Trapped Lung as a Sequela of Dramatic Tumor Shrinkage of Lung Cancer.

Herein, we report a case of 72-year-old man who had L858R EGFR-mutated lung adenocarcinoma. Chest computed tomography revealed a large lung mass that had completely replaced the right upper lobe. Although the mass dramatically shrank after initiating chemotherapy, non-malignant pleural effusion appeared. Because diffuse pleural thickening and shrinking of the thoracic cage gradually became apparent, the patient was diagnosed with trapped lung. Despite the stabilization of his lung cancer, he experienced severe dyspnea and significant weight loss, ultimately leading to a decreased performance status. Chest physicians should recognize that trapped lung can develop as a sequela of dramatic tumor shrinkage in lung cancer.

Successful pembrolizumab treatment for microsatellite instability-high thymoma: A case report.

Microsatellite instability (MSI) is a valuable biomarker for immune checkpoint inhibitors. We report the first case of MSI-high thymoma successfully treated with pembrolizumab. This patient had pleural dissemination and was treated with two cytotoxic chemotherapy regimens including carboplatin and paclitaxel combination therapy and pemetrexed, which did not have the desired effect. Because MSI status was high by using the surgical specimen, pembrolizumab was administered as 3rd line chemotherapy. After three courses, the pleural lesions dramatically shrunk, which confirmed a partial response. Although MSI-high thymoma is rare, our results suggest the necessity to evaluate MSI status in patients with thymoma.

Drug-related pneumonitis caused by amikacin liposome inhalation suspension: One pathologically proven case and single-center experience.

Amikacin liposome inhalation suspension (ALIS) is known to cause drug-related pneumonitis, which has been described as "hypersensitivity pneumonitis (HP)". However, its clinical and pathological characteristics have never been reported. We retrospectively evaluated 18 patients treated with ALIS. Three (16.7%) patients developed HP-pattern pneumonitis on high-resolution computed tomography. Serum eosinophil counts were elevated up to above 1000/µL in these three patients, which decreased with ALIS discontinuation only. Of note, the specimen obtained by transbronchial lung cryobiopsy in one patient revealed a mild degree of lymphocyte and eosinophil infiltration. Rather, the findings of acute lung injury such as an edematous thickening of the alveolar walls, and an accumulation of foamy degenerative macrophages in the alveolar lumina was prominent. A pulmonary alveolar proteinosis reaction was also observed. HP-pattern pneumonitis due to ALIS may pathologically correspond to acute lung injury and a pulmonary alveolar proteinosis reaction despite increasing serum eosinophil counts.

Favorable treatment response of bevacizumab-combined chemotherapy for advanced or recurrent invasive mucinous adenocarcinoma of the lung: A retrospective observational study.

Invasive mucinous adenocarcinoma (IMA) of the lung is a rare variant of adenocarcinoma characterized by abundant intracytoplasmic mucin within the tumor. Although IMA has poor sensitivity to conventional chemotherapy regimens used for non-small cell lung cancer, we observed a better response to the bevacizumab (BEV) regimen. In this retrospective study, we aimed to investigate the response to BEV-combined regimens in patients with IMA. Among 16 consecutive patients diagnosed with IMA between January 2016 and December 2020 at our institution and treated with systemic chemotherapy, seven patients were treated with BEV-combined regimens. The overall response rate to BEV-combined regimens was 85.7%, with six patients showing a partial response. The median progression-free survival was 6.1 months. One patient experienced respiratory failure, which was improved after administration of BEV-combined regimen. BEV-combined systemic therapy may have a favorable effect on advanced or recurrent IMA of the lung.

Spontaneous regression of acute fibrinous organizing pneumonia induced by COVID-19 vaccination: A case report.

