David Cangemi

Small bowel tumors discovered during double-balloon enteroscopy: Analysis of a large prospectively collected single-center database

Background: The emergence of capsule endoscopy and double-balloon enteroscopy (DBE) has greatly enhanced the management of small bowel tumors (SBTs). DBE is particularly useful as a diagnostic modality because it allows for direct investigation of the gastrointestinal lumen, yet little data exist regarding its clinical efficacy. Aim: To determine the diagnostic yield of DBE in detection of SBTs. Methods: We restrospectively reviewed our large prospectively collected DBE database from September 2005 to May 2012. Patients who were diagnosed with SBTs by DBE were included in the study. The diagnostic yield of DBE in detection of SBTs was calculated by frequency analysis. Results: A total of 1106 patients underwent 1652 DBE procedures. Of these patients, 134 (12.1%) were found to have an SBT. The majority (56.7%) of patients diagnosed with SBT were male, and the average age at the time of diagnosis was 64 years (SD±14 y). Indications for performing DBE included suspected mass lesion in 54.5% (73/134) of SBT patients, obscure gastrointestinal bleeding in 26.9% (36/134), and overt gastrointestinal bleeding in 14.9% (20/134). The most common SBTs identified were: carcinoid (26/134, 19.4%), hamartoma (14/134, 10.4%), inflammatory polyp (11/134, 8.2%), gastrointestinal stromal tumor (10/134, 7.5%), and lymphoma (10/134, 7.5%). Conclusions: DBE is a valuable tool in the evaluation of SBTs. The incidence of SBTs in our patient population was significantly higher than the generally accepted incidence for the overall population, but was comparable with other similar studies. Carcinoid tumor was the most common SBT identified, and was most often seen in the ileum.

Predictors of esophageal stricture formation post endoscopic mucosal resection.

Background/Aims Stricture formation is a common complication after endoscopic mucosal resection. Predictors of stricture formation have not been well studied. Methods We conducted a retrospective, observational, descriptive study by using a prospective endoscopic mucosal resection database in a tertiary referral center. For each patient, we extracted the age, sex, lesion size, use of ablative therapy, and detection of esophageal strictures. The primary outcome was the presence of esophageal stricture at follow-up. Multivariate logistic regression was used to analyze the association between the primary outcome and predictors. Results Of 136 patients, 27% (n=37) had esophageal strictures. Thirty-two percent (n=44) needed endoscopic dilation to relieve dysphagia (median, 2; range, 1 to 8). Multivariate logistic regression analysis showed that the size of the lesion excised is associated with increased odds of having a stricture (odds ratio, 1.6; 95% confidence interval, 1.1 to 2.3; p=0.01), when controlling for age, sex, and ablative modalities. Similarly, the number of lesions removed in the index procedure was associated with increased odds of developing a stricture (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.2; p=0.007). Conclusions Stricture formation after esophageal endoscopic mucosal resection is common. Risk factors for stricture formation include large mucosal resections and the resection of multiple lesions on the initial procedure.

Survival in esophageal high-grade dysplasia/adenocarcinoma post endoscopic resection

BACKGROUND Endoscopic resection followed by ablative therapy is frequently used to treat esophageal high-grade dysplasia or early esophageal adenocarcinoma. AIMS To study outcomes in patients with high-grade dysplasia compared to those with esophageal adenocarcinoma after endoscopic resection. METHODS Retrospective, observational, descriptive, single-centre study from a prospective database. We extracted data from 116 endoscopic resections. Survival was plotted using Kaplan-Meier curves multivariable Cox-proportional hazard assess for possible predictors of survival post-endoscopic resection was performed. RESULTS 116 patients (64 esophageal adenocarcinoma, 52 high-grade dysplasia) underwent endoscopic resection from May 2003 to June 2010. Mean age was 71 ± 11 years for high-grade dysplasia and 72 ± 10 years for esophageal adenocarcinoma. Median follow-up was 17 months. Eighty-five patients had negative margins on endoscopic resection. Five-year survivals for high-grade dysplasia and esophageal adenocarcinoma were 86% (range 68-100%) and 78% (59-96%), respectively. Survival was not significantly different between groups (p=0.20). Overall mortality rate was 10.6% (9/85). At multivariable Cox regression increased Barretts oesophagus length was associated with worse survival (HR 1.18 [1.06-1.33], p=0.0039). Survival was not affected by the pathology before resection: HR 2.4 [95%CI, 0.70-8.4], p=0.16. CONCLUSIONS Survival in patients with high-grade dysplasia of the oesophagus is similar to those with esophageal adenocarcinoma. Longer Barretts oesophagus segments are associated with decreased survival.

