Search

Objectives: Comprehensive assessments of the long‐term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long‐term prognosis after ESD for EGC among patients aged ≥75 years. Methods: We conducted retrospective studies of two cohorts: a single‐center cohort (2006–2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012–2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. Results: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low‐ and high‐score groups, respectively. In comparisons based on Kaplan–Meier curves, the 5‐year survival rate was 91.5% in the low‐score group and 57.8% in the high‐score group (log‐rank test; P < 0.001). Conclusion: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long‐term prognosis of elderly patients aged ≥75 years after ESD for EGC. [ABSTRACT FROM AUTHOR]

Background and Aim: In colorectal endoscopic submucosal dissection (ESD), post‐ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure. Methods: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses. Results: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264–8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317–28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053–6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090–13.61, P = 0.036) were independent risk factors for PECS. Conclusions: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers. [ABSTRACT FROM AUTHOR]

Background and Aim: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology. Methods: Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE‐L*a*b* color space were calculated in the original and enhanced images. Results: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5‐point (−2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36). Conclusion: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists. [ABSTRACT FROM AUTHOR]

Background and Aim: Needle‐based confocal laser endomicroscopy (nCLE) allows for real‐time optical biopsies during endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA). Little is known about nCLE imaging of gastrointestinal subepithelial lesions (GI‐SEL); therefore, we determined its feasibility. Methods: We carried out EUS, nCLE, and finally FNA in 25 patients with GI‐SEL between November 2015 and December 2018. We retrospectively compared nCLE findings with pathological findings of EUS‐FNA or surgical specimens. For concordance analysis, two endoscopists independently validated representative nCLE images 5 months or more after examinations. Results: Adequate sample acquisition rate of EUS‐FNA was 67% per needle pass and 96% per patient. EUS‐FNA was diagnostic in 80% (20/25), suspicious in 4% (1/25), and nondiagnostic in 16% (4/25). nCLE image acquisition rate was 100% and its concordance rate with final pathology was 88% (22/25), which was not significantly different from diagnostic and suspicious EUS‐FNA. nCLE could differentiate GI stromal tumors (GISTs) from leiomyoma, in that GISTs were characterized by contrast‐enhanced densely populated spindle cell tumors with unenhanced rod‐shaped nuclei in 93% of 14 patients, whereas leiomyomas were characterized by narrower spindle cell tumors with fewer and smaller unenhanced nuclei in 100% of three patients. In rectal metastasis from lung adenocarcinoma, some pleomorphic dark nests were observed. At concordance analysis between the two endoscopists' validation results, κ value was 0.560 (P < 0.001), indicating moderate agreement. There were no adverse events associated with nCLE and EUS‐FNA. Conclusion: Needle‐based confocal laser endomicroscopy can be safe and useful for on‐site detection of abnormalities of GI‐SEL (UMIN 000013857). [ABSTRACT FROM AUTHOR]

Geochronological and geochemical studies reveal the possible origin of the restricted body of mylonite rocks occurring at the eastern edge of Kyushu Island, Japan, just in contact with the Sashu Fault, a part of the Paleo‐Median Tectonic Line (Paleo‐MTL). The LA‐ICP‐MS zircon U–Pb dating of the quartz diorite mylonite in this mylonitic body indicates a crystallization age of 114.0 ±1.7 Ma. Moreover, the two tonalite samples appear as thin layers within the Permian fine‐grained mafic mylonite; a part of the same body yields the age of 113.7 ±2.3 Ma and 116.9 ±1.3 Ma, with extremely low Th/U ratio. These quartz diorite mylonite and tonalite are consistent with the late Early Cretaceous magmatism and coeval metamorphism similar to those in the Higo Plutono‐metamorphic Complex in western Kyushu, Japan. This newly characterized complex occurs just south of the Cretaceous Sambagawa metamorphic rocks. The newly characterized mylonitic rocks are lying structurally above the Sambagawa Metamorphic Complex and are distributed along the Paleo‐MTL. The extension of the Higo Plutonometamorphic Complex, as well as the structural relationship between this complex and the Sambagawa Metamorphic Complex, is still controversial but holds a key to reconstruct the tectonic evolution of Southwest Japan during the Late Mesozoic to Early Cenozoic period. Hence, this article provides new insight into the reconstruction of the evolution history of East Asia as an active convergent margin. [ABSTRACT FROM AUTHOR]

Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance‐related miRNA in colorectal cancer. We established 4 types of 5‐fluorouracil (5‐FU)‐resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance‐related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5‐FU resistance by miRNA arrays. We then examined the relationship between miR‐31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR‐31 showed significant 5‐FU resistance in the parental DLD‐1 cells, while anti–miR‐31 caused significant growth inhibition in DLD/F cells; that is, 5‐FU‐resistant colon cancer cell line DLD‐1 under exposure to 5‐FU. When we exposed high doses of 5‐FU to parent or 5‐FU‐resistant cells, the expression levels of miR‐31 were raised higher than those of controls. Notably, the expression levels of miR‐31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia‐inducible factor 1 were downregulated by transfection of mimic miR‐31 into DLD‐1 cells. This study provides evidence supporting the association of miR‐31 with 5‐FU drug resistance and clinical stages of colorectal tumors. [ABSTRACT FROM AUTHOR]

Molecular irreversibleness with Helicobacter pylori (H. pylori) infection might have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp‐), gastric body without cancer after H. pylori eradication (cancer‐free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was also used to characterize the methylation status of greater than 850,000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer‐free body + EGC body), methylation levels were significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome‐wide methylation analysis demonstrated strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication. What's new? Molecular irreversibleness caused by Helicobacter pylori infection might play a role in gastric tumorigenesis sometimes observed after successful eradication, but the mechanisms remain unclear. This study documents DNA methylation accumulation in the mucosa adjacent to gastric cancer after H. pylori eradication, supporting the concept that DNA methylation is associated with molecular irreversibleness and gastric carcinogenesis and could help find biomarkers. The discovery of frequently methylated genes that code zinc finger proteins also emphasizes the importance of pathway‐specific molecular changes, and suggests that targeted epigenetic therapies could be useful in the treatment and chemoprevention of gastric cancer after H. pylori eradication. [ABSTRACT FROM AUTHOR]

Atypical Stevens‐Johnson syndrome (SJS) is a variant of SJS with complete absence of or only few cutaneous manifestations. It usually affects children with Mycoplasma‐induced respiratory infection. It was unique because our case was induced by drug and occurred in an adult. [ABSTRACT FROM AUTHOR]

Abstract: Basic dykes crosscutting the crystalline basement in Valsugana (Southern Alps, Italy) have been investigated for the first time in the framework of the known tectonomagmatic cycles. Petrographic observations and bulk rock analyses suggest a serial affinity variable between calc‐alkaline (subordinate) and shoshonitic (prevalent), which are generally ascribed to a convergent plate setting. This is confirmed by Sr‐Nd‐Pb isotopic analyses that display extreme values that are often observed in postcollisional settings. A bulk rock Rb‐Sr pseudoisochron suggests an age of the magmatism around 260 Ma, whereas K‐Ar datings yield ages between 227 and 251 Ma, suggesting that these dykes plausibly represent a transition between the Permian and the Triassic volcanic episodes that are known in neighboring sectors of the Southern Alps. Considering that Permo‐Triassic active subduction beneath the South Alpine is scarcely constrained, we ascribe the metasomatism of the related mantle sources to the Variscan cycle, proposing that magma genesis was delayed with respect to the time of the active subduction(s). According to recent reconstructions, parts of southeastern Europe, including the South Alpine domain, were formed by the breakup of the northern Gondwana margin from the Late Cambrian, in connection with important transtensional movements, leaving rifted continental basins or narrow oceanic seaways. In our view, the subduction processes that induced metasomatism in mantle sources of the South Alpine region occurred in the connection with the subsequent (Carboniferous?) consumption of lithosphere of these basins, a framework that is compatible with pervasive recycling of continental crust components within the mantle wedge. Then, calc‐alkaline/shoshonite magmatism was triggered in the Early Triassic by postcollisional extensional tectonics that followed the Variscan orogenic cycle. [ABSTRACT FROM AUTHOR]

