[A Case Report of Metachronous Multiple Cancers Including Triple Lung Cancers, Gastric Cancer, and Double Urothelial Cancers].

A male patient in his 60s at the time of the first medical examination had a smoking history of 50 years with 25 cigarettes a day. He was diagnosed with double urothelial cancers. In 200a, total left pelvic ureterectomy(pT2N0M0, Stage Ⅱ)and transurethral bladder tumorectomy(pTisN0M0, Stage Ⅰ)were performed. For his gastric cancer with malignant pleural effusion(cT3N0M1, Stage Ⅳb), in 200a plus 2, downstaging was acquired after chemotherapy. In 200a plus 5, subtotal gastrectomy D1 dissection was performed(W/D adenocarcinoma, pT2N0M0, Stage ⅠA, Ef 1). For the first lung cancer, in 200a plus 5, thoracoscopic lung wedge resection of the left lower lobe was performed(P/D adenocarcinoma, pT1aN0M0, Stage ⅠA1, R0, Ef 1). For the second lung cancer, in 200a plus 13, thoracoscopic lung wedge resection of the right upper lobe was performed after chemotherapy(P/D adenocarcinoma, pT1bN0M0, Stage ⅠA2, R0). For the third lung cancer, in 200a plus 17, immunotherapy was performed for the left upper lobe lung cancer(P/D adenocarcinoma, cT3N1M1a, Stage ⅢA). All the cancers were diagnosed as primary lesions by immunohistological examination. For the metachronous multiple cancers, multidisciplinary treatment was necessary for each cancer considering the patient's physical condition. Moreover, strict follow-up was necessary because of the high risk of carcinogenesis.

[A Case of Pulmonary Enteric Adenocarcinoma with Soleus Muscle Metastasis].

Pulmonary enteric adenocarcinoma is a unique pulmonary adenocarcinoma subtype and has histopathological findings that are similar to those of colorectal adenocarcinoma. A man in his 50s visited our hospital because of discomfort in his right lower leg for the last 9 months. Imaging studies revealed a mass in his right soleus muscle, and needle biopsy was performed. Histological findings revealed adenocarcinoma, and immunohistochemical staining showed that the tumor cells were positive for CK20 and CDX-2. The tumor was first suspected to be metastasis of gastrointestinal malignant tumors. FDG-PET/CT showed increased FDG uptake in the right soleus muscle mass and presented with increased FDG uptake in a right upper lobe mass and right mediastinum lymphadenopathy. There were no findings in other organs. Scraping cytology of a transbronchial biopsy indicated adenocarcinoma. Upper and lower gastrointestinal endoscopy showed no findings of malignancy. He was finally diagnosed with pulmonary enteric adenocarcinoma(cT3N2M1b, Stage ⅣA). Treatment with cisplatin(CDDP), pemetrexed( PEM), and bevacizumab(BEV) was initiated. After 4 courses of the regimen, the tumor was partially reduced, and the patient showed stable disease(SD).

Molecular typing of methicillin-resistant Staphylococcus aureus: Comparison of PCR-based open reading frame typing, multilocus sequence typing, and Staphylococcus protein A gene typing.

The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA.

Radiopathological Features and Identification of Mycobacterial Infections in Granulomatous Nodules Resected from the Lung.

