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Background

CA19-9 is an oncofetal antigen, expressed by several different cancers, but especially carcinomas of the gastrointestinal tract. Along with CEA, it may be a useful marker to determine prognosis and tumor recurrence.

CLINICAL UTILITY CHARACTERIZATION
COLON CANCER  

Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma.

Kouri M, Pyrhonen S, Kuusela P.

Department of Radiotherapy and Oncology, Helsinki University Central Hospital, Finland.

J Surg Oncol 1992 Feb;49(2):78-85 Abstract quote

Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma.

Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals.

In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival.

In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%.

When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma.

Poor prognosis associated with elevated serum CA 19-9 level in advanced colorectal carcinoma, independent of DNA ploidy or SPF.

Kouri M, Nordling S, Kuusela P, Pyrhonen S.

Department of Radiotherapy and Oncology, Helsinki University Central Hospital, Finland.

Eur J Cancer 1993;29A(12):1691-6 Abstract quote

DNA ploidy, S-phase fraction (SPF) for the tumours, serum tumour markers such as carcinoembryonic antigen (CEA) and serum CA 19-9 and major clinical parameters were analysed as prognostic factors in 105 patients with advanced colorectal carcinoma.

All 105 were treated with a three-drug schedule including low dose epirubicin and sequential methotrexate, 5-fluorouracil, followed by leucovorin rescue. In univariate analysis, gender, Karnofsky index, extent of metastases, presence of abdominal metastases, CEA and CA 19-9 correlated with survival. Age, presence of liver or of lung metastases, DNA ploidy or SPF were not significantly associated with survival.

In stepwise multivariate analysis an elevated serum CA 19-9 level, a poor Karnofsky index and multiple sites of metastases were independent adverse prognostic factors. Based on the multivariate analysis, patients were grouped in three categories. Group 1 consisted of 32 patients with Karnofsky > or = 80, with a normal serum CA 19-9 level and a single site of metastases. Group 2 consisted of 48 patients with Karnofsky > or = 80 and with an elevated serum CA 19-9 level or multiple sites of metastases. Group 3 consisted of 14 patients with Karnofsky < or = 70. This classification gave a highly significant correlation with survival (chi 2 = 45.52, P < 0.001, log rank test). The median survival in group 1, group 2 and group 3 was 30.1 months, 13.5 months and 3.9 months, respectively.

Based on these results we suggest that trials involving advanced colorectal cancer should include the measurement of serum CA 19-9 levels as one of the most important prognostic factors, but also include documentation of other independent prognostic factors.

The significance of CEA, CA19-9 and CA72-4 in the detection of colorectal carcinoma recurrence.

Holubec L Jr, Topolcan O, Pikner R, Pecen L, Vaclavickova J, Wirthova M, Molacek J, Stieber P, Holdenrieder S, Sen LH, Finek J.

2nd Dept. of Internal Medicine, Clarles University Hospital, E. Benese 13, 30599 Pilsen, Czech Republic.

Anticancer Res 2000 Nov-Dec;20(6D):5237-44 Abstract quote

The significance of CEA, CA19-9 and CA72-4 was evaluated the for early detection of disease recurrence, on the basis of retrospective evaluation of routine data in patients with colorectal carcinoma. They also considered the dependence of the results of these data analyses on the definition of groups of patients, both with no evidence of disease (NED) and with recurrence of disease (RD).

PATIENTS AND METHODS: From January 1994 to March 1999 serum levels of CEA, CA19-9 and CA72-4 were determined in the follow-up of 517 patients with colorectal cancer and compared with the retrospectively confirmed clinical status of the patients.

RESULTS: CEA and CA19-9 showed comparable sensitivities in the detection of locoregional recurrence of colorectal carcinoma, whilst the sensitivity of CA72-4 was considerably lower. CEA is an optimal marker for detecting distant metastases, in particular liver metastases, since its sensitivity considerably exceeds the sensitivities of the other two monitored markers.

