Diagnosis of ulcerative colitis and Crohn's disease using transabdominal ultrasonography.

The following are some common features of ulcerative colitis (UC) and Crohn's disease (CD) on transabdominal ultrasonography (TUS). UC, which consists primarily of mucosal inflammation, is seen on TUS as wall thickening with preserved layer structure continuing from the rectum in the active phase of UC. Inflammation confined to the mucosa is seen as thickening of the mucosal/submucosal layers. When the inflammation becomes severe, the echogenicity of the submucosal layer decreases and the layer structure becomes indistinct. CD, which consists primarily of discontinuous transmural inflammation, shows more pronounced hypoechoic wall thickening than UC at the transmural inflammation. On TUS, the layer structure becomes indistinct and gradually disappears due to the depth of the myriad inflammation during the active phase of CD. It is important to evaluate the changes in wall thickening and layer structure when diagnosing UC and CD with TUS. In addition, diagnostic techniques such as color Doppler and contrast-enhanced ultrasonography, which can be used to assess blood flow, and elastography, which can be used to evaluate stiffness, are also used. Thus, TUS is a noninvasive and convenient modality that shows promise as a useful examination for diagnosis of UC and CD.

Injury to the muscle layer, increasing the risk of post-colorectal endoscopic submucosal dissection electrocoagulation syndrome.

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.

Endoscopic imaging in inflammatory bowel disease.

In inflammatory bowel disease, including Crohn's disease and ulcerative colitis, an excessive immune response due primarily to T-cell lymphocytes causes inflammation in the gastrointestinal tract. Lesions in Crohn's disease can occur anywhere in the gastrointestinal tract, i.e., from the oral cavity to the anus. Endoscopically, aphthoid lesions/ulcers believed to be initial lesions progress to discrete ulcers, which coalesce to form a longitudinal array and progress to longitudinal ulcers with a cobblestone appearance, which is a typical endoscopic finding. Before long, complications such as strictures, fistulas, and abscesses form. Lesions in ulcerative colitis generally extend continuously from the rectum and diffusely from a portion of the colon to the entire colon. Endoscopically, lack of vascular pattern, fine granular mucosa, erythema, aphthae, and small yellowish spots are seen in mild cases; coarse mucosa, erosions, small ulcers, bleeding (contact bleeding), and adhesion of mucous, bloody, and purulent discharge in moderate cases; and widespread ulcers and marked spontaneous bleeding in severe cases.

Lower effectiveness of intravenous steroid treatment for moderate-to-severe ulcerative colitis in hospitalised patients with older onset: a multicentre cohort study.

BACKGROUND: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking. AIMS: To evaluate the association between onset age and effectiveness of intravenous steroids in UC. METHODS: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis. RESULTS: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively). CONCLUSIONS: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC.

Safety of Polyethylene Glycol Solution plus Ascorbic Acid for Bowel Preparation for Colonoscopy in Patients with Chronic Kidney Disease.

INTRODUCTION: Polyethylene glycol-electrolyte lavage solution plus ascorbic acid (PEG-ELS-Asc) has been recommended for colonoscopy, but little is known about the safety of PEG-ELS-Asc in patients with chronic kidney disease (CKD). The aim of this study was to determine its safety and efficacy in CKD patients. METHODS: Blood and urine samples prospectively collected before and after same-day bowel preparation for colonoscopy with the conventional volume of PEG-ELS-Asc, vital signs before and after colonoscopy, and adverse events within 30 days postcolonoscopy were analyzed in consenting patients with CKD. The cleansing level was evaluated with the Boston bowel preparation score (BBPS) from colonoscopic findings. RESULTS: Of 57 patients enrolled, 1 was excluded for refusal. Serum bicarbonate significantly dropped, and blood hemoglobin, serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, and uric acid significantly rose after bowel preparation, although these changes were not clinically important. Only in nondialysis patients did the platelet count and potassium significantly rise, although these changes were not clinically important either. Renal function, such as the urea, creatinine, and estimated glomerular filtration rate, was not significantly altered. An adequate bowel cleansing score, BBPS ≥ 6, was achieved in 94% of patients. The blood pressure and heart rate were not significantly different between before and after colonoscopy in either nondialysis (n = 32) or dialysis (n = 19) patients. There were no adverse events associated with bowel preparation and colonoscopy within 30 days postcolonoscopy. CONCLUSIONS: The conventional volume of same-day bowel preparation with PEG-ELS-Asc may be safe and effective in CKD patients.

