5 OP Keratin 8 gene mutation in patients with chronic pancreatitis

Pancreatic diseases

5OP

7P

KERATIN 8 GENE MUTATION M PATIENTS WITH CHRGNK PANCREATlTlS CM. Ca\esrro*, L. Fmllo”~“, A Nouvenne’, B. Calore”. L Cavalkxo*, P. S&I”,*, TM Neri. L. Gkoluanyi”, F. DI Mano’, G. Cavalbm” ‘Univrmti di Puma, D~perbmentodt SclenzeCl&he, Cattedradotiastroenterologia; ~Univers~tkdl Verona,Dipartimentodi ScienceChmxglche e Gastroenterologiche,*AZ. O\pedalieradi Puma, Laboratorio di GeneticaMolecolare e Biotecnologie Diag”ostiche Background. The pathogen&s ofchronic pancreatzt~s(CP) is still onknow. Genetic mutmons in the SPMKI, CFTR andPRSSI genehas bee” assocmtedwth CP.Keratin 8 (KS) and 18(KIS) are the major componentsbf the intemwdiate filament cytoskeleton of pancreaticacinat cells and play a relevantrole in pancreahcexocrine omeostesis.In transgenicmice,disruption ofthe normally regulatekeratin expression in viva could be related to inflammatorv ozmcreaticdisorders. We therefore investieatedmutat#o”s in the Kerati” 8 genees a geneiic’backgroundof CP Methods,The substitutionof cysteme for glycine at poution 6 I (G6,C mutation),and the substitutionof hmtldme for tyrosine at position 53 (Y53H mutation) in the keratm 8 gene, were determmedby PCRRestnct~o” Fragment Length Polymorphism(RFLP) m 75 CP patients(57 male, 18 female)and 100healthy “anna, conhols (70 male, 30 female)of the sameethnicalgroup. Sequenceanalysis, was performed when the digestmnof PCR products resultedin two different-sized tiagmentssuggestingthe presenceof mutation. All p&en& andcontrols gave their informed consent. Results: ‘TheG61C heterorygous mutatm” ofthe keratin 8 genewas found in six patients with chrome pancreatitw “one of the 1W normal co”tmls preserxtedthe mutation (8% YS 0%. o=O.M)6.Fisher ‘s exact test). No Y53H mubtio” was detected in B”Ysubiect. Co&ton: Mutatwns in the K&tin 8 gene,togetherwth other environ&en&l factors (alcohol intake,smoking habtts) and/or genetncfactors, could predisposeto chronic pancreatitisby mterfering with the normal orgamzatm” of keratm filaments

FREQUENCY OF CFTR GENE MUTATIONS ,N CONSECUTIVE PATIENTS SUFFERING FROM CHRONIC PANCXEATITIS. L. Fm,,o”i*, M. Cavrstro’, L. Bemarda”i*, S. Bru”elli*, L. Cavallaro”. B Calore’, C Lm”?, A. Cantonc’, B. Furi*, E. Coat”*, F. DI Mario’, G. Cavalbni’. *Cartedra dl Ga.stme”tero,ogia,Universita di Verona; ‘Cattedradl Gastrwnterolopw “n,vers,td dl Parma. Background: Cystic Fibrosis Trans.membraneConductawe Regulator(CFTR) gene mutationshasbeendescribed in patxots suffering from recurre”t idiopathic pancreatitis.The frequency of thesegenetic mutationsin patiolts with chronic pancrzatitis (CP) is unkmw”. Am ofthis study was to evaluatethe FrequencyofCFTR genemutationsin a consecutwe seriesof patiemssuffering from CP. Patlent?.:62 patients(45 males, 17 females,mea” age 51.4 + 12.3years) with a defmitwe dwgnosls of CP, consecutively enrolledfrom September 2oW to December2W1 were studied.Methods: Thirty-three of the most common CFTR mutationswere analysed,covering 75% of mutationsofthe Italian population.We used B commercial kit for cystic fibrosa: F’CRiOLAISequence-CodedSeparationbased onoligonueleotidespecific ligation assay. Results: 10patients,one of ti with painlessCP, (I 6. I %; 8 males,2 females,mean age45 f 14.3years) were heterozygous for mutation in the CFTR gene(CFTR +/-): 9 patientswere positive for SF508delmutation,onepatient was pmtive for RI 17H mutation. SingleCFTR genemutation is present in 3,5% of the generalpopulation andthe frequency observed is 4.26 timeshigher in CP patients@
6P ROLE Ok DYNAb”C MT, PANCREATOGRMHY IN THE EVALUATION OF CHRONIC HYPERAMYLAESEMI.4

EPILESSYAND IPOGLlCEMY POSSIBLEROLE ENDOSDNOGRAPHY i-4 Musca”cllo*, A Sa,cunP,MC Nocchxem’,E lerardi*, A Contdlo”,D Faleo*,M Gws,,mnP. C Natsle~.C Panella*

