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This case is a 62-year-old man diagnosed with metastatic renal cell carcinoma. He was referred to our department due to the left renal mass pointed with ultra sound examination. Radiographical examination showed left-side 42 mm renal tumor with multiple lung tumors, suggesting renal cell carcinoma, cT1bN0M1 (pul). As an induction therapy, we selected Pembrolizumab plus Axitinib combination therapy. After 4 course of the therapy, the left kidney tumor shrank to 27 mm, and the lung metastasis disappeared with computed tomography imaging. For the next step, we performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell carcinoma, grade 2 with central necrosis. Since then, complete remission has been maintained without any treatment for 21 months.

Objective　This study aimed to evaluate the treatment outcome of latent tuberculosis infection (LTBI) in persons with fibrotic pulmonary lesions, treated with isoniazid (INH) or rifampicin (RFP) in Nishinari Ward, Osaka City.Methods　As part of a tuberculosis screening program by chest X-ray (CXR), we selected persons who met the following four criteria for initiation of LTBI treatment:①Anti-tuberculosis treatment has not been performed for more than one month in the past. ②CXR shows fibrotic pulmonary lesions.③Fibrotic pulmonary lesions with CXR have not changed for more than one year.④QuantiFERON TB Gold-in-tube (QFT) shows positive values (≥0.35 IU/mL).　Before treatment, the blood samples were within the standard values for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and serum creatinine. Treatment with INH was stopped when AST or ALT levels were elevated to more than 150 IU/L, or symptoms of liver dysfunction appeared even when AST or ALT levels were less than 150 IU/L. After liver dysfunction improved, treatment with RFP was started.　Treatment completion was defined as being dispensed with INH for ≥180 days or RFP for ≥120 days.Results　The 27 participants were all male and their age was 68.4±6.6 years. Of the 27 participants, 14 (51.9%) completed treatment with INH. Of the remaining 13 persons, nine (69.2%) stopped treatment with INH because of liver dysfunction. Nine restarted RFP treatment and all participants completed the treatment without interruption by liver dysfunction. In total, 23 (85.2%) completed the treatment.Conclusion　LTBI treatment with INH in persons with fibrotic pulmonary lesions in the area where people in financial need live was stopped because of liver dysfunction; however, changes from INH to RFP could improve treatment outcomes.

Background: Mycobacterium kansasii is the second most common nontuberculous mycobacterial pulmonary disease pathogen in Japan. Fibrocavitary disease is characteristic of M. kansasii pulmonary disease in male patients., Objective: To clarify the clinico-microbiological characteristics of M. kansasii pulmonary disease in recent years in a Tokyo hospital specializing in mycobacteriosis., Methods: A retrospective chart review was performed on 77 M. kansasii culture-positive cases from January 2003 to December 2010. Sequence analysis of the hsp65 gene using PCR-restriction enzyme pattern analysis (hsp65-PRA) was used to identify bacterial genotypes., Results: Seventy-four cases fulfilled the diagnostic criteria for inclusion. Female patients comprised 22% of cases (16 cases, 63.2 ± 24.6 years of age) and were older than male patients (58 cases, 55.5 ± 17.5 years of age). Although the peak distribution among men was patients in their 50s, female patients showed a bimodal distribution with increased occurrence in older women. Radiological examination showed that approximately 90% of male and younger female patients had fibrocavitary disease. However, elderly female patients tended to have nodular bronchiectatic disease. Genotype analysis revealed that all bacterial strains from both genders were subtype I., Conclusions: Compared to previous reports, the number of female patients with M. kansasii pulmonary disease had increased, with an unusual age distribution. These different age-related radiological findings might be due to host factors.

Background: Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used., Purpose: Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan., Patients and Method: We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted., Result: The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients., Conclusion: In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Objectives: To clarify whether rifabutin (RBT) can be used for treating tuberculosis in elderly Japanese patients in the clinical setting., Method: We performed a clinical chart review from Oct 2008 to Dec 2011, for patients who were diagnosed with tuberculosis and were prescribed rifabutin, at the Fukujuji Hospital (180 beds for respiratory medicine, including 60 for TB). Primarily, we focused on characteristics of patients, the cause for RBT indication, and success rate of treatment., Results: During the study period, 1129 patients were diagnosed with tuberculosis, and among these, 42 (3.7%) patients were prescribed RBT. Of these, 39 patients were included in this study (3 were excluded because their prescription was terminated within 2 weeks because of reasons other than adverse effects). In all, 69% patients were male. Mean age was 69 years, and mean body mass index was 19.1 +/- 3.4 kg/m2. RFP-related adverse effects were observed in 28 patients (72%; age, 73 years); these included gastrointestinal complications in 16, liver dysfunction in 7, skin rashes in 6, and renal dysfunction and thrombocytopenia in 1 each). Additional medication was required in 6 patients, and RBT-resistant TB was noted in 5 patients (28%; age, 60 years). A success rate of 71.4% was observed in cases of RFP-related adverse effects, and that of 81.8% was observed in cases of other reasons. Except for the patient who experienced renal dysfunction, RBT could be used in all patients who experienced RFP-related adverse effects., Conclusion: RBT showed a relatively good success rate, even in patients who experienced RFP-related adverse effects. Thus, RBT could be an alternative in cases of RFP-related adverse effects, even in elderly patients.

