Serum Carcinoembryonic Antigen Concentration Research Articles

The Importance of Determining Preoperative Serum Concentration of Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen in Assessing the Progression of Colorectal Cancer

Introduction:Many evidence indicates that Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA 19-9) have strong reactivity with tumor cells and may serve as a useful marker in identifying patients with colorectal cancer (CRC).Objectives:The goal of this study was to evaluate the relationship between preoperative concentration of serum levels of CEA and CA 19-9 and progression of colorectal cancer.Methods:The retrospective study included 80 patients operated for colorectal cancer at the Clinic for General and Abdominal Surgery, Clinical Center of University of Sarajevo, from 2013 to 2018. The following clinical and laboratory parameters were observed: age, sex, preoperatively measured concentrations of CEA and CA 19-9 antigens, CRC localization, postoperative histopathological findings and CRC stage (TNM classification). All of the data above were processed by relevant statistical methods, with an accepted level of statistical significance of p <0.05.Results:The highest serum levels of CEA and CA 19-9 were observed in stage IV of CRC. Average CEA and CA 19-9 values did not differ significantly between tumor stages (p>0.05). Preoperatively measured serum concentrations of CEA and CA 19-9 in patients with CRC were significantly correlated (rho = 0.328, p = 0.001). An increase in the depth of tumor invasion of the intestinal wall tumor (pT) is followed by an increase in the serum value of the CEA marker, but this ratio was not statistically significant (rho=0.194, p=0.080), while the relationship between depth of intestinal wall invasion and serum level of CA 19-9 was significantly positive correlation (rho = 0.252, p = 0.024). However, the linear regression analysis model showed that serum levels of CEA and CA 19-9 could not be predictors of CRC stage and depth of tumor invasion of the intestinal wall (p> 0.05).Conclusion:Preoperatively measured serum values of CEA and CA 19-9 cannot indicate the specific stage and histopathological size of the CRC.

Frequent Novel Variations Within MSH2 and MLH1 Genes in a Subset of Iranian Families With Hereditary Non-Polyposis Colorectal Cancer Shadi

Abstract- Hereditary non-polyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition for development of colorectal cancer (CRC) caused by germline defects in mismatch repair (MMR) genes. Current study was aimed to find genetic variations in MSH2 and MLH1 genes and their correlation with the serum levels of Carcinoembryonic Antigen (CEA) in seven Iranian HNPCC families. Seven unrelated Iranian families including 11 HNPCC patients and 7 affected family members were selected. They were initially screened for mutations in exons 7 of MSH2 and exon 15 of MLH1 gene through polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Positive PCR results were further analyzed through exon sequencing. Serum CEA level was determined using the ELISA test. PCRSSCP was positive in 8 out of 18 patients (44%) for exons 7 of MSH2 gene, whereas two samples (11%) demonstrated to bear a mutation in exon 15 of the MLH1 gene. Sequencing analysis of both amplified exons in positive and negative samples have confirmed no mutation in negative samples while revealed 5 and 7 novel mutations in exons 7 and 15, respectively. The mean serum concentration of CEA had a significant difference between HNPCC patients and their healthy family members. Our results demonstrated that the PCR-SSCP method has high specificity and sensitivity in the first step of mutation screening of HNPCC families. High frequency of novel alterations found in the current assay may revise the mutation screening of MSH2 and MLH1 genes and abet further assessment of their frequency among individual HNPCC patients.

A Silicon Nanowire Array Biosensor Fabricated by Complementary Metal Oxide Semiconductor Technique for Highly Sensitive and Selective Detection of Serum Carcinoembryonic Antigen.

