Stereohaptic Vibration: Out-of-Body Localization of Virtual Vibration Source Through Multiple Vibrotactile Stimuli on the Forearms.

This paper proposes a novel concept of "stereohaptic vibration," which employs distributed vibration to localize vibration sources outside the body. Inspired by amplitude panning, a stereophonic sound display technique, we developed a method to localize a virtual vibration source (VVS) by polarizing the perceived intensity of multiple vibration stimuli to a specific orientation. Considering the perceptual characteristics of high-frequency vibration, the perceived intensity of the VVS was allocated to multiple vibrators according to the distance and direction of the target. The velocity discrimination performance was confirmed by utilizing four stimuli around the arm and one vibration stimulus to the palm to localize the movement of a VVS throughout the arm. Discrimination experiments of the trajectory of outgoing objects with a single arm and dual arms revealed that our approach could localize in three dimensions, even outside the body. The proposed technology for localizing external virtual vibration sources is expected to enhance the virtual reality experience.

Long­term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli: A case report.

Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.

EGFR Mutated Non-Small Cell Lung Cancer Complicated by Cancer Associated Ischemic Stroke.

We describe herein two patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) who developed cancer-associated ischemic stroke (CAIS), infarction caused by thromboembolism in the central nervous system. Case 1 was a 63-year-old man with Exon 19 deletion type EGFR mutated lung adenocarcinoma presenting with CAIS. Case 2 was a 71-year-old woman with Exon 21 L858R type EGFR mutated lung adenocarcinoma who developed CAIS during chemotherapy after EGFR-tyrosine kinase inhibitor (TKI) resistance. Although there was no recurrence of CAIS in these patients, anticancer therapy could be hampered by the comorbidity of CAIS. This can develop anytime from before clinical manifestations of NSCLC to the next treatment after EGFR-TKI resistance. The development of CAIS should be noted in patients with EGFR mutated NSCLC, who have a promising long-term prognosis. Anticancer and anticoagulant therapies as well as rehabilitation are important for patients who develop CAIS. Establishment of measurement tests to detect CAIS before onset is desired.

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.

Atypical Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome in an Elderly Lung Cancer Patient.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome develops in patients with various underlying diseases. The involvement of vascular endothelial growth factor in the development of this syndrome has been suggested and malignant disease could be one of the underlying diseases of RS3PE syndrome. This syndrome is interpreted as one of the paraneoplastic syndromes that often have a poor prognosis. There have been few reports of lung cancer patients who developed RS3PE syndrome, and the prognosis of these patients has been rarely discussed. The present case report describes a very elderly lung cancer patient with RS3PE syndrome. We believe he is the oldest patient with advanced lung cancer to have developed RS3PE syndrome. Edema of the dorsum of both hands disappeared by one month after the start of first-line chemotherapy. The relatively long disease control period of the first and later lines of chemotherapy led to a long-term survival of 45 months. The existence of a patient with such a slow clinical course should be considered valuable for future research. It is important to continue optimal treatment even in elderly patients with RS3PE syndrome, one of the paraneoplastic syndromes.

A Malignant Tumor Developed Seven Years After Small Cell Lung Cancer Treated With Etoposide-containing Chemotherapy.

BACKGROUND/AIM: Long-term survival of patients with small cell lung cancer (SCLC) is rare, and, to the best of our knowledge, there has been no SCLC patient who developed second malignancy after long-term survival. CASE REPORT: A 66-year-old woman with a history of smoking was admitted to our hospital with a nodule in her right lung. She was diagnosed with cT2aN3M0 localized-SCLC. Chest irradiation and chemotherapy including etoposide was performed. A new nodule appeared in the right lung more than 7 years after the end of treatment for SCLC. A specimen obtained by bronchoscopic biopsy was pathologically confirmed to be a non-SCLC malignancy. CONCLUSION: There is a possibility of tumor development associated with etoposide, which is known to be carcinogenic, or residual tumor development from combined type SCLC. We could not confirm whether it was second malignancy or recurrence after long-term interval. The number of long-term survivors of SCLC is likely to increase in the future. The clinical course of this patient is interesting from the perspective of long-term survival of SCLC patients and might have implications for the treatment of patients with similar clinical course in the future.

Five-year Disease Control With Alectinib in a Patient With Metastatic ALK-rearranged Lung Adenocarcinoma.