Objective and Methods: In our hospital, we analyzed the clinical factors of pulmonary tuberculosis (TB) diagnosed in non-TB wards and the incidence of TB infection among contact patients and healthcare workers (HCWs) using QuantiFERON-TB GOLD (QFT) testing., Material: This study included 16 patients who were diagnosed with pulmonary TB in non-TB wards in our hospital from January 2008 to May 2011. Eight contact patients and 120 HCWs were also enrolled., Results: The 16 TB patients comprised 11 men (77.7 years) and 5 women (74.4 years). Among them, only 9 patients exhibited positive results for Mycobacterium tuberculosis after the first acid-fast bacterial examination; the other 7 patients presented positive results only after the second or third examinations. Moreover, there were 3 cases of positive Mycobacterium avium samples in the first acid-fast bacterial examination. Among 16 pulmonary Mycobacterium tuberculosis cases, 8 were sputum smear and culture positive, 7 were sputum smear negative and culture positive, and 1 was sputum smear and culture negative. Moreover, 17 days had elapsed from the time of admission to the non-TB ward to diagnosis. TB contact examination revealed that QFT results for 2 HCWs changed from negative to positive., Discussion: We suspected pulmonary aspergillosis or old TB when presented with cases with a history of TB. Moreover, we believe that the periods from admission to diagnosis were delayed when the first acid-fast bacterial sputum examination was negative or showed non-tuberculous mycobacteria.

Objective: The QuantiFERON-TB (QFT) blood test is the major tool for the diagnosis of Mycobacterium tuberculosis (TB) infection among healthcare workers (HCWs). We used QFT tests to estimate the prevalence of TB infection among HCWs in our hospital., Material and Methods: Between 2003 and 2010, a total of 733 HCWs were enrolled in this study, and the prevalence of TB infection was analyzed according to the HCWs' jobs and work place., Results: Among the 152 men and 581 women who were evaluated, 3 female HCWs had a history of TB. Fifty-eight HCWs (8 men and 50 women with a mean age of 56.3 years and 48.4 years, respectively) demonstrated positive QFT tests. The positive rate was 7.9% for all staff members throughout the study period. The QFT test was positive for 1 HCW who was treated for TB in 1998, and negative and inconclusive for 2 other HCWs treated for TB in 2002. The positive rate for QFT was 16.0% in the TB ward (12/75, 95% confidence interval [CI]: 7.7-24.3%), 9.9% in the other wards (22/222, 95% CI: 7.9-11.9), and 1.1% in the outpatient department (1/91, 95% CI: 0-2.2). According to the job category, the QFT positive rates were as follows: doctors, 4.3% (3/70, 95% CI: 1.9-6.7); nurses, 10.3 (4/35, 95% CI: 6.0-16.8). The positive rate among doctors working in the TB ward was 10.0%, and that for nurses was 24.3%. This indicates that the prevalence of infection among HCWs in the TB ward was significantly higher than that in other work places. A comparison of the results from 2003 through 2007 revealed that for a total of 307 workers, 90.6% and 5.2% remained negative and positive, respectively, while 1.6% converted from negative to positive, and 2.6% from positive to negative., Conclusion: The positive rate among HCWs in the TB ward was higher than that in other wards. This is especially remarkable for doctors and nurses working in the TB ward.

Objectives: QuantiFERON-TB Gold (QFT-G) test has been recommended as a new tool for the diagnosis of latent tuberculosis (TB) infection. However, the risk of development of active TB in the future depends on the period after the infection. The aim of this study was to evaluate the risk of development of active TB in individuals who have been infected., Methods: Clinical development of TB in subjects with positive baseline QFT test results was retrospectively analyzed. The subjects included healthcare workers, since 2003, at the Fukujuji Hospital who were examined at employment., Results: In total, 667 subjects were examined using the QFT-2G test, and 62 subjects were QFT positive at the first examination. One was treated using isoniazid, and 61 subjects were followed up for an average of 4.7 years (286 person-years). None of the subjects developed active TB during the observation period, and the probability of clinical breakdown (95% confidence interval) was 0-0.0104/person-year., Conclusion: The risk of development of active TB among subjects with positive QFT-G test results at baseline was low. Treatment of latent TB infection is not recommended, unless an individual has been recently infected.

A 53-year-old female was admitted to our hospital complaining of disturbance of consciousness and hallucinations. About one year and 5 months ago she had adenocarcinoma of the lung, which was treated with surgery and chemotherapy. Computed tomography and magnetic resonance imaging revealed that her lung cancer had relapsed as caricinomatous meningitis and multiple lung metastases. She was treated with erlotinib, which rapidly resulted in disappearance of her symptoms. She still continues to receive erlotinib therapy without suffering from evident relapse 7 months after the initiation of the treatment.

We report a case of adrenal pheochromocytoma in a patient with neurofibromatosis type 1 (NF1). A 65-year-old female patient was admitted to our hospital for examination of a right adrenal mass. The adrenal tumor was incidentally discovered by abdominal computed tomography during examination for hypertension in another hospital. She had large multiple neurofibromatous lesions and café-au-lait spots on the trunk. We thought that it was difficult to make a skin incision on normal skin. Serum and urinary catecholamines were markedly increased. Magnetic resonance imaging revealed a solid round tumor 3 cm in diameter, located in the right adrenal gland. Laparoscopic right adrenalectomy was performed. Serum and urinary catecholamines returned to the normal range on post-operative day 10. Laparoscopic surgery may be a good option for NF1 patients with pheochromocytoma, especially those who had multiple neurofibromatosis on the trunk.

Bortezomib (Velcade(®)), a proteasome inhibitor, was launched for the treatment of relapsed or refractory multiple myeloma in Japan in December 2006. Prior to approval in Japan, high incidence (15.2%) and mortality (6.5%) of bortezomib therapy-related lung disorders were reported with private import treatment. Therefore the Velcade Lung Disorder Panel (the Panel) was established and the cases have been reviewed. A total of 3,556 patients, including 823 post-marketing surveillance (PMS) patients, have received bortezomib since April 25, 2009. The incidence of lung disorders associated with bortezomib therapy was 2.33% (3.77% in case of PMS). The panel reviewed the detailed information of 70 cases and classified the CT and X-ray images as follows: (1)Interstitial pneumonia; diffuse alveolar damage pattern, hypersensitivity pneumonia pattern and others (2)Vascular hyperpermiability; (non-cardiogenic) pulmonary edema pattern and capillary leak syndrome-like pattern (3)Hypoxia. These post-marketing data showed that the incidence of lung disorders in Japan was lower than expected based on private import data.

