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April 2000 AGAA753 4061 MOLECULAR EPIDEMIOLOGY AMONG PALESTINIANS, ASH- KENAZI AND SEPHARDIC JEWS WITH COLORECTAL CAN- CER (CRC), Hisham Darwish, Maher Zugheir, Leonor E. Trejo, Meital Shaked, Hanina Hibshoosh, Baruch Stern, Menahem Moskowitz, Jacob Rattan, Zamir Halpern, Nadir Arber, Al-Quds Univ, Jerusalem, Israel; Tel-Aviv Med Ctr, Tel-Aviv, Israel; Columbia Univ, New-York, NY. Background:While Jews and Arabs have a common genetic and geographic origin, the Israeli Cancer Registry figures revealed that CRC is twice as common in Israelis of European (Ashkenazi) origin than in Non- European (Sephardic) origin, and 5 times than that of Palestinians. Aim:To evaluate and compare differences in the molecular genetics of high risk (Ashkenazi Jews), intermediate risk (Sephardic Jews) and low risk (Palestinians) groups for CRC. Patients and Methods: The 1995-6 records from the Tel-Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified 25 patients in each ethenic group. Epidemiology data was ob- 4060 INFLAMMATION AND INTESTINAL METAPLASIA OF GAS- TRIC CARDIA : HEUCOBACTER PYLORI OR GASTROESOPH- AGEAL REFLUX DISEASE (GERD)? Justin C. Wu, Joseph J. Sung, Francis K. Chan, Minnie Y. Go, Kf To, Teresa K. Cheung, Alex Kw Ng, Alex Cw Lai, Simon Kh Wong, Sc Sydney Chung, Dept of Medicine, The Chinese Univ of Hong Kong, Hong Kong, Hong Kong; Dept of Pathology, The Chinese Univ of Hong Kong, Hong Kong, Hong Kong; Dept of Surg, The Chinese Univ of Hong Kong, Hong Kong, Hong Kong. BACKGROUND. The etiology of intestinal metaplasia (CIM) and inflam- mation (carditis) of cardia has been a subject of dispute. AIM. To study the relationship between (I) CIM and (2) carditis with Hp and GERD. METH- ODS. Consecutive GERD patients (with weekly reflux symptoms and/or erosive esophagitis) and non-reflux! non-ulcer controls undergoing upper endoscopic examinations were studied. Patients with previous gastric sur- gery, Hp eradication, use of PPI and NSAID were excluded. Two biopsies were obtained from antrum, corpus, cardia (defined as Icm within esopha- gogastric junction (EGJ») and distal esophagus (2 em above EGJ). Speci- mens were stained by H&E, Giemsa and PAS/Alcian blue at pH 2.5 for assessment of gastritis and 1M using updated Sydney classification and reflux esophagitis by a single pathologist blinded to the diagnosis. Hp was diagnosed by biopsy urease test. CagA status of Hp+ patients was deter- mined by Western blot. Esophageal manometry and pH-metry were per- formed for GERD patients. RESULTS. 400 Chinese patients were studied. (I) CIM was found in 25 (6.25%) patients. CIM+ patients were associated with older age (62.3:': 13.4 yrs Vs 53.3:': 14.7 yrs, P=0.05), higher preva- lence of Hp (80% Vs 50.4%, P=0.OO4) and lower prevalence of GERD (12% Vs 50.7%, P<O.OOI).Barrett's esophagus was found in 3.6% (7/193) of GERD patients and none of them had associated CIM or Hp infection. (2) Carditis was found in 198 (49.5%) patients and 178 (88%) of them were Hp+. It was associated with antral gastritis and was more severe in cagA + Hp infected patients (median score: 2.5 Vs 1.5, P=O.OI). There was no correlation between carditis with DeMeester score (P=0.23), histological (P=0.85) or endoscopic esophagitis (P=0.64). Multivariate analysis showed that Hp infection was an independent predictor for both carditis (P=0.02) and CIM (P=O.OOI). Advanced age was positively correlated (P=O.04) and GERD negatively correlated (P=0.02) for CIM. CONCLU· SIONS. Hp infection is associated with both carditis and CIM. GERD is negatively associated with CIM and did not correlate with carditis. No. of patients Carditis CIM Hp+ GERD 88 70 (80%) 