CONCLUSION: Using routine data required detailed analysis and clear definitions of groups of patients with NED and RD. The following conclusions for the evaluation of data were drawn from this analysis: a) Tumor marker cut-off values and sensitivities related to 95% specificity of remission values depended strongly on the given definition of the groups of patients with NED and RD. b) The patient group with NED is best characterized as the group of patients who never developed progression and where all the values which were assessed within a period shorter than six months from the end of therapy and follow-up, or less than six months before progression, death, or before the last marker assessment in the patient, were excluded. c) For the optimal characterisation of the group of patients with RD it is recommended only to consider values obtained during the first progression, after the period of complete post-operative or post-therapeutic remission. d) These conclusions refer not only to routine data, where this correction represents a condition for reliable evaluation, but also to any research done, since they ensure complete homogeneity of the group and mutual comparability of the results.

Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer.

Reiter W, Stieber P, Reuter C, Nagel D, Lau-Werner U, Lamerz R.

Institute of Clinical Chemistry, Klinikum of the University Munich, Grosshadern, Germany.

Anticancer Res 2000 Nov-Dec;20(6D):5195-8 Abstract quote

Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most commonly used tumor-associated antigens in the management of patients with colorectal cancer. The aim of this study was to evaluate the prognostic value of preoperative serum levels of CEA and/or CA 19-9 and the classical prognostic factors (age, sex, tumor infiltration and staging) in 495 patients.

PATIENTS AND METHODS: The retrospective study was performed on frozen sera (stored at -70 degrees C) of patients with histologically proven colorectal cancer. Survival function estimates were calculated (Kaplan-Meier). The patients were separated into two groups according to the preoperative marker levels. Cut-off levels calculated at a specificity of 100% versus healthy individuals were used: < 4 ng/mL versus > or = 4 ng/mL for CEA and < 60 U/mL versus > or = 60 U/mL for CA 19-9. Survival curve differences were assessed using the log-rank-test. Mulivariate Cox's proportional hazard regression analysis was performed to examine the association between tumor marker levels and survival time. Classical prognostic factors such as age, sex, tumor infiltration, tumor stage (Dukes' classification) were included as covariants. The mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages.

RESULTS: The Dukes' stages (log-rank chi-square = 231.9; p < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (p < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only items of statistically significant prognostic relevance (univariate analysis) were used for this analysis. Estimated relative risks of death adjusted for tumor stage were 5.5 considering Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively, and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (p < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (p < 0.001) and for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-years survival rate of 100% was found.

CONCLUSION: The postoperative Dukes' classification represents the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by preoperative CA 19-9 serum levels is independent from that obtained by the other factors investigated. Only Dukes' classification and CA 19-9 levels showed statistical significance (p < 0.001).

PANCREATIC CANCER  

The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients.

Frebourg T, Bercoff E, Manchon N, Senant J, Basuyau JP, Breton P, Janvresse A, Brunelle P, Bourreille J.

Clinique Medicale A, C.H.U. de Rouen, Hopital de Bois-Guillaume, France.

Cancer 1988 Dec 1;62(11):2287-90 Abstract quote

To establish if CA 19-9 could detect early pancreatic cancer, we measured its serum concentration in 866 patients admitted for benign diseases and observed for 2 years.

All patients with an elevated CA 19-9 level (greater than 40 units (U)/ml) were submitted to a computed tomography (CT) scan of the pancreas. The CA 19-9 level was increased in 117 patients. One hundred fifteen of these 117 patients had false-positive elevations. The CA 19-9 concentration was elevated mostly in benign hepatobiliary diseases. In this group of patients, CA 19-9 was correlated to alkaline phosphatase values. Eleven patients showed an elevated CA 19-9 level for 10 months without any malignancy developing. One patient had a normal CA 19-9 concentration 8 months before clinical signs of pancreatic carcinoma developed.

We conclude that CA 19-9 measurement is of no value for the early detection of this malignancy.

CA 19-9 serum course and prognosis of pancreatic cancer.

