CEA Values Research Articles

Assessment of the diagnostic value of CEA, CA125, and CRP and their cut-off point for discrimination of exudative pleural effusions

Pleural effusion is divided into exudative and transudative effusion, and the distinction between exudate and transudate requires multiple investigations of biochemical parameters and their comparison in pleural fluid and serum. This study aimed to assess the diagnostic value of CEA, CA125, and CRP and their cut-off point for discrimination of exudative pleural effusions. This epidemiological and cross-sectional study was performed on 50 patients aged between 18 to 90 years with the diagnosis of exudative pleural effusion referred to Imam Khomeini Hospital in Ahvaz in 2018 and 2019. Demographic and clinical information of patients were collected. The pleural effusion was diagnosed based on physical examination and chest radiography. Pleural effusion was confirmed by thoracentesis. A pleural fluid sample was taken from all patients, and the levels of CEA, CA125, and CRP markers were measured in the pleural fluid. Differentiation of transudate and exudate pleural effusions was performed using Light criteria. The mean CEA and CA125 level of pleural fluid were significantly higher, and the mean CRP level of pleural fluid was significantly lower in patients with malignant diagnoses (P <0.05). Cut-off value with highest sensitivity and specificity in differentiating types of exudative pleural effusions was obtained for CEA tumor marker (greater than 49.8), CA125 tumor marker (greater than 814.02), and CRP marker (less than 7.56). Also, in differentiating types of exudative pleural effusions, CEA tumor marker had sensitivity (89.03%) and specificity (78.42%); CA125 tumor marker had sensitivity (53.18%) and specificity (62.44%), and CRP marker had sensitivity (82.16%), and specificity (89.05%) were. Although the tumor markers had high specificity in the present study, the low sensitivity of some of these tumor markers reduced their diagnostic value. On the other hand, given the numerous advantages of tumor markers, such as low cost and non-invasive, combining them with another can increase the diagnostic value and accuracy.

Cross-Sectional Study to Establish the Utility of Serum Tumor Markers in the Diagnosis of Lung Cancer.

Background:Reliable blood markers for aiding lung cancer (LC) diagnosis and differentiating LC from tuberculosis are lacking in India. Methodology:In this single-centre, cross-sectional, real-world study, serum levels of 5 TMs (CEA, CYFRA 21-1, SCC, ProGRP, NSE) were measured from consented patients with suspicious lung nodules who were candidates for biopsy, and also from healthy controls. TM level measurement was done through electrochemiluminescent immunoassay, followed by histological diagnosis on the biopsied specimen. Using package insert cut-offs, sensitivity and specificity of the 5 TMs were evaluated individually and in combination. Using receiver operating characteristic (ROC) curves of individual TMs, the ability of CEA, CYFRA 21-1, and ProGRP taken together was evaluated for its ability to differentiate LC from no-LC. Results:Out of 178 subjects, 160 had LC (147 NSCLC; 13 SCLC). NSCLC patients had higher median values of CYFRA 21-1 and SCC; SCLC patients had higher median values of CEA, NSE, and ProGRP. Adenocarcinoma-NSCLC patients had higher median values of CEA, CYFRA 21-1, NSE, and ProGRP; squamous-NSCLC patients had higher median value of SCC. For differentiating LC from no-LC, the combination of all 5 TMs (sensitivity:97.5%, specificity:33.3%) and combination of CEA, CYFRA 21-1 and ProGRP (sensitivity:91.3%, specificity:88.9%) were found suitable. Conclusion:Combination of all 5 TMs, and combination of CEA, CYFRA 21-1, and ProGRP represents an easy and non-invasive method for aid in LC diagnosis that does not require technical expertise. TM evaluation can also supplement histological diagnosis of LC.

Microplastic Fibers Increase Sublethal Effects of AgNP and AgNO3 in Daphnia magna by Changing Cellular Energy Allocation.

