Efficacy and Safety of Endobronchial Ultrasonography with a Guide-sheath for Acute Pulmonary Lesions in Patients with Haematological Diseases.

Objective Acute pulmonary lesions (APLs), defined as an acute infiltrate or nodular lung field, are a major complication in patients with haematological diseases. Recently, endobronchial ultrasonography with a guide-sheath (EBUS-GS) was established as a useful technique for diagnosing pulmonary lesions. This study aimed to evaluate the efficacy and safety of EBUS-GS for managing APLs in patients with haematological diseases. Methods Our single-centre, retrospective, observational, single-arm, descriptive study enrolled 22 consecutive adult (>20-year-old) patients with haematological diseases and concomitant APL who underwent EBUS-GS between January 2011 and June 2016 at Kameda Medical Center, Chiba, Japan. The primary endpoint was the contribution of EBUS-GS to clinical decision-making. Secondary endpoints were an adequate tissue collection rate, diagnostic yield, complication rate, and 30-day mortality. Results The median patient age was 70 years old, and 63.6% were men. Acute myeloid leukaemia was the most frequent underlying disease, accounting for 54.5% of patients. The contribution of EBUS-GS to clinical decision-making was recognised in 11 (50.0%) patients. Adequate tissue collection was achieved in 21 (95.5%) patients. The aetiology of the APL was identified in 9 (40.9%) patients. No complications, including severe haemorrhaging and pneumothorax, were observed in any patients, and the 30-day mortality rate was 0%. Conclusion EBUS-GS may be a suitable diagnostic option for APL in patients with haematological diseases. Further larger-scale and randomised controlled trials are needed to confirm our results.

A case of asthma-complicated influenza myocarditis.

A 36-year-old man with a history of asthma visited an outpatient clinic complaining of high fever and general fatigue, and was diagnosed as having influenza type A by influenza antigen test. Laboratory findings revealed mild inflammation, mild acidemia, and hypercapnea with radiologic infiltrations in the right lung, and remarkable wheezes in both lungs were heard on auscultation. He was diagnosed with asthma exacerbation and having influenza pneumonia, and was referred to us. Therapy was begun with oseltamivir for influenza infection and intravenous infusions of betamethasone and aminophylline with non-invasive pulmonary ventilation for asthma exacerbation and acute respiratory failure. Although he was weaned from mechanical ventilation and his general condition became good, electrocardiogram showed sinus bradycardia and negative T waves in V1-4 without any symptoms. Blood test and echocardiography showed almost normal findings except for slight elevation of LDH and AST. Influenza A antigen was already confirmed and he was diagnosed as having influenza myocarditis clinically. Although it is well known that influenza can cause asthma exacerbation and encephalopathy, influenza myocarditis is regarded as rare by physicians. In fact, the number of case reports about influenza myocarditis is few. Myocarditis may not appear to be serious, but could cause fatal arrhythmia and heart failure. All clinicians should be aware of the overall clinical picture and the possibility of severe complications of myocarditis caused by flu infection.

[Prognostic lung abscess factors].

BACKGROUND: Lung abscess, although curable when caught early and treated appropriately, still may recur repeatedly or require surgery. We retrospectively assessed prognostic lung abscess factors and predictive recurrence factors. We evaluated comorbidity using the Charson comorbidity index (CCI). METHODS: Subjects numbered 44 hospitalized for lung abscesses between June 2004 and May 2009 and classified as; elderly (over 65 years) or non-elderly and cured treatment failed. RESULTS: Mean age and the CCI of failed treatment were statistically higher than in cures at 80.8 years and 3.25 vs 64.1 years and 1.25 (p < 0.05). Abscess location, smoking habits, symptoms, white blood cell count and C-reactive protein did not differ on day 1. The causative organism, fistula presence at 65.6% vs 45.5% (p = 0.30) and lesion size at 59.8 mm vs 71.6 mm (p = 0.14) did not differ between groups, but the degree of lesion size reduction in treatment failures was lower than cures at 24.9% vs 69.1% (p < 0.05). CONCLUSIONS: Lung abscess prognosis is thus adversely affected by age and comorbidity. In Japan, subjects having multiple comorbidities are expected to increase with aging. The degree of lesion size reduction appears to be a predictive factor in recurrence, underscoring the importance of follow-up in imaging, including chest computed tomography.

Positron Emission Tomography in T3/T4 Non-Small Cell Lung Cancer After Induction Chemoradiotherapy.

