High Carcinoembryonic Antigen Levels Research Articles

Colorectal Cancer Survival and Its Prognostic Factors in Karachi, Pakistan.

To determine the survival rates of colorectal cancer (CRC) in the Pakistani population and determine the prognostic factors for survival among the CRC patients. Retrospective cohort study. Place and Duration of the Study: The cancer registry of the Aga Khan University Hospital, Karachi, Pakistan, from 2010 to 2016. The abstracted data from the cancer registry was cleaned and updated regarding the vital status at the last follow-up. Survival analyses were performed using the Kaplan-Meier method. Adjusted hazard ratios (aHR) and their 95% confidence intervals (CIs) were estimated using a cox regression model to assess the prognostic factors for survival. The overall proportion of late-onset CRC (>50 years of age) was 55.3% and early-onset CRC (<=50 years of age) was higher than expected (45.7%). A high level of carcinoembryonic antigen (CEA) (>5 ng/ml) was associated with poor survival compared to patients with CEA levels of ≤5 ng/ml (aHR = 1.68, 95% CI = 1.04, 2.72). Patients, who experienced recurrence, showed poorer survival (aHR = 4.27, 95% CI = 2.55, 7.14). Patients, who did not undergo surgery, showed significantly poorer survival compared to those who underwent surgery (aHR = 5.53, 95% CI = 2.35, 13.03). The findings suggest that monitoring CEA levels, ensuring prompt surgical treatment and follow-up care for recurrent cases can improve survival outcomes in patients with colorectal cancer. Colorectal cancer (CRC), Surgery, Recurrence, Grade, Cancer registry.

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 μmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 μmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Presence of CD44v9-Expressing Cancer Stem Cells in Circulating Tumor Cells and Effects of Carcinoembryonic Antigen Levels on the Prognosis of Colorectal Cancer.

Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions.

The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers.

In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

Evolving survival gains in patients with young-onset colorectal cancer and synchronous resectable liver metastases

We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998–2011) and 179 in the contemporary era (CE, 2012–2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients.

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.

Quantitative analysis of contrast-enhanced ultrasound in neoadjuvant treatment of locally advanced rectal cancer: a retrospective study.

To explore the clinical value of contrast-enhanced ultrasound (CEUS) quantitative analysis in the evaluation and prognosis of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Eighty-three consecutive patients undergoing neoadjuvant chemoradiotherapy and total mesorectal excision for LARC were retrospectively included. According to pathological results, patients were categorized into complete or incomplete response groups. Differences in ultrasonic parameters, pathological results, and clinical data between groups were evaluated. The cutoff point for a complete response as determined by quantitative analysis of CEUS was assessed using a receiver operating characteristic curve; additionally, overall survival (OS) and progression-free survival (PFS) were analyzed. Of the 83 patients, 12 (14.5%) achieved a complete response and 71 (85.5%) did not. There were significant between-group differences in carcinoembryonic antigen (CEA) levels, differentiation degree, proportion of tumor occupying the lumen, anterior-posterior and superior-inferior diameters of the lesion, and intensity of enhancement (P<0.05). CEUS quantitative analysis showed significant between-group differences in peak intensity (PI) and area under the curve (AUC) values (P<0.05). The OS and PFS of patients with high PI, high AUC value, and poorly differentiated cancer were significantly worse than those with low PI, low AUC values, and moderately to highly differentiated cancer (P<0.05). High CEA levels (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04; P=0.002) and low differentiation (2.72, 1.12-6.62; P=0.028) were independent risk factors for PFS and OS. CEUS can predict the response to neoadjuvant treatment in patients with LARC. CEUS quantitative analysis is helpful for clinical prognosis.

Preoperative Neutrophil–Lymphocyte Ratio and Serum Carcinoembryonic Antigen as Predictive Factors of Colorectal Cancer Survival

