[A CASE OF CLINICALLY AMYOPATHIC DERMAMYOSITIS WITH INTERSTITIAL LUNG DISEASE SHOWING TWO DETERIORATIONS IN 4 YEARS].

We report the case of a 45-year-old man who was diagnosed with clinically amyopathic dermamyositis (CADM) and interstitial lung disease (ILD) after presenting with skin lesions typical of CADM and testing positive for anti-Melanoma Diferentiation-Associated gene 5 (anti-MDA5) anti-bodies. He was treated with a regimen including steroid pulse therapy, intravenous cyclophosphamide (IVCY), and calcineurin Inhibitor drug, which initially improved his ILD. However, three months post-treatment, the first deterioration of his conditions occurred, necessitating further administration of steroid pulse therapy and IVCY. After eight cycles of IVCY therapy, the serum levels of KL-6 and anti-MDA5 antibodies decreased, and reaching their lowest values. Nevertheless, two years and six months after the first observed deterioration, the second deterioration of his conditions occurred, leading to acute respiratory failure, treated again with steroid pulse therapy and IVCY. This treatment did not result in improvement of respiratory failure, therefore plasma exchange was attempted, which demonstrated a beneficial effect on the ILD for a short time. This case suggests that IVCY and plasma exchange might be effective therapeutic options for CADM with ILD.

Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week dosing period in elderly patients with advanced non-small cell lung cancer.

BACKGROUND: S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established. METHODS: We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA). The primary endpoint was the disease control rate. RESULTS: Forty patients were enrolled. The disease control and response rates were 89.5% (95% confidence interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median progression-free survival and overall survival times were 4.4 months (95% CI = 4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia, anorexia, hyponatremia, hypokalemia, and pneumonia of grade ≥ 3 occurred in 5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient-reported outcomes, most of the individual factors in the patients' quality of life, including upper intestine-related symptoms improved with the treatment, except for dyspnea, which slightly albeit continuously worsened throughout the study. CONCLUSIONS: In elderly patients with previously untreated advanced NSCLC, a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1-week interval was well tolerated and demonstrated promising efficacy. This study was registered at the University Hospital Medical Information Network (UMIN) Center (ID: UMIN000002035), Japan.

Carboplatin plus Weekly Paclitaxel with Bevacizumab for First-line Treatment of Non-small Cell Lung Cancer.

AIM: The present study aimed to evaluate the effectiveness and safety of weekly paclitaxel (PTX) combined with carboplatin (CBDCA) plus bevacizumab (BEV), followed by maintenance BEV in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with unresectable stage IIIB and IV NSCLC (n=43) were treated with CBDCA (AUC 6, day 1), BEV (15 mg/kg, day 1), and PTX (70 mg/m(2), days 1, 8, 15) intravenously every 4 weeks, for 3 to 6 cycles, followed by maintenance BEV (15 mg/kg) every 3 weeks. RESULTS: The objective response rate and disease control rate were 67.4% and 90.7%, respectively. The median progression-free survival was 7.6 months. The median overall survival was 17.7 months. Common adverse events were tolerable bone marrow suppression, fatigue, hypertension, and nasal bleeding. CONCLUSION: Weekly administration of PTX combined with CBDCA plus BEV therapy was effective, and well-tolerated by advanced NSCLC patients.

[A case of refractory pulmonary peripheral T cell lymphoma successfully treated with Cisplatin Plus Gemcitabine Plus Solumedrol].

A 56-year-old man had an endoscopic examination for dysphagia in March 2007 which revealed tumors in the esophagus and stomach. Pathological examination of the esophagus biopsy specimens showed an unspecified peripheral T cell lymphoma. The esophagus tumor was tolerant to CHOP and EPOCH therapy. After an autologous peripheral blood stem cell transplantation, a complete response was observed in the patient. However, a lymphoma relapse was diagnosed in the lung in September 2008. The relapsed lung lymphoma was tolerant to EPOCH therapy. The refractory pulmonary peripheral T cell lymphoma was remarkably reduced by PEGS therapy. PEGS therapy is useful for relapsed peripheral T cell lymphoma cases that tolerated standard chemotherapy. An allogenic hematopoietic stem cell transplantation or new molecular target therapy might be finally selected for refractory peripheral T cell lymphoma. However, an allogenic transplantation has some severe complications. Furthermore we could not easily try phase I or II new molecular target drug treatment. We think that PEGS therapy is a useful treatment for refractory peripheral T cell lymphoma before allogenic transplantation or new molecular target drug treatment.

