Univariate Cox Survival Analysis Research Articles

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer.

Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243–1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283–1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers. Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

Prognostic Dynamic Nomogram Integrated with Inflammation-Based Factors for Non-Small Cell Lung Cancer Patients with Chronic Hepatitis B Viral Infection.

Chronic inflammation plays an important role in tumor progression. The aim of this study was to develop an effective predictive dynamic nomogram integrated with inflammation-based factors to predict overall survival (OS) of non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. We retrospectively analyzed NSCLC patients with HBV infection from Sun Yat-sen University Cancer Center between 2008 and 2010. Univariate and multivariate Cox survival analyses were performed to identify prognostic factors associated with OS of patients. All of the independent prognostic factors were utilized to build the dynamic nomogram. The predictive accuracy of the dynamic nomogram was evaluated concordance index (C-index), decision curve analysis and were compared with previous reported model and traditional TNM staging system. According to the total points (TPS) by dynamic nomogram, we further stratified patients into different risk groups. A total of 203 patients were included. Multivariate Cox analysis showed TNM stage (P = 0.019), treatment (P < 0.001), C-reactive protein (P = 0.020) and platelet (P = 0.012) were independent prognostic factors of OS. The dynamic nomogram was established by involving all the factors above. The C-index of dynamic nomogram for predicting OS was 0.76 (95%CI: 0.72-0.80), which was statistically higher than that of traditional TNM staging system (0.70, 95%CI: 0.66-0.74, P<0.001). Decision curve analysis demonstrated that the dynamic nomogram was better than the TNM staging system. The predictive accuracy of the current model keeping almost the same accuracy as previous one. Based on the total points (TPS) of dynamic nomogram, we divided the patients into 3 subgroups: low risk (TPS ≤ 107), intermediate risk (107< TPS ≤ 149), and high risk (TPS > 149). The differences of OS rates were significant in the subgroups. We propose a novel dynamic nomogram model based on inflammatory prognostic factors that is highly predictive of OS in NSCLC patients with HBV infection and outperforms the traditional TNM staging system.

Disparities in care for elderly women with endometrial cancer adversely effects survival.

Elderly women with endometrial cancer are at increased risk of local recurrence and cancer-specific death compared to younger women. We sought to investigate adjuvant radiotherapy (RT) practice patterns and effects on survival in elderly women with endometrial cancer. Women from the National Cancer Data Base (NCDB) with FIGO IA grade 3 to FIGO IVA endometrial cancer diagnosed from 2004-2013 were included. Chi square analysis was used to compare the elderly (80+) and non-elderly women (18-79) and women who received RT and those that did not. Univariate and multivariate logistic regression were used to determine predictors of receipt of oncologic surgery and adjuvant RT. Univariate and multivariate Cox survival analyses were performed to examine the effect of radiotherapy on survival. Propensity score matching and shared frailty analysis were done in the elderly cohort. We identified 48,871 women for analysis. Rates of oncologic surgery were higher in the women 80+ compared with rates of adjuvant RT (95% versus 34%). Rates of RT receipt were higher in non-elderly women (48% versus 34%, p<0.001). Age over 80 was a negative predictive factor (OR 0.62, p<0.001) for receipt of adjuvant RT and oncologic surgery (OR 0.81, p=0.03). Adjuvant RT was associated with a decreased risk of death in elderly (HR 0.79, p<0.001) and non-elderly women (HR 0.77, p<0.001). Endometrial cancer patients over age 80 have similar rates of oncologic surgery as younger women but are significantly less likely to receive adjuvant RT, and this negatively impacts their survival.

Comparison of five tumor regression grading systems for gastric adenocarcinoma after neoadjuvant chemotherapy: a retrospective study of 192 cases from National Cancer Center in China

BackgroundNeoadjuvant chemotherapy has been increasingly practiced on gastric cancer (GC), and histological evaluation to predict outcome is urgent in clinical practice. There are five classic tumor regression grading (TRG) systems, including Mandard-TRG system, the Japanese Gastric Cancer Association (JGCA)-TRG system, College of American Pathologists (CAP)-TRG system, China-TRG system and Becker-TRG system.MethodsTotally, 192 patients of gastric adenocarcinoma (including adenocarcinoma of the esophagogastric junction) treated by neoadjuvant chemotherapy and surgery were evaluated using the above five TRG systems. The clinicopathological characteristics were also assessed. The correlation among TRG systems, clinicopathological characteristics and prognosis were analyzed.ResultsAll the five TRG systems were significantly correlated with differentiation, postsurgical T category, postsurgical N category, American Joint Committee on Cancer (AJCC) stage, lymph-vascular invasion, perineural invasion, as well as tumor size. All the five TRG systems were statistically significant in univariate Cox survival analysis. However, only postsurgical T category, postsurgical N category and R0 resection were independent in multivariate Cox survival analysis. The tight correlation between the TRG systems and other characteristics such as postsurgical stage might affect the independent prognostic role of the TRG systems. As compared with other TRG systems, the hazard ratio of no/slightly response in both Mandard TRG system and JGCA TRG system revealed higher hazard of death and disease progression than that of severe response when using univariate Cox survival analysis. The median survival time of complete response and nearly complete response were much longer than that of partial response, all classified by Mandard-TRG system. This could help clinicians predict prognosis more reasonably than JGCA-TRG which does not have the category of nearly complete response.ConclusionWe recommend Mandard-TRG system for GC after neoadjuvant chemotherapy due to its better prediction of prognosis.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study

