Elevated Carcinoembryonic Antigen Research Articles

Preoperative Patient and Lesion Features Are Valuable for Predicting the Prognosis of Resectable Peripheral Non-Small Cell Lung Cancer.

The aim of the study was to investigate the preoperative factors affecting the survival of patients with resectable peripheral non-small cell lung cancer (NSCLC) to improve the management of NSCLC. One hundred ninety-nine patients with peripheral NSCLC diagnosed clinically without lymph node metastasis were enrolled. The preoperative computed tomography characteristics of the tumors were retrospectively analyzed and the preoperative clinical data were collected. The size of the solid components for lung adenocarcinomas containing ground-glass opacity (GGO) component were measured. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Univariate and multivariate cox regression analyses were used to identify prognostic factors. Survival analysis showed that the OS of the group with a tumor of 3 cm or less was longer than that of the group with a tumor greater than 3 cm, the OS of the group with GGO component was superior to that of the group without GGO component, and the OS of the group with elevated carcinoembryonic antigen (CEA) levels was inferior to that of the group with normal CEA levels. Multivariate Cox regression analysis showed that tumor size, density, and preoperative CEA level were independent factors affecting OS, with hazard ratios of 2.401, 0.457, and 1.948, respectively. The analysis of lung adenocarcinomas with GGO component demonstrated that the mean size of the solid component in the nonsurviving group was significantly larger than that in the surviving group (mean, 23 ± 6.4 vs 8.6 ± 7.0 mm). The area under the receiver operating characteristic curve of the solid component size of lung cancer containing GGO component to predict postoperative death was 0.932. Tumor size, density, and preoperative CEA level were independent prognostic factors of patients with resectable peripheral NSCLCs. Preoperative computed tomography findings can be valuable for predicting the prognosis of patients with NSCLC after surgery.

FDG PET/CT in a Case With Primary Poorly Differentiated Urothelial-Type Adenocarcinoma of the Prostate.

Primary urothelial-type adenocarcinoma of the prostate is extremely rare. We describe FDG PET/CT findings in a case with primary poorly differentiated urothelial-type adenocarcinoma of the prostate with pelvic lymph node metastases. Both the prostate tumor and its metastatic lesions showed intense FDG uptake. The patient had normal serum prostate-specific antigen and elevated carcinoembryonic antigen levels, which may be helpful for the differential diagnosis.

The High Prevalence of Short-Term Elevation of Tumor Markers Due to Hyperglycemia in Diabetic Patients.

IntroductionThe relationship between diabetes and cancer is uncertain. However, tumor markers in diabetic patients are significantly elevated. The prevalence of diabetic inpatients with elevation of tumor markers and its relationship to blood glucose is needed to be studied.MethodsA total of 102 diabetic inpatients were included in this study. We collected information from diabetic inpatients and tested tumor markers. Patients with elevation of tumor markers were rechecked.ResultsWe found that up to 73.3% of diabetic inpatients had one or more tumor markers elevated. The proportion of diabetic inpatients with higher than normal cytokeratin 19 fragment (CYFRA 21–1) was 54.5%. Most of them did not return to normal after controlling the blood glucose. A short-term elevation of carcinoembryonic antigen (CEA) was present in 15.8% of diabetic inpatients, and 19.8% of diabetic inpatients had a short-term elevation of carbohydrate antigen. CEA and carbohydrate antigen including CA19-9, CA72-4, CA125 and CA15-3 returned to normal or became significantly reduced within 2 weeks after good control of blood glucose.ConclusionOur study showed that the elevation of tumor markers was common in diabetic inpatients, especially those with poor blood glucose control. It indicated that re-checking the tumor markers after controlling blood glucose might be better than conducting large-scale test for cancer.

Perineural invasion is a prognostic factor in stage II colorectal cancer but not a treatment indicator for traditional chemotherapy: a retrospective cohort study.