Clinical response and changes in the fecal microbiota and metabolite levels after fecal microbiota transplantation in patients with inflammatory bowel disease and recurrent Clostridioides difficile infection.

OBJECTIVES: We determined the efficacy of fecal microbiota transplantation (FMT) and subsequent changes in fecal microbiota and short-chain fatty acid (SCFA) levels in patients with ulcerative colitis (UC), Crohn's disease (CD), and recurrent Clostridioides difficile infection (rCDI). METHODS: A filtered solution of Japanese donor feces was endoscopically administered. The efficacy of FMT was evaluated after 8 weeks using the Mayo score, Crohn's Disease Activity Index (CDAI), and the absence of diarrhea with stool toxin negativity in patients with active UC, CD, and rCDI, respectively. For fecal microbiota analysis, the 16S ribosomal RNA gene was sequenced, and fecal SCFA levels were measured. RESULTS: Clinical response was achieved in 5/20 (25%), 3/4 (75%), and 4/4 (100%) patients with UC, CD, and rCDI, respectively. Clinical remission was achieved in 4/20 (20%) and 1/4 (25%) patients with UC and CD, respectively. Linear discriminant analysis illustrated that UC responders had lower counts of Clostridium cluster XIVa before FMT and higher counts after FMT. Higher Fusicatenibacter saccharivorans counts in donors were significantly correlated with 8-week clinical remission. Patients with CD exhibited lower Blautia, Dorea, and Eubacterium counts before FMT and higher Collinsella, Dorea, and Eubacterium counts after FMT, accompanied by functional profiles predictive of SCFA fermentation and elevated fecal butyrate concentrations. Patients with rCDI displayed significantly lower abundances of Clostridium clusters IV and XIVa before FMT and higher abundances after FMT accompanied by elevated fecal propionate concentrations. CONCLUSIONS: FMT exhibited various efficacy against UC, CD, and rCDI by altering the gut microbiota and SCFA production.

Molecular subtyping of gastric cancer combining genetic and epigenetic anomalies provides distinct clinicopathological features and prognostic impacts.

Both genetic and epigenetic abnormalities play important roles in gastric cancer (GC) development. We investigated whether the molecular subtypes of gastric cancer by combining genetic and epigenetic anomalies define its clinicopathological features and prognosis. The CpG island methylator phenotype (CIMP), MLH1 methylation, TP53, and KRAS mutation statuses were characterized in 214 GCs in relation to their clinicopathological features and prognosis. The molecular subtypes based on CIMP and TP53 hot spot mutation status (R175, G245, R248, R273, and R282) best predicted prognosis of GC. These subtypes contained 120 CIMP-positive (CIMP+) TP53 hot spot mutation-negative (TP53 hot spot-) cases, 81 CIMP-negative (CIMP-) TP53 hot spot- cases, 8 CIMP+TP53 hot spot mutation-positive (TP53 hot spot+) cases, and 5 CIMP- TP53 hot spot+ cases. The CIMP-TP53 hot spot+ group presented the worst overall survival (OS) and progression-free survival (PFS), followed by the CIMP+TP53 hot spot+, CIMP-TP53 hot spot- and CIMP+TP53 hot spot- groups (both P < 0.0001). These subtypes also correlated well with several aggressive clinicopathological features in that order. The molecular subtypes were independent factors for predicting overall survival (hazard ratio = 1.66, 95% CI = 1.07-2.57, P = 0.006). The molecular subtypes combining the CIMP and TP53 hot spot mutation status provide distinct clinicopathological features and prognostic impacts in GC.

Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients.

DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.

Potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis.

BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of >450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/neg) samples (P<0.01). Genes hypermethylated in FB-high samples included well-known type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.