The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

A novel prognostic inflammation score predicts outcomes in patients with ovarian cancer

BackgroundSystemic inflammation and host immunological nutritional status play important roles in the tumorigenesis of malignant cancer. A novel prognostic inflammation score (PIS) based on preoperative serum albumin and neutrophil to lymphocyte ratio (NLR) was designed. We explored its prognostic value in ovarian cancer. Methods143 patients with ovarian cancer were enrolled in this retrospective study. The association of the PIS with clinicopathologic parameters was analyzed. The prognostic significance was determined by univariate and multivariate cox survival analyses. ResultsBoth univariate and multivariate analyses showed that NLR and albumin were independent prognostic factors for overall survival (OS) and progression-free survival (PFS). An inverse correlation was observed between the NLR and serum albumin concentration. The novel prognostic inflammation score (PIS) was shown to be a significant predictor for OS and PFS (both P<0.001) according to multivariate analysis. Additionally, low PIS was associated with advanced tumor stage (P<0.001), metastasis (P<0.001) and preoperative high PLR (P<0.001). ConclusionsThe PIS is a novel but promising prognostic score in ovarian cancer. It is a significant prognostic marker adjusted for clinicopathologic characteristics to further identify patients' survival differences.

Clinical significance of preoperative neutrophil–lymphocyte vs platelet–lymphocyte ratio in primary operable patients with non–small cell lung cancer

BackgroundOur aim was to determinate the prognostic value of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in primary operable patients with non–small cell lung cancer (NSCLC). MethodsSix hundred seventy-eight NSCLC patients were enrolled in this study. The prognostic significance of both markers was determined by both univariate and multivariate Cox survival analysis. The cut-off value for NLR and PLR was selected by using receiver operating characteristic curve analysis. ResultsMultivariate analysis showed that NLR was an independent prognostic factor for disease-free survival (hazard ratio = 1.593, 95% confidence interval [CI] 1.277 to 1.988, P < .001) and overall survival (hazard ratio = 1.624, 95% CI 1.304 to 2.022, P < .001). The area under the curve was .640 (95% CI .599 to .682, P < .001) for NLR and .547 (95% CI .503 to .590, P = .036) for PLR, indicating that NLR was superior to PLR as a predictive factor in primary operable NSCLC patients. ConclusionsPreoperative NLR represents a significant independent prognostic indicator in primary operable NSCLC patients. Our results also demonstrate that high-risk patients based on the NLR do not benefit from adjuvant chemotherapy.

Number of negative lymph nodes can predict survival after postmastectomy radiotherapy according to different breast cancer subtypes.

Purpose: To assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with positive axillary lymph nodes after mastectomy and its predictive value for radiotherapy efficacy of different breast cancer subtypes (BCS).Methods: The records of 1,260 breast cancer patients with positive axillary lymph nodes who received mastectomy between January 1998 and December 2007 were reviewed. The prognostic impact and predictive value of the number of NLNs with respect to locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were analyzed.Results: The median follow-up time was 58 months, and 444 patients (35.2%) received postmastectomy radiotherapy (PMRT). Univariate and multivariate Cox survival analysis indicated the number of NLNs was an independent prognostic factor of LRFS, DFS, and OS. Patients with a higher number of NLNs had better survival. PMRT improved the LRFS of patients with ≤ 8 NLNs ( p < 0.001), while failing to improve the LRFS of patients with > 8 NLNs (p = 0.075). In patients with luminal A subtype, PMRT improved the LRFS, DFS, and OS of patients with ≤ 8 NLNs, but in patients with > 8 NLNs only the LRFS was improved. For patients with luminal B subtype, PMRT only improved the LRFS of patients with ≤ 8 NLNs. The number of NLNs had no predictive value for the efficacy with PMRT in Her2+ and triple-negative subtypes.Conclusions: The number of NLNs is a prognostic indicator in patients with node-positive breast cancer, and it can predict the efficacy of PMRT according to different BCS.