Perineural invasion (PNI) is considered a risk factor of survival but does not yet inform treatment decisions, and has not been studied separately in stage II colorectal cancer (CRC) patients whose postoperative traditional chemotherapy is controversial. This cohort study aimed to assess the association of PNI with basic clinicopathological features and patient outcomes after curative resection and the effects of PNI on responses to adjuvant chemotherapy in stage II CRC. The clinical data of 371 stage II CRC patients who underwent curative-intent surgery at the National Cancer Center/Cancer Hospital in 2014 were retrospectively reviewed. The adjuvant chemotherapy data were acquired from follow-up information. PNI status was examined, and the overall survival (OS) and disease-free survival (DFS) rates were analyzed. PNI was detected in 82 of the 371 patients (22.1%) and was closely correlated with preoperative serum carcinoembryonic antigen (CEA) levels (P=0.030), gross tumor type (P=0.010), tumor differentiation (P=0.010), p stage (P<0.001), and extramural vascular invasion (EMVI) (P<0.001). The median follow-up time was 71 months. The 5-year OS was 84.1% and 96.5% (P<0.001), and the 5-year DFS was 75.6% and 91.3% (P<0.001) for PNI-positive (+) and PNI-negative (-) patients, respectively. The multivariate regression analyses identified PNI as an independent negative prognostic factor for DFS [hazard ratio (HR): 2.95; 95% confidence interval (CI), 1.546-5.626; P=0.001] and OS (HR: 3.966; 95% CI, 1.642-9.575; P=0.002). Among PNI (+) patients, DFS and OS were positively correlated with CEA levels (P=0.005 and P=0.004, respectively). Postoperative chemotherapy failed to improve DFS (P=0.480 and P=0.267, respectively) and OS (P=0.940 and P=0.077, respectively) regardless of whether the patients were PNI positive or not. In stage II CRC patients, PNI was a poor independent predictor for DFS and OS. Among PNI (+) patients, CEA levels were positively correlated with DFS and OS. Traditional postoperative adjuvant chemotherapy does not improve outcomes of PNI (+) patients. Therefore, as to the active role of PNI and vacancy for treatment in allusion to PNI, follow-up of PNI (+) patients with elevated CEA level should be strengthened and further research on drug conducted on PNI deserve to be carried on.

Importance of Extracellular Vesicle Derived RNAs as Critical Colorectal Cancer Biomarkers.

Colorectal cancer typically begins from a nonmalignant polyp formation in the large intestine that, over time, develops into colorectal cancer. The growth of benign polyps can be checked if detected in the early stages of the disease. Doctors usually recommend colonoscopy to average and high-risk individuals for colorectal cancer screening. Elevated carcinoembryonic antigen (CEA) is a broadly used biomarker for colorectal cancer. The genetic and epigenetic alteration of genes such as p53, BRAF, APC, and PIK3CA is also correlated with colorectal cancer in various clinical studies. In general, tissue biopsy is most frequently used for colorectal cancer diagnosis, but the whole tumor heterogeneity cannot be accessed by this technique. Furthermore, such a highly invasive technique is not suitable for repeated testing. Recently, extracellular vesicles (EVs), lipid bilayer enclosed sacs secreted from colorectal cancer cells, are emerging as a diagnostic tool for colon cancer detection. The major advantages of using EVs for colon cancer diagnosis are (i) EVs can be isolated in a noninvasive manner from the body fluid and (ii) EV incorporated cargoes (mostly RNAs) reveal various aspects of colorectal cancer. EV-RNAs are also implicated in tumor invasion and influence the immune system for the further spread of tumors. However, due to the lack of standardized EV detection strategies, diagnostic applicability is limited. Herein, we review the recent literature on the pathobiological dependence of colorectal cancer on EV-RNAs. Further, we present the advantages of identification and characterization of EV-RNAs to explore the connection between differential expression of extracellular vesicle incorporated RNAs and colorectal cancer. How this approach may potentially translate into point of care colorectal cancer diagnostics is also discussed.

The Index of Esophageal Cancer Related Ischemic Stroke: A Retrospective Patient Control Study.

PurposeTo investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke.MethodsWe retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden’s J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors.ResultsA total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051–1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002–1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628–3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index.ConclusionIt was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.

Identification of Predictive Factors for Lymph Node Metastasis in pT1 Stage Colorectal Cancer Patients: A Retrospective Analysis Based on the Population Database.

