CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis

AIMS/BACKGROUND: Diagnosis of early cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis with available radiological methods is very difficult. This type of tumor is the second most common cause of mortality after liver failure in these patients. The recognition of CC is important for the selection of patients for, and the results of, liver transplantation (Ltx). In this study our aim was to investigate the value of measuring cancer markers (CA 19-9 and CEA) in patients with PSC for early diagnosis of CC. METHODS: 72 PSC patients who were followed at our institution for a long period were included in the study; 9 with CC and 63 without CC. Furthermore, nine patients with CC but without concomitant PSC were included, as well as 24 patients with various cholestatic liver diseases. Serum levels of CA 19-9 and CEA were measured, in 39 PSC patients without CC, on multiple occasions. Moreover, bile was collected during a diagnostic ERCP from 20 patients for measurements of CA 19-9 and CEA. RESULTS: In those PSC patients without CC during the follow-up and with more than one year of follow-up, 15 patients had increased values of CA 19-9 (>37 ng/ml) on some of the occasions. Four of them demonstrated large fluctuations (more than 100 ng/ml difference at different occasions) in serum levels of Ca 19-9. A significant correlation between high CA 19-9 values and serum alkaline phosphatase levels was observed in these patients. The sensitivity of CA 19-9 in detecting CC in PSC patients was only 63%. The sensitivity of CEA and the combination of CA 19-9 and CEA (marker product; King's College formula) were still lower (33%) although the specificity was relatively high (85%). Bile levels of the tumor markers did not demonstrate any clinically useful differences between the different patient groups. CONCLUSIONS: Tumor markers as a diagnostic tool in diagnosing CC in patients with PSC are unfortunately not as valuable as previously reported. The serum levels of CA 19-9 can rise temporarily in association with a "biochemical relapse" of PSC (increased values of serum alkaline phosphatase). The marker product of CA 19-9 and CEA has a low sensitivity but a relatively high specificity for the detection of CC in PSC patients.     

Markedly elevated serum CA 19-9 levels in association with a benign biliary stricture due to primary sclerosing cholangitis

We report on the case of a 55-year-old man with long-standing ulcerative colitis who developed jaundice. This led to a diagnosis of primary sclerosing cholangitis being made, with a dominant stricture in the common bile duct. Serum CA 19-9 was initially markedly raised at 26,321 U/mL but fell promptly into the normal range after stenting of the stricture. Long-term follow up of this patient has failed to show evidence of cholangiocarcinoma. We conclude that serum CA 19-9 levels need to be assessed in the clinical context of biliary obstruction and should ideally be measured after relief of that obstruction, as it may be falsely elevated due to benign biliary strictures.     

Assessment of serum and bile levels of CA19-9 and CA125 in cholangitis and bile duct carcinoma

In this study, CA19-9 and CA125 in serum and bile were measured to evaluate their diagnostic value in cholangitis and bile duct carcinoma. Patients were classified into three groups: group A, the control group, had cholelithiasis without infection (n = 23), group B had acute cholangitis (n = 25) and group C had bile duct carcinoma without bacterial infection (n = 18). All patients had undergone surgery, and bile and serum of the patients were measured for the two tumour markers by radio-immunoassay. The positivity rate for serum CA19-9 was 4.4% in the control group, 28.0% in group B and 61.1% in group C. The positivity rates for serum CA125 in groups control, B and C were 0%, 4% and 27.78% respectively. The diagnostic accuracy for bile duct carcinoma was 67.4% for both CA19-9 or CA125. The concentration of CA19-9 in bile was more than 1200 ng/mL in 72% of patients with acute cholangitis, in 61.1% of all patients with bile duct carcinoma and 0% in the control group. The frequency of concentrations of CA125 in bile greater than 200 ng/mL was 38.89% in bile duct carcinoma and none was observed in the control or acute cholangitis groups. In conclusion, the concentration of CA19-9 was increased not only by the tumour itself, but also by infection. In the diagnosis of bile duct carcinomas, the sensitivity of CA125 was low but its specificity was very high.     

A case of common bile duct stone with cholangitis presenting an extraordinarily high serum CA19-9 value.

