Novel potential biomarkers for the diagnosis and monitoring of patients with ulcerative colitis Unambiguously, great progress has been achieved in the unraveling of more pathological pathways implicated in the development and progression of ulcerative colitis during the last decades. Novel effective drugs that have augmented the management armamentarium have been developed alongside this growing comprehension of the disease, rendering mucosal healing not only a feasible but the optimal goal of every therapy. Clinical evaluation, colonoscopy and biomarkers are the tools used by practitioners for the diagnosis and assessment of the status of the disease in order to achieve clinical remission and mucosal healing for their patients. Among these tools, colonoscopy is the gold method for the cause but is still an invasive, high-cost procedure with possible adverse events such as perforation. While clinical evaluation entails much subjectivity, biomarkers are objective, easily reproducible, non-invasive, cheap and potent surrogate tools of mucosal inflammation. Unfortunately, the well-established, currently in use serum biomarkers, such as C-reactive protein, erythrocyte sedimentation rate and others, do not display sufficiently acceptable sensitivity and specificity rates for the diagnosis of ulcerative colitis and, most importantly, do not represent precisely the mucosal inflammation status of the disease. Therefore, the discovery of new serum biomarkers has been the cause of several studies attempting to discover an “optimal” serum biomarker during the recent years. After thorough research, collection and examination of current data, this review focuses on and selectively presents promising, potential, novel serum biomarkers of ulcerative colitis as they are indicated by studies on the patient over the last years.

Systematic review: role of elevated plasma von-Willebrand factor as predictor of mortality in patients with chronic liver disease In this systematic review, we aimed to assess role of plasma von-Willebrand factor (vWF), an endothelial activation marker, as prognostic marker in patients with chronc liver disease [cirrhosis and acute-on-chronic liver failure (ACLF)]. We searched published databases using predefined keywords to identify all studies up to June 2018, in which plasma vWF (antigen or activity assay) was used as prognostic marker predicting mortality in patients with chronic liver disease. Relevant extracted data from selected studies were narratively summarized. The individual study’s area under ROC curve for plasma vWF as a predictor of mortality was pooled and meta-analyzed. Six studies (cirrhosis: 5; ACLF: 1) with an aggregate data of 765 patients (cirrhosis: 715 patients; ACLF: 50 patients) were included. Baseline plasma vWF-antigen was an independent predictor of medium-term mortality in patients with cirrhosis (summary area under the curve: 0.74; 95% confidence interval: 0.70–0.79) with an optimal cutoff of 318% (216–390%; median, range) over a period of 25.6 months (23.6–33 months). Plasma vWF also predicted short-term (over 7 days) mortality in patients with ACLF. Plasma vWF levels correlated with Child’s score, model for end-stage liver disease (MELD) score and hepatic venous pressure gradient and performed as well as MELD score in predicting mortality in patients with cirrhosis and ACLF. Baseline plasma vWF level predicts mortality over a medium term (1–3 years) in cirrhosis and over a short term (1 week) in ACLF patients. The marked elevation of baseline plasma vWF levels in ACLF patients was associated with drastic truncation of survival when compared with cirrhosis patients.

Trends in survival based on treatment modality for esophageal cancer: a population-based study Objectives The primary objective was to examine the trends in treatment modalities and the respective survival rates for esophageal cancer in the province of Ontario, Canada. Methods This is a population-based study of all esophageal cancer cases diagnosed in Ontario between 2007 and 2015, including squamous cell carcinoma and adenocarcinoma, with known disease stage. Other characteristics include sex, age, date of diagnosis, and treatment modalities. Treatment modalities were classified as no-treatment, radiation only or chemotherapy only, chemoradiation, and surgical resection. Results In total, 2572 patients were identified with esophageal cancer from 2007 to 2015, of which 2014 (78.3%) were male. The mean age at diagnosis was 66.6 (SD = 11.7) years. Survival rate increased over time in patients who underwent chemoradiation or surgical resection but remained unchanged for the radiation-only or chemotherapy-only group and decreased for the no-treatment group. Survival considerably improved (15–20%) for patients with stages I–III disease. Conclusions The positive trends in the survival rate for esophageal patients could be due to adoption of multimodal therapy. Despite a lower proportion of advanced disease among patients over 80, they received less curative treatments compared with other age groups. Further studies are required to identify strategies to maximize survival for patients with stage IV disease, and patients 80 years and older.

