Blood Carcinoembryonic Antigen 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.

Role of Carcinoembryonic Antigen in Severity Assessment and Mortality Prediction in COVID-19 Patients.

Background Early risk stratification of COVID-19 may yield a better prognosisby tailoring effective treatment strategies. Recent studies have identified that elevated carcinoembryonic antigen (CEA) has prognostic value in terms of disease severity and mortality in patients with pneumonia. This study aims to explore the potential of CEA as a marker for both severity assessment and mortality prediction in COVID-19 patients. Methods From August 2020 to October 2021, we conducted this observational study in which patients who tested positive for COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) or had high-resolution computed tomography (HRCT) chest suggestive of COVID-19 were includedon day 0 of their admission to the COVID unit. Patients were classified into mild, moderate, severe, and critical according to the World Health Organization (WHO) guidelines. Blood samples were collected for complete blood count (CBC), C-reactive protein (CRP), ferritin, and CEA on days 0, 3, 7, and 14 of admission. The patient's profile was used to obtain lactate dehydrogenase (LDH), D-dimer, and HRCT scores [based on COVID-19 reporting and data system (CO-RADS) grade]. We used receiver operating characteristic (ROC) curves with Youden's index to find the initial (day 0) critical values of CEA for each of mild, moderate, severe, and critical COVID-19. The Kaplan-Meier survival curve was used to predict mortality with the best initial(day 0) cut-off value of CEA. Results Among 75 patients in this study, 15, 20, 19, and 21 were in the mild, moderate, severe, and critical groups, respectively;most were male (68%), and mortality was 18 (24%). Spearman's rank correlation test demonstrates a strong correlation between COVID-19 severity and changes in CEA. In the ROC curves, the area under the curve (AUC) value of CEA was higher among markers in all classifications except for mild to moderate disease. The AUC and critical values of CEA were as follows: for mild to moderate (0.948), 2.5 ng/ml; moderate to severe (1.000), 6.02 ng/ml; and severe to critical (0.769), 11.75 ng/ml. The survival curve shows the best initial cut-off values for mortality outcomes: CEA ≥7.15, CRP ≥81.52, ferritin ≥680.68, lymphocyte percentage ≤7.5, and neutrophil lymphocyte ratio ≥12.7. Conclusions The initial levels of CEA can serve as markersfor severity assessment and mortality outcome prediction of COVID-19.

Clinical and biological significance of microRNA-127 and microRNA-138 expression in women with breast cancer: response to treatment and survival impact

Background and ObjectiveGenetic and epigenetic changes characterize the multi-step process of breast carcinogenesis. It is believed that abnormal microRNA (miRNA) expression has a role in the onset and progression of breast cancer. This study aimed to examine the link between miRNA-127 and miRNA-138 and metastasis, tumor invasion, and apoptosis in Egyptian women with breast cancer, as well as their correlation with its molecular types.MethodologyA total of 150 participants were included in this study, including 75 women with breast cancer and 75 supposedly healthy women who were age and gender-matched. Every patient underwent a thorough physical examination, a general clinical examination, a mammogram, and lab tests, such as the determination of the levels of miRNA-127 and miRNA-138 expression by real-time PCR and the measurement of blood carcinoembryonic antigen (CEA) and carcinoma antigen 15–3 (CA15-3) and CA15-3 and CEA levels.ResultsThere was a significant low expression of miRNA-127 in favor of high TNM stage (Classification of Malignant Tumors), left-sided tumor, metastasis, high-grade disease, increased axillary nodal involvement, absence of estrogen and progesterone receptors, and low antigen Kiel 67 (Ki67) expression. Also, a significant expression of miRNA 127 in triple-negative breast cancer was found, followed by human epidermal growth factor receptor 2 (HER2/neu) overexpression, then luminal B, and the highest expression was with the Luminal A molecular subtype. A significant negative correlation existed between miRNA 127 and miRNA 138 with CEA and CA15.3 levels.ConclusionThe miRNA-127 and miRNA-138 suppression may promote metastasis. Consequently, the restoration of miRNA-127 and miRNA-138 in breast cancer may have therapeutic potential; so, the miRNA-127 and miRNA-138 may play a role in breast cancer development.