Objective: To analyze the clinical characteristics of multi- (extensively-) drug-resistant tuberculosis (M/XDR-TB) in our hospital., Materials and Methods: One-hundred and forty-one cases diagnosed with MDR-TB and thirteen cases with XDR-TB admitted to our hospital over the last nine years were enrolled in this study., Results: The gender distribution was: ninety-nine males and forty-two females in MDR-TB and nine males and four females in XDR-TB. The mean age was 52.0 years in males and 43.1 years in females in the MDR-TB patients, and 49.1 years in males and 42.0 years in females in the XDR-TB patients. There were 11 Chinese patients and 7 Koreans, as well as 8 patients from other countries abroad. Eighty-four (59.6%) MDR-TB patients and 9 (69.2%) XDR-TB patients had a smoking history. Diabetes mellitus was seen in 30 MDR-TB and 3 XDR-TB patients. The period from manifestation to the first visit to our hospital was 41.5 months on average in the MDR-TB patients, and 79.6 months in the XDR-TB patients. The average period from first diagnosis of TB to that of M/XDR-TB was 30.9 months in the MDR and 56.8 months in the XDR. Thirty (21.3%) MDR-TB patients and one (7.7%) XDR-TB patient were first diagnosed in our hospital. One-hundred and fifteen patients (81.6%) with MDR-TB and 6 (46.1%) with XDR-TB achieved negative sputum bacteriological conversion. Fifty-six cases (48.7%) of 115 MDR-TB and all (100%) of the XDR-TB patients underwent surgical treatment. Sixteen (11.3%) MDR-TB and 3 (23.1%) XDR-TB patients died. Thirty of the MDR-TB and 1 of the XDR-TB patients had never been previously treated for tuberculosis. Twelve (8.5%) MDR-TB and 5 (38.5%) XDR-TB patients had been treated with four drugs including isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), and either ethambutol (EB) or streptomycin (SM) in previous hospitals. Twenty-five (17.7%) MDR-TB and 5 (38.5%) XDR-TB patients had been treated with three drug regimens not including PZA in previous hospitals., Conclusion: M/XDR-TB is a man-made disease and can be infectious. Even the current standard regimens can produce M/ XDR-TB, if they are used improperly and carelessly. Great care should be taken to prevent XDR and MDR-TB.

We report a case of drug-induced pneumonitis caused by saikokeishikankyoto. A 68-year-old woman was admitted to our hospital complaining of dry cough, fever, and dyspnea after taking saikokeishikankyoto for 16 days. A chest radiograph showed widespread ground-glass shadows in both lung fields. Chest CT showed ground-glass opacities and thickening of the interlobular septum in both lung fields. Bronchoalveolar lavage fluids and transbronchial lung biopsy specimen showed findings consistent with drug-induced pneumonitis, therefore we diagnosed drug-induced pneumonitis caused by saikokeishikankyoto. Three years previously she had suffered from a similar illness after taking hangeshashinto. Ougon is suspected to be a causative component for her saikokeishikankyoto-induced pneumonitis, because it has been reported to be as a main cause for kampo-induced pneumonitis.

Tuberculosis can be cured by 6 months chemotherapy, consisting of isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), and ethambutol (EB). However, the patients with tuberculosis caused by multi-drug resistant tuberculosis (MDR-TB) bacilli, defined as resistance to at least INH and RFP, poorly respond to this resimen. To work out the strategy for the elimination of MDR-TB, chemotherapy resume must be changed from standard resume to special one, that are made from effective and stronger at least three anti-tuberculosis drugs. The duration of treatment will be 18-24 months usually. If decreasing of tuberculosis bacilli in sputum is failed under new effective resume, surgical treatment may be indicated. Treatment results of MDR-TB are not satisfactory. But we need to not to make new MDR-TB cases.

Unlabelled: The aim of this research was to clarify epidemiological characteristics of nontuberculous mycobacteriosis deaths in Japan. We analyzed the frequency of deaths due to nontuberculous mycobacteriosis (NTM) and regional differences using the Vital Statistics of Japan, published by the Ministry of Health, Labour and Welfare. The crude death rate was calculated using the Population Census of Japan published every 5 years (Ministry of Internal Affairs and Communications). In addition, changes in the proportions of death cases due to NTM disease among total autopsies were calculated using the Annual of the Pathological Autopsy in Japan (The Japanese Society of Pathology)., Results: NTM disease deaths appeared for the first time in 1970, with a marked increase by 2007, when there were 912 certified deaths. The increase was more marked after the mid-1990s. The number of women's deaths exceeded 300 in 1999 and reached 570 in 2007, while that of men exceeded 300 in 2001 and remained at nearly the same level until 2007. The death rate increased in all eight regions of Japan. The highest single-year regional death rate was 212 in Kanto in 2005. However, correcting by population size, the crude death rate was higher in the western regions of Japan than in the eastern ones. The proportion of NTM among total autopsies also showed an increase from 0.066% in 1993 to 0.304% in 2007. Included in the report is a comparison of trends of NTM deaths with those of major respiratory diseases including tuberculosis, emphysema, bronchial asthma and airway cancers.

