Search

Pancreatobiliary strictures are a common source of false negatives for malignancy detection. UroVysion is more sensitive than any other method but remains underutilized because of conflicting sensitivities and specificities due to a lack of standardized cutoff criteria and confusion in interpreting results in the context of primary sclerosing cholangitis. We set out to determine the sensitivities and specificities of UroVysion, brushing cytology, forceps biopsies, and fine needle aspiration (FNAs) for pancreatobiliary stricture malignancy detection. A retrospective review was performed of all biopsied pancreatobiliary strictures at our institution over 5 years. UroVysion was unquestionably the most sensitive method and all methods were highly specific. Sensitivity was highest while maintaining specificity when a malignant interpretation was limited to cases with 5+ cells with the same polysomic signal pattern and/or loss of one or both 9p21 signals. Only UroVysion detected the metastases and a neuroendocrine tumor. In reviewing and analyzing the signal patterns, we noticed trends according to location and diagnosis. Herein we describe our method for analyzing signal patterns and propose cutoff criteria based upon observations gleaned from such analysis., Fluorescent in situ hybridization has been the most sensitive method for detecting pancreatobiliary stricture malignancy in biopsy specimens but is underutilized because of confusion from inconsistent and suboptimal criteria. This article presents refined criteria based on the literature, our experience, and a method for signal pattern analysis that we illustrate in this article.

Background and Aims Reports on fluorescent in situ hybridization (FISH) of pancreatobiliary strictures have shown a wide range of sensitivities for malignancy detection. Our aim was to determine the sensitivity and specificity at our institution of biliary brushings, forceps biopsies, fine needle aspirations, FISH, and their combinations. Methods The study entailed a retrospective review of all cases with pancreatobiliary stricture specimens at our institution over a 5-year period. The medical record for each case was reviewed to independently confirm the presence or absence of malignancy. Sensitivities and specificities were calculated for each method. Results The cohort consisted of 181 sampling procedures from 154 patients. Of the patients, 39 (25.3%) had primary sclerosing cholangitis (PSC) and 41 (26.6%) had malignancy. Brush cytology sensitivity ranged from 24 to 63%. Forceps biopsy sensitivity ranged from 24 to 49%. FNA sensitivity ranged from 32 to 60%. Brush FISH ranged from 58 to 95%. Specificity was 99% for brush FISH and 100% for all other methods. The one false positive was an isolated FISH result in a case of PSC. Conclusion FISH should be performed since it is more sensitive than all other methods and nearly perfect in specificity outside the context of PSC. In PSC, isolated positive FISH results should be interpreted with caution.

Background and study aims The adenoma detection rate (ADR) is an important quality metric of colonoscopy. Higher ADR correlates with lower incidence of interval colorectal cancer. ADR is variable between endoscopists and depends upon the withdrawal technique amongst other factors. Dynamic position change (lateral rotation of patients with a view to keep the portion of the colon being inspected at a higher level) helps with luminal distension during the withdrawal phase. However, impact of this on ADR is not known in a pooled sample. We performed a systematic review and meta-analysis to study the impact of dynamic position changes during withdrawal phase of colonoscopy on ADR Methods A comprehensive search of MEDLINE, EMBASE, Google Scholar, and the Cochrane Database was conducted from each database’s inception to search for studies comparing dynamic position changes during colonoscope withdrawal with static left lateral position (control). The primary outcome of interest was ADR. Other studied outcomes were polyp detection rate (PDR) and withdrawal time. Outcomes were reported as pooled odds ratio (OR) with 95 % confidence intervals (CI) with statistical significance (P Results Six studies were included in our analysis with 2860 patients. Of these, dynamic position change was implemented in 1177 patients while 1183 patients served as the controls. ADR was significantly higher in the dynamic position change group with pooled OR 1.36 (95 % CI, 1.15–1.61; P Conclusion Position change during the withdrawal phase of colonoscopy can increase the ADR compared to static left lateral position. This is an easy and practical technique that can be implemented to improve ADR.

Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.