A 42-year-old woman visited our hospital with complaints of fever, muscle pain, and dyspnea one week after receiving the coronavirus disease 2019 (COVID-19) vaccine. Chest high-resolution computed tomography showed a patchy consolidation and ground-glass attenuation in the both lungs, consistent with acute interstitial pneumonia. Transbronchial lung cryobiopsy revealed organizing pneumonia with marked intra-alveolar fibrin, and pathologically diagnosed as acute fibrinous organizing pneumonia (AFOP). Other causative diseases such as dermatomyositis was clinically ruled out, and COVID-19 vaccine-induced AFOP was diagnosed. Physician should check the history of COVID-19 vaccination when encountering a case of AFOP with an unknown cause.

Safety and Efficacy of Combination Therapy of Remdesivir, Baricitinib, and High-dose Steroids in Patients Hospitalized with Moderate to Severe COVID-19.

Objective Dexamethasone, remdesivir (REM), and baricitinib (BAR) are commonly used to treat coronavirus disease 2019 (COVID-19). High-dose steroids have also been reported to be well tolerated, even when used in combination with multiple drugs. In this retrospective study, we assessed the safety and therapeutic efficacy of a three-drug combination of high-dose steroids, REM, and BAR in hospitalized COVID-19 patients. Methods We retrospectively evaluated the safety and efficacy of three-drug combination therapy. Patients We evaluated 107 patients hospitalized with moderate or severe COVID-19 who underwent 3-drug combination therapy with high-dose steroids (80 mg of methylprednisolone or more, REM, and BAR) in our institution from December 2020 to June 2021. The mean age was 62.1±13.7 years old, and 71.2% were men. The severity of the study patients was as follows: 18 (16.8%) with an 8-category ordinal score of 4, 84 (78.5%) with a score of 5, and 5 (4.7%) with a score of 6. Results The frequency of high-grade adverse events was low, except for hyperglycemia (n=59, 45.8%). The median duration from symptom onset to the start of three-drug combination therapy was eight days. All but one of the patients treated with the combination therapy improved. The median time to improvement by 1 category of the eight-category ordinal score was 6 days, and the 28-day mortality was 0.9%. Conclusion This study showed the safety profile of three-drug combination therapy of high-dose steroids, REM, and BAR in moderate to severe COVID-19 patients. The three-drug combination therapy is well tolerated and has the potential to prevent exacerbation of severity.

Successful tepotinib treatment of adenocarcinoma with MET exon 14 skipping and discordant results between Oncomine Dx target test and ArcherMET: A case report.

Patients with non-small cell lung cancer (NSCLC) are often positive for oncogenic driver mutations, such as EGFR, ALK, BRAF, RET and MET exon 14 skipping mutations (METex14 skipping). Recently, METex14 skipping has become a functional biomarker for NSCLC with the approval of MET kinase inhibitors. Tepotinib is an oral MET kinase inhibitor. Its overall response rate is 46%, and the median duration of the response is 11.1 months. In Japan, companion diagnostics for tepotinib are limited with the ArcherMET and AmoyDx test, but not with Oncomine Dx target test. The present study reports the case of a 60-year-old male patient with lung adenocarcinoma harboring METex14 skipping, which was positive on Oncomine DxTT, but not on ArcherMET. In his sample used for Oncomine DxTT, the read count of MET(13)-MET(15) products was only 46. He was treated with various chemotherapeutic agents, but developed cardiac tamponade due to the progression of the disease of mediastinal lymph node metastases. Tepotinib was administered following pericardial drainage, resulting in an immediate response in all lesions. The majority of the discordant samples between Oncomine DxTT and ArcherMET had read counts <800, and the patient described herein had only 46. Therefore, the results of the present study indicate that the use of tepotinib should be considered even in patients whose METex14 skipping results were negative with ArcherMET, yet positive on Oncomine DxTT, particularly relatively with low lead counts.

Cumulative Incidence of Thromboembolism and Prognostic Impact of Stroke in BRAF V600E-mutant Non-small-cell Lung Cancer.

