Publications by authors named "Kota Arima"

Background: Growing evidence supports the importance of characterizing the organizational patterns of various cellular constituents in the tumor microenvironment in precision oncology. Most existing data on immune cell infiltrates in tumors, which are based on immune cell counts or nearest neighbor-type analyses, have failed to fully capture the cellular organization and heterogeneity.

Methods: We introduce a computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), that jointly measures immune cell partitioning between tumor epithelial and stromal areas and immune cell clustering versus dispersion.

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Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains . We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue . We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies.

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Background & Aims: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited.

Methods: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pksEscherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019).

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Evidence indicates that combinations of anti-EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer.

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Article Synopsis
  • - The study aimed to investigate whether having an appendectomy reduces the long-term risk of colorectal cancer, particularly for tumors associated with the bacterial species Fusobacterium nucleatum, which is linked to colorectal tumor development.
  • - Using data from extensive cohort studies, researchers found that 2811 cases of colorectal cancer were recorded, with appendectomy appearing to lower the incidence of F. nucleatum-positive cancers (hazard ratio of 0.53) but not F. nucleatum-negative cancers (hazard ratio of 0.98).
  • - The findings suggest that while appendectomy may reduce the risk of developing certain types of colorectal cancer (specifically F. nucleatum-positive ones), it does not significantly impact the risk for other types,
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Article Synopsis
  • Research suggests that enterotoxigenic Bacteroides fragilis (ETBF) may play a role in colorectal cancer development, particularly in tumors with specific genetic markers like high-level CpG island methylator phenotype (CIMP-high) and BRAF mutations.
  • The study utilized quantitative PCR to measure levels of Bacteroides fragilis and ETBF in colorectal cancer cases, finding that high levels of these bacteria are significantly linked to the presence of CIMP-high and MSI-high tumors.
  • Overall, the results provide evidence that Bacteroides fragilis and ETBF may influence colorectal cancer progression through particular genetic pathways, although they do not appear to affect patient survival rates.
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Background & Aims: Hepatocellular carcinoma (HCC) mainly develops from chronic hepatitis. Metabolic dysfunction-associated steatohepatitis (MASH) has gradually become the main pathogenic factor for HCC given the rising incidence of obesity and metabolic diseases. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin 2 (PGE2), which is known to exacerbate inflammatory responses.

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Article Synopsis
  • Immune checkpoint inhibitors (ICIs) like pembrolizumab are being explored as new treatments for microsatellite instability-high (MSI-H) colorectal cancer (CRC), which could be a promising option for patients.
  • An 80-year-old woman with advanced bowel obstruction due to descending colon cancer received surgery and two cycles of pembrolizumab but unfortunately showed no improvement and passed away five months later.
  • This case highlights the need to check specific genetic markers (like HLA status and beta-2-microglobulin) before starting ICI therapy in MSI-H CRC patients, as these factors may impact treatment effectiveness.
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Routine tumor-node-metastasis (TNM) staging of colorectal cancer is imperfect in predicting survival due to tumor pathobiological heterogeneity and imprecise assessment of tumor spread. We leveraged Bayesian additive regression trees (BART), a statistical learning technique, to comprehensively analyze patient-specific tumor characteristics for the improvement of prognostic prediction. Of 75 clinicopathologic, immune, microbial, and genomic variables in 815 stage II-III patients within two U.

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Background: Plant-based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant-based diets with the incidence of CRC and its molecular subtypes.

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The arachidonic acid cascade is a major inflammatory pathway that produces prostaglandin E (PGE2). Although inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is reported to lead to PGE2 accumulation, the role of 15-PGDH expression in the tumor microenvironment remains unclear. We utilized Panc02 murine pancreatic cancer cells for orthotopic transplantation into wild-type and 15-pgdh mice and found that 15-pgdh depletion in the tumor microenvironment leads to enhanced tumorigenesis accompanied by an increase in cancer-associated fibroblasts (CAFs) and the promotion of fibrosis.

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Article Synopsis
  • - The study aimed to identify risk factors for nonalcoholic fatty liver disease (NAFLD) in patients after undergoing pancreaticoduodenectomy (PD), focusing on the remnant pancreatic volume (RPV) as assessed by CT scans.
  • - Out of 101 patients studied, 39.6% developed NAFLD three months post-surgery, with significant differences in RPV ratios between reconstruction methods: pancreaticogastrostomy (PG) had lower ratios compared to pancreaticojejunostomy (PJ).
  • - The research found key risk factors for NAFLD to be female sex, PG reconstruction, and an RPV ratio of 60% or less, suggesting that maintaining better pancreatic function (as seen
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Background & Aims: Evidence supports a carcinogenic role of Escherichia coli carrying the pks island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of the Western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pksE coli.

Methods: Western diet score was calculated using food frequency questionnaire data obtained every 4 years during follow-up of 134,775 participants in 2 United States-wide prospective cohort studies.