BACKGROUND & AIMS: Acetaminophen (APAP) overdose remains a frequent cause of acute liver failure, which is generally accompanied by increased levels of serum bile acids (BAs). However, the pathophysiological role of BAs remains elusive. Herein, we investigated the role of BAs in APAP-induced hepatotoxicity. METHODS: We performed intravital imaging to investigate BA transport in mice, quantified endogenous BA concentrations in the serum of mice and patients with APAP overdose, analyzed liver tissue and bile by mass spectrometry and MALDI-mass spectrometry imaging, assessed the integrity of the blood-bile barrier and the role of oxidative stress by immunostaining of tight junction proteins and intravital imaging of fluorescent markers, identified the intracellular cytotoxic concentrations of BAs, and performed interventions to block BA uptake from blood into hepatocytes. RESULTS: Prior to the onset of cell death, APAP overdose causes massive oxidative stress in the pericentral lobular zone, which coincided with a breach of the blood-bile barrier. Consequently, BAs leak from the bile canaliculi into the sinusoidal blood, which is then followed by their uptake into hepatocytes via the basolateral membrane, their secretion into canaliculi and repeated cycling. This, what we termed 'futile cycling' of BAs, led to increased intracellular BA concentrations that were high enough to cause hepatocyte death. Importantly, however, the interruption of BA re-uptake by pharmacological NTCP blockage using Myrcludex B and Oatp knockout strongly reduced APAP-induced hepatotoxicity. CONCLUSIONS: APAP overdose induces a breach of the blood-bile barrier which leads to futile BA cycling that causes hepatocyte death. Prevention of BA cycling may represent a therapeutic option after APAP intoxication. LAY SUMMARY: Only one drug, N-acetylcysteine, is approved for the treatment of acetaminophen overdose and it is only effective when given within ∼8 hours after ingestion. We identified a mechanism by which acetaminophen overdose causes an increase in bile acid concentrations (to above toxic thresholds) in hepatocytes. Blocking this mechanism prevented acetaminophen-induced hepatotoxicity in mice and evidence from patients suggests that this therapy may be effective for longer periods after ingestion compared to N-acetylcysteine.

TPS4195 Background: The efficacy of chemotherapy is often compromised due to poor penetration of drugs in solid tumors. The tumor microenvironment, which is characterized by dense extracellular matrix‐rich stroma that creates a physical barrier to penetration of anti‐cancer drugs, is especially pronounced in Pancreatic Ductal Adenocarcinoma (PDAC) and in peritoneal metastases from Colorectal/Appendiceal Adenocarcinoma. CEND‐1 is a tumor‐penetrating peptide (scientifically also known as iRGD) that has preclinically demonstrated to enhance the tumor penetration of chemotherapy agents through binding and activation of alphav-integrins and neuropilin‐1 (NRP-1). The 2-step mechanism leads to a higher delivery and concentration of chemotherapeutics selectively in the tumor, while sparing normal tissue. Hence CEND-1 therapy has the potential to improve the efficacy of anti‐cancer therapies and reduce side effects through increased tumor access, specificity, and sensitivity. We hypothesize that CEND‐1 may become a powerful adjuvant that safely enhances standard anti‐neoplastic therapy in the neoadjuvant setting for the above populations. Methods: A safety lead-in 6-9 patients (Phase Ib) will be followed by an open label, single arm, parallel (3 cohorts) Phase IIa study. A total of 50 patients (20 PDAC, 15 colorectal/appendiceal with peritoneal metastases, 15 oligometastatic colorectal) will be enrolled. A starting CEND-1 dose of 3.2 mg/kg in combination with the standard doses of FOLFIRINOX (+/- Panitumumab if RAS/RAF wild type) will be used for the safety lead-in. CEND-1 dose will be lowered for Phase IIa if > 1/6 patients experienced DLTs. Participants enrolled will receive standard doses of FOLFIRINOX q2w +/- Panitumumab q2w 6mg/kg IV q2w (14-day cycles) for Cycles 1-3. After a subsequent research biopsy, the CEND-1 + chemotherapy combo will be continued at RP2D q2w for cycles 4-6, followed by CEND-1 +/- Panitumumab ̃72h prior to resection. Assessment of tumor response using RECIST v1.1 will be done every 3 cycles. Up to 10 patients may receive Panitumumab. Eligible Pts are untreated, newly diagnosed, resectable/borderline resectable PDAC or colorectal/appendiceal adenocarcinoma with peritoneal metastases or oligometastases eligible for cytoreductive surgery, as determined by multidisciplinary evaluation. Inclusion criteria also include ECOG PS 0-1, adequate organ function, measurable or evaluable disease. Primary objectives are safety and biological activity of CEND‐1. Secondary objectives include ORR, R0 resection rate, DFS, OS. Exploratory objectives include pathologic response, tissue immune response, EGFR expression, tumor tissue-to-plasma concentration of Panitumumab pre and post CEND-1 treatment. Enrollment to the CENDIFOX trial is currently ongoing. Clinical trial information: NCT05121038.

