記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture. METHODS: In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR). RESULTS: In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred. CONCLUSION: Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.

DOI： 10.1007/s00464-023-09988-7

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記述言語：英語  

A 78-year-old man was admitted to our hospital with a tarry stool. Esophagogastroduodenoscopy identified tiny oozing on the greater curvature at the antrum. Despite repeated endoscopic hemostasis by coagulation and clipping, rebleeding occurred. On the third rebleeding, we performed endoscopic hand suturing to completely close the ulcer surface. Biopsy showing massive infiltration of eosinophils at the ulcer edge indicated eosinophilic gastritis. After the endoscopic closure by endoscopic hand suturing, the patient had no symptoms of bleeding thereafter and was discharged 19 days after the procedure by taking oral prednisolone. The patient remained well and was continuously treated with a small dose of steroids in outpatient. This is the first case report of the successful application of endoscopic hand suturing to a refractory hemorrhagic ulcer. Further accumulation of clinical experiences is desired to confirm the usefulness of this technique for the prevention of refractory ulcer bleeding.

DOI： 10.1002/deo2.207

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management. METHODS: Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases. RESULTS: The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend. DISCUSSION: Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.

DOI： 10.14309/ajg.0000000000002171

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. METHODS: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. RESULTS: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. CONCLUSIONS: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

DOI： 10.1007/s00535-023-01955-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines have been recommending tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, to be included as risk factors for lymph node metastasis (LNM) in T1 colorectal carcinoma (CRC) patients. In this study, a novel nomogram was developed and validated using large-scale real-world data, including the JSCCR risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4,673 T1 CRC patients treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathological findings were extracted from the medical records of each participating institution. The discrimination ability was measured using the concordance index, and the variability in each prediction was evaluated using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was 0.784 for the clinical calculator in the development cohort and 0.790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathological diagnosis based on data from a nationwide multi-institutional study. With this nomogram developed with real-world data decision-making for an appropriate treatment strategy for T1 CRC should improve.

DOI： 10.1016/j.gie.2023.01.022

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Linked color imaging (LCI) improves detection of colorectal neoplastic lesions during colonoscopy. However, polyps <5 mm in diameter often do not require resection, and the benefits of LCI are unclear for detection of colorectal polyps ≥5 mm that are indicated for endoscopic resection in clinical practice. This randomized controlled trial compared rates of detection of adenoma polyps, stratified by size, for LCI and white light imaging (WLI). METHODS: We compared ADR (5 mm-) and PDR (5 mm-), which were defined as the proportion of patients with at least one adenoma or polyp with a diameter of 5 mm or larger in the LCI and WLI groups. Moreover, we estimated ADR and PDR for diameters between 5 and 10 mm (ADR (5-9 mm), PDR (5-9 mm) ) and for diameters larger than 10 mm (ADR (10 mm-), PDR (10 mm-) ). RESULTS: Data from 594 patients (LCI, n=305; WLI, n=289) were analyzed. ADR (5 mm-) and PDR (5 mm-) were significantly higher in the LCI group than in the WLI group (ADR (5 mm-): P=0.016, PDR (5 mm-): P=0.020). In the assessment of adenoma and polyp size, ADR (5-9 mm) and PDR (5-9 mm) were significantly higher in the LCI group than in the WLI group, although no significant differences were seen in ADR (10 mm-) and PDR (10 mm-) between these groups. CONCLUSIONS: Polyps ≥5 mm, which are indicated for endoscopic treatment, were more easily visualized with LCI mode than with WLI mode. The improvement in detection rate was obvious for polyps <10 mm, which are easier to miss.

DOI： 10.1272/jnms.JNMS.2023_90-117

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma. METHODS: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations. RESULTS: Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively (P trend = 0.032). CONCLUSIONS: Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.

DOI： 10.1002/cti2.1453

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing. METHODS: Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated. RESULTS: A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively. DISCUSSION/CONCLUSION: The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

DOI： 10.1159/000527350

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti-tumor immune responses and tumor behavior. We hypothesized that pro-inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses. METHODS: We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow-up Study. Using Cox proportional hazards regression analyses, we examined the prognostic association of EDIP scores and whether it might be modified by histopathologic immune reaction (in 1192 patients with available data). RESULTS: Higher EDIP scores after colorectal cancer diagnosis were associated with worse survival, with multivariable-adjusted hazard ratios (HRs) for the highest versus lowest tertile of 1.41 (95% confidence interval [CI]: 1.13-1.77; Ptrend = 0.003) for 5-year colorectal cancer-specific mortality and 1.44 (95% CI, 1.19-1.74; Ptrend = 0.0004) for 5-year all-cause mortality. The association of post-diagnosis EDIP scores with 5-year colorectal cancer-specific mortality differed by degrees of tumor-infiltrating lymphocytes (TIL; Pinteraction = .002) but not by three other lymphocytic reaction patterns. The multivariable-adjusted, 5-year colorectal cancer-specific mortality HRs for the highest versus lowest EDIP tertile were 1.59 (95% CI: 1.01-2.53) in TIL-absent/low cases and 0.48 (95% CI: 0.16-1.48) in TIL-intermediate/high cases. CONCLUSIONS: Pro-inflammatory diets after colorectal cancer diagnosis were associated with increased mortality, particularly in patients with absent or low TIL.

DOI： 10.1002/ctm2.1114

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

DOI： 10.3748/wjg.v28.i39.5658

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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. METHODS: While 123 773 participants of the Nurses' Health Study and the Health Professionals Follow-up Study had been followed up (3 143 158 person-years), 3077 of them had developed CRC. Healthy and unhealthy plant-based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. RESULTS: Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P-trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P-trend = .005). The association of hPDI significantly differed by KRAS status (P-heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P-trend = .004) but not KRAS-mutant CRC (P-trend = .22). CONCLUSIONS: While unhealthy plant-based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant-based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS-wildtype CRC.

