T1736
CC. Results 9 patients with crohns disease (CD) and 7 patients with ukerative colitis (UC) were evaluated Overall 101 of 112 colon parts (902%) were filled and depicted adequately tar diagnosia. In patients with CD there were no pathological flndiugs in 2 patients with both methods. In 7 patients inflammation of the caecum or typieall skip lesions were assessed with MRC and CC In one of these patients inflammation of the sigma and a stenosis, which could be passed endoscopically, were assessed by CC, bnt not with MR(:. In patients with CD MR(: had a sensitivity of 89% with a specifity of 100% tar all diagnosed lesions using CC as gnld standard~ In 3 paoems with UC mild inflammation of the colon was diagnosed endoscopically, which was not seen in MR(:. One patient with UC had an acute severe inflammation of the whole colon, not seen based on MRC. In 2 patients with intlanmlation of the whole cokin a f01d rarefication was noticed. Only in one patient endoscopicaily diagnosed mflarnmation of the sigma was seen as a ,,vail thickening wdth MRC. MR1 based diagnosis had a sensiti~qty of only 43% with a specihty of 100% Virtual endoscopy did not add aW relevant intonnation Raretication of bowel tolds was depicted impressively. Additionally pseudopolyps in the caecum in 2 patients were diagmosed based on VE, which were overlooked on 2D image readings. ( onclusion MRI based colonography appears to be usefi.d m the assessrnent and tallow up of patients with CD whereas in UC only a poor sensitivity can be achieved because at the mucosal character of disease
Prospective Comparison of Hydrogen Peroxide-Enhanced 3D endoanal Uhrasonography and Endoanal MR Imaging for Perianal Fistulas Rachel L West, Soender Dwarkasing, David D. E. Zimmerman, Shahid M. Hnasain, Wim C. J, Hop, Willem R. Schotuen, Ernst J. Kuipers, BachelleJ. F. Feh-Bersma Objectives: Successful fistula surgery depends on accurate preoperative assessment This is important so tit_at recurrence of fistulas does not occur and the continence mechanism is preserved. Magnetic resonance imaging (MR1) and anal endosonography (AES) ate both used to assess perianal fistulas and have an excellent correlation with surgical findings. Several studies have compared the results of MRI and AES. The resuhs in these studies differ However there are no studies comparing hydrogen peroxide-enhanced 3D endoanal uhrasonography (HPUS) and endoanal MR] The purpose of our study was to assess agreement between 3D HPUS and endoanal MRI in perlanal fistulas. Methods: Patients referred to the surgeon for perianal fistulas underwent 3D HPUS and endoanal MR1. The 3D HPUS and endoanal MRI results were assessed separately by experienced observers. Both were blinded tO1each other's findings. A description of each fistula was made and the following characteristins were recorded: classification according to Parks, presence of secondary tracts (circular or linear) and identification of toe internal opening. Results: in total 24 patients (20 M, aged 27-71) were included and underwent 3D HPUS and eudoanal MR1. The median time betsveen 3D HPUS and endoanal MRI was 66 days (IQR 21-160). The methods agreed in 92% (22/24) for the Parks classification, in 71% (17/24) for the circular secondary tracts, in 96% (23/24) for the linear secondary tracts, and in 92% (22/24) lot the internal opening. Conclusions: For evaluating periamal fistulas 3D HPUS and endoanal MRI have a good agreement, especially for the Parks classification and the internal opening. There is a poor agreement in evaluating the circular secondary tracts. Differences could be explained by the nine interval between 3D HPUS and endoanal MR1. 3D HPUS and endoanal MRI oftor comparable results in evaluating single perianal tlatulas and both can be used for reliable preoperative assessment.