4047 Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach. The primary objective is pathological response rate (ypRR with tumor regression score, TRS ≤ 2). Methods: Newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m2, Leucovorin 400mg/m2, 5-FU bolus 400mg/m2, and 5-FU 2400mg/m2 infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Up to 2/10/2021, all 37 patients eligible for the study finished preoperative treatment. 27 had curative intended operations, and all had R0 resection. 5 of 27 (19%) achieved ypCR and 6/27 (22 %) with regression score of 0 in the primary cancer. All except 2 patients (25/27, 93%) had shown pathologic response to the treatment with TRS ≤ 2. 21 patients completed all planned treatment with an average follow-up of 27 months. 2 patients had recurrence/metastatic disease (at 9 and 10 months from the enrollment) with 1 died at 23 months, and the other is still alive at 20 month. The rest patients (19/21) are all free of disease. G3/4 toxicities were reported in 21 of all 37 treated patients. There were no unexpected toxicities. Conclusions: The combination of mFOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe. The preliminary benefit data are very encouraging with ypRR of 93%, ypCR of 19 %, and the long-time survival. The data support the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. In addition, the data supports the staging laparoscopy for peritoneal disease assessment as the standard in resctacbility evaluation. Clinical trial information: NCT03488667.

Introduction Microsatellite instability (MSI) testing is recommended for all colonic and endometrial carcinomas to screen for Lynch syndrome. The role of MSI testing in pancreatic adenocarcinoma has not been well-established. Screening can be done via immunohistochemical (IHC) staining for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2). We report our experience and the clinical utility of MMR IHC on pancreatic adenocarcinomas in fine-needle aspiration (FNA) specimens. Materials and methods We performed a retrospective review to identify all patients diagnosed with pancreatic adenocarcinoma by FNA at our institution between December 2017 and September 2019. For cases with sufficient tumor cells for testing, the MMR results and morphology were summarized, as well as corresponding clinical information, including age, clinical stage, treatment, and concurrent other cancers. Results From December 2017 to September 2019, there were a total of 184 pancreatic FNAs with a diagnosis of adenocarcinoma. Of these 184 FNAs, 65 (35%) contained sufficient material in the cell block to perform IHC for MMR. The cell block material was collected in either RPMI or CytoLyt. Poor technical quality precluded interpretation of PMS2 in 4 cases and MSH6 in 2 cases. All other cases showed intact expression of all four proteins. Conclusions IHC for MMR proteins can be done on specimens collected in RPMI or CytoLyt, but RPMI appears to be more reliable. None of the pancreatic adenocarcinomas in this study showed loss of MMR protein expression. Routine testing of MMR loss may not be indicated in pancreatic adenocarcinomas in the general patient population.

Summary Esophageal foreign body impaction (EFBI) is a gastrointestinal emergency, mostly requiring endoscopic management. The aim of this study is to evaluate the epidemiology, adverse events, and outcomes of patients following the episode of EFBI. All esophagogastroduodenoscopy (EGD) reports of admitted patients for EFBI at the University of Kansas Medical Center between 2003 and 2018 were retrospectively reviewed. Of 204 patients, who met the inclusion criteria, 60% were male and the mean age was 54.7 ± 17.7 years. The encounter was the first episode of EFBI in 76% of cases. EGD in less than 24 hours of patients’ admission was required in 79% of cases. The distal esophagus was the most common site of impaction (44%). Push and pull techniques were used in 38 and 35.2% of cases, respectively, while 11% were managed by a combination of both techniques. Structural causes were the most common etiologic findings including benign strictures and stenosis in 21.5% of patients, followed by Schatzki’s ring (7.8%) and hiatal hernia (6.9%). Of all cases, 45% did follow-up in up to 1 year, and biopsy was done in 34% of cases. Out of 43 patients who had endoscopic findings suspicious for eosinophilic esophagitis (EoE), the diagnosis was confirmed by pathology in 37. The rate of recurrence EFBI was significantly higher in patients with EoE (P