Telomere Length in Leukocyte DNA in Gastric Cancer Patients and its Association with Clinicopathological Features and Prognosis.

BACKGROUND/AIM: Telomere shortening in leukocytes has been thought to be associated with reduced immune response capacity and increased chromosome instability. Several studies indicate that telomere length in the peripheral blood leukocyte DNA can predict clinical outcome of several cancers. We evaluated the potential association between telomere shortening in the leukocyte DNA and clinicopathological features and prognosis of gastric cancer (GC) in Japanese patients. MATERIALS AND METHODS: Telomere length in leukocyte DNA was measured using quantitative real-time polymerase chain reaction (PCR) in 207 GC patients. The association between telomere length and clinicopathological features and prognosis was evaluated. RESULTS: These short-telomere group was significantly associated with advanced stage (p=0.015), worse overall survival (OS) and progression-free survival (PFS) (p=0.046 and 0.026, respectively). The same group was also weakly associated with overall and peritoneal recurrences (p=0.052 and 0.059, respectively). CONCLUSION: Telomere shortening in leukocyte DNA is associated with advanced stage and poor prognosis of GC, which may reflect their reduced immune response capacity or increased chromosome instability.

Relationship between expression of onco-related miRNAs and the endoscopic appearance of colorectal tumors.

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We examined the expression of onco-related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52 sporadic flat elevated adenomas or early cancers to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. The expression levels of miR-143, -145, and -34a were significantly reduced in most of the exophytic tumors compared with those in the flat elevated ones. In type 2 cancers, the miRNA expression profile was very similar to that of the exophytic tumors. The expression levels of miR-7 and -21 were significantly up-regulated in some flat elevated adenomas compared with those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down-regulated cases of the adenoma-carcinoma sequence and in some of the de novo types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed to the triggering mechanism leading to the carcinogenetic process. These findings indicated that the expression of onco-related miRNA was associated with the morphological appearance of colorectal tumors.

Examination of serum pepsinogen in functional dyspepsia.

BACKGROUND/AIMS: Although serum pepsinogen (PG) is considered as a marker of gastric atrophy, it also reflects gastric acid secretion, which closely influences dyspeptic symptoms. We investigated serum PG levels and PGI/PGII ratios in dyspeptic patients, in relation to various different subtypes of symptoms including Rome III classifications. METHODOLOGY: Serum PGs were measured in 75 subjects with dyspeptic symptoms and 42 asymptomatic healthy subjects. RESULTS: PG II level was significantly higher (p=0.0001) and PG I/II ratio was significantly lower (p<0.0001) in subjects with H. pylori infection than those without, while no associations were found between PG levels and usage of H2 receptor antagonists or proton-pump inhibitors. In all subjects with pain in stomach, abdominal bloating and PDS-like symptoms according to Rome III criteria, presented significantly higher levels of PGI, compared to subjects without symptoms (p=0.043, 0.015 and 0.037, respectively). In addition, burning sensation and abdominal pain presented significantly higher PGI/II ratios (p=0.0005 and 0.003, respectively), and higher PGI/II ratio was also positively correlated with a number of symptoms (p=0.04). When subjects were divided according to H. pylori infection status, higher PGI/II ratio was significantly associated with abdominal pain in H. pylori negative subjects (p=0.03), while higher PGI level was significantly associated with functional esophageal disorders (FEG) according to Rome III criteria, and higher number of dyspeptic symptoms in H. pylori positive subjects (p=0.016). CONCLUSIONS: Our data suggest that subjects with higher PGI level, and PG I/II ratio are more likely to develop several dyspeptic symptoms.

Role of heat-shock protein (HSP) 70-2 genotype in peptic ulcer in Japanese population.

