Sharma Vikas, Chauhan Vikrant Singh, Nath Gopal, Kumar Anil, Shukla Vijay Kumar
Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Hepatogastroenterology. 2007 Sep;54(78):1622-5.
BACKGROUND/AIMS: Long standing calculus disease has been observed to be a risk factor for gallbladder carcinoma. However it is possible that calculi may be incriminated by some means other than just chronic irritation. Calculi may induce an element of stasis, promoting chronic infection leading to increased turnover of primary bile acids to secondary bile acids, which are known tumor promoters and initiators. This study aimed to find the prevalence of biliary microflora in gallbladder carcinoma and association of gallbladder carcinoma with chronic bacterial infection and bile acid profile.
Bile culture was done in 390 patients divided into 3 groups--gallbladder carcinoma 65 (17%), cholelithiasis 125 (32%) and control group 200 (51%). Serum samples were analyzed for presence of Vi antibody for chronic typhoid carrier state and bile acid analysis was done in 10 patients in each group.
116 (30%) patients had culture positive bile. Significantly higher number of patients with gallbladder carcinoma 40 (65%) had culture positive bile as compared to cholelithiasis 52 (42%) and control 24 (12%). Vi Antibodies suggestive of chronic typhoid carrier state were found to be significantly higher in the gallbladder carcinoma group 20 (31%) as compared to controls 22 (11%) (OR 3.596, p < 0.05) however, the difference was statistically insignificant in the cholelithiasis group 12 (11%) (OR 0.859, p > 0.05). There was a 6.84 times higher risk of developing gallbladder carcinoma in culture positive cholelithiasis patients and 5.14 times if both Vi antibody and cultures were positive. Bile analysis showed primary bile acids cholic acid and chenodeoxycholic acid to be lower while secondary bile acids deoxycholic acid and lithocholic acid to be more in the gallbladder carcinoma group (7.268 mg/mL, 9.183 mg/ mL, 14.468 mg/mL, 3.312 mg/mL respectively) than cholelithiasis (17.50 mg/mL, 13.80 mg/mL, 6.07 mg/ mL, 2.05 mg/mL) and control group (19.85 mg/mL, 16.53 mg/mL, 2.71 mg/mL, 1.128 mg/mL respectively). The difference was statistically significant.
Chronic bacterial infection of bile leading to production of carcinogenic precursors might be one of the etiological factors in the pathogenesis of gallbladder carcinoma and hence a target for its prevention.
背景/目的：长期存在的结石病被认为是胆囊癌的一个危险因素。然而，结石可能通过除慢性刺激之外的其他方式致病。结石可能导致胆汁淤积，促进慢性感染，从而使初级胆汁酸向次级胆汁酸的转化率增加，而次级胆汁酸是已知的肿瘤促进剂和启动剂。本研究旨在探讨胆囊癌中胆汁微生物群的患病率，以及胆囊癌与慢性细菌感染和胆汁酸谱的相关性。
对390例患者进行胆汁培养，分为3组——胆囊癌组65例（17%）、胆石症组125例（32%）和对照组200例（51%）。分析血清样本中Vi抗体以检测慢性伤寒带菌状态，并对每组10例患者进行胆汁酸分析。
116例（30%）患者胆汁培养呈阳性。胆囊癌组中胆汁培养呈阳性的患者数量显著高于胆石症组（40例，65%）和对照组（24例，12%）。与对照组22例（11%）相比，胆囊癌组中提示慢性伤寒带菌状态的Vi抗体显著更高（20例，31%）（OR 3.596，p < 0.05），然而，胆石症组12例（11%）的差异无统计学意义（OR 0.859，p > 0.05）。胆汁培养呈阳性的胆石症患者发生胆囊癌的风险高6.84倍，若Vi抗体和培养均呈阳性则风险高5.14倍。胆汁分析显示，胆囊癌组中初级胆汁酸胆酸和鹅去氧胆酸含量较低，而次级胆汁酸脱氧胆酸和石胆酸含量高于胆石症组（分别为7.268 mg/mL、9.183 mg/mL、14.468 mg/mL、3.312 mg/mL）和对照组（分别为19.85 mg/mL、16.53 mg/mL、2.71 mg/mL、1.128 mg/mL）。差异具有统计学意义。
胆汁的慢性细菌感染导致致癌前体的产生可能是胆囊癌发病机制中的病因之一，因此是预防胆囊癌的一个靶点。