DOI： 10.1002/ctm2.893

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-1884-0065

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence of early-onset colorectal cancer (CRC) diagnosed before age 50 has been increasing over the past decades. Hence, we examined the global, regional, and national burden of early-onset CRC and its risk factors from 1990 to 2019. METHODS: Using data from the Global Burden of Disease (GBD) Study 2019, we reported the incidence, deaths, and disability-adjusted life-years (DALYs) attributable to the risk factors of early-onset CRC. All estimates were reported with 95% uncertainty intervals (UIs). RESULTS: The global numbers of early-onset CRC for incidence, deaths, and DALYs in 2019 were 225,736 (95% UI, 207,658 to 246,756), 86,545 (80,162 to 93,431), and 4,259,922 (3,942,849 to 4,590,979), respectively. Despite large variations at the regional and national levels, the global incidence rate, death rate, and DALY rate increased from 1990 to 2019. Diets low in milk, diets low in calcium, and alcohol use were the leading risk factors in 2019. From 1990 to 2019, a high body mass index and high fasting plasma glucose ranked remarkably higher among males and females, while smoking and diets low in fiber ranked lower among both sexes, with a more profound change among females. CONCLUSIONS: Despite large variations in regional and national levels, the global incidence rate, death rate, and DALY rate increased during the past three decades. These findings may provide policymakers with an accurate quantification of the burden of early-onset CRC and targeted identification of those most at risk to mitigate the burden of early-onset CRC.

DOI： 10.3390/cancers14143502

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). METHODS: We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. RESULTS: The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. CONCLUSIONS: SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.

DOI： 10.1186/s12885-022-09824-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Evidence supports a carcinogenic role of Escherichia coli carrying the polyketide synthase (pks) island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+ E. coli. METHODS: Western diet score was calculated using food frequency questionnaire data obtained every four years during follow-up of 134,775 participants in two U.S.-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pks+ E. coli DNA in 1,175 tumors among 3,200 incident colorectal cancer cases that had occurred during the follow-up. We utilized the 3,200 cases and inverse probability weighting (to adjust for selection bias due to tissue availability), integrated in multivariable-adjusted duplication-method Cox proportional hazards regression analyses. RESULTS: The association of the western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+ E. coli (Pheterogeneity = 0.014). Multivariable-adjusted hazard ratios (with 95% confidence interval) for the highest (vs. lowest) tertile of the western diet score were 3.45 (1.53-7.78) (Ptrend = 0.001) for pks+ E. coli-high tumors, 1.22 (0.57-2.63) for pks+ E. coli-low tumors, and 1.10 (0.85-1.42) for pks+ E. coli-negative tumors. The pks+ E. coli level was associated with lower disease stage but not with tumor location, microsatellite instability, or BRAF, KRAS, or PIK3CA mutations. CONCLUSIONS: Western-style diet is associated with higher incidence of colorectal cancer containing abundant pks+ E. coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.

DOI： 10.1053/j.gastro.2022.06.054

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Surgery is recommended in early gastric cancer (EGC) after noncurative endoscopic submucosal dissection (ESD), although observation can be an alternative. We aimed to develop a tailor-made treatment strategy for noncurative EGCs by comparing the lymph node metastasis risk (LNMR) and the surgical risk. METHODS: We retrospectively identified 485 patients with differentiated-type, noncurative EGCs removed by ESD and classified them into two groups: a surgery-preferable group and an observation-preferable group, according to the clinical courses. Subsequently, LNMR and surgery-related death risk were assessed using a published scoring system and a risk calculator for gastrectomy, respectively. Finally, we investigated the optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to efficiently allocate these cases into either of two groups, surgery-preferable or observation-preferable. RESULTS: In 485 patients (surgery in 322, observation in 163), 57 and 428 patients were classified into the surgery-preferable group and the observation-preferable group, respectively. The optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to allocate the cases to the two preferable groups was 7.85 with the highest area under the curve (0.689). When cases with >7.85 LNMR over the surgery-related death risk were allocated into the surgery-preferable group and vice versa, the discriminability was 73.2%, which was sufficiently higher than that in the clinical decision (44.5%). CONCLUSION: Personalized comparison of LNMR and surgery-related death risk is helpful to provide a favorable treatment option for each patient with EGCs after noncurative ESD.

DOI： 10.1159/000523972

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: It is unclear whether prophylactic endoscopic closure after colorectal endoscopic submucosal dissection (ESD) reduces the risk of postoperative adverse events due to variability in lesion characteristics. Therefore, we conducted a retrospective study using propensity score matching to evaluate the efficacy of prophylactic clip closure in preventing postoperative adverse events after colorectal ESD. METHODS: This single-center retrospective cohort study included 219 colorectal neoplasms which were removed by ESD. The patients were allocated into the closure and non-closure groups, which were compared before and after propensity-score matching. Post-ESD adverse events including major and minor bleeding and delayed perforation were compared between the two groups. RESULTS: In this present study, 97 and 122 lesions were allocated to the closure and non-closure groups, respectively, and propensity score matching created 61 matched pairs. The rate of adverse events was significantly lower in the closure group than in the non-closure group (8% vs. 28%, P = 0.008). Delayed perforation occurred in two patients in the non-closure group, whereas no patient in the closure group developed delayed perforation. In contrast, there were no significant differences in other postoperative events including the rate of abdominal pain; fever, white blood cell count, and C-reactive protein; and appetite loss between the two groups. CONCLUSIONS: Propensity score matching analysis demonstrated that prophylactic closure was associated with a significantly reduced rate of adverse events after colorectal ESD. When technically feasible, mucosal defect closure after colorectal ESD may result in a favorable postoperative course.

DOI： 10.1186/s12876-022-02202-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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, 0.93; 95% CI, 0.84 to 1.03). Although statistical significance was not reached at the stringent level (α=.005), the association of coffee intake with colorectal cancer-specific mortality differed by Crohn disease-like lymphoid reaction (Pinteraction=.007). Coffee intake was associated with lower colorectal cancer-specific mortality in patients with high Crohn disease-like reaction (multivariable HR for 1-cup increase of coffee intake per day, 0.55; 95% CI, 0.37 to 0.81; Ptrend=.002) but not in patients with intermediate Crohn disease-like reaction (the corresponding HR, 1.02; 95% CI, 0.72 to 1.44) or negative/low Crohn disease-like reaction (the corresponding HR, 0.95; 95% CI, 0.83 to 1.07). The associations of coffee intake with colorectal cancer-specific mortality did not significantly differ by levels of other lymphocytic reaction or any T-cell subset (Pinteraction>.18). There is suggestive evidence for differential prognostic effects of coffee intake by Crohn disease-like lymphoid reaction in colorectal cancer.

DOI： 10.1016/j.mayocp.2021.09.007

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：英語  

Esophageal submucosal hematoma is a rare disease mainly caused by mechanical stimulation to the esophageal wall. We reported a case of esophageal submucosal hematoma after transesophageal echocardiography (TEE) which was performed during cardiovascular surgery. The stimuli of TEE insertion under general anesthesia and the perioperative use of multiple antithrombotic agents were considered as a possible cause. This is the first report of esophageal submucosal hematoma related to TEE, and endoscopic ultrasonography should be carefully performed in patients, particularly at bleeding tendency and without consciousness.

