Publications by authors named "Takuo Hayashi"

The standard treatment for hormone receptor-positive breast cancer in good general condition is curative surgery followed by endocrine therapy. However, for older patients, endocrine therapy alone is sometimes chosen instead of curative surgery due to health conditions or personal preference, though this is not yet a standard approach. It is crucial to develop elderly-specific treatment strategies, potentially establishing endocrine therapy alone as a standard option.

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Aims: In non-small cell lung cancer, alterations in mesenchymal-epithelial transition (MET) have been recognized as novel therapeutic targets. In particular, the MET exon 14 skipping mutation (METex14s) is a rare oncogenic driver. Targeted therapy with MET tyrosine kinase inhibitors has recently been approved for this mutation.

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Introduction: With the implementation of low-dose computed tomography screening, multiple pulmonary tumor nodules are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication.

Methods: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing comprising small- or large-scale multi-gene panels.

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  • Primary mediastinal apocrine adenocarcinoma is exceptionally rare, with just one documented case prior to this report, involving a 51-year-old female undergoing hemodialysis.
  • A 19 mm anterior mediastinal cystic tumor was discovered via CT scan, which was surgically removed and showed no signs of spreading to other organs.
  • The tumor exhibited unique microscopic features and immunohistochemical markers, and the patient has been recurrence-free for 6 years post-surgery without any additional treatment.
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Background: Granulomatous mastitis is a relatively rare benign inflammatory disease of the breast, but it is sometimes difficult to distinguish from breast cancer by imaging. We experienced a case that was definitively diagnosed as granulomatous mastitis from the surgical specimen. The mass appeared as a large cystic lesion on imaging, which is unusual for granulomatous mastitis, and was initially suspected to be an encapsulated papillary carcinoma.

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  • The study examined the effects of combining pembrolizumab and ramucirumab as neoadjuvant therapy for patients with PD-L1-positive non-small cell lung cancer (NSCLC).
  • Results showed a 50% major pathologic response rate among 24 patients, with six achieving complete pathologic response.
  • The combination was feasible, indicating that angiogenesis inhibitors like ramucirumab could enhance the effectiveness of immune checkpoint inhibitors against tumors.
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Purpose: MDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified. amplification (MDM2amp) is mutually exclusive with mutation and is seen in 6% of patients with lung adenocarcinoma (LUAD), with significant enrichment in subsets with receptor tyrosine kinase (RTK) driver alterations. Recent studies have shown synergistic activity of MDM2 and MEK inhibition in patient-derived LUAD models with MDM2amp and RTK driver alterations.

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Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers.

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  • Small cell lung cancer (SCLC) is a very aggressive and hard-to-treat cancer that hasn't seen much improvement in treatments for over 15 years.
  • Researchers looked at a database to find weak points in SCLC that could help develop new therapies.
  • They discovered that two important genes, SKP2 and CKS1B, are crucial for SCLC and blocking SKP2 could be a promising way to treat patients, no matter what specific type of cancer they have.
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Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma.

Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas.

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  • Non-small cell lung cancer (NSCLC) patients with pleural dissemination usually can't have surgery, but this study looked at whether removing the primary tumor helps them survive better.
  • Out of nearly 5,000 NSCLC patients who had surgery, only 90 had unexpected pleural nodules, and their survival was analyzed using techniques like Kaplan-Meier methods.
  • The results indicated that while primary tumor removal did not significantly improve overall survival compared to just exploratory surgery, receiving targeted therapy was linked to better survival rates.
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  • * Data from 114 Japanese women revealed that low tumor grade, high progesterone receptor (PgR) expression, and low Ki67 labeling index (LI) were significantly associated with lower recurrence scores.
  • * The findings suggest that PgR expression and Ki67 LI are independent predictors of recurrence score, and MUC1 staining patterns could also be valuable in identifying patients who may not benefit from the test.
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Accidentally extruded root canal filler within the sinuses may induce maxillary sinusitis with fungal mass. The authors describe 2 cases of gutta-percha-induced fungal masses in the left maxillary sinus of 2 women. The lesions were evaluated preoperatively using both computed tomography and magnetic resonance imaging, providing comprehensive insights into the condition.

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Immunoglobulin G4-related disease (IgG4RD) is a relatively new disease concept that is most common in Asia. It is a systemic chronic lymphoproliferative disease that is diagnosed by mass formation or thickened lesion, a high serum IgG4 level (≥135 mg/dL), and confirmation of lymphocytes and plasma cells by histopathological examination. The precise mechanism of this disease remains elusive; however, distinguishing IgG4RD from malignancy proves challenging due to its manifestation of swollen lymph nodes and retroperitoneal thickening and fibrosis.

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Background And Objective: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease.

Methods: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population.

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Background: Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC.

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Erdheim-Chester disease (ECD) is a rare inflammatory myeloid neoplasm affecting multiple systems and organs. The patient is a 38-year-old male with ECD complicated with pulmonary and cutaneous manifestations but without bone lesions diagnosed in 2008. Initial treatment with oral and inhaled corticosteroids achieved persistent favorable disease remission.

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  • BAP1 is a crucial tumor suppressor gene linked to various cancers, especially malignant pleural mesothelioma (DPM), and its inactivation leads to heightened DNA damage in specific cell types.
  • The study identifies a significant interaction between BAP1 and the DNA-PKcs enzyme, which is essential for the nonhomologous end-joining (NHEJ) pathway that repairs DNA damage.
  • BAP1's role in DNA repair was demonstrated through experiments showing that its knockdown decreased NHEJ activity and that combining X-ray treatment with gemcitabine effectively inhibited the growth of BAP1-deficient cancer cells, suggesting potential new cancer therapies.
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  • Additional surgical resection is typically recommended for patients with positive surgical margins after breast-conserving surgery, but radiation therapy is often used in practice, although data on its efficacy is limited.
  • A study involving 85 patients who had positive margins treated with irradiation from 2006-2013 found a relatively low rate of intrabreast tumor recurrence (8.2%) over an average follow-up of about 10 years.
  • The findings suggest that irradiation can be a viable alternative to further surgery for positive margins and provide groundwork for future research in this area.
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Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST.

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  • A small percentage (1%) of certain tyrosine kinase fusions have been identified in soft tissue sarcomas through DNA sequencing, but these fusions are not common among the 80% of fusion-negative sarcomas, which remain genetically unexplored.
  • The study aims to investigate whether DNA/RNA analysis can reveal genetic changes and identify potential tyrosine kinase fusions in tumor-specific, fusion-negative sarcomas, particularly focusing on their response to drug treatment in vitro.
  • Research was conducted on 100 patients with bone and soft tissue sarcomas between 2017 and 2020, with 90 patients being found eligible for the study despite some exclusions due to follow-up
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  • There is currently limited understanding of how alterations in fibroblast growth factor receptor 3 (FGFR3) affect bladder cancer (BLCA) and its tumor microenvironment (TME).
  • A study involving multi-omics analysis of BLCA tissues showed that aFGFR3 alterations are found in 44% of non-muscle invasive cases and 15% of muscle-invasive cases, affecting their immune response and tumor characteristics.
  • Notably, the LumP subtype in aFGFR3 cases responded significantly better to checkpoint inhibitors compared to their intact FGFR3 counterparts, suggesting that FGFR3 status influences treatment outcomes in bladder cancer.
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A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine-specific demethylase 5D (KDM5D) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia-telangiectasia and Rad3-related (ATR) inhibitor treatment. We evaluated KDM5D copy number loss in 173 surgically resected SCCs from male patients using fluorescence in situ hybridization.

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