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The association between intraductal papillary mucinous neoplasms (IPMNs) and extra-pancreatic malignancies is controversial. This cross-sectional study compared esophagogastroduodenal findings in 340 IPMN patients to those of age- and gender-matched controls without known IPMNs who underwent esophagogastroduodenoscopies (EGDs) for similar clinical reasons. The presence of gastric and esophageal cancer, Barrett’s esophagus, neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), gastric adenomas, and ampullary tumors was assessed. The results showed that 4/340 (1.2%) of the IPMN patients had gastric cancer and 1/340 (0.3%) had esophageal cancer. The matched control group had a similar incidence of gastric cancer (5/340) (1.5%), with no esophageal cancer cases (p > 0.999). The overall incidence of other esophagogastroduodenal conditions did not significantly differ between the IPMN patients and the controls. However, the incidence of gastric cancer in the IPMN patients was higher than expected based on national cancer registry data (standardized incidence ratio of 31.39; p < 0.001; CI 8.38–78.76). In conclusion, IPMN patients have a significantly higher incidence of gastric cancer compared to the general population. However, the incidence of esophagogastroduodenal findings, including gastric and esophageal cancer, is similar between IPMN patients and those who undergo an EGD for similar clinical indications. Further research is needed to determine optimal surveillance strategies for IPMN patients regarding their risk of developing gastric cancer.

Endoscopic ultrasound (EUS) was born from the combination of a high-frequency ultrasound probe with an endoscope to assess in detail the walls of the upper and lower gastrointestinal tract and surrounding organs and structures. The subsequent possibility of EUS-guided tissue acquisition has rapidly established the irreplaceable role of EUS in the management of a wide range of benign and malignant gastrointestinal diseases. The actual diagnostic armamentarium involving fine-Doppler, elastography, and contrast enhancement has significantly improved its diagnostic yield, which could be even more refined by newer ways of interrogating data and images, such as artificial intelligence. Technological development (e.g., new echendoscopes, larger operative channels, special-design needles, lumen apposing metal stents, and dedicated biliary stents) and the clinical need for new, more effective, and less-invasive procedures has rapidly evolved EUS from a purely diagnostic tool to a therapeutic modality, that is making increasingly outdated some surgical or radiological procedures that have hitherto been considered standard of care.

BACKGROUND Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bacteremia (PEB) occurs in up to 5% of cases, while antibiotic prophylaxis is recommended only when an ERCP is unlikely to achieve complete biliary drainage. However, the current recommendations may not cover all potential risk factors for PEB. AIM To identify novel risk factors for PEB and evaluate appropriateness of antibiotic prophylaxis. METHODS A retrospective study of 1082 ERCP procedures performed between January 2012 - December 2013 in a single tertiary medical center. Data collection included: Demographic and clinical characteristics such as pre and post procedure antibiotic treatment and bacterial blood cultures. Exclusion criteria were: (1) Age < 18 years; (2) Positive bacterial blood culture before ERCP; (3) Scheduled antibiotic treatment prior to ERCP; (4) Hospitalization longer than 14 d before ERCP; and (5) missing critical data. Stepwise Logistic Regression analysis and Decision Tree algorithms were used for prediction modeling of PEB. RESULTS A total of 626 ERCPs performed in 434 patients were included. Mean age 66.49 ± 15.4 years and 46.5% were males. PEB prevalence was 3.7%. Antibiotic prophylaxis was administrated in 139/626 (22.2%) cases but was indicated according to the guidelines only in 44/626 (7%) cases. In all the PEB cases, prophylaxis was deemed not indicated. A stepwise logistic regression [receiver operating characteristic (ROC), 0.766], identified 3 variables as independent risk factors for PEB: Age at ERCP ≥ 75 years (OR, 3.780, 95%CI: 1.519-9.408, P = 0.004); Tandem EUS/ERCP with fine needle aspiration (FNA) (OR, 14.528, 95%CI: 3.571-59.095, P < 0.001); ERCP duration longer than 60 min (OR, 5.396, 95%CI: 1.86-15.656, P = 0.002). In a decision tree model (ROC, 0.778) the probability for PEB without any risk factors was 1% regardless of prophylaxis administration. CONCLUSION The prevalence of PEB in our study is similar to previous reports, despite the fact that antibiotic prophylaxis was administrated more readily than recommended. ERCP duration longer than 60 min, tandem EUS-ERCP with FNA and age above 75 years are significant risk factors for PEB. These factors should be further evaluated as indications for prophylactic antibiotic treatment before ERCP.

