Stones from cancerous and benign gallbladders are different: A proton nuclear magnetic resonance spectroscopy study

Aim: Gallbladder cancer (GBC) is frequently associated with gallstones (GS). At the same time, however, a very small number of patients with GS develop GBC. Cholesterol and metal salts are the common constituents of all GS. To understand their role in the etiopathogenesis of GBC, cholesterol, calcium, and magnesium composition in GS is compared in cancerous and benign gallbladders. Methods: GS from patients with GBC ( n = 11), chronic cholecystitis (CC; n = 23), and xanthogranulomatous cholecystitis (XGC; n = 11) undergoing cholecystectomy were analyzed using proton nuclear magnetic resonance spectroscopy. The diagnosis of the gallbladder disease was based on histopathological examinations. Cholesterol, calcium, and magnesium in the GS of GBC, XGC, and CC were analyzed, compared, and correlated using statistical methods. Results: The quantity of cholesterol was significantly less in the GS of GBC than in benign gallbladder diseases (CC or XGC, P < 0.0001 for both). Both calcium and magnesium were significantly higher in GBC than in benign disease (calcium: P < 0.0005 and magnesium: P < 0.0001 for GBC vs CC; calcium: P < 0.02 and magnesium: P < 0.04 for GBC vs XGC). In all the GS, calcium was higher than magnesium. Calcium and magnesium were positively correlated in GBC ( R = 0.69) and XGC ( R = 0.75), and cholesterol and calcium were negatively correlated in CC ( R =−0.61). Conclusion: Differences in the GS composition between malignant and benign gallbladder patients may provide useful clues to the etiopathogenesis of GBC. These clues could lead to the identification of patients with GS in vivo who are at high risk of developing GBC, and advocate prophylactic cholecystectomy to prevent GBC.