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Randomized Controlled Trial of Esophageal Capsule Endoscopy VersusStandard Endoscopy for Screening in Patients Pre-Liver Transplantation.Assessment of Inter-Observer Variability and Patient PreferencesLauren B. Gerson, Ahmad Kamal, Nighat Ullah, Aijaz Ahmed

Introduction: Patients awaiting liver transplantation (OLT) are recommended to undergoendoscopic screening (EGD) for the presence of varices. The esophageal capsule (PillCamESO capsule, ECE) has shown accuracy for detection of varices (Endoscopy 2006). The aimof this randomized controlled trial was to determine the utility of ECE in a pre-transplantpopulation. Secondary aims were to define inter-observer variability between ECE readers,patient preferences, and the prevalence of extraesophageal findings. Methods: We invitedpatients scheduled for EGD pre-OLT. Patients received ECE prior to EGD. An experthepatologist performed the EGDs. Two blinded independent faculty experts interpreted ECEimages. Varices were graded as F1=small straight varices; F2= enlarged tortuous varices <1/3 of the lumen; and F3= large coil-shaped varices ≥ 1/3 lumen. Portal HTN gastropathywas rated as mild=no erosions; moderate=erosions/heme spots; and severe=active bleeding.We used the kappa statistic to determine inter-observer variability. Results: We invited 39patients to participate. 24 (62%) patients (mean age 52±8.4 (range 36-70) years, 14 (58%)men, 17 (71%) Child's B, and 19 (79%) HCV) were enrolled. Esophageal varices weredetected in 12 (50%) by EGD and in 11 (46%) by ECE. The varices were significant (gradeF2-F3) in 8 (33%) by both ECE and EGD. ECE visualization was deemed adequate in 11/24 (46%). The mean esophageal transit time was 260±336 seconds (range 2-840 seconds).All patients had portal HTN gastropathy. Portal HTN jejunopathy was present in the 9patients with transit to the duodenum, with a mean GE time of 9.7±5.5 (range 2.4-18.3)minutes. 61% of patients preferred ECE, 9% EGD, and 33% had no preference. Patientsreported less discomfort (p=0.03), greater satisfaction (p=0.03), and less fatigue(p<0.001)with ECE. Kappa coefficients for inter-observer variability are shown in the table.For the presence of varices, the sensitivity was 75% with a specificity of 92% for reader 1and 75% and 83% for reader 2. There was perfect (100%) agreement between ECE readersand EGD findings for combined grades F0/F1 and 88% agreement for combined grades F2/F3. Conclusions: In patients pre-OLT undergoing screening for esophageal varices, ECEappears to be sensitive, specific, and preferred by patients. There was good agreementbetween ECE experts. Visualization of portal HTN enteropathy occurred in approximately1/3 of the patients.Inter-Observer Variability

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Autofluorescence Assessment in the Surveillance of Barrett's Oesophagus: ARandomised Trial Comparing Standard 4 Quadrant Biopsy and AF DirectedBiopsyAudrey L. McCallum, Mairi Macpherson, John T. Jenkins, Peter S. Chong, Derek Gillen,Fraser Duthie, Karin Oien, Grant M. Fullarton

Background: Barrett's oesophagus is associated with an increased risk of oesophageal aden-ocarcinoma. Currently patients with Barrett's undergo endoscopic surveillance in an attemptto detect dysplasia and/or early cancer. Autofluorescence (AF) has been developed to enhanceconventional white light (WL) endoscopy in the diagnosis of GI lesions. Our preliminaryresults assessing AF in the detection of dysplasia in Barrett's patients have been encouraging.Aim: A randomised crossover trial to compare AF versus WL endoscopy in Barrett's oeso-phagus in the detection of dysplasia and early cancer. Method: Patients with establisheddiagnosis of Barrett's were invited to participate in the trial. Patients were randomised toeither WL or AF endoscopy and returned in 8 weeks for crossover endoscopy. WL assessmentinvolved standard biopsies following the Seattle protocol and in AF assessment the highest AFreadings were recorded and biopsied. The histology was blindly reported by two pathologistsscoring them according to the Vienna classification. Results: 111 patients were recruited tothe study. A total of 1180 WL and 162 AF guided biopsies were taken (Wilcoxon-SignedRank Test p=0.0005). Intestinal metaplasia was detected in 83 patients with WL and 67with AF (p=0.003). WL detected low grade dysplasia in 5, high grade in 4 and cancer in1 patient and AF detected low grade in 1, high grade in 2 and cancer in 1 patient (all p=ns). Conclusion: Our randomised crossover trial has found 1) a higher detection of Barrett'sepithelium with WL compared to AF, 2) a similar dysplasia rate with AF having the advantageof requiring fewer biopsies. With refinement of the technique it is hoped it can be used toenhance the detection of dysplasia in Barrett's oesophagus.

