Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Reproducibility of visual estimation of lung adenocarcinoma subtype proportions.

In 2011, a new classification of lung adenocarcinoma was published. Since then there have been multiple studies regarding observer variability in predominant subtype determination, with levels of agreement generally in the weak to moderate range. In the 2011 and subsequent WHO 2015 classification, a recommendation was also made to visually assess and record the percentage of each subtype in 5% increments. The present study was initiated to determine the reproducibility of such gestalt assessments and to compare these data to a formal morphometric assessment. Five experienced pathologists reviewed multiple single images of 25 adenocarcinomas, taken at 2× and 10×, and estimated the percentage of lepidic, acinar, papillary, micropapillary, and solid components in 5% increments. After 2 months all the pathologists again reviewed the same images presented to them in a different order. We found that there was poor reproducibility within observers at 2× power using a 5% evaluation, but that this improved using 10% or 25% cutoffs. Use of 10× magnification allowed weak to moderate reproducibility at 5% increments, and this was again improved using 10% or 25% cutoffs. Correlation with morphometric assessment was poor except for the papillary and micropapillary subtypes. Differences among pathologists were generally low except for the acinar and, to a lesser degree, lepidic subtypes, which showed a wide spread of data. When estimating tumor subtype proportions, use of a 10× objective, and utilization of 10% or preferably 25% cutoffs provides a greater degree of consistency than a 5% cutoff.

Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

BACKGROUND: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. METHODS: The evidence syntheses were discussed and recommendations formulated by a multidisciplinary committee of IPF experts. The evidence was appraised and recommendations were formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The guideline panel updated the diagnostic criteria for IPF. Previously defined patterns of usual interstitial pneumonia (UIP) were refined to patterns of UIP, probable UIP, indeterminate, and alternate diagnosis. For patients with newly detected interstitial lung disease (ILD) who have a high-resolution computed tomography scan pattern of probable UIP, indeterminate, or an alternative diagnosis, conditional recommendations were made for performing BAL and surgical lung biopsy; because of lack of evidence, no recommendation was made for or against performing transbronchial lung biopsy or lung cryobiopsy. In contrast, for patients with newly detected ILD who have a high-resolution computed tomography scan pattern of UIP, strong recommendations were made against performing surgical lung biopsy, transbronchial lung biopsy, and lung cryobiopsy, and a conditional recommendation was made against performing BAL. Additional recommendations included a conditional recommendation for multidisciplinary discussion and a strong recommendation against measurement of serum biomarkers for the sole purpose of distinguishing IPF from other ILDs. CONCLUSIONS: The guideline panel provided recommendations related to the diagnosis of IPF.

Efficacy and safety of transbronchial lung biopsy for the diagnosis of lymphangioleiomyomatosis: A report of 24 consecutive patients.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease that occurs in women of childbearing age. LAM can be diagnosed on a clinical basis in patients with typical high-resolution computed tomography (HRCT) patterns and at least one other corroborating disease feature, such as chylothorax, angiomyolipoma, tuberous sclerosis complex or elevated serum vascular endothelial growth factor (VEGF)-D. However, patients who do not meet these criteria require tissue confirmation for a definitive diagnosis, and the utility of methods that are less invasive than surgical lung biopsy, such as transbronchial lung biopsy (TBLB), are not well studied. We retrospectively studied the efficacy and safety of TBLB for the diagnosis of LAM. METHODS: From January 1991 to August 2015, 131 consecutive LAM patients were prospectively registered in our study, and a TBLB was conducted for 24 patients. We retrospectively studied the yield and safety of TBLB in this cohort. RESULTS: All 24 patients were women; the median age was 42 years. HRCT showed multiple round thin-walled cysts diffusely scattered throughout the lungs. The median level of serum VEGF-D was 2109 pg/mL. Characteristic pathological findings for LAM were identified in 17 patients (70.8%) by two expert pathologists. The %predicted value for diffusing capacity of carbon monoxide was significantly lower in the 17 TBLB-positive LAM patients compared to the seven TBLB-negative LAM patients (P = 0.046). There were no serious adverse events such as pneumothorax or uncontrollable bleeding due to TBLB. CONCLUSION: TBLB is a safe and effective method for the pathological diagnosis of LAM.