T1734 Usefulness of MRI in Assessing The Necessity of Surgery for Acute Small-Bowel Obstruction gel Aoki~ "faro Takafiara, Yasuharu Yamaguchi, Yasuyuki [mao, Yasushi Morita, Miki Minra, Naoya Katsumi, Kenli Nakamura, Taro Yamam, Shin-Idli Takahashi [Objective] In acute small-bowel obstruction, it is very important to assess whether emergency surgery is required or a conservative follow-up is selected. However, the conventional diagnostic imaging has not always provided a satisfactory assessment. This time we have tested the usefultmss ok Clue-MR1 in assessnig the necessity of emergency surgeD'. [Sub[ectsl Thirty-eight cases (18 males and 20 t~emales)with an average age of 57.5 years were admitted to our hospital because of acute small-bowel obstruction tx:tweenJanuary, 2001 and October, 2002, and were examuled by MR1 at the onset of the disease. [Methods] The Philips or Toshiba I.ST MRI machine was used, and for Cine-MRI, Single-Shot High-Speed SE imaging methods or Balanced TEE were ernployed. Emergency surgery was required when ClueMR1 showed no penstalsis in the intestinal tract associated with obstruction such as dosed loop while showed peristalsis in the surrounding intestine (peristalsis gap sign; PG), and either of intralumniat bleednig sign (IB) exfiit)itnig low MRI signal on both the T2 weighted image and tim tht-suppressed 1"2 weighted image was positive. On the other hand, We choc~sed either palliative surgery or conservative treatment based on the MRI fniding that obstruction sites ,.,,'eremultiple and that a large amount of ascites was present in the cases assessed as requiring no emergency stugeD,. [Results] MR1 findings revealed that 12 cases required emeLgcncy surgery, 9 ca~s of which received surgery, with a 90% specificity and a 100% sensitivity In contrast, MR[ findings revealed that 26 cases required no emergency surgery, all cases of which actually eliminated the necessity of emergency surgery (NPV 100%). Thirteen cases expected to receive palliative surgery, 5 cases of which recewed palliative sin\gory. The auother thirteen cases were considered to conservatively improve, ordy 1 case of which received palliative surgery', and the remaining 12 cases of which impruved conservatively. [Conclusion] MRI findings allow to evaluate the necessity of eme> gency surgery with high specificity and setksitiviD. ni acute small-bowel obstruction. It is also considered that MN findings may be an exceIlent index of the prediction for conservative improvement
T1737 Endoscopic Ultrasound (EUS) Evaluation of Perianal Fistulas: Comparing Two Probes and Assessing the Role of Hydrogen Peroxide Injection Yaakov Maor, Yehuda Chowers, Benjamin Avidan, Moshe Koller, Oded Zmora, Simon Ba>Meir Introduction: EUS is one of the most accurate methods for the assessment of perianal fistulas. Conventional radial instruments are often used, Hydrogen peroxide (H202) injection into the fistula was claimed to improve fistula visualization. Aims: To compare conventional radial and dedicated rectal EUS probes for the evaluation of perianal fistulas and to determine the role of H202 injection in outlniing fistula tracts. Methods: Patients with perianal hstulas were evaluated using the GF-UM20 radial instrument (Olympus) and the EUP-R53 MonaPlane rectal probe (Bentax). External openings were located and assessed for active drainage. Fistula tracts were delineated according to Parks' classification. Abscesses were located and measured. Repeated evaluation was preformed following H202 ir~jection. Results: Thirtynine patients: male-28, female-11, age 40 (16-58) years, underwent 42 studies. Seventeen patients had 1BD: Crohn's disease-15, ulcerative colitis-2. Injection of H202 was the only way to visualize fistulas in 3 patients using EUP-R53; it miproved ~:sualization of hstula in 7 and 1 using EUP-R53 and GF-UM20, respectively. Injection of H202 improved visualization of abscesses m 3 and 1 using EUP-R53 and GF-UM20, respectively, Conclusions: EUPR53 rectal probe is superior to the GF-UM20 instrument in the evaluation of perianal fistulas. H202 injection improved fistula visualization and probably the therapeutic approach
T1735
GF,UM20 and EUP.R53for detectionof fistulas and abscesses Rstulas Detected
Radiologic Assessment of the Upper GI Tract: Does it Play a Role in Determining Bariatric Surgical Approach? Ravi N Sharaf Elizabeth H~ Weinshel, Edmund J. Bnii, Jonathan Rosenberg, Christine Pen
TransSphlncte~
~ Sphinct~c
De~Aed
Su~aSupecRclal Levator
EUPR53
27
1
19
7
19
15
4
GF.
