Radioimmunoscintigraphy using monoclonal antibodies to CEA, CA 19-9 and CA 125

131I labelled F (ab')2 fragments of monoclonal antibodies against CA 19-9 and CEA ("radioimmunococktail" IMACIS 1) were used in a prospective study (n = 60 patients) and in a retrospective study (n = 32 patients) for the detection of colorectal carcinomas (n = 67) and other gastrointestinal CEA/CA 19-9-producing tumors (n = 32). Sensitivity was 82% and specificity 90%. Immunoscintigraphy proved useful and complementary to CT scan and sonography, especially in the diagnosis of pelvic recurrences and intra-abdominal metastases. In addition, monoclonal antibody OC 125 (IMACIS 2) was used for the detection of ovarian carcinomas (n = 10) and other CA 125 producing tumors. Immunoscintigraphy was positive in all patients (n = 18) suggesting that this radioimmunological approach could be of use in the staging, therapeutic control and earlier diagnosis of recurrent epithelial ovarian carcinoma.     

CA 19-9 assay in patients with extrahepatic cholestatic jaundice

Serum concentrations of the CA 19-9 tumour marker were determined in 35 patients with histologically proven bilio-pancreatic malignancies associated with obstructive jaundice and in 35 patients with benign extrahepatic jaundice due to choledocholithiasis. At a cut-off level of 37 U/ml the sensitivity of this assay was 82.8%, but the specificity was very low (45.7%). Thus CA 19-9 can not be employed to differentiate between malignant and benign extrahepatic jaundice. Serial samples of CA 19-9 were achieved in 7 patients with benign and in 6 patients with malignant biliary obstruction, before and after the disappearance of jaundice. Serum concentrations of this tumour-antigen returned to normal concurrently with the bilirubin values only in patients with benign obstruction, remaining unchanged in all cases of malignancies. The data suggest that patients with extrahepatic jaundice should be evaluated by other examinations or by collecting serial samples for this assay.     

肺癌患者血清CEA，CA19-9，CA125 及CA153 围手术期动态监测的临床 意义

目的:探讨动态监测肺癌患者围手术期血清CEA、CA19-9、CA125及CA153水平变化的临床意义。方法:随机选取2014年5月至2015年5月收治的肺癌患者58例为研究对象,另选取同期在我院接受体检的健康人群15例为对照组。分别测定肺癌患者手术前及术后1天、1周、1个月、3个月的血清CEA、CA19-9、CA125、CA153水平,并与对照组的上述各血清肿瘤标志物进行比较。结果:肺癌患者术前空腹血清CEA、CA19-9、CA125、CA153水平明显高于对照组,差异具有统计学意义(P0.01)。肺癌患者术后1天、1周、1个月及3个月的血清CEA、CA19-9、CA125、CA153水平明显低于术前,差异具有统计学意义(P0.05)。肺癌患者术后1个月的平均空腹血清CEA、CA19-9、CA125、CA153水平高于术后3个月平均水平,但差异不具有统计学意义(P0.05)。结论:对肺癌患者的血清CEA、CA19-9、CA125、CA153水平进行围手术期动态监测有助于评估手术治疗效果。     

Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis

BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test. RESULTS: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels. CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.     

Serum levels and thyroid tissue expression of CA50 and CA 19-9 in patients with thyroid tumor.

A 77-year-old man was admitted to the hospital with a thyroid nodule. The levels of serum tumor-associated carbohydrate antigens (CA 50, CA 19-9) and thyroglobulin (HTG) were markedly increased. We performed total thyroidectomy and right neck lymph node dissection. After treatment, the serum CA 50, CA 19-9 and HTG levels were markedly decreased. Histological examination of the thyroid tumor showed papillary adenocarcinoma and the dissected neck lymph nodes contained metastatic adenocarcinoma. The expression of CA 50 and CA 19-9 (defined by the monoclonal antibodies) was studied by immunoperoxidase staining from the normal and carcinomatous thyroid tissues and the dissected neck lymph node. CA 50 was expressed more strongly by the carcinoma cells than CA 19-9. The positive rates for serum CA 50 and CA 19-9 levels in other patients with papillary adenocarcinoma were not significantly higher compared with patients with benign nodules and normal subjects. But a significant positive correlation was found between the diameter of the carcinoma and the serum levels of CA 50 and CA 19-9. These results suggest that the serum levels of CA 50 and CA 19-9 might not become useful markers for diagnosing carcinoma of the thyroid, but might be useful markers for monitoring the growth or recurrence of papillary adenocarcinoma of the thyroid in patients with high serum levels of CA 50 and CA 19-9.     

