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Purpose:Despite the well-known prognostic value of the tumor–immune microenvironment (TIME) in colorectal cancers, objective and readily applicable methods for quantifying tumor-infiltrating lymphocytes (TIL) and the tumor–stroma ratio (TSR) are not yet available.Experimental Design:We established an open-source software-based analytic pipeline for quantifying TILs and the TSR from whole-slide images obtained after CD3 and CD8 IHC staining. Using a random forest classifier, the method separately quantified intraepithelial TILs (iTIL) and stromal TILs (sTIL). We applied this method to discovery and validation cohorts of 578 and 283 stage III or high-risk stage II colorectal cancers patients, respectively, who were subjected to curative surgical resection and oxlaliplatin-based adjuvant chemotherapy.Results:Automatic quantification of iTILs and sTILs showed a moderate concordance with that obtained after visual inspection by a pathologist. The K-means–based consensus clustering of 197 TIME parameters that showed robustness against interobserver variations caused colorectal cancers to be grouped into five distinctive subgroups, reminiscent of those for consensus molecular subtypes (CMS1-4 and mixed/intermediate group). In accordance with the original CMS report, the CMS4-like subgroup (cluster 4) was significantly associated with a worse 5-year relapse-free survival and proved to be an independent prognostic factor. The clinicopathologic and prognostic features of the TIME subgroups have been validated in an independent validation cohort.Conclusions:Machine-learning–based image analysis can be useful for extracting quantitative information about the TIME, using whole-slide histopathologic images. This information can classify colorectal cancers into clinicopathologically relevant subgroups without performing a molecular analysis of the tumors.

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Dietary therapy for diabetes is the most basic way to manage blood glucose. Currently, the nutritional intake rate of diabetic patients in Korea is beyond the recommended rate of the Korean Diabetes Association, showing large amounts of carbohydrates in foods consumed as snacks with an additional focus on sugar. Thus, it is necessary to support healthy dietary habits through snack control. This study is a random assignment experimental study with a total of 56 participants; 28 participants were in the control group, while the remaining 28 patients had type 2 diabetes and had visited Kyung Hee University Hospital. The experimental group with snack control education and telephone coaching exhibited a higher self-management score (t = –9.494, P < 0.001), perceived social support score (t = 7.201, P < 0.001), and self-efficacy score (t = 7.185, P < 0.001) than the control group. Additionally, the experimental group showed lower levels of glycosylated hemoglobin and average blood glucose compared to the control group (t = –4.820, P < 0.001). Thus, snack control education and telephone coaching are effective in improving diabetes self-management behavior, perceived social support, self-efficacy, and reducing glycosylated hemoglobin and average blood glucose. These results confirm the usefulness of snack education materials, and I suggest snack control education as a means of arbitration to improve the self-care of diabetics.

Objective To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared with pathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserver agreement for evaluating mrTRG. Materials and methods Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; mean age, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologists independently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologists graded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models were used for survival analysis. Cohen's kappa analysis was used to determine interobserver agreement. Results According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5. By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantly different according to the 5-point grading mrTRG (p = 0.024) and pTRG (p = 0.038). The 5-year disease-free survival (DFS) was significantly different among the five mrTRG groups (p = 0.039), but not among the five pTRG groups (p = 0.072). OS and DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio = 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, k value between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI. Conclusion mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weighted MRI may improve interobserver agreement on mrTRG.

Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs.Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups.The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses.The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.

Coronavirus disease (COVID-19) has infected more than 50 million people and killed more than one million, worldwide, during less than a year course. COVID-19, which has already become the worst pandemic in the last 100 years, is still spreading worldwide. Since the beginning of the outbreak, it has been of particular interest to understand whether COVID-19 is seasonal; the finding might help for better planning and preparation for the fight against the disease. Over the past 12 months, numerous empirical and epidemiological studies have been performed to define the distinct diffusion patterns of COVID-19. Thereby, a wealth of data has accumulated on the relationship between various seasonal meteorological factors and COVID-19 transmissibility at global and local scales. In this review, we aimed to discuss whether COVID-19 exhibits any seasonal features in a global and local perspective by collecting and providing summaries of the findings from empirical and epidemiological studies on the COVID-19 pandemic during its first seasonal cycle.