Background: Recent advances in EUS techniques (real-time EUS elastography and contrast-enhanced EUS) have allowed a better characterization of focal pancreatic masses. Mean strain histograms (SHs) are considered a good parameter for the semi-quantitative evaluation of focal pancreatic masses, alongside complementary contrast-enhanced EUS parameters which can be quantified during both the early arterial and late venous phase. Materials and Methods: The study design was prospective, blinded, and multicentric, assessing real-time EUS elastography and contrast-enhanced EUS results for the characterization of focal pancreatic masses using parametric measurements, in comparison with pathology which is the gold standard. SHs were performed based on the embedded software of the ultrasound system, with the values being reversed as opposed to our initially published data on hue histograms. Consequently, a cutoff of 80 was derived from previous multicentric trials. Contrast-enhanced EUS also allowed the focal masses to be classified as hyper-, iso-, or hypoenhanced in comparison with the normal pancreatic parenchyma. EUS-FNA was then performed for all patients, with a positive cytological diagnosis taken as a final proof of malignancy for the pancreatic masses. The diagnoses obtained by EUS-FNA were verified further either by surgery or during a clinical follow-up of at least 6 months. Results: A total number of 97 consecutive patients with focal pancreatic masses were included in the study. Based on previously defined cutoffs of 80, the values of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the mean SHs for the diagnosis of pancreatic cancer were 100%, 29.63%, 78.65%, 100%, and 80.41%, respectively. Corresponding values for contrast-enhanced EUS (taking into consideration hypoenhencement as a predictive factor of malignancy) were 98.57%, 77.78%, 92%, 95.45%, and 92.78%, respectively. Combining contrast enhancement-EUS (hypoenhencement) and semi-quantitative EUS elastography (SH cutoffs

Background Instead of choosing one endoscopic ultrasound (EUS) needle over the other, some advocate the use of fine-needle aspiration (FNA) and fine-needle biopsy (FNB) consecutively. We explored the yield of combined use of 20 G FNB and 25 G FNA needles in patients with a suspicious solid gastrointestinal lesion. Methods Patients from the ASPRO study who were sampled with both needles during the same procedure were included. The incremental yield of dual sampling compared with the yield of single needle use on the diagnostic accuracy for malignancy was assessed for both dual sampling approaches – FNA followed by FNB, and vice versa. Results 73 patients were included. There were 39 (53 %) pancreatic lesions, 18 (25 %) submucosal masses, and 16 (22 %) lymph nodes. FNA was used first in 24 patients (33 %) and FNB was used first in 49 (67 %). Generally, FNB was performed after FNA to collect tissue for ancillary testing (75 %), whereas FNA was used after FNB to allow for on-site pathological assessment (76 %). Diagnostic accuracy for malignancy of single needle use increased from 78 % to 92 % with dual sampling (P = 0.002). FNA followed by FNB improved the diagnostic accuracy for malignancy (P = 0.03), whereas FNB followed by FNA did not (P = 0.13). Conclusion Dual sampling only improved diagnostic accuracy when 25 G FNA was followed by 20 G FNB and not vice versa. As the diagnostic benefit of the 20 G FNB over the 25 G FNA needle has recently been proven, sampling with the FNB needle seems a logical first choice.

In "What should be known prior to performing EUS exams, Part I," the authors discussed the need for clinical information and whether other imaging modalities are required before embarking EUS examinations. Herewith, we present part II which addresses some (technical) controversies how EUS is performed and discuss from different points of view providing the relevant evidence as available. (1) Does equipment design influence the complication rate? (2) Should we have a standardized screen orientation? (3) Radial EUS versus longitudinal (linear) EUS. (4) Should we search for incidental findings using EUS?

Negative endoscopic retrograde cholangiopancreatography (ERCP) for suspected common bile duct stones (CBDS) may be associated with significant morbidity and should be avoided. Between 2010 and 2018, 85 patients who have undergone negative ERCP for suspected CBDS were retrospectively evaluated and compared with 318 patients with positive findings. Predictors for negative ERCP were assessed. Patients with negative ERCP were younger; had increased levels of serum amylase, alanine transaminase, and lactate dehydrogenase; and increased hemoglobin. Even though preprocedure computed tomography (CT) or ultrasonography demonstrating CBDS were highly predictive of positive findings on ERCP, of the 212 patients with CBDS on computed tomography or ultrasonography, 17 (8%) eventually had a negative ERCP, suggesting spontaneous stone passage. An increased serum amylase level was the only predictor for negative ERCP in multivariate analysis, including in patients with preprocedure CBDS on imaging. The data suggest that assessing serum amylase may assist in avoiding unnecessary examinations.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P

