Diagnostic Assessment of Endoscopic Ultrasonography-Fine Needle Aspiration Cytology in the Pancreas: A Comparison between Liquid-Based Preparation and Conventional Smear.

Background and Objectives: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods: The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results: The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions: Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.

The Association of Chronic Periodontitis as a Potential Risk Factor with Rheumatoid Arthritis: A Nested Case-Control Study Using a Korean National Health Screening Cohort.

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002-2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma.

INTRODUCTION: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD). METHODS: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model. RESULTS: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening. CONCLUSION: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies.

Significant Genes Associated with Mortality and Disease Progression in Grade II and III Glioma.

BACKGROUND: The Wnt/ß-catenin pathway plays a critical role in the tumorigenesis and maintenance of glioma stem cells. This study aimed to evaluate significant genes associated with the Wnt/ß-catenin pathway involved in mortality and disease progression in patients with grade II and III glioma, using the Cancer Genome Atlas (TCGA) database. METHODS: We obtained clinicopathological information and mRNA expression data from 515 patients with grade II and III gliomas from the TCGA database. We performed a multivariate Cox regression analysis to identify genes independently associated with glioma prognosis. RESULTS: The analysis of 34 genes involved in Wnt/ß-catenin signaling demonstrated that four genes (CER1, FRAT1, FSTL1, and RPSA) related to the Wnt/ß-catenin pathway were significantly associated with mortality and disease progression in patients with grade II and III glioma. We also identified additional genes related to the four significant genes of the Wnt/ß-catenin pathway mentioned above. The higher expression of BMP2, RPL18A, RPL19, and RPS12 is associated with better outcomes in patients with glioma. CONCLUSIONS: Using a large-scale open database, we identified significant genes related to the Wnt/ß-catenin signaling pathway associated with mortality and disease progression in patients with grade II and III gliomas.

Clinicopathological significances of cribriform pattern in lung adenocarcinoma.

The present study aimed to investigate the clinicopathological and prognostic implications of the cribriform pattern in lung adenocarcinoma through a meta-analysis. The estimated rates of cribriform pattern in lung adenocarcinomas were investigated. The correlations between cribriform pattern and clinicopathological characteristics, including genetic alterations and prognosis were evaluated. The estimated rate of cribriform pattern was 0.150 (95% confidence interval [CI], 0.101-0.218) in lung adenocarcinoma. The estimated rates of cribriform pattern in the 5% and 10% criteria were 0.230 (95% CI 0.125-0.386) and 0.130 (95% CI 0.062-0.252), respectively. The presence of cribriform pattern was significantly correlated with larger tumor size (> 30 mm), spread through air spaces, and lymph node metastasis (P < 0.001, P < 0.001, and P = 0.007, respectively, in the meta-regression test). There were no significant differences between cribriform pattern, smoking history, and vascular and lymphatic invasion. In lung adenocarcinoma with cribriform pattern, the estimated rates of ALK rearrangement, KRAS, and EGFR mutations were 0.407 (95% CI 0.165-0.704), 0.330 (95% CI 0.117-0.646), and 0.249 (95% CI 0.125-0.437), respectively. ALK rearrangement was significantly more frequent in lung adenocarcinomas with cribriform pattern than in those without. The overall survival rate was significantly worse in lung adenocarcinomas with a cribriform pattern than in those without (hazard ratio 2.051, 95% CI 1.369-3.075). In conclusion, the presence of a cribriform pattern can be a useful predictor of the clinicopathological characteristics and prognosis of patients with lung adenocarcinoma.

JAK2 Loss Arising From Tumor-Spread-Through-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma: A Machine Learning Approach.

BACKGROUND: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. METHODS: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. CONCLUSION: In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Comparison between Peritumoral and Intratumoral Budding in Colorectal Cancer.

