- Email: [email protected]
Incidence of p53 gene mutations in 93 consecutive long-segment Barrett's patients
Oesophagus
33 IS IT POSSIBLE TO REDUCE COSTS OF THE DL4GNOSTIC ALGORITHM OF GASTROESOPHAGEAL REFLUX DISEASE (GERD)? THE ROLE OF CONVENTIONAL HISTOLOGY Di StefanoM, Missanclli A, Luinetti 0, Alvisi C, Veneto G, Sol&E, Corazza GR. Gastmenterology andPathologyUnits, IRCCS “S.Matteo” Hospital, Univemity of Pavia,Italy. Policlinico S.Matten Background & Aims: Tbe absenceof endoscopicesopbagitisdoes not exclude GERD, as only up to half of patientswith typical reflex symptoms show this alteration.In the absolce of erosions,Non Erosive Reflex Disease(NERD) may be present andadditional investigationsmust be performed, such as 24-hour ambulatcnypH monitorinp. However, the sensitivity of this test is not satisfactory, andthere is a risk that useful indications may not be obtained.Tbe aim of this study was to evaluate how many 24-hour ambulatory pH monitoring we could have saved if, during upper endoscopy,the fust choice investigation esophagealhistology, bad beenperformed in patientswith NERD Patients& Methods: Twenty consecutive patients(7 females,mean age449yrs, range 31-63) with typical nflux symptoms, such as heartburn andregurgitation severa time a week anda nonml appearanceof the distal esophagusat upper endoswpy took part in the study. In all of them, 2 biopsy specimens3 cm abovethe gzstmesopbagcaljunction were collected andprocessed for conventionalhistology Tbc presenceof esophagi& was defined by the presenceof basalcell hyperplasia>15% of tie total epithelium, increazd papillary Ier@b >66% of the squamous epithelium,infiltration by polymnphonuclear cells and/or wsinopbils andintercellular space dilation. On a separateday, a two-channel, 24-hour ambulatmy pH monitoring test was pafomxd The test was consideredpositive if one oftbe following criteria was present: with respect to total time of recording, total acid exposurehigher than 4.2%, acid exposure in supineposition bigber than 1.2% andacid exposurein erect position higher than 6.3%. DeMeester score higher than 18. Results:In l6/20 patient (80%) histology was indicative of esophagitis.The patientswith normal histolom’ showed a 24-hour ambulatoryOH monitorirx indicative of oatboloeic reflu. On the cons, 24-hour ambulatorypH moni&ing was posiiivc in 13120patients (165%).All the seven patientswith normal pH monitoring showed apositive histology. Conclusions: In NERD Datients histology may addus&d diagnosticticnmati& and 24.hour &bulatory pH monitoring can often beavoided.
35 INCIDENCE OF ~53 GENE MUTATIONS IN 93 CONSECUTIVE LONG-SEGMENT BARRETT’S PATIENTS. A. Rcpici, L. Dughem,E. Battaglia, A. S&IO, C. Barletti, C. De Angelis, A. Musso, M. Navino, S. Camma, S. Pagmin, M. Rizmtto, G. Saracw. Dept of Gashnentemlogy,Molinette Hospital, Torino molinette Backgmundand Aims: BarrettOfs esophaausis a Iota-term comulication of esouhaEealreflex that can p&ress to adenocarcinoma.Se&al &tic andfigsutalalt&tions have b&n b&stigated in order to identify a marker that can predict the risk of mali8nmt progression. Tbe am of tbe present study was to evaluatethe incidenceof p53 mutationsin p&cnui with long-segmentBamtt without cancer. PatientsandMethods: 93 consecutive patientswith histologically pi-ovenBaren q fs esophaguslonger than2 cm were enrolledinto the study. Biopsy specimenswere obtainedwith a Jumbo forceps andwere taken one for eachquadrantevery 2 cm. One specimen for each2 cm level was analyzedfor ~53 mutations.Mutation in pS3 Emus 5 to 9 were de&ted by polymemse chain reaction-sizzle-strand umformation wlvmombisms @CR-SSCPlandcontinned bv direct DNA sequencing.