Background and Aim: Early‐stage gastric cancer (EGC) found after Helicobacter pylori (Hp) eradication often displays non‐tumorous regenerative epithelium and/or maturated tumorous epithelium overlying the cancerous tissue, which may confuse endoscopic and histological diagnosis. Probe‐based confocal laser endomicroscopy (pCLE) enables in vivo real‐time optical biopsy. We compared the diagnostic yields for these EGC cases using conventional white light endoscopy (WL), magnifying endoscopy with narrow‐band imaging (ME‐NBI), pCLE, and endoscopic biopsy; we also compared the accuracy of the horizontal extent diagnosis between ME‐NBI and pCLE. Methods: This study enrolled 30 patients with 36 EGC lesions after successful Hp eradication. Diagnostic yields of WL, ME‐NBI, pCLE, and endoscopic biopsy were prospectively compared. Four points of cancerous margins (oral, anal, anterior, and posterior sites) were also prospectively evaluated with M‐NBI and pCLE to determine the horizontal extent of the EGC. Results: Diagnostic yield was significantly higher with pCLE than with WL and endoscopic biopsy (97 vs 72%, 97 vs 72%, P = 0.0159, 0.0077, respectively), whereas it did not differ from ME‐NBI (88.9%, P = 0.371). Height of non‐tumorous regenerative epithelium or maturated atypical glands was 104.7 ± 34.2 μm in the pCLE‐positive cases, whereas it was 188.3 ± 27.1 μm in a pCLE‐negative case (P = 0.0004). Diagnostic accuracy of the horizontal margin of EGC was significantly higher with pCLE than with ME‐NBI (92 vs 70%, P = 0.0159). Conclusion: pCLE may be helpful for the diagnosis of ambiguous ECG found after Hp eradication because it enables real‐time scanning throughout the lesion and detection of subsurface microstructure. [ABSTRACT FROM AUTHOR]

Residual DNA methylation in the gastric mucosa after Helicobacter pylori ( H. pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non-neoplastic gastric mucosa especially after H. pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6 months of post-eradication period were examined. The magnifying narrow-band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Methylation status of five candidate genes ( MYOD1, SLC16A12, IGF2, RORA, and PRDM5) were examined by bisulfite pyrosequencing. The atrophic type, informative endoscopic features of intestinal metaplasia, demonstrated higher methylation levels in all five genes compared to the restored type (all P < 0.0001). In the restored type, methylation levels were significantly lower among the samples with longer post-eradication period (for all genes, P < 0.0001), which was not observed in atrophic type (for all genes, P > 0.1). Multivariate analysis demonstrated that atrophic type or presence of intestinal held an independent factor for hyper methylation (odds ratio: 24.69, 95% confidence interval: 6.95-87.76, P < 0.0001). The atrophic type by the magnifying NBI and presence of intestinal metaplasia are the morphologic characteristics of residual DNA methylation of after H. pylori eradication, regardless of the post-eradication period and it might be considered as the epigenetic irreversible point with H. pylori eradication. [ABSTRACT FROM AUTHOR]

Chromoendoscopy, narrow-band imaging ( NBI), and confocal laser endomicroscopy ( CLE) have been introduced in ulcerative colitis ( UC)-associated neoplasia surveillance. We aimed to determine the ability of CLE to differentiate among UC-associated neoplasia (differentiated type or undifferentiated type), sporadic adenoma, and circumscribed regenerative lesions. Of 665 patients with UC, we carried out probe-based CLE ( pCLE) on 12 patients with suspected UC-associated neoplasia in addition to magnifying chromoendoscopy with crystal violet and NBI. We compared pCLE findings with pathological diagnoses. pCLE could differentiate UC-associated differentiated cancer from other pathologies such as solitary adenoma and non-neoplastic circumscribed regenerative lesions on the basis of back-to-back orientation of crypts ( P = 0.048), and UC-associated undifferentiated cancer from other pathologies on the basis of dark trabecular architecture ( P = 0.015). Sensitivity, specificity, and accuracy of combination of back-to-back orientation of crypts and dark trabecular architecture for carcinoma or dysplasia were 100%, 83%, and 92%, respectively. In vivo microscopic observation with pCLE was helpful to evaluate the suspected UC-associated neoplasia. [ABSTRACT FROM AUTHOR]

Objective Taste is an important element in food preferences. Gastroesophageal reflux disease ( GERD) is related to lifestyles including eating habits. We aimed to investigate the relationship between responses to specific tastes and GERD. Methods Altogether 280 patients including 170 men with a mean age of 58.6 years were included in the study to determine the relationship between their liking for specific tastes and GERD using a new self-administered questionnaire (responses to various tastes and participants' sensitivity to taste and hot food and on the frequency of stomatitis). Another self-administrated questionnaire was administrated for a diagnosis of GERD (the frequency scale for the symptoms of GERD cut-off score of 10). Furthermore, 142 of 280 patients who had received esophagogastroduodenoscopy (EGD) were investigated on the association between endoscopic esophagitis and their favorite tastes. Results In the association analyses between responses to specific tastes and GERD, the group liking salty food and the group with a high frequency of stomatitis had a significantly higher incidence of GERD (salty food: odds ratio [OR] 2.059, 95% confidence interval [CI] 1.215-3.488, P = 0.0073; stomatitis: OR 2.861, 95% CI 1.558-5.253, P = 0.0007, respectively). In association analyses with endoscopic esophagitis, the groups liking salty and sour food had a significantly higher incidence rate of endoscopic esophagitis (salty: OR 2.718, 95% CI 1.330-5.555, P = 0.0061; sour: OR 3.267, 95% CI 1.491-7.160, P = 0.0031, respectively). Conclusions Sensitivity and response to specific food taste were associated with GERD. The results of a preference to hot or salty food and endoscopic esophagitis suggest that physical stimuli are important for esophageal injuries. [ABSTRACT FROM AUTHOR]

