High Serum Carcinoembryonic Antigen Research Articles

Serum tumor markers expression (CA199, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus.

Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important. To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM. For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), etc. were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve. The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels (P < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels (P < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c (r = 0.308, 0.426, and 0.551, respectively) and FBG levels (r = 0.236, 0.231, and 0.298, respectively). As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.

Is there any diagnostic value of serum caveolin-1 levels on the determination of pancreatic adenocarcinoma?

Caveolin-1 (CAV-1) is a vital component in cancer pathogenesis, as its expression determines the survival of patients with cancer. This study investigates CAV-1 serum levels in pancreatic adenocarcinoma (PA) patients and their role in tumor progression and prognostic factors. The trial included 33 patients with pathologically confirmed pancreatic cancer (PC). The enzyme-linked immunosorbent assay (ELISA) method was used to measure the concentrations of CAV-1 in the blood. The study also included 20 healthy subjects. The statistical analysis was two-sided, and a P value of ≤ 0.05 was determined as statistically significant. The median age of the subjects was 59 years (32-84 years) at the time of diagnosis. There were 13 (39%) female participants. In 21 (63%) patients, the primary focus was the pancreatic head. In 23 stage IV patients, hepatic metastasis (n = 19, 83%) was observed. Only one patient (3%) was still alive at the end of the study period. Palliative chemotherapy (CTx) was provided, with 39% of the 23 patients responding to it. The overall survival (OS) rate in this cohort was 41.3 ± 8.3 weeks at a 95% confidence interval (CI), after 25-58 weeks. Serum baseline CAV-1 values among patients with PA were significantly higher compared with controls (p = 0.009). Patients with poor performance status, a pancreatic head tumor, lower albumin levels, higher serum carcinoembryonic antigen (CEA) levels, and higher CA 19.9 levels had significantly higher serum CAV-1 levels (p = 0.01, P = 0.05, P = 0.03, P = 0.02, and P = 0.04, respectively). However, CAV-1 did not show any prognostic value (p = 0.75). Although serum CAV-1 is a useful diagnostic marker in PC patients, it is not a prognostic or predictive marker.

Preoperative metabolic parameters of 18F-FDG PET/CT are associated with TNM stage and prognosis of colorectal cancer patients.

Colorectal cancer (CRC) is the third most frequent cause of cancer-related death, while tumor/node/metastasis (TNM) stage of American Joint Committee on Cancer is the guideline of making treatment strategy and predicting survival. The aim of this study is to investigate the association of preoperative 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), TNM stage, and prognosis of patients with CRC. From September 2016 to August 2022, a total of 132 patients were retrospectively and consecutively enrolled in this cross-sectional study, who were diagnosed as CRC by histopathology and received preoperative 18F-FDG PET/CT. Firstly, the correlation between the metabolic parameters and clinicopathological features of the primary tumors was investigated. Secondly, univariate and multivariate logistic regression analyses were used to estimate the odds ratio of the association between the clinical and metabolic parameters and the advanced TNM stage (stage III-IV). Thirdly, progression-free survival (PFS) was analyzed using Kaplan-Meier curves and Log-rank test. The results revealed that the metabolic tumor volume (MTV) >6.6 cm3 and serum carcinoembryonic antigen (CEA) >5.84 ng/mL were independently associated with advanced TNM stage (P=0.0009, 0.0011, respectively). Larger tumor size, higher tumor-to-liver standardized uptake value ratio, MTV, and total lesion glycolysis (TLG) were significantly correlated with advanced pT stage (stage 4), and higher TLG and MTV were significantly correlated with advanced pN stage (stage 1-2) (P<0.05), while no metabolic parameters were significantly correlated with metastasis status (P>0.05). Higher serum CEA and carbohydrate antigen 19-9 levels were significantly correlated with advanced pT, pN stage, and metastasis status (P<0.05). Patients were followed up for at least 1 year. The MTV >6.6 cm3 was significantly associated with worse PFS (P=0.032). 18F-FDG PET-CT can serve as a noninvasive tool for preoperatively staging CRC. The MTV >6.6 cm3 might be associated with advanced TNM stage and worse PFS.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis.

Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

Clinicopathologic study of stage I adenosquamous carcinoma of the lung.