A 63-year-old male complained of right upper abdominal pain and jaundice. Laboratory data on admission showed hyperbilirubinemia, elevation of biliary enzymes and an extraordinarily high value of serum CA19-9 (60,000 U/ml). Diagnostic imaging modalities including abdominal ultrasonogram, abdominal CT and PTC suggested a stone impaction of the common bile duct. Jaundice subsided after PTC-drainage in association with decreasing serum CA19-9 value, which returned to the normal level six weeks later. Spontaneous delivery of the stone via the fistula was confirmed by cholangiography through the drainage tube. Though there are few reports of such a high serum CA19-9 level, the possibility of benign biliary tract disease should be considered in patients showing an extraordinarily high serum CA19-9 value.     

Impact of dominant stenoses on the serum level of the tumor marker CA19-9 in patients with primary sclerosing cholangitis

BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing hepatobiliary tumors. The tumor marker CA19-9 was claimed to indicate the occurrence of bile duct carcinoma. This study aimed to assess whether increased serum levels of CA19-9 in PSC patients with dominant stenoses indicate bile duct carcinoma. METHODS: The study cohort comprised 106 patients treated over a median time of 5.0 years (range 0.5 - 13 years). All patients were treated with ursodeoxycholic acid (UDCA) and whenever they developed dominant stenoses by endoscopic dilatation of these stenoses. In endoscopically treated patients, CA19-9 levels were measured before and 3, 6, 12 and 24 months after endoscopic dilatation. RESULTS: Of the 106 patients, 22 carcinoma-free patients and 3 patients with bile duct carcinoma had elevated CA 19 - 9 levels. In 14 out of 25 patients with elevated CA19-9 levels, dominant stenoses were diagnosed and treated by endoscopic dilatation. In 71.4 % of the endoscopically treated patients, CA19-9 levels decreased following the endoscopic intervention. CONCLUSIONS: In PSC patients, increased serum levels of CA19-9 are rarely due to the development of bile duct carcinoma. In patients with dominant stenoses, the relief of biliary obstruction by endoscopic dilatation may lead to a decrease of the serum levels of CA19-9.     

The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis

OBJECTIVES: The diagnosis of cholangiocarcinoma is often difficult, making management approaches problematic. A reliable serum tumor marker for cholangiocarcinoma would be a useful additional diagnostic test. Previous studies have demonstrated that elevated serum concentrations of CA 19-9, a tumor-associated antigen, have good sensitivity and specificity for cholangiocarcinoma in patients with primary sclerosing cholangitis. However, the value of this tumor marker for cholangiocarcinoma unassociated with primary sclerosing cholangitis is unclear. Thus, the aims of this study were to determine the usefulness of a serum CA 19-9 determination in the diagnosis of de novo cholangiocarcinoma. METHODS: We prospectively measured serum CA 19-9 concentrations in patients with cholangiocarcinoma (n = 36), nonmalignant liver disease (n = 41), and benign bile duct strictures (n = 26). Serum CA 19-9 concentrations were measured by an immunoradiometric assay (CIS Bio International) without knowledge of the clinical diagnosis. RESULTS: The sensitivity of a CA 19-9 value >100 U/ml in diagnosing cholangiocarcinoma was 53%. When compared with the nonmalignant liver disease and the benign bile duct stricture groups, the true negative rates were 76% and 92%, respectively. Patients with unresectable cholangiocarcinoma had significantly greater mean CA 19-9 concentrations compared to patients with resectable cholangiocarcinoma. CONCLUSIONS: These data suggest that the serum CA 19-9 determination is a useful addition to the available tests for the differential diagnosis of cholangiocarcinoma.     

