Malignant, but not benign, intraductal papillary mucinous neoplasm preferentially associates with prior extrapancreatic malignancies

Kato,Takaharu; Alonso,Sergio; Noda,Hiroshi; Miyakura,Yasuyuki; Tsujinaka,Shingo; Saito,Masaaki; Muto,Yuta; Fukui,Taro; Ichida,Kosuke; Takayama,Yuji; Watanabe,Fumiaki; Kakizawa,Nao; Perucho,Manuel; Rikiyama,Toshiki

doi:10.3892/or.2016.4755

Malignant, but not benign, intraductal papillary mucinous neoplasm preferentially associates with prior extrapancreatic malignancies

Authors:
- Takaharu Kato
- Sergio Alonso
- Hiroshi Noda
- Yasuyuki Miyakura
- Shingo Tsujinaka
- Masaaki Saito
- Yuta Muto
- Taro Fukui
- Kosuke Ichida
- Yuji Takayama
- Fumiaki Watanabe
- Nao Kakizawa
- Manuel Perucho
- Toshiki Rikiyama
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Affiliations: Department of Surgery, Saitama Medical Center, Jichi Medical University, Omiya-ku, Saitama 330-8503, Japan, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'Investigació en Ciéncies de la Salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona, Spain
Published online on: April 19, 2016 https://doi.org/10.3892/or.2016.4755
Pages: 3236-3240

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Abstract

Intraductal papillary mucinous neoplasm (IPMN) has been associated with a high incidence of extrapancreatic malignancies (EPMs). However, it is controversial whether IPMN is prognostic for EPM. We aimed to help clarify the issue studying this association in patients with histologically proven IPMN. We reviewed 51 surgically resected IPMNs in Saitama Medical Center, Jichi Medical University between January 1991 and June 2012. Mean follow-up was 63.7±47.8 months. The observed EPM incidence was compared with the expected incidence of cancer in Japan. Of the 51 IPMNs, 14 were malignant and the rest benign. Seventeen EPMs developed in 15 patients (29.4%), nine of which occurred prior to IPMN diagnosis. For all IPMNs, the standardized incidence ratio (SIR) was significantly increased for the six types of reported EPMs (SIR=2.18, CI=1.31-3.42, P=0.004). Benign IPMNs showed no association with EPMs (SIR=0.92, CI=0.43-1,76, P=0.87). In contrast, malignant IPMNs showed a higher association (SIR=3.83, CI=1.87-7.03, P=0.0009). However, the association was mostly due to the prior EPMs, as removal of metachronous EPMs had no significant effect (SIR=3.63, CI=1.59-7.17, P=0.005). Thus, only malignant IPMNs drive the significant association with prior EPMs, showing a near 4-fold increased incidence compared to the general Japanese population. Histological characterization of IPMNs may offer clinical value for EPM patient management. We hypothesize that these observations may be explained if some patients with EPMs present a higher risk to develop IPMNs (and vice versa), possibly resulting from an uncharacterized multiple cancer predisposition condition.

