临床经验 Open Access
Copyright ©The Author(s) 2010. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2010-02-08; 18(4): 400-403
在线出版日期: 2010-02-08. doi: 10.11569/wcjd.v18.i4.400
胆总管结石对血清CA19-9的影响
谢华平, 问明瑶
谢华平, 华中科技大学同济医学院附属同济医院消化内科 湖北省武汉市 430030
问明瑶, 华中科技大学同济医学院附属同济医院耳鼻喉-头颈外科 湖北省武汉市 430030
作者贡献分布: 此课题由谢华平设计; 研究过程由谢华平与问明瑶完成; 分析工具部分由谢华平提供; 数据分析由谢华平与问明瑶完成; 本论文写作由谢华平完成.
通讯作者: 谢华平, 主治医师, 430030, 湖北省武汉市, 华中科技大学同济医学院附属同济医院消化内科. rainerxie@126.com
收稿日期: 2009-11-21
修回日期: 2009-12-15
接受日期: 2009-12-21
在线出版日期: 2010-02-08

目的: 探讨胆总管结石对血清CEA、CA19-9的影响.

方法: 回顾经ERCP或手术证实、治疗的胆总管结石患者68例, 分析血清CEA, 特别是血清CA19-9与胆总管结石患者总胆红素、直接胆红素的相关性; 并对20例血清CA19-9值超过正常上限两倍以上的患者统一时间进行随访, 分析治疗前后血清CA19-9变化值与总胆红素、直接胆红素变化值的相关性.

结果: 血清CA19-9与总胆红素、直接胆红素存在明显相关性(r = 0.813, 0.786, 均P = 0.000); 血清CEA与总胆红素、直接胆红素不存在相关性; 治疗前后血清CA19-9变化值与总胆红素、直接胆红素变化值存在明显相关性(r = 0.787, 0.806, 均P = 0.000).

结论: 胆总管结石合并阻塞性黄疸时, 可导致血清CA19-9升高, 此时血清CA19-9作为肿瘤标志物的特异性差.

关键词: 胆总管结石; 阻塞性黄疸; CA19-9
引文著录: 谢华平, 问明瑶. 胆总管结石对血清CA19-9的影响. 世界华人消化杂志 2010; 18(4): 400-403
Elevated serum CA19-9 levels in patients with common bile duct stones
Hua-Ping Xie, Ming-Yao Wen
Hua-Ping Xie, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Ming-Yao Wen, Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Correspondence to: Hua-Ping Xie, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. rainerxie@126.com
Received: November 21, 2009
Revised: December 15, 2009
Accepted: December 21, 2009
Published online: February 8, 2010

AIM: To observe changes in serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels in patients with common bile duct stones.

METHODS: A total of 68 patients with surgically confirmed common bile duct stones were included in the study. The correlations of serum CEA and CA19-9 with total bilirubin and direct bilirubin were analyzed. For 20 patients whose serum CA19-9 levels were twice more than the upper limit of normal values, a consistent follow-up was conducted to analyze the correlations of the difference between preoperative and postoperative serum CA19-9 levels with total bilirubin and direct bilirubin.

RESULTS: Significant correlations were noted between serum CA19-9 and total bilirubin and direct bilirubin (r = 0.813 and 0.786, respectively; both P = 0.000) in patients with common bile duct stones. No significant correlations were noted between serum CEA and total bilirubin and direct bilirubin. The difference between preoperative and postoperative serum CA19-9 levels has significant correlations with total bilirubin and direct bilirubin (r = 0.787 and 0.806, respectively; both P = 0.000).

CONCLUSION: Elevated serum CA19-9 levels are noted in patients with concurrent common bile duct stones and obstructive jaundice. In these patients, serum CA19-9 as a tumor marker has a poor specificity.

Key Words: Common bile duct stone; Obstructive jaundice; CA19-9
0 引言

糖类抗原CA19-9在上消化系肿瘤细胞中普遍表达[1], 其测定是临床上诊断恶性胰胆疾病的可靠手段[2]. 但是, 很多的良性疾病也可以导致血清CA19-9升高[3-9]. 本文结合胆总管结石患者接受ERCP或手术治疗前后的情况, 对胆总管结石导致血清CA19-9升高进行分析.

