Abstract Background Colorectal Cancer (CRC) is the second leading cause of cancer mortality worldwide. Effective and non-invasive biomarkers are needed to improve early diagnosis and disease management. Immune cells play a key role in tumor progression. Circulating immune cell count is a potential cancer biomarker, as indicated by the association of high blood neutrophil-to-lymphocyte ratio with poor prognosis in patients with cancer. The study goal was to determine the correlation between circulating immune cell counts and immune cell-specific RNA signatures and to evaluate the signature potential for CRC detection. Methods The transcriptome profiles of peripheral blood mononuclear cells from 561 Asian and Caucasian subjects (189 CRC, 115 advanced adenomas, 39 other cancers, 218 controls without colorectal lesions (CON)) were generated by RNA-seq on the Illumina platform. Neutrophils, lymphocytes and monocytes counts were obtained by standard hematology testing. Specific RNA signatures for neutrophils, monocyte/macrophages, T cells, CD4, CD8, B cells, NK cells were compiled from literature. The mean expression level of all genes in each Immune cell signature was calculated and used for statistical analyses. Results The main immune cell type RNA signatures showed correlation with the relative cell counts (r: 0.4-0.6), indicating the validity of the RNA signatures. Myeloid cell (monocyte/macrophage and neutrophil) RNA signatures were the most significantly upregulated in CRC compared to CON (p  Conclusion This study shows that measuring specific immune cell type by RNA signatures correlate with traditional cell counting methods, enabling the extraction of valuable clinical information from blood transcriptomic data. This data suggests that both blood myeloid and T cells RNA signatures are promising biomarkers for CRC detection. Further biomarker development would require the optimization of the RNA signatures to validate and increase their diagnostic power. Legal entity responsible for the study Novigenix. Funding Novigenix. Disclosure S. Morgenthaler: Advisory / Consultancy: Novigenix. L. Ciarloni: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novigenix. G. Dorta: Advisory / Consultancy: Novigenix. S. Hosseinian Ehrensberger: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novigenix. All other authors have declared no conflicts of interest.

Background Colorectal Cancer (CRC) is the second leading cause of cancer mortality worldwide. An effective and convenient blood test for early detection of CRC is urgently needed to increase screening compliance and reduce mortality. The development of a new blood test for early CRC detection was initiated that leverage the transcriptome analysis of circulating immune cells (ImmunoTranscriptomics) using artificial intelligence and machine learning tools. Methods To identify new transcriptional biomarkers for CRC and adenoma detections, peripheral blood mononuclear cells (PBMC) transcriptome were analyzed by RNA-sequencing of 561 subjects (300 Caucasians and 261 Asians) enrolled in the DGNP-COL-0310 study (Ciarloni et al., 2016), a multi-centers case-control study. The cohort included 189 subjects with CRC, 115 with advanced adenoma (AA), 39 with other types of cancer (OC) as well as 218 individuals without any colorectal lesions (CON). Several univariate and multivariate methods were applied to the discovery set (n = 282) and results were integrated into a ranking system. Top ranked genes were selected for further validation and algorithm development in an independent set (n = 279). Results A large panel of differentially expressed genes were identified in non-metastatic CRC (I-II-III) and AA compared to CON and OC with significantly high power of discrimination (P-value = 10-13). The novel developed data analytics pipeline was used to analyse the transcriptomic data measurements and the diagnostic accuracy of the new gene signature for CRC, through application of Machine Learning (ML) and bootstrap, was 82% sensitivity and 88% specificity and AUC of 90%. The signature was enriched in genes associated with myeloid cells activation, inflammation and hemostasis, suggesting a key role of the innate immunity in the early response to cancer. Conclusions Mapping the reaction of the immune system to onset of cancer and disease identification through application ML methods is a new approach to ensure an unbiased, genome-wide, unsupervised gene expression analysis for a highly specific biomarker identification. Legal entity responsible for the study Novigenix SA. Funding Novigenix SA. Disclosure S. Hosseinian Ehrensberger: Shareholder / Stockholder / Stock options: Novigenix SA. L. Ciarloni: Shareholder / Stockholder / Stock options: Novigenix. All other authors have declared no conflicts of interest.

Foreign body (FB) ingestion is a frequent reason for gastroenterology consulting. Eighty percent of these ingestions are accidental and observed among paediatric subjects. However, intentional repetitive ingestions are also observed, especially amongst prisoners or psychiatric patients. Most FBs pass throughout the digestive tract without any complication and without any need for surgical or endoscopic intervention. Nevertheless, around 10-20% of cases require an endoscopy examination and 1% will lead to a surgical intervention. Management approaches should favor inter-disciplinarity, balance benefits and risks of FB removal based on its location, and integrate psychiatric comorbidities into the decision process.