3(3.4%) Hp+ control 110 104(95%) 17(155%) Hp-GERD 105 18(17%) 0(0%) Hp- control 97 6(6%) 5(5.2%) tained from interviewing the patients and their hospital charts. The levels of cyclin DI, f3-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. Results:There were no statistical differences in the expression of p53 (around 80%), f3-catenine (30%)and Her-2/neu (30%) among the 3 groups. There was a statistically significant correlation between the expression of f3-catenine and cyclin Dl (p<0.05). Conclusions: Ashkenazi Jews have the highest rate of CRC, yet they have the best 5yr survival rate. The Sephardic Jews are diagnosed at a more advanced stage, the tumors are PD and they lack p27. Palestinians have significantly higher cyclin D I levels. This can explain the reason for the lower mortality rate among Ashekanazi Jews. Comparison between Ashkenazi Jews Sephradic Jews and Palestinians Parameters Ashekanazi Sephardic Palestinian M/F 45% /55% 53% /47% 59%/41% Age 68±16 67±17 62±1 Grade' (PDIWD) 68% /32% 0/100% 62%/38% Smoking- 37% 45% 55% Duke A&BlC&D 72%/28% 50%/50% 67%/33% 5yrsurvival' 70% 47% 40% p2T 75% 33% 67% CyclinDf 25% 33% 57% p<0.05 PD· differentiated- WD·well differentiated 4062 ROLE OF HEPATOTROPIC VIRUSES IN THE DEVELOPMENT OF LYMPHOPROLIFERATIVE DISORDERS IN ORGAN TRANS- PLANT RECIPIENT, Andrea Buda, Alida Caforio, Fiorella Calabrese, Savina Aversa, Sara Pevere, Stefano Fagiuoli, Antonio Gambino, Umberto Cillo, Marial.uisa Valente, Patrizia Burra, Gastroenterological and Surg Sci Dept, Padova, Italy; Cardiology, Padova, Italy; CV Pathology, Padova, Italy; Oncology, Padova, Italy; Surg and Gastroenterological Sci Dept, Padova, Italy; CV Surg, Padova, Italy. Post transplant Iymphoproliferative disorder (PTLD), typically presenting as non-Hodgkin lymphoma, is a well documented complication following organ transplantation. Epstein Barr Virus (EBV) infection and/or riactiva- tion is considered the main risk factor for the development of PTLD. The association between HCV infection and B-cell NHL has been reported both in patients with HCV-related essential mixed cryoglobulinemia (EMC) and in patients without EMC ("idiopathic" NHL) in general population. Aim of this study was to investigate the possible relationship between HCV infection and the occurrence of PTLD in a population of liver and heart transplant recipients. 693 adult transplanted patients with at least 1 month of follow up were studied. Serum samples from all patients were screened for HCV infection. Anti-HCV antibodies were assessed by a third gener- ation enzyme-linked immuno-assay (ELISA II-III). Qualitative HCV-RNA was assessed by nested-R'I' PCR (5 UTR primer). EBV genome was assessed by PCR within lymphoma tissue in patients with PTLD. Eleven (1.6%) patients (mean age 52.3; range 18-69 years)developed PTLD during the follow up. PTLD's were as follows:small and large bowel in 6, cervical nodes in 3,larynx in I, thigh in I, lung in 1 patient.PTLD patients were aged 52.3 years (range 18-69), with a mean post-transplant interval of 43.4 months (range 4-79) at disease onset. Histological diagnosis was B-cell NHL, high grade in 10 and low grade in one. Cryoglobulinemia was negative in all PTLD's patients. A significant higher proportion of anti- HCVIHCV-RNA positive patients (4/85=4.7%) developed lymphoma compared to those (7/608= 1.1%) who were negative (p=0.014). Epstein Barr virus (EBV) genome was assessed in 9 patients and was positive in 6 of them. Two out of 3 EBV negative patients were anti-HCVIHCV-RNA positive. EBV remains the most important etiologic factor for the onset of PTLD. The role of HCV infection should be considered, especially in cases in which EBV cannot be found.