Objective: The purpose of this study was to identify predictive factors for lymph node metastasis (LNM) in pT1 stage colorectal cancer (CRC) patients. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 2,697 consecutive pT1 stage patients who underwent surgical resection were retrospectively reviewed. Predictive factors for LNM were identified by the univariate and multivariate logistic regression analysis. The Kaplan-Meier curves and multivariate Cox regression analysis were used to evaluate the relationships between LNM and overall survival (OS) as well as cancer specific survival (CSS) of pT1 stage CRC patients. Results: The prevalence of LNM in pT1 stage CRC patients was 15.2% (410/2,697). Patient age <60 years (OR:1.869, 95% CI: 1.505–2.321, p < 0.001), poorly differentiated or mucinous or signet ring cell adenocarcinoma (OR:2.075, 95% CI: 1.584–2.717, p < 0.001), elevated carcinoembryonic antigen (CEA) level (OR:1.343, 95% CI: 1.022–1.763, p = 0.033) and perineural invasion (PNI) (OR:6.212, 95% CI: 3.502–11.017, p < 0.001) were significantly associated with LNM in pT1 stage patients. The survival analysis demonstrated that pT1 stage patients with LNM had a worse OS (5-year OS: 82.2% vs 88.7%, p = 0.020) and CSS (5-year CSS: 74.9% vs 81.5%, p = 0.041) than those without lymph node metastasis. Lymph node metastasis was an independent predictor of poor OS (HR: 1.543, 95% CI: 1.156–2.060, p = 0.003) and CSS (HR: 1.614, 95% CI: 1.121–2.324, p = 0.010) for pT1 stage colorectal cancer patients. Conclusion: Age, differentiation type, CEA level and perineural invasion were independent predictive factors for LNM in pT1 stage CRC patients. These findings might provide further risk stratification for pT1 stage patients and help clinicians identify high-risk individuals.

Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Prognostic role of preoperative carcinoembryonic antigen level in part-solid lung adenocarcinoma.

Part-solid lung adenocarcinoma appears as a heterogeneous subgroup, and its surgical management is controversial. This study aimed to elucidate whether preoperative carcinoembryonic antigen, a time-honored tumor marker, can be used as a prognostic factor that contributes to its management. We retrospectively reviewed consecutive patients with clinical-T1a-cN0M0 part-solid adenocarcinoma who underwent surgical resection between January 2011 and December 2015 at two institutions. Overall, 288 patients were identified. The median age was 69 years with 176 patients (61%) being female. The median follow-up time was 5.6 years. Lymph node metastases were found in 6 (15%) of 41 patients with elevated carcinoembryonic antigen levels, while 10 (4.0%) of 247 patients had normal carcinoembryonic antigen levels (P = 0.016). The 5-year overall survival rates in patients with normal and elevated carcinoembryonic antigen levels were 96.9% and 87.2%, respectively (P = 0.006), and the 5-year relapse-free survival rates were 91.8% and 62.8%, respectively (P < 0.001). The multivariable analysis revealed that preoperative carcinoembryonic antigen level was a significant prognostic factor for relapse-free survival (hazard ratio [HR] = 2.92, 95% confidence interval [CI] = 1.63-5.25, P < 0.001). Among the patients with elevated carcinoembryonic antigen levels, the 5-year overall survival rates in those undergoing lobar resection and segmentectomy were 87.0% and 88.9%, respectively (P = 0.59), and the 5-year relapse-free survival rates were 61.7% and 66.7%, respectively (P = 0.84). Our data suggest that preoperative carcinoembryonic antigen level appears to be an important predictor of postoperative survival outcomes in early-stage part-solid adenocarcinoma. Further studies are required to optimize management of patients with elevated preoperative carcinoembryonic antigen levels, although segmentectomy appeared acceptable in those patients.

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.

Overall Survival Rate of Vietnamese Patients with Colorectal Cancer: A Hospital-Based Cohort Study in the Central Region of Vietnam.

