Preoperative Serum Carcinoembryonic Antigen Research Articles

Prognostic Value of Preoperative Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Levels for Adjuvant Chemotherapy in Stage II Colorectal Cancer: A Nationwide Multicenter Retrospective Study.

Adjuvant chemotherapy for stage II colorectal cancer patients with high-risk factors for recurrence can be useful; however, its advantage in prognosis remains to be controversial. Thus, in this study, we aimed to assess whether a combination of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels can predict the prognosis and advantage of adjuvant chemotherapy. Using a Japanese nationwide database, in total, 3,688 patients with curative resected stage II colorectal cancer were registered retrospectively between 2008 and 2012 in 24 referral institutions. Patients were classified into three groups as follows: Group A (both non-high levels of CEA and CA19-9), Group B (either high levels of CEA or CA19-9), and Group C (both high levels of CEA and CA19-9). Multivariable Cox regression analysis, adjusting the depth of tumor invasion, number of dissected lymph nodes, tumor differentiation, lymphatic and venous invasion, and other covariates, showed that the 5-year disease-free survival and overall survival were shorter in Group C than in Groups A and B. Furthermore, in Group C, the 5-year disease-free survival rate was improved in the surgery-plus-AC group compared to the surgery-alone group. As with existing high-risk factors for recurrence, the combination assessment of preoperative serum CEA and CA19-9 can predict the prognosis for colorectal cancer. Adjuvant chemotherapy may provide a prolonged disease-free survival advantage in stage II colorectal cancer patients with high levels of both tumor markers.

Novel machine learning algorithm can identify patients at risk of poor overall survival following curative resection for colorectal liver metastases.

The primary cause of mortality in colorectal cancer is metastatic disease. We investigated the ability of a machine learning (ML) algorithm to stratify overall survival (OS) of patients undergoing curative resection for colorectal liver metastases (CRLM). Patients undergoing curative liver resection for CRLM between 2010-2021 at the University Hospital RWTH Aachen were eligible for this retrospective study. Patients with recurrent metastases, incomplete resections, or early deaths, were excluded. A gradient-boosted decision tree (GBDT) model identified patients at risk of poor OS, based on clinicopathological characteristics. Differences in survival were compared with Kaplan-Meier analysis and the log-rank test. A total of 487 patients were split into training (n=389, 80%) and test cohorts (n=98, 20%). Of the latter, 20 (20%) were identified by the GBDT model as high-risk and showed significantly reduced OS (23 months vs 52 months, P=.005) and increased hazard ratio (2.434, 95%CI 1.280-4.627, P=.007). The strongest predictors were preoperative serum carcinoembryonic antigen (CEA), age, diameter of the largest metastasis, number of metastases, body mass index, and primary tumor grading. A GBDT model can identify high-risk patients regarding OS after curative resection of CRLM. Closer follow-up and aggressive systemic treatment strategies may be beneficial to these patients.

Preoperative serum CA19-9 should be routinely measured in the colorectal patients with preoperative normal serum CEA: a multicenter retrospective cohort study

ObjectiveWhether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified.MethodsConsecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale.ResultsA total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724).ConclusionsPreoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Predictive Value of Preoperative Serum AFP, CEA, and CA19-9 Levels in Patients with Single Small Hepatocellular Carcinoma: Retrospective Study.

PurposeThis study aimed to explore the relationship between the tumor marker score (TMS) and the postoperative recurrence of single small hepatocellular carcinoma (HCC).Patients and MethodsA total of 409 patients with one resectable HCC with a diameter of 3 cm or less who visited Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2014 were included in this study. Their alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) levels were classified into low and high groups using X-tile software. Each patients' TMS was calculated as the sum of each tumor marker (low = 0; high = 1).ResultsA total of 142 patients were classified as TMS0, 171 as TMS1, and 96 as TMS2. Kaplan–Meier analysis illustrated that TMS could divide the patients into groups with remarkably different prognoses, and the patients with high TMS had worse recurrence-free survival (RFS) than those with low TMS. Multivariate analysis showed that TMS, age, and HBeAg positive were the independent predictors of RFS rate. Subgroup analysis revealed that high TMS was a stable risk factor relative to TMS0. Receiver operating curves showed that the 1-, 3-, and 5-year area under curve (AUC) values of TMS were 0.698, 0.662, and 0.673, respectively. The AUC of TMS was higher than that of other common prognostic models in time-dependent receiver operating curve.ConclusionTMS was an independent prognostic factor for the postoperative recurrence of a single small HCC and can provide a well-discriminated risk stratification, thus contributing to prognostic prediction and adjuvant therapeutic development.