In this paper, we present a highly sensitive and selective detection of serum carcinoembryonic antigen (CEA) based on silicon nanowire (SiNW) array device. With the help of traditional microfabrication technology, low-cost and highly controllable SiNW array devices were fabricated. After a series of surface modification processes, SiNW array biosensors show rapid and reliable response to CEA; the detection limit of serum CEA was 10 fg/mL, the current signal is linear with the logarithm of serum CEA concentration in the range of 10 fg/mL to 100 pg/mL. In this work, SiNW array biosensors can obtain strong signal and high signal-to-noise ratio; these advantages can reduce the production cost of the SiNW-based system and promote the application of SiNWs in the field of tumor marker detection.

Optimized Cutoff Value of Serum Squamous Cell Carcinoma Antigen Concentration Accurately Predicts Recurrence After Curative Resection of Squamous Cell Carcinoma of the Esophagus.

Squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are widely used in clinical practice to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, their predictive values for prognosis are controversial. This study determined optimal cutoff values of serum SCC-Ag and CEA concentrations for predicting postoperative recurrence of ESCC, which enabled selection of high-risk patients. The study retrospectively analyzed 427 patients who underwent curative resection for ESCC. The optimal cutoff values of preoperative SCC-Ag and CEA concentrations for predicting postoperative recurrence were determined using combined analysis of hazard ratios and sensitivities for recurrence. Using the optimal cutoff value, the study evaluated survival, recurrence patterns, and temporal changes in marker concentrations. The preoperative SCC-Ag concentration of 1.1ng/ml was the optimal cutoff value for predicting postoperative recurrence, whereas precise cutoff values could not be determined for preoperative CEA concentrations. High preoperative SCC-Ag concentrations (> 1.1ng/ml), which were significantly associated with more aggressive tumor phenotypes and shorter disease-free survival, were identified as an independent prognostic factor in the multivariable analysis. High preoperative SCC-Ag concentrations were significantly associated with greater prevalence of lung/pleura and local recurrences. Normalization of serum SCC-Ag concentrations after neoadjuvant treatment or esophagectomy was not associated with a decreased risk of postoperative recurrence. The optimal cutoff value of preoperative SCC-Ag concentrations that predicted recurrence of ESCC was 1.1ng/ml, illuminating the utility of serum SCC-Ag concentrations as an easily measurable tool for selecting a perioperative management strategy.

Does Carcinoembryonic Antigen Serum Concentration Decrease Predicts Overall Survival in Patients with Unresectable Rectal Cancer after Radical Radiotherapy or Radiochemotherapy?

To evaluate whether post-treatment carcinoembryonic antigen (CEA) serum concentration decrease corresponds with the outcome of definitive radiotherapy (RT) or radiochemotherapy (RT-CHT) in primary unresectable rectal cancer patients (pts). Inclusion criteria of this retrospective study were: primary unresectable, locally advanced rectal cancer with histopathological confirmation, RT/RT-CHT as a radical treatment and measured CEA post-treatment level. Between 2000 and 2016 145 pts were treated due to unresectable rectal cancer. Primary aim of the treatment was tumor downsizing allowing further radical surgery. Among them, 71 had pre- and post-treatment CEA and 10 post-treatment CEA measurements, therefore the group of 81 pts (60 men, 21 women) was evaluated in this study. Out of 81 pts: 33 (41%) received RT (accelerated hyperfractionation: 66 Gy in 1.5 Gy fx twice a day or conventional fractionation: 60-66 Gy in 2 Gy fx) and 48 (59%) RT-CHT (54 Gy/1.8 Gy fx +2 cycles of 5-Fu LV). Six to eight weeks after RT or RT-CHT tumor resectability was evaluated again using physical examination and imaging studies. Pts were divided in two groups: group A: pts with CEA post-treatment concentration decrease or below 5 ng/ml and group B: pts without post-treatment decrease of CEA or concentration above 5 ng/ml. Statistical test used were Kaplan-Meyer survival analysis, log rank test and Cox regression model. Median follow-up after the end of RT/ RT-CHT was 5.5 years. Fifty four pts (67%) had radical resection after neoadjuvant RT/RT-CHT and 27 (33%) were still unresectable. CEA serum concentration decrease or level below 5ng/ml (group A) was observed in 63 pts (77%), CEA serum concentration increase or level above 5ng/ml (group B) in 18 (23%). In univariate analysis pts in group A had better overall survival (OS) compared to group B (p=0.039, median OS of 40 months vs 87 months, respectively). Five-year OS was 62% in group A compared to 30% in group B. Moreover, pts who received RT-CHT had better 5-year OS compared to RT (63 vs 44%) respectively (p=0.04). Pts after radical resection had better 5-year OS than those still unresectable (71% vs 21%, p=0,000). Significant factors were then checked in multivariate analysis. Only radical surgery had reached statistical significance (p=0,000) for OS. Pts with post-treatment serum CEA concentration decrease or level below 5 ng/ml tend to have better overall survival compared to those in whom CEA concentration did not decrease after the neoadjuvant treatment. Post-treatment decrease in serum CEA concentration in primary unresectable rectal cancer patients who received definitive RT/RT-CHT can be a useful predictor of outcome.