Background:This study investigated the overall survival (OS) at 1-year, 3-years, and 5-years after colorectal cancer (CRC) diagnosis and examined the prognostic factors of mortality among patients with CRC in Vietnam’s central region. Methods:This ambidirectional cohort study included patients newly diagnosed with CRC at a tertiary hospital in Vietnam’s central region between 2013 and 2019. Survival duration was calculated from the surgery date or the first day of CRC-specific treatment until the date of death or the study’s end date, July 31, 2020. Kaplan-Meier methods and log-rank test were used to estimate and compare the OS between the subgroups, respectively. The Cox proportional-hazards (PH) regression analysis was applied to estimate the magnitude of the effects between prognostic factors and outcome. Results:The median follow-up was 24 months (interquartile range: 13–43 months). The OS rate dropped significantly to 84.7%, 56.19%, and 45.01% at 1-year, 3-years, and 5-years after diagnosis, respectively. The median OS was 48.59 months (39.34 –57.93 months) for the rectum and colon cases. In the multivariate analysis, a higher mortality risk was observed in patients with an advanced-stage CRC (HRadj, 3.04; 95% confidence interval [CI], 1.79–5.18), who were underweight (<18.5 kg/m2; HRadj, 1.65; 95%CI, 1.03–2.65), and had elevated preoperative carcinoembryonic antigen (CEA) level (>5.0 ng/mL; HRadj, 1.63; 95%CI, 1.03–2.59). Additionally, younger patients (<50 years) had a poorer OS than the middle-aged group (60–69 years). Conclusion:Our findings indicate that <50% of Vietnamese patients with CRC survive until 5-years after diagnosis. Several individual factors that contribute to the poor OS of patients with CRC, including young age, underweight, and elevated preoperative CEA level, should be evaluated and managed. Early diagnoses through active routine examination of or screening programs for high-risk groups should be prioritized.

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 < 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 < 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 < 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 < 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 < 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.

The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective study.

BackgroundDespite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. MethodsWe reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020.ResultsAmong 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57–62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5–8.6 months) and 4.5 months (95% CI, 2.7–6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS.ConclusionThe survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

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.

The Correlation Between Survival Benefit of Preoperative Radiotherapy and Pretreatment Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer.

BackgroundPreoperative radiotherapy followed by radical surgery is the standard treatment for locally advanced rectal cancer; however, its long-term survival benefit remains controversial. This study aimed to determine the relationship between pretreatment carcinoembryonic antigen (CEA) levels and the long-term prognosis of preoperative radiotherapy in locally advanced rectal cancer (LARC) patients.MethodsData of LARC patients who underwent surgery between 2011 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients were accordingly divided into surgery (S) group and radiotherapy followed by surgery (RT+S) group. The primary outcomes were cancer-specific survival (CSS) and cancer-specific mortality (CSM). CSS was evaluated using Kaplan-Meier analysis, while CSM was evaluated using a competitive risk model. Subgroup analysis was also conducted, which was stratified by pretreatment CEA levels.ResultsA total of 2,760 patients were eligible for this study, including 350 (12.7%) patients in the S group and 2,410 (87.3%) in the RT+S group. There were no significant differences in the CSS and CSM rates at 1, 3, and 4 years between the S and RT+S groups before and after PSM (all p > 0.05). Pretreatment CEA levels were independently associated with CSS and CSM after adjusting for age, sex, stage, pathological factors, and treatment factors (all p < 0.05). Subgroup analysis showed that preoperative radiotherapy would benefit patients with elevated CEA in terms of CSS and CSM (both p < 0.05) but not those patients with normal CEA (both p > 0.05). Further analysis showed that preoperative radiotherapy was an independent protective factor for CSS and CSM in patients with elevated CEA levels (both p < 0.05).ConclusionsPretreatment CEA level may be considered a potential biomarker to screen LACR patients who would benefit from preoperative radiotherapy in terms of long-term prognosis.

Clinical Significance of and Predictive Risk Factors for the Postoperative Elevation of Carcinoembryonic Antigen in Patients With Non-Metastatic Colorectal Cancer.