BACKGROUND:Early detection and treatment of colorectal adenomatous polyps (AP) and colorectal cancer (CRC) is associated with decreased mortality for CRC. However, accurate, non-invasive and compliant tests to screen for AP and early stages of CRC are not yet available. A blood-based screening test is highly attractive due to limited invasiveness and high acceptance rate among patients.AIM:To demonstrate whether gene expression signatures in the peripheral blood mononuclear cells (PBMC) were able to detect the presence of AP and early stages CRC.METHODS:A total of 85 PBMC samples derived from colonoscopy-verified subjects without lesion (controls) (n = 41), with AP (n = 21) or with CRC (n = 23) were used as training sets. A 42-gene panel for CRC and AP discrimination, including genes identified by Digital Gene Expression-tag profiling of PBMC, and genes previously characterised and reported in the literature, was validated on the training set by qPCR. Logistic regression analysis followed by bootstrap validation determined CRC- and AP-specific classifiers, which discriminate patients with CRC and AP from controls.RESULTS:The CRC and AP classifiers were able to detect CRC with a sensitivity of 78% and AP with a sensitivity of 46% respectively. Both classifiers had a specificity of 92% with very low false-positive detection when applied on subjects with inflammatory bowel disease (n = 23) or tumours other than CRC (n = 14).CONCLUSION:This pilot study demonstrates the potential of developing a minimally invasive, accurate test to screen patients at average risk for colorectal cancer, based on gene expression analysis of peripheral blood mononuclear cells obtained from a simple blood sample.

Barrett's esophagus consists of the replacement of normal squamous epithelium by a specialised columnar lined epithelium referred to as intestinal metaplasia in the esophagus. It represents a premalignant lesion. The prevalence of Barrett's esophagus is around 1.6%. Esophageal adenocarcinoma results from the development of dysplasia progressing from low to high grade dysplasia and finally adenocarcinoma. Radiofrequency ablation currently represents the treatment of choice in eradicating Barrett's esophagus with associated dysplasia. The technique is based on the application of a radiofrequency current that enables the destruction of the superficial modified epithelium. This new approach presents a good security profile and, compared to other ablative techniques, shows superior results regarding Barrett's eradication.

Although generally considered as rare, incidence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing. The general practitioner has thus to be familiar with the vast array of clinical presentations and the growing family of diagnostic tools that can be used. Symptoms can be related to their hormonal production, their local extent or a bleeding complication. The prognosis depends on the grade of tumor, its local extent at diagnosis and its localization. The diagnosis relies on radiologic, endoscopic and nuclear medicine strategies. In case of typical symptoms, a hormonal secretion should be sought. Treatment options are extensive and should be discussed in an interdisciplinary manner.

Small intestine bacterial overgrowth (SIBO) is a condition characterised by nutrient malabsorption and excessive bacteria in the small intestine. It typically presents with diarrhea, flatulence and a syndrome of malabsorption (steatorrhea, macrocytic anemia). However, it may be asymptomatic in the eldery. A high index of suspicion is necessary in order to differentiate SIBO from other similar presenting disorders such as coeliac disease, lactose intolerance or the irritable bowel syndrome. A search for predisposing factor is thus necessary. These factors may be anatomical (stenosis, blind loop), or functional (intestinal hypomotility, achlorydria). The hydrogen breath test is the most frequently used diagnostic test although it lacks standardisation. The treatment of SIBO consists of eliminating predisposing factors and broad-spectrum antibiotic therapy.

BACKGROUND AND STUDY AIMS The current gold standard in Barrett's esophagus monitoring consists of four-quadrant biopsies every 1-2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett's esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett's esophagus in Switzerland. METHODS One hundred sixty-four patients with Barrett's esophagus underwent 239 endoscopies with biopsy and brush cytology. DICM was carried out on 239 cytology specimens. Measures of the test accuracy of DICM (relative risk, sensitivity, specificity, likelihood ratios) were obtained by dichotomizing the histopathology results (high-grade dysplasia or adenocarcinoma vs. all others) and DICM results (aneuploidy/intermediate pattern vs. diploidy). RESULTS DICM revealed diploidy in 83% of 239 endoscopies, an intermediate pattern in 8.8%, and aneuploidy in 8.4%. An intermediate DICM result carried a relative risk (RR) of 12 and aneuploidy a RR of 27 for high-grade dysplasia/adenocarcinoma. Adding DICM to the standard biopsy protocol, a pathological cytometry result (aneuploid or intermediate) was found in 25 of 239 endoscopies (11%; 18 patients) with low-risk histology (no high-grade dysplasia or adenocarcinoma). During follow-up of 14 of these 18 patients, histological deterioration was seen in 3 (21%). CONCLUSION DICM from brush cytology may add important information to a standard biopsy protocol by identifying a subgroup of BE-patients with high-risk cellular abnormalities.