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Background: Appendicitis caused by a foreign body is extremely rare. We report a case of chronic appendicitis caused by a perforating fish bone.

Case Report: The patient was a 50-year-old Japanese man.

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Background: The relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized.

Methods: In 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)].

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Article Synopsis
  • Accidental ingestion of foreign bodies, particularly fish bones, can lead to serious issues like gastrointestinal (GI) perforation, with this case highlighting a specific incident involving a 64-year-old man.
  • After a fish bone perforated his colorectal tumor, the patient underwent an emergency Hartmann's operation and lymph node dissection, which was crucial for his survival.
  • Post-surgery, the patient successfully battled liver recurrence using systemic chemotherapy, ultimately achieving a 5-year relapse-free status, underscoring the importance of timely diagnosis and treatment for better patient outcomes.
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Background: The albumin-bilirubin (ALBI) grade was developed to predict the prognosis of patients with hepatocellular carcinoma (HCC), which can stratify the prognosis even in HCC patients with Child-Pugh A. We evaluated the prognostic efficacy of the ALBI grade and Child-Pugh classification in HCC patients with Child-Pugh A stratified by the presence or absence of advanced fibrosis or a preoperative biomarker for advanced fibrosis.

Methods: We retrospectively analyzed 490 consecutive HCC patients with Child-Pugh A who underwent initial hepatectomies.

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Given previous biologic evidence of immunomodulatory effects of coffee, we hypothesized that the association between coffee intake of colorectal cancer patients and survival differs by immune responses. Using a molecular pathologic epidemiology database of 4465 incident colorectal cancer cases, including 1262 cases with molecular data, in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association between coffee intake of colorectal cancer patients and survival in strata of levels of histopathologic lymphocytic reaction and T-cell infiltrates in tumor tissue. We did not observe a significant association of coffee intake with colorectal cancer-specific mortality (multivariable-adjusted hazard ratio [HR] for 1-cup increase of coffee intake per day, 0.

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Background: A desmoid tumor is a rare neoplasm that is derived from soft tissues. Although it shows benign characteristics pathologically, local recurrence can occur.

Case Report: We herein report the case of a patient with an intraabdominal desmoid tumor that developed 3 years after laparoscopic appendectomy for acute appendicitis.

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Article Synopsis
  • Tumor-infiltrating T cells are beneficial for colorectal cancer prognosis, but the roles of other lymphocytes like NK and NKT-like cells are less understood.
  • A new multiplex immunofluorescence assay was developed to measure the presence and characteristics of these immune cell populations in colorectal carcinoma, revealing that T cells are far more abundant than NK and NKT-like cells.
  • Higher densities of T and NKT-like cells, along with specific expressions of granzyme B and NK-cell maturity indicators, were linked to longer cancer-specific survival, emphasizing the importance of both cell type density and their spatial arrangement near tumor cells for patient outcomes.
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Background: Despite heightened interest in early-onset colorectal cancer (CRC) diagnosed before age 50, little is known on immune cell profiles of early-onset CRC. It also remains to be studied whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We therefore hypothesized that immune cell infiltrates in CRC tissue might show differential heterogeneity patterns between three age groups (< 50 "early onset," 50-54 "intermediate onset,"  ≥ 55 "later onset").

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Cancer cells craftily adapt their energy metabolism to their microenvironment. Nutrient deprivation due to hypovascularity and fibrosis is a major characteristic of pancreatic ductal adenocarcinoma (PDAC); thus, PDAC cells must produce energy intrinsically. However, the enhancement of energy production via activating Kras mutations is insufficient to explain the metabolic rewiring of PDAC cells.

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Immunotherapy targeting the CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint axis has emerged as a promising treatment strategy for various cancers. Experimental evidence suggests that phosphatidylinositol-4,5-bisphosphonate 3-kinase (PI3K) signaling may upregulate CD274 expression. Thus, we hypothesized that mutation, PTEN loss, or their combined status might be associated with CD274 overexpression in colorectal carcinoma.

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Background: Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates.

Methods: Using the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts.

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Background: Myeloid cells represent an abundant yet heterogeneous cell population in the colorectal cancer microenvironment, and their roles remain poorly understood.

Methods: We used multiplexed immunofluorescence combined with digital image analysis to identify CD14 monocytic and CD15 granulocytic cells and to evaluate their maturity (HLA-DR and CD33), immunosuppressive potential (ARG1) and proximity to cytokeratin (KRT)-positive tumor cells in 913 colorectal carcinomas. Using covariate data of 4465 incident colorectal cancers in two prospective cohort studies, the inverse probability weighting method was used with multivariable-adjusted Cox proportional hazards models to assess cancer-specific mortality according to ordinal quartiles (Q1-Q4) of myeloid cell densities.

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