Criteria for difficult biliary cannulation: start to count Objective In European Society of Gastrointestinal Endoscopy guidelines, biliary cannulation of native papilla is defined as difficult in the presence of >5 papilla contacts, >5 min cannulation time or >1 unintended pancreatic duct cannulation (5-5-2). The aim is to test 5-5-2-criteria in a single-center practice predicting the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), and to study the efficacy of transpancreatic biliary sphincterotomy (TPBS) as an advanced method for biliary cannulation. Methods Prospectively collected data of 821 patients with native papilla were analyzed. Primary cannulation was the first method chosen for cannulation (sphincterotome and a guidewire). Advanced cannulation method was endoscopist-chosen cannulation method after failed primary cannulation. Results Primary cannulation succeeded in 599 (73%) patients in a median of 2 min. TPBS ± needle knife resulted in a 90% success rate. The final cannulation success was 814 (99.1%) cases in a median of 5.3 min. PEP risk was 4.0%. When primary cannulation succeeded, the PEP rate was 2.3%. When advanced methods were needed, the PEP rate increased to 13.5%. Altogether 311 (37.9%) patients fulfilled at least one 5-5-2-criterion. In patients without 5-5-2-criteria, the primary cannulation succeeded in 79.6% (n = 477), compared to 20.4% (n = 122) with the criteria, P < 0.001, indicating the need to exchange the cannulation method instead of persistence. If all the 5-5-2-criteria were present, the risk of PEP was 12.7%. Conclusion The results support the use of the 5-5-2-criteria for difficult cannulation. TPBS is an effective advanced cannulation method with an acceptable complication rate.

Optimal duration of concomitant nonbismuth quadruple therapy as first-line therapy for Helicobacter pylori: a prospective, open-label, comparative study Background Concomitant nonbismuth quadruple therapy is recommended as first-line treatment for Helicobacter pylori infection in high clarithromycin resistance areas, but the ideal duration of the regimen remains elusive. Aim of this study was to assess the efficacy and tolerability of 10- versus 14-day concomitant therapy for H. pylori eradication in an area of high clarithromycin and low dual clarithromycin/metronidazole resistance. Methods This was a prospective, open-label study including adult patients with H. pylori infection without previous treatment, from September 2014 to June 2017. Concomitant therapy consisting of pantoprazole 40 mg, amoxicillin 1g, clarithromycin 500 mg, and a nitroimidazole 500 mg was administered twice daily for 10 days in the first phase and for 14 days in the second phase of the study. Efficacy and side effects were compared between groups using chi-square and Fisher’s exact tests. Results In per protocol analysis, rates of eradication for the 10- and 14-day regimen were 91.9% (114/124) and 90.9% (110/121), respectively (P = 0.77). In intention to treat analysis, rates of eradication were lower than 90%. Specifically, rates were 86.3% (114/132) for the 10-day regimen and 85.2% (110/129) for the 14-day regimen (P = 0.8). Side effects, present in 31.3% of treated patients, were significantly more common in the 14-day group (P = 0.015). Four patients discontinued treatment, all in the 14-day group. Conclusions Ten day concomitant nonbismuth quadruple therapy for H. pylori is highly efficacious and better tolerated than the 14-day regimen. Thus, 10-day therapy may be preferred as first-line treatment in clinical practice.