A rare case of esophageal metastasis from signet-ring cell carcinoma of the cecum

BackgroundMetastatic esophageal cancer is rare. Its common primary lesions include lung cancer and breast cancer. Metastatic esophageal cancer originating from colorectal cancer is rarer.Case presentationA 79-year-old woman visited our hospital because of lower abdominal discomfort. She was endoscopically diagnosed with type 0–IIa + IIc cancer of the cecum, and biopsy of the lesion showed signet-ring cell carcinoma. With a preoperative clinical staging of cStage I (cT2, cN0, cM0), the patient underwent laparoscopic ileocecal resection with D3 lymphadenectomy. Histopathological examination of the resected specimens revealed signet-ring cell carcinoma [type 4, pT4a, pN3 (No. 203), M0, pRM1, stage IIIc, R1]. Despite radial margin positivity, the patient refused resection of the residual tumor and received oral tegafur and uracil. KRAS mutation test showed KRAS wild-type colon cancer, but she refused anti-epidermal growth factor receptor therapy. One year after surgery, her blood carcinoembryonic antigen concentration elevated. Colonoscopy showed anastomotic recurrence and biopsy of the lesion showed signet-ring cell carcinoma. Upper gastrointestinal endoscopy showed multiple longitudinal submucosal tumors with erosions on their surfaces in the esophagus. Tumor biopsy revealed signet-ring cell carcinoma. Immunohistochemistry showed that the histological type of the esophageal tumors was the same as that of the primary colon cancer. Based on these findings, the esophageal tumors were diagnosed with metastasis from signet-ring cell carcinoma of the cecum. The oral chemotherapy was replaced with FOLFOX plus bevacizumab. However, the patient’s condition required treatment discontinuation, and she died of cancer progression 1 year and 5 months after surgery.ConclusionsTo our knowledge, this is the first case report on metastatic esophageal cancer from signet-ring cell carcinoma of the cecum. Esophagoscopy showed multiple longitudinal submucosal tumors, which is similar to an endoscopic finding of intramural metastasis from primary esophageal cancer. We consider that the multiple longitudinal submucosal tumors are a notable feature of our case. When metastatic esophageal cancer is suspected, clinicians, endoscopists, and pathologists should consider signet-ring cell carcinoma of the colon as one of potential primary lesions. This consideration could lead the specialists to appropriate examinations and treatments, thereby improving clinical outcomes in patients with the metastasis.

A biosensor based on graphene oxide nanocomposite for determination of carcinoembryonic antigen in colorectal cancer biomarker

Colorectal cancer is still a major global health concern, and early detection and accurate biomarker analyses are critical to its successful management. This paper describes the design and testing of a new biosensor based on a graphene oxide (GO) nanocomposite for the exact measurement of carcinoembryonic antigen (CEA), a well-known biomarker for colorectal cancer. The current study attempted to create a highly sensitive immunosensor for sensitive measurement of CEA based on a polypropylene-imine-dendrimer (PPI) and GO nanocomposite on GCE (PPI/GO/GCE). The PPI/GO nanocomposite served as an appropriate biocompatible nanostructure with a large surface area for immobilizing carcinoembryonic antigen (anti-CEA) and bovine serum albumin (BSA) molecules (BSA/anti-CEA/PPI/GO/GCE), thereby promoting the selectivity of electrochemical immunosensors, according to structural and electrochemical studies. Results showed that the BSA/anti-CEA/PPI/GO/GCE as a selective, sensitive, and stable immunosensor revealed a wide linear response from 0.001 to 2000 ng/mL, and a limit of detection of 0.3 pg/mL, which indicated comparable or better performance towards the CEA immunosensors in recent reports in the literature. This was due to the synergetic effect of the GO nanosheets and PPI with porous structure and more conductivity. Analytical results showed values of RSD (4.49%–5.04%) and recovery (90.00%–99.98%) are suitable for effective and accurate practical assessments in CEA in clinical samples. The capacity of the BSA/anti-CEA/PPI/GO/GCE to determine CEA in human blood was studied.

