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Prospective Evaluation of Psychological Impact of Pancreatic CancerSurveillance in High-Risk IndividualsFemme Harinck, Tanja Nagtegaal, Irma Kluijt, Cora M. Aalfs, Ellen Smets, Jan-WernerPoley, Anja Wagner, Grace N. Sidharta, Jeanin E. van Hooft, Hendrik van Dullemen, RolfH. Sijmons, Paul Fockens, Marco J. Bruno, Eveline Bleiker

Background: The success of pancreatic cancer (PC) surveillance depends to a large extenton the commitment of participants to adhere to the repeated follow-up investigations. Thoughthe results of our recently conducted retrospective study showed that the burden of PCsurveillance is acceptable, a prospective assessment was warranted to document the mentaland psychological impact of PC screening. We aimed to investigate possible changes incancer worries and levels of anxiety and depression in high-risk individuals participatingin a PC surveillance program. Methods Eligible for this prospective questionnaire study werehigh-risk individuals participating in our multicenter nationwide endoscopic ultrasound(EUS)-MRI-based PC-surveillance study. High-risk individuals were those with a strongfamily history of PC or carriers of PC-prone gene mutations. Questionnaires, administeredboth before (pretest) and after (posttest) the baseline PC screening investigations, assessedconcerns about developing cancer (CancerWorry Scale), and levels of anxiety and depression(Hospital Anxiety and Depression scale). Results Of the 54 high-risk individuals, 47 (87%)completed both the pretest and posttest questionnaires (38% male, mean age= 52 yr., range20-74 yrs.). Of these, 44 participated in the PC screening and 3 declined. All participantsunderwent both EUS and MRI. Prior to undergoing PC screening, 36% of the participantsreported being fearful about undergoing EUS, whereas 5% was fearful about the MRI. Afterscreening, 2.3% of all participants feared the next EUS (p<.001) and 2.3% the next MRI.The mean level of depression was significantly higher prior to screening as compared toafter screening (p<.001). However, the number of participants with clinical levels of anxietyand/ or depression was low (n=5) and remained stable over time. Prior to, as well as afterscreening the most frequently reported worries were about the possibility of developingcancer themselves (29% at both time points) and the chance that relatives would developcancer (19% and 21%, respectively). The 3 individuals who did not undergo screeningindicated that they were not very fearful of the MRI or EUS. They also had low levels ofanxiety, depression and cancer worries. Conclusion: The results of this prospective studyindicate that: (1) the expected burden of EUS is higher than the actual experienced burden;and that (2) mean levels of anxiety, depression and cancer worries are not significantlyinfluenced by participating in the PC screening program. This finding is of great importancefor this group that is at high risk of developing pancreatic cancer and might benefit fromparticipation in a life-long repeated PC surveillance program.

Su1817

EUS Features of Chronic Pancreatitis Do Not Correlate With PathologicFindings of Abnormal Parenchyma in High-Risk Pancreas Cancer PatientsUndergoing Pancreatic ResectionLauren G. Khanna, Marcela Salomao, Sheila Kumar, Caroline Hwang, Aimee L. Lucas,Elana B. Mitchel, Stavros N. Stavropoulos, Heidrun Rotterdam, Harold Frucht