BACKGROUND: Pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG). Mycobacterial infection is a common cause of granulomas. OBJECTIVE: The purpose of this study was to evaluate the radiopathological features and the methods for identifying mycobacterial infections in granulomatous nodules resected from the lung. METHODS: Thirty-five solitary lesions resected because of suspected lung cancer were enrolled, including 22 nonfungal granulomatous lesions and 13 benign lesions as controls. The radiological, microbiological, and histological findings were reviewed. To identify mycobacterial infection, immunohistochemical (IHC) staining, IS6110 polymerase chain reaction (PCR), and real-time PCR for the detection of Mycobacterium tuberculosis (TB) were performed using formalin-fixed and paraffin-embedded tissue specimens. The correlations between the radiopathological features and the median maximum standardized uptake value (SUVmax) of 18F-FDG PET were also evaluated. RESULTS: Mycobacteria were isolated from the cultures of 10 of the granulomatous lesions, including TB from 2 and Mycobacterium avium complex from 8. The mean size of the nodules in the culture-positive group was significantly larger than that of those in the culture-negative group (30.5 ± 13.1 vs. 15.1 ± 6.3 mm, p = 0.003). IHC stainings were positive in 15 granulomas. Eight granulomas were positive in IS6110 PCR, and 7 of them were also positive in real-time PCR. SUVmax was ≥2.5 in all of the PCR-positive granulomas. CONCLUSION: The most frequent cause of granulomatous lesions was mycobacterial infection. It seemed that the culture result was associated with nodule size and that the results of IS6110 were associated with 18F-FDG-uptake.

First report of KPC-2 Carbapenemase-producing Klebsiella pneumoniae in Japan.

We investigated a novel Japanese isolate of sequence type 11 (ST11), the Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing K. pneumoniae strain Kp3018, which was previously obtained from a patient treated at a Brazilian hospital. This strain was resistant to various antibiotic classes, including carbapenems, and harbored the gene blaKPC-2, which was present on the transferable plasmid of ca. 190 kb, in addition to the blaCTX-M-15 gene. Furthermore, the ca. 2.3-kb sequences (ISKpn8-blaKPC-2-ISKpn6-like), encompassing blaKPC-2, were found to be similar to those of K. pneumoniae strains from China.

Serodiagnosis of Mycobacterium avium complex pulmonary disease in rheumatoid arthritis.

BACKGROUND: Mycobacterium avium complex (MAC) pulmonary disease (PD) is often difficult and complicated to diagnose or to discriminate from follicular bronchitis, bronchiectasis, or other conditions associated with rheumatoid arthritis (RA) lung in the clinical setting. OBJECTIVE: We investigated whether a serologic test for anti-glycopeptidolipid (GPL) antibody was useful for distinguishing MAC-PD from RA lung in diagnosis. METHODS: Serum IgA antibody to MAC-specific GPL core antigen was measured by an enzyme immunoassay. Antibody levels were measured in sera from 14 RA patients with MAC-PD (RA + MAC), 20 RA patients with bronchial or bronchiolar lesions without MAC-PD (RA w/o MAC), 20 RA patients without pulmonary lesions (RA only), and 25 healthy volunteers (HV). RESULTS: The levels of serum anti-GPL antibodies were higher in the RA + MAC group than in the RA w/o MAC, RA-only, and HV groups (2.87 ± 2.83 vs. 0.50 ± 0.45, 0.31 ± 0.24, and 0.38 ± 0.10 U/ml, respectively; p < 0.001). With the cutoff point in receiver-operating characteristic analysis set at 0.7 U/ml, the serologic test differentiated RA + MAC from RA w/o MAC with a sensitivity of 100% and specificity of 90%. CONCLUSIONS: This serologic test for anti-GPL antibody is useful for diagnosing MAC-PD in RA.

[Fatal nontuberculous mycobacterial lung disease caused by Mycobacterium kyorinense: a case report with five years of follow-up].

An 85-year-old man with dementia first visited our hospital 5 years ago, complaining of hemoptysis. He was hospitalized 2 years later owing to fever, cough, and dyspnea. A chest computed tomography scan showed infiltration with a cavity in the left upper lobe. He was diagnosed with nontuberculous mycobacterial lung infection on the basis of the presence of acid-fast bacilli in the sputum and repeated bronchoalveolar lavage specimens; however, we were unable to identify the isolate by DNA-DNA hybridization. Although his general condition had slightly improved after treatment initiation, intermittent chemotherapy owing to the adverse effects of the drugs and dementia led to rapid disease progression and death. After his death, the isolated mycobacterium was identified as Mycobacterium kyorinense by sequence analysis of the hsp 65 and rpoB genes.

