The tumour marker CA 195 in colorectal and pancreatic cancer.

The aim of this study was to measure the serum level of the tumour markers CA 195 and CEA in patients with either colorectal or pancreatic cancer both before and at serial intervals after operation. CA 195 and CEA were measured in 199 patients with colorectal cancer and 52 patients with pancreatic cancer. The median concentrations of CA 195 were 3.0 u/ml (interquartile range 3.0-4.5 u/ml) in patients with a Dukes' stage A lesion, 5.8 u/ml (3.0-18.2 u/ml) in patients with a Dukes' stage B lesion, 6.1 u/ml (3.0-24.7 u/ml) in patients with a Dukes' stage C and 23.8 u/ml (11.1-409.0 u/ml) in patients with metastatic disease (normal range 0-7 u/ml). The median levels of CEA were 2.6 ng/ml (1.7-3.3 ng/ml) for Dukes' stage A, 3.3 ng/ml (1.7-7.2 ng/ml) for Dukes' stage B, 3.7 ng/ml (2.2-7.9 ng/ml) for Dukes' stage C and 34.5 ng/ml (13.3-289.4 ng/ml) for metastatic disease. A rising level of CA 195 or CEA after operation suggested recurrence of the tumour. In none of these patients was the recurrence operable. In patients with pancreatic adenocarcinoma, the level of CA 195 was significantly higher in patients with metastatic disease but it did not discriminate between resectable and unresectable disease. The duration of survival correlated with the initial level of CA 195 (Rs = -0.66, p less than 0.001).     

Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to cor-relate with prognosis in this patient subgroup.     

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.     

Assessment of the value of preoperative serum levels of CA 242 and CEA in the staging and postoperative survival of colorectal adenocarcinoma patients

INTRODUCTION: CEA is the most frequently used tumor marker in colorectal cancer. There may be an improvement in its efficacy when used in association with CA 242. AIM: The purpose of this study was to evaluate the efficacy of preoperative serum levels of the tumor markers CA 242 and CEA in the staging and postoperative follow-up of colorectal adenocarcinoma patients. PATIENTS AND METHODS: Of a series of 134 patients with colorectal adenocarcinomas 90 underwent radical surgery and 44 palliative surgery. The control group consisted of 22 organ donors. The cutoff serum levels utilized were 5 ng/mL for CEA and 20 U/mL for CA 242. The mortality during follow-up was recorded in order to determine the duration of survival. The data were submitted to statistical analysis using diagnostic tests, the chi-square test, survival analysis (Kaplan and Meier) and ROC curves. A significance level of p < or = 0.05 was applied. RESULTS: The sensitivity of CEA in Dukes' stages A, B, C and D was 27.8%, 32.4%, 32.1% and 66.7%, respectively. The sensitivity of CA 242 was 11.1%, 16.2%, 30.8% and 50%. When both markers were combined, the sensitivity was 33.3%, 48.6%, 40.7% and 72.5%. In the group of patients who underwent radical surgery the mean survival was 60.47 months for those with high preoperative CEA levels, 52.22 months for those with high preoperative CA 242 levels, and 44.80 months for those with elevated levels of both markers. There was a statistically significant difference in survival between patients undergoing radical surgery with elevated CA 242 levels, especially when CEA was also elevated, and patients without elevated CA 242. CONCLUSION: Preoperative serum levels of CA 242 showed less efficacy than CEA levels for the staging of colorectal adenocarcinoma patients. Elevated preoperative serum levels of CA 242 alone were related to poor survival, especially in association with high levels of CEA.     

Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly increased in patient sera, the median level was 8.4 ng/mL versus 2.1 ng/mL in 90 healthy blood donors (p < 0.0001). A weak association of cathepsin H levels was found with patient age (p = 0.02) but not with Dukes' stage, sex, or the level of carcinoembryonic antigen (CEA). In survival analysis a significant difference was found between the group of patients with low cathepsin H (first tertile) who had a poor prognosis and the remaining patients (p = 0.03). The risk of patients was further stratified when cathepsin H levels were combined with CEA. Patients with high CEA and low cathepsin H had the highest risk of death with a hazard ratio of 2.72 (95% CI 1.73-4.28), p < 0.0001. Our results show that the prognostic information of cathepsin H differs from that of the related cathepsins B and L and suggest different roles during the progression of malignant disease.     

The prognostic value of the tumor marker CA 15-3 at initial diagnosis of patients with breast cancer

CA 15-3 has been most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. In this study we have specifically focused upon the prognostic implications and utility of preoperative CA 15-3 levels. We have identified on our database 414 patients with breast cancer in whom serial levels of the serum tumor marker CA 15-3 had been determined at diagnosis and follow-up. We have analyzed the follow-up and clinical outcomes in these patients and from this data we have assessed the potential of CA 15-3 as a predictor of five-year overall and disease-free survival. Our results show that an initially elevated CA 15-3 level is associated with a very poor prognosis in both early and late stage disease. Elevated pre-biopsy CA 15-3 levels are associated with 14% five-year disease-free survival rates and 17% overall survival rates at five years. In contrast, normal CA 15-3 levels are associated with 47% five-year disease-free survival rates and 54% overall survival rates at five years (p<0.01). Comparison of five-year survival rates between patients with elevated and normal CA 15-3 levels in early breast cancer (stage I and II) also showed significant differences, with survival being 41% and 75%, respectively (p<0.01).     

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)     

Clinical significance of preoperative serum sialic acid levels in colorectal cancer: utility in the detection of patients at high risk of tumor recurrence

This study was conducted to evaluate the significance of preoperative serum sialic acid levels in the diagnosis and prognosis of colorectal cancer (CRC). Total sialic acid (TSA) was determined by the thiobarbituric acid method and normalized to total protein (TP). A postoperative follow-up of CRC patients classified as Dukes' stages A, B or C was performed and survival analysis was carried out to evaluate the impact of sialic acid levels on tumor recurrence. Our diagnostic studies indicate that TSA/TP is a better marker than either TSA or carcinoembryonic antigen (CEA), especially for the detection of CRC patients at an early stage. At a cutoff of 30.90 nmol/mg of protein, TSA/TP showed a sensitivity of 85% with a specificity of 97% to discriminate CRC patients from healthy donors. In survival analysis, both TSA and TSA/TP were found to be significant prognostic factors for tumor recurrence in CRC. Furthermore, TSA/TP could distinguish patients at high risk of recurrence within Dukes' stage B and in multivariate analysis it was identified as the best independent prognostic factor. According to our results, preoperative serum TSA/TP content could supply additional information to that provided by Dukes' stage about the prognosis of CRC patients.     

Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-Receptor and Biomarker Group collaboration

BACKGROUND AND AIMS: Since approximately 30% of patients with Dukes' stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer. METHODS: suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n = 354) and a Danish (n = 255) cohort of rectal cancer patients. RESULTS: In both cohorts the suPAR concentration was significantly higher in Dukes' stage D patients than in Dukes' stage A-C patients (p < 0.0001). Among Dukes' stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p < 0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes' stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes' stage. CONCLUSIONS: This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.     

Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis

Abstract

Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.

Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.

Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0?ng/ml for CEA and 305.0?U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p?=?0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p?=?0.007).

Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.     

Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer

BACKGROUND: Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. METHOD: Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age (< or > 70 years), sex, Dukes' stage (A&B versus C), tumour size (< or > 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. RESULTS: Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p<0.05). Factors associated with a poorer prognosis were age >70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. CONCLUSION: Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.     