7
0
6
1
2
2
0
UM~
BACKGROUND:The role of upper GI series (UGIS) prior to bariatric surgery' is controversial. l'he aim of tbis study was to evaluate the diagnostic yield and cost effectiveness of routine UGIS prior to bariatric surgery. METHODS: The medical records of consecutive obese patients who nnderwent UGIS prior to bariatric surgery between 4/01 and 10/02 were reviewed UGIS reports were reviewed by two experienced gastroenterologists and the findings were divided into 4 groups based on predetermined criteria: group 0 (normal stud),'), group 1 (abnormal findings that did not change surgical approach), group 2 (abnormal findings that did change surgical approach m"postpone surgery), and goup 3 (results which were an absolute contraindication to surgery), Clinically important findings included lesions in groups 2 and 3. The cost of an upper G1 series ($10080) was estimated from the physician tee under Medicaid reimbursement. RESULTS: During the 18-month study' period, 171 patients were evaluated by UGIS prior to bariau'ic smgmT The mean age of the patients was 39.4 +/- 10.6 years, 667% were ti'male, 825% were Caucasian, and the mean BMI was 482 +/- 78 kg/m2 Upper GI symptoms were" present in 29.2%, and 14.0% were taking a H2 blocker or proton pump irihibitor. One or more lesions were identified in 48.0% of patients, ~;~ith only 5.3% having clinically important findings Tire prevalence of ra&ologic findings using the classification system above was as tallows: group 0 (52.0%), group I (42 7%), group 2 (5 3%), and group 3 (0.0%). The most common findings identified were esopMgeal reflux (21 6%), hiataI hernias (18.7%), Schatzkl's ring (1,8%), and esophagitis (1 2%). There were no significant diffi:rences between patients with and those without clinically important findings with regard to age, gender, race, BMI, G1 symptoms, H2 or proton pump inhibitor use, smoking, alcohol use, or hemoglobin levels. The cost of performing rmltine UGIS on all patients prior to bariatric surgery was $1,915.20 per clinically important finding detected, The type of bariatric surgery perfomled did not differ between patients with and those without clinically important findings (p = 0.78) although the ma/onty at the patients had laparoscopic adjustable gastric banding (93%), CONCLUSIONS: In this retrospective study, routine UG1S prior to bariatric surgery had a kiw diagnostic ymld, however, it changed the surgical approach o1"delayed surgeD*in 5% of patients. "*Veildesigned prospective studies to address these issues are warranted.
Abscesm~ Sapedlcial
T1738 Role of Endoscopic Ultrasound Guided Fine Needle Aspiration in the Diagnosis of Extrahepatic Biliary Tract and Gallbladder Lesions Jan R Steinhauer, Darshana N Jhala, Mahmoud A. El Oubeidi, lsam A. Eltoum, David C Chhieng, Ann P. Loam, Nirag C Jhala Intruduction: Ultrasound guided, percutaneous fine needle aspiration (FNA) is infrequently used tor the evaluation of mass lesions of the biliary tract. Endoscopic ultrasound (EUS) guicted FNA is used more frequently kir the diagnosis of pancreaticobihary tract malignancies with a high level of diagnostic accuracy. However, its utility in the evaluation of lesions of the gallbladder and extrahepatic bile duct has not been ,,yell investigated. At our institution, EUS-FNA is combined with on-site interpretation to provide an immediate feedback on specimen adequacy and a provisional diagnosis. We report our experience of EUS-FNA in the diagnosis of lesions of the gallbladder and the extrahepatic bile duct at our institution. Materials and Methods: All EUS-FNA (n = 29) specimei~sof the extrahepatic bile duct (n = 25) and gallbladder (n = 4) fl'om 27 patients (17 males aged 37-81 years and 10 females aged 49-74 }'ears) over a 22 month penod were evaluated. All reports were broadly categnrized as positive or negative for malignancy, atypical or unsadsfactory. Tissue diagnosis and clinical Mlow-up information were correlated with cytological resnhs, and frequency of procedural complications was recorded. Sensitivity, specificity and diagnostic accuracy of each method were detem'lined. Results: Eighteen (62%), 8 (28%) and 3 (10%) EUS-FNA samples were characterized as positive for malignancy, negatwe {or malignancy and atypical, respectively. No unsatisfactory"speciulens ,,,,'ereidentified (0%). Of the three atypical results, two patients
