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Texture and color enhancement imaging (TXI) may improve the visibility of gastric tumors and allow their early detection. However, few reports have examined the utility of TXI. Between June 2021 and October 2022, 56 gastric tumors in 51 patients undergoing endoscopic submucosal dissection at Fukuchiyama City Hospital were evaluated preoperatively using conventional white light imaging (WLI), narrow-band imaging (NBI), and TXI modes 1 and 2. The color differences of the tumors and surrounding mucosae were evaluated using the CIE 1976 L*a*b color space, Additionally, the visibility scores were scaled. Of the 56 gastric tumors, 45 were early gastric cancers, and 11 were adenomas. Overall, the color difference in TXI mode 1 was considerably higher compared to WLI (16.36 ± 7.05 vs. 10.84 ± 4.05; p < 0.01). Moreover, the color difference in early gastric cancers was considerably higher in TXI mode 1 compared to WLI, whereas no significant difference was found in adenomas. The visibility score in TXI mode 1 was the highest, and it was significantly higher compared to WLI. Regarding adenomas, the visibility score in TXI mode 1 was also significantly higher compared to that in WLI. TXI may provide improved gastric tumor visibility. [ABSTRACT FROM AUTHOR]

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET. [ABSTRACT FROM AUTHOR]

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-high) pancreatic cancer are rare, and information is lacking. Based on the C-CAT database, we analyzed the clinical and genomic characteristics of patients with these subtypes. Methods: We retrospectively reviewed data on 2206 patients with unresectable pancreatic adenocarcinoma enrolled in C-CAT between July 2019 and January 2022. The clinical features, proportion of genomic variants classified as oncogenic/pathogenic in C-CAT, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) of chemotherapy as first-line treatment were evaluated. Results: Numbers of patients with MSI-H and TMB-high were 7 (0.3%) and 39 (1.8%), respectively. All MSI-H patients were TMB-high. MSI-H and TMB-high patients harbored more mismatch repair genes, such as MSH2, homologous recombination-related genes, such as ATR and BRCA2, and other genes including BRAF, KMT2D, and SMARCA4. None of the 6 MSI-H patients who received chemotherapy achieved a clinical response, including 4 patients treated with gemcitabine plus nab-paclitaxel (GnP) therapy, whose DCR was significantly lower than that of microsatellite stable (MSS) patients (0 vs. 67.0%, respectively, p = 0.01). Among the TMB-high and TMB-low groups, no significant differences were shown in ORR, DCR (17.1 vs. 23.1% and 57.1 vs. 63.1%, respectively), or median TTF (25.9 vs. 28.0 weeks, respectively) of overall first-line chemotherapy. Conclusions: MSI-H and TMB-high pancreatic cancers showed some distinct genomic and clinical features from our real-world data. These results suggest the importance of adapting optimal treatment strategies according to the genomic alterations. [ABSTRACT FROM AUTHOR]

Introduction: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. Patients and Methods: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. Results: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). Conclusions: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Special subtypes of pancreatic cancer, such as acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), and anaplastic carcinoma of the pancreas (ACP), are rare, and so data on them are limited. Using the C-CAT database, we analyzed clinical and genomic characteristics of patients with these and evaluated differences on comparison with pancreatic ductal adenocarcinoma (PDAC) patients. Methods: We retrospectively reviewed data on 2691 patients with unresectable pancreatic cancer: ACC, ASC, ACP, and PDAC, entered into C-CAT from June 2019 to December 2021. The clinical features, MSI/TMB status, genomic alterations, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) on receiving FOLFIRINOX (FFX) or GEM + nab-PTX (GnP) therapy as first-line treatment were evaluated. Results: Numbers of patients with ACC, ASC, ACP, and PDAC were 44 (1.6%), 54 (2.0%), 25 (0.9%), and 2,568 (95.4%), respectively. KRAS and TP53 mutations were prevalent in ASC, ACP, and PDAC (90.7/85.2, 76.0/68.0, and 85.1/69.1%, respectively), while their rates were both significantly lower in ACC (13.6/15.9%, respectively). Conversely, the rate of homologous recombination-related (HRR) genes, including ATM and BRCA1/2, was significantly higher in ACC (11.4/15.9%) than PDAC (2.5/3.7%). In ASC and ACP, no significant differences in ORR, DCR, or TTF between FFX and GnP were noted, while ACC patients showed a trend toward higher ORR with FFX than GnP (61.5 vs. 23.5%, p = 0.06) and significantly more favorable TTF (median 42.3 vs. 21.0 weeks, respectively, p = 0.004). Conclusions: ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. Methods: This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30 min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50 kg were administered a 50 mg dose, while those weighing < 50 kg were administered a 25 mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. Results: Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). Conclusions: The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP. [ABSTRACT FROM AUTHOR]

