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.

Clinicopathological Characteristics, Survival Outcomes, and Genetic Alterations of Younger Patient With Gastric Cancer: Results From China National Cancer Center and cBioPortal

BackgroundSurvival outcomes of younger patients with gastric cancer (GC) remains controversial. The present study sought to explore clinicopathological characteristics, survival outcomes, and genetic alterations in the younger and older patients with GC.MethodsPatients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998–2018. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models. Sequencing data were enrolled from the China National Cancer Center, TCGA, and MSKCC databases. ResultsA total of 1146 younger and 16988 older cases were included. Patients in the younger group were predominant in poor differentiation (53.7% versus 33.8%, P<0.0001), and pTNM stage IV (19.5% versus 11.8%, P<0.001). The 5-year overall survival (OS) of patients in NCCGCDB has noticeable increased from 1998 to 2018. Younger age was an independent prognostic factor for GC patients in pTNM stage III (P=0.014), while other stages showed no difference. Compared to the younger, older patients had a higher mutation frequency in LRP1B, GNAS, APC, KMT2D genes (all P< 0.05). In addition, although no significant difference, results of the China National Cancer Center, TCGA, and MSKCC cohorts indicated that younger patients dominated in CDH1, RHOA, and CTNNB1 mutations.ConclusionsStable proportion of younger cases and noticeable survival improvements were reported in the China National Cancer Center. Younger patients with pTNM stage III had a worse survival than older, while other tumor stages showed no difference. Furthermore, distinctive molecular characteristics were identified in younger GC patients, which might partly explain histopathological behaviors and prognosis of in this subpopulation.

Effect of Long Term Prediagnostic Aspirin Intake on the Prognosis of Esophageal Squamous Cell Carcinoma Receiving Radical Surgery

Background:The effect of long term prediagnostic aspirin intake on the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. We aimed to reveal the effect of long term prediagnostic aspirin intake on survival of ESCC patients receiving radical surgery. Methods:147 eligible ESCC patients who received radical surgery for primary treatment were enrolled in this study. Patients who had used aspirin regularly for more than 3 months before diagnose were classified as aspirin group and patients who had never used aspirin before diagnose and surgery were served as non-aspirin group. The recurrence rate, disease-free survival (DFS) and overall survival (OS) were compared between the two groups to verify the effect of aspirin. Results:Patients were clarified into aspirin group (n=57) and non-aspirin group (n=90). The DFS and OS were both significantly shorter in aspirin group than non-aspirin group (DFS: 23.1±18.0 months vs. 30.9±19.8 months, P=0.018; OS: 29.8±17.4 months vs. 35.2±18.2 months, P=0.082). Survival analysis revealed that OS decreased in aspirin group than in non-aspirin group, however, it did not reach significance (P=0.074). DFS decreased significantly in aspirin group than non-aspirin group in both univariate (P=0.007) and multivariate (P=0.002) survival analysis. Subgroup analysis revealed that in pTNM stage 2, OS and DFS were reduced in non-aspirin group compared with aspirin group (P=0.048 and P=0.003, respectively), while no difference was found in stage 3.Conclusions:Long term prediagnostic aspirin intake may cause poor DFS in ESCC patients receiving radical surgery, especially for those in pTNM stage 2.

A prognostic model for stratification of stage IB/IIA esophageal squamous cell carcinoma: a retrospective study

Background To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). Methods Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. Results Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). Conclusion Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

Efficacy of Postoperative FOLFOX Versus XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet–Lymphocyte Ratio in Patients Receiving XELOX

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P &lt; 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.

Prognostic impact of preoperative immunonutritional status in rectal mucinous adenocarcinoma

Aim: To explore the impact of preoperative the albumin-to-globulin ratio (AGR) and the prognostic nutritional index (PNI) on prognosis in rectal mucinous adenocarcinoma (MAC). Methods: A total of 128 patients were included. Results: According to the X-tile analysis, cutoff values of AGR and PNI were 1.1 and 43.8. Preoperative AGR (p = 0.041), preoperative PNI (p = 0.036) and pTNM stage (p = 0.003) were independently associated with overall survival in rectal MAC patients. Distance from the anal verge (p = 0.005), preoperative AGR (p = 0.021), preoperative PNI (p = 0.007) and pTNM stage (p < 0.001) were significantly associated with disease-free survival in rectal MAC patients. Nomograms for overall survival and disease-free survival were developed (C-index: 0.739 and 0.764). Conclusion: Preoperative AGR and PNI can act as effective predictors for survival for rectal MAC patients.