DOI： 10.1159/000525036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias. Results: Immature desmoplastic reaction was associated with lower densities of intraepithelial CD3+CD8+CD45RO+ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29-0.62; Ptrend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28-0.70; Ptrend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3+CD8+CD45RO+ cells (Ptrend <0.0001) and stromal M1-like macrophages (Ptrend = 0.0007)] and for keloid-like collagen bundles (Ptrend <0.0001 for intraepithelial CD3+CD8+CD45RO+ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23-0.44; Ptrend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16-0.39; Ptrend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05-0.28; Ptrend <0.0001) for absent (vs. marked) keloid-like collagen bundles. Conclusions: Immature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.

DOI： 10.3389/fimmu.2022.840198

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3-), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1-CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (P trend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (P trend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (P trend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3-GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.

DOI： 10.1158/2326-6066.CIR-21-0772

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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"). METHODS: We examined 1,518 incident CRC cases with available tissue data, including 35 early-onset and 73 intermediate-onset cases. To identify immune cells in tumor intraepithelial and stromal areas, we developed three multiplexed immunofluorescence assays combined with digital image analyses and machine learning algorithms, with the following markers: (1) CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 for T cells; (2) CD68, CD86, IRF5, MAF, and MRC1 (CD206) for macrophages; and (3) ARG1, CD14, CD15, CD33, and HLA-DR for myeloid cells. RESULTS: Although no comparisons between age groups showed statistically significant differences at the stringent two-sided α level of 0.005, compared to later-onset CRC, early-onset CRC tended to show lower levels of tumor-infiltrating lymphocytes (P = 0.013), intratumoral periglandular reaction (P = 0.025), and peritumoral lymphocytic reaction (P = 0.044). Compared to later-onset CRC, intermediate-onset CRC tended to show lower densities of overall macrophages (P = 0.050), M1-like macrophages (P = 0.062), CD14+HLA-DR+ cells (P = 0.015), and CD3+CD4+FOXP3+ cells (P = 0.039). CONCLUSIONS: This hypothesis-generating study suggests possible differences in histopathologic lymphocytic reaction patterns, macrophages, and regulatory T cells in the tumor microenvironment by age at diagnosis.

DOI： 10.1007/s00262-021-03056-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.). METHODS: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012). RESULTS: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers. DISCUSSION: Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC.

DOI： 10.14309/ctg.0000000000000338

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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: Utilizing 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. Multiplexed immunofluorescence [for CD68, CD86, IRF5, MAF, and MRC1 (CD206)] combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability-weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias due to tissue data availability. All statistical tests were 2-sided. RESULTS: During follow-up of 131,144 participants (3,648,370 person-years), we documented 3,092 incident colorectal cancer cases including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity=.003). Compared to never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for ≥40 pack-years (Ptrend=.004). In contrast, pack-years smoked were not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend>.009, with the α level of 0.005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages. CONCLUSIONS: The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.

DOI： 10.1093/jnci/djab142

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Three-dimensional (3D) technology has been used in many fields, including flexible endoscopy. We evaluated the usefulness of 3D visualization for endoscopically diagnosing superficial gastric neoplasia. METHODS: Twelve participants (4 novices, 4 trainees and 4 experts) evaluated two-dimensional (2D) and 3D endoscopic still images of 28 gastric neoplasias, obtained before ESD with white-light imaging (WLI) and narrow-band imaging (NBI). Assessments of the delineation accuracy of tumor extent and tumor morphology under 2D and 3D visualization were based on the histopathological diagnosis of ESD specimens. Participants answered visual analog scale (VAS) questionnaires (0-10, worst to best) concerning the (a) ease of recognition of lesion morphology, (b) lesion extent and (c) comprehensive endoscopic cognition under 2D and 3D visualization. The endpoints were the accuracy of tumor extent and morphology type and the degree of confidence in assessing (a)-(c). RESULTS: The delineation accuracy of lesion extent [mean (95% confidence interval)] with WLI under 3D visualization [60.2% (56.1-64.3%)] was significantly higher than that under 2D visualization [52.3% (48.2-56.4%)] (P < 0.001). The accuracy with NBI under 3D visualization [70.3% (66.8-73.7%)] was also significantly higher than that under 2D visualization [64.2% (60.7-67.4%)] (P < 0.001). The accuracy of the morphology type with NBI under 3D visualization was significantly higher than that under 2D visualization (P = 0.004). The VAS for all aspects of endoscopic recognition under 3D visualization was significantly better than that under 2D visualization (P < 0.01). CONCLUSIONS: Three-dimensional visualization can enhance the diagnostic quality for superficial gastric tumors.

DOI： 10.1186/s12876-021-01829-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50-54 (hereafter referred to as "intermediate-onset") remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55-69, 61.0 (SD 10.2) in age 50-54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was -1.38 (-2.47 to -0.30) for age 55-69, -2.82 (-5.29 to -0.34) for age 50-54, and -4.54 (-8.24 to -0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45-55, and 55-65 (vs. >65) were 2.33 (1.49-3.64), 1.39 (1.05-1.85), and 1.29 (1.02-1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.

DOI： 10.3390/cancers13092016

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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. Immune cell-tumor cell proximity was measured with the nearest neighbor method and the G-cross function, which determines the likelihood of any tumor cell having at least one immune cell of the specified type within a certain radius. RESULTS: Higher intraepithelial (P trend=0.0002; HR for Q4 (vs Q1), 0.48, 95% CI 0.31 to 0.76) and stromal (P trend <0.0001; HR for Q4 (vs Q1), 0.42, 95% CI 0.29 to 0.63) densities of CD14+HLA-DR+ cells were associated with lower colorectal cancer-specific mortality while, conversely, higher intraepithelial densities of CD14+HLA-DR- cells were associated with higher colorectal cancer-specific mortality (P trend=0.0003; HR for Q4 (vs Q1), 1.78, 95% CI 1.25 to 2.55). Spatial analyses indicated that CD15+ cells were located closer to tumor cells than CD14+ cells, and CD14+HLA-DR+ cells were closer to tumor than CD14+HLA-DR- cells (p<0.0001). The G-cross proximity measurement, evaluating the difference in the likelihood of any tumor cell being colocated with at least one CD14+HLA-DR+ cell versus CD14+HLA-DR- cell within a 20 µm radius, was associated with lower colorectal cancer-specific mortality (P trend <0.0001; HR for Q4 (vs Q1), 0.37, 95% CI 0.24 to 0.57). CONCLUSIONS: Myeloid cell populations occur in spatially distinct distributions and exhibit divergent, subset-specific prognostic significance in colorectal cancer, with mature CD14+HLA-DR+ and immature CD14+HLA-DR- monocytic phenotypes most notably showing opposite associations. These results highlight the prognostic utility of multimarker evaluation of myeloid cell infiltrates and reveal a previously unrecognized degree of spatial organization for myeloid cells in the immune microenvironment.

