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A Human Model of Restricted UES Opening and Its Characteristic Pharyngealand UES Deglutitive Pressure PhenomenaHongmei Jiao, Ling Mei, Arash Babaei, Tarun Sharma, Patrick Sanvanson, Mark Kern,Sudarshan R. Jadcherla, Reza Shaker

Introduction: Human disease models can help to better understand the pathophysiology andsystematically characterize its consequences. Upper esophageal sphincter (UES) dysphagia isa common sequela of a number of disorders including CVA, reflux disease and aging.Intrinsic disorders of the UES such as fibrosis and inflammation can result in its diminisheddistensibility and restrict its opening causing dysphagia. Aim: To characterize the pharyngealand UES deglutitive pressure phenomena in an experimentally induced restricted UES modelin humans. Methods: We studied 15 patients (8 male, age 65±11 years) with varioussupraesophageal reflux symptoms. To induce UES restriction, we used a handmade simpledevice comprised of two components that could be comfortably worn around the neck: anelastic band and a cushion (5 X 3 X 2.5 CM). The cushion was placed horizontally at thecenter of the cricoid cartilage. By adjusting the elastic band, we selectively applied 0, 20,30, 40 mmHg pressure perpendicular to the cricoid laryngeal structure inducing equivalentresistance against UES opening. In this model, the UES, in addition to relaxation, has toovercome the externally imparted pressure to open. Deglutitive pharyngeal and UES pressurephenomena were determined using high-resolution manometry, which recorded from entirepharynx, UES and proximal esophagus. We tested dry, 5 and 10ml swallows x 3. Results:Application of the external pressure band increased the length of the UES high pressurezone from 2.5 cm without the band to 3.1, 3.5 and 3.7 cm for 20, 30, 40mmHg cricoidrestrictive pressure, respectively (p<0.05). Increased restrictive pressure against UES resultedin a significant increase in hypopharyngeal intra-bolus pressure (IBP) during all swallowedvolumes (figure). Similarly, increased UES restrictive pressure resulted in increased UESnadir deglutitive relaxation pressure for all swallowed volumes (table, p<0.05). Swallowedvolume had no effect on pharyngeal peak pressure, duration or velocity. None of these wereaffected by restrictive external UES pressures. Deglutitive velopharygeal pressure progres-sively increased with increased swallowed volume (p<0.05). These pressures were also notaffected by UES restrictive external pressure. Conclusions: Acute experimental restriction ofUES opening by external cricoid pressure in humans manifests the pressure characteristicsof increased resistance to UES trans-sphincteric flow observed in disorders that are accompa-nied by reduced UES opening. These pressure characteristics include increased hypopharyn-geal intra-bolus as well as nadir deglutitive UES relaxation pressures. This model canpotentially be helpful in better understanding of UES pathophysiology.The effect of external cricoid (UES restrictive) pressure on UES nadir pressure

* P <0.05: compared with UES external restrictive pressure of zero # P <0.05: comparedwith dry swallow DS: dry swallow

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Pharyngeal Electrical Stimulation (PES) Expedites Swallowing Recovery inDysphagia Post-Acute Stroke: a Phase II Double-Blinded RandomisedControlled TrialDipesh H. Vasant, Emilia Michou, Pippa Tyrrell, Satish Mistry, Vanoo Jayasekeran,Shaheen Hamdy

Introduction: Post-stroke dysphagia has a high-prevalence and potentially devastating conse-quences including aspiration pneumonia and death. Swallowing recovery occurs in somecases but can take several months with current therapies having limited evidence-base.Pharyngeal Electrical Stimulation (PES) is a promising treatment, already known to activatepharyngeal motor pathways and in pilot studies in acute stroke improved swallowing function

S-77 AGA Abstracts

2-weeks post treatment [1-2]; however the longer-term effects on swallowing remain unex-plored. Methods: 36 hospitalised patients with new-onset dysphagia (22 males, mean age70 ± 2.1 years), were recruited within 6 weeks of stroke after failing a standardised swallowingscreening test [3]. Patients were randomised with an intention-to-treat approach to eitherActive (n=18) or Sham (n=18) PES via an intraluminal pharyngeal catheter at 5Hz, at 75%maximum-tolerated intensity for 10 minutes, for 3 days. A validated Dysphagia SeverityRating (DSR) scale (0-12 (normal-severe)) [2] was applied by independent, blinded speechtherapists at baseline, 2-weeks and 3-months post-intervention. Data were compared usingnon-parametric tests (Mann-Whitney U test). Results: Active but not Sham PES improvedDSR at 2-weeks (Figure 1), (Active: baseline median 9 (Inter-Quartile Range (IQR) 4-12),2-weeks median 3 (IQR 1-9), U=81,*p=0.015, Sham: baseline median 7 (IQR 3-10), 2-weeks median 3 (IQR 1-8), U=103.5, p=0.1). By 3-months, compared to baseline swallowingthere was overall improvement in DSR in both groups (Active: 3-months median 0 (IQR 0-3), U=43.5, **p=0.001, Sham: 3-months median 1 (IQR 0-3), U=52, **p=0.001). Discussion:These data provide further evidence that PES expedites swallowing recovery in post-strokedysphagia compared to standard therapy, an effect that is maintained at 3-months afterintervention. References: 1. Fraser, C., et al., Neuron 2002. 2. Jayasekeran, V., et al.,Gastroenterology, 2010. 3. Martino, R., et al., Stroke, 2009.

