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BACKGROUND AND AIMS. Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS. A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a one-day virtual meeting to reach consensus on each team’s opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS. Symptom features and complications, and inflammatory and fibrostenotic features on both endoscopic and histologic examination, were collated into a simplified scoring system, the Index of Severity for Eosinophilic Esophagitis (I-SEE), that can be completed at routine clinic visits to assess disease severity using a point scale of 0–6 for mild, 7–14 for moderate, and ≥15 for severe EoE. CONCLUSIONS. A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated I-SEE to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

Inflammatory bowel disease (IBD) patients in apparent clinical remission who present with irritable bowel syndrome (IBS)-like symptoms pose a diagnostic and therapeutic dilemma that is called post-IBD IBS. When associated with a diarrheal IBS presentation, this clinical syndrome is known as post-IBD IBS-D.We review and describe the literature regarding the clinical overlap of IBD and IBS. We discuss prevalent theories regarding the pathophysiology of post-IBD IBS-D and whether this presentation represents coincident inherent IBS-D, IBS-D triggered by IBD, or an even more subtle level of IBD activity that is unrecognized by available laboratory modalities. We also discuss observations that post-IBD IBS-D patients harbor significantly increased colon mucosal eosinophils and appear to respond to a GI-hypoallergenic diet and budesonide therapy.The symptoms overlap between IBD and IBS complicates diagnosis and subsequent management of patients with post-IBD IBS-D. In addition to current theories regarding the pathophysiology of this condition such as alterations in mucosal inflammation, the microbiota, mucosal permeability, and gut-brain interactions. This new avenue of eosinophilic colopathy and therapy directed toward food-derived immune response in patients with post-IBD IBS-D deserves additional investigation.

Introduction Inflammatory bowel disease (IBD) patients in remission who present with irritable bowel syndrome with diarrhea (IBS-D) like symptoms pose a diagnostic and therapeutic dilemma that is called post-IBD IBS-D. This syndrome was first reported by Isgar et al. who documented IBS-type symptoms in 33% of their patients with chronic ulcerative colitis (CUC) in remission in 1983. In their meta-analysis of 13 studies incorporating 1,703 patients, Halpin and Ford in 2012 calculated a pooled prevalence of 35% for IBS symptoms among IBD subjects in remission. The post-IBD IBS-D syndrome represents a source of considerable stress, incurs morbidity and impairs quality of life of these patients. The etiology of this syndrome is unknown and may be multifactorial such as environmental, psychological, GI motility disarray, genetic components and possibly by gut microbiome. Methods We conducted a retrospective, single-center study of patients with history of IBD and IBS-D like symptoms. The demographic characteristics, type of IBD, colonoscopy, biopsy findings and empirical medical management outcome were analyzed. Results We have found significantly increased mucosal eosinophils (>50 HPF in both side of the colon examined) in our patients with post-IBD IBS-D syndrome. In this study, 15 CUC patients and 20 Crohn’s disease patients with this syndrome were investigated and showed no clinical, serological, mucosal or microscopic IBD activity. These patients had non-bloody diarrhea (5–20 x daily), lower abdominal cramps (%90), mild weight loss (4–6 lbs) and fecal incontinence (%25) who were placed on the GI-hypoallergenic diet and budesonide therapy. Sixty seven percent of these 35 patients with post-IBD IBS-D responded well clinically to this management. Increased mucosal eosinophils in these patients with post-IBD IBS-D may have eosinophilic colopathy that may be related to intestinal permeability disarray. The epithelium in these IBD patients who are in remission may have the production of pro-inflammatory cytokines by the eosinophils, especially IL-23 and IL-33. This interesting area investigation is in progress by our research faculty. Conclusion In summary, this is an exciting new finding that significantly increased mucosal eosinophils in our patients with post-IBD IBS-D syndrome may have a new avenue, eosinophilic colopathy. Interestingly, these patients have responded to the GI-hypoallergenic diet and budesonide therapy. Obviously, we need more patients in the near future with longer follow-up and we hope that the other investigators may confirm our findings.