Exclusion of the proximal gut from nutrient absorption entails significant metabolic benefits. The duodenal-jejunal bypass liner (DJBL) is the first endoscopic device that excludes the first part of the gut by covering it.To assess weight and glycemic control at the end of treatment and after 1 year of follow-up.Bariatric endoscopy service in a tertiary medical center.Diabetic patients were treated with DJBL and followed prospectively between 2013 and 2016. Data were collected during scheduled visits.Out of 51 patients treated, 39 completed at least 9 months with the device. Complications were recorded for the entire cohort. Percent of total weight loss was 15.05% ± 6.0% after 12 months of treatment (P.001 versus baseline). Twelve months postretrieval, percent of total weight loss decreased to 8.75% ± 5.07% (P.001 versus baseline). Patients with baseline body mass index ≥35 kg/mProximal bowel bypass by DJBL is an effective tool for weight reduction and glycemic control. Metabolic achievements are partially preserved at 1 year after device removal. Because DJBL entails a considerable rate of side effects, strategies to mitigate them are warranted.

BackgroundAntibiotic-associated colitis caused by Clostridium difficile (C. difficile) is the most common cause of hospital-acquired diarrhea. The pathogenesis of C. difficile colitis is mediated b...

Although screening colonoscopy is effective for early detection of colorectal cancer (CRC), screening rates remain low. Multiple factors are thought to be responsible for the low rates of screening colonoscopy, but bowel preparation appears to be a key deterrent. Tolerability issues with bowel preparations may lead to poor patient compliance, inadequate colon cleansing, and reduced detection of colonic polyps.The aim of this article is to evaluate the feasibility, safety, and outcomes of minimally prepared intra-procedural hydroflush technique as an alternative to traditional bowel preparation in screening colonoscopy.We conducted a prospective feasibility study of intraprocedural hydroflush technique aided by water-jet pumps and a mechanical suction novel device following minimal bowel preparation for CRC screening.Nine procedures were performed in nine healthy individuals scheduled for routine screening colonoscopy. Preparation included mild diet restriction, laxative tablets two to three days prior to the procedure and two Fleet enemas one to two hours before the colonoscopy. The cleanliness of the colon was assessed by using the Boston bowel preparation scale. Insertion and withdrawal times were recorded.Complete colonoscopy to the cecum was performed in all patients (100%). Mean time to the cecum was 5.78 ± 2.68 minutes, and mean withdrawal time was 15.33 ± 3.94 minutes. Endoscopic visualization of the entire mucosa was achieved in all cases with no colonoscopy repeated because of inadequate preparation. Four polyps have been detected and removed in three patients. Mild mucosal erosions were seen in some areas where the suction was used extensively, similar to those that can be seen during conventional colonoscopy. Mild stiffness of the shaft of the scope was noted.This was an uncontrolled feasibility study of selected patients.Minimally prepared colonoscopy with the intra-procedural hydroflush technique for colorectal screening is feasible. The water exchange technology compensates for the mild stiffness of the scope. This technique might increase patients' compliance for CRC screening.

Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle.Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders.A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836).The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Patients with unresectable pancreatic cancer have a poor prognosis. The analysis of prognostic factors before treatment may be helpful in determining the best therapeutic strategies. The aim of the PEACE study is to assess the vascularity of pancreatic malignant tumors using contrast-enhanced harmonic EUS (CEH-EUS) and to clarify the prognostic value of tumor vascularity in patients with locally advanced and metastatic pancreatic cancer. Hereby, we present the protocol of a prospective, nonrandomized, single-arm, multicenter study aiming to assess changes in tumor vascularity using CEH-EUS before and 2 months after treatment initiation in patients with unresectable, locally advanced/metastatic pancreatic cancer and to examine the correlation between vascular changes and treatment response, progression-free survival, and overall survival.

Up to 3.4% of Crohn's disease (CD) patients will be diagnosed with concomitant primary sclerosing cholangitis (PSC). Despite the worldwide increase incidence of CD, data on the clinical characteristics of PSC-CD patients are scarce.To clinically characterize CD in patients who have concomitant PSC.A retrospective case-control analysis was conducted with 18 CD patients with concomitant PSC who attended the Inflammatory Bowel Disease Center at the Tel Aviv Sourasky Medical Center between 2011-2014 (PSC-CD patients). They were matched by age, gender, and disease duration to 90 control patients (those with CD who did not have concomitant PSC). Disease phenotype (according to the Montreal classification), demographics, and clinical data were compared in the two groups.PSC-CD patients were characterized by a disease that was more frequently limited to the colon (L2) (50% vs. 16%, P = 0.004) and by a non-stricturing and non-penetrating inflammatory phenotype (83% vs. 33%, P = 0.0001) compared to controls who had an increased prevalence of the penetrating phenotype (B3) (6% vs. 33% P0.05). Use of 5-aminosalicylic acid agents as a single therapy was significantly more prevalent among PSC-CD patients than in controls (39% vs. 7%, P0.005). In contrast, biologic therapy was significantly less common among PSC-CD patients compared to controls (17% vs. 52%, P = 0.0086).Patients with PSC-CD are clinically distinct from patients with isolated CD, and are characterized by predominant colonic involvement and an inflammatory, non-stricturing and non-penetrating phenotype.