Clinical and prognostic significance of detecting CEA, EGFR, LunX, c-met and EpCAM mRNA-positive cells in the peripheral blood, tumor-draining blood and bone marrow of non-small cell lung cancer patients.

Surgical treatment of early-stage non-small cell lung cancer (NSCLC) yields highest expectations for recovery. However, the frequency of further disease progression remains high since micro-metastatic disease may be undetected by conventional diagnostic methods. We test the presence and prognostic impact of circulating tumor cells (CTCs) in peripheral blood (PB), tumor-draining pulmonary blood (TDB) and bone marrow (BM) samples from NSCLC patients. The presence of circulating/disseminated tumor cells (CTCs/DTCs) was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis in PB, TDB and BM samples before surgery in 119 stage IA-IIIA NSCLC patients (Clinical Trial NS10285). NSCLC patients with the presence of carcinoembryonic antigen (CEA) mRNA-positive CTCs/DTCs in TDB and BM had significantly shorter cancer-specific survival (CSS) (P<0.013, resp. P<0.038). Patients with the presence of epithelial cellular adhesion molecule (EpCAM) mRNA-positive CTCs in TDB samples had significantly shorter CSS and disease-free survival (DFS) (P<0.031, resp. P<0.045). A multivariate analysis identified the presence of CEA mRNA-positive CTCs in the PB as an independent negative prognostic factor for DFS (P<0.005). No significant correlation of CTCs/DTCs presence and other prognostic factors was found. In NSCLC patients undergoing radical surgery, the presence of CEA and EpCAM mRNA-positive CTCs/DTCs is associated with poorer survival.

A Novel Fluorescent Aptamer Sensor with DNAzyme Signal Amplification for the Detection of CEA in Blood.

Carcinoembryonic antigen (CEA) is a tumor-specific biomarker; however, its low levels in the early stages of cancer make it difficult to detect. To address the need for analysis of ultra-low-level substances, we designed and synthesized a fluorescent aptamer sensor with DNAzyme signal amplification and used it for the detection of CEA in blood. In the presence of the target protein, the aptamer sequence in the recognition probe binds to the target protein and opens the hairpin structure, hybridizes with the primer and triggers a polymerization reaction in the presence of polymerase to generate double-stranded DNA with two restriction endonuclease Nb.BbvCl cleavage sites. At the same time, the target protein is displaced and continues to bind to another recognition probe, triggering a new round of polymerization reaction, forming a cyclic signal amplification triggered by the target. The experimental results show that the blood detection with CEA has a high sensitivity and a wide detection range. The detection range: 10 fg/mL~10 ng/mL, with a detection limit of 5.2 fg/mL. In addition, the sensor can be used for the analysis of complex biological samples such as blood.

DIAGNOSTICS OF LYMPHOGENIC METASTASIS IN PATIENTS WITH RECTAL CANCER BY COMBINING MRI WITH BLOOD CEA ASSESSMENT.

To improve the diagnostics of lymphogenic metastasis in patients with rectal cancer (RCa) by combining magnetic resonance imaging (MRI) with the blood carcinoembryonic antigen (CEA) level assessment. We have systematized and analyzed the results of the examination and treatment of 77 patients with stage II-III rectal adenocarcinoma (T2-3N0-2M0). Before the start of neoadjuvant treatment as well as 8 weeks after its completion, computed tomography (CT) and MRI were performed. We analyzed such prognostic criteria as the size, shape, and structure of lymph nodes as well as the patterns of contrast accumulation. As a prognostic marker, CEA levels in the blood of patients with RCa before surgical treatment were assessed. Radiological exams showed a rounded shape and heterogeneous structure to be the most informative for predicting metastatic lymph node damage, increasing the probability by 4.39 and 4.98 times, respectively. After neoadjuvant treatment, the percentage of positive histopathological reports on lymph node involvement decreased significantly to 21.6% (р ˂ 0.001). MRI showed 76% sensitivity and 48% specificity for assessing lymphogenic metastasis. CEA levels differed significantly between stages II and III (N1-2) (р ˂ 0.032) with a threshold value of 3.95 ng/ml. In order to increase the effectiveness of the diagnosis of lymphogenic metastasis using radiological examination methods in RCa patients, such prognostic criteria as the round shape and heterogeneous structure of the lymph nodes and the threshold level of CEA should be considered.

