Crack Detecting Method Based on Grid-Type Sensing Networks Using Electrical Signals.

Cracks have a primary effect on the failure of a structure. Therefore, the development of crack sensors with high accuracy and resolution and cracks detection method are important. In this study, the crack sensors were fabricated, and the crack locations were detected with the electrical signal of the crack sensor. First, a metal grid-type micro-crack sensor based on silver was fabricated. The sensor is made with electrohydrodynamics (EHD) inkjet printing technology, which is well known as the next generation of printed electronics technology. Optimal printing conditions were established through experiments, and a grid sensor was obtained. After that, single cracks and multiple cracks were simulated on the sensor, and electrical signals generated from the sensor were measured. The measured electrical signal tracked the location of the cracks in three steps: simple cross-calculation, interpolation, and modified P-SPICE. It was confirmed that cracks could be effectively found and displayed using the method presented in this paper.

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers.

GOALS: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. BACKGROUND: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. STUDY: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. RESULTS: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). CONCLUSION: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Prediction model for bleeding after endoscopic submucosal dissection of gastric neoplasms from a high-volume center.

BACKGROUND AND AIM: Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS: We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS: Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age <62 years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%. CONCLUSIONS: We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding.

Virtually-Planned Orthognathic Surgery Achieves an Accurate Condylar Position.

PURPOSE: Accuracy in orthognathic surgery with virtual planning has been reported, but detailed analysis of accuracy according to anatomic location, including the mandibular condyle, is insufficient. The purpose of this study was to compare the virtual plan and surgical outcomes and analyze the degree and distribution of errors according to each anatomic location. PATIENTS AND METHODS: This retrospective cohort study evaluated skeletal class III patients, treated with bimaxillary surgery. The primary predictor was anatomic locations that consisted of right and left condyles, maxilla, and the distal segment of the mandible. Other variables were age and gender. The primary outcome was surgical accuracy, defined as mean 3-dimensional distance error, mean absolute error, and mean error along the horizontal, vertical, and anteroposterior axes between the virtual plan and surgical outcomes. Landmarks were compared using a computational method based on affine transformation with a 1-time landmark setting. The mean errors were visualized with multidimensional scattergrams. Bivariate and regression statistics were computed. RESULTS: This study included 52 patients, 26 men and 26 women, with a mean age of 21 years and 3 months. The mean 3D distance errors for condylar landmarks, maxillary landmarks, and landmarks on the distal segment of the mandible were 1.03, 1.25, and 2.24 mm, respectively. Condylar landmarks, maxillary landmarks, and the landmarks on the distal segment of the mandible were positioned at 0.49 mm inferior, 0.28 mm anterior, and 1.25 mm inferior, respectively. The landmark errors for the distal segment of the mandible exhibited a wider distribution than those for condylar and maxillary landmarks. CONCLUSIONS: Agreement between the planned and actual outcome aided by virtual surgical planning was highest for the condyles, followed by the maxilla, and the distal segment of the mandible. It is important to consider the tendency for surgical errors in each anatomic location during operations.

Profiling of Steroid Metabolic Pathways in Human Plasma by GC-MS/MS Combined with Microwave-Assisted Derivatization for Diagnosis of Gastric Disorders.

Steroid hormones are associated in depth to cellular signaling, inflammatory immune responses, and reproductive functions, and their metabolism alterations incur various diseases. In particular, quantitative profiling of steroids in plasma of patients with gastric cancer can provide a vast information to understand development of gastric cancer, since both sex hormones and glucocorticoids might be correlated with the pathological mechanisms of gastric cancer. Here, we developed a gas chromatography-tandem mass spectrometry-dynamic multiple reaction monitoring (GC-MS/MS-dMRM) method combined with solid-phase extraction (SPE) and microwave-assisted derivatization (MAD) to determine 20 endogenous steroids in human plasma. In this study, MAD conditions were optimized with respect to irradiation power and time. The SPE enabled effective cleanup and extraction for profiling of steroid hormones in human plasma samples. The MAD could improve laborious and time-consuming derivatization procedure, since dielectric heating using microwave directly increase molecular energy of reactants by penetrating through medium. Furthermore, dMRM method provided more sensitive determination of 20 steroids, compared to traditional MRM detection. The limits of quantification of steroids were below 1.125 ng/mL and determination coefficients of calibration curves were higher than 0.9925. Overall precision and accuracy results were below 19.93% and within ±17.04%, respectively. The developed method provided sufficient detection sensitivities and reliable quantification results. The established method was successfully applied to profile steroid metabolism pathways in plasma of patients with chronic superficial gastritis (CSG), intestinal metaplasia (IM), and gastric cancer. Statistical significances of steroid plasma levels between gastric disorder groups were investigated. In conclusion, this method provided comprehensive profiling of 20 steroids in human plasma samples and will be helpful to discover potential biomarkers for the development of gastric cancer and to further understand metabolic syndrome.