Small-bowel bleeding comprises a majority of obscure gastrointestinal bleeding, but is caused by various kinds of diseases. For its diagnosis, history-taking and physical examination is requisite, leading to a suspicion of what diseases are involved. Next, cross-sectional imaging such as computed tomography should be done, followed by the latest enteroscopy, videocapsule endoscopy and deep enteroscopy according to the severity of hemorrhage and patient conditions. After comprehensive diagnosis, medical, enteroscopic, or surgical treatment should be selected. [ABSTRACT FROM AUTHOR]

Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa. XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR = 0.30, 95%CI = 0.13-0.71, p = .0055) and CIHM high (OR = 0.42, 95%CI = 0.19-0.97, p = .04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes ( p = .02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50 years and older generations (OR = 1.63, 95%CI = 1.01-2.62, p = .045). XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori-induced gastritis in Japanese population. The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non-cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non-ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases. The rs2910164 CC genotype held a significantly higher risk of GC when compared to non-cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02-1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non-cancer and non-ulcer subjects (OR = 1.39, 95%CI = 1.00-1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09-2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non-cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0-1 vs 2∼, adjusted OR = 1.62, 95%CI = 1.05-2.49, p =.03). The rs2910164 (G>C) SNP in the miR-146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR-196a2 is associated with the degree of H. pylori-induced mononuclear cell infiltration. [ABSTRACT FROM AUTHOR]

There have been reports showing a protective role of nonsteroidal anti-inflammatory drugs (NSAIDs) against gastrointestinal cancers. CpG island hyper methylation (CIHM) of tumor suppressor genes is a major event in carcinogenesis. We investigated the CIHM status of non-cancerous gastric mucosa in chronic NSAID users and non-users and assessed the effect of NSAIDs on CIHM. Gastric mucosa samples were obtained from 51 chronic NSAID users and 180 non-users. CIHM of p14(ARF), p16(INK4a), death-associated protein kinase (DAP-kinase), and E-cadherin (CDH1) genes were determined by methylation-specific PCR. CIHM high was defined as two or more CpG islands methylated. CIHM of p14, p16, CDH1, and CIHM high were lower in chronic NSAID users than in non-users (p14: non-users vs users = 32.2% vs 9.8%, P = 0.003; p16: non-users vs users = 35.0% vs 15.7%, P = 0.02; CDH1: non-users vs users = 36.1% vs 9.8%, P = 0.0009; CIHM high: non-users vs users = 44.4% vs 17.6%, P = 0.0009). NSAID use was also associated with decreased number of CIHM byanova ( R = –0.32, P < 0.0001). Multivariate logistic regression analysis with adjustment for sex, age, Helicobacter pylori infection, and NSAID use revealed that NSAID use was inversely correlated with all four CIHM and CIHM high as an independent factor (p14: odds ratio [OR] = 0.17, 95% confidence interval [CI] = 0.06–0.48; p16: OR = 0.32, 95% CI = 0.14–0.75; DAP-kinase: OR = 0.45, 95% CI = 0.22–0.92; CDH1: OR = 0.18, 95% CI = 0.06–0.48; CIHM high: OR = 0.21, 95% CI = 0.09–0.49). No association was found between CIHM status and the duration or dose of NSAIDs. Chronic NSAID use suppresses CIHM in human gastric mucosa. NSAIDs may have a suppressive role against methylation-related gastric carcinogenesis. ( Cancer Sci 2009; 100: 1192–1197) [ABSTRACT FROM AUTHOR]

Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2–196 to –174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. ( Cancer Sci 2007; 98: 1790–1794) [ABSTRACT FROM AUTHOR]

Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 ( MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23–0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23–0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17–0.77), advanced cancer (OR = 0.31; 95% CI = 0.13–0.73), venous invasion (OR = 0.30; 95% CI = 0.10–0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13–0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population. [ABSTRACT FROM AUTHOR]

