Publications by authors named "Kojima Motohiro"

The depth of invasion plays a critical role in predicting the prognosis of early esophageal cancer, but the reasons behind invasion and the changes occurring in invasive areas are still not well understood. This study aimed to explore the morphological differences between invasive and non-invasive areas in early esophageal cancer specimens that have undergone endoscopic submucosal dissection (ESD), using artificial intelligence (AI) to shed light on the underlying mechanisms. In this study, data from 75 patients with esophageal squamous cell carcinoma (ESCC) were analyzed and endoscopic assessments were conducted to determine submucosal (SM) invasion.

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Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced changes in immune checkpoint molecule expression and interaction with their ligand(s) remain unclear. Herein, we demonstrated the dynamics of lymphocyte-mediated molecular interactions in tissue samples from esophageal cancer patients throughout RT schedules.

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Background: The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer (BTC). Based on the results of the TOPAZ-1 trial, a gemcitabine and cisplatin plus durvalumab (GCD) regimen was recently approved as first-line therapy for patients with advanced BTC. However, post-GCD conversion surgery has not been previously studied.

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The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses.

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Pulmonary pleomorphic carcinoma (PC) is a rare non-small-cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil-specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy-six patients with pulmonary PC who underwent complete resection were enrolled.

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  • Endoscopic resection (ER) is commonly used for early colorectal cancer, but the need for further surgery in cases of pathological T1 colorectal cancer (pT1CRC) is debated due to uncertain risks of lymph node metastasis (LNM).
  • This study analyzed 600 pT1CRC patients to explore the clinicopathological characteristics and LNM risk for those with lymphoid follicular replacement (LFR).
  • Findings revealed that 6.7% of patients had pT1CRC with LFR, and notably, none experienced LNM during a median follow-up of 61 months, suggesting that patients with LFR might not require additional surgical intervention even with deeper submucosal invasion.
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We used a mathematical approach to investigate the quantitative spatial profile of cancer cells and stroma in lung squamous cell carcinoma tissues and its clinical relevance. The study enrolled 132 patients with 3-5 cm peripheral lung squamous cell carcinoma, resected at the National Cancer Center Hospital East. We utilized machine learning to segment cancer cells and stroma on cytokeratin AE1/3 immunohistochemistry images.

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Gremlin 1 (GREM1) is an antagonist of bone morphogenetic protein (BMP). GREM1 is expressed in the stromal cells of various carcinomas and promotes tumor progression by suppressing BMP signaling. We designed this study to establish an evaluation strategy for GREM1 expression, focusing on the tumor stroma, and to examine its clinicopathological significance in gastric cancer (GC) progression.

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Researchers have attempted to identify the factors involved in lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1-2, N0 (cT1-2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information.

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  • The IASLC grading system effectively predicts outcomes for early lung adenocarcinoma, specifically in Stage I EGFR-mutated cases.
  • A study involving 296 patients assessed the association between the grading system and various aspects of the tumor microenvironment (TME), examining factors like cancer cell behavior and immune cell presence.
  • Results indicated that Grade 3 tumors had significantly worse recurrence-free survival rates and a higher presence of tumor-associated macrophages and cancer-associated fibroblasts, suggesting a correlation between grading and poor patient prognosis.
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  • Tumor budding has been linked to prognosis in non-small cell lung cancer, but the significance of larger formations like Micronest in cancer stroma (MICS) is less understood.
  • This study focused on 198 lung squamous cell carcinoma patients, defining MICS as small clusters of cancer cells that are somewhat detached from the main tumor.
  • Results showed that patients with MICS had significantly poorer overall and recurrence-free survival, indicating that MICS serves as an independent poor prognostic marker for these cancer patients.
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  • The study aimed to evaluate the long-term outcomes, specifically overall survival (OS), of patients with T1 colorectal cancer (CRC) who underwent endoscopic resection (ER) followed by additional surgery (AS) compared to those who had primary surgery (PS) alone.
  • It involved analyzing data from 6,105 patients treated at various high-volume Japanese institutions and utilized propensity score matching to ensure comparability between the two groups.
  • The findings suggested that patients who underwent AS after ER had a 5-year OS rate of 97.1%, comparable to 96.0% for the PS group, indicating that ER before AS does not adversely affect long-term outcomes.
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  • A trial studying preoperative chemoradiotherapy (CRT) followed by nivolumab for locally advanced rectal cancer (LARC) reported promising 3-year outcomes with 39 microsatellite stable (MSS) and 5 microsatellite instability-high (MSI-H) patients.
  • For the MSS group, the 3-year relapse-free survival (RFS) rate was 79.5%, while the MSI-H group had a remarkable 100% RFS rate; overall survival (OS) rates were similarly high for both groups.
  • Key biomarkers like PD-L1 positivity and a high CD8+ T cell/effector regulatory T cell ratio appeared to contribute to better outcomes in MSS patients, highlighting potential prognostic indicators
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Objectives: We aimed to reveal the clinicopathological differences between epidermal growth factor receptor (EGFR)-mutated and wild-type (WT) lung adenocarcinoma (LUAD) focusing on the predominant subtype.

