Safety of bronchoscopy in patients with malignant hematologic disorders.

BACKGROUND: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. METHODS: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. RESULTS: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09-0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18-25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14-0.73, p = 0.01). CONCLUSIONS: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.

Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.

BACKGROUND: Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. CASE PRESENTATION: A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. CONCLUSIONS: Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Gefitinib successfully administered in a lung cancer patient with leptomeningeal carcinomatosis after erlotinib-induced pneumatosis intestinalis.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. CASE PRESENTATION: A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. CONCLUSION: PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

[CLINICAL ANALYSIS OF 115 PULMONARY TUBERCULOSIS PATIENTS WITH SPUTUM SMEAR-NEGATIVE].

[Methods] We retrospectively studied 115 con- secutive pulmonary tuberculosis patients whose sputum smear was .negative, diagnosed by positive culture and/or PCR of various samples, or positive QFT. [Results] The culture positive rate of tuberculosis by spu- tum, gastric aspirate, bronchoscopy, and computed tomogra- phy (CT)-guided needle biopsy samples was 55.7%, 45.6%, 73.2%, and 71.4%, respectively. In multivariate analysis, negative or unknown sputum PCR, negative or unknown gastric aspirate, and minimal spread of tuberculosis were risk factors for negative culture from both sputum and gas- tric aspirate. Sputum culture was positive in only one of the four patients with multi-drug resistant Mycobacterium tuberculosis. [Conclusion] Invasive diagnostic procedures such as fiber- optic bronchoscopy should be considered in patients with negative sputum PCR and minimal spread of tuberculosis.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult. CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass. CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2-positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM.

[Evaluation of mycobacterial infections using 18F-fluorodeoxyglucose-positron emission tomography: results of nine cases].

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) is a useful technique for distinguishing malignant and benign lesions, although the occurrence of false-positive results in cases involving benign lesions is possible. We evaluated nine patients with mycobacterial infections who underwent FDG-PET/CT from April 2008 to July 2010. FDG-PET/CT was performed 1-2h (during the early and late phases) after administration of FDG at a dose of 185 MBq/individual after fasting for at least 5h. Out of the nine patients, four were diagnosed with pulmonary nonmycobacterium tuberculosis, two with pulmonary tuberculosis, two with tuberculous lymphadenopathy, and one with pleural tuberculoma. All patients had a maximum standardized uptake value (SUV(max)) of > 2.5, and the SUV(max) increased from the early to the late phase. One lesion that occurred due to tuberculous pleurisy after treatment demonstrated high FDG uptake, similar to the other cases. It is difficult to distinguish mycobacterial infections from malignant diseases using FGD-PET alone; hence, the use of high-resolution CT and bacteriological tests is required for diagnosis and distinction.

Mendelson's syndrome complicated by bacterial aspiration pneumonia triggered by right putamen bleeding: A case report.

We present the case of an 80-year-old woman with Mendelson's syndrome complicated by bacterial aspiration pneumonia caused by consciousness loss followed by vomiting resulting from putamen bleeding. Her condition worsened rapidly to develop respiratory failure, within a few hours; thereafter, she was intubated. Streptococcus agalactiae and Klebsiella oxytoca were detected from the aspirated sputum sample culture. She was diagnosed with acute respiratory distress syndrome with Mendelson's syndrome complicated by bacterial aspiration pneumonia. Corticosteroid and antibiotic administration improved her condition and led to successful extubation; therefore, these treatment modalities were invaluable. We suggest the clinical considerations for the corticosteroid and antibiotic use in such cases.

[A case of allergic bronchopulmonary mycosis caused by Schizophyllum commune presenting with hyperattenuated mucoid impaction].

A 64-year-old woman was admitted to our hospital because of cough, bloody sputum and chest pain in January 2007. Chest computed tomography (CT) on admission revealed hyperattenuated mucoid impaction and consolidation in the right S3b. She was given a diagnosis of allergic bronchopulmonary mycosis caused by Schizophyllum commune. Treatment with 200 mg/day itraconazole and 15 mg/day oral prednisolone was begun, and her symptoms and consolidation resolved. In December 2007, consolidation in the left lower lobe appeared after itraconazole was stopped and replaced with oral prednisolone with inhaled fluticasone propionate. She again received 200 mg/day itraconazole and 15 mg/day oral prednisolone, resulting in a reduction in her consolidation. In May 2008, itraconazole was stopped and oral prednisolone was changed to inhaled salmeterol fluticasone propionate. In November 2008, her symptoms appeared again, and chest CT demonstrated hyperattenuated mucoid impaction and consolidation in the right S8. A transbronchial biopsy revealed granulomatosis, Charcot-Leyden crystals, and mucus infiltrated by eosinophils and fungi. Schizophyllum commune was isolated from her bronchial lavage fluid. A recurrence of allergic bronchopulmonary mycosis was diagnosed. Retreatment with itraconazole and oral prednisolone resulted in improvement of her symptoms and chest radiographic findings. To the best of our knowledge this is the first reported case of allergic bronchopulmonary mycosis caused by Schizophyllum commune presenting with hyperattenuated mucoid impaction.

