A 67-year-old woman who was followed as a patient with bronchial asthma for 1.5 years visited our hospital with progressive dyspnea. Although the chest radiography findings were normal, a chest computed tomography scan revealed a mass obliterating the intrathoracic tracheal lumen. The patient's symptoms disappeared immediately after tumor excision, and no recurrence was observed during a 1.5-year follow-up period. Microscopically, the tumor was composed of densely packed polygonal-, oval- and spindle-shaped cells that were positive for pan-cytokeratin, ?-smooth muscle actin and p63. These pathological findings confirmed the diagnosis of benign myoepithelioma. Chest physicians should recognize that benign myoepithelioma can develop in the trachea, although it is very rare.
Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease and is an important cause of morbidity worldwide. The aim of this study was to evaluate whether pulmonary rehabilitation (PR) improves the oxidant/antioxidant imbalance, exercise capacity and health-related quality of life (HRQL) in patients with different stages of COPD. Eighteen stable COPD patients participated in 8-week PR; the exercise intensity was set at 70% of the VO2 peak. Subjects were divided into 2 groups: moderate to severe (stages II/III: n = 12) and very severe COPD with FEV1 < 30% predicted (stage IV: n = 6). In patients at stages II/III, PR improved exercise capacity (6-minute walking test: 431.2 ± 26.6 vs. 489.1 ± 26.5 m, P < 0.01 and shuttle walking test: 329.2 ± 41.4 vs. 378.2 ± 41.5 m, P < 0.01) and HRQL, whereas no significant change was observed in erythrocyte lipid peroxidation and urinary 8-hydroxydeoxyguanosine, a marker for DNA damage. In contrast, PR for stage IV patients did not improve exercise capacity and HRQL, but significantly increased urinary 8-hydroxydeoxyguanosine (14.5 ± 1.7 vs. 24.3 ± 2.6 ng/mg Cr, P < 0.05). In both groups, erythrocyte antioxidants (superoxide dismutase, glutathione peroxidase, and catalase) did not change significantly after PR. Thus, urinary 8-hydroxydeoxyguanosine is a useful indicator for the PR-induced oxidative stress in COPD patients. In conclusion, appropriate exercise program in COPD patients can improve exercise capacity and HRQL without further increase of oxidative stress. However, PR for very severe COPD patients enhanced exercise-induced oxidative stress.
The aim of this study was to explore prognostic factors for non-small cell lung cancer (NSCLC) patients with brain metastases (BM) on the basis of EGFR mutation status. Among 779 consecutive NSCLC patients who underwent EGFR mutation screening, all 197 patients with BM were divided according to the EGFR mutation status. The prognostic factors, including patient characteristics at the time of BM diagnosis, treatment history, and radiologic features, were analyzed. Of 197 patients with BM, 108 had wild-type EGFR and 89 had EGFR mutation. The patients with EGFR mutation presented longer overall survival after BM diagnosis (OS) than those with wild-type EGFR, regardless of whether BM was synchronous or metachronous. For the patients with EGFR mutation, favorable prognostic factors in multivariate analysis were age<65 (p=0.037), good performance status (PS) (p<0.0001), cranial radiotherapy (p=0.020), previous chemotherapy?1 regimen (p=0.009), stable extracranial disease at BM diagnosis (p=0.022), and erlotinib therapy after BM diagnosis (p=0.0015). On the other hand, favorable prognostic factors for the patients with wild-type EGFR were only good PS (p=0.0037) and cranial radiotherapy (p=0.0005). Among patients treated with erlotinib after BM diagnosis, the patients with exon 19 deletion showed longer OS than those with exon 21 point mutation (p=0.019). The prognostic factors for NSCLC patients with BM were different according to the EGFR mutation status. Particularly in NSCLC patients with EGFR mutation and stable extracranial disease, regular cranial evaluation for detecting asymptomatic BM would lead to good prognosis. In addition, erlotinib therapy would be preferable in NSCLC patients with BM and EGFR mutation, especially those with exon 19 deletion.
Long-acting ?2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the ?2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of ?2-agonists. We hypothesized that differential responses to long-acting ?2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients.
Interstitial lung disease is the most common complication and cause of death among patients with scleroderma. Scleroderma-related interstitial lung disease has usually been treated with cyclophosphamide; however, its effect was evaluated to be modest and long-term administration of this drug is associated with adverse effects. Herein, we report our clinical experience of administering pirfenidone, which is an antifibrotic agent, in five patients with scleroderma-related interstitial lung disease. All patients demonstrated an increase in vital capacity.