磁共振胰胆管成像联合血清CA125、CA19-9、CEA对良恶性梗阻性黄疸的诊断价值

摘要 目的：研究磁共振胰胆管成像（MRCP）联合血清糖类抗原125（CA125）、糖类抗原19-9（CA19-9）、癌胚抗原（CEA）对良恶性梗阻性黄疸的诊断价值。方法：将医院从2018年1月～2020年2月期间收治的90例良恶性梗阻性黄疸患者纳入研究。将其按照良恶性的差异分为良性梗阻性黄疸51例以及恶性梗阻性黄疸39例。分别对所有患者进行MRCP检测,并分析良恶性梗阻性黄疸MRCP影像学表现特征的差异。此外,采集所有患者清晨空腹静脉血,检测血清CA125、CA19-9、CEA水平并进行对比。通过受试者工作特征（ROC）曲线分析明确MRCP联合血清CA125、CA19-9、CEA对良恶性梗阻性黄疸的诊断价值。结果：恶性梗阻性黄疸部位为十二指肠乳头区人数占比明显高于良性梗阻性黄疸,而胰头上区、胰头区人数占比均明显低于良性梗阻性黄疸;且恶性梗阻性黄疸梗阻重度扩张人数占比明显高于良性梗阻性黄疸,而梗阻轻度扩张人数占比明显低于良性梗阻性黄疸,差异均有统计学意义（均P＜0.05）。恶性梗阻性黄疸患者血清CA125、CEA水平均明显高于良性梗阻性黄疸患者（均P＜0.05）;而两组血清CA19-9水平对比不明显（P＞0.05）。MRCP联合血清CA125、CA19-9、CEA诊断良恶性梗阻性黄疸的曲线下面积、灵敏度、特异度、约登指数均明显高于MRCP和血清CA125、CA19-9、CEA单独诊断。结论：MRCP联合血清CA125、CA19-9、CEA对良恶性梗阻性黄疸的诊断价值较高,值得临床推广应用。     

The significance of CA19-9 tumor antigen in the serum of patients with carcinomas

The concentration of serum CA19-9TM in 101 patients with colorectal adenocarcinoma (CRC), and 109 patients with carcinomas of lung, breast, stomach and pancreas and hepatoma, and 40 normal healthy controls including an equal number of smokers and nonsmokers were determined by solid phase radioimmunoassay of CA19-9 assay kits (Centocor). Of the normal sera, only 1 out of 40 (2.5%) was over 37.6 U/ml. No significant difference of CA19-9 levels was found between smokers (14.4 +/- 9.0 U/ml) and non-smokers (16.0 +/- 10.2 U/ml) of normal control. In patients sera, the mean value of CA19-9 levels was significantly higher in patients with Dukes B (P less than 0.05) and in patients with Dukes C and D (P less than 0.001) than the normal healthy control (15.2 +/- 10.2 U/ml). Analysis of serum CEA concentrations has shown a similar result in patients with all Dukes staged CRC. The CA19-9 levels was also significantly elevated in patients with gastric carcinoma, lung carcinoma, hepatoma, and especially in patients with pancreatic carcinoma (P less than 0.0001). The levels of CA19-9 elevated in 50% (22/44) of patients with advanced CRC while the elevation was 8 of 43 (18.6%) patients with localized CRC. A comparison of CA19-9 and CEA assays showed no correlation (r = 0.125) between the two assays. Although the CA19-9 assay (26.4%) was less sensitive than the CEA assay (51.7%), the specificity of CA19-9 assay (97.5%) was better than that of CEA assay (87.5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between mesenteric and peripheral blood levels of CA 19-9 in patients with colorectal cancer

INTRODUCTION: CA19-9 is one of the most important tumor markers used in patients with colorectal cancer, mainly in radical surgery follow-up. AIM: The purpose of this study was to evaluate the preoperative CA19-9 level obtained from a peripheral vein (PV) and compare it to the level obtained from the mesenteric vein (MV). MATERIALS AND METHODS: Blood was collected from a PV of the arm and from the MV of 59 patients with colorectal cancer before primary surgery. Of these 59 patients fourteen had stage I disease, 10 stage II, 22 stage III, and 13 stage IV. CA19-9 was determined in serum by immunoenzymatic assay (Abbott Diagnostica). RESULTS: Fifteen patients (24%) had elevated serum levels of CA19-9 in the MV and 13 (22%) in the PV. None of the stage I or II patients had elevated serum levels of CA19-9. There were no differences between marker levels in blood collected from the MV or PV, independent of clinical stage. The CA19-9 values obtained from the MV differed significantly in the different stages of the disease according to the Kruskal-Wallis analysis (p=0.026); this difference was not statistically significant (p=0.08) in serum from the PV. There was no correlation between venous infiltration by the tumor and positivity of CA19-9 serum levels collected from the mesenteric vein. We observed a close correlation between the serum levels of CA19-9 collected from the PV and from the MV (r=0.9). CONCLUSION: The current study demonstrates a close correlation between the serum levels of CA19-9 collected from a peripheral vein and from the mesenteric vein. Our results confirmed the poor sensitivity of serum CA19-9 at diagnosis, independent of the collection site.     

TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis

The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.     