Tumor budding (TB) is classified, based on location, into peritumoral budding (PTB) or intratumoral budding (ITB). This study aimed to evaluate the relationship between PTB and ITB in colorectal cancers (CRCs). PTB and ITB were investigated and subsequently divided into high and low groups. CRCs were divided into three groups: (1) high PTB/ITB, (2) high PTB or ITB, and (3) low PTB/ITB. The clinicopathological and prognostic significances were evaluated according to the three tumor budding (TB) groups. High PTB/ITB and low PTB/ITB were identified in 32 (12.0%) and 135 (50.8%) patients, respectively. A total of 99 patients (37.2%) were found to have high PTB or ITB. TB was significantly correlated with lymphatic and perineural invasion, lymph node metastasis, metastatic lymph node ratio, distant metastasis, and a higher pTNM stage. A significant correlation was found between high PTB and high ITB (p = 0.010). The amount of PTB was found to increase significantly with the amount of ITB (p < 0.001) in a linear regression test. Patients with high PTB/ITB had worse overall and recurrence-free survival than those with high PTB or ITB. Conversely, patients with low PTB/ITB had better overall and recurrence-free survival rates than those with high PTB or ITB. However, there was no significant difference in overall and recurrence-free survival between patients with high PTB/low ITB and high ITB/low PTB (p = 0.336 and p = 0.623, respectively). In summary, the presence of TB, regardless of PTB or ITB, was significantly correlated with aggressive tumor behavior and a worse prognosis than the absence of TB. Additionally, the present study demonstrated that it is feasible to stratify the prognosis of patients based on whether they have both PTB and ITB or only one of the two.

Cancer-Associated Fibroblasts Together with a Decline in CD8+ T Cells Predict a Worse Prognosis for Breast Cancer Patients.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in tumor microenvironment regulation and cancer progression. This study assessed the significance and predictive potential of CAFs in breast cancer prognosis. METHODS: The study included 1503 breast cancer patients. Cancer-associated fibroblasts were identified using morphologic features from hematoxylin and eosin slides. The study analyzed clinicopathologic parameters, survival rates, immune cells, gene sets, and prognostic models using gene-set enrichment analysis, in silico cytometry, pathway analysis, in vitro drug-screening, and gradient-boosting machine (GBM)-learning. RESULTS: The presence of CAFs correlated significantly with young age, lymphatic invasion, and perineural invasion. In silico cytometry showed altered leukocyte subsets in the presence of CAFs, with decreased CD8+ T cells. Gene-set enrichment analysis showed associations with critical processes such as the epithelial-mesenchymal transition and immune modulation. Drug sensitivity analysis in breast cancer cell lines with varying fibroblast activation protein-α expression suggested that CAF-targeted therapies might enhance the efficacy of certain anticancer drugs including ARRY-520, ispinesib-mesylate, paclitaxel, and docetaxel. Integrating CAF presence with machine-learning improved survival prediction. For breast cancer patients, CAFs were independent prognostic markers for worse disease-specific survival and disease-free survival. CONCLUSION: This study highlighted the significance of CAFs in breast cancer biology and provided compelling evidence of their impact on patient outcomes and treatment response. The findings offer valuable insights into the potential of CAFs as prognostic and predictive biomarkers and support the development of CAF-targeted therapies to improve breast cancer management.

Clinicopathological Significances of Peritumoral Budding in Colorectal Cancer: A Detailed Analysis Based on Mucinous and Micropapillary Pattern.

The present study aimed to evaluate the correlations between peritumoral tumor budding (PTB) and the clinicopathological characteristics of colorectal cancer (CRC) according to histological components. The PTBs were investigated and divided into high and low groups. The clinicopathological significance and prognostic implications of PTB in CRC were evaluated. High PTB was found in 104 of 266 CRCs (39.1%). High PTB was significantly correlated with left-sided tumors, lymphatic invasion, lymph node metastasis, distant metastasis, and high pTNM stage. However, there was no significant correlation between PTB and the other clinicopathological characteristics. PTB was significantly higher in CRCs without the mucinous component than those with the mucinous component (p = 0.008). However, there was no significant difference between CRCs with and without the micropapillary pattern (p = 0.123). Patients with high PTB had worse recurrence-free survival than those with low PTB (p = 0.031). In the subgroup analysis based on histological components, a significant correlation between PTB and recurrence-free survival was found in CRC with a micropapillary pattern but not in those without a micropapillary pattern (p = 0.010 and p = 0.178, respectively). These findings indicate that high PTB is significantly correlated with aggressive tumor behaviors and worse survival in patients with CRC. However, the prognostic implications of PTB can differ according to histological components.

