Chest wall subcutaneous mass leading to the diagnosis of pericostal tuberculosis.

When diagnosing a chest wall mass, even in the absence of pulmonary lesions, it is crucial to consider pericostal tuberculosis as a differential diagnosis. Attention must be paid to the characteristic findings on contrast-enhanced computed tomography, such as central low attenuation, peripheral rim enhancement of soft tissue, and pleural involvement.

Acute pulmonary thromboembolism with high-density emboli in the pulmonary artery detected on non-enhanced computed tomography.

The presence of high-density emboli in the pulmonary artery on non-enhanced computed tomography (CT) has high diagnostic performance for acute central pulmonary thromboembolism. Acute pulmonary thromboembolism is usually diagnosed by contrast-enhanced CT. However, it may be possible to achieve early diagnosis by identifying characteristic findings on non-enhanced CT.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Atezolizumab for EGFR-mutated Non-small Cell Lung Cancer Patients: An Observation Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab, an anti-programed death-ligand 1 monoclonal antibody, targets programed death-ligand 1 expressed on cancer cells and antigen-presenting cells and is now commonly used in combination with chemotherapy. We conducted a study to clarify the efficacy of atezolizumab in epidermal growth factor receptor (EGFR)-mutated patients who are considered less responsive to immune checkpoint inhibitors. PATIENTS AND METHODS: A retrospective review of patients with advanced non-small cell lung cancer (NSCLC) who received atezolizumab-containing therapy at 11 hospitals from April 2018 to March 2023 was performed. RESULTS: Median progression-free survival and overall survival in 33 EGFR-mutated patients treated with atezolizumab monotherapy were 2.0 and 9.0 months, respectively, and those in 19 patients who received combined atezolizumab plus chemotherapy were 12.0 and 17.0 months, respectively. When comparing EGFR-mutated and EGFR-negative patients after propensity score matching, there were no significant differences in progression-free survival and overall survival between the two groups, whether atezolizumab monotherapy or combined atezolizumab plus chemotherapy. Among EGFR-mutated patients, being male was a significant favorable factor in both atezolizumab treatment groups. None of the EGFR-mutated patients had grade 5 immune-related adverse events. CONCLUSION: Efficacy of atezolizumab in EGFR-mutated NSCLC patients could be comparable to that for EGFR-negative patients. To prolong the survival of EGFR-mutated NSCLC patients, appropriate selection and sequencing of EGFR for tyrosine kinase inhibitors, as well as immune checkpoint inhibitors, anti-tumor agents, and anti-angiogenic agents are important.

Atezolizumab Monotherapy for Non-small Cell Lung Cancer Patients: An Observational Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) expressed on cancer cells derived from various organs and antigen-presenting cells and is currently commonly used in combination with chemotherapy. We conducted a study to clarify the current status of response to atezolizumab monotherapy in clinical practice and clarify the factors that contribute to long-term response and survival. PATIENTS AND METHODS: We conducted a retrospective review of patients with advanced non-small cell lung cancer (NSCLC) treated with atezolizumab monotherapy from April 2018 to March 2023 at 11 Hospitals. RESULTS: The 147 patients evaluated had a progression-free survival (PFS) of 3.0 months and an overall survival of 7.0 months. Immune-related adverse events of any grade were observed in 13 patients (8.8%), grade 3 or higher in nine patients (6.1%), and grade 5 with pulmonary toxicity in one patient (0.7%). Favorable factors related to PFS were 'types of NSCLC other than adenocarcinoma'. Favorable factors for overall survival were 'performance status 0-1' and 'treatment lines up to 3'. There were 16 patients (10.9%) with PFS >1 year. No characteristic clinical findings were found in these 16 patients compared to the remaining 131 patients. CONCLUSION: Efficacy and immune-related adverse events of NSCLC patients associated with atezolizumab monotherapy were comparable to those of previous clinical trial results. Knowledge of characteristics of patients who are most likely to benefit from atezolizumab monotherapy is a crucial step towards implementing appropriate prescribing.

A phase II feasibility study of carboplatin and nab-paclitaxel for advanced non-small cell lung cancer patients with interstitial lung disease (YLOG0114).