The stool syndecan2 methylation test is more robust than blood tests for methylated septin9, CEA, CA19-9 and CA724: a diagnostic test for the early detection of colorectal neoplasms.

Methylated syndecan2 (mSDC2) in stool samples has been found to be associated with colorectal cancer (CRC) and precancerous lesions. However, the available data are limited, and no previous studies have compared the analysis of mSDC2 with other diagnostic tests. Thus, we aimed to evaluate the clinical performance of a stool mSDC2 test and compare its performance with that of blood-based tests for methylated septin9 (mSEPT9), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA724) in detecting colorectal neoplasms. The gold standard diagnostic technique that was used was colonoscopy combined with a pathological analysis of biopsied tissue. Stool DNA was extracted from 1,002 stool samples (445 from CRCs, 115 from adenomas, and 442 from controls) and then bisulfite-converted, followed by real-time quantitative methylation-specific polymerase chain reaction. Blood mSEPT9 levels were quantified by the Epi proColon 2.0 assay, and serum CEA, CA19-9 and CA724 levels were measured by electrochemiluminescence. The main indexes used during the evaluation were sensitivity, specificity and the area under the receiver operating characteristic curve (AUC). Stool mSDC2 detected 69.7% of CRCs, which was significantly higher than 53.8% by plasma mSEPT9, 37.2% by CEA, 13.1% by CA19-9 and 17.5% by CA724; for adenoma, the detection rates were 31.3%, 11.1%, 2.3% and 11.9%, respectively. The AUC of mSDC2 in detecting CRC was 0.83, compared to 0.72, 0.75, 0.63 and 0.54 for mSEPT9, CEA, CA19-9 and CA724, respectively. mSDC2 identified patients with stage I-III CRC with a sensitivity of 71.6%, which was significantly higher than that of mSEPT9, CEA, CA19-9 and CA724 (54.2%, 35.5%, 11.9%, and 15.0%, respectively); for stage IV CRC, the sensitivities of mSDC2, mSEPT9, CEA, CA19-9 and CA724 were 75.9%, 82.6%, 79.3%, 36.0% and 56.5%, respectively. SDC2 and CEA had a significantly higher sensitivity for distal CRC than for proximal CRC. The stool SDC2 methylation test had a better performance in detecting nonmetastatic CRC and adenoma than evaluations of mSEPT9, CEA, CA19-9 and CA724 in blood. Our findings could be used to modify approaches for CRC prevention and early detection.

Prognostic Value of the Expression of Myeloid Leukemia Factor 1-Interacting Protein in Gastric Cancer and Its Regulatory Role in Tumor Progression

