Endoscopist-Level and Procedure-Level Factors Associated With Increased Adenoma Detection With the Use of a Computer-Aided Detection Device.

INTRODUCTION: To investigate the impact of procedure-related and endoscopist-related factors on the effectiveness of a computer-aided detection (CADe) device in adenomas per colonoscopy (APC) detection. METHODS: The SKOUT clinical trial was conducted at 5 US sites. We present prespecified analyses of procedure-related and endoscopist-related factors, and association with APC across treatment and control cohorts. RESULTS: There were numeric increases in APC between SKOUT vs standard colonoscopy in community-based endoscopists, withdrawal time of ≥8 minutes, for endoscopists with >20 years of experience, and endoscopists with baseline adenoma detection rate <45%. DISCUSSION: The application of CADe devices in clinical practice should be carefully evaluated. Larger studies should explore differences in endoscopist-related factors for CADe.

Pancreatic Cystic Neoplasms.

Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".

Inflammation and Gastric Cancer.

Gastric cancer remains a major killer globally, although its incidence has declined over the past century. It is the fifth most common cancer and the third most common reason for cancer-related deaths worldwide. Gastric cancer is the outcome of a complex interaction between environmental, host genetic, and microbial factors. There is significant evidence supporting the association between chronic inflammation and the onset of cancer. This association is particularly robust for gastrointestinal cancers in which microbial pathogens are responsible for the chronic inflammation that can be a triggering factor for the onset of those cancers. Helicobacter pylori is the most prominent example since it is the most widespread infection, affecting nearly half of the world's population. It is well-known to be responsible for inducing chronic gastric inflammation progressing to atrophy, metaplasia, dysplasia, and eventually, gastric cancer. This review provides an overview of the association of the factors playing a role in chronic inflammation; the bacterial characteristics which are responsible for the colonization, persistence in the stomach, and triggering of inflammation; the microbiome involved in the chronic inflammation process; and the host factors that have a role in determining whether gastritis progresses to gastric cancer. Understanding these interconnections may improve our ability to prevent gastric cancer development and enhance our understanding of existing cases.

Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice.

BACKGROUND: Alcohol use disorder is a significant societal and medical burden that is associated with both organ pathology and addiction. Excessive alcohol use results in neuroinflammation characterized by activation of the inflammasome, a multiprotein complex, and IL-1ß increase in the brain. Recent studies suggest that inflammation could contribute to alcohol addiction. Here, we targeted components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome cascade, which senses and responds to immunologic stimuli, to determine whether NLRP3 inhibition modulates alcohol consumption. METHODS: C57BL/6J male and female mice were provided a 2-bottle choice of alcohol at increasing concentrations (3, 6, 9, and 12%, 4 days each) or water, and some were treated with daily injections of an NLRP3 inhibitor (MCC950), a caspase-1 inhibitor (VX765), IL-1 receptor antagonist (IL-1ra; anakinra), or vehicle injection. RESULTS: Treatment with VX765, MCC950, and IL-1ra significantly reduced alcohol consumption and preference in female mice (p < 0.05). Treatment with MCC950 and IL-1ra reduced alcohol consumption, while IL-1ra reduced alcohol preference in male mice (p < 0.05). VX765 did not affect alcohol consumption or preference in male mice. CONCLUSIONS: These findings highlight gender differences in alcohol preference and demonstrate that inhibition of different steps in inflammasome signaling can reduce alcohol consumption in females. Inhibition of NLRP3 inflammasome activation and the inflammasome-IL-1ß cascade opens novel insights into the development of new therapies to address alcohol use disorder in an era of targeted and precision medicine.

Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice.

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed in vitro, macrophages endocytosed these rationally designed complexes through scavenger receptors. A 5-week alcohol feeding with the Lieber-DeCarli diet in mice resulted in increased serum alanine aminotransferase (ALT), liver steatosis, and increased proinflammatory cytokines in the liver. TREM-1 messenger RNA (mRNA) expression was significantly increased in alcohol-fed mice, and TREM-1 inhibitors significantly reduced this increase. TREM-1 inhibition significantly attenuated alcohol-induced spleen tyrosine kinase (SYK) activation, an early event in both TLR4 and TREM-1 signaling. The TREM-1 inhibitors significantly inhibited macrophage (epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 [F4/80], clusters of differentiation [CD]68) and neutrophil (lymphocyte antigen 6 complex, locus G [Ly6G] and myeloperoxidase [MPO]) markers and proinflammatory cytokines (monocyte chemoattractant protein 1 [MCP-1], tumor necrosis factor α [TNF-α], interleukin-1ß [IL-1ß], macrophage inflammatory protein 1α [MIP-1α]) at the mRNA level compared to the HDL vehicle. Administration of TREM-1 inhibitors ameliorated liver steatosis and early fibrosis markers (α-smooth muscle actin [αSMA] and procollagen1α [Pro-Col1α]) at the mRNA level in alcohol-fed mice. However, the HDL vehicle also reduced serum ALT and some cytokine protein levels in alcohol-fed mice, indicating HDL-related effects. Conclusion: HDL-delivered novel TREM-1 peptide inhibitors ameliorate early phases of inflammation and neutrophil and macrophage recruitment and activation in the liver and attenuate hepatocyte damage and liver steatosis. TREM-1 inhibition represents a promising therapeutic approach for further investigations in ALD.

