557

Cancer in Elderly-Onset Inflammatory Bowel Disease: A Population-BasedStudyHalima Cheddani, Luc Dauchet, Cloe Charpentier, Mathurin Fumery, Julia Salleron,Anne-Marie Bouvier, Jean-Louis Dupas, Francis Vasseur, Eric Lerebours, Eric Laberenne,Laurent Peyrin-Biroulet, Jean-Frederic Colombel, Guillaume Savoye, Corinne Gower-Rousseau

The ageing of the population makes elderly-onset inflammatory bowel diseases (IBD) a risingproblem. Risk of cancer is unknown in this population. We studied this risk in a population-based cohort of patients with IBD. Patients and methods: In a French population-basedcohort, we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006,including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC)1. We compared incidenceof cancer among patients with IBD with that observed in the French Network of population-based Cancer Registries (FRANCIM). Only cancers occurring after IBD diagnosis were takeninto account. Confidence interval (CI) was estimated assuming a Poisson specific law forrare events. Results were expressed using the standardized ratios of incidence (SIR) andtheir CI 95%. Results: After a median follow-up of 6 years [2-11], 103 (12.3%) patientswith IBD including 42 CD and 61 UC developed a cancer corresponding to a SIR of 1.00[0.83-1.21]. Eleven patients (1.3%) developed at least 2 cancers.There was no increasedrisk of colorectal cancer in IBD (SIR=1.06 [0.65-1.72], CD (SIR=1.15 [0.54-2.40] and UC(SIR=0.99 [0.52-1.91] without significant protective role of 5-ASA (HR=0.7 [0.2-2.6]). Anincreased risk of malignant lymphoproliferative disorders was found in IBD (SIR=2.71 [1.41-5.20] and in UC (SIR=3.05 [1.37-6.79]) but not in CD (SIR=2.21 [0.71-6.86]). An increasedrisk of extraintestinal tumors was observed only for the liver in CD (SIR=3.25 [1.04-4.07]).Immunomodulator exposure (n=26) was not associated with an increased risk of cancer(SIR=0.75 [0.43-1.29]) nor with any specific risk including malignant lymphoproliferativedisorders (SIR=1.89 [0.26-13.44]). Only 2 patients of this cohort received biotherapy.Conclusions: There is no increased risk for developing intestinal cancer among patients withelderly-onset IBD in this population-based cohort. There is an increased risk of developingmalignant lymphoproliferative disorders in UC and an increased risk for developing livercancer in CD. These data reinforce the peculiarity of elderly-onset IBD as compared withyounger age at onset IBD1. 1 Charpentier C et al. Gut 2013

558

Reactivity of Lower Esophageal Sphincter (LES) Upon Pharyngeal Provocationin Infants With Hypoxic Ischemic Encephalopathy (HIE)Ish K. Gulati, Theresa Shubert, Xiaoyu Gao, Sudarshan Jadcherla

BACKGROUND: Feeding difficulties in infants with HIE manifest as oro-pharyngeal dyspha-gia, aerodigestive symptoms, delayed transit and gastro-esophageal reflux (GER). Pharyngealstimulation occurs during feeding and also during supra-esophageal GER events. Timelinessof reflexes and appropriate LES relaxation during pharyngeal stimulation are crucial forsmooth pharyngo-esophageal transit and aerodigestive protection. The relationship betweenpharyngeal stimulation and LES functions in infants with HIE is not known. AIMS: Wehypothesized that pharyngeal provocation results in altered LES relaxation kinetics in infantswith HIE, when compared to control infants. METHODS: Provocative pharyngo-esophagealmotility studies were performed using a water perfused pneumohydraulic micromanometricsystem with a catheter assembly specially designed for dedicated pharyngeal provocation,and comprised of upper esophageal sphincter (UES) and LES sleeves, and a pharyngeal and3 esophageal channels. Participants were 10 oral-fed controls (32.0 ± 4.7 weeks gestation)and 25 HIE infants (38.1 ± 2.0 gestation) evaluated at 39.7 ± 2.8 weeks and 41.9 ± 2.9weeks post menstrual age (PMA) respectively. Median APGAR scores for control vs. infantswith HIE respectively at 1minute were 6 vs. 1 (P<0.05) and at 5 minutes were 8 vs. 3 (P<0.05).RESULTS: The duration of infusion were similar in HIE vs Control groups respectively (5.7± 0.6 seconds vs 6.5 ± 0.9 seconds, P=0.5). Timing of stimuli with respect to the respiratoryphase (Inspiration: Expiration: Interphase) was (54: 36: 10% vs 44.4: 49.2: 6.4%, P=0.2). were similar in HIE vs Control groups respectively. The characteristics of pharyngealprovocation induced responses were distinct, and are summarized (Table 1). Volume depen-dent increase in LES Nadir duration was noted in infants with HIE (P<0.01) but not so incontrols (P=0.1). CONCLUSION: Compared with controls, upon pharyngeal provocation,infants with Hypoxic Ischemic Encephalopathy have dysregulation of LES functions. Theunderlying mechanisms supporting our conclusions are that resting LES tone is low, frequencyof LES relaxation is less and duration of complete relaxation is prolonged. Modulation ofinhibitory activity at LES with pharyngeal provocation is impaired. Delays in resting excitatoryinput at LES or profound inhibitory activity at LES may be contributory. Nuclear or supranu-clear pathways may be abnormal in infants with HIE. *Supported in part by 2RO1DK068158 (Jadcherla)Table 1. Effect Of Pharyngeal Provocation on LES Relaxation Kinetics