False-positive elevated CEA during colon cancer surveillance: a cholecystitis case report diagnosed by PET-CT scan

A 53-year-old man with previous history of sigmoid colon adenocarcinoma who had undergone surgical resection and adjuvant chemotherapy presented with slightly rising carcinoembryonic antigen (CEA), while anatomical imaging modalities were unremarkable. FDG PET-CT study did not identify residual tumoral disease; however, there were abnormalities in the gallbladder most likely suggestive of cholecystitis. Eight weeks after cholecystectomy, serum CEA concentration reached normal values. Final histopathology of the gallbladder was also consistent with acute on chronic cholecystitis.

Enumerating Circulating Tumor Cells with a Self-Assembled Cell Array (SACA) Chip: A Feasibility Study in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(−)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during surgery. We found that the CTC count in PB but not IMV correlates with disease stages. Neoadjuvant chemotherapy did not lead to decreased CTC count in both types of blood samples. With cutoffs of four CTCs per 2 mL of blood, and serum carcinoembryonic antigen (CEA) level of 5 ng/mL, patients with non-metastatic disease were more likely to experience recurrence if they had high PB CTC count and high serum CEA concentration (odds ratio, 8.9). Our study demonstrates the feasibility of enumerating CTCs with a SACA chip in patients with colorectal cancer.

Prognostic value of the systematic immune-inflammation index among patients with operable colon cancer: A retrospective study.

The systematic immune-inflammation index (SII) has been used to predict the prognosis of patients with various cancers. This study aimed to determine whether the preoperative SII was associated with postoperative survival among patients with operable colon cancer.This retrospective study included 118 age- and sex-matched healthy subjects and 118 patients who underwent radical surgery for colon cancer between January 2011 and December 2013. The preoperative SII was calculated based on counts of neutrophils, lymphocytes, and platelets in the peripheral blood. Pearson correlation analysis was used to analyze the relationships between the SII and carcinoembryonic antigen (CEA) concentration, average length of stay (ALOS), and medical costs during hospitalization. The χ2 test or Fisher exact test was used to analyze the relationship between the preoperative SII and the postoperative survival rate.The median SII value was 667.75 among patients with colon cancer, which was higher than the value among healthy subjects. A high SII (>667.75) was associated with a large tumor size and advanced TNM stage, although it was not associated with age, sex, tumor location, or pathological grade. Pearson correlation analysis revealed that the SII was positively correlated with serum CEA concentration, ALOS, and medical costs. Relative to a low SII, a high SII was significantly associated with a lower overall survival rate at 3 years and 5 years after surgery.The present study's findings suggest that the preoperative SII is a useful prognostic index for patients with operative colon cancer.

Identifying the Best Marker Combination in CEA, CA125, CY211, NSE, and SCC for Lung Cancer Screening by Combining ROC Curve and Logistic Regression Analyses: Is It Feasible?