BACKGROUND: To predict pathological response and survival in T3/T4 non-small cell lung cancer after induction chemoradiotherapy by assessing fluorodeoxyglucose uptake with positron emission tomography. METHODS: In this retrospective observational study, standard uptake values of whole tumors and extrapulmonary involvement sites were measured after induction chemoradiotherapy. The values were then compared with pathological responses and recurrence-free survival. RESULTS: Fifty-seven patients with clinical T3/T4 tumors were treated by chemoradiotherapy followed by surgery. Pathological complete response was observed in 33% of patients (19 of 57). With the cutoff value of 3.3 for whole tumor fluorodeoxyglucose uptake for estimating complete response, 38% patients (9 of 24) with values lower than the cutoff value were false-negative. Tumor remission at extrapulmonary involvement sites was observed in 82% patients (47 of 57), and the cutoff value of the extrapulmonary uptake was 3.0 without any false negatives. Recurrence-free survival was significantly better in patients with values lower than both the whole- and extrapulmonary-uptake cutoff values than in patients with higher values (P = .016 and P = .001, log-rank test, respectively). Among 7 patients who avoided en bloc resections of involved structures because of lowered extrapulmonary uptakes and negative findings in intraoperative frozen sections, none experienced margin recurrence. CONCLUSIONS: Even when whole tumor uptakes in patients with T3/T4 tumors markedly decrease after induction chemoradiotherapy, surgical treatment is still indicated because of possible residual tumors. Tumor remission at extrapulmonary involvement sites could be predicted by extrapulmonary uptake values. Both whole- and extrapulmonary-uptake values after induction chemoradiotherapy could be used to predict prognosis.

[Cryptococcemia with a severe bronchial asthma: case report and review of the literature].

A 64-year old hospitalized male for severe bronchial asthma began to complain fatigue and appetite loss. His asthma had been treated with oral bethamethasone. The Chest CT at this time revealed a bilateral consolidation of the lower lung. Despite a week of treatment with antibiotics and anti-fungals, the patient expired from DIC progression. His premortem sputum and blood culture grew Cryptococcus Neoformans. We concluded his diagnosis as cryptococcal pneumonia and sepsis. Sepsis by Cryptococcus neoformans is a rare clinical event, and only 20 cases have been reported in Japan. Although 16 of the 20 had preexisting medical conditions, a case with underlying bronchial asthma has never been reported. A comparison of the reported cases of the US and Europe to that of Japan revealed differences in the patients' underlying conditions. We report a case with a brief review of the literature and summarize the 20 cases that have been reported in Japan.

[Splenic metastasis of lung cancer].

A 71-year-old man was referred for a chest x-ray of the right upper lobe lung mass in August 2005. Bronchoscopy and transbronchial biopsy revealed squamous cell carcinoma. A routine metastatic workup revealed his clinical stage to be IIIA (cT2N2M0). We treated him with chemotherapy and radiotherapy. However, an abdominal CT scan showed an 8 cm nodule in the spleen in June 2006. Splenic metastasis from lung cancer is rare. Only 13 cases have been reported from 1990 to 2008. Four of 6 cases (67%) who did not have splenectomy reported splenic rupture and had poor outcomes. Therefore, we considered that splenectomy could possibly improve the prognosis of this patient with isolated splenic metastasis. We report a case with a brief review of the literature and summarize the 13 reported cases.

Pembrolizumab-induced pneumonitis with a perilymphatic nodular pattern in a lung cancer patient: A radio-pathologic correlation.

A 66-year-old Japanese man with recurrent adenocarcinoma of the lung p-stage IIIA (pT2bN2M0; version 8) on pembrolizumab was present with gradually worsening dyspnea. Although history and physical examination were unremarkable, high-resolution CT showed the perilymphatic distribution of the pembrolizumab-induced pneumonitis. Consistent with the CT result, biopsy revealed the aggregation of the cytotoxic (CD8+) T-lymphocytes around the lymph tracts. Given the clinical, radiological and pathological findings, pembrolizumab-induced pneumonitis was confirmed. The patient was discharged after terminating the pembrolizumab with ameliorated symptoms. This report, in conjunction with existing literature, illustrates the wide variety of the pembrolizumab-induced pneumonitis and bolsters the current understanding of its pathophysiology.

