BACKGROUND: 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. METHODS: 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). RESULTS: 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 pi (GST-pi), suggesting that GST-pi is a putative target molecule for sulindac. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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). RESULTS: 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 pi (GST-pi), suggesting that GST-pi is a putative target molecule for sulindac. CONCLUSIONS: 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.
Authors: Monica M Bertagnolli; Craig J Eagle; Ann G Zauber; Mark Redston; Scott D Solomon; KyungMann Kim; Jie Tang; Rebecca B Rosenstein; Janet Wittes; Donald Corle; Timothy M Hess; G Mabel Woloj; Frédéric Boisserie; William F Anderson; Jaye L Viner; Donya Bagheri; John Burn; Daniel C Chung; Thomas Dewar; T Raymond Foley; Neville Hoffman; Finlay Macrae; Ronald E Pruitt; John R Saltzman; Bruce Salzberg; Thomas Sylwestrowicz; Gary B Gordon; Ernest T Hawk Journal: N Engl J Med Date: 2006-08-31 Impact factor: 91.245
Authors: Nadir Arber; Craig J Eagle; Julius Spicak; István Rácz; Petr Dite; Jan Hajer; Miroslav Zavoral; Maria J Lechuga; Paola Gerletti; Jie Tang; Rebecca B Rosenstein; Katie Macdonald; Pritha Bhadra; Robert Fowler; Janet Wittes; Ann G Zauber; Scott D Solomon; Bernard Levin Journal: N Engl J Med Date: 2006-08-31 Impact factor: 91.245
Authors: Robert S Sandler; Susan Halabi; John A Baron; Susan Budinger; Electra Paskett; Roger Keresztes; Nicholas Petrelli; J Marc Pipas; Daniel D Karp; Charles L Loprinzi; Gideon Steinbach; Richard Schilsky Journal: N Engl J Med Date: 2003-03-06 Impact factor: 91.245