Changes in the tumor marker concentration in female patients with hyper-, eu-, and hypothyroidism

The levels of 6 circulating tumor markers were evaluated in a total of 131 female subjects with altered thyroid states; 36 normal subjects, 46 hyperthyroid patients with Graves' disease, and 49 primary hypothyroid patients. The mean CEA concentration was observed to be significantly higher (p less than 0.02) in hypothyroid patients than in normal and hyperthyroid patients (1.1 +/- 0.1 ng/ml, 0.8 +/- 0.1 ng/ml and 0.8 +/- 0.1 ng/ml, respectively). Similarly, the mean serum CA 125 concentration in hypothyroid patients was higher (p less than 0.02) than in normal and hyperthyroid patients (13.0 +/- 2.6 U/ml, 7.6 +/- 1.1 U/ml and 5.5 +/- 0.8 U/ml, respectively), and the mean serum CA 15-3 concentration in hypothyroid patients was significantly higher than in normal subjects (p less than 0.01) and hyperthyroid patients (p less than 0.001) (16.2 +/- 0.9 U/ml, 13.9 +/- 0.6 U/ml and 10.6 +/- 0.5 U/ml, respectively). No statistical difference was found in mean CA 19-9 in the three subject groups. AFP in the hypothyroid patients (3.6 +/- 0.3 ng/ml) was significantly higher (p less than 0.05) than in normal subjects (2.6 +/- 0.2 ng/ml) and hyperthyroid patients (1.7 +/- 0.2 ng/ml) (p less than 0.01). On the other hand, serum ferritin was low in the hypothyroid patients (65.9 8.0 ng/ml) and significantly increased (69.1 +/- 9.0 ng/ml) (p less than 0.02) with the normalization of thyroid function. In hyperthyroidism, serum ferritin (70.2 +/- 7.0 ng/ml) was significantly higher than in the hypothyroid patients (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

CEA is an Independent Prognostic Indicator that is Associated with Reduced Survival and Liver Metastases in SCLC

Small-cell lung cancer (SCLC) is classified into two stages, limited-stage small-cell lung cancer (LS-SCLC) and extensive-stage small-cell lung cancer (ES-SCLC), with ES-SCLC being associated with reduced survival. However, disease stage alone is not a very precise predictor of survival time. The aim of this study is to search for a prognostic indicator that can be used in conjunction with the staging system in SCLC. We performed a prospective analysis of 116 patients with SCLC undergoing standard chemotherapy with or without radiotherapy. Expression levels of 12 tumor markers were measured at the time of diagnosis by a commercial protein chip system, and patients were followed up for a maximum of 54 weeks. CEA was the most frequently detected tumor marker in SCLC, with 32.8% of samples scoring positive, and was also the only marker that correlated with overall survival. The average survival time was 16.78 months for patients with CEA below 5 ng/ml and 11.4 months for patients with CEA above 5 ng/ml (P < 0.001). In contrast, no association was found between tumor stage and overall survival. CEA expression was independent of tumor stage (P = 0.930). CEA is an independent prognostic factor that can be used in conjunction with disease stage in SCLC.     

胰腺癌患者血清CEA、CA242、CA199水平变化及联合诊断的ROC曲线分析

目的:探讨胰腺癌患者血清癌胚抗原(CEA)、糖类抗原242(CA242)、糖类抗原199(CA199)水平变化,并分析上述指标对胰腺癌的联合诊断价值,为胰腺癌的临床诊断提供参考。方法:选择2014年2月至2018年2月我院收治的186例胰腺癌患者(胰腺癌组)、89例胰腺炎患者(胰腺炎组)作为研究对象,并取同期来我院检查的268例健康人作为对照组。比较三组受试者的血清CEA、CA242、CA199水平变化,对比分析血清CEA、CA242、CA199的单一以及联合诊断的准确度、特异度以及灵敏度,并绘制ROC曲线以分析上述指标的诊断价值。结果:三组受试者血清CEA、CA242、CA199水平差异具有统计学意义(P<0.05)。且胰腺炎组和胰腺癌组的血清CEA、CA242、CA199水平明显高于对照组,胰腺癌组患者的血清CEA、CA242、CA199水平明显高于胰腺炎组,差异均有统计学意义(P<0.05)。ROC曲线结果显示,CEA诊断价值最大,CA199诊断价值最小。CEA是胰腺癌单项肿瘤标志物中敏感度最高的,为85.48%;特异度最高的为CA242(96.72%);三项肿瘤标志物联合诊断的准确度增加至92.27%,敏感度增加至95.16%,特异度相比略有下降。结论:与单一肿瘤标记物诊断胰腺癌相比,CEA、CA242、CA199联合诊断的敏感度和准确度均明显升高,可以明显改善胰腺癌的漏诊率,提高患者的生存率,具有较好的临床应用价值。     