BackgroundRecently, a few researches focus on the correlation between postoperative carcinoembryonic antigen (post-CEA) and the outcome of colorectal cancer (CRC), but none investigates the predictive value of post-CEA in a prognostic model. Besides, current recommendations on the frequency of post-CEA surveillance are not individualized and well followed. There is an absence of identification of patients who are more likely to have abnormal post-CEA levels and need more frequent CEA measurements.MethodsConsecutive CRC patients who underwent curative surgery were enrolled and randomly divided into the discovery (n=352) and testing cohort (n=233). Impacts of preoperative CEA (pre-CEA) and post-CEA on prognosis were assessed. Cox regression model was applied to develop prognostic nomograms, which were validated by the concordance index (C-index), calibration curve, and receiver operating characteristic curve (ROC) analysis. And prediction improvement of the nomograms was assessed with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Logistic regression was used to identify predictive risk factors and construct the prediction model for post-CEA elevation.ResultsPost-CEA independently predicted overall survival (OS) and disease-free survival (DFS), while pre-CEA did not. Post-CEA elevation represented higher risks in patients with normal pre-CEA, compared to those with persistent elevated CEA. The nomograms for OS and DFS were established with body mass index, tumor differentiation, N stage, lymphocyte-to-monocyte ratio, and post-CEA. The nomograms showed good calibration and superior discrimination than pTNM stage, with the C-index of 0.783 and 0.759 in the discovery set and 0.712 and 0.774 in the testing set for OS and DFS, respectively. Comparisons between models using IDI and NRI implied that the nomograms performed better than pTNM stage and the predictive power could be improved with the addition of post-CEA. The prediction model for post-CEA elevation was established with age, platelet-to-lymphocyte ratio, preoperative CA19-9, and pre-CEA. The AUC of the model in the two cohorts was 0.802 and 0.764, respectively.ConclusionsElevated post-CEA was a strong indicator of poor prognosis. The addition of post-CEA significantly enhanced the performance of prognostic nomograms. And the prediction model for post-CEA elevation may help identify patients who ought to reasonably receive more intensive postoperative surveillance of CEA levels.

S1721 A Rare Finding in the Colon: Undifferentiated Pleomorphic Sarcoma

Introduction: Undifferentiated pleomorphic sarcoma (UPS) is a rare and incompletely understood condition that commonly appears in the extremities and retroperitoneum. Involvement of the bone and digestive organs is rare. We describe the case of a 78-year-old man who was incidentally diagnosed with UPS of the colon after workup of uncontrolled lower back pain. Case Description/Methods: A 78-year-old man with extensive tobacco use initially presented to his primary care provider with intractable back pain and a 10lb weight loss. His exam was notable for paraspinal muscle tenderness, but otherwise unremarkable. A subsequent computed tomography (CT) abdomen and pelvis was negative. Given these findings and a suspicion for a musculoskeletal diagnosis, he was treated conservatively. Despite initial therapies, he experienced no clinical improvement. Further imaging with magnetic resonance imaging (MRI) of the spine showed a pathologic fracture of T12 and metastatic vertebral disease causing spinal cord compression. A follow up CT showed pulmonary nodules at the lung bases also concerning for metastatic disease. A set of follow up labs showed an elevated carcinoembryonic antigen (CEA) level of 7.4 ng/mL. He was referred to gastroenterology for expedited colonoscopy and malignancy workup in the setting of an elevated CEA. Colonoscopy revealed one 5-9 mm sessile cecal polyp. Cold snare removal of the polyp was unsuccessful because of resistance and the firmness of the lesion. A biopsy was obtained instead. While awaiting pathology, he underwent decompressive laminectomy and spinal stabilization with tumor biopsy of T12 for further neoplastic workup. Pathology of both the cecal polyp and the T12 intervertebral disc revealed high-grade UPS. Given the extent of disease, palliative radiation and chemotherapy were offered however the patient passed away shortly thereafter. Discussion: UPS is a rare and aggressive neoplasm; diagnosis is challenging because patients are often asymptomatic unless there is nerve involvement and because of its rapid development. Our patient presented with back pain which was attributed to a musculoskeletal ailment. Upon further investigation with a colonoscopy and biopsy, UPS was discovered. Although gastrointestinal metastasis is rare, it is important to consider a broad differential when a benign appearing polyp cannot be excised in a standard fashion.