High-dose prednisolone after intravenous methylprednisolone improves prognosis of acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (AE-IPF) is a poor prognostic disorder. AE is also reported to occur in other idiopathic interstitial pneumonias (IIPs). There are limited data available regarding the effectiveness of treatment for AE-IIPs. The objective of this study was to clarify the prognostic impact of the initial dose of prednisolone (PSL) for treating AE-IIPs. METHODS: Eighty-five patients with AE-IIPs, diagnosed according to the criteria of the Japanese Respiratory Society, were enrolled in this study (IPF/non-IPF: 63/22 patients) from 2004 to 2013. We performed multivariate Cox proportional hazard regression analysis to identify poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as diffuse or non-diffuse. We evaluated the prognostic significance of the initial dose of PSL by adjusting for other prognostic factors. RESULTS: Median survival time (MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non-IPF was 39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher serum surfactant protein-D at AE diagnosis, long-term oxygen therapy (LTOT) before AE and positive pressure ventilation (PPV) use for AE were significant poor prognostic factors for all patients, as were LTOT before AE and lower serum IgG for no-PPV patients. High-dose PSL ≥ 0.6 mg/kg was a significant prognostic factor for no-PPV patients after adjusting for other prognostic factors. CONCLUSION: We concluded that a dose of PSL ≥ 0.6 mg/kg after i.v. high-dose methylprednisolone therapy should be recommended for the treatment of AE-IIPs.

Pulmonary Fibrosis on High-Resolution CT of Patients With Pulmonary Alveolar Proteinosis.

OBJECTIVE: The CT findings of pulmonary fibrosis in patients with pulmonary alveolar proteinosis (PAP) are not yet well defined. The objective of this study was to evaluate the CT findings of PAP with a focus on pulmonary fibrosis secondary to PAP. MATERIALS AND METHODS: High-resolution CT (HRCT) scans of 44 patients with PAP were evaluated retrospectively with a focus on pulmonary fibrosis: 33 patients had autoimmune PAP, and 11 patients had secondary PAP. The intervals between the initial and last CT examinations ranged from 1 to 284 months (median, 60 months). The HRCT images were assessed by two chest radiologists independently; when the two radiologists disagreed, a final decision was made by consensus. RESULTS: A crazy-paving pattern was a more common HRCT finding in patients with autoimmune PAP than in those with secondary PAP. Traction bronchiectasis was found in four patients (9%) on the initial scans and in 10 patients (23%) on the last scans. There was no honeycombing on the initial scans. Honeycombing developed in two patients (5%): It was detected on 2-year follow-up in one patient and on 6-year follow-up in the other patient. Among the patients with autoimmune PAP, those with fibrosis detected on HRCT during follow-up had a worse prognosis than those without fibrosis detected on HRCT (p = 0.041). CONCLUSION: Fibrosis develops in approximately 20% of patients with PAP. The CT findings of parenchymal fibrosis suggest a poor outcome.

Heterogeneity of incidence and outcome of acute exacerbation in idiopathic interstitial pneumonia.