BACKGROUND Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. METHODS Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. RESULTS SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). CONCLUSIONS Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Aims The precise profile of aberrant expression of thyroid transcription factor-1 (TTF-1) according to antibody clones in colorectal carcinomas (CRCs) has been controversial. Moreover, the detailed clinicopathological and molecular features of CRCs with TTF-1 expression have rarely been investigated. Here, we evaluated the TTF-1 expression status in a large series of CRC cases using three different antibody clones. Methods and Results Immunohistochemistry for TTF-1 using clones 8G7G3/1, SPT24, and SP141 was performed on tumour tissues of 1,319 primary CRCs and 98 corresponding metastatic lesions. Among the 1,319 CRCs, TTF-1 expression was detected in 68 cases using both clones SPT24 and SP141. TTF-1 expression was not detected in any of the cases when clone 8G7G3/1 was used. The 68 CRCs with TTF-1 expression detected using both the SPT24 and SP141 clones were considered TTF-1-positive in this study. TTF-1 positivity was significantly associated with distal tumour location, non-mucinous histology, intact CDX2 expression, and low frequency of KRAS mutations in CRCs. Nearly all TTF-1-positive CRCs showed microsatellite-stable and CpG island methylator phenotype-negative statuses. TTF-1 positivity was also found in all metastatic lesions of the five TTF-1-positive primary CRCs. TTF-1 negativity was maintained in all metastatic lesions of the 93 TTF-1-negative primary CRCs. Conclusions Our study confirmed that the frequency and characteristics of aberrant TTF-1 expression in CRCs vary depending on the antibody clone. Aberrant TTF-1 expression detected by clone SPT24 or SP141 may be encountered preferentially in distally located, conventional pathway-type CRCs. This article is protected by copyright. All rights reserved.

In the present study, we developed a computational method and panel markers to assess microsatellite instability (MSI) using a targeted next-generation sequencing (NGS) platform and compared the performance of our computational method, mSILICO, with that of mSINGS to detect MSI in CRCs. We evaluated 13 CRC cell lines, 84 fresh and 119 formalin-fixed CRC tissues (including 61 MSI-high CRCs and 155 microsatellite-stable CRCs) and tested the classification performance of the two methods on 23, 230, and 3,154 microsatellite markers. For the fresh tissue and cell line samples, mSILICO showed a sensitivity of 100% and a specificity of 100%, regardless of the number of panel markers, whereas for the formalin-fixed tissue samples, mSILICO exhibited a sensitivity of up to 100% and a specificity of up to 100% with three differently sized panels ranging from 23 to 3154. These results were similar to those of mSINGS. With the application of mSILICO, the small panel of 23 markers had a sensitivity of ≥95% and a specificity of 100% in cell lines/fresh tissues and formalin-fixed tissues of CRC. In conclusion, we developed a new computational method and microsatellite marker panels for the determination of MSI that does not require paired normal tissues. A small panel could be integrated into the targeted NGS panel for the concurrent analysis of single nucleotide variations and MSI.

This study was conducted in order to determine the prognostic value of MRI for extramural venous invasion (EMVI) in rectal cancer compared to pathology and to assess the diagnostic performance of multireaders. We retrospectively enrolled 222 patients (M:F = 148:74; mean age ± standard deviation, 61.5 ± 12 years) with histopathologically proven rectal cancers who underwent preoperative MRI between 2007 and 2016. Among them, 74 patients had positive EMVI on pathology (pEMVI) and 148 patients had negative pEMVI. Three radiologists with 7 (reviewer 1), 3 (reviewer 2), and 1 (reviewer 3) year of experience in rectal MR imaging determined the presence of EMVI on MRI (mrEMVI) using a 5-point grading system. Using histopathologic results as the reference standard, radiologists’ performances were analyzed and compared with receiver operating characteristic (ROC) analysis. For assessment of interobserver variation, intraclass correlation coefficients (ICC) were used. Lastly, Kaplan–Meier estimation and Cox proportional hazard models were used for survival analysis. The area under the ROC curve (AUC) was highest in reviewer 1 (0.829), followed by reviewer 2 (0.798) and reviewer 3 (0.658). Differences in AUCs between reviewer 1 or 2 and reviewer 3 were statistically significant (p

The aim of this study is to establish heat shock protein 110 (HSP110) as a prognostic biomarker of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) by considering the intratumoral heterogeneity of HSP110 expression. We performed whole-section immunohistochemistry (IHC) for wild-type HSP110 (HSP110wt) in 164 MSI-H CRCs. The intensity of the HSP110wt expression in tumor cells was semiquantitatively scored (0/1/2/3), and the HSP110wt expression status of each tumor was classified as low or high using the following four scoring criteria: H-score, dominant intensity score, lowest intensity score, and highest intensity score. Among the four criteria, only the dominant intensity score-based dichotomous classification of HSP110wt expression was significantly associated with a difference in disease-free survival (log-rank p = 0.035) in 164 MSI-H CRCs. The HSP110wt-low MSI-H CRCs were significantly correlated with larger deletions in the HSP110 T17 mononucleotide repeat (≥4 bp; p

The purpose of this study is to analyze the effect of "resident participatory education programs". This study methods was that applied this education programs to the residents of the fishing village after develop of education programs, and was surveyed to ninety five residents of these. As a result of the survey, "community attachment" and "sense of community" showed statistically significant differences from consciousness before and after education. Also, difference of residents consciousness according to the presence or absence of an education showed the same trend too. And, If in the presence or absence of the educational experience, residents consciousness was improved after the education programs. In other words, an education programs applied to in this study can be said to effective to that raise awareness of the residents. And this can be said to contribute in empowerment too.