A-557
AGA Abstracts
were diagnosed later wuh adenocarcinoma, and one was diagnosed with pancreatins Sensitivity of EUS FNA was 78%, specificity was 83%, and diagnostic accuracy was 88% EUSFNA was more informative than bile duct bmshings in 4 instances. Three false negative aspirates were identified. One patient was later diagnosed with adenecarcinoma of the gallbladder, the other two wilh adenocarcinoma of the common bile duct. Two of the false negative diagnoses resnlmd flonr an associated increase in background inflammation. No false positive results were idennbed. Condnsion: EUS-FNA is a powerful modality in the diagnosis of gallbladder and extrahapatic bile duct lesions. Knowledge of the pitMls may ihrther enhance the utdity of this technique
(p<0.001), and diminished neutrophil infiltration (p<0.05) and congestion and edema (p<0.001) compared to vehicle. In contrast, vanconrycm treatment resulted in reduced congestion and edema (p<0,05), but failed to prevent neutrophil inflhration and epithdial damage In addition, 50% of t~amsters became moribund and C. difficfle toxin positive 1015 d after discontinuation of vancomycm treatment. In contrast, none of the rilalazil-treated hamsters showed any sign of disease (p<0.05) or presence of C. difficile toxins 30 d after discontinuation of treatment. Conclusion: RiMazfl, like vancomycin prevents and treats C difficile infection in Syrian hamsters, However, rifalazfl, in contrast to vancomycin, is associated with dimimshed C. diffieile associated histologic changes and no relapses. Our results indicate that rifalazfl may be superior to vancomycin t0r treatment for C. dill'idle infection Supported by" a grant from ActivBiotics, lnc., Cambridge, MA
T1739 Inhibition of Cyelooxygenase-2 Activity Reduces Rotavirus Infection John W, Rossen Jarmeke Bouma, Rdien C. Raatgeep, Hans A. Buller, AIexandra W. Einerband
T1742 Characterization of In Vitro and In Vivo Murine Models of Human Enteropathogenic E. colt (EPEC) Infection Suzana D. Savkovm, Farol L, Tomson, Michelle Muza, Gaff Hecht
Rotavirns (RV) diarrheal illness is one of the most common intectious diseases in young children. RVs uiii:ct mature enterocyles in the small intestine leading to induction of vires gene expression and a variety of intlammatory cytokines, reduction of entemcyte gene expression and vacuolization. Cyclooxygenases, COX1 and COX2, are enzymes that synthesize prostaglandins (PGs). Two observations point toward a role of (COXs) in RV mfectinn: 1. The duration ot RV diarrheal dlness is reduced alter oral aspirin, a non-specific COX inhibitor, 2 Elevated levels of PGs have been recorded in the plasma and stool of RVinfected children. Aim: "1"osntdy the role of COXs and PGs in rotavirus infection. Methods: Human intestinal Caco-2 cells, known to be susceptible to rota,Arns inl?ctinn, were incubated with COX1 -specific (SC-5601, COX2-speciflc (NS-398) or non-specific (Indomethacin) COXinhlhito~ prior to arid/or during inoculation with 100 [bcus forming units of the human rotavirns WA strain. Subsequently, the number ot intected ceils was monitored using an indirect immunofluorescence assay nsmg an anti-rotavims polyclonal antiserum In addition, PGE2 levela were deterrmncd at different time-points (0, 2, 4, 8 and 15 h) postinfectinn (p.i.) using the PGE2 enzyme niununoassay system (Amersham Pharmacia Biomch) and the kinetics of the intection was monitored by Western blot analysis. Results: In infected Caco2 cells viral replication was detectable by Western blotting starting from 4 h p.i. which coincided with an nicrease in PGE2 levels, lndomethacin was able to reduce rotavims nifl:ction by 75% Yhe COX1 mhiNtor did not bawe a significant effect on infection, whereas COX2 inhibinon was able to block the rotavirns intection by' more than 50%. Exogenous addition of PGE2 counteracted the inhibitory effect of nidomethacni and NS398. Conclusion: These findings suggest that COX2 and PGE2 are involved in RV infection.