Clinicopathological Characteristics of Primary Appendiceal Mucinous Neoplasm and Recurrence After Radical Resection.

ObjectiveAppendiceal mucinous neoplasm (AMN) is a rare obstructive dilatation of the appendix caused by an intraluminal accumulation of mucoid material, showing an insidious onset and few specific clinical manifestations. The purpose of the study is to analyze clinicopathological characteristics of primary AMN and recurrence after radical resection.MethodsA total of 50 patients were included in the retrospective cohort study of AMN. Patient data, such as demographics, tumor characteristics, surgical management, preoperative serum carcinoembryonic antigen (CEA), and carcinoembryonic antigen 19-9 (CA19-9) levels, were collected. All patients were followed-up with interval CT scans until the end of December 2021, with overall survival (OS) and progression-free survival (PFS) being calculated.ResultsAll patients were confirmed as AMN by pathological diagnosis after surgery, including 28 cases (56.00%) of low-grade AMN (LAMN) and 22 cases (44.00%) of non-LAMN. Among 50 patients with AMN, there were 12 cases (24.00%) complicated with pseudomyxoma peritonei (PMP). Higher proportions of patients with pTis, pT3, pT4a, ruptured at presentation, and PMP were found in patients with non-LAMN patients than LAMN (p < 0.05). There was a remarkable difference about preoperative serum CA19-9 levels between patients with LAMN and non-LAMN (p = 0.044). Patients complicated with PMP had a higher proportion of patients with ruptured at presentation than those who were not (p < 0.001). The patients with PMP had increased tumor size compared with those without PMP (p = 0.031). Remarkable differences were observed in terms of preoperative serum CA19-9 (p = 0.009) levels between patients with PMP and without PMP. We performed a multivariate analysis of the presence or absence of PMP and found that ruptured at presentation was found to be a risk factor for PMP in patients with AMN (p = 0.003). The PFS in the patients with PMP and those without was 33.33% (4/12) and 2.63% (1/38), showing a significant difference (P = 0.002).ConclusionThe study demonstrates that ruptured at presentation and PMP may influence the prognosis and survival of patients with AMN.

Comparison of Clinical Efficacy of Thermal Ablation vs. Surgical Resection of Metachronous Colorectal Liver Metastasis

To compare the treatment efficacy of thermal ablation versus surgical resection of metachronous colorectal liver metastasis (CRLM) and to explore the potential candidates suited for thermal ablation. The data of 319 patients with CRLM who underwent radical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2007 and January 2021 were retrospectively collected. The patients were divided into two groups, the thermal ablation group and the surgical resection group, according to the actual treatments they received. Propensity score matching (PSM) was applied to balance the baseline characteristics between the two groups. Cox regression analysis was conducted to identify the risk factors for recurrence and survival. Survival analysis was performed for intergroup comparison. Using PSM at 1∶1 ratio, 92 patients were included in the thermal ablation group and 92 patients were included in the surgical resection group.The median overall survival (OS) in the thermal ablation group was 49 (95% confidence interval, 37-76) months, which was shorter than that of the surgical resection group ( P<0.01). Multivariate Cox regression analysis indicated that the T staging of primary tumor, number of metastatic tumor, maximum diameter of metastatic tumor, preoperative serum carcinoembryonic antigen (CEA) level, and treatment method were independent risk factors affecting OS. Compared with the surgical resection group, the thermal ablation group demonstrated higher hepatic recurrence rate (59.8% vs. 23.9%, P<0.01), shorter disease-free survival (DFS) (10 months vs. 33 months, P<0.01), and shorter length of hospital stay (7 days vs. 14 days, P<0.01). Subgroup analysis, conducted with the data of the 319 patients before PSM, showed that early recurrence patients who underwent thermal ablation or surgical resection had comparable median OS (29 months vs. 42 months, P=0.35). For the non-early recurrence patients, the median OS of the thermal ablation group was shorter than that of the surgical resection group ( P<0.01). For the treatment of CRLM, the efficacy of surgical resection was better than that of thermal ablation. However, the efficacy was comparable between the two treatments for early recurrence patients of CRLM.

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.

Factors Associated with Nodal Upstaging in Clinical T1a-bN0M0 Non-Small Cell Lung Cancers.