The detection of serum biomarkers can aid in the diagnosis of lung cancer. In recent years, an increasing number of lung cancer markers have been identified, and these markers have been reported to have varying diagnostic values. A method to compare the diagnostic value of different combinations of biomarkers needs to be established to identify the best combination. In this study, automatic chemiluminescence analyzers were employed to detect the serum concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), cytokeratin 19 fragment (CY211), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC) in 780 healthy subjects, 650 patients with pneumonia, and 633 patients with lung cancer. Receiver operating characteristic (ROC) curve and logistic regression analyses were also used to evaluate the diagnostic value of single and multiple markers of lung cancer. The sensitivities of the five markers alone were lower than 65% for lung cancer screening in healthy subjects and pneumonia patients. SCC was of little value in screening lung cancer. After combining two or more markers, the areas under the curves (AUCs) did not increase with the increase in the number of markers. For healthy subjects, the best marker for lung cancer screening was the combination CEA + CA125, and the positive cutoff range was 0.577 CEA + 0.035 CA125 > 2.084. Additionally, for patients with pneumonia, the best screening markers displayed differences in terms of sex but not age. The best screening marker for male patients with pneumonia was the combination CEA + CY211 with a positive cutoff range of 0.008 CEA + 0.068 CY211 > 0.237, while that for female patients with pneumonia was CEA > 2.73 ng/mL, which could be regarded as positive. These results showed that a two-marker combination is more suitable than a multimarker combination for the serological screening of tumors. Combined ROC curve and logistic regression analyses are effective for identifying the best markers for lung cancer screening.

Comparison of chemiluminescent microparticle immunoassay (CMIA) with electrochemiluminescence immunoassay (ECLIA) for Carcinoembryonic antigen (CEA)

Introduction: Carcinoembryonic antigen (CEA) is used for monitoring of disease progression and treatment response in cancer patients. Our aim was to compare the performance of chemiluminescent microparticle immunoassay (CMIA) with electrochemiluminescence immunoassay (ECLIA) for CEA.&#x0D; Methods: A total of 115 samples were collected during routine diagnostic, prognostic and therapy monitoring procedures in patients with colorectal and pancreatic cancer. We used ARCHITECT i2000SR and Cobas E601 for CEA analysis in sera samples.&#x0D; Results: The correlation coefficient of 0.984 [95% CI: 0.972 to 0.991] for results obtained on both platforms was observed for CEA≤10 ng/mL group. Moreover, intercept of 0.9027 [95% CI: 0.705 to 1.099] and slope 0.8076 [95% CI: 0.765 to 0.8498] (p &lt; 0.0001) was observed in this group. In CEA &gt;10 ng/mL group we observed slope = 1.1986 [95%CI: 1.1474 to 1.2498] (p &lt; 0.0001), intercept = -11.69 [-17.53 to - 5.84] and correlation coefficient of 0.985 [95% CI: 0.976 to 0.9914]. Mean differences between assays in group ≤10 ng/mL and &gt;10 ng/mL were 0.2066 (95% CI: 0.0019 to 0.4113) and –2.66 (95% CI: -10.10 to 4.76) ng/mL, respectively.&#x0D; Conclusion: Although there were differences, based on 20 days precision tests, overall results showed a good analytical performance and correlation between CEA assays on ARCHITECT i2000SR and Cobas E601 platforms. Reference intervals appropriate for the method of CEA measurement should be used. The standardization and harmonization of serum CEA concentration assays are needed.

Validation of Assaying Carcinoembryonic Antigen in Human Serum by Using Immunomagnetic Reduction

Immunomagnetic reduction (IMR) is a method to assay biomolecules by utilizing antibody functionalized magnetic nanoparticles. For clinical validation, important analytic performances of assaying carcinoembryonic antigen (CEA) using IMR are characterized. Furthermore, IMR is applied to assay carcinoembryonic antigen (CEA) in human serum for clinical validation. A total of 118 healthy controls and 79 patients with colorectal cancer (CRC) are recruited in this study. For comparison, assays using chemiluminometric immunoassay (CLIA) are also done for quantizing CEA in these serum samples. The results reveal a high correlation in terms of serum CEA concentration detected via IMR and CLIA is found (r = 0.963). However, IMR shows higher clinical sensitivity and specificity than those of CLIA. Moreover, the rate of false positives for smoking subjects is clearly reduced through the use of IMR. All the results demonstrate IMR is a promising alternative assay for serum CEA to diagnose CRC.

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

BackgroundMutation status of RAS and BRAF, as well as serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are biomarkers used in clinical management of patients with gastrointestinal cancers. This study aimed to examine the prognostic role of these biomarkers in a patient population that started first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC) in the NORDIC-VII study.MethodsCEA and CA 19-9 were measured in serum samples from 545 patients obtained before the start of chemotherapy. Four hundred and ninety-four patients had detectable levels of carbohydrate antigen 19-9 (CA 19-9). RAS (exons 2–4) and BRAF (V600E) mutation status were available from 440 patients. Overall survival (OS) was estimated in patient groups defined by serum CEA or CA 19-9 levels using cut-off values of 5 µg/L and 35 kU/L, respectively, in the total population and in subgroups according to RAS and BRAF mutation status.ResultsFor both CEA and CA 19-9, elevated serum levels were associated with reduced OS in adjusted analyses which included RAS and BRAF mutation status, baseline World Health Organization performance status, and levels of alkaline phosphatase and C-reactive protein. The negative prognostic information provided by an elevated CA 19-9 level was particularly marked in patients with BRAF mutation (hazard ratio = 4.35, interaction P = 0.003, in an adjusted model for OS).ConclusionsHigh baseline serum concentrations of CEA and CA 19-9 provide independent information of impaired prognosis in mCRC. In patients with BRAF-mutant tumours, elevated serum CA 19-9 may identify a subgroup with highly aggressive disease and could contribute to improving therapeutic decisions.

Lysyl oxidase: A colorectal cancer biomarker of lung and hepatic metastasis.

BackgroundColorectal cancer (CRC) is a common and lethal disease in which distant metastasis remains the primary cause of death. Paradoxical roles of LOX have been reported in CRC, and the intracellular function of LOX has also recently been determined. Correlations of LOX expression and its intracellular localization with clinicopathological features in CRC patients remain largely unknown. The aim of the present study was to explore the potential roles of LOX in CRC.MethodsLOX messenger RNA expression was assayed by quantitative PCR in eight paired normal mucosa and tumor tissues. Immunohistochemistry was conducted using tissue arrays to investigate LOX expression in 201 CRC patients. Regulation of LOX by YAP and TEAD4 was explored by YAP or TEAD4 short hairpin RNA interference in a LoVo cell line.ResultsLOX messenger RNA expression was elevated in some CRC specimens, and LOX nuclear localization was detected in CRC tumor tissues. LOX nuclear localization was found to correlate with lung/hepatic metastasis, elevated serum carcinoembryonic antigen concentration, and mucinous tumor type (P < 0.05). Nuclear LOX expression was found to be associated with poor overall and disease‐free survival (P < 0.05), and postoperative lung/hepatic metastasis (P < 0.05). Knockdown of YAP or TEAD4 induced downregulation of LOX expression.ConclusionsLOX nuclear localization was significantly associated with poor survival in patients with CRC. Nuclear LOX expression was correlated with synchronous or postoperative lung/hepatic metastasis. LOX may prove to be a potential target gene of YAP and TEAD4.

Analysis of risk factors for cervical lymph node metastases in patients with sporadic medullary thyroid carcinoma.

ObjectiveMedullary thyroid carcinoma (MTC) is classified as either sporadic or inherited. This study was performed to analyze the risk factors for cervical lymph node metastases and predict the indication for prophylactic lateral neck dissection in patients with sporadic MTC.MethodsSixty-five patients with sporadic MTC were retrospectively reviewed. Univariate analysis with the chi-square test and multiple logistic regression analysis were applied to identify the clinicopathological features (sex, age, tumor size, number of tumor foci, capsule or vascular invasion, and others) associated with cervical lymph node metastases.ResultsThe metastasis rates in the central and lateral compartments were 46.2% (30/65) and 40.0% (26/65), respectively. The incidence of cervical lymph node metastases was significantly higher in patients with a tumor size of >1 cm, tumor multifocality, and thyroid capsule invasion. Only thyroid capsule invasion was an independent predictive factor for central compartment metastases and lateral neck metastases. The possibility of central compartment metastases was significantly higher when the preoperative serum carcinoembryonic antigen concentration was >30 ng/mL (60.0% vs. 34.3%).ConclusionsMTC is associated with a high incidence of cervical lymph node metastases. Prophylactic lateral node dissection is necessary in patients with thyroid capsule invasion or a high serum carcinoembryonic antigen concentration.

Evaluation of the expression and clinical value of lncRNA AC010761.9 in human gastric adenocarcinoma

BackgroundThe current study determined the expression and clinical value of lncRNA AC010761.9 in human gastric adenocarcinoma (GA).MethodsReal-time quantitative reverse transcription (qRT)-PCR was used to detect the level of lncRNA expression in 145 GA tissues and three GA cell lines, and the correlation between its level and clinicopathologic characteristics and potential corresponding mRNA of TNF receptor-associated factor 4 gene (TRAF4) was then evaluated.ResultsElevated lncRNA AC010761.9 was detected in all 6 GA tissues by previous lncRNA expression profile microarray assay. LncRNA AC010761.9 was over-expressed in 99 of 145 GA tissues (68.3%) with an elevated fold change of up to 35.14 compared to matched paracancerous tissues (p < 0.05), and was also over-expressed in the 3 GA cell lines (MGC803, BGC823, and SGC7901) compared to the normal gastric mucosal epithelial cell line (GES-1 cells; p < 0.05) by qRT-PCR. The elevated expression of this lncRNA was related to tumor size (p = 0.028), degree of differentiation (p = 0.047), and serum carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA) concentrations (p = 0.026 and p = 0.037, respectively). Multivariate analysis further confirmed that the expression of lncRNA AC010761.9 was related to the degree of tumor differentiation (p = 0.015). Additionally, the expression of lncRNA AC010761.9 had a positive correlation with the mRNA expression of the potentially associated gene (TRAF4) in GA tissues (r = 0.385, p < 0.01).ConclusionsLncRNA AC010761.9 may be linked to GA progression and is a potential new biomarker for GA.

Evaluation of the diagnosis value of carcinoembryonic antigen in malignant pleural effusion

Objective: To investigate the diagnostic value of serum and pleural fluid carcinoembryonic antigen (CEA) for malignant pleural effusion (MPE). Methods: The concentration of CEA in serum and pleural fluid of 286 patients with the diagnosis confirmed by pleural biopsy through medical thoracoscopy were retrospectively analyzed. MPE was confirmed in 171 cases which were divided into two groups (adenocarcinoma group with 121cases and non-adenocarcinoma group with 50 cases) and benign pleural effusion in 115 cases. The optimal cutoff for MPE and MPE caused by adenocarcinoma were determined by using the ROC curve. Results: The concentration of serum CEA 12.27(3.80, 58.45) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.91(1.08, 4.55) μg/L and benign effusion 1.32(0.86, 2.27) μg/L (both P<0.001), but there was no statistically significant difference between benign and non-adenocarcinoma effusion (P=0.728). The concentration of pleural fluid CEA 160.70(30.48, 1 000.00) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.77(0.51, 11.39) μg/L and benign effusion 1.09(0.60, 1.68) μg/L (both P<0.001), and higher in non-adenocarcinoma effusion than that of benign effusion (P<0.05). The cutoff value of serum and pleural fluid CEA for MPE was 3.10 and 5.83 μg/L, the sensitivity respectively was 67.3% and 74.3%, the specificity respectively was 87.8% and 98.3%, positive predictive value respectively was 89.2% and 98.5%, negative predictive value respectively was 64.3% and 72.0%. The cutoff value of serum and pleural fluid CEA for MPE caused by adenocarcinoma was 3.54 and 7.30 μg/L, the sensitivity respectively was 76.0% and 91.7%, the specificity respectively was 74.0% and 72.0%, positive predictive value respectively was 87.6% and 88.8%, negative predictive value respectively was 56.1% and 78.3%. Conclusions: The concentration of serum and pleural fluid CEA have diagnostic significance to MPE, especially MPE caused by adenocarcinoma. The diagnostic value of pleural fluid CEA is superior to serum CEA.

Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study

Tumour-targeted fluorescence imaging has the potential to advance current practice of oncological surgery by selectively highlighting malignant tissue during surgery. Carcinoembryonic antigen (CEA) is overexpressed in 90% of colorectal cancers and is a promising target for colorectal cancer imaging. We aimed to assess the tolerability of SGM-101, a fluorescent anti-CEA monoclonal antibody, and to investigate the feasibility to detect colorectal cancer with intraoperative fluorescence imaging. We did an open-label, pilot study in two medical centres in the Netherlands. In the dose-escalation cohort, we included patients (aged ≥18 years) with primary colorectal cancer with increased serum CEA concentrations (upper limit of normal of ≥3 ng/mL) since diagnosis, who were scheduled for open or laparoscopic tumour resection. In the expansion cohort, we included patients (aged ≥18 years) with recurrent or peritoneal metastases of colorectal cancer, with increasing serum concentrations of CEA since diagnosis, who were scheduled for open surgical resection. We did not mask patients, investigators, or anyone from the health-care team. We assigned patients using a 3 + 3 dose design to 5 mg, 7·5 mg, or 10 mg of SGM-101 in the dose-escalation cohort. In the expansion cohort, patients received a dose that was considered optimal at that moment of the study but not higher than the dose used in the dose-escalation cohort. SGM-101 was administered intravenously for 30 min to patients 2 or 4 days before surgery. Intraoperative imaging was done to identify near-infrared fluorescent lesions, which were resected and assessed for fluorescence. The primary outcome was tolerability and safety of SGM-101, assessed before administration and continued up to 12 h after dosing, on the day of surgery, the first postoperative day, and follow-up visits at the day of discharge and the first outpatient clinic visit. Secondary outcomes were effectiveness of SGM-101 for detection of colorectal cancer, assessed by tumour-to-background ratios (TBR); concordance between fluorescent signal and tumour status of resected tissue; and diagnostic accuracy in both cohorts. This trial is registered with the Nederlands Trial Register, number NTR5673, and ClinicalTrials.gov, number NCT02973672. Between January, 2016, and February, 2017, 26 patients (nine in the dose-escalation cohort and 17 in the expansion cohort) were included in this study. SGM-101 did not cause any treatment-related adverse events, although three possibly related mild adverse events were reported in three (33%) of nine patients in the dose-escalation cohort and five were reported in three (18%) of 17 patients in the expansion cohort. Five moderate adverse events were reported in three (18%) patients in the expansion cohort, but they were deemed unrelated to SGM-101. No changes in vital signs, electrocardiogram, or laboratory results were found after administration of the maximum dose of 10 mg of SGM-101 in both cohorts. A dose of 10 mg, administered 4 days before surgery, showed the highest TBR (mean TBR 6·10 [SD 0·42] in the dose-escalation cohort). In the expansion cohort, 19 (43%) of 43 lesions were detected using fluorescence imaging and were not clinically suspected before fluorescent detection, which changed the treatment strategy in six (35%) of 17 patients. Sensitivity was 98%, specificity was 62%, and accuracy of fluorescence intensity was 84% in the expansion cohort. This study presents the first clinical use of CEA-targeted detection of colorectal cancer and shows that SGM-101 is safe and can influence clinical decision making during the surgical procedure for patients with colorectal cancer. Surgimab.

