorbid pulmonary non-tuberculosis mycobacteriosis in the patients with allergic bronchopulmonary mycosis (ABPM). SUBJECTS AND METHODS: Patients treated with ABPM at our hospital in the past 8 years were extracted from medical records, and 32 patients who met the clinical diagnostic criteria were retrospectively examined. RESULTS: The median age was 62.5 years (range 24-79 years), and 21 patients were female. Twenty-two had asthma, and four had old tuberculosis. CT findings showed central bronchiectasis in 29 cases, centrilobular nodulars in 26 cases, and mediastinal lymphadenopathy in 3 cases. Pulmonary M. avium complex (pMAC) disease was complicated in 4 cases. Regarding the time of diagnosis of pMAC disease, 2 cases were diagnosed concurrently with ABPM, 1 case was before ABPM diagnosis, and 1 case was during ABPM treatment. The main lesion of ABPM occurred in a different site from that of pMAC disease. CONCLUSIONS: ABPM and mycobacterial infection not only have similar imaging findings, but they can also occur synchronously and metachronously. Complication of ABPM and pMAC disease may be due to risk factors common to both diseases, such as the patient's constitution and living environment.

[A CASE OF EOSINOPHILIC GRANULOMATOUS WITH POLYANGIITIS WITH SKIN LESIONS ASSOCIATED WITH PSORIASIS].

A 72-year-old woman who was undergoing treatment for bronchial asthma and psoriasis vulgaris experienced malaise three months earlier and visited our hospital on account of abnormal lung shadows. Chest computed tomography revealed ground-glass opacities in the peripheral lung fields and eosinophilia in the bronchoalveolar lavage fluid, which suggested eosinophilic pneumonia. Antineutrophil cytoplasmic antibody was negative. Her lower limbs had multiple palpable papules mixed with well-treated psoriasis and the histopathology of the skin biopsy revealed eosinophil infiltration around small vessels, suggesting the occurrence of eosinophilic granulomatosis with polyangiitis (EGPA). We were able to evaluate minor skin lesions mixed with psoriasis through collaboration between the pulmonologist and the dermatologist. In the diagnosis of EGPA, it is important to carefully examine the whole body and not overlook minor findings before starting steroids.

[A CASE OF PROBABLE LATE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS WHERE THE INITIAL MANIFESTATION WAS A UNILATERAL PLEURAL EFFUSION].

A 74-year-old man developed with left pleural effusion and was suspected of benign asbestos pleural effusion and tuberculous pleurisy. Because of elevation of ADA level in the pleural effusion, diagnostic treatment for tuberculous pleurisy by anti-tuberculosis drugs was performed. However, right pleural effusion, cutaneous/mucosal lesions, leukocytopenia, and fever elevation occurred. The pathology of skin biopsy was consistent with systemic lupus erythematosus (SLE). Since clinical findings did not improve even after discontinuation of all drugs, he received steroid therapy was started and clinical findings improved. He was suspected of late-onset SLE. In conclusion, lupus pleurisy should also be differentiated when pleural effusion is seen in older. Late-onset SLE and drug-induced lupus should be carefully differentiated based on the clinical course.

[A CASE OF SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS DURING IMMUNOSUPPRESSIVE TREATMENT FOR SYSTEMIC SCLEROSIS].

A 70-year-old woman undergoing long-term treatment for systemic scleroderma and secondary Sjögren syndrome developed fever during tapering of steroids. Chest CT showed centrilobular granular shadow and ground glass opacities. The pathology of transbronchial lung biopsy and the findings of bronchoalveolar lavage fluid were consistent with hypersensitivity pneumonitis and positive for anti-Trichosporon asahii antibody. Because her symptoms and imaging findings improved after house cleaning, she was diagnosed with summertype hypersensitivity pneumonitis. When lung lesions are found in patients with collagen disease, it is necessary to distinguish various diseases. In particular, allergic diseases can be difficult to diagnose by steroid therapy. In order to make an accurate diagnosis, medical history and image interpretation should be performed carefully and histologically searched as much as possible.

[Development of Pulmonary Pleomorphic Carcinoma after Treatment for Infectious Bulla].