Future Directions for Endoscopic Ultrasound: Where Are We Heading?

Endoscopic ultrasound (EUS) plays an important role as a diagnostic and therapeutic modality in gastroenterology. New developments have emerged, especially in the last decade, and are being introduced to endoscopists. The ability to readily visualize and access organs in the gastrointestinal tract has allowed endoscopists to perform new interventional procedures. EUS procedures have taken the place of conventional approaches for the treatment of various gastrointestinal diseases, including pancreatic cystic lesions. This article focuses on the advances and future of diagnostic and therapeutic EUS.

The Role of M30 in Predicting the Severity of Liver Fibrosis and Inflammation in Chronic Hepatitis B Patients.

BACKGROUND: Liver biopsy is an invasive procedure that is currently still necessary for predicting underlying hepatic injury related to chronic viral hepatitis B (CVHB). To date, none of the studied non-invasive methods have been able to replace liver biopsy. An apoptotic serum marker, M30, which has been reported to indicate ongoing liver fibrosis, has been popular in recent years. OBJECTIVES: We aimed to investigate the possible role of M30 in predicting CVHB-associated hepatic injury and its severity. METHODS: Forty-eight patients undergoing liver biopsy for evaluation of the severity of CVHB-related liver injury and 40 healthy controls were included in this cross-sectional study. M30 levels were determined for all CVHB patients and controls, and other laboratory parameters and demographic features were obtained from our hospital's database. RESULTS: The mean ages of patients and controls were 39.7 and 45.7 years, respectively, and 35% of the controls and 52% of the patients were male. In contrast to lower platelet counts, transaminase and M30 levels were both higher in the patient group than in the controls. Among the investigated parameters, only transaminase increased as the fibrosis stage changed from mild to moderate; however, none of the laboratory parameters, including M30, differed as the histological activity index (HAI) score increased. CONCLUSIONS: M30 levels were higher in CVHB patients compared to healthy controls. However, M30 levels were similar in the mild and moderate stages of fibrosis, so they did not indicate the severity of underlying fibrotic or inflammatory processes in CVHB patients.

Evaluation of Early Atherosclerosis Markers in Patients with Inflammatory Bowel Disease.

BACKGROUND The aim of this study was to investigate relationships between early atherosclerosis and inflammatory bowel disease (IBD) using laboratory, functional, and morphological markers of atherosclerosis. MATERIAL AND METHODS In the present prospective single-center study, 96 patients with IBD (58 patients with ulcerative colitis and 36 patients with Crohn's disease) and 65 healthy control subjects were included. The demographic data of each patient and control subject were recorded. The patients with IBD and healthy controls were compared in terms of the carotid intima-media thickness (CIMT), the values of flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD), and the levels of von Willebrand factor antigen (VWF-Ag), D-dimer, and lipoprotein (a). RESULTS There were no significant differences between the IBD patients and controls in terms of age, sex, BMI, systolic and diastolic BPs, serum levels of total cholesterol, low-density lipoprotein, or triglycerides. IBD patients had significantly higher levels of VWF-Ag (156.6±58.9 vs. 104.2±43.3, P<0.001) and D-dimer (337.2±710.8 vs. 175.9±110.9, P<0.001) as compared to the controls. No significant differences were determined between the 2 groups in terms of FMD and NMD values. Although statistically not significant, the CIMT values were higher in the IBD patients than in the controls (0.517±0.141 mm vs. 0.467±0.099 mm, P=0.073). In the correlation analysis, the CIMT was found to be correlated negatively with FMD and positively with high sensitive C-reactive protein, VWF-Ag, and D-dimer. CONCLUSIONS These findings suggest that VWF-Ag and D-dimer can be beneficial early atherosclerosis markers in IBD patients.

