Effective management of lung spindle cell carcinoma with ipilimumab, nivolumab, carboplatin, and paclitaxel, demonstrating efficacy in brain metastases treatment.

A 76-year-old woman with cT1bN2M1b stage IVA spindle cell carcinoma of the right lower lobe of the lung, no driver gene mutation, and programmed death ligand 1 < 1%, was started on ipilimumab+nivolumab+carboplatin+paclitaxel. After two courses, the patient initiated maintenance therapy with ipilimumab+nivolumab. New multiple brain metastases were observed during treatment but resolved with continued treatment. We report a unique case of spindle cell carcinoma treated with ipilimumab+nivolumab+carboplatin+paclitaxel that resulted in long-term response and resolution of new brain metastasis.

Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib.

BACKGROUND: First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown. PATIENTS AND METHODS: This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with osimertinib. Computed tomography images were obtained and evaluated independently by three pulmonologists in a blinded manner. Factors associated with lung injury were assessed using a logistic regression model. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test. RESULTS: Of the 195 patients, 40 had pre-ILS, and 21 (8 with and 13 without pre-ILS) developed lung injury during the observation period. Multivariate analysis revealed that pre-ILS was independently associated with lung injury (odds ratio, 3.1; 95% confidence interval [CI], 1.1-8.2; p = 0.025). Severe (≥Grade 3) lung injury was observed in eight (4.1%) patients, of whom, two (5%) and six (3.9%) had and did not have pre-ILS (p = 0.67), respectively. Grade 5 lung injury was not observed, and survival curves were similar between the patients who developed lung injury and those who did not (median 11 vs. 12 months; hazard ratio, 1.2; 95% CI, 0.56-2.7; p = 0.60). CONCLUSIONS: Pre-ILS increased the risk of lung injury in patients of non-small cell lung cancer treated with osimertinib, while the severity of lung injury was not clearly affected by the presence of pre-ILS.

The causes of acute cough: a tertiary-care hospital study in Japan.

OBJECTIVES: Cough is the most frequent presenting complaint in general practice and has an adverse effect on an individual's well-being. Understanding the causes of cough is critical for appropriate patient management. According to its duration, cough is classified as acute, subacute, and chronic. While acute respiratory infection is considered to be the major cause of acute cough, there is little evidence. METHODS: We retrospectively assessed the prevalence of acute cough in all patients presenting with cough to the respiratory clinic of Japanese Red Cross Wakayama Medical Center from May 2018 to April 2019. We subsequently assessed the causes of acute cough, after stratifying patients with acute cough into two subgroups based on the chest X-ray findings. RESULTS: Among 685 patients (329 males; mean age, 61.8 ± 18.6 years) who presented with cough as a chief complaint, 274 (125 males; mean age, 57.6 ± 20.9 years) reported to have acute cough; chest X-ray abnormalities were detected in 113 of these patients. The most frequent cause of acute cough among 113 patients with chest X-ray abnormalities was pneumonia (55.8%), followed by lung cancer (9.7%) and pneumonia exacerbating asthma (7.1%). Among the 161 patients with acute cough without chest X-ray abnormalities, the most frequent cause was upper respiratory tract infection (57.1%), followed by asthma (23.6%) and cough variant asthma (6.2%). CONCLUSIONS: Cough is the most frequent presenting complaint in general practice. Infections are the most frequent causes of acute cough regardless of the chest X-ray findings.

Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab. The purpose of this study was to determine the correlation between immune-related adverse events and the effects of pembrolizumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: From February 2017 to August 2019, we conducted a retrospective analysis of the effects of pembrolizumab treatment and immune-related adverse events in 94 patients with non-small-cell lung cancer treated with pembrolizumab only. RESULTS: In 63 cases, irAEs were observed. The most common irAE was rash. PD-L1 positivity ≥ 50% tended to cause irAEs. The median progression-free survival (PFS) rates with and without irAEs were 371 days (95% CI, 184-NR) and 67 days (95% CI, 51-87 days), respectively. In a multivariate analysis, irAEs and Eastern Cooperative Oncology Group performance status (PS) were the factors related to PFS. CONCLUSION: In patients with lung cancer, who were treated with pembrolizumab monotherapy, the development of irAEs was likely indicative of the positive effects of pembrolizumab. This novel finding appears to be useful for clinicians who work with pembrolizumab for lung cancer treatment.

Visceral pleural biopsy under medical thoracoscopy for the diagnosis of lung adenocarcinoma.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for diagnostic procedures. The diagnostic yield of medical thoracoscopy is high and is generally based on parietal pleural biopsy findings. Pleural biopsies are valuable for a diagnosis. However, visceral pleural biopsies are uncommon because of the risk of prolonged air leak. In this study, we report a rare case of the successful diagnosis of lung adenocarcinoma, based on the findings of visceral pleural biopsy under medical thoracoscopy. To avoid lung injury and pneumothorax, we focused on maintaining the thoracoscope and biopsy forceps in a straight angle as much as possible. While looking straight ahead at the visceral pleural nodule as closely as possible, biopsy samples were carefully obtained while confirming that the normal lung was not held. With careful consideration, visceral pleural biopsies may expand the diagnostic capability of medical thoracoscopy.

Intrapleural urokinase directly under medical thoracoscopy for the diagnosis of tuberculous pleurisy.