BACKGROUND AND OBJECTIVE: Acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonia (IIP) have a poor prognosis. This study aims to clarify the incidence and prognosis of AE in IPF and the other IIP. METHODS: A total of 229 patients were enrolled, of whom 92 had IPF and 137 had 'IIP other than IPF' based on the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) 2011 IPF Guidelines. IIP other than IPF included 11 patients with a surgical lung biopsy (SLB) and the remainder without such a biopsy. IIP other than IPF was further classified into IIP with a 'possible usual interstitial pneumonia (UIP)' pattern on HRCT (n = 75) and IIP with 'inconsistent with UIP' pattern (n = 62) based on published guidelines. Predictors of AE and the prognosis after AE were examined in these groups. RESULTS: The 1-year incidence of AE in IPF, IIP with possible UIP HRCT patterns and IIP with inconsistent with UIP HRCT patterns was 16.5%, 8.9% and 4.0%, respectively. AE occurred significantly more frequently in IPF than in IIP with possible UIP and inconsistent with UIP HRCT patterns after adjustment for BMI, modified Medical Research Council score and %forced vital capacity. Prognosis of AE-IIP with possible UIP HRCT pattern was significantly worse than that of AE-IPF. CONCLUSION: Although AE occurred significantly less frequently in IIP with possible UIP and inconsistent with UIP HRCT patterns than in IPF, the prognosis of AE-IIP with possible UIP HRCT patterns might be worse than that of AE-IPF.

Clinical Impact of Emphysema Evaluated by High-Resolution Computed Tomography on Idiopathic Pulmonary Fibrosis Diagnosed by Surgical Lung Biopsy.

BACKGROUND: The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. OBJECTIVE: The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). METHODS: One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. RESULTS: Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant protein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. CONCLUSIONS: The prognosis of IPF-emphysema was significantly worse than that of IPF alone.

[Pulmonary Carcinosarcoma Presenting Hemothorax Caused by Pleural Invasion;Report of a Case].

A 71-year-old man presented with hemothorax with cough, sputa and worsening dyspnea. On chest X-ray and computed tomography(CT), a huge tumor in the right upper lobe with hematoma and small amount of gas suggesting hemopneumothorax was revealed. No apparent lymphadenopathy nor intrapulmonary metastases were observed. The tumor showed a little enhancement on the contrastenhanced CT. Then the resction of the tumor was performed, and the pathological evaluation revealed a carcionosarcoma (adenocarcinoma+osteosarcoma) pT3N0 (stage II B) G4 pl2. Sarcomatoid carcinoma such as carcinosarcoma should be considered as a possible cause of hemothorax in making a diagnosis of hemorrhagic hypovascular huge lung tumor.

A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins.

UNLABELLED: This report demonstrates a late presenter and long-term survivor (38 months old) of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) and with a heterozygous frameshift mutation in FOXF1. The mild phenotype may be due to his residual normal lung tissue as demonstrated in the chest computed tomography (CT) and histopathological findings. CONCLUSION: We report the longest survivor of ACD/MPV. The mild phenotype is most likely due to the patient's residual normal lung tissue.

An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.

BACKGROUND: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. PURPOSE: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. METHODS: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. RESULTS: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. CONCLUSIONS: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

Utility of expiratory thin-section CT for fibrotic interstitial pneumonia.

BACKGROUND: Collagen vascular disease-associated interstitial lung disease (CVD-ILD) must be differentiated from idiopathic pulmonary fibrosis (IPF) since prognosis and treatment strategies differ between these two conditions. However, differentiating between CVD-ILD and IPF is often difficult. PURPOSE: To examine the utility of expiratory high-resolution computed tomography (HRCT) for differentiating between CVD-ILD and IPF. MATERIAL AND METHODS: Seventy patients were examined with expiratory and inspiratory HRCT with CVD-ILD (n = 36) or IPF (n = 34). Associated diagnoses in patients with CVD-ILD were rheumatoid arthritis (n = 22), Sjögren syndrome (n = 3), scleroderma (n = 2), polymyositis/dermatomyositis (n = 1), and unspecified connective tissue disease (n = 8). Parenchymal abnormalities on inspiratory HRCT and visual extent of air trapping on expiratory HRCT were evaluated, statistical differences in HRCT findings between the two conditions were determined, and air trapping CT scores were correlated with the results of pulmonary function testing. RESULTS: Air trapping was found in 27 (75%) of 36 cases of CVD-ILD and four (12%) of 34 cases of IPF. Seventeen of the 27 cases for which air trapping was exhibited with CVD-ILD were diagnosed with rheumatoid arthritis. A significant difference in frequency of air trapping was seen between CVD-ILD and IPF (P < 0.0001). Frequency of centrilobular nodules was significantly higher in CVD-ILD than in IPF (P = 0.021). In contrast, frequencies of interlobular interstitial thickening and traction bronchiectasis were significantly higher in IPF than in CVD-ILD (P = 0.005, P = 0.007, respectively). Correlations were seen between visual extent of air trapping and pulmonary function test results such as air trapping index (P = 0.004, r = 0.34), closing volume/vital capacity (P = 0.0002, r = -0.47), and closing capacity/total lung capacity (P < 0.0001, r = -0.51). CONCLUSION: The presence of air trapping on expiratory HRCT suggests CVD-ILD rather than IPF.

