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1.
Respir Med Case Rep ; 46: 101918, 2023.
Article in English | MEDLINE | ID: mdl-37822764

ABSTRACT

We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly.

2.
J Immunother Cancer ; 11(7)2023 07.
Article in English | MEDLINE | ID: mdl-37500182

ABSTRACT

BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. RESULTS: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. CONCLUSIONS: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. TRIAL REGISTRATION NUMBER: jRCT: 1041190029.


Subject(s)
Neoplasms , Pneumonia , Humans , Prospective Studies , Prednisolone/therapeutic use , Neoplasms/drug therapy , Recurrence
3.
Ther Adv Respir Dis ; 17: 17534666231172924, 2023.
Article in English | MEDLINE | ID: mdl-37218674

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Many patients with COPD experience exacerbations that require hospitalization, which is associated with an increased risk of in-hospital death and impaired ability to perform activities of daily living (ADL). Declining ability to perform ADL is a critical issue for these patients. OBJECTIVES: To identify predictors of poor clinical outcomes, including in-hospital death and low ability to perform ADL at discharge, in patients who are hospitalized with exacerbation of COPD. DESIGN: This retrospective study involved a cohort of patients with exacerbation of COPD who were admitted to Iwata City Hospital in Japan between July 2015 and October 2019. METHODS: We collected clinical data, measured the cross-sectional area of the erector spinae muscles (ESMCSA) on computed tomography (CT) scans at admission, and investigated the associations of poor clinical outcomes (in-hospital death and severe dependence when performing ADL, defined as a Barthel Index (BI) of ⩽40 at discharge) with clinical parameters. RESULTS: Overall, 207 patients were hospitalized for exacerbation of COPD during the study period. The incidence of poor clinical outcomes was 21.3%, and the in-hospital mortality rate was 6.3%. Multivariate logistic regression analyses showed that older age, long-term oxygen therapy, an elevated D-dimer concentration, and a reduced ESMCSA on chest CT at admission were significantly associated with poor clinical outcomes (in-hospital death and a BI of ⩽40). CONCLUSION: Hospitalization for exacerbation of COPD was associated with high rates of in-hospital mortality and a BI of ⩽40 at discharge, which may be predicted by assessment of ESMCSA.


Subject(s)
Activities of Daily Living , Pulmonary Disease, Chronic Obstructive , Humans , Hospital Mortality , Retrospective Studies , Patient Discharge , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/complications , Hospitalization , Disease Progression
4.
Cancer Immunol Immunother ; 72(8): 2717-2728, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37099186

ABSTRACT

Whether circulating levels of specific cytokines at baseline link with treatment efficacy of immune checkpoint blockade (ICB) therapy in patients with non-small cell lung cancer remains unknown. In this study, serum samples were collected in two independent, prospective, multicenter cohorts before the initiation of ICB. Twenty cytokines were quantified, and cutoff values were determined by receiver operating characteristic analyses to predict non-durable benefit. The associations of each dichotomized cytokine status with survival outcomes were assessed. In the discovery cohort (atezolizumab cohort; N = 81), there were significant differences in progression-free survival (PFS) in accordance with the levels of IL-6 (log-rank test, P = 0.0014), IL-15 (P = 0.00011), MCP-1 (P = 0.013), MIP-1ß (P = 0.0035), and PDGF-AB/BB (P = 0.016). Of these, levels of IL-6 and IL-15 were also significantly prognostic in the validation cohort (nivolumab cohort, N = 139) for PFS (log-rank test, P = 0.011 for IL-6 and P = 0.00065 for IL-15) and overall survival (OS; P = 3.3E-6 for IL-6 and P = 0.0022 for IL-15). In the merged cohort, IL-6high and IL-15high were identified as independent unfavorable prognostic factors for PFS and OS. The combined IL-6 and IL-15 status stratified patient survival outcomes into three distinct groups for both PFS and OS. In conclusion, combined assessment of circulating IL-6 and IL-15 levels at baseline provides valuable information to stratify the clinical outcome of patients with non-small cell lung cancer treated with ICB. Further studies are required to decipher the mechanistic basis of this finding.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Interleukin-15 , Interleukin-6 , Lung Neoplasms , Nivolumab , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Nivolumab/therapeutic use , Immune Checkpoint Proteins/therapeutic use , Antineoplastic Agents/therapeutic use , Prognosis , Interleukin-6/blood , Interleukin-15/blood , Male , Female , Aged , Lung Neoplasms/blood , Lung Neoplasms/drug therapy
5.
Respir Med Case Rep ; 42: 101823, 2023.
Article in English | MEDLINE | ID: mdl-36915472

