Blood Carcinoembryonic Antigen Levels Research Articles

Mid-level data fusion strategy based on urinary nucleosides SERS spectra and blood CEA levels for enhanced preoperative detection of lymph node metastasis in colorectal cancer

BackgroundPreoperative prediction of lymph node metastasis (LNM) plays a crucial role in the treatment and prognosis of colorectal cancer (CRC). The traditional histopathological examination is invasive and time-consuming, providing pathological features only postoperatively. Preoperative serum carcinoembryonic antigen (CEA) is strongly correlated with postoperative LN status. However, the detection accuracy of LNM based on a single preoperative CEA level is low. Therefore, developing a more powerful and sensitive diagnostic tool would be of great clinical value for improving the accurate preoperative prediction of LNM in CRC patients. ResultsThis study aimed to develop a mid-level fusion approach using urinary nucleosides Raman spectra and blood CEA data to enhance the preoperative discrimination of CRC patients with and without LNM. Surface-enhanced Raman scattering (SERS) spectra of urinary modified nucleosides, isolated by affinity chromatography, were first acquired from 48 patients with LNM and 49 patients without LNM. The principal component analysis (PCA) scores obtained from the SERS spectra were then combined with preoperative blood CEA values to create a fused data array. The discriminant accuracy based on either dataset alone or the fused data was evaluated using three machine learning algorithms: linear discriminant analysis, k-nearest neighbors, and support vector machine. Results showed that the fused data could discriminate between the two groups with an accuracy of up to 91 %, outperforming SERS alone (86 %) and CEA alone (69 %). SignificanceTo our knowledge, this is the first report of mid-level data fusion of urinary nucleosides SERS spectra with blood CEA levels for the preoperative prediction of LNM in CRC. This work demonstrates that the mid-level data fusion strategy aided by SVM algorithm can greatly improve the preoperative prediction accuracy of LNM. This is crucial for therapeutic decision-making and prognostic assessment in CRC.

Abstract CT079: The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei

Abstract Background: Pseudomyxoma peritonei (PMP) is a rare cancer originating from appendiceal mucinous tumors, which may spread to encompass the entire peritoneal cavity. Complete surgical removal and hyperthermic intraperitoneal chemotherapy cures approximately half of the patients, but patients with recurrent or non-resectable disease have no efficacious treatment options. These patients have a high unmet need for novel treatment options, and in the Pseudovax trial we will explore a novel therapeutic concept. A main molecular driver of PMP (in up to 90% of cases) is otherwise rare mutations in the GNAS oncogene, coding for the Gsα protein. We hypothesized that mutated Gsα would be a tumor neoantigen, and in T cells isolated from peripheral blood of PMP patients, a strong T cell proliferative response was observed. In the corresponding tumors, T cells with up-regulated immune checkpoint molecules PD-1 and TIGIT were detected. Study hypotheses: Patients with GNAS-mutated PMP has a preexisting, attenuated immune response directed against mutated Gsα protein. Vaccination with mutated Gsα peptides can be combined with immune checkpoint inhibition (ICI) with acceptable toxicity. The vaccine will reactivate the immune response and ICI will restore measurable anticancer immunity in patients. Study design: The Pseudovax trial is a small (10 patients) first-in-human, proof-of-concept, prospective, open label, phase I trial. Patients with recurrent or non-resectable PMP are eligible for inclusion. During a treatment period of 12 months, a mutated Gsα peptide vaccine + adjuvant (GM-CSF) will be administered as intradermal injections. After 12 weeks, treatment with ICI will be initiated. The primary endpoints are toxicity and circulating immune response against the vaccine, measured as increase in interferon-gamma production or proliferation of circulating vaccine-specific T cells compared to pre-vaccination baseline. Secondary endpoints are progression-free survival (abdominopelvic CT scans, blood levels of carcinoembryonic antigen (CEA) and/or detection of GNAS mutation by ctDNA analysis). Citation Format: Kjersti Flatmark, Annette Torgunrud, Fleten G. Karianne, Ben Davidson, Hedvig V. Juel, Nadia Mensali, Christin Lund Andersen, Else Marit Inderberg. The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT079.