Objective: We analyzed the clinical characteristics of extensively-drug resistant tuberculosis (XDR-TB)., Materials and Methods: Thirteen cases diagnosed with XDR-TB encountered in our hospital over the last ten years were enrolled in our study., Results: The patients included 9 males and 4 females. The mean age was 49.1 years old in males and 42.0 years old in females. Eight patients were Japanese and 5 were foreigners (Chinese, 3; Korean, 1; Nepali, 1). Nine cases had a smoking history and 6 had underlying diseases, including 1 with bacterial pneumonia, 3 with diabetes mellitus, 1 with chronic renal failure, and 1 with collagen vascular disease receiving immunosuppressive treatment. All 13 cases had been diagnosed at other hospitals. The mean period from TB diagnosis to XDR-TB diagnosis was 56.8 months, and the mean period from TB diagnosis to referral to our hospital was 81.6 months. Among the 13 cases, 3 had no drug sensitivity, 1 was sensitive to only 1 drug, 2 were sensitive to 2 drugs, 6 were sensitive to 3 drugs, and 1 was sensitive to 4 drugs. Nine of the 13 cases had surgical treatment. Six cases, all of whom had surgical treatment, showed negative conversion in sputum examinations. Three patients died, including two who had surgical treatment. Among the 3 cases with no drug sensitivity, 1 was cured after surgical treatment. Another case had been working in the same hospital with two other MDR-TB cases. Two of the three had the same RFLP pattern., Conclusion: XDR-TB and MDR-TB are man-made diseases. We need to take measures not to create more XDR strains and induce more MDR-TB cases.

An 82-year old man was admitted to our hospital for evaluation of progressive general malaise. He had previously been in good health. His chest roentgenogram showed reticular shadows and we suspected interstitial lung disease. On admission, his roentgenographic images showed deterioration compared with previous images. Acute lung injury was diagnosed by transbronchial lung biopsy, and steroid administration was started. He initially responded to treatment, but bilateral spontaneous pneumothorax occurred. Despite treatment, he died of respiratory failure. Amitani disease (idiopathic pulmonary upper lobe fibrosis) was suspected based on postmortem pathology, but his lung parenchyma was poor due to the presence of changes producing diffuse alveolar damage. We report and discuss this case because there are apparently no previous similar cases.

Background: Hospitalized cases of community-acquired pneumonia (CAP) of the elderly with a history of neurologic diseases have not been examined in detail in the past., Subjects and Methods: We extracted 15 cases with a history of neurologic disease (neurological history group, NH, all cases were over 70 years old), and 22 age-matched cases without a history of neurological diseases (non neurologic history group, non-NH) among 47 CAP patients who admitted to our hospital from home during the past year, and compared the two groups in terms of: (1) the score of severity of pneumonia by A-DROP system, (2) outcome (3) the duration of hospitalization, (4) the duration from end of treatment of antibiotic treatment to discharge, compared between the survival discharge cases out of two groups (11 vs 22 cases), (5) the bacteria that were detected., Results: (1) In the NH group, the score was significantly higher than that in the non-NH group. (2) In the NH group, 4 cases died while none did in the non-NH group. (3) In the NH group, it was 30.8 +/- 22.8 (average +/- standard deviation) days, significantly higher than the 17.6 +/- 5.9 days in the non-NH group, (4) In the NH group, it was 16.6 +/- 14.1 days, which was significantly higher than the 6.7 +/- 4.8 days in the non-NH group. (5) In the NH group, there was a high rate of detection of Klebsiella pneumoniae, Escherichia coli and Serratia marcesscense., Conclusion: An original comprehensive plan of treatment and care support is necessary for NH because the NH is different from other CAP conditions.

The SD-101 (Kenzmedico co. Ltd., Saitama, Japan), a non-invasive medical device capable of measuring respiratory parameters during sleep, has recently been developed. It operates while placed under the body like a bed pad equipped with 162 pressure sensors, with the patient in bed. To evaluate the efficacy and safety of the SD-101 for the diagnosis of sleep apnea syndrome (SAS), we enrolled 52 patients with suspected SAS (45 men and 7 women; mean age, 45.6 +/- 10.9 years) in this study. Each subject underwent measurement using the SD-101 and a polysomnograph simultaneously, and we analyzed and compared them. In addition, health-economic benefits of the SD-101 were estimated based on the results. A significantly strong correlation was obtained between the apnea hypopnea index of PSG and its of SD-101 (r = 0.86, p < 0.0001). No adverse event due to the SD-101 occurred, while use of the SD-101 greatly reduced "feeling of being constrained" and discomfort during examination (Wilcoxon test: p < 0.0001). These findings could indicate that the SD-101 is clinically useful and will make a contribution to health-economic benefits for SAS in Japan.

A 24-year-old man experienced gross haematuria and dysuria several times a year from the age of 19, presenting to this Department for the first time at age 21, when he was given standard antibiotic treatment for acute cystitis. Although urinary symptoms persisted, he failed to attend for follow-up. He attended another clinic at the age of 24 with increased urinary frequency. Transrectal ultrasonography revealed thickening of the bladder wall, concavity of the right bladder neck, and nodular changes extending from the left bladder neck to the left bladder wall, so he was referred to this department for further investigation. Mycobacterium tuberculosis was detected in the urine by the referring doctor, so the diagnosis was made of bladder tuberculosis (TB). We treated him with rifampicin (RFP), isoniazid (INH) and pyrazinamide (PZA) triple therapy for 2 months, followed by RFP and INH dual therapy for 4 months. His urinary frequency improved markedly after one month, and his bladder capacity was 420 ml after 4 months of treatment. After 2 and half year follow-up he remains well without any signs of relapse. To our knowledge, this is only the ninth case of teenage onset of urinary tract TB in Japan since 1995. As specified in Clause 22 of the Enforcement Regulations of the Tuberculosis Control Law, chemotherapy and surgical treatment of TB, the mainstays of treatment, should be administered in accordance with the 'Standards for the Treatment of Tuberculosis', issued by the Japanese Minister of Health and revised in 2004. The level of recognition of the 'Standards for the Treatment of Tuberculosis' is low, however. Although the incidence of TB of the urinary tract has dropped dramatically, as urologists we must be aware that treatment of this condition must be given in accordance with the Standards.