CA 19–9 and CE A are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis

Abstract: Aims/Background: Diagnosis of early cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis with available radiological methods is very difficult. This type of tumor is the second most common cause of mortality after liver failure in these patients. The recognition of CC is important for the selection of patients for, and the results of, liver transplantation (Ltx). In this study our aim was to investigate the value of measuring cancer markers (CA 19–9 and CEA) in patients with PSC for early diagnosis of CC. Methods: 72 PSC patients who were followed at our institution for a long period were included in the study; 9 with CC and 63 without CC. Furthermore, nine patients with CC but without concomitant PSC were included, as well as 24 patients with various cholestatic liver diseases. Serum levels of CA 19–9 and CEA were measured, in 39 PSC patients without CC, on multiple occasions. Moreover, bile was collected during a diagnostic ERCP from 20 patients for measurements of CA 19–9 and CEA. Results: In those PSC patients without CC during the follow-up and with more than one year of follow-up, 15 patients had increased values of CA 19–9 (>37 ng/ml) on some of the occasions. Four of them demonstrated large fluctuations (more than 100 ng/ml difference at different occasions) in serum levels of Ca 19–9. A significant correlation between high CA 19–9 values and serum alkaline phosphatase levels was observed in these patients. The sensitivity of CA 19–9 in detecting CC in PSC patients was only 63%. The sensitivity of CEA and the combination of CA 19–9 and CEA (marker product; King's College formula) were still lower (33%) although the specificity was relatively high (85%). Bile levels of the tumor markers did not demonstrate any clinically useful differences between the different patient groups. Conclusions: Tumor markers as a diagnostic tool in diagnosing CC in patients with PSC are unfortunately not as valuable as previously reported. The serum levels of CA 19–9 can rise temporarily in association with a “biochemical relapse” of PSC (increased values of serum alkaline phosphatase). The marker product of CA 19–9 and CEA has a low sensitivity but a relatively high specificity for the detection of CC in PSC patients.     

A case of primary sclerosing cholangitis

A case of primary sclerosing cholangitis (PSC) is reported. A 16 year-old female developed right hypochondralgia and nausea without jaundice. Examination on admission showed elevation of SGOT, SGPT, Al-P, gamma-GTP and LAP activities, but T-Bil, AFP and CEA were within normal limits. Peripheral eosinocytes increased by 10%, and tests for HBsAg, antiHBs, antimitochondrial antibody and anti-smooth muscle antibody were all negative. ERCP revealed a narrowing of the proximal portion of the common the hepatic duct, and beading of the intrahepatic bile ducts. Liver scintigram and CT revealed no tumors in the liver, biliary tract or pancreas. Laparoscopy showed a smooth liver without swelling and a slightly swollen gallbladder. Histologically, the liver biopsy specimen showed ductal proliferation of small interlobular bile ducts and periductal fibrosis. No bile plugs, granuloma or distinct cholangitis were observed. No abnormal findings, including evidence of inflammatory bowel disease, were detected by barium enema. At present, one year after discharge, although her symptoms and liver function test abnormalities continue, she has been attending high school. Although 58 cases of PSC have been reported in Japan, juvenile cases occurring before the third decade number only 3 including ours.     

Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn's disease. A case report

The prevalence of primary sclerosing cholangitis (PSC) in Crohn's disease (CD) patients is up to 8.5%. Although cholangiocarcinoma may complicate long-standing PSC in one third of the cases if follow-up is extended long enough, hepatocellular carcinoma (HCC) is a rare complication of PSC. The concomitant presence of PSC, HCC and CD have been reported sporadically. We discuss here a case of association of these three conditions.     

Elevated serum levels of tumor marker CA19-9 in acute cholangitis

The purpose of the present study was to examine the relationship between the tumor marker, CA19-9, and benign biliary tract disease. We measured serum and bile CA19-9 in 40 patients with (1) symptomatic cholelithiasis (N=14), (2) common bile duct obstruction without cholangitis (N=8), (3) acute cholangitis secondary to gallstone disease (N=7), and (4) acute cholecystitis (N=11). All seven patients with acute cholangitis had marked elevations of serum CA19-9 (range 190-32,000 units/ml; 75 units/ml cutoff), whereas none of the patients in the other groups had elevated levels despite similar degrees of cholestasis and similarly high levels of CA19-9 in gallbladder and common duct bile (range 7.3×10⁴–2.3×10⁹ units/ml). Of the three patients with cholangitis in whom CA19-9 levels were followed serially, all had rapid return of levels to normal after successful treatment. We conclude that the tumor marker CA19-9 is markedly elevated in the serum of patients with acute cholangitis but not in patients with other forms of benign biliary tract disease.     