The Suggestion of Revised Criteria for Endoscopic Resection of Differentiated-Type Submucosal Gastric Cancer.

BACKGROUND: Early gastric cancer that meets the expanded criteria for endoscopic resection (ER) is expected to be associated with a negligible risk for lymph node metastasis (LNM); however, recent studies have reported LNM in submucosal gastric cancer patients who met the existing criteria. In this study, we develop the revised criteria for ER of submucosal gastric cancer with the aim of minimizing LNM. METHODS: We analyzed the clinicopathological data of 2461 patients diagnosed with differentiated, submucosal gastric cancer who underwent surgery at three tertiary hospitals between March 2001 and December 2012, and re-analyzed the pathological slides of all patients. The depth of submucosal invasion was measured histopathologically in two different ways (the classic and alternative methods) to obtain accurate data. RESULTS: Of the enrolled subjects, 306 (17.0%) had LNM. The width of submucosal invasion correlated well with the LNM. We defined the depth and width of submucosal infiltration associated with the lowest incidence of LNM. None of the 254 subjects developed LNM when the following criteria were met: tumor diameter ≤ 3 cm, submucosal invasion depth < 1000 µm (as measured using the alternative method), submucosal invasion width < 4 mm, no lymphovascular invasion, and no perineural invasion; however, LNM was observed in 2.7% of subjects (6/218) who met the existing criteria. CONCLUSIONS: We revised the criteria for ER by adopting the alternative method to measure the depth of submucosal invasion and adding the width of such invasion. Our criteria better predicted LNM than the current criteria used to select ER to treat submucosal gastric cancer.

miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells.

In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

Role of probe-based confocal laser endomicroscopy-targeted biopsy in the molecular and histopathological study of gastric cancer.

BACKGROUND AND AIM: A high yield of biopsy is mandatory to perform molecular genetic research with endoscopically obtained gastric cancer tissues. We evaluated whether probe-based confocal laser endomicroscopy (pCLE) can increase the yield of endoscopic biopsy for gastric cancer compared with white light endoscopy (WLE). METHODS: All lesions in the pCLE and WLE groups were initially evaluated through WLE. In the pCLE group, lesions were further examined through pCLE. In the pilot study, five and three biopsy specimens were obtained for histopathological examination and tumor marker analysis, respectively. In the confirmatory study, six biopsy specimens for histopathological evaluation were obtained. RESULTS: A total of 30 gastric cancers and 61 undifferentiated-type gastric cancers were analyzed in the pilot and confirmatory studies, respectively. The proportion of cancer cells in biopsy samples of poorly differentiated adenocarcinoma or signet ring cell carcinoma was higher in the pCLE group than in the WLE group in both the pilot and confirmatory studies (pilot: median proportion, 65% vs 30%, P = 0.010; confirmatory: mean ± standard deviation, 49.5 ± 29.3 vs 29.3 ± 13.7, P = 0.002). The expression ratio of tumor markers including carcinoembryonic antigen, GW112, HOX transcript antisense RNA, and H19 tended to be higher in the pCLE group than in the WLE group. CONCLUSION: Probe-based confocal laser endomicroscopy-targeted biopsy provided superior results in terms of the proportion of cancer cells in biopsy samples compared with WLE-targeted biopsy in gastric cancer with undifferentiated histology.

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment.

BACKGROUND AND AIMS: We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD. METHODS: Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD. RESULTS: The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P =.030; and 92.5%, 73.6%, and 63.0%, respectively; P < .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P = .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P = .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P = .003). CONCLUSIONS: In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival.

Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial.

BACKGROUND AND AIM: This study aimed to investigate the effectiveness of scheduled second-look endoscopy (EGD) with endoscopic hemostasis on peptic ulcer rebleeding and to identify the risk factors related to the need for second-look EGD. METHODS: We prospectively randomized patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of active bleeding, visible vessel, or adherent clot into 2 groups between August 2010 and January 2013. Hemoclip application or thermal coagulation and/or epinephrine injection were allowed for initial endoscopic therapy. The same dosage of proton pump inhibitor was injected intravenously. The study group received scheduled second-look EGD 24 to 36 hours after the initial hemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. Those patients who developed rebleeding underwent operation or radiologic intervention despite the additional endoscopic therapy. Outcome measures included rebleeding, amount of transfusion, duration of hospitalization, and mortality. RESULTS: After initial endoscopic hemostasis, 319 eligible patients were randomized into 2 groups. Sixteen (10.1%) and 9 (5.6%) patients developed rebleeding (P = .132), respectively. There was also no difference in surgical intervention (0, 0% vs 1, .6%, P >.999) or radiologic intervention (3, 1.9% vs 2, 1.2%, P = .683), median duration of hospitalization (6.0 vs 5.0 days, P = .151), amount of transfusion (2.4 ± 1.7 vs 2.2 ± 1.6 units, P = .276), and mortality (2, 1.3% vs 2, 1.2%, P > .999) between the 2 groups. Multivariate analysis showed that grades 3 to 4 of endoscopists' estimation to success of initial hemostasis, history of nonsteroidal anti-inflammatory drug (NSAID) use, and larger amounts of blood transfusions (≥4 units of red blood cells) were the independent risk factors of rebleeding. CONCLUSIONS: A single EGD with endoscopic hemostasis is not inferior to scheduled second-look endoscopy in terms of reduction in rebleeding rate of peptic ulcer bleeding. Repeat endoscopy would be helpful in the patients with unsatisfactory initial endoscopic hemostasis, use of NSAIDs, and larger amounts of transfused blood. (Clinical trial registration number: KCT0000565; 4-2010-0348.).