BACKGROUND/AIM: Cancer and ischemic stroke are closely associated. Thromboembolism susceptibility in lung cancer may differ depending on oncogenic alterations. However, the clinical characteristics of thromboembolism in patients with BRAF-mutant non-small-cell lung cancer remain unknown. Thus, this study aimed to evaluate the cumulative incidence of thromboembolism in this population and describe such cases in detail. PATIENTS AND METHODS: We retrospectively investigated consecutive patients with BRAF V600E-mutant non-small-cell lung cancer. Cumulative incidence was calculated using a competing risk analysis. RESULTS: Of 10 patients with BRAF-V600E mutant lung cancer, five developed a total of seven thromboembolic events, showing a 1-year cumulative incidence of 43% (95% confidence interval=11-72%). These events consisted of four cancer-related stroke (CRS) events and three venous events including deep vein thrombosis or pulmonary embolism. Of note, most of the early thrombotic events were CRS. Two patients with CRS had multiple brain infarctions during anticancer drug therapy, characterized by high D-dimer levels, resulting in short-term mortality (13 and 22 days after stroke onset). CONCLUSION: A substantial proportion of patients with BRAF V600E-mutant lung cancer experienced thromboembolism during their disease course. CRS of undetermined source may predict a worse prognosis in this population.

A Retrospective Study of the Clinical, Radiological, and Pathological Characteristics of Patients with Interstitial Pneumonia Preceding Rheumatoid Arthritis.

Objective Interstitial lung disease (ILD) is the most critical manifestation in patients with rheumatoid arthritis (RA). In some cases, ILD may appear before the RA onset. Some patients with an initial diagnosis of idiopathic interstitial pneumonia (IIPs) develop RA; however, few studies have reported on its features, and the details remain unknown. In the present study, the clinical, radiological, and pathological features were evaluated in patients with ILD preceding RA. Methods The clinical, radiological, and pathological features of patients with ILD preceding RA were retrospectively reviewed using the medical records. Patients Ten patients with ILD preceding RA out of 883 IIP patients who underwent a surgical lung biopsy at our hospital from 2004 to 2018 were retrospectively examined. Results The median patient age was 59 (range 50-76) years old, and 7 of the patients were women. The median time from the ILD diagnosis to the RA onset was 50 (range 33-65) months. Regarding the high-resolution computed tomography pattern, the "indeterminate for UIP" pattern was the most popular, and cysts were seen in all cases. Attenuation around the cyst was prominent. Pathological findings showed plasma cell infiltration, bronchus-associated lymphoid tissue (BALT), and bronchiolitis in the lobules. Cellular and destructive bronchiolitis was noticeable in many patients with ILD preceding RA and contributed to the destruction and dilation of the bronchiole. Conclusion In ILD patients with IIP, radiological and pathological findings with increased attenuation around the cysts, prominent inflammatory cell infiltration (especially in plasma cells), an increase in the BALT number, and cellular and destructive bronchiolitis might serve as helpful RA development indicators.

Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

Radiological unilateral pleuroparenchymal fibroelastosis as a notable late complication after lung cancer surgery: incidence and perioperative associated factors.

OBJECTIVES: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural-parenchymal involvement, predominantly in the upper lobes. Unilateral upper lung field pulmonary fibrosis (upper-PF) that is radiologically consistent with PPFE reportedly develops after lung cancer surgery in the operated side and presents many clinical characteristics in common with PPFE. However, the incidence and perioperative associated factors remain unclear. METHODS: All consecutive patients with lung cancer resected completely from 2008 to 2016 were investigated retrospectively. Pre-/postoperative characteristics were compared between patients with and without unilateral upper-PF. Cumulative incidence curves were estimated using competing risk analysis. RESULTS: Among the 587 included patients, 25 patients (4.3%) were diagnosed as unilateral upper-PF. The 3-, 5- and 10-year cumulative incidence of unilateral upper-PF was 2.3%, 3.3% and 5.3%, respectively. In multivariable analysis, male sex, presence of a pulmonary apical cap, lobar resection and low % vital capacity (%VC < 80%) were independent perioperative associated factors. The 10-year cumulative incidence was 6.3% in patients treated with lobar resection, 8.0% in male patients, 10.3% in patients with pulmonary apical cap and 14.5% in patients with low %VC. Postoperative pleural effusion at 6 months after surgery was much more common in the patients who later developed unilateral upper-PF (96.0% vs 24.2%). This pleural effusion persisted and was accompanied thereafter by pleural thickening and subpleural pulmonary fibrosis. During the clinical courses of 25 patients with unilateral upper-PF, 18 patients presented symptoms related to upper-PF and 6 patients died. CONCLUSIONS: Unilateral upper-PF is an occasional but under-recognized late complication after lung cancer surgery.

