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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Abbreviations

IAP:

International Association of Pancreatology

BD-IPMNs:

Branch duct intraductal papillary-mucinous neoplasm

MD-IPMN:

Main duct intraductal papillary-mucinous neoplasm

ERP:

Endoscopic retrograde pancreatography

CT:

Computed tomography

MRCP:

Magnetic resonance cholangiopancreatography

EUS:

Endoscopic ultrasonography

NSAIDs:

Non-steroidal anti-inflammatory drugs

COX-1:

Cyclooxygenase-1

COX-2:

Cyclooxygenase-2

GST-π:

Glutathione-S-transferase π

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Authors and Affiliations

  1. Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

    Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Hideyuki Ihara, Yutaka Kawano, Koichi Takada, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto & Junji Kato

  2. Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan

    Tomoko Sonoda

  3. Department of Gastroenterology and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Sapporo, Japan

    Tetsuji Takayama

  4. Department of Molecular Target Exploration, Sapporo Medical University School of Medicine, South-1, West-16 Chuo-ku Sapporo, Hokkaido, 060-8556, Japan

    Yoshiro Niitsu

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  1. Tsuyoshi Hayashi
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Correspondence to Yoshiro Niitsu.

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Hayashi, T., Ishiwatari, H., Ihara, H. et al. Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms. J Gastroenterol 44, 964–975 (2009). https://doi.org/10.1007/s00535-009-0089-8

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  • DOI: https://doi.org/10.1007/s00535-009-0089-8

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