Analysis of gene expression in chronic pancreatitis

of ICP and autoantibodies were associated to autoimmune disorders. CONCLUSIONS:Our study shows original evidence that JCP has a strong association with class II (DR 17) and class I (A 24 and BS) HLA antigens. This relationship was not detected in patients with ACP. The presenceof autoimmune features (increaseof autoantibodiesand autoimmunedisorders) in patientswith ICPsuggestthat the disorder can present,at leastin part, an autoimmune pathogenesis. Class I and Class II HLA.ICP versuscontrol population. HLA DR 17 B8 A 24

Genotipic frec.ence

p

26.7%vs 6.5% 20.0%vs 3.8% 23.3%vs 9.5%

0.0001 0.0009 0.0109

RR Iracti~ 7.81 7.97 3.92

0.47 0.35 0.35

confirmed by three blinded therapeutic endoscopists scoring retrograde pancreatograms (Cambridge II, III, IV). Group I pts: Endoscopiccollection. Group II pts: DT collection. Group I pts had IV cbolecystokinin (CCK, 40 ng/kg/h) started m pre-procedure area. Duodenal fluid collected (on ice) with upper endoscope (Olympus GIF 130) via aspiration trap at baseline and in four aliquots (1-3mL) @ 30, 40, 50, 60 minutes. All Group II pts underwent standard DT placementand IV CCK stimulation with fluid collection in the post-procedure area. Lipase concentration was calculated in IU/L by an autoanalyzer. RESULTS:There were 24 pts in Group I (13 HS, 11 CP) and 37 pts in Group II (19 HS, 18 CP). Peaklipase occurred between 30-50 minutes of stimulation in each group. Both DT and EPFTmethods clearly distinguished CP from HS (Table). EPFTwas shorter in duration, 30% less in cost, required only 1-3 mL of fluid for analysis and eliminated the need for fluoroscopy, There were no complications or episodesof pancreatitis.CONCLUSIONS:1)Simple, timed endoscopicaspirations of duodenal drainagefluid between30-50 minutes of hormonal stimulation can distinguish healthysubjects from chronic pancraati'ds.2)Endoscopicpancreaticfunction testing is safe, less cumbersome, time efficient, and more cost effective than DT methods. 3) This novel diagnostic test will broaden the availability of pancreaticfunction testing to the clinical gastroenterologist.

3272

Peak I ~

Immunohiatochemical Study Of Antoimmune Pansreatitis Takayoshi Nishino, Fumitake Toki, Shin-lchiro Watanabe, Hiroyasu Oyama, Keiko Shiratori, Eli Karasawa,Makio Kobayashi,Naoaki Hayashi,Tokyo Women's Medical Univ, Tokyo Japan

~ I)reUMgTubeO~"