To investigate the prognostic value of the expression of myeloid leukemia factor 1-interacting protein (MLF1IP) in gastric cancer tissue and its regulatory role in tumor progression. Gene Expression Omnibus (GEO) database was used to analyze the expression level of MLF1IP in tumor tissues of gastric cancer patients. Kaplan-Meier Plotter database was used to analyze the relationship between MLF1IP expression level and patient prognosis. We conducted a retrospective analysis of 108 gastric cancer patients who had undergone radical surgery at our hospital between January 2015 and December 2015. The expression of MLF1IP in gastric cancer tissue and adjacent tissues was examined. We analyzed the relationship between MLF1IP and the clinicopathological parameters of gastric cancer patients and its impact on the long-term prognosis of gastric cancer patients. Univariate and multivariate regression analyses were done to identify the risk factors affecting the long-term prognosis of gastric cancer patients. The assessment value of MLF1IP for long-term prognosis of gastric cancer was analyzed with ROC curve. The effects of MLF1IP on the proliferation, migration, and invasion of gastric cancer cells were analyzed in vitro with gastric cancer cell line (MGC803). A xenograft tumor model was established with nude mice to analyze in vivo the effect of MLF1IP on tumor growth. The results of the gastric cancer cohort GSE29272 of GEO database showed that the expression level of MLF1IP in gastric cancer tissues was significantly higher than that in normal tissues ( P<0.05). Analysis with Kaplan-Meier Plotter database indicated that high MLF1IP expression was correlated with poor prognosis in gastric cancer patients. Immunohistochemical analysis showed that the expression level of MLF1IP in gastric cancer tissues was higher than that in adjacent tissues ( P<0.05). Correlation analysis showed that the MLF1IP level in gastric cancer tissue was positively correlated with Ki67 ( r=0.609, P<0.01), peripheral blood carcinoembryonic antigen (CEA) ( r=0.572, P<0.01) and carbohydrate antigen 19-9 (CA19-9) ( r=0.623, P<0.01). Kaplan-Meier (K-M) survival analysis showed that the 5-year survival rate of patients in the MLF1IP high expression group was significantly lower than that in the MLF1IP low expression group ( P<0.01). Cox regression analysis showed that independent risk factors for 5-year survival after radical gastrectomy for gastric cancer included the expression of MLF1IP ( HR=2.508, 95% CI: 1.259-4.999), CEA≥5 μg/L ( HR=2.171, 95% CI: 1.152-4.092), CA19-9≥37 kU/L ( HR=2.401, 95% CI: 1.094-5.269), and T3-T4 stages ( HR=2.779, 95% CI: 1.049-7.358) and N2-N3 stages ( HR=2.072, 95% CI: 1.100-3.904). ROC analysis showed that the sensitivity, specificity, and accuracy of MLF1IP (the cut-off value was 3.00 relative protein expression level) in assessing the 5-year survival rate after radical gastrectomy for gastric cancer was 75.00%, 76.92%, and 76.2%, respectively ( P<0.05). CCK-8, Transwell assay, and scratch assays showed that in vitro knocking down of MLF1 IP gene expression significantly inhibited the proliferation, migration and invasion of gastric cancer cells. Subcutaneous tumor xenograft experiment in nude mice showed that knocking down MLF1 IP gene significantly inhibited tumor growth. Increased expression of MLF1IP in gastric cancer tissue, which may be involved in the malignant activities of proliferation, migration, and invasion of gastric cancer cells, has a certain predictive value for poor prognosis.

Consensus molecular subtyping improves the clinical usefulness of canonical tumor markers for colorectal cancer.

Transcriptome-based classification, such as consensus molecular subtyping, is expected to be applied to colorectal cancer (CRC). However, the relationship between molecular profiles and classical tumor markers, which are already used in clinical practice, has not been analyzed in a large cohort and remains unclear. We classified more than 1,500 Japanese patients with CRC based on consensus molecular subtyping and investigated the clinically available blood carcinoembryonic antigen (CEA) concentrations of each subgroup. To precisely distinguish CRCs, we allocated them to five subgroups, including tumors that were difficult to classify using the consensus molecular subtypes (CMSs), and extracted a heterogeneous population with somatic mutations and expression profiles that differed from those of the CMSs 1-4. For patients allocated to the CMS4 subgroup of stage III CRCs, elevated blood CEA concentrations may identify a subgroup with highly aggressive disease and contribute to improving therapeutic decisions. Furthermore, gene expression and pathway analyses of tumor and non-tumor tissues revealed that tumor immunity was "cold" in this subgroup with high CEA concentrations. The combination of emerging molecular profiling and classical tumor markers may have greater clinical utility than either used alone.

Development of Carcinoembryonic Antigen Rapid Detection System Based on Platinum Microelectrode.