1 材料和方法
1.1 材料

收集2004-01/2009-08华中科技大学同济医学院附属同济医院经ERCP或者外科手术治疗的胆总管结石患者68例, 其中男40例, 女28例, 年龄17-83(平均54)岁. 所用病例均无肿瘤病史及罹患肿瘤的依据. 术前均进行相关的影像学检查(包括腹部超声、CT或者MRI检查)提示存在胆总管结石, 再经ERCP或者手术证实及治疗.

1.2 方法

术前检查此类患者的胆红素等生化指标、血清CEA(本院参考值: 0-5 µg/L)及CA19-9(本院参考值: 0-37 kU/L)等肿瘤标志物. 对血清CA19-9升高超过正常值上限两倍以上(CA19-9>74 kU/L)的患者进行随访. 根据血清总胆红素的水平, 将所有患者分成3组: 重度黄疸组(总胆红素大于170 µmol/L)、轻-中度黄疸组(总胆红素介于34-170 µmol/L)、无明显黄疸组(总胆红素小于34 µmol/L), 并统计患者的血清总胆红素、直接胆红素、CEA、CA19-9值.

统计学处理 应用统计软件包SPSS18.0, 计量资料数据用mean±SD表示, 进行近似t检验或配对t检验及相关性分析, P<0.05为差异有统计学意义.

2 结果
2.1 血清CA19-9、CEA与血清总胆红素、直接胆红素的关系

血清CA19-9与血清总胆红素、直接胆红素明显相关(r = 0.813, P = 0.000; r = 0.786, P = 0.000). 血清CEA与血清总胆红素、直接胆红素不相关(r = 0.061, P = 0.622; r = 0.109, P = 0.378, 表1).

表1 各组患者血清CA19-9、CEA、总胆红素及直接胆红素水平.
分组n总胆红素(µmol/L)直接胆红素(µmol/L)CEA(µg/L)CA-199(kU/L)
重度黄疸组8252.65±60.65172.10±33.542.95±7.051263.70±719.73
轻-中度黄疸组2783.87±35.8349.86±24.732.43±0.92123.51±231.29
无明显黄疸组3312.83±7.053.90±3.002.14±0.659.09±9.41
2.2 黄疸程度不同组间血清CA19-9、CEA值的比较

重度黄疸组与轻-中度黄疸组、重度黄疸组与无明显黄疸组、轻-中度黄疸组与无明显黄疸组之间血清CA19-9的水平均有统计学意义(t = 4.415, P = 0.003; t = 4.894, P = 0.002; t = 2.326, P = 0.028). 重度黄疸组与轻-中度黄疸组、重度黄疸组与无明显黄疸组、轻-中度黄疸组与无明显黄疸组血清CEA的水平均无统计学意义(t = 0.701, P = 0.504; t = 1.111, P = 0.302; t = 1.378, P = 0.175).

2.3 治疗前、后血清CA19-9变化分析

治疗后, 随着血清总胆红素及直接胆红素的下降, 血清CA19-9值也明显下降, 血清CA19-9的变化值(640.69 kU/L±709.00 kU/L)与总胆红素变化值(144.45 μmol/L±92.71 μmol/L)、直接胆红素变化值(93.93 μmol/L±62.30 μmol/L)存在明显相关(r = 0.078, 0.806, 均P = 0.000).