Backgmud and Aim: Toki et al. first reported the existence of a special type of chronic pancreatifis characterizedby diffuse irregular narrowing of the main pancreatic duct on ERP (Endoscopy 1992;24:640), and then Yoshida et al. subsequently proposed the concept of autoimmune pancreatitis (ALP) and the diagnosis criteria (Dig Dis Sci 1995;40:1561-1568). Histologically, AlP is known to exhibit predominant infiltrates of inflammatory small round cells in the pancreas, however,the immunohistochemical features of the intiltrates ware still unclear. The present study was undertaken to clarify the immunohistechemical features of AlP. Patients and Methods: .We studied 7 consecutive cases (6 males, 1 female, mean age 60 years) surgically treated because of suspicion of pancreatue cancer between 1987 and 1995. AlP was dignosed on the basis of Yoshida's criteria. Immunohistocbemicalstudies for UCHL-1, L-26, CD3, CD4, and CD8 were performed by the ABC method. Results: The most striking finding in AlP was dense lymphocyte and plasma cell infiltrates around the main and interlohular ducts with fibrotic change. Lymphoid follicula formation was often observed. Immunohistochemically, the periductal infiltrates consisted predominantly of CD3-positive T lymphocytes rather than L26-positive lymphocytes. The periductal inflammation focally destroyed the duct epithelium, and T lympocytes were occasionally found in the ductal epithelium itself. The T lympocytes that had infiltrated periductally and had invaded the epithelium were mostly CD8-pesitive rather than CD4-posifive. Conclusions: An autoimmune mechanismagainst pancreaticducts characterizedby the periductal infiltrations and epithelium invasion by CD8-positive T lymphocyte, may be involved in AlP. 3273 Transition Of Pancreatic Endocrine And Exocrine Functions Before And After EndoscopicTherapy Of Panereatis Duct Stones Takanori Hirai, Hidemi Guru, Yoshiki Hirooka, Akibiro Itoh, Senju Heshimoto, Katsushi Niwa, Tetsuo Hayakawa,nagoya Univ Gch of medicine, NagoyaJapan Introduction- We performed endoscopJctherapy of pancreatic duct stones, which includes endoscopic removal, pancreatoscopiclaser lifhotripsy and extracorporeal shock wave ifihotripsy. In this study, we evaluatedtransition of pancreatic endocrine and exocrine functions before and after the therapy. Subjects and Methods: The subjects were 34 symptomatic patients who underwent endoscopic managementof pancreaticduct stones from April 1993 to March 2000 in our department. We measured pancreaticinsulinogenic index (AIRI//~BG) of the 75-g oral glucose tolerance test (DGT~ and urinary C-papt)defor endocrine function; and fecal chymctrypsin test, N-benzoI-L-tyrosyl-p-aminobenzoicacid (BT-PABA) excretion test and secratin test for exocrine function. We evaluatedthe value of each parameterat the following points: before the endoscopic procedure,just after, one year later, and two years later. Results: Endocrine function - Insclinogenic index was 0.33, 0.27, 0.18, and O.23 on average, respectively.Urinary C-paptidewas 64.4, 80.8,141.4, and 256.1p.o/dayon average, respectively. Exocrine function - Fecal chymotripsin test was 16.7, 19.7, 18.8, and 11.6U/g on average,respectively.BT-PABAexcretiontest was 65.3, 64.3, 63.4, and 53.3% on average, respectively, in these four tests, there were no significant differences among any periods. In the secretin test, total volume of pancreatic juice was 135.5, 133.1, 95.5(n=12, p
A-64-6

Concenltalions (IU/L) in DuodenalDrainageFluid Hen~Subjec~ 16x1~ 18x1P

ChronkPanc 4.4x1P 4.8x1P

pvalua p
ZLr/S Pnwaluce Of CIFTRGiBe MMatimm In Patients Witti Idiopattiic Chronic Pancroatitis Frederique Maire, Hosp 8eaujon, CIJchyFrance; Thierry Bienvenu, CecileAquaviva, Florence Triwh, Philippe Levy, Philippe Ruszniewski The prevalence of mutations in the cystic fibrosis transmembrane conductance regu/ator (CFTR) gene in patients with idiopathic CP have been previously shown to be increased. We performed a prospective study for the presenceof CFTR gene mutations in a homogeneous group of patients with idiopathic chronic pancreatifis(CP). Patients and methods: 28 patients (19 men), median age 35 years (range: 1660) with idiopathic CP were studied. Other causes of CP [alcoholic, metabolic, intreductal tumors, auto-immune, HIV, hereditary (caused by frypsinogencationic genemutations)J, were extensivelysearchedfor and excluded.No patients had personal or familial history evocative of cystic fibrosis. Genetic analysis for 31 known mutations in the CFTR gene was pedormed using an oligonucleotid ligation assay (Perkin* Elmer Biosystems, CA, USA), following informed written consent. Results: Eight mutations in the CFTRgenewere detectedin 7 patients (25%) as follows: L~F508(n = 2), L997F (n = 2), variants 5T (n=2) or E528E(n=2). A composite beterozygotemutation (Z~F508/L997F) was found in one palJent. No patient had 2 major mutations. The median age at diagnosis of CP was 29 years (range: 1960) in patients with at least one mutation vs 38 years in those without mutations (p=O.05). CFTR mutations were present in 50% of patients aged < 35 years and in 6% in those _ 35 years (p
table. CONCLUSION:In our pancreatic referral practice, 40% of patients referred for UAP had CP based on ST. There was a general correlation betweenST and EUS,with more substantial abnormalities on EUS associated with more common functional abnormalities on ST. No optimal EUS threshold was defined, although a cut-off of > 4 features maximized EUS test performance. At this cut-off, EUS had a sensitivity of 57% and a specificity of 64%, utilizing ST as the gold standard.At any chosencut-off, a substantialnumberof patientshavediscordant test results.