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer. [ABSTRACT FROM AUTHOR]

Small intestinal lipomas are rare, but may cause obscure gastrointestinal bleeding. The endoscopic unroofing technique excises only the upper third of the lipoma and allows both histological confirmation and complete treatment with minimal risk of perforation. We present a rare case of obscure gastrointestinal bleeding caused by a jejunal lipoma. A 75-year-old man on antiplatelet therapy presented to our department with melena and anemia. Computed tomography revealed he had a 45-mm jejunal submucosal tumor with fat attenuation. Endoscopic resection using an endoscopic unroofing technique with double balloon enteroscopy was successfully performed. The tumor was confirmed to be a lipoma. [ABSTRACT FROM AUTHOR]

Background and Objective: This study aimed to evaluate endoscopic findings using linked color imaging (LCI) and blue laser imaging (BLI) and to determine a diagnostic predictor for duodenal adenocarcinomas. Methods: All consecutive patients who underwent endoscopic resection for superficial non-ampullary duodenal epithelial tumors (SNADETs) between October 2012 and June 2019 were enrolled in this study. Two highly experienced endoscopists investigated six morphological findings using both white light imaging and LCI and three magnifying endoscopic findings using magnifying BLI (M-BLI). Results: A total of 90 patients with 110 SNADETs, including 87 adenocarcinomas and 23 adenomas, were analyzed in this study. Among the non-magnifying endoscopic findings, the presence of reddish color, orange color on LCI (orange color sign), lobulation, depression, and marginally white opaque substance were found significantly more frequently in adenocarcinomas than in adenomas (p = 0.015, p < 0.001, p = 0.048, p < 0.001, and p = 0.007, respectively). Among the magnifying endoscopic findings, a mixed microsurface pattern (MSP), irregular MSP, and irregular microvascular pattern were found significantly more frequently in adenocarcinomas than in adenomas (p < 0.001, p < 0.001, and p = 0.002, respectively). In the multivariate analysis of all endoscopic findings associated with adenocarcinoma, orange color sign (odds ratio [OR] 10.46; 95% confidence interval [CI]: 1.42–77.08; p = 0.021), mixed MSP (OR 4.66; 95% CI: 1.02–21.40; p = 0.048), and irregular MSP (OR 13.11; 95% CI: 1.41–121.99; p = 0.024) were independent predictors of adenocarcinoma. Conclusions: The presence of orange color sign on LCI and mixed/irregular MSP on M-BLI were independent diagnostic predictors that were frequently observed in duodenal adenocarcinoma. [ABSTRACT FROM AUTHOR]

An 84‐year‐old woman who was admitted for protein‐losing gastroenteropathy associated with radiation enteritis 10 years after pelvic radiotherapy developed pyelonephritis. She became anuric despite having an indwelling bladder catheter. Imaging studies revealed bladder wall thickening, bilateral hydroureter formation, and hydronephrosis. Autopsy findings led to a diagnosis of gangrenous cystitis (GC). Our case indicates that radiation‐induced late effects may be an indirect cause of GC, not a direct cause as previously suggested, and that GC may induce bilateral vesicoureteral junction obstruction. [ABSTRACT FROM AUTHOR]

Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach. [ABSTRACT FROM AUTHOR]

Background: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. Aim: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. Methods: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. Results: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. Conclusion: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy. [ABSTRACT FROM AUTHOR]

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20 μg/g b.w.) or a vehicle as a control for 5 days, and pegfilgrastim was administered subcutaneously at 1 μg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells. [ABSTRACT FROM AUTHOR]

Background and Aim: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. Methods: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor‐α, interferon γ, interleukin‐1β, interleukin‐2, interleukin‐4, interleukin‐5, interleukin‐6, interleukin‐7, interleukin‐8, interleukin‐9, interleukin‐10, interleukin‐12, interleukin‐13, interleukin‐15, interleukin‐17A, interleukin‐17F, interleukin‐18, interleukin‐21, interleukin‐22, interleukin‐23, interleukin‐27, and interleukin‐33 was measured by quantitative real‐time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. Results: Ten cytokines, including interleukin‐2, interleukin‐4, interleukin‐8, interleukin‐10, interleukin‐12, interleukin‐15, interleukin‐17A, interleukin‐21, interleukin‐23, and interleukin‐33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin‐8 expression was the most useful predictor. Conclusions: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin‐8 expression was the most useful for predicting relapse. [ABSTRACT FROM AUTHOR]

