Coherent Doppler LIDAR with long-duration frequency-modulated pulses for wind sensing.

A coherent Doppler LIDAR (CDL) with long-duration frequency-modulated pulses was demonstrated and validated by analyzing the data observed by a prototype. In traditional CDL using short-duration single-frequency pulses (PCDL; pulsed CDL), there exists a trade-off relationship between distance and velocity resolution. Meanwhile, in earlier work, a theoretical framework of CDL using long-duration frequency-modulated pulses (FMCDL; frequency-modulated CDL) was put forth to eliminate the trade-off. We developed the prototype to be operated as both a PCDL and FMCDL. Analyses of data observed by the PCDL and FMCDL modes showed that the FMCDL worked in good agreement with the PCDL for wind ranging and velocimetry. Furthermore, the performance of the FMCDL in terms of received power and resolution of distance and velocity was quantitatively consistent with ones theoretically expected.

Left-atrial volume reduction reflects improvement of cardiac sympathetic nervous function in patients with severe aortic stenosis after transcatheter aortic valve replacement.

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85 years, IQR 82-88 years; 81% female) before and after TAVR. CSN function was assessed by performing 123I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6 months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7 mL/m2 [37.8-56.3] vs. 41.2 mL/m2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (ß = - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery.

P-Wave Terminal Force V1 Is Associated with Left Ventricular Diastolic Function in Patients with No Significant Perfusion Abnormality.

P-wave terminal force in lead V1 (PTFV1) is a marker of increased left atrial (LA) overload. Whether PTFV1 is associated with left ventricular (LV) diastolic function remains undetermined. We tested the hypothesis that PTFV1 is associated with LV diastolic parameters derived from gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with no significant perfusion abnormalities.The study population included 158 patients with preserved ejection fraction and no significant perfusion abnormalities. The amplitude and duration of the P-wave negative phase in lead V1 were measured using an electrocardiogram, and PTFV1 was calculated. The peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were obtained as LV diastolic parameters using gated SPECT.PTFV1 showed a weak correlation with the LA volume index (r = 0.31; P < 0.001). Significant associations were observed between PTFV1 and PFR (r = -0.27; P < 0.001) and 1/3 MFR (r = -0.26; P = 0.001). A multivariate linear regression analysis showed that age (ß = -0.26; P < 0.001), LV end-diastolic volume index (ß = -0.27; P = 0.001), and PTFV1 (ß = -0.15; P = 0.036) were significant factors associated with PFR. Moreover, male gender (ß = -0.16; P = 0.041), LV mass index (ß = -0.17; P = 0.046), and PTFV1 (ß = -0.17; P = 0.022) were significant factors associated with the 1/3 MFR.PTFV1 is associated with LV diastolic function, as derived from gated SPECT in patients with no significant perfusion abnormalities.

New Minimally Invasive and Tailor-Made Strategy for Cryoballoon Ablation in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: The optimal dosage for cryoballoon ablation (CBA) of atrial fibrillation (AF) is still unknown. OBJECTIVE: This study aimed to evaluate the clinical implications of a reduction in the freezing duration to <180 seconds during CBA guided by the time to the target temperature. METHODS: This study enrolled 325 consecutive paroxysmal AF patients who underwent CBA. It was a retrospective observational study in a single centre. It compared 164 patients who underwent a tailor-made CBA procedure (group T) with 161 who had a standard CBA procedure (group S). In group T, the freezing duration was reduced to 150 seconds when the temperature reached ≤ -40 °C within 40 seconds. Furthermore, it was reduced to 120 seconds when it reached ≤ -50 °C within 60 seconds. In the other patients, the freezing duration was 180 seconds, except for excessive freezing of ≤ -60 °C and/or emergent situations while monitoring the oesophageal temperature, and for phrenic nerve injury, as in group S. RESULTS: In group T, 89 patients (83%) underwent CBA with a reduction in the freezing duration. The total freezing time for each pulmonary vein was significantly shorter in group T than group S, and the total procedure time in group T decreased by an average of 4 minutes compared with group S. The rate of requiring additional radio frequency ablation following the CBA was significantly lower in group T than group S. The AF-free survival rate during the follow-up period (median, 366 days) was similar between the two groups. CONCLUSION: The safety and efficacy of the new CBA strategy were non-inferior to the standard procedure.