Increased esophagectomy procedures over the past four decades have correlated with the rise in incidence of esophageal adenocarcinoma. Despite advances in technology and procedural expertise, esophagectomy remains a high-risk surgical procedure. Higher volume facilities have more experience with esophagectomy and would be expected to have a lower incidence of surgical complications and attendant morbidity and mortality. By analyzing information from a nationwide United States hospital database, we sought to find out if there is a significant difference between facilities stratified by case volume, with regards to 30-day readmission after esophagectomy. The findings of this study indicated that even with a large applied differential, early readmissions did not differ significantly between high- and low-volume centers. Also, analyzed and discussed were any associated demographic and comorbidity factors as they relate to early readmissions after esophagectomy for esophageal adenocarcinoma across the country. This is the first study to specifically address these variables.

329 Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach with the primary objectives of pathological response rate (ypRR with tumor regression score, TRS ≤ 2). We are reporting the preliminary analyses while the study nears completion. Methods: Patients with newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m2, Leucovorin 400mg/m2, 5-FU bolus 400mg/m2, and 5-FU 2400mg/m2 infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Of 35 patients enrolled (age range 44-86, mean of 65 years; with male:female of 28:7), 33 finished preoperative treatment, 26 had curative intended operations with R0 resection for all, 1 is pending for surgery, and 2 are still on pre-operative treatment. 5 of 26 pts achieved ypCR (19% regression score of 0). All except 2 patients (24/26, 92%) had shown pathologic response to the treatment with TRS ≤ 2. 23/26 (88%) finished post-operative treatment. 20 patients completed all planned treatment with an average follow-up of 22.7 months. Amount them, 2 patients had recurrence/ metastatic disease (at 9 and 10 months, respectively) with 1 died 23.3 months from enrollment, and the rest are all free of disease. G3/4 toxicities were reported in 19 of all 35 treated patients. There were no unexpected toxicities. Conclusions: The combination of FOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe and preliminary benefit data are very encouraging with ypRR of 92% and ypCR of 19% and supporting the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. Clinical trial information: NCT03488667.

Objectives The present study describes the use of octreotide (OCT) in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC) who have gastrointestinal (GI) bleeding related to arteriovenous malformations (AVMs), as well as its effect on OAC tolerance and subsequent rebleeding. Background AVMs cause significant GI bleeding, especially in patients with AF who are receiving OAC for stroke prevention. OCT has been shown to minimize recurrent GI bleeds related to AVMs. Methods In a multicenter, observational study, 38 AF patients with contraindications to OAC because of AVM-related GI bleeding were started on 100 μg of subcutaneous OCT twice daily. OAC was resumed in all patients within 48 h. Incidence of recurrent GI bleeds was calculated, and hemoglobin levels were recorded at enrollment and at 3 and 6 months’ follow-up. Results After a median follow-up of 8 months, 36 patients (mean age 69 ± 8.0 years; mean CHA2DS2-VASc score 3 ± 1 and mean HAS-BLED score 3 ± 1) were available for analysis. All were able to successfully resume OAC, and 28 of 36 (78%) remained on OAC at the conclusion of the study, whereas 8 underwent left atrial appendage closure with subsequent OAC discontinuation. No systemic thromboembolic events occurred in follow-up. Of the 28 patients who continued receiving OAC, 19 (68%) were free of recurrent GI bleed, 4 had minor GI bleeds, 4 required transfusion, and 1 required colectomy for GI bleeding. Mean hemoglobin levels in all patients receiving OAC were significantly higher at 3- and 6-month follow-up than at baseline (p Conclusions Subcutaneous OCT therapy is an attractive option in AF patients receiving OAC who have AVM-related GI bleeds. It allows successful reinitiation of OAC as a bridge to left atrial appendage exclusion or short-term relief from bleeding.

From the early days of gastrointestinal endoscopy, there has been remarkable progress in imaging technology. High-definition endoscopes are now part of the standard armamentarium and a variety of other advanced imaging modalities jostle for space. However, the objective of each of these remains much the same; the enablement of the endoscopist to accurately characterize early gastrointestinal mucosal lesions, which are beyond the capability of standard devices. The benefit of doing so, may be manifold. First, during surveillance of gastrointestinal malignancy, the endoscopist may choose to eschew random biopsies in favor of targeted ones from areas of suspicious mucosa. Second, early mucosal lesions may be detected, which are typically amenable to endoscopic therapy. The ultimate result is improved clinical outcomes and in many cases, the avoidance of surgery. The goal of this review is to summarize for the reader, the most important technologies in advanced endoscopic imaging and their applicability to clinical practice with emphasis on their functioning, implementation, and effect on therapeutic endoscopy.