Adenosquamous carcinoma of the lung is a characteristic tumor that has both adenocarcinoma and squamous cell carcinoma components. Adenosquamous carcinoma is reported to have an aggressive clinical course, but its clinicopathological features and prognosis are unclear in the early stage. Patients who underwent surgical resection for pathological stage I non-small cell lung cancer between April 2009 and December 2014 were retrospectively reviewed. Preoperative and postoperative data, histologic characteristics and outcomes of patients with adenosquamous carcinoma (n=40) were compared to adenocarcinoma (n=598) and squamous cell carcinoma (n=131) patients. Factors affecting prognosis, particularly on recurrence, were assessed via Cox regression analyses. Patients with adenosquamous carcinoma had a worse prognosis than did patients with adenocarcinoma and squamous cell carcinoma in terms of 5year overall (66.7%) and recurrence-free survival rates (44.9%), as well as a significantly higher recurrence rate (13/40 patients, 32.5%). Multivariable Cox regression analysis for recurrence-free survival rates revealed that the histology of adenosquamous carcinoma was an independent factor for recurrence (hazard ratio: 2.473, 95% confidence interval: 1.328-3.367; P=0.0004). High serum carcinoembryonic antigen levels (hazard ratio: 5.962) and vascular invasion (hazard ratio: 4.899) were identified as risk factors for recurrence, and patients with adenosquamous carcinoma tended to have distant relapses, such as in the brain. Early-stage adenosquamous carcinoma of the lung is a histological type associated with severe prognosis and postoperative recurrence, often in distant sites, in approximately one-third of cases. High serum carcinoembryonic antigen levels and vascular invasion might be risk factors of recurrence.

39. HIGH PREOPERATIVE PLATELET TO LYMPHOCYTE RATIO IS ASSOCIATED WITH A GREATER RISK OF POSTOPERATIVE COMPLICATIONS AND RECURRENCES IN ESOPHAGEAL CANCER

Abstract Background Neoadjuvant treatment is currently the gold standard for advanced esophageal squamous cell carcinoma (ESCC). Several studies have examined the value of blood count-based indexes for predicting short- and long-term outcomes after esophagectomy for ESCC, but the relative predictive value of pretreatment, preoperative, and postoperative indexes has not yet been examined. Methods This study included 320 patients with thoracic ESCC who underwent subtotal esophagectomy after neoadjuvant chemotherapy or chemoradiotherapy at our institution. A total of 19 candidate blood parameters were measured before neoadjuvant treatment as well as preoperatively and postoperatively. The ability of the parameters to predict postoperative complications, overall survival (OS), and relapse-free survival (RFS) were assessed using receiver operating characteristic (ROC) curve analysis and Cox regression analysis. Results ROC curve analysis indicated that preoperative platelet to lymphocyte ratio (PLR) had the best predictive value with an optimal cutoff value of 166. Patients with high preoperative PLR (≥166) had significantly shorter OS and RFS and significantly higher incidences of hematogenous recurrence and postoperative pneumonia compared with patients with low preoperative PLR (&amp;lt;166). In multivariate analysis, high preoperative PLR and high preoperative serum carcinoembryonic antigen level were independent predictors of poor prognosis. Conclusion Preoperative PLR is a good predictor of short- and long-term prognosis in patients with advanced ESCC who receive neoadjuvant treatment followed by radical resection.

Incidence, clinicopathological features, and clinical outcomes of low HER2 expressed, inoperable, advanced, or recurrent gastric/gastroesophageal junction adenocarcinoma

According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma. This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+). In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n= 410; HER2-low, n= 154, and HER2-positive, n= 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR)= 0.73, 95% confidence interval (CI) 0.59-0.89; P= 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR= 1.01, 95% CI 0.82-1.23; P= 0.843). Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.