Pulmonary Pleomorphic Carcinoma Harboring EGFR Mutation Successfully Treated with Osimertinib: A Case Report.

Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. A 43-year-old female patient presenting with a lung mass with multiple brain metastases, carcinomatous pericarditis, and multiple bone metastases was referred to our department. Transbronchial biopsy confirmed the diagnosis of PPC harboring an EGFR mutation with exon 19 deletion. Subsequently, she was treated with osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, which resulted in partial response with shrinkage of the primary lesion and brain metastases. This partial response remained durable for 11 months with an ongoing regimen. The current case suggests that osimertinib would show promising effects as a first-line treatment for PPCs harboring EGFR mutations, as well as a reasonable sequence of therapy followed by immune checkpoint inhibitor-based regimens.

Involvement of Lamin B1 Reduction in Accelerated Cellular Senescence during Chronic Obstructive Pulmonary Disease Pathogenesis.

Downregulation of lamin B1 has been recognized as a crucial step for development of full senescence. Accelerated cellular senescence linked to mechanistic target of rapamycin kinase (MTOR) signaling and accumulation of mitochondrial damage has been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. We hypothesized that lamin B1 protein levels are reduced in COPD lungs, contributing to the process of cigarette smoke (CS)-induced cellular senescence via dysregulation of MTOR and mitochondrial integrity. To illuminate the role of lamin B1 in COPD pathogenesis, lamin B1 protein levels, MTOR activation, mitochondrial mass, and cellular senescence were evaluated in CS extract (CSE)-treated human bronchial epithelial cells (HBEC), CS-exposed mice, and COPD lungs. We showed that lamin B1 was reduced by exposure to CSE and that autophagy was responsible for lamin B1 degradation in HBEC. Lamin B1 reduction was linked to MTOR activation through DEP domain-containing MTOR-interacting protein (DEPTOR) downregulation, resulting in accelerated cellular senescence. Aberrant MTOR activation was associated with increased mitochondrial mass, which can be attributed to peroxisome proliferator-activated receptor γ coactivator-1ß-mediated mitochondrial biogenesis. CS-exposed mouse lungs and COPD lungs also showed reduced lamin B1 and DEPTOR protein levels, along with MTOR activation accompanied by increased mitochondrial mass and cellular senescence. Antidiabetic metformin prevented CSE-induced HBEC senescence and mitochondrial accumulation via increased DEPTOR expression. These findings suggest that lamin B1 reduction is not only a hallmark of lung aging but is also involved in the progression of cellular senescence during COPD pathogenesis through aberrant MTOR signaling.

Bevacizumab-Containing Chemoimmunotherapy for Recurrent Non-Small-Cell Lung Cancer after Chemoradiotherapy: Case Report.

Chemoimmunotherapy has become the standard of care as the first-line treatment of advanced or recurrent non-small-cell lung cancer (NSCLC). The bevacizumab-containing chemoimmunotherapy regimen is theoretically more effective than a non-bevacizumab-containing regimen via two mechanisms: a superior outcome of bevacizumab-containing chemothrerapy than the standard platinum doublet regimen, and the synergistic effect of bevacizumab with an immune checkpoint inhibitor (ICI). Bevacizumab effectively normalizes vascularization, especially when the vascular bed is damaged by previous treatment. Bevacizumab promotes immunomodulation when used with ICI. We describe a patient with nonsquamous NSCLC who returned 2.5 years after definitive chemoradiotherapy for postoperative locoregional recurrence in the right supraclavicular lymph node. Considering the destroyed vascular bed due to prior chemoradiotherapy, attaining vascular normalization was critical for effective drug delivery. The patient was treated with a bevacizumab-containing chemoimmunotherapy regimen, which resulted in a complete metabolic response. The patient responded well for 23 months and is receiving ongoing treatment. Thus, bevacizumab-containing chemoimmunotherapy could be advantageous in some recurrent cases after chemoradiotherapy.

[Jogging/running activity and quality of life in the elderly].