Disease progression in idiopathic pulmonary fibrosis without pulmonary function impairment.

BACKGROUND AND OBJECTIVE: Despite significant recent progress in the understanding of idiopathic pulmonary fibrosis (IPF), the early phase of the disease is still poorly understood. We studied patients with IPF without pulmonary function impairment in order to determine the clinical features, natural history and key findings for physiological progression. METHODS: Twenty-five patients without pulmonary function impairment were identified from among patients with previously diagnosed IPF who underwent surgical lung biopsies between January 1997 and December 2006 at our institutions. 'Without pulmonary function impairment' was defined as both forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) >80% predicted. Patients diagnosed with IPF through multidisciplinary discussion based on the new IPF guidelines were the subjects of this study. RESULTS: Sixteen patients had a confirmed diagnosis of IPF. Eleven patients presented with chest X-ray abnormality found during an annual health examination. Seven patients were asymptomatic. Eleven patients showed physiological disease progression (median time; 19.9 ± 12.3 months) defined by a decline of at least 10% in FVC or at least 15% in DLco. Univariate analysis revealed that both usual interstitial pneumonia pattern and extent of honeycombing on high-resolution computed tomography (HRCT) were factors associated with disease progression (odds ratio 5.634, 95% confidence interval 1.364-23.278; odds ratio 2.371/5%, 95% confidence interval 1.042-5.395). CONCLUSIONS: IPF patients without pulmonary function impairment have a progressive but slow clinical course. The existence and extent of honeycombing on HRCT are predictive of disease progression.

Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined. OBJECTIVES: To investigate the role of tetraspanin CD151 in pulmonary fibrosis. METHODS: CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF. MEASUREMENTS AND MAIN RESULTS: A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF. CONCLUSIONS: CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Low Wilms' tumor gene expression in tumor tissues predicts poor prognosis in patients with non-small-cell lung cancer.

We elucidated the relationship between prognosis of non-small-cell lung cancer (NSCLC) and Wilms' tumor gene (WT1) mRNA expression in tumor tissue. The WT1 mRNA expression levels of the fatal cases were lower as compared with those of the survival cases. Overall survival (OS) and disease-free survival (DFS) of the high WT1 expression group were longer than of the low expression group. As for squamous cell lung cancer (SQLC), low WT1 expression was significantly associated with lymph node metastasis. Cox analysis revealed that the gene level was a significant prognostic factor in OS and DFS. Low WT1 expression predicted poor prognosis in patients with NSCLC.

[Enlargement of intrathoracic diffuse large B-cell lymphoma during treatment of pulmonary tuberculosis: a case report].

We described enlargement of intrathoracic diffuse large B-cell lymphoma (DLBCL) during treatment of pulmonary tuberculosis in a 78-year-old man. The patient had previously undergone treatment for pulmonary tuberculosis about 50 years ago and showed disease recurrence in 2010. Although after tuberculosis treatment with the standard chemotherapy regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide, we observed a clear resolution of the main X-ray shadows, a nodular shadow in the right upper lung field was observed to have increased in size. After evaluation by transbronchial biopsy of the upper right lung lobe, we diagnosed DLBCL with subepithelial infiltration of an airway. This is a rare case of coexistence of active pulmonary tuberculosis and intrathoracic DLBCL.

