Endoscopic ultrasonography is a valuable tool with high yield in screening of patients at high-risk for pancreatic cancer

. Kluijt1, J.W. Poley, E. Kuipers, A. Cats, P. Fockens, C. Aalfs, A. Wagner, D. Gouma, Y. Nio, C. van Eijck, M. Bruno
1Familial Cancer Department, Antoni van Leeuwenhoek Hospital, Amsterdam

Introduction: Approximately 10-15% of all pancreatic cancers (PC) are familial or hereditary in origin. Despite improvements in imaging technology and surgery, survival remains dismal in patients with PC. We investigated the use of endoscopic ultrasonography (EUS) in screening patients at high-risk of developing PC.

Methods: Patients eligible for screening were 1st degree members of families with familial PC as well as mutation carriers of PC prone hereditary syndromes (CDKN2A, PRSS1, STK11, p16) or patients with Peutz-Jeghers syndrome, or mutation carriers of other PC prone hereditary syndromes and clustering (>2 case per family) of PC (BRCA1/2, APC, p53, mismatch repair genes). All patients were asymptomatic and had not undergone EUS before. EUS was performed in 2 academic medical centers.

Results: 43 patients (M/F 18/25), age 32 - 75 years, median 51 years, underwent their first screening with EUS. No complications occurred. Genetic background was diverse: 13 patients (8 were known p16 mutation carriers) were from families with FAMMM (familial atypical multiple mole melanoma), 21 patients were from families with familial PC, 3 patients were diagnosed with hereditary pancreatitis (proven mutations in PRSS1 gene), 2 Peutz-Jeghers patients, 3 BRCA1 and 2 BRCA2 mutation carriers with familial clustering of PC and 1 patient with a p53 mutation. In three patients (2 proven FAMMM syndrome, 1 with a BRCA2 mutation) asymptomatic mass lesions (12, 27 and 50 mm) were found in the body and tail of the pancreas. The smallest lesion was not visualised on subsequent CT and MRI. All underwent surgery and were found to have moderately differentiated adenocarcinomas. All lesions were competely removed, however the patients with the larger lesions were found to have N1 disease (5/11 and 1/9 nodes positive). Sidebranch intraductal papillary mucinous neoplasias (IPMN)-like lesions were found in 7 patients: 3 with FAMMM syndrome, 3 in patients with familial PC (1 multifocal) and 1 in a BCRA1 mutation carrier.

Conclusion: Screening patients at high-risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings is high with 7% asymptomatic cancers and 16% premalignant lesions in this series. Whether screening improves survival remains to be investigated, as is the optimal interval for screening. Sidebranch IPMN-like lesions is frequently encountered in these patients and may serve as a precancerous marker lesion for early intervention to improve survival.