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Article / Publication Details
Background: Nearly 10% of pancreatic cancers are hereditary in origin, and in some individuals, the risk of pancreatic cancer approaches 50%. A number of defined syndromes can predispose families to pancreatic cancer, although many of the mechanisms that result in familial pancreatic cancers are unknown. This article reviews current knowledge regarding familial pancreatic cancers and highlights the rationale for screening and surveillance. Methods for screening and surveillance of these high-risk individuals are described that allow the detection of pancreatic dysplasia, the precursor to pancreatic cancer. We also describe a single-center experience with the management and surveillance of familial pancreatic cancer kindreds. Methods: Thirty-five patients from 13 familial pancreatic cancer kindreds underwent screening and/or surveillance. Endoscopic ultrasound (EUS) is the initial test of choice. Endoscopic retrograde cholangiopancreatography (ERCP) is reserved for symptomatic individuals or to investigate abnormal findings on EUS. In the proper clinical setting, patients with abnormal findings on both EUS and ERCP are candidates for total pancreatectomy. Results: Twelve of 35 patients were noted to have abnormal findings on EUS and ERCP. All of these individuals underwent pancreatectomy, 10 total and 2 partial. The patients who underwent partial pancreatectomy are currently awaiting resection of the pancreatic remnant. Histopathologic examination of all 12 specimens demonstrated pancreatic dysplasia (the precursor lesion to pancreatic cancer). These specimens had no evidence of pancreatic cancer; nor were any of the resected pancreata normal. Follow-up of the 35 high-risk patients at present varies from 1 to 48 months, and none of the patients under surveillance have developed pancreatic cancer. Conclusion: The screening and surveillance of high-risk members of familial pancreatic cancer kindreds using EUS and ERCP is an effective method for identifying individuals with pancreatic dysplasia prior to the onset of invasive pancreatic cancer. The surveillance needs to be performed by a team of specialists who have experience in dealing with pancreatic cancer and its precursors.
Article / Publication Details
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- Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–31.
- Warshaw AL, Fernandez-Del Castillo C: Pancreatic carcinoma. N Engl J Med 1992;326:455–465.
- Lynch HT, Smyrk T, Kern SE, Hruban RH, Lightdale CJ, Lemon SJ, Lynch JF, Fusaro LR, Fusaro RM, Ghadirian P: Familial pancreatic cancer: A review. Semin Oncol 1996;23:251–255.
- Evans JP, Burke W, Chen R, Bennett RL, Schmidt RA, Dellinger EP, Kimmey M, Crispin D, Brentnall TA, Byrd DR: Familial pancreatic adenocarcinoma: Association with diabetes and early molecular diagnosis. J Med Genet 1995;32:330–335.
- Efthimiou E, Brentnall TA, Crnogorac-Jurcevic T, Lemoine NR: Inherited predisposition to pancreatic cancer. Gut 2001;48:143–147.
- Goldstein AM, Fraser MC, Struewing JP, Hussassian CJ, Ranade Z, Zametking DP, Fontaine LS, Organic SM, Dracopoli NC, Clark WH, et al: Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995;333:970–974.
- Whelan A, Bartsch D, Goodfellow P: A brief report: A familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med 1995;333:975–977.
- Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, Yeo CJ, Jackson CE, Lynch HT, Hruban RH, Kern SE: Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996;56:5260–5264.
- Ozcelik H, Schmocker B, DiNicola N, Shi XH, Langer B, Moore M, Taylor BR, Narod SA, Darlington G, Andrulis IL, Gallinger S, Redston M: Germline BRCA2 617delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 1997;16:17–18.
- Lynch HT, Voorhees G, Lanspa S, McGreevy PS, Lynch JF: Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: A family study. Br J Cancer 1985;52:271–273.
- Goggins M, Kern SE, Offerhaus JA, Hruban RH: Progress in cancer genetics: Lessons from pancreatic cancer. Ann Oncol 1999;10(suppl 4):S4–S8.
- Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV, Kelley NC, Hamilton SR: Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 1993;34:1394–1396.
- Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD: Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316:1511–1514.
- Lowenfels AB, Maisonneuve P, DiMagno EP, Elitsur Y, Gates LK, Perrault J, Whitcomb DC: Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997;89:442–446.
- Neglia JP, Fitzsimmons SC, Maisonneuve P, Schoni MH, Schoni-Affolter F, Corey M, Lowenfels AB: The risk of cancer among patients with cystic fibrosis. N Engl J Med 1995;332:494–499.
- Bergman W, Watson P, de Jong J, Lynch HT, Fusaro RM: Systemic cancer and the FAMMM syndrome. Br J Cancer 1990;61:932–936.
- Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, DiMagno EP, Andren-Sandberg A, Domellof L: Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993;328:1433–1437.
- Hruban RH, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Falatko F, Yeo CJ, Kern SE: Familial pancreatic cancer. Ann Oncol 1999;10(suppl 4):S69–S73.