Introduction. Colorectal cancer is the second leading cause of death worldwide, with a high mortality rate. This study investigates the predictive value of the neutrophil–lymphocyte ratio (NLR) and carcinoembryonic antigen (CEA) in predicting the survival rates of colorectal cancer patients in Indonesia. Method. This retrospective cohort study enrolled the colorectal cancer stage I–IV patients treated at Cipto Mangunkusumo General Hospital (CMGH). The independent variables are NLR and CEA, while the dependent variable is the five–year survival of colorectal cancer. The log rank test proceeded to find a correlation between NLR and CEA with 5–year survival, and the Cox proportional hazard regression proceeded to analyze the predictive value. Results. Of the ninety–six subjects who met the inclusion and exclusion criteria who were enrolled, 6.25% had high NLR, and 66.6% had high CEA levels. The overall five–year survival rate was 35.4%. However, the proportion of subjects with normal NLR had a higher five–year survival rate compared to those with high NLR, and the same pattern was observed for CEA levels. Subgroup analysis based on the cancer stage showed a significant association between high NLR and increased risk of mortality in TNM stages I–II. Still, no significant difference in survival based on NLR was observed in stages III–IV. Conclusion. The preoperative NLR ratio and preoperative CEA did not show a predictive role in colorectal cancer survival. However, when stratifying by cancer stage, there was a significant difference in preoperative NLR levels between the deceased and non–deceased groups in patients with stage I–II colorectal cancer.

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.

Unexplained increases in serum carcinoembryonic antigen levels in colorectal cancer patients during the postoperative follow-up period: an analysis of its incidence and longitudinal pattern

Background Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. Materials and methods We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. Results CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. Conclusions Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Factors Affecting the Survival of Patients with Synchronous Metastatic Colorectal Cancer in a Tertiary Hospital in Indonesia: A Retrospective Study

Introduction: Little is known about Indonesian metastatic CRC patients’ survival and prognostic factors, although this malignancy is one the most frequent cancer in the country. We aimed to investigate the survival outcome and the factors influencing local CRC patients presenting with a metastatic stage at diagnosis.Methods: A retrospective cohort study was done on 441 data of synchronous metastatic CRC cases treated between January 2016 and December 2019 at Dr. Sardjito Hospital, Yogyakarta, Indonesia. Secondary data were collected from the CRC clinical registry database. Demographic, clinicopathology and the type of treatment were collected. Survival staus was obtained from the registry database and communication to patients or caring families. Kaplan-Meier curves were used to estimate the overall survival (O.S). The Cox proportional hazards regression mode was applied to analyzethe potential factors affecting survival. Results: The median follow up of the recent study was 17 months, The median overall survival was 13 months. Two-year overall survival was 37% and the estimated 5-year overall survival was 16.1%. Multivariate cox analyses identified poor performance status (HR 2.639, 95% CI 1.438-4.842, p = 0.002), elevated carcinoembryonic antigen (CEA) (HR 2.795, 95% CI 1.509-5.176, p = 0.001) and higher histological grade (HR 2.019, 95% CI 1.112-3.667, p = 0.021) were associated with poorer overall.Conclusion: Poor performance status, high CEA level, and higher histological grade as factors that were associated with unfavourable overall survival of patients with synchronous metastatic colorectal cancer in Yogyakarta, Indonesia.

Digestive cancer surgery in low-mid income countries: analysis of postoperative mortality and complications in a single-center study.

This study aimed to analyze postoperative and 90-day morbidity and mortality and their risk factors in all digestive cancer curative intent resections of a single digestive surgical department in a low-mid income country. All consecutive patients who underwent a surgical resection for digestive cancer with a curative intent between January 1, 2021, and December 31, 2021, were included. This is a retrospective analysis of a prospective cancer surgery database managed during the period. Patterns and factors associated with increased morbidity and mortality were analyzed and presented in tabular and descriptive forms. Seventy-six patients were included, 38 (50%) were men with a mean age of 59 years (±13.5). Forty patients (52.63%) had tumors locally advanced, staged CT3-CT4 on preoperative imagery. Thirty-three of our population (43.42%) had laparoscopic surgery (conversion rate at 12.12%). In immediate preoperative, the morbidity rate was 36.84%; among each, 7 patients (9.21%) had serious complications (>2 Clavien-Dindo grade), and mortality rate was 5.26%. At 90 days after surgery, morbidity remained the same, and mortality increased to 7.9%. Risk factors for increased morbidity and mortality were female gender, obesity, high levels of carcinoembryonic antigen, hypoalbuminemia, laparotomy approach, hand sewn anastomosis, prolonged operating time, and wide drainage (p < 0.05). This study provides figures on mortality and morbidity related to digestive cancer curative surgery in a low-mid income country digestive department and discusses risk factors increasing postoperative complications and death.

Sublobar resection is not always superior for early-stage lung cancer in high-risk patients.

The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients. Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group. There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P < 0.001). More patients in the high-risk group died of lung cancer (P < 0.001) and non-lung cancer deaths (P < 0.001) than patients in the normal-risk group.In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy. Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance.