BACKGROUND: A standard treatment regimen for advanced non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has not been established since most clinical trials exclude such patients because of the high risk of acute exacerbation of ILD. This study aimed to prospectively investigate the efficacy and safety of carboplatin and nab-paclitaxel as a first-line regimen for NSCLC patients with ILD. METHODS: The enrolled patients had treatment-naïve advanced NSCLC with ILD. The patients received 4-6 cycles of carboplatin (area under the curve = 5) on day 1 and nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the completion rate of four or more cycles. Secondary endpoints included toxicity, overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-five patients were enrolled in this study. Nine patients had adenocarcinoma, 11 had squamous cell carcinoma, one had large cell carcinoma, and four had NSCLC, not otherwise specified. The completion rate of ≥4 cycles was 76% (95% confidence interval: 56.2%-88.8%), which met the primary endpoint. The ORR and DCR were 44% and 88%, respectively. The median PFS and OS were 5.8 months and 15.8 months, respectively. Three patients experienced grade ≥2 pneumonitis, and one patient met the acute exacerbation criteria. CONCLUSION: The 4-week modified regimen of carboplatin and nab-paclitaxel showed tolerable toxicity with favorable efficacy in NSCLC patients with ILD. This regimen may be an effective treatment option for patients in real clinical settings.

Corrigendum: A Glycosylphosphatidylinositol-Anchored α-Amylase Encoded by amyD Contributes to a Decrease in the Molecular Mass of Cell Wall α-1,3-Glucan in Aspergillus nidulans.

[This corrects the article DOI: 10.3389/ffunb.2021.821946.].

Non-inferior clinical outcomes of immune checkpoint inhibitors in non-small cell lung cancer patients with interstitial lung disease.

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with pre-existing interstitial lung disease (ILD) is unclear. MATERIALS AND METHODS: Retrospective medical data from advanced or recurrent NSCLC patients who were treated with nivolumab or pembrolizumab at ten institutions in Japan between January 2016 and September 2018 were analyzed. Eligible patients were divided into two groups according to the presence of pre-existing ILD. RESULTS: A total of 461 NSCLC patients were enrolled, 412 without ILD (Non-ILD group) and 49 with ILD (ILD group). The response rate (RR) and disease control rate (DCR) of the ILD group were not inferior to those of the Non-ILD group [RR: 49.0 % (24/49) vs. 30.1 % (124/412), P < 0.01 and DCR: 69.4 % (34/49) vs. 51.2 % (211/412), P = 0.016, respectively]. Non-inferior outcomes were also observed with respect to progression-free survival (PFS) and overall survival (OS) (median PFS: 5.9 months vs. 3.5 months, P = 0.14 and median OS: 27.8 months vs. 25.2 months, P = 0.74 in the ILD and Non-ILD groups, respectively). Among immune-related adverse effects (irAEs), checkpoint inhibitor pneumonitis (CIP) was more frequently observed among NSCLC patients in the ILD group [30.6 % (15/49) vs. 9.5 % (39/412), P < 0.01]. The frequency of irAEs other than CIP and infusion reactions was not significantly different between the ILD group and the Non-ILD group. CONCLUSION: These results suggest that the clinical outcomes of ICIs are not significantly affected by pre-existing ILD despite the increased frequency of CIP. NSCLC patients with ILD are therefore probable candidates for ICIs.

A Glycosylphosphatidylinositol-Anchored α-Amylase Encoded by amyD Contributes to a Decrease in the Molecular Mass of Cell Wall α-1,3-Glucan in Aspergillus nidulans.

α-1,3-Glucan is one of the main polysaccharides in the cell wall of Aspergillus nidulans. We previously revealed that it plays a role in hyphal aggregation in liquid culture, and that its molecular mass (MM) in an agsA-overexpressing (agsAOE) strain was larger than that in an agsB-overexpressing (agsBOE) strain. The mechanism that regulates its MM is poorly understood. Although the gene amyD, which encodes glycosylphosphatidylinositol (GPI)-anchored α-amylase (AmyD), is involved in the biosynthesis of α-1,3-glucan in A. nidulans, how it regulates this biosynthesis remains unclear. Here we constructed strains with disrupted amyD (ΔamyD) or overexpressed amyD (amyDOE) in the genetic background of the ABPU1 (wild-type), agsAOE, or agsBOE strain, and characterized the chemical structure of α-1,3-glucans in the cell wall of each strain, focusing on their MM. The MM of α-1,3-glucan from the agsBOE amyDOE strain was smaller than that in the parental agsBOE strain. In addition, the MM of α-1,3-glucan from the agsAOE ΔamyD strain was greater than that in the agsAOE strain. These results suggest that AmyD is involved in decreasing the MM of α-1,3-glucan. We also found that the C-terminal GPI-anchoring region is important for these functions.