3 讨论

CA19-9属于Ⅰ型糖类抗原, 主要分布于正常胎儿胰腺、胆囊、肝、肠等组织, 成人则存在于胰、胆管上皮处, 以唾液黏蛋白形式存在于血清中, 含量甚微. 自从Korprowski等[10]发现人类结肠肿瘤细胞产生CA19-9以来, 血清CA19-9作为临床常用的肿瘤标志物, 应用于胰腺癌、胆管癌、结肠癌、胃癌等恶性疾病的诊断、治疗、预后和复发的判断[11-22]. 但也发现, 临床上很多良性疾病可以引起CA19-9升高[3-9]. 原因可能是与半抗原结合的载体, 在组织损伤或破坏时, 神经苷脂增加, 进入血液循环, 这时单克隆抗体只识别抗原, 导致假阳性增加[23]. 本文的资料显示, 胆总管结石引起CA19-9升高, 与总胆红素及直接胆红素明显相关, 而且总体趋势而言, 这种CA19-9的升高随着黄疸的程度增加而增加, 又随着黄疸的下降而下降. 这说明阻塞性黄疸可引起CA19-9值的升高, 这与有关文献[3,8,9,24-29]提示良性疾病引起阻塞性黄疸可导致CA19-9升高的报道相符. 因而在阻塞性黄疸时, 血清CA19-9作为肿瘤标志物的特异性差, 这与相关文献[16,19,30,31]报道CA19-9作为胰腺癌、胆管癌等的肿瘤标志物特异性不高相符. 在解除阻塞性黄疸后, 血清CA19-9又可以恢复到正常水平, 这与Marrelli等[28]的报道相符. 因而血清CA19-9值升高而并无黄疸或者黄疸程度不足以解释时, 或者黄疸减退后CA19-9值仍保持高值甚或有增加趋势时, 仍需警惕肿瘤的可能性.

癌胚抗原(CEA)在1965年由Gold等[32]和Chen等[34]进行了描述, 是临床常用的肿瘤标志物, 也应用于消化系恶性疾病, 包括引起阻塞性黄疸的胰腺癌、胆管癌的诊断、治疗、预后及复发的评估[17,22,30,33-38]. 本研究中, 即使合并明显黄疸的胆总管结石患者, 血清CEA也在正常范围, 血清CEA与总胆红素、直接胆红素也无明显关联. 鉴于CEA对引起阻塞性黄疸的恶性肿瘤有一定的灵敏性和特异性, 在阻塞性黄疸时, 血清CEA的检测, 可能有利于良、恶性疾病的鉴别.

评论
背景资料

CA19-9是临床常用的肿瘤标志物, 对引起阻塞性黄疸的胰腺癌、胆管癌等均有一定的诊断价值. 但一些良性疾病合并阻塞性黄疸时, 也可以引起CA19-9升高. 本文结合胆总管结石患者相关临床资料, 分析治疗前的肿瘤标志物CA19-9、CEA与总胆红素、直接胆红素的关联性, 以及治疗前后CA19-9变化与总胆红素、直接胆红素变化的关联性.

同行评议者

黄恒青, 主任医师, 福建省第二人民医院消化内科

研发前沿 黄河等用免疫组织化学法发现肝癌细胞中BMP2的表达强度明显低于肝癌癌旁组织, 提示PHC发生可能与肝细胞中BMP2的含量减少有关.

相关报道

Marrelli等报道, 良性疾病引起的阻塞性黄疸中, 61%的患者有CA19-9升高. 在解除阻塞性黄疸的患者中, 38例恶性肿瘤中有18例患者, 以及几乎所有的良性疾病患者CA19-9下降. 在成功解除阻塞性黄疸的情况下, CA19-9保持不变或者测量值大于90 kU/L, 强烈提示恶性原因所致的阻塞性黄疸.

同行评价

胆总管结石合并阻塞性黄疸时, 血清CA19-9升高十分常见, 本文回顾分析认为血清CA19-9作为肿瘤标记物的特异性差, 对临床具有一定的指导意义.