The effects of combined exposure to microplastics and contaminants are still not completely understood. To fill this gap, we assessed the effects of polyethylene terephthalate microplastic fibers (100 mg/L; 360 µm average length) on the toxicity of silver nanoparticles (AgNPs; 32 nm) and silver nitrate (AgNO3 ; 0.1-10 µg Ag/L) to Daphnia magna. Acute immobilization (median effect concentration [EC50]) and cellular energy allocation (CEA; ratio between available energy and energy consumption) were determined in neonates (<24 h old) and juveniles (7 d old), respectively. The 48-h EC50 for AgNP and AgNO3 (2.6 and 0.67 µg Ag/L, respectively) was not affected by the presence of microplastic fibers (2.2 and 0.85 µg Ag/L, respectively). No decrease in the available energy was observed: lipid, carbohydrate, and protein contents were unaffected. However, a significant increase in energy consumption was observed in animals exposed to AgNO3 (250% compared with control) and to the combination of microplastic fibers with AgNP (170%) and AgNO3 (260%). The exposure to microplastic fibers alone or in combination with both Ag forms decreased the CEA (values were 55-75% of control values). Our results show that after short-term exposure (48 h), microplastic fibers increased Ag toxicity at a subcellular level (i.e., CEA), but not at the individual level (i.e., immobilization). These results highlight the importance of combining different levels of biological organization to fully assess the ecotoxicological effects of plastics in association with environmental contaminants. Environ Toxicol Chem 2022;41:896-904. © 2021 SETAC.

Prognostic Value of Combined Preoperative Carcinoembryonic Antigen and Prognostic Nutritional Index in Patients With Stage II-III Colon Cancer.

Background: Tumor status can affect patient prognosis. Prognostic nutritional index (PNI), as a nutritional indicator, is closely related to the prognosis of cancer. However, few studies have examined the combined prognostic value of CEA and PNI in patients. This study investigated the relationship between CEA/PNI and prognosis of colon cancer patients.Methods: A total of 513 patients with stage II–III colon cancer who underwent curative resection at two medical centers from 2009 to 2019 were included. Clinicopathological factors were assessed and overall survival (OS) was assessed in a cohort of 413 patients. Multivariate analysis was used to identify independent prognostic variables to construct histograms predicting 1-year and 3-year OS. Data from 100 independent patients in the validation group was used to validate the prognostic model.Results: The median OS time was 33.6 months, and mortality was observed in 54 patients. Multivariate analysis revealed that preoperative CEA/PNI, lymph node metastasis, peripheral nerve invasion, operation mode, and postoperative chemotherapy were independent factors for prognosis evaluation and thus were utilized to develop the nomogram. The C-index was 0.788 in the learning set and 0.836 in the validation set. The calibration curves reached favorable consensus among the 1-, 3-year OS prediction and actual observation.Conclusion: The combined use of CEA and PNI is an independent prognostic factor and thus can serve as a basis for a model to predict the prognosis of patients with stage II–III colon cancer.

CEA increase as a marker of disease progression after first-line induction therapy in metastatic colorectal cancer patients. A pooled analysis of TRIBE and TRIBE2 studies.

In mCRC, CEA is used to monitor response to systemic therapy together with imaging. After the end of induction, no major improvement in tumour shrinkage is expected, and the availability of a marker able to predict progressive disease (PD) versus no-PD might allow avoiding CT scans. We pooled data from patients with baseline CEA ≥ 10 ng/mL included in TRIBE and TRIBE2 studies with the aim of identifying a threshold for percent increase of CEA from nadir able to predict PD after the end of the induction therapy. In total, 1178 paired CEA and radiological assessments from 434 patients were included. According to the optimal cut-off determined by ROC, a CEA increase of at least 120% from nadir differentiated between PD and no-PD with a sensitivity of 74% and a specificity of 78%, excluding PD in the 92% of radiological assessments and allowing to avoid the 67% of CT scans. However, CEA cut-off of 120% was not able to detect radiological PD in 26% of cases. In order to mitigate this issue, a different clinically relevant threshold was evaluated based on the best sensitivity cut-off. Therefore, using any CEA increase from nadir as a threshold, the sensitivity grew to 93% and only in the 7% of cases the radiological PD was not detected. In mCRC with baseline CEA ≥ 10 ng/mL, CEA values can accurately predict PD versus no-PD after the end of the first-line induction therapy.