Overexpression of periostin predicts poor prognosis in non-small cell lung cancer

The periostin protein, encoded by the POSTN gene, is a component of the extracellular matrix, which is expressed by fibroblasts and has been observed in a variety of human malignancies. The present study aimed to detect the expression of periostin in the tissues of non-small cell lung cancer (NSCLC) patients and benign lung tumors, and to correlate the results with the clinicopathological data of the subjects, in order to evaluate periostin as a potential prognostic marker. In total, 49 NSCLC patients and 6 benign lung tumors were included in this study. The protein level of periostin was detected in paired normal/paratumor/cancer tissues by a western blot analysis and the mRNA level in paired normal/cancer tissues was detected by quantitative polymerase chain reaction (qPCR). The results were then correlated with established biological and prognostic factors. Immunohistochemistry was used to confirm the location of periostin in the NSCLC tissues. Uni- and multivariate analyses were performed using Cox’s proportional hazards regression model. The protein level of periostin was elevated in the cancer tissue of the NSCLC patients compared with the normal (P=0.017) and paratumor (P=0.000) tissues. The expression level in the male patients was much higher than in the female patients at the protein (P=0.001) and mRNA (P=0.010) levels. The mRNA level in the non-adenocarcinoma (non-ADC) patients was much higher than in the adenocarcinoma (ADC) patients (P=0.029). Periostin was demonstrated higher expression at the protein level in the pseudotumors and tuberculosis patients than in the adjacent (P=0.016) and surrounding tissues (P=0.001). Immunostaining indicated that high levels of periostin were present in the mesenchymal areas, but not in the cancer cells themselves. The patients with tumors exhibiting high-level periostin expression showed a significantly shorter survival time (P=0.036, log-rank test). The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27) and 45.4% for patients with high-level periostin expression (periostin-H; n=22). Similarly, pathological node (pN) status was a significant prognostic marker in the univariate Cox survival analysis. Notably, periostin-H expression was also identified as an independent prognostic factor by the multivariate analysis (P=0.011). These results showed that the overexpression of periostin predicts a poor prognosis, therefore it may be regarded as a novel molecule in the progression and development of NSCLC. The results provide an additional target for the adjuvant treatment of NSCLC.

Overexpression of CPE-ΔN predicts poor prognosis in colorectal cancer patients

Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-ΔN) has been detected and the mechanism of CPE-ΔN action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-ΔN expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-ΔN isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-ΔN mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan-Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-ΔN is overexpressed in colorectal tumor tissue and that high CPE-ΔN mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis (P = 0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-ΔN expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-ΔN expression had a significantly shorter survival (P < 0.001, logrank test). Tumor differentiation, gross feature, pT classification, pN classification, tumor recurrence, lymph node metastasis, and CPE-ΔN status were significantly associated with poor prognosis after performing a univariate Cox survival analysis. High CPE-ΔN expression was also identified as an independent prognostic factor using a multivariate analysis (P = 0.011). Based on these results, we can conclude that CPE-ΔN expression might be a potential prognostic marker for colorectal cancer patients.

Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma

Angiolymphatic invasion (ALI), representing lymphatic invasion (Ly) and intratumoral vascular invasion (V), is considered to be a useful prognostic factor for pathological stage I non-small cell lung carcinoma (NSCLC). However, the types of tumor for which prognoses are most influenced by ALI positivity have not previously been discussed, nor has the question of whether these findings should influence postoperative therapeutic decision-making after complete resection. The present study investigated 195 cases of stage I NSCLC treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. ALI-positive (ALI(+)) results were found in 31.8% of tumors, and 5.1% exhibited both Ly(+) and V(+). Five-year recurrence-free survival was significantly lower in ALI(+) cases (50.6%) than in ALI(−) cases (85.9%; p<0.0001, log-rank test). In particular, 5-year recurrence-free survival rate was only 10.0% for Ly(+)V(+) cases. ALI(+) correlated with high age, male sex, tumor size (>2.0cm), elevated preoperative serum carcinoembryonic antigen level (≥5.0ng/mL), high maximum standard uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) (≥5.0), pleural invasion, and histological classification of non-adenocarcinoma (ADC). According to histopathological subset analyses, ALI(+) was associated with shorter recurrence-free survival than ALI(−) only among ADC patients (p<0.0001, log-rank test), and not among non-ADC patients (p=0.7710). High preoperative serum CEA level, high SUVmax on FDG-PET, pleural invasion, Ly(+), and V(+) were significant risk factors for recurrence in univariate Cox survival analysis among stage I ADC patients. Importantly, Ly(+) and V(+) were identified as independent risk factors for recurrence by multivariate analysis. Histopathological detection of ALI as a risk factor for recurrence should be considered for inclusion in the staging criteria and as additional information for determining postoperative adjuvant treatment of stage I NSCLC, particularly among ADC patients, but not among non-ADC patients.

P-1263 - Antipsychotic treatment for patients with schizophrenia; patient-decided and clinician-decided discontinuations

Introduction Antipsychotic maintenance treatment for patients with schizophrenia has been demonstrated to be the single most important modifiable factor to prevent unplanned readmissions. Effectiveness studies have indicated different risk for drug discontinuation between current antipsychotics. Objectives & aims To evaluate time until discontinuation of antipsychotic treatment, and specifically to investigate if differences between the prescribed antipsychotics could be detected. Methods 396 patients with schizophrenia were included in an open cohort study and followed through treatment until all antipsychotics prescribed at inclusion were discontinued, predictors for time to discontinuation were analysed with univariate and multivariate Cox