Double-balloon enteroscopy and outcomes in patients older than 80

BACKGROUND double-balloon enteroscopy (DBE) is becoming more commonly used for investigation of small bowel pathology. Currently, there are limited data to describe its safety and efficacy in the population over age 65. AIM to investigate the indications, findings and outcomes of DBE performed in patients older than 80, as well as the correlation between DBE and prior capsule endoscopy (CE) findings. METHODS we retrospectively reviewed our large DBE database, including procedures from January 2006 to September 2012. Patients aged 80 or older at the time of DBE were included in the study. The indications, findings, outcomes and diagnostic yield of DBE were calculated by frequency analysis. RESULTS two hundred and fifteen DBEs were performed in 130 patients aged 80 or older. The mean age was 83.6 ± 3.03 years (range: 80-94). Twelve patients (9.2%) were assigned an American Society of Anaesthesiologists score of II prior to procedure, 102 patients (78.4%) were assigned a score of III and 16 patients (12.3%) were given a score of IV. The most common indication for DBE was obscure gastrointestinal bleeding (N = 204, 94.9%). One hundred and fourteen patients (87.7%) underwent CE prior to DBE, and correlation between findings of CE and DBE occurred in 74.6% of these patients. The overall diagnostic yield of DBE was 77.2% (N = 166). There were no immediate post-procedural complications or failed procedures. CONCLUSION DBE is a safe and effective technique for investigation of the small bowel in patients aged 80 and older. Age alone should not be a contraindication to performing DBE when clinically indicated.

Changes in efficiency and resource utilization after increasing experience with double balloon enteroscopy

AIM To investigate changes in efficiency and resource utilization as a single endoscopists experience increased with each subsequent 100 double balloon enteroscopy (DBE) procedures. METHODS We reviewed consecutive DBE procedures performed by a single endoscopist at our center over 4 years. DBE was employed when the clinician deemed the procedure was needed for disease management. The approach (oral, anal or both) was chosen based on suspected location of the target lesion. All DBE was performed in a standard endoscopy room with a portable fluoroscopy unit. Fluoroscopy was used to aid in shortening the small intestine and reducing bowel loops. For oral DBE, measurements were taken from the incisors. For anal DBE, measurements were taken from the anal verge. Enteroscopy continued until the target lesion was reached, until the entire small intestine was examined, or until no further progress was deemed possible. The length of small intestine examined (cm), procedure duration (min), and fluoroscopy time (s) were analyzed for sequential groups of 100 DBE. Sub-groups of diagnostic and therapeutic procedures were analyzed using multivariable linear regression. RESULTS 802 consecutive DBE procedures were analyzed. For oral DBE, median [interquartile range (IQR)] length of small bowel examined was 230.8 cm (range: 210-248 cm) and for anal DBE was 143.5 cm (range: 100-180 cm). No significant increase in length examined was noted for either the oral or anal approach with advancing position in series. In terms of duration of procedure, the median (IQR) for oral DBE was 86 min (range: 71-105 min) and for anal DBE was 81.3 min (range: 67-105 min). When comparing by the position in series, there was a significant (P value < 0.001) decrease in procedure duration for both upper and lower procedures with increasing experience. Median (IQR) time of exposure to fluoroscopy for oral DBE was 190 s (114-275) compared to anal DBE which was 196.4 s (312-128). This represented a significant (P value < 0.001) decrease in the amount of fluoroscopy used with increasing position in series. For both oral and anal DBE, fluoroscopy time was reduced by greater than 50% over the course of 802 total procedures performed. Sub-group analysis was conducted on therapeutic and diagnostic groups. Out of 802 procedures, a total of 434 were considered therapeutic. Argon plasma coagulation was by far the most common therapeutic intervention performed. There was no evidence of a difference in length examined or fluoroscopy exposure among oral DBE for diagnostic and therapeutic procedures, P = 0.91 and P = 0.32 respectively. The median (IQR) for length was 235 cm (range: 178-280 cm) for diagnostic vs 230 cm (range: 180-275 cm) for therapeutic procedures; additionally, fluoroscopy time median (IQR) was 180 s (range: 110-295 s) and 162 s (range: 102-263 s) for no intervention and intervention. However, there was a significant difference in procedure duration among oral DBE (P < 0.001). The median (IQR) was 80 min (range: 60-97 min) and 94 min (range: 77-110 min) for diagnostic and therapeutic interventions respectively. CONCLUSION For a single endoscopist, increased DBE experience with number of performed procedures is associated with increased efficiency and decreased resource utilization.

A Comparison of Patient Satisfaction With Sedation Between Fentanyl/Midazolam and Meperidine/Midazolam in Patients Undergoing Endoscopy

A Comparison of Patient Satisfaction With Sedation Between Fentanyl/Midazolam and Meperidine/Midazolam in Patients Undergoing Endoscopy