High Preoperative Platelet to Lymphocyte Ratio Is Associated with a Greater Risk of Postoperative Complications and Hematogenous Recurrences in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Treatment

Introduction: Neoadjuvant treatment is currently the gold standard for advanced esophageal squamous cell carcinoma (ESCC). Several studies have examined the value of blood count-based indexes for predicting short- and long-term outcomes after esophagectomy for ESCC, but the relative predictive value of pretreatment, preoperative, and postoperative indexes has not yet been examined. Methods: This study included 320 patients with thoracic ESCC who underwent subtotal esophagectomy after neoadjuvant chemotherapy or chemoradiotherapy at our institution. A total of 19 candidate blood parameters were measured before neoadjuvant treatment as well as preoperatively and postoperatively. The ability of the parameters to predict postoperative complications, overall survival (OS), and relapse-free survival (RFS) was assessed using receiver operating characteristic (ROC) curve analysis and Cox regression analysis. Results: ROC curve analysis indicated that preoperative platelet to lymphocyte ratio (PLR) had the best predictive value with an optimal cutoff value of 166. Patients with high preoperative PLR (≥166) had significantly shorter OS and RFS and significantly higher incidences of hematogenous recurrence and postoperative pneumonia compared with patients with low preoperative PLR (<166). In multivariate analysis, high preoperative PLR and high preoperative serum carcinoembryonic antigen level were independent predictors of poor prognosis. Conclusion: Preoperative PLR is a good predictor of short- and long-term prognosis in patients with advanced ESCC who receive neoadjuvant treatment followed by radical resection.

Association between serum carcinoembryonic antigen and cardiometabolic risks: Implication for cardiometabolic prevention.

Serum carcinoembryonic antigen (CEA) is a biomarker commonly used to detect colorectal cancer. CEA levels are affected by many factors, including cardiometabolic diseases, such as cardiovascular diseases (CVDs) and diabetes. Cardiometabolic diseases and cancer share a similar pathological inflammatory pathway, which correlates with an unhealthy lifestyle. Hence, establishing an adequate CEA cut-off value might be a valuable reference for developing precision healthcare programs for cardiometabolic disease prevention. This study aimed to investigate the association between cardiometabolic risks and serum CEA and the underlying factors. A community-based, cross-sectional study was conducted between March and December 2021 on the western coast of Taiwan. Lifestyle data were assessed using a structured questionnaire. The cardiometabolic biomarkers, serum CEA, urine malondialdehyde, and 1-hydroxypyrene were quantified by the central laboratory of the collaborating hospital. Chi-square and binary multivariable logistic regression implemented in R version 4.0.2 were used to identify factors defining the risk of high serum CEA levels. A total of 6,295 adult residents without cancer-related diseases completed the study. The mean age was 48.6 (SD = 16.4) years, 56% were female, 32% had metabolic syndrome, and 23% and 10% had CVDs and diabetes, respectively. Multivariate logistic regression showed that age ≥ 65 years, male sex, alcohol consumption, smoking, infrequent use of dental floss, fewer remaining teeth, CVDs, diabetes, and oxidative stress were significantly associated with serum CEA ≥ 3 ng/mL. The discriminatory performance of the area under the receiver operating characteristic curve was 0.75 (0.73-0.76), showing that this model was suitable for distinguishing high CEA levels. Our findings highlight the importance of understanding cardiometabolic diseases, unhealthy lifestyles, and oxidative stress, which contribute to high serum CEA. This study demonstrates that CEA, a well-known tumor marker, can help the early detection and prevention of cardiometabolic diseases via personalized lifestyle modification.

A clinicopathological study of the correlation of level of carcinoembryonic antigen in colorectal carcinoma in a tertiary care medical college in Eastern India

Background: For different cancers, different tumor markers are overexpressed. Carcinoembryonic antigen (CEA) levels are raised commonly in adenocarcinoma of colon, breast, and lung. About 80% of primary colorectal cancers (CRCs) show high serum CEA levels. Hence, CEA levels can be used as a prognostic factor - for both metastasis and recurrence - with persistent high levels. Currently, the American Society of Clinical Oncology recommends CEA as tumor marker and prognostic indicator in CRC patients. Aim and Objectives: The aim of the study was to determine the high level of CEA in CRCs and to study the level of CEA in cases of metastases and recurrence and to determine the sensitivity of CEA value in prognosis of CRCs. Materials and Methods: It was a prospective observational study. All the patients more than 20 years of age and of both sexes were included in this study who were diagnosed with primary localized CRC, metastatic CRC, or recurrent disease. The study was performed in the Department of General Surgery, R. G. Kar Medical College and Hospital between January 2020 and August 2021. Results: Total cases were classified according to Duke staging - 10% in Group A, 19% in Group B, 38% in Group C, and 33% in Group D. In Group A and B, about 35% of patients had increased CEA levels, whereas in Group C and D, more than 90% of patients had increased CEA levels with significant P &lt; 0.05. Overall 80% of the patients had elevated CEA levels, so remaining 20% had normal values. In cases of recurrent colorectal carcinoma, &gt;90% of patients had raised CEA levels, and in metastatic disease cases, CEA level was significantly raised in 82% of patients. Conclusion: In case of colorectal CA, preoperative raised serum CEA level is associated with poor prognosis, as chance of recurrence increased. Along with that increased CEA level is also associated with increased chance of metastatic disease. Hence, serial monitoring of serum CEA level in postoperative period may help to detect any recurrence early, thus reducing chance of mortality and morbidity.