Pulmonary arterial hypertension (PAH) trial has mostly enrolled patients with World Health Organization functional class (WHO FC) III or IV. However, PAH is rapidly progressive in nature even in patients with less severe forms at diagnosis. Following the recent studies in Western population, here we assessed the efficacy of bosentan in Japanese patients with WHO FCII PAH. In this open-label trial, bosentan 125 mg twice daily was administered for 12 weeks in 16 patients, and a hemodynamic evaluation was performed. Treatment was continued for a further 12 weeks, where the effect on exercise capacity was assessed in 13 patients. In 16 patients, mean pulmonary arterial pressure decreased from 40.4 ± 10.4 to 35.6 ± 12.6 mmHg (p = 0.018) and cardiac index increased from 2.54 ± 0.73 to 2.96 ± 0.82 L/min/m(2) (p = 0.023). Thus, pulmonary vascular resistance decreased from 792 ± 565 to 598 ± 558 dyn·sec/cm(5) (p = 0.006). In 13 patients followed up for 24 weeks, 6-min walking distance increased from baseline at Week 12 (p = 0.003) and Week 24 (p = 0.011). All patients were mildly symptomatic at baseline with dyspnea index (Borg scale) of 2.50 ± 1.58 and the specific activity scale (SAS) of 5.0 ± 1.4 METs. These values remained unchanged throughout the study. These results suggest that bosentan treatment was beneficial for Japanese patients with WHO FC II PAH and treatment should be started in the early stage of the disease.
Multidrug resistance (MDR) involves resistance to both isoniazid and rifampicin, which makes the treatment of tuberculosis very difficult. Extensive drug resistance (XDR) occurs when, in addition to isoniazid and rifampicin resistance, the microorganisms are resistant to a fluoroquinolone and an injectable agent (e.g., kanamycin, amikacin, or capreomycin). Generally, drug susceptibility testing takes more than 3-4 weeks after the initial cultivation. There is an urgent need to identify methods that can rapidly detect both the presence of Mycobacterium tuberculosis and the status of drug resistance.
The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study. The patients were divided into two groups on the basis of the EGFR mutation status: the mutation-positive group (n=19) and the wild-type group (n=69). The results of radiographic assessment via computed tomography (CT) and pulmonary function analysis were compared between the two groups. In the radiological evaluation, CT images at three levels were evaluated by two reviewers. Radiographic assessment revealed that the mutation-positive group tended to have milder emphysematous changes and a lower prevalence of interstitial changes compared with the wild-type group (P=0.13, 0.06). When the analysis was limited to the ipsilateral lung at the nearest CT level to the tumor, emphysematous changes were found to be less common in the mutation-positive group (P=0.02). The prevalence of the emphysematous and/or interstitial changes in the ipsilateral lung at the nearest CT level to the tumor was lower in the mutation-positive group compared to the wild-type group (P=0.005). In the pulmonary function test, the results were comparable between the two groups. In conclusion, according to our results, EGFR-mutant lung cancer was commonly observed in the areas where emphysematous and interstitial changes were absent. EGFR-mutant lung cancer may develop in radiographically normal areas of the lungs, even in smokers. It would be of importance to evaluate the EGFR mutation status in patients with no emphysematous or interstitial changes in the ipsilateral lung near the tumor, regardless of their smoking history. These results should be confirmed in a future prospective study.
A thin, 63-year-old man was receiving low-dose macrolide therapy for a diagnosis of chronic lower respiratory tract infection, but frequent exacerbations due to Streptococcus pneumoniae were observed. High-resolution computed tomography (CT) of the chest showed bronchiectasis and small centrilobular nodules in the right lower lobe. He had previously had several episodes of exacerbation of chronic lower respiratory tract infection, for which he had received antibiotic treatments (oral fluoroquinolones or intravenous cephems). However, he continued to experience recurrent exacerbations, and Pseudomonas aeruginosa was also isolated from his sputum. To improve his general condition, Hochuekkito, a herbal medicine, was initiated. His body weight and serum albumin level gradually increased, and after 6 months of administration, neither S. pneumoniae nor P. aeruginosa were isolated from his
A 25-year-old man presented with a 2-month history of bloody sputum and unilateral gynecomastia. High-resolution computed tomography (HRCT) of his chest showed multiple nodules and masses. On physical examination, no enlargement of the testes was noted, but a tiny calcified lesion in his left testis was detected on a genital CT scan. He was referred to the urology department with a suspected testicular germ cell tumor. An echogram showed a micronodule in his left testis. A testicular mixed germ cell tumor was diagnosed on the basis of the histological features of the tumor removed by high orchiectomy, and systemic chemotherapy with bleomycin, etoposide, and cisplatin (BEP) was initiated. Testicular germ cell tumor should be considered in the differential diagnosis of multiple pulmonary nodules or masses in young men. Because high orchiectomy is indispensable for the treatment of testicular germ cell tumor, aggressive investigative studies of the testis are essential in patients with pulmonary, mediastinal, and retroperitoneal germ cell tumors.