A 54-year-old man with a history of smoking developed infectious bullae at the apex of his left lung and underwent long-term antimicrobial treatment. The bullae gradually reduced in size along with a slight left pleural thickening. Left back pain relapsed after a year, and CT revealed a rapid increase in pleural thickening. Left upper lobectomy led to the diagnosis of pulmonary polymorphic carcinoma. Chronic inflammation due to infection could contribute to carcinogenesis; therefore, post-inflammatory changes should be carefully followed-up.

[A Case of Lung Cancer Discovered Due to Unresponsive Course of Corticosteroids for Rheumatoid-Associated Interstitial Lung Disease].

A 76-year-old female was followed up for rheumatoid arthritis-associated interstitial lung disease(RA-ILD). Consolidation and ground-glass opacities were observed in the right lung. When the corticosteroid was restarted due to a relapse of RA-ILD, most of the shadows disappeared. However, ground-glass nodules remained in the apex of the right lung. Thoracoscopic segmentectomy was performed, and lung cancer was diagnosed. Patients with rheumatoid arthritis suffer from complications such as RA-ILD, drug-induced pneumonia, pulmonary infections, and malignancies. A careful assessment of treatment response should be made in case of a differential diagnosis.

[A Case of Small Cell Lung Cancer Diagnosed with Metastasis-Induced Acute Pancreatitis].

A 56-year-old man was admitted to our hospital for management of acute epigastric abdominal pain and elevation of pancreatic enzymes. The CT scan revealed enlargement ofthe pancreatic body as well as the lung tumor ofthe right hilar and superior mediastinum. Therefore, bronchoscopy was performed and a diagnosis of small cell lung cancer with metastasisinduced acute pancreatitis(MIAP)was made. Prompt improvement in pancreatic findings was observed following chemotherapy. MIAP, which is a rare complication of lung cancer may affect the prognosis and quality of life of the patients; therefore, rapid diagnosis and appropriate treatment are important.

[Usefulness of semi-quantitative procalcitonin test in respiratory medical practice].

PURPOSE: A lot of investigators have reported about the diagnostic and prognostic value of procalcitonin (PCT) for severe bacterial infection. We evaluated the usefulness of semi-quantitative PCT test in respiratory medical practice. METHODS: A retrospective study was performed from June to December 2008 at the Chugoku Rosai General Hospital, Hiroshima, Japan. This study analyzed consecutive adult patients, including outpatients and inpatients, who developed systemic inflammatory response syndrome (SIRS) and their PCT were measured semi-quantitatively within the first 24 hours of onset or first visit. We extracted 87 patients with respiratory disease and analyzed their clinical data. RESULTS: Study patients were divided into two groups: 61 patients with bacterial infection and 26 patients without it. Semi-quantitative PCT test (cut-off value; > or = 0.5 ng/ml) showed sensitivity of 55.7% and specificity of 84.6% for diagnosis of bacterial infection. The diagnostic value of PCT was higher than that of CRP and WBC but it was thought to be not enough to accurate diagnosis. The patients with high PCT value (> or = 2.0 ng/ml) showed higher death rate than the patients without it (36.4% vs 7.7%, P = 0.016). CONCLUSION: Semi-quantitative PCT test, which anyone can use quickly and easily, has great prognostic value and limited diagnostic value for respiratory bacterial infection.

The STOP-Bang Test Is Useful for Predicting the Severity of Obstructive Sleep Apnea.

INTRODUCTION: The STOP-Bang test was used to detect patients at high risk of obstructive sleep apnea (OSA). We evaluated the usefulness of the STOP-Bang test for predicting the severity of OSA in Japanese patients. METHODS: We retrospectively evaluated the patients who performed full polysomnography at the Mihara Medical Association Hospital. We evaluated the correlation between the STOP-Bang score and the apnea hypopnea index (AHI) using Spearman's rank correlation analysis. We then used multivariate analyses to examine the independent risk factor for severe OSA (AHI ≥ 30/hr). RESULTS: One hundred seven patients were diagnosed as no (n = 5), mild (n = 17), moderate (n = 30), and severe (n = 55) OSA. The median age was 67 years old (range: 35-84), and 73 of the 107 patients were males. The correlation coefficient between the STOP-Bang score and AHI was 0.701 (P < 0.001). A STOP-Bang score ≥ 5 had sensitivity of 80.0% and specificity of 76.9% for detecting severe OSA. A STOP-Bang score ≥ 5 and BMI ≥ 30 kg/m2 were the independent risk factor for severe OSA. CONCLUSIONS: The STOP-Bang score correlates with AHI and is useful for predicting OSA severity. Polysomnography should be performed actively for the patients with high STOP-Bang scores.