Simple SummaryThe incidence rate of lymph nodal upstaging after curative surgical resection is approximately 10% in clinical stage I non-small cell lung cancer (NSCLC), which can significantly affect the prognosis. The aim of our retrospective study was to reassess the predictive factors of nodal upstaging in patients with clinical T1a-bN0M0 adenocarcinoma. In a cohort of 352 patients with clinical T1a-bN0M0 adenocarcinoma who received standard lobectomy and lymph nodal dissection, 28 (7.95%) patients had lymph nodal upstaging. The significant risk factors include abnormal serum carcinoembryonic antigen levels, solid part tumor diameter ≥ 1.3 cm, and consolidation–tumor ratio ≥ 0.50 on chest computed tomography. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.Nodal upstaging of lung adenocarcinoma occurs when unexpected pathological lymph node metastasis is found after surgical intervention, and may be associated with a worse prognosis. In this study, we aimed to determine the predictive factors of nodal upstaging in cT1a-bN0M0 primary lung adenocarcinoma. We retrospectively reviewed a prospective database (January 2011 to May 2017) at National Taiwan University Hospital and identified patients with cT1a-bN0M0 (solid part tumor diameter ≤ 2 cm) lung adenocarcinoma who underwent video-assisted thoracoscopic lobectomy. Logistic regression models and survival analysis were used to examine and compare the predictive factors of nodal upstaging. A total of 352 patients were included. Among them, 28 (7.8%) patients had nodal upstaging. Abnormal preoperative serum carcinoembryonic antigen (CEA) levels, solid part tumor diameter ≥ 1.3 cm, and consolidation–tumor (C/T) ratio ≥ 0.50 on chest computed tomography (CT) were significant predictive factors associated with nodal upstaging, and patients with nodal upstaging tended to have worse survival. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.

A nomogram to predict the recurrence-free survival and analyze the utility of chemotherapy in stage IB non-small cell lung cancer.

BackgroundLarge part of patients of stage IB non-small cell lung cancer (IB NSCLC) may suffer recurrence after surgery. This study is to determine risk factors and establish a nomogram for postoperative recurrence and to provide a reference for adjuvant chemotherapy selection in patients with stage IB NSCLC.MethodsA total of 394 patients with postoperative stage IB NSCLC who visited Fujian Medical University Union Hospital between January 2010 and June 2016 were selected. Patients were divided into training and validation cohorts based on the time of diagnosis. Independent risk factors were identified using a Cox proportional hazards regression model. A nomogram was created to predict recurrence-free survival (RFS) and was validated with an independent cohort. The predictive ability of the nomogram was evaluated using the concordance index (C-index) and calibration curve. RFS between the high- and low-risk groups was determined using Kaplan-Meier curves, and subgroup analysis of chemotherapy was performed.ResultsVisceral pleura invasion, micropapillary structures, tumor size, preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum cytokeratin-19 fragments (Cyfra21-1) level, and postoperative histology were identified as independent risk factors for stage IB NSCLC recurrence. Discrimination of the nomogram showed good prognostic accuracy and clinical applicability, with a C-index of 0.827 and 0.866 in the training and validation cohorts, respectively. The difference in RFS between the high- and low-risk groups in both cohorts was significant (P<0.05). Finally, a significant difference was observed on whether high-risk group should accept postoperative chemotherapy (P<0.05).ConclusionsThis nomogram can predict postoperative recurrence probability in patients with stage IB NSCLC, and can select patients with risk factors who need adjuvant chemotherapy.

Prognostic Implication of Preoperative Serum Albumin to Carcinoembryonic Antigen Ratio in Colorectal Cancer Patients.

Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17−0.56, P < .01) and OS (HR = 0.33, 95% CI: 0.16−0.66, P < .01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival.

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen for Overall Survival and Recurrence-Free Survival in Resectable Thymic Epithelial Tumors.

Introduction: Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P < .05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P < .05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs.

Prognostic significance of the postoperative/preoperative serum CEA level ratio in patients with solitary adrenal metastasis from lung cancer.