SMARCA4-deficient sarcoma was first reported in the chest and recently in the uterus, but not in the stomach. Here, we present a patient diagnosed with SMARCA4-deficient sarcoma of the stomach, using histochemistry. An emergency operation was performed due to perforation of the tumor. However, one month after the operation, two nodes recurred, and six cycles of combination chemotherapy consisting of adriamycin and ifosfamide were administered. The combination chemotherapy showed a remarkable effect, and complete remission was achieved. The patient was alive without recurrence after 48-month follow-up. SMARCA4-deficient sarcoma is an exceedingly rare tumor with an extremely poor therapeutic response to anticancer drugs. Herein, we present the first case of SMARCA4-deficient sarcoma of the stomach, where a complete response to chemotherapy was achieved. [ABSTRACT FROM AUTHOR]

Background: In Japan, laser light source (Laser) endoscopy is widely available, and the characteristics of light-emitting diode light source (LED) endoscopy have not been clarified. Aims: We assessed the visibility of early gastric cancers (EGCs) and Helicobacter pylori (H. pylori)-associated gastritis for LED endoscopy compared with laser endoscopy using white-light imaging (WLI) and linked color imaging (LCI). Methods: We assessed 99 lesions between February 2019 and March 2020. The visibility was scored from four (excellent visibility) to one (poor visibility) by evaluating videos including EGCs and gastric mucosa captured using WLI and LCI with LED endoscopy (LED-WLI and LED-LCI, respectively) and laser endoscopy (Laser-WLI and Laser-LCI, respectively). The primary end point was the non-inferiority of the visibility of EGCs and H. pylori-associated gastritis between LED-/Laser-WLI and LED-/Laser-LCI. Results: The visibility scores of EGCs for LED-/Laser-WLI and LED-/Laser-LCI were 3.14/2.97 and 3.39/3.35, respectively. The visibility scores of H. pylori-associated gastritis [intestinal metaplasia (IM), diffuse redness (DR), regular arrangement of collecting venules (RAC) and map-like redness (MR)] for LED-/Laser-WLI and LED-/Laser-LCI were 3.05/2.85 and 3.60/3.50 (IM), 2.76/2.50 and 2.96/2.86 (DR), 2.69/2.44 and 2.77/2.62 (RAC) and 2.97/2.75 and 3.39/3.27 (MR). Non-inferiority was demonstrated for visualizing EGCs and H. pylori-associated gastritis. Conclusions: LED-WLI and LED-LCI can be used to visualize EGCs and H. pylori-associated gastritis with non-inferiority to Laser-WLI and Laser-LCI. Furthermore, even with LED, LCI was more effective than WLI for evaluating EGCs and H. pylori-associated gastritis. Therefore, LED endoscopy can be used to detect EGCs and evaluate H. pylori-associated gastritis accurately. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in some cancers. This study aimed to evaluate the effect of PPIs on 5-Fuorouracil (5-FU)-based therapy for advanced esophageal cancer based on in vitro experiments and a clinical study. In the present study, PPIs showed a dose-dependent antitumor effect on esophageal cancer cells and enhanced the sensitivity of esophageal cancer cells to 5-FU at sublethal concentrations. In the clinical setting, patients treated with oral PPIs showed a superior tumor response to 5-FU and better overall survival in comparison to the non-PPI group. These results indicate that PPIs can enhance chemosensitivity in esophageal cancer patients treated with 5-FU. Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. Methods: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. Results: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12–0.76). Conclusions: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients. [ABSTRACT FROM AUTHOR]

The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 patients with qUC and 59 healthy controls (HCs) were enrolled (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and the Kyoto Encyclopedia of Genes and Genomes database. There were significant differences in fecal microbiota diversity between HC and qUC subjects, with 13 taxa characterizing each subject. Despite no significant difference in variation of microbiota in a single sample (α diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (β diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan–Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways. [ABSTRACT FROM AUTHOR]