ABSTRACT

Severe immune thrombocytopenia is a rare side-effect of rifampicin (RFP) and can be life-threatening. Here, we report the case of a 74-year-old male with tuberculous pleurisy who developed severe thrombocytopenia after first exposure to RFP. Platelet count decreased to 1 × 103/µL after 7 days of treatment with RFP, isoniazid, ethambutol, and pyrazinamide. After all the drugs were discontinued, the platelet count recovered. As thrombocytopenia did not occur after re-administration of drugs other than RFP, the patient was diagnosed with RFP-induced thrombocytopenia. Clinicians should be aware that RFP can induce acute and severe thrombocytopenia even without previous exposure to this drug.

6.
J Cancer Res Clin Oncol ; 149(7): 2963-2974, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35834011

ABSTRACT

PURPOSE: Identifying patients at high risk of immune-related adverse events (irAEs) that impede the achievement of durable efficacy of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy is important in improving their management. Identification of a novel predictive factor of therapeutic benefit is also important in improving patient selection for treatment with PD-1/PD-L1 inhibitors. Further determinants driving response and linking with irAEs are urgently required. METHODS: To address these unmet needs in the field, we explored whether 27 soluble checkpoint proteins and immunomodulatory proteins in serum at the therapy baseline and after week 3 were associated with irAE onset and therapeutic efficacy using MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel assays in a prospective, multicenter cohort of 81 patients with non-small cell lung cancer (NSCLC) receiving atezolizumab monotherapy. RESULTS: By competing-risks regression analysis, we identified that high levels of B cell-activating factor (BAFF) at baseline were a significant and strong risk factor of irAEs (hazard ratio, 5.61; 95% confidence interval, 2.43-12.96; P < 0.0001). We also identified that increased inducible T cell co-stimulator (ICOS) during the first therapeutic cycle was an independent factor associated with prolonged progression-free survival and overall survival. CONCLUSION: These findings are in keeping with the reported mechanistic basis of these molecules and may provide potential guidance for clinical decision-making to improve patient care. Further validation studies are warranted. Trial registration UMIN000035616 (January 28, 2019).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Programmed Cell Death 1 Receptor , Prospective Studies , Immunologic Factors , B7-H1 Antigen , Retrospective Studies
7.
Medicine (Baltimore) ; 101(39): e30806, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36181091

ABSTRACT

RATIONALE: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis. INTERVENTION AND OUTCOME: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses. LESSONS: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA.


Subject(s)
Arthritis, Rheumatoid , COVID-19 Vaccines , COVID-19 , Pulmonary Eosinophilia , Aged, 80 and over , Anti-Inflammatory Agents , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Inflammation , Methylprednisolone/therapeutic use , Pulmonary Eosinophilia/etiology , Rheumatoid Factor , Vaccination
8.
Ther Adv Chronic Dis ; 13: 20406223221108395, 2022.
Article in English | MEDLINE | ID: mdl-35782342

ABSTRACT

Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66-95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4-29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00-1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31-53)/8.9 months (95% CI: 7.6-11.8) and 91% (95% CI: 76-98)/12.2 months (95% CI: 9.2-14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

9.
Respir Med Case Rep ; 36: 101606, 2022.
Article in English | MEDLINE | ID: mdl-35242519

ABSTRACT

Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are two major myositis-specific autoantibodies with distinct clinical features. However, the clinical course remains unclear in patients with clinically amyopathic dermatomyositis (CADM)-interstitial lung disease (ILD) who have co-existing anti-MDA5 and anti-ARS antibodies. Here, we describe the case of a 32-year-old woman with CADM-ILD who had anti-MDA5 and anti-PL12 antibodies. Her serum ferritin level was within the normal range. However, chest computed tomography revealed bilateral lower-lobe consolidation and ground-glass opacities. Treatment with prednisolone and immunosuppressants was successful in improving the skin lesion and ILD, but relapse occurred on reducing the dose of prednisolone. These clinical features match those of anti-ARS antibody-positive dermatomyositis-ILD. Because these two conditions show significantly different clinical features and require different intensities of treatment, clinicians should carefully follow-up these patients throughout the course of the disease.