Feasibility study of adjuvant chemotherapy of S-1 and carboplatin for completely resected non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer (NSCLC) of pathological stage IB-IIIB. METHODS: S-1 was given orally at a dose of 80 mg/m²/day for 2 weeks, followed by a 2-week period of no treatment. Carboplatin was given intravenously on day 8 at an area under the curve of 6. This regimen was repeated for four to six 28-day courses. RESULTS: Seventeen patients were enrolled in this study. Fourteen of them completed at least 4 cycles of chemotherapy. Nine patients had grade 2 and three patients had grade 3 thrombocytopenia, respectively. Severe nonhematologic toxicities were uncommon. Treatment was delayed in a few patients because of prolonged thrombocytopenia. CONCLUSION: We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy.

Impairment of Social-Related Quality of Life in COVID-19 Pneumonia Survivors: A Prospective Longitudinal Study.

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients' health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease.

BACKGROUND: There is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease. METHODS: We conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model. RESULTS: Mean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups. CONCLUSIONS: Mild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.

Factors associated with positive inhalation provocation test results in subjects suspected of having chronic bird-related hypersensitivity pneumonitis.

BACKGROUND: Chronic bird-related hypersensitivity pneumonitis (BRHP) is often misdiagnosed as other interstitial lung diseases. While the utility of the inhalation provocation test (IPT) has been reported, the test is not commonly performed. In this study, we aimed to identify significant clinical variables associated with positive inhalation provocation test results in subjects suspected of having chronic BRHP. This would help clinicians decide whether to perform IPT in patients suspected of having chronic BRHP in real-life practice. METHODS: We retrospectively evaluated 107 patients who underwent the IPT for suspected chronic BRHP. We used the IPT as the gold standard diagnostic tool for chronic BRHP. RESULTS: Specific antibodies against pigeon dropping extract were documented in 52% of the IPT-positive patients but also in 38% of the IPT-negative patients (p=0.172). By using the logistic regression model, three significant predictors of IPT results were identified as follows: (1) a history of raising birds (odds ratio [OR] 3.112), (2) exposure to birds from the surrounding environment (OR 7.321), (3) white blood cell count (×102/µl; OR 0.959). CONCLUSIONS: This study demonstrates that current or past exposure to avian antigens is a positive predictor of positive IPT results in patients suspected of having chronic BRHP.

Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan.

Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels. Methods The data were collected from the medical records. Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement. Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time. Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required.

Antigen avoidance tests for diagnosis of chronic hypersensitivity pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (HP) is induced by the inhalation of specific antigens. Patients with chronic HP may be able to improve their prognosis by avoiding these antigens. Chronic HP is often difficult to distinguish from idiopathic interstitial pneumonias (IIPs). OBJECTIVE: This study was performed to find out how antigen avoidance tests contribute to the diagnosis of chronic HP. METHODS: A retrospective analysis was conducted on 265 patients who underwent 2-week antigen avoidance tests between April 2002 and March 2012. The patients were classified into the following categories: acute HP, chronic HP, collagen vascular disease-associated interstitial pneumonia (CVD-IP), lung dominant connective tissue disease (LD-CTD), and IIPs. The following seven clinical parameters were evaluated: vital capacity, alveolar-arterial oxygen pressure difference, Krebs von den Lungen-6, surfactant protein-D, white blood cell count, C-reactive protein, and body temperature. These parameters were compared between the chronic HP group and a control group consisting of CVD-IP, LD-CTD, and IIPs. RESULTS: One-hundred and ninety-six patients with chronic HP and 43 control subjects were evaluated. All clinical parameters improved significantly in the chronic HP group but showed no significant changes in the control group. Four of the parameters changed significantly compared with the control group. Diagnostic criteria established using these data had a sensitivity of 51.0% and a specificity of 80.7%. CONCLUSIONS: It was difficult to diagnose chronic HP based solely on 2-week antigen avoidance tests; however, improved clinical parameters among patients supported the diagnosis of HP.