[A case of pulmonary tumor thrombotic microangiopathy caused by carcinoma (salivary duct carcinoma) ex pleomorphic adenoma].

A 53-year-old man with carcinoma (salivary duct carcinoma) ex pleomorphic adenoma was admitted to our hospital because of dyspnea. He received chemotherapy in July 2007, and was subsequently followed up without chemotherapy. A chest CT scan revealed multiple faint ground glass attenuation bilaterally. Contrast-enhanced CT did not reveal any emboli in the large pulmonary arteries. An echocardiogram showed severe pulmonary hypertension. Tc-99m-MAA lung perfusion images showed multiple small defects in both lungs. The serum level of vascular endothelial growth factor (VEGF) was normal. He died of heart failure 23 days after admission. An autopsy was performed, and microscopic examination revealed tumor cell embolism, intimal fibrocellular proliferation of the small arteries, fibrin thrombi and recanalization. A diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM) was made. Immunohistochemical staining of the tumor cells for VEGF was weakly positive. To the best of our knowledge this is the first reported case of PTTM caused by a salivary gland tumor.

IgG4-related disease in the differential diagnosis of lung nodules.

IgG4-related disease is an evolving entity of immune-mediated origin. We report a case of IgG4-related disease mimicking lung cancer with pleural dissemination. A 76-year-old male non-smoker was admitted to our hospital because of chest X-ray abnormality. Chest computed tomography scan showed a lung nodule measuring 26 × 14 mm with tiny nodules on the adjacent pleural surface. Wedge resection by video-assisted thoracoscopic surgery (VATS) was performed to aid diagnosis. Pathological findings of the nodule consisted of lymphoid follicular hyperplasia with lymphoplasmacytic infiltrate, fibrosis, and obstructive vasculitis. Focal and scattered thickening of the pleura with lymphoplasmacytic infiltrate was also observed. The IgG4/IgG ratio in the most prominent area exceeded 80%. Thus, we made a diagnosis of IgG4-related lung and pleural disease. To our knowledge, there has been no report of IgG4-related lung disease mimicking lung cancer with pleural dissemination.

Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis with a unique imaging presentation of organizing pneumonia: A case report.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of blood vessel inflammation diseases of autoimmune origin. Myeloperoxidase (MPO) ANCA is closely related to ANCA associated AAV. The MPO-ANCA positive AAV patients have lung involvement at high rates; however, there are only a few reported cases with organizing pneumonia (OP). A 78-year-old man was presented to our hospital due to a fever of 38 °C despite a whole month of antibiotics treatment. Chest computed tomography image revealed restricted consolidations visible in the middle lobe of the right lung and the upper lobe of the left lung, which suggested an OP pattern. MPO-ANCA and urine occult blood tests were positive. Histopathological examination of the transbronchial biopsy revealed OP and mucus plug. Histological findings on renal biopsy showed necrotizing glomerulonephritis related to AAV. The patient was diagnosed with MPO-ANCA positive AAV and was treated with systemic corticosteroid therapy, from which he recovered rapidly. Thus, when diagnosing OP, the possibility of AAV should be considered by ordering patients' serum ANCA and occult hematuria tests.

[A case of Candida glabrata empyema].

A 72-year-old man was admitted to our hospital because of a low grade fever and malaise. He had received a middle to lower esophagectomy and proximal gastrectomy with reconstruction of a gastric conduit for esophageal cancer 12 years previously. Chest X-ray and CT scan revealed massive pleural effusion and consolidations on the right side. Candida glabrata was isolated 4 times from pleural fluid specimens. Candida antigen was negative in both serum and pleural effusion. However, while serum beta-D-glucan was negative, the level of beta-D-glucan in pleural effusion was extremely elevated. Thus, the patient was diagnosed as having C. glabrata empyema. He was treated with insertion of a thoracostomy tube followed by intrapleural instillation of amphotericin B and intravenous administration of micafungin. Pleural effusion was reduced and the repeated culture of the pleural effusion became negative after 27 days of treatment. Empyema with C. glabrata is rare and the present case is the second report of the disease in the Japanese literature.