A 69-year-old man who had been followed for pneumoconiosis complained of dyspnea with effort. He was hospitalized because chest roentogenography showed pleural effusion. Further examination of this pleural effusion revealed an eosinophilic cell population and with a varied appearance. First, we suspected tuberculous pleuritis from the characteristics of the pleural effusion, but we could not demonstrate the existence of any acid-fast bacilli. During diagnostic studies, the patient's respiratory status gradually worsened, making it impossible to obtain essential findings. We initiated steroid administration as an antidote to progressive respiratory failure, and carried out bronchoscopy; As a result, we diagnosed secondary pulmonary cryptococcosis from bronchoalveolar lavarge and transbronchial lung biopsy. Pulmonary cryptococcosis with pleural effusion is rare, and this may be the first report of a case involving a type 1 allergy. We speculate that immunological dysfunction contributed to disease progression in this case.

Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). In addition, there are no reports that reveal clinicopathological differences between the various eosinophilic pneumonias. A problem persists in describing what the essential histological differences are between the different types of IEP. In this context, we examined the histological findings of acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) and contrasted them with the clinical features and radiological findings. Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases studied, while air space consolidation was seen in all CEP cases. Histologically, interstitial edema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, though the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls. From these findings, we conclude that the histological differences between AEP and CEP are the severity of basal lamina damage, the amount of subsequent intraluminal fibrosis, and the severity of interstitial edema. Especially in AEP, interstitial edema is an essential histological finding and this finding explains the acute onset, and the radiographic findings, as well as the rapid and complete improvement noted in such cases.

This case is a 56-year old woman. Steroids were being administered perorally after a thymectomy for myasthenia gravis. A fever of 38-39 degrees Celsius appeared during night, an abnormal shadow showed up on a chest X-ray and the patient was hospitalized. Gaffky No. 2 acid-fast bacilli were detected in the patient's sputum and the chest CT showed diffuse granular-like shadow, the patient was diagnosed as miliary tuberculosis and treatment with combined use of INH, RFP, EB, and PZA was started. Subsequently, fever started to subside and the miliary shadow on chest X-ray improved, however, six weeks after the start of treatment, hoarseness and dysphagia appeared. From the cervical CT and cervical angiography findings, the diagnosis of right subclavian artery impending ruptured aneurysm was made. Because the patient's sputum was acid-fast bacilli positive and because the patient had undergone thymectomy, it was decided that it would be difficult to treat her by a thoracotomy again. Therefore, a right subclavian artery stent insertion, right subclavian artery-right common carotid artery bypass creation operation was carried out with the objective of blocking the flow of blood to the aneurysm. The hoarseness and dysphagia improved post-operatively and the patient's progress is being monitored. Tuberculous aneurysms are a rare affection and they are mostly discovered when the autopsy is done, however, this case was diagnosed due to the manifestation of subjective symptoms. While this case was not diagnosed histopathologically, it is envisaged from the clinical progress that this was a tuberculous subclavian aneurysm complicated during the treatment for miliary tuberculosis.

Some large-scale clinical investigations on gefitinib-induced lung injury have been performed,which have much new information about anticancer drug-induced lung injuries and indicated significant problems in the development of new anticancer drugs. Analysis of gefitinib-induced lung injury revealed varying patterns of clinical features, ethnic differences in onset, risk factors for development and diagnostic difficulties in anticancer drug-induced lung injuries. Furthermore, we realized again underlying problems in the process of developing new anticancer drugs and the importance of post-marketing surveillance. We must elucidate the mechanism of anticancer drug-induced lung injuries to manage them effectively.

A 31-year-old woman was admitted to our hospital because of progressive dyspnea and chest X-ray abnormality. She was given a diagnosis of bronchial asthma 3 years previously. She had received medical treatment, but her dyspnea did not improve. Chest CT showed multiple thin-walled cysts and centrilobular nodules throughout both lungs. Video-assisted thoracoscopic lung biopsy revealed remarkable plasmacytic infiltration in the bronchioles and its surrounding interstitium. Small cystic lesions were detected and with remarkable mural plasmacytic infiltration. The immunohistochemistry showed infiltrated plasmacytes with polyconal characteristics. Her biochemical examinations showed polyclonal hyperimmunoglobulinemia and a high range of serum IL-6. In addition, CT scans showed multiple mediastinal and intraperitoneal lymphadenopathy. From these examinations, she was given a diagnosis of multicentric Castleman disease (MCD) with pulmonary involvement showing diffuse cystic change. This case showed an unusual pattern of MCD with pulmonary involvement. However, we suggest that MCD also should be considered as a differential diagnosis in cases with diffuse lung cystic changes.

A total of 101 strains of Mycobacterium avium complex (MAC), consisting of 86 M. avium and 15 M. intracellulare strains, were examined by DNA sequencing. The frequency of radiological types [cavitary (Cav) type and nodular bronchiectatic (NB) type] was similar in each species, thus, both species are equal causes of the two radiological types of MAC disease. We also examined serovars of the isolated strains using extracted glycopeptidelipid antigens and thin layer chromatography. Cav type patients discharged a single serovar MAC, while NB type patients discharged two serovar MACs simultaneously. RFLP pattern obtained by the use of IS1245, revealed no clustering of the strains specific for Cav type and NB type. Histopathological examinations of the bronchial lesions in 40 MAC cases and 49 multi-drug resistant tuberculosis (MDR-TB) cases were performed on the surgically removed lung specimens. Lymphocytic infiltration, epithelioid cell granuloma formation, epithelial desquamation and ulceration, as well as smooth muscle atrophy as a cause of bronchiolectasis, were observed more often and were more severe in the peripheral bronchial walls of the NB type than the Cav type of MAC, and as compared with those of MDR-TB cases.