Inflammation and intestinal metaplasia of gastric cardia : Helicobacter pylori or gastroesophageal reflux disease (GERD)?

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April 2000 AGAA753

4061MOLECULAR EPIDEMIOLOGY AMONG PALESTINIANS, ASH­KENAZI AND SEPHARDIC JEWS WITH COLORECTAL CAN­CER (CRC),Hisham Darwish, Maher Zugheir, Leonor E. Trejo, Meital Shaked, HaninaHibshoosh, Baruch Stern, Menahem Moskowitz, Jacob Rattan, ZamirHalpern, Nadir Arber, Al-Quds Univ, Jerusalem, Israel; Tel-Aviv Med Ctr,Tel-Aviv, Israel; Columbia Univ, New-York, NY.

Background:While Jews and Arabs have a common genetic and geographicorigin, the Israeli Cancer Registry figures revealed that CRC is twice ascommon in Israelis of European (Ashkenazi) origin than in Non- European(Sephardic) origin, and 5 times than that of Palestinians. Aim:To evaluateand compare differences in the molecular genetics of high risk (AshkenaziJews), intermediate risk (Sephardic Jews) and low risk (Palestinians)groups for CRC. Patients and Methods: The 1995-6 records from theTel-Aviv Medical Center and Muqased hospital (East Jerusalem) randomlyidentified 25 patients in each ethenic group. Epidemiology data was ob-

4060INFLAMMATION AND INTESTINAL METAPLASIA OF GAS­TRIC CARDIA : HEUCOBACTER PYLORI OR GASTROESOPH­AGEAL REFLUX DISEASE (GERD)?Justin C. Wu, Joseph J. Sung, Francis K. Chan, Minnie Y. Go, Kf To,Teresa K. Cheung, Alex Kw Ng, Alex Cw Lai, Simon Kh Wong, ScSydney Chung, Dept of Medicine, The Chinese Univ of Hong Kong, HongKong, Hong Kong; Dept of Pathology, The Chinese Univ of Hong Kong,Hong Kong, Hong Kong; Dept of Surg, The Chinese Univ of Hong Kong,Hong Kong, Hong Kong.

BACKGROUND. The etiology of intestinal metaplasia (CIM) and inflam­mation (carditis) of cardia has been a subject of dispute. AIM. To study therelationship between (I) CIM and (2) carditis with Hp and GERD. METH­ODS. Consecutive GERD patients (with weekly reflux symptoms and/orerosive esophagitis) and non-reflux! non-ulcer controls undergoing upperendoscopic examinations were studied. Patients with previous gastric sur­gery, Hp eradication, use of PPI and NSAID were excluded. Two biopsieswere obtained from antrum, corpus, cardia (defined as Icm within esopha­gogastric junction (EGJ») and distal esophagus (2 em above EGJ). Speci­mens were stained by H&E, Giemsa and PAS/Alcian blue at pH 2.5 forassessment of gastritis and 1M using updated Sydney classification andreflux esophagitis by a single pathologist blinded to the diagnosis. Hp wasdiagnosed by biopsy urease test. CagA status of Hp+ patients was deter­mined by Western blot. Esophageal manometry and pH-metry were per­formed for GERD patients. RESULTS. 400 Chinese patients were studied.(I) CIM was found in 25 (6.25%) patients. CIM+ patients were associatedwith older age (62.3:': 13.4 yrs Vs 53.3:': 14.7 yrs, P=0.05), higher preva­lence of Hp (80% Vs 50.4%, P=0.OO4) and lower prevalence of GERD(12% Vs 50.7%, P<O.OOI).Barrett's esophagus was found in 3.6% (7/193)of GERD patients and none of them had associated CIM or Hp infection.(2) Carditis was found in 198 (49.5%) patients and 178 (88%) of them wereHp+. It was associated with antral gastritis and was more severe in cagA +Hp infected patients (median score: 2.5 Vs 1.5, P=O.OI). There was nocorrelation between carditis with DeMeester score (P=0.23), histological(P=0.85) or endoscopic esophagitis (P=0.64). Multivariate analysisshowed that Hp infection was an independent predictor for both carditis(P=0.02) and CIM (P=O.OOI). Advanced age was positively correlated(P=O.04) and GERD negatively correlated (P=0.02) for CIM. CONCLU·SIONS. Hp infection is associated with both carditis and CIM. GERD isnegatively associated with CIM and did not correlate with carditis.

