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Background: The transcription factor nuclear factor-κB (NF-κB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-κB activation in gastric cancer cell lines, there is little information on cellular localization of NF-κB in H. pylori-infected gastric mucosa. Methods: H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-κB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-κB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1β levels as measured with enzyme-linked immunosorbent assay with the degree of NF-κB expression. Results: NF-κB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-κB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-κB expression also correlated with mucosal IL-8 levels but not with IL-1β. Conclusions: H. pylori infection increases the expression of NF-κB in gastric mucosa, suggesting that NF-κB is involved in inflammatory responses to H. pylori. [ABSTRACT FROM AUTHOR]

Background: Although the pathogenesis of gastric xanthoma (GX) remains unclear, an association of GX with atrophic gastritis has been reported. Helicobacter pylori is closely related to atrophic gastritis. The aim of this study was to investigate the relationship among GX, H. pylori, and atrophic gastritis. Methods: Sixty-seven patients with GX were assessed for H. pylori infection by serum anti-H. pylori IgG antibody, in addition to the rapid urease test, culture, and histologic examination using biopsy specimens of the antrum and corpus. The findings were compared with 67 age- and sex-matched control subjects without GX. The distribution of atrophic gastritis was assessed endoscopically. The severity of atrophic gastritis was determined endoscopically and histologically. Serum pepsinogen (PG) levels were also measured. Immunohistochemical staining of GX samples for H. pylori antigen was performed. H. pylori clinical isolates from patients with GX and controls were assessed for cagA by means of polymerase chain reaction. Results: The prevalence of H. pylori was significantly higher in patients with GX than in controls (94% and 72%, respectively). A significantly more extensive atrophic gastritis was present in patients with GX, as determined endoscopically and histologically, than in controls. Serum PG-I levels and the PG-I/PG-II ratio were significantly lower in the GX group than in the control group. H. pylori antigens were frequently identified in the cytoplasm of xanthoma cells in H. pylori-positive specimens of GX (54 of 63 specimens, 86%), whereas no immunoreactivity for H. pylori antigens was detected in H. pylori-negative specimens of GX. There was no significant difference in the positive rate of cagA between the two groups. Conclusions: Our results identified a close relationship among H. pylori infection, GX, and atrophic gastritis. A proportion of GXs may be provoked by H. pylori infection. [ABSTRACT FROM AUTHOR]

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II. [ABSTRACT FROM AUTHOR]

Abstract Background Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. Methods This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. Results POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p Conclusions POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.

Abstract Background Endoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD. Methods Seven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia. Results En bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions. Conclusions Use of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn's disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000-1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson's r = - 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000-1.002). GDF-15 levels may indicate a low SMI with CD., (© 2022. The Author(s).)

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD., (© 2021. The Author(s).)

Background: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD)., Methods: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn's disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC., Results: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426)., Conclusions: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) can significantly reduce a patient's quality of life. GERD in SSc is occasionally resistant to conventional anti-acid treatment. Vonoprazan is an H + /K + -ATPase blocker that is approved in Japan for treatment of GERD. The aim of the present study was to evaluate the efficacy of vonoprazan in SSc-related GERD. The frequency scale for symptoms of GERD (FSSG) scores were collected before and after vonoprazan treatment in 15 SSc patients with GERD. Additionally, endoscopic esophagogastroduodenoscopy was performed in select patients. Conventional proton pump inhibitors or histamine-2 receptor antagonists had been previously administered in 93% (14/15) of the patients. Although the baseline esophagogastroduodenoscopy examination did not show severe erosion in the majority of patients, the mean total FSSG score before vonoprazan treatment was notably high (25.2±10.7) compared to a normal score of <8. After vonoprazan treatment, the FSSG score decreased to 9.6±7.0. The mean improvement rate of the total FSSG, acid reflux and dysmotility scores were 60.8±21.2% (P=0.0004), 67.3±24.8% (P<0.0001) and 55.4±26.0% (P=0.0022), respectively. These results suggest that vonoprazan may be a potentially effective treatment for GERD in patients with SSc., (Copyright: © Tabuchi et al.)

While retrospective studies have compared the efficacy of anti-tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.

[This corrects the article DOI: 10.1371/journal.pone.0170591.].