3277 Clinical Analysis Of Diabetes Mellitus In Patients With Autoimmune-Related Pancreatitis Kazuichi Okazaki, KazushigeUchida, Toshiki Nishi, MasayaOhana, Hiroshi Nakase,Suguru Uose, Masahiro Iwano, Tsutomu Chiba, Kyoto Univ Hosp, Kyoto Japan

Background & Aim: Recently, an unique clinical concept of autoimmune-relatedpancreatitis (ALP) has been proposed, in which an autoimmune mechanism is thought to be involved. Although steroid is very useful for the treatment of AlP, the effect of steroid therapy is still controversialin associateddiabetesmellitus. We analyzedclinical findings of diabetesmellitus (DM) including autoantihodiesin patients with AlP. Subjects and Methods: Sixty-two patients in multicenter trials were diagnosed as autoimmune-related pancreatitis according to the following characteristics: (1) increased pancreatic enzymes,pancreatic exocrine dysfunction, and abnormal pancreatogram,(2) hyper-gammaglohulinemia,autoantibodies,or complication with other autoimmune diseases, (3) histopathologically, infiltration of lymphocytes, and (4) effective steroid therapy. Forty one of 62 patients (66%) were complicated with DM. Autoantibodies against glutamic acid dehydrogenase(AGAD), insulin (AI), nuclear antigen (ANA), lactoferrin (ALF)and carbonicanhydraseII (ACAII)were measuredby radio-immunoassay or enzyme-linked immunosorbent assay. Results: 1) All patients had hyper gammaglobulinemia (85%) and/or autoantibodiessuch as ANA(75%), ALF(75%) or ACAII(60%). 2) In 41 patientswith DM, 9 patients (21.9%) had AGADor AI, which suggestedtype la diabetes mellitus. AGAD was detected in 6 (14.5%) and AI in 6 patients (14.5%), respectively.Three patients (7.3%) showed both antibodies.However,the ratio of type la DM in AlP is remarkably high compared with that in Japanese general population (1.1% in total DM patients). 3) Effective steroid therapy were performed in 25 patients with AlP. HbAlc in 15 of 41 patients (36%) with OM mellitus were improved. Conclusion: The present study showed that major cases of DM associated with AlP are not type la, although the morbidity of type la DM in AlP is remarkably high compared with that in Japanesegeneral population. Steroid therapy is effective in some cases of OM associated AlP.

If EUS criteriaconsideredpositivefor CP is set at:

Sensitivity Specificity

z3

_>4

>-5

0.714 0.357

0.571 0.643

0.286 0.786

>_6

0.143 0.929

3280 Gastric Electrical Stimulation Is Associated with Increased Pancreatic Synthetic Function When Compared to Normals and Medical Controls A AI-Juburi, Jean Luo, Univ of Arkansas for Medical Science, Little Rock, AR; Hani Rashed, Univ of TennesseeHealth Science Ctr, Memphis, TN; T. Odorisio, Univ of Iowa, Iowa City, IA; Benoit Marchal, Warren Starkehaum, Medtronic, Inc, Minneapolis, MN; Thomas L. Abell, Univ ol Arkansas for Medical Science, Little Rock, AR