Background and Aim: Trypsin acting at protease-activated receptor 2 (PAR2) contributes to a progression of malignant tumors. An abnormal DNA methylation has been recognized as an important molecular mechanism for the genesis of various types of cancers. We attempted to clarify the relationship between the promoter methylation of PAR2 and gastric cancer. Method: We estimated the methylation of the PAR2 promoter in both antral non-cancerous mucosa and cancer lesions in 94 patients with gastric cancer. We employed a methylation-specific PCR method. Results: Regarding the methylation ratio (MR) of antral-non-cancerous mucosa, no significant difference was despite among gender, age and Helicobacter pylori infection status, whereas MR increased rising inflammation scores. The MR of cancer lesions was significantly lower than that of antral non-cancerous mucosa. This finding was not dependent on tumor staging, but also histological classification. In venous invasion, lymph node metastasis, or peritoneal dissemination negative cases, this significant lower MR was also seen. Conclusion: The promoter methylation of PAR2 seems to be increased with a progression of chronic inflammation and has an inhibitory effect on carcinogenesis of the stomach. [ABSTRACT FROM AUTHOR]

Background and Aim: Ulcerative colitis (UC) is a multifactorial disease resulting from a complex interaction of genetic and environmental factors. Identifying genetic variants that alter the innate immune response is highly relevant to understanding the pathogenesis of UC. The aim of this study was to investigate the association between CD14 and Toll-like receptor-2 ( TLR2) genetic polymorphisms and chronic UC in Japanese patients. Methods: The study population consisted of 102 chronic UC patients and 146 healthy control subjects. Polymorphisms in the promoter at C-260T of CD14 gene were investigated by PCR restriction fragment length polymorphism, and −196 to −174 del of TLR2 was investigated by allele-specific PCR. Results: The frequencies of CD14 TT and T carrier were significantly higher in UC patients than in controls (TT: OR = 3.98, 95% CI 1.82–8.71, P = 0.0005; T carrier: OR = 2.98, 95% CI 1.47–6.01, P = 0.002). In addition, TT and T carrier were more closely associated with distal colitis phenotype (TT: OR = 7.78, 95% CI 2.14–28.28, P = 0.0007; T carrier: OR = 6.30, 95% CI 2.71–14.58, P = 0.005), onset after 20 years of age (TT: OR = 5.28, 95% CI 2.18–12.79; T carrier: OR = 3.79, 95% CI 1.67–8.59), chronic continuous type (TT: OR = 4.26, 95% CI 1.56–11.64; T carrier: OR = 3.09, 95% CI 1.33–7.82), and fewer than two hospitalizations (TT: OR = 4.44, 95% CI 1.81–10.89; T carrier: OR = 3.26, 95% CI 1.43–7.27). There was no significant difference in TLR2 –196 to −174 del/del and del/ins carrier frequencies between UC patients and healthy controls. However, these frequencies were significantly higher in steroid-dependant patients than in controls ( del/ del: OR = 6.08, 95% CI 1.41–26.21; del carrier: OR = 3.00, 95% CI 1.13–7.98). Conclusion: The results suggest that existence of a mutation in the CD14 gene is associated with an increased susceptibility to developing UC, especially chronic continuous distal colitis phenotypes that develop after 20 years of age. Furthermore, polymorphism of TLR2 may be related to an increased risk of intensive types such as steroid-dependent patients. [ABSTRACT FROM AUTHOR]

Volcanic rocks from the Upper Keewatin assemblage ( ca 2720 Ma) were geochemically classified into five groups; komatiites, tholeiitic rocks having near-flat primitive mantle-normalized abundance patterns, Nb-enriched basalts and andesites (NEBA) plus normal calc-alkaline (NCA) rocks, adakites and shoshonites. The adakites having [La/Yb]N >30 and <30 were probably derived from felsic magmas formed by partial melting of a subducted slab at relatively greater and smaller depths, respectively. Ascending adakite magmas, by interaction with the overlying mantle wedge, decreased in Al2O3 / Y ratio and selectively lost high-field strength elements, thereby forming mantle sources for both NEBA + NCA and shoshonite magmas. Under the influence of a mantle plume, the source of komatiites, the NEBA + NCA magmas were generated from that part of the mantle wedge metasomatized by adakite magmas having [La / Yb]N <30, and tholeiitic magmas from unmetasomatized part of the same mantle wedge. Magmas of both adakites having [La / Yb]N >30 and shoshonites were generated in a normal Archean Arc system setting. [ABSTRACT FROM AUTHOR]

1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol−0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol–HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions. [ABSTRACT FROM AUTHOR]