No. ofpatientsCarditisCIM

Hp+ GERD

8870 (80%)3(3.4%)

Hp+ control

110104(95%)17(155%)

Hp-GERD

10518(17%)0(0%)

Hp- control

976(6%)

5(5.2%)

tained from interviewing the patients and their hospital charts. The levelsof cyclin DI, f3-catenine, p27, p53, Ki-67 and Her-2/neu proteins weredetermined by immunohistochemistry. Results:There were no statisticaldifferences in the expression of p53 (around 80%), f3-catenine (30%)andHer-2/neu (30%) among the 3 groups. There was a statistically significantcorrelation between the expression of f3-catenine and cyclin Dl (p<0.05).Conclusions: Ashkenazi Jews have the highest rate of CRC, yet they havethe best 5yr survival rate. The Sephardic Jews are diagnosed at a moreadvanced stage, the tumors are PD and they lack p27. Palestinians havesignificantly higher cyclin D I levels. This can explain the reason for thelower mortality rate among Ashekanazi Jews.

Comparison between Ashkenazi Jews Sephradic Jews and Palestinians

Parameters Ashekanazi Sephardic Palestinian

M/F 45% /55% 53% /47% 59%/41%Age 68±16 67±17 62±1

Grade' (PDIWD) 68% /32% 0/100% 62%/38%Smoking- 37% 45% 55%

Duke A&BlC&D 72%/28% 50%/50% 67%/33%5yrsurvival' 70% 47% 40%

p2T 75% 33% 67%CyclinDf 25% 33% 57%

p<0.05 PD·differentiated- WD·well differentiated

4062ROLE OF HEPATOTROPIC VIRUSES IN THE DEVELOPMENTOF LYMPHOPROLIFERATIVE DISORDERS IN ORGAN TRANS­PLANT RECIPIENT,Andrea Buda, Alida Caforio, Fiorella Calabrese, Savina Aversa, SaraPevere, Stefano Fagiuoli, Antonio Gambino, Umberto Cillo, Marial.uisaValente, Patrizia Burra, Gastroenterological and Surg Sci Dept, Padova,Italy; Cardiology, Padova, Italy; CV Pathology, Padova, Italy; Oncology,Padova, Italy; Surg and Gastroenterological Sci Dept, Padova, Italy; CVSurg, Padova, Italy.

Post transplant Iymphoproliferative disorder (PTLD), typically presentingas non-Hodgkin lymphoma, is a well documented complication followingorgan transplantation. Epstein Barr Virus (EBV) infection and/or riactiva­tion is considered the main risk factor for the development of PTLD. Theassociation between HCV infection and B-cell NHL has been reported bothin patients with HCV-related essential mixed cryoglobulinemia (EMC) andin patients without EMC ("idiopathic" NHL) in general population. Aim ofthis study was to investigate the possible relationship between HCVinfection and the occurrence of PTLD in a population of liver and hearttransplant recipients. 693 adult transplanted patients with at least 1 monthof follow up were studied. Serum samples from all patients were screenedfor HCV infection. Anti-HCV antibodies were assessed by a third gener­ation enzyme-linked immuno-assay (ELISA II-III). Qualitative HCV-RNAwas assessed by nested-R'I' PCR (5 UTR primer). EBV genome wasassessed by PCR within lymphoma tissue in patients with PTLD. Eleven(1.6%) patients (mean age 52.3; range 18-69 years)developed PTLD duringthe follow up. PTLD's were as follows:small and large bowel in 6, cervicalnodes in 3,larynx in I, thigh in I, lung in 1 patient.PTLD patients wereaged 52.3 years (range 18-69), with a mean post-transplant interval of 43.4months (range 4-79) at disease onset. Histological diagnosis was B-cellNHL, high grade in 10 and low grade in one. Cryoglobulinemia wasnegative in all PTLD's patients. A significant higher proportion of anti­HCVIHCV-RNA positive patients (4/85=4.7%) developed lymphomacompared to those (7/608= 1.1%) who were negative (p=0.014). EpsteinBarr virus (EBV) genome was assessed in 9 patients and was positive in 6of them. Two out of 3 EBV negative patients were anti-HCVIHCV-RNApositive. EBV remains the most important etiologic factor for the onset ofPTLD. The role of HCV infection should be considered, especially in casesin which EBV cannot be found.