Pulmonary Tumor Thrombotic Microangiopathy Mimicking Inhalation Lung Injury.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a complication characterized by dyspnea, pulmonary hypertension, and occasionally sudden death. We encountered a man who developed PTTM and had an inhalation history of chemical herbicides and abnormal findings on chest computed tomography, mimicking chemical inhalation lung injury. He was diagnosed with PTTM with adenocarcinoma by a transbronchial lung biopsy and received chemotherapy and anticoagulant therapy. He survived for one month. An autopsy revealed primary gastric cancer with PTTM that can have a presentation similar to diffuse pulmonary diseases, including chemical inhalation lung injury. The examination of a biopsy specimen is crucial in such patients.

[The efficacy of influenza vaccine for acute exacerbation of chronic obstructive lung disease in elderly patients].

OBJECTIVE: Acute exacerbations adversely affect the quality of life and prognosis of patients with chronic obstructive lung disease (COPD). Prevention of future exacerbations is extremely important, especially for elderly patients. In this study, we evaluated the efficacy of influenza vaccine for acute exacerbation of COPD in elderly patients. METHODS: A prospective cohort study was conducted among 289 patients over 65 years of age with COPD (FEV1/FCV<0.70) during the 2001-2002 influenza season. Background data, outpatient visits for wheezing and hospitalizations were compared between the vaccinated group (n = 189) and the unvaccinated group (n = 100). RESULTS: The number of patients who visited hospital for wheezing was 11 of 189 (5.8%) in the vaccinated group and 23 of 100 (23%) in the unvaccinated group (RRR: relative risk reduction 74.7%, 95% CI: confidence interval 0.51-0.87). The number of hospitalizations for pneumonia was 8 of 189 (4.2%) in the vaccinated group and 14 of 100 (14%) in the unvaccinated group (RRR 69.8%, 95% CI: 0.32-0.87). The costs of hospitalization were lower in the vaccinated group with direct savings of 91,525 yen per patient. CONCLUSIONS: For elderly COPD patients, influenza vaccine decreases acute exacerbation due to pneumonia and bronchoconstriction, and also may minimize the costs of hospitalization.

Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: A single-center retrospective observational cohort study.

BACKGROUND/PURPOSE: The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. METHODS: We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10 mg/kg/day; SMX, 20-50 mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). RESULTS: The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. CONCLUSION: Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Impact of induction chemoradiotherapy on pulmonary function after lobectomy for lung cancer.

OBJECTIVE: Our study aim was to determine whether there are differential changes in whole-lung and regional lung functions after lobectomy for lung cancer between propensity score-matched patients treated with and without induction chemoradiotherapy, by using single-photon emission computed tomography lung perfusion. METHODS: This study was a retrospective matched cohort study of consecutively acquired data. Pulmonary function test and perfusion scintigraphy were conducted before lobectomy and 6 months after lobectomy in patients treated with induction therapy (n = 72) and in those not treated (n = 170), for measuring functional changes of whole lung, contralateral lung, and lobes. After exact matching on resected lobe site, propensity scores for age, smoking status, preoperative pulmonary functions, and predicted postoperative pulmonary function were used to match the groups. RESULTS: After the matching, 46 patients were selected from the groups. Standardized mean differences of the 5 matched variables were <0.1. Whole lung function significantly decreased after lobectomy in the induction therapy group than in the noninduction therapy group (P < .001). Although ipsilateral preserved lobe function before surgery was not different between the groups (P = .33), postoperative value was significantly lower in the induction therapy group than in the noninduction therapy group (P < .001). Although both groups showed a significant increase of contralateral lung function after lobectomy (P < .01), the increases were not significantly different between the groups (P = .81). CONCLUSIONS: Induction chemoradiotherapy was associated with reduced pulmonary function after lobectomy because of a decrease in ipsilateral preserved lobe function, which could be caused by the chronic effects of the induction chemoradiotherapy.

Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Immunogenicity of trivalent influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy.

Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4-6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

Rice-Field Drowning-Associated Pneumonia in which Pseudomonas spp., Aspergillus fumigatus, and Cunninghamella sp. Are Isolated.

We herein report the case of an 84-year-old who developed pneumonia after drowning in a rice field. Besides Aspergillus fumigatus, many pathogens previously not reported in drowning-associated pneumonia (such as Pseudomonas fluorescens, Pseudomonas putida, Nocardia niigatensis, and Cunninghamella sp.) were isolated from his sputum. He received sulbactam/ampicillin, trimethoprim/sulfamethoxazole, voriconazole, levofloxacin and liposomal amphotericin B, but died due to respiratory failure. Because the patient had drowned in a contaminated stagnant rice field and had multiple lung cavities, zygomycosis was suspected. This report provides invaluable information for the consideration of zygomycosis after an individual drowning in a rice field, even in an immunocompetent patient.