[A case of cryptococcal empyema successfully treated by debridement by medical thoracoscopy with local anesthesia].

Cryptococcal empyema is a rare disease which usually occurs in immunocompromised patients. We describe a 57-year-old man with diabetes mellitus with a mass-like shadow in the right middle lung field. Transbronchial lung biopsy of the right lung revealed numerous yeast-like fungi in fibrotic and necrotic lesions. These findings, together with positive serum cryptococcal antigen yielded a diagnosis of pulmonary cryptococcosis secondary to diabetes mellitus. Despite treatment with several anti-fungal drugs, and dyspnea and pleural effusion developed. He was referred to our hospital for further examination and therapy. The presence of positive cryptococcal antigen and numerous yeast-like fungi were confirmed cytologically in the pleural effusion. Therefore, we suspected that pulmonary cryptococcosis had perforated into the thoracic space and empyema had developed. Because antifungal drugs were ineffective, debridement of the fibrinopurulent material by medical thoracoscopy and chest drainage were performed. The clinical symptoms of this patient improved with antifungal treatment for 1 year, and we successfully treated the cryptococcal empyema without recurrence. Debridement by medical thoracoscopy and chest drainage were useful for this case of cryptococcal empyema.

[An autopsy case of gastric cancer presenting as acute respiratory failure due to pulmonary tumor thrombotic microangiopathy with concomitant high serum level of vascular endothelial growth factor-D].

A 49-year-old man consulted our hospital several days after the onset of dyspnea and was admitted because it rapidly exacerbated 9 days after presentation. Diffuse centrilobular micronodular shadows and diffuse opacities in all lung fields were noted on high-resolution computed tomography of the chest. Severe pulmonary hypertension and dilatation of the right ventricle was observed on echocardiography. Although there was no evidence of thrombus in the central portion of the pulmonary artery or deep veins of the lower limbs, the patient's respiratory insufficiency rapidly progressed and he died about 14 hours after admission. A postmortem examination revealed widespread gastric cancer and tumor emboli in the pulmonary arterioles, complicated with intraluminal organization, which is consistent with pulmonary-tumor thrombotic microangiopathy (PTTM). His serum level of vascular endothelial growth factor-D (VEGF-D) was elevated, but VEGF-D was not detected by immunohistological staining. A possible pathophysiological association with PTTM and VEGF-D should be examined in future studies.

[Multidisciplinary assessment of effects, safety and procedure of whole lung lavage for 8 patients with autoimmune pulmonary alveolar proteinosis].

We treated 8 cases of autoimmune pulmonary alveolar proteinosis (APAP) with whole lung lavage (WLL) in our hospital and evaluated the disease severity of APAP before and after WLL, adverse events (AEs) and recurrence-free survival in those cases who improved. In all cases, unilateral WLL was performed in both lungs. The median of total lavage volume in unilateral WLL was 17.9 L, and the median procedure time of unilateral WLL was 105 min. Fever was the most frequently observed AE (87.5% of all procedures). Pulmonary function tests (percentage of predicted value of VC, FEV1 and diffusing capacity of carbon monoxide), serum markers (KL-6, surfactant apoprotein (SP)-D, SP-A and carcinoembryonic antigens), arterial blood gas analyses (PaO2, AaDO2) and disease severity score all significantly improved after WLL. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody temporarily decreased after unilateral WLL, but returned to previous levels (before WLL) in 7 cases. The radiological findings improved in 6 cases. In the 7 improved cases in whom AaDO2 decreased more than 10 Torr, the median recurrence-free survival of APAP after WLL was 17.5 months. We concluded that WLL is an effective and safe method for the treatment of APAP, and all parameters except for anti GM-CSF antibody are useful to evaluate the effect of WLL.