Carbohydrate antigen 19-9 is a valuable prognostic factor in colorectal cancer patients with normal levels of carcinoembryonic antigen and may help predict lung metastasis

Purpose

We retrospectively analyzed preoperative levels of carbohydrate antigen (CA) 19-9 in colorectal cancer (CRC) patients to determine the prognostic value of CA19-9 in CRC patients with normal carcinoembryonic antigen (CEA) levels.

Methods

A total of 639 patients who underwent curative surgery at Taipei Veterans General Hospital between 2002 and 2006 were enrolled. We excluded 254 patients (39.7?%) with high preoperative CEA levels and analyzed 385 patients with normal CEA levels. The measured endpoint was the postoperative disease-free survival (DFS). The prognostic value of CA19-9 was determined using log-rank test and Cox regression analysis.

Results

High CA19-9 levels were significantly associated with advanced disease and were detected in 5.8?% of patients with stage I disease, 11.7?% of those with stage II disease, and 22.5?% of those with stage III disease (P?P?Conclusions CA19-9 may be a prognostic factor for CRC patients with normal CEA levels. An aggressive follow-up protocol for lung metastasis should be used for these patients.     

Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer

Background

Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration.

Methods

We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data.

Results

From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28–2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58–3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03–3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12–2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44–3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11–2.28) were negative prognostic factors for overall survival.

Conclusions

K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.     

Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma

Aims

The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection.

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

Objectives

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched.

Methods

Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated.

Results

Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p ≤ 0.001 and p = 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p = 0.008). For patients with higher preoperative and postoperative CA 19–9 values, OS and DFS were shorter (p = 0.013 and p ≤ 0.001) and (p = 0.042 and p ≤ 0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p = 0.008, Pearson correlation coefficient = 0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p ≤ 0.001, Pearson correlation coefficient = 0.603).

Conclusion

In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.     

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

BackgroundThe prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described.MethodsPre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery.ResultsPre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02].ConclusionsAmong patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic.     

Increased Serum Levels of Carbohydrate Antigen 19-9 and Outcomes in Primary Sclerosing Cholangitis Patients Without Cholangiocarcinoma

Background

Carbohydrate antigen 19-9 (CA 19-9) is the serum marker used to diagnose cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC).

Aim

We investigated long-term outcomes in patients with PSC and elevated CA 19-9 levels without CCA.

Methods

A total of 166 PSC patients with serum levels of CA 19-9 without CCA followed at a single center from 1998 to 2011 were included. Patients with and without elevated CA 19-9 levels (greater than 129 U/ml) were compared.

Results

Fifty-two (31.3 %) of the 166 patients with PSC without CCA had elevated serum CA-19-9. Patients with elevated CA-19-9 were followed for a mean of 4 years and 12 (23.1 %) died. They were more likely to have higher PSC risk score (1.67 ± 1.30 vs. 0.91 ± 1.53, p = 0.003) and dominant strictures (31 (59.6 %) vs. 21 (18.4 %), p < 0.001). In 17/52 (32.7 %) of patients with elevated CA-19-9, no etiology was identified; cholestasis and cholangitis were associated with elevated levels in 24/52 (48.1 %) and 11/52 (21.2 %), respectively. There were 32 of 52 (62.5 %) that underwent orthotopic liver transplantation (OLT) in elevated CA 19-9 group compared to 66/114 (56.9 %) without (p = 0.66). The median OLT-free survival with elevated CA 19-9 was 9 years from PSC diagnosis compared to 14 years without. Although there was a trend, there was no significant difference in the OLT-free survival on Kaplan–Meier analysis (log rank p = 0.12).

Conclusions

Thirty-two percent of patients with PSC had elevated serum CA 19-9 in the absence of CCA. There was a trend towards shorter OLT-free survival in PSC patients with elevated CA-19-9.     

Radical radiotherapy in high-risk prostate cancer patients with high or ultra-high initial PSA levels: a single institution analysis

Purpose

Purpose of this study is to analyze outcomes and pre-treatment prognostic factors in high-risk prostate cancer patients with initial PSA ≥20 ng/mL, treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) in a single institution.

Methods

Between March 2003 and December 2011, 155 consecutive high-risk prostate cancer patients (a) presenting with pre-treatment PSA level ≥20 ng/mL, (b) treated with definitive EBRT, and (c) with a minimum follow-up of 24 months were included in this retrospective analysis. Phoenix definition was used to define biochemical control. Primary endpoints were as follows: biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Multivariate analysis was performed to determine the independent prognostic impact of pre-treatment clinical factors [T stage, PSA, and Gleason score (GS)].