10.
Cancer Immunol Immunother ; 71(1): 203-217, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34091744

ABSTRACT

BACKGROUND: Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS: The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS: When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS: Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , Carcinoma, Non-Small-Cell Lung/blood , Cholesterol/blood , Fatty Acids/biosynthesis , Gene Expression Regulation, Neoplastic , Lung Neoplasms/blood , Nivolumab/pharmacology , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Disease-Free Survival , Female , Humans , Immune Checkpoint Inhibitors/metabolism , Lipids/chemistry , Lung Neoplasms/drug therapy , Male , Middle Aged , Prospective Studies , Treatment Outcome
11.
Respir Med Case Rep ; 34: 101458, 2021.
Article in English | MEDLINE | ID: mdl-34381678

ABSTRACT

A 41-year-old man presented with multiple superficial lymph nodes (LNs) swollen with elevated levels of serum immunoglobulin (Ig)G4 and C-reactive protein. Histological findings of his left inguinal LN revealed lymphoplasmacytic infiltration with numerous IgG4-positive plasma cells; IgG4+/IgG+ plasma cell ratio >40%. Chest computed tomography (CT) showed poorly defined centrilobular nodules, interlobular septal thickening, consolidations, and mediastinal LNs swelling. Bronchoalveolar lavage fluid (BALF) showed elevated eosinophils. A surgical lung biopsy showed focal dense eosinophil infiltration, in addition to lymphoplasmacytic infiltration, but few IgG4+ plasma cells. The diagnosis of multicentric Castleman disease (MCD) was made because of serum interleukin-6elevation. Treatment with prednisolone and tocilizumab improved his symptoms and lung lesions. This case shows that overlapping clinical and pathological features of MCD and IgG4-related disease may present in a single patient, showing the difficulty in distinguishing between these two diseases.

12.
Invest New Drugs ; 39(1): 210-216, 2021 02.
Article in English | MEDLINE | ID: mdl-32803701

ABSTRACT

The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations are unknown. Elderly patients aged ≥75 years old with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria (n = 2), gastrointestinal perforation (n = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients with EGFR-positive NSCLC.


Subject(s)
Antineoplastic Agents/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Erlotinib Hydrochloride/therapeutic use , Lung Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carcinoma, Non-Small-Cell Lung/genetics , Dose-Response Relationship, Drug , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Female , Humans , Lung Neoplasms/genetics , Male
13.
JAMA Netw Open ; 3(9): e2011818, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32955570