We investigated the clinical, laboratory and radiological findings of 273 newly diagnosed cases of pulmonary Mycobacterium avium complex (MAC) disease, who were diagnosed in our hospital during 7 years from January 1996 to December 2002. Radiological findings of all cases were classified at the time of diagnosis into 2 patterns, the cavitary (Cav) type and the nodular bronchiectasis (NB) type. Clinical and laboratory findings at the time of diagnosis of 44 death cases were compared with those of 273 newly diagnoses cases, to analyze the prognostic factors of this disease. MAC disease cases showed a marked increase in number in recent years, but only in women. Mean age at the first visit was 65.7 years in men and 63.2 years in women, and when limited to fatal cases, it was 72.3 years in men and 69.4 years in women. Low body weight in terms of body mass index (BMI) and moderately low serum albumin level were found at the time of the first hospital visit in all the newly diagnosed and death cases. In the fatal cases, the peripheral blood lymphocyte counts revealed a relatively smaller number than the normal range, and the PPD skin test showed a negative reaction in 57.7% of all cases, suggesting the presence of lowered cell-mediated immunity at the time of diagnosis. Whether malnutrition occurs as a result of MAC disease or the individuals with lower nutrition level are easy to develop to MAC disease remains to be clarified. In regard to radiological findings, many cavitary (Cav) type cases were found in men and nodular bronchiectasis (NB) type in women among newly diagnosed cases, while the cavitary type was observed in many in both men and women fatal cases. The mean duration period from diagnosis to death was 28.3 months in men and 60.2 months in women, showing a longer survival after diagnosis, perhaps due to earlier hospital visits by women. The average age at death was 74.4 years old in men and 73.8 years old in women, and the two radiological patterns did not change throughout the entire disease course.

We evaluated the clinical features of pneumocystis jiroveci pneumonia (PCP) as a complication of glucocorticoid therapy for interstitial pneumonia We analyzed 74 interstitial pneumonia patients receiving glucocorticoid therapy, of whom 7 patients developed PCP. At the time of PCP diagnosis, the average duration of the glucocorticoid therapy was 71 days and the average daily dose of predonisolone was 37 mg. Circulating CD4+ lymphocyte counts were 370/microl on the average and more than 200/microl in three cases. PCP cases showed less circulating lymphocyte counts four weeks after the initiation of the therapy. Any cases receiving sulfamethoxazole-trimethoprim (TMP-SMX) did not develop PCP. In conclusion, interstitial pneumonia patients, who are treated with glucocorticoid, are benefit from TMP-SMX as PCP prophylaxis, but CD4 + lymphocyte counts greater than 200/microl is no reason to denying PCP.

Recently, a noninvasive medical device (SD-101) capable of detecting breathing pattern changes in a subject lying supine or on the side has been developed. We therefore tested whether the SD-101 would be useful for diagnosing sleep apnea syndrome (SAS). Seventy patients who had been suspicious of SAS were enrolled (M/F = 61/9, mean age +/- SD = 46.6 +/- 14.7 y/o). They took 2 distinct screening tests for SAS (using the SD-101 and one of the most popular screeners for SAS in Japan (Apnomonitor III: AP, Chest Co., Tokyo)) and a simultaneously performed standard polysomnography (PSG). All patients were then asked to respond to a questionnaire on awareness of invasiveness experienced during each study (both from the screeners and from the standard PSG). The data were then compared with those from PSG mainly using correlation coefficients and the x2 test for analysis of subjective invasiveness. Statistical significance was defined as a p value of less than 0.05. As a result, the apnea-hypopnea index (AHI) from SD-101 (r=0.947, p<0.0001) had a significantly higher correlation coefficient (p<0.0001) than that from the AP (r=0.601, p<0.0001) in relation to that from PSG. The SD-101 had a significantly lower invasiveness than either AP or PSG (p<0.0001). In conclusion, SD-101 could be much more useful for checking AHI than other conventional screeners, such as AP, which suggests that SD-101 is more useful for defining SAS.

The current status and measures for anticancer drug-induced lung injury and radiation pneumonia in cancer treatment were reviewed. Interstitial pneumonia induced by anticancer drugs is pathologically classified into the following: chronic interstitial pneumonia (CIP) or nonspecific interstitial pneumonia (NSIP), eosinophlic pneumonia (EP), bronchiolitis obliterans-organizing pneumonia (BOOP), diffuse alveolar damage (DAD), and hypersensitivity pneumonia (HP). In these pulmonary reactions to anticancer drugs, interstitial pneumonia manifested by DAD, which shows the acute or chronic clinical course, presents high mortality rates. Therefore, special care should be taken when DAD develops. Radiation pneumonia has two clinical phases, an acute phase of injury termed radiation pneumonitis, and a chronic phase of injuring termed lung fibrosis. It is usually confined to the irradiated area. On the other hand, sporadic radiation pneumonitis occurring outside the irradiated area has been reported besides classic radiation pneumonitis. Pathologically, it shows lymphocytic alveolitis or BOOP. Although radiation pneumonia has a good prognosis, mortality is rarely observed when lesion spreads outside the irradiated area.

The multinational, multi-institutional clinical Phase II trial of gefitinib monotherapy, IDEAL (IRESSA Dose Evaluation in Advanced Lung Cancer) 1, included Japanese and non-Japanese patients with advanced non-small-cell lung cancer (NSCLC) pretreated with one or more chemotherapy regimens, at least one including platinum. To investigate whether survival is affected by gender or histological type of cancer, a retrospective, exploratory subset analysis was conducted including only Japanese patients from IDEAL 1 (n = 102 in total, 51 each in 250 and 500 mg/day groups). The median survival time of the 102 patients was 12.0 months and the one year survival rate was 50%. The median survival time was 13.8 months for the 250 mg/day group and 11.2 months for the 500 mg/day group and the one-year survival rate was 57% and 45% respectively. Survival was longer in patients with adenocarcinoma than those with other histological types of cancer, and was longer in those with symptom improvement than without. The median survival time in females was longer than that in males. The results suggest that gefitinib could be superior to classical anticancer agents with regard to not only the response rate but also survival time in patients with NSCLC, particularly adenocarcinoma, previously treated with chemotherapy. Further studies are needed to identify factors affecting survival.