High Prevalence of Abnormal Carcinoembryonic Antigen in Diabetic Inpatients with Poor Glycemic Control

IntroductionHigher serum carcinoembryonic antigen (CEA) was found in diabetic patients rather than controls. However, the prevalence of abnormal CEA among diabetic inpatients with a large proportion of poor glycemic control is unclear.MethodsA total of 385 diabetic inpatients were included in this study. We collected information from a large clinical database. Patients with malignant tumors were excluded by examination and follow-up.ResultsWe found a surprisingly high prevalence (14.3%) of diabetic inpatients with CEA above normal. The proportion of patients with abnormal CEA was significantly different in subgroups with different blood glucose levels, 20.4% in the HbA1c ≥ 9% group, and 8.5% in the HbA1c < 9%, p = 0.000. We found that the CEA levels were correlated with age, body mass index and HbA1c. The regression coefficient of HbA1c was the highest, B = 0.284, p = 0.000. We also found that the CEA levels were higher in diabetic inpatients with BMI < 24 kg/m2 than the overweight or obesity patients. There was a significant difference in the insulin level and C peptide level between the elevated CEA group and the non-elevated CEA group.ConclusionThe elevation of CEA is common in diabetic inpatients, especially those with poor hyperglycemia controlled (HbA1c ≥ 9%). The underlying mechanism may be related to glucose toxicity.

Prognostic value of serum CEA and CA19-9 levels in pancreatic ductal adenocarcinoma.

The present study investigated the associations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels with clinicopathological variables and survival outcomes in Libyan patients with pancreatic ductal adenocarcinoma (PDAC). The clinicopathological variables of 123 patients with PDAC registered at the National Cancer Institute in Misurata, Libya, between 2010 and 2018 were retrospectively analyzed. Blood samples from these patients were analyzed for serum CEA and CA19-9 levels before treatment by electrochemiluminescence immunoassay (double antibody sandwich ELISA) on a Roche cobas e 602 modules. The relationships between CA19-9 and CEA serum levels with clinicopathologic variables and survival outcomes were analyzed using the Kaplan-Meier method, log-rank test and Cox regression analyzes. Cut-off values for serum CEA and CA19-9 levels were 5 ng/ml and 400 U/ml, respectively. The median serum levels of all patients with PDAC for CEA and CA19-9 were 8 ng/ml (1.1-377 ng/ml) and 389 U/ml (1-10,050 U/ml), respectively. Tumors with higher serum CEA and CA19-9 levels were found in 63 and 48% of patients, respectively. Higher CEA and CA19-9 serum levels were significantly associated with more indicators of a malignant phenotype, including a surgically unresectable tumor, unevaluable lymph nodes, advanced stages and distant metastases. Regarding survival, patients with higher serum levels of the biomarkers CEA and CA19-9 had shorter overall survival rates (P<0.016 and (P<0.014, log-rank, respectively) and lower disease-free survival rates (P<0.002 and P<0.0001, log-rank, respectively). The present study demonstrated significant clinical and prognostic value of serum levels of biomarkers CEA and CA19-9 for Libyan patients with PDAC. Moreover, patients with PDAC with higher serum CEA and CA19-9 levels had more aggressive tumors, higher rates of disease recurrence and shorter overall survival rates and thus required more vigilant follow-up. Further multinational studies with larger PDAC cohorts are warranted to confirm these findings in terms of improved clinical decision making, more effective management and improved survival.