Objectives　The number of elderly joggers/runners in Japan has been on the rise. This study aimed to investigate the practice of jogging/running activity, features of quality of life (QOL) among the elderly, and the relationships between jogging/running activity and QOL features.Methods　A questionnaire survey was conducted with 83 older adults aged 60-81 who had participated in 7 marathons held from November 2014 to July 2015. Sex, age, experience (years), mileage (kms/month), frequency of jogging/running activity (times/week), frequency of participation in marathons (times/year), and QOL were assessed. QOL was measured with the WHOQOL26, which is composed of "overall QOL", "physical," "psychological," "social relationships," and "environment." The relations between these variables were estimated using correlation and multiple regression analyses.Results　In the majority of the participants, experience was 5 or more years, mileage was less than 150 kms/month, frequency of jogging/running activity was 1-4 times a week, and frequency of participation in marathons was 1-10 times a year. As for the participants above the age of 65, the mean QOL for men was 3.8 (standard deviation (SD)=0.4) and for women was 4.1 (SD=0.5). These scores were higher than those previously reported in studies among Japanese older adults. And there was no evidence which showed the bodily pain such as lower limb disorders, which older joggers or runners may often get. Overall QOL was positively associated with age and frequency of jogging/running activity. The social relationships domain was positively associated with sex and experience. The environment domain was positively correlated with experience. All these associations were significant.Conclusions　The results suggest that among the elderly, a high frequency and/or experience of jogging/running activity is significantly associated with a high level of QOL. In the future, a case-control or longitudinal study with a larger sample size and/or more variables is required to obtain a more definitive interpretation of the present findings.

[Intraoperative Navigation System during Thoracoscopic Segmentectomy for Non-palpable Pulmonary Tumors;Infrared Thoracoscopy (IRT)-Indocyanine Green (ICG) and Intraoperative Computed Tomography(CT)-assisted Method].

OBJECTIVES: Recently, the use of video-assisted thoracoscopic surgery (VATS) segmentectomy for pulmonary malignancies has increased. For non-palpable lesions, securing a sufficient surgical margin is more likely to be uncertain. The purpose of this study was to evaluate the usefulness of our intraoperative navigation system in combination with the infrared thoracoscopy (IRT)-indocyanine green (ICG) method and intraoperative computed tomography (CT) during VATS segmentectomy for non-palpable pulmonary malignancies. METHODS: This study involved 12 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy. Identification of the intersegmental line on the visceral pleura was visualized using IRT-ICG. The intersegmental line was marked by clipping, and intraoperative CT scan was performed under bilateral lung ventilation. The intraoperative CT images were used by the surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 83.3% of the patients. The rate of concordance between 3-dimensional (3D)-CT images reconstructed from intraoperative CT and preoperative simulation 3D-CT imaging was 91.7%. The mean surgical margin assessed on gross examination by the pathologist was 22.3 ± 4.5 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Imaging support including preoperative simulation, IRT-ICG and intraoperative CT enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

Cross-linking multiwall carbon nanotubes using PFPA to build robust, flexible and highly aligned large-scale sheets and yarns.

Multi-walled carbon nanotube (CNT) structures, including unidirectionally aligned sheets and spun yarns, were fabricated by direct dry-spinning methods from spinnable CNT arrays. We improved the mechanical properties of the CNT structures. CNTs were tailored in sheets and yarns using perfluorophenyl azide (PFPA) as a binding agent. The azide group of PFPA bonds to graphene crystal surfaces under UV radiation exposed for 1 h. For the CNT sheet, Young's modulus increased from 1.6 to 32.9 GPa and tensile strength increased from 35.9 MPa to 144.5 MPa. For the CNT yarns Young's modulus increased from 29.5 to 78.0 GPa and tensile strength increased from 639.1 to 675.6 MPa. With this treatment, the CNT sheets became more robust and more flexible materials. Since cross-linking of CNTs by PFPA is a simple and rapid process, it is suitable for fabrication of enhanced CNT materials.

[Pulmonary Metastasis from a Phyllodes Tumor of the Breast Developing Sixteen Years after Initial Surgery].