Safi F, Schlosser W, Falkenreck S, Beger HG.

Department of General Surgery, University Hospital of Ulm, Germany

Int J Pancreatol 1996 Dec;20(3):155-61 Abstract quote

CONCLUSION: CA 19-9 measurement is a simple test that can be used for diagnosis as well as for prediction of resection, survival rate after surgery, and recurrences.

METHODS: Serum expression of the tumor marker CA 19-9 was studied in 2119 patients.

RESULTS: The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n = 347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%.

CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, p < 0.0001) (sensitivity 74 vs 90%). CA 19-9 dropped sharply after resection, but normalized only in 29, 13, and 10% in patients with stage I, II, and III, respectively.

In unresectable tumors no significant decrease of CA 19-9 after laparotomy or bypass operation was found. In patients of the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those with postoperative CA 19-9 levels that decreased, but did not return to normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III, 28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels.

Diagnostic Value of CA 19-9 in Patients With Pancreatic Cancer and Nonspecific Gastrointestinal Symptoms.

Safi F, Schlosser W, Kolb G, Beger HG.

Department of General Surgery, University Hospital of Ulm, Ulm, Germany.

J Gastrointest Surg 1997 Mar;1(2):106-112 Abstract quote

Serum expression of the tumor marker CA 19-9 was studied in 2119 patients.

The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n = 347).The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, P <0.0001; sensitivity 74% vs. 90%). CA 19-9 levels dropped sharply after resection but normalized in only 29%, 13%, and 10% of patients with stage I, II, and III tumors, respectively. In unresectable tumors no significant decrease in CA 19-9 levels after laparotomy or bypass surgery was found. Among patients with the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those who had postoperative CA 19-9 levels that decreased but did not return to normal (stage I, 33 months vs. 11.3 months; stage II, 41 months vs. 8.6 months; and stage III, 28 months vs. 10.8 months).

In patients with recurrent disease, 88% had an obvious increase in CA 19-9 levels. CA 19-9 measurement is a simple test that can be used for diagnosis, for evaluation of resectability, and for prediction of survival after surgery and recurrences.

Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas.

Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Ann Surg Oncol 1997 Oct-Nov;4(7):551-6 Abstract quote

BACKGROUND: CA 19-9 levels are useful for the diagnosis of patients with pancreatic adenocarcinoma. However, interest has recently turned toward its use as a prognostic indicator. The purpose of this study is to determine whether postoperative CA 19-9 levels predict disease-free survival (DFS) and median survival (MS) in patients after resection.

METHODS: Between 1988 and 1996, 40 patients underwent resection for pancreatic adenocarcinoma and were evaluated with postoperative CA 19-9 assays. Eight patients had low preoperative levels of CA 19-9 (< 2) and were excluded.

RESULTS: CA 19-9 levels are good predictors of DFS and MS. Patients whose postoperative CA 19-9 values normalized by 3 to 6 months (< 37 U/ml) had longer DFS (24 vs. 10 months, p < 0.04) and MS (34 vs. 13 months, p < 0.04). Patients with postoperative CA 19-9 values less than 180 U/ml at 1 to 3 months had a similar DFS (19 vs. 5 months, p < 0.0009) and MS (34 vs. 13 months, p < 0.0001) compared to patients with normal values at 3 to 6 months.

CONCLUSIONS: Postoperative measurements of CA 19-9 were the best predictors of DFS and MS. Values < 180 U/ml at 3 months were as predictive as normal values by 3 to 6 months postoperatively. Consequently, CA 19-9 levels should be obtained for use as a stratification parameter in phase III trials.

Clinical usefulness of CA-19-9 in pancreatic carcinoma.

Nakao A, Oshima K, Nomoto S, Takeda S, Kaneko T, Ichihara T, Kurokawa T, Nonami T, Takagi H.

Department of Surgery II, Nagoya University School of Medicine, Japan.

Semin Surg Oncol 1998 Jul-Aug;15(1):15-22 Abstract quote

Preoperative and postoperative serum levels of carbohydrate antigen-(CA)19-9 in 148 patients with carcinoma of the pancreas were studied.