Methods: This study included 352 with EGFR mutation and 370 with WT patients in consecutive stage I LUAD classified by the predominant subtype, and their clinicopathological characteristics and prognosis were analyzed. Using the Cancer Genome Atlas Program (TCGA) cohort, we analyzed differences in gene expression between EGFR mutation and WT groups.

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  • A study in Norway found that many patients had local recurrence of rectal cancer after transanal total mesorectal excision, possibly due to cancer cells spilling during surgery.
  • The research involved 40 patients, whose surgical field was monitored for cancer cells through washing cytology at different stages of the operation.
  • Initial samples revealed a high presence of malignant cells, but significantly fewer were found later on, with no cancer cells detected in the final sample, suggesting the need for more in-depth studies.
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  • The study assessed the spatial variability of PD-L1 protein expression in non-small cell lung cancer (NSCLC) and how it affects patient outcomes after surgery.
  • Researchers analyzed data from 239 NSCLC specimens, using a mathematical model that examined the texture of images to determine the heterogeneity index for PD-L1, linking it to tumor characteristics and survival rates.
  • Findings revealed that a high heterogeneity index of PD-L1 is associated with poorer recurrence-free survival, particularly in specific histological subtypes, establishing it as an independent risk factor for tumor recurrence.
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One drawback of existing artificial intelligence (AI)-based histopathological prediction models is the lack of interpretability. The objective of this study is to extract p16-positive oropharyngeal squamous cell carcinoma (OPSCC) features in a form that can be interpreted by pathologists using AI model. We constructed a model for predicting p16 expression using a dataset of whole-slide images from 114 OPSCC biopsy cases.

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  • The study aimed to assess the effectiveness of pathological criteria from the JSCCR guidelines for determining the need for additional treatment in patients with pT1 colorectal carcinoma who had undergone local resection.
  • Researchers analyzed data from 4,667 patients and found that those with risk factors for lymph node metastasis had a significantly higher incidence of metastasis and recurrence, while those without risk factors had excellent survival rates.
  • Overall, the findings support the JSCCR criteria, highlighting their importance in identifying low-risk patients who can expect favorable outcomes post-resection.
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  • Immune checkpoint inhibitors (ICIs) show varied effectiveness in treating microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC), leading researchers to investigate biomarkers predicting patient response to ICI combinations.
  • The study utilized whole-exome sequencing, RNA sequencing, and immunohistochemistry in a cohort of patients who participated in trials for two different ICI combinations (REGONIVO and TASNIVO).
  • Results indicated that specific pathways related to tumor environments, such as the epithelial-mesenchymal transition and G2M checkpoint pathways, were linked to treatment responses, highlighting the importance of tumor microenvironment factors in ICI efficacy and patient outcomes.
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Introduction: Adjuvant chemotherapy (AC) with S-1 or capecitabine monotherapy is now the standard of care for resected biliary tract cancer (BTC) according to the Adjuvant S-1 for Cholangiocarcinoma Trial (ASCOT) and the BILCAP study. Patients selection criteria, especially regarding pT1N0 BTC, differed in both trials. We aimed to clarify the survival outcomes regarding resected pT1N0 BTC without AC.

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  • - The study focused on patients with stage II-III EGFR-mutant lung adenocarcinoma to identify factors linked to cancer recurrence and assess the tumor microenvironment, analyzing 387 cases from 2008 to 2018.
  • - It found that EGFR-mt tumors had a higher rate of lymph node and lung metastases and shorter disease-free survival (DFS) compared to EGFR-wild-type tumors, particularly in the papillary subtype.
  • - Factors like male sex, advanced stage, and specific tumor characteristics were shown as poor prognostic indicators in EGFR-mt cases, and analysis indicated a correlation between certain tumor subtypes and higher counts of specific tumor-promoting immune cells.
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  • Combining radiotherapy and immunotherapy shows potential, but the immune response after radiotherapy is still not well understood.
  • Recent analyses revealed that immune cells infiltrate tumors and undergo significant changes in gene expression in response to radiotherapy over time.
  • Myeloid cells, in particular, were found to have increased expression of both stimulating and suppressive immune genes, indicating they might be valuable targets for future immunotherapy approaches alongside PD-L1 inhibitors.
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Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/μm ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/μm ) (p = 0.

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Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non-SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death-ligand 1 (PD-L1) expression.

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