Prevalence and indicators of use of complementary and alternative medicine in Austrian patients with inflammatory bowel disease Objective Complementary and alternative medicine (CAM) seems to be frequently used among patients with inflammatory bowel disease (IBD). We aimed to determine the prevalence and indicators of CAM use in Austrian IBD patients. Methods In a multicentre cross-sectional study, adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded use of CAM as well as medical and socioeconomic characteristics. Patients were recruited between June 2014 and June 2015. The study outcome was the prevalence of CAM use and its socioeconomic and disease-related associations. Results A total of 1286 patients (Crohn’s disease 830, ulcerative colitis 435, IBD unclassified 21; females 651) with a median age of 40 years (interquartile range 31–52 years) and a median disease duration of 10 years (4–18 years) were analysed. The prevalence of previous and/or current CAM use was 50.7%, with similar results for Crohn’s disease and ulcerative colitis. In the multivariable analysis, female gender and a university education were independent socioeconomic indicators of CAM use. IBD-related indicators were longer duration of the disease and previous and/or current treatment with steroids and TNF-α inhibitors. Conclusion CAM use for IBD is frequent in Austrian IBD patients and associated with female gender, higher educational level of university degree, longer duration of the disease, and treatment with steroids and TNF-α inhibitors.

Colorectal cancer detection by biomarker quantification in noninvasively collected colorectal mucus: preliminary comparison of 24 protein biomarkers Objectives Noninvasive colorectal cancer detection and screening remain global diagnostic challenges because the existing stool tests either lack sensitivity or are complex and expensive. Moreover, colorectal cancer screening uptake is low due to stool sampling inconvenience. We have developed a simple and patient-friendly noninvasive technique for collecting highly informative colorectal mucus. In this study, we aimed to comparatively assess a range of candidate biomarkers in colorectal mucus samples for colorectal cancer detection. Methods The study included 17 patients with colorectal cancer and 35 healthy controls, who provided noninvasively collected colorectal mucus samples. Protein biomarker quantification in these samples by enzyme-linked immunosorbent assays allowed comparing diagnostic performances of 24 candidate biomarkers that comprised haemoglobin, D-dimer, M2-pyruvate kinase, carcinoembryonic antigen, C-reactive protein, calprotectin, eosinophil-derived neurotoxin, protein S100A12, tumour necrosis factor α, clusterin, soluble cytokeratin 18, caspase-cleaved cytokeratin 18, citrullinated histone H3, peptidyl arginine deiminase 4, epidermal growth factor, epidermal growth factor receptor, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, periostin, vascular endothelial growth factor A, vascular endothelial growth factor receptor 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and mucin 2. Tested biomarkers were ranked for colorectal cancer detection efficiency using receiver operating characteristic curve analysis. Results High area under the curve values between 0.943 and 0.768 were observed for haemoglobin, tissue inhibitor of metalloproteinase 1, M2-pyruvate kinase, peptidyl arginine deiminase 4, C-reactive protein, matrix metalloproteinase 9, epidermal growth factor receptor, eosinophil-derived neurotoxin and calprotectin. Conclusion Quantification of protein biomarkers in noninvasively collected samples of colorectal mucus certainly allows detecting colorectal cancer. Further clinical evaluation of the optimal biomarkers identified by this study is needed.

Time to antibody detection and associated factors for presence of anti-drug antibodies in pediatric inflammatory bowel disease patients treated with anti-TNF therapy Background: Loss of response in pediatric inflammatory bowel disease patients treated with biologic medications can be due to development of anti-drug antibodies. Natural history of anti-drug antibodies development has not been well described in pediatric inflammatory bowel disease. The primary aim of this study was to describe a single-center experience for the temporal onset of anti-drug antibodies detection. Methods: We performed a retrospective, single-center chart review of pediatric inflammatory bowel disease patients at the Division of Pediatric Gastroenterology, Hepatology, and Nutrition at Rainbow Babies and Children’s Hospital from 2010 to 2015. Patients were treated with infliximab or adalimumab and had at least two evaluations for anti-drug antibodies with the homogenous mobility shift assay. Demographics, laboratory and medication data, and clinical disease activity were collected. Results: A total of 75 subjects are included in the analysis. Eighty-one percent of subjects were treated with infliximab. Eleven subjects developed anti-drug antibodies; average time to anti-drug antibodies detection was 13.2 ± 7.3 months. Longer duration of inflammatory bowel disease, L1 location in Crohn’s disease, and not having immunomodulatory therapy before biologic was associated with higher risk of antibody detection. Antibody detection occurred more frequently with infliximab vs. adalimumab. Time-to-antibody detection for infliximab and adalimumab was 14.83 and 23.48 months, respectively. Conclusion: Chances of anti-drug antibodies detection in the infliximab group were higher than the adalimumab group. Time-to-antibody detection was 8.65 months longer in patients who received adalimumab when compared to infliximab. These results may have implications for long-term therapy and help guide use of concomitant immunomodulators.