Preoperative serum macrophage activated biomarkers soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163), as novel markers for the diagnosis and prognosis of gastric cancer.

Soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163) are macrophage activation markers which have previously been demonstrated to be increased in patients with inflammation, auto-immunity and malignancies. To investigate the clinical diagnostic and prognostic significance of preoperative serum sMR and sCD163, the present study investigated 143 gastric cancer (GC) patients, 66 subjects with benign gastric disease and 59 healthy controls, using an ELISA assay. Preoperative serum levels of sMR and sCD163 ranged from 0.165 to 0.885 µg/ml (median=0.374 µg/ml) and from 0.291 to 1.760 µg/ml (median=0.628 µg/ml) in GC patients, respectively. The expression levels of sMR and sCD163 were elevated compared with all controls (P<0.0001). Receiver operating characteristic analyses suggested that the optimum diagnostic cut-offs for sMR and sCD163 were 0.3405 µg/ml [area under curve (AUC) 0.7284, sensitivity 61.54%, and specificity 73.60%] and 0.6645 µg/ml (AUC 0.7766, sensitivity 53.85%, and specificity 86.40%), respectively. Notably, the measurement of serum sMR and sCD163 levels in conjugation, markedly enhanced the diagnostic accuracy (AUC 0.8490, sensitivity 70.63% and specificity 84.00%). Preoperative serum sMR and sCD163 levels correlated significantly with serum carcinoembryonic antigen, CA199, CA724 and CA125 concentrations in GC patients (P<0.05), however this association was not observed with sMR and CA724. High preoperative serum sMR and sCD163 levels correlated significantly with shorter overall survival (P=0.0041; P<0.0001, respectively) and were demonstrated to act as adverse prognostic factors (P=0.006; P<0.001, respectively). Furthermore, preoperative serum sMR and sCD163 levels correlated positively with the degree of lymphatic and distant metastasis of GC. In conclusion, preoperative serum sMR and sCD163 may be novel diagnostic and prognostic markers for GC and further studies are required in order to elucidate the underlying molecular mechanisms of sMR and CD163 in the development and progression of GC.

Impact and Prediction of Lymph Node Involvement in Patients with Intrahepatic Cholangiocarcinoma After Curative Resection

The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factors. Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy.

Early Assessment of Colorectal Cancer by Quantifying Circulating Tumor Cells in Peripheral Blood: ECT2 in Diagnosis of Colorectal Cancer.

Circulating tumor cells (CTCs) in peripheral blood is an indication of poor prognosis for patients with different cancer types. However, most of the available technologies for detecting CTCs show low sensitivity and specificity. Therefore, we attempted to find an alternative marker for CTCs of colorectal cancer. We have directly extracted RNA from CTCs contained in 1.5 mL peripheral blood from 90 colorectal cancer patients and 151 healthy donors, and screened these samples for candidate marker genes by nested real-time quantitative polymerase chain reaction (PCR). From genes selected from a public database of microarray analyses, we successfully identified epithelial cell transforming sequence 2 oncogene (ECT2) as a gene that exhibits high differential expression ratios (p < 0.01). ECT2 displays good sensitivity and specificity, with an area under the curve (AUC) value of 0.821. This marker gene also has a high detection rate in patients with serum carcinoembryonic antigen (CEA) concentrations below the diagnostic threshold of 5 ng/mL. The expression of ECT2 can therefore serve as an alternative measurement that can compensate for the inadequacy of the current CEA test in the diagnosis and monitoring of colorectal cancer patients.