Background and study aim: This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC). Patients and methods: All consecutive patients who underwent endoscopic submucosal dissection (ESD) for primary superficial ESCC (SESCC) without a history of ESCC between January 2013 and January 2016 were enrolled. Three highly experienced endoscopists investigated seven endoscopic findings using non-magnifying BLI as follows: (1) a brownish area with unclear margin, (2) white flat deposits, (3) multiple foci of dilated vessels, (4) low capillary permeability, (5) multiple glycogenic acanthosis, (6) horizontal lines, and (7) a nonuniform color tone. Furthermore, Lugol-voiding lesions (LVLs) were graded according to the number of LVLs per endoscopic view (A, no lesions; B, 1–9 lesions; C, ≥ 10 lesions). Results: A total of 102 SESCC patients who underwent ESD were included. Multivariate analyses showed that multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone were significantly associated with metachronous ESCC (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.01–5.46; P = 0.049, HR 5.25; 95% CI 1.86–15.01; P = 0.002 and HR 3.17; 95% CI 1.11–9.43; P = 0.032, respectively). The three-year cumulative incidence of metachronous ESCC was significantly higher in patients with low capillary permeability and a nonuniform color tone than in patients without these findings. (41.1% vs. 6.0%, 45.0% vs. 12.7%, respectively, P < 0.001 for both). Conclusion: BLI findings of multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone in the background esophageal mucosa were risk factors for patients with metachronous ESCC after ESD. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinoma (NEC) of the esophagus at early-stage is very rare due to its rapidly progression. Here, we reported a case of esophageal NEC at early stage treated with endoscopic submucosal dissection (ESD). A 63-year-old man underwent esophagogastroduodenoscopy (EGD) and a lesion was detected in the thoracic esophagus. The preoperative diagnosis was squamous cell carcinoma (SCC) based on magnifying endoscopy; however, the pathological diagnosis was NEC with an invasion of muscularis mucosa accompanied by lymphovascular invasion. Adjuvant chemoradiotherapy was recommended after ESD; however, the patient did not accept additional treatments. The patient was alive with no recurrence 15 months after ESD. In this case, there were three malignant components among SCC, NEC, and adenocarcinoma with transitional areas among each component in the superficial part of the lesion. [ABSTRACT FROM AUTHOR]

Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach. [ABSTRACT FROM AUTHOR]

Background: Hemophilia A causes a bleeding tendency due to the congenital absence of coagulation factor VIII or the production of antibodies against it. It is challenging to perform invasive procedures in patients with hemophilia A. Walled-off necrosis (WON) is a serious complication of acute pancreatitis. Recently, a new metallic stent has been used to drain WON. Clinical course: We treated a 32-year-old man who developed WON due to acute pancreatitis and has severe congenital hemophilia A. Since conservative treatment was ineffective, he underwent endoscopic ultrasonography (EUS)-guided transgastric WON drainage using a new metallic stent Hot AXIOS System. The procedure was successful without any severe hemorrhagic complications. Before and after the procedure, his clotting factors were strictly monitored by a hemophilia specialist. Conclusion: EUS-guided pancreatic cyst drainage can be an effective option for WON in patients with severe congenital hemophilia, under adequate management. [ABSTRACT FROM AUTHOR]

Background and Aim: Efficient intestinal wound healing is essential for good prognoses of ulcerative colitis (UC). Although bile acids and the transmembrane G‐protein‐coupled receptor (TGR) 5 have been reported to affect wound healing in intestinal epithelial cells, the detailed underlying mechanisms are unclear. Here, we investigated the role of TGR5 in wound healing in the context of colonic epithelial cells in the presence of bile acids. Methods: The expression of TGR5 in the colonic epithelium of both a dextran sulfate sodium (DSS)‐induced colitis mouse model (recovery phase), and UC patients in clinical remission, was evaluated. Young adult mouse colonic epithelial (YAMC) cells were then used to evaluate wound healing after treatment with deoxycholic acid (DCA); TGR5 was silenced in YAMC cells via shRNA‐transfection, and a wound‐healing assay in the presence of DCA was performed. Furthermore, we investigated the role of the activation of AKT in the context of wound healing. Results: The expression of TGR5 was decreased in the colonic epithelium of both mice with DSS‐induced colitis and UC patients. Additionally, DCA significantly delayed wound healing in YAMC cells but not in TGR5 silenced ones. Of note, the DCA‐induced activation of AKT signaling in YAMC cells was inhibited by TGR5 silencing, and AKT inhibitors prevented the wound healing delay induced by DCA. Conclusions: Overall, we show that DCA delays wound healing in the context of colonic epithelial cells through AKT activation. These results may support the development of new therapeutic approaches for epithelial regeneration in UC. [ABSTRACT FROM AUTHOR]