The aim was to present the workup of patients with acute recurrent pancreatitis (ARP) for genetic analysis and electrophysiological testing.Patients with ARP with unknown etiology were referred for genetic testing and evaluation of cystic fibrosis transmembrane conductor regulator (CFTR) function by nasal potential difference (NPD) testing.A total of 67 patients were evaluated. The mean age was 23 ± 17 years (median 17.0 years, range 1.5-72 years); 90% were Jewish and 10% Arab. Ten (15%) patients carried PRSS1 gene mutation (K23R(7), R122H(2), and D21A(1)). One patient had K172E/- (chymotrypsin C [CTRC]) mutation, 1 had I42M (serine protease inhibitor Kazal type 1 [SPINK1])/V235I (CTRC) together with ΔF508/5T, 1 patient had R67H (SPINK1)/V235I (CTRC), and 1 patient had V235I (CTRC)/-. Ten of 67 (15%) patients submitted for CFTR gene testing carried mutations (ΔF508/L997F, ΔF508/5T(11TG), W1282/5T(12TG), W1282X/Y1014C, ΔF508/R31C, R117H/-, R117H/Y1014C, D1152H/-, 5T(11TG)/-, and L997F/-). Fifty-four (80%) patients underwent sweat testing. Of these, 5 had sweat chloride ≥60 mEq/L, and 22 patients had sweat chloride from 40 to 60 mEq/L. Of the 56 (83%) patients had nasal potential difference testing, 4 (6%) with abnormal results.One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis including rare mutations (K23R), and 12.5% have evidence of cftr mutations and 10% had CFTR dysfunction underscoring the importance of genetic and functional workup of these patients.

Retrospective studies suggest that coffee consumption may exert beneficial effects in patients with nonalcoholic fatty liver; however, prospective data supporting a protective role on liver steatosis development are lacking. In this study, we aimed to evaluate the association between coffee consumption and fatty liver onset in the general population. The analysis was performed both in a cross-sectional cohort (n = 347) and, prospectively, in a subcohort of patients without fatty liver at baseline and followed-up for 7 years (n = 147). Fatty liver was diagnosed with abdominal ultrasound and liver steatosis was quantified noninvasively by hepatorenal index (HRI) and SteatoTest, whereas FibroTest was used to assess fibrosis degree. A structured questionnaire on coffee consumption was administrated during a face-to-face interview. Neither the incidence nor the prevalence of fatty liver according to ultrasonography, SteatoTest, and the HRI was associated with coffee consumption. In the cross-sectional study, high coffee consumption was associated with a lower proportion of clinically significant fibrosis ≥F2 (8.8% vs 16.3%; P = 0.038); consistently, in multivariate logistic regression analysis, high coffee consumption was associated with lower odds for significant fibrosis (odds ratio = 0.49, 95% confidence interval, 0.25–0.97; P = 0.041) and was the strongest predictor for significant fibrosis. No association was demonstrated between coffee consumption and the new onset of nonalcoholic fatty liver, but coffee intake may exert beneficial effects on fibrosis progression.

CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8–83.2%) and 83.8% (95% CI, 74.6–92.7%) and for adenomas 84.2% (95% CI, 60.4–96.4%) and 73.5% (95% CI, 61.4–83.5%), respectively. In the second trial (n= 149), a similar specificity but higher sensitivity was achieved: 80.0% (95% CI, 63.1–91.6%) for CRC and 89.2% (95% CI, 74.6–97%) for adenomas. A simple noninvasive blood test evaluating CD24 levels has high sensitivity and specificity for detecting colorectal adenomas and cancer in patients undergoing colonoscopy at an urban medical center. Larger multicenter studies are warranted to establish the potential of this promising test.