BACKGROUND/AIMS: There have been reports showing the protective role of inducible heat-shock protein (HSP) 70 in gastric epithelial cells. An A to G transition at the 1267 position HSP70-2 gene has been shown to be associated with a different level of HSP70 mRNA expression. We aimed to clarify the effect of HSP70-2 polymorphism on the risk of peptic ulcer diseases in a Japanese population. METHODOLOGY: A total of 519 subjects participated in this study. All subjects underwent upper gastroscopy. Restriction fragment length polymorphism analysis was performed for polymorphisms at 1267 of HSP70-2 gene in all the subjects. RESULTS: After gastroscopy, 109, 53 and 357 subjects were diagnosed as gastric ulcer, duodenal ulcer and non-ulcer subjects, respectively. Although, there were no significant differences of HSP70-2 genotype distributions among nonulcer subjects, overall ulcer, gastric and duodenal ulcers when the subjects were divided into two groups according to age distribution, logistic regression analysis showed that the BB genotype increased the risk of duodenal ulcer in subjects 60 years and older. (Gender, status of H. pylori infection and NSAID use adjusted OR=3.12, 95%CI=1.33-7.35, p=0.009). CONCLUSIONS: It appears that polymorphism of HSP70-2 gene is not directly associated with the susceptibility to peptic ulcer diseases but BB genotype is associated with an increased risk of duodenal ulcer in older subjects in the Japanese population.

Correlation between magnifying narrow band imaging and histopathology in gastric protruding/or polypoid lesions: a pilot feasibility trial.

BACKGROUND: Several study showed usefulness of microscopic capillaries, seen by magnifying narrow band imaging (NBI) endoscopy for predicting histopathology among superficial depressed or flat elevated gastric neoplasia (GN). Here we assessed the diagnostic efficacy of magnifying NBI for predicting histopathology among gastric protruding/or polypoid lesions. METHODS: Using endoscopic pictures of magnifying NBI from 95 protruding/or polypoid lesions (19 fundic gland polyps: FGP, 47 hyperplastic polyps: HP, and 29 GN), fine mucosal patterns were classified into four categories: small round, prolonged, villous or ridge, and unclear patterns, and micro vascular patterns were classified into five categories: honey comb, dense vascular, fine net work, core vascular, and unclear patterns. RESULTS: Most suggestive micro vascular patterns for predicting FGP, and HP were honeycomb (sensitivity 94.7%, specificity 97.4%), and dense vascular patterns (sensitivity 93.6%, specificity 91.6%), respectively. Fine net work, core vascular, and unclear patterns presented higher specificity (97%, 100%, and 100%) for predicting GN, and diagnostic efficacy of combined of those patterns was favorable (sensitivity 86.2%, specificity 97.0%). CONCLUSION: Micro vascular patterns by using magnifying NBI provides meaningful information for predicting the histopathology of gastric protruding/or polypoid lesions.

Effect of genetic polymorphisms related to DNA repair and the xenobiotic pathway on the prognosis and survival of gastric cancer patients.

BACKGROUND: A number of association studies have focused on the effect of polymorphisms related to DNA repair or the xenobiotic pathway, on the susceptibility to gastric cancer (GC). Here, the possible association between common polymorphisms in the X-ray repair cross-complementing groups (XRCC) 1, and glutathione-S-transferase (GST) genes and various clinicopathological characteristics, including overall survival, in GC patients were evaluated. PATIENTS AND METHODS: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were determined in 130 GC patients. RESULTS: XRCC1 codon 194 Trp carriers (Trp/Trp + Arg/Trp) held a significantly higher risk of venous invasion (OR = 3.76, 95%CI = 1.05-13.51, p = 0.043). A similar trend was also found for the XRCC1 codon 194 Trp/Trp genotype (OR = 2.15, 95% CI = 0.87-5.34, p = 0.099). The frequencies of the XRCC1 codon 399 Gln/Gln and Arg/Gln genotypes tended to be lower in lymphatic invasion-positive GC (XRCC1 codon 399 Gln/Gln: OR = 0.27, 95% CI = 0.06-1.15, p = 0.075, Gln/Gln + Arg/Gln: OR = 0.46, 95% CI = 0.20-1.06, p = 0.069), while the frequencies of the XRCC1 codon 194 Trp/Trp genotype tended to be higher in lymphatic invasion-positive GC (XRCC1 codon 194 Trp/Trp: OR = 7.70, 95% CI = 0.95-62.60, p = 0.056). The patients with the GSTT1 null genotype showed significantly better overall survival than the patients with the GSTT1 present genotype (p = 0.019). CONCLUSION: XRCC1 codon 194 Trp carrier status is correlated with more aggressive biological behavior of GC, such as venous invasion, and the GSTT1 null genotype is associated with better survival in GC patients.