Borderline ovarian tumors: twenty years of experience at a tertiary center

Aims: To investigate whether there is a difference between serum tumor markers panel (CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA)) and tumor size and histopathology in well-staged patients with borderline ovarian tumors (BOTs). &#x0D; Methods: Over the past 20 years (January 2001 to January 2021), the results of four tumor markers (CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA)) have been clinically analyzed for for this retrospective cohort study of 156 patients who underwent surgery and were diagnosed with histopathology consistent with a borderline ovarian tumor.&#x0D; Results: The average age of patients with borderline ovarian tumors was determined to be 51.67 (4.726) years. Before the first surgery, high CA 125 levels (&gt;35 U/l) were found in 53 patients (34%), high CEA levels (&gt;4 ng/ml) were found in 24 patients (15.4%), high CA 19-9 levels (&gt;37 U/ml) were found in 29 patients (18.6%), and high CA 15-3 (&gt;30 ng/ml) levels were found in 12 patients (7.7%). The average CA 125 levels in tumors with serous histopathology [372.8 (1805.2)] were higher than those in tumors with mucinous histopathology (p=0.006). There was no statistically significant difference in tumor markers between tumors smaller than 8 cm and larger than 8 cm [(CA 125 p=0,257), (CEA p=0.9), (CA 19-9 p=0.295), (CA 15-3 p=0.404)].&#x0D; Conclusion: Our primary outcome of the study is an increase in CA 125 levels, which indicates serous histopathology. Our secondary outcome is the higher levels of tumor markers, but it does not suggest larger tumors.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer

BackgroundInterindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent.MethodsWe conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico’s National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS).ResultsWe included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9–147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6–71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6–81.6). Group B: 75.7 months (95% CI 66.8–84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8–76.3) months] than in group A [82.8 (95% CI 78.6–86.9 months] and group B [87.1 (95% CI 79.6–94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031).ConclusionsWhen assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Diagnostic Accuracy of Carcinoembryonic Antigen (CEA) in Detecting Colorectal Cancer Recurrence Depending on Its Preoperative Level

BackgroundSerum carcinoembryonic antigen (CEA) increase in patients with colorectal cancer (CRC) recurrence was observed to vary depending on their initial values. This study aimed to evaluate the diagnostic accuracy of CEA for detecting CRC recurrence in patients with normal and elevated initial CEA levels. MethodsA total of 261 CRC recurrence patients who underwent curative resection were included and divided into two groups, normal and elevated initial CEA. Analysis was performed comparing patient, tumor, and recurrence characteristics retrospectively. ResultsThere were 192 patients with normal and 69 with high initial CEA levels. Patient and tumor characteristics were similar. Eighty-six patients had elevated CEA at the time of recurrence, and the overall sensitivity of CEA for recurrence was 33.0%. In the high initial CEA group, 59.4% exhibited increased CEA level at recurrence, whereas in patients with normal initial CEA levels, only 23.4% showed elevated levels (p < 0.001). Patients with both high CEA preoperatively and at recurrence had more local recurrence, but there was no statistical significance (p = 0.053), and the rate of lung metastasis was higher in patients whose CEA remained normal at recurrence (38.3% vs. 24.4%, p = 0.026). The overall survival of patients with elevated CEA at recurrence was worse than those with normal CEA levels (56.9% vs. 42.4%, p = 0.003). ConclusionThe diagnostic accuracy of CEA for detecting recurrence depends on initial CEA level. Regardless of the initial CEA level, elevation at recurrence was significantly associated with overall survival in patients with recurrent CRC.

Elevated CEA Levels in Non-smoker and Non-malignant Condition

Carcinoembryonic Antigen (CEA) is a non-specific tumor marker often found in the blood. High levels of CEA are commonly associated with the progression of wide range of tumors. It is currently used as a biomarker for malignant tumors of the lung and colon, but due to its limited specificity and clinical implication, it can be used only for monitoring rather than tumor diagnosis.1 Certain non-malignant conditions like diabetes mellitus and gastric disease may also affect the CEA levels. These may be relevant particularly in early stages of colorectal cancers. Hence, elucidating the factors that affect the CEA levels might improve the accuracy and utility of its measurement.

Hepatectomy Before Primary Tumor Resection as Preferred Approach for Synchronous Liver Metastases from Rectal Cancer.