EPEC infection of model human intestinal epithelia alters bamer function and induces inflammation. The lack of small animal modds has restricted in vivo study of EPEC/host interactions. Deletion of the bundle forming pflus (bfp) gene diminishes species-specific adherence of EPEC. The aim of this study was to develop in vitro and in vivo murme models of EPEC infection and characterize effects on tight junction (TJ) barrier function and inihmmation. Cultured monolayers of murine intestinal epithelial CMT-93 cells and C57BL/6J mice were used. Bacterial adherence, transepithelial electrical resistance (TER) and inflammatory responses were examined. WT adhered to mouse cells but less efficiently (5+/-3%) than to human T84 cells (~20%). Mutation of the bjp gene did not increase adherence to CMT-93 cells, but immunofluorescent staining showed that VvT adhered as microcolonies whereas bfp- adhered as single organisms. WT and bfp- decreased TER of CMT-93 monolayers 32 +/-6 and 37 + A8%, respectively at 6 h (n = 6). Immnnofluoreseent staining of the TJ protein occludin in uninfected monolayers showed a uniform line at the perimeter of ceils while infection with WT caused marked loss of occludm fron'L TJs. Concerning intlammation, both WT and bfp- induced ERK1/2 phosphorylation, PKC{ translocation, and 1KBc~degradation. For in vivo studies, C57BL/J6 mice were infected with V'vq" (amp resistant) and bfp- (tet resistant) by gastric garage, belucosally adherent bacteria were plated on antibiotic selective media after 3d and colony" forming units determined (Table). PCR for espB gene confirmed organisms as EPEC. WT and b3~- colonized murine intestine, hut bfp- adherence was greater than WT in small and large intestine. Myeloperoxidase (MPO) content, a measure of intestinal inflammation, in \u and bfp- infected animals increased 1.6 and 2.7 fold in cecum and 1.4 and 1.6 in colon, respectively, compared to uninfected animals. Increased fluid was noted in the small intestine of bfp- infected animals. In conclusion, WT and l?fp-EPEC adhere to culntred murine intestinal epitheiial CMT-93 cells, perturb TJs, and induce inflammatory cascades, In vivo, bfp- colonizes to a greater extent than ~ yet both induce inflammation. These data strongly support further characterization of EPEC inti:ction in mnrine models.
T1740 Infection, Latency, and Reactivation of Varicella Zoster Virus in Enteric Neurons: Ocoarrence in Human Subjects and Analysis of an Animal Model Jason J~ Chert, Shflni Wan, Stephan C. Bischolf, Anne A. Gershon, Mict~ael D. Gershon Varicella zoster vires (VZV) cau~'s varicdla (&ickenpox), an acute primary intection, and zoster (shingles), a secondary infection resulting from reactivation of latent VZV. Although latent VZV is thought to be restricted to sensory ganglia, the known occurrence of pseudoobstruction associated with refection of the entenc nervous system (ENS) by VZV in immunocompromised patients, raises the possibility that VZV becomes latent in enteric neurons. We thus detemfined whether mRNAs encoding latency-associamd VZV proteins are present in the human bowel and analyzed the ability of \~ZV to infect and establish latency in guinea pig enteric nectrnns. Muscularis extema and mucosa-submucosa were separated from unmvolw:,d human bowel (2 duodenum, I jejunum, 4 colon, 1 rectum) resecmd during surgery for caucer attd analyzed by- RT-PCR. We detected expression ot at least one latencyassociated VZV gene m each specimen. "iI~e most common transcript encoded ORF62 but ORY4 and ORF63 were also expressed. Myenteric ganglia were isolated and cultured from guinea pig inmaine Neurons exposed to cefld}ee VZV expressed only, 6 latency-associamd VZV proteins, confined them to the cytoplasm and survived indefmitely (latent infection). Neurons exposed to VZV in Ihe presence of non-neuronal cells expressed all VZV genes, contained intranuclear ORF 62p and ORF29p, and died within 2 day's (lyric infection). Expression of the HSV orthologne of ORF61, 1CP0 (delivered with an adenoviral vector), reactivated latent VZV These studies establish that the ENS is a target for VZV, which h'equently k~!cornes latent and thus can reactivate in enteric neurons. Visceral zoster without com:omitant rash may be an undiagnosed cause of abnormal GI motility and/or niflammation.