ABSTRACT

Importance: Robust predictors for response to anti-programmed death 1 and its ligand (PD-1/PD-L1) immunotherapy in non-small cell lung cancer (NSCLC) are not fully characterized. Objective: To evaluate whether PD-L1 (CD274) copy number gains (CNGs), comprising amplification and polysomy, in pretreatment specimens assessed by fluorescence in situ hybridization are associated with response to nivolumab monotherapy in NSCLC. Design, Setting, and Participants: This multicenter cohort study enrolled 200 patients, of whom 194 had assessable tumors, with advanced or recurrent NSCLC who were treated with nivolumab after progression following prior treatment at 14 institutions in Japan between July 2016 and December 2018. Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months. Data were analyzed from December 2019 to February 2020. Exposures: Sequential nivolumab was given on day 1 of a 14-day cycle. Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1. Main Outcomes and Measures: Overall response rate (ORR) according to the PD-L1 copy number status. Additional end points were progression-free survival, overall survival, and PD-L1 tumor proportion score (TPS) assessed by immunohistochemistry based on PD-L1 copy number status. Results: A total of 6 of the 200 patients were excluded because of poor-quality tumor specimens for the biomarker study, resulting in 194 assessable patients. Of these, 155 (79.9%) were men, with a median (range) age of 69 (43-83) years. PD-L1 CNGs were identified in 32 patients (16.5%), including 5 (2.6%) with amplification and 27 (13.9%) with polysomy. The ORR among patients with and without PD-L1 CNGs was 28.1% (95% CI, 13.7%-46.7%) and 17.9% (95% CI, 12.3%-24.7%), respectively. Although patients with PD-L1 polysomy did not demonstrate improved ORR (18.5% [95% CI, 6.3%-38.1%]) compared with those without PD-L1 CNGs, 4 of 5 patients (80.0% [95% CI, 28.4%-99.5%]) with PD-L1 amplification showed response, among whom median duration of response was not reached. Patients with PD-L1 amplification showed excellent survival outcomes for progression-free and overall survival. Overall, 3 PD-L1-amplified tumors (60.0%) showed PD-L1 TPS of at least 80%, but 2 (40.0%) had PD-L1 TPS of 15% or less. Conclusions and Relevance: In this study, tumor PD-L1 amplification but not polysomy was associated with response to nivolumab monotherapy among patients with NSCLC. External validation with a larger sample size is warranted.


Subject(s)
B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Gene Amplification , Lung Neoplasms , Neoplasm Recurrence, Local , Nivolumab , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , DNA Copy Number Variations , Female , Humans , Japan/epidemiology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nivolumab/administration & dosage , Nivolumab/adverse effects , Polyribosomes , Response Evaluation Criteria in Solid Tumors
14.
Respirol Case Rep ; 8(6): e00612, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32670585

ABSTRACT

We present a 67-year-old man with allergic bronchopulmonary aspergillosis (ABPA), whose chest computed tomography (CT) scans showed localized circumferential bronchial wall thickening in the right main bronchus to middle truncus. Chest CT scans showed high-attenuation mucus in the right B8 bronchus. Bronchoscopy showed narrowing of the right main bronchus and inspissated mucus plugging in the right B8 bronchus. Histological examination of the right main bronchus revealed bronchial inflammation with numerous neutrophils and plasma cells. Treatment with corticosteroid and antifungal agents resulted in resolution of the symptoms and right bronchial lesions. The clinical course may indicate that the bronchial lesions were associated with ABPA.

15.
J Thorac Oncol ; 15(8): 1317-1327, 2020 08.
Article in English | MEDLINE | ID: mdl-32289515

ABSTRACT

INTRODUCTION: Programmed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting. METHODS: This is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed. RESULTS: Among the 138 patients with NSCLC who received anti-programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29-147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development. CONCLUSIONS: The incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Diseases, Interstitial , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immune Checkpoint Inhibitors , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/drug therapy , Lung Neoplasms/drug therapy , Prospective Studies
16.
Respir Med Case Rep ; 29: 100975, 2020.
Article in English | MEDLINE | ID: mdl-31886124

ABSTRACT

Bronchoscopic findings often show mucoid impaction in patients with allergic bronchopulmonary aspergillosis (ABPA); however, endobronchial mucosal nodular lesions have not been reported. We herein present the first such case of a 52-year-old woman with ABPA with endobronchial mucosal nodular lesions. The endobronchial lesions were located in the orifice of the mucoid impaction, and disappeared after 4 weeks of treatment with prednisolone and itraconazole. Aspergillus fumigatus was cultured from bronchial lavage fluid collected from the site of mucoid impaction. Based on these clinical findings, we speculate that the bronchial lesions were caused by an inflammatory and allergic reaction to Aspergillus antigens.

17.
Intern Med ; 59(5): 701-704, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-31708544

ABSTRACT

Invasion of the endobronchial mucosa by cancer cells is frequently seen in small cell lung cancer (SCLC), but an intraluminal polypoid growth pattern is extremely rare. We herein describe the case of a 69-year-old woman with limited-stage SCLC who had a pedunculated mass in the orifice of the right upper bronchus. Thin-section CT of the lung showed an endobronchial protruding mass accompanied by tubular and branching opacities (the so-called finger-in-glove sign) in the right upper lobe bronchus, which were enhanced by contrast media. She responded well to chemotherapy with concurrent radiation therapy. Although very rare, SCLC patients can have intraluminal polypoid growth, as was observed in this case.