Dynm,x MR pancreatography(MRP) 1sbecomInga prormsmgaltematl~eto ERCPfor the dmgnosisafexocrine pancreaticdiseasesThesdmuta”o” of pancreaticsecretm” by secre”” mpraves the visualisatio”ofthe Wnsungduct andIS ableto demonstratedrainageof pmcrestic juiceinto theduodenumwbxb may beexplortedfor the assessment oftbe exomhepancreaticreserve Am to evaluatetheusefulnessof dynamicMRP In patients wth cbron~cbyperamylaesemia Patients 12with chronicu”exp,plsi”ed pancreatic hyperamylaesemia (CH), 8 with provenchronicpancreatitns (CP,. and6 with post-acute pancreamis(post-AI’) Methodsto eliminateovalappingfluid-containingorgans.asaper psramgretic suspensmn(Lummm) wasgnvenSmgle-shotturbo spin-echoTt-weighted cbolangio-wlrrung-~ephicsequenceswereobtined in acorn”&oblique plane Following stmulatumwth 1v secrets”(1 CUlkg). acquisntio”ofthe optimalsectionwasrepeatedafter 1.3, 5. IO, I5 and20mi” Results prior to i v secreti”, theWirsungduct wasvisiblem all the patientsbut 3 wth post-AP ARerstimulation,it becamevisiblein Z afthe 3 pattents andbecamec,esrer in 17oftbe remarnrng23 In thepauentswth CK theWirsungduct was dilatedm 2, the drsnageof pancreatxjuice wasnormalin al, butone,who showeda return to thebase-linediameterof theWnsung ductafter 20mi” The exocrinesew&o” was opumd m all but two cases,wherethe duo&m, tilling was impaired(Mates grading
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Wniti dsGastroenteralogmOspedabera,OspedabRiunttl,Foggia,‘2* Uniti di MedicinaInterna Ospedaliera,OspedaliRiuniti, Foggia,~IstLutoO”ca,ag~co.Pauli-Calmntcr,Marngba,gU”tta dl Chhrgm Gene& Orpeddma. OspedabRaunm,Fog& Unzti di Gastmentemlogia Uaverntarm OspedaliRiuniti, Foggia Girl 17yeas old(159cm,Kg 74,BMI 29 3 Kgimz)wasadmmedat the Medicine-depanments of our Hospitalce”tre M accou”t of ocasvanal,pog,icemy.Pos”weana”mes!sconcernmg Epdepsyin cue stnce2 yearwith BC.Valproic01dosz IOM)&die The patientpresented nordity of following laboratorydataG”,IGFI.TSHACTH.PRL.FSKLKCo~i~o,o,NSES-OH-md while the PTH resulted increasedin oneat-therede,em,inst,o”Theonly valuesconstmtly alteredwerelow levelsof glicemybothbans,andpost-pm”&, andmodest~“creaseofpancreatic isoamdasy valuesBecauseoftbwc resultsthe patients&n executingM abdomi”J routine-ultrasound with negativeexits. exguted a spna,TAC afabdome~alwayswith negativeexits.executed for diagnosticcompletinga NMR of turcica, saddlewith negativeexits A gastroentemgical advicerequiredaPmxreasBUS for dmgnoniccomplettngof iperamilasemyEUS showedthe presenceof ipoecogenovaliformimageat definedbordemwithgreatestdimensionabout14 mm placedin the pancreastad that showedrich vasadarizatio”to investigatio”color-powerdoppler.withoutewdenceoflinphonodalinugesThe patientswassubmittedto surgical t”terve”i”g with smultaneousdrawingof bloodchampionsfioomportalvein andfrom a peripheralveinboth atto,beforeenucleationandTl.after 20 minutessi”ce mucleationof pancreatic“eoformatio”.Reductio”ofmsubnomawas followedby rapid r&coo” of ~nsdinemyboth81pond kel andperipheralAt theendof intewenlngthegbeemiaand msulinemievaluesresultednormalandwe proceededto suspendthe cure wnb a.c Valprolc wth absenceof epdepticmanifestat~o”Hlstologxal xnvsnt~gatm”confirmedthedmgnosnof insulinomawith hismcbemxalpositwely aboutmsuuli”andcromograninaA C”“C,“Sl”” Althoughthei”su,i”oma in a very unusual“eoplasiwt cansometwes beresponsiblefor a smtom~ologyonly of neurologicaltype epilepsyThereforeclimca,caseI” subjectinvitesto consxderamongdiagnosticallyinvestigationthatcan beperfomxd m patientswth episodes oftpoglicemyandneurologicalma”lfestatio”&o endoscopyconsideringthatabovemethod IScertainlyamongthereliabenI” dmgnosuofpancreaticlesionof dmmeterunder I 5 em