Decreased Preoperative Estimated Glomerular Filtration Rate Was Related With Poor Prognosis of NSCLC Patients

(1) Background: The coexistence of chronic kidney disease (CKD) and cancer is common due to the increased incidence of cancer in patients with CKD. Glomerular filtration rate is the optimal way to measure kidney function. To date, little is known about the role preoperative renal function plays in the prognosis of NSCLC patients. (2) Methods: The study enrolled 140 patients who had been newly diagnosed NSCLC and received potential radical surgery for treatment from 2009 January to 2012 December. The detailed characteristics were collected including gender, age, smoking and drinking habits, KPS score, hemoglobin levels, tumor size, pathology type, differentiation, pTNM stage and serum creatinine before surgery. Univariate and multivariate analyses of overall survival (OS) and disease-free survival (DFS) were performed using Kaplan-Meier method and Cox model. (3) Results: The univariate analysis identified that the pTNM stage ( p < 0.001), eGFR level ( p = 0.006), and adjuvant treatment ( p = 0.007) were prognostic factors for OS, while drinking habit ( p = 0.032), pTNM stage ( p = 0.002) and eGFR level ( p = 0.006) were the prognostic factors for DFS. Further multivariate analysis found that pTNM stage (HR = 2.091, 95% CI 1.424-3.071; p < 0.001) and eGFR level (HR = 1.890, 95% CI 1.424-3.071; p = 0.004) were independent factors associated with OS. The pTNM stage (HR = 1.735, CI 1.215-2.479; p = 0.002) and eGFR (HR = 1.793, CI 1.193-2.696; p = 0.005) were independent factors associated with DFS. Further subgroup analyses found that in female patients/ no smoking patients/ patients younger than 60 years, better eGFR level was significantly associated with better OS and DFS. (4) Conclusions: Decreased preoperative eGFR was associated with poor clinical outcome of NSCLC patients.

A Novel Three-Gene Model Predicts Prognosis and Therapeutic Sensitivity in Esophageal Squamous Cell Carcinoma

To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (P=0.011), and PDIA3 and ITGA5B1 were correlated with both lymph node metastasis (PDIA3: P<0.001; ITGA5B1: P=0.001) and pTNM-stage (PDIA3: P=0.001; ITGA5B1: P=0.009). Furthermore, we found that, compared with the current TNM staging system, the molecular model elicited from the expression of MYC, PDIA3, and ITGA5B1 shows higher accuracy in predicting OS (P<0.001) or DFS (P<0.001) in ESCC patients. Moreover, ROC and regression analysis demonstrated that this model was an independent predictor for OS and DFS, which could also help determine a subgroup of ESCC patients that may benefit from chemoradiotherapy. In conclusion, our study has identified a novel molecular prognosis model, which may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for ESCC treatment.

Discussion of relationships among changes of pathological indicators, postoperative lymphedema of the upper limb, and prognosis of patients with breast cancer

Objectives: The present study aimed to discuss the impacts of changes to pathological indicators of patients with breast cancer upon the incidence of postoperative lymphedema of the upper limb and prognosis. Methods: 2597 female patients with breast cancer who received surgical treatment in our hospital were enrolled in the present study to evaluate the incidence of these patients’ postoperative lymphedema of the upper limb. Results: For patients with breast cancer, the incidence of postoperative lymphedema of the upper limb was related to T stage of breast cancer, lymph node metastasis, the number of metastatic lymph nodes, pTNM stage, and pathological types of breast cancer (P&lt;0.05). Lymph node metastasis was an independent risk factor of lymphedema of the upper limb; lymph node metastasis and Ki-67 expression level were independent factors that impacted pathologic complete response rate of neoadjuvant chemotherapies. Patients’ mortality was correlated to pathological and molecular subtypes, Ki-67 expression level, ER expression level, PR expression level, and pTNM stage (P&lt;0.05), among which the pTNM stage, Ki-67 expression level, and PR expression level were independent factors that affected prognosis of patients with breast cancer. Conclusion: Patients with lymph node metastasis were more prone to lymphedema of the upper limb, while it was easier for those whose Ki-67 expression level was high and who were not subject to lymph node metastasis to get a pathological complete response after receiving neoadjuvant chemotherapies. The prognosis was poorer among patients whose progesterone receptors were negative and Ki-67 expression levels were high at the advanced pTNM stage.