A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.

e16123 Background: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as second-line treatment for biliary tract cancer (BTC) has demonstrated moderate efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in BTC patients. Methods: This was a single-arm, multi-center, open-label phase 2 study conducted in China. The study enrolled eligible BTC patients who progressed after fist-line chemotherapy. Patients received surufatinib monotherapy as second-line treatment, at doses of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks ± 7 days according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: As of Nov. 30, 2018, a total of 39 BTC patients, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. Sixteen-week progression-free survival (PFS) rate was 46.33% (95% confidence interval [CI], 24.38‒65.73), with median PFS of 3.7 months and median overall survival (OS) of 6.9 months. In addition, results from subgroup and post-hoc analyses suggested the trends of better clinical efficacy in patients with tumor locations inside the liver, or with lower baseline values of CA19-9 (≤ 1000 IU/mL) and CEA (≤ 3 ng/mL). The top three treatment-related adverse events (TRAEs) with severity of Grade ≥ 3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). Conclusions: When applied in the treatment of BTC patients, surufatinib monotherapy has offered moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. Moreover, surufatinib further boosting the antitumor effects of cancer immunotherapy is desirable. Clinical trial information: NCT02966821.

Large cell neuroendocrine carcinoma of the lung: Prognostic factors to predict clinical outcomes.

e20515 Background: Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare tumor, with clinical and molecular features between non-small cell and small-cell lung cancer (NSCLC and SCLC, respectively). To date, little is known about factors able to predict clinical outcome of these patients. We sought to identify prognostic factors in LCNEC. Methods: We retrospectively collected pathologically-confirmed LCNEC patients treated at the S. Orsola Malpighi Hospital of Bologna between 01/01/2009 and 31/12/2020. LCNEC was defined as tumor with neuroendocrine morphology, expression of ≥2 neuroendocrine markers (including chromogranin A, synaptophysin, or CD56) at immunohistochemistry and high tumor grade (defined as necrosis and high Ki67 ≥ 50% or high mitotic rate, ≥ 10 mitoses per 2 mm2). Clinical features, pathological features, and blood test values (including neuron-specific enolase [NSE], carcinoembryonic antigen [CEA], cytokeratin 19 fragment [cyfra 21-1]) were correlated with progression-free survival to first-line chemotherapy (PFS) and overall survival from the diagnosis of extensive disease (OS). Results: Eighty-one LCNEC patients (median age 69 years, range 63-76) were identified. Twenty-seven (33.3%) had limited-stage disease and 52 patients (67.5%) had Eastern cooperative oncology group performance status (ECOG PS) ≥ 1 at diagnosis. When extensive disease was found (ED-LCNEC, N = 67), 23 patients (34.3%) had liver metastases, 10 (14.9%) had brain metastases and 24 (35.8%) had bone metastases. Treatment in ED-LCNEC was platinum plus etoposide in 45 patients (81.9%) and platinum plus paclitaxel in 10 patients (18.1%). Among 55 patients treated with platinum-based chemotherapy, 5 patients (9.1%) received cisplatin, while 50 (90.9%) received carboplatin. Overall, OS was 9.17 months (95% confidence interval [95%CI]7.17-13.87), PFS was 4.87 months (95%CI 4.21-6.02) and ORR was 38.2% (95%CI 25.4-42.3, N = 21/56). At univariate analysis, ECOG PS ≥ 1 (P = 0.049), presence of liver (P = 0.004) and bone metastases (P = 0.009), ≥ 2 non-nodal metastatic sites (P &lt; 0.001), elevated NSE (P = 0.009) and CEA level at diagnosis (P = 0.011) were associated with increased risk of death. At multivariate analysis, ECOG PS ≥ 1 (P = 0.020), ≥ 2 metastatic sites (P = 0.002), and elevated NSE level at diagnosis (P = 0.009) were independently associated with the risk of death. At univariate analysis brain metastases (P = 0.017), ≥2 metastatic sites (P = 0.006) and elevated value of CEA at baseline (P = 0.026) were associated with increased risk of progression. At multivariate analysis, only the presence of brain metastases (P = 0.043) retained its association with the risk of progression. Conclusions: In ED-LCNEC of the lung, ECOG PS, number of non-nodal sites of metastases and NSE at baseline are associated with worse survival, while the presence of brain metastases is associated with shorter PFS.