Objectives Dipeptidyl peptidase 4 (DPP4) inhibitors, used in obese diabetic patients, reduce inflammation in several models. The role of chronic DPP4-deficiency (DPP4-) in diet-induced obesity with respect to insulin sensitivity and adipose tissue inflammation was investigated. Design and Methods Insulin resistance was induced by 2 months high fat diet (HFD). In vitro effects of glucose-dependent insulinotropic polypeptide (GIP) were assessed in adipose tissue explants and stromal vascular fraction (SVF). Results HFD-fed DPP4-rats gained significantly more weight and visceral fat mass, yet were more insulin sensitive. Adipose tissue of DPP4- rats demonstrated increased adipocyte maturation and increased expression of enzymes involved in triglyceride uptake and synthesis, yet increased adiponectin mRNA, reduced mRNA of proinflammatory cytokines and reduced vascular adhesion molecules, suggesting reduced inflammation. In vitro and in vivo experiments explored the role of GIP in inducing this phenotype. Indeed, we demonstrated that GIP directly enhanced adiponectin expression in rat and human adipose tissue explants and in SVF. Lastly, GIP administration to normal or HFD-fed rats elevated serum adiponectin and improved their glucose tolerance test. Conclusion In a HFD model, DPP4-rats exhibited reduced adipose tissue inflammation and improved insulin resistance, which may be mediated in part by GIP induction of adiponectin.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre-DM in a 7-year prospective follow-up of healthy volunteers. Methods: A prospective cohort of a subsample of the Israeli National Health Survey evaluated at baseline and after 7 years by identical protocols. Metabolic parameters and ultrasonographic evidence of NAFLD were evaluated in 213 subjects, without known liver disease or history of alcohol abuse. Exclusion criteria were pre-DM at the baseline survey. Steatosis was quantified by ultrasound with the hepatorenal ultrasound index (HRI). Results: The study included 141 volunteers (mean age 48.78 ± 9.68, 24.82% with NAFLD) without pre-DM/DM at baseline. Both NAFLD on regular US (OR=2.93, 1.02–8.41 95%CI) and HRI (OR=7.87, 1.83–33.82) were independent predictors for the development of pre-DM, adjusting for age, gender, BMI, family history of DM, baseline insulin, adiponectin and glucose. Further adjustment for physical activity and dietary intake did not weaken the association. Furthermore, NAFLD was a stronger predictor for pre-DM than the metabolic syndrome. Subjects with both NAFLD and glucose 89 had 93.3% incidence rate of pre-DM. Conclusion: Non-alcoholic fatty liver disease is a strong and independent risk factor for pre-DM in the general adult population; thus, NAFLD patients should be classified as a population at risk.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN).METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence.RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one.CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

AIM: To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI (OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m2) and older age (OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception (OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed (naive) and previously diagnosed (at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician’s visits (general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups. CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on self-health perception.

Background Staple-line leak following laparoscopic sleeve gastrectomy is a dire adverse event. While the treatment of acute and early leaks is well established, there is still dispute regarding late and chronic leaks. We describe an endoscopic approach combining septotomy and sleeve stricture dilation for treating late/chronic leaks. Methods Ten consecutive patients with late/chronic proximal leaks were treated at our center. The septum separating the sleeve lumen from the perigastric cavity was progressively dissected over several sessions and the downstream stricture was pneumatically dilated. The technical and clinical success rates were evaluated. Results: All ten patients were treated successfully. Eight patients had sleeve strictures that were dilated in conjunction with septotomy. A mean of five sessions over the course of 43 days was needed to complete treatment. In two patients with a small perigastric cavity and no stricture, septotomy was achieved with through-the-scope balloon dilation of the fistula. No adverse events were encountered. Conclusions Septotomy accompanied by stricture dilation seems highly effective and safe in late and chronic leaks following sleeve gastrectomy.

Background Biliary strictures (BS) are a common complication of liver transplantation. The standard treatment is sequential insertion of increasing numbers of plastic stents by endoscopic retrograde cholangiopancreatography (ERCP). Despite high success rates, some strictures fail to resolve and require surgery as definitive treatment. Goals To identify predictors of response or failure of standard endoscopic treatment, allowing earlier referral to alternative modalities when needed and avoiding unnecessary procedures. Study Database of Gastroenterology Department at Tel Aviv Medical Center was retrospectively reviewed, and data regarding patients who underwent liver transplantation and developed BS were analyzed. Results Thirty-one patients met the study criteria. Twenty-four (77.4%) resolved with plastic stenting and 7 ultimately required surgery. There were no significant differences between stent responders and nonresponders regarding demographics, transplant and postoperative hospitalization data, time from transplantation to presentation with stricture, total number of ERCP sessions, or maximal number of stents.A trend toward difference was noted in the time elapsed between the first and the second ERCP, whereby ERCP nonresponders required a second procedure sooner than responders. Patients presenting to their second procedure as scheduled ultimately had a 95% endoscopic success rate, whereas those presenting urgently with acute cholangitis had a 55% failure rate (P=0.02). Conclusions Urgent repeat ERCP is a harbinger of ultimate failure of plastic stent treatment for BS after liver transplant. This finding may assist earlier triage of these patients toward alternative treatment such as metal stents or surgery, thus sparing needless procedures and complications.

