S0117 Risk of Gallbladder Cancer With Increasing Gallstone Size: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Gallbladder (GB) cancer (GBC) accounted for 3960 deaths in the US in 2019. With only 1 in 5 GBCs diagnosed at early stage, the overall 5-year survival rate is a meager 19%. Given the low 5-year survival, the best treatment is prevention. Risk factors for GBC include age, ethnicity, GB polyps >1 cm, primary sclerosing cholangitis, anomalous pancreaticobiliary junction, toxins, and GB stones. There remains controversy as to whether size of GB stones increases the risk of GBC. The aim of this systematic review and meta-analysis was to determine if risk of GBC increases with increasing size of GB stones. METHODS: A systematic search was conducted using the terms “gallbladder cancer,” “cholelithiasis,” “gallstones,” and “gallstone size” with all permutations of pubmed/medline, google scholar, embase, and cochrane. Papers were translated, if necessary. A recursive search of bibliographies of included articles was also performed. GB stone size was primarily determined post-cholecystectomy. The relevant data was inputted into RevMan 5.4 in order to generate odds ratios and Forest plots. RESULTS: The search yielded 357 total articles, of which 8 met our final inclusion criteria with GB stone measurement and prevalence of GBC in each study population. The data was then divided into 3 groups, based on size of GB stones, greater or lesser than 3 cm, 2 cm, or 1 cm. We found that the OR of developing GBC was 1.93 [1.29–2.90], 1.42 [1.06–1.90], and 1.62 [1.24–2.11] for stones greater than 3 cm, 2 cm, and 1 cm, respectively. CONCLUSION: Patients with GB stones >1 cm had increased odds of developing GBC, however we did not observe a linear relationship between GBC and increasing stone size. Our meta-analysis found an OR of 1.93 for stones >3 cm which is significantly less than the 9.1 previously reported. The association between GB stone size and GBC is likely related to the chronicity of GB stones rather than absolute size. Jain et al. proposed that chronic inflammation could subsequently lead to loss of heterozygosity of tumor suppressor genes. In summary, we found the risk of GBC is similar regardless of size of stones >1 cm. Therefore while we usually observe asymptomatic GB stones, clinicians should be aware that GB stones >1 cm may have increased risk of GBC in symptomatic individuals. Further studies are needed in asymptomatic individuals to define the optimal GB stone size cutoff to perform cholecystectomy to reduce GBC risk.Figure 1.: Odds of developing gallbladder cancer with increasing size of gallstones. (Events = # of cases of gallbladder cancer; Total = # of cases of patients with gallstones > or < the specified size).