BACKGROUND: Endoscopic ultrasound (EUS) is increasingly used to identify lesions con-cerning for early neoplasia in patients at high risk for pancreatic cancer (PDAC) due to ahereditary disposition. It has been suggested that the EUS features of chronic pancreatitis(CP) may correlate with pancreatic parenchymal changes. AIMS: To correlate EUS featuresof CP with pathology in high risk patients who had pancreatic resection versus average riskcontrol patients who had pancreatic resection for other indications. To assess prevalence ofEUS features of CP in high risk patients with and without pancreatic resection and averagerisk control patients. METHODS: We identified all patients enrolled in our high risk pancre-atic cancer screening program who had EUS and pancreatic resection (Group 1) and twosets of age and gender-matched controls: average risk patients who had EUS and pancreaticresection for duodenal lesions (Group 2) and high risk patients who had EUS but did nothave resection (Group 3). EUS images were reviewed by a blinded expert endosonographerfor features of CP (echogenic foci, echogenic strands, lobularity, main duct dilation, visibleside branches, echogenic duct walls, duct irregularity, cysts, stones). Pathology specimenswere reviewed by a blinded expert pathologist to assess the pancreatic parenchyma apartfrom the primary lesion for resection. Correlation of EUS with pathology was defined aseither EUS CP score 3 or above and pathology with abnormal parenchyma defined by CP,atrophy, PanIN-3 or IPMN; or EUS CP score less than 3 and pathology absent of thepreceding features or with PanIN-1 or -2. McNemar test and Student's t-test were utilizedfor statistical analysis. RESULTS: Each group had 4 males (mean age 72) and 5 females(mean age 60). In Group 1, 3/9 had EUS score 3 or above (mean 1.8) and 7/9 patients hadabnormal parenchyma (p=0.13). In Group 2, 3/9 had EUS score 3 or above (mean 1.6) and2/9 had abnormal parenchyma (p=1.0). In Group 3, 2/9 had EUS score 3 or above (mean1.1). There was no significant difference in mean EUS score, with Group 1 versus Group2 (p=0.7); or Group 3 versus Group 2 (p=0.5); or Group 1 versus Group 3 (p=0.14).CONCLUSIONS: Our data demonstrate no significant difference in features of CP seen onEUS in patients at high risk for the development of PDAC versus average risk patients.Among high risk patients, there is a trend toward more features of CP in those who havesurgical resection compared to those who do not, even though resection was for a separatelesion. There is no significant correlation between EUS features of CP and pathologicalfindings of abnormal pancreatic parenchyma. Our study is limited by small sample size,but indicates that further investigation is needed to determine the relationship between EUSfeatures of CP and pathological findings of abnormal pancreatic parenchyma.

S-511 AGA Abstracts

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Barriers to Genetic Testing for Lynch SyndromeCeline H. Leenen, Conny van der Meer, Reinier Timman, Ernst J. Kuipers, Monique vanLeerdam, Anja Wagner

Background: Lynch syndrome (LS) is a genetic predisposition for colorectal carcinoma,endometrial cancer and other malignancies and is caused by inherited germline mutationsinmismatch repair (MMR) genes. Despite the fact that genetic testing and targeted surveillancecan have a major impact on cancer survival, the uptake of genetic testing by family membersof LS carriers is far from complete. The objective of this study therefore was to investigatebarriers to genetic testing for LS. Methods: 177 individuals tested for LS between 2003-2008 at a tertiary center, were invited by phone and mail to participate. Furthermore, theywere asked to approach non-tested family members to participate in this survey study. Aquestionnaire was sent to all family members who consented to participate, addressingmotivation, Hospital Anxiety and Depression scale (HADS), cancer worry scale, familydynamics, and risk knowledge. Tested and non-tested family members were compared usingthe Fisher's exact test and Mann-Whitney U test. Results: In total 129/177 tested (73%,39% male) and 16/38 non-tested (42%, 38% male) family members from 40 LS familiescompleted the questionnaire. Median age of tested family members was higher than non-tested family members (59 vs 38 yrs; p=0.007). There were no differences between testedand non-tested family members in anxiety, cancer worry scores and risk knowledge on LS-associated cancer risks. Regarding family communication, there were no differences in timingand communication tools for communicating the diagnosis of LS in the family. However,tested family members knew significant more first degree relatives (FDR) (median: 2 vs 1FDR; p=0.004) and second degree relatives (SDR) (median: 2 vs 1 SDR, p=0.05) with cancerthan non-tested family members. The most important reasons for genetic testing for LSwere: 1) availability of surveillance programmes for LS (61%), 2) to end insecurity regardingLS diagnosis (47%), 3) fear for cancer (22%). The three most important reasons for declininggenetic testing were: 1) problems with life insurance and mortgage (50%), 2) being happywith life as it is (44%), and 3) not experiencing any physical complaints (37%). Conclusion:Although the number of included non-tested family members is limited, the most importantbarriers for genetic testing in LS are not related to anxiety, cancer worry, or impaired riskknowledge, but to the personal situation and the limited contact with family membersaffected by cancer. Anticipated problems with life insurance and mortgage are important toabstain from genetic testing. Younger age and knowing fewer family members with cancerinfluence the urge to be tested.