Biliary Carcinoembryonic Antigen (CEA) Levels: The Role in Detection of Occult Hepatic Metastases in Colorectal Carcinoma

Objective: Colorectal carcinoma (CRC) is a major public health concern, often complicated by hepatic metastasis. Despite the widespread use of serum Carcinoembryonic Antigen (CEA) for postoperative monitoring, early detection of hepatic metastasis remains elusive. This study aims to evaluate the prognostic significance of CEA levels in both peripheral blood and gallbladder bile for predicting hepatic metastasis in CRC patients, and to explore its potential utility for personalized treatment regimens. Materials and Methods: A prospective randomized study was conducted over three years, enrolling 31 participants, 21 of whom underwent curative operations for CRC. Preoperative and postoperative CEA levels were assessed with rigorous diagnostic imaging and histological examinations. Patients were stratified into groups based on liver metastasis, postoperative chemotherapy, and CEA levels in both blood and bile. Results: A statistically significant difference was found in biliary CEA levels between patients with (mean = 129.22 ng/ml) and without intraoperative liver metastasis (mean = 33.16 ng/ml), p-value = 0.01. Serum and biliary CEA levels were robustly correlated, p > 0.05. Biliary CEA values differed significantly across Duke's stages, with particular significance between the control group and Duke's stage D (p < 0.001). Among patients without intraoperative liver metastasis but with biliary CEA >10 ng/ml, 80% developed liver metastasis postoperatively despite undergoing chemotherapy. Conclusion: This research highlights the pivotal role of biliary CEA levels in diagnosing latent hepatic metastases in colorectal cancer. Demonstrating superior sensitivity compared to traditional serum tests, biliary CEA presents a potential shift in early detection. Elevated levels suggest expanded therapeutic options, from timely hepatectomies to adopting radiofrequency ablation and anti-CEA monoclonal antibodies, enhancing the likelihood of better patient outcomes. Essentially, these findings enhance our understanding of colorectal cancer, emphasizing the importance of personalized care, early diagnosis, and customized treatments, thereby directing us toward better patient outcomes.

Clinical value of preoperative serum tumor markers CEA, CA19-9, CA125, and CA15-3 in surgically treated urachal cancer.

Urachal adenocarcinoma (UrAC) is a very rare malignancy with a poor prognosis. The role of preoperative serum tumor markers (STMs) in UrAC is unknown. The aim of this study was to assess the clinical value of elevated STMs including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and cancer antigen 15-3 (CA15-3) in surgically treated UrAC, and to evaluate their prognostic significance. This was a retrospective study of consecutive patients with histopathologically confirmed UrAC who underwent surgical treatment at a single tertiary hospital. Blood levels of CEA, CA19-9, CA125, and CA15-3 were determined before surgery. The proportion of patients with elevated STMs was calculated, as well as the association between elevated STMs and clinicopathological characteristics, recurrence-free survival and disease-specific survival. Of the 50 patients included; CEA, CA 19-9, CA125, and CA15-3 were elevated in 40%, 25%, 26%, and 6% respectively. Elevated CEA was associated with higher pT-stage (odds ratio [OR] 3.3 [95% confidence interval 1.0-11.1], P = 0.003), higher Sheldon stage (OR 6.9 [95% CI 0.8-60.4], P = 0.01), male sex (OR 4.7 [95% CI 1.2-18.3], P = 0.01), and the presence of peritoneal metastases at the time of diagnosis (OR 3.5 [95% CI 0.9-14.2], P = 0.04). Elevated CA19-9 was associated with signet-cell component (OR 1.7 [95% CI 0.9-3.3], P = 0.03) and elevated CA125 was associated with peritoneal metastases at the time of diagnosis (OR 6.0 [95% CI 1.2-30.6], P = 0.04). Elevated STMs before surgery were not associated with recurrence-free survival and/or disease-specific survival. A subset of patients with surgically treated UrAC has elevated STMs preoperatively. CEA was most frequently (40%) elevated and correlated with unfavorable tumor characteristics. However, STM levels did not correlate with prognostic outcomes.

