ORIGINAL ARTICLE

Pancreatic cancer after remote peptic ulcer surgery

M Tascilar¹, B P van Rees¹, P D J Sturm¹, G N J Tytgat², R H Hruban³, S N Goodman⁴, F M Giardiello⁵, G J A Offerhaus¹ and A C Tersmette¹

¹ Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
² Department of Gastroenterology, Academic Medical Center, University of Amsterdam
³ Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
⁴ Department of Oncology, The Johns Hopkins Medical Institutions
⁵ Department of Gastroenterology, The Johns Hopkins Medical Institutions

Correspondence to:
Correspondence to:
Dr G J A Offerhaus, Academic Medical Center, University of Amsterdam, The Netherlands;
g.j.offerhaus{at}amc.uva.nl

Background: Peptic ulcer surgery may carry an increased risk for pancreatic cancer development. Molecular analysis of K-ras codon 12, frequently mutated in conventional pancreatic cancers, might provide insight into the aetiological mechanisms.

Methods: The relative risk of pancreatic cancer was computed by multivariate and person–year analysis in a cohort of 2633 patients who had undergone gastrectomy. Lung cancer risk was analysed as an indirect means of assessing smoking behaviour. K-ras codon 12 mutational analysis was performed on 15 postgastrectomy pancreatic cancers.

Results: There was an overall increased risk of pancreatic carcinoma of 1.8 (95% confidence interval, 1.3 to 2.6) five to 59 years postoperatively, which gradually increased to 3.6 at 35 years or more after surgery (² test for trend, p < 0.05). Multivariate analysis indicated that parameters other than postoperative interval did not influence the risk. Lung cancer risk was significantly increased after surgery, but no time trend was observed. The spectrum and prevalence of K-ras codon 12 mutations were comparable to conventional pancreatic cancer.

Conclusions: Remote partial gastrectomy is associated with an increased risk of pancreatic cancer. Postgastrectomy and non-postgastrectomy pancreatic cancers may share similar aetiological factors, such as smoking. However, the neoplastic process in patients who have undergone gastrectomy appears to be accelerated by factors related to the surgery itself.

Keywords: pancreatic cancer; postgastrectomy; peptic ulcer; epidemiology; K-ras codon 12

Abbreviations: ASO, allele-specific oligonucleotide; CCK, cholecytokinin; CI, confidence interval; df, degrees of freedom; PCR, polymerase chain reaction; RR, relative risk

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