Recent advances in magnifying endoscopy with narrow-band imaging/blue laser imaging have aided in the diagnosis of gastrointestinal lesions. However, it requires knowledge of the relationship between magnifying endoscopic and histopathological images. We propose a novel method which makes possible a complete correspondence between magnifying endoscopic and histopathological images at the single glandular duct level. The KOTO method II enables three-dimensional visualization of the correlation between the endoscopic surface pattern of the mucosa and histopathological images. This method may be helpful in the development of diagnosis using magnifying endoscopy. [ABSTRACT FROM AUTHOR]

Background and Aim: The Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are used to assess endoscopic mucosal healing in patients suffering from ulcerative colitis. Although mucosal healing is defined by MES 0, relapse of ulcerative colitis is often observed. Over a 48‐month period, this study investigated the efficacy of linked color imaging (LCI) in predicting the long‐term prognosis of ulcerative colitis patients diagnosed with MES 0. Methods: Overall, 26 patients in ulcerative colitis remission, diagnosed with MES 0, were enrolled. Using a LASEREO endoscopic system (Fujifilm Co., Tokyo, Japan), endoscopic colonic images were assessed with linked color imaging and the colitis endoscopic index of severity. Endoscopic LCI images were separated into three subgroups (A, no redness; B, redness with visible vessels; and C, redness without visible vessels). The Geboes score was used to evaluate histology; active mucosa was defined as GS > 2B.1. Results: Linked color imaging classification subdivided colonic mucosa, which had been diagnosed with MES 0, into two classes. The LCI‐A group did not relapse, and the non‐relapse rate was significantly higher (P = 0.018) than that in the LCI‐B group. No difference in relapse rates was observed between patients with a colitis endoscopic index of severity of 0 and 1 (P = 0.655). There was no statistical difference between the composition of LCI‐A group and the relapse rate between active and inactive mucosa diagnosed by Geboes score. Conclusions: This methodology can be used to evaluate mucosal healing and predict long‐term outcomes in ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

A 60-year-old man with autosomal dominant polycystic kidney disease presented with malaise, melena, and epigastric discomfort. Esophagogastroduodenoscopy revealed a massive elevated gastric cancer lesion involving the cardia. Histopathological evaluation of a biopsy specimen showed poorly differentiated adenocarcinoma. Fluorodeoxyglucose-positron emission tomography revealed significant fluorodeoxyglucose uptake in the stomach, liver, bones, and bone marrow. He was diagnosed with metastatic gastric cancer resistant to chemotherapy, and he developed bone marrow carcinomatosis and disseminated intravascular coagulation and died 8 weeks after disease onset. A statistically significant association is reported between autosomal dominant polycystic kidney disease and gastric cancer. Moreover, the specific clinical features observed in our patient could be attributed to the molecular disorders like PC-1 and mechanistic target of rapamycin that are known to occur in autosomal dominant polycystic kidney disease. [ABSTRACT FROM AUTHOR]

Colonoscopy is the gold standard for detecting earlier stages of CRC, although screening of patients is difficult because of invasiveness, low compliance and procedural health risks. Therefore, the need for new screening methods for CRC is rising. Previous studies have demonstrated the diagnostic ability of serum BAs; however, the results have been inconsistent. In this study, we conducted a comprehensive analysis of serum BAs from patients with CRC and verified their diagnostic ability to detect CRC. A total of 56 CRC patients (n = 14 each of stages I–IV), 59 patients with colonic adenoma and 60 healthy controls were included. Age and sex were matched for each group. Serum BA compositions were measured by LC-MS/MS and serum concentration of 30 types of BAs were analysed by discriminant analysis with multidimensional scaling method. Free CA, 3epi-DCA&CDCA, 3-dehydro CA, GCA and TCA were extracted as principal component (PC) 1 and free 3-dehydroDCA as PC 2 by canonical discriminant function coefficients. The verification of discriminability using cross-validation method revealed that the correct classification rate was 66.3% for original data and 52.6% for cross-validation data. A combined analysis using comprehensive serum BA concentration can be an efficient method for screening CRC. [ABSTRACT FROM AUTHOR]