The present study aimed to evaluate the prognostic significance of the postoperative to preoperative serum carcinoembryonic antigen (CEA) level ratio (CEA ratio) in patients with lung cancer with solitary metastasis of the adrenal gland after adrenalectomy. Furthermore, the optimal CEA ratio cutoff value for predicting disease-free survival (DFS) in patients with lung cancer after adrenalectomy was determined. The medical records of patients with lung cancer with isolated adrenal metastasis who underwent adrenalectomy at the National Cancer Center Hospital East (Kashiwa, Japan) between January 2013 and December 2020 were retrospectively reviewed. Receiver operating characteristic curve analysis was used to segregate patients into two groups (high and low CEA groups) and the clinical prognosis for the two groups was determined. In addition, the association between the CEA ratio and clinical factors was determined. A total of 14 patients with a median age of 68 years (range, 50-75 years) were analyzed, of which 9 (64%) were males. The optimal cutoff value for the CEA ratio to predict DFS was 0.60. The high CEA ratio group (≥0.60) displayed poorer DFS and cancer-specific survival (P=0.03 and 0.02, respectively). The CEA ratio was significantly associated with the preoperative CEA level (P=0.01) and the high CEA ratio (≥0.60) group had lower preoperative CEA levels. The study suggested that the perioperative CEA ratio may be an important emerging prognostic factor for patients with lung cancer with solitary adrenal gland metastasis. As the sample size was limited, a further study with a larger cohort is required to validate the present findings.

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.

Risk factors for lymph node metastasis and surgical scope in patients with cN0 non-small cell lung cancer: a single-center study in China

BackgroundIt is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC.MethodsWe conducted a retrospective study of patients with tumor size ≤ 30 mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors.ResultsOverall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5 mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI 0.780–0.870); the cut-off value of serum CEA level was 1.765 μg/L, and the AUC was 0.661 (p < 0.001, 95% CI: 0.568–0.754). Moreover, 8 of 461 patients with tumor parenchyma ≤ 16.5 mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5 mm had lymph node metastasis.ConclusionTumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size ≤ 30 mm. For patients with tumor parenchyma > 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. For patients with tumor parenchyma ≤ 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible.

The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer.

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

Optimal adjuvant chemotherapy completion time for stage III colon cancer: a cohort study.

Adjuvant chemotherapy for 6 months following surgery is the standard treatment plan for stage III colon cancer. The aim of the present study was to determine whether the adjuvant chemotherapy completion time for stage III colon cancer had an effect on prognosis and cut-off time that affected the prognosis. This was a retrospective study of stage III colon cancer patients who completed adjuvant chemotherapy at Guangzhou Red Cross Hospital from January 2010 to December 2017. Univariate and multivariate analyses were used to determine the association between adjuvant chemotherapy completion time and the 3-year disease-free survival (DFS). The restricted cubic spline model was used to analyze the cut-off time that affected the 3-year DFS. A total of 431 patients were included in the study. The 3-year DFS was associated with a combination of obstruction or perforation, preoperative serum carcino-embryonic antigen (CEA) concentration, T stage, N stage, pathological stage, and adjuvant chemotherapy completion time in the univariate analysis (P<0.05). A combination of obstruction or perforation, preoperative serum CEA concentration, N stage, and adjuvant chemotherapy completion time were independent prognostic factors in the multivariate analysis (P<0.05). The cut-off time was 28 weeks for adjuvant chemotherapy completion time in the restricted cubic spline model analysis. For those whose adjuvant chemotherapy completion time was >28 weeks, the risk of 3-year recurrence was 1.428 times higher compared with those whose adjuvant chemotherapy completion time was ≤28 weeks. [P=0.032, 95% confidence interval (CI): 1.034-2.055]. The 3-year DFS of stage III colon cancer was related to the adjuvant chemotherapy completion time. For those who completed adjuvant chemotherapy >28 weeks, the risk of 3-year recurrence increased.

Osteogenic and brain metastases after non-small cell lung cancer resection.

A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery, however, routine chest computed tomography (CT) sometimes fails to diagnose these recurrences. We investigated the incidence of BMs and OMs after pulmonary resection and aimed to identify candidates who can benefit from brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in addition to CT. We retrospectively reviewed medical records of 1099 NSCLC patients who underwent pulmonary resection between 2002 and 2013. Clinicopathological factors associated with OM and/or BM were investigated using univariate and multivariate analyses. Postoperative recurrence occurred in 344 patients (32.6%). OMs were diagnosed in 56 patients (5.6%) with 93% within 3years. BMs were identified in 72 patients (6.6%) with 91.1% within 3years. Multivariate analysis revealed that poorly differentiated tumor and the presence of pathological nodal metastases were significantly associated with postoperative BM (p = 0.037, < 0.001), preoperative serum carcinoembryonic antigen (CEA) level of 5ng/mL or higher and the presence of pathological nodal metastases were significantly associated with OM (p = 0.034, < 0.001). The prevalence of OM and/or BM in 5years was as high as 25.9% in patients with pathological nodal metastases. We identified significant predictive factors of postoperative BM and OM. Under patient selection, the effectiveness of intensive surveillance for the modes of recurrence should be investigated with respect to earlier detection, maintenance of quality of life, and survival outcomes.

