Real-time EndoFaster improves Helicobacter pylori detection in chronic active gastritis.

Helicobacter pylori is the most frequent cause of chronic active gastritis (CAG), namely the first step for gastric cancer development. When infection is not detected at histology, another test is advised. EndoFaster is novel device that reveal the presence of H. pylori by determining ammonium concentration in the gastric juice during endoscopy. We evaluated whether this test may improve etiological diagnosis in CAG patients. In 595 consecutive patients who underwent upper endoscopy gastric juice was analysed with EndoFaster and standard biopsies were taken. CAG with typical bacteria was detected in 102 (17.1%) patients, and CAG without H. pylori was found in 36 (6.3%) cases. EndoFaster detected the infection in 22 (61.1%) of these patients. Neither ongoing proton pump inhibitor therapy nor previous eradication therapy affect the test accuracy. By using EndoFaster, another test to search for the infection in H. pylori-negative CAG patients may be avoided in more than 60% of cases, impacting on both patients discomfort and health resources use.

pCLE highlights distinctive vascular patterns in early gastric cancer and in gastric diseases with high risk of malignant complications.

Endoscopy is widely used to detect and diagnose precancerous lesions and gastric cancer (GC). The probe-based Confocal Laser Endomicroscopy (pCLE) is an endoscopic technique suitable for subcellular resolution and for microvasculature analyses. The aim of this study was to use pCLE to identify specific vascular patterns in high-risk and early stage GC. Mucosal architecture, vessel tortuosity, enlargements and leakage were assessed in patients with autoimmune gastritis and early gastric cancer (EGC). We were able to stratify gastritis patients by identifying distinct vascular profiles: gastritis was usually associated with increased vascularization characterized by a high number of tortuous vessels, which were also found in atrophic autoimmune disease. Leaky and tortuous vessels, distributed in a spatially irregular network, characterized the atrophic metaplastic mucosa. The mucosal vasculature of EGC patients displayed tortuous vessels, but unlike what detected in atrophic gastritis, they appeared patchy, as is in neoplastic gastric tissue. Very importantly, we detected vascular changes even in areas without lesions, supporting the contention that vascular alterations may provide a favorable microenvironment for carcinogenesis. This report confirms that pCLE is a valid endoscopic approach to improve the definition of patients with malignant lesions or at increased risk for GC by assessing vascular changes.

Novel 1-L polyethylene glycol + ascorbate versus high-volume polyethylene glycol regimen for colonoscopy cleansing: a multicenter, randomized, phase IV study.

BACKGROUND AND AIMS: Adequate bowel cleansing is critical to ensure quality and safety of a colonoscopy. A novel 1-L polyethylene glycol plus ascorbate (1L-PEG+ASC) regimen was previously validated against low-volume regimens but was never compared with high-volume regimens. METHODS: In a phase IV study, patients undergoing colonoscopy were randomized 1:1 to receive split-dose 1L PEG+ASC or a split-dose 4-L PEG-based regimen (4L-PEG) in 5 Italian centers. Preparation was assessed with the Boston Bowel Preparation Scale (BBPS) by local endoscopists and centralized reading, both blinded to the randomization arm. The primary endpoint was noninferiority of 1L-PEG+ASC in colon cleansing. Secondary endpoints were superiority of 1L-PEG+ASC, patient compliance, segmental colon cleansing, adenoma detection rate, tolerability, and safety. RESULTS: Three hundred eighty-eight patients (median age, 59.8 years) were randomized between January 2019 and October 2019: 195 to 1L-PEG+ASC and 193 to 4L-PEG. Noninferiority of 1L-PEG+ASC was demonstrated for cleansing in both the entire colon (BBPS ≥ 6: 97.9% vs 93%; relative risk [RR], 1.03; 95% confidence interval [CI], 1.001-1.04; P superiority = .027) and in the right-sided colon segment (98.4% vs 96.0%; RR, 1.02; 95% CI, .99-1.02; P noninferiority = .013). Compliance was higher with 1L-PEG+ASC than with 4L-PEG (178/192 [92.7%] vs 154/190 patients [81.1%]; RR, 1.10; 95% CI, 1.05-1.12), whereas no difference was found regarding safety (moderate/severe side effects: 20.8% vs 25.8%; P = .253). No difference in adenoma detection rate (38.8% vs 43.0%) was found. CONCLUSIONS: One-liter PEG+ASC showed noninferiority compared with 4L-PEG in achieving adequate colon cleansing and provided a higher patient compliance. No differences in tolerability and safety were detected. (Clinical trial registration number: NCT03742232.).

Low Pepsinogen I/II Ratio and High Gastrin-17 Levels Typify Chronic Atrophic Autoimmune Gastritis Patients With Gastric Neuroendocrine Tumors.

INTRODUCTION: Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis. METHODS: We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017. RESULTS: A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET. DISCUSSION: This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Probe-based confocal laser endomicroscopy (pCLE) is a suitable method for extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) evaluation.

The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.

Intracorporeal versus Extracorporeal Anastomoses Following Laparoscopic Right Colectomy in Obese Patients: A Case-Matched Study.

