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Background It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model. Results Oral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella , which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides , the relative abundances of Parabacteroides distasonis , Parabacteroides goldsteinii , and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups. Conclusion Combined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit.

BackgroundIn Japan, endoscopic submucosal dissection (ESD) has been widely performed for ESD-adapted gastric cancer, but little is known about the prognostic factors after ESD for gastric cancer in older patients. The psoas muscle index (PMI) is an indicator of sarcopenia calculated from computed tomography images and reportedly related to the prognosis of some diseases. This study aimed to explore factors related to long-term survival after ESD for gastric cancer in patients aged ≥ 80 years.MethodsWe retrospectively reviewed 88 patients (63 men, 25 women) with early gastric cancer who underwent ESD at ≥ 80 years. Possible factors related to death after gastric ESD were analyzed by univariate and multivariate analyses using a Cox proportional hazards model. The estimated overall survival (OS) was compared between the groups stratified by significant factors.ResultsThe 5-year OS rate was 73.9% (median follow-up period, 5.4 years). In the multivariate analysis, a low PMI (< 6.36 in men, < 3.92 in women) (hazard ratio [HR] 2.89, 95% confidence interval [CI] 1.11–7.54) and high Charlson comorbidity index (CCI) (≥ 3) (HR 1.87, 95% CI 1.14–3.09) were independently related to death after ESD. The 5-year OS rates were significantly higher in the high PMI group (82.3% vs. 70.7%, P = 0.026) and the low CCI group (76.0% vs. 37.9%, P = 0.002).ConclusionIn addition to low CCI, high PMI is a predictor of long-term survival after ESD for gastric cancer in patients aged ≥ 80 years.

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. In this study, we mainly analyzed the relationship between 5‐FU resistance and the miRNA profile of colorectal tumors. Moreover, the expression level of miR‐31 was higher in carcinomas invading submucosa and advanced cancer than in carcinomas in situ and adenomas. These data might suggest that the increased expression level of miR‐31 caused 5‐FU resistance in colorectal cancer through maintenance of the Warburg effect.

Background and aimEsophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC.MethodsA total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated.ResultsMore patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043).ConclusionThe post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.

Background An accurate diagnosis of pancreatic fibrosis is clinically important and may have potential for staging chronic pancreatitis. The aim of this study was to diagnose the grade of pancreatic fibrosis through a quantitative analysis of endoscopic ultrasound elastography (EUS-EG). Methods From September 2004 to October 2010, 58 consecutive patients examined by EUS-EG for both pancreatic tumors and their upstream pancreas before pancreatectomy were enrolled. Preoperative EUS-EG images in the upstream pancreas were statistically quantified, and the results were retrospectively compared with postoperative histological fibrosis in the same area. For the quantification of EUS-EG images, 4 parameters (mean, standard deviation, skewness, and kurtosis) were calculated using novel software. Histological fibrosis was graded into 4 categories (normal, mild fibrosis, marked fibrosis, and severe fibrosis) according to a previously reported scoring system. Results The fibrosis grade in the upstream pancreas was normal in 24 patients, mild fibrosis in 19, marked fibrosis in 6, and severe fibrosis in 9. Fibrosis grade was significantly correlated with all 4 quantification parameters (mean r  = −0.75, standard deviation r  = −0.54, skewness r  = 0.69, kurtosis r  = 0.67). According to the receiver operating characteristic analysis, the mean was the most useful parameter for diagnosing pancreatic fibrosis. Using the mean, the area under the ROC curves for the diagnosis of mild or higher-grade fibrosis, marked or higher-grade fibrosis and severe fibrosis were 0.90, 0.90, and 0.90, respectively. Conclusions An accurate diagnosis of pancreatic fibrosis may be possible by analyzing EUS-EG images.

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence‐based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS‐guided fine needle aspiration (EUS‐FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator‐dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast‐enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast‐enhanced EUS for differentiation of intra‐cystic MNs from mucous clots, and (3) pathological diagnosis using EUS‐FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

Background It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to assess the severity of CP, but the diagnosis of CP using EUS depends on an endosnonographer. The aim of this study was to establish an objective diagnostic method for CP using EUS elastography (EUS-EG). Methods A retrospective study was designed and 96 patients underwent EUS-EG for follow-up of known CP, or who were clinically suspected as having CP. CP patients were categorized CP patients as 4 stages using the Rosemont classification (RC). EUS-EG was performed and the “Mean value”, which was negatively correlated with pancreatic fibrosis, was calculated using histogram analysis. Results The “Mean value” of each RC stage (normal, indeterminate for CP, suggestive of CP, and consistent with CP) was 90.1 ± 19.3, 73.2 ± 10.6, 63.7 ± 14.2, and 56.1 ± 13.6, respectively, and showed significant differences for each stage ( p  < 0.001). There was a significant negative correlation between the “Mean value” and the number of EUS features ( r s  = −0.59, p  < 0.001). Multiple linear regression analysis was used to assess the diagnostic finding of the “Mean value” and showed that hyperechoic foci with shadowing and lobularity with honeycombing maintained their independent diagnostic findings. Conclusions EUS-EG was an objective diagnostic apparatus for CP and provided objective information to support EUS features.

BackgroundEndoscopic ultrasonography (EUS) and high-resolution manometry (HRM) can be used in the evaluation of eosinophilic esophagitis (EoE) for frequent symptoms such as dysphagia. However, the role of these examinations is not clear.AimsThe aim of this study was to objectively evaluate the subjective symptoms of EoE patients with EUS and HRM.MethodsPatients who had endoscopic findings indicative of EoE and matched the number of eosinophil infiltrates used as diagnostic criteria were recruited between September 2018 and August 2019. Evaluable subjects underwent EUS and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The esophageal wall thickness (evaluated with EUS) and HRM parameters between patients with and without symptoms were retrospectively compared. Symptomatic patients were re-examined using EUS and HRM 6 months after treatment.ResultsA total of 35 patients (29 males, median age of 49 years) were divided into symptomatic (20 patients) and asymptomatic groups (15 patients). The esophageal wall was thicker, and the distal contractile integral (DCI) values were higher in the symptomatic group (P < 0.001). In addition, DCI values were positively correlated with esophageal wall thickness. After treatment, the GSRS scores showed an improving trend for each item. Esophageal wall thickness and DCI values were significantly decreased (Ps < 0.001).ConclusionsEsophageal wall thickening and increased esophageal body pressure may be involved in subjective symptoms. In addition, treatment may reduce esophageal thickness and pressure along with improvement of subjective symptoms.

Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples ( P  < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression ( P  = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

The striatin family of proteins, comprising STRN, STRN3 and STRN4, are multidomain‐containing proteins that associate with additional proteins to form a large protein complex. We previously reported that STRN4 directly associated with protein kinases, such as MINK1, TNIK and MAP4K4, which are associated with tumor suppression or tumor progression. However, it remains unclear whether STRN4 is associated with tumor progression. In this report, we examined the role that STRN4 plays in cancer malignancy. We show that depletion of STRN4 suppresses proliferation, migration, invasion and the anchorage‐independent growth of cancer cells. In addition, STRN4 knockdown increases the sensitivity of pancreatic cancer cells to gemcitabine. Finally, we show that STRN4 knockdown suppresses the proliferation and metastasis of cancer cells in mice. Our results demonstrate a possible role of STRN4 in tumor progression. STRN4 is a multidomain‐structured proteins that associate with numerous proteins to form a large protein complex. We show that STRN4 is associated with malignant characteristics of cancer cells.