Development of a CT image case database and content-based image retrieval system for non-cancerous respiratory diseases: Method and preliminary assessment.

BACKGROUND: To evaluate the benefits of using a CT image case database (DB) with content-based image retrieval system for the diagnosis of typical non-cancerous respiratory diseases. METHODS: Using this DB, which comprised data on 191 cases covering 69 diseases, 933 imaging findings that contributed to differential diagnoses were annotated. Ten test cases were selected. Image similarity between each marked test case lesion and the lesions of the top 10 retrieved cases were assessed and classified as similar, somewhat similar, or dissimilar by two physicians in consensus. Additionally, the accuracy of five internal medicine residents' abilities to interpret CT findings and provide disease diagnoses with and without the proposed system was evaluated by image interpretation experiments involving five test cases. The rates of concordance between the subjects' interpretations and the correct answers prepared in advance by two specialists in consensus were converted into scores. RESULTS: The mean (± SD) of image similarity among the 10 test cases was as follows: 5.1 ± 2.7 (similar), 2.9 ± 1.0 (somewhat similar), and 2.0 ± 2.4 (dissimilar). Using the proposed system, the subjects' mean score for the correct interpretation of CT findings improved from 15.1 to 28.2 points (p = 0.131) and for the correct disease diagnoses, from 9.3 to 28.2 points (p = 0.034). CONCLUSIONS: Although this was a preliminary small-scale assessment, the results suggest that this system may contribute to an improved interpretation of CT findings and differential diagnosis of non-cancerous respiratory diseases, which are difficult to diagnose for inexperienced physicians.

Clinicoradiological Features of Pulmonary Tuberculosis with Interstitial Pneumonia.

Objective Although rare, pulmonary tuberculosis occasionally develops in patients with interstitial pneumonia (IP). In this study, we aimed to evaluate the clinicoradiological features of pulmonary tuberculosis associated with IP. Methods In this retrospective, observational, single-center study, the medical charts, high-resolution computed tomography (HRCT) findings, and bacteriological test results of patients with IP who also tested positive for Mycobacterium tuberculosis were reviewed. Patients The study included 20 patients with IP out of 329 who tested positive for M. tuberculosis in sputum or bronchoalveolar lavage fluid cultures at Toranomon Hospital between January 2006 and December 2017. Results The HRCT patterns were usual interstitial pneumonia (UIP) in 11 patients and non-UIP in 9 patients. Consolidations (80%) were the most frequent HRCT findings, followed by cavities (60%) and nodules (45%), which are generally characteristic of pulmonary tuberculosis. Consolidations often developed in relation to fibrotic or emphysematous lesions. Tuberculosis lesions could not be identified in one patient. All patients were treated with anti-tuberculosis drugs according to WHO guidelines, and 13 patients achieved a WHO category of "Treatment success." No patient died of tuberculosis, and the median survival time for the 20 patients was 1,196 days. Conclusion Although the HRCT findings for pulmonary tuberculosis associated with IP are atypical, appropriate tuberculosis treatments can lead to favorable outcomes.

Treatment outcome of patients with unresectable stage III non-small cell lung cancer and interstitial pneumonia.

BACKGROUND: The standard treatment for unresectable stage III non-small cell lung cancer (LC) is chemoradiation therapy (CRT); however, the optimal treatment for LC in patients with interstitial pneumonia (IP) (LC-IP) has not been determined. This study compared the clinical course of LC-IP patients to that of patients without IP (LC without IP) and determined the key factors of survival. METHODS: We retrieved the records of 52 consecutive LC patients treated at our institution between January 2011 and September 2016. The characteristics and outcomes of LC patients with and without IP were compared. Survival was analyzed using the Kaplan-Meier method and univariate and multivariate analyses of two-year survival were also conducted. RESULTS: Forty-two men and 10 women were evaluated. Eleven patients (21%) had IP as their underlying disease. Except for age, the backgrounds of LC patients with and without IP were almost identical. Among LC-IP patients, the median predicted forced vital capacity was 86% and the Gender-Age-Physiology (GAP) index was 3. None of the LC-IP patients received CRT but 32 (78%) of the LC without IP patients underwent CRT. Chemotherapy alone was the main treatment for LC-IP. The median survival times were 485 and 1271 days in LC patients with and without IP, respectively (p=0.419). Multivariate analysis of survival longer than two years revealed CRT as the only predictive factor. CONCLUSIONS: CRT was the only predictive factor for longer survival in LC patients; however, no LC-IP patients received CRT, possibly because of the underlying IP.

Reduced area of the normal lung on high-resolution computed tomography predicts poor survival in patients with lung cancer and combined pulmonary fibrosis and emphysema.