To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations.We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma (AA) and colorectal cancer (CRC) were determined in the 40's and 50's age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations.We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men (P0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups.The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.

Background Endoscopic retrograde cholangiopancreatography–induced perforation (EP) is a rare but severe complication. We describe the risk factors, management, and outcome of ERCP-induced perforations in a tertiary center. Methods This is a case-control study. All EP cases between March 2004 and February 2015 were compared to a control group without perforation. Data on patients, procedures, presentation, perforation type, radiologic findings, management, and outcome were assessed. Results Of 6,934 endoscopic retrograde cholangiopancreatographies, 37 patients (0.53%) had EP. Independent risk factors included failure of cannulation, a procedure described as “difficult,” performing a precut and resection of a periampullary adenoma. Perforation was diagnosed during the procedure in 7 patients (19%). Median interval for diagnosis was 11 hours (range: 0–201 hours), with 84% diagnosed within 30 hours. The periampullary region was the most common EP site (51%). Twenty-nine patients (78%) were managed conservatively and 8 (22%) were operated. Three patients failed conservative management and required delayed operation. Failure of conservative management had a detrimental effect on morbidity and duration of stay. All patients who required operative intervention had perforation of either the duodenal free wall or the periampullary region. Conclusion Clear risk factors can be used to raise suspicion of EP. Early diagnosis and management are critical for better outcome. This is especially important when operative intervention is indicated. Nonetheless, the majority of patients may be managed conservatively.

To improve the preoperative assessment of pancreatic incidentalomas (PIs) by analysis of 1 index case and characterization of the published features of intrapancreatic accessory spleen (IPAS) compared to pancreatic neuroendocrine tumor (PNET).A search of the literature using the online database MEDLINE.In all, 46 cases of IPAS have been described to date: 17 were "presumed" as IPAS based on technetium-99m (Tc-99m) scanning, fine-needle aspiration (FNA) stain for CD8, or contrast-enhanced sonography; 29 were misdiagnosed as PNET and underwent surgery. The pancreatic lesions were 1) mostly solitary; 2) solid on imaging; 3) well defined; 4) located predominantly at the pancreatic tail; 5) not exceeding 3 cm in the largest diameter; 5) all detected in adults (22-81 years); 6) not related to sex. In subjects referred for surgery, standard imaging studies/imaging protocols did not differentiate between IPAS and PNET. FNA was performed in 5/46 cases, all of which were false-positive for PNET. Immunohistochemical staining for T-cells on FNA material and specific imaging features (characteristic arciform splenic enhancement pattern on dynamic computed tomography [CT]; nuclear scintigraphies with radioisotope specifically trapped by splenic tissue [Tc-99m]) or contrast-enhanced sonography offered valuable clues. Still, distal pancreatectomy and splenectomy was carried out in 72%, and the rest had distal pancreatectomies.IPAS should be considered before surgery in patients with PIs. A new practical algorithm is presented for better preoperative evaluation of such lesions; it combines the recognition of early indicators and sequential consideration of cytologic and imaging features to decrease the hazards of unnecessary major surgery.CT = computed tomography EUS = endoscopic ultrasound FNA = fine-needle aspiration HDRBC = heat-damaged red blood cells IPAS = intrapancreatic accessory spleen MRI = magnetic resonance tomography NF-PNET = nonfunctioning pancreatic neuroendocrine tumor PET = positron emission tomography PNET = pancreatic neuroendocrine tumor PI = pancreatic incidentalomas SPIO = superparamagnetic iron oxide Tc-99m = technetium-99m.

The milieu of the liver, and in particular hepatocyte-derived extracellular matrix (hECM), is a critical factor regulating development of liver metastases of colorectal cancer (CRC) cells. The present study has investigated genes altered by hECM in CRC cells and particularly by heparan sulfate chains of hepatocyte proteoglycans. Gene profiling analysis shows that after 2 days on hECM, 226 genes are up-regulated more than 2-fold in strongly metastatic SM cells, including genes involved in growth arrest and apoptosis, signal transduction, cell migration, proliferation, communication and angiogenesis, with activation of the erbB signaling network and p53 effectors. Genes down-regulated by hECM include genes involved in lipogenesis and the S phase of the cell cycle. Further studies exploring the kinetics of gene expression after 4 and 7 days culture on hECM show induction of EGF family members and of stem cell markers. In particular, hECM, but not collagen, increases mRNA expression of HB-EGF and colon stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). Expression of these genes is not induced by hECM depleted of the heparan sulfate chains of proteoglycans. Lastly, a specific cell population positive for cancer stem cell (CSC) markers LGR5, epCAM and CD133, but negative for CD44, appears after 7 days culture on hECM, a population which is reduced by 50 % in cells grown on heparan sulfated-depleted hECM. Collectively, the data suggest that hECM induces growth factors and receptors regulating proliferation of metastatic CRC in the liver and offers a growth advantage for specific populations expressing CSC markers.