Efficacy of hemostatic powder in preventing bleeding after gastric endoscopic submucosal dissection in high-risk patients.

BACKGROUND AND AIM: The prevention of post-endoscopic submucosal dissection (ESD) bleeding in high-risk patients is an important problem. This study evaluated the efficacy of polysaccharide hemostatic powder in preventing post-ESD bleeding in high-risk patients. METHODS: Patients at high risk for post-ESD bleeding were prospectively enrolled between December 2015 and July 2016. A high risk of post-ESD bleeding was considered if the patients were taking antithrombotic agents or had undergone a large resection (specimen size ≥ 40 mm). The endpoints were Forrest classification of the post-ESD ulcer on second-look endoscopy 2 days after the procedure and bleeding rates within 48 h and at 4 weeks. RESULTS: Forty-four patients underwent gastric ESD and treatment with hemostatic powder. Among them, 33 patients (70.5%) underwent large resection (≥ 40 mm) without antithrombotic therapy, and 13 patients (29.5%) received antithrombotic therapy. The mean resected specimen size was 55.3 ± 13.9 mm. The proportion of high-risk delayed bleeding lesions (Forrest IIa) at second-look endoscopy was 4.5% (2/44). The overall bleeding rate was 9.1% (4/44). There was no early bleeding event. The median (interquartile range) timing of bleeding after the procedure was 12.5 (interquartile range 10.3-15.5) days. The bleeding rate in the large resection (≥ 40 mm) group without antithrombotic therapy and the antithrombotic therapy group was 3.2% (1/33) and 23.1% (3/13), respectively. CONCLUSIONS: Hemostatic powder may be a promising new simple and effective method to prevent early post-ESD bleeding in high-risk patients, especially for those with larger resection. (Clinical trial registration number: NCT02625792).

Effect of the midazolam added with propofol-based sedation in esophagogastroduodenoscopy: A randomized trial.

BACKGROUND AND AIM: Although propofol has been widely used for sedation during esophagogastroduodenoscopy (EGD), adverse events including hypoxia and hypotension may be a concern in the propofol-based sedation. We aimed to analyze whether administration of midazolam would improve safety and efficacy of propofol-based sedation in EGD. METHODS: One hundred twenty patients who were scheduled to undergo diagnostic EGD were randomly assigned to either midazolam plus propofol (MP) or propofol alone groups. In the MP group, 2 mg of midazolam and 10 mg of propofol were given initially. In the propofol alone group, 40-60 mg of propofol was given initially. In both groups, 20 mg of propofol was given repeatedly to maintain moderate sedation as needed. Vital signs including oxygen saturation were monitored every 2 min. After the patients fully recovered, satisfaction score was investigated from endoscopists, nurses, and patients, respectively. RESULTS: The baseline characteristics did not differ between the MP and propofol alone groups. The mean required doses of propofol was (mean ± standard deviation) 0.3 ± 0.3 and 0.8 ± 0.2 mg/kg in the MP and propofol alone groups, respectively (P < 0.001). In addition, sedation-related adverse events and recovery time did not differ between the two groups. The proportion of satisfactory did not differ between the two groups (MP vs propofol alone; proportion; patient, 95.0% vs 93.3%, P > 0.999; endoscopist, 73.3% vs 80.0%, P = 0.064; nurse, 73.3% vs 76.7%, P = 0.551). CONCLUSION: Adding midazolam to propofol did not reduced the safety and efficacy, and sedation using propofol alone could be suitable for sedation during diagnostic EGD.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

BACKGROUND AND AIM: Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. METHODS: We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. RESULTS: Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. CONCLUSIONS: Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

Neuronal Nitric Oxide Synthase Is a Novel Biomarker for the Interstitial Cells of Cajal in Stress-Induced Diarrhea-Dominant Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. AIM: The aim of this study was to discover the novel and reliable biomarker for IBS. METHOD: In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. RESULTS: Male pups developed symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. CONCLUSION: Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.