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse.Methods: Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively.Results: The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the "relapse" group, while those from patients that did not relapse formed the "remission" group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046).Conclusions: Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: There are few studies reporting the clinical outcomes of noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) from the perspective of patient health condition/status. Thus, the aim of this study was to investigate clinical outcomes of noncurative ESD considering not only curability but also patient factors such as advanced age, comorbidities, and nutritional status. Methods: Between April 2007 and March 2012, 95 patients who underwent noncurative ESD for EGC were enrolled in the study. Patients were categorized by treatment after ESD: additional gastrectomy (49 patients) and follow-up (46 patients). Clinical outcomes were evaluated between the 2 groups for overall survival (OS). Results: The absence of lymphovascular involvement and age ≥80 years were significantly associated with decision-making for observation after noncurative ESD. The OS rates were higher in female patients, patients with better Eastern Cooperative Oncology Group performance status (≤1) or low-risk comorbidity (Charlson Comorbidity Index [CCI ≤ 2]), patients with ulcerative findings, and those who underwent radical gastrectomy. Multivariate Cox proportional hazards analysis indicated that presence of a high-risk comorbidity (CCI ≥ 3) was a significant prognostic factor (hazard ratio: 16.43, p = 0.024) in patients who underwent noncurative ESD for EGC. Conclusion: High-risk comorbidity is the primary prognostic parameter in terms of patient factors after noncurative ESD for EGC. The CCI should be considered as a prognostic factor in patients who underwent noncurative ESD for EGC. [ABSTRACT FROM AUTHOR]

Identifying the depth of invasion (DOI) of superficial esophageal squamous cell carcinoma (SESCC) is crucial to determine the indication for endoscopic resection. This retrospective, single-center study aimed to evaluate the diagnostic efficacy of magnifying blue laser imaging (M-BLI) compared with white-light imaging (WLI) or magnifying narrow-band imaging (M-NBI) for identifying the DOI of SESCC. A total of 160 consecutive patients with SESCCs who underwent endoscopic submucosal dissection were enrolled in this study. Still images of the lesion were obtained using WLI, M-BLI and M-NBI prior to endoscopic submucosal dissection. Three endoscopists retrospectively evaluated the DOI using WLI according to non-magnifying findings and using M-BLI and M-NBI images according to the magnifying endoscopic classification of the Japan Esophageal Society. The diagnostic accuracy of each modality was compared using the chi-square test. The DOIs in 160 SESCCs evaluated pathologically were as follows: invasion to the epithelium or lamina propria mucosa in 130, invasion to the lamina muscularis mucosa or submucosa to a depth ≤ 200 μm in 18, and invasion to the submucosa to a depth > 200 μm in 12. The overall diagnostic accuracy rates of WLI, M-BLI, M-NBI, WLI with M-BLI (WLI + M-BLI), and WLI with M-NBI (WLI + M-NBI) were 86.9, 91.2, 90.6, 95.6 and 94.4%, respectively. Significant differences were found between WLI and WLI + M-BLI or WLI + M-NBI (P  = 0.006 and P  = 0.021, respectively). The concordance of intrapapillary capillary loops between M-BLI and M-NBI was 91.2%. The kappa coefficients for interobserver variability of the three endoscopists for M-BLI and M-NBI were 0.728/0.649/0.792 and 0.729/0.666/0.791, respectively, while those for intraobserver variability were 0.919/0.746/0.778 and 0.736/0.720/0.745, respectively. Similar to M-NBI, M-BLI was useful in predicting the DOI of SESCCs. [ABSTRACT FROM AUTHOR]

Background and Aim: Several studies have identified postinduction therapy predictors of long‐term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC. Methods: Ninety‐five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5‐aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti‐Tumor Necrosis Factor (TNF)‐α antibodies], and laboratory data (hemoglobin, albumin, C‐reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P < 0.05 was considered significant. Results: All clinical parameters were not significant predictors of colectomy. Among laboratory parameters, the serum albumin level on admission was a significant independent predictor of colectomy (odds ratio: 6.097, 95% confidence interval: 1.8310–20.3047). Receiver operating characteristic curves were plotted for the serum albumin levels of the 95 patients at admission. The cut‐off value of serum albumin was 2.45 g/dL. Conclusions: When the serum albumin level of UC patients at admission is below 2.45 g/dL, we should consider presenting the option of surgical treatment to patients. [ABSTRACT FROM AUTHOR]