Suicide gene therapy using keratin 19 enhancer and promoter in malignant mesothelioma cells.

To achieve the specific expression of a transfected suicide gene in malignant mesothelioma cells, we applied the enhancer-promoter fusion sequence of the keratin 19 (K19) gene. Northern blot analysis of three mesothelioma cell lines demonstrated that K19 mRNA was expressed most abundantly in the H2052 mesothelioma cell line. Subsequently, in a luciferase reporting assay, K19 promoter (260 bp) exhibited higher promoter activity in H2052 cells than in the other two cell lines. In addition, ligation of a 3' enhancer (80 bp) of the K19 gene to upstream of the K19 promoter sufficiently enhanced the promoter activity. After transfecting an expression vector containing the K19 enhancer-promoter bound thymidine kinase gene (pK19-TK) into the H2052 cells, the pK19-TK transfected cells became more sensitive to GCV than non-transfected cells in vitro and in vivo. In a mouse peritoneal model of malignant mesothelioma, in vivo transfection of pK19-TK by cationic liposome and systemic administration of GCV inhibited the growth of peritoneal tumors. The K19 enhancer-promoter sequence seemed to be specific and efficient enough for the expression of the transfected suicide gene in malignant mesothelioma cells.

Effect of chest wall vibration on dyspnea during exercise in chronic obstructive pulmonary disease.

To elucidate the effect of in-phase chest wall vibration (IPV) during exercise, 17 COPD male patients performed two constant-load exercise tests on a cycle ergometer with and without IPV. The Borg dyspnea score significantly decreased from IPV (-) to IPV (+) (from 13.6+/-2.9 to 12.5+/-2.9, P<0.01). IPV elicited a significant increase in V(O(2)) (P<0.005) and significant decreases in both VE/V(O(2)) (P<0.05) and respiratory frequency (P<0.05), but it did not elicit any changes in VE. The change in Borg score between IPV (+) and IPV (-) showed a significant positive correlation with % predicted V(O(2),max) (r=0.71) and FEV(1)/FVC (r=0.69). Patients in the responsive group (n=11) showed significantly lower FEV(1) (P<0.05) and higher DeltaN(2)/L (P<0.01) than patients in the non-responsive group (n=6). We conclude that IPV reduces dyspnea and improves respiratory efficiency during aerobic exercise in severe COPD.

Amyopathic dermatomyositis complicated with eosinophilic pneumonia.

A 67-year-old woman was admitted to our hospital due to dyspnea on exertion with lung abnormal shadows. A transbronchial lung biopsy specimen demonstrated eosinophilic pneumonia (EP). The patient also exhibited heliotrope eyelids without muscle weakness, which led to a diagnosis of amyopathic dermatomyositis (ADM). As we were unable to find any other causes of EP, we diagnosed her as having EP associated with ADM. Dermatomyositis (DM) has been reported to be associated with various interstitial lung diseases; however, only one case of EP associated with DM has been reported. We herein report the first case of EP complicated with ADM.

Bronchiolitis obliterans organising pneumonia syndrome presenting with neutrophilia in bronchoalveolar lavage fluid after breast-conserving therapy.

A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer. Chest radiography and CT demonstrated consolidation with air bronchogram outside the irradiated area. Neutrophil granulocytes were abundant in bronchoalveolar lavage fluid (BALF) (39.6% of total cells), and transbronchial lung biopsy revealed organising pneumonia (OP) histologically. Antibiotic therapy had no effect, but corticosteroid therapy brought about clinical improvement. Her condition was diagnosed as bronchiolitis obliterans OP (BOOP) syndrome. Lymphocytic BALF has been identified as a characteristic of BOOP syndrome induced after RT for breast cancer. The BALF in this case, however, was neutrophilic. In our analysis of differential cell counts in the BALF of 24 patients with BOOP syndrome, the BALF was neutrophilic (>5%) in 16 (76%) cases, and the neutrophilia was severe in some of those patients.