Rapid and highly sensitive detection of carcinoembryonic antigen (CEA) in blood could effectively improve the diagnostic sensitivity of colorectal cancer. In this work, a platinum microelectrode (PtμE) modified with gold nanoparticles was developed as a microsensor for the detection of CEA. As the recognition element, a CEA aptamer modified with sulfhydryl could be conjugated onto the surface of the PtμEs/Au. The quantitative analysis of the concentration of CEA [CEA] by the prepared PtμEs/Au aptasensor was carried out through square wave voltammetry. Under the optimized conditions, the PtμEs/Au aptasensor exhibits a linear response toward [CEA] in the range of 1.0 × 10–11—1.0 × 10–7 g/ml (S = 5.5 nA/dec, R 2 = 0.999), and the detection limit is 7.7 × 10–12 g/ml. The PtμEs/Au aptasensor also has good selectivity against other types of proteins existing in blood. The availability of the developed assay toward [CEA] in blood samples was investigated, and the results agreed well with those obtained through electrochemiluminescence provided by the hospital, and the volume of the blood sample for detection is only 20 μl. Herein, the proposed detection system could be used for the quantitative analysis of CEA in blood, with the advantages of high sensitivity, short time, and low cost. Moreover, the PtμEs/Au aptasensor has a potential application in clinical diagnosis.

Abstract 1949: Circulating tumor cells presence shorten the cancer specific survival in colorectal cancer: 10 years follow-up study

Abstract Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide and metastases-related death is the main cause of its high mortality. Circulating/disseminated tumor cells (CTCs/DTCc) are considered as precursors of distant metastatic spread and can act as an independent prognostic biomarker. The impact of CTCs/DTCs presence in perioperative period on long-term cancer specific survival (CSS) was assessed. Patients and methods: The presence of CTCs/DTCs in peripheral blood, tumor-draining blood, and bone marrow of 188 colorectal cancer patients was analyzed before, immediately after, and one month after surgery using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to detect the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA-positive CTCs. The trial was registered at ClinicalTrials.gov (NCT 03337347), patients were followed-up and the cause of death was determined. Results: Over a median follow-up period of 116.5 months, 81 of 148 (54.7%) stage I-III CRC patients died. In total, 40.7% of them (33/81) died of cancer. The presence of CTCs/DTCs did not correlate with any conventional clinical or pathological features (tumor node metastasis (TNM) stage, grade, KRAS mutations or microsatellite instability). Patients with CTCs/DTCs in the peripheral blood and bone marrow one month after surgery had significantly shorter CSS (p=0.013, HR=2.6; resp. p=0.019, HR=2.3) than those without CTCs/DTCs. Shorter overall survival was also observed in patients with tumor-draining blood CEA mRNA-positive CTCs before surgery (p=0.014). Conclusion: The presence of CK20 mRNA-positive CTCs/DTCs in blood and bone marrow after surgery was confirmed as an independent negative prognostic factor for the long-term cancer-specific survival in stage I-III colorectal cancer patients.The study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132; LM2018133), Palacky University Olomouc (LF 2021_019) and European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868, ACGT CZ.02.1.01/0.0/0.0/16_026/0008448). Citation Format: Josef Srovnal, Pavel Skalicky, Alona Rehulkova, Kamil Vyslouzil, Monika Vidlarova, Jana Vrbkova, Marian Hajduch. Circulating tumor cells presence shorten the cancer specific survival in colorectal cancer: 10 years follow-up study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1949.

A case of radical resection for brain metastases of pancreatic cancer after curative chemotherapy for para-aortic lymph node metastases

BackgroundThe incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood–brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature.Case presentationA 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors.ConclusionsAggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.

Preoperative C-reactive protein and other inflammatory markers as predictors of postoperative complications in patients with colorectal neoplasia

BackgroundInflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied.AimThe aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery.MethodsThis is a retrospective study which catalogs 218 patients undergoing elective, potentially curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics.ResultsElevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6, and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC = 0.871), and values above 17.5 mg/L predicted severe complications (AUC = 0.934).ConclusionsElevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.