编辑:李军亮 电编:何基才

1.  Atkinson BF, Ernst CS, Herlyn M, Steplewski Z, Sears HF, Koprowski H. Gastrointestinal cancer-associated antigen in immunoperoxidase assay. Cancer Res. 1982;42:4820-4823.  [PubMed]  [DOI]
2.  Steinberg W. The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol. 1990;85:350-355.  [PubMed]  [DOI]
3.  Robertson AG, Davidson BR. Mirizzi syndrome complicating an anomalous biliary tract: a novel cause of a hugely elevated CA19-9. Eur J Gastroenterol Hepatol. 2007;19:167-169.  [PubMed]  [DOI]
4.  Ito S, Gejyo F. Elevation of serum CA19-9 levels in benign diseases. Intern Med. 1999;38:840-841.  [PubMed]  [DOI]
5.  Maestranzi S, Przemioslo R, Mitchell H, Sherwood RA. The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA. Ann Clin Biochem. 1998;35:99-103.  [PubMed]  [DOI]
6.  Mauer KR, Lopatin RN, Hoffman WA, Grossman ET, Russo RD. Decrease in a markedly elevated CA19-9 level after stenting of a benign pancreatic ductal stricture. Gastrointest Endosc. 1995;42:261-263.  [PubMed]  [DOI]
7.  Ye C, Ito K, Komatsu Y, Takagi H. Extremely high levels of CA19-9 and CA125 antigen in benign mucinous ovarian cystadenoma. Gynecol Oncol. 1994;52:267-271.  [PubMed]  [DOI]
8.  Murohisa T, Sugaya H, Tetsuka I, Suzuki T, Harada T. A case of common bile duct stone with cholangitis presenting an extraordinarily high serum CA19-9 value. Intern Med. 1992;31:516-520.  [PubMed]  [DOI]
9.  Turtel PS, Kreel I, Israel J, Frager D, Berman D. Elevated CA19-9 in a case of Mirizzi's syndrome. Am J Gastroenterol. 1992;87:355-357.  [PubMed]  [DOI]
10.  Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5:957-971.  [PubMed]  [DOI]
11.  Park IJ, Choi GS, Jun SH. Prognostic value of serum tumor antigen CA19-9 after curative resection of colorectal cancer. Anticancer Res. 2009;29:4303-4308.  [PubMed]  [DOI]
12.  Formica V, Massara MC, Portarena I, Fiaschetti V, Grenga I, Del Vecchio Blanco G, Sileri P, Tosetto L, Skoulidis F, Pallone F. Role of CA19.9 in predicting bevacizumab efficacy for metastatic colorectal cancer patients. Cancer Biomark. 2009;5:167-175.  [PubMed]  [DOI]
13.  Kim YC, Kim HJ, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI, Shin JH. Can preoperative CA19-9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma? J Gastroenterol Hepatol. 2009;24:1869-1875.  [PubMed]  [DOI]
14.  Snozek CL, Mascarenhas RC, O'Kane DJ. Use of cyst fluid CEA, CA19-9, and amylase for evaluation of pancreatic lesions. Clin Biochem. 2009;42:1585-1588.  [PubMed]  [DOI]
15.  Waraya M, Yamashita K, Katagiri H, Ishii K, Takahashi Y, Furuta K, Watanabe M. Preoperative serum CA19-9 and dissected peripancreatic tissue margin as determiners of long-term survival in pancreatic cancer. Ann Surg Oncol. 2009;16:1231-1240.  [PubMed]  [DOI]
16.  Li YG, Zhang N. Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma. Dig Liver Dis. 2009;41:605-608.  [PubMed]  [DOI]
17.  Kim HJ, Lee KW, Kim YJ, Oh DY, Kim JH, Im SA, Lee JS. Chemotherapy-induced transient CEA and CA19-9 surges in patients with metastatic or recurrent gastric cancer. Acta Oncol. 2009;48:385-390.  [PubMed]  [DOI]
18.  Wong D, Ko AH, Hwang J, Venook AP, Bergsland EK, Tempero MA. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37:269-274.  [PubMed]  [DOI]
19.  Zhang S, Wang YM, Sun CD, Lu Y, Wu LQ. Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma. World J Gastroenterol. 2008;14:3750-3753.  [PubMed]  [DOI]
20.  Smith RA, Bosonnet L, Ghaneh P, Raraty M, Sutton R, Campbell F, Neoptolemos JP. Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma. Dig Surg. 2008;25:226-232.  [PubMed]  [DOI]
