胆汁端粒酶活性联合血清CEA、CA19-9检测在胆道恶性梗阻诊断中的价值

目的 探讨胆汁端粒酶活性联合血清CEA、CA19-9检测对胆道恶性梗阻的诊断价值.方法 应用TRAP-ELISA法检测66例胆道恶性梗阻患者(恶性组)和28例胆管结石引起胆道梗阻患者(良性组)胆汁脱落细胞端粒酶活性,并检测血清CEA、CA19-9水平.结果 恶性组端粒酶活性、CEA、CA19-9阳性率均高于良性组(P均<0.05),端粒酶阳性率与病灶转移无相关性;胆汁端粒酶活性联合血清CEA、CA19-9检测的敏感性、特异性均高于单独检测,但无统计学意义.结论 胆汁端粒酶活性联合血清CEA、CA19-9检测可提高恶性胆道疾病的诊断率.     

CEA,CA 19-9与CA 125联合检测对良恶性腹水的鉴别诊断价值

目的探讨联合检测腹水和血清CEA,CA 19-9和CA 125对良恶性腹水鉴别诊断的价值。方法应用蛋白质芯片技术分别测定良性和恶性腹水病人腹水和血清的CEA、CA 19-9和CA 125水平,并评价多项肿瘤标志物联合检测对良恶性腹水的诊断价值。结果恶性腹水组腹水和血清CEA,CA 19-9水平较良性腹水组升高(P0.01),恶性腹水组腹水CA125水平较良性腹水组升高(P0.05),但两组血清CA 125水平没有显著性差异(P0.05)。腹水CEA、CA 19-9、CA 125联合检测诊断恶性腹水的敏感性、特异性和准确性分别为81.8%、68.0%和85.1%;血清CEA、CA 19-9联合检测的敏感性、特异性和准确性分别为77.3%、56.0%和83.0%。结论检测肿瘤标志物CEA、CA 19-9及CA 125有助于良恶性腹水的鉴别诊断,腹水利血清CEA、CA 19-9和CA 125联合检测可提高诊断恶性腹水的敏感性和准确性。     

探讨胆汁肿瘤标志物对胆管良恶性疾病的诊断价值

目的探讨胆汁肿瘤标志物对胆管良恶性疾病的诊断价值。方法160例因胆道疾病需要ERCP治疗者,ERCP时取胆汁检测胆汁肿瘤标志物（CA19-9、CEA和CA242）和细菌培养。结果恶性狭窄组与良性疾病组间胆汁和血清CA19-9、CEA、CA242水平差异均有统计学意义（P〈0．05）;根据ROC曲线制定恶性狭窄的胆汁肿瘤标志物界限值：CA19-9239ku／L,CEA40ng／ml,CA24260ku／ml。CEA敏感度、准确度、阴性预测值与血液标志物比较差异有统计学意义（P〈O．05）。3种胆汁标志物的特异性与血清比较差异无统计学意义。胆管癌、胰腺癌、十二指肠乳头癌与胆管旁转移癌、肝癌比较CA19-9水平差异有统计学意义（P〈0．05）;无论是恶性狭窄组还是良性疾病组,细菌阳性胆汁与阴性胆汁组间CA19-9水平比较差异均有统计学意义（P〈0．05）。结论胆汁CA19-9、CEA、CA242水平对鉴别胆道良恶性疾病有一定帮助,但并不明显优于血清标志物。胆汁细菌感染可引起胆汁CA19-9水平升高,但不影响良恶性诊断结果。     