Comparison of long-term clinical outcomes between endoscopic and surgical resection for early-stage adenocarcinoma of the esophagogastric junction.

BACKGROUND: The aim of this study was to analyze long-term clinical and oncologic outcomes in patients with early-stage adenocarcinoma of the esophagogastric junction (AEG) managed with either endoscopic resection (ER) or surgery. METHODS: The inclusion criteria were AEG, meeting classic or expanded indications for ER of early gastric cancer, and complete resection. A total of 66 patients with Siewert type II AEG were included (ER group, n = 38; vs. surgery group, n = 28). RESULTS: The mean age of the ER group was greater than that of the surgery group (mean ± SD, 66.9 ± 9.7 vs. 58.5 ± 10.4 years, respectively; p = 0.001). Compared to the ER group, macroscopically flat or depressed-type lesions were more common (47.4 vs. 89.3%; p = 0.001), and mean lesion size was larger in the surgery group (13.3 ± 8.4 vs. 18.6 ± 11.0 mm; p = 0.039). One intensive care unit admission and subsequent surgery-related death occurred in the surgery group (1/28 vs. 0/38 in the ER group; p = 0.424). During follow-up, recurrence was detected in both groups (4/38 vs. 1/28; p = 0.385). Overall survival and 5-year disease-free survival did not differ between the groups (93.3 vs. 92.9%; p = 0.282 and 88.0 vs. 100.0%; p = 0.066). CONCLUSIONS: Once complete resection is achieved in patients with AEG who met the expanded criteria for endoscopic submucosal dissection of gastric cancer, there was no significant difference in clinical outcomes between ER and surgery.

Long-term outcomes of endoscopic submucosal dissection in comparison to surgery in undifferentiated-type intramucosal gastric cancer using propensity score analysis.

BACKGROUND: The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs. METHODS: A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1-1 propensity score-matched 81 pairs of patients were also compared. RESULTS: In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088). CONCLUSIONS: ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.

Comparative study between endoscopic submucosal dissection and surgery in patients with early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. The aim of this study was to compare the short-term and long-term outcomes between ESD and surgery in patients with EGC that fulfilled the expanded indication of ESD on their final pathologic report. METHODS: We reviewed the clinical data of patients who underwent gastric ESD and surgery between January 2007 and December 2012. Patients with pathologically confirmed EGC that fulfilled the expanded indication of ESD on their final pathologic report were analyzed. RESULTS: Among 2023 patients, 817 (40.4%) underwent ESD and 1206 (59.6%) underwent surgery. The proportion of cases meeting the absolute indication was significantly higher in the ESD group than in the surgery group (66.0 vs. 26.2%). Lesions on the middle third, >3 cm in size, flat or depressed, and of undifferentiated histology were significantly more common in the surgery group than in the ESD group. The ESD group showed lower acute complication rates [8.1% (66 of 817) vs. 18.1% (218 of 1206), P ≤ 0.001] and procedure-related mortality [0 vs. 0.3% (4 of 1206), P = 0.153] than the surgical group. The annual incidence of recurrent gastric cancer was 2.18% in the ESD group and 0.19% in the surgery group. The 5-year overall and disease-specific survival rates were not significantly different between the ESD group and the surgery group (overall survival: 96.4 vs. 97.2%, P = 0.423; disease-specific survival: 99.6 vs. 99.2%, P = 0.203). CONCLUSIONS: Although EGC lesions had poorer features in the surgery group than in the ESD group, ESD was comparable to surgery for EGCs that fulfilled the expanded indication of ESD, with lower rates of acute complication and comparable overall survival.

Potential miRNA-target interactions for the screening of gastric carcinoma development in gastric adenoma/dysplasia.

Although miRNA markers have been identified for the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism are still not fully understood. Moreover, some gastric adenoma/dysplasia may progress to GAC. In this study, the miRNA expression profiles in normal and paired low-/high-grade dysplasia were analyzed using Affymetrix Gene-Chip miRNA arrays. Of the total 2578 mature miRNA probe sets, ~1600 showed positive signals when the between normal and paired low-/high-grade dysplasia were compared. To verify the miRNA expression, qRT-PCR analysis was performed to quantify the expression of altered miRNAs between normal and paired low-/high-grade dysplasia. The analysis revealed that hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p were overexpressed in gastric low-/high-grade dysplasia and that based on these miRNA-target interactions, FBXO11 and CREBZF could be considered convincing markers for gastric cancer (GC) progression. Thus, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the GC development from premalignant adenomas. Furthermore, these two target mRNAs and three miRNAs were predicted to be potential biomarkers for the progression of GC by miRNA-target interaction analysis.