Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms.
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.
Hayashi
Tsuyoshi
T
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Ishiwatari
Hirotoshi
H
Ihara
Hideyuki
H
Kawano
Yutaka
Y
Takada
Koichi
K
Miyanishi
Koji
K
Kobune
Masayoshi
M
Takimoto
Rishu
R
Sonoda
Tomoko
T
Takayama
Tetsuji
T
Kato
Junji
J
Niitsu
Yoshiro
Y
D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000473:pathology; D049448:Cholangiopancreatography, Magnetic Resonance / Q000379:methods; D016503:Drug Delivery Systems; D019160:Endosonography / Q000379:methods; D005260:Female; D051549:Glutathione S-Transferase pi / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013467:Sulindac / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods
D000897:Anti-Ulcer Agents; D000970:Antineoplastic Agents; D013467:Sulindac; D051549:Glutathione S-Transferase pi; D009853:Omeprazole