DOI： 10.1136/jitc-2020-002297

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

DOI： 10.1038/s41571-020-00445-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 PIK3CA mutation, PTEN loss, or their combined status might be associated with CD274 overexpression in colorectal carcinoma. We assessed tumor CD274 and PTEN expression by immunohistochemistry and assessed PIK3CA mutation by pyrosequencing in 753 patients among 4,465 incident rectal and colon cancer cases that had occurred in two U.S.-wide prospective cohort studies. To adjust for potential confounders and selection bias due to tissue availability, inverse probability weighted multivariable ordinal logistic regression analyses used the 4,465 cases and tumoral data including microsatellite instability, CpG island methylator phenotype, KRAS and BRAF mutations. PIK3CA mutation and loss of PTEN expression were detected in 111 of 753 cases (15%) and 342 of 585 cases (58%), respectively. Tumor CD274 expression was negative in 306 (41%), low in 195 (26%), and high in 252 (33%) of 753 cases. PTEN loss was associated with CD274 overexpression [multivariable odds ratio (OR) 1.83; 95% confidence interval (CI), 1.22-2.75; P = .004]. PIK3CA mutation was statistically-insignificantly (P = .036 with the stringent alpha level of 0.005) associated with CD274 overexpression (multivariable OR, 1.54; 95% CI, 1.03-2.31). PIK3CA-mutated PTEN-lost tumors (n = 33) showed higher prevalence of CD274-positivity (82%) than PIK3CA-wild-type PTEN-lost tumors (n = 204; 70% CD274-positivity) and PTEN-expressed tumors (n = 147; 50% CD274-positivity) (P = .003). Our findings support the role of PI3K signaling in the CD274/PDCD1 pathway.

DOI： 10.1080/2162402X.2021.1956173

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Colorectal cancer (CRC) is a heterogeneous disease that can develop via three major pathways, including the conventional, serrated, and alternate pathways. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes.


</sec>
<sec>
<title>Methods</title>
We examined the association of 24 risk factors with four CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutations by collecting data from two large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes.


</sec>
<sec>
<title>Results</title>
We documented 1,175 CRC cases with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low/negative, BRAF-wildtype, KRAS-wildtype), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wildtype), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low/negative, BRAF-wildtype, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13-3.26; HR for female = 2.65, 95% CI = 1.60-4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14-1.45) than other CRC subtypes (All P for heterogeneity &amp;lt; 0.005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women, and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α = 0.005 level.


</sec>
<sec>
<title>Conclusions</title>
Risk factor profiles may differ for CRC arising from different molecular pathways.


</sec>

DOI： 10.1093/jncics/pkaa089

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Macrophages are among the most common cells in the colorectal cancer microenvironment, but their prognostic significance is incompletely understood. Using multiplexed immunofluorescence for CD68, CD86, IRF5, MAF, MRC1 (CD206), and KRT (cytokeratins) combined with digital image analysis and machine learning, we assessed the polarization spectrum of tumor-associated macrophages in 931 colorectal carcinomas. We then applied Cox proportional hazards regression to assess prognostic survival associations of intraepithelial and stromal densities of M1-like and M2-like macrophages while controlling for potential confounders, including stage and microsatellite instability status. We found that high tumor stromal density of M2-like macrophages was associated with worse cancer-specific survival, whereas tumor stromal density of M1-like macrophages was not significantly associated with better cancer-specific survival. High M1:M2 density ratio in tumor stroma was associated with better cancer-specific survival. Overall macrophage densities in tumor intraepithelial or stromal regions were not prognostic. These findings suggested that macrophage polarization state, rather than their overall density, was associated with cancer-specific survival, with M1- and M2-like macrophage phenotypes exhibiting distinct prognostic roles. These results highlight the utility of a multimarker strategy to assess the macrophage polarization at single-cell resolution within the tumor microenvironment.

DOI： 10.1158/2326-6066.CIR-20-0527

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cgh.2019.07.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods: We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results: We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P < .001) and better model fitting (Akaike information criteria = 70 937 vs 71 238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts. Conclusions: The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

DOI： 10.1093/jncics/pkaa093

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
We hypothesized that the associations between coffee intake and colorectal cancer (CRC) incidence might differ by immune cell densities in CRC tissue. Utilizing the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association of coffee intake with incidence of CRC classified by intraepithelial or stromal T-cell subset densities by multiplex immunofluorescence assay for CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3. We applied inverse probability weighted Cox proportional hazards regression model to control for selection bias and potential confounders. During follow-up of 133,924 participants (3,585,019 person-years), we documented 3,161 incident CRC cases, including 908 CRC cases with available data on T-cell densities in tumor tissue. The association between coffee intake and CRC was not statistically significantly different by intraepithelial or stroma T-cell subset (Pheterogeneity &amp;gt; .38). Hence, there is no sufficient evidence for differential effect of coffee intake on incidence of CRC subtypes classified by T-cell infiltrates.

DOI： 10.1093/jncics/pkaa068

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although high T-cell density is a well-established favorable prognostic factor in colorectal cancer, the prognostic significance of tumor-associated plasma cells, neutrophils, and eosinophils is less well-defined. EXPERIMENTAL DESIGN: We computationally processed digital images of hematoxylin and eosin (H&E)-stained sections to identify lymphocytes, plasma cells, neutrophils, and eosinophils in tumor intraepithelial and stromal areas of 934 colorectal cancers in two prospective cohort studies. Multivariable Cox proportional hazards regression was used to compute mortality HR according to cell density quartiles. The spatial patterns of immune cell infiltration were studied using the GTumor:Immune cell function, which estimates the likelihood of any tumor cell in a sample having at least one neighboring immune cell of the specified type within a certain radius. Validation studies were performed on an independent cohort of 570 colorectal cancers. RESULTS: Immune cell densities measured by the automated classifier demonstrated high correlation with densities both from manual counts and those obtained from an independently trained automated classifier (Spearman's ρ 0.71-0.96). High densities of stromal lymphocytes and eosinophils were associated with better cancer-specific survival [Ptrend < 0.001; multivariable HR (4th vs 1st quartile of eosinophils), 0.49; 95% confidence interval, 0.34-0.71]. High GTumor:Lymphocyte area under the curve (AUC0,20μm; Ptrend = 0.002) and high GTumor:Eosinophil AUC0,20μm (Ptrend < 0.001) also showed associations with better cancer-specific survival. High stromal eosinophil density was also associated with better cancer-specific survival in the validation cohort (Ptrend < 0.001). CONCLUSIONS: These findings highlight the potential for machine learning assessment of H&E-stained sections to provide robust, quantitative tumor-immune biomarkers for precision medicine.