A nomogram combining thoracic CT and tumor markers to predict the malignant grade of pulmonary nodules ≤3 cm in diameter.

With the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging. A retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors. A total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful. The nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery.

The prognostic value of tumor markers in patients (pts) with resectable gastric cancer (GC) receiving perioperative therapy in the CRITICS trial.

4024 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are well-known tumor markers. Most studies on CEA and CA 19-9 in pts with GC were performed in Asia, and/or in the metastatic setting. The aim of this study was to investigate the prognostic value of blood derived laboratory parameters in a cohort of European pts with resectable non-metastatic GC. Methods: In the CRITICS trial, 788 pts with resectable GC underwent perioperative therapy (preoperative chemotherapy plus either postoperative chemotherapy or postoperative chemoradiotherapy). Blood levels of CEA, CA 19-9, alkaline phosphatase (AP), creatinine, neutrophils, hemoglobin (Hb) and lactate dehydrogenase (LDH) were determined prior to treatment. Data for these variables were available for at least 89% of the pts. Factors significant on univariable cox regression analysis were further explored in multivariable analysis. Probabilities to undergo potentially curative surgery was investigated for factors significant on multivariable analysis. The relationship between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 pts with available ctDNA data. Results: CEA and CA 19-9 were identified as independent prognostic factors for survival (Table). Probabilities to undergo potentially curative surgery were 86%, 77% and 60% for pts with no elevated tumor makers versus those with elevated CEA or elevated CA 19-9 versus those with both tumor markers elevated, respectively (p<0.001). No relationship was found between elevated tumor marker(s) and the presence of ctDNA neither pretreatment nor preoperatively. Conclusions: Pretreatment blood levels of CEA and CA 19-9 were identified as prognostic factors for overall survival in a large cohort of European GC pts with potentially curable disease. These factors may guide treatment choices at an early phase and should be included in future trials to determine their role in clinical decision making.[Table: see text]

Brain Metastases from Colorectal Cancer: A Systematic Review of the Literature and Meta-Analysis to Establish a Guideline for Daily Treatment.

Simple SummaryBrain metastases (BM) from colorectal cancer (CRC) are rare. There is little available information regarding incidence, risk factors, prognostic factors, treatment, and overall survival (OS). In this systematic review we performed a research of the current literature and exposed an average incidence of 2.10%. The most-reported risk factors for developing BM were KRAS mutations and lung metastases. The majority of patients with brain metastases did not show neurological symptoms. Treatment options included surgery, radiation, or chemotherapy. While patients who received surgery had prolonged survival, the best survival time was found with a multimodality treatment regimen including neurosurgery.Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words “brain”, “metastas*”, “tumor”, “colorectal”, “cancer”, and “malignancy”. In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1% and 11.5%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.

The Relationship between Tumor Size and Carcinoembryonic Antigen (CEA) Levels in Stage IV Colorectal Adenocarcinoma Patients at Dr. Moewardi Hospital, Indonesia