338

Maturation and Stimulus-Volumes Modulate Pharyngeal Provocation InducedPharyngeal Rhythms in Human Premature InfantsKathryn Hasenstab, Xiaoyu Gao, Sudarshan Jadcherla

BACKGROUND: Swallowing and breathing dysregulation is a frequent problem in neonatesthat interferes with efficient oral intake and delays growth and hospital discharge. Effectsof maturation and stimulus volumes on the variability of respiratory and pharyngeal rhythmsas well as pharyngeal reflexive swallowing (PRS) are unclear. AIMS: To determine the effectof a) maturation and b) graded pharyngeal stimulus-volumes on the frequency, stability andmagnitude of pharyngeal and respiratory interactions. METHODS: 18 infants (11 male, 23to 37 wks gestation) were studied at 40 and 45 wks postmenstrual age (PMA) using concurrentpharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflowthermistor to test pharyngeal and respiratory interactions upon graded water stimuli (0.1,0.3, 0.5 ml, in triplicate). Respiratory adaptation measures included frequency and durationof deglutition apnea. Upon pharyngeal stimulation, initial pharyngeal response was definedas the first pharyngeal burst and composite pharyngeal response was defined as presenceof pharyngeal activity until the terminal swallow restored aerodigestive quiescence to respira-tory and esophageal normalcy. Recruitment, frequency, variability, and stability of initialand composite pharyngeal responses were characterized. Linear mixed, GEE, and generalizedlinear models were applied; data presented as median (IQR), mean ± SEM, or %. RESULTS:Overall, 250 stimuli were given. Prevalence (%) of feeding methods (gavage: transitional:full oral) at 40 wks vs. 45 wks PMA were 17:44:39 vs. 0:0:100 respectively (P<0.01).Background number of clinically significant cardiopulmonary events (CSCPE) 1-wk priorto initial vs. subsequent evaluations respectively were: 12.5 ± 16.8 vs. 4.4 ± 5.6 (P=0.05).Number of CSCPEs during feeding 1-wk prior to initial vs. subsequent evaluations respec-tively were: 5.6 ± 9.1 vs. 1.9 ± 2.6 (P=0.05). As stimulus volume increases, pharyngealresponse recruitment increases (β ± SE, 7.7 ± 2.0, P<0.01) and duration increases (β ± SE,12.8 ± 2.8, P<0.01). Respiratory and pharyngeal response characteristics are shown (Table1). CONCLUSIONS: 1) Brain stem-modulated vagal and respiratory pathways undergofurther maturation. 2) Volume-dependent increase in recruitment of adaptive responsesoccur. 3) Maturation modulates pharyngeal reflexes and respiratory adaptation by the follow-ing regulatory mechanisms: a) The occurrence of deglutition apnea is similar, but durationdecreases with maturation. b) Pharyngeal waveform recruitment and duration decreases withmaturation. c) Frequency, variability and stability of the pharyngeal waveforms in the initialburst are similar. d) Although pharyngeal waveform frequency is similar, variability andstability of the composite burst is improved with maturation. *Supported in part by 2RO1DK068158 (Jadcherla)Table 1. Effect of maturation on pharyngeal stimulation induced respiratory and pharyn-geal rhythms

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*Data are stated as % or mean ± SEM. Initial: first pharyngeal burst response, Composite:total pharyngeal response until aerodigestive normalcy

339

Nadir UES Relaxation and Hypopharyngeal Intra Bolus Pressures Are MoreSensitive to Consistency and Viscosity Challenge Than Pharyngeal PeristalsisParameters Measured by High Resolution ManometryTarun Sharma, Ling Mei, Hongmei Jiao, Reza Shaker