The genes significantly associated with an improved prognosis and long-term survival of glioblastoma.

BACKGROUND AND PURPOSE: Glioblastoma multiforme (GBM) is the most devastating brain tumor with less than 5% of patients surviving 5 years following diagnosis. Many studies have focused on the genetics of GBM with the aim of improving the prognosis of GBM patients. We investigated specific genes whose expressions are significantly related to both the length of the overall survival and the progression-free survival in patients with GBM. METHODS: We obtained data for 12,042 gene mRNA expressions in 525 GBM tissues from the Cancer Genome Atlas (TCGA) database. Among those genes, we identified independent genes significantly associated with the prognosis of GBM. Receiver operating characteristic (ROC) curve analysis was performed to determine the genes significant for predicting the long-term survival of patients with GBM. Bioinformatics analysis was also performed for the significant genes. RESULTS: We identified 33 independent genes whose expressions were significantly associated with the prognosis of 525 patients with GBM. Among them, the expressions of five genes were independently associated with an improved prognosis of GBM, and the expressions of 28 genes were independently related to a poorer prognosis of GBM. The expressions of the ADAM22, ATP5C1, RAC3, SHANK1, AEBP1, C1RL, CHL1, CHST2, EFEMP2, and PGCP genes were either positively or negatively related to the long-term survival of GBM patients. CONCLUSIONS: Using a large-scale and open database, we found genes significantly associated with both the prognosis and long-term survival of patients with GBM. We believe that our findings may contribute to improving the understanding of the mechanisms underlying GBM.

Prognostic impact of chemerin expression in colorectal cancer: A detailed analysis based on histological components and meta-analysis.

This study aimed to elucidate the clinicopathological significance of chemerin immunohistochemical expression in colorectal cancer (CRC) based on histologic components. Immunohistochemistry was performed to detect chemerin in 266 human CRC tissues. Correlation between chemerin expression, clinicopathological characteristics, and survival in CRC. A meta-analysis was performed to claify the prognostic role of chemerin tissue expression in malignant tumors. Chemerin was expressed in 125 of 266 CRC tissues (47.0 %) and was significantly correlated with distant metastasis (P = 0.012). However, no significant correlation was observed between chemerin expression and other clinicopathological parameters. Subgroup analyses based on histological components showed that chemerin expression was significantly higher in CRCs with the mucinous component than in those without the mucinous component (P 0.001). However, there was no significant correlation between chemerin expression and the micropapillary component. Patients with chemerin expression had worse overall and recurrence-free survival rates (P = 0.017 and P = 0.009, respectively). The prognostic significance of chemerin was found in CRCs without the mucinous component but not in those with the mucinous component. Chemerin expression was significantly correlated with poor survival in breast and ovarian cancers in the meta-analysis. Chemerin expression significantly correlated with distant metastasis and poor survival in CRCs. The predictive role of patient prognosis is useful for CRCs, especially those with no mucinous component.

Clinicopathological significance and the associated signaling pathway of p21-activated kinase 1 (PAK1) in colorectal cancer.

The aim of this study was to evaluate the clinicopathological significance and associated signaling pathways of p21-activated kinase 1 (PAK1) in colorectal cancer (CRC). PAK1 immunohistochemical expression was investigated in 246 human CRC tissues to evaluate its clinicopathological significance and prognostic role. Correlations between PAK1 and the immunoscore, HIF-1α, and pFOXO1 were also evaluated. PAK1 was expressed in 169 of 246 CRC tissues (68.7%). PAK1 expression significantly correlated with the metastatic lymph node ratio (P = 0.023). However, PAK1 expression did not correlate with tumor size, tumor location, tumor differentiation, lymphovascular and perineural invasion, or distant metastasis. PAK1 expression was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P = 0.017). In addition, there were significant correlations between PAK1, HIF-1α, and pFOXO1 expression (P = 0.001 and P = 0.024, respectively). Patients with PAK1 expression had worse overall and recurrence-free survival than those without PAK1 expression (P 0.001 and P = 0.001, respectively). PAK1 expression was significantly correlated with worse prognosis in CRCs patients. In addition, PAK1 expression was significantly correlated with a low immunoscore and high expression of HIF-1α and pFOXO1 in CRCs.

Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms.

BACKGROUND: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. RESULTS: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. CONCLUSIONS: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

Alzheimer's Disease and Different Types of Cancer Likelihood: Unveiling Disparities and Potential Protective Effects in a Korean Cohort Study.

The link between Alzheimer's disease and cancer risk is a concern in public health. However, research has yielded limited and sometimes contrasting results, suggesting the need for more validation. We analyzed a large cohort to examine the long-term association between Alzheimer's disease (AD) and the risk of developing cancer. In total, 24,664 AD patients and 98,656 control participants were selected from the National Health Insurance Cohort database of Korea, spanning from 2002 to 2019. Propensity score matching and overlap-weighted adjustment techniques were used to balance the standardized differences between the AD and control groups. The Cox proportional hazards model was applied to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for various cancers, considering relevant covariates. Results indicated that patients with AD had a significantly lower likelihood of overall malignancy (HR 0.63; 95% CI, 0.59-0.68) and each of the 10 site-specific cancers compared to the control group. Among these, pancreatic cancer (HR, 0.50) exhibited the strongest inverse association, followed by hepatic (HR, 0.60), gastric (HR, 0.63), kidney (HR, 0.63), lung (HR, 0.64), thyroid (HR, 0.65), colorectal (HR, 0.67), gallbladder and biliary duct (HR, 0.73), hematologic malignancy (HR, 0.73), and bladder cancers (HR, 0.76). This protective effect against certain organ-specific cancers persisted over the 16-year follow-up period, except for in kidney cancer and hematologic malignancies. The protective effect against specific cancer types (gastric, colorectal, lung, hepatic, and pancreatic) was more prominent in individuals aged 60 years and older, regardless of their sex. However, there were some variations in the specific types of cancer observed between males and females. In summary, Korean patients with AD had a lower risk of cancer, especially in individuals 60 years and older, during the 16-year follow-up period.

Diagnostic Roles of Immunohistochemical Markers CK20, CD44, AMACR, and p53 in Urothelial Carcinoma In Situ.

Background and Objectives: This study aimed to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in urothelial carcinoma in situ (uCIS) through a meta-analysis and review of diagnostic test accuracy. Materials and Methods: The IHC markers CK20, CD44, AMACR, and p53 were evaluated in the present study. We analyzed the expression rates of the IHC markers and compared their diagnostic accuracies. Results: The estimated expression rates were 0.803 (95% confidence interval [CI]: 0.726-0.862), 0.142 (95% CI: 0.033-0.449), 0.824 (95% CI: 0.720-0.895), and 0.600 (95% CI: 0.510-0.683) for CK20, CD44, AMACR, and p53, respectively. In the comparison between uCIS and reactive/normal urothelium, the expression of CK20, AMACR, and p53 in uCIS was significantly higher than in reactive/normal urothelium. CD44 showed significantly lower expression in uCIS than in the reactive/normal urothelium. Among the markers, AMACR had the highest sensitivity, specificity, and diagnostic odds ratio. The AUC on SROC was the highest for CK20. Conclusions: In conclusion, IHC markers, such as CK20, CD44, AMACR, and p53, can be useful in differentiating uCIS from reactive/normal urothelium.

Diagnostic and Prognostic Roles of GATA3 Immunohistochemistry in Urothelial Carcinoma.

This study aimed to evaluate the diagnostic and prognostic roles of GATA-binding protein 3 (GATA3) immunohistochemistry in urothelial carcinoma (UC) using a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and -negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704-0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727-0.818) and 0.614 (95% CI: 0.426-0.774), respectively. The GATA3 expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938-0.980) and 0.644 (95% CI: 0.581-0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883-0.967 vs. 0.753, 95% CI: 0.645-0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724-0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311-0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes, and one should be careful while interpreting GATA3 expression.

Clinicopathological significance and prognostic implication of nuclear fatty acid-binding protein 4 expression in colorectal cancer.