Gastric endoscopic submucosal dissection: a systematic review and meta-analysis on risk factors for poor short-term outcomes Objective Endoscopic submucosal dissection (ESD) is now established as the first option to manage early gastric neoplasms, but its efficacy may vary according to diverse factors. We aimed to systematically identify risk factors for poor short-term outcomes of gastric ESD with the purpose to improve patients’ selection and management. Methods Three online databases (MEDLINE, ISI Web of Knowledge and Scopus) were searched (last search on June 2018) for poor outcomes of gastric ESD (deep submucosal invasion, piecemeal/incomplete resection, noncurative resection and local recurrence). Results One hundred five studies were included referring to 52.126 ESDs. Undifferentiated histology and upper location (vs lower) were associated with submucosal invasion [odds ratio (OR) = 2.42 [95% confidence interval (CI), 1.62–3.61] and OR = 3.20 (1.04–9.86), respectively] and deep submucosal invasion [OR = 2.98 (2.02–4.39) and OR = 2.35 (1.45–3.81), respectively]. Lesion size greater than 30 mm and ulceration were associated with piecemeal resection [OR = 2.78 (1.17–6.60) and OR = 2.76 (1.23, 6.20), respectively]. Lesion size greater than 30 mm, ulceration, upper location and fibrosis were risk factors for incomplete resection [OR = 3.83 (2.68–5.49), OR = 4.06 (1.62–10.16), OR = 3.71 (2.49–5.54) and OR = 4.46 (1.66–11.96), respectively]. A noncurative resection was more often observed for lesions located in the upper third of the stomach [OR = 1.49 (1.24–1.79)], depressed morphology [OR = 1.49 (1.04–2.12)] and those outside standard criteria [OR = 3.56 (2.31–5.48)]. Older age was significantly linked with local recurrence rates [OR = 3.08 (1.13–5.02)]. Conclusion Several risk factors influence poor efficacy short-term outcomes of gastric ESD that may be used to inform both patients and health providers about the expected efficacy.

Changing epidemiology of chronic hepatitis C: patients are older and at a more advanced stage at the time of diagnosis Introduction and aim Over the years, there has been a change in the profile of patients with chronic hepatitis C (CHC). In recent years, more patients with CHC have presented to the clinics at the cirrhotic stage, with decompensated liver disease, and with hepatocellular carcinoma. The aim of this study was to investigate the changing epidemiological, clinical, and virological characteristics of CHC patients. Patients and methods A total of 313 CHC patients were included in this study. The patients were classified into group 1 (1996–2001) and group 2 (2011–2016). Epidemiological, clinical, and virological differences were investigated between two periods. Results Overall, 44.7% (n = 140) of the patients were in group 1. The sex distribution between the two groups was similar. The patients in group 2 was older than those in group 1 (54 ± 15 vs. 45 ± 12 years, retrospectively, P < 0.001). Whereas 19.8% of the patients in group 1 were treatment-experienced, this rate was found to be 35.5% in group 2 (P = 0.01). Patients who presented in the first period had fewer comorbidities compared with group 2 (P < 0.001). More patients in group 2 had liver cirrhosis than group 1 (45.1 vs. 18.6%, respectively, P < 0.001). Among the patients with cirrhosis, the rate of decompensation was higher in group 2 (46.7 vs. 23.3%, P = 0.03). The presence of hepatocellular carcinoma was significantly higher in group 2 than group 1 (12.8 vs. 3.6%, respectively, P = 0.004). Conclusion In recent years, CHC patients have presented to hospitals with advanced stage of liver disease; these patients are older and have more comorbidities.