Treatment of Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in Clinical Practice.

BACKGROUND/AIM: To describe real clinical outcomes in patients with non-small cell lung cancer who have uncommon epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: We performed a retrospective chart review from 15 medical institutes that cover a population of three million people from April 2008 to March 2019. RESULTS: There were 102 patients with uncommon EGFR mutation. Progression-free survival (PFS) tended to be longer in patients receiving afatinib compared with first-generation EGFR tyrosine kinase inhibitors. PFS in patients treated with afatinib or osimertinib was significantly longer than in patients treated with gefitinib or erlotinib (p=0.030). Multivariate analysis also revealed the contribution of afatinib or osimertinib to increased survival. In patients with exon 20 insertions, chemotherapy was efficacious. CONCLUSION: In treating patients with uncommon EGFR mutations, our results indicate longer-term survival might be achieved with second-generation or later TKIs and cytotoxic chemotherapeutic drugs.

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients.

AIM: To clarify the clinicopathological features in elderly anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A retrospective study was performed in 129 ALK rearranged NSCLC patients diagnosed between April 2008 and March 2019 in fifteen Institutions of the Ibaraki prefecture, Japan. RESULTS: Median age of patients was 63 years. In 59 patients aged 65 and older, the proportions of patients with advanced stage and those treated with ALK-tyrosine kinase inhibitor (TKI) were lower than those younger than 65 years. There was no difference in overall survival (OS) between the two age groups. Among the elderly patients, no difference was observed in OS between the patients aged 65-69 and those aged 70 and older. In 89 patients treated with TKI, no significant differences were observed in the progression-free survival of TKIs and OS between patients aged 65 and older and those younger than 65, respectively. CONCLUSION: Evaluation of ALK gene status and TKI treatment are desirable even for elderly patients.

Serum CEA and CYFRA Levels in ALK-rearranged NSCLC Patients: Correlation With Distant Metastasis.

AIM: To clarify the correlation between serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) and metastasis and survival in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: CEA and CYFRA levels in 131 ALK-rearranged NSCLC patients were determined using fluorescence in situ hybridization (FISH), real time-reverse transcription polymerase chain reaction, and immunohistochemistry, using biopsy specimens, cytology specimens, and plasma specimens. Cut-off value of each marker was determined as 10 ng/ml. RESULTS: In logistic regression analysis, higher levels of both markers had a positive relationship with bone metastases, and higher levels of CYFRA was relevant to liver metastases, and multiple-organ metastases. However, these markers were not proven to be poor prognostic factors in Cox's proportional model analysis. CONCLUSION: Elevated serum CEA and CYFRA levels seem to provide useful clinical information about presence of bone and liver metastasis and multiple-organ metastases, although they were not a powerful indicator of prognosis. These two markers may suggest the extension of metastasis and would be helpful in considering treatment options.

Real Clinical Practice in ALK-rearranged NSCLC Patients: A Retrospective Observational Study.

BACKGROUND/AIM: To describe real clinical outcomes when using systemic therapy to treat non-small cell lung cancer (NSCLC) patients who have anaplastic lymphoma kinase (ALK) fusion gene mutation. PATIENTS AND METHODS: We performed a retrospective chart review from April 2008 to March 2019 sourced from 16 medical institutes that cover a population of three million people. RESULTS: There were 129 ALK rearranged NSCLC patients. Among them, 103 patients including 40 recurrent disease cases received ALK-tyrosine kinase inhibitors (TKI) and chemotherapy. Our treatment results were comparable to previously reported clinical trials and clinical practice studies. First-line alectinib, treatment sequence of ALK-TKI followed by another ALK-TKI, and pemetrexed-containing chemotherapy contributed to the outcome of treatment. CONCLUSION: By arrangement of treatment such as treatment sequence of ALK-TKI and chemotherapy regimen, it might be possible to obtain a treatment outcome almost equivalent to those of clinical trials even in real clinical practice.