DOI： 10.1158/1078-0432.CCR-20-0071

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. Methods: Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses' Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn's-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results: The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer-specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided Pinteraction = .009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. Conclusions: The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.

DOI： 10.1093/jncics/pkaa040

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. METHODS: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. FINDINGS: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35-0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31-0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57-2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. INTERPRETATION: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion.

DOI： 10.1016/j.ebiom.2020.102860

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Copyright © 2020 Korean Society of Gastrointestinal Endoscopy. Background/Aims: Three-dimensional (3D) flexible endoscopy, a new imaging modality that provides a stereoscopic view, can facilitate endoscopic hand suturing (EHS), a novel intraluminal suturing technique. This ex-vivo pilot study evaluated the usefulness of 3D endoscopy in EHS. Methods: Four endoscopists (two certified, two non-certified) performed EHS in six sessions on a soft resin pad. Each session involved five stitches, under alternating 3D and two-dimensional (2D) conditions. Suturing time (sec/session), changes in suturing time, and accuracy of suturing were compared between 2D and 3D conditions. Results: The mean suturing time was shorter in 3D than in 2D (9.8±3.4 min/session vs. 11.2±5.1 min/session) conditions and EHS was completed faster in 3D conditions, particularly by non-certified endoscopists. The suturing speed increased as the 3D sessions progressed. Error rates (failure to grasp the needle, failure to thread the needle, and puncture retrial) in the 3D condition were lower than those in the 2D condition, whereas there was no apparent difference in deviation distance. Conclusions: 3D endoscopy may contribute to increasing the speed and accuracy of EHS in a short time period. Stereoscopic viewing during 3D endoscopy may help in efficient skill acquisition for EHS, particularly among novice endoscopists. Clin Endosc 2020;53:334-338

DOI： 10.5946/CE.2019.207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Background: Three-dimensional (3D) visualization offers better depth recognition than two-dimensional (2D) imaging, thus helping to provide more useful information. We compared 3D and 2D endoscopy with regard to endoscopic recognition and endoscopic submucosal dissection (ESD) marking for superficial gastric neoplasia. Methods: ESD marking was performed on half of a neoplasia margin under 2D observation and the on other half under 3D observation for 28 gastric lesions (26 early gastric cancers and 2 adenomas). The accuracy of ESD marking was evaluated based on the distance between the pathological and endoscopic neoplasia margins measured on histology sections of ESD specimens. The technical ease of ESD marking and endoscopic lesion recognition (lesion morphology, lesion extent, and comprehensive endoscopic cognition) were assessed using visual analog scale (VAS) questionnaires. Results: The mean distance between the pathological and endoscopic margins under 3D observation (1.03 ± 0.80 mm) was significantly (p = 0.002) shorter than that under 2D observation (1.94 ± 1.96 mm). The VAS for technical ease of ESD marking under 3D observation was significantly better (p < 0.01) than that under 2D observation. The VAS for all aspects of endoscopic recognition under 3D observation was significantly better (p < 0.01) than under 2D observation. Conclusions: 3D flexible endoscopy achieved more accurate endoscopic recognition and ESD marking for superficial gastric neoplasia than a 2D approach in a clinical setting of ESD.

DOI： 10.1007/s00464-020-08124-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019, Spandidos Publications. All rights reserved. Angiopoietin-like protein (ANGPTL) 8 regulates the partitioning of triglycerides by inhibiting lipoprotein lipase in muscle and adipose tissues. ANGPTL8 is expressed in the liver and adipose tissue and secreted into the blood. However, the precise localization of ANGPTL8-expressing cells in these tissues remains unknown. The aim of the present study was to investigate the localization of ANGPTL8-expressing cells in human tissues. Using formalin-fixed paraffin-embedded human tissue specimens, the expression of ANGPTL8 was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC) and in situ hybridization (ISH). The expression level of ANGPTL8 mRNA was the highest in the liver, followed by lipoma, hibernoma and normal adipose tissue. In the liver, wild type (KF809856) and two splice variants of ANGPTL8 mRNA (KF809857 and KF809858) were found to be expressed. The expression level of the splice variant KF809858, which produces a short form of ANGPTL8, accounted for <1% of ANGPTL8 in the liver. IHC revealed that ANGPTL8 was expressed in hepatocytes in zone 1 of the hepatic acinus in the liver. In the adipose tissue, mature adipocytes weakly expressed ANGPTL8, while immature adipocytes strongly expressed it. ISH confirmed ANGPTL8 mRNA expression in portal hepatocytes and immature adipocytes. ANGPTL8 was expressed in the cells, which actively uptake and metabolize triglycerides. In hibernoma, the ANGPTL8 protein and mRNA were homogeneously expressed in tumor cells. The expression of ANGPTL8 was associated with the differentiation state and activity of lipid metabolism in a subpopulation of cells in the liver and adipose tissue. The association may be helpful for the understanding of local metabolic state in organs and diseases associated with the lipid metabolism.

DOI： 10.3892/br.2019.1243

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

© 2018 S. Karger AG, Basel. Background and Aim: Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury. Methods: Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared. Results: A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001). Conclusion: There is a possibility that H. pylori infection induces small intestinal mucosal injury.