Background: Colorectal adenocarcinoma is one of the most common types of colorectal cancer based on histopathology, accounting for about 10% of cancer cases diagnosed worldwide each year. Tumor size and levels of carcinoembryonic antigen (CEA) are used to determine the presence and evaluation of colorectal cancer. However, studies on the correlation between the size of colorectal cancer based on CT scan abdominal with contrast and the CEA levels are still very minimal in the Indonesian population. This study aimed to analyze the relationship between tumor size examined by abdominal CT scan with contrast and carcinoembryonic antigen (CEA) levels in stage IV colorectal adenocarcinoma patients. Subjects and Method: A cross-sectional study was conducted at the radiology department, Dr. Moewardi hospital, Surakarta, from February 2021 to July 2021. A total of 40 patients with stage IV colorectal adenocarcinoma were selected in this study. The patient already had the examination results of blood CEA levels and performed an abdominal CT scan with contrast. The dependent variable was blood CEA levels. The independent variable was tumor size. Data were collected from medical records and analyzed by the Spearman test. Results: There was a positive and significant relationship between tumor size and CEA levels (r= 0.47; p= 0.003). Conclusion: Tumor size is positively correlated to blood CEA levels in patients with stage IV colorectal adenocarcinoma. Keywords: colorectal adenocarcinoma, contrast abdominal CT scan, carcinoembryonic antigen (CEA). Correspondence: Sulistyani Kusumaningrum. Department of Radiology Dr. Moewardi Hospital/ Faculty of Medicine of Universitas Sebelas Maret, Surakarta. Email: sulistyani_sprad@staff.uns.ac.id Indonesian Journal of Medicine (2021), 06(03): 285-290 https://doi.­org/10.26911/theijmed.2021.06.03.05

CYFRA 21‐1 and CEA combination assay in EMPD

Extramammary Paget's disease (EMPD) is a rare skin cancer affecting the genitals and armpit regions. EMPDs occur mainly in Caucasian women and Asian men over the age of 60, in less than 0.6 per 100,000 people. Basic treatment is excision (removal) by operation, yet metastasis, meaning that it has spread, is seen in around 10% of patients. If the cancer is spreading, it is really important to detect this and start treatment as early as possible, since in late stages the disease can be hard to treat. A biomarker, or marker, is a molecule found in blood, different levels of which correspond with how well the body responds to a treatment, or to how the disease will progress. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) are both biomarkers for certain other cancers, and it has been suggested that they might also be markers for monitoring tumour progression in EMPD; however, neither the accuracy of, nor correlation between, these markers have been examined in EMPD patients. This study from Japan aimed to find out the usefulness and relationship of CEA and CYFRA21-1 levels in blood of EMPD patients in various progression states of the disease. A total of 30 EMPD cases were included in this study. In all early-stage patients, CEA and CYFRA were within normal levels. In advanced-stage patients, CEA and CYFRA were elevated in 79% and 63%, respectively. Either CEA or CYFRA was found to be elevated in 95% of the advanced patients, indicating that a certain number of patients have raised levels of only one of the markers. In addition, both of the markers also correlated well with the treatment responses in all patients. This study revealed that examining both CEA and CYFRA may help to detect advanced-stage EMPD patients, and that they are useful for monitoring treatment responses.

Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

To study the clinical significance of serum epidermal growth factor receptor (EGFR) gene mutation and serum tumor markers in the prediction of tyrosine kinase inhibitor (TKI) efficacy in patients with lung adenocarcinoma. Ninety patients with pathologically diagnosed lung adenocarcinoma were enrolled. Further, 51 out of 90 patients received the EGFR-TKI therapy, oral gefitinib. The correlations among serum EGFR gene mutations in exons 18-21, serum tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), carbohydrate antigen 125, carbohydrate antigen 15-3 as well as carbohydrate antigen 19-9 (CA19-9) levels, and EGFR-TKI efficacy were determined. There was a high consistency of EGFR gene mutation rate between serum and tissue samples. The serum EGFR gene mutation rate in female patients or non-smokers was significantly higher than that in male patients or smokers, respectively. Serum CA19-9, CA24-2, and CEA levels were significantly correlated with serum EGFR mutation. After receiving gefitinib, the progression-free survivals (PFSs) of patients with high serum CEA level, high serum CA19-9 level, or serum EGFR gene mutation were significantly higher than those of normal patients, respectively. The PFSs were significantly prolonged in patients with EGFR gene mutation and high serum CEA level or patients with EGFR gene mutation and high serum CA19-9 level compared with those in patients with one abnormal biomarker and normal patients. Combined detection of EGFR gene mutations as well as CA19-9 and CEA levels in peripheral blood can predict the efficacy of EGFR-TKI in the treatment of patients with lung adenocarcinoma.