A 69-year-old man was admitted complaining of macroscopic hematuria. Cystoscopic examination revealed a non-papillary tumor at the anterior wall of the urinary bladder. A pelvic computed tomographic (CT) scan showed marked thickening of the anterior bladder wall. Radical cystectomy and bilateral ureterocutaneostomy were performed. Histopathological examination revealed signet ring cell carcinoma of the bladder, stage pT3bN1M0. This tumor is rare, and has a poor prognosis. Our patient has been well without any evidence of disease 6 months after surgery. To the best of our knowledge, there are 44 reported cases, and our case is the 45th in Japan.

Since the incidence of tuberculosis (TB) has markedly decreased over the last half-century, dedicated TB hospitals in Japan have been reducing the beds or have been merging with other hospitals. In accordance with this situation, less than 30% of medical school hospitals (MSHs) have facilities for infectious TB patients. In the meantime, and contrary to the previous trend, elderly TB patients or those who have serious underlying diseases have been increasing. MSHs have therefore not only to take care of these patients, but at the same time they have to reform their TB education system in addition to upgrading TB infection control. To elucidate the current problem regarding TB in MSHs, the survey in the current study was performed for 80 MSHs in Japan in January 2002. Two sets of questionnaires were prepared and delivered to doctors in these hospitals. One set mainly asked about the status of TB examination and education, and was aimed at doctors in the division of respiratory diseases of the department of internal medicine (Rs); and the other mainly asked about the status of TB infection control and was aimed at doctors in the divisions of infectious diseases, or whoever in charge of hospital infection control (Is). Response rates from Rs and Is were 75.0% (60/80) and 65.0% (52/80), respectively. Seventy-three point three percent (44/60) of Rs and 73.1% (38/52) of Is were working in hospitals without TB beds. Because of the current incidence of TB, the number of TB patients they examined in a year was small (35/60 of hospitals examined less than 20 TB patients in a year). Although there were some experienced doctors on TB in each hospital, most MSHs had only a small number of experienced nurses. Nevertheless, 89.3% of doctors in MSHs (a total of 100/112 Rs and Is) believed that they required TB rooms exclusively for TB patients who have some underlying diseases, and for TB education. Regarding the role of MSHs for TB patients care, the majority of doctors (70.5% of Rs and 68.4% of Is) considered MSHs should be able to offer treatment to TB patients with underlying complications. As to the educational aspect, most medical schools (MSs) devoted little time to lectures on TB (the median was 1 to 1.5 hour); on the other hand, some MSs (31.8%: 14/44 of MSHs without TB rooms) included a clinical practices in TB hospitals for TB education, although its term was short. Regarding TB infection control issues, most of the MSHs had active infection control committees in their hospitals and TB was thought to be one of the most important targets for these committees. About 40% (20/51) of these hospitals over the past few years had experienced nosocomial TB infection due in part to the so called "Doctor's delay". As one of the strategies to prevent nosocomial TB infection, special education sessions, not only for staff and residents but also students, were therefore performed in 60.8% (31/51) of MSHs. As to the evaluation of the tuberculin skin test (TST) status of medical students, the two-step TST was performed in 47.1% (24/51) of MSs (as most Japanese underwent their BCG vaccination in their childhood) and 54.9% (28/51) of MSs had a BCG revaccination policy for TST negative students. Although steps toward reforms in TB issues in MSHs were slow, some minor progress had been made as compared with previous surveys performed by us and others. Even though the numbers of TB patients examined in MSHs have been smaller than before, MHSs still have to take care of some TB patients with some complications. A great deal of effort still needs to be expended to establish efficient and effective TB education and infection control systems. Even though many ideas have been put forward to improve the current situation, one of the most successful answers is to set up small number of special rooms, not only for TB patients but also for other airborne infectious diseases, in all MHSs. The other clue is to establish an intimate collaboration between MSHs and TB hospitals with regard to clinical TB education not only for medical students but also for medical staff.

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor that is reported to be well tolerated and active in patients with chemotherapy-resistant non small cell lung cancer. On the other hand, gefitinib was also reported to produce a severe adverse event, interstitial lung disease, in less than 2% of treated patients. Given these circumstances, it is important to evaluate this drug and to establish its use clinically. We do not have sufficient data to evaluate gefitinib at this time. Phase III study of second/third line or maintenance therapy using gefitinib is required for such an evaluation. The development of individualized therapy with gefitinib might be also be required.

It is widely known that patients with idiopathic pulmonary fibrosis (IPF) are frequently associated with lung cancer. Although a complication with lung cancer is an important prognostic factor for IPF, standard treatments for lung cancer cannot be given because of IPF. Especially, the administration of many anticancer agents is limited by a complication with IPF, which is recognized as a risk factor for the development of fatal lung injury in cancer chemotherapy. Epidemiological studies reveal that cigarette smoking and occupational and environmental exposure to toxic substances are common risk factors for both IPF and lung cancer. It has been assumed that metaplasia in fibrous lesions is pathologically a precancerous lesion, but it is necessary to prove several genetic abnormalities in the process of carcinogenesis in order to clarify that. Currently, several genetic abnormalities in IPF, including in p53, K-ras, FHIT and transforming growth factor (TGF)-beta 1 type II receptor, have been reported.

