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Mucosal expression of CDK cell cycle activators in patients with H. pylori-positive or H. pylori-negative chronic gastritis
Abstracts
17 PROGNOSTIC FACTORS FOR RESPONSETO ANTIBIOTIC THERAPY OF LOW-GRADE GASTRIC MALT LWHOMA: THE IMPORTANCE OF TNM STAGING BY ENDOSCOPlC ULTRASONOGRAPHY P. Fusamli, E. Bwtini, F. Parente,T. Federic,,S. Peyre, G. Banamo, C. De Angelis, P. Bmsolo, S. Amplatz, E. Mani, V. Napcditano,A. Tempesta,M. Oppezzi, A. Pisam,M. Schiavo,T. Togham, G. Caletti. Dept. ofGastmenterology, Univers,ty of Bologna, Bologw+ Italy. Universitl Bologna Backgmund.Endoscopic ultrasonography(EUS) 1sa very accurate techniquefor the stagingof eastic Ivmphoma.Althowh cure of Helicobacta pylori (HP) infection has given good remission ktes in he’low-gmde gas& mucosa-asociated IGphoid &sue (MALT) Iymphomapatients,it remainsunclearwhich patients standto benefit fmm front-line tie&nerd with antibiotics.An it&an multicenterstudy amlyzed the relation&p betweenIymphomaEUS stagingand remissionrates after antibiotic therapy. Methods. 51 patientsaffectedby gastric Iymphomawere emoIled; everyone underwentupperG.I. endoscopy,rapid weax Hp test, histology and immunohistochemistryon endoscopicbiopsies,gastric endoscopicultrasanogsaphy(EUS), tomcc-abdominalCT scan,bone marrow citology. All patientshadM Hp-relatedlow-grade gastric MALT lymphoma;they were treatedfor Ho infection with UDto two reximens of antibiotics.All patientswere monitoredby cndoscopy, &tology, immmmbistochem&ry andEUS during the &a 24-months follow-up. Results.All 51 patientswere in stageTl or TZ, NO or Nl, MO; completeMALT lymphoma remissionwas observedin 31 (61%) patientswith a median time required to achieve histologic regressionof 6 months(range, l-14 months). Analyzing thesedataaccmding to EUS-TNM stages, we pointed out thathealing was obtained in 13 out of I6 (81%) patientsin Tlm NO stage;only 12 out of 19(63%) patients inTlsm NO stagehealed,while only 6 out of 16(38%) patientsm more advancedstages(TZ or Nl) achtcved remission. Three afthese 31 (10%) healed patientswere still positive for Hp at the endof the antibiotic heatmentandother 3 out of 31 (10%) had a local relapse within the frst 20 months.Conclusions.EUS is a fundamentaltechniqueto get a precise TNM stagingof HP-relatedlow-g&e gastic MALT lymphomas:patientssuffering from lymphomas limited to the mucosa andwithout enlargedregionallymph nodesseemto be thebest candidatesfor cure with the antibiotics alone. In follow-up also, BUS can play a pivotal role for the evaluationof long-term completeremission or early detectionof relapses.