ERCP胆管刷检联合血清、胆汁中CA19-9、CEA对胆管良、恶性狭窄鉴别诊断的价值

目的探讨ERCP胆管刷检联合血清、胆汁中CA19-9、CEA在胆管良、恶性狭窄定性诊断中的价值。方法77例胆管狭窄患者ERCP术中行胆管细胞刷检并留取血清、胆汁标本,测定CA199、CEA水平,比较在胆管良恶性狭窄中的变化规律。结果胆管良、恶性狭窄中血清、胆汁CA19-9,CEA水平均有差异性,恶性组明显高于良性组(P0.05)。根据ROC曲线,AUC_((胆汁CA19-9))AUC_((胆汁CEA))AUC_((血清CA19-9))AUC_((血清CEA))。两两联合后诊断的敏感性较单独检测明显提高,其中胆汁CA19-9、CEA联合检测时,诊断敏感性为92.6%,特异性为78.3%。54例胆管癌组患者行胆管刷检阳性率为40.7%,特异性为100%。胆管刷检及胆汁CA19-9、CEA联合检测,诊断胆管恶性狭窄的敏感性为96.2%,特异性为82.6%。结论在胆管恶性狭窄的诊断中,ERCP下刷检及胆汁CA19-9、CEA联合检测大大提高诊断率。     

胆汁和血清KL-6黏蛋白在良恶性梗阻性黄疸中的表达及临床意义

目的探讨良恶性梗阻性黄疸患者血清和胆汁KL-6黏蛋白的表达差异及其在良恶性梗阻性黄疸鉴别诊断中的临床应用价值。方法采集41例确诊的恶性梗阻性黄疸患者（恶性梗阻组）和15例确诊的良性梗阻性黄疸患者（良性梗阻组）的胆汁和血清样本,酶联免疫法检测胆汁和血清KL-6黏蛋白水平,放射免疫法测定血清AFP、CEA和CA19-9水平,对各检测指标组间间表达差异以及鉴别诊断良恶性梗阻性黄疸的效能行统计学分析。结果血清CEA、CA19-9、KL-6黏蛋白及胆汁KL-6黏蛋白在恶性梗阻组中的表达水平显著高于良性梗阻组,差异均有统计学意义（P〈0．01）;而血清AFP的表达水平在两组间差异无统计学意义（P=0．302）。血清AFP、CEA、CA19-9、KL-6黏蛋白及胆汁KL-6黏蛋白的ROC曲线下面积分别为0．657、0．753、0．894、0．846和0．954,以各检测指标的最佳临界值为界,胆汁KL-6黏蛋白鉴别诊断良恶性梗阻性黄疸的灵敏度、特异度、阳性预测值、阴性预测值、阳性似然比、阴性似然比均优于血清AFP、CEA、CA19-9和KL-6黏蛋白。结论胆汁KL-6黏蛋白对鉴别良恶性梗阻性黄疸具有一定的临床应用价值,有望成为鉴别诊断良恶性梗阻性黄疸的特异性肿瘤标记物。     

血清糖链抗原19-9、糖链抗原24-2对良恶性胆道疾病的诊断价值

目的探讨并分析血清糖链抗原(CA)19-9、CA24-2在良恶性胆道疾病中的诊断价值。方法选取2012年1月-2015年10月于河北北方学院附属第一医院消化内科和普外科住院的胆道疾病患者214例,根据病变性质分为胆道良性病变组(n=162)和恶性病变(胆管癌)组(n=52),另选取同期体检中心健康体检者作为正常对照组(n=40)。所有研究对象均在空腹状态下抽取外周静脉血,检测血清TBil、DBil、IBil,采用放射免疫法测定血清CA19-9、CA24-2水平。计量资料多组样本间比较采用Kruskal-Wallis H检验,进一步两两比较采用Wilcoxon秩和检验;计数资料组间比较采用χ~2检验;采用Pearson相关分析法进行相关性分析。结果与正常对照组相比,良、恶性胆道病变组患者血清TBil、CA19-9水平均升高,差异均有统计学意义(P值均0.01);与胆道良性病变组相比,胆道恶性病变患者血清CA19-9和CA24-2水平均显著升高,差异均有统计学意义(P值均0.01)。血清CA19-9、CA24-2水平与胆管癌组织学肿瘤位置无关,与组织学不同分化程度有关(χ~2值分别为6.860、9.010,P值均0.05)。联合检测CA19-9与CA24-2诊断胆管癌的敏感度为88.5%,特异性为82.1%,高于二者单独检测的敏感度和特异性,差异均有统计学意义(P值均0.01)。良性胆道疾病与胆管癌患者血清CA19-9水平与血清TBil水平均呈正相关(r值分别为0.634、0.346,P值均0.05)。结论联合检测CA19-9和CA24-2对胆管癌早期诊断具有临床意义。     

