Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms

Background and study aims: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs), and associated synchronous and metachronous pancreatic cancers are increasingly detected as imaging modalities become more sensitive. We investigated the natural history of SB-IPMN, and the incidence and characteristics of pancreatic cancers among patients undergoing long-term follow-up.

Patients and methods: We reviewed the clinical, imaging, and pathological features in 103 patients, diagnosed at the Aichi Cancer Center between September 1988 and September 2006 as having SB-IPMN, and conservatively followed up for ≥ 2 years (median 59 months) based on an endoscopic ultrasonography (EUS) database.

Results: 74 (71.8 %) patients had nonprogressive lesions. Overall, six patients (5.8 %) developed pancreatic cancers during follow-up, with intraductal papillary mucinous (IPM) carcinoma in four, and ductal carcinoma of pancreas that was not IPMN in two patients. Of the six pancreatic cancers, five were diagnosed at a resectable stage. The 5-year and 10-year actuarial rates of development of pancreatic cancer were 2.4 % and 20.0 %, respectively. Although, at the last follow-up, cyst size, main pancreatic duct (MPD) diameter, mural nodule size, and frequency of metachronous and/or synchronous cancers of other organs were significantly higher in patients who developed IPM carcinoma, resected SB-IPMNs without mural nodules and dilated MPDs had no IPM carcinomas.

Conclusions: The frequency of pancreatic cancers is high on long-term follow-up of SB-IPMN. Although conservative management is appropriate for selected patients, regular and long-term imaging, especially by EUS is essential, even if SB-IPMN remains unchanged for 2 years. Presence of mural nodule and dilated MPD seem to be more appropriate indicators for resection than cyst size alone for SB-IPMNs.

References

• 1 Ohhashi K, Murakami Y, Maruyama M. et al . Four cases of mucous secreting pancreatic cancer [in Japanese].  Prog Dig Endosc. 1982;  20 348-351
• 2 Kloppel G, Solcia E, Longnecker D S. et al .World Health Organization international histological classification of tumors. Histological typing of tumors of the exocrine pancreas. 2nd edn. Berlin; Springer 1996
• 3 Solcia E, Capella C, Kloeppel G. Tumors of the pancreas. In: Rosai J, ed Atlas of tumor pathology. Fascicle 20. Washington; Armed Forces Institute of Pathology 1997: 31-144
• 4 Yamao K, Nakazawa S, Fujimoto M. et al .Intraductal papillary tumors, non-invasive and invasive. In: Pour PM, Konishi Y, Kloppel G, Longnecker DS, eds Atlas of exocrine pancreatic tumors. Tokyo; Springer 1994: 43-66
• 5 Azar C, Van de Stadt J, Rickaert F. et al . Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients.  Gut. 1996;  39 457-464
• 6 Loftus E V, Olivares-Pakzad B A, Batts K P. et al . Intraductal papillary-mucinous tumors of the pancreas: clinicopathological features, outcome, and nomenclature.  Gastroenterology. 1996;  110 1909-1918
• 7 Hruban R H, Takaori K, Klimstra D S. et al . An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms.  Am J Surg Pathol. 2004;  28 977-987
• 8 Furukawa T, Kloppel G, Volkan Adsay N. et al . Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study.  Virchows Arch. 2005;  447 794-799
• 9 Tanaka M, Chari S, Adsay V. et al . International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.  Pancreatology. 2006;  6 17-32
• 10 Conlon K C. Intraductal papillary mucinous tumors of the pancreas.  J Clin Oncol. 2005;  23 4518-4523
• 11 Wada K, Kozarek R A, William Traverso L. Outcomes following resection of invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas.  Am J Surg. 2005;  189 632-636
• 12 Salvia R, Fernandez-del Castillo C, Bassi C. et al . Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.  Ann Surg. 2004;  239 678-685
• 13 Yamaguchi K, Ohuchida J, Ohtsuka T. et al . Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinoma of the pancreas.  Pancreatology. 2002;  2 484-490
• 14 Tada M, Kawabe T, Arizumi M. et al . Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients.  Clin Gastroenterol Hepatol. 2006;  4 1265-1270
• 15 Uehara H, Nakaizumi A, Ishikawa O. et al . Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas.  Gut. 2008;  57 1561-1565
• 16 Tanno S, Nakano Y, Koizumi K. et al . Pancreatic ductal adenocarcinomas in long-term follow-up patients with branch duct intraductal papillary mucinous neoplasms.  Pancreas. 2010;  39 36-40
• 17 Chari S, Yadav D, Smyrk T. et al . Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas.  Gastroenterology. 2002;  123 1500-1507
• 18 Ingkakul T, Sadakari Y, Ienaga J. et al . Predictors of the presence of concomitant invasive ductal carcinoma in intraductal papillary mucinous neoplasm of the pancreas.  Ann Surg. 2010;  251 70-75
• 19 Japan Pancreas Society .Classification of pancreatic cancer. 6th edn. Tokyo, Japan; Kanehara 2009
• 20 Schmidt C M, White P B, Waters J A. et al . Intraductal papillary mucinous neoplasms: predictors of malignant and invasive pathology.  Ann Surg. 2007;  246 644-651
• 21 Salvia R, Crippa S, Falconi M. et al . Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not?.  Gut. 2007;  56 1086-1090
• 22 Tanno R, Nakano Y, Nishikawa T. et al . Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas without mural nodules: long term follow-up results.  Gut. 2008;  57 339-343
• 23 Sadakari Y, Ienaga J, Kiichiro K. et al . Cyst size indicates malignant transformation in branch duct intraductal papillary mucinous neoplasm of the pancreas without mural nodules.  Pancreas. 2010;  39 232-236
• 24 Jang J Y, Kim S W, Ahn Y J. et al . Multicenter analysis of clinicopathologic features of intraductal papillary mucinous tumor of the pancreas: is it possible to predict the malignancy before surgery?.  Ann Surg Oncol. 2005;  12 124-312
• 25 Baba T, Yamaguchi T, Ishihara T. et al . Distinguish benign from malignant intraductal papillary mucinous tumors of the pancreas by imaging techniques.  Pancreas. 2004;  29 212-217
• 26 Yamaguchi K, Ogawa Y, Chijiiwa K. et al . Mucin-hypersecreting tumors of the pancreas: assessing the grade of malignancy preoperatively.  Am J Surg. 1996;  171 427-431
• 27 Yamao K, Ohashi K, Nakamura T. et al . Evaluation of various imaging methods in the differential diagnosis of intraductal papillary-mucinous tumor (IPMT) of the pancreas.  Hepatogastroenterology. 2001;  48 962-966
• 28 Sugiyama M, Atomi Y. Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas.  Am J Gastroenterol. 1999;  94 470-473
• 29 Osanai M, Tanno S, Nakano Y. et al . Extrapancreatic neoplasms in patients with intraductal papillary tumors of the pancreas: analysis in surgical and follow up series [in Japanese with English abstract].  J Jpn Pancreas Soc. 2003;  18 5665-5669
• 30 Kamisawa T, Tu Y, Egawa N. et al . Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas.  World J Gastroenterol. 2005;  11 5688-5690
• 31 Lee S Y, Lee K T, Lee J K. et al . Long-term follow up results of intraductal papillary mucinous tumors of pancreas.  J Gastroenterol Hepatol. 2005;  20 1379-1384