Acetyl-CoA synthetase-2 is an emerging key enzyme for cancer metabolism, which supplies acetyl-CoA for tumor cells by capturing acetate as a carbon source under stressed conditions. However, implications of acetyl-CoA synthetase-2 in colorectal carcinoma may differ from other malignancies, because normal colonocytes use short-chain fatty acids as an energy source, which are supplied by fermentation of the intestinal flora. Here we analyzed acetyl-CoA synthetase-2 mRNA expression by reverse-transcription quantitative PCR in paired normal mucosa and tumor tissues of 12 colorectal carcinomas, and subsequently evaluated acetyl-CoA synthetase-2 protein expression by immunohistochemistry in 157 premalignant colorectal lesions, including 60 conventional adenomas and 97 serrated polyps, 1,106 surgically resected primary colorectal carcinomas, and 23 metastatic colorectal carcinomas in the liver. In reverse-transcription quantitative PCR analysis, acetyl-CoA synthetase-2 mRNA expression was significantly decreased in tumor tissues compared with corresponding normal mucosa tissues. In acetyl-CoA synthetase-2 immunohistochemistry analysis, all 157 colorectal polyps showed moderate-to-strong expression of acetyl-CoA synthetase-2. However, cytoplasmic acetyl-CoA synthetase-2 expression was downregulated (acetyl-CoA synthetase-2 low expression) in 771 (69.7%) of 1,106 colorectal carcinomas and 21 (91.3%) of 23 metastatic lesions. The colorectal carcinomas with acetyl-CoA synthetase-2-low expression were significantly associated with advanced TNM stage, poor differentiation, and frequent tumor budding. Regarding the molecular aspect, acetyl-CoA synthetase-2-low expression exhibited a tendency of frequent KRT7 expression and decreased KRT20 and CDX2 expression. In survival analysis, acetyl-CoA synthetase-2-low expression was an independent prognostic factor for poor 5-year progression-free survival (hazard ratio, 1.39; 95% confidence interval, 1.08-1.79; P=0.01). In conclusion, these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma.

Background: The aim of this study was to reveal the clinicopathological and molecular characteristics of microsatellite instability-high (MSI-H) colorectal cancers (CRCs) showing programmed death ligand-1 (PD-L1) positivity, which are good candidates for anti-PD-1/PD-L1 immunotherapy. Methods: The PD-L1 expression status of 208 MSI-H CRCs was retrospectively analysed using immunohistochemistry. PD-L1 positivity in tumour cells (PD-L1+(T)) and PD-L1 positivity in immune cells (PD-L1+(I)) were separately evaluated. Results: Programmed death ligand-1 positivity in tumour cells and PD-L1+(I) were observed in 26 (12.5%) and 62 (29.8%) MSI-H CRCs, respectively, and occasionally overlapped (n=12; 5.8%). Programmed death ligand-1 positivity tumours in MSI-H CRCs were significantly associated with older age, female sex, non-mucinous-type poor differentiation, infiltrating growth, tumour budding, advanced stage, CpG island methylator phenotype-high, MLH1 promoter methylation, and BRAF V600E mutations. However, PD-L1+(I) MSI-H CRCs were characterised by high-density tumour-infiltrating immune cells, including T cells and macrophages, and intense peritumoural lymphoid reactions. In patients with stage IV MSI-H CRCs who had undergone metastatectomy (n=4), the PD-L1 status of primary tumours was maintained in corresponding distant metastatic lesions. Conclusions: In MSI-H CRCs, PD-L1+(T) and PD-L1+(I) are linked to a sporadic hypermethylated subtype and an immune cell-rich subtype, respectively. Potential differential therapeutic implications of PD-L1+(T) and PD-L1+(I) in CRCs should be further investigated.

Objective : The high-dose vitamin C is useful in the cancer. Consequently its use should have become how many help even from gynecological cancer patient who is in chemotherapy. Methods : The study was performed prospective on 57 patients who is diagnosed initially the gynecological cancer during chemotherapy at Gospel Hospital of Kosin University between January 2005 and October 2006. The study was divided to its use 29 (cervix cancer: 17, ovarian cancer 12) and no high-dose vitamin C use 28 (cervix cancer: 11, ovarian cancer 17). The cervix cancer was treated by FP chemotherapy for all stage and the ovarian cancer was treated by CC chemotherapy for stage 1, CT or PT chemotherapy for advanced stage for 6 times respectively regarding a treatment in tumor marker change aspect and the side effect researched GOG classifications. Results : It evaluated the nausea and vomiting significantly in ovarian cancer (p＜0.05). It evaluated for liver enzyme, Hb, WBC, platelet serum creatinine, sensory, motor nervous system and tumor marker with the high-dose vitamin C group does not have the difference from the control group statistically. Conclusion : The high-dose vitamin C is a possibility of reducing nausea and vomiting in the ovarian cancer chemotherapy without other side effect. The regarding a tumor marker change it was not significantly but when it analyzed a recurrence a survival rate with more patient and follow up in long period, its use of should have become how many help in gynecological cancer treatment.