Su1819

Diagnosis of MYH Associated Polyposis in Patients With Multiple ColonicPolypsCarla Guarinos, Miriam Juarez-Quesada, Ramón Salas-Rico, Lucía Pérez-Carbonell, MariaRodriguez-Soler, Joaquin Cubiella, Francisco Rodriguez-Moranta, Enrique Quintero, MaiteHerraiz, Luis Bujanda, Luisa De-Castro, Fernando Fernández-Bañares, Alberto Herrerosde Tejada, Anna Serradesanferm, Ana Guerra, Angeles Pizarro, Josep-Maria Reñé, AdelaCastillejo, Victor M. Barberá, Artemio Payá, Cristina Alenda, José-Luis Soto, Rodrigo Jover

OBJECTIVE: MYH-associated polyposis (MAP) usually appears with an attenuated polyposisphenotype, with frequent existence of both adenomatous and hyperplastic polyps. Thissyndrome has autosomal recessive inheritance, is associated with biallelic mutations in MYHand 80% of European population cases are due to 2 prevalent hotspot mutations. The aimof this study is to estimate the prevalence of mutations in the MYH gene in cases of attenuatedpolyposis and to explore different approaches to genetic diagnosis of this disease. METHODS:This study included 443 patients (66.6% males) coming from the EPIPOLIP study, a multic-enter nationwide project aimed to investigate causes of multiple colonic polyps that includespatients from 24 Spanish hospitals. Patients with more than 10 adenomatous and/or hyperpl-astic polyps were included. We excluded patients diagnosed with FAP, Lynch syndrome,inflammatory bowel disease, or those who had only hyperplastic rectosigmoid polyps. Westudied by direct sequencing the two most frequent hotspot mutations in the MYH gene inall the cases. In patients heterozygous in either of this two mutations, mutational analysisof the complete gene was carried out to determine the existence of a second mutationalevent in trans. The absence of mutations in the APC gene was confirmed in cases with morethan 15 adenomas. RESULTS: The mean age at diagnosis was 58 years (range 18-85). Atotal of 171 patients (38.5%) had first-degree relatives with colorectal polyps and 141patients (35%) were diagnosed with CRC. The mean total number of polyps in patients ofthis series was 18.5 (range 10-207). According to the histology of polyps, cases were classifiedas adenomatous polyposis (33.33%); mixed hyperplastic/adenomatous polyposis (60.91%)and pure hyperplastic polyposis (5.75%). After studying the two most common hotspots,only 22 out of 443 cases had biallelic mutations. A total of 20 cases were heterozygous and,after studying the complete gene, 10 of them (50%) showed a pathogenic mutation in theother allele. Therefore, 32 out of 443 cases (5.6%) had a diagnosis of MAP and only 68%could be explained by the hotspot mutations. These patients with MAP showed a medianof 55 polyps (range 10-207) with a median age at diagnosis of 54. Family history wasreported in 34% of the cases and CRC was detected in 33%. In addition, 40.6% of thesecases have had both adenomas and hyperplastic polyps. CONCLUSIONS: There is a lowfrequency of MYH mutations among patients with attenuated polyposis. The phenotype ofMAP includes frequently patients with hyperplastic polyps. Our results support the needfor the complete analysis of the MYH gene in patients heterozygous for recurrent variants.

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