Background and study aims: Complete bowel cleansing is mandatory for effective colon cancer screening and surveillance. The aim of the current pilot study, which was conducted in humans, was to test the safety and efficiency of a newly developed disposable cleaning device, the MedJet, for intraprocedural bowel cleansing. Patients and methods: Patients with screening or surveillance colonoscopy after previous polypectomy were included. The colonoscope was first inserted to the cecum and the overall cleansing was assessed according to the Ottawa scale. The MedJet device was used if colon cleansing had been incomplete. The MedJet catheter was passed over the working channel of the colonoscope and the colon was cleaned during withdrawal. The MedJet device delivered controlled jets comprising compressed CO 2 and minimal amounts of sterile water, which allowed disintegration and removal of residual stool. The efficiency of cleaning was assessed according to the Boston scale. Results: A total of 32 patients (16 female; mean age 61 years) were treated with the device. No device-related adverse or serious adverse events were noted. MedJet application during withdrawal provided effective and significant improvement in bowel cleansing ( P = 0.005). Furthermore, 18 adenomas and 1 colon cancer, which were hidden behind stool remnants, could be identified in 11 patients following use of the MedJet device. However, the withdrawal times were prolonged (11.4±6.0 minutes) due to the additional cleaning procedure. All patients tolerated the procedure well. Conclusions: The new MedJet device enabled highly effective and safe bowel cleansing during colonoscopy. The catheter-based system was easy to use and CO 2 was applied for cleansing. The procedure was well tolerated by patients.

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Quantification of liver steatosis is clinically relevant in various liver diseases but cannot be done by conventional sonography, which only provides a qualitative assessment with significant observer variability. The aim of this study was to assess sonography as an objective tool for the quantification of liver steatosis.Files of 111 patients with chronic liver disease who were referred for sonographically guided liver biopsy were collected. A hepatorenal sonographic index was calculated on the basis of the ratio between the echogenicity of the liver and that of the right kidney cortex using histogram echo intensity. Liver steatosis was graded by histology.A significant correlation was found between histologic steatosis and the hepatorenal sonographic index (r = 0.82, p0.001). The validity of the hepatorenal sonographic index for the diagnosis of fatty liver was compared with liver biopsies with a steatosis level5%. The area under the receiver operating characteristic curve was 99.2% (95% CI, 98-100%). The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis5% was 1.49, with sensitivity of 100% and specificity of 91%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis/= 25% was 1.86, with sensitivity of 90% and specificity of 90%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis/= 60% was 2.23, with sensitivity of 90% and specificity of 93%.The hepatorenal sonographic index is a sensitive noninvasive method for steatosis quantification. It can diagnose small amounts of liver fat that would be missed by conventional sonography. It is reproducible and operator independent and can serve as an efficient tool to follow patients with steatosis and evaluate the efficacy of new treatment techniques.

BACKGROUND Endoscopic ultrasound is a diagnostic tool for evaluation of gastrointestinal diseases in adults, but in children the use of endoscopic ultrasound is limited. This study retrospectively evaluates endoscopic ultrasound indications in, safety in, and impact on children. PATIENTS AND METHODS We reviewed the data of all of the pediatric patients (

Background and study aims: The Aer-O-Scope™ Colonoscope System (AOS) combines panoramic 360° view with standard forward view. We assessed the AOS’s ability to identify lesions implanted in live swine, compared to conventional colonoscopy (CC). Patients and methods: Twelve swine colons were surgically ligated and beads sewn within. Five procedures (3 AOS and 2 CC) were performed on each swine and findings reported. Physicians were blinded to number, size, and color of beads. The sequence of procedures and physicians was randomized. Pigs, physicians, and colonoscopes were randomly alternated between examination rooms, maintaining physician blindness. Two independent blinded physicians interpreted procedure videos offline. Results: A total of 259 /273 (94.9 %) of lesions were visualized by AOS compared to 158 /182 with CC (86.8 %) (P = 0.002). Miss rates of lesions ≥ 6 mm were 2.6 % and 10.5 %, respectively (P = 0.022), and 6.9 % and 15.1 %, respectively, for lesions