INTRODUCTION:GastricElectricalStimulation (GES), usedfor the treatment of drug refractory gastroparesis,has been reportedto effect pancreaticoutput measuredby PancreaticPolypeptide and PancreaticElastase (GE 118(4) Al150, 2000). To better define the possible effects of GES on pancreaticfunction we measuredstool PancreaticElastase(PE) values in patients (pts) with their GES device ON & GES OFF, in pts who did and did not respond to prokinetic drugs, and in healthy controls. PATIENTS:Stool PE values were measured in 36 individuals in 5 groups: First, pts with GES devices: GES-ON & GES-OFF(n=9, 3m, 6f); next, pts who did NOT respond (NR) to prokinetic medications (n = 9, lm, 8f); pts who DID respond (RES) to prokinetic medications (n=9, lm, 8f); and normal controls (n=9, 5m, 4f) METHODS: Pancreatic Elastasewas measured in stool, as previously reported (GE above). Results were reported as mean-+SEand were compared by one-way ANOVA with repeated measuresfor the five groups. RESULTS:PE values for GES-ONand RES were similar (mean: 494.2+-93.4 vs. 496.0_+85.6; p>O.05). The PE values for GES-OFFwere significantly lower than GES-ON (392.3_+88.5 vs. 494.2+-93.4; p
3278 The Usefulness Of Secretin-Enhanced MR Cholangiopancreatography(S-MRCP) For Evaluation Of Pancreatic Exocrine Function Laszlo Czako, Univ of Szeged,1st Dept of Medicine, SzegedHungary; Janus Endes, Diagnostic Ctr, Szolnok Hungary; Tamas Takacs, Univ of Szeged, 1st Dept of Medicine, Szeged Hungary; Krisztina Boda, Univ of Szeged,Computer Ctr, SzegedHungary; Janus Lonovics, Univ of Szeged, 1st Dept of Medicine, SzegedHungary

The aim of this study was to assessthe feasibility and usefulness of S-MRCPfor evaluation of the pancreatic exocrine function. Patients and Methods. S-MRCP was performed in 20 patients with mild (n = 8) or severe (n = 12) chronic pancreatitis (according to the grade of exocrine pancreatic insufficiency indicated by the Lundh test) and in 10 volunteers without pancreaticdisease.MRGPimageswere evaluatedbeforeand 10 rain after the i.v. administration of 0.5 IU/kg secretin. The changesin pancreatictissue 12 signal intensity and duodenalfilling after the injection of secretin were determined by means of S-MRCP. The S-MRCP findings were then compared with those of the Lundh test. Results. The pancreaticT2 signal intensity exhibited a significant elevationafter secretin administration both in the volunteers and in the patients with mild or severe chronic pancreatitis. This elevation was significantly lower in both the mild and the severechronic pancreatitispatientsthan in the volunteers (66.85+-15.77 and 24A5+_5.85, respectively, vs, 200.0+- 45.07). After the administration of secretin, the diameter of the duodenumwas significantly increasedin all three groups. This duodenalfilling was significantly reduced in patients with a mild or a severe exocdne pancreatic insufficiency as compared with the volunteers (4.12_+1.33 and 1.70_+0.77 vs. 15.38+- 1.73). There was no significant difference in pancreatic T2 signal intensity changes or in duodenal filling in patients with a mild or a severe exocrine pancreatic insufficiency. There were significant correlations betweenthe pancreaticT2 signal intensity changes and the duodenal filling and the results of the Lundh test (r= -0.616 and 0.78). Conclusion. These results demonstrate that the administration of secretin increasesthe 12 signal intensity of the pancreatic tissue and the diameter of the duodenum to different extents in normal subjects and in patients with chronic pancreatitis.This suggeststhat S-MRCPcan provide information of value in the assessmentof an exocrine pancreaticinsufficiency. This work was supported in part by grants from the Hungarian National ResearchFund (OTKANo. O34004) and the HungarianAcademy of Sciences.