Background and study aim: This study aimed to assess the safety and feasibility of endoscopic submucosal dissection (ESD) using a scissors‐type knife with prophylactic closure using over‐the‐scope clip (OTSC) for superficial non‐ampullary duodenal epithelial tumors (SNADETs). Patients and methods: Consecutive patients who underwent ESD for SNADETs >10 mm between January 2009 and July 2019 were retrospectively enrolled. We performed ESD using either a needle‐type knife (Flush Knife‐ESD) or a scissors‐type knife (Clutch Cutter‐ESD). Mucosal defects were prophylactically closed using three methods: conventional clip, laparoscopic closure, or OTSC. Results: A total of 84 lesions were resected using the Flush Knife‐ESD and the Clutch Cutter‐ESD (37 and 47 patients, respectively), and conventional clip, laparoscopic closure, and OTSC for mucosal defect closure after ESD were applied in 13, 13, and 56 lesions, respectively. The R0 resection rate was significantly higher in the Clutch Cutter‐ESD than that in the Flush Knife‐ESD (97.9% vs 83.8%, respectively, P = 0.040). The intraoperative perforation rate was significantly lower in the Clutch Cutter‐ESD than in the Flush Knife‐ESD (0% vs 13.5%, respectively, P = 0.014). Complete closure rates of conventional clip, laparoscopic closure, and OTSC were 76.9%, 92.3%, and 98.2%, respectively (P = 0.021); and delayed perforation rates were 15.4%, 7.7%, and 1.8%, respectively (P = 0.092). Conclusions: Endoscopic submucosal dissection using a scissors‐type knife with prophylactic OTSC closure is safe and feasible for the low‐invasive treatment of SNADETs. [ABSTRACT FROM AUTHOR]

Background: Local recurrence after cold snare polypectomy (CSP) of colorectal polyps has not been well analyzed. In this study, we analyzed the characteristics of local recurrence.Methods: We retrospectively reviewed consecutive lesions resected by CSP from 2014 to 2016 and lesions that were followed up at ≥ 10 months after CSP, were analyzed. Our indication for CSP was a benign tumor of < 15 mm in size. We analyzed local recurrence and its risk factors using multivariate analyses. In addition, we compared lesions of ≥ 10 mm and < 10 mm. Moreover, therapeutic methods for recurrence were analyzed.Results: Finally, we analyzed 554 cases out of 820 consecutive cases. The mean polyp size was 5.3 ± 2.8 mm and the en bloc resection and histopathological complete resection rates were 99.3% and 70.2%, respectively. The overall recurrence rate was 1.9% (mean follow-up period: 13.0 ± 4.0 months). Significant differences were observed between 11 recurrent lesions and 543 lesions without recurrence regarding polyp size (8.0 ± 3.7 mm vs. 5.2 ± 2.7 mm, p < 0.001), rate of sessile-serrated polyp (27.3% vs. 3.0%, p < 0.001), and histopathological positive margin (45.4% vs. 3.7%, p = 0.019). Multivariate analyses showed that a histopathological positive margin was the only significant risk factor for local recurrence (OR 16.600, 95% CI 3.707-74.331, p < 0.001). Regarding the comparison between 74 lesions of ≥ 10 mm and 480 lesions of < 10 mm, significant differences were observed in the en bloc resection rate (93.2% vs. 100%, p < 0.001), high-grade dysplasia rate (8.1% vs. 0.8%, p < 0.001), and histopathological complete resection rate (54.0% vs. 72.7%, p = 0.001). The recurrence rates of these two groups were 5.4% and 1.4%, respectively (p = 0.069). All recurrent cases could be resected with repeat CSP.Conclusions: The local recurrence rate after CSP for lesions of < 10 mm was 1.4%. CSP was not recommended for lesions of ≥ 10 mm due to high rates of recurrence and malignancy. [ABSTRACT FROM AUTHOR]

Background and Aim: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short‐chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. Methods: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen‐activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. Results: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c‐Jun N‐terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate‐induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. Conclusions: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Signet-ring cell carcinoma, a colorectal cancer (CRC) subtype, sometimes shows metastases to uncommon metastatic sites. However, gastric metastasis is extremely rare. Here, we describe a case of gastric metastasis from colonic cancer. A 76-year-old woman presented with anemia. Colonoscopic biopsy revealed a CRC on the transverse colon showing a poorly differentiated adenocarcinoma with a partial component of the signet-ring carcinoma. Computed tomography revealed multiple subcutaneous nodules on her chest and back, and a tumor in the left lower lobe of her lung. Esophagogastroduodenoscopy showed a submucosal tumor-like lesion in the upper gastric body, and endoscopic biopsy revealed the poorly differentiated adenocarcinoma along with the partial component of the signet-ring carcinoma as well as the colonic, subcutaneous, and pulmonary lesion. The findings of endoscopic and microscopic examinations revealed gastric metastasis from CRC on the transverse colon. A systemic chemotherapy was given, and the biopsy conducted 1 year after the initial chemotherapy revealed no evidence of the residual tumor tissue in the gastric lesion. However, best supportive care was recommended depending on metastasis to the rectum. Our case suggests that gastric metastases from CRC should be considered in patients with lesions resembling a submucosal tumor accompanied by central depression and erosion. [ABSTRACT FROM AUTHOR]