The utility of ground-glass attenuation score for anticancer treatment-related acute exacerbation of interstitial lung disease among lung cancer patients with interstitial lung disease.

BACKGROUND: Acute exacerbation (AE) of interstitial lung disease (ILD) is a fatal adverse event in the treatment of lung cancer patients with ILD. The value of pre-treatment radiological findings obtained by high-resolution computed tomography for the detection of anticancer treatment-related AE of ILD has not been established. METHODS: Two medical record-based retrospective studies were performed. The chemotherapy cohort included 105 lung cancer patients with ILD who received chemotherapy at Tokyo Medical and Dental University between October 2008 and December 2017. The immune checkpoint inhibitor (ICI) cohort included 48 advanced non-small cell lung cancer patients with ILD treated with ICIs at nine institutions between January 2016 and September 2018. Variables were compared between AE-positive and -negative groups. Candidate variables were analyzed by multivariate logistic regression. A P value < 0.05 was considered statistically significant. RESULTS: Anticancer treatment-related AE of ILD occurred in 12 patients (11.4%) in the chemotherapy cohort and seven patients (14.5%) in the ICI cohort. In the multivariate logistic regression analysis, ground-glass attenuation (GGA) score was the only factor significantly associated with the development of AE of ILD in both cohorts (P = 0.037 and 0.01 in the chemotherapy and ICI cohorts, respectively). CONCLUSION: Evaluation of GGA may help predict anticancer treatment-related AE of ILD.

Hematogenous pleural infection caused by Achromobacter xylosoxidans in a patient undergoing maintenance hemodialysis.

A 78-year-old Japanese man, undergoing maintenance hemodialysis for 20 years and having received coronary artery bypass grafting two months before, was hospitalized because of fever with subclinical left-sided pleurisy. Achromobacter xylosoxidans strains exhibiting identical genomic patterns on a macrorestriction analysis were isolated from the blood and the pleural effusion obtained on admission. Physical and radiological examinations did not reveal any lesions in either chest wall or lung adjacent to the effusion, indicating that the organism in the effusion had entered the pleural space via the bloodstream. Immunocompromising conditions due to undergoing maintenance hemodialysis and the presence of the antecedently accumulated pleural effusion may have been associated with the development of hematogenous dissemination. The patient fully recovered only with antibiotic therapy. To our knowledge, the present report is the first describing a case of hematogenous pleural infection caused by A. xylosoxidans.

Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an Acquired EGFR T790M Mutation.

BACKGROUND/AIM: To describe real clinical outcomes when using afatinib therapy to treat non-small cell lung cancer patients who have an acquired EGFR T790M mutation. MATERIALS AND METHODS: A retrospective chart review was conducted from January 2013 to November 2017 sourced from 15 medical institutes that cover a population of three million people. RESULTS: There were 74 patients who met the above-mentioned criteria. Treatment outcomes with afatinib, in patients with or without tyrosine kinase inhibitor (TKI) therapy prior to afatinib, were similar to previously reported clinical trials. Stratification of patients by the presence or absence of TKI pretreatment before afatinib, and the presence or absence of an acquired T790M mutation found no statistical difference in overall survival. CONCLUSION: This population-based study found that the disadvantages of pretreatment before afatinib, and absence of an acquired T790M EGFR mutation, could be overcome by an appropriate treatment strategy in clinical practice.

Acquired EGFR T790M Mutation After Relapse Following EGFR-TKI Therapy: A Population-based Multi-institutional Study.

AIM: To describe the prevalence and determinants of acquired epidermal growth factor receptor (EGFR) T790M gene mutation in a clinical practice setting. MATERIALS AND METHODS: We performed a retrospective chart review study between January 2013 and November 2017 across multiple institutes, covering a population of 3 million people. RESULTS: We reviewed the charts of 233 patients non-small cell lung cancer with EGFR mutations. Of them, 99 (42.5%) patients had acquired T790M mutations in EGFR. Patients ≥75 years old and patients with an exon 19 deletion had higher rates of acquired T790M mutation than did younger patients and those with an exon 21 L858R mutation. In 75 patients treated with afatinib, 34 (45.3%) patients had acquired T790M mutation. The sensitivity of T790M mutation detection was lower in plasma specimens than in biopsy specimens. CONCLUSION: This population-based study confirms previous studies and highlights potential determinants of acquired T790M mutation to be considered in clinical practice.