Patients diagnosed as influenza who were prescribed zanamivir were surveyed from December 2001 to April 2002 in Japan as the same 2000/2001 influenza season. A total of 751 survey questionnaires were returned. We analyzed the efficacy of zanamivir against 367 patients who were diagnosed as influenza by rapid diagnosed kit and took zanamivir within 48 hours after onset of symptoms. Following the first zanamivir treatment, symptom relief was reported by 24.0% of the patients within 12 hours, 52.6% within 24 hours and 79.6% within 48 hours. The patients reported that the severest influenza symptom was fever, 28.4% of the patients started to feel reduction of fever within 12 hours, 62.2% within 24 hours. All of the 751 patients, 98.8% reported that the Diskhaler could be used as instructed by the doctor or pharmacist and 91.3% found the device easy or very easy to use. These results showed that the effect of zanamivir started very fast and the diskhaer was well accepted. This was the same as the previous results.

A 55-year-old man was admitted to our hospital because of progressive dyspnea. Chest radiography showed interstitial shadows in the upper lobe. The pathological diagnosis of lung biopsy specimens obtained from upper and middle lobes by video-assisted thoracoscopy was non-specific interstitial pneumonia, group 2. Administration of glucocorticoids improved the symptoms, the chest radiography findings, and the serum KL-6 level. This patient may belong to the new category of idiopathic interstitial pneumonia, though he exhibited several features of idiopathic pulmonary upper lobe fibrosis originally described by Amitani et al.

Histopathological examinations were carried out on 2 cases of Mycobacterium avium complex (MAC) disease of nodular bronchiectasis (NB) type on radiograms. The removed lung specimens revealed histological findings of granulomatous bronchiolopneumonia, consisting of epithelioid cell granulomas with lymphocytic infiltrations without exudation in the alveolar areas surrounding the respiratory bronchiole. The central bronchiolar walls were also affected by epithelioid cell granulomas with lymphocytic infiltration, occasionally showing polypoid protrusion into the bronchiolar lumen accompanying emphysema in the peripheral alveolar area. Bronchial lesions seemed to progress from peripheral to central airway with consequent atrophy and disappearance of intramural smooth muscles, resulted in bronchioloectasis. These histological findings well correspond to radiographical 'nodular bronchiectasis'. Large histiocytic granulomas without caseous necrosis developed in some area, which are not usually found in tuberculosis lesions. Epithelioid cell granulomas were occasionally found in the hilar lymph nodes as well as in the walls of lymphatic vessel in the pulmonary interlobular tissues, indicating intrapulmonary lymphatic spread of the mycobacteria.

Nine patients undergoing video-assisted thoracoscopic surgical (VATS) lung biopsy over a five-year period from 1997 to 2001 with the ultimate diagnosis of usual interstitial pneumonia without underlying connective tissue disease were identified. In two of nine patients, acute exacerbation occurred six days after VATS lung biopsy. We reviewed the clinical records and pathology of all nine cases, and found that the two cases of exacerbation had higher peripheral white blood cell counts and KL-6, lower PaO2, VC and FEV 1, and a longer inhalation of FIO 2 = 1.0 during VATS, and needed a longer period of chest drainage after VATS. Abundant inflammatory cell infiltration and fibroblastic foci were observed in the exacerbation cases. Thus, patients with usual interstitial pneumonia of the idiopathic type, who have high disease activity and low pulmonary function, may be at high risk of acute exacerbation following VATS lung surgery.

Two different processes have been proposed for pathogenesis of Mycobacterium avium complex (MAC) disease which show the middle lobe syndrome: 1) middle lobe bronchiectasis followed by MAC infection and 2) MAC disease resulted in secondary bronchiectasis. Two surgical specimen from MAC cases showing middle lobe syndrome were studied histo-pathologically. The first case was a 60 year-old female with frequent bloody sputum, who had been diagnosed as bronchiectasis in her childhood. Pathological examination of the resected middle lobe showed prominent cylindric bronchiectasis in the indurated middle lobe, and epithelioid cell granulomas were scattered limited to the fibrous bronchial walls, without any granulomas in the lung parenchyma. These findings suggested a secondary infection of MAC to the non-specific pre-existed bronchiectasis. The second case of a 55 year-old female having repeated bloody sputum, who was diagnosed to be tuberculosis but no improvement with anti-tuberculosis drugs. Pathological examination of the middle lobe showed scattered epithelioid cell granulomas with lymphocytic infiltration in the lung parenchyma. A few epithelioid cell granulomas were also found in the mucosa of middle lobe bronchi. In this case, pulmonary MAC lesions seemed to precede the central bronchial lesion with later development of bronchiectasis. Summarizing above findings two different mode of pathogenesis ways may be considered; one is non-specific bronchiectasis followed by middle lobe MAC disease and the other is pulmonary MAC lesion in the middle lobe as a primary change.

Irinotecan and its active metabolite, SN-38, were reported to have the absorption characteristics of weakly basic drugs. Moreover, stasis of these compounds is thought to induce damage to the intestinal mucous membrane. The purpose of this report was to examine whether oral alkalization (OA) combined with control of defecation (CD) might prevent irinotecan-induced side effects. From day one of irinotecan infusion to day four, OA & CD were practiced using orally administered sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid. Thirty-two lung cancer patients were treated with irinotecan in combination with cisplatin in the absence of OA & CD (Group A). Thirty-seven patients matched for background characteristics were treated with the same regimen in the presence of OA & CD (Group B). Group B had a reduced incidence of delayed diarrhea (Grade 2 < or = Group A 32.3% vs. Group B 9.4%), nausea, vomiting, and myelotoxicity, especially granulocytopenia compared with Group A. In addition, dose intensification was well-tolerated in Group B. Tumor response rates for non-small cell lung cancer were 59.3% (16/27 patients) in Group B against 38.5% (10/26 patients) in Group A. OA & CD appears to reduce the irinotecan-induced side effects, especially delayed diarrhea. Risk factors statistically associated with delayed diarrhea include advanced age and the use of irinotecan without OA & CD.