All 18 patients with carcinoma of the pancreas of Stage I, II, and III were resectable, and their pre-operative serum levels of CA-19-9 were under 1,344 U/ml. Pre-operative serum levels of CA-19-9 in patients with Stage IV ranged widely between 5 and 32,240 U/ml.

The postoperative survival rate was significantly superior in patients (n = 15) whose CA-19-9 pre-operative serum levels were less than 2,000 U/ml compare to those (n = 64) whose levels were over that level. Fifteen resectable patients who showed serum levels of CA-19-9 over 2,000 U/ml pre-operatively died within 2 years postoperatively due to recurrence, especially by liver metastasis in spite of aggressive surgery. I

Intraoperative quick immunostaining of CA-19-9 and carcinoembryonic antigen (CEA) was useful to diagnose intrapancreatic carcinoma development on frozen sections of cut margin of the pancreas and also useful in abdominal washing cytology combined with conventional staining.

A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases.

Hayakawa T, Naruse S, Kitagawa M, Ishiguro H, Kondo T, Kurimoto K, Fukushima M, Takayama T, Horiguchi Y, Kuno N, Noda A, Furukawa T.

Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.

Int J Pancreatol 1999 Feb;25(1):23-9 Abstact quote

CONCLUSION: A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer.

BACKGROUND: No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other.

METHODS: A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers.

RESULTS: Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA 19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.

Are elevated levels of the tumour marker CA19-9 of any clinical significance?--an evaluation.

McLaughlin R, O'Hanlon D, Kerin M, Kenny P, Grimes H, Given HF.

Department of General Surgery, University College Hospital, Galway.

Ir J Med Sci 1999 Apr-Jun;168(2):124-6 Abstract quote

CA 19-9 is a tumour marker which has been used widely in patients with pancreatic adenocarcinoma. Elevated levels are associated with advanced disease at presentation and disease progression during follow-up. CA19-9 levels may also be elevated in a variety of other malignant and benign conditions.

This study examined the significance and implications of elevated CA19-9 levels. An analysis of all CA19-9 measurements performed over a 4 yr period was undertaken and 204 patients with elevated CA19-9 levels were identified. One hundred and thirty patients (63.7 per cent) had malignant conditions and 74 (36.3 per cent) had benign conditions or no definite cause was found. There was a significant correlation between CA19-9 levels and CEA (r = 0.3137; P < 0.001) as well as alkaline phosphatase, ALT, AST, bilirubin, gamma glutamyl transpeptidase and lactate dehydrogenase. CA19-9 levels were significantly lower in patients with benign pathology than those with malignant pathology. Similar differences were observed for CEA. CA19-9 levels were in fact highest in patients with pancreatic carcinoma (P < 0.05) while no significant differences were observed for CEA.

In conclusion CA19-9 may be elevated in both benign as well as malignant conditions and interpretation of CA19-9 results must be made in light of the clinical condition of the patient.

Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis.

Nishida K, Kaneko T, Yoneda M, Nakagawa S, Ishikawa T, Yamane E, Nishioka B, Miyamoto Y, Takano H, Yoshikawa T, Kondo M.

Gastroenterology, Shakaihoken Kobe Central Hospital, Kobe, Japan.

J Surg Oncol 1999 Jul;71(3):140-6 Abstract quote

BACKGROUND AND OBJECTIVES: Pancreatic cancer is generally a disease with a poor prognosis, and relationship between change of serum CA 19-9 level and progression of this disease was investigated with regard to clinical pace of disease and tumor growth.

METHODS: CA 19-9 doubling time was examined in 75 patients with pancreatic cancer, including 41 inoperable cases. Then, its relation with their prognosis and change in tumor was evaluated.

RESULTS: The doubling time of CA 19-9 and CEA could be calculated in 90.2% and 58.5% of patients with inoperable pancreatic cancer. CA 19-9 doubling time was clearly associated with survival time in inoperable and palliatively operated cases, but not with sex, age, site of the lesion, or liver metastasis, and was significantly correlated with the tumor volume doubling time.