BACKGROUND: This study aimed to determine the radiologic predictors and clarify the clinical features related to survival in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer. METHODS: We retrospectively reviewed the medical chart data and high-resolution computed tomography (HRCT) findings for 81 consecutive patients with CPFE and 92 primary lung cancers (70 men, 11 women; mean age, 70.9 years). We selected 8 axial HRCT images per patient, and visually determined the normal lung, modified Goddard, and fibrosis scores. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The major clinical features were a high smoking index of 54.8 pack-years and idiopathic pulmonary fibrosis (n = 44). The major lung cancer profile was a peripherally located squamous cell carcinoma (n = 40) or adenocarcinoma (n = 31) adjacent to emphysema in the upper/middle lobe (n = 27) or fibrosis in the lower lobe (n = 26). The median total normal lung, modified Goddard, and fibrosis scores were 10, 8, and 8, respectively. TNM Classification of malignant tumors (TNM) stage I, II, III, and IV was noted in 37, 7, 26, and 22 patients, respectively. Acute exacerbation occurred in 20 patients. Multivariate analysis showed that a higher normal lung score and TNM stage were independent radiologic and clinical predictors of poor survival at the time of diagnosis of lung cancer. CONCLUSIONS: A markedly reduced area of normal lung on HRCT was a relevant radiologic predictor of survival.

Various Bronchiolar Lesions Accompanied by Idiopathic Pleuroparenchymal Fibroelastosis with a Usual Interstitial Pneumonia Pattern Demonstrating Acute Exacerbation.

A 63-year-old man presented with persistent cough and progressive dyspnea. Computed tomography showed irregular pleural thickening and fibrotic changes with volume loss in the upper lobes, and subtle reticulation in the lower lobes. Pleuroparenchymal fibroelastosis (PPFE) was diagnosed based on the findings of a surgical lung biopsy. Bronchiolar lesions, including proliferative bronchiolitis, constrictive bronchiolitis obliterans, and peribronchiolar metaplasia were evident on pathology. A usual interstitial pneumonia (UIP) pattern was also observed in the lower lobes. Three weeks after the biopsy, an acute exacerbation occurred. We herein describe a rare case of idiopathic PPFE with various bronchiolar lesions and a UIP pattern in which an acute exacerbation developed.

[A case of pulmonary tumor thrombotic microangiopathy associated with lung adenocarcinoma diagnosed by CT-guided lung biopsy].

A 46-year-old woman was admitted to our hospital because of bloody and chest pain. Chest X-ray and CT scan revealed a 17-mm nodule in the left upper lobe, consolidations in both lower lobes, and mediastinal and hilar lymphadenopathy. CT-guided lung biopsy from the right lower lobe revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi and recanalization. Embolic tumor cells were adenocarcinoma and immunohistologial staining for TTF-1 was positive. The patient was diagnosed as having pulmonary tumor thrombotic microangiopathy (PTTM) associated with clinical stage IV primary lung adenocarcinoma. Although chemotherapy with carboplatin and paclitaxel resulted in improvement of pulmonary consolidations, multiple bone metastatic lesions appeared. The patient was subsequently treated with docetaxel, and gemcitabine thereafter. This was the first reported case of PTTM associated with lung cancer and diagnosed antemortem by CT-guided biopsy. This suggests that CT-guided lung biopsy may be useful for diagnosis of PTTM, and enable establishment of appropriate cancer chemotherapy.

[Case of hot tub lung with confirmation of exacerbation following jet bath use].

A 49-year-old woman presented with exertional dyspnea. Chest CT revealed patchy areas of ground-glass attenuation and ill-defined centrilobular nodules scattered in both lungs. Bronchoalveolar lavage (BAL) fluid showed lymphocytosis. Transbronchial lung biopsy revealed bronchiolocentric alveolitis and well-formed non-necrotizing granulomas were present. She had used a jet bath before the onset of symptoms and mycobacterial culture revealed the presence of Mycobacterium avium complex (MAC) in sputum sample, BAL samples and jet bath water. Restriction fragment length polymorphism (RFLP) analysis revealed that the isolated MAC were essentially clonal. She had used the jet bath for the inhalation provocation study, and after the challenge she complained of dyspnea and have body temperature increased. We diagnosed hot tub lung due to Mycobacterium avium complex. Because avoidance of the jet bath caused improvement of her symptoms and reduced her fever and PaO2 increased by 10 Torr but did not improve the CT findings, antimycobacterial drugs were prescribed. The patient recovered fully. This case proves that the cause of hot tub lung is the use of jet bath through the inhalation provocation study.