Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms
- 136 Downloads
When considering surgery for branch duct-intraductal papillary mucinous neoplasms (BD-IPMNs) with suspected malignancy, it should be recognized that these lesions are frequently multifocal and are usually found in elderly patients with potential comorbidities that could affect the outcome of surgery. Clinical trials of chemoprevention have been conducted for a wide variety of malignancies.
Twenty-two BD-IPMN patients participated in the trial at our institution from June 2004 to January 2007. Ten of the 22 patients who rejected surgical therapy although their lesions or clinical symptoms met the criteria for surgical resection of the International Association of Pancreatology guidelines were assigned to the treatment group. Sulindac (150 mg twice daily) and omeprazole (20 mg once daily) were administered to these patients for 18 months. The remaining 12 patients comprised the control group. Branch duct diameter and mural nodule heights were monitored by either magnetic resonance cholangiopancreatography (MRCP) or computed tomography (CT) and by endoscopic ultrasonography (EUS).
Both branch duct diameter and mural nodule height of BD-IPMNs in the treatment group were significantly reduced, while those in the control group were unchanged. Immunohistochemical staining for cyclooxygenase-1 and -2 was negative in hyperplasia, adenoma and carcinoma portions of resected pancreatic specimens but was clearly positive for glutathione-S-transferase π (GST-π), suggesting that GST-π is a putative target molecule for sulindac.
Although a larger scale randomized controlled study is needed in future, the present results suggest the promise of chemoprevention of carcinoma derived from BD-IPMNs by sulindac.
KeywordsIntraductal papillary-mucinous neoplasm Chemoprevention Non-steroidal anti-inflammatory drugs Glutathione-S-transferase π
International Association of Pancreatology
Branch duct intraductal papillary-mucinous neoplasm
Main duct intraductal papillary-mucinous neoplasm
Endoscopic retrograde pancreatography
Magnetic resonance cholangiopancreatography
Non-steroidal anti-inflammatory drugs
- 2.Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, et al. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol. 2000;24:1372–7.PubMedCrossRefGoogle Scholar
- 6.Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, et al. International Association of Pancreatology International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.PubMedCrossRefGoogle Scholar
- 13.Crowell PL, Schmidt CM, Yip-Schneider MT, Savage JJ, Hertzler DA 2nd, Cummings WO. Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia. Neoplasia (New York). 2006;8:437–45.Google Scholar
- 17.Kloppel G, Longnecker DS, Capella C. Histological typing of tumours of the exocrine pancreas. World Health Organization international histological classification of tumours. Berlin: Springer-Verlag; 1996.Google Scholar
- 18.Hruban RH, Pitman MB, Klimstra DS. Atlas of tumor pathology. Tumors of the pancreas, 4th series, fascicle 6. Washington: Armed Forces Institute of Pathology; 2007.Google Scholar
- 19.Gong W, Wang L, Yao JC, Ajani JA, Wei D, Aldape KD, et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res. 2005;11:1386–93.PubMedCrossRefGoogle Scholar
- 25.Nakajima T, Takayama T, Miyanishi K, Nobuoka A, Hayashi T, Abe T, et al. Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione S-transferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-d-phenylglycine ethylester. J Pharmacol Exp Ther. 2003;306:861–9.PubMedCrossRefGoogle Scholar