To analyze visits to and admissions from the emergency department (ED) in children with a primary diagnosis of functional abdominal pain (FAP). This was a cross-sectional study using data from the Nationwide Emergency Department Sample (HCUP-NEDS 2008–2012). FAP-related ED visits were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The most frequent secondary diagnoses associated with FAP-related ED visits were also extracted. In 2012, a total of 796,665 children presented to the ED with a primary diagnosis of FAP. This correlated to a rate of 11.5 ED visits/1000 population. The highest incidence of ED visits was observed for children in the 10–14-year age group; median (IQR) age of 11 (8) years. In analyzing the temporal trends associated with FAP-related ED visits, we observed an increase in both the overall number of visits (14.0%) as well as the population-adjusted incidence (16.0%) during the period 2008–2012. This coincided with a decreasing trend in hospital admissions from the ED; from 1.4% in 2008 to 1.0% in 2012 (−28.5%). The overwhelming majority (96.7%) of patients with FAP who presented to the ED were treated and released. On multivariate analysis, the leading factor associated with an increased likelihood of admission from the ED was teaching hospital status (aOR 2.07; 95% CI 1.97 to 2.18). The secondary diagnosis most commonly associated with FAP-related ED visits was nausea and/or emesis (19.8%). Pediatric FAP-related ED visits increased significantly from the period 2008 to 2012. However, the incidence of hospital admissions from the ED declined during the same period.

Objective: Regulation of TF (tissue factor):FVIIa (coagulation factor VIIa) complex procoagulant activity is especially critical in tissues where plasma can contact TF-expressing cells. One example is the liver, where hepatocytes are routinely exposed to plasma because of the fenestrated sinusoidal endothelium. Although liver-associated TF contributes to coagulation, the mechanisms controlling the TF:FVIIa complex activity in this tissue are not known. Approach and Results: Common bile duct ligation in mice triggered rapid hepatocyte TF-dependent intrahepatic coagulation coincident with increased plasma bile acids, which occurred at a time before observable liver damage. Similarly, plasma TAT (thrombin-antithrombin) levels increased in cholestatic patients without concurrent hepatocellular injury. Pathologically relevant concentrations of the bile acid glycochenodeoxycholic acid rapidly increased hepatocyte TF-dependent procoagulant activity in vitro, independent of de novo TF synthesis and necrotic or apoptotic cell death. Glycochenodeoxycholic acid increased hepatocyte TF activity even in the presence of the phosphatidylserine-blocking protein lactadherin. Interestingly, glycochenodeoxycholic acid and taurochenodeoxycholic acid increased the procoagulant activity of the TF:FVIIa complex relipidated in unilamellar phosphatidylcholine vesicles, which was linked to an apparent decrease in the K m for FX (coagulation factor X). Notably, the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, a bile acid structural analog, did not increase relipidated TF:FVIIa activity. Bile acids directly enhanced factor X activation by recombinant soluble TF:FVIIa complex but had no effect on FVIIa alone. Conclusions: The results indicate that bile acids directly accelerate TF:FVIIa–driven coagulation reactions, suggesting a novel mechanism whereby elevation in a physiological mediator can directly increase TF:FVIIa procoagulant activity.

While short bowel syndrome (SBS) is the leading cause of intestinal failure in children, little objective data are available regarding hospital readmissions for children with SBS. This study sought to investigate rehospitalizations related to SBS in young children. Data for study were obtained from the 2013 Nationwide Readmissions Database (NRD). Using data from the 2013 NRD, we identified a total of 1898 hospitalizations in children with SBS aged 1–4 years. A total of 901 index cases and 997 rehospitalizations were noted. Of these, 425 children (47.2%) underwent rehospitalizations. The most frequent diagnoses and procedures associated with readmission of children with SBS were related to infections and intravenous catheter placement. This is the first study to use US nationwide data to report on the incidence of readmissions in children with SBS. The results from this study indicate that improving central line care and providing home healthcare resources to families at discharge may help in preventing SBS-related rehospitalizations.