Summary Background Data suggest that esomeprazole decreases gastric secretion. Aims To assess the effect of a single i.v. esomeprazole dose on gastric secretion volume 3 h after drug administration, as a primary endpoint, and to evaluate, as secondary endpoints, the reduction 1 and 5 h after dosing; time when the gastric pH was <2.5 and esomeprazole’s safety. Methods In all, 23 healthy Helicobacter pylori ‐negative volunteers (10 men, 13 women, mean age 28.2 ± 6) participated in this single‐centre, randomized, double‐blind, placebo‐controlled, 2‐way, single‐dose cross‐over study. In different sessions, volunteers received i.v. either esomeprazole 40 mg or placebo. An inserted double‐lumen nasogastric tube perfused and aspirated gastric liquid. Mechanical fractioned aspiration measured secretion volume; aliquot spectrophotometry assessed gastric secretion volume lost to the duodenum. Results Three hours post‐i.v. esomeprazole, average gastric secretion decreased by 77.6% (vs. baseline) compared to placebo. Values 1 and 5 h after dosing were 73.5% and 74.5%. Five hours after esomeprazole, the gastric pH was <2.5 3.9% of the time and 73.3% after placebo ( P < 0.002). Esomeprazole was well‐tolerated. No serious adverse events occurred. Conclusions Intravenous esomeprazole decreases gastric secretions. The potential clinical impact in averting bronchoaspiration during anaesthesia induction and in intensive care patients should be investigated in further studies.

Background and study aims: Patients and methods: Results: Conclusions:

Background and study aims: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. Patients and methods: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. Results: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). Conclusions: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

Gastrointestinal bleeding is still one of the most frequent medical emergencies. Despite improvements in endoscopic diagnosis and therapy, mortality from bleeding is still high (15%). Since conclusive trials are lacking, the endoscopist often has to rely on personal experience in the selection of therapeutic options. Therefore this article gives an overview of new publications in this field and recommendations based on personal experience.

Background and Aims: Flowcytometry on biopsy specimens has been previously shown to identify patients with Barrett's esophagus at high risk for progression to cancer. Patients with aneuploidy or increased 4N have a 5-yr cumulative cancer incidence of 28% (Am J Gastroenterol 2000;95:1669-1676). Using endoscopic brush cytology we studied the additional diagnostic benefit of Image Cytometry (ICM) of specialised intestinal metaplasia (SIM) compared to the histological diagnosis obtained from two separate endoscopies. Primary endpoints were detection of early cancer (EC) and high-grade dysplasia (HGD), secondary endpoint was low-grade dysplasia (LGD). Methods: 200 patients (73% male; mean age 67 yrs) with Barrett's esophagus (BE, mean segment length: 4.6 cm) were included, of whom 61% underwent two endoscopies (total of 325 examinations). In total, ICMs were obtained in 240 endoscopies from 162 patients. ICM was performed with a CCD 3-chip color videocamera Sony and AutoCyte QUIC DNA workstation on Feulgen restained cytology smears. DNA patterns were defined as diploid (2c), intermediate (diploid stemline and >10% cells below 4.5c threshhold) and aneuploid (>15% aneuploid cells or >3 cells > 9c). Results: 20 (8.3%) of 240 ICM examinations showed aneuploidy with the corresponding histological diagnosis of 3 EC (15%) , 8 HGD (40%), 5 LGD (30%), 1 indefinite for dysplasia (5%) and 3 SIM (15%) without dysplasia. 21 (8.8%) intermediate DNA-patterns at ICM were recorded at 2 endoscopies with EC, 3 endoscopies with HGD and 16 with indefinite for dysplasia. 199 (82.9%) ICMs showed diploidy in patients with EC (n = 1, 0.5%), HGD (n = 3, 1.5%), LGD (n = 10, 5%), indefinite for dysplasia (n = 20, 10%) and SIM (n = 164, 82.9%). Thus, ICM detected 25 additional high risk constellations in endoscopies with histology of LGD, indefinite for dysplasia (ID) and SIM or 1 in every 10 endoscopies with low-risk histology from modified gold standard four-quadrant biopsies. Conclusions: The data suggest that in this population of patients referred to a tertiary center, combined brush cytology and image cytometry in Barrett's esophagus identifies 1 additional high risk patients with aneuploid and intermediate DNA-pattern in every 10 endoscopies. Prospective studies need to demonstrate that this additional information affects patient management in a way ultimately improving outcomes.

