Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA

BackgroundSerum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.MethodsPatients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.ResultsWe included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient’s prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).ConclusionsEarly postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

A Potential Serum Biomarker for Screening Lung Cancer Risk in High Level Environmental Radon Areas: A Pilot Study

Radon is a major cause of lung cancer (LC) deaths among non-smokers worldwide. However, no serum biomarker for screening of LC risk in high residential radon (HRR) areas is available. Therefore, the aim of this study was to determine diagnostic values of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), human epididymis protein 4 (HE4), interleukin 8 (IL-8), migration inhibitory factor (MIF), tumor nuclear factor-alpha (TNF-α) and vascular endothelial growth factors (VEGF) occurring in high radon areas. Seventy-five LC non-smoker patients and seventy-five healthy controls (HC) were enrolled in this study. Among the HC groups, twenty-five HC were low residential radon (LRR) and fifty HC were HRR. Significantly higher (p < 0.0004) serum levels of CEA, Cyfra21-1, IL-8 and VEGF were found in the LC compared with the LRR and HRR groups. More importantly, significantly higher levels (p < 0.009) of serum CEA, Cyfra21-1 and IL-8 were observed in HRR compared with the LRR group. Likewise, a ROC curve demonstrated that serum CEA and Cyfra21-1 could better distinguish LC risk from HRR groups than IL-8. These results indicated that serum CEA and Cyfra21-1 were significantly increased in the HRR group and may be considered as potential biomarkers for individuals at high-risk to develop LC.

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive liver cancer patients from Eastern and Southern China

Background Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative primary liver cancer (PLC) patients to allow for improved clinical management and prognostication of the disease. Methods This study observed a cohort of PLC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. Results Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Serum AFP status was inversely associated with serum carcinoembryonic antigen (CEA). Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). Conclusions The are significant differences in clinical pathologic characteristics between AFP positive and negative PLC patients which may be helpful for the management and prognostication of the disease.

Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p &lt; 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p &lt; 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p &lt; 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p &lt; 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p &lt; 0.001).Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.

Association Between Serum Carcinoembryonic Antigen Levels at Different Perioperative Time Points and Colorectal Cancer Outcomes

BackgroundWhether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial.Patients and MethodsPrimary and sensitivity analysis populations were obtained from a retrospective, multicenter longitudinal cohort including consecutive patients without neoadjuvant treatment undergoing curative resection for stage I–III CRC. Serum CEA levels before (CEApre-m1) and within 1 (CEApost-m1), 2–3 (CEApost-m2–3), and 4–6 months (CEApost-m4–6) after surgery were obtained, and their associations with recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox regression. Sensitivity and subgroup analyses were performed.ResultsPrimary and sensitivity analysis populations included 710 [415 men; age, 54.8 (11.6) years] and 1556 patients [941 men; age, 56.2 (11.8) years], respectively. Recurrence hazard ratios (HRs) in the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups were 1.30 (95% CI: 0.91–1.85), 1.53 (95% CI: 0.89–2.62), 1.88 (95% CI: 1.08–3.28), and 1.15 (95% CI: 0.91–1.85), respectively. The HRs of the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups for OS were 1.09 (95% CI: 0.60–1.97), 2.78 (95% CI: 1.34–5.79), 2.81 (95% CI: 1.25–6.30), and 3.30 (95% CI: 1.67–.536), respectively. Adjusted multivariate analyses showed that both in the primary and sensitivity analysis populations, elevated CEApost-m2–3, rather than CEApre-m1, CEApost-m1, and CEApost-m4–6, was an independent risk factor for recurrence, but not for OS. The RFS in the elevated and normal CEApost-m2–3 groups differed significantly among patients with stage II disease [n = 266; HR, 2.89; 95% CI, 1.02–8.24 (primary analysis); n = 612; HR, 2.69; 95% CI, 1.34–5.38 (sensitivity analysis)].ConclusionsElevated postoperative CEA levels are prognostic in patients with stage II CRC, with 2–3 months after surgery being the optimal timing for CEA measurement.

Serum carcinoembryonic antigen elevation in benign lung diseases

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94–3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.

Maffucci Syndrome with Intrahepatic Cholangiocarcinoma: A Case Report

Maffucci syndrome is characterized by multiple hemangiomas and enchondromas. Somatic mutations in <i>IDH1</i> and <i>IDH2</i> are associated with the development of Maffucci syndrome, and these patients develop various malignant nonskeletal tumors in addition to malignant skeletal tumors. We report a case of Maffucci syndrome with <i>IDH1</i> mutation complicated by intrahepatic cholangiocarcinoma. The patient was a 35-year-old woman who was diagnosed with Maffucci syndrome in childhood. She was referred to our department because of a large hepatic tumor. Serum carcinoembryonic antigen was 27.1 ng/mL upon laboratory examination. CT scanning showed a large low-density tumor (90 × 70 mm) in the right lobe of the liver, and MRI revealed a multilobulated and fibrous tumor, which was observed as high signal intensity on T2- and diffusion-weighted images and low signal intensity on T1-weighted images. Positron emission tomography-CT revealed peritoneal dissemination and cancer spread to the muscles of the back. Finally, she was diagnosed with intrahepatic cholangiocarcinoma with dissemination and metastases. We performed a tumor biopsy to determine a treatment plan for chemotherapy. Sanger sequencing of a tumor biopsy identified a mutation in <i>IDH1</i> at c.394C&#x3e;T (R132C), but the patient died of rapid cancer progression before the chemotherapy could be initiated. Although rare, malignant tumors can develop in patients with Maffucci syndrome; therefore, it is necessary to monitor these tumors through careful and periodic observation.