We report a case of fatal pulmonary infection caused by Mycobacterium abscessus in a middle-aged patient with acquired esophago-pulmonary fistula which contributed to repeated exacerbation. Acquired benign esophago-pulmonary fistula is uncommon. After a 55-year-old woman was diagnosed with pulmonary Mycobacterium avium disease in 1989 and improved with multidrug chemotherapy, she developed pulmonary M. abscessus in 2001. Despite multi-drug treatment, she suffered repeated exacerbation and her condition gradually deteriorated. Chest computed tomography (CT) showed esophago-pulmonary fistula which was comfermed by esophagoscopy. An M. abscess infection may give rise to adhesions between the tracheobronchial lymph nodes and the neighboring esophagus, with subsequent development of a traction diverticulum which may extend to the tracheobronchial tree. In the present case, aspiration of liquids through the fistula induced a cough reflex, and M. abscessus spread through the airway. It might be possible that esophago-pulmonary fistula is not only a complication of pulmonary M. abscessus infection but also an exacerbation factor.
For the past 10 years (2000-2009), 50 patients of pulmonary mycobacteriosis underwent surgical treatment at Ibarakihigashi National Hospital. Three MDR-TB cases received lobectomy and one case of MDR-TB received intracavity aspiration and thoracoplasty. One bronchial tuberculosis received sleeve lobectomy. Two cases with hemoptysis due to M. avium pulmonary disease underwent pulmonary resection (lobectomy and completion pneumonectomy). One nontuberculous mycobacteriosis case accompanied by lung cancer received lobectomy. In one case because cavity lesion remained after chemotherapy she received lobectomy. All of patients were discharged without complication after operation. For the purpose of definite diagnosis 41 cases (38 cases with a solitary pulmonary nodule and 3 cases with multiple pulmonary nodules) were received surgical procedures. Results of culture examination for the resected lesion were 4 M. tuberculosis complex, 8 M. avium and 4 M. intracellulare. There was only one case with M. avium who needed additional lobectomy because scattered lesions became worse after the previous pulmonary partial resection. The remaining patients were discharged without complication.
We report one Japanese familial line in which there were three pulmonary MAC patients and one suspected patient over two generations, most of whom were diagnosed with the nodular/bronchiectatic type. In all patients, life circumstances and bacterial strains differed at the time of diagnosis. This suggests that the genes thought to affect patient susceptibility to pulmonary MAC disease may be involved in this family line. Comprehensive genotypic analysis of the CFTR gene, HLA typing, and analysis of the NRAMP1 polymorphisms were performed in seven members of this family. The results suggest that female sex and menopause might be associated with onset of pulmonary MAC of the nodular/bronchiectatic type, and HLA-A26 antigen and diabetes mellitus might be involved in disease exacerbations.
We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.
A 67-year-old woman was admitted to our hospital because of progressive dyspnea, cough, bloody sputum, and backache. Chest radiography and CT scans showed bilateral diffuse interstitial shadows, bilateral pleural effusion and dilatation of the pulmonary artery. Echocardiography indicated pulmonary hypertension, and the serum tumor marker levels were elevated. We performed right cardiac catheterization, and withdrew some blood from a pulmonary artery catheter in the wedge position. We confirmed moderate pulmonary hypertension, and adenocarcinoma-like malignant cells were seen in the aspirated blood. The patient died of progressive respiratory failure despite supportive care. In addition to PTTM and lymphangiosis carcinomatosa, autopsy of the right lung revealed interstitial pneumonia and lipoid pneumonia, both of which were not reported before to be associated with PTTM.