Increased esophageal cyclooxygenase-2 (COX-2) expression has been associated with Barrett’s esophagus (BE); however, it is unknown whether COX-2 expression varies among patient groups with different clinical or socio-demographic factors. We conducted a case–control study among eligible patients scheduled for elective esophagogastroduodenoscopy and patients eligible for screening colonoscopy recruited from primary clinics. We compared 39 BE tissue samples and 47 squamous tissue samples from BE cases and 240 squamous tissue samples from controls. Clinical and socio-demographic data were prospectively collected. Immunohistochemical staining for esophageal COX-2 was performed and scored. The median COX-2 score was significantly higher in BE tissue than squamous tissue from cases or controls (p

Question: A 48year-old Hispanic man developed melena after 25 days of hospitalization. He was initially brought to the emergency department after a motor vehicle accident that resulted in hemopneumothorax, multiple fractures, and blunt abdominal trauma. No past medical history was reported. After emergent endotracheal intubation and chest tubes placement, he underwent splenectomy, subtotal colectomy, and distal ileum resection. In the intensive care unit (ICU), he developed septic shock requiring broad-spectrum antibiotics, vassopressors, corticosteroids, and hemodialysis. Repeat laparotomy on day 9 revealed colocolostomy disruption, requiring additional bowel resection. Vassopressors and steroids were stopped after 5 days. His course was complicated by pulmonary embolism and persistent hyperglycemia. Multiple intra-abdominal washouts were required and abdominal cavity was closed on day 24. On day 25, melena was noted. He was tachycardic, afebrile, and normotensive. Surgical wound was clean, and abdominal examination revealed diffuse tenderness. Hemoglobin acutely dropped from 9 to 6.7 g/dL. Anticoagulation was stopped and an inferior vena cava filter placed. Upper endoscopy showed diffuse friable mucosa of the entire stomach. Large exudative ulceration was found in the gastric body (Figure A) from where biopsy specimens were taken. Other, scattered, clean-based ulcers were seen in the antrum and fundus (Figure B). The esophagus and duodenum were normal. A representative histopathology is provided (Figure C, D). What is the diagnosis? Look on page 1136 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Summary Background : Gastro-oesophageal reflux has been shown to induce oxidative DNA damage. Aim : To determine whether oxidative DNA damage, detected in oesophageal biopsies by simple immunohistochemical staining, correlates with gastro-oesophageal reflux disease as determined by pH monitoring. Methods : The study included 47 patients with reflux symptoms who had oesophageal biopsy and 24-h pH monitoring studies performed within 3 months of each other with no variation in treatment in the time between the two procedures. Sections of formalin-fixed and paraffin-embedded oesophageal biopsies were stained for 8-hydroxy-2′-deoxyguanosine using the standard immunoperoxidase method. Positive nuclear immunoreactivity was considered to indicate oxidative DNA damage. Results : Seven (33%) of the 21 cases with normal 24-h pH monitoring results were negative for oxidative DNA damage, compared with only two (8%) of the 26 cases with abnormal 24-h pH results (P = 0.058, two-sided Fisher's exact test). Five of the patients with normal 24-h pH results had oesophageal biopsies performed within 24 h of the monitoring procedure and, of these, four (80%) were positive for oxidative DNA damage, including a case in which both biopsy and 24-h pH monitoring were performed on the same day whilst the patient was on proton pump inhibitor therapy. All cases with normal 24-h pH results and positive oxidative DNA damage showed features of reflux on routine morphological evaluation. Conclusions : Oxidative DNA damage can occur in the absence of acid reflux and despite adequate antisecretory therapy. This may indicate that other agents, such as bile, can induce oxidative DNA damage in an acid-suppressed environment. The significant discordance between oxidative DNA damage and 24-h pH results makes the determination of oxidative DNA damage a poor surrogate marker for 24-h pH monitoring.

It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known.Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC.The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors.The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.