DOI： 10.1159/000494415

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記述言語：日本語   出版者・発行元：日本小腸学会  

【目的】

Peutz-Jeghers症候群（PJS) は大きな有茎性ポリープを切除することが腸重積の予防に非常に有効である．ダブバルーン小腸内視鏡（DBE）でのクロスドクリップ法によるポリープ切除は，ポリープ数の増加，偶発症の減少が見込める．一方で大きなポリープは癌化することがあるため，ポリペクトミー後の検体回収が必要になる．さらにPJSは開腹歴の既往のためDBE挿入困難例で長時間の検査が多い為，安全で確実なDBE処置が求められる．

【方法】

2006年6月より2018年9月までに，DBEを施行したPJS12例，全検査37件を分析し，クロスドクリップ併用群と非併用群に分けて後ろ向きに比較し，当科におけるPJSの小腸ポリープ切除の特徴を遡及的に検討した．

【結果】

男性4例，女性８例．初回検査時の平均年齢は34.7(16-64) 歳，12例中開腹歴があったのは11例で，そのうち10例で癒着高度のため挿入困難であった．DBEによる小腸ポリープ切除施行例が10例（クロスドクリップ併用4例），2例は観察のみであった．全小腸が観察可能であったのは，13例中9例で，全小腸の平均挿入時間（検査時間）は122分（207分）であった．ポリープ切除10例中クロスドクリップ併用群4例の平均ポリープ処置数は17.5個，非併用群6例の平均ポリープ切除数3.5個であった．合併症に関しては，6例で高度の出血が見られたが，いずれもクロスドクリップ非併用群であった．

【結論】

PJSに対する内視鏡的ポリープ切除では，クロスドクリップを併用することで，より多くのポリープ処置が安全に可能であった．

DOI： 10.32264/shocho.2.0_38

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

© 2015 Wolters Kluwer Health, Inc. All rights reserved. Goals: The aim is to elucidate the efficacy and safety of doubleballoon endoscopy (DBE) for small bowel capsule endoscopy (SBCE) retrieval from small bowel stricture and to follow the outcome of the stricture where the SBCE was entrapped. Background: The retention of SBCE is a serious adverse event and most retained capsules are retrieved by surgery. There is still no report analyzing the follow-up of patients with stricture after retrieval of entrapped SBCEs by DBE. Methods: This study was designed a retrospective cohort study. Subjects were 12 consecutive patients with small bowel stricture where retrieval of entrapped SBCE was attempted using DBE. Success rate of the SBCE retrieval by DBE, surgical rate of the small bowel stricture, adverse events of DBE, and outcomes in the follow-up period were evaluated. Results: Diagnoses were Crohn's disease, nonsteroidal antiinflammatory drugs-induced enteropathy, ischemic enteritis, and carcinoma in 8, 2, 1, and 1 patients, respectively. SBCE was successfully retrieved in 11 of the 12 patients (92%). No adverse events were encountered in all endoscopic procedures such as retrieval of SBCEs and dilation of the strictures. Nine of the 12 patients (75%) did not undergo surgical treatment for the stricture where SBCE was entrapped through the follow-up period (mean, 1675 ± 847 d). Conclusions: Retrieval of SBCEs using DBE was safe, had a high success rate, and was useful to evaluate the need for surgery. Seventy-five percent of patients with small bowel stricture where the SBCE was entrapped did not require surgery through approximately 5 years.

DOI： 10.1097/MCG.0000000000000335

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Colorectal cancer is a frequently occurring cancer whose incidence has shown a marked increase in recent years. Additionally, an increase in right side colon in elderly patients has been identified. Therefore, a clinicopathological study was conducted in 49 patients with unresectable advanced colorectal carcinomas to elucidate the association of clinicopathological characteristics and K-ras mutation. Of the 49 patients included in this study, 24 were aged <60 years with a male/female (M/F) ratio of 16/8 and 25 patients were aged ≥60 years with a M/F ratio of 16/9. Of the patients aged ≥65 years, 15 patients were enrolled as controls and the M/F ratio was 9/6. Results revealed that with regard to the subsite of cancer, unresectable advanced colorectal carcinomas developed in the right-sided colon in 13 patients, left-sided colon in 19 patients and rectum in 17 patients. Right-sided colon carcinomas were commonly identified in the elderly patients aged ≥65 years, with a marked tendency in the female patients (P=0.024). Immunostaining was performed for the epidermal growth factor receptor (EGFR) antibody in 40 patients to determine whether the K-ras gene would yield positive results. The mutant K-ras gene was identified in 8 patients (20%) and the frequency was lower compared with that of the normal colorectal carcinomas. Anti-EGFR antibody (cetuximab) is considered to be a molecularly targeted agent for unresectable advanced colorectal carcinomas. The increase in incidence of right-sided colon carcinomas as well as the increase in the number of patients presenting with colorectal carcinomas means this issue should be addressed. Sessile serrated adenoma/polyp (SSA/P) with b-raf mutation and CIMP (CpG island methylator phenotype) abnormality as a precursor lesion of right-sided colon carcinoma is common and since cetuximab refractory wild-type K-ras/mutant b-raf colorectal carcinoma may increase in elderly patients and patients with right-sided colon carcinoma, a simultaneous examination for the K-ras and b-raf gene abnormalities for the treatment of colorectal cancer using anti-EGFR antibody (cetuximab) is crucial. In addition, the multidisciplinary assessments regarding the effect of such treatments is likely to be determined based on cumulative results, such as the duration of patient survival.

DOI： 10.3892/mco.2013.62

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掲載種別：研究論文（学術雑誌）  

The use of antibodies against epidermal growth factor receptor (EGFR) in conjunction with conventional chemotherapy for metastatic colorectal cancer (CRC) in patients with KRAS wild-type tumors has been proven to be efficacious. Recently, KRAS testing prior to anti-EGFR therapy has become mandatory for metastatic CRC patients. Although newly developed pyrosequencing is expected to be one of the high throughput procedures detecting such mutations, the accuracy of the procedure has not been well evaluated. In the present study, we aimed to validate the accuracy, especially the potential for a false-negative result, in detecting KRAS mutations by pyrosequencing using cultured tumor cells. DNA extracted from cultured ìNOZî gallbladder cancer cells (known to contain KRAS mutation G12V) at concentrations of 1%, 5%, 10%, and 25%, as well as 2 DNA samples extracted from a resected CRC specimen (known to contain another KRAS mutation, G12C) at concentrations of 5% and 25%, were prepared. We analyzed KRAS mutational status and nonexistent and/or nonfunctional mutations of these 6 samples using pyrosequencing. The KRAS mutation detection rates in the 4 NOZ samples (1%, 5%, 10%, and 25%) were 0.37%, 2.79%, 5.28%, and 13.85%, respectively. Some artifacts of KRAS mutations unlikely to be present were detected in 1% samples of NOZ at a rate similar to that of the G12V mutation (G12C, 0.29%; G13C, 0.42%). Although the KRAS mutation G12C was detected at rates of 1.26% and 6.49% in samples with 5% and 25% DNA extracted from resected CRC specimen, respectively, no other type of KRAS mutation was detected in such samples. Pyrosequencing could not detect KRAS mutations correctly in the sample containing 1% DNA. This might cause false negatives. A sample mutated DNA concentration of at least 5% was necessary for precise analyses by this procedure.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI PUBLISHING CORPORATION  