CONCLUSIONS: Examination of CA 19-9 doubling time may be useful in clinical evaluation of the prognosis for patients with pancreatic cancer and could possibly prove valuable in terms of the analysis of the growth process in this disease.

Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer.

Halm U, Schumann T, Schiefke I, Witzigmann H, Mossner J, Keim V.

Department of Internal Medicine II, University of Leipzig, Germany.

Br J Cancer 2000 Mar;82(5):1013-6 Abstract quote

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19-9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients.

Forty-three consecutive patients (median age 61 years, range 39-76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index > or = 60 were treated with gemcitabine in a dose of 1,000 mg/m(-2) weekly x 7 followed by 1 week of rest during the first cycle and thereafter 1,000 mg/m(-2) weekly x 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19-9 could be performed. Patients with a decrease of > 20% of the baseline CA 19-9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease < or = 20% (n = 11) (268 vs 110 days; P < 0.001).

The response of CA 19-9 was the strongest independent predictor of survival (P < 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19-9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer.

Serial measurements of CA 19-9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated.

The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma.

Nazli O, Bozdag AD, Tansug T, Kir R, Kaymak E.

Ataturk Training Hospital 3. Surgical Clinic Izmir, Turkey.

Hepatogastroenterology 2000 Nov-Dec;47(36):1750-2 Abstract quote

BACKGROUND/AIMS: CA 19-9 and CEA were evaluated for their specificity and sensitivity in the early diagnosis of pancreatic carcinoma.

METHODOLOGY: This prospective study included 40 patients with pancreatic carcinoma. A control group of 60 patients were divided into two subgroups as upper gastrointestinal system malignancies and benign pancreatic disorders. CEA and CA 19-9 levels were measured in all the patients.

RESULTS: When the reference value of CA 19-9 was accepted as 74 U/mL, the specificity was 100% when pancreatic carcinoma was compared with benign disorders of the pancreas, but it's specificity for upper gastrointestinal malignancies was 60-90%. When the reference value of CEA was increased, the sensitivity had been decreased but the specificity had been increased when compared with the control group. If the reference value of CEA was accepted as 5 ng/mL, the specificity was 100% when pancreatic carcinoma was compared with acute or chronic pancreatitis, but it is less specific for the differential diagnosis of pancreatic carcinoma from the upper gastrointestinal malignancies.

CONCLUSIONS: With the progression of the pancreatic carcinoma, serum CEA level and the specificity of CEA were elevated similar to that of CA 19-9. However, the elevation of CEA specificity when compared with the control group was lower than the specificity of the CA 19-9 and the sensitivity of CA 19-9 was superior to that of CEA for pancreatic carcinoma. The level of CA 19-9 was increased with the development of early pancreatic cancer and this elevation steadily continued with the progression of the cancer.

GASTRIC CANCER  

The prognostic value of preoperative serum levels of CEA and CA19-9 in patients with gastric cancer.

Kodera Y, Yamamura Y, Torii A, Uesaka K, Hirai T, Yasui K, Morimoto T, Kato T, Kito T.

Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan.

Am J Gastroenterol 1996 Jan;91(1):49-53 Abstract quote

OBJECTIVES: The clinical significance of preoperative serum levels of tumor markers CEA and CA19-9 was evaluated in gastric cancer patients.

METHODS: Serum levels of CEA and CA19-9 were measured in 663 patients with gastric cancer who underwent laparotomies over a recent 4-yr period (1990-1993). The correlations between the serum levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed by multivariate analysis.

RESULTS: The positivity rates of CEA and CA19-9 were 16.6% and 16.0%, respectively. The positivity of CEA correlated well with the sex of the patients, hepatic, peritoneal, and nodal metastases and the depths of tumors, but it correlated weakly with a tumor's histological type. The positivity of CA19-9 correlated well with various forms of metastases, depths, and tumor size. A significant in prognosis was observed between patients positive and negative for CA19-9 among those undergoing R0 resection. Multivariate analysis also revealed that serum CA19-9 was better than CEA as a prognostic factor.