Assessment of the preventive effect of dietary inclusion of Cucurbita maxima (Duch.) leaf on N-methyl-N-nitrosourea (MNU) induced colon carcinogenesis in Wistar rats

The preventive effect of Cucurbita maxima leaf inclusion at 2.5%, 5% and 10% in colon carcinogenesis induced by N-methyl-N-nitrosourea (MNU) for 12 weeks was evaluated. A significantly lower level of carcinoembryonic antigen (CEA) values was observed in the serum of rats fed with various percentages of C. maxima leaf included diet in comparison with the MNU control group (administered MNU without treatment), which showed high serum CEA values (238.77 ± 38.95 ng/ml). The result shows that the MNU control group has the highest level of oxidative stress in the colon (78.51 ± 6.88 nMol/mg/ml) when compared to the normal control groups (56.30 ± 5.82 nMol/mg/ml). There was no significant difference in the level of MDA in the 10% dietary inclusion control group of the colon (52.08 ± 7.63 nMol/mg/ml) when compared to the normal control groups. Analysis of the experimental diets revealed a significant presence of total polyphenols and flavonoids content which increases from 0.256 mg/g GAE and 0.068 mg/g QU respectively in basal diets towards 0.287 mg/g and 0.085 mg/g respectively in the 10% C. maxima leaf-included. The polyphenol and flavonoid content of the formulated diet at 5% and 10% shows significantly higher values than the basal diet. The data showed an increase in crude fibre content, 3.05 mg/g, 3.1 mg/g, 4.2 mg/g in the 2.5%, 5% and 10% inclusions respectively. The results demonstrated a strong negative correlation coefficient (-0.715, -0.799, -0.944) between CEA and the crude fibre, flavonoid and polyphenol respectively when C. maxima percentage was increased in the experimental diets. Similarly, the rats MDA values also showed a negative correlation coefficient (-0.271, -0.398, -0.147) with crude fibre, polyphenol and flavonoid content respectively. However, the enzymatic antioxidants (superoxide dismutase and catalase) showed a positive correlation (0.355, 0.411, 0.488 and 0.112, 0.241, 0.380) with the crude fibre, polyphenols and flavonoid content respectively. Histological observation of colon tissue showed severe damage to the mucosa cell, with mucosa ulceration and sclerosis in the MNU control group, whereas groups fed with experimental diets concurrently with MNU administration showed mild damage to the normal architecture of the cells. The results demonstrated the ability of C. maxima leaf dietary inclusion to improve endogenous antioxidant system, lower oxidative stress and protect against organ damage by MNU carcinogen.

The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer.

ObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.MethodsFlow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.ResultsWe found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.ConclusionThe mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.

A rare case of PSA-negative metastasized prostate cancer to the stomach with serum CEA and CA19-9 elevation: a case report

BackgroundMetastatic cancer to the stomach is relatively rare. Prostate-specific antigen (PSA) is a reliable biomarker used in the screening and management of patients with prostate cancer. However, it is difficult to definitively diagnose a PSA-negative metastatic gastric tumor of prostate cancer because the cancer sometimes resembles primary gastric cancer in clinical images. It is also difficult to distinguish metastatic cancer from primary cancer even in the pathological examination of biopsy samples when the lesion is poorly differentiated adenocarcinoma. There is a possibility that the characteristics of the cancer are changed during treatment such as chemotherapy or radiation therapy. Therefore, careful consideration is required for surgical indication.Case presentationA 60-year-old male underwent radical prostatectomy and subsequent radiation therapy for advanced prostate cancer (pT3N1M0) 10 years previously, and hormone therapy was started for metachronous multiple bone metastasis 10 months before. Upper gastrointestinal endoscopy revealed an irregular depressed lesion with a convergence of folds at the greater curvature of the upper gastric body. Biopsy showed poorly differentiated adenocarcinoma that was negative for PSA upon immunohistochemistry. He had high serum carcinoembryonic antigen (CEA) (946.1 ng/ml) and carbohydrate antigen 19-9 (CA19-9) (465.1 U/ml) levels with no elevation of PSA (0.152 ng/ml). The tumor was diagnosed as primary gastric cancer based on the clinical imaging and pathological examination of the biopsy sample including the PSA staining. Based on the diagnosis, laparoscopic proximal gastrectomy with lymphadenectomy was performed. However, pathological examination of the resected specimen revealed poorly differentiated adenocarcinoma that was positive for other prostate markers such as androgen receptor. Thus, the patient was diagnosed with metastasized prostate cancer to the stomach.ConclusionsWe report a case of metastatic gastric cancer of prostate cancer 10 years after radical prostatectomy. In the present case, it was difficult to diagnose a metastatic gastric tumor of prostate cancer preoperatively, because of its resemblance to primary gastric cancer without PSA expression and no serum PSA elevation. Although a rare case entity, it is important to consider the possibility of a metastatic gastric tumor when the surgical indication is determined in cases with another co-existing cancer.