Rapidly Progressive Interstitial Lung Disease Associated with Dermatomyositis Treated with Combination of Immunosuppressive Therapy, Direct Hemoperfusion with a Polymyxin B Immobilized Fiber Column and Intravenous Immunoglobulin.

Rapidly progressive interstitial lung disease (ILD) is associated with dermatomyositis (DM) and has a high mortality rate even with immunosuppressive agents. For such cases, there is no evidence on the combined effect of direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin. We herein report a case of 61-year-old woman who presented with respiratory failure. She showed ILD associated with DM which did not improve with immunosuppressive agents, but was improved with the addition of both direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin.

Inhibition of human telomerase enhances the effect of chemotherapeutic agents in lung cancer cells.

Telomerase is a ribonucleoprotein enzyme that maintains protective structures at the ends of eukaryotic chromosomes. Earlier studies have reported that the presence of telomerase activity in tumors of patients with non-small cell lung cancer patients correlates with a high proliferation rate and advanced pathological stage. Thus, the modification of telomerase activity may be a potential therapeutic modality for the treatment of lung and other cancers. We introduced vectors encoding dominant negative (DN)-hTERT, or wild-type (WT)-hTERT, or a control vector expressing only a drug-resistance marker, into the A549 lung cancer cell line, and assessed the biological effect of telomerase inhibition on cellular immortality. Ectopic expression of DN-hTERT resulted in complete inhibition of telomerase activity and reduction of telomere length. The entire population of telomerase-inhibited A549 cells exhibited cytoplasmic blebbling and chromatin condensation, which are features of apoptosis. In contrast, A549 cells expressing wild-type hTERT, which differs from the mutants by only two amino acids, exhibited normal morphology. Evidence for apoptosis in the telomerase-inhibited cells was provided by flow cytometric analysis with APO2.7 monoclonal antibody. We also observed enhanced induction of apoptosis by chemotherapeutic reagents, including cisplatin, docetaxel and etoposide, in DN-hTERT-expressing A549 cells, as compared with WT-hTERT-expressing cells. These results demonstrate that disruption of telomere maintenance limits the cellular lifespan of lung cancer cells, and show that the combined use of chemotherapeutic agents and telomere maintenance inhibition may be effective in the treatment of patients with non-small cell lung cancer.

[A case of spinal sarcoidosis complaining of chest and back pain as a first manifestation and mimicking syringomyelia on MRI].

The patient was a 24-year-old female complaining of bell-shaped chest and back pain with visual disturbance. Chest X-ray showed bilateral hilar lymphadenopathy without the presence of pleural effusion. Bronchoalveolar fluid showed lymphocytosis with an elevated CD 4/CD 8 ratio. Transbronchial lung biopsy demonstrated a non-caserous granulomatous lesion with an accumulation of epitheloid cells, suggesting lung sarcoidosis. No abnormality of electrocardiogram was detectable, and spinal tap for examination of chest and back pain demonstrated on elevated level of beta 2-microglobulin, and a normal angiotensin converting enzyme level. Spinal MRI showed a lineal lesion mimicking syringomyelia on T 2-weighted image. Steroid administration was started for the chest and back pain, since the spinal lesion was suspected due to spinal sarcoidosis. All clinical and laboratory findings, without the presence of pleural effusion or cardiac fluid, supported the diagnosis of spinal sarcoidosis causing chest and back pain. In the literature, patients with spinal sarcoidosis manifesting chest and back pain and with a MRI finding mimicking syringomyelia have been rarely reported. This case might be important in considering spinal cord sarcoidosis as a differential diagnosis of chest and back pain.

[A case of primary pulmonary cavitation with thin smooth walls in sarcoidosis].

A 27-year-old female was admitted to our hospital after a regular medical check revealed BHL and cavitation in the right upper lung field on a chest radiograph. Ga scintigraphy showed abnormal uptake bilaterally in the mediastinal and hilar lymph nodes. We strongly suspected lung sarcoidosis, then performed TBLB and BAL. BAL fluid disclosed a high proportion of lymphocytes with a marked elevation of the CD4/CD8 ratio, compatible with sarcoidosis. A TBLB specimen revealed non-caseating epithelioid cell granuloma compatible with a diagnosis of lung sarcoidosis. From the clinical and radiological observations, it was concluded that the cavitation in the present case was primary pulmonary cavitation in sarcoidosis, as distinct from infection, malignancy, bulla or cystic bronchiectasis. Chest radiographs taken a half year after diagnosis showed reduction of the cavitary lesion and disappearance of BHL.