Single and combined use of neutrophil–lymphocyte ratio, platelet–lymphocyte ratio and carcinoembryonic antigen in diagnosing gastric cancer

To investigate the value of neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and carcinoembryonic antigen (CEA), alone or in combination, in diagnosing gastric cancer (GC), we retrospectively analyzed a cohort of 201 patients with GC, 161 patients with benign gastric lesions, and 157 healthy subjects. We obtained routine blood indices and CEA levels to evaluate the diagnostic value of NLR, PLR and CEA for GC, based on receiver operating characteristic (ROC) curves. We found that serum NLR, PLR and CEA in the GC group were significantly higher than those in the benign lesion group (PNLR < 0.001,PPLR < 0.001,PCEA = 0.034) or the healthy control group (PNLR < 0.001,PPLR < 0.001,PCEA = 0.028). Moreover, there were significant differences in NLR and PLR among different serosa invasion, lymph node metastasis, tumor size and stage. CEA showed a difference in distant metastasis and tumor size. Combining PLR with CEA produced a larger AUC (AUC: 0.780, 95% CI: 0.734–0.822) than using PLR (P = 0.011) or CEA (P < 0.001) alone. Similarly, NLR + CEA produced a larger AUC (AUC: 0.756, 95% CI:0.709–0.800) than using NLR (P = 0.004) or CEA (P = 0.001) alone. Whereas NLR, PLR and CEA are known to help distinguish GC from benign gastric lesions, combining CEA with PLR or NLR offers better diagnostic value for GC than any of them used alone.

The prognostic value of carcinoembryonic antigen levels in blood and intraoperative pleural lavage fluid in non-small-cell lung cancer.

IntroductionThere is no specific marker for lung cancer, but, in some lung cancer types, carcinoembryonic antigen (CEA) can reach high levels in the blood and pleural fluid.AimThis study investigated the relationship of CEA levels in blood (CEAB) and intraoperative pleural lavage fluid (CEAP) in non-small-cell lung cancer (NSCLC) with the type, stage, and extent of lung cancer.Material and methodsA total of 50 patients, who underwent surgery at our clinic due to NSCLC (group I) or benign lung pathology (group II), were assessed. For this prospectively designed study, 25 consecutive patients were included in each group, and their CEAB and CEAP levels were investigated.ResultsWhen the levels of CEAP were compared, the average value of group I (1.35 ng/ml) was significantly higher than the average value of group II (0.04 ng/ml) (p = 0.027). When CEA levels were examined separately, and average values were taken according to surgical pathology results, both CEAB and CEAP levels of adenocarcinoma patients were found to be higher than those of the other groups. This difference was only significant for the level of CEAP (p = 0.026).ConclusionsAlthough the average CEAB levels of patients with adenocarcinoma were higher than those of patients with other histopathological types, this difference was not statistically significant. However, we found that CEAP levels were significantly higher in patients with adenocarcinoma. These results have led us to consider that CEAP elevation is a more sensitive marker than the elevation of CEAB.

Blood CEA levels for detecting recurrent colorectal cancer.

Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation. To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice. We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index & Conference Proceedings Citation Index - Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library. We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy. Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots. In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%). CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).

Colonoscopy and carcinoembryonic antigen variations.

Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1) before bowel cleaning, (2) before colonoscopy and (3) immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by "Sandwich" immunoassay. The statistical methods used were the paired t-test and ANOVA. Thirty-seven patients (22M/15F) were included; age range 28-84 (mean 56 years). Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1), (2) and (3), respectively. An increase in value (2) compared with (1) was observed in 20/37 patients (P = 0.018), mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2) to (3) (P = 1.3x10-7). A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

An isolation technique to prevent the spread of tumor cells during radical gastrectomy for gastric carcinoma located on the anterior wall of the gastric antrum