19 LONG-TERM FOLLOW-UP IN HELICOBACTER PYLORI (HP) STILL INFECTED AND ERADICATED ASYMPTOMATIC DONORS Rtcci C, Vaim D, RuggeM, Russo V, Lemdm G, Menegatti M, Gatta L, Miglioli M. Dept of InternalMedicine & Gastmentemlogy,Bologna, Histopatbolagy Unit Padova,lRCCS Castellana Grotte, (BA), Italy
s. O”ola Aim: to determmethe outcomeofpersIstent HP infection in &symptomaticpopulation compared to subjectswith successful eradicationover a IO year time frame.Methods: During 2OC0,after a mean follow-up of 8.5years, from an initial endoscopy (range 85-l 12 mts), all the 276 donors originally cndoscoped1990191,were sentpostal invitatmn and 188wreed to be intaviewed by the same valid& symptomatic questio&aire. Three donors died when the family was interviewed (two colon cancers,one m&w&al infarction). 71 wem not awnme available;17 retied the interview, 13 donors refusedto undergo endoscopyau& Bnally, 20 donors developedupper gastrointestinal symptoms during the follow-up period and thereforeunderwentcndoscopy becauseof symptoms. The rem&tine 152 (65%) donors who acceptedto be m-em&coped were compktel~ asymptomatic in 2000.Five&t oil52 &e excluded be&se were foundto be HP negative‘m 2&, despiteof a positive tindings in 1991(spontaneuoseradication7 assumptionof antibiotics?). Of remaining 147 donors, 93 had acceptedto be n-endoscoped in 1990/91andat that time 50 were found to be still infectedand 43 eradicated.These 93 donors representthe object of the presentstudy. At endoscopy HP statuswas assessedby biopsiestaken for histology, urea& test and &me (a&m + corpus+an8ulus).HP infection was defined when culture or at least two tests were positive. All the 93 donors underwent a 13C-UreaBreath Test fI3C-UBTl andstool test fHoSA). Semm fastinn PgI, II, theu ratio andgasbin were evaluated.I&Its: O&all 43193b&d &a& bad success~l eradication.Intestinalmet&,&x develop& in the Bnhum of 17/50patients(34%) of HP oositive patientscomparedto 5143(12%) wrth s&esstid eradicationof HP..UIcem de&ped in s HP positive donors (16%, 7 duodenal,1 gastric) and 1 in HP negativedonors (2%) with an the odds ratlo of4.7 195%CI 1.19-18.521.Fo, HP+ve blood donors the odds ratio for IM was 3.4 (95% CI 1.31-8 84). i7 HP+ve blood dot&s with IM, 12 (70.5%) harbared CagA+ strains. For CagA+ve blood donors the odds ratio for IM was 15.1(95% CI 2.14-107.15).Conclusions: 1. Over a prolonged follow-up periodHP+ve asymptomaticblood donors had a 3.4 fold increasedodds of developing,IM. 2. CagA+ve strains were associatedwith a 15.1fold increasedodds of IM 3. HP+v;blwd donors iad a 1.SYdyear risk of developingulcers. 4. These results support the need for emdxation in asymptomatic subjects.
18 ESOPHAGEAL EXPRESSION OF THE RECEPTOWLIGAND SYSTEM (c-KIT/SCF) IN BARRETT’S ESOPHAGUSAND ESOPHAGITIS IS ASSOCIATED WITH ACID REFLUX E.Battaglia,L.Dugherq ‘A. Repici, M.Navino, G.Buonafede,D.Tibaudi, l G.Samcco,G.Bellone, l M.Rizetto, “P.R.Mioli, G.Bassotti, G.Emanuelli. Dpt FisiopatologiaClinica, *opt Ma&tie dell’AppamtoDigeremte,“Cbimrgia d’UrgenzaA.S.O. San Giovanni Bat&a di Torino; Laboratorio di m&it& Dpt Gastmentemlogiaed Epatologia, Pen@, Italy. A.S.O. S. Giovanni Bat&a Gasmx.mphagcal actd retlux is the main causeofBarrett’s Esophagus(BE).Tbe BE speaalized epithehm has heenlinked to increasedrisk of esophagealadenocarcinomaand that can be related to specific geneticabnommlitiesinvolving oncogenesandtumor suppressor genes.Recent studies demonakat~ that deregulatedexprasion of mccptorfigand system (c-kitiSCF) could be presentm various hutmum,including gastrointestinalneoplasiaandthat could be associatedwith malignant evolution in patientswith BE. The AEvl of this study is to evaluatethe expression of c-kit/SCF expression in oewphageal mucosafrom BE or csophagitispatientsin order to establishthepossible correlation with acid reflex. MATHBRLU AND METHODS. We have analysedocsophageal specimensfmm 44 patientswith bistologicai diagnosisof BE.18 patientswith gradeU-III esophagitisaccording to Sway classification and 25 patientswith normal Oesophagwandno history of GERD. All patients undewent 24-h ambulatory pH reading using an antimony electide with extental refemxe connectedto a portablepH-recorder (Medtronic, Denmark). Immunobistochemicalstaining of formalin-fixed, par&m-embedded tissue sections was performedusing specific polyclonal antib-zdiesto c-kit andSCF anddiaminobenzidine tetmbydrc&ride as chromogen.RESULTS. c-kit immmmreactivity is sigoiticantly increasedin BE andesophagitiscomparedwith controls (p