S1841 Colorectal Squamous Cell Carcinoma: An Usual Presentation of an Unusual Cancer

Introduction: Squamous cell carcinoma (SCC) is an extremely rare cause of colorectal malignancy and makes up to 0.025% of all colorectal malignancies. Clinically, it presents with similar signs and symptoms as colorectal adenocarcinoma. Due to the rarity of this pathology, there is limited information on optimal treatment and disease prognosis, making early identification with a diagnostic colonoscopy and biopsies essential. Here, we present a rare case of colorectal SCC in the hepatic flexure with local invasion to the gallbladder and liver in a patient with chronic abdominal discomfort. Case description/methods: A 54-year-old female with hypertension and diabetes mellitus presented to the clinic complaining of abdominal discomfort for one year. She denied hematochezia, melena, hematemesis, weight loss, and changes to her bowel habits. Abdominal examination demonstrated epigastric and right upper quadrant tenderness. Initial routine laboratory studies were unremarkable. Ultrasound of the abdomen showed a right hepatic lesion which was confirmed on follow up CT scan of the abdomen that demonstrated a 7.1 × 6.7 × 7.6 cm heterogeneous mass in the transverse colon, inseparable from the gallbladder and left hepatic lobe. A subsequent MRI of the abdomen demonstrated consistent findings. Analysis of tumor markers demonstrated elevated carcinoembryonic antigen at 69.4 ng/mL (reference range: ≤5.0 ng/mL). Whereas, alpha-fetoprotein and cancer antigen 19-9 were negative. The patient also tested negative for Hepatitis C, HIV, and HPV and was found to be non-immune to Hepatitis B. Considering a high suspicion for malignancy, a diagnostic colonoscopy was performed which revealed a 5 cm polypoid, partially circumferential, non-obstructing erythematous mass at the hepatic flexure (Figure 1). Immunohistochemical stains of the biopsies including CK7, P40, and KI-67 (50-60%) were found to be positive. The pathology of the hepatic flexure mass was consistent with squamous cell carcinoma. She successfully underwent surgical resection of the malignancy followed by chemotherapy treatment. Discussion: In conclusion, patients with colorectal SCC is extremely rare, but presents later in the disease process with a worse prognosis. Practicing clinicians should be aware of less common causes of colorectal malignancy as early identification with a diagnostic colonoscopy is essential. Due to the rarity of the case, extensive evaluation is needed to confirm the absence of primary disease anywhere else in the body.Figure 1.: Colonoscopy revealing a 5 cm polypoid mass at the hepatic flexure.

Serum Biomarker Status with a Distinctive Pattern in Prognosis of Gastroenteropancreatic Neuroendocrine Carcinoma

Objective: Gastroenteropancreatic neuroendocrine carcinoma (GEPNEC) is a major research focus, but the application of biomarkers to guide its prognostication and management is unsatisfying. Clinical values of conventional serum biomarkers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) warrant scrutiny. Methods: Patients diagnosed with GEPNEC with baseline NSE, CEA, and CA199 levels provided in Peking University Cancer Hospital were retrospectively studied. Relationships between biomarkers and prognosis were investigated by the χ2 test, Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses. Results: A total of 640 GEPNEC patients were enrolled. NSE, CEA, and CA199 were elevated in 59.5%, 28.5%, and 21.3% of the population, respectively. Higher NSE had worse median overall survival (OS) (17.0 months vs. not reached, hazard ratio = 2.77 [2.06, 3.73], p < 0.001), and so did patients with higher CEA and CA199. Multivariable analysis confirmed that NSE and CA199 correlated with OS independently. Baseline NSE level and NSE remission predicted OS and the response of patients with first-line etoposide plus cisplatin (EP) treatment. Furthermore, we combined NSE/CEA/CA199 to segregate GEPNEC into novel subgroups, namely, adenocarcinoma-like NEC (ALN), neuroendocrine-like NEC (NLN), and triple-normal NEC (TNN). The groups shared distinctive clinicopathologic features and prognosis (21.0 months vs. 17.1 months vs. not reached, p < 0.001). The EP regimen remained the priority treatment option in NLN/TNN, while ALN was predisposed to “adenocarcinoma-like chemotherapy.” Conclusions: Elevation of NSE, CEA, or CA199 was common and independently indicates poor prognosis in GEPNEC patients. Serum biomarker-based subtypes suggest meaningful clinical implications and appropriate therapeutic approaches, illuminating promising ways to characterize the prognosis of GEPNEC.

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.