Risk Stratification Based on Synchronous Neoplasia and Clinical Physicochemical Characteristics Predicts a Higher Incidence of Metachronous Advanced Neoplasia in Patients Undergoing Colorectal Resection for Colorectal Cancer.

PurposePatients who undergo primary colorectal cancer (CRC) resection remain at increased risk for metachronous advanced neoplasia (MAN) in the remnant colorectum. This study aimed to investigate the incidence and clinicopathological characteristics predictive of MAN development in the residual colon after surgery.Patients and MethodsWe retrospectively reviewed 450 primary CRC cases referred to our hospital during a 4-year period. Univariate and multivariate analyses were performed to identify risk factors for MAN. The cumulative incidence of MAN was evaluated by the Cox proportional hazards model.ResultsMAN development was confirmed in 78 of the 450 patients (17.3%). Overall 1-, 2-, 3-, and 5-year cumulative probabilities were 0.9%, 4.8%, 9.8%, and 16.1%, respectively, for MAN. Among the clinical and colonoscopic factors at baseline, the independent factors that were significantly associated with MAN were synchronous neoplasia, carcinoembryonic antigen (CEA) level ≥10.0 ng/mL, and index cancer size ≥50 mm. The cumulative probability of MAN was significantly higher for patients with synchronous advanced neoplasia (SAN) than for those without synchronous neoplasia (P = 0.000). A subgroup analysis of patients based on the CEA level and index cancer size indicated that CEA ≥10 ng/mL and index cancer ≥50 mm resulted in a significantly higher cumulative probability of MAN (P = 0.039).ConclusionPatients with SAN or high preoperative serum CEA levels and large index cancer are at increased risk for early-onset MAN. More intensive surveillance strategies may be appropriate for these groups. Risk stratification based on synchronous neoplasia and clinical physicochemical characteristics requires further investigations involving modified appropriate postoperative colonoscopic surveillance schedules.

Why recurrence was initially suspected during colorectal cancer postoperative surveillance?: A retrospective analysis.

Routine postoperative surveillance is recommended for the patients with colorectal cancer (CRC). This study aimed to clarify the conditions indicate initial suspicion of CRC recurrence in different preoperative serum carcinoembryonic antigen (CEA) level groups, including positive physical signs/symptoms, elevated CEA level, positive radiologic studies results, and other elevated tumor markers.A total of 2268 patients with recurrence after curative surgery for CRC were enrolled in this study. The patients were classified into 3 groups according to preoperative serum CEA level (low, <2 ng/mL; intermediate, ≥2 and <5 ng/mL; and high, ≥5 ng/mL).Up to 63.6% of recurrence was suspected based on elevated CEA level in the high preoperative serum CEA level group. Patients in the low preoperative serum CEA level group had a higher rate of initial suspicion of recurrence based on positive physical signs or symptoms (36.7% vs 26.9% vs 20.4%, P < .001) and positive radiologic findings (51.4% vs 40.7% vs 29.5%, P < .001) than those in the intermediate and high preoperative serum CEA groups.Conditions indicate initial suspicion of recurrence varied in the different preoperative serum CEA level groups. In patients with low preoperative serum CEA level, the detection of recurrence depend on abnormal CEA level is less sensitive than intermediate and high preoperative serum CEA groups. We suggest that the strategy for CRC surveillance should not depend on serum CEA level alone. The signs or symptoms of patients, changes in postoperative serial CEA level, and ongoing radiologic or imaging findings must be cautiously monitored.