BACKGROUND/AIM: Therapy with alectinib could achieve prolonged progression-free and overall survival in patients with anaplastic lymphoma kinase gene (ALK)-rearranged non-small-cell lung cancer (NSCLC). However, a large proportion of the patients discontinue alectinib treatment due to recurrence. CASE REPORT: A 41-year-old male patient presented with cellulitis of the right upper extremity that had developed in the past 3 weeks. Chest radiograph at the time of admission incidentally revealed a nodule in the right lung. At diagnosis, the patient had spinal bone metastases and thrombosis in the common jugular vein subclavian veins. Therefore, in addition to warfarin therapy and irradiation to the bone metastases, chemotherapy was started. After identifying the presence of the ALK rearranged gene, alectinib therapy was initiated. Since then, alectinib treatment has been continued for more than 5 years. CONCLUSION: Although very rare, there are patients who might be able to maintain a long-term response to alectinib. It is important for chest physicians to manage such patients so that the effects of alectinib can be maintained for a long time.

Discontinuation of Immune Checkpoint Inhibitor and Survival in Patients With Non-small-cell Lung Cancer Without a Driver Gene Mutation.

BACKGROUND/AIM: Patients with non-small-cell lung cancer treated with immune checkpoint inhibitors (ICI) might be forced to discontinue treatment for various reasons. We conducted a retrospective study to evaluate the impact of discontinuation of ICI treatment on patient prognosis. PATIENTS AND METHODS: We performed a retrospective study that reviewed the medical charts of 86 patients treated with ICI monotherapy and 34 patients treated with a combination of ICI and chemotherapy during the period from February 2016 to February 2022 at our two hospitals. 'Discontinuation' was defined as a cessation of ICI treatment for more than two cycles for any reason. RESULTS: The two most common reasons for discontinuation were immune-related adverse events and at the request of the patient. Nineteen patients who had discontinued ICI, resumed ICI or another therapy. Discontinuation of ICI treatment was a favorable factor in overall survival in 84 patients with ICI monotherapy as well as in 34 patients treated with chemotherapy combined with ICI. CONCLUSION: This analysis found discontinuation of ICI treatment did not adversely affect prognosis. This suggests that when treating patients with non-small-cell lung cancer with ICI, chest physicians should respond flexibly, and, with careful monitoring, consider discontinuation of ICI.

Body Weight Change in Non-small Cell Lung Cancer Patients Treated With EGFR-TKI.

BACKGROUND/AIM: Body weight (BW) changes in epidermal growth factor inhibitor-tyrosine kinase (EGFR-TKI) treated non-small cell lung cancer patients has yet to be fully investigated. For the purpose of clarifying changes in body weight in patients who received EGFR-TKI treatment in clinical practice, we performed a retrospective study. In this study, comparison between pretreatment BW and those at 12, 24 weeks, and 12 months in these patients was performed. PATIENTS AND METHODS: We included all the patients diagnosed with EGFR mutated NSCLC in two tertiary hospitals between April 2009 and March 2021. BW records in the medical chart of each patient who was treated with EGFR-TKI for more than 12 weeks were surveyed. In each patient, BW at 12, 24 weeks, and 12 months from the initiation of EGFR-TKI treatment were compared with pretreatment BW. RESULTS: Sixty-three patients obtained TKI treatment for more than 12 weeks and had comparable body weight records. Compared with the pretreatment BW, decreased BW was observed at 12, 24 weeks, and 12 months from the initiation of TKI treatment. CONCLUSION: Even in patients treated with EGFR-TKI, which is evaluated as less toxic and a more effective therapy, there might be patients who lose weight during the treatment period. Chest physicians will be required to provide medical care even for EGFR mutated patients, taking into consideration changes in BW.

Eosinophilic Pneumonia with Marked Peripheral Eosinophilia during the Course of Sarcoidosis.

Patients with sarcoidosis are known to have peripheral blood eosinophilia (PBE). However, most of them had PBE slightly above the upper limit of the normal range. Few patients had increased eosinophils in the bronchoalveolar lavage fluid (BALF), and eosinophilia in BALF enough to be diagnosed as eosinophilic pneumonia (EP) was extremely rare. We present herein a sarcoidosis case with PBE. There were fluctuations in peripheral eosinophils consistent with sarcoidosis disease activity, and peripheral blood eosinophils increased up to 50%, 12500/mm3, although the patient was affected by cough variant asthma and multimodal therapies for breast cancer. Some case reports showed EP in patients with sarcoidosis. To our best knowledge, however, no sarcoidosis patient presented with such a high level of PBE. In this report, we would like to emphasize that there might be patients with sarcoidosis who have a marked increase in peripheral blood eosinophils.

Nintedanib-mediated improvement in CT imaging in pulmonary fibrosis associated with systemic scleroderma.