Tumor markers, liver function tests and symptoms in 115 patients with isolated colorectal liver metastases

Development of the hybridoma technique has made the identification of several new tumor antigens possible. Although it was hoped that they would be more tumor-specific, none of these markers are found exclusively in tumor or in serum of tumor patients. Compared with carcinoembryionic antigen (CEA) and liver function tests, the roles of these markers (CA 19-9, CA 125, CA 15-3) were prospectively evaluated in 115 patients with colorectal liver metastases. Patients were classified according to tumor volume (T1 less than 25%, T2 25-75%, T3 greater than 75%), and the extension of infiltration (solitary/multiple/diffuse; unilateral, bilateral). Patients with benign liver or biliary disease served as a control group (n = 63). Overall sensitivity was 87% for *1, 50% for *2 and 38% for *3, with a significant correlation with tumor size. CEA serum levels were elevated in 88% of all patients. CA 19-9 was less sensitive: positive in 59%. Because of some complementary elevations, the combined use of CEA, CA 19-9 and CA 125 raised sensitivity to 94%. CA 19-9 and LDH could be useful for confirmation because of their higher specificity; however, the specificity of CEA rose to 93% on using a cut-off of 10 ng/ml instead of 3 ng/ml. The results indicate that CEA and CA 19-9 as well as liver function tests are helpful for preoperative staging in conjunction with imaging procedures before liver resection or regional chemotherapy.     

Serum tumor markers may precede instrumental response to chemotherapy in patients with metastatic cancer

PURPOSE: Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. METHODS: STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. RESULTS: The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p < 0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p < 0.0005) and CA 125 (p = 0.006), good for CA 15.3 (p < 0.0005) and CA 19.9 (p = 0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p = 0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p = 0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p = 0.24 and p=0.42, respectively). CONCLUSION: This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.     

Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer

This retrospective study was undertaken in order to assess the prognostic value of prechemotherapy serum CA125 level, CA125 kinetics, and CA125 half-life compared to the ten common clinicopathological variables in patients with advanced ovarian cancer (AOC). CA125 serum levels were determined before and during induction cisplatin polychemotherapy in 222 patients. A prechemotherapy CA125 level higher than 35 U/mL was found in 134 patients. Blood samples were further obtained before each course of chemotherapy (CT). CA125 half-life values were calculated in 112 patients with CA125 levels above 60 U/mL using van der Burg's exponential regression model. The prechemotherapy CA125 level had no prognostic value for survival. However, the median survival time of patients with CA125 levels below the upper normal limit of normality after two courses of CT was 101 months compared to a median survival of 21 months in patients without CA125 normalization (p=0.0000). Half-life calculation showed a significant correlation with survival. The median survival times of patients with T1/2 <20 days and T1/2 >20 days were 101+ and 18 months, respectively (p=0.0003). In a survival analysis using the Cox proportional hazard model, independent prognostic variables for survival included therapeutic response (p<0.0001), Karnofsky index (p<0.0001), residual disease (p<0.0001), tumor grade (p=0.0002), CA125 half-life (p=0.007), and CA125 kinetics (p=0.04). As a consequence, the possibility to predict treatment response by the CA125 half-life during chemotherapy and the time needed for normalization of CA125 levels can divide patients into good and poor prognostic groups early during chemotherapy.     