CA125: A superior prognostic biomarker for colorectal cancer compared to CEA, CA19-9 or CA242.

The tumor stage represents the single most important prognostic factor for colorectal cancer (CRC), although more accurate prognostics remain much needed. Previously, we identified CA125 as an independent significant prognostic factor, which we have further validated along with CEA, CA19-9, and CA242 in a large cohort of CRC patients. Using enzyme-linked immunosorbent assays, we analyzed preoperative serum samples in 322 CRC patients operated on between 1998 and 2003. Using the Spearman's rho model, we calculated the correlation between our previous findings on MUC16 and CA125, for which the correlation coefficient was 0.808 (p < 0.001). The Cox regression analysis of the linear and logarithmic values of CEA, CA125, CA242, and CA19-9 identified only CA125 (hazard ratio [HR] 1.03; 95% confidence interval [95% CI] 1.02-1.04; p < 0.001) as significant when using the linear values. Survival among CRC patients with a high CA125 level was poor compared with CRC patients with a low CA125 level (HR 2.48; 95% CI 1.68-3.65; p < 0.001). In subgroup analyses, patients with high CA125 levels and aged ≤67 or >67, with stage I-II or III-IV, and both colon and rectal cancer exhibited poor prognoses. In the multivariate analysis, we used clinical pathological variables in the model, where age, gender, and stage served as the background characteristics. We dichotomized CA125 using the Youden maximal cutoff point, and the median values for CEA, CA19-9, and CA242. CA125 emerged as the only marker remaining significant and independent together with stage, location, and age (HR 1.91; 95% CI 1.24-2.95; p 0.003). CA125 represents a significant and independent prognostic factor in CRC patients, superior to CEA. Furthermore, CA242 served as a better prognostic marker than both CEA and CA19-9. We recommend including both CA125 and CA242 in prognostic clinical trials among CRC patients.

Prediction of Prognosis for cHCC-CC Patients After Surgery: Comparison of Tumor Marker Score Based on AFP, CEA, CA19-9, and Other Clinical Stages.

The effectiveness of clinical stage as a prognostic factor in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) patients is controversial. Medical records of all pathologically confirmed cHCC-CC patients from 2000 to 2017 at West China Hospital were retrieved. Tumor marker score (TMS) was determined from optimal AFP, CEA, and CA19-9 cutoff values. Interaction and subgroup analysis were conducted according to potential confounders. Prognostic value of TMS and other prognostic models were evaluated by Kaplan-Meier (K-M) analysis, c-index, and time-dependent receiver operating curves (td-ROC). Optimal cutoff values for preoperative AFP, CEA, and CA19-9 were 10.76 ng/mL, 5.24 ng/mL, and 31.54 U/mL, respectively. Among 128 patients, 24, 58, and 46 were classified into TMS 0, TMS 1, and TMS ≥ 2, respectively. TMS could stratify our series into groups of statistically different prognosis. Subgroup analysis according to potential confounders and test for interactions showed that TMS 1 and TMS ≥ 2 were stable risk factors relative to TMS 0. Univariate (HR: TMS1 = 2.30, p = 0.014; TMS ≥ 2 = 5.1, p < 0.001) and multivariate Cox regression analyses (HR: TMS1 = 1.72, p = 0.124; TMS ≥ 2 = 4.15, p < 0.001) identified TMS as an independent prognostic risk factor. TMS had good discrimination (c-index 0.666, 95% CI 0.619-0.714), and calibration plots revealed favorable consistency. Area under the curve (AUC) value of td-ROC for TMS and integrated AUC was higher than for other clinical stages at any month within 5 years postoperation. TMS exhibited optimal prognostic value over other widely used clinical stages for cHCC-CC after surgery and may guide clinicians in prognostic prediction.

The relation between inflammation-based parameters and survival in metastatic pancreatic cancer.