Bi-allelic MUTYH gene mutations are associated with a clinical phenotype of multiple colorectal adenomas and an increased risk for colorectal cancer (CRC). It is unclear whether mono-allelic MUTYH gene carriers (heterozygotes) are also at increased risk for even few adenomas or cancer. In order to clarify an association between MUTYH heterozygotes and adenomas, we evaluated the frequency and types of MUTYH mutations and variants in 72 North-African Jews having few (≥3) colorectal adenomas with or without early onset (50 years) CRC compared to 29 healthy controls. Germ-line DNA was analyzed for a panel of 6 MUTYH mutations and variants, and Sanger sequencing of the entire MUTYH gene was performed for mono-allelic MUTYH mutation carriers. APC gene mutations and Lynch syndrome were excluded in the relevant cases according to accepted clinical criteria. Twenty-two of the 72 adenoma subjects (30.5%) had MUTYH mutations or variants. Nine were homozygotes or compound heterozygotes: all had10 adenomas and one had CRC. Thirteen others were mono-allelic carriers (heterozygotes) of a single MUTYH mutation: six had more than ten adenomas and seven had less than ten adenomas; of these 13 mono-allelic carriers, six had a neoplasm: three CRCs and three extra-intestinal tumors. Eleven of the thirteen mono-allelic carriers with adenomas had a family history of cancer in first or second degree relatives. A multivariable model showed positive correlation between G396D, Y179C and 1186 ins GG mutations and number of adenomas (OR 8.6, 10.2 and 14.4, respectively). The Q324H variant was negatively associated with the number of adenomatous polyps (OR -5.23). In conclusion, MUTYH mutations are prevalent among Jews of North-African origin with colorectal adenomas with or without early onset CRC. Mono-allelic MUTYH carriers with a family history of cancer had a clinical phenotype that varied from having only few adenomas to multiple (10) adenomas. These findings support MUTYH testing in patients with even few adenomas and suggest the consideration of increased surveillance in mono-allelic carriers with a family history of cancer.

Although colonoscopy is the "gold standard" for colorectal cancer screening, a significant number of adenomas are still missed during standard colonoscopy, often because they are hidden behind colonic folds and flexures. The aim of this study was to assess the ability of a novel balloon colonoscope (G-EYE endoscope; Smart Medical Systems, Ra'anana, Israel) to increase adenoma detection and reduce the miss rate compared with standard colonoscopy.This was a multicenter, randomized, prospective, controlled study in patients (age ≥ 40 years) undergoing colonoscopy for screening or diagnostic work-up (including surveillance). Patients underwent same-day, back-to-back tandem colonoscopy. Patients in Group A underwent standard colonoscopy followed by balloon colonoscopy, and patients in Group B underwent balloon colonoscopy followed by the standard technique. The adenoma detection and miss rates were compared between the two colonoscopy procedures.A total of 126 patients were enrolled and randomized into Group A (n = 60) or Group B (n = 66). The adenoma miss rate of balloon colonoscopy was significantly lower than that of standard colonoscopy (7.5 % vs. 44.7 %; P = 0.0002). The detection of additional adenomas by balloon colonoscopy was significant (81.0 %; P = 0.0002), in particular, the relative amount of adenomas detected in the ascending colon by balloon colonoscopy was 41 % versus 14 % for standard colonoscopy.A novel balloon colonoscopy technique detected significantly more adenomas than standard colonoscopy, and missed fewer adenomas. Balloon colonoscopy has the potential to increase the effectiveness of colorectal cancer screening and surveillance colonoscopy.

BACKGROUND Patients with ulcerative colitis undergoing total proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. Alpha-1-antitrypsin (AAT) is an acute phase reactant produced mainly by hepatocytes, but also locally in the gut. Data on noninvasive biomarkers of pouchitis are scarce. METHODS To identify biomarkers that correlate with pouch inflammation, ulcerative colitis pouch patients were prospectively recruited and underwent clinical, endoscopic, and histologic evaluations. The Pouchitis Disease Activity Index (PDAI) was calculated, and pouchitis was defined by a score ≥7. Serum and fecal AAT, C-reactive protein (CRP), fecal calprotectin, ferritin and albumin levels were measured. RESULTS Seventy-one ulcerative colitis pouch patients (mean age 43.8 ± 8.3 yr, 50.7% males) were included. The main indication for ileal pouch-anal anastomosis was intractable colitis (83.1%). Median serum AAT level (183.0 mg/dL, 155.1-232.0) was significantly higher in patients with a PDAI ≥7 compared with those with a PDAI

Background and Objectives: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed. Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD. Results: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the First choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended. Conclusion: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.