Background and Aims Antithrombotic therapy among patients undergoing GI procedures is frequently encountered and can impact the procedure and patient outcomes. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines help to manage these medications before endoscopy depending on the patient’s clinical status and the type of GI procedure. However, currently there is no readily available electronic tool that can assist in decision-making regarding preprocedural management of these agents. Our aim was to develop an electronic application, endoscopy + aid (ENDOAID), to help manage antithrombotic agents before endoscopy and to perform a validation study to test its accuracy. Methods ENDOAID, a web-based application, was developed using JavaScript software (Oracle Corporation, Redwood Shores, Calif, USA) based on an algorithm to categorize patients and procedures into low and high risk as outlined in the updated ASGE guidelines published in 2016. Once pertinent information regarding a patient’s clinical status and the procedure are entered, the application generates recommendations for the management of antithrombotic agents based on their cardiovascular risk and published ASGE guidelines. We performed a validation study with 52 patients who were referred to endoscopy and were taking antithrombotic agents. The patients were divided into groups of 5, and in the simulation each patient had 4 procedures. Different GI procedures were used in the simulation for each group of patients to ensure the entire spectrum of procedures were covered for analysis. Every simulation was then run through ENDOAID. The results from ENDOAID were compared with recommendations based on ASGE guidelines. The latter was derived by consensus between 2 endoscopists (the criterion standard). The personnel using the ENDOAID and those using the ASGE guidelines were different to avoid bias. Any clinical scenario that was unclear or not clearly outlined in ASGE guidelines was discussed with expert endoscopists for a final decision. We evaluated ASGE recommendations and calculated concordance rates between guidelines and ENDOAID results. The Pearson correlation coefficient (r) was calculated to assess the correlation between ENDOAID results to guidelines. Results There was a total of 208 simulated encounters, including 26 procedures. Initial concordance between ENDOAID recommendations and the criterion standard was seen in 206 encounters (99.03%). The 2 encounters that needed further review occurred among patients with Factor V Leiden mutation and deep vein thrombosis from antiphospholipid antibody syndrome and who were undergoing high-risk procedures that had ambiguous guidelines. ENDOAID suggested consultations with an expert before the elective procedure. This suggestion was agreed on by expert endoscopist consensus. Thus, ENDOAID showed a 100% concordance with the ASGE guideline for managing antithrombotics. There was a high degree of correlation (r = .996, P Conclusions We have developed and validated an easy-to-use web-based application that can help in periprocedural management of antithrombotics. Such an application has the potential to simplify the management of these agents and potentially prevent procedural delays, cancellations, or unnecessary consults.

Background and Aims Minimum EUS and ERCP volumes that should be offered per trainee in “high quality” advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an “average” advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. Methods American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. Results Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. Conclusion The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.)

Introduction Smartphone-based applications (apps) have been used to improve the quality of bowel preparation (prep) but the success rates have been variable. We have performed a systematic review and meta-analysis to evaluate the impact of smartphone apps on bowel preparation. Methods Electronic databases (MEDLINE, Embase, CINAHL and Cochrane) were reviewed for eligible studies of smartphone apps versus standard education before colonoscopy. The following outcomes were analyzed: pooled rate of adequacy of bowel prep among both arms and Boston bowel preparation score (BBPS) when reported. Pooled analysis was reported as odds ratio (OR) or mean difference in random effect model with Review Manager 5.3 (P ≤ 0.05 for statistical significance). Results Six studies were eligible with smartphone app (810 patients) vs. standard education (855 patients, control group) for bowel prep. The smartphone app group had a higher proportion of adequate bowel prep compared to the control group: 87.5 % vs 77.5 % (five studies), pooled OR 2.67; 95 %CI 1.00 – 7.13 with P = 0.05. There was substantial heterogeneity in studies with I 2 = 78 %. When analysis was limited to randomized controlled trials (RCTs), smartphone app users had a numerically higher rate of bowel cleansing: 87.1 % vs 76.9 %; however, pooled OR was not statistically significant (OR 2.66, 95 %CI 0.92 – 7.69, P = 0.07). When studies using BBPS were evaluated (n = 3), smartphone app users had higher mean scores (better bowel prep) with a mean difference of 0.9 (95 %CI 0.5 – 1.3), which was statistically significant (P Conclusion The smartphone app is a novel educational tool that can assist in achieving adequate and better bowel cleansing before colonoscopy.