Nintedanib is an antifibrotic drug that has an inhibitory effect on growth factor tyrosine kinases. In patients with idiopathic pulmonary fibrosis and systemic scleroderma-associated interstitial pneumonia (SSc-IP), nintedanib has been effective in suppressing the decline in forced vital capacity over time and the onset of acute exacerbation of interstitial pneumonia. Here, we report a SSc-IP patient who showed an improvement on CT images following nintedanib treatment. To our knowledge, this is the first report of such a case. Although SSc-IP patients are very rare, additional clinical experience and understanding will be required to prove the therapeutic benefit of nintedanib in these cases in relation to improved chest images.

Imaging characteristics of nontuberculous mycobacterial pulmonary nodules.

Introduction. Nontuberculous mycobacteriosis (NTM) of the lungs can develop nodules. In order to clarify some of the characteristics of lung NTM nodules, we examined volume doubling time (VDT) and maximum standardized uptake value (SUVmax) in positron emission tomography (PET) of pathologically diagnosed NTM nodules. Methods. From November 2012 to August 2018, clinical and radiological information were retrospectively investigated in eight patients who were surgically resected and diagnosed as NTM. These eight patients were followed up until November 2020 and were confirmed to have no appearance of lung cancer or reappearance of lung NTM nodules. The VDT was calculated using the Schwartz formula. Results. The median maximum diameter of the nodule at the time of the first CT scan was 16.0 (range: 9.9-20.0) mm. The median maximum diameter of the nodule on CT performed before the surgical biopsy was 18.8 (range: 10.4-32.8) mm. The median doubling time calculated from these results was 203 (range: 20-568) days. Caseous granulomas and acid-fast bacilli were histologically confirmed in all eight patients. Culture of excised nodules revealed Mycobacterium intracellulare in five patients and Mycobacterium avium in three patients. Six patients received PET, and median SUVmax was: 7.0 (range: 3.3-21.0). Median VDT was around 200 days. Some patients had irregular-shaped nodules. Conclusions. CT/PET-CT characteristics of lung nodules are not reliable in differentiating lung NTM nodules from malignant ones. To avoid unnecessary resection, it may be better to collect various information on imaging findings in the nodule itself and in opacities other than the nodule.

Effect of Shakuyakukanzoto on Chemotherapy-Induced Hiccups in Patients with Lung Cancer.

OBJECTIVE: Shakuyakukanzoto, one of the traditional herbal medicines commonly used in North-East Asian countries, is known to be effective for muscle cramps. This retrospective study aimed to evaluate the effect of shakuyakukanzoto on chemotherapy-induced metoclopramide-uncontrolled hiccups. MATERIALS AND METHODS: We retrospectively investigated the medical records of all the consecutive patients with lung cancer who were prescribed with shakuyakukanzoto (Tsumura Co. Tokyo, Japan) for chemotherapy-induced hiccups in our hospital from September 2013 to November 2017. In the medical record from the initiation of shakuyakukanzoto until the start of the next chemotherapy, when there was description of "complete or partial disappearance of hiccups" after the prescription of shakuyakukanzoto, it was judged as a complete or partial response. A statement of "unchanged," no description of improvement, or exacerbation was judged as no change. RESULTS: Of the 49 chemotherapy courses in 15 patients with lung cancer, 93.9% had a "partial or complete" response within a few hours after the administration of shakuyakukanzoto. The effect of shakuyakukanzoto was observed irrespective of the pathological type of lung cancer, platinum-containing or non-platinum chemotherapy, and with or without other anti-hiccup drugs. No adverse event was observed. CONCLUSION: Shakuyakukanzoto may offer an effective pharmacological approach to treat chemotherapy-induced metoclopramide-uncontrolled hiccups. Well-planned prospective studies will confirm our results.

Association between peripheral eosinophils and clinical outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

INTRODUCTION: Programmed cell death ligand 1 is considered a predictor of the therapeutic effect of immune checkpoint inhibitors (ICPIs), but a more simple and useful predictor is needed. OBJECTIVES: The aim of this study was to identify the relationship between eosinophil counts and percentages and response to ICPI therapy. PATIENTS AND METHODS: In 190 patients with non-small cell lung cancer (NSCLC) treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of ICPI therapy initiation, the maximum counts and percentages of eosinophils during ICPI therapy, response to therapy, and time to treatment failure (TTF) were investigated. RESULTS: Both an increase in the peripheral eosinophil count and an elevation of eosinophil percentage following the initiation of ICPI therapy were observed, regardless of whether the patients had controlled or progressive disease. The median time to the maximum eosinophil percentage was 5 weeks in patients with controlled disease and 2 weeks in those with progressive disease. The cutoff value for the maximum eosinophil counts and percentage during ICPI therapy was set at 300/µl and 5%, respectively, to identify the presence or absence of a therapeutic effect. Time to treatment failure was longer in patients with maximum eosinophil counts exceeding 300/µl and a maximum eosinophil percentage above 5%. In a multivariable analysis, a maximum eosinophil percentage of 5% during ICPI therapy was a significant predictive factor for therapeutic efficacy. CONCLUSIONS: The measurement of peripheral eosinophils up to around 5 weeks following the initiation of treatment, especially the maximum eosinophils count and percentage, might provide useful information about the efficacy of ICPIs.

Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients.

Background/Aim: To clarify the clinical significance of the absolute increase in the number and proportion of peripheral eosinophils associated with immune checkpoint inhibitor (ICPI) treatment in non-small cell lung cancer (NSCLC) patients. Patients and Methods: We performed a retrospective study, by reviewing the medical charts of 191 patients who were treated with ICPI monotherapy and 80 patients treated with the combination of ICPI and chemotherapy during the period from February 2016 and April 2021. Results: In patients treated with ICPI monotherapy, there was a significant difference in time to treatment failure (TTF) between the two groups divided by eosinophils ≥ or <10%. Similarly, a significant difference was found in TTF between the two groups divided by eosinophils ≥ or <1,500/µl. Factors related to both an increase in the number and percentage of peripheral eosinophils were "immune-related adverse effects (irAE) that did not lead to discontinuation of administration". Conclusion: Some patients with irAE might have a 'favorable' absolute increase in peripheral eosinophils.

Long-term Survival With Afatinib in a Patient With Lung Adenocarcinoma Harboring Double Uncommon EGFR L861Q and G719X Mutations.

BACKGROUND: In the majority of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations, first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are ineffective. The second-generation TKI, afatinib, is considered effective in patients with uncommon mutations, however, long-term survivors have been rare. CASE REPORT: We report herein a patient with lung adenocarcinoma harboring double uncommon EGFR L861Q and G719X mutations, who is free of disease 32 months after initiation of afatinib therapy. To our best knowledge, this patient has the longest response among other patients with double uncommon mutations. CONCLUSION: Patients with this type of NSCLC may obtain long-term survival with afatinib.

Long-term maintenance of nutritional status with ninjinyoueito in terminal patients with chronic respiratory disease: Two case reports.

Ninjinyoeito, is a traditional herbal (Kampo) medicine which is administered to patients with debilitating diseases in North-East Asia. Ninjinyoeito has been reported to be effective against loss of physical strength, fatigue and loss of appetite in patients with wasting diseases. The present study described long-term maintenance of body weight with ninjinyoueito in 2 terminal patients with chronic respiratory diseases. The first patient was a 75-year-old with chronic obstructive pulmonary disease (COPD) who took ninjinyoueito for ≥5 years and the second patient was a 72-year-old man with metastatic lung cancer with combined pulmonary fibrosis and emphysema (CPFE) who took ninjinyoueito for ≥1 year. Both of them maintained their physique and nutritional status during the terminal stages of disease and there were no adverse effects observed in these 2 patients which could be attributed to ninjinyoueito. The results suggest that ninjinyoueito may be a supplementary treatment for the maintenance of nutritional status in patients with a chronic respiratory disease accompanied by wasting, such as COPD.

Combined Atezolizumab and Chemotherapy for a Patient With Double Primary Cancers.

BACKGROUND: Immune checkpoint inhibitors are indicated for non-small cell lung cancer (NSCLC) and head and neck cancer, and combined treatment of immune checkpoint inhibitor and chemotherapy has recently been carried out in patients with NSCLC. However, there is no established standard therapy for synchronous locally advanced or metastatic cancers of lung and nasopharynx. CASE REPORT: We report a case of a metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma successfully treated with chemotherapy and immune checkpoint inhibitor, paclitaxel, carboplatin, bevacizumab and atezolizumab. The tumor proportion score of programmed death ligand 1 was 5-10% and 70-80% for metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma, respectively. Shrinkage of both carcinomas was confirmed, and the treatment effect was judged to be a partial response. CONCLUSION: This was the first patient who was treated with this combination treatment. Our clinical experience suggests that this treatment could be one of the options for patients with these advanced cancers and an overall good clinical condition.

Oligo-recurrence from anaplastic lymphoma kinase-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase rearranged non-small-cell lung cancer is arare disease. Among them, asubset of patients exist who exhibit relatively slowly progressing symptoms and have oligo-metastases. In this article, we present two cases of ALK rearran-ged lung adenocarcinoma in patients who experienced postoperative oligo-recurrence. Both cases were treated with surgical resection and gamma knife irradiation for oligo-recurrence. After local therapy, the first patient remained disease free for over 23 months; the second for over 18 months. It appears that some patients with ALK rearranged NSCLC experience oligo-recurrence in their clinical course. For such patients, appropriate local therapy may be beneficial in improving both the quality of life and the prognosis.