BACKGROUND Gastroesophageal reflux and progressive esophageal dilatation can develop after gastric banding (GB). HYPOTHESIS Gastric banding may interfere with esophageal motility, enhance reflux, or promote esophageal dilatation. DESIGN Before-after trial in patients undergoing GB. SETTING University teaching hospital. PATIENTS AND METHODS Between January 1999 and August 2002, 43 patients undergoing laparoscopic GB for morbid obesity underwent upper gastrointestinal endoscopy, 24-hour pH monitoring, and stationary esophageal manometry before GB and between 6 and 18 months postoperatively. MAIN OUTCOME MEASURES Reflux symptoms, endoscopic esophagitis, pressures measured at manometry, esophageal acid exposure. RESULTS There was no difference in the prevalence of reflux symptoms or esophagitis before and after GB. The lower esophageal sphincter was unaffected by surgery, but contractions in the lower esophagus weakened after GB, in correlation with preoperative values. There was a trend toward more postoperative nonspecific motility disorders. Esophageal acid exposure tended to decrease after GB, with fewer reflux episodes. A few patients developed massive postoperative reflux. There was no clear correlation between preoperative testing and postoperative esophageal acid exposure, although patients with abnormal preoperative acid exposure tended to maintain high values after GB. CONCLUSIONS Postoperative esophageal dysmotility and gastroesophageal reflux are not uncommon after GB. Preoperative testing should be done routinely. Low amplitude of contraction in the lower esophagus and increased esophageal acid exposure should be regarded as contraindications to GB. Patients with such findings should be offered an alternative procedure, such as Roux-en-Y gastric bypass.

Background and Aims: The current reference method surveillance method for Barrett's esophagus (BE) is four quadrant biopsies (4-QB). Autofluorescence endoscopy (AF-E) claims the promise of visualization of otherwise unrecognized dysplasias. Hitherto, findings from small studies have been conflicting. We conducted a multicenter randomized controlled trial to elucidate whether AF-E in addition to the gold-standard improves diagnostic workups. Methods: We enrolled 200 patients with BE (73% male; mean age 67 yrs, BE mean segment length: 4.6 cm) from four tertiary referral centers.

BACKGROUND AND STUDY AIMS:In previous randomized trials, early endoscopy improved the outcome in patients with bleeding peptic ulcer, though most of these studies defined "early" as endoscopy performed within 24 hours after admission. Using the length of hospital stay as the primary criterion for the clinical outcome, we compared the results of endoscopy done immediately after admission (early endoscopy in the emergency room, EEE) with endoscopy postponed to a time within the first 24 hours after hospitalization, but still during normal working hours ("delayed" endoscopy in the endoscopy unit, DEU).PATIENTS AND METHODS:We conducted a retrospective analysis of data from 81 consecutive patients with bleeding peptic ulcer admitted in 1997 and 1998 (age range 16 - 90 years). Of these 81 patients, 38 underwent DEU (the standard therapy at the hospital) and 43 underwent EEE. Patients in the two groups were comparable with regard to admission criteria, were equally distributed with respect to their risk of adverse outcome (assessed using the Baylor bleeding score and the Rockall score), and differed only in the treatment they received. Endoscopic hemostasis was performed whenever possible in all patients with Forrest types I, IIa, and IIb ulcer bleeding.RESULTS:We found similar rates in the two groups for recurrent bleeding (16 % in DEU patients vs. 14 % in EEE patients), persistent bleeding (8 % in DEU patients vs. none in EEE patients), medical complications (21 % in DEU patients vs. 26 % in EEE patients), the need for surgery (8 % in DEU patients vs. 9 % in EEE patients), and the length of hospital stay (5.1 days for DEU patients vs. 5.9 days for EEE patients). None of the differences between the two groups in these parameters were statistically significant. None of the patients died.CONCLUSIONS:Early endoscopy in an emergency room did not improve the clinical outcome in our 81 consecutive patients with bleeding peptic ulcer.