Optimal cutoff value of preoperative CEA and CA19-9 for prognostic significance in patients with stage II/III colon cancer.

This unicentric, retrospective cohort study aimed to identify the optimal cutoff values of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for the prognosis in patients with stage II/III colon cancer. After excluding 43 patients with CA19-9 levels < 0.2 U/mL, 588 were included. Receiver operating characteristic curves were constructed to determine the optimal cutoff values of CEA and CA 19-9 for disease relapse. The median CEA and CA19-9 values were 3.6 (interquartile range: 2.1-7.2ng/mL) and 14.3 (interquartile range: 8.1-30.0) U/mL, respectively. The optimal cutoff values of CEA and CA19-9 were 5.4ng/mL and 22.4 U/mL, respectively. A multivariate analysis of relapse-free survival (RFS) showed that cancer stage, CEA, and CA19-9 were significant independent factors. The RFS of patients with stages II and III colon cancer was significantly stratified by CEA (< 5.4/ ≥ 5.4ng/mL) and CA19-9 (< 22.4/ ≥ 22.4 U/mL). Prognostication based on the reference values (< 5.0ng/mL for CEA and < 37.0 U/mL for CA19-9) was less significant than that based on the optimal cutoff values. Both elevated CEA and CA19-9 had no value dependency on RFS: RFS curves were similar between extremely elevated CEA (≥ 54.0ng/ml) and intermediate CEA (5.4-54.0ng/ml) and between extremely elevated CA19-9 (≥ 224.0 U/ml) and intermediate CA19-9 (22.4-224.0 U/ml). The optimal cutoff values of preoperative CEA and CA19-9 for RFS were 5.4ng/ml and 22.4 U/mL, respectively, in patients with stages II and III colon cancer. Further relapse risk stratification is possible using these values.

Thoracoscopic Wedge Resection Versus Segmentectomy for cT1N0 Lung Adenocarcinoma.

The choice between wedge resection and segmentectomy as a sublobar resection method for patients with cT1N0 lung cancer remains debatable. This study aimed to evaluate the clinical outcomes after wedge resection and segmentectomy for patients with cT1N0 lung adenocarcinoma. The study enrolled 1002 consecutive patients with cT1N0 lung adenocarcinoma who underwent sublobar resection at the authors' institution between 2011 and 2017. A propensity score-matching analysis was used to compared the clinical outcomes between the wedge resection and segmentectomy groups. Wedge resection was performed for 810 patients (80.8%), and segmentectomy was performed for 192 patients (19.2%). Wedge resection resulted in better perioperative outcomes than segmentectomy. The multivariate analysis showed that the significant risk factors for poor disease-free survival (DFS) were elevated preoperative serum carcinoembryonic antigen levels, total tumor diameter greater than 2 cm, and a consolidation-to-tumor (C/T) ratio higher than 50%. After propensity-matching, no differences in overall survival or DFS were noted between the two matched groups. However, subgroup analysis showed that segmentectomy was associated with better DFS than wedge resection (p = 0.039) for the patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. Segmentectomy is the appropriate surgical method for sublobar resection in cT1N0 lung adenocarcinoma patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. Wedge resection may be a safe and feasible sublobar resection method for patients with a tumor diameter of 2 cm or smaller or a C/T ratio of 50% or lower.

Serum carcinoembryonic antigen pre-operative level in colorectal cancer: revisiting risk stratification.

Biomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre-operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut-off values. A retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease-free survival at 3-years and risk of local, loco-regional and distant recurrence during follow-up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre-operative values and follow-up data in order to estimate the optimal cut-off values. A total of 559 patients were considered. The mean CEA value was 12.1 ± 54.1ng/mL, and the median 29.3 (0-4995) ng/mL. The ROC curve analysis identified 12.5ng/mL as the best CEA cut-off value to predict the risk of metastatic development after surgery in stage I-III colorectal cancer patients, and 10ng/mL as the best CEA cut-off value to predict overall survival and disease-free survival in stage III-IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA <10 ng/mL), a moderate risk class (CEA 10-12.5 ng/mL) and a high risk class (CEA >12.5 ng/mL). In conclusion, pre-operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy.