Phase I/II Study of Docetaxel and S-1 in Previously-Treated Patients with Advanced Non-Small Cell Lung Cancer: LOGIK0408.

BACKGROUND: As docetaxel plus S-1 may be feasible for cancer treatment, we conducted a phase I/II trial to determine the recommended docetaxel dose and the fixed S-1 dose (phase I), as well as confirm the regimen's efficacy and safety (phase II) for previously-treated patients with advanced non-small cell lung cancer. METHODS: Patients ≤75 years with performance status ≤1 and adequate organ function were treated at three-week intervals with docetaxel on day 1 and 80 mg/m2 oral S-1 from days 1-14. The starting docetaxel dose was 45 mg/m2 and this was escalated to a maximum of 70 mg/m2. In phase II, response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. RESULTS: The recommended doses were 50 mg/m2 docetaxel (day 1) and 80 mg/m2 S-1 (days 1-14). Grades 3 and 4 leukocytopenia and neutropenia occurred in 44% and 67% of patients, respectively. Nonhematologic toxicities were generally mild. Overall response to chemotherapy was 7.7% (95% confidence interval (CI), 1.6-20.9%), and median PFS and OS were 18.0 weeks (95% CI; 11.3-22.9 weeks) and 53.0 weeks, respectively. CONCLUSION: Fifty mg/m2 docetaxel plus 80 mg/m2 oral S-1 had a lower response rate than anticipated; however, the survival data were encouraging. A further investigation is warranted to select the optimal patient population.

Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF. METHODS: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death. RESULTS: The median age at autopsy was 71 years (range 47-86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections. CONCLUSIONS: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.

High-resolution CT scoring system-based grading scale predicts the clinical outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines. METHODS: Consecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis. RESULTS: The HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95% CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95% CI 1.003-4.791; p = 0.0491). CONCLUSIONS: Our data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.

Phase II study of concurrent thoracic radiotherapy in combination with weekly paclitaxel plus carboplatin in locally advanced non-small cell lung cancer: LOGIK0401.

OBJECTIVES: Concurrent chemoradiotherapy for regionally advanced stage III non-small cell lung cancer is the standard treatment method. However, the clinical implications of consolidation chemotherapy following chemoradiation have been unclear. Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy. The primary endpoint was the 1-year survival rate. PATIENTS AND METHODS: Chemonaive PS 0-1 patients with stage IIIA/B NSCLC were enrolled. During the concurrent chemoradiation phase, patients were treated with weekly paclitaxel 40 mg/m(2) plus carboplatin AUC 2. The primary tumor and involved nodes received 60 Gy in 2-Gy fractions over 6 weeks. During the consolidation phase, vinorelbine 25 mg/m(2) on days 1 and 8 was repeated for three cycles. RESULTS: A total of 40 eligible patients (72.5 % male; median age, 63 years; range 29-74 years) were analyzed for efficacy. Squamous cell carcinoma was the most common histology (47.5 %), and more patients had clinical stage IIIB (55 %) cancer. The average radiation dose was 56.5 Gy, and the average number of carboplatin plus paclitaxel cycles was 4.93. Seventeen patients proceeded to the consolidation chemotherapy phase, and 14 completed three cycles of vinorelbine monotherapy. The objective response rate was 75.0 %, including 1 patient who achieved a complete response. Progression-free survival and overall survival (OS) were 46 weeks [95 % confidence interval (CI) 31-64 weeks] and 110 weeks (95 % CI 90-184 weeks), respectively. The OS rate at 1 and 2 years was 85.0 % (95 % CI 69.6-93.0 %) and 53.9 % (95 % CI 37.1-68.0 %), respectively. CONCLUSION: Concurrent chemoradiation with weekly carboplatin and paclitaxel followed by vinorelbine consolidation is effective for stage III non-small cell lung cancer and shows a generally mild toxicity profile.

[A brain abscess as a complication of hepatopulmonary syndrome coexisting with interstitial pneumonia].

A 76-year-old woman with a 20-year history of chronic hepatitis C was referred to our hospital for worsening exertional dyspnea. She had been given a diagnosis of interstitial pneumonia based on chest computed tomography findings 5 years previously. Contrast-enhanced echocardiography confirmed an intrapulmonary right-to-left shunt, and therefore we diagnosed hepatopulmonary syndrome comorbid with interstitial pneumonia. In July 2009 she was admitted to our hospital with a low grade fever, headache, and vomiting. We diagnosed a left cerebellar brain abscess caused by Streptococcus intermedius. She underwent stereotactic burr-hole drainage and received vancomycin, piperacillin and cefotaxime. Cases of brain abscess secondary to hepatopulmonary syndrome are rare. Nevertheless, we should be aware of this complication of hepatopulmonary syndrome.

[Efficacy and safety of sitafloxacin for lower respiratory tract infections].

We investigated the efficacy and safety of sitafloxacin (STFX) in patients with mild to moderate community-acquired pneumonia or secondary infections of chronic respiratory tract diseases. The results showed that the efficacy rate was 96.5% (111/115) in patients analyzed for efficacy. The efficacy rate by STFX administration method was 93.9% (46/49) at 50mg b.i.d., 100% (37/37) at 100 mg q.d. and 96.6% (28/29) at 100mg b.i.d. In chest X-rays, the image improvement rate in 102 patients with shadows before treatment was 94.1% (96/102). The image improvement rate by STFX administration method was 90.5% (38/42) at 50 mg b.i.d., 97.1% (33/34) at 100mg q.d. and 96.2% (25/26) at 100mg b.i.d. Side effects occurred in five out of 115 patients (4.3%). Abnormalities in hepatic function test values appeared in two patients and abnormalities in renal function test values appeared in three patients. In four cases, the abnormalities were very mild and STFX administration was continued without any treatment. In the other patient, the abnormal value rapidly returned to normal after STFX administration was discontinued. These findings indicated that STFX can be used safety in routine practice by adjusting the administration within the approved dose based on patient characteristics. Good therapeutic effects can be expected in patients with respiratory tract infections.

[A case of IgG4-positive multi-organ lymphoproliferative syndrome associated with Kimura disease].

A 46-year-old man, who had been treated for Kimura disease, was found to have abnormal findings on a chest radiograph. Chest CT showed a mass shadow in the right lower lobe. Histological findings of a transbronchial biopsy specimen showed inflammatory cells infiltrating the alveolar septum. Inflammatory cells consisted of plasma cells, lymphocytes and eosinophils. He had had sustained eosinophilia and elevation of IgE for 8 years, and his serum IgG and IgG4 (3480 mg/dl) levels were elevated. Contrast-enhanced computed tomography showed multiple low density areas in both kidneys. Since immunohistochemical staining of the lung specimens revealed infiltration of IgG4-positive plasma cells (IgG4-positive/IgG-positive plasma cells=35%), we diagnosed IgG4-positive multiorgan lymphoproliferative syndrome. The mass shadow had disappeared after treatment with celestamine (0.25 mg betamethasone and 2 mg dexchlorpheniramine) for Kimura disease, but another solid consolidation appeared in the contralateral lower lobe 5 months later. After the steroid dosage was increased, the consolidation improved. To the best of our knowledge, this case is the first report of IgG4-positive multi-organ lymphoproliferative syndrome associated with Kimura disease.

Increased levels of platelet-associated immunoglobulin G in a patient with pulmonary adenocarcinoma.

This report describes a rare case of thrombocytopenia with high levels of platelet-associated immunoglobulin G (PA-IgG) in a patient with an adenocarcinoma of the lung. After surgical resection, the platelet count gradually increased and the serum PA-IgG levels decreased to within normal reference ranges. These findings suggest a relationship between pulmonary adenocarcinoma and PA-IgG.

[Case of pulmonary tumor thrombotic microangiopathy diagnosed by transbronchial lung biopsy].

A 69-year-old man was admitted to our hospital with dyspnea on effort. A chest high resolution CT showed enlargement of peripheral vessels and small nodules in both lower and peripheral lung fields. We diagnosed this case as pulmonary tumor thrombotic microangiopathy, because histological findings of specimen obtained by transbronchial lung biopsy revealed microscopic tumor emboli and intimal proliferation in small pulmonary vessels. After conducting systemic examinations, it was found that the patient had gastric cancer. Generally it is difficult to diagnose pulmonary tumor thrombotic microangiopathy in patients during life. To the best of our knowledge, this is the first case of pulmonary tumor thronbotic microangiopthy diagnosed on the basis of transbronchial lung biopsy.

[A case of Osler-Weber-Rendu syndrome: therapeutic embolization of the pulmonary artery and bronchial artery].

We encountered a case in which the symptoms of hypoxia and hemoptysis improved after performing repeated pulmonary artery embolizations and bronchial artery embolization. A 22-year-old man was hospitalized in our institution with high fever, headache and unconsciousness in May of 2001. Subendocranial abscess was diagnosed, so we performed antibiotic therapy and drainage, but at that time he showed symptoms of hypoxia. We diagnosed Osler-Weber-Rendu syndrome because of multiple small nodular shadows in his chest CT, multiple arteriovenous fistulae in both lungs on pulmonary arteriography, and telangiectasis. We performed pulmonary artery embolization 6 times, and his hypoxia and right to left shunts improved. In the course of our therapy, hemoptysis appeared and dilatation of vessels was detected in the left bronchial arteriography, so we performed embolization of the left bronchial artery and the symptom improved. We concluded that we should take care to detect not only pulmonary arterial lesions but also bronchial arterial leisions in the diagnosis and therapy of respiratory symptoms of Osler-Weber-Rendu syndrome.

[A case of MPO-ANCA positive vasculitis associated with diffuse alveolar hemorrhage and various cardiac conducting system abnormalities following propylthiouracil treatment].

A 50-year-old woman had been treated with propylthiouracil (PTU) for hyperthyroidism. She was admitted to our hospital because of hemosputum, and severe hypoxemia developed. The CT scan showed diffuse infiltration in both lung fields, bronchoalveolar lavage fluid revealed diffuse alveolar hemorrhage, and the level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high; and therefore diffuse alveolar hemorrhage associated with MPO-ANCA positive vasculitis induced by PTU was diagnosed. Following corticosteroid therapy initiated after the termination of PTU, the pulmonary infiltration rapidly improved and the patient's MPO-ANCA level returned to normal. Recrudescence of diffuse alveolar hemorrhage occurred following a reduction in steroids, but no recurrence was found after cyclophosphamide therapy was combined with steroid therapy. During the course of therapy, various cardiac conducting system abnormalities which correlate with the course of steroid therapy were found, indicating that cardiac conducting system abnormalities may be associated with MPO-ANCA-positive vasculitis.

[Measurement of anti-type II collagen antibody diagnosis and follow-up useful in a case of relapsing polychondritis].

A 68-year-old man had been suffering from swelling and deformation of both auricles, hoarseness, hearing loss, and a productive cough since November, 1999. Elevation of the inflammatory reaction was noted, together with swelling of the glottis and inflammation of the bronchial mucosa on bronchoscopy. Relapsing polychondritis was diagnosed when an auricle biopsy specimen demonstrated auricle chondritis. The laboratory findings revealed high titers of anti-type II collagen antibody. After steroid treatment, the symptoms improved and the titer of anti-type II collagen antibody decreased. The measurement of this antibody was useful for the diagnosis and follow-up of this disease. To prevent the impairment of organs and sudden death, early diagnosis involving the use of anti-type II collagen antibody and the commencement of therapy are important in this disease.

Welder's pneumoconiosis: diagnostic usefulness of high-resolution computed tomography and ferritin determinations in bronchoalveolar lavage fluid.

OBJECTIVE: We assessed the usefulness of high-resolution computed tomography (HRCT) and ferritin determinations in bronchoalveolar lavage (BAL) fluid for diagnosis of welder's pneumoconiosis. PATIENTS AND METHODS: We investigated 11 patients with welder's pneumoconiosis who were 34 to 67 years old and had been welding for 17 to 45 years. Ten patients were current smokers. We performed chest radiography and HRCT, and measured serum ferritin on all 11 patients. We obtained BAL fluid in 9 cases and transbronchial lung biopsy (TBLB) specimens in 7. Ferritin concentrations in BAL fluid were compared with those in welders without pneumoconiosis and other pneumoconiosis cases. RESULTS: HRCT revealed small centrilobular nodules in 9 cases, mild fibrotic changes in 3, and emphysematous changes in 3. Serum ferritin concentrations were elevated (>240 ng/ml) in 10 cases. Ferritin concentrations in BAL fluid were higher in welder's pneumoconiosis than in the occupational control group. CONCLUSION: In welder's pneumoconiosis, small centrilobular nodules are frequently seen on HRCT, and ferritin shows elevations in serum and/or BAL fluid. Such ferritin determinations are of value in diagnosis.