血清肿瘤标志物CEA、CA19-9、CA242及CA724联合检测在胃癌诊断中的价值分析

目的研究血清肿瘤标志物癌胚抗原(CEA)、糖链抗原19-9(CA19-9)、糖链抗原242(CA242)及糖链抗原724(CA724)联合检测在胃癌诊断中的价值。方法纳入2016年12月至2018年12月于我院收治的84例胃癌患者为A组,另选取同期收治的58例胃良性疾病者和58例健康体检者分别设为B、C组。采集血液标本,检测上述对象CEA、CA19-9、CA242、CA724水平并进行比较。分析胃癌不同分期患者上述血清肿瘤标志物水平,并观察上述血清肿瘤标志物对胃癌的预测价值,探讨血清CEA、CA19-9、CA242、CA724联合诊断胃癌的敏感性与特异性。结果 A组CEA、CA19-9、CA242、CA724均显著高于B、C组(P 0. 05),B组上述血清肿瘤标志物较C组比较差异均无统计学意义(P 0. 05)。胃癌Ⅰ期患者CEA、CA19-9、CA242、CA724显著高于Ⅱ、Ⅲ、Ⅳ期患者(P 0. 05),Ⅱ期患者上述指标均显著高于Ⅲ、Ⅳ期者(P 0. 05),Ⅲ期患者上述指标均显著高于Ⅳ期者(P 0. 05)。经ROC曲线处理,结果显示血清肿瘤标志物CEA、CA19-9、CA242、CA724对胃癌均有一定预测价值,曲线下面积分别为0. 807、0. 764、0. 823、0. 816。血清肿瘤标志物CEA、CA19-9、CA242、CA724联合诊断胃癌灵敏度为94. 05%,特异度为63. 79%。结论血清肿瘤标志物CEA、CA19-9、CA242、CA724联合诊断胃癌灵敏度较高,联合检测CEA、CA19-9、CA242及CA724有助于胃癌的早期筛查。     

红细胞体积分布宽度对胆道良恶性病变的诊断价值

目的探讨红细胞体积分布宽度对胆道良恶性狭窄的诊断价值。方法回顾性分析135例恶性胆道狭窄及53例良性胆道狭窄患者,将2组红细胞体积分布宽度（RDW）值进行对比,进一步分析RDW与胆道狭窄的部位、具体病因的关系,并与传统肿瘤标志物CA19-9、癌胚抗原（CEA）进行相关性检测分析。结果胆道恶性狭窄组54．1％的患者RDW升高,明显高于良性狭窄组的18．9％,差异有统计学意义（P〈0．05）。以RDW〉15．O％为界,发现其诊断恶性胆道狭窄的灵敏度和特异度分别为47％和81％。对于低位胆道梗阻（BismuthⅠ＋Ⅱ）,良恶性组间RDW值比较,差异有统计学意义（P〈0．001）,恶性组明显升高;对于高位胆道梗阻（Bismuth Ⅲ＋Ⅳ）,两者比较差异无统计学意义（P=0．505）。同为良性狭窄或者恶性狭窄时,不同狭窄部位的RDW之间差异无统计学意义（P均〉0．05）。相关性分析显示,RDW值与CA19-9（r=0．099,P：0．201）和CEA（r=0．115,P=0．152）均无明显相关性。CA19-9、CEA和RDW用于诊断恶性胆道狭窄的准确度分别为79％、69％和64％。结论RDW值检测对胆道梗阻的定性诊断具有一定的价值,可作为独立于CA19-9、CEA的生化指标,用于鉴别胆道良恶性肿瘤。     