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An Implantable, Wireless and Batteryless Impedance Sensor Capsule forDetecting Acidic and Non-Acidic RefluxThermpon Ativanichayaphong, Shou Jiang Tang, Jianqun Wang, Wen-Ding Huang, HarryF. Tibbals, Stuart J. Spechler, Jung-Chih Chiao

Introduction: Wireless esophageal pH monitoring, in which a radiotelemetry pH sensor(Bravo capsule, Medtronic) is attached to esophageal mucosa, is more comfortable andacceptable to patients than conventional, catheter-based esophageal pH monitoring. Thewireless system has a limited battery life and cannot detect the reflux of non-acidic materials,however. Esophageal impedance monitoring can detect non-acidic reflux, but availablesystems all are catheter-based. We have developed an implantable, wireless and batterylessimpedance sensor, comparable in size to the Bravo capsule, that might be used for long-term monitoring of both acidic and non-acidic reflux. Methods: Our system includes atransponder with an impedance electrode that is implanted in esophagus, and an externalreader that records the wireless signals. Communication between the devices occurs viainductive coupling between coils in the transponder and the reader. The transponder receivespower through its coil, converts impedance variations caused by contact between refluxedmaterial and the electrode into modulated frequency shifts, and transmits those signals tothe reader. In this system, impedance is inversely correlated with frequency. We comparedreadings of our impedance sensor and a Bravo pH sensor in a number of different testsolutions. We also tested our system in 3 pigs (75 lbs each), which were sacrificed immediatelybefore the start of the experiments. For the animal studies, our impedance sensor and theBravo pH sensor were tied together and positioned in the distal esophagus, 3cm proximalto the gastroesophageal junction, using endoscopic guidance. The external reader was placedagainst the pig's skin around the chest. Test solutions were flushed into the esophagus, andsimultaneous impedance and pH signals were recorded. Results: For water, orange juice,Diet Coke, vinegar and HCl solutions in beakers, the Bravo recorded pH values of 7.05,3.9, 3.5, 2.25 and 2.05 while our impedance sensor recorded frequencies of 9.49, 10.69,9.86, 10.51 and 11.07 kHz, respectively. The BRAVO capsule malfunctioned in air andalkaline solutions, while our sensor could still detect frequencies of 7.3 and 10.35 kHz,respectively. In the pigs, we found a good correlation between the impedance and pH valuesof the solutions flushed into the esophagus. Only the impedance sensor could distinguishwater from air, however. Conclusions: Our implantable, wireless and batteryless impedancesensor can detect acidic solutions in a manner comparable to the Bravo wireless pH sensor.Unlike the Bravo capsule, however, our sensor also can detect nonacidic materials such asair and water.

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Role of L-Type Calcium Channels, Membrane Potential and Nitric Oxide inthe Control of Myogenic Activity in the Primate Internal Anal SphincterNaomi Harvey, Bronagh McDonnell, Melanie McKechnie, Kathleen Keef

Myogenic activity in the internal anal sphincter (IAS) is critical for the maintenance offecal continence. However, the mechanisms controlling myogenic activity are still poorlyunderstood. The present study examined the role of L-type calcium channels (Cav), mem-brane potential (Em) and nitric oxide in the control of myogenic activity in the monkeyIAS (n=13). Isolated strips of the Cynomolgus monkey IAS developed spontaneous contractileactivity consisting of phasic contractions superimposed upon tone. Phasic contractions wereassociated with membrane potential oscillations (MPOs 5-25 mV in amplitude; 15-25 cpm).MPOs, phasic contractions and 95% of tone were abolished by the Cav antagonist nifedipine(1 µM). The NOS inhibitor L-NA (100 µM) depolarized Em (from a mean of -44 to -38mV), increased tone and significantly reduced phasic contractile and electrical activity. Theneurotoxin TTX (1 µM) had similar effects. The actions of L-NA were reversed by the NOdonor sodium nitroprusside (SNP 10 nM-0.3 µM) which increased membrane polarization(i.e., to -49 mV with 0.1 µM SNP), restored phasic electrical and contractile activity andreduced tone. Higher concentrations of SNP (1-10 µM) further increased membrane polariza-tion, eliminated MPOs and abolished all contractile activity. The effects of SNP were reversedby the guanylyl cyclase inhibitor ODQ (3 µM). The Katp channel opener pinacidil (0.3-10µM) had similar concentration-dependent effects on electrical and contractile activity tothose observed with SNP and these were reversed by the Katp channel blocker glibenclamide(3 µM). In summary our results provide evidence that the pattern of contractile activity inthe monkey IAS is dependent on Em, Cav and ongoing release of nitric oxide from nerves.Phasic activity predominates when Em is more polarized and regenerative Cav activity occurswhereas tone predominates at more depolarized potentials where sustained Cav windowcurrent predominates. Ongoing release of NO from nerves depresses tone and augmentsphasic contractile activity in part by increasing membrane polarization. To achieve a betterunderstand how myogenic activity is controlled in the primate IAS it is therefore importantto identify and characterize the ionic conductances which underlie membrane potential andhence Cav activity in this muscle.

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VIP Prevents Smooth Muscle Dysfunction in Colonic Inflammation ByBlocking the Activation of Transcription Factor Nf-κBXuan-Zheng P. Shi, Barun K. Choudhury, Sushil K. Sarna

Background and aim: Colonic inflammation suppresses circular smooth muscle contractil-ity,which is a major contributing factor to diarrhea. Our hypothesis is that VIP is a protectiveenteric neurotransmitter that blocks smooth muscle dysfunction by inhibiting the activationof NF-κB. Methods: We used primary cultures of human colonic circular smooth musclecells (HCCSMCs) and freshly obtained circular smooth muscle strips. Results: The incubationof human colonic circular smooth muscle strips with 20 ng/mL TNFα for 24 hours suppressedtheir contractile response to acetylcholine (ACh, 0.1 µm to 1mM range); it also suppressedthe expression of the α1C subunit of Cav1.2 (L-type) calcium channels to 34 ± 6% of control(p<0.05, n=3). The addition of 0.1 µM VIP to the incubation medium significantly reversedthe suppression of cell contractility as well as the down regulation of α1C subunit by TNFα.

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