Subject(s)
Lung Neoplasms/pathology , Small Cell Lung Carcinoma/pathology , Aged , Bronchi/pathology , Female , Humans , Lung Neoplasms/diagnostic imaging , Polyps/pathology , Small Cell Lung Carcinoma/diagnostic imaging
18.
Intern Med ; 59(7): 987-990, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31839658

ABSTRACT

We herein report a 38-year-old woman with breast cancer who developed Pneumocystis jirovecii pneumonia (PCP) during neoadjuvant dose-dense chemotherapy combined with dexamethasone as antiemetic therapy. Chest computed tomography showed bilateral ground-glass opacities and consolidation. The serum ß-D-glucan levels were elevated, and P. jirovecii DNA was detected from the bronchoalveolar lavage fluid by polymerase chain reaction. Her clinical findings improved with trimethoprim/sulfamethoxazole and adjunctive steroid therapy. Clinicians must be mindful of the manifestations of PCP in non-human immunodeficiency virus (HIV)-infected immunocompromised patients and include the possibility of PCP in the differential diagnosis when confronted with breast cancer on dose-dense chemotherapy showing diffuse lung disease.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Pneumonia, Pneumocystis/chemically induced , Pneumonia, Pneumocystis/drug therapy , Adult , Female , Humans , Neoadjuvant Therapy/adverse effects , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/physiopathology , Treatment Outcome
19.
Intern Med ; 58(21): 3149-3152, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31327818

ABSTRACT

Chest computed tomography (CT) findings of minute pulmonary meningothelial-like nodules (MPMNs) usually show tiny nodules (2-5 mm in diameter) of ground-glass attenuation. However, diffuse, thin-walled cavities have rarely been reported. We herein report a 56-year-old woman with MPMNs showing diffuse, thin-walled cystic lesions on a thin-section chest CT scan. Clinicians need to be aware of the imaging characteristics of this conditions to guide appropriate management of lung diseases, as these CT findings may resemble certain metastatic lung neoplasias and primary adenocarcinoma of the lung.


Subject(s)
Lung Neoplasms/pathology , Lung/pathology , Multiple Pulmonary Nodules/pathology , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Multiple Pulmonary Nodules/diagnostic imaging , Tomography, X-Ray Computed
20.
Cancer Chemother Pharmacol ; 84(1): 147-153, 2019 07.
Article in English | MEDLINE | ID: mdl-31087137

ABSTRACT

PURPOSE: There remains an unmet clinical need for the control of chemotherapy-induced nausea and vomiting (CINV), particularly in the prevention of nausea and the delayed phase control. We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and dexamethasone in patients receiving carboplatin-containing chemotherapy. Olanzapine inhibits signalling via multiple neurotransmitter receptors involved in CINV. METHODS: Chemotherapy-naïve patients with lung cancer who received carboplatin-containing chemotherapy were enrolled in this phase-II study. Patients received olanzapine, aprepitant, a 5-HT3 receptor antagonist and dexamethasone. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during 120 h after administration of chemotherapy agents. RESULTS: Thirty-three patients received olanzapine-containing antiemetic therapy. The overall complete response rate was 93.3% (95% confidence interval, 80.4-98.3%). The frequency of nausea was 15.2% in the delayed phase and 18.2% in the overall phase. Somnolence was observed in 16 patients. CONCLUSION: Adding olanzapine to antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist and dexamethasone improved CINV control in patients receiving carboplatin-containing chemotherapy.


Subject(s)
Antiemetics/administration & dosage , Carboplatin/adverse effects , Nausea/prevention & control , Olanzapine/administration & dosage , Vomiting/prevention & control , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Aprepitant/administration & dosage , Carboplatin/administration & dosage , Dexamethasone/administration & dosage , Drug Therapy, Combination , Female , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Nausea/chemically induced , Prospective Studies , Vomiting/chemically induced
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