Adherent coloniez of WT and bfp- EPEC Small I~e~lne Cecum WT 12+/- 03 X lOe3 6.4+/1,3 XlOe3 bfp1.6§ XlOe6 4,9+/-0.4 X1(~6 Data expressedas mean § SEM/gm tissue; n=3.
T 1743 Effects of Cholera Toxin (CT), Escherichia colt Heat Labile Toxin (LT) and Heat Stable Toxin (STAYon Distant (Neurogenic) Intestinal Fhfid and Electrolyte Transport Anna C. Casburn-Jones, Matthew R. Banks Michael J, Farthing INTRODUCTION: We have shown previously that CT, LT and STa have distant effects on intestinal fluid and electrolyte transport via neural mechanisms. Intestinal trar~section can abolish or reduce the distant eft~:cts of CT, LT and STa supporting a role for the intnmic intramural neurones of the enteric nervous system. 5-hydroxy'tryptamme (5-HT) release and activation of the 5-HT3 receptor have been implicated in the afferent sensor,/neural reflex of cholera toxin. Vasoactive intestinal peptide ~rlp) has also been suggested as a neumsecretory nenrotransmitmr in the rat and human intestine. AIM: (a) To determine the role of vagotomy in the remote actions of CT, LT and STa. (bY To determine the effects of granisetron, a selective 5-HT~ receptor antagonist, and PG 97-269, a selecnve VIP1 antagonist in CTinduced effects on distant mmstinal transport. METHOD: A jejunal and ileal loop were fashioned in rico, in anaesthetised 200g Wistar rats, to cream a model of distant intestinal secretion. CT (50btg/ml), LT (50~g/ml), STa (2~g/ml) and hyper-osmolar mannito[ (600mOstM
T1741 Rifalazil Prevents and Treats Clostridium difflcile-Associated Infection in Hamsters Pauhne M. Anion, Michael O'Bnen Barry Eisenstein, Chamlabos Pothonlakis Background and Objectives. C. difttcile-inlection is treamd effectively with vancomycin or metmnidazole However, the main drawback with use of these antibiotics is the high incidence of relapsing C difficfle infection and the spread of vancomycin-resistance enterococci. RiMazil, also known as R~d-1648, of the benzoxazinoritZamycni class, is a ritamycin derivative possessing activity against Mycobacterium tuberculosis. Here we compared Ihe efficacy of ritalazfl vs vancomycin in preventing or treating cflndamycin-induced cecitis in a hamster model of C difficfle inffction. Methods: Golden Syrian hamsters (100-125g) were injected s.c. with dindamycin phosphate (10 mg/kg) followed, 24 hrs later, by C difficile gavage (105 CFU) Hamsters (8-9 per group) were administered by garage daily" for 5 days (d) vehicle, or vancomycm (50 rng/kg), or rflalazfl (20 mg/kg) either together (prophylactic protocol) or 1 d after C, difflcde administration (treatment protocol). C difficile toxins were identified by ELISA in cecal contents. Ceca, fixed in 10% fbrmalin and stained with hematoxylir~teosin, were ex~ammed for histologic damage. Results: While vehide-admniistm~'d animals became monhund 2 d alter C. difl-tcde garage, none of rifalazil or vancomycintreated anmMs in the prophylactic or the treatment protocol showed signs of morbidity after 7 d Moreover, *~falazi/-treated animals showed absence of epithehaI cell damage
AGA Abstracts
Colon 1,3-~-fl,6 • t0e3 3,2+/-0.1 X 10e6
A-558