Preoperative or induction chemotherapy with docetaxel, cisplatin, plus 5‐fluorouracil (DCF) is a promising regimen for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). However, the current guidelines fail to recommend an optimal dosing schedule of pegfilgrastim along with the DCF regimen to prevent FN. In the present study, we assessed the efficacy and safety of giving pegfilgrastim early on day 3 during DCF therapy for esophageal cancer. In this single‐arm phase II study, patients with squamous cell carcinoma of the esophagus were recruited. They were treated with the DCF therapy on days 1‐5, with pegfilgrastim given on day 3. Primary endpoint was the occurrence of grade 4 neutropenia. Secondary endpoints included the incidence of FN, grade 3 neutropenia, dose delays/reductions, antitumor effect, and safety. Between July 2016 and December 2018, 23 patients were enrolled. The incidence of grade 4 neutropenia was 8.7% (95% confidence interval 1.1%‐28.0%). No patient experienced FN. Of the 19 patients who received two cycles of DCF, one required a dose reduction/treatment delay due to hematological toxicity in the second treatment cycle. No serious adverse events, considered relevant to pegfilgrastim, were observed. This is the first prospective study that showed an efficacious dosing schedule of pegfilgrastim for preventing hematological toxicity during DCF therapy. The results might be generalized to other similar regimens where continuous infusions of 5‐fluorouracil are used. [ABSTRACT FROM AUTHOR]

Background/Aims: The purpose of this study was to evaluate the safety and efficacy of gastric endoscopic submucosal dissection (ESD) using the Clutch Cutter (CC), a scissor-type knife, compared with those of procedures using conventional devices. Methods: This single-center retrospective study evaluated 237 patients with early gastric cancer: 83 who underwent ESD using the CC group and 154 who underwent ESD using the insulated-tip knife 2 (IT2 group). Clinicopathological features and technical outcomes were compared between the 2 groups using a propensity score-matched analysis. Results: In 61 pairs of matched patients, there was no significant difference in R0 resection, perforation, or postoperative bleeding between the CC and IT2 groups. Comparisons between the 2 groups showed similar treatment outcomes for an expert endoscopist. Nevertheless, there were significant differences between the 2 groups for nonexperts in terms of self-completion (61.7 and 24.5%, respectively, p < 0.001), mean procedure times (45 and 61 min, respectively, p = 0.002), and mean numbers of intraoperative bleeding points and bleeding points requiring hemostatic forceps (3 and 0 vs. 8 and 3, respectively, p < 0.001). Conclusion: Better self-completion rates and shorter procedure times were noted for gastric ESD using the CC by nonexperts than for that using IT2, probably due to hemostatic efficacy. [ABSTRACT FROM AUTHOR]

Background: Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis. Methods: One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy. Results: The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased. Conclusions: This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti‐inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. Methods: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound‐healing assay. Results: The colon epithelial regeneration ratio in the daikenchuto‐treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1‐induced enhancement was inhibited by extracellular signal‐regulated kinase and Rho inhibitors. Conclusions: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Human gut microbiota is involved in host health and disease development. Investigations of age-related and sex-related alterations in gut microbiota are limited, and the association between stool consistency and gut microbiota has not been fully investigated. We investigated gut microbiota differences related to age, sex, and stool consistency in healthy Japanese subjects.Methods: Two-hundred and seventy-seven healthy Japanese subjects aged 20-89 years were enrolled. Fecal samples were obtained to analyze the gut microbiome. We evaluated the association between stool consistency [Bristol stool scale (BSS)] and gut microbiota.Results: Although there were significant differences in the microbial structure between males and females, the α-diversity of gut microbiota showed no difference between males and females or among age groups. There were significant increases in genera Prevotella, Megamonas, Fusobacterium, and Megasphaera and Bifidobacterium, Ruminococcus, and Akkermansia in males and females, respectively. The ratio of hard stools (BSS types 1 and 2) was higher in females; the ratio of loose stools (BSS type 6) was higher in males. No younger male had BSS type 1 or type 2. Fusobacterium in males was significantly higher in the loose consistency group, and Oscillospira was significantly higher in the hard consistency group in males; Campylobacter, SMB53, and Turicibacter were significantly higher in the hard consistency group in females.Conclusions: Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function. [ABSTRACT FROM AUTHOR]