Barrett's esophagus occurs more frequently than previously anticipated. Detection of Barrett's esophagus is by endoscopic biopsy in which normal squamous epithelium of the esophagus is replaced by a specialized columnar epithelium of any length. Patients with more than five years of gastroesophageal reflux symptoms, particularly those 50 years of age or older, should have upper endoscopy to detect Barrett's esophagus. With recognition of Barrett's esophagus as a premalignant lesion, the crucial issue is surveillance for detection of dysplasia. Although the natural history of dysplasia is incompletely defined, it is clear that patients with dysplasia have a higher risk for adenocarcinoma than those without dysplasia. Dysplasia is not the ideal marker for selecting patients at high risk for adenocarcinoma, however; recent studies have shown that p53 protein accumulation appears to be earlier and more specific/sensitive marker of malignant potential in Barrett's esophagus. Management of Barrett's esophagus often involves a multidisciplinary evaluation and its current status is reviewed.

Our aim was to determine the sensitivity andspecificity of p53 accumulation as a marker of malignantpotential in Barrett's metaplasia (BM). One hundredeighty biopsies from 61 patients with BM were evaluated for p53 accumulation by immunohistochemistry.Of 25 patients with LGD, 9 had p53-positive biopsies,and of these 5 (56%) developed HGD/CA, whereas 16 hadp53-negative biopsies and none (0%) developed HGD/CA after similar follow-up times (P = 0.0108). Asa marker of malignant potential in BM, p53 accumulationhas a sensitivity of 100%, specificity of 93%, and apredictive value of a positive test of 0.56, compared to sensitivity of 100%, specificity of 64%, andpredictive value of a positive test of 0.2 for ahistologic diagnosis of LGD. We conclude that: (1) p53accumulation is more specific and has better predictive value for subsequent development of HGD/CA thanhistologic diagnosis of LGD. (2) Patients with LGD andp53-positive biopsies are more likely to develop HGD/CA;therefore, they should be followed up more closely than those with LGD and p53-negativebiopsies.

Background: There is a significant interobserver and intraobserver variation in grading dysplasia in Barrett's metaplasia. New markers are needed to optimize the assessment of potential risk of cancer development in these patients. The aim of this study is to explore the use of p53 as a marker of neoplastic progression in Barrett's metaplasia. Methods: Immunohistochemistry was used to study p53 protein accumulation in 114 specimens from 54 patients with Barrett's metaplasia. Results: Positive staining was found in 0% of the cases negative for dysplasia, 9% of those with lowgrade dysplasia, 55% of those with high-grade dysplasia, and 87% of those with adenocarcinoma. Follow-up was available on 24 patients. Two patients who showed low-grade dysplasia and who were positive for p53 on biopsy showed high-grade dysplasia in follow-up biopsies. Of 21 patients who had biopsy specimens negative for p53, only one showed high-grade dysplasia on subsequent biopsy specimens. Conclusions: Our data support the hypothesis that p53 plays an important role in the progression of Barrett's metaplasia to adenocarcinoma. The follow-up study indicates that positive immunostaining for p53 may be an objective marker of neoplastic progression in Barrett's metaplasia.

interval (CI) 0.19 to 2.12), with limits of agreement from -2.78 to 3.58 cm. For M, the mean difference between pull and push endoscopy was 0.77 cm (95% CI -0.19 to 2.18), with limits of agreement from -2.33 to 3.86 cm. The mean difference in C between doctor and nurse was -0.17 cm (95% CI -0.92 to 2.77), with limits of agreement from -4.20 to 3.87 cm. For M the mean difference between doctor and nurse was -0.63 cm (95% CI -1.35 to 2.63), with limits of agreement from -4.47 to 3.21 cm. Conclusions: The correlation coefficients for pull against push endoscopy and doctor against nurse demonstrate the strong relationship between these variables. However, there were considerable discrepancies between C & M values in both comparisons, with wide limits of agreement. Possible explanations for a reduced level of agreement in this real-time clinical setting include: patient movement and retching, differences in landmark interpretation and measurement technique, and the lack of 1 cm markings on the endoscope.