We report a case of solitary pulmonary metastasis from a phyllodes tumor of the breast appearing 16 years after initial surgery. The patient was a 56-year-old woman who had undergone surgical extirpation of a left breast tumor diagnosed as phyllodes tumor (borderline malignancy) in 1998, and a right breast tumor diagnosed as fibromatosis in 2000. Sixteen years after the initial operation, she consulted our hospital because of a chest X-ray abnormality detected at a screening examination. Chest computed tomography revealed a well defined nodular shadow in the left upper lobe of the lung. Surgery was done since primary lung cancer was suspected. However, pathological diagnosis was a pulmonary metastasis from the phyllodes tumor of the left breast. Right breast tumor was also diagnosed as a metastasis from the left breast tumor by histopathological re-evaluation.

In vitro anticancer activity of loquat tea by inducing apoptosis in human leukemia cells.

Fresh loquat leaves have been used as folk health herb in Asian countries for long time, although the evidence supporting their functions is still minimal. This study aimed to clarify the chemopreventive effect of loquat tea extract (LTE) by investigating the inhibition on proliferation, and underlying mechanisms in human promyelocytic leukemia cells (HL-60). LTE inhibited proliferation of HL-60 in a dose-dependent manner. Molecular data showed that the isolated fraction of LTE induced apoptosis of HL-60 as characterized by DNA fragmentation; activation of caspase-3, -8, and -9; and inactivation of poly(ADP)ribose polymerase. Moreover, LTE fraction increased the ratio of pro-apoptotic Bcl-2-associated X protein (Bax)/anti-apoptotic myeloid cell leukemia 1 (Mcl-1) that caused mitochondrial membrane potential loss and cytochrome c released to cytosol. Thus, our data indicate that LTE might induce apoptosis in HL-60 cells through a mitochondrial dysfunction pathway. These findings enhance our understanding for chemopreventive function of loquat tea.

Association between the Mean Platelet Volume and Prosthesis-patient Mismatch after Transcatheter Aortic Valve Replacement.

Objective The mean platelet volume (MPV), a marker of platelet activity, is significantly higher in patients with aortic stenosis (AS) than in those without AS. The association between the platelet function and prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) remains unknown. Therefore, we investigated this association by measuring the MPV. Methods Of 237 patients who underwent TAVR, 148 with a median age of 84 years old were enrolled in this study. Blood tests and transthoracic echocardiography were performed at baseline and approximately six months after TAVR. PPM was defined as an aortic valve area index ≤0.85 cm2/m2 after TAVR. Variable changes from baseline to six-month follow-up were compared between patients with and without PPM. Results Forty-five patients (30%) developed PPM. The MPV was significantly higher in patients with PPM than in those without PPM. However, regarding the magnitude of change, the MPV was significantly less reduced in patients with PPM, and the percentage of patients with reduced MPV was lower in patients with PPM than in those without PPM. A logistic regression analysis revealed that a higher MPV and lack of MPV reduction at the six-month follow-up were independent predictors of PPM. Conclusion MPV values at the six-month follow-up were associated with PPM after TAVR in patients with AS. MPV values increase when PPM is present after TAVR and may be an indicator during the postoperative follow-up.

Relationship between the Selvester QRS Score and Coronary Microvascular Dysfunction Assessed by the Index of Microcirculatory Resistance.

Objective The index of microvascular resistance (IMR) is an invasive method for quantifying the coronary microvasculature independent of the presence and degree of epicardial stenosis during cardiac catheterization, whereas the Selvester QRS score, which is related to myocardial damage, is a relatively simple and non-invasive measurement procedure. We investigated the relationship between the QRS score and coronary microvascular dysfunction (CMD) assessed via IMR. Methods Data from 74 patients who underwent invasive coronary physiological measurements were retrospectively reviewed. Using a coronary wire, we measured IMR by the hyperemic mean transit time and distal coronary pressure. We also determined a simplified QRS score following the Selvester QRS score criteria by 12-lead electrocardiography. After determining the best cutoff value for the QRS score to predict IMR ≥25, which was defined as CMD by the Coronary Vasomotion Disorders International Study Group, patients were categorized into the QRS score ≥3 (n=16) and the QRS score 0-2 (n=58) groups. Results IMR in the QRS score ≥3 group was significantly higher in comparison to the QRS score 0-2 group (31; IQR: 19-57 vs. 20; IQR: 14-29, p<0.01). The percentage of patients with IMR ≥25 in the QRS score ≥3 group was significantly higher than that in the QRS score 0-2 group (69% vs. 34%, p=0.01). Conclusion A higher QRS score was associated with CMD, as estimated by IMR. The Selvester QRS score is noninvasive parameter that is potentially useful for predicting CMD.