Mucosal expresstonof CDK cell cycle actwators in pattentswth H. pylmi-positive or H. pylorinegativechronic gastritis
A. Rocco,I L. Schandl.2Z.Tulassay,Z P. Malfertheiner,3M. Ebert,3 G. Bu&llon,l G. Nardonel IGastmentemlogy Unit, University ‘Federica II”, Naples, Italy 211Departmentof InternalMedicine SemmelweisUniversity, Budapest,Hungary 3Depxtment of Gastmenterology,Otto-van-Guericke-University, Magdebwg, Germany
Opt Medicim Clinica e Sperimentale Cancermay be consideredthe fina stepof a cbmmc imbalancebetweencell proliferation and apotosis. The cell cycle is a complex process contmllcd by many molecules. CDC25A and CDCZSBphohowbatasa area novel class of CDK activators involved in nxulatbm the transition from onehell &le step to another.Being overexpressedin gastric cancer~tbeae&teins are considereda pmgnostic factor. To date,little is knowt abat CDC25 pimsphataseserpmssion in the early StigcSof gastric caminogenesisaadin relation to H. pylori in&tion.‘H. pylori ii a first class gastric carcinogenthat inducescell hyperpmlifemtionand apoptosis.Aim: To investigatethe expressionof CDC25A andCDC25B phospbataseain patientswith H. pylori-positive or H. pylorinegativechronic gastritis. Methods: The study populationconsisted of 40 patients(MiF 22118: mean age50.5 yea’s) ofwhom 20 with H. pylori-positive cbmnic gastritis and 20 with H. pylonnegativechronic gastitis. CDC25A and CDC25B expnssion wa8 investigatedon gastric biopsies by immunohistochemistyand specific monocImm,lantibodies(SantaCmz Biotechnology). Results: CDC25A andCDC25B proteinswere sigaificantly ovemxpmssedin patientswith H. pylori infectioncomparedwith unintated patients(see Table). He-negative HP-positive p* N.20 N.20 CDC25 A 2(5%) 11(28%) 0.005 CDC25 B 4(10%) 14(35%) 0.003* Fisher’s exact test Conclusions:In our study the expressionof CDC25 proteins ww correlatedwith H. pylori infection. We postulatethatactivation of CDC25 phosphatasesis involved in the cascadeof H. pylori-related inflammatory events andmay play a key role in cancer development.
A5
17 PROGNOSTIC FACTORS FOR RESPONSETO ANTIBIOTIC THERAPY OF LOW-GRADE GASTRIC MALT LWHOMA: THE IMPORTANCE OF TNM STAGING BY ENDOSCOPlC ULTRASONOGRAPHY P. Fusamli, E. Bwtini, F. Parente,T. Federic,,S. Peyre, G. Banamo, C. De Angelis, P. Bmsolo, S. Amplatz, E. Mani, V. Napcditano,A. Tempesta,M. Oppezzi, A. Pisam,M. Schiavo,T. Togham, G. Caletti. Dept. ofGastmenterology, Univers,ty of Bologna, Bologw+ Italy. Universitl Bologna Backgmund.Endoscopic ultrasonography(EUS) 1sa very accurate techniquefor the stagingof eastic Ivmphoma.Althowh cure of Helicobacta pylori (HP) infection has given good remission ktes in he’low-gmde gas& mucosa-asociated IGphoid &sue (MALT) Iymphomapatients,it remainsunclearwhich patients standto benefit fmm front-line tie&nerd with antibiotics.An it&an multicenterstudy amlyzed the relation&p betweenIymphomaEUS stagingand remissionrates after antibiotic therapy. Methods. 51 patientsaffectedby gastric Iymphomawere emoIled; everyone underwentupperG.I. endoscopy,rapid weax Hp test, histology and immunohistochemistryon endoscopicbiopsies,gastric endoscopicultrasanogsaphy(EUS), tomcc-abdominalCT scan,bone marrow citology. All patientshadM Hp-relatedlow-grade gastric MALT lymphoma;they were treatedfor Ho infection with UDto two reximens of antibiotics.All patientswere monitoredby cndoscopy, &tology, immmmbistochem&ry andEUS during the &a 24-months follow-up. Results.All 51 patientswere in stageTl or TZ, NO or Nl, MO; completeMALT lymphoma remissionwas observedin 31 (61%) patientswith a median time required to achieve histologic regressionof 6 months(range, l-14 months). Analyzing thesedataaccmding to EUS-TNM stages, we pointed out thathealing was obtained in 13 out of I6 (81%) patientsin Tlm NO stage;only 12 out of 19(63%) patients inTlsm NO stagehealed,while only 6 out of 16(38%) patientsm more advancedstages(TZ or Nl) achtcved remission. Three afthese 31 (10%) healed patientswere still positive for Hp at the endof the antibiotic heatmentandother 3 out of 31 (10%) had a local relapse within the frst 20 months.Conclusions.EUS is a fundamentaltechniqueto get a precise TNM stagingof HP-relatedlow-g&e gastic MALT lymphomas:patientssuffering from lymphomas limited to the mucosa andwithout enlargedregionallymph nodesseemto be thebest candidatesfor cure with the antibiotics alone. In follow-up also, BUS can play a pivotal role for the evaluationof long-term completeremission or early detectionof relapses.