We aimed to evaluate whether tumor markers and inflammation parameters effect on survival in patients with metastatic pancreatic cancer (MPC). This retrospective analysis included 170 patients with pancreatic cancer who were admitted to the oncology clinic at the metastatic stage. Basic patient demographic characteristics, chemotherapy (CT) that patients received in the first line, complete blood count, neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), albumin/globulin ratio (AGR), prognostic nutritional index (PNI), tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA19-9]), and survival were analyzed. Receiver operating characteristic analysis was used to determine the optimum cutoff value of NLR, PLR, AGR, PNI, CEA, and CA 19-9, which could predict survival. The median age of the patients was 63 years (range, 33-87). About 63.5% of the patients were male and 44.5% were female. 161 (94.7%) patients died, and the median overall survival (OS) was 8.0 months (95% confidence interval = 6.6-9.4) for all patients. In univariate analysis, age (P < 0.001), CT regime (P < 0.002), AGR (P < 0.006), PNI (P < 0.017), NLR (P < 0.001), PLR (P < 0.062), and CA19-9 (P < 0.002) were statistically significant. In multivariate analysis, age (hazard ratio [HR] 1.534 95% 1.079-2.182 P < 0.017) CA19-9 (HR1.410 95% 1.001-1.989, P ≤0.005) and, NLR (HR 1.569 95% 1.001-2.463, P < 0.049) were significant. We determined, age, CA19-9, and basal high NLR as independent adverse prognostic factors for OS in APC. Fluorouracil, leucovorin, irinotecan, and oxaliplatin CT resulted in a significant increase in OS.

Combined detection of CA15-3, CEA, and SF in serum and tissue of canine mammary gland tumor patients

The purpose of this study is to evaluate the levels and clinical diagnosis value of CA15-3, CEA, and SF in canine mammary gland tumors (CMGTs). In this study, the levels of tissues/serum CA15-3, CEA, and SF in 178 CMGT patients or healthy dogs were determined by ELISA and qRT-PCR assay. CA15-3, CEA, and SF levels of the malignant tumor group were significantly higher than that of the benign tumor group and the healthy control group. In the malignant tumor group, CA15-3 held a sensitivity of 51.8%, a specificity of 93.9%, and an accuracy of 76.8%. The sensitivity, specificity, and accuracy of CEA were 44.6%, 84.1%, and 68.1% respectively. SF held a sensitivity of 62.5%, a specificity of 85.4%, and an accuracy of 76.1%. SF showed the highest sensitivity and CA15-3 showed the highest specificity. The sensitivity, specificity, and accuracy of the combined detection of the three biomarkers in malignant tumor groups were 80.4%, 78.0%, and 80.0%, respectively, therefore combined detection increased sensitivity and accuracy but decreased specificity. In conclusion, the combined detection of serum/tissue markers CA15-3, CEA, and SF may improve the detection sensitivity of CMGTs, providing reference value for clinical application.

Diagnostic and Prognostic Value of CEA and CA19-9 in Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. A diagnosis at early stages with enhanced screening methods is vital as metastases and recurrences increase mortality. The aim of this study was to analyze the tumor markers CEA and CA19-9 combined in correlation with diagnostics and prognosis. Therefore, 1487 patients with CRC who were diagnosed and treated between 2000 and 2015 at the University Hospital Ulm, Germany, were retrospectively evaluated. Overall and recurrence-free survival was analyzed in association with preoperative CEA and CA19-9 separately and combined and a multivariate analysis was performed. The 5-year overall survival was significantly shorter in patients with a CEA or CA19-9 level ≥200 compared to patients with an increased, but <200, or normal level (CEA: 69%/44%/7%; CA19-9: 66%/38%/8%). Patients with both tumor markers increased also showed a remarkably shorter 5-year survival rate (CEA+/CA19-9+: 23%). The multivariate analysis emphasizes these results (p-value < 0.0001). Patients with both tumor markers elevated had the shortest 5-year recurrence-free survival rate, followed by patients with either CEA or CA19-9 elevated (CEA-/CA19-9-: 79%; CEA+/CA19-9; CEA-/CA19-9+: 65%; CEA+/CA19-9+: 44%). In conclusion, measuring CEA and CA19-9 preoperatively in CRC patients is reasonable and could be useful as a prognostic factor.