Results

At a median follow-up time of 62 months, actuarial bDFS, DMFS, CSS, and OS at 5 years were 64.8, 85.2, 95.8, and 94.4 %, respectively. On multivariate analysis, only GS was significantly associated with three clinical endpoints (bDFS: HR 1.6; p = 0.022, CSS: HR 4.27, p = 0.044, OS: HR 2.6; p = 0.038). Pre-treatment zenith PSA was associated only with bDFS (HR 1.87; p = 0.027).

Conclusions

Patients with “high” PSA levels (≥20 ng/mL) showed favorable clinical outcomes, supporting the role of local radiotherapy as primary therapy in combination with long-term ADT in patients with high PSA levels at diagnosis. A GS of 8–10 is the strongest predictor of outcome.     

KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer

Background

It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC).

Methods

AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc).

Results

KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc.

Conclusion

This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.     

Prognostic impact of pretherapeutic laboratory values in head and neck cancer patients

Purpose

The high comorbidity in patients with head and neck cancer (HNC) is mainly caused by the high incidence of tobacco and alcohol abuse and has direct impact on overall survival. We investigated whether HNC and its comorbidity also influence routine laboratory values and whether these values have influence on overall survival.

Methods

A retrospective cohort of 261 patients with primary squamous cell carcinoma of the oral cavity, pharynx, or larynx diagnosed between 2001 and 2006 with a complete set of pretherapeutic laboratory values was identified. The influence of standard oncological parameters, comorbidity, and each laboratory value on overall survival (OS) was investigated in univariate and multivariate analyses.

Results

Two-thirds of patients were active smokers and about one half reported high alcohol consumption. 40 % of patients had severe comorbidity according to Charlson comorbidity index. The most frequent laboratory pathologies were elevated C-reactive protein (CRP) values (66 %), impaired liver enzymes (30–50 %), decreased urea levels (33 %), leukocytosis (20 %), and anemia (10 %). In multivariate analysis for OS, a comorbidity index ≥5 (Hazard ratio [HR], 2.008; 95 % confidence interval [CI], 1.117–3.610; p = 0.020), high CRP level (HR, 2.469; CI, 1.414–4.310; p = 0.001), and abnormal low red-cell count (HR, 2.525; CI, 1.250–5.102; p = 0.010) were independent prognostic variables.

Conclusions

Comorbidity reflected by pathologic laboratory values is a major issue in HNC patients. Several pretherapeutic laboratory values have prognostic relevance for overall survival in HNC patients.     

Serum tumor markers enhance the predictive power of the AJCC and LCSGJ staging systems in resectable intrahepatic cholangiocarcinoma

Background

While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ).

Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma

Objective

To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA.

Prognostic relevance of preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 in a multicenter subset analysis of 179 patients with distal cholangiocarcinoma

BackgroundDistal cholangiocarcinoma (DCC) is a rare malignancy and validated prognostic markers remain scarce. We aimed to evaluate the role of serum CA19-9 as a potential biomarker in DCC.MethodsPatients operated for DCC at 6 high-volume surgical centers from 1994 to 2015 were identified from prospectively maintained databases. Patient baseline characteristics, surgical and histopathological parameters, as well as overall survival after resection were assessed for correlation with preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 (CA19-9). Preoperative CA19-9 to bilirubin ratio (CA19-9/BR) was classified as elevated (≥ 25 U/ml/mg/dl) according to the upper serum normal values of CA19-9 (37 U/ml) and bilirubin (1.5 mg/dl) giving a cut-off at ≥ 25 U/ml/mg/dl.ResultsIn total 179 patients underwent resection for DCC during the study period. High preoperative CA19-9/BR was associated with advanced age and regional lymph node metastases. Median overall survival after resection was 27 months. Elevated preoperative serum CA19-9/bilirubin ratio (HR 1.6, p = 0.025), T3/4 stage (HR 1.8, p = 0.022), distant metastasis (HR 2.5, p = 0.007), tumor grade (HR 1.9, p = 0.001) and R status (HR 1.7, p = 0.023) were identified as independent negative prognostic factors following multivariable analysis.ConclusionElevated preoperative bilirubin-adjusted serum CA19-9 correlates with regional lymph node metastases and constitutes a negative independent prognostic factor after resection of DCC.     

Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikarderg��ssen

Background

The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA?19-9, CA?72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion.

Methods

We investigated the pericardial fluid of 29?patients with proven malignant pericardial effusion and 25?patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15?patients with autoreactive effusion and 10?patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)?19-9, carbohydrate antigen (CA)?72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE).