血清和胆汁CEA、CA19-9对肝外胆管癌诊断的对比研究

目的探讨血清与胆汁CEA、CA19-9测定对肝外胆管癌诊断的对比意义。方法采用化学发光法检测34例肝外胆管癌的血清和胆汁CEA、CA19-9值。结果胆汁CEA高于血清CEA（P〈0.05）,血清CA19-9高于胆汁CA19-9（P〈0.05）;血清CEA、CA19-9灵敏度分别为11.8%、79.4%;胆汁CEA、CA19-9灵敏度分别为52.9%、55.9%。血清CA19-9的灵敏度高于其他三者。结论血清CA19-9对胆管癌的诊断价值高于血清与胆汁CEA和胆汁CA19-9。     

CA19-9对结石与肿瘤性胆道梗阻的临床判别价值

目的 评估血 CA19-9水平是否能作为结石与肿瘤性胆道梗阻的有效判别指标.方法 对2008年2月至2010年10月期间,我院113例经ERCP诊断为胆道梗阻患者的血CA19-9和直接胆红素水平行回顾性统计分析.结果 所有胆道梗阻患者中经ERCP诊断为良性胆道梗阻者62例,均为胆道结石;肿瘤性胆道梗阻51例,其中胰腺肿瘤24例,胆管肿瘤18例,十二指肠乳头肿瘤9例.CA19-9的中位数水平分别为胰腺肿瘤654.6 u/ml,胆管肿瘤410.3μ/ml,十二指肠乳头肿瘤259.1 μ/ml,胆道结石29.9 μ/ml.肿瘤性梗阻的CA19-9水平明显高于结石性.ROC曲线面积为0.880(0.810～0.951),判别结石与胆道梗阻的最佳Cut-off值为73.5 μ/ml.结石性梗阻中,CA19-9与血清胆红素水平呈正相关,而肿瘤性梗阻的CA19-9则与胆红素水平无明显相关性.结论 以73.5 μ/ml为CA19-9的参考界值,将为临床医生鉴别良恶性胆道梗阻提供相当有价值的参考信息.     

Alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 19-9-producing gallbladder cancer

We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase inLens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.     

Sensitivity of monoclonal antibodies to carcinoembryonic antigen,tissue polypeptide antigen,alpha-fetoprotein,carbohydrate antigen 50, and carbohydrate antigen 19-9 in the diagnosis of colorectal adenocarcinoma

PURPOSE: This study was designed to establish the sensitivity of monoclonal antibodies to carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), tissue polypeptide antigen (TPA), carbohydrate antigen 50 (CA 50), and carbohydrate antigen 19-9 (CA 19-9) and the efficacy of the joint determination of several tumor markers, as well as the dynamics of postoperative normalization of each marker in the absence of recurrence. MATERIALS AND METHODS: A prospective study was carried out in 100 patients subjected to surgical resection of colon adenocarcinoma. Serum concentrations of these markers were determined the day before surgery and seven days, two months, and six months after surgery. RESULTS: The results demonstrate that sensitivity increased as the disease spread and that CA 19-9 was the most sensitive tumor marker. The rate of false negatives was 40 percent for Dukes Stage A lesions, 19 percent for Dukes Stage B, 7 percent for Dukes Stage C, and 0 percent for Dukes Stage D. Determination of two markers (CA 19-9 and CEA) provided the greatest sensitivity in Stages A and D tumors (60 percent and 100 percent, respectively); the incidence did not change when measurements of other antigens were associated. For Stages B and C, determination of at least three markers was necessary, the association of CEA, TPA, and CA 19-9 being that which showed the greatest sensitivity, 78 percent and 91 percent, respectively. CONCLUSIONS: It would be advisable to include monoclonal antibody determination of CEA, TPA, and CA 19-9 in the diagnosis of adenocarcinoma, despite the fact that ultimate sensitivity will depend on the degree of tumor extension or on the presence of metastasis.     