[Pulmonary embolism in a patient with large cell lung carcinoma during chemotherapy-case report].

The patient, a 64-year-old woman, was diagnosed as having large cell carcinoma(stageIV)eighteen months ago. She received long-term chemotherapy, and her disease stabilized. She was admitted to our hospital with dyspnea and diagnosed with a pulmonary embolism by chest computed tomography(CT)and angiography of pulmonary artery. As a result of thrombolytic therapy and anticoagulant therapy, the thrombus decreased in size and her condition improved. Insertion of a vena cava filter and continuation of anticoagulant therapy were performed to prevent recurrence of PE. In this case, there were many prothrombogenic factors such as advanced malignancy, a long period of chemotherapy, corticosteroids, granulocyte-colony stimulating factor(G-CSF)and decreased physical activity. Thrombosis is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. Great care should be taken for complications of thrombosis in cancer treatment.

[A case of hearing loss and diffuse alveolar hemorrhage associated with microscopic polyangitis].

We report a rare case of bilateral hearing loss and diffuse alveolar hemorrhage associated with microscopic polyangitis (MPA). A 75-year-old woman complained of hearing loss. Two months later, she was admitted due to rapidly progressing dyspnea. Chest radiography and CT scan showed diffuse bilateral consolidations. Mechanical ventilation was required for respiratory insufficiency. Laboratory data demonstrated anemia and renal failure. Steroid pulse therapy and antibiotics were initiated. On day 2, bronchoalveolar lavage showed fresh blood-like fluid, which suggested diffuse alveolar hemorrhage (DAH). Serum level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was elevated. Therefore, DAH and rapidly progressive glomerulonephritis associated with MPA were diagnosed. Treatment was also performed with cyclophosphamide pulse therapy and plasmapheresis. Her pulmonary lesion improved dramatically. We emphasize the effectiveness of bronchoalveolar lavage for prompt and accurate diagnoses. Moreover, this case report also suggests that early cyclophosphamide therapy and plasmapheresis may be an effective treatment for MPA with diffuse alveolar hemorrhage. In contrast, hearing loss did not improve after therapy. Some cases reported hearing loss as a rare symptom of MPA. We also suspect that hearing loss may be a complication of MPA. We reported this case because there has been no description of hearing loss accompanying DAH associated with MPA.

RASEF is a novel diagnostic biomarker and a therapeutic target for lung cancer.

UNLABELLED: Genome-wide gene expression profiling revealed that the Ras and EF-hand domain containing (RASEF) transcript was significantly transactivated in the majority of lung cancers. Using lung cancer cells, transient expression of RASEF promoted cell growth, whereas RASEF knockdown not only reduced its expression but resulted in growth suppression of the cancer cells. Immunohistochemical staining using tumor tissue microarrays consisting of 341 archived non-small cell lung cancers (NSCLC) revealed the association of strong RASEF positivity with poor prognosis (P = 0.0034 by multivariate analysis). Mechanistically, RASEF interacted with extracellular signal-regulated kinase (ERK) 1/2 and enhanced ERK1/2 signaling. Importantly, inhibiting the interaction between RASEF and ERK1/2 using a cell-permeable peptide that corresponded to the ERK1/2-interacting site of RASEF, suppressed growth of lung cancer cells. This study demonstrates that elevated RASEF promoted cell growth via enhanced ERK signaling and is associated with poor prognosis of NSCLC. IMPLICATIONS: RASEF may play an important role in lung carcinogenesis and could serve as a vaiable prognostic biomarker and target for the development of new molecular therapies.