Relationship Between Attenuated Plaque Identified by Intravascular Ultrasound and Thrombus Formation After Excimer Laser Coronary Angioplasty.

BACKGROUND: Excimer laser coronary angioplasty (ELCA) has been reported to be a safe and effective atherectomy device in percutaneous coronary intervention (PCI). However, thrombotic complications after ELCA have been occasionally observed. In this study, we evaluated the impact of attenuated plaque on thrombus formation and transient no-reflow after ELCA. METHODS: This study enrolled 58 lesions in 56 patients who underwent PCI with ELCA. It was a retrospective observational study at a single center. All lesions were imaged by intravascular ultrasound (IVUS) before and immediately after ELCA. On the plaque with ultrasound attenuation, attenuation angle per millimeter and attenuation length were measured. ELCA-induced thrombus was detected by IVUS, and transient no-reflow after ELCA was recorded. RESULTS: Thrombus was detected in 14 lesions (30 %), and transient no-reflow occurred in 3 lesions (5 %). Lesions with thrombus had a higher mean attenuation angle (median [interquartile range] 142° [112°-152°] vs. 64° [0°-115°]; p = 0.001), maximum attenuation angle (209° [174°-262°] vs. 86° [0°-173°]; p < 0.001), and longer attenuation length (12 mm [8 mm-17 mm] vs. 2 mm [0 mm-5 mm]; p < 0.001). Lesions with thrombus leading to transient no-reflow had a longer lipid length and a significantly higher troponin I level after PCI. CONCLUSIONS: IVUS-identified attenuated plaque was strongly correlated with ELCA-induced thrombus. Furthermore, attenuation length may predict transient no-reflow.

Efficacy and safety of immuno-chemotherapy in patients with advanced non-small-cell lung cancer harboring oncogenic mutations: a multicenter retrospective study.

PURPOSE: The effect of immuno-chemotherapy on patients with advanced non-small-cell lung cancer (NSCLC) harboring oncogenic mutations remains poorly understood. This study aimed to characterize the efficacy of immuno-chemotherapy and determine the optimal treatment strategy for such patients. METHODS: We conducted this retrospective cohort study on patients with NSCLC harboring oncogenic driver alterations and treated with an immune checkpoint inhibitor combined with chemotherapy at five institutions. The clinical characteristics and outcomes of immuno-chemotherapy for NSCLC with oncogenic mutations in a real-world setting were analyzed. RESULTS: Among 846 patients diagnosed with advanced or recurrent NSCLC between April 2017 and April 2021, 43 patients with oncogenic mutations were treated with immuno-chemotherapy. The median age of patients was 68 (range 44-78) years; 42% of patients never smoked, and adenocarcinoma was the most common histology (95%). In patients with KRAS mutations (n = 10) or PD-L1 expression of 50% or greater (n = 10), the disease control rate was 100%. The median progression-free survival (PFS) was 5.4, 6.3, and 8.9 months in patients harboring mutations in EGFR, KRAS, and other genes, respectively (P = 0.22). Patients with PD-L1 expression of 50% or greater had significantly longer median PFS than patients with PD-L1 expression of less than 50% (16.4 vs. 5.1 months; P = 0.001). Two patients experienced grade 3 immuno-related adverse events. CONCLUSION: Immuno-chemotherapy has a clinical benefit and is safe for patients with oncogenic mutations. Notably, patients with PD-L1 expression of 50% or more experience greater benefit from immuno-chemotherapy than those with PD-L1 expression of less than 50%.

Exploratory analysis of immunochemotherapy compared to chemotherapy after EGFR-TKI in non-small cell lung cancer patients with EGFR mutation: A multicenter retrospective study.

BACKGROUND: Patients with epidermal growth factor receptor (EGFR)-mutated, advanced non-small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. METHODS: We retrospectively examined EGFR-mutant patients treated with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) therapy or platinum-based chemotherapy (Chemo) after EGFR-TKI therapy at five institutions in Japan. RESULTS: A total of 57 patients with EGFR mutation were analyzed. The median progression-free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death-ligand 1 (PD-L1)-positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD-L1-negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. CONCLUSION: The effect of ABCP therapy and chemotherapy was comparable in EGFR-mutant patients in a real-world setting. The indication for immunochemotherapy should be carefully considered, especially in PD-L1-negative patients.