Validation of inhalation challenge test and serum immunoglobulin G test for bird-related fibrotic hypersensitivity pneumonitis.

BACKGROUND: The inhalation challenge test is considered to be the item for diagnosis of hypersensitivity pneumonitis (HP) and identifying the causative antigen in patients with fibrotic HP. However, the inhalation challenge test is not widely used. OBJECTIVE: To evaluate the values of the inhalation challenge test by comparing with serum immunoglobulin (Ig)G test. METHODS: This was a single-center, retrospective study. The patients with fibrotic HP were diagnosed pathologically by surgical lung biopsy or transbronchial lung cryobiopsy and were assumed to have bird-related fibrotic HP if they had a history of obvious avian exposure. RESULTS: On the basis of pathologic findings and history of avian exposure, 43 of 86 patients were diagnosed with having bird-related fibrotic HP. In 43 patients with bird-related fibrotic HP, 15 (35%) were positive for anti-bird IgG antibody and 36 (84%) were positive for the inhalation challenge test; in addition, the specificity of the inhalation challenge test was 67%. Patients with both positive results from inhalation challenge test and anti-bird IgG antibodies had a 2.7% decline in annual forced vital capacity (FVC) before the inhalation (P = .02). In patients with positive result from inhalation challenge test and negative result from anti-bird IgG antibodies, the annual FVC decreased by 5.8% (P = .03). FVC was not consistent in patients with positive result from the anti-bird IgG antibodies. CONCLUSION: The inhalation challenge test for bird-related fibrotic HP was more sensitive than the anti-bird IgG antibodies. Furthermore, the inhalation challenge test could select patients with similar disease progression.

Disease activity of lung cancer at the time of acute exacerbation of interstitial lung disease during cytotoxic chemotherapy.

BACKGROUND: The prognosis of lung cancer patients with interstitial lung disease (ILD) is poor, and acute exacerbation (AE) of ILD can occur during chemotherapy as a fatal adverse event. Although AE-ILD development is correlated with various factors, no reports are investigating the disease activity of lung cancer at the time of AE-ILD development. METHODS: All consecutive lung cancer patients with ILD who developed chemotherapy-related AE-ILD within 28 days after the last administration of cytotoxic chemotherapy between 2011 and 2020 were retrospectively reviewed. RESULTS: Among 206 lung cancer patients with ILD who were treated with cytotoxic chemotherapy, 30 patients were included. The median age was 72 years and all patients were men with smoking history. Usual interstitial pneumonia (UIP) and non-UIP patterns of ILD was observed in 17 and 13 patients. Most of AE-ILD occurred during second- or later-line (22/30, 73.3%) and developed within first or second courses during chemotherapy (19/30, 63.3%). Regarding tumor response to chemotherapy at AE-ILD development, majority of patients (18 patients, 60.0%) experienced progressive disease and only one patient (3.3%) experienced a partial response. Notably, 27 patients (90.0%) did not exhibit any tumor shrinkage of the thoracic lesions. CONCLUSION: Lung cancer was uncontrolled with cytotoxic chemotherapy at the time of AE-ILD development. Although AE-ILD during chemotherapy has been generally discussed in terms of drug-specific adverse effects, uncontrolled lung cancer may be also correlated with AE-ILD development.