Will a second biopsy sample affect treatment decisions in patients with chronic hepatitis B?

BACKGROUND AND AIM: Liver biopsy is the gold standard for assessment of fibrosis in patients with hepatitis B. However, it has some disadvantages, including inter-observer and intra-observer variability in biopsy interpretation and specimen variation. A standard biopsy specimen represents only about 0.0002 % of the whole liver. It has been shown that two biopsy samples collected during a procedure have significant influence on the diagnostic performance of interpretation in patients with hepatitis C or non-alcoholic steatohepatitis. Therefore, we aimed to assess the influence of collecting two liver biopsy samples during a single procedure for staging and grading chronic hepatitis B. PATIENTS AND METHODS: 27 patients were included in the study. The median age of the patients was 43.51 ± 11.69. Fifteen patients were female, 12 patients were male. In the biopsy procedure, two samples of liver lobes were obtained. Grade and stage scores were compared between the two samples. Fibrosis staging and grading were assessed according to the Ishak scoring system. RESULTS: Numbers of portal tract and biopsy size were equal in the two samples. There was a significant difference between the samples in terms of histological activity index (p value = 0.04). However, the difference was not enough to distinguish the mild and moderate stages. On the other hand, no significant difference in fibrosis staging between the two samples was found. CONCLUSIONS: With this relatively small size of patients, in this study, we showed that a proper liver biopsy size is sufficient to predict treatment decisions in chronic hepatitis B patients. However, further studies are needed to show the association of sampling variability in patients with hepatitis B.

The efficiency of endoclips in maintaining the gastrointestinal bleeding-related Dieulafoy's lesion.

BACKGROUND: Dieulafoy's lesion (DL) is a relatively uncommon medical condition characterized by a large tortuous arteriole in the submucosa of any part of gastrointestinal (GI) tract wall that bleeds via erosion likely caused in the submucosal surface by protrusion of the pulsatile arteriole. Compared with other endoscopic hemostatic techniques, clipping alone for DL is limited. AIMS: The aim of the present case series study is to identify common clinical and endoscopic features, rates of occurrence, to review the outcome of endoscopic management of upper GI tract DL, and to illustrate the use and the efficiency of endoclips in maintaining the GI bleeding due to DL. PATIENTS AND METHODS: This case series was conducted at Department of Gastroenterology, Diskapi Yildirim Beyazit Educational and Research Hospital. The patients who were admitted to the emergency department of Diskapi Yildirim Beyazit Educational and Research Hospital underwent gastrointestinal system (GIS) endoscopy between 2008 and 2013 and were assessed retrospectively. Five cases of GI bleeding related to DL were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: The median number of endoscopic hemoclips application in first endoscopy was 4 (2-9). Rebleeding developed in all patients who had hemoclips applied. Re-endoscopy was performed in three of these patients, which controlled the bleeding. Two patients were transferred to surgery. CONCLUSIONS: Combination of endoscopic injection and mechanical therapies seems a suitable method for maintaining upper GIS bleeding due to DL. Also, further studies are needed to better define the best endoscopic approach for the treatment of DL.

Metastatic lung adenocarcinoma related α-Fetoprotein elevation in a patient with HBV-related cirrhosis.

HCC is the most common type of primary liver tumor. The Practice Guideline, AASLD, for HCC recommended surveillance of HBV carriers at high risk of HCC with US every 6-12 months. Laboratory surveillance option is the measurement of serum α-fetoprotein level which has long been used for the diagnosis of HCC. But, increased serum levels of α-fetoprotein are also seen in acute hepatitis, cirrhosis, and malignancies include yolk sac carcinoma, neuroblastoma, hepatoblastoma, gastric and lung carcinoma. Because of elevation α-fetoprotein in these malignancies, liver mass with an elevated α-fetoprotein does not directly indicate HCC. For these reason, clinicians evaluating patient with liver mass and HBV-related cirrhosis should be vigilant for other case of α-fetoprotein elevation.

Tenofovir-best hope for treatment of chronic hepatitis B infection?