Medical thoracoscopy, also called "local anesthetic thoracoscopy" and "pleuroscopy," is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surfaces and channels to conduct diagnostic and therapeutic procedures. However, this technique is not helpful when substantial fibrous adhesions exist. We reported the first case of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of malignant pleural mesothelioma with severe multiloculated pleural effusions in 2019. This is the second report regarding the efficacy of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of multiloculated pleural effusions. Urokinase-induced intrapleural fibrinolysis, which removed the fibrous septa, consequently improved the field of view under endoscopy within only 10 min. Fibrinolytic effect appeared very rapidly. This technique is available for tuberculous pleurisy with severe multiloculated pleural effusion.

Osimertinib Administration as the Primary Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy for Brain Metastasis of De Novo T790M-positive Lung Cancer.

A 69-year-old woman underwent left upper lobectomy for left upper lobe lung adenocarcinoma. She later perceived a left visual field defect, and a brain metastasis was detected on head magnetic resonance imaging (MRI). Epidermal growth factor receptor (EGFR) testing identified two separate EGFR mutations: an L858R mutation in exon 21 and a de novo T790M mutation in exon 20. Treatment with osimertinib was started. After one month, head MRI showed that the brain metastasis had shrunk, and the visual field defect had also improved. In this case, first-line osimertinib was effective for treating brain metastasis of de novo T790M-positive lung cancer.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer Patient.

Nivolumab, an anti-PD-1 antibody, inhibits binding between PD-1 and PD-1 ligand and activates antigen-specific T cells that have become unresponsive to cancer cells. Although it is recommended as a second-line therapy in gene mutation-negative non-small-cell lung cancer, interstitial pneumonia is a well-known side effect of the drug; however, granulomatous lesions have rarely been reported. We describe the case of an 81-year-old male with cT1aN2M1b stage IV pleomorphic carcinoma of the left upper lobe of the lung. After primary treatment with carboplatin and paclitaxel, recurrence was observed in the left supraclavicular lymph node and left adrenal gland. We initiated the administration of nivolumab as a secondary treatment. Reduction was observed in the swelling of the left supraclavicular lymph node and left adrenal gland, but the tumor shadow in the right upper lobe appeared to increase. Bronchoscopy was performed, and the biopsy result showed granulomas; the findings resembled a sarcoid-like granulomatous reaction. The shadows eventually disappeared with nivolumab discontinuation; thus, we concluded that the sarcoid-like granulomatous reaction had resulted from nivolumab administration. Based on our observations, we suggest that when invasive shadows are observed after nivolumab administration, it is necessary to differentiate between disease progression and interstitial pneumonia. Moreover, the decision to reinitiate nivolumab treatment requires careful judgment in future instances of cancer recurrence.

Desmoplastic Small Round Cell Tumor of the Pleura Successfully Treated with a Lower Dose of Pazopanib.

Desmoplastic small round cell tumor (DSRCT) is an aggressive mesenchymal tumor which primarily affects the abdomen. Even a multimodal approach rarely achieves durable remission and the optimal therapy for extended disease is unknown. We herein describe a rare case of DSRCT arising from the pleura in a 32-year-old man. Initial therapy, which included chemotherapy, surgery and radiotherapy, achieved a partial response for only two months. Although salvage chemotherapies had no effect, pazopanib treatment shrank the tumors and was well-tolerated on an outpatient basis. From the viewpoint of quality of life, pazopanib may therefore be a good therapeutic option for this aggressive disease.

[Multiple lung metastases from cutaneous adenoid cystic carcinoma resected 21 years before].

A 79-year-old woman whose cutaneous tumor had been resected 21 years and 12 years (local recurrence)before pathologically confirmed as primary cutaneous adenoid cystic carcinoma (ACC), was referred to our hospital for the abnormal shadow on chest X-ray. Chest computed tomography (CT)revealed 3 nodules in the peripheral field of both lungs, which were diagnosed by echo-guided needle biopsy as metastasis from the cutaneous ACC, and were completely resected at 5 months intervals. Any recurrences have not been detected for 2 years after the lung resection. In primary cutaneous ACC, not only complete resection with adequate margin but long-term follow up is recommended.

73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin.

Although gentamicin (GM) has been used widely as an antibiotic, the specific binding protein of the drug has not yet been understood sufficiently. Here we show that GM specifically associates with the 73-kDa molecular chaperone HSP73 and reduces its chaperone activity in vitro. In the present study, we investigated GM-specific binding proteins using a GM-affinity column and porcine kidney cytosol. After washing the column, only the 73-kDa protein was eluted from the column by the addition of 10 mm GM. None of the other proteins were found in the eluant. Upon immunoblotting, the protein was identical to HSP73. Upon CD spectrum analysis, the binding of GM to HSP73 resulted in a conformational change in the protein. Although HSP73 prevents aggregation of unfolded rhodanese in vitro, the chaperone activity of HSP73 was suppressed in the presence of GM. Using limited proteolysis of HSP73 by TPCK-trypsin, the GM binding site is a COOH-terminal for one third of the protein known to be a peptide-binding domain. During immunohistochemistry, HSP73 and GM were co-localized in enlarged lysosomes of rat kidneys with GM-induced acute tubular injury in vivo. Our results suggest that the specific association between HSP73 and GM may reduce the chaperone activity of HSP73 in vitro and/or in vivo, and this may have an interaction with GM toxicity in kidneys with GM-induced acute tubular injury.