Original Article
Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach

Presented in part at the American Gastroenterological Association Plenary Abstract, Digestive Disease Week, San Francisco, California, May 19, 2002.
https://doi.org/10.1016/S1542-3565(04)00244-7Get rights and content

Abstract

Background & Aims: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals. Methods: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery. Results: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with ≥3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients. Conclusions: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.

Section snippets

Study design and patients

In 1998, we established a screening program at Johns Hopkins Hospital for high-risk individuals. Three sources of high-risk individuals provided patients for screening (see flow diagram in Figure 1). The first source was the NFPTR. This registry, based at Johns Hopkins Hospital, was established in 1994 and it tracks patients and families with sporadic and familial pancreatic cancer.17 Families with 2 first-degree relatives affected by pancreatic cancer were defined as having familial

Patients

We received responses from 61 (74%) of the 82 high-risk individuals from NFPTR kindreds with 3 or more affected members who were invited for screening; 54 (88%) of those who responded were interested in participating in the study. The first 30 of these 54 respondents eventually were enrolled. Seven respondents were not interested in screening; one man said that he was “74 years old with adopted children” and the other 6 did not provide a specific reason for not joining the study.

The demographic

Potential clinical use of screening

This study provides important information on the feasibility and the possible importance of screening and early detection in asymptomatic high-risk individuals with a strong family history of pancreatic adenocarcinoma. From our experience to date, most individuals from our high-risk familial pancreatic cancer kindreds were interested in and willing to undergo screening, even traveling long distances at their own expense. We diagnosed and treated 6 pancreatic neoplastic masses in 7 study

Conclusions

In summary, high-risk individuals are highly interested in being screened. Our small study of highly selected subjects suggests that EUS-based screening of asymptomatic high-risk individuals can detect pancreatic neoplasia, but larger multicenter studies are needed before clinical screening recommendations can be made. Distinguishing neoplastic from nonneoplastic pancreatic lesions using imaging tests remains a challenge. The impact of pancreatic cancer screening studies may improve with the

Acknowledgements

The authors thank Lori Wroblewski, R.N., for her assistance with communicating with patients and coordinating this study.

References (66)

  • C.P. Raut et al.

    Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer

    J Gastrointest Surg

    (2003)
  • T. Rosch et al.

    A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures

    Gastrointest Endosc

    (2002)
  • F. Obuz et al.

    Pancreatic adenocarcinomadetection and staging with dynamic MR imaging

    Eur J Radiol

    (2001)
  • S. Kahl et al.

    EUS in the diagnosis of early chronic pancreatitisa prospective follow-up study

    Gastrointest Endosc

    (2002)
  • H. Witt

    Gene mutations in children with chronic pancreatitis

    Pancreatology

    (2001)
  • P. Ghadirian et al.

    Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada

    Int J Pancreatol

    (1991)
  • G. Lal et al.

    Inherited predisposition to pancreatic adenocarcinomarole of family history and germ-line p16, BRCA1, and BRCA2 mutations

    Cancer Res

    (2000)
  • S.A. Hahn et al.

    BRCA2 germline mutations in familial pancreatic carcinoma

    J Natl Cancer Inst

    (2003)
  • K.M. Murphy et al.

    Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancerdeleterious BRCA2 mutations in 17%

    Cancer Res

    (2002)
  • M. Goggins et al.

    Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas

    Cancer Res

    (1996)
  • D.K. Bartsch et al.

    CDKN2A germline mutations in familial pancreatic cancer

    Ann Surg

    (2002)
  • H.F. Vasen et al.

    Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden)

    Int J Cancer

    (2000)
  • S.B. Gruber et al.

    Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome

    Cancer Res

    (1998)
  • M.S. van der Heijden et al.

    Fanconi anemia gene mutations in young-onset pancreatic cancer

    Cancer Res

    (2003)
  • C. Rogers et al.

    The genetics of FANCC and FANCG in familial pancreatic cancer

    Cancer Biol Ther

    (2004)
  • A.B. Lowenfels et al.

    Hereditary pancreatitis and the risk of pancreatic cancer

    J Natl Cancer Inst

    (1997)
  • H.T. Lynch et al.

    Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome

    Pancreas

    (1991)
  • W. Bergman et al.

    Familial melanoma and pancreatic cancer

    N Engl J Med

    (1996)
  • A.M. Goldstein et al.

    Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations

    J Natl Cancer Inst

    (2000)
  • M. Mantelli et al.

    High prevalence of the G101W germline mutation in the CDKN2A P16(ink4a) gene in 62 Italian malignant melanoma families

    Am J Med Genet

    (2002)
  • A.P. Klein et al.

    Evidence for a major gene influencing risk of pancreatic cancer

    Genet Epidemiol

    (2002)
  • H. Ozcelik et al.

    Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients

    Nat Genet

    (1997)
  • A. Tersmete et al.

    Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer

    Clin Cancer Res

    (2001)
  • Cited by (0)

    Supported in part by the National Cancer Institute Specialized Program in Research Excellence (SPORE) grant number 2 P50 CA62924.

    View full text