Unilateral Autoimmune Pulmonary Alveolar Proteinosis with Polymyositis-related Interstitial Lung Disease.

A 61-year-old patient with cystic bronchiectasis and bronchial artery hyperplasia in the left lung was diagnosed with polymyositis-related interstitial lung disease. After nine months of immunosuppressive therapy, he developed unilateral autoimmune pulmonary alveolar proteinosis (APAP) in the right lung with respiratory failure. After bronchial artery embolization to prevent massive hemoptysis, whole-lung lavage was performed using veno-venous extracorporeal membrane oxygenation. His respiratory condition improved, and he was discharged from the hospital with supplemental oxygen. Three reported cases of APAP with polymyositis-related interstitial lung disease, including the present case, were all positive for anti-glycyl tRNA synthetase antibody and were under immunosuppressive treatment.

Clinical characteristics of pulmonary hypertension in patients with pleuroparenchymal fibroelastosis.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of patients with pleuroparenchymal fibroelastosis (PPFE) and pulmonary hypertension (PH). METHODS: We retrospectively analyzed the data of patients who were diagnosed with PPFE and underwent transthoracic echocardiography (TTE) for the evaluation of their right heart systems within 3 months of their first visit between 2011 and 2018. Patients were divided into the PH and non-PH groups based on their peak tricuspid regurgitation velocity (TRV) on TTE (cutoff, 2.8 m/s). The clinical characteristics of PH and association between PH and survival among patients with PPFE were investigated. RESULTS: In total, 83 patients were enrolled. Sixteen (19.3%) patients were included in the PH group. The PH group had a lower body mass index, percent predicted forced vital capacity (FVC), 6-min walk distance, and partial pressure of arterial oxygen than the non-PH group. There was no significant difference in the presence of usual interstitial pneumonia patterns in the lower lobes between the two groups. The survival period was significantly shorter in the PH group than in the non-PH group (median survival 16.3 versus 50.2 months, log-rank p < 0.001). The multivariate Cox proportional hazard model showed that male sex (hazard ratio [HR] = 4.83, p < 0.001), Krebs von den Lungen-6 (KL-6) > 550 U/mL (HR = 3.48, p = 0.005), %FVC < 50% (HR = 3.04, p = 0.028), and peak TRV > 2.8 m/s (HR = 3.26, p = 0.038) were independently associated with poor survival. CONCLUSIONS: PH was not rare in patients with PPFE. Male sex, increased KL-6, lower FVC, and PH were independently associated with poor survival in patients with PPFE.

Usefulness and safety of transbronchial lung cryobiopsy for reassessment of treatment in the clinical course of diffuse parenchymal lung disease.

BACKGROUND: The usefulness and safety of transbronchial lung cryobiopsy (TBLC) for reassessment of diffuse parenchymal lung disease (DPLD) with progression is still unknown. Our purpose was to clarify the usefulness and safety of TBLC for reassessment of DPLD with progression. METHODS: This retrospective study included 31 patients with DPLD diagnosed by surgical lung biopsy who progressed in the clinical course and underwent TBLC for reassessment between January 2017 and September 2019 at Kanagawa Cardiovascular & Respiratory Center. Two pulmonologists independently selected the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy based on clinical and radiological information with and without pathological information from TBLC. A consensus was reached among the pulmonologists regarding the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy. Complications of TBLC were also examined. RESULTS: Seven (22.6%), 5 (16.1%), and 6 (19.4%) of clinical diagnosis was changed after TBLC for Pulmonologist A, for Pulmonologist B, and for consensus, respectively. The treatment strategy was changed in 7 (22.6%), 8 (25.9%), and 6 (19.4%) cases after TBLC for Pulmonologist A, for Pulmonologist B and for consensus, respectively. The definite or high confidence level of the consensus treatment strategy was 54.8% (17/31) without TBLC and 83.9% (26/31) with TBLC. There were 6 cases of moderate bleeding, but no other complications were noted. CONCLUSIONS: Pathological information from TBLC may contribute to decision-making in treatment strategies for the progression of DPLD, and it may be safely performed.