Using HE4, RMI, ROMA and CPH-I in the differential diagnosis of adnexal masses

Objectives: In order to improve the early diagnosis of ovarian cancer (OC), we evaluated human epididymis secretory protein 4 (HE4), the risk of malignancy index (RMI), the risk of ovarian malignancy algorithm (ROMA), and the Copenhagen Index (CPH-I) in their ability to predict the risk of adnexal masses being malignant, and in discriminating between serous and mucinous ovarian tumors. Methods: A study consisting of 509 patients who were diagnosed with benign, borderline, and malignant adnexal tumors was conducted. We analyzed the values of HE4, RMI, ROMA, and CPH-I. In addition, CA125, CEA, CA125/CEA ratio, CA199, and CA125/CA199 ratio were also assessed to determine their predictive values to diagnoses serous or mucinous ovarian tumors. Results: To differentiate between benign and borderline ovarian tumors, we evaluated RMI and CPH-I scores which showed high AUC (0.7593, and 0.7128, respectively), but neither of them showed both high sensitivity and specificity. When discriminating benign and malignant tumors, RMI and CPH-I performed the best for premenopausal women; whereas ROMA and HE4 performed the best for postmenopausal women. Patients with values above the cutoff for CA125 (&gt; 328.3 U/mL), CA125/CEA (&gt; 82.26), and CA125/CA199 (&gt; 5.633), were more likely to be diagnosed with serous carcinoma. Whereas those with higher values for CEA (&gt; 3.7 μμg/L) and CA199 (&gt; 27.81 ng/mL) were more likely to have a mucinous carcinoma. Conclusion: RMI and CPH-I for premenopausal women, ROMA and RMI for postmenopausal women were reliable indicators to differentiate between women with benign versus malignant tumors. In addition, the ratios CA125/CEA and CA125/CA199 could be used to distinguish serous from mucinous ovarian carcinomas.

Limits of serum carcinoembryonic antigen and carbohydrate antigen 19-9 as the diagnosis of gallbladder cancer.

PurposeAlthough serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC.MethodsBetween January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated.ResultsIn terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively.ConclusionSerum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.

Study of Serum CEA and Ca 19.9 in Esophageal Squamous Carcinoma and ROC Curve Analysis

Background: There are very few studies on the comparative diagnostic value of CEA and Ca19.9 in esophageal squamous cell carcinoma (ESCC).Aims and objectives: The aim of the present study was to access the clinical relevance of CEA and CA19.9 in ESCC and to determine whether combined use of these marker could improve diagnostic sensitivity and specificity. Material and Method: Venous blood Samples were collected from total 68 individuals, divided into two categories, group 1 includes 18 healthy individuals and group 2 includes 50 patients with already diagnosed cases of ESCC prior to any treatment. Tests were performed to estimate the value of CEA and Ca19.9. Different statistical analysis has been performed to derive a clinically meaningful value.Results: The mean serum CEA and CA 19.9 levels and also the ratio of CEA/Ca19.9 were higher in patients with ESCC than healthy subjects. In ESCC, the optimal combination of sensitivity and specificity for CEA were determined as 48% and 94% and for CA19.9 were determined as 76% and 72% respectively, whereas combined analysis of CEA/CA19.9 were lower than individual value in patients. Over all accuracy rate was better with CA19. The diagnostic power of CEA and CA19-9 as a screening test for ESCC were assessed by ROC curve analysis. The cut-off value for CEA and CA19-9 in ESCC were found to be 2.9 2 ng/ml and 7.4 ng/ml and were found to be above the cut-off value in 25 (50%) and 42 (84%) of the patients with ESCC respectively.Conclusion: The results of our study indicated that serum CA19.9 has a higher positivity than serum CEA in esophageal cancer. The combined use of CA19-9 and CEA (ratio) could not increase the diagnostic sensitivity in esophageal cancers in our study.

BRAF Mutated Metastatic Colorectal Carcinoma (mCRC): A case report

Colorectal cancer (CRC) is the third and second most frequent cancer in men and women respectively. Although histologically similar, CRCs are diverse with respect to the underlying molecular mechanism which could be explored for planning treatment strategies. Chromosomal instability, microsatellite instability, and errors in the DNA repair mechanism are the most frequent molecular aberrations involved in various sub groups of CRCs.&#x0D; BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutation is seen in 5-15 % of CRC, with a higher mutation rate in right sided colon cancer. Patients with BRAF V 600E mutation tends to have a poor prognosis with a median survival rate of less than 12 months. In terms of treatment these patients do not benefit from therapeutics targeting the EGFR so it is important for clinicians to be aware. Treatment options beyond standard chemotherapy are crucial to achieve better outcomes and the role of anti-EGFR therapy alone remains controversial. Current trials assessing combinations of molecular targeted agents have shown some promise.&#x0D; We report a case of a 32 year old female who presented with features of intestinal obstruction and pallor of skin and mucous membranes. Her blood test showed low Hb and a high serum CEA value and CT Abdomen revealed a large hepatic flexure growth with multiple liver metastasis. Colonoscopic biopsy showed moderately differentiated adenocarcinoma and molecular assay confirmed wild type K RAS and mutated BRAF. To the best of our knowledge there are no reported cases of BRAF mutated metastatic carcinoma colon from Nepal.

Utility of triple tumor markers CA19-9, CA125 and CEA in predicting advanced stage of carcinoma gallbladder: a retrospective study

Background: A combination of serum tumor markers are used in the evaluation and prognosis of carcinoma gallbladder (GBC). Aim of the study was to find the significance of combined use of CA19-9, CA125 and CEA in advanced stage of GBC and to find the cut-off value of each of these tumor markers in metastatic GBC. Methods: This was a retrospective observational cohort study over 1 year, which was carried out in 42 cases of advanced GBC. The patients were grouped in to locally advanced and metastatic stage on the basis of CECT scan findings. CA19-9, CA125 and CEA were assayed in all patients. These tumor markers were analysed with these two groups of GBCs. Statistical analysis was performed using R statistical software v3.6.2.Results: Out of 42 cases CA19-9 was elevated in 18 (78%), CA125 in 16 (70%) and CEA in 9 (39%) patients with metastatic disease. The cut-off value of CA19-9, CA125 and CEA was determined by ROC curve were &gt;109 U/ml, 55.4 U/ml and 2.56 μg/l respectively. CA19-9 had the highest sensitivity 78.3% followed by CA125 69.6% and CEA has the highest specificity 68.4% for the diagnosis of metastatic stage of the disease. Specificity of these tumor markers were highest when used in combination.Conclusions: Combined use of triple tumor markers increases its specificity in the diagnosis of advanced stage of GBC but their cut-off level is statistically not significant in predicting metastatic GBC.

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

Differential diagnosis of liver metastases of gastrointestinal stromal tumors from colorectal cancer based on combined tumor biomarker with features of conventional ultrasound and contrast-enhanced ultrasound.

To explore the value of tumor marker CA125 and CEA linked with conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) features in differentiating gastrointestinal stromal tumors liver metastases (GISTLM) from colorectal cancer liver metastases (CRCLM). From December 2005 to February 2019, eighty patients with pathologically proven GISTLM together with 80 CRCLM patients were retrospectively evaluated with contrast-enhanced ultrasound (CEUS). Clinical characteristics such as CA125 and CEA were documented to compare the difference between GISTLM and CRCLM. Univariate analysis was performed to determine significant features in ultrasound and then these features were entered into multivariate logistic regression model to determine diagnostic criteria. By analyzing the tumor marker and imaging features, diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. The sensitivity, specificity and accuracy were calculated for the diagnosis of GISTLM. Multiple logistic regression analysis showed that increased CA125 and normal CEA were the independent variables of GISTLM. On conventional US, the features of hypo- or mix-echogenicity and anechoic area were associated with GISTLM. On CEUS, capsule enhancement, starting time of washout > 40s and proportion of non-enhancement area > 20% were the features indicating GISTLM. All of the p values were < 0.05. When linking tumor marker with imaging features, the diagnostic sensitivity improved from 36.3-57.5% to 70.0%, and the area under the ROC (AUROC) curve improved from 0.681-0.750 to 0.838, with a specificity of 97.5%. Combining the imaging features of conventional US and CEUS with serum tumor markers provides a potentially effective diagnostic method in differentiation of GISTLM and CRCLM.

Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial.

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p &lt; 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p &lt; 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p &lt; 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .