Clinical Outcomes of Follow-Up Observation After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma Invading the Muscularis Mucosa Without Lymphovascular Involvement.

BACKGROUND: The therapeutic approach after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) diagnosed as pathological T1a-muscularis mucosa (pT1a-MM) without lymphovascular involvement (LVI) remains uncertain. We aimed to determine whether observation after ESD is acceptable for patients without LVI showing pT1a-MM cancer. METHODS: We retrospectively registered 566 ESCC patients who were treated with ESD at ten institutions between January 2007 and December 2015. Of those, 447 cases showing pT1a-epithelium/lamina propria mucosa (EP/LPM) without LVI and vertical margin (VM) (EP/LPM group), and 41 cases showing pT1a-MM without LVI and VM (MM group) were analyzed in this investigation. The clinical outcomes were assessed between the groups. RESULTS: The 5 year cumulative incidence of metastatic recurrence was 0.5% and 3.3% in the EP/LPM and MM groups, respectively (P = 0.121). Two cases showing pT1a-EP/LPM and one showing pT1a-MM experienced lymph node recurrence. The 5 year cumulative incidence of local recurrence was 1.5% and 3.8% in the EP/LPM and MM groups, respectively (P = 0.455). The 5 year disease-specific survival (DSS) rate was 99.3% and 96.6% in the EP/LPM and MM groups, respectively (P = 0.118), whereas the 5 year overall survival rate was significantly higher in the EP/LPM group than in the MM group (92.6% versus 81.1%, respectively; P = 0.021). CONCLUSIONS: As regards metastatic recurrence and DSS, ESCC patients with pT1a-MM without LVI showed favorable outcomes that were equivalent to those with pT1a-EP/LPM, even when they were not treated with additional therapy after ESD.

Risk and prognostic factors of invasive gastric cancer detection during surveillance endoscopy: Multi-institutional cross-sectional study.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is important for the detection of curable gastric cancer (GC). However, there are no appropriate surveillance data during routine endoscopic inspections. This study aimed to clarify the risk factors of pT1b or deeper GC detection during surveillance endoscopy. METHODS: This was a retrospective, multicenter, cross-sectional study conducted in 15 Japanese hospitals. We retrospectively analyzed patients with GC who had previously undergone surveillance endoscopy at each institution from January 2014 to March 2020. Patients who had undergone gastrectomy, non-infection of Helicobacter pylori (Hp), and those with intervals <3 months or >10 years from a previous endoscopy were excluded. RESULTS: In total, 1085 patients with GCs detected during surveillance endoscopy were enrolled. The multivariate logistic analysis revealed that current Hp infection (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.50-3.16) and a surveillance interval of >1.5 years (OR 1.96; 95% CI 1.35-2.84) were independent risk factors for pT1b or deeper GC. The 5-year disease-specific survival (5y-DSS) rate of GC was significantly lower in patients with surveillance interval of >1.5 years than in those with surveillance interval of ≤1.5 years (93.7% vs. 98.3%, P < 0.001). Similarly, the 5y-DSS rate of GC was significantly lower in patients with active Hp infection than in those without (93.7% vs. 99.4%, P < 0.001). CONCLUSION: In this study, a surveillance interval of >1.5 years and current Hp infection were independent risk factors for detecting pT1b or deeper GC. Additionally, these factors were poor prognostic factors of the detected GC during surveillance endoscopy.

Upacicalcet Is a Novel Secondary Hyperparathyroidism Drug that Targets the Amino Acid Binding Site of Calcium-Sensing Receptor .

The human calcium-sensing receptor (CaSR) is a G protein-coupled receptor that maintains extracellular Ca2+ homeostasis by regulating the secretion of parathyroid hormone. Upacicalcet is a novel positive allosteric modulator of CaSR that is used for the treatment of secondary hyperparathyroidism. In the present study, to clarify the binding site of upacicalcet to CaSR, we conducted binding studies and agonistic activity studies in HEK-293T cells expressing human CaSR (intact and mutant) and an in silico docking-simulation analysis. As a result, upacicalcet competed with L-tryptophan and was thought to affect the amino acid binding site. In addition, the effects of substitutions at the amino acid binding site on the binding abilities to upacicalcet as well as the effects on receptor function as measured using inositol-1 monophosphate accumulation were examined. Upacicalcet interacted with several CaSR residues that constitute the amino acid binding site. Based on these results, we performed an in silico analysis and obtained a binding mode, consistent with the in vitro study results. Our study revealed that upacicalcet is a novel secondary hyperparathyroidism drug that targets the amino acid binding site of CaSR. Upacicalcet is expected to become a new treatment option for secondary hyperparathyroidism because the binding site differs from that of conventional drugs; consequently, it may be effective for patients who are not sensitive to conventional drugs, and it may have a superior safety profile. SIGNIFICANCE STATEMENT: Upacicalcet interacts with several residues that constitute the amino acid binding site of the calcium-sensing receptor (CaSR) and shows a potent positive allosteric activity. This mechanism differs from those of conventional drugs. Therefore, upacicalcet can be regarded as a novel secondary hyperparathyroidism drug that acts on the amino acid binding site of CaSR.

Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged 85 Years Old or Older Is Associated with a Good Prognosis Compared to Conservative Treatment without Any Invasive Procedure.

INTRODUCTION: Studies have reported the feasibility of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in elderly people with respect to both short- and long-term outcomes. As the elderly population in society increases, the requirement for managing super-elderly patients aged ≥85 years with EGC will also increase. This study aims to identify the long-term clinical outcomes of ESD for clinical T1N0 EGC in patients aged ≥85 years. METHODS: A total of 370 consecutive patients aged ≥85 years with clinical T1N0 EGC who were managed in 11 institutions were reviewed retrospectively. On the basis of treatment strategy, we compared the overall survival (OS) and disease-specific survival (DSS) after performing propensity score-matched analysis between patients undergoing ESD (ESD group) and those not undergoing treatment (conservative treatment group). The potential prognostic factors were also investigated in the propensity score-matched patients. RESULTS: After propensity score matching, we found that the 3-year OS and DSS rates were significantly higher in the ESD group than in the conservative treatment group (OS, 82.2% vs. 50.5%; p < 0.001; DSS, 100% vs. 80.1%; p = 0.008). Furthermore, ESD was identified as a significant factor for prolonged OS, whereas Charlson comorbidity index (CCI) ≥3 and prognostic nutritional index (PNI) <36.2 were associated with reduced OS. CONCLUSION: ESD was associated with improved OS in patients with clinical T1N0 EGC aged ≥85 years compared with the absence of treatment. Furthermore, CCI and PNI were helpful for patient selection.

Prognostic risk factors associated with esophageal squamous cell carcinoma patients undergoing endoscopic submucosal dissection: a multi-center cohort study.

BACKGROUND: Long-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) have not been assessed in a large, multicenter cohort. We aimed to evaluate long-term outcomes of ESD for ESCC in a real-world setting. METHODS: We retrospectively recruited 659 patients who underwent ESD for ESCC at ten institutions from January 2007 to December 2015. Of these, 566 patients were analyzed and classified into three groups according to the pathologic invasion depth after ESD: epithelium/lamina propria mucosa (EP/LPM group: 454 patients), muscularis mucosa/submucosa invasion ≤ 200 µm below the inferior margin of the muscularis mucosa (MM/SM1 group: 81 patients), and submucosa invasion > 200 µm below the MM inferior margin (SM2 group: 31 patients). RESULTS: The 5-year overall survival rates in the EP/LPM, MM/SM1, and SM2 groups were 92.6%, 80.0%, and 62.7%, respectively, while the 5-year disease-specific survival rates were 99.7%, 96.9%, and 88.3%, respectively. Multivariate analyses revealed that the invasion depth, Charlson Comorbidity Index (CCI), and prognostic nutritional index (PNI) were independent prognostic factors. Hazard ratios in the MM/SM1 and SM2 groups were 2.25 (95% confidence interval [CI] 1.04-4.83; P = 0.038) and 3.18 (95% CI 1.08-9.34; P = 0.036), respectively, compared to those in the EP/LPM group, while those for patients with a CCI ≥ 3 and PNI ≤ 47.75 were 3.25 (95% CI 1.79-5.89; P < 0.001) and 2.42 (95% CI 1.26-4.65; P = 0.008), respectively. CONCLUSIONS: This study identified that invasion depth, presence of comorbid diseases and preoperative nutritional status are independent prognostic risk factors associated with ESCC patients undergoing ESD.

Efficacy and Feasibility of Magnifying Blue Laser Imaging without Biopsy Confirmation for the Diagnosis of the Demarcation of Gastric Tumors: A Randomized Controlled Study.