To report an isolation technique for reducing the spread of tumor cells during radical gastrectomy for lesions located on the anterior wall of the gastric antrum. The isolation technique involves using linear cutting staplers and a waterproof membrane to completely "block" and isolate the area to be resected. Blood samples from the portal vein and peritoneal wash samples were obtained immediately after laparotomy and during surgical resection. RT-PCR was used to determine levels of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). Carbon nanoparticles were injected into the subserosa of the blocked region before resection to determine lymph flow out of the region. A total of 76 patients (median age, 59 years; range, 22-73 years), with tumors on the anterior wall of the gastric antrum were included (blocking group, n = 40; non-blocking group, n = 36). In the blocking group, the carbon nanoparticles did not flow beyond the blocking line. There were no significant differences between the groups in CEA or CK20 mRNA levels in portal vein blood or peritoneal wash fluid immediately after laparotomy. CEA and CK20 levels were significantly lower in portal vein blood in the blocking group during tumor resection. During a median follow-up of 30 months, the incidence of metastasis or recurrence in the blocking group was lower than the non-blocking group, although it did not reach statistical significance (17.9% vs. 25.0%, respectively). The blocking technique can reduce hematogenous and lymphatic spread of tumor cells into the systemic circulation, and may prevent metastasis or recurrence after radical gastrectomy for gastric carcinoma.

Existe-t-il une relation entre les habitudes alimentaires en Tunisie et le cancer colorectal ? Éléments de réponse à partir d’un échantillon de population

Summary Introduction In Tunisia, colorectal cancer (CRC) is the first digestive cancer. Many factors can contribute to its development, including food and lifestyle. Our aim is to investigate foods that may increase the risk of its development. Methods Our study was carried out of 100 CRC cases and 100 controls. For each subject, we completed a questionnaire regarding his identification, clinical information, personal and family history, diet and lifestyle before CRC onset. We evaluated blood levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Results The concentrations of CEA and CA 19-9 were significantly higher in patients with stage IV compared to patients with stages II and III. Patients were less physically active than controls. Tobacco, alcohol, canned vegetables, fresh fruits, starches, sweets, lipids, frying, green tea and coffee consumptions are lower in patients than in controls. However, patients eat more red meat, raw vegetables and black tea than the controls. The consumption of raw vegetables, canned tomato, fresh fruits, starches and sweets showed a significant association with CRC occurrence. Conclusion Our study has to be supported by a statistical approach on bigger samples. Nevertheless, the data suggest that the consumption of tobacco, alcohol, canned vegetables, fresh fruits, starches, sweets, lipids, green tea and coffee may not be risk factors for CRC development; on the contrary, the consumption of red meat, raw vegetables and black tea may be risk factors.

Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer

Novel strategies are needed to identify more efficient biomarkers to accurately diagnose prognose and improve the treatment outcome of colorectal cancer. To analyze the functional and morphological features of colorectal cancer to identify the neoplastic patterns that affect patient survival. Forty-five patients with colorectal cancer were followed for a minimum of 3 years. Blood levels of carcinoembryonic antigen (CEA) were measured by chemiluminescence and immunohistochemical analysis of tissue expression followed by computer-assisted image processing. Tumors were assigned to three morphofunctional classes. The morphofunctional classification was based on combination between histological differentiation and cell polarization. The functional characterization was based on the CEA cell polarization. The tissue polarization of CEA was classified in well-polarized, moderately polarized or nonpolarized cells. Morphofunctional staging was defined by the association between morphofunctional class (polarization and histological differentiation) and TNM by score given to each one classification. There was an association between increased CEA tissue expression and loss of histological differentiation (P = 0.01) or loss of polarization capacity (P = 0.03). There was a progressive increase in tissue CEA quantities in accordance with the proposed morphofunctional grading system. Plasma levels of CEA were increased in advanced tumor stages. Blood levels of CEA were increased in advanced morphofunctional stages (P = 0.001). There was a relationship between survival outcome and morphofunctional staging (P = 0.005). Morphofunctional staging is a valuable prognostic factor for colorectal cancer and it correlates with plasma CEA levels.

220 Targeting CEA Rescues Proliferation Inhibiting Effects of TGF-β Signaling Pathway in Colorectal Cancers

Carcinoembryonic antigen (CEA) is a tumor marker for the clinical management of colorectal cancer (CRC). The elevated blood levels of CEA are associated with metastasis and poor prognosis in CRC. There is mounting evidence that CEA enhances the metastatic potential of cancer cells. CEA increases the ability of weakly metastatic CRC to colonize the liver and to develop spontaneous hematogeneous liver and lung metastases. CEA expression has also been related with resistance to cytotoxic chemotherapy and to anoikis, a form of apoptosis caused by detachment from cell matrix. Yet the mechanism of CEA mediated metastasis is only partially understood. The TGF-β (transforming growth factor beta) signaling pathway contributes to tumorigenesis by controlling several biological processes, including cell proliferation, differentiation, migration and apoptosis. It has been reported that TGF-β regulates CEA transcription and secretion, however, little is known about the effects of CEA on TGFβ signaling. Aims: Based on the above facts, we focused on the influence of CEA on the TGF-β signaling in both normal cells and colorectal cancer cells. Results: Our preliminary data showed that CEA directly interacted with TGF-β receptors. Overexpression of CEA blocked TGF-β induced SMAD3 phosphorylation, SMAD3 translocation to nuclear and the downregulation of c-myc transcription. Targeting CEA with anti-CEA antibody rescued TGFβ response in CRC cell lines with elevated CEA expression, thereby restoring the inhibitory effects of TGF-β on the proliferation of these cancer cells. Finally, in animal experiment, we found that CEA enhanced survival of colorectal cancer cell in both local colonization and liver metastasis. Conclusion: Since CEA is a well-characterized tumor-associated antigen that is frequently overexpressed in tumors, specific antibodies targeting CEA have been developed as a novel therapeutic approach for treatment of tumors expressing CEA on their surface. Based on our study, it may be helpful to combine CEA antibody and TGF-β to inhibit cancer cell proliferation and metastasis in some cases.

224 Specific Nucleotides That Flank Coding Microsatellites of Activin Receptor 2 (ACVR2) Determine Exonic Selectivity and Control Frameshift Mutation Rates in Defective DNA Mismatch Repair (MMR)

Carcinoembryonic antigen (CEA) is a tumor marker for the clinical management of colorectal cancer (CRC). The elevated blood levels of CEA are associated with metastasis and poor prognosis in CRC. There is mounting evidence that CEA enhances the metastatic potential of cancer cells. CEA increases the ability of weakly metastatic CRC to colonize the liver and to develop spontaneous hematogeneous liver and lung metastases. CEA expression has also been related with resistance to cytotoxic chemotherapy and to anoikis, a form of apoptosis caused by detachment from cell matrix. Yet the mechanism of CEA mediated metastasis is only partially understood. The TGF-β (transforming growth factor beta) signaling pathway contributes to tumorigenesis by controlling several biological processes, including cell proliferation, differentiation, migration and apoptosis. It has been reported that TGF-β regulates CEA transcription and secretion, however, little is known about the effects of CEA on TGFβ signaling. Aims: Based on the above facts, we focused on the influence of CEA on the TGF-β signaling in both normal cells and colorectal cancer cells. Results: Our preliminary data showed that CEA directly interacted with TGF-β receptors. Overexpression of CEA blocked TGF-β induced SMAD3 phosphorylation, SMAD3 translocation to nuclear and the downregulation of c-myc transcription. Targeting CEA with anti-CEA antibody rescued TGFβ response in CRC cell lines with elevated CEA expression, thereby restoring the inhibitory effects of TGF-β on the proliferation of these cancer cells. Finally, in animal experiment, we found that CEA enhanced survival of colorectal cancer cell in both local colonization and liver metastasis. Conclusion: Since CEA is a well-characterized tumor-associated antigen that is frequently overexpressed in tumors, specific antibodies targeting CEA have been developed as a novel therapeutic approach for treatment of tumors expressing CEA on their surface. Based on our study, it may be helpful to combine CEA antibody and TGF-β to inhibit cancer cell proliferation and metastasis in some cases.

A strategy for blood biomarker amplification and localization using ultrasound

Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.