Unresectable colorectal carcinomas (CRCs) as considered incurable even if the primary tumors and the metastatic ones can undergo resection are correlated with poor prognosis. We evaluated the association between micropapillary pattern at the invasive front and unresectable CRCs. Thirty-four out of 264 (12.9%) CRC patients with stages III and IV were unresectable cases. The patients with unresectable CRCs had significantly worse survival than those with resectable CRCs (P < 0.001). Micropapillary pattern was evident in 12 (4.5%) out of 264 cases. This pattern was observed in 6 of 34 (17.6%) unresectable CRCs and in 6 of 230 (2.6%) resectable cases (P = 0.002). Unresectable CRCs revealed more frequently deeper invasion (odds ratio (OR), 1.175; 95% confidence interval (CI), 1.113-1.241), lymph node metastasis (OR, 2.356; 95% CI, 1.132-4.905), and presence of micropapillary pattern at the invasive front (OR, 8.000; 95% CI, 2.415-26.504) as compared to resectable cases. By multivariable logistic regression analysis, only micropapillary pattern was shown to be an independent predictor of unresectable CRCs (OR, 9.451; 95% CI, 2.468-36.196; P < 0.001). In conclusion, micropapillary pattern at the invasive front is associated with unresectable CRCs, and detection of it could help identify unresectable CRC cases.

DOI： 10.1155/2013/851623

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

＜文献概要＞クローン病の治療法を決めるには病型や病勢評価が重要であり,小腸検査は欠かせない.カプセル内視鏡は簡便かつ患者の負担が少ない小腸内視鏡検査として本邦で広く使用され,クローン病にも使用されている.カプセル内視鏡は病変部の能動的な詳細観察ができないが,病変が多発し,病変に長さがあるクローン病では病変の検出に関する問題は少ない.とくに病初期・軽度小腸病変の経過観察においてカプセル内視鏡の有用性は高いと考えられている.ただし,腸管に狭窄を合併しやすいクローン病では,カプセルが狭窄部位に滞留する可能性が高く注意が必要であり,クローン病にカプセル内視鏡を使用する場合にはパテンシーカプセルによる消化管通過試験を事前に行う必要がある.

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本大腸肛門病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/link/ui/2019219004

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：日本小腸学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞消化管出血では,顕出血を伴わないときも常に小腸上皮性腫瘍を疑う必要がある.特に小腸癌は臨床症状を契機に精査されるとき,病変の検出は容易であり,速やかに診断し適切な治療へ導く.腹部-骨盤部X線造影CT検査で所見がないとき,カプセル内視鏡による精査は有用である.今日,小腸癌に対する補助化学療法の有用性を検証する動きが加速している.検査方法は進歩しているが,診断契機は臨床症状の出現であることは以前と変わりがない.そのため,診断時には既に進行していることが多く,早期診断が課題である.また,本邦の罹患率や予後などの疫学データの集積も,診断や治療の進歩を検証するために必要であり,今後の課題である.

DOI： 10.11477/mf.1403201389

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

虚血性小腸炎は腸管の血流不全に伴う組織障害をきたす疾患で,特発性と続発性に分類される.虚血性大腸炎と異なりまれな疾患であるが,小腸内視鏡検査の普及により診断契機が増えつつある.一過性型,狭窄型,壊死型に分類され,狭窄型の頻度が高く,治療はこれまで外科手術が中心であったが,近年,内視鏡による拡張術が試みられるようになっている.(著者抄録)

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記述言語：日本語   出版者・発行元：(株)文光堂  

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記述言語：日本語   出版者・発行元：(NPO)日本消化吸収学会  

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記述言語：日本語   出版者・発行元：(NPO)日本消化吸収学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

本邦において,原因不明消化管出血に対してカプセル内視鏡を施行した場合,およそ30%の対象に潰瘍性病変が指摘される.NSAIDsを服用している場合においてはNSAIDs起因性と診断されることが多いが,正確な診断は簡単ではない.さらに,健常者においても10%程度は無症候性の小腸潰瘍性病変を有しており,原因疾患の診断は困難を極めている.近年,腸内細菌叢が小腸潰瘍性病変に深く関与している可能性が指摘されており,今後の解明が望まれている.(著者抄録)

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記述言語：日本語   出版者・発行元：(株)医学書院  

内視鏡技術の進歩に伴い,大腸早期癌のうち粘膜下層深達度が1,000μm以深のT1b(SM2)癌について内視鏡治療の適応拡大が考慮されることとなった.しかし,T1b(SM2)癌には内視鏡切除材料の病理診断では評価できない,癌の直接浸潤先進部とは連続せず,粘膜下層より深い層に脈管侵襲が存在する,いわゆる「非連続脈管侵襲」がある.その一部は肝・肺転移を来し,予後不良である.このような点を踏まえ,大腸癌取扱い規約第8版では癌の脈管侵襲陽性部を壁深達度として取り扱うように改訂された.T1b(SM2)癌に対する内視鏡治療の適応拡大に際しては,非連続脈管侵襲なども考慮した慎重な対応が望まれる.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

大腸の5mm以下の過形成性ポリープに対しては内視鏡での切除はせず,5mm以下の微小腺腫に対しては内視鏡での切除は行うが病理診断は行わないという新しい概念(Resect and Discard strategy)の実践により,病理診断にかかるコストは削減できる可能性がある.しかし,これには内視鏡での的確な診断が前提条件として必要になり,頻度としては決して高くないが微小でも浸潤癌があることを踏まえ,慎重な適用とエビデンスの蓄積が必要である.(著者抄録)

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：SPANDIDOS PUBL LTD  

Web of Science

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

潰瘍性大腸炎(ulcerative colitis;UC)の発癌過程では、感染因子、サイトカイン、活性酸素などが腫瘍関連遺伝子の(エピ)ジェネティックな変化や腫瘍関連マイクロRNAの発現変化を引き起こす。UCの大腸癌発生率は一般人よりも高く、その予後を左右する因子として大腸癌の発生があげられるが、その前癌病変(dysplasia)は炎症を背景にした境界不明瞭な平坦病変が多く、発見は容易でない。また、dysplasiaは組織異型に乏しいため、組織診断一致率が低いという問題点もある。組織診断上重要な点は、再生異型上皮とdysplasia、low-grade dysplasiaとhigh-grade dysplasia、散発性腺腫とdysplasiaとの鑑別であり、各々、経過観察法や治療法が異なる。日常の病理診断において、これらの補助的鑑別診断法としてp53免疫染色が最も有用で汎用されているが、p53陰性のdysplasiaを拾い上げに役立つ他の免疫染色法の開発が期待される。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J05173&link_issn=&doc_id=20140128260002&doc_link_id=%2Fai1coloe%2F2013%2F000602%2F003%2F0092-0097%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1coloe%2F2013%2F000602%2F003%2F0092-0097%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