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1	Sugiyama M and Atomi Y: Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol. 94:470–473. 1999. View Article : Google Scholar : PubMed/NCBI
2	Yamaguchi K, Ohuchida J, Ohtsuka T, Nakano K and Tanaka M: Intraductal papillary-mucinous tumor of the pancreas concomitant with ductal carcinoma of the pancreas. Pancreatology. 2:484–490. 2002. View Article : Google Scholar : PubMed/NCBI
3	Bassi C, Sarr MG, Lillemoe KD and Reber HA: Natural history of intraductal papillary mucinous neoplasms (IPMN): Current evidence and implications for management. J Gastrointest Surg. 12:645–650. 2008. View Article : Google Scholar
4	Choi MG, Kim SW, Han SS, Jang JY and Park YH: High incidence of extrapancreatic neoplasms in patients with intra-ductal papillary mucinous neoplasms. Arch Surg. 141:51–56; discussion 56. 2006. View Article : Google Scholar
5	Eguchi H, Ishikawa O, Ohigashi H, Tomimaru Y, Sasaki Y, Yamada T, Tsukuma H, Nakaizumi A and Imaoka S: Patients with pancreatic intraductal papillary mucinous neoplasms are at high risk of colorectal cancer development. Surgery. 139:749–754. 2006. View Article : Google Scholar : PubMed/NCBI
6	Baumgaertner I, Corcos O, Couvelard A, Sauvanet A, Rebours V, Vullierme MP, Hentic O, Hammel P, Lévy P and Ruszniewski P: Prevalence of extrapancreatic cancers in patients with histologically proven intraductal papillary mucinous neoplasms of the pancreas: A case-control study. Am J Gastroenterol. 103:2878–2882. 2008. View Article : Google Scholar : PubMed/NCBI
7	Yoon WJ, Ryu JK, Lee JK, Woo SM, Lee SH, Park JK, Kim YT and Yoon YB: Extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasm of the pancreas: Prevalence, associated factors, and comparison with patients with other pancreatic cystic neoplasms. Ann Surg Oncol. 15:3193–3198. 2008. View Article : Google Scholar : PubMed/NCBI
8	Reid-Lombardo KM, Mathis KL, Wood CM, Harmsen WS and Sarr MG: Frequency of extrapancreatic neoplasms in intraductal papillary mucinous neoplasm of the pancreas: Implications for management. Ann Surg. 251:64–69. 2010. View Article : Google Scholar
9	Larghi A, Panic N, Capurso G, Leoncini E, Arzani D, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, Zerbi A, et al: Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Oncol. 24:1907–1911. 2013. View Article : Google Scholar : PubMed/NCBI
10	Kawakubo K, Tada M, Isayama H, Sasahira N, Nakai Y, Yamamoto K, Kogure H, Sasaki T, Hirano K, Ijichi H, et al: Incidence of extrapancreatic malignancies in patients with intra-ductal papillary mucinous neoplasms of the pancreas. Gut. 60:1249–1253. 2011. View Article : Google Scholar : PubMed/NCBI
11	Marchegiani G, Malleo G, D'Haese JG, Wenzel P, Keskin M, Pugliese L, Borin A, Benning V, Nilsson L, Oruc N, et al: Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies. Clin Gastroenterol Hepatol. 13:1162–1169. 2015. View Article : Google Scholar
12	Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, et al International Association of Pancreatology: International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 12:183–197. 2012. View Article : Google Scholar : PubMed/NCBI
13	International Rules for Multiple Primary Cancers ICD-O. Third Edit. (Internal Report). Lyon: IARC; 2004
14	Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W and Sobue T; Japan Cancer Surveillance Research Group: Cancer incidence and incidence rates in Japan in 2003: Based on data from 13 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Jpn J Clin Oncol. 39:850–858. 2009. View Article : Google Scholar : PubMed/NCBI
15	R Development Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing; 2011
16	Sullivan KM, Dean A and Soe MM: OpenEpi: A web-based epidemiologic and statistical calculator for public health. Public Health Rep. 124:471–474. 2009.PubMed/NCBI
17	World Medical A; World Medical Association: World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI
18	Tabuchi T, Ito Y, Ioka A, Miyashiro I and Tsukuma H: Incidence of metachronous second primary cancers in Osaka, Japan: Update of analyses using population-based cancer registry data. Cancer Sci. 103:1111–1120. 2012. View Article : Google Scholar : PubMed/NCBI
19	Chen T, Fallah M, Jansen L, Castro FA, Krilavicuite A, Katalinic A, Eisemann N, Emrich K, Holleczek B, Geiss K, et al GEKID Cancer Survival Working Group: Distribution and risk of the second discordant primary cancers combined after a specific first primary cancer in German and Swedish cancer registries. Cancer Lett. 369:152–166. 2015. View Article : Google Scholar : PubMed/NCBI
20	Lee SY, Choi DW, Jang KT, Lee KT, Choi SH, Heo JS, Lee JK, Paik SW and Rhee JC: High expression of intestinal-type mucin (MUC2) in intraductal papillary mucinous neoplasms coexisting with extrapancreatic gastrointestinal cancers. Pancreas. 32:186–189. 2006. View Article : Google Scholar : PubMed/NCBI
21	Hong SM, Omura N, Vincent A, Li A, Knight S, Yu J, Hruban RH and Goggins M: Genome-wide CpG island profiling of intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res. 18:700–712. 2012. View Article : Google Scholar :
22	Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N and Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 53:549–554. 1988. View Article : Google Scholar : PubMed/NCBI
23	Schönleben F, Qiu W, Ciau NT, Ho DJ, Li X, Allendorf JD, Remotti HE and Su GH: PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res. 12:3851–3855. 2006. View Article : Google Scholar : PubMed/NCBI
24	von Figura G, Fukuda A, Roy N, Liku ME, Morris Iv JP, Kim GE, Russ HA, Firpo MA, Mulvihill SJ, Dawson DW, et al: The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 16:255–267. 2014. View Article : Google Scholar : PubMed/NCBI