CA19-9、CA125、CEA及Ferritin联合检测诊断非小细胞肺癌脑、骨转移的临床价值研究

目的:研究CA19-9、CA125、癌胚抗原(CEA)以及铁蛋白(Ferritin)四种肿瘤标志物联合检测用于诊断非小细胞肺癌(NSCLC)脑或(和)骨转移的临床价值。方法:选取2011年5月至2012年5月于我院就诊的NSCLC患者184例。将发现脑或(和)骨转移者归为转移组,共96例;将未发现脑、骨转移者归为无转移组,共88例,采用电化学发光免疫分析法测定各组患者血清中CA19-9、CA125、CEA以及Ferritin的水平,探讨其在NSCLC患者脑或(和)骨转移中的诊断效能。结果:在发生脑或(和)骨转移的NSCLC患者中,CA19-9、CA125、CEA及Ferritin四种肿瘤标志物的水平和阳性率均显著高于未发生骨、脑转移的患者。ROC曲线分析显示,以上四种肿瘤标志物对诊断NSCLC骨或(和)脑转移的敏感度分别为73.48%、69.13%、66.35%和61.34%;特异度分别为80.02%、32.51%、65.11%和62.58%;将四种肿瘤标志物联合进行诊断的敏感度和特异度分别为91.21%和88.64%,显著高于单一标志物诊断。结论:发生脑或(和)骨转移的NSCLC患者血清中CA19-9、CA125、CEA以及Ferritin四种肿瘤标志物水平均显著升高,以上标志物联合检测可提高NSCLC患者脑或(和)骨转移的诊断效能,可作为早期诊断NSCLC患者脑或(和)骨转移的辅助检测指标。     

CA 72-4 compared with CEA and CA 19-9 as a marker of some gastrointestinal malignancies

The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA 72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.     

Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma

BACKGROUND: Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. CASE REPORT: A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. CONCLUSION: Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.     

Value of CA 19-9 assay in serum and duodenal juice in the differential diagnosis of pancreatic disease

Levels of CA 19-9 in the serum and duodenal juice of nine patients with pancreatic adenocarcinoma (PC), ten patients with chronic calcifying pancreatitis (CCP) and ten healthy volunteers (C) were determined by immunoassay. Duodenal juice was obtained by duodenal intubation during the secretin caerulein test. Elevated CA 19-9 levels in the serum were significantly more frequent in PC than in CCP patients, but two PC patients gave levels only slightly above the cut-off value of 37 U/ml. CA 19-9 levels in duodenal juice were significantly higher in PC than in CCP patient, but there was some overlap between them; no overlapping was seen between PC or CCP group and controls. Two PC patients with duodenal juice CA 19-9 levels overlapping those of CCP were the same who showed only a slight rise in serum CA 19-9 levels. The CA 19-9 to total protein ratio in duodenal juice did not permit better discrimination between PC and CCP. We conclude that CA 19-9 assay in duodenal juice can differentiate healthy subjects from patients with pancreatic diseases, but it cannot improve the differential diagnosis between CCP and PC patients with a slight rise of CA 19-9 levels in serum.     

Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait

Preoperative CEA and CA 19-9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes' stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19-9 have been found than those usually employed. In the present study 62 patients with Dukes' stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes' B (69%) versus Dukes' C (48%) patients (p = 0.09). On the other hand, Dukes' stage B + C patients with elevated preoperative levels of CEA or CA 19-9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p = 0.003); for CA 19-9 levels below or above the cutoff the DFS was 71% versus 33% (p = 0.004). In 54 patients with Dukes' stage B + C for whom preoperative levels of both CEA and CA 19-9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19-9 elevated (chi-square 7.09; p = 0.008), CA 19-9 elevated (chi-square 6.27; p = 0.01), CEA elevated (chi-square 5.47; p = 0.02), and Dukes' C (chi-square 2.08; p = 0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19-9 prior to treatment.     

Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients

This study was carried out to evaluate the usefulness of determining urinary levels of carcinoembryogenic antigen (CEA), tissue-polypeptide antigen (TPA), and gastro-intestinal cancer antigen (Ca19-9) in addition to the usual diagnostic procedures for bladder cancer. Sixty-seven patients with transitional bladder cancer, 40 healthy controls and 20 patients with inflammatory diseases of the urinary tract were considered. All urine samples were obtained from patients with intact renal function and no urinary tract infection. TPA and Ca19-9 urinary levels in patients with G3 bladder tumors were significantly higher than in those with lower graded neoplasms. The sensitivity, specificity, and predictive value of a positive (PV+) or negative (PV-) test and the diagnostic accuracy were also evaluated. Ca19-9 was the best urinary marker for bladder cancer (sensitivity 71.6%, specificity 91.6%, PV+ 90.5%, PV- 74.3%, diagnostic accuracy 81%).     

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.     

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.     

Roles of CA19-9 in pancreatic cancer: Biomarker,predictor and promoter

Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.