BACKGROUND/AIMS: To evaluate the effectiveness of tenofovir in patients with chronic hepatitis B infection in a real life setting. MATERIALS AND METHODS: We performed a retrospective analysis of data from 164 patients with chronic hepatitis B who were treated with Tenofovir. Eighty-six patients (52.4%) were naïve. Seventy-seven (46.9%) patients were previously treated with anti-viral drugs, including standard interferon (n=4), pegylated (PEG) interferon (n=14), standard interferon together with lamivudine (n=13), lamivudine alone (n=41), adefovir (n=2), lamivudine together with adefovir (n=1), and entecavir (n=2). Six patients (3.7%) had liver cirrhosis before treatment of tenofovir. RESULTS: The patients who have hepatitis B viral DNA>104 copy/mL with chronic hepatitis B infection were included in the treatment of Tenofovir. Average follow up time was 30.31±14.33 months. HBV DNA negativity and alanine aminotransferase (ALT) normalization were 86.5% and 71.3%, respectively, at the last visit. Hepatitis B e-Antigen (HBeAg) seroconversion occurred in 11 (19.6%) out of 164 patients. During the follow-up period, 4 (2.4%) patients developed liver cirrhosis and in 5 (3%) patients hepatocellular carcinoma (HCC) occurred out of 164 patients. HBsAg seroconversion occurred in one patient (0.6%). CONCLUSION: Tenofovir can be used safely and successfully in those patients that were naive, experienced with immune modulators and/or antivirals, HBeAg-positive, and HBeAg-negative patients.

Two gastrointestinal conditions with similar symptoms and endoscopic appearance: irritable bowel syndrome and microscopic colitis.

BACKGROUND/AIM: Irritable bowel syndrome (IBS) is a gastrointestinal condition characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any organic cause. This trial investigated the presence of microscopic colitis (MC) and associated factors related to MC in patients diagnosed with IBS. MATERIALS AND METHODS: The study group (group I) consisted of 91 consecutive patients diagnosed with IBS based on the Rome III Criteria for whom colonoscopic examination was requested. The control group (group II) had 41 patients diagnosed with IBS considered as eligible for colonoscopic investigation due to specific conditions, and for whom colonoscopic examination was recommended for screening purposes due to a familial history of colon cancer. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: In the diarrhea-predominant IBS group, nine patients (9.89%) were diagnosed with microscopic colitis, seven with lymphocytic colitis (7.69%), and two with collagenous colitis (CC) (2.19%). None of the patients in group II were found to have MC (P = 0.007). There were no diagnoses of MC in the constipation-predominant and mixed type IBS groups. CONCLUSION: Clinicians should keep MC in mind for patients presenting with diarrhea-predominant IBS symptoms.

What is the main target: a clearer colon with a sennoside-based regime, or adequate bowel cleansing before colonoscopy with a PEG-EL-based regime?

BACKGROUND/AIM: Even though polyethylene glycol-electrolyte lavage (PEG-EL)-based regimes have become the gold standard in recent years, to finish drinking 4 L of PEG-EL solution can be difficult. The quality of sennoside-based bowel-cleansing regimes used in Turkey has been known for some time. Therefore, we aimed to investigate the efficacy of both bowel-cleansing regimes. MATERIALS AND METHODS: Patients over 18 years old undergoing elective colonoscopic procedures between January and March 2011 were included in the study. The patients were divided into 2 groups; in Group 1, 91 patients were given sennoside a + b calcium 500 mg/250 mL (X-M solution, Yenisehir Laboratuari, Ankara, Turkey), and in Group 2, 94 patients were given 4 L of PEG-EL (Golytely, Boston, MA, USA). RESULTS: The mean age of the patients and the male distribution were similar in the 2 groups. Both inadequate bowel cleansing and the best cleansed bowels were seen in Group 1. The number of inadequate colonoscopies declined when using a whole bowel-cleansing regime from 24.5% to 19.3% in Group 2, but it did not decline in Group 1. CONCLUSION: The best bowel cleansing can be achieved with sennoside-based regimes, whereas a greater proportion of adequate results via colonoscopy were reached with the PEG-EL-based regimes.

Utility of M30, an apoptotic serum marker, in liver diseases.

The aim of this paper is to evaluate the role of apoptosis in some common liver diseases, and the utility of M30, an apoptotic serum marker, in the diagnosis of the severity of underlying hepatic injury. As is widely known, apoptosis is programmed cell death, and its deregulation results in an uncontrolled inflammatory process leading to upregulation of liver fibrogenesis. Both extrinsic and intrinsic pathways are crucial in apoptosis, and caspase cleavage of cytokeratin proteins occurs in both. Therefore, the measurement of caspase- cleaved cytokeratin fragments could be a novel method to assess the intensity of apoptotic cell numbers in epithelial tissue damage. M30 levels were found to increase not only in acute liver disorders, but also in some chronic liver injuries. We tried to summarize the recent studies focused on the role of apoptotic processes in liver diseases, mainly those that investigated the use of M30 in determining the severity of, or in predicting, ongoing liver injury.