The safety and efficacy of radiofrequency ablation (RFA) in treatment of Barrett's esophagus (BE)-associated dysplasia has been well established. The effectiveness of focal and balloon RFA devices has not been compared. Therefore, the aim of our study was to assess the effectiveness of focal and balloon RFA devices in the treatment of BE by calculating absolute and percentage change in BE length with RFA therapy by comparing pre- and post-treatment BE length.This is a retrospective cross-sectional study of patients who underwent at least one treatment with either focal and/or balloon RFA devices who were identified from two tertiary centers. Patients' demographics, hiatal hernia, pre- and post-treatment BE length, prior use of endoscopic therapies and number of sessions were recorded.Sixty-one patients who had undergone 161 RFA treatment sessions met inclusion criteria. There was no significant difference in percentage change in BE length with greater number of RFA sessions. RFA with a focal device resulted in greater percentage reduction in BE length compared to the balloon system (73% vs. 39%, p 0.01). After adjusting for initial BE length, pre-treatment BE length, hernia status, prior endoscopic mucosal resection (EMR), prior RFA, and prior EMR/RFA sessions, RFA with a focal device at each session remained an independent predictor for a significant reduction in BE extent as compared to the balloon system.The focal RFA device alone was more effective in treatment of BE compared to the balloon system, with a greater reduction in extent of BE. The focal RFA device for endoscopic eradication therapy of BE should be considered the preferred technique.

Background The incidence of Clostridium difficile infection (CDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for CDI in part because of chemotherapy and prolonged hospitalization. Methods We utilized data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to study the incidence and outcomes related to CDI as a complicating factor in pediatric recipients of SOT. Results Our results demonstrate that hospitalized children with SOT have increased rates of infection, with the greatest risk for younger children with additional comorbidities and severe illness. The type of transplanted organ affects the risk for CDI, with the lowest incidence observed in renal transplant patients. Conclusion The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, CDI is not an independent predictor of increased in- hospital mortality in these patients.

Endoscopic ultrasound (EUS)-guided tissue acquisition has emerged over the last decade as an invaluable diagnostic tool in approaching the different pancreatic lesions. Given the safety and minimal invasiveness of this approach combined with the high diagnostic yield, it became the standard of care when dealing with different pancreatic pathologies. However, some variables regarding this procedure remain not fully understood. These can influence the diagnostic yield of the procedure and include the presence of the on-site cytopathologist, the type and size of the needle used as well as obtaining aspiration versus core biopsy, the number of passes and the sampling technique, and the role of suction and stylet use among others. We performed a comprehensive literature search using PubMed, Google Scholar, and Embase for studies that assessed these variables. Eligible studies were analyzed using several parameters such as technique and procedure, with the aim of reviewing results from an evidence-based standpoint.

Hepatorenal syndrome (HRS) is one of the leading causes of hospitalizations in patients with chronic liver disease (CLD). We conducted a retrospective national database study to determine the epidemiology of HRS in hospitalized patients with CLD. Data from a Nationwide Inpatient Sample were extracted from 2002 to 2012 using ICD-9-CM codes related to CLD and HRS. The following outcomes were examined: in-hospital mortality, total charges, length of stay (LOS), patient demographics, procedures, complications, and comorbidities. Statistical analysis including regression was performed to examine factors associated with HRS. During 2002–2012, hospital discharges related to CLD increased from 407,246 to 836,475 with an increase of 37.9% for HRS as a complication in this population. Patients with CLD and HRS had worse outcomes compared with patients with CLD without HRS. This was manifested as a higher mortality rate (32.0% vs 10.3%), increased LOS (median 7 vs 5 days), and increased hospital costs (median $16,000 vs $11,000). Logistic regression demonstrated that HIV/AIDS (adjusted OR 2.9, 95% CI 2.2 to 3.9), pneumonia (aOR 2.8, 95% CI 2.3 to 3.2), and esophageal variceal bleeding (aOR 1.9, 95% CI 1.7 to 2.0) were associated with higher mortality in patients with HRS. Conversely, liver transplantation (aOR 0.1, 95% CI 0.1 to 0.1), transjugular intrahepatic portosystemic shunt (aOR 0.5, 95% CI 0.4 to 0.6), and hospitalization in the Midwest region of the USA (aOR 0.7, 95% CI 0.6 to 0.7) were associated with reduced mortality. The incidence of HRS in hospitalized patients with CLD increased during 2002–2012. HRS is associated with significant mortality and morbidity in these patients.