Effect of IL-1ß and TNF-α polymorphisms on the prognosis and survival of gastric cancer patients.

So far, a number of association studies have focused on the effect of polymorphisms in IL-1ß and TNF-α genes on the susceptibility to gastric cancer (GC). Here, we evaluate the possible association between common polymorphisms in the IL-1ß and TNF-α genes with various clinicopathological characteristics, including overall survival of GC patients. Restriction fragment length polymorphism analysis was performed for IL-1ß-31(T > C) and IL-1ß-511(C > T) and TNF-α-857 (C > T) polymorphisms in 130 GC patients. IL-1ß-31CC and IL-1ß-511TT genotypes held a significantly lower risk of lymphatic invasion (IL-1ß-31CC vs. others: adjusted OR = 0.39, 95% CI = 0.15-0.96, P = 0.04, IL-1ß-511TT vs. others: adjusted OR = 0.23, 95% CI = 0.08-0.67, P = 0.007). The IL-1ß-31CC and IL-1ß-511TT genotypes were weakly associated with reduced risk of venous invasion (IL-1ß-31CC vs. others: adjusted OR = 0.35, 95% CI = 0.12-1.05, P = 0.06, IL-1ß-511TT vs. others: adjusted OR = 0.32, 95% CI = 0.08-1.20, P = 0.09). The IL-1ß-511TT genotype was also weakly associated with reduced risk of lymph node metastasis (IL-1ß-511TT vs. others: adjusted OR = 0.42, 95% CI = 0.17-1.04, P = 0.06). When the TNF-α-857CT and TNF-α-857-TT genotypes were considered as T carrier, the patients with TNF-α-857T carrier showed significantly better overall survival than patients with CC genotype (P = 0.011). GC patients who have both IL-1ß-31 CC and IL-1ß-511 TT genotypes and have at least one of protective genotypes (IL-1ß-31 CC, IL-1ß-511 TT, TNF-α-857 T carrier) were also associated with better prognostic factors, such as lymphatic and venous invasion better survival. IL-1ß-31CC, IL-1ß-511TT genotype, and TNF-α-857T carrier may have protective effect against GC progression.

Gastrointestinal Stromal Tumor of the Stomach with Narrow Stalk-Like Based, Uneven Protruding Appearance Presenting with Severe Acute Anemia despite Small Size.

We report the case of a 56-year-old woman who had a gastrointestinal stromal tumor (GIST) of the stomach. She was admitted to our hospital for epigastric pain, nausea, and severe acute anemia (hemoglobin level 4.3 g/dl). Esophagogastroduodenoscopy revealed a narrow stalk-like based, hemorrhagic and uneven protruding lesion in the lesser curvature of the gastric upper corpus. Although the tumor was less than 2 cm in diameter and was probably a benign GIST according to histology, laparoscopy-assisted local resection was needed because the patient had continuous severe anemia and epigastric pain. Histological assessment showed that the elongated spindle-like tumor cells originated from the intrinsic muscle layer, and was shown with growth to the mucosal side, cropping out to the surface in most areas of the protruding lesion. Only a small part of the tumor was within nontumoral gastric mucosa. Most of the tumor cells demonstrated immunoreactivity for KIT and CD34 in the cytoplasm but not for αSMA, S100, and desmin. Mitotic activity (0/50 high power field) and the labeling index for MIB-1 (about 1%) were low. The GIST of the stomach described in this report was a rare case with a narrow stalk-like based, uneven protruding mass presenting with severe acute anemia despite small size.

Association between cyclin D1 polymorphism with CpG island promoter methylation status of tumor suppressor genes in gastric cancer.

BACKGROUND: CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis. AIMS: We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer. METHODS: Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands. RESULTS: Although no association was found between methylation status and different stages and Lauren's subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017). CONCLUSIONS: Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.