Evaluation of the Time-Dependent Changes and the Vulnerability of Carotid Plaques Using Contrast-Enhanced Carotid Ultrasonography.

BACKGROUND: The association of carotid plaque enhancement on contrast-enhanced carotid ultrasound (CEUS) and plaque vulnerability evaluated by magnetic resonance imaging (MRI) was to be determined. MATERIALS AND METHODS: The 103 patients underwent CEUS from May 2013 until June 2016. CEUS images of the carotid plaque were obtained offline. Plaque images obtained at 1, 3, 5, and 10 minutes were compared with the reference image, defined as the image obtained at 0 minute. Plaque brightness was assessed using the gray-scale median during contrast enhancement (GSM-C). Plaque vulnerability was evaluated using T1- and T2-weighted MRI and Volume ISotropic TSE Acquisition (VISTA), with a VISTA cutoff value for the plaque muscle ratio (PMR) of 1.5. Time-dependent changes in the GSM-C were evaluated, and those between 0 and 1 minute were compared with the PMR values determined on MRI. FINDINGS: GSM-C decreased significantly over time, from 32.0 at 0 minute to 28.0 at 1 minute, 25.0 at 3 minutes, and 19.0 at 10 minutes. The greater the increase in the changes in the GSM-C from 0 to 1 minute, the more significant the association with a PMR higher than the median on T1 (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .015), a PMR less than or equal to the median on T2 (0 min: 35.0, 1 min: 28.0, P = .003), and a PMR more than 1.5 determined on VISTA (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .005). CONCLUSIONS: Early changes in the GSM-C evaluated with CEUS indicate significant plaque vulnerability on MRI.

Neurological Symptoms of Sarcoidosis-induced Small Fiber Neuropathy Effectively Relieved with High-dose Steroid Pulse Therapy.

A 59-year-old woman was admitted to our hospital for an evaluation of a 10-day history of progressive pain and hypoesthesia of the right lower back associated with fever and constipation. Sarcoidosis was confirmed on mediastinal lymph node and skin biopsies. Although the neurological symptoms were suspected due to sarcoidosis-induced nerve dysfunction, nerve conduction studies and other routine examinations did not show any abnormalities. The intraepidermal nerve fiber density assessed on a skin biopsy was significantly reduced, suggesting small-fiber neuropathy (SFN). The patient was finally diagnosed with sarcoidosis-induced SFN, and her neurological symptoms were effectively relieved with high-dose steroid therapy.

Serum γ-glutamyltransferase, triglyceride and total cholesterol are possible prediabetic risk markers in young Japanese men.

Serum profiles of lipids and/or liver enzymes are established markers for the estimation of insulin resistance and diabetic risk in the non-diabetic middle-aged population. To identify prediabetic markers in young subjects, 110 young male subjects (20-29 years of age) with normal glucose tolerance (NGT) were divided into two groups by median body mass index (BMI), <22.18 (n=55) and ≥22.18 (n=55) kg/m(2). Indices of insulin sensitivity including HOMA-IR and ISI composite, indices of ß-cell function including HOMA-ß, insulinogenic index (ΔI(30)/ΔG(30)) and ΔI(30)/ΔG(30)/ HOMA-IR were calculated. Statistical associations between these parameters and the serum lipid profiles and liver function were evaluated. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), total cholesterol (TC) and triglyceride (TG) levels were inversely correlated with the ISI composite among individuals with BMI ≥22.18 kg/m(2) but not those with BMI <22.18 kg/m(2). Multivariate regression analysis revealed that, in Group N, the plasma glucose levels at 60 min (PG(60)) were inversely correlated with the ISI composite and the insulinogenic index, and were positively correlated with the GGT, TC and TG levels. On the other hand, in Group L, PG(60) was correlated with the insulinogenic index, TC and TG levels. In conclusion, elevated levels of GGT, TC and TG are good clinical markers to predict diabetic risks, even in young NGT males. Of these, GGT was the most strongly related factor among subjects with relatively high BMI.