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Purpose

We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.

Patients and Methods

In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.

Results

Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).

Conclusions

Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.     

直肠系膜切除术对直肠癌根治术后局部复发患者MMPs、CEA、CA199及生存率的影响

目的:探讨直肠系膜切除术对直肠癌根治术后局部复发患者血清基质金属蛋白酶、肿瘤标志物(CEA、CA199)及生存率的影响。方法:收集直肠原发癌位于直肠中下段的病例,行直肠癌根治术复发再入院患者48例(均为本院2010年4月-2014年3月手术后的病例),按照手术方式的不同分为2组,分别24例。对照组采用姑息性手术治疗,研究组采用直肠系膜切除术治疗,采用ELISA法测定血清MMP-2、MMP-9、CEA、CA199水平,记录所有患者术后并发症状况,术后进行随访时间为3年,比较两组1年、3年的生存率状况。结果:对照组在手术时间、出血量、住院时间上高于研究组,(P0.05);对照组在肛门排气时间上低于研究组,(P0.05);与治疗前比较,两组患者治疗2周后MMP-2、MMP-9表达水平降低,治疗2周后血清CEA、CA199表达水平降低(P0.05);与对照组比较,研究组患者治疗2周后MMP-2、MMP-9表达水平较低,治疗2周后血清CEA、CA199表达水平较低(P0.05);两组患者治疗期间并发症无差异(P0.05);两组间术后1年生存率,无差异(P0.05);研究组术后3年生存率(66.67%)高于对照组(37.50%),(P0.05)。结论:直肠系膜切除术可提高直肠癌根治术后局部复发患者的长期生存率,降低血清MMP-2、MMP-9、CEA、CA199水平,安全性高,值得广泛推广。     

The Prognostic Significance of Pretreatment Serum CEA Levels in Gastric Cancer: A Meta-Analysis Including 14651 Patients

Background

Carcinoembryonic antigen (CEA) is commonly used as a serum tumor marker in clinical practice; however, its prognostic value for gastric cancer patients remains uncertain. This meta-analysis was performed to assess the prognostic value of CEA and investigate CEA as a tumor marker.

Methods

PubMed, EMBASE and other databases were searched for potentially eligible studies. Forty-one studies reporting the prognostic effect of pretreatment serum CEA expression in gastric cancer patients were selected. Data on 14651 eligible patients were retrieved for the meta-analysis. Based on the data extracted from the available literature, the hazard ratio (HR) and 95% confidence interval (CI) for an adverse prognosis were estimated for gastric cancer patients with elevated pretreatment serum levels of CEA (CEA+) relative to patients with normal pretreatment CEA levels (CEA-).

Results

The CEA+ patients had a significantly poorer prognosis than the CEA- patients in terms of overall survival (OS: HR 1.716, 95% CI 1.594 - 1.848, P< 0.001), disease-specific survival (DSS: HR 1.940, 95% CI 1.563 - 2.408, P< 0.001), and disease-free survival (DFS: HR 2.275, 95% CI 1.836 - 2.818, P< 0.001). Publication bias and an influence of different cut-off values were not observed (all P> 0.05). In the pooled analyses of multivariate-adjusted HRs, the results suggested that pretreatment serum CEA may be an independent prognostic factor in gastric cancer (OS: HR 1.681, 95% CI 1.425 - 1.982; DSS: HR 1.900, 95% CI 1.441 - 2.505; DFS: HR 2.579, 95% CI 1.935 - 3.436).

Conclusion/Significance

The meta-analysis based on the available literature supported the association of elevated pretreatment serum CEA levels with a poor prognosis for gastric cancer and a nearly doubled risk of mortality in gastric cancer patients. CEA may be an independent prognostic factor for gastric cancer patients and may aid in determining appropriate treatment which may preferentially benefit the CEA+ patients.