Atezolizumab in combination with carboplatin plus nab-paclitaxel for managing combined large-cell neuroendocrine carcinoma: A case report.

Large-cell neuroendocrine carcinomas (LCNECs), categorized as high-grade neuroendocrine carcinomas, account for approximately 3% of resected lung cancers. LCNECs containing other components are called 'combined LCNECs' and have no standard treatment. A 73-year-old male with a metastatic brain tumour from a combined LCNEC of the lung containing adenocarcinoma and sarcomatoid components was referred to our department. The patient was treated with chemotherapy consisting of carboplatin and nanoparticle albumin-bound (nab)-paclitaxel in combination with atezolizumab, which was decided in accordance with the histological evaluation of the components. This treatment resulted in partial response and remained durable for 12 months with an ongoing regimen. The current case suggests that the constituents of chemoimmunotherapy should be selected in accordance with the reported efficacy of relevant regimens for each component of the combined LCNEC.

Nasogastric administration of osimertinib suspension for an epidermal growth factor receptor-mutated lung cancer causing an esophageal stricture: case report.

An esophageal stricture is an abnormal esophageal narrowing, usually caused by esophageal diseases and rarely by lung cancer. They cause malnutrition, performance status (PS) deterioration, and difficulty in the oral administration of antitumor drug tablets. A 78-year-old female patient with lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR)-sensitizing mutation, experienced dysphagia due to an esophageal stricture caused by retrotracheal lymph node metastases. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor that is efficacious against EGFR-sensitizing mutations. The esophageal stricture hampered food intake and oral administration of osimertinib, causing severe malnutrition and deterioration to PS 3. Esophagogastroduodenoscopy (EGD) revealed severe and entire circumferential stenosis (7 cm in length) of the upper esophagus without mucosal abnormality. A nasogastric tube was inserted under EGD guidance, and an osimertinib suspension was administered accordingly: a tablet containing 80 mg of osimertinib was suspended in 50 mL of sterile hot water (55 ℃) for ten minutes, and the suspension was administered through a nasogastric tube once daily. Dysphagia improved 15 days after the introduction of osimertinib. After 21 days, the patient could take foods and drugs orally, and her PS improved to 1. Administering an osimertinib suspension via a nasogastric tube was a viable option in managing esophageal strictures in patients with EGFR-sensitizing mutations.

Efficacy and Safety of Programmed Death-Ligand 1 Inhibitor Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC: A Prospective Observational Study.

Introduction: To date, the efficacy and safety of programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy for patients with extensive-stage SCLC (ES-SCLC), with real-world evidence, stratified on the basis of age and performance status (PS), have not been fully investigated. The aim of this study was to evaluate the efficacy and safety of PD-L1 inhibitor plus platinum-etoposide chemotherapy in patients with ES-SCLC. Methods: This multicenter prospective study evaluated patients with ES-SCLC who received PD-L1 inhibitor plus platinum-etoposide chemotherapy between September 2019 and October 2021. Results: A total of 45 patients with ES-SCLC received the aforementioned treatment, including 18 elderly (≥75 y old) patients and six patients with a PS of 2. Multivariate analysis indicated that a PS of 2 was a significant independent prognostic factor for progression-free survival and overall survival (p = 0.008 and p = 0.001, respectively). Of patients with PS of 2 at the initial phase, those that achieved PS improvement during treatment had significantly longer progression-free survival and overall survival than those who did not (p = 0.02 and p = 0.02, respectively). The incidence of adverse events accompanied with treatment discontinuation was significantly higher in the elderly patients than in the non-elderly patients (p = 0.03). Conclusions: This real-world prospective study found that PD-L1 inhibitor plus platinum-etoposide chemotherapy had limited efficacy in patients with ES-SCLC with a PS of 2, except for cases with improvement of PS during treatment. Owing to the emergence of adverse events and treatment discontinuation, this treatment should be administered with caution in elderly patients with ES-SCLC.