摘要目的 探讨持续性胰液胆管逆流(pancreaticobiliary reflux,PBR)初期及潜在性PBR胆囊黏膜的病理变化.方法 将仓鼠分为4组:PBR造模组(手术造模),空白对照组,造模+N-亚硝基双胺(BOP)组(诱导胆囊癌)和单纯BOP组;另选择87例正常胰胆管汇合行胆囊切除或经皮经肝胆囊镜治疗的胆囊结石患者,根据胆汁淀粉酶(BA)值升高和正常分为PBR组和对照组.对比胆囊黏膜的病理变化.结果 动物实验中PBR造模组胆囊上皮增生6/6,幽门腺化生3/6、肠上皮化生4/6以及细胞低级别瘤变2/6,其中上皮增生与空白对照组(0/5)比较差异有统计学意义(P＜0.05).造模+ BOP组胆囊癌(3/6)和高级别瘤变(1/6)与BOP组(0/5)比较明显增高.临床研究中胆囊结石患者PBR组中70.6％ (24/34)BA呈高值(＞1 000 U/L),PBR组胆囊上皮低级别瘤变者(73.5％,25/34)明显多于对照组(24.5％,13/53,P＜0.05).结论 持续性PBR初期阶段即可引起胆囊黏膜增生,有上皮化生发生频度高的倾向.PBR造模仓鼠用BOP可高频度诱发胆囊癌或高级别瘤变.潜在性PBR患者可导致细胞低级别瘤变,可能是引起胆囊恶变倾向的因素.

abstractsObjective To investigate pathologic changes of gallbladder mucosa induced by continuous pancreaticobiliary reflux(PBR) in the preliminary stage and occult PBR stage.Methods Female Syrian golden hamsters were assigned into four groups : PBR model group (established by surgery), the blank control group, PBR with BOP group (to induce gallbladder cancer) and the simple BOP group.In addition, 87 patients with normal pancreaticobiliary junction (NPBJ) who underwent cholecystectomy or percutaneous transhepatic cholecystoscopy for gallbladder stones were assigned into two groups based on the value of bile amylase (BA) : PBR group and the control group.Pathological changes of gallbladder mucosa between groups were analyzed and compared.Results In PBR model group, the incidences of gallbladder epithelial hyperplasia, pyloric gland metaplasia, intestinal metaplasia and low-grade neoplasia were 6/6, 3/6, 4/6 and 2/6, respectively.The incidence of gallbladder epithelial hyperplasia in PBR model group (6/6) was significantly higher than that of the blank control group (0/5).Incidence of gallbladder cancer (3/6) and highgrade neoplasia(1/6) was higher in PBR with BOP group than in the simple BOP group(0/5).In the clinical study, 70.6％ (24/34) patients in PBR group presented high BA value (＞ 1 000 U/L).Significantly higher occurrence of low-grade neoplasia can be observed in this group (73.5％ ,25/34) compared with the control group (24.5％, 13/53, P ＜ 0.05).Conclusion Gallbladder mucosal hyperplasia and the tendency of high incidence of metaplasia can be detected in the preliminary stage of continuous PBR.High probability of gallbladder carcinoma or high-grade neoplasia can be induced with BOP in PBR model hamsters.Occult PBR can lead to low-grade cell dysplasia and therefore may be the factor of gallbladder malignancy.