21.  Smith RA, Ghaneh P, Sutton R, Raraty M, Campbell F, Neoptolemos JP. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. J Gastrointest Surg. 2008;12:1422-1428.  [PubMed]  [DOI]
22.  Qin XL, Wang ZR, Shi JS, Lu M, Wang L, He QR. Utility of serum CA19-9 in diagnosis of cholangiocarcinoma: in comparison with CEA. World J Gastroenterol. 2004;10:427-432.  [PubMed]  [DOI]
23.  邓 辉洲, 周 载平, 陈 宏, 胡 泽民. 阻塞性胆道疾病中血清CA199水平分析. 中华普通外科学文献(电子版). 2008;2:46-47.  [PubMed]  [DOI]
24.  Principe A, Del Gaudio M, Grazi GL, Paolucci U, Cavallari A. Mirizzi syndrome with cholecysto-choledocal fistula with a high CA19-9 level mimicking biliary malignancies: a case report. Hepatogastroenterology. 2003;50:1259-1262.  [PubMed]  [DOI]
25.  Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26:474-479.  [PubMed]  [DOI]
26.  Ohshio G, Manabe T, Watanabe Y, Endo K, Kudo H, Suzuki T, Tobe T. Comparative studies of DU-PAN-2, carcinoembryonic antigen, and CA19-9 in the serum and bile of patients with pancreatic and biliary tract diseases: evaluation of the influence of obstructive jaundice. Am J Gastroenterol. 1990;85:1370-1376.  [PubMed]  [DOI]
27.  Albert MB, Steinberg WM, Henry JP. Elevated serum levels of tumor marker CA19-9 in acute cholangitis. Dig Dis Sci. 1988;33:1223-1225.  [PubMed]  [DOI]
28.  Marrelli D, Caruso S, Pedrazzani C, Neri A, Fernandes E, Marini M, Pinto E, Roviello F. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg. 2009;198:333-339.  [PubMed]  [DOI]
29.  Sheen-Chen SM, Sun CK, Liu YW, Eng HL, Ko SF, Kuo CH. Extremely elevated CA19-9 in acute cholangitis. Dig Dis Sci. 2007;52:3140-3142.  [PubMed]  [DOI]
30.  Ni XG, Bai XF, Mao YL, Shao YF, Wu JX, Shan Y, Wang CF, Wang J, Tian YT, Liu Q. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol. 2005;31:164-169.  [PubMed]  [DOI]
31.  秦 兴雷, 石 莉, 王 林. 胆道良恶性病变中CA19-9检测的临床意义. 世界华人消化杂志. 1999;7:814-815.  [PubMed]  [DOI]
32.  Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467-481.  [PubMed]  [DOI]
33.  Klapdor R, Bahlo M, Babinsky A. Further evidence for prolongation of survival of pancreatic cancer patients by efficacy orientated sequential polychemotherapy (EOSPC) based on serial tumor marker determinations (CA 19-9/CEA). Anticancer Res. 2005;25:1687-1691.  [PubMed]  [DOI]
34.  Chen CY, Shiesh SC, Tsao HC, Lin XZ. The assessment of biliary CA 125, CA 19-9 and CEA in diagnosing cholangiocarcinoma--the influence of sampling time and hepatolithiasis. Hepatogastroenterology. 2002;49:616-620.  [PubMed]  [DOI]
35.  Charalabopoulos K, Kotsalos A, Batistatou A, Charalabopoulos A, Peschos D, Vezyraki P, Kalfakakou V, Metsios A, Charalampopoulos A, Macheras A. Serum and tissue selenium levels in gastric cancer patients and correlation with CEA. Anticancer Res. 2009;29:3465-3467.  [PubMed]  [DOI]
36.  D'Armento G, Daniele L, Mariani S, Ottaviani D, Mussa A, Cassoni P, Sapino A, Bussolati G. Added value of combined gene and protein expression of CK20 and CEA in non-macroscopically involved lymph nodes of colorectal cancer. Int J Surg Pathol. 2009;17:93-98.  [PubMed]  [DOI]
37.  Yamamoto M, Baba H, Toh Y, Okamura T, Maehara Y. Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients. J Cancer Res Clin Oncol. 2007;133:471-476.  [PubMed]  [DOI]
38.  Lee IK, Kim do H, Gorden DL, Lee YS, Sung NY, Park GS, Kim HJ, Kang WK, Park JK, Ahn CH. Prognostic value of CEA and CA 19-9 tumor markers combined with cytology from peritoneal fluid in colorectal cancer. Ann Surg Oncol. 2009;16:861-870.  [PubMed]  [DOI]