A 77-year-old woman was admitted to our hospital because of an abnormal chest shadow. She complained of shortness of breath on effort. Chest CT showed patchy areas of ground-glass opacity in right S2 and S6. A high titer of antinuclear antibody with a discrete speckled pattern on immunofluorescent staining was disclosed, and she was positive for anticentromere antibodies. Pulmonary arterial hypertension was found by right heart catheterization. Biopsy by video-assisted thoracoscopic surgery was performed. About one month after surgery, she started to need to inhale oxygen due to gradually progressing dyspnea. Continuous PGI2 administration was not very effective, but administration of methylprednisolone and prednisolone induced improvement of her symptoms. Histopathologic examination of biopsy revealed extensive and diffuse occlusion of pulmonary veins. The pathological diagnosis suggested a pulmonary veno-occlusive disease. Clinical data suggested the association between systemic sclerosis sine scleroderma and probable pulmonary veno-occclusive disease.
A 29-year-old man with a history of resected bulbar hemangioblastoma was admitted to hospital with nighttime breathing disturbance, but with apparently normal breathing while awake. After diagnostic work-up, including polysomnographic testing, he was diagnosed as having central alveolar hypoventilation syndrome due to surgical resection for bulbar hemangioblastoma. Non-invasive positive pressure ventilation (NIPPV) via oronasal facemask was given for nocturnal ventilatory support. Two months after leaving our hospital, he was readmitted because of aspiration pneumonia. The pneumonia was successfully treated with antibiotics, but the desaturation during sleep worsened despite non-invasive ventilatory support. Higher bi-level positive pressure using a full facemask successfully alleviated sleep hypoventilation and apnea. To the best of our knowledge, this is the first case report of central alveolar hypoventilation syndrome due to surgical resection for bulbar hemangioblastoma.
A 58-year-old man presented with right backache and bloody sputum. Chest X-ray revealed a nodular opacity in the right lung. Since could not obtain a diagnosis by bronchoscopy, we performed a lower lobectomy. Histopathologically, there were irregularly shaped necrotizing granulomas and an area of acute hemorrhagic, eosinophilic abscess. We suspected paragonimiasis. The diagnosis of paragonimiasis miyazakii was confirmed by ELISA. This is a valuable case of suspected paragonimiasis confirmed pathologically.
To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC patients were evaluated at 14 sites (17 hospital departments) in a prefecture of Japan between December 2009 and August 2011. Complete data sets were obtained from 159 patients with NSCLC. The median age was 66 years, and 34.0 % of the patients were 70 years or older. The overall response rate to bevacizumab therapy was 41.6 %, and the disease control rate was 78.5 %. In 88 patients who received bevacizumab-containing chemotherapy as first-line therapy, the response and disease control rates were 55.0 and 78.9 %, respectively. The incidence of clinically significant (grade 3 or more) adverse events was generally low: proteinuria occurred in 2 (1.3 %) patients, hypertension in 2 (1.3 %), hemoptysis in 1 (0.6 %), and interstitial pneumonia in 1 (0.6 %). The time to treatment failure (TTF) in the 159 patients was 169 days, and the median overall survival (OS) was 580 days. In patients who received bevacizumab-containing chemotherapy as first-line therapy, the TTF and OS were 152 and 520 days, respectively. The difference in TTF between patients who received bevacizumab-containing chemotherapy as first-line therapy and those who received it as second-line or later-line therapy was not significant (p = 0.4971). With regard to first-line therapy, the difference in TTF between patients treated with carboplatin + pemetrexed + bevacizumab and those treated with carboplatin + paclitaxel + bevacizumab was not significant (p = 0.9435). We deduced that bevacizumab-containing chemotherapy is effective against NSCLC and also tolerable in clinical practice.
Here, we report 2 cases of drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine and allopurinol during tuberculosis treatment. Both patients also developed multiple drug hypersensitivity (MDH) to several antituberculosis drugs that were used at around the period of DIHS onset, and thus, the treatment could not be successfully completed. Our cases show that MDH can easily occur after development of DIHS. Considering that treatment for tuberculosis requires long-term management with several drugs, it is important to refrain from administering drugs that can cause DIHS during tuberculosis treatment.
Miliary brain metastasis is a rarity and refers to the presence of numerous small tumors in a perivascular distribution without intraparenchymal invasion and focal edema. Although the presence of epidermal growth factor receptor (EGFR) mutation and good response to gefitinib have been reported in non-small cell lung cancer (NSCLC) patients with miliary brain metastases, the influence of the EGFR mutations on the radiographic features remains unclear.
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