For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038-0.64, p = 0.010). The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

Imaging features based on CT and MRI for predicting prognosis of patients with intrahepatic cholangiocarcinoma: a single-center study and meta-analysis

BackgroundTo evaluate the prognostic role of imaging features based on CT and MRI in intrahepatic cholangiocarcinoma (ICC).MethodsTwo hundred and four patients from a single-center database who underwent radical ICC surgery from 2010 to 2019 were enrolled in the study. Cox proportional hazard model was used for survival analysis of imaging features. A meta-analysis was performed to determine imaging features that predict overall survival (OS) and event-free survival (EFS) in ICC.ResultsIn the CT group of the retrospective cohort, tumor multiplicity, infiltrative tumor margin, lymph node metastasis, enhancement pattern in hepatic arterial phase and tumor necrosis correlated with poorer EFS and OS; moreover, enhancing capsules, high carcinoembryonic antigen levels contributed to poor OS. In the MRI group, tumor multiplicity and enhancement pattern were prognostic factors for OS; tumor multiplicity and enhancement pattern resulted in poor EFS. A total of 13 articles containing 1822 patients with ICC were enrolled in the adjusted hazard ratios meta-analysis. The results showed that enhancement pattern and infiltrative tumor margin were predictors of OS and EFS, whereas bile duct invasion was a predictor of OS.ConclusionsArterial enhancement patterns and tumor margin status were associated with both OS and EFS of ICC patients following resection.

Plasma-based methylated SEPTIN9 circulating tumor DNA to predict progression-free and overall survival in metastatic colorectal cancer.

e15615 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, as about half of cases develop incurable metastatic disease. Recent studies have shown circulating tumor DNA (ctDNA) markers reflect disease burden and responses to neoadjuvant therapy in metastatic CRC more accurately than carcinoembryonic antigen (CEA). We aimed to determine if a semi-quantitative evaluation of the methylated SEPTIN9 (mSEPT9) ctDNA marker, used in a CRC screening test, is capable of predicting progression free survival (PFS) and overall survival (OS) in a longitudinal cohort of metastatic CRC cases. Methods: A longitudinal cohort of 70 CRC cases who presented with stage IV disease, or experienced recurrent disease, was prospectively assembled from patients undergoing treatment at Cedars-Sinai Medical Center. Blood samples were drawn either prior to, or within 2 weeks following, treatment initiation, and 1-2 monthly thereafter for two years or until death. mSEPT9 ctDNA levels were measured in 1 mL plasma using a modified Epi-proColon V2.0 (Epigenomics) protocol. Univariate and multivariate analyses of clinical endpoints, PFS and OS, were conducted using a Cox regression model with CEA and mSEPT9 ctDNA as time-dependent covariates, with and without adjustments for multiple confounding factors (sex, age, race, organ of metastasis, neo- and adjuvant chemotherapy, immunotherapy, surgery, mismatch repair, KRAS and BRAF mutation status). Results: In univariate analysis, higher level of ctDNA, peritoneal metastasis, gynecologic metastasis, and additional liver metastasis, were associated with poor PFS. Elevated CEA was not associated with PFS either as a continuous variable or as a categorical variable (threshold 10ng/mL). In multivariable analysis, higher level of ctDNA (HR: 1.41; 95% CI: 1.17-1.71; P&lt; 0.001) remained associated with poor PFS after adjusting for adjuvant chemotherapy and peritoneal metastasis. CEA remained not associated with PFS. In univariate analyses, high level of CEA, high level of mSEPT9 ctDNA, neoadjuvant chemotherapy, male sex, and peritoneal metastasis were associated with poor OS. In multivariable analysis, higher level of CEA (HR: 1.63; 95% CI: 1.12-2.36; P= 0.011) and mSEPT9 ctDNA (HR: 1.50; 95% CI: 1.22-1.84; P&lt; 0.001) remained associated with poor OS after adjusting for sex and peritoneal metastasis. Conclusions: Semi-quantification of the single ctDNA marker, mSEPT9, a prevalent biomarker of CRC, was an independent predictor of PFS whereas CEA was not. High levels of both CEA and mSEPT9 ctDNA were independent predictors of OS, showing that mSEPT9 ctDNA added value to CEA in evaluation of OS. The mSEPT9 ctDNA test is rapid turn-around and easy to perform in molecular diagnostic pathology laboratories, thus may serve as a valuable adjunct to CEA for frequent testing in the setting of metastatic CRC.