BACKGROUND: Accurate diagnosis of the demarcation line (DL) of gastric tumors is essential for curative complete resection by endoscopic submucosal dissection (ESD). It is controversial to perform only magnifying endoscopy for diagnosing the DL of gastric tumors prior to ESD. This study aimed to evaluate the diagnostic accuracy for the DL of gastric adenomas and well-differentiated adenocarcinomas using only magnifying blue laser imaging (M-BLI) compared with that using both M-BLI and biopsy confirmation. METHODS: In this prospective, single-center study, 96 well-differentiated adenocarcinomas and 32 gastric adenomas were enrolled between July 2015 and December 2016. A total of 122 lesions with a clear DL on M-BLI were randomly allocated to undergo M-BLI only (the M-BLI group) or M-BLI with biopsy confirmation (the M-BLI-BC group), performed as biopsies in 4 directions from noncancerous tissues ≈ 5 mm outside the lesion before ESD. The primary end point was to clarify the noninferiority of M-BLI without biopsy confirmation compared with that with biopsy confirmation, in terms of the diagnostic accuracy and complete resection. RESULTS: There were no significant differences in sex, median age, color, circumference, macroscopic type, biopsy-based diagnosis, and Helicobacter pylori infection between the 2 groups. The diagnostic accuracy for the DL was 100 and 95.0% and the complete resection was 100 and 100% in the M-BLI and M-BLI-BC groups, respectively. CONCLUSION: The diagnostic ability of M-BLI is excellent in diagnosing the demarcation of gastric adenoma and well-differentiated adenocarcinoma. Biopsy confirmation is not needed for these lesions with a clear DL by M-BLI.

Clinical Outcomes of Vonoprazan-Treated Patients after Endoscopic Submucosal Dissection for Gastric Neoplasms: A Prospective Multicenter Observation Study.

BACKGROUND: Vonoprazan (VPZ) has the potential to prevent delayed bleeding and promote ulcer healing after endoscopic submucosal dissection (ESD) similar to proton pump inhibitors (PPIs). OBJECTIVE: We aimed to evaluate the outcomes of VPZ-treated patients after ESD and compared the efficacy and feasibility in preventing a delayed bleeding and in healing an artificial ulcer after ESD between the VPZ and PPI therapies. METHODS: This was a prospective, observation study in 11 Japanese medical institutions. We enrolled and evaluated 223 patients who underwent gastric ESD followed by VPZ treatment (VPZ group). We selected 385 patients who underwent gastric ESD followed by PPI treatment as historical controls (PPI group) to compare the outcomes between the VPZ and PPI groups using a propensity score matching analysis. RESULTS: Among the 223 patients treated with VPZ, 173 were men and 50 were women with a median age of 72 years and with a median tumor size of 12.0 mm. Rates of en bloc resection and complete resection were 99.1 and 94.2%, respectively. Lymphovascular invasion was found in 6 (6.3%) cases. Intraoperative perforation and delayed bleeding occurred in 3 (1.3%) and 10 patients (4.5%), respectively. Scarring of artificial post-ESD ulcer was found in 153 patients (68.6%) at 6 weeks after ESD. The 205 pairs of propensity score-matched patients were comparable between the VPZ and PPI groups. The rate of delayed bleeding in the VPZ and PPI groups was 3.9 and 4.4%, respectively (difference, 0.5 percentage points; 95% confidence interval, -3.7 to 2.8%; non-inferiority, p = 0.01). Therefore, VPZ therapy demonstrated non-inferiority against PPI therapy in reducing the rate of delayed bleeding. The scar-stage ulcer at 6 weeks in the VPZ group and 8 weeks in the PPI group was 68.3 and 74.6%, respectively (p = 0.19). CONCLUSIONS: VPZ therapy showed an efficacy and feasibility in preventing a delayed bleeding after ESD similar to the PPI therapy. VPZ for 6 weeks and PPI for 8 weeks were similarly effective for an artificial ulcer healing after ESD.

Clinical and Pathological Challenges in the Diagnosis of Gastric-Type Differentiated Adenocarcinoma in the Stomach: A Study of Endoscopic Submucosal Dissection Cases.

BACKGROUND/AIMS: Gastric-type differentiated adenocarcinoma (GDA) of the stomach is a rare variant of gastric cancer that is highly infiltrating and exhibits early metastasis. However, the endoscopic and pathological features of "early-stage" GDA remain unknown. The aim of this study is to characterize early-stage GDA. METHODS: We retrospectively enrolled 479 differentiated-type early gastric cancer cases who underwent endoscopic submucosal dissection (ESD). GDA cases were selected based on morphology and immunohistochemistry. Clinicopathological data were compared between gastric- and intestinal-type differentiated adenocarcinomas (IDAs). RESULTS: Thirteen lesions were classified as GDAs. GDAs as well as IDAs showed irregular microvascular and microsurface patterns with clear demarcation line on magnifying endoscopy with narrow band imaging (M-NBI). The rate of pathological misdiagnosis of GDAs in biopsy specimens was higher than that of IDAs (p = 0.016). GDA was significantly associated with positive lymphovascular invasion (p = 0.016). There was one intramucosal lesion with lymphatic invasion in GDA. CONCLUSIONS: Although M-NBI is useful to detect GDA, the pathological diagnosis of GDAs in biopsy specimens often remains challenging. When suspicious lesions are not diagnosed as GDA, they should be followed up intensively, or diagnostic ESD has to be performed. ESD specimens should be carefully evaluated because of a higher incidence of lymphovascular invasion.

Efficacy of Magnifying Narrow Band Imaging for Delineating Horizontal Margins of Early Gastric Cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the diagnostic accuracy of magnifying narrow-band imaging (M-NBI) with histopathological confirmation in identifying the demarcation line (DL) of early gastric cancer (EGC). METHODS: EGCs resected by endoscopic submucosal dissection after identifying the DL using M-NBI following histopathological confirmation were included. After determining the DL for the entire EGC lesion using M-NBI, at least 4 biopsies were taken from non-cancerous tissues outside the EGC lesion for histopathological confirmation. RESULTS: A total of 330 EGCs were analyzed in this study. The rate of biopsy-negative and negative horizontal margin were 96.7% (319/330) and 97.9% (323/330) in EGC respectively. Tumors larger than 20 mm showed a higher risk for showing remnant cancer cells on biopsies taken outside the DL. Risk factors for a positive horizontal resection margin were tumor size > 20 mm and moderately or poorly differentiated adenocarcinomas. CONCLUSION: The assessment of demarcation of EGC using M-NBI was excellent in well-differentiated (WD) adenocarcinoma and lesions below 20 mm in size. However, histopathological confirmation is needed to assess the demarcation of non-WD adenocarcinomas and EGC over 20 mm in size.

Diagnostic ability of magnifying endoscopy with blue laser imaging for early gastric cancer: a prospective study.

BACKGROUND: Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation. The aim of this study was to evaluate the usefulness of BLI for the diagnosis of early gastric cancer. METHODS: This single center prospective study analyzed 530 patients. The patients were examined with both conventional endoscopy with white-light imaging (C-WLI) and magnifying endoscopy with BLI (M-BLI) at Kyoto Prefectural University of Medicine between November 2012 and March 2015. The diagnostic criteria for gastric cancer using M-BLI included an irregular microvascular pattern and/or irregular microsurface pattern, with a demarcation line according to the vessel plus surface classification system. Biopsies of the lesions were taken after C-WLI and M-BLI observation. The primary end point of this study was to compare the diagnostic performance between C-WLI and M-BLI. RESULTS: We analyzed 127 detected lesions (32 cancers and 95 non-cancers). The accuracy, sensitivity, and specificity of M-BLI diagnoses were 92.1, 93.8, and 91.6 %, respectively. On the other hand, the accuracy, sensitivity, and specificity of C-WLI diagnoses were 71.7, 46.9, and 80.0 %, respectively. CONCLUSIONS: M-BLI had improved diagnostic performance for early gastric cancer compared with C-WLI. These results suggested that the diagnostic effectiveness of M-BLI is similar to that of magnifying endoscopy with narrow-band imaging (M-NBI).

Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model.

Secondary hyperparathyroidism (SHPT) is a major comorbidity of chronic kidney disease (CKD). Chronic elevation of PTH levels is associated with cortical bone deterioration and increase in the risk of fractures in CKD patients. Here, we evaluated the effect of repeated administration of upacicalcet, a novel positive allosteric modulator of the calcium-sensing receptor, in a rat model of adenine-induced renal failure, by determining serum levels of intact PTH (iPTH), calcium, phosphorus, creatinine, and urea nitrogen. Furthermore, parathyroid hyperplasia (parathyroid gland weight and Ki-67-positive cell density), ectopic calcification (calcium content in the thoracic aorta, kidney and heart and positive von Kossa staining in the thoracic aorta), and bone morphometry parameters (cortical porosity and fibrosis volume) were evaluated. Rats treated with either 0.2 mg/kg or 1 mg/kg upacicalcet exhibited significantly lower serum iPTH levels than CKD-control rats, as early as 7 days after the first dose. Repeated administration of upacicalcet reduced serum iPTH levels and inhibited parathyroid hyperplasia in rats with adenine-induced severe renal failure. Moreover, it suppressed ectopic calcification and cortical pore formation. In contrast, serum calcium and phosphorus levels were not significantly affected, suggesting a low risk of hypocalcemia, which often occurs with SHPT treatment. In conclusion, repeated administration of upacicalcet decreased serum iPTH levels and suppressed parathyroid hyperplasia in the adenine-induced CKD rat model of SHPT. Furthermore, ectopic calcification and cortical pore formation were suppressed without significant changes in blood mineral parameters. Upacicalcet safely inhibited the progression of SHPT in an adenine-induced CKD rat model.

Simultaneous resection of gastric and gallbladder metastasis from renal cell carcinoma treated by laparoscopic and endoscopic cooperative surgery: a case report.

BACKGROUND: Metastases to the stomach or gallbladder from any malignancy is rarely noted, and simultaneous metastases to both organs are atypical. We present a unique case of simultaneous multifocal metastases of the stomach and gallbladder from renal cell carcinoma (RCC). CASE PRESENTATION: The case involved a 60-year-old man, with a past history of RCC (clear cell type, G2, T1b N0 M0 Stage I) treated by a right nephrectomy. Three years after the nephrectomy, a routine gastrointestinal endoscopy found an ulcerative lesion in the greater curvature of the gastric body. The gastric tumor was pathologically proven to be a metastasis from RCC. Furthermore, computed tomography incidentally revealed a mass lesion in the fundus of the gallbladder, which was also diagnosed as a potential metastasis from RCC. As endoscopic ultrasonography of the gastric tumor suggested the tumor potentially invaded to the submucosal layer, gastric wedge resection via a laparoscopic and endoscopic cooperative surgery (LECS) technique was applied to the gastric tumor, and laparoscopic cholecystectomy to the gallbladder tumor was simultaneously performed. Histological examination confirmed that the tumors of the stomach and gallbladder were both metastatic RCC. The hospitalization period after surgery was not eventful, and the patient was discharged on postoperative day 7. Thereafter, the patient required examination every 3 months, did not use anticancer agents, and has survived without relapse to 9 months after the surgery. CONCLUSIONS: For patients with locally resectable RCC metastases, complete metastasectomy may bring long-term tumor control. Moreover, LECS for gastric metastasis is a reasonable approach for minimal invasiveness and an oncologically feasible outcome.

Magnifying Endoscopy with Blue Laser Imaging Improves the Microstructure Visualization in Early Gastric Cancer: Comparison of Magnifying Endoscopy with Narrow-Band Imaging.

BACKGROUNDS: Magnifying endoscopy with blue laser imaging (ME-BLI) for diagnosis of early gastric cancer (EGC) is as effective as magnifying endoscopy with narrow-band imaging (ME-NBI). However, there are different EGCs in microstructure visualization between ME-BLI and ME-NBI. This study aimed to clarify the pathological features of the EGCs, in which microstructure visualization was different between ME-NBI and ME-BLI. METHODS: EGCs were classified into groups A (irregular microsurface pattern (MSP) in ME-BLI and absent MSP in ME-NBI), B (irregular MSP in two modalities), or C (absent MSP in two modalities), according to the vessel plus surface classification. We compared the pathological features of EGCs between the three groups. RESULTS: 17, four, and five lesions could be evaluated in detail in groups A, B and C, respectively. Well-differentiated adenocarcinomas with shallow crypts were more frequent in group A than in group B (58.8 and 0%, resp.). The mean crypt depth of group A was significantly shallower than that of group B (56 ± 20, 265 ± 64 µm, resp., P = 0.0002). CONCLUSIONS: ME-BLI could better visualize the microstructures of the EGCs with shallow crypts compared with ME-NBI. Therefore, ME-BLI could enable a more accurate diagnosis of EGC with shallow crypts.

Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation.

Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell­like cells. Using Reb­treated LS174T cells, the level of mucin content was assessed by periodic acid­Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel­forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentration­dependent manner. The p­Akt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via p­Akt. Reb­increased mucin may act as a strong non­specific barrier against pathogenic stimulants in various intestinal diseases.

Partially hydrolyzed guar gum enhances colonic epithelial wound healing via activation of RhoA and ERK1/2.

BACKGROUND AND AIMS: Healing of the intestinal mucosal epithelium was found to be a critical factor in the treatment of inflammatory bowel disease (IBD). In this study, we provide further evidence that partially hydrolyzed dietary fiber (PHGG) enhances colonic epithelial cell wound healing, and partially characterize the mechanism that governs this process. MATERIALS AND METHODS: Young adult mouse colonic (YAMC) epithelial cells were scraped with a 10 µl micro-pipette tip to denude a round of the monolayer and were incubated with PHGG. The area of cell migration was measured using Image J software. Meanwhile, Rho activation assays were utilized to monitor Rho activation levels. To assess in vivo effects, C57B6 mice were treated with DSS for 7 days and then provided food supplemented with PHGG for 8 days. RESULTS: YAMC cells treated with PHGG exhibited significantly enhanced wound healing compared to the control cells; however, this enhancement was inhibited by both Y-27632 (RhoA inhibitor) and U0126 (ERK1/2 inhibitor). Likewise, there was a PHGG-dependent increase in F-actin accumulation and Rho kinase activity that was blocked by U0126. Meanwhile, PHGG-dependent ERK1/2 activity was not inhibited by Y-27632. In the DSS-induced mouse colitis model, animals that received food supplemented with PHGG exhibited significant recovery of the colonic mucosa. CONCLUSIONS: In this study, we demonstrate that PHGG promotes colonic epithelial cell wound healing via activation of RhoA, which occurs downstream of ERK1/2 activation. These findings indicate that PHGG could be utilized as a therapeutic agent for patients with intestinal mucosal damage such as those with IBD.

Blue Laser Imaging-Bright Improves Endoscopic Recognition of Superficial Esophageal Squamous Cell Carcinoma.

Background/Aims. The aim of this study was to evaluate the endoscopic recognition of esophageal squamous cell carcinoma (ESCC) using four different methods (Olympus white light imaging (O-WLI), Fujifilm white light imaging (F-WLI), narrow band imaging (NBI), and blue laser imaging- (BLI-) bright). Methods. We retrospectively analyzed 25 superficial ESCCs that had been examined using the four different methods. Subjective evaluation was provided by three endoscopists as a ranking score (RS) of each image based on the ease of detection of the cancerous area. For the objective evaluation we calculated the color difference scores (CDS) between the cancerous and noncancerous areas with each of the four methods. Results. There was no difference between the mean RS of O-WLI and F-WLI. The mean RS of NBI was significantly higher than that of O-WLI and that of BLI-bright was significantly higher than that of F-WLI. Moreover, the mean RS of BLI-bright was significantly higher than that of NBI. Furthermore, in the objective evaluation, the mean CDS of BLI-bright was significantly higher than that of O-WLI, F-WLI, and NBI. Conclusion. The recognition of superficial ESCC using BLI-bright was more efficacious than the other methods tested both subjectively and objectively.

Linked color imaging improves endoscopic diagnosis of active Helicobacter pylori infection.

BACKGROUND AND STUDY AIMS: Linked color imaging (LCI) is a new image-enhanced endoscopy technique using a laser light source to enhance slight differences in mucosal color. The aim of this study was to compare the usefulness of LCI and conventional white light imaging (WLI) endoscopy for diagnosing Helicobacter pylori (H. pylori). PATIENTS AND METHODS: We retrospectively analyzed images from 60 patients examined with WLI and LCI endoscopy between October 2013 and May 2014. Thirty patients had H. pylori infections, and other thirty patients tested negative for H. pylori after eradication therapy. Four endoscopists evaluated the 2 types of images to determine which was better at facilitating a diagnosis of H. pylori infection. RESULTS: H. pylori infection was identified with LCI by enhancing the red appearance of the fundic gland mucosa. The accuracy, sensitivity, and specificity for diagnosing H. pylori infection using WLI were 74.2 %, 81.7 %, and 66.7 %, respectively, while those for LCI were 85.8 %, 93.3 %, and 78.3 %, respectively. Thus, the accuracy and sensitivity for LCI were significantly higher than those for WLI (P = 0.002 and P = 0.011, respectively). The kappa values for the inter- and intraobserver variability among the 4 endoscopists were higher for LCI than for WLI. CONCLUSIONS: H. pylori infection can be identified by enhancing endoscopic images of the diffuse redness of the fundic gland using LCI. LCI is a novel image-enhanced endoscopy and is more useful for diagnosing H. pylori infection than is WLI.