門脈圧亢進症患者の小腸・大腸には、血管拡張性病変、静脈瘤、浮腫などの病変が知られている。しかし、門脈圧亢進症患者の多くは、同時に深刻な肝障害を伴っており、それらの腸病変が門脈圧と直接相関しているとは限らない。門脈圧と、小腸病変の相関を検討したところ、浮腫と門脈圧の相関は明らかであったが、孤立性の血管拡張性病変(angioectasia)との相関は明らかではなかった。このように門脈圧亢進症性腸症の解明には、門脈圧との相関を調べると同時に、門脈圧亢進をきたす原疾患との関連を顧慮しなければならない。この報告で主要な内視鏡像を紹介するが、この分野は用語の統一も十分ではなく、論文報告もここ数年以内が大半であり、これからの解明の待たれる分野である。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)先端医学社  

炎症性腸疾患(IBD)関連腫瘍の遺伝子異常、マイクロサテライト不安定性、遺伝子メチル化などに関する多くの報告がある。IBD関連大腸癌の癌化過程では、散発性大腸癌の発癌過程に密接に関与するAPC、K-ras、p53遺伝子異常の頻度やタイミングは異なる。p53免疫染色はその遺伝子自体の変異を反映しており、IBD関連大腸発癌過程の早期からp53過剰発現がみられるため、簡便で有用な早期病変検出法といえる。IBDの非腫瘍粘膜においても、高頻度にp16INK4a、p14ARF遺伝子のメチル化がみられることやIBD関連腫瘍非合併例にくらべ、腫瘍合併例における非腫瘍粘膜のエストロゲンレセプターのメチル化の頻度が高いことも示されており、IBD関連大腸発癌過程の早期病変の発見に役立つ可能性を示唆している。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

リンチ症候群の大腸癌の組織学的特徴は,髄様癌や低分化腺癌が多く,粘液癌,印環細胞癌への分化を示し,腫瘍内リンパ球浸潤およびクローン病様のリンパ球反応などであるが,これらの所見は高度のマイクロサテライト不安定性を示す大腸癌の特徴と共通している.そのため,リンチ症候群の確定診断には,DNAミスマッチ修復遺伝子の生殖細胞での遺伝子変異を証明する必要があるが,これらの組織所見は本症候群の拾い上げに有用である.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

大腸癌は遺伝性の有無により遺伝性大腸癌と散発性大腸癌に分けられる。遺伝性大腸癌とは、体細胞系列の遺伝子異常が原因で発生するが、FAP、MAP、リンチ症候群がある。それぞれに関して、原因遺伝子や臨床像に関して概説した。散発性大腸癌の発生については以前から、主に1.adenoma-carcinoma sequence説と2.de novo carcinoma説が議論されてきたが、その他にも3.cancerization by progression、4.serrated neoplasia pathway、5.dysplasia carcinoma sequenceなども提唱されている。それぞれの説について、歴史的な流れと現在までにわかっている分子病理学的な事項に関して簡単に概説した。発育進展については、特異な形態としてLSTに関して、その他SM浸潤とEMTについても概説した。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J05173&link_issn=&doc_id=20121225270002&doc_link_id=%2Fai1coloe%2F2012%2F000504%2F003%2F0296-0301%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1coloe%2F2012%2F000504%2F003%2F0296-0301%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)東京医学社  

症例は50歳代男性。10年前に小腸型Crohn病と診断され、外来で継続治療中であったが、回腸狭窄による閉塞性イレウスを発症し、イレウス解除目的に回腸部分切除が施行された。組織学的に狭窄部に進行癌を認め、その周囲には比較的広い範囲にdysplasiaや粘膜内癌を伴っていた。炎症性腸疾患の患者数は近年増加傾向にあり、それに伴いcolitic cancerの患者数も増加していくことが予想されている。現在のところ、本邦ではCrohn病の癌化症例の報告は少数であるが、Crohn病患者数自体は増加傾向にあり、今後増加が予想される癌化例への対応が必要である。(著者抄録)

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)東京医学社  

潰瘍性大腸炎(ulcerative colitis:UC)の長期罹患に伴い、潰瘍性大腸炎関連大腸癌(UC-associated cancer)の発症が高まることが知られている。UCを基礎とした大腸癌発生率は罹病期間との関連が認められ、発症後10年で2%、20年で8%、30年で18%と報告され、現在サーベイランス大腸内視鏡検査による定期的な経過観察が行われている。罹病期間14年のUCに発症したUC-associated cancerの1例を経験したので報告した。症例は34歳女性。20歳時に発症した再燃寛解型全大腸炎型UCであった。サーベイランス大腸内視鏡検査で進行直腸癌を認め、生検組織では印環細胞癌を認めた。手術検体では多彩な病理所見を認め、その病理組織学的所見について検討した。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)東京医学社  

大腸の慢性的な炎症を背景として発生する癌(carcinoma associated with inflammatory bowel disease:colitic cancer)は、散発性大腸癌とは発生経路が異なる。分子生物学的特徴も異なる点が多く、colitic cancer症例では、非腫瘍性粘膜においてもすでに遺伝子変化が起こっている。したがって、潰瘍性大腸炎をはじめとする炎症性腸疾患の長期経過例では、腫瘍発生を早期に発見するためにサーベイランスが重要である。しかし、colitic cancerの初期像は、内視鏡的にも組織学的にも炎症性変化との鑑別がしばしば困難であり、診断に苦慮する。この鑑別に分子生物学的特徴を考慮した診断が補助的診断として有用である。また、これらの手法はサーベイランスにおける腫瘍発生の高危険群の拾い上げに有用であるとの報告もみられ、今後の発展が期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

症例は61歳女性。4ヵ月前に健診で胸部単純X線上右上肺野に腫瘤影を指摘され、精査で類上皮血管内皮腫が疑われた。連続する右腕頭静脈壁を合併切除した。肉眼的に乳白色調充実性の腫瘍で、周囲との境界は不鮮明であった。組織では、紡錘形から多形性の上皮様腫瘍細胞の充実性増殖部の他、線維性間質や粘液腫様背景の中でコード状配列を示す領域も見られ、一部腫瘍細胞に空胞形成が認められた。本腫瘍の縦隔血管からの発生は稀であり、報告する。(著者抄録)

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記述言語：日本語  

CiNii Books

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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