A γ-glutamyl hydroxymethyl rhodamine green probe (gGlu-HMRG) reacts with γ-glutamyltranspeptidase (GGT) and immediately produces fluorescence, is clinically applied for real-time cancers' visualization. Since Helicobacter pylori produces GGT, this study aimed to investigate whether gGlu-HMRG can be used to detect H. pylori infections. A wild-type H. pylori strain and the ggt gene-disrupted mutant were cultured and treated with gGlu-HMRG. This fluorescent probe assay was used to quantify GGT activity of H. pylori ex vivo using gastric biopsy specimens. The H. pylori diagnostic capabilities of the assay were determined from altered fluorescence intensity (FI) values at 5 min (FIV-5) and 15 minutes (FIV-15). Distinct fluorescence was identified in wild H. pylori strain, using gGlu-HMRG, whereas no fluorescence was observed in ggt gene-disrupted mutant strain. On ex vivo imaging of gGlu-HMRG, fluorescence intensity increased markedly with time in H. pylori-positive specimens; however, the H. pylori-negative specimens displayed a slight increase in FI. FIV-5 and FIV-15 differed significantly between H. pylori-positive and -negative specimens. FIV-15 differed significantly between H. pylori-positive and -eradicated group. This assay sensitivity and specificity were 75.0% and 83.3% in the antrum and 82.6% and 89.5% in the stomach body. GGT-activatable fluorescence probe is applicable for rapid diagnosis of H. pylori.

Background and Aim: The aim of this study was to clarify the additional effect of a concomitant elemental diet (ED) for patients with Crohn's disease on maintenance anti-tumor necrosis factor-α antibody (anti-TNF)., Methods: Crohn's disease patients who received anti-TNF induction therapy were enrolled. Patients who achieved clinical response (defined as delta Crohn's disease activity index [CDAI] > 70 and CDAI < 200) at 10-14 weeks after the start of infliximab or adalimumab were included. Eligible patients took a tolerability test of ED (900 kcal/day) for 3 days. Then, patients who preferred concomitant ED and whose ED tolerance was confirmed were allocated to the ED group and given Elental 900 kcal/day or more. Other patients were allocated to the non-ED group. The primary endpoint was the cumulative remission rate at 2 years after baseline. Clinical relapse was defined as CDAI > 200 and/or need for additional treatment. Adherence to the ED was confirmed at each visit., Results: Seventy-two patients were included. Thirty-seven were allocated to the ED group, and 35 were allocated to the non-ED group. The cumulative remission rate at 2 years was not significantly different between the two groups (60.9% vs 56.7%, P = 0.98). Adherence to the ED in the ED group was relatively low, and only 11 patients were maintained on an ED of 900 kcal/day., Conclusions: The addition of ED for Crohn's disease patients who responded to initial anti-TNF induction therapy was not found to improve outcomes. The efficacy of concomitant ED in other clinical settings, such as loss of response, needs to be clarified in the future (UMIN000009789)., (© 2018 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The present study was conducted to explore the association of endocytoscopy (EC) classification with microscopic inflammatory features of ulcerative colitis (UC) and disease relapse.EC was performed for mild-to-moderate UC 32 cases from January 2010 to August 2016. EC appearance was stratified into 4 categories: EC-A, regular arrangement of round to oval pits; EC-B, irregular arrangement with/without enlarged spaces between regular pits; EC-C, deformed pits with distorted crypt lumen which are unordered in arrangement but not disrupted; and EC-D, disruptive or disappeared pits. We evaluated the association of EC classification with Mayo endoscopic subscores (MES) and the clinically active state. Microscopic features including the severity in mucosal inflammatory infiltrates the presence of crypt abscess and goblet cell depletion were assessed by an experienced pathologist who was blinded to clinical and endoscopic information. Clinical follow-up was provided for treating 22 UC patients more than 60 months after EC.There were 15 cases in EC-A, 8 in EC-B, 5 in EC-C, and 4 in EC-D. Interobserver agreement was excellent with κ value of 0.77. There were 13 patients in active disease stage, while 19 in remission. Each EC-A case was in clinically remission stage, while all the EC-C and EC-D cases were in the active stage. There were 4 and 4 EC-B cases in remission and active stage, respectively. The EC-A group consisted of 11 MES0 and 4 MES1 cases, whereas the EC-B group consisted of 2 MES0 and 6 MES1 cases. There were no cases of MES0 in the EC-C and -D groups. The EC stratification was significantly associated with pathognomonic microscopic features for UC. There were significant differences in the remission rate among the EC groups. None had relapse in the EC-A group during the follow-up period.EC stratification could be predictive for relapse in UC. Moreover, EC is reliable to assess UC specific microscopic features.

Background: Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored., Summary: This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman's correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission., (© 2018 S. Karger AG, Basel.)