Chondrolectin is a novel diagnostic biomarker and a therapeutic target for lung cancer.

PURPOSE: This study aims to identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies for lung cancer. EXPERIMENTAL DESIGN: We screened for genes that were highly transactivated in a large proportion of 120 lung cancers by means of a cDNA microarray representing 27,648 genes and found chondrolectin (CHODL) as a candidate. Tumor tissue microarray was applied to examine the expression of CHODL protein and its clinicopathologic significance in archival non-small cell lung cancer (NSCLC) tissues from 295 patients. A role of CHODL in cancer cell growth and/or survival was examined by siRNA experiments. Cellular invasive effect of CHODL on mammalian cells was examined by Matrigel assays. RESULTS: Immunohistochemical staining revealed that strong positivity of CHODL protein was associated with shorter survival of patients with NSCLC (P = 0.0006), and multivariate analysis confirmed it to be an independent prognostic factor. Treatment of lung cancer cells with siRNAs against CHODL suppressed growth of the cancer cells. Furthermore, induction of exogenous expression of CHODL conferred growth and invasive activity of mammalian cells. CONCLUSIONS: CHODL is likely to be a prognostic biomarker in the clinic and targeting CHODL might be a strategy for the development of anticancer drugs.

Identification of Epstein-Barr virus-induced gene 3 as a novel serum and tissue biomarker and a therapeutic target for lung cancer.

PURPOSE: This study aims to identify novel biomarkers and therapeutic targets for lung cancer. EXPERIMENTAL DESIGN: We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus-induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non-small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3. RESULTS: Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity. CONCLUSIONS: EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.

Semi-quantitative procalcitonin test for the diagnosis of bacterial infection: clinical use and experience in Japan.

BACKGROUND/PURPOSE: The efficacy of the rapid semi-quantitative procalcitonin (PCT) test for the diagnosis of bacterial infection was evaluated in patients with systemic inflammatory response syndrome. METHODS: A retrospective observational study was performed from June to December 2008 at the Chugoku Rosai General Hospital, Japan. This study analyzed consecutive patients (both outpatients and inpatients) who developed systemic inflammatory response syndrome and whose PCT test was measured semi-quantitatively within 24 hours of onset, or at the first hospital visit. Based on the clinical diagnosis, the patients were divided into two groups. Group I comprised patients with a bacterial infection, and group II comprised patients with a non-bacterial infection, or non-infectious disease. Receiver operating characteristic curves were used to evaluate the diagnostic value of the semi-quantitative PCT test kit, C-reactive protein levels and white blood cells counts for the detection of bacterial infections, and the areas under the resulting curves were compared. RESULTS: A total of 168 patients were included and divided into groups I (n=112) and II (n=56). Group I showed a significantly higher percentage of positive PCT tests (≥ 0.5 ng/mL) than group II (67.8%vs. 19.6%, p < 0.001). PCT showed a sensitivity of 67.8% [95% confidence interval (CI)=58.4-76.4] and a specificity of 80.4% (95% CI=67.6-89.8). The areas under the resulting curves for PCT (0.764) were significantly larger than those seen for C-reactive protein (0.650, p=0.02) and white blood cells (0.618, p=0.006). CONCLUSION: The semi-quantitative PCT test is as useful for distinguishing bacterial infection from other inflammatory diseases in common clinical practice as the quantitative PCT.

Wegener's granulomatosis in which rheumatoid factor was useful for evaluating the disease status: a case report.

INTRODUCTION: Accurate evaluation of disease status is very important in treatment of Wegener's granulomatosis CASE PRESENTATION: A 73-year-old Japanese man presented with chronic sinusitis and otitis media. He was admitted to our hospital because of bilateral lung nodules. Cytoplasmic antineutrophil cytoplasmic antibody was negative but his rheumatoid factor was high. He was diagnosed with limited Wegener's granulomatosis and received remission induction therapy. His serum rheumatoid factor level correlated with the Wegener's granulomatosis state when he experienced a severe infection and recurrence due to Wegener's granulomatosis. CONCLUSION: We describe a case of Wegener's granulomatosis in which rheumatoid factor was helpful for evaluating the therapeutic effect.