Successful Treatment of Chylothorax and Chylopericardium by Radiotherapy in Lung Cancer.

A 58-year-old man was diagnosed with stage IVB lung adenocarcinoma in the right upper lobe and underwent systemic chemotherapy. Seven months after the diagnosis, large left pleural and pericardial effusion was detected. The patient developed both chylothorax and chylopericardium following superior vena cava (SVC) obstruction with mediastinal lymphadenopathy caused by lung carcinoma. Since conservative treatment of the chyle leakage was ineffective, we administered radiotherapy to treat the SVC obstruction and mediastinal lymphadenopathy. After radiotherapy, the chylothorax and chylopericardium gradually resolved, and no further chyle leaks were identified on follow-up computed tomography. This case indicates that radiotherapy can be used to ameliorate lung cancer-related chylothorax and chylopericardium.

A case of cervical lymph node tuberculosis and metastatic squamous cell carcinoma in the same lymph node.

We report a rare coexistence of tuberculosis and squamous cell carcinoma (SCC) of the same lymph node (LN). A 74-year-old woman with a swollen right cervix underwent computed tomography, which showed a nodule in the right lung and swollen LNs of the mediastinum and right supraclavicular fossa. She was diagnosed with LN tuberculosis; the puncture cytology of the clavicular LN was class IV. Anti-tuberculosis treatment was initiated. Her neck was compressed due to LN enlargement, and dyspnea appeared. A biopsy was performed to diagnose the SCC. We propose that malignancy should be considered if the patient has a narrowed airway due to an enlarged LN or if the response to tuberculosis treatment is poor.

Successful treatment with afatinib following the failure of osimertinib rechallenge with osimertinib-induced interstitial lung disease: A case report.

Herein, we report the case of an 84-year-old woman with epidermal growth factor receptor (EGFR) mutation exon 19 deletion postoperative recurrent lung adenocarcinoma. Osimertinib was administered as a first-line treatment; however, she was urgently admitted to our hospital due to dyspnea on the 46th day. Chest computed tomography revealed bilateral diffuse ground-glass opacities (GGOs) suggestive of grade 3 osimertinib-induced interstitial lung disease (ILD). After discontinuation of osimertinib in combination with short-term corticosteroid therapy, widespread GGOs were promptly resolved. As the disease gradually deteriorated after discontinuation of osimertinib, we administered osimertinib (80 mg every other day) followed by careful observation. However, bilateral GGOs re-appeared on the 15th day, and the diagnosis of osimertinib-induced ILD was established. After the improvement in ILD following corticosteroid therapy, afatinib was administered as salvage therapy, resulting in desirable control of lung cancer without any relapse of ILD. Our results indicate that afatinib would be a promising alternative treatment option even in patients who develop osimertinib-induced ILD and experience failure of osimertinib rechallenge.

Spontaneous regression following endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients.

Spontaneous regression (SR) is defined as a complete or partial, temporary or permanent disappearance of a tumor without anticancer treatment, which potentially develops after surgery or biopsy for primary and metastatic tumors despite unknown incidence rate. Here, we report the incidence rate of SR after endobronchial ultrasound-guided transbronchial nodal needle aspiration (EBUS-TBNA) in lung cancer patients. Among 96 patients evaluable with chest CT before and after EBUS-TBNA, SR was found in three patients (3.1%). With regards to patient characteristics, two patients had small cell lung cancer (SCLC), and one patient had adenocarcinoma. All patients had stage 3 disease with a bulky N2 stage and a history of smoking. Two patients also had interstitial lung disease. Notably, SR was observed not only at the biopsied site, but also at the non-biopsied site. Our results indicate that SR can develop following EBUS-TBNA in a substantial proportion of lung cancer patients.