Data are stated as % or mean ± SEM. PRS - Pharyngeal reflexive swallow, PUCR - Pharyngo-UES Contractile Reflex, PMW - Polymorphic waveforms, # - Number of responses per stim-ulus.

S-101 AGA Abstracts

559

The Use of Combine Pressure-Impedance Measurement to Define NeurallyMediated Contraction and Relaxation in the Human Oesophagus In VivoLukasz Wiklendt, Marcello Costa, Nathalie Rommel, Claudia Liesenborghs, Jan F. Tack,Philip G. Dinning, Taher Omari

An excitatory-inhibitory imbalance has been implicated in the aetiology of primary esophagealmotor disorders which are now defined by the Chicago Classification. Measurement of activeinhibition of oesophageal circular muscle has not been possible based on intraluminalmanometry alone. Recently, combined spatiotemporal mapping of changes in intraluminalpressure and impedance has been developed as a technique to quantify the degree of neutrallymediated active and passive contraction and relaxation that is occurring in real time withinmuscle during peristalsis. Proof of concept for this method has been achieved in the in-vitro colon (1). Our aim was to apply this same technique to quantify active contraction/relaxation during normal esophageal bolus transport and to examine regional differences inthe proportions of different states. Methods: Videofluoroscopic images, impedance andpressure were recorded simultaneously in 8 healthy control subjects (2M; age 22-36) whoswallowed liquid(L), semi-solid (SS) and solid (S) barium boluses. A 3.6mm diameter solid-state catheter with 36 x 1cm pressure sensors and 24 x 2cm impedance segments wasused (Solar GI system, MMS). Swallowed bolus clearance was confirmed on simultaneousfluoroscopy. Using impedance and pressure to define changes in luminal diameter andpressure during peristalsis, dominant excitatory/inhibitory states could be determined. Thesewere; i) passive distension (pd) ii) isotonic relaxation (itr); iii) isotonic contraction (itc); iv)auxotonic contraction (atc); v) isometric contraction (imc); vi) isometric relaxation (imr)and vii) auxotonic relaxation (atr) (see Figure 1). All inferences of the mechanical stateswere objectively calculated using Hidden Markov Models. The relative proportion of differentexcitatory/inhibitory states were compared for the proximal esophagus from upper sphincterto transition zone (UES-TZ) and distal esophagus from TZ to contraction decelerationpoint (TZ-CDP) and from CDP to esophago-gastric junction (CDP-EGJ). Results: Significantregional differences in excitatory/inhibitory states were seen independent of bolus effects.Specifically the distal esophagus demonstrated a different distribution compared to proximalesophagus (refer to Figure 2). Most notably the distal esophagus was characterised by amarkedly greater proportion of active isotonic relaxation. Conclusion: Using techniquesdeveloped and validated in an animal preparation we have demonstrated that it is possibleto estimate when and where the human esophagus is actively contracting or relaxing inrelation to bolus flow. This technique may provide new insights into bolus transport physiol-ogy and pathological mechanisms governing heighted perception in patients with dysphagia.(1) Costa, M.et al. Frontiers in Systems Neuroscience, 2013, 7, 1-18

Figure 1.

Figure 2. Regional differences in the average proportion of dominant excitatory-inhibitorystates. *Two Way Repeated Measures ANOVA indicates significant regional differencesallowing for bolus type effects.

560

Assessing the Esophagogastric Pressure Gradient (EGPG) Using NadirImpedance Pressures During the 4 Phases of Bolus TransitZhiyue Lin, Peter J. Kahrilas, Chen-Yuan Lin, Laurel Friesen, Benjamin Mogni, BrandonH. Yim, John E. Pandolfino

Background and Aims: Bolus transit through the esophagus is a complex process thathas 4 distinct phases defined by spatiotemporal manometric landmarks: Phase I entailsaccommodation of the bolus during the oropharyngeal swallow; during Phase II the bolusis compartmentalized into the distal esophagus; Phase III empties the esophagus with peristal-sis and forms the ampulla; Phase IV completes transit with ampullary emptying via a non-peristaltic mechanism. Given that each phase is functionally distinct, we hypothesized thatthe measure of intrabolus pressure (IBP) would be different in each phase. Hence, ouraim was to compare the esophagogastric pressure gradient (EGPG) during each phase of

AG

AA

bst

ract

s