Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 44, Issue 9, pp 964-975

Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms

  • Tsuyoshi HayashiAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Hirotoshi IshiwatariAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Hideyuki IharaAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Yutaka KawanoAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Koichi TakadaAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Koji MiyanishiAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Masayoshi KobuneAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Rishu TakimotoAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Tomoko SonodaAffiliated withDepartment of Public Health, Sapporo Medical University School of Medicine
    • , Tetsuji TakayamaAffiliated withDepartment of Gastroenterology and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • , Junji KatoAffiliated withFourth Department of Internal Medicine, Sapporo Medical University School of Medicine
    • , Yoshiro NiitsuAffiliated withDepartment of Molecular Target Exploration, Sapporo Medical University School of Medicine Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Backgound

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 π (GST-π), suggesting that GST-π 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.

Keywords

Intraductal papillary-mucinous neoplasm Chemoprevention Non-steroidal anti-inflammatory drugs Glutathione-S-transferase π