19 LONG-TERM FOLLOW-UP IN HELICOBACTER PYLORI (HP) STILL INFECTED AND ERADICATED ASYMPTOMATIC DONORS Rtcci C, Vaim D, RuggeM, Russo V, Lemdm G, Menegatti M, Gatta L, Miglioli M. Dept of InternalMedicine & Gastmentemlogy,Bologna, Histopatbolagy Unit Padova,lRCCS Castellana Grotte, (BA), Italy
s. O”ola Aim: to determmethe outcomeofpersIstent HP infection in &symptomaticpopulation compared to subjectswith successful eradicationover a IO year time frame.Methods: During 2OC0,after a mean follow-up of 8.5years, from an initial endoscopy (range 85-l 12 mts), all the 276 donors originally cndoscoped1990191,were sentpostal invitatmn and 188wreed to be intaviewed by the same valid& symptomatic questio&aire. Three donors died when the family was interviewed (two colon cancers,one m&w&al infarction). 71 wem not awnme available;17 retied the interview, 13 donors refusedto undergo endoscopyau& Bnally, 20 donors developedupper gastrointestinal symptoms during the follow-up period and thereforeunderwentcndoscopy becauseof symptoms. The rem&tine 152 (65%) donors who acceptedto be m-em&coped were compktel~ asymptomatic in 2000.Five&t oil52 &e excluded be&se were foundto be HP negative‘m 2&, despiteof a positive tindings in 1991(spontaneuoseradication7 assumptionof antibiotics?). Of remaining 147 donors, 93 had acceptedto be n-endoscoped in 1990/91andat that time 50 were found to be still infectedand 43 eradicated.These 93 donors representthe object of the presentstudy. At endoscopy HP statuswas assessedby biopsiestaken for histology, urea& test and &me (a&m + corpus+an8ulus).HP infection was defined when culture or at least two tests were positive. All the 93 donors underwent a 13C-UreaBreath Test fI3C-UBTl andstool test fHoSA). Semm fastinn PgI, II, theu ratio andgasbin were evaluated.I&Its: O&all 43193b&d &a& bad success~l eradication.Intestinalmet&,&x develop& in the Bnhum of 17/50patients(34%) of HP oositive patientscomparedto 5143(12%) wrth s&esstid eradicationof HP..UIcem de&ped in s HP positive donors (16%, 7 duodenal,1 gastric) and 1 in HP negativedonors (2%) with an the odds ratlo of4.7 195%CI 1.19-18.521.Fo, HP+ve blood donors the odds ratio for IM was 3.4 (95% CI 1.31-8 84). i7 HP+ve blood dot&s with IM, 12 (70.5%) harbared CagA+ strains. For CagA+ve blood donors the odds ratio for IM was 15.1(95% CI 2.14-107.15).Conclusions: 1. Over a prolonged follow-up periodHP+ve asymptomaticblood donors had a 3.4 fold increasedodds of developing,IM. 2. CagA+ve strains were associatedwith a 15.1fold increasedodds of IM 3. HP+v;blwd donors iad a 1.SYdyear risk of developingulcers. 4. These results support the need for emdxation in asymptomatic subjects.