BACKGROUND/AIMS: To compare short- and long-term outcomes of intracorporeal anastomosis (IA) versus extracorporeal anastomosis (EA) in obese (body mass index >30 kg/m2) patients. PATIENTS AND METHODS: Sixty-four consecutive obese patients who underwent laparoscopic (LPS) right colectomy with IA were matched with 64 patients who underwent LPS right colectomy with EA. Intraoperative variables, short-term outcomes, readmission rates, and morbidity and mortality rates were analyzed along with long-term outcomes. RESULTS: Conversion to open surgery occurred in 4 patients in the IA group and 11 patients in the EA group (p = 0.097). The overall 30-day morbidity rate was 29.6% in the IA and 32.8% in the EA (p = 0.70). No 30-day mortality occurred. Anastomotic leak occurred in 4.7% of patients in the IA group vs. 7.8% in the EA group (p = 0.71). In the IA group, an earlier recovery of bowel function was observed (p = 0.01). No differences were observed with respect to the length of stay and reoperation rate. No 30-day readmission occurred in the IA compared to 5 patients readmitted in the EA group (p = 0.058). A higher incidence of incisional hernia was observed in the EA group (p = 0.033). CONCLUSION: IA in obese patients is associated with similar short-term outcomes, lower incidence of incisional hernias, and might possibly reduce the risk of hospital readmission.

Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa.

In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1) commitment in Helicobacter pylori-infected human gastric mucosa. The levels of gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-12 in total extracts of gastric biopsies taken from H. pylori-infected and uninfected patients were determined by an enzyme-linked immunosorbent assay. The levels of signal transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed in T cells (T-bet) in total proteins extracted from gastric biopsies were determined by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on expression of Th1 transcription factors and the levels of IFN-gamma in organ cultures of H. pylori-infected biopsies was examined. Increased levels of IFN-gamma and IL-12 were found in gastric biopsy samples of H. pylori-infected patients compared to the levels in uninfected patients. In addition, H. pylori-infected biopsies exhibited high levels of expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-gamma and expression of Th1 transcription factors were associated with greater infiltration of mononuclear cells in the gastric mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6 were not associated with the intensity of mononuclear cell infiltration. In ex vivo organ cultures of H. pylori-infected biopsies, neutralization of endogenous IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced IFN-gamma production. Our data indicated that IL-12 contributes to the Th1 cell commitment in H. pylori-infected human gastric mucosa.

Giardia lamblia infection in patients with irritable bowel syndrome and dyspepsia: a prospective study.

AIM: To evaluate the prevalence of Giardia lamblia (G. lamblia) infection in patients with irritable bowel syndrome (IBS) and dyspepsia and to establish which is the most accurate test to diagnose the infection in this setting. METHODS: One hundred and thirty-seven patients who consecutively attended the Outpatient Gastroenterology Clinic for the first time between January 2002 and December 2003 due to symptoms of IBS and/or dyspepsia were recruited. All patients underwent clinical evaluation, first-step haematology and chemistry tests, serologic assays for celiac disease, lactose-H(2) breath test, abdominal ultrasonography, and esophagogastroduodenoscopy. Helicobacter pylori status was evaluated. In patients with symptoms of IBS older than 45 years, colonoscopy was also performed. In all patients, duodenal biopsies and stool samples were examined for trophozoites and cysts of G. lamblia by several methods. RESULTS: G. lamblia was identified in 9 patients. The following diagnoses were also made: IBS (100/137, 73%), functional dyspepsia (62/137, 45%), organic dyspepsia (33/137, 24%), and lactose intolerance (75/137, 55%). A significant association was found between giardiasis and H pylori infection (c2=6.632, OR=12.4, CI=1.5-68.1). There were no symptoms that reliably allowed the recognition of giardiasis. Direct search of the parasite in duodenal biopsy and stool sample examinations gave concordant results in all cases while histological examination of duodenal biopsies displayed a low sensitivity (e.g., 22.2%). CONCLUSION: In this consecutive series, diagnosis of G. lamblia infection accounted for 6.5% of patients with IBS and dyspepsia. Duodenal biopsies for diagnosis of giardiasis may be unnecessary if stool sample examination is performed.

Extracellular signal-regulated protein kinase mediates interleukin 17 (IL-17)-induced IL-8 secretion in Helicobacter pylori-infected human gastric epithelial cells.

Helicobacter pylori-induced mucosal inflammation results in high production of interleukin 17 (IL-17), a potent inducer of IL-8 in gastric epithelial cells. The aim of this study was to investigate signaling pathways by which IL-17 regulates IL-8 production in human gastric epithelial cells. Activation of mitogen-activated protein (MAP) kinases in both IL-17-stimulated MKN28 cells and epithelial cells isolated from H. pylori-colonized gastric mucosa was assessed by Western blotting. In IL-17-stimulated MKN28 cells the activation of activatior protein 1 (AP-1), nuclear factor (NF)-IL-6, and NF-kappaB was also assessed by electrophoretic mobility shift assay. IL-8 production was evaluated by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA) both for IL-17-stimulated MKN28 cells treated with specific MAP kinase inhibitors and gastric biopsy cultures treated with a neutralizing IL-17 antibody. Serum from H. pylori-infected patients was tested for immunoglobulin G response to CagA by ELISA. Treatment of MKN28 cells with IL-17 caused activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) but not other MAP kinases and had the downstream effects of AP-1 and NF-kappaB activation and IL-8 synthesis. Blocking ERK 1/2 activity inhibited AP-1-mediated, but not NF-kappaB-mediated, IL-8 induction. Enhanced activation of ERK 1/2 was seen in gastric epithelial cells isolated from H. pylori-infected patients in comparison to uninfected controls, and this was associated with high IL-8. These effects were even more pronounced in patients seropositive for CagA than in seronegative ones. In gastric biopsy cultures, the addition of a neutralizing IL-17 antibody decreased ERK 1/2 activation, thus resulting in a significant inhibition of IL-8. In H. pylori-colonized gastric epithelial cells, IL-17-induced IL-8 synthesis is associated with and depends at least in part on the activation of ERK 1/2 MAP kinase.