Background: High Resolution Manometry (HRM) is increasingly being used in clinical practicefor evaluation of patients with dysphagia. While ample data about esophageal pressurephenomena exists by this recording modality, information on pharyngeal and Upper Esopha-geal Sphincter (UES) pressure phenomena is limited. Because varying consistency and viscos-ity can serve to stress the pharynx and UES and reveal subtle abnormalities which mayescape routine evaluation, the AIM of the present study was to determine the effect of bolusconsistency and viscosity on pharyngeal and UES pressure parameters using HRM technique.Methods: We studied 7 healthy volunteers (3F, 24±4 years) in supine and upright positions.All subjects were studied with HRM catheter and analysis software (Given Imaging). Subjectswere intubated transnasally and the manometric catheter which had 36 recording sensorswith 1 cm interval was positioned such that it covered the entire pharynx, UES and proximalesophagus. We tested room temperature boluses with high viscosity (450 kcPs), high consis-tency (mashed potato) as well as water. We tested 5 and 10 ml boluses in triplicate. Wealso tested 60°C and ice cold water. Pharyngeal pressures were measured for ContractileIntegral using smart mouse tool with Manoview software while UES data was calculated withUES sleeve (Manoview 3.0). Results: Overall, there was significant variability in pharyngealperistaltic pressure parameters in both Velopharynx as well as Hypopharyngeal sites acrossconsistency, volume, viscosity and temperature. Difference in pharyngeal peristaltic ampli-tude, velocity and duration did not reach statistical significance for any tested materials. Onthe contrary, hypopharyngeal Intra Bolus Pressure (IBP) and UES nadir relaxation pressureswere more reproducible and sensitive to bolus variations. IBP for 5ml viscous and mashedpotato swallows in supine position 12±1.3 and 13.3±3.5 mmHg respectively were significantlyhigher than that of water, 8.5±1.7 mmHg (p < 0.05). These differences persisted for uprightposition as well as 10 ml swallows. Overall, nadir UES relaxation pressure in upright positionwas lower than that of supine for water swallows with different temperatures. Nadir UESrelaxation pressure for 5 ml water swallows in supine (4.6±6.4, 6.2±6.7 (60°C), 7.4±4.6(Ice cold)) were significantly higher than the same volume and temperature water swallowin upright position (0.01±4.4, 0.6±4.2, 1.2±3.7 respectively. (p< 0.001, ANOVA) Thisposture effect did not reach statistical significance for mashed potato and viscous swallows.Conclusions: Bolus viscosity and consistency significantly affects the hypopharyngeal intrabo-lus and nadir UES relaxation pressures. These measures could potentially be used to detectsubtle abnormalities of pharyngo-UES motor function that may escape routine clinical evalua-tion.Values ± Standard Deviations for 5ml Supine Swallows

*Both values significantly different from all water swallows. P(0.05) CI- Contractile Integral

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340

Anti-TNF is Safe to Stop in the Second Trimester of Pregnancy in IBD Womenin RemissionAlison de Lima, Zuzana Zelinkova, Cokkie van der Ent, Christien J. van der Woude

Background Anti-TNF is relatively safe during pregnancy in Inflammatory Bowel Disease(IBD) females. Continuation of anti-TNF during pregnancy is related to high anti-TNF inthe newborn and might have immunological consequences. We earlier reported that stoppingaround week 24 seems feasible and safe. In this study, we further evaluated the maternalsafety of discontinuing anti-TNF in the 2nd trimester and compared relapse between femalesthat stopped and continued anti-TNF. Methods Out of a prospective cohort of 210 pregnantIBD patients (pts), all pts on anti-TNF were selected. IBD pts in remission around gestationalweek 20 stopped anti-TNF before gestational week 25 (study group), and IBD pts not inremission around week 20 continued anti-TNF until at least week 30 (control group).Disease activity and pregnancy outcomes were compared between the study and the controlgroup. Results The study and control group were drawn from a population of 210 pregnantIBD pts. Anti-TNF was used in 74 pregnancies (44 infliximab (IFX), 30 adalimumab (ADA)),resulting in 59 live births, 12 miscarriages, 1 elective abortion and 2 pts were still pregnantat the time of analysis. In the study group, 32 pts stopped anti-TNF before week 25 andin the control group 22 pts continued anti TNF until at least week 30. Reasons for continuationincluded disease activity around week 20 (n=6), anti-TNF start in first trimester (n=1) anddifficult to control disease (n=15). Median gestational week of anti-TNF cessation was 22weeks (IQR: 12-29). A total of 8 pts in the study group had concomitant drugs (aminosalicy-lates (n=2), corticosteroids (n=1), azathioprine (n=5)) , compared to 6 women in the controlgroup (azathioprine (n=6) combined with aminosalicylates (n=1) and corticosteroids (n=1))(p=1.000).In the study group, 2 pts relapsed in week 30 and 36 after anti-TNF cessationin week 22, while in the control group 1 pt relapsed (p=1.000). There were no significantdifferences in birth weight, gestational term, congenital abnormalities and APGAR scoresbetween the study and the control group. As reported previously, the anti-TNF levels inthe cord blood from children from females that stopped anti-TNF prior to week 25 weresignificantly lower compared to females that continued anti-TNF until the 3rd trimester(1.48 μg/ml vs 8.65 μg/ml, p>0.0001). Conclusion Anti-TNF is safe to stop in the 2ndtrimester in IBD women in sustained remission. Anti-TNF cessation before gestational week25 is not associated with a higher risk of relapse compared to women who continue anti-TNF treatment.

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Risk of Incident Cancer in Patients With Inflammatory Bowel Disease StartingAnti-TNF Therapy While Having Prior Malignancy Within Past 5 YearsFlorian Poullenot, Philippe Seksik, Laurent Beaugerie, Aurelien Amiot, Maria Nachury,Vered Abitbol, Carmen Stefanescu, Catherine Reenaers, Mathurin Fumery, Anne-LaurePelletier, Stephane Nancey, Laurent Peyrin-Biroulet, Arnaud Bourreille, Xavier Hebuterne,Hedia Brixi, Guillaume Savoye, Nelson Lourenco, Romain Altwegg, Bommelaer Gilles,Christine Cazelles-Boudier, Antoine Racine, David Laharie

Background: Management of inflammatory bowel disease (IBD) patients with past or currentmalignancies is a challenge in clinical practice. Having prior malignancy within the last 5years is considered as a contra-indication for anti-TNF while there is no scientific evidenceto support this recommendation in IBD. Aim: To assess survival without incident cancer ina cohort of patients with IBD exposed to anti-TNF therapy while having prior malignancywithin past 5 years. Patients & methods: From September 2011 to May 2013, the GETAIDconducted an ambispective survey collecting all IBD patients with malignancy diagnosedwithin the last 5 years before starting an anti-TNF agent. Date of study inclusion correspondedto the first anti-TNF administration after cancer diagnosis. The primary objective was toevaluate the cumulative incidence of incident (new or recurrent) cancer. Results: TwentyGETAID centres identified 79 cases of IBD patients (49W; median age: 47 [range: 18-84]years; 61 with Crohn's disease) with prior malignancy diagnosed 17 [1-65] months beforeinclusion. The most frequent cancer locations were breast (n=17), skin (n=15), urinary tract(n=12) and those that can be attributed to chronic inflammation (n=8 - including 3 smallbowel and 2 colorectal adenocarcinomas). After a median follow up of 21 [1-119] months,15 (19%) patients developed an incident cancer: 8 recurrent cancers and 7 new cancers,including 5 basal cell carcinomas. Survival without incident cancer was 96%, 86% and 72%at 1, 2 and 5 years, respectively. Two cases of unexpected recurrence were judged to bepossibly related to anti-TNF administration: one case of metastatic rectal adenocarcinomaoccurring 10 years after initial diagnosis and one case of early cerebral metastatic after lungsurgery for T1N0M0 carcinoma. Conclusion: In a cohort of 79 IBD patients exposed to ananti-TNF agent within 5 years following cancer diagnosis, survival without incident cancerwas 96% and 72% at 1 and 5 years, respectively. Of these 15 incident cancers, 5 were newbasal cell carcinomas. Pending large prospective studies, a case by case joint decision takenwith the oncologist is recommended in this situation.

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Retreatment With Infliximab in Inflammatory Bowel Disease: Tolerability andEffectiveness of Different Re-Induction RegimensCarla Felice, Daniela Pugliese, Luisa Guidi, Manuela Marzo, Gianluca Andrisani, Italo DeVitis, Gian Ludovico Rapaccini, Alfredo Papa, Alessandro Armuzzi

Background: Patients with inflammatory bowel disease (IBD) who discontinue therapy withinfliximab may require a retreatment with the same agent after a variable time from discontin-uation. Few data available so far are encouraging as regard to effectiveness, but conflictingresults have been reported on infusion reaction rates after infliximab drug-holiday. No clearindications are described about the choice of a specific induction regimen of re-infusions.Methods: In this single-centre retrospective study, all consecutive IBD patients who requireda retreatment with infliximab after at least 6 months of discontinuation from the firsttreatment were included. Patients were classified in 3 groups depending on the prescribedinduction regimen: 5 mg/kg at week 0-2-6 (group 0) or at week 0-4-8 (group 1) or at week