-Results:Among tie 93 ,&ds, i2 w&male and2i female with a “&a ageof 61. I year (range37.84). BanettOfs length was between2 and 3 cm in 46/93 pts (49.5%), between3 and 5 cm in 30/93 pts (31.2%) andlonger than 5 cm in 17193(18.3%). At histology 7/93pts had an indeterminatedysplasia,l2/93 a low gndc dysplasia, 4 an high grade dysplasiawithout endoscopic evidenceof well debed massesor lesions.Three mutationswere detectedin the 93 pts studied (3.2%). All thesewere missense(PISIT PmOTreo, M246Y Met 0” Tyr and P.248GArgo” Gly), andwere detectedin 2 patientswith bigb gradedysplasiaand in onepatientwith low &e dysplasia ~53 mutationswere detectedsignificantly mom fixquently in high gradedysplasia(50%) than in low gradedysplasia (8%) andno dysplasia (0%) (P
34 DIAGNOSIS OF CHRONIC COUGH DUE TO G-O REFLUX: DUAL PROBE OESOPHAGEAL pH-METRY YSPPI TEST, R. Cappiello, S. Ghersi, A. Zanasi*, U. Caliceti , F. Tomesan,C. Cavoli, F. Baldi, E. Roda. Service of Gashventemlogy, *of Pneumology, of ENT. S.Orsola-MalpigbiHospital, Bologna s. Orsola G-O reflux has beenshown to be the most fceeeuent cause.after asthmaandwst-nasal drin of chronic persistentcough (CPC) (I). Fur&m&e, CPC may be the only cl& manifestati~ in 10to 35% of GORD patients.Both thepH monitoring of proximal oesopbagusand a short course with high doseof anti-secretmy drugs (PPI test) have beenpmposcd for tbc diagnostic work-up of these patients(2). However, their diagnosticefficacy hasnot yet beemwell established. MATERIAL AND METHODS: 19 patients(I7 F, mean age57.8 range42-74) with CPC (daily episodesof cough lastingfrom at least 3 months) astheir main symptom, not dueto ENT and/or respiratory diseases,were studied.AtIer a clinic evduation with 61,assessmentof the freq,,ency and severity of CPC andof the presenceof oesophsgealsymptoms (heartburn, dyspbagia,regurgitation), all the patientsunderwent a dual probe 24-esophagealOH-metry (the distal eloctmde was wsitioned 5 cm abovethe LES andthe pmtial one 2-S cm under UBSj id a therapeutictrial with PPI at a double daily dosagefor four weeks. A visual anlogue scale(O-IO) was usedto evaluatethe outcomeof trial @ositive iftbc post-timmt valueWBS0 or if the difference pmpost was 5). RESULTS: oesophagealsymptoms were found in 8119pts. (42.1%)).A pathologicGOR (%T==4, ti.74 in distal aesophagusan&r xl.5 in proximal cesopbagus)was documentedin 13119pts. (68.4%) and in 618pts. with associatedcesophagealsymptoms (75%). only I l/l9 pts.(57.9%)repmtcd the presenceof co@ during the 24 h pa-m&y; of them 8 showed a positive SymptomIndex (S.I.) (>50% and >30%, respectively in distal andpmximal oesopbagus).PPItest was positive in 8/l9 pts (42.1%). In particular it was positive in 318ptxwitb ocsopbagcalsymptoms (37.5%) and in 6/13 pts (46.1%) with pathologicGOR.CONCLUSIONS:tbe results of our study show that tbc establishmentof a casualLinLbetweenG-O mflux and CPC still representsa difficult task since it doesnot seemta exist a direct r&tionsbip betweenthe presenceof G-O reflex and the outcomeof the therapeutictest with potentanti-secretory dmgs.However, with the combineduse of PPI test andof S.I.dming pH-metry, an aesopbagealorigin of the cough was establishedin about 2/3(63.1%) of the cases. We suggestthat both thesetests shouldbe used for the diagnosticwork-up ofthese patients.(l) bwin RS et al. Chest 1998; 114~133-8(2) Irwin RS et al. Am I Gastmenteml 1999;94:3095-98.
INFLUBNCE OF UDC-ENRICHED DiET ON TUMOR GROWTH IN TRANSGENIC MICE HYPEREXPRBSSING HBV X PROTEIN Michclc Bamnel, Roberta Lad&J, PasqualeBerlocoZ, Maria Lucia Camso3,Anna Maria Valentini3, Eugenio Maioranc4, Antonia Peed, A&do Di Leo2, Antonio Francavillal. IDepartment of Emergencyand Organ Transplantation(D.E.T.O.), Dir. Prof. A. Fmncavilla,and Inst. of Pathology,Univ. ofBai, Italy; Lab. of 2Biochemistry and 3Patbology,IRCSS “S. De Bellis”, CastelImaGmtte, Bai, Italy. policlinico bari Background: Tmsgmic mice containingHBV-DNA scquaces Wdi,,8 for HBV X protein, spataneously developcbmnic active hepatitisassc&ted to active pmlifcraton. Tbis chronic insult represent?aprecancemuscondition as demonstratedby tbc fact that they constantly develop nmplastic lesionsin the liver witbin the 16th-18thmonth of life. We haveprwiouly demonstrated thatthe adminiseationof UDC-auiched diet is able to inmase hepatocytepmlifaation and therefarecould potent& tumour developmentin Thea animals.Goal of the study: To define if the adnhhation of UDC-enriched diet canmodify timiog andmagnitude of tumour devclopementm tmsgenic mice.Methods: Star& two months after bbtb, 22 male tmnsgenic mice wae divided in 2 sups fed on standardand a O.Z%UDCaricbed diet mspec+ivcly.In both groups, 6 mice at the ageof titleen months and 5 at the age of sevmteenmonths were sacrificed. The cxcisscd liver was weighted,fixed, paraflin embcbbed,and cut in I-2mm thin consecutive slices from which 4mm sections were obtainedand stainedwith citber H-E or PAS or Gomori. Necmsis imd inflammation were scored using s semiquaaitativc methcd (G= absent, I=focal alterations,2= difise alterations). Results: At the time of sacrifice animalswere neithercacbectic nor as&c. and no sitificcant variation of body wei8btwas observedbetweencontrols andIJDC groups: Treat&t Liver weight Nmsis Irdhmdon % ofmice Montbddiet with tumours 13/st 2.4+1.0 O.Iao.4 0.33zto.5 33% l3NDC 3.1M.7’ 1.oko.9 0.83a.4 100%** 15,st 2.8+l.O 1.2wO.4 1.4&1.l 40% wlJDc 4.c&0.3** I&O.7 1.4tio.5 IO+??** Statisticalanalysis: T-test, cZ test (‘pcO.05 **p<0.001). Conclusions:UDC-emichcd diet si&icantly augmentedtumor developmentwithout causingany signiecsrd increaseof necmintlammatoydamage.Futhu studies am in progress to establishif our findings arerelatedto the ability of UDC to further stimulateliver cell proliferation.
Al5
33 IS IT POSSIBLE TO REDUCE COSTS OF THE DL4GNOSTIC ALGORITHM OF GASTROESOPHAGEAL REFLUX DISEASE (GERD)? THE ROLE OF CONVENTIONAL HISTOLOGY Di StefanoM, Missanclli A, Luinetti 0, Alvisi C, Veneto G, Sol&E, Corazza GR. Gastmenterology andPathologyUnits, IRCCS “S.Matteo” Hospital, Univemity of Pavia,Italy. Policlinico S.Matten Background & Aims: Tbe absenceof endoscopicesopbagitisdoes not exclude GERD, as only up to half of patientswith typical reflex symptoms show this alteration.In the absolce of erosions,Non Erosive Reflex Disease(NERD) may be present andadditional investigationsmust be performed, such as 24-hour ambulatcnypH monitorinp. However, the sensitivity of this test is not satisfactory, andthere is a risk that useful indications may not be obtained.Tbe aim of this study was to evaluate how many 24-hour ambulatory pH monitoring we could have saved if, during upper endoscopy,the fust choice investigation esophagealhistology, bad beenperformed in patientswith NERD Patients& Methods: Twenty consecutive patients(7 females,mean age449yrs, range 31-63) with typical nflux symptoms, such as heartburn andregurgitation severa time a week anda nonml appearanceof the distal esophagusat upper endoswpy took part in the study. In all of them, 2 biopsy specimens3 cm abovethe gzstmesopbagcaljunction were collected andprocessed for conventionalhistology Tbc presenceof esophagi& was defined by the presenceof basalcell hyperplasia>15% of tie total epithelium, increazd papillary Ier@b >66% of the squamous epithelium,infiltration by polymnphonuclear cells and/or wsinopbils andintercellular space dilation. On a separateday, a two-channel, 24-hour ambulatmy pH monitoring test was pafomxd The test was consideredpositive if one oftbe following criteria was present: with respect to total time of recording, total acid exposurehigher than 4.2%, acid exposure in supineposition bigber than 1.2% andacid exposurein erect position higher than 6.3%. DeMeester score higher than 18. Results:In l6/20 patient (80%) histology was indicative of esophagitis.The patientswith normal histolom’ showed a 24-hour ambulatoryOH monitorirx indicative of oatboloeic reflu. On the cons, 24-hour ambulatorypH moni&ing was posiiivc in 13120patients (165%).All the seven patientswith normal pH monitoring showed apositive histology. Conclusions: In NERD Datients histology may addus&d diagnosticticnmati& and 24.hour &bulatory pH monitoring can often beavoided.
35 INCIDENCE OF ~53 GENE MUTATIONS IN 93 CONSECUTIVE LONG-SEGMENT BARRETT’S PATIENTS. A. Rcpici, L. Dughem,E. Battaglia, A. S&IO, C. Barletti, C. De Angelis, A. Musso, M. Navino, S. Camma, S. Pagmin, M. Rizmtto, G. Saracw. Dept of Gashnentemlogy,Molinette Hospital, Torino molinette Backgmundand Aims: BarrettOfs esophaausis a Iota-term comulication of esouhaEealreflex that can p&ress to adenocarcinoma.Se&al &tic andfigsutalalt&tions have b&n b&stigated in order to identify a marker that can predict the risk of mali8nmt progression. Tbe am of tbe present study was to evaluatethe incidenceof p53 mutationsin p&cnui with long-segmentBamtt without cancer. PatientsandMethods: 93 consecutive patientswith histologically pi-ovenBaren q fs esophaguslonger than2 cm were enrolledinto the study. Biopsy specimenswere obtainedwith a Jumbo forceps andwere taken one for eachquadrantevery 2 cm. One specimen for each2 cm level was analyzedfor ~53 mutations.Mutation in pS3 Emus 5 to 9 were de&ted by polymemse chain reaction-sizzle-strand umformation wlvmombisms @CR-SSCPlandcontinned bv direct DNA sequencing.-Results:Among tie 93 ,&ds, i2 w&male and2i female with a “&a ageof 61. I year (range37.84). BanettOfs length was between2 and 3 cm in 46/93 pts (49.5%), between3 and 5 cm in 30/93 pts (31.2%) andlonger than 5 cm in 17193(18.3%). At histology 7/93pts had an indeterminatedysplasia,l2/93 a low gndc dysplasia, 4 an high grade dysplasiawithout endoscopic evidenceof well debed massesor lesions.Three mutationswere detectedin the 93 pts studied (3.2%). All thesewere missense(PISIT PmOTreo, M246Y Met 0” Tyr and P.248GArgo” Gly), andwere detectedin 2 patientswith bigb gradedysplasiaand in onepatientwith low &e dysplasia ~53 mutationswere detectedsignificantly mom fixquently in high gradedysplasia(50%) than in low gradedysplasia (8%) andno dysplasia (0%) (P
34 DIAGNOSIS OF CHRONIC COUGH DUE TO G-O REFLUX: DUAL PROBE OESOPHAGEAL pH-METRY YSPPI TEST, R. Cappiello, S. Ghersi, A. Zanasi*, U. Caliceti , F. Tomesan,C. Cavoli, F. Baldi, E. Roda. Service of Gashventemlogy, *of Pneumology, of ENT. S.Orsola-MalpigbiHospital, Bologna s. Orsola G-O reflux has beenshown to be the most fceeeuent cause.after asthmaandwst-nasal drin of chronic persistentcough (CPC) (I). Fur&m&e, CPC may be the only cl& manifestati~ in 10to 35% of GORD patients.Both thepH monitoring of proximal oesopbagusand a short course with high doseof anti-secretmy drugs (PPI test) have beenpmposcd for tbc diagnostic work-up of these patients(2). However, their diagnosticefficacy hasnot yet beemwell established. MATERIAL AND METHODS: 19 patients(I7 F, mean age57.8 range42-74) with CPC (daily episodesof cough lastingfrom at least 3 months) astheir main symptom, not dueto ENT and/or respiratory diseases,were studied.AtIer a clinic evduation with 61,assessmentof the freq,,ency and severity of CPC andof the presenceof oesophsgealsymptoms (heartburn, dyspbagia,regurgitation), all the patientsunderwent a dual probe 24-esophagealOH-metry (the distal eloctmde was wsitioned 5 cm abovethe LES andthe pmtial one 2-S cm under UBSj id a therapeutictrial with PPI at a double daily dosagefor four weeks. A visual anlogue scale(O-IO) was usedto evaluatethe outcomeof trial @ositive iftbc post-timmt valueWBS0 or if the difference pmpost was 5). RESULTS: oesophagealsymptoms were found in 8119pts. (42.1%)).A pathologicGOR (%T==4, ti.74 in distal aesophagusan&r xl.5 in proximal cesopbagus)was documentedin 13119pts. (68.4%) and in 618pts. with associatedcesophagealsymptoms (75%). only I l/l9 pts.(57.9%)repmtcd the presenceof co@ during the 24 h pa-m&y; of them 8 showed a positive SymptomIndex (S.I.) (>50% and >30%, respectively in distal andpmximal oesopbagus).PPItest was positive in 8/l9 pts (42.1%). In particular it was positive in 318ptxwitb ocsopbagcalsymptoms (37.5%) and in 6/13 pts (46.1%) with pathologicGOR.CONCLUSIONS:tbe results of our study show that tbc establishmentof a casualLinLbetweenG-O mflux and CPC still representsa difficult task since it doesnot seemta exist a direct r&tionsbip betweenthe presenceof G-O reflex and the outcomeof the therapeutictest with potentanti-secretory dmgs.However, with the combineduse of PPI test andof S.I.dming pH-metry, an aesopbagealorigin of the cough was establishedin about 2/3(63.1%) of the cases. We suggestthat both thesetests shouldbe used for the diagnosticwork-up ofthese patients.(l) bwin RS et al. Chest 1998; 114~133-8(2) Irwin RS et al. Am I Gastmenteml 1999;94:3095-98.
INFLUBNCE OF UDC-ENRICHED DiET ON TUMOR GROWTH IN TRANSGENIC MICE HYPEREXPRBSSING HBV X PROTEIN Michclc Bamnel, Roberta Lad&J, PasqualeBerlocoZ, Maria Lucia Camso3,Anna Maria Valentini3, Eugenio Maioranc4, Antonia Peed, A&do Di Leo2, Antonio Francavillal. IDepartment of Emergencyand Organ Transplantation(D.E.T.O.), Dir. Prof. A. Fmncavilla,and Inst. of Pathology,Univ. ofBai, Italy; Lab. of 2Biochemistry and 3Patbology,IRCSS “S. De Bellis”, CastelImaGmtte, Bai, Italy. policlinico bari Background: Tmsgmic mice containingHBV-DNA scquaces Wdi,,8 for HBV X protein, spataneously developcbmnic active hepatitisassc&ted to active pmlifcraton. Tbis chronic insult represent?aprecancemuscondition as demonstratedby tbc fact that they constantly develop nmplastic lesionsin the liver witbin the 16th-18thmonth of life. We haveprwiouly demonstrated thatthe adminiseationof UDC-auiched diet is able to inmase hepatocytepmlifaation and therefarecould potent& tumour developmentin Thea animals.Goal of the study: To define if the adnhhation of UDC-enriched diet canmodify timiog andmagnitude of tumour devclopementm tmsgenic mice.Methods: Star& two months after bbtb, 22 male tmnsgenic mice wae divided in 2 sups fed on standardand a O.Z%UDCaricbed diet mspec+ivcly.In both groups, 6 mice at the ageof titleen months and 5 at the age of sevmteenmonths were sacrificed. The cxcisscd liver was weighted,fixed, paraflin embcbbed,and cut in I-2mm thin consecutive slices from which 4mm sections were obtainedand stainedwith citber H-E or PAS or Gomori. Necmsis imd inflammation were scored using s semiquaaitativc methcd (G= absent, I=focal alterations,2= difise alterations). Results: At the time of sacrifice animalswere neithercacbectic nor as&c. and no sitificcant variation of body wei8btwas observedbetweencontrols andIJDC groups: Treat&t Liver weight Nmsis Irdhmdon % ofmice Montbddiet with tumours 13/st 2.4+1.0 O.Iao.4 0.33zto.5 33% l3NDC 3.1M.7’ 1.oko.9 0.83a.4 100%** 15,st 2.8+l.O 1.2wO.4 1.4&1.l 40% wlJDc 4.c&0.3** I&O.7 1.4tio.5 IO+??** Statisticalanalysis: T-test, cZ test (‘pcO.05 **p<0.001). Conclusions:UDC-emichcd diet si&icantly augmentedtumor developmentwithout causingany signiecsrd increaseof necmintlammatoydamage.Futhu studies am in progress to establishif our findings arerelatedto the ability of UDC to further stimulateliver cell proliferation.
Al5