[Improvement of neurologic symptoms after chemoradiotherapy in a patient with small cell lung cancer associated with paraneoplastic neurologic syndrome].

A 53-year-old man was referred to our hospital for dry cough and a mass in the hilum of the right lung on chest CT which was diagnosed as small cell lung cancer by bronchofiberscopy (T3N2M0, stage IIIB). Also, he was aware of progressive muscle weakness in the lower extremities on the first consultation. An electromyogram showed neuropathic changes and did not show waxing phenomenon in response to high frequency repetitive stimulation. Sensory nerve conduction velocity was low, so we diagnosed small cell cancer associated with paraneoplastic sensory neuropathy. Serum antineuronal antibodies were negative. His neurological symptoms improved dramatically after chemoradiotherapy for small cell lung cancer. A complete response was obtained by concurrent chemoradiotherapy and prophylactic cranial irradiation was administrated. He is alive without recurrence at 11 months after the treatment.

Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant.

Human cathepsin G (EC 3.4.21.20) has been reported to have the in vitro chemotactic activity for human monocytes. In this study, we examined the role of cathepsin G in monocyte involvement in joint inflammation of rheumatoid arthritis (RA) as a monocyte chemoattractant. Eighteen patients with RA and four patients with osteoarthritis (OA) were used in this study. Thiobenzylester substrate, Succ-Phe-Leu-Phe-S-Bzl, was used to measure the activity of cathepsin G in synovial fluids. Monocyte migration induced by cathepsin G and synovial fluids was assessed by a 48-well microchemotaxis chamber technique. Immunohistochemical staining was performed to determine the cellular origin of cathepsin G in RA synovial tissue. A very low activity of cathepsin G was detected in synovial fluids from patients with OA. On the other hand, significantly increased activity of cathepsin G was detected in patients with RA when compared with the value of OA patients. A considerable monocyte chemotactic activity was detected in the synovial fluid of RA patients, and the activity was partially decreased by the treatment with inhibitors for cathepsin G, alpha1-antichymotrypsin and phenylmethylsulfonyl fluoride. The activity of cathepsin G was significantly correlated with the neutrophil counts in synovial fluids and the concentration of interleukin-6. Immunohistochemical studies showed that cathepsin G was strongly expressed by synovial lining cells, and weakly expressed by macrophages and neutrophils in synovial tissues. This study indicates that the monocyte chemotactic activity of cathepsin G may have a role in the pathogenesis of RA synovial inflammation.

Defensins- and cathepsin G-ANCA in systemic lupus erythematosus.

In this study, we examined the content of antineutrophil cytoplasmic antibodies (ANCA) against defensins and cathepsin G in sera from systemic lupus erythematosus (SLE) patients and their significance in estimating the activity of SLE. Defensins- and cathepsin G-ANCA in sera from 28 patients with SLE, eight patients with rheumatoid arthritis (RA) and eight patients with microscopic polyangitis (mPA) were measured by ELISA. Significantly increased defensins- and cathepsin G-ANCA were found in sera of patients with SLE and mPA when compared with the value of normal controls. Though significantly higher defensins- and cathepsin G-ANCA were detected in both active and inactive SLE patients, the value in active SLE patients was significantly higher than inactive SLE patients. After the therapy with high dose of prednisolone, the serum level of defensins- and cathepsin G-ANCA was decreased, and this decrease was sustained for at least 16 weeks. This study suggests that defensins- and cathepsin G-ANCA may serve as useful markers of the disease activity of SLE.

The significance of cathepsins, thrombin and aminopeptidase in diffuse interstitial lung diseases.

To determine the significance of proteases in interstitial lung diseases, we examined the activity of cathepsins, thrombin, and aminopeptidase in bronchoalveolar lavage (BAL) fluid from patients with these disorders. Significantly increased activities of cathepsin H and aminopeptidase were detected in BAL fluid from patients with idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), chronic eosinophilic pneumonia (CEP) and hypersensitivity pneumonitis (HP). Significantly higher activity of cathepsin B was found in BAL fluid from patients with CEP. The activity of thrombin was significantly higher in patients with IPF and CEP. In patients with IPF, there were significant correlations between neutrophil number and the activity of cathepsin B, cathepsin H or aminopeptidase. In patients with COP and HP, the activity of the proteases was significantly higher in patients with higher number of lymphocytes than in those with lower number of lymphocytes. The present study suggests that the activity of the proteases is a useful marker in activity of the interstitial lung diseases, and may have a role in the pathogenesis of these disorders.