- Falk RT, Pickle LW, Fontham ET, Correa P, Fraumeni JF Jr: Life-style risk factors for pancreatic cancer in Louisiana: A case-control study. Am J Epidemiol 1988;18:324–336.
- Fernandez E, La Vecchia C, D’Avanzo B, Negri E, Franceschi S: Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol Biomarkers Prev 1994;3:209–212.
- Ghadirian P, Boyle P, Simard A, Baillargeon J, Maisonneuve P, Perret C: Reported familial aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol 1991;10:183–196.
- Silverman DT, Schiffman M, Everhart J, Goldstein A, Lillemow KD, Swanson GM, Schwartz AG, Brown LM, Greenberg RS, Schoenberg JB, Pottern LM, Hoover RN, Fraumeni JF: Diabetes mellitus, other medical conditions, and family history of cancer as risk factors for pancreatic cancer. Br J Cancer 1999;80:1830–1837.
- Brentnall TA: Cancer surveillance of patients from familial pancreatic cancer kindreds. Med Clin North Am 2000;84:707–718.
- Lowenfels AB, Maisonneuve P: Pancreatic cancer: Development of a unifying etiologic concept. Ann NY Acad Sci 1999;880:191–200.
- Longnecker MP: Alcohol consumption and risk of cancer in humans: An overview. Alcohol 1995;12:87–96.
- Silverman DT, Dunn JA, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB, Brown LM, Greenberg RS, Hayes RB, Swanson M, Wacholder S, Schwartz AG, Liff JM, Pottern LM: Cigarette smoking and pancreas cancer: A case-control study based on direct interviews. J Natl Cancer Inst 1994;86:1510–1516.
- Lowenfels AB, Maisonneuve P, Whitcomb DC: Smoking and the risk of pancreatic cancer in patients with hereditary pancreatitis. International Hereditary Pancreatitis Study Group (abstract). Pancreas 1999;19:430.
- Cubilla AL, Fitzgerald PH: Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res 1976;36:2690–2698.
- Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH: Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol 1998;22:163–169.
- DiGiuseppe JA, Hruban RH, Offerhaus GJ, Clement MJ, van den Berg FM, Cameron JL, van Mansfeld AD: Detection of K-ras mutations in mucinous pancreatic duct hyperplasia from a patient with a family history of pancreatic carcinoma. Am J Pathol 1994;144:889–895.
- Moskaluk CA, Hruban RH, Kern SE: p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res 1997;21:205–217.
- DiGiuseppe JA, Hruban RH, Goodman SN, Polak M, van den Berg FM, Allison DC, Cameron JL, Offerhaus GJ: Overexpression of p53 protein in adenocarcinoma of the pancreas. Am J Clin Pathol 1994;101:684–688.
- Kloppel G, Bommer G, Ruckert K, Seifert G: Intraductal proliferation in the pancreas and its relationship to human and experimental carcinogenesis. Virchows Arch 1980;387:221–233.
- Klimstra DS, Hameed MR, Marrero AM: Ductal proliferative lesions associated with infiltrating ductal adenocarcinoma of the pancreas. Int J Pancreatol 1994;16:224–225.
- Hruban RH, Wilentz RE, Goggins M, Offerhaus GJA, Yeo CJ, Kern SE: Pathology of incipient pancreatic cancer. Ann Oncol 1999;10(suppl 4):S9–S11.
- Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB: Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999;131:247–255.
- Sugio K, Molberg K, Albores-Saavedra J, Virmani AK, Kishimoto Y, Gazdar AF: K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers. Int J Pancreatol 1997;21:205–217.
- Luttges J, Schlehe B, Menke M, Vogel I, Henne-Bruns D, Kloppel G: The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic epithelium. Cancer 1999;85:1703–1710.
- Furuya N, Kawa S, Akamatsu T, Furtihata K: Long-term follow-up of patients with pancreatitis and the K-ras gene mutation detected in pancreatic juice. Gastroenterology 1997;113:593–598.
- Uehara H, Nakaizumi A, Tatsuta M, Baba M, Takenaka A, Uedo N, Sakai N, Yano H, Iishi H, Ohigashi H, Ishikawa O, Okada S, Kazikoe T: Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: Comparison with K-ras mutations. Am J Gastroenterol 1999;94:2513–2518.
- Howes N, Greenhalf W, Neoptolemos J: Screening for pancreatic ductal adenocarcinoma in hereditary pancreatitis. Med Clin North Am 2000;84:719–737.
- Karpoff HM, Klimstra DS, Brennan MF, Conlon KC: Results of total pancreatectomy for adenocarcinoma of the pancreas. Arch Surg 2001;136:44–47.
- Huang JJ, Yeo CJ, Sohn TA, Lillemoe KD, Sauter PK, Coleman J, Hruban RH, Cameron JL: Quality of life and outcomes after pancreaticoduodenectomy. Ann Surg 2000;231:890–898.