A66 GASTRIC HETEROTOPIA OF THE COLON IN A PATIENT WITH A POSITIVE FECAL IMMUNOCHEMICAL TEST

Abstract Background Gastric heterotopia (GH), indicates the presence of ectopic gastric tissue and is a rare entity outside of the small intestine. Abdominal pain and bleeding are described but most colonic GH is found incidentally. Aims We report a case of colonic GH found on routine screening colonoscopy. Methods Case report and review of the literature. Results Case Report: A 60-year-old woman with a history of alcohol use disorder, chronic Hepatitis C, and gastroesophageal reflux disease was referred for colonoscopy after a positive fecal immunochemical test. Remote colonoscopy was notable for a large tubular adenoma with low-grade dysplasia. The patient denied constitutional symptoms, change in bowel habits, or evidence of gastrointestinal (GI) bleeding. No family history of colorectal cancer was reported. Complete blood count, renal function, electrolytes, and carcinoembryonic antigen were normal. At colonoscopy, a 2 cm sessile polyp (0-Is Paris classification) was identified with a normal vascular pattern, but unclassifiable pit pattern. Submucosal injection was suboptimal suggesting tethering. However, given the history of previous polypectomy and favorable endoscopic appearance, piecemeal resection was attempted and achieved fair results. Histology showed abundant pyloric-type glands with overlying foveolar epithelium (Figure 1). Endoscopic follow-up at 8 months confirmed complete resection. Literature Review GH is observed throughout the GI tract but is predominantly seen in the esophagus and duodenum. Colonic involvement is uncommon with only 12 cases reported. Despite the lack of epidemiological studies, there is a male predominance across all age groups. Pathogenesis is thought to be either congenital, with deposition as the stomach descends during embryogenesis, or acquired secondary to metaplasia following injury to normal intestinal mucosa. Presenting complaints may include altered bowel habits or haematochezia, but most lesions are detected incidentally on surveillance colonoscopy. Endoscopic descriptions are diverse with variations in size (1-60mm), Paris classification (sessile or pedunculated), and appearance (erythematous patch, ulcer, or diverticulum). Endoscopic resection is recommended given association with bleeding but may be technically difficult due to submucosal involvement which may theoretically increase risk of complications such as perforation. Definitive diagnosis rests on histological examination. The risk of malignant transformation of GH in the colon is unknown with only two such cases reported. However, some propose the incidence of malignant change is underestimated as the growing tumor may eliminate the focus of heterotopic gastric mucosa. Conclusions GH in the colon is a rare entity with diverse endoscopic appearances and poorly understood natural history. Careful endoscopic resection is feasible in the absence of other high-risk endoscopic features. Funding Agencies None

Diagnostic Value of Chitinase-3-like Protein 1 and Keratin 5 in Bronchoalveolar Lavage Fluid of Lung Cancer

To investigate the diagnostic value of chitinase-3-like protein 1 and keratin 5 in bronchoalveolar lavage fluid in 88 patients with lung disease. This was a case control study to collect 50 patients with lung cancer (malignant disease group) and 38 patients with benign lung disease (benign disease group) who were admitted to the respiratory medicine department in the affiliated hospital of medical school of Ningbo university from December 2019 to March 2020. The enzyme-linked immunosorbent assay was applied to detect the expression levels of chitinase-3-like protein 1 and keratin 5 in bronchoalveolar lavage fluid of the two groups of the patients. The diagnostic effect was evaluated using the subject's working characteristics to establish a diagnostic mathematical model. The levels of chitinase-3-like protein 1 and keratin 5 in bronchoalveolar lavage fluid were significantly higher in the malignant disease group than in the benign disease group (p<0.05). These two (chitinase-3-like protein 1 and keratin 5) were significantly correlated and positively correlated and the combined test could significantly improve the sensitivity and specificity of lung cancer diagnosis. The diagnostic rate of chitinase-3-like protein 1 and keratin 5 for lung cancer. The chitinase-3-like protein 1 in bronchoalveolar lavage fluid and carcinoembryonic antigen in blood combined was superior to chitinase-3- like protein 1 or keratin 5 alone in the diagnosis of lung cancer. Chitinase-3-like protein 1 and keratin 5 in bronchoalveolar lavage fluid contribute to the early diagnosis of lung cancer and can be used as biomarkers for the diagnosis of lung cancer with high sensitivity and specificity. The application of the two combined assays as molecular markers for clinical diagnosis and as targeted therapeutic agents needs to be further studied.