62-Year-Old Man With Painless Jaundice and Hyponatremia

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Jacksonville, FL (D.J.C., S.T.D.); Adviser to resident and Consultant in Pulmonary and Allergy Medicine, Mayo Clinic, Jacksonville, FL (M.M.J). A 62-year-old man was admitted to our facility with a 1-week history of progressive jaundice and malaise. He denied abdominal pain, nausea, vomiting, change in bowel habits, fever, recent travel, intravenous drug abuse, or excessive alcohol intake. A review of systems was significant for dark urine but otherwise produced negative results. The patient’s medical history included poorly controlled type 2 diabetes mellitus and dyslipidemia. He had undergone no prior operations, and he had no personal or family history of liver disease. Home medications included pravastatin, insulin glargine, insulin lispro, and occasional as-directed use of naproxen. He denied using any other anti-inflammatory medications or herbal supplements. He had completed a 14-day course of combination trimethoprim and sulfamethoxazole for cellulitis 1 week before admission. On physical examination, the patient was alert, oriented, afebrile, and hemodynamically stable. He was grossly jaundiced with scleral icterus. Cardiopulmonary examination results were unremarkable. He had no abdominal tenderness to palpation and no hepatosplenomegaly. Stigmata of chronic liver disease, including palmar erythema, telangiectasias, and spider angiomas, were absent. Laboratory results were notable for the following (reference ranges provided parenthetically): total bilirubin, 25.8 mg/dL (0.11.1 mg/dL): direct bilirubin, 18.9 mg/dL (0.0-0.3 mg/dL): alkaline phosphatase, 1515 U/L (98-251 U/L): alanine aminotransferase, 425 U/L (10-45 U/L): aspartate aminotransferase, 211 U/L (12-31 U/L): platelet count, 311 10/mL (150-450 10/mL); and albumin, 3.3 g/dL (3.5-5.0 g/dL). Prothrombin time, partial thromboplastin time, and international normalized ratio were within normal limits. Serologic test results for antiehepatitis A virus IgM, antiehepatitis B surface antibody, hepatitis B surface antigen, antiehepatitis B

P2-347: BRI2 (ITM2B) inhibits Aβ deposition

one protein located on the endoplasmic reticulum (ER) membrane, precisely at focal contacts between the ER and mitochondria (Hayashi & Su, Cell 131:596, 2007). The protein regulates the activity of different ER proteins, like IP3 receptors or ER stress sensors (GRP78/BiP, PERK, ATF-6). The 1 chaperone has the unique particularity to be sensitive to synthetic ligands, which therefore allow a very focal regulation of intracellular calcium homeostasis at ER and/or mitochondria contacts. As a consequence, 1 activators/agonists have been shown to induce acute modulation of transduction pathways, effective at the behavioral level. 1 Activators are indeed anti-amnesic, antidepressant and neuroprotective compounds. We validate new 1 activator compounds as neuroprotective agents against amyloid toxicity and analyze their mechanism of action. Methods: PRE-084 is a morpholine piperidine derivative acting as a high affinity and selective 1 activator. ANAVEX1-41 is a tetrahydro-furanmethanamine that shows high affinity for M1, M2, M4 muscarinic acetylcholine receptors and 1 protein. Both compounds are potent anti-amnesic drugs alleviating learning impairments observed in mice after the central (i.c.v.) injection of amyloid 25-35 peptide (A 25-35). Results: Central administration of A 25-35 induces within one week histological and biochemical changes, memory deficits, oxidative stress and ER stress in sensitive brain structures (hippocampus, cortex), highly reminiscent of the amyloid toxicity observed in Alzheimer’s disease. A 25-35 also provokes the induction of intracellular pro-apoptotic caspases and Bax-related proteins, markers of the induction of apoptosis. At the morphological level, A 25-35 induces a marked glial (astroglia, microglia) reaction and cell loss quantifiable in pyramidal layers of the hippocampus. Pre-administration of PRE-084 or ANAVEX1-41 prevents significantly all these pathological changes, showing that 1 activators are effective neuroprotectants. Part of the mechanism involves regulation of the expression of activity of IP3 receptors or ER stress sensors, in relation with the massive calcium overload induced by A 25-35. Conclusions: 1 Activators/agonists show potent neuroprotective and putatively disease-modifying activity against amyloid toxicity. Moreover, ANAVEX1-41 is active at 30-100 g/kg i.p., suggesting a cooperative action between muscarinic and 1 targets.

P3-276: BRI2 (ITM2B) shows genetic association with late-onset Alzheimer's disease

both with and without adjustment for genomic control (GC) as well as empirical p values. We also compared our LOAD GWAS results with the Braak GWAS results. Results: After stringent quality control based on Hardy-Weinberg disequilibrium, missing genotypes and minor allele frequencies, high quality genotypes were obtained for 306,672 SNPs. We analyzed the AD cases and controls separately to avoid stratification bias. None of the SNPs had genome-wide significance after Bonferroni correction. In the AD cases, there were 79 SNPs with GC adjusted p 0.0002. In the controls, there were 81 such SNPs. These represent an excess of 17-27 SNPs under the null hypothesis of no association. The unadjusted, GC adjusted and empirical p values were highly correlated. There were SNPs with evidence of Braak NFT stage association in both the cases and controls. There were SNPs with evidence of association with both AD and Braak stage. Linear regression analysis of Braak NFT stage in the ADs, after including age, sex and ApoE as covariates, led to the identification of 78 SNPs with p 0.0002. Conclusions: These results suggest the presence of variants in the human genome that may be associated with both risk of AD and brain NFT pathology. Given that the Braak GWAS is performed in only a subset of our total series, constituting 12-16% of the subjects from our LOAD GWAS, use of Braak stage endophenotype deserves further exploration as a methodology to detect susceptibility variants for late onset Alzheimer’s disease. (*) Equal contribution.