CONCLUSIONS: CA19-9 in the preoperative sera is a good prognostic factor in gastric cancer patients, although tumor markers continue to have only limited diagnostic usefulness.

CHOLANGIOCARCINOMA  

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

Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Am J Gastroenterol 2000 Jan;95(1):204-7 Abstract quote

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.

 

INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION

Elevated tumor-associated antigen CA 19-9 in a patient with an enlarged pancreas: does it always imply malignancy?

Tolliver BA, O'Brien BL.

Division of Gastroenterology, University of South Alabama College of Medicine, Mobile 36617, USA.

South Med J 1997 Jan;90(1):89-90 Abstract quote

Carbohydrate antigen 19-9 (CA 19-9) has been used as a serum tumor marker for adenocarcinoma of the upper gastrointestinal tract, particularly primary adenocarcinoma of the pancreas. This tumor marker has also been used to differentiate benign from malignant diseases of the pancreas. However, significant elevations of CA 19-9 levels in the absence of pancreatic malignancy have also been reported.

This case illustrates a marked elevation of CA 19-9 due to an infectious process in a patient with a pancreatic mass suggestive of malignancy.

The effect of colonoscopy on tumor markers.

Scapa E, Broide E, Pinhasov I.

Institute of Gastroenterology, Liver Diseases, and Nutrition, Assaf Harofeh Medical Center, Zerifin, Israel.

Surg Laparosc Endosc 1997 Dec;7(6):477-9 Abstract quote

As preoperative elevated serum levels of carcinoembryonic antigen (CEA) and CA19.9 are markers for bad prognosis in colorectal cancer patients, it is important to decide whether preoperative total colonoscopy would make a significant change in their serum levels. CEA and CA 19.9 were evaluated in three groups of patients before and after colonoscopy.

The groups comprised the following: Group A, 20 patients with colorectal cancer; Group B, 17 patients with colorectal polyp of > or = 1-cm diameter; Group C, 16 patients with no colorectal pathology. CEA serum levels were found to be significantly lower after colonoscopy in all groups. CA19.9 was found to be significantly lower after colonoscopy only in Group B; it did not reach significance in Group A and was found not to be significantly higher in Group C.

False elevation of CA 19-9 levels in a patient with a history of pancreatic cancer.

Goetz M, Steen PD.

University of North Dakota School of Medicine and MeritCare Roger Maris Cancer Center, Fargo 58122, USA.

Am J Gastroenterol 1997 Aug;92(8):1390-1 Abstract quote

CA 19-9 is the most sensitive and specific marker currently used in the diagnosis of pancreatic cancer. Its interpretation, however, can be limited in the presence of certain nonmalignant diseases that have been correlated with elevated serum levels of CA 19-9.

We report an unusual case of falsely elevated CA 19-9 levels in a patient with a history of resected pancreatic cancer. This patient presented 4 yr after resection with painless jaundice and markedly elevated CA 19-9 levels (2327 U/ml). Although it was initially suspected that the patient had recurrent cancer, further evaluation proved that her jaundice and increased CA 19-9 value were due to a benign stricture that led to cholestatic jaundice and concomitant cholangitis. No previous cases of falsely elevated CA 19-9 levels have been reported in the context of a known history of pancreatic cancer.

Physicians should be aware of the perturbations that extrahepatic cholestasis and certain inflammatory diseases of the pancreas and hepatobiliary system may impose on CA 19-9 levels. Furthermore, this case demonstrates that even markedly elevated CA 19-9 levels in patients being assessed for recurrence of pancreatic cancer need to be carefully interpreted in the context of other clinical findings.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.


Commonly Used Terms

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Colon Cancer

Pancreatic Cancer

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Pathologists actively oversee every area of the laboratory to ensure your report is accurate


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