Results

Of the tumor markers tested the mean concentrations of the CEA, CA?72-4 and CA?19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58???g/l vs. 0.72 ±1.49???g/l, p<0.001; CA?19-9 1331.31 ±3420.87?kU/l vs. 58.85 ±17.53?kU/l, p=0.04; CA?72-4 707.90 ±2397.55?kU/l vs. 0.48 ±2.40?kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA?72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74?C0.95), followed by CEA with 0.80 (95% confidence interval 0.68?C0.92). Pericardial fluid CA?72-4 levels >1.0?kU/l had 72% sensitivity (95% confidence interval 53%?C87%) and 96% specificity (95% confidence interval 80%?C99.9%) and CA?72-4 levels >2.5?kU/l had 69% sensitivity (95% confidence interval 49%?C85%) and 96% specificity (95% confidence interval 80%?C99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions.

Conclusion

Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA?72-4 and CA?19-9. Of the tested tumor markers, measurement of CA?72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA?72-4 levels. Under these circumstances the elevation of pericardial fluid CA?72-4 levels should include malignancy as a probable diagnosis.     

Molecular determinants of outcome in sorafenib-treated patients with hepatocellular carcinoma

Purpose

Preclinical studies show that sorafenib, a multitarget kinase inhibitor, displays anti-proliferative, anti-angiogenic, and pro-apoptotic properties in hepatocellular carcinoma (HCC). However, the determinants of sorafenib sensitivity in vivo remain largely unknown.

Methods

We assessed the expression of Mcl-1, activated/phosphorylated extracellular signal-regulated kinase (pERK) 1/2, and activated/phosphorylated AKT (pAKT) in pretreatment tumor specimens from 44 patients with advanced HCC who received sorafenib. Furthermore, we assessed MYC and MET gene copy numbers (GCN) by fluorescence in situ hybridization.

Results

Poorer overall survival (OS) times were correlated with pERK expression [hazard ratio (HR) 1.013; 95 % CI 1.003–1.035] and Mcl-1 expression (HR 1.016; 95 % CI 1.002–1.030) in pretreatment tumor samples. Expression levels of pERK and Mcl-1, however, were not correlated with time to tumor progression (TTP). Increased pERK expression was positively associated with higher Cancer of Liver Italian Program scores (P = 0.012) and was prognostic in patients with scores 2–6 but not in those with scores 0–1. pERK expression was significantly less frequent in specimens sourced from previous surgical procedures compared to biopsy samples (9.6 vs. 92.3 %, respectively; P < 0.0001). Analysis of pAKT expression, MET and MYC GCN, did not indicate any prognostic nor predictive values for these biomarkers in terms of survival.

Conclusions

Expression levels of Mcl-1 and pERK are associated with reduced OS in HCC patients treated with sorafenib and might be useful markers for risk stratification. However, in contrast to previous findings, pERK expression levels, as well as other biomarkers tested, did not affect TTP.     

Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer

Objectives

The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT).

Methods

This study included all patients with borderline resectable pancreatic cancer, a serum CA 19-9 level of ≥40 U/ml and bilirubin of ≤2 mg/dl, in whom NT was initiated at one institution between 2001 and 2010. The study evaluated the associations between pre- and post-NT CA 19-9, resection and overall survival.

Results

Among 141 eligible patients, CA 19-9 declined during NT in 116. Following NT, 84 of 141 (60%) patients underwent resection. For post-NT resection, the positive predictive value of a decline and the negative predictive value of an increase in CA 19-9 were 70% and 88%, respectively. The normalization of CA 19-9 (post-NT <40 U/ml) was associated with longer median overall survival among both non-resected (15 months versus 11 months; P = 0.022) and resected (38 months versus 26 months; P = 0.020) patients. Factors independently associated with shorter overall survival were no resection [hazard ratio (HR) 3.86, P < 0.001] and failure to normalize CA 19-9 (HR 2.13, P = 0.001).

Conclusions

The serum CA 19-9 level represents a dynamic preoperative marker of tumour biology and response to NT, and provides prognostic information in both non-resected and resected patients with borderline resectable pancreatic cancer.     

Cyclooxygenase-2 Expression Is Associated with Poor Overall Survival of Patients with Gastric Cancer: A Meta-Analysis

Background

Cyclooxygenase-2 (COX-2) is believed to be involved in gastric carcinogenesis. However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for gastric cancer patients.

Aim

To obtain a more accurate relationship between COX-2 overexpression and prognosis in gastric cancer by meta-analysis.

Method

Relevant articles published up to May 2013 were searched by use of several keywords in electronic databases. Separate hazard ratio (HR) estimates and 95 % confidence intervals (95 % CI) for COX-2 overexpression and overall survival (OS) and disease-free survival (DFS) with gastric cancer were extracted. Combined HR with 95 % CI was calculated by use of Stata11.0 software to estimate the size of the effect. Publication bias testing and sensitivity analysis were also performed.