Lynch syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome with lifetime CRC risks of up to 70%.1 Conventionally, CRC specimens are screened for LS postoperatively but preoperative diagnosis of LS could impact decisions, such as the extent of resection and the need for additional risk-reducing surgeries for uterine and ovarian cancers. Few studies have addressed this issue2-5 and surveys indicate that most gastroenterologists are unsure that LS can be screened for preoperatively.6 We compared the yield of preoperative versus postoperative screening of LS by immunohistochemistry (IHC) and microsatellite instability (MSI) in unselected patients with newly diagnosed CRC who underwent testing under real-life laboratory conditions to mimic clinical practice.

Background and study aims Standard colonoscopy (SC) is the preferred modality for screening for colon cancer; however, it carries a significant polyp/adenoma miss rate. Cap-assisted colonoscopy (CC) has been shown to improve polyp/adenoma detection rate, decrease cecal intubation time and increase cecal intubation rate when compared to standard colonoscopy (SC). However, data on adenoma detection rate (ADR) are conflicting. The aim of this meta-analysis was to compare the performance of CC with SC for ADR among high-quality randomized controlled trials. Patients and methods We performed an extensive literature search using MEDLINE, EMBASE, Scopus, Cochrane and Web of Science databases and abstracts published at national meetings. Only comparative studies between CC and SC were included if they reported ADR, adenoma per person (APP), cecal intubation rate, and cecal intubation time. The exclusion criterion for comparing ADR was studies with Jadad score ≤ 2. The odds ratio (OR) was calculated using Mantel-Haenszel method. I2 test was used to measure heterogeneity among studies. Results Analysis of high-quality studies (Jadad score ≥ 3, total of 7 studies) showed that use of cap improved the ADR with the results being statistically significant (OR 1.18, 95 % CI 1.03 – 1.33) and detection of 0.16 (0.02 – 0.30) additional APP. The cecal intubation rate in the CC group was 96.3 % compared to 94.5 % with SC (total of 17 studies). Use of cap improved cecal intubation (OR 1.61, 95 % CI 1.33 – 1.95) when compared to SC (P value Conclusions Meta-analysis of high-quality studies showed that CC improved the ADR compared to SC.

BACKGROUND There is a lack of large database research relating to the epidemiology and health resource utilization associated with short bowel syndrome (SBS) in the United States. METHODS We analyzed the Kids' Inpatient Database for the year 2012 and utilized International Classification of Diseases, Ninth Revision, and Clinical Modification ( ICD-9-CM) diagnosis codes to identify patients 0-3 years of age with SBS, who were matched by age and sex to children without SBS. The study variables included patient and hospital demographics, All Patient Refined Diagnosis Related Groups, in-hospital mortality, hospital length of stay, and hospitalization costs. We also determined the most frequent ICD-9-CM diagnostic and procedural codes associated with SBS. RESULTS Children with SBS demonstrated a higher rate of mortality than that of children without SBS (1.6% vs 0.7%; P < .001). Children with SBS also experienced a longer length of stay (median days [interquartile range]: 8 [15] vs 2 [3]; P < .001) and higher hospital costs ($17,000 [$34,000] vs $3000 [$5000]; P < .001). The most frequent medical diagnoses associated with SBS were infection (62%), anemia (29%), and liver disease (17%). Children with SBS also demonstrated more severe illness as assessed by an All Patient Refined Diagnosis Related Group score of 3 or 4 (94.30% vs 16.20%; P < .001). CONCLUSIONS Children hospitalized with SBS have a high severity of illness and experience complicated inpatient courses related to their disease. Our study represents the first use of national U.S. data to study the epidemiology and health resource utilization associated with SBS.

Esophageal variceal bleeding (EVB) is a frequent complication in cirrhotic patients resulting in considerable mortality and morbidity. The aim of this study was to investigate the occurrence, impact, and trends of EVB in hospitalized cirrhotic patients on a nationwide level in the United States. We interrogated data from the Nationwide Inpatient Sample from 2002 to 2012. Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification codes, we analyzed hospital discharges for cirrhosis and related EVB in adult patients. EVB in cirrhotic patients was independently associated with overall worse outcomes with respect to in-hospital mortality (10% vs 5%; P