Intratumoural immune signature to identify patients with primary colorectal cancer who do not require follow-up after resection: an observational study.

Following surgical and adjuvant treatment of primary colorectal cancer, many patients are routinely followed up with axial imaging (most commonly computerised tomography imaging) and blood carcinoembryonic antigen (a tumour marker) testing. Because fewer than one-fifth of patients will relapse, a large number of patients are followed up unnecessarily. To determine whether or not the intratumoural immune signature could identify a cohort of patients with a relapse rate so low that follow-up is unnecessary. An observational study based on a secondary tissue collection of the tumours from participants in the FACS (Follow-up After Colorectal Cancer Surgery) trial. Formalin-fixed paraffin-embedded tumour tissue was obtained from 550 out of 1202 participants in the FACS trial. Tissue microarrays were constructed and stained for cluster of differentiation (CD)3+ and CD45RO+ T lymphocytes as well as standard haematoxylin and eosin staining, with a view to manual and, subsequently, automated cell counting. The tissue microarrays were satisfactorily stained for the two immune markers. Manual cell counting proved possible on the arrays, but manually counting the number of cores for the entire study was found to not be feasible; therefore, an attempt was made to use automatic cell counting. Although it is clear that this approach is workable, there were both hardware and software problems; therefore, reliable data could not be obtained within the time frame of the study. The main limitations were the inability to use machine counting because of problems with both hardware and software, and the loss of critical scientific staff. Findings from this research indicate that this approach will be able to count intratumoural immune cells in the long term, but whether or not the original aim of the project proved possible is not known. The project was not successful in its aim because of the failure to achieve a reliable counting system. Further work is needed to perfect immune cell machine counting and then complete the objectives of this study that are still relevant. Current Controlled Trials ISRCTN41458548. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 2. See the NIHR Journals Library website for further project information.

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

Outcomes of Laparoscopic Surgery for Mucinous Colorectal Adenocarcinoma.

Background: Mucinous colorectal adenocarcinoma (MAC) has a higher incidence of local extension, leading to lower overall resection rates. Few studies have investigated the outcomes of laparoscopic surgery for MACs to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for mucinous adenocarcinoma (MAC). Methods: This study analyzed short-term and long-term outcomes between laparoscopic and open surgery for MACs from 2008 to 2018. Multivariate analyses were used to define prognostic factors of overall survival (OS) and disease-free survival (DFS). Results: Patients in the laparoscopy (LAP) group had significantly less blood loss, fewer days to first flatus and to diet, and shorter length of hospital stay. The 3-year and 5-year DFS rates for all stages combined were 65.7% and 62.5% in the LAP group compared with 60.5% and 57.6% in the open (OPEN) surgery group (P = .521). The 3-year and 5-year OS rates for all stages combined were 72.3% and 67.3% in the LAP group compared with 72.6% and 67.8% in the OPEN group (P = .934). OS and DFS in stage II, stage III, and pathological T4 (pT4) stage patients who underwent laparoscopic surgery did not differ from patients who underwent open surgery. Multivariate analysis showed that stage pT4, pN2, and carcinoembryonic antigen (CEA) were significant predictors of OS. Independent factors, including intraoperative blood transfusion, stage pT4, pN2, CEA, and CA19-9, carbohydrate antigen 19-9, have a great effect on DFS. Conclusions: Laparoscopic surgery is a safe and feasible option for mucinous colorectal AC, which provides faster postoperative recovery and less intraoperative blood loss.