Association Between Pretransplant Serum Carcinoembryonic Antigen Levels and Immunohistochemical Staining of Explanted Native Lungs in Patients Who Underwent Lung Transplantation

Some patients show high serum carcinoembryonic antigen (CEA) levels in the evaluation of candidate patients for lung transplantation, which might be a challenge because high serum CEA potentially implies an existence of malignancy. For further understanding of the true meaning of high serum CEA levels in lung transplantation, we retrospectively investigated the relationship between serum CEA and clinical data. We also performed immunohistochemical analysis of explanted native lungs and evaluated its relationship with serum CEA levels. Retrospective chart review was performed in consecutive patients who underwent lung transplantation with measurement of serum CEA before and after transplantation at our institution between August 2008 and June 2017. Histopathological analysis was also performed in the same cohort of patients. Survival outcomes and pathohistological findings were compared between the high serum CEA and the normal CEA group, adjusting for potential confounding factors. One hundred and fifteen patients were eligible for analysis. High serum CEA levels before lung transplantation in most cases were decreased after the transplantation (35/39, 90%, P < 0.001). Preoperative serum CEA levels were not associated with postoperative survival. The percentage of CEA-positive alveolar cells was significantly higher in the high serum CEA group (P < 0.0001). After adjusting for potential confounding factors, there was a significant difference between the high serum CEA group and normal serum CEA group (CEA-positive alveolar cells; P = 0.002). High serum CEA levels before lung transplantation might derive from native lungs in the recipients and that they were not associated with overall survival after lung transplantation.

Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases

PurposeAccumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection. MethodsWe retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. ResultsA higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63–4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02–2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications. ConclusionA high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.

Abstract 3626: Genomic characterization of primary tumor in colorectal cancer according to serum carcinoembryonic antigen level

Abstract Background: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers in colorectal cancer (CRC). High preoperative concentrations of CEA correlate with poor survival outcomes. Serial CEA measurements have been used for detecting recurrent CRC. However, the genomic characteristics of primary CRC according to the blood CEA level are still not clear. Though patients with low CEA levels are associated with good prognosis, some of these patients have progression of their tumor. It would aid in applying careful surveillance to identify a subset of patients at high risk for poor prognosis among those with low CEA level. In this study, the different types of molecular profiles were compared between CRC with low and high serum CEA levels. In addition, we compared the genomic characteristics between CRC without progression and with progression among patients with low CEA levels. Methods: Using data acquired from The Cancer Genome Atlas (TCGA), we performed survival and genomic analyses on 381 CRC patient samples with serum CEA levels. Differential mRNA expression, miRNA expression and DNA methylation were examined between CRC with low serum CEA levels (low CEA group; ≤ 5 ng/mL) and high serum CEA levels (high CEA group; &amp;gt; 5 ng/mL). Among the 140 patients with low CEA levels, the same analyses were performed between CRC without progression and with progression. Results: High CEA group was associated with higher pathologic stage, more venous and lymphatic invasion. High CEA group had worse overall and progression-free survival than low CEA group (p &amp;lt;0.001 and p &amp;lt;0.001, respectively). A total of 28 genes were identified as significantly differentially expressed genes between low and high CEA group. Functional annotation and pathway analyses of the differentially expressed genes identified the possible association of cell adhesion, cytokine-cytokine receptor interaction and Wnt signaling network. Two differentially expressed miRNAs (mir-486 and mir-509-1) and 3 differential CpG sites (cg07530063, cg24216966 and cg11622162) were identified between low and high CEA group. Between CRC without progression and with progression in low CEA group, we identified 20 differentially expressed genes that were associated with epithelial to mesenchymal transition and transport of organic acid, metal ion and amine compounds. Four differentially expressed miRNAs (mir-483, mir-9-1, mir-9-2, and mir-31) and no differential CpG sites were identified between CRC with and without progression. Conclusions: In this study, we have identified different molecular features between primary CRC with low and high CEA levels. Notably, specific genomic profiles may contribute to discriminating patients with poor outcomes in CRC with low CEA level. Citation Format: Ji Won Park, Manu Shivakumar, Eun Kyung Choe, Dokyoon Kim. Genomic characterization of primary tumor in colorectal cancer according to serum carcinoembryonic antigen level [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3626.