A case of segmental primary sclerosing cholangitis

A 74-year-old man was admitted to the Yokohama City University School of Medicine for investigation of high values of ALP and Y-GTP. Radiographic examinations, including abdominal computed tomography and percutaneous transhepatic cholangiography, strongly suggested bile duct cancer in the hepatic hilus. After left lobectomy, pathological examination disclosed segmental primary sclerosing cholangitis. Clinical examination cannot always distinguish primary sclerosing cholangitis from cancer. We report a case of segmental primary sclerosing cholangitis and discuss the diagnosis and the treatment of this disease.     

Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study

BackgroundPrimary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids.AimsThis study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors.MethodsSeventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry. Serum samples from cholestatic patients were compared with those of non-cholestatic donors.ResultsThe concentration of total bile acids, taurine and glycine conjugates of primary bile acids was elevated in both patients with primary biliary cirrhosis and primary sclerosing cholangitis when compared to non-cholestatic donors. Samples from primary sclerosing cholangitis patients displayed reduced levels of secondary acids, when compared to non cholestatic and primary biliary cirrhosis sera. The ratio of total glycine versus total taurine conjugates was reduced in patients with primary biliary cirrhosis, but not in primary sclerosing cholangitis.ConclusionThe present study suggests that circulating bile acids are altered differentially in primary biliary cirrhosis and primary sclerosing cholangitis patients.     

胆总管结石对血清CA19-9的影响

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.     

血清糖链抗原19-9对梗阻性黄疸患者发生急性胆管炎的预测价值

目的探讨梗阻性黄疸患者发生急性胆管炎的预测因子。方法回顾性分析海口市第四人民医院2010年10月-2015年10月收治的358例胆总管结石合并梗阻性黄疸患者的临床资料。根据患者是否发生急性胆管炎,分为急性胆管炎组(n=223)和梗阻性黄疸组(n=135)。比较两组患者的年龄、性别和合并症,评估血清肿瘤标志物及肝功能指标的异常与急性胆管炎发生的关系。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。选取有统计学意义的指标构建受试者工作特征曲线(ROC),评价其对急性胆管炎诊断的敏感度和特异度。结果急性胆管炎组血清糖链抗原(CA)19-9、CA12-5水平明显高于梗阻性黄疸组[(82.33±23.01)k U/L vs(36.75±12.58)k U/L,(30.21±9.59)k U/L vs(18.62±5.27)k U/L],差异均有统计学意义(t值分别为11.028、8.597,P值均0.001)。ROC曲线分析显示,血清CA19-9、CA12-5曲线下面积分别为0.891、0.705,对应诊断准确度最高的临界值分别为61.01 k U/L、22.56 k U/L,敏感度分别为82.1%、77.6%,特异度分别为79.8%、69.5%。结论血清CA19-9升高对胆总管结石合并梗阻性黄疸发生急性胆管炎有较大的预测价值。     

The significance of serum IgG4 and CA19-9, autoantibodies in diagnosis and differential diagnosis of IgG4-related sclerosing cholangitis

Objective: To investigate the value of serum levels of IgG₄ and CA19-9, and autoantibodies in the diagnosis of IgG₄-related sclerosing cholangitis (IgG₄-SC).

Methods: We detected the serum IgG₄ and CA19-9 of 45 IgG₄-SC patients, 173 non-IgG₄-SC patients and 48 healthy controls by immunoassay and chemiluminescence, respectively, with antinuclear antibody (ANA), anti-neutrophil antibody (ANCA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA) level detected by indirect immunofluorescence. Then analyze the detection results.

Results: (1) The positive rates of ANA, ANCA, SMA and AMA in patients with IgG₄-SC were 40%, 6.67%, 0 and 2.22%. Among them, the positive rate of ANA was significantly higher than that of the healthy control group (p?4-SC group (p?4 and CA19-9 increased significantly in patients with IgG₄-SC compared with the healthy controls (p?4 and CA19-9 were 0.9750 and 0.6498, respectively (p?Conclusion: The high levels of serum IgG₄ and CA19-9, and autoantibodies detections are of great important clinical value in diagnosis and differential diagnosis of IgG₄-SC.