Results

A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. Combined results suggested that COX-2 overexpression was associated with an unfavorable OS (HR 1.58, 95 % CI 1.36–1.84) but not DFS (HR 1.15, 95 % CI 0.93–1.43) among patients with gastric cancer. Publication bias was absent. Sensitivity analysis suggested that the results of this meta-analysis were robust.

Conclusions

The results of this meta-analysis suggest that high COX-2 expression may be an independent risk factor for poor OS of patients with gastric cancer. More large prospective studies are now needed to further clarify the prognostic value of COX-2 expression for DFS in gastric cancer.     

Prognostic impact of LDH levels in patients with relapsed/refractory seminoma

Purpose

To evaluate the impact of age and LDH levels in patients with relapsed seminoma.

Methods

Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010).

Results

The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06–3.61) and multivariate analysis (HR 1.90; CI 1.00–3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: “very low risk” (n = 23) 85.7 % (95 % CI 62–95), “low risk” (n = 44) 62.7 % (95 % CI 46–75) and “intermediate risk” (n = 36) 35.1 % (95 % CI 20–51). Overall survival at 3 years: “very low risk” 88.8 % (95 % CI 62–97), “low risk” 71.3 % (95 % CI 55–83) and “intermediate risk” 51.3 % (95 % CI 33–67).

Conclusion

The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.     

Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer

BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal cancer.AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012.These patients were randomly divided into two cohorts for cross-validation:training cohort and validation cohort.The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model.Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size.The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size.The primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),respectively.RESULTS In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per cm.Comparison of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size group.Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS(training cohort:hazard ratio(HR)=2.18,95%confidence interval(CI):1.28-3.73,P=0.004;validation cohort:HR=4.83,95%CI:2.21-10.52,P<0.001)as well as DFS(training cohort:HR=1.47,95%CI:0.93-2.33,P=0.096;validation cohort:HR=2.61,95%CI:1.38-4.95,P=0.003).CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer.Higher CEA/tumor size is associated with worse OS and DFS.     

Preoperative Serum CA125 Levels Predict the Prognosis in Hyperbilirubinemia Patients With Resectable Pancreatic Ductal Adenocarcinoma

Serum carbohydrate antigen 19-9 (CA19-9) is widely used to predict the prognosis for pancreatic ductal adenocarcinoma (PDAC). However, hyperbilirubinemia and the CA19-9 nonsecretor phenotype restrict the usage of serum CA19-9 alone. The goal of this study was to confirm the prognostic role of preoperative serum CA125 in PDAC, especially in patients with jaundice.A total of 211 patients with resected PDAC were eligible for this retrospective study, and were classified into 2 groups based on serum bilirubin levels. The prognostic significance of all clinicopathologic factors was evaluated by univariate and multivariate analyses, and the performance of each factor in predicting overall survival (OS) and recurrence-free survival (RFS) was compared.High preoperative CA125, high TNM stage, and lymph node metastasis were independent risk predictors for OS and RFS in all patients and the 2 subgroups, but high CA19-9 was only significant when considering all patients and those with nonelevated bilirubin. Using time-dependent receiver-operating characteristic analysis, better predictive performance for OS and RFS was observed for serum CA19-9 as compared to serum CA125 in these patients.High serum CA125 can independently predict poor prognosis. Importantly, in PDAC patients with hyperbilirubinemia, preoperative serum CA125 can predict the prognosis, whereas CA19-9 cannot. Preoperative CA19-9 had better predictive performance for survival than CA125, and the performance of CA19-9 did not decline between all patients and those with nonelevated bilirubin, but was significantly affected by hyperbilirubinemia.     

结直肠癌患者根治术前血清CEA和CA19-9表达水平对预后的预测价值

目的探讨结直肠癌患者根治术前CEA、CA19-9水平对预后的预测价值。 方法回顾性分析复旦大学附属肿瘤医院2003年12月至2007年1月间491例接受根治性切除的Ⅱ、Ⅲ期结直肠癌患者临床资料,包括患者术前血清CEA和CA19-9水平、临床病理资料及预后情况。利用单变量和多变量分析患者年龄、性别、肿瘤部位、肿瘤分化、TNM分期、肿瘤侵犯深度及淋巴结转移个数与预后的关系。 结果患者术前血清CEA和CA19-9水平、TNM分期、淋巴结转移数、肿瘤侵犯深度、肿瘤的分化都与预后相关。在多变量分析中,CEA和CA19-9水平、TNM分期、肿瘤分化是总生存的独立预测因素,CA19-9水平、TNM分期、肿瘤分化是无病生存的独立预测因素。 结论术前血清CA19-9与CEA水平均对结直肠癌患者的预后有预测价值。CA19-9水平应该作为常规的术前检查指标,对CEA检测结果有补充作用。