18 ESOPHAGEAL EXPRESSION OF THE RECEPTOWLIGAND SYSTEM (c-KIT/SCF) IN BARRETT’S ESOPHAGUSAND ESOPHAGITIS IS ASSOCIATED WITH ACID REFLUX E.Battaglia,L.Dugherq ‘A. Repici, M.Navino, G.Buonafede,D.Tibaudi, l G.Samcco,G.Bellone, l M.Rizetto, “P.R.Mioli, G.Bassotti, G.Emanuelli. Dpt FisiopatologiaClinica, *opt Ma&tie dell’AppamtoDigeremte,“Cbimrgia d’UrgenzaA.S.O. San Giovanni Bat&a di Torino; Laboratorio di m&it& Dpt Gastmentemlogiaed Epatologia, Pen@, Italy. A.S.O. S. Giovanni Bat&a Gasmx.mphagcal actd retlux is the main causeofBarrett’s Esophagus(BE).Tbe BE speaalized epithehm has heenlinked to increasedrisk of esophagealadenocarcinomaand that can be related to specific geneticabnommlitiesinvolving oncogenesandtumor suppressor genes.Recent studies demonakat~ that deregulatedexprasion of mccptorfigand system (c-kitiSCF) could be presentm various hutmum,including gastrointestinalneoplasiaandthat could be associatedwith malignant evolution in patientswith BE. The AEvl of this study is to evaluatethe expression of c-kit/SCF expression in oewphageal mucosafrom BE or csophagitispatientsin order to establishthepossible correlation with acid reflex. MATHBRLU AND METHODS. We have analysedocsophageal specimensfmm 44 patientswith bistologicai diagnosisof BE.18 patientswith gradeU-III esophagitisaccording to Sway classification and 25 patientswith normal Oesophagwandno history of GERD. All patients undewent 24-h ambulatory pH reading using an antimony electide with extental refemxe connectedto a portablepH-recorder (Medtronic, Denmark). Immunobistochemicalstaining of formalin-fixed, par&m-embedded tissue sections was performedusing specific polyclonal antib-zdiesto c-kit andSCF anddiaminobenzidine tetmbydrc&ride as chromogen.RESULTS. c-kit immmmreactivity is sigoiticantly increasedin BE andesophagitiscomparedwith controls (p
Mucosal expresstonof CDK cell cycle actwators in pattentswth H. pylmi-positive or H. pylorinegativechronic gastritis
A. Rocco,I L. Schandl.2Z.Tulassay,Z P. Malfertheiner,3M. Ebert,3 G. Bu&llon,l G. Nardonel IGastmentemlogy Unit, University ‘Federica II”, Naples, Italy 211Departmentof InternalMedicine SemmelweisUniversity, Budapest,Hungary 3Depxtment of Gastmenterology,Otto-van-Guericke-University, Magdebwg, Germany
Opt Medicim Clinica e Sperimentale Cancermay be consideredthe fina stepof a cbmmc imbalancebetweencell proliferation and apotosis. The cell cycle is a complex process contmllcd by many molecules. CDC25A and CDCZSBphohowbatasa area novel class of CDK activators involved in nxulatbm the transition from onehell &le step to another.Being overexpressedin gastric cancer~tbeae&teins are considereda pmgnostic factor. To date,little is knowt abat CDC25 pimsphataseserpmssion in the early StigcSof gastric caminogenesisaadin relation to H. pylori in&tion.‘H. pylori ii a first class gastric carcinogenthat inducescell hyperpmlifemtionand apoptosis.Aim: To investigatethe expressionof CDC25A andCDC25B phospbataseain patientswith H. pylori-positive or H. pylorinegativechronic gastritis. Methods: The study populationconsisted of 40 patients(MiF 22118: mean age50.5 yea’s) ofwhom 20 with H. pylori-positive cbmnic gastritis and 20 with H. pylonnegativechronic gastitis. CDC25A and CDC25B expnssion wa8 investigatedon gastric biopsies by immunohistochemistyand specific monocImm,lantibodies(SantaCmz Biotechnology). Results: CDC25A andCDC25B proteinswere sigaificantly ovemxpmssedin patientswith H. pylori infectioncomparedwith unintated patients(see Table). He-negative HP-positive p* N.20 N.20 CDC25 A 2(5%) 11(28%) 0.005 CDC25 B 4(10%) 14(35%) 0.003* Fisher’s exact test Conclusions:In our study the expressionof CDC25 proteins ww correlatedwith H. pylori infection. We postulatethatactivation of CDC25 phosphatasesis involved in the cascadeof H. pylori-related inflammatory events andmay play a key role in cancer development.
A5