This study aimed to evaluate the clinicopathological significance and prognostic role of fatty acid-binding protein 4 (FABP4) expression in colorectal cancer (CRC). Nuclear expression of FABP4 was investigated by immunohistochemistry for FABP4 on 246 human CRC tissues. The correlations between FABP4 expression, and clinicopathological characteristics and survival, was evaluated in patients with CRC. FABP4 was expressed in 91 of the 246 CRC tissues (37.0%). FABP4 expression was significantly correlated with older age, right-sided colon cancer, perineural invasion, higher pT stage, lymph node metastasis, and higher pTNM stage. However, there was no significant correlation between FABP4 expression and sex, tumor size, tumor differentiation, vascular or lymphatic invasion, or distant metastasis. Nuclear FABP4 expression was not significantly correlated with cytoplasmic FABP4 expression (P = 0.412). FABP4 expression was significantly correlated with nuclear pNF-κB expression (P = 0.001), and was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P < 0.001). There were significant correlations between FABP4 expression and worse overall and recurrence-free survival rates (P < 0.001 and P = 0.007, respectively). FABP4 expression was significantly correlated with aggressive tumor behaviors and pathological characteristics. In addition, patients with CRC with FABP4 expression had worse survival rates.

Significance of Tumor-Stroma Ratio (TSR) in Predicting Outcomes of Malignant Tumors.

Background and Objectives: The present study aimed to elucidate the distribution and the prognostic implications of tumor-stroma ratio (TSR) in various malignant tumors through a meta-analysis. Materials and Methods: This meta-analysis included 51 eligible studies with information for overall survival (OS) or disease-free survival (DFS), according to TSR. In addition, subgroup analysis was performed based on criteria for high TSR. Results: The estimated rate of high TSR was 0.605 (95% confidence interval (CI) 0.565-0.644) in overall malignant tumors. The rates of high TSR ranged from 0.276 to 0.865. The highest rate of high TSR was found in endometrial cancer (0.865, 95% CI 0.827-0.895). The estimated high TSR rates of colorectal, esophageal, and stomach cancers were 0.622, 0.529, and 0.448, respectively. In overall cases, patients with high TSR had better OS and DFS than those with low TSR (hazard ratio (HR) 0.631, 95% CI 0.542-0.734, and HR 0.564, 95% CI 0.0.476-0.669, respectively). Significant correlations with OS were found in the breast, cervical, colorectal, esophagus, head and neck, ovary, stomach, and urinary tract cancers. In addition, there were significant correlations of DFS in breast, cervical, colorectal, esophageal, larynx, lung, and stomach cancers. In endometrial cancers, high TSR was significantly correlated with worse OS and DFS. Conclusions: The rate of high TSR was different in various malignant tumors. TSR can be useful for predicting prognosis through a routine microscopic examination of malignant tumors.

Exploring the Link between Chronic Kidney Disease and Alzheimer's Disease: A Longitudinal Follow-Up Study Using the Korean National Health Screening Cohort.

Chronic kidney disease (CKD) and Alzheimer's disease (AD) are common chronic diseases in the elderly population. Although a relationship between CKD and the occurrence of AD has been proposed, previous research results have been disputed, and further investigation is necessary to confirm this relationship. In this longitudinal follow-up study, we examined data from the Korean National Health Insurance Service-Health Screening Cohort, consisting of 15,756 individuals with CKD and 63,024 matched controls aged ≥40 years who received health check-ups between 2002 and 2019. Overlap-weighted Cox proportional hazard regression models were exploited to calculate hazard ratios (HRs) for the association between CKD and AD. During the monitoring period, individuals with CKD had a greater incidence of AD than those without CKD (15.80 versus 12.40 per 1000 person years). After accounting for various factors, CKD was significantly associated with a 1.14-fold increased likelihood of developing AD, with a 95% confidence interval ranging from 1.08 to 1.20. In subgroup analysis, this relationship persisted irrespective of age (≥70 or <70), sex, income, smoking status, alcohol consumption, place of residence, or fasting blood glucose level. Additionally, the association between CKD and AD was still evident among patients who were overweight or obese, those with normal blood pressure or cholesterol levels, and those without any other health conditions or with a CCI score of ≥2. These results suggest that CKD could increase the probability of developing AD in the Korean adult population irrespective of demographic or lifestyle conditions. This may make it challenging to predict AD in patients with CKD, emphasizing the importance of frequent AD screening and management.