3281 Deterioration Of Quality Of Life In Patients With Chronic Pancreatitis Markus Wehler, Ralf Nichterlein, Bernhard P. Fischer, Michael Farnbachar, Oept of Medicine I, Univ of Erlangen-Nuernberg,Erlangen Germany; Udo Reulbach, Inst of Medical Informatics, Biometry and Epidemiology U, Erlangen Germany; Eckhart G. Hahn, Thomas Schneider, Dept of Medicine I, Univ of Erlangen-Nuernberg,Erlangen Germany

BACKGROUND. Health-related quality of life (I-IRQOL) is affected in patients with chronic pancreatitis (CP). Few data are available assessing limitations in HRQOL with standardized instruments. METHODS.HRQOLdata were collected by administering the Short Form (SF)36 HealthSurvey to CP patients (n = 221) using personal interview. The diagnosis of CP was made by clinical, laboratory and imaging findings. CP patients with a malignant tumour were excluded. SF-36 data were compared with recently published data for the German general population (n = 6964) and for patients with epilepsy (n = 77) and malignant diseases(n = 232) using t statistics. RESULTS.Comparedwith the Germangeneralpopulation CP patients (mean age 52+- 12, 69% male) reportedsignificantly (p
3279 Comparative Analysis of Pancreatic Function Testing versus Morphological Assessment (by EUS) for the Evaluation of Chronic Unexplained Abdominal Pain (UAP) Riaz S. Chowdhury, Manoop S. Bhutani, Girish Mishra, Chris E. Forsmark, Phillip P. Toskes, Univ of Florida, Gainesville,FL

BACKGROUND/OBJECTIVES:Abdominalpainthat is unexplaineddespitea conventionalevaluation (laboratory tests, endoscopy,and US or CT) remains a diagnostic challengefor clinicians. The diagnosis of chronic pancreatitis(CP), and particularly "minimal-change" chronic pancreatitis (MCCP), is often considered when conventional studies are unrevealing. The secretin test (ST) is considered the gold standard and correlates well with histology (Am J Castro, 1992; 87:1170), but is not widely availableto clinicians. EUS a!lows detailed examination of pancreatic parenchymabut it's ability to diagnose MCCP remains to be validated.We sought to comparethe utility of EUS and pancreaticfunction testing in patients with UAP. METHODS: Seventy-four patients referred to our pancreas clinics with UAP had a ST. Twenty one of these 74 patients also underwent EUS, performed by 2 experiencedendosonographerswho were blinded to the secretintest results. The pancreaswas examinedfor the presence/absence of 9 abnormal features (5 parenchymaland 4 ductal). Sensitivity and specificity of EUS for MCCP was calculated for different test cut-offs with the ST serving as the gold standard. RESULTS: The ST diagnosed CP in 40% patients with UAP. Sensitivity and specificity in the group who also underwent EUS varied with the cut-off chosen as shown in the following

3282 Exocriee Pancreatic Schirmer's Test Involvement in Primitive Sjogren's Syndrome and His Correlation to Schirmer's Test Marcelio Candelli, Chiara Manganelli, Enrico C. Nista, Alessandro Armuzzi, Maria A. Zocco, Simona Turco, Luigi Scullica, Giovanni Gasbarrini, Antonio Gasharrini, Catholic Univ, Rome Italy

Background & Aims: Sjogren's diseaseis an autoimmune syndrome that induces impairment of salivary and lacrimal glands. Recently Sjogren s disease has been related to exocrine pancreaticinvolvementand chronic pancreaUtis.Aim of this study was to confirm the exocrine pancreaticimpairment in patientwith pSS by fecal chymotrypsin and by 13C-MixedTrygliceride Breath Test (MTBT)and to evaluatethe presenceof a relation betweenlacrimal and pancreatic exocrinefunction. Methods: We enrolled 11 patients (9 female an 2 male, mean age:47.09+-8

A-647