Hepatocellular carcinoma producing carcinoembryonic antigen and carbohydrate antigen 19-9.

A case of hepatocellular carcinoma producing carcinoembryonic antigen and carbohydrate antigen 19-9 is reported. The serum level of carcinoembryonic antigen was 26,800 ng/ml and carbohydrate antigen 19-9, 5,500 U/ml on the final day. Immunohistochemical study revealed positive monoclonal antibodies for these two antigens within the cytoplasm of the hepatocellular carcinoma cells.     

Noninvasive diagnosis of advanced pancreatic cancer by real-time ultrasonography, carcinoembryonic antigen, and carbohydrate antigen 19-9

One-hundred-forty patients with clinical impression of pancreatic cancer were examined prospectively with three noninvasive tests: real-time ultrasonography, determination of serum carcinoembryonic antigen (CEA), and carbohydrate antigen (CA 19-9). Among them, 24 (17.1%) patients were found to have pancreatic cancer. The sensitivity of ultrasonography, CEA, and CA 19-9 was 72.9%, 70.8%, and 83.3%, respectively; the specificity was 94.0%, 77.6%, and 90.5%, respectively, and the diagnostic accuracy was 91.4%, 76.4%, and 89.3%, respectively. The combination of ultrasonography and determination of serum CA 19-9 had better sensitivity (95.8%), comparable specificity (84.5%), and comparable diagnostic accuracy (86.4%) to any individual test alone or any other combination. It was suggested that combined use of real-time ultrasonography and determination of serum CA 19-9 provided excellent noninvasive screening for patients suspected of having pancreatic cancer.     

Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic)

In this chapter the epidemiology, pathogenesis, and natural history of CBD stones (choledocholithiasis) and intrahepatic stones (hepatolithiasis) have been reviewed. Gallstones are extremely common in Western countries, where the prevalence of bile-duct stones is relatively low. In contrast, primary choledocholithiasis and hepatolithiasis appear to be more frequent in East Asian countries than in Western societies, where bile-duct stones are mostly secondary to gallbladder stones passing through the cystic duct. Primary bile-duct stones are composed predominantly of calcium bilirubinate, namely brown-pigment stones. The pathogenesis of primary bile-duct stones is based upon bile stasis and infection, which are associated with bile-duct strictures, extrahepatic anomalies and biliary parasites. In contrast, secondary stones are considered to originate from gallbladder stones, and are commonly composed of cholesterol. Congenital and acquired risk factors predisposing to bile-duct stones include anatomical anomalies, genetic diseases of bilirubin and cholesterol, bacterial infection, and socio-economic problems. Bile-duct stones typical present with fever, abdominal pain, and jaundice (Charcot's triad), and in severe cases also hypotension and mental confusion (Raynold's pentad) which predicts a poor clinical outcome. Furthermore, silent cholangiocarcinoma develops in 10% of the intrahepatic stone cases even after the removal of stones, and therefore the follow-up of these cases is of clinical importance.     

Isolation and culture of biliary epithelial cells from the biliary tract fraction of normal rats

ABSTRACT— A method has been developed for the isolation of a population of cells enriched in epithelial lining cells from the bile ducts of normal rats. The procedure utilized digestion by pronase of the white strands of biliary and connective tissue which remained after hepatocytes had been mechanically removed from collagenase-perfused liver. The resulting cell population was enriched in cells whose ultrastructure resembled that of the epithelial cells of intrahepatic bile ducts. Contamination with hepatocytes, hepatocyte nuclei and erythrocytes was less than 2%. The cells have been maintained in short-term culture. The major morphological change during the first 2 days of culture was proliferation of microvilli, but cell protein composition was unchanged when analysed by polyacrylamide gel electrophoresis. A rabbit antiserum against bovine hoof prekeratin was used to immunohistochemically stain the intermediate filaments of biliary epithelium and was shown to stain more than 90% of the cells in the isolated cell population.     

Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer

Although serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured before surgery for gastric carcinoma, this clinical significance is not fully understood. We evaluated a total of 549 patients with gastric cancer who underwent gastrectomy. Levels of CEA and CA19-9 were measured preoperatively in all patients. We retrospectively analyzed correlations between CEA or CA19-9 and clinicopathologic features, and estimated the prognostic utility of the tumor markers by analyzing clinicopathologic characteristics of the carcinoma as a function of seropositivity or negativity of the antigens in combination or by raising the levels. The positivity rates of CEA (> or =5 ng/mL) and CA19-9 (> or =37 U/mL) were 19.5% and 18%, respectively. Serum CEA and CA19-9 positivity significantly correlated with depth of invasion, hepatic metastasis, and curativity. Forty-nine patients positive for both CEA and CA19-9 had significantly higher frequencies of lymph node metastasis, deeper invasion by the tumor, lower rates of curative resection (p < 0.01), and higher rates of hepatic metastasis (p < 0.05) than 377 patients with normal levels of CEA and CA19-9. Surgical outcomes of patients who were CEA- and CA19-9-positive were poorer than those of patients with normal CEA and CA19-9 levels (p < 0.01). Significant correlation was found between serum CEA and CA19-9 level (p < 0.001, r = 0.24). Doubling the threshold level of serum positivity to 10 ng/mL (CEA) and 74 U/mL (CA19-9) improved the prognostic value of these factors. However, multivariate analysis using Cox's hazards model revealed that only CEA positivity using the doubled threshold value (10 ng/mL) (p = 0.04, hazard ratio = 1.7), nodal involvement (p = 0.01, hazard ratio = 1.9), and depth of invasion (p = 0.02 hazard ratio = 1.5) significantly predicted prognosis. Carcinoembryonic antigen positivity using the doubled threshold level (10 ng/mL) was an important prognostic factor in patients with gastric cancer.     

Secretion of biliary calcium is increased in dogs with pigment gallstones

We have previously demonstrated that gallbladder bile is supersaturated with calcium bilirubinate in a canine dietary model of pigment gallstones. Supersaturation resulted from combined increases in the concentrations of both biliary calcium and unconjugated bilirubin. The elevations in biliary calcium and unconjugated bilirubin concentrations remain unexplained but could possibly be due to increases in hepatic or ductular secretion, alterations in bile composition with respect to calcium- or bilirubin-binding affinity, decreases in absorption from the gallbladder lumen, or, in the case of unconjugated bilirubin, production within the lumen by hydrolysis of conjugated bilirubin. Here, we study a single possible cause for the observed increase in biliary calcium concentration during pigment gallstone formation in dogs. Secretion of calcium into bile in dogs with pigment gallstones before and after infusion of the bile salt, taurocholate, was compared to normal dogs. A significant increase in bile acid-independent bile flow and calcium output (CaO) was observed at any given bile acid output. Thus, plots of bile flow and CaO versus bile acid output yielded two separate functions in normal dogs and dogs with pigment gallstones. The slopes of these functions were similar, but intercepts extrapolated to zero bile acid output were markedly different, indicating that bile acid-independent, but not bile acid-dependent, bile flow and CaO was increased. The increase in CaO was not due to secretion of bile with increased concentrations of calcium but rather to the increases in the rate of bile flow. These findings might, in part, explain elevated calcium concentrations since increased amounts of calcium would be presented to the gallbladder in these animals during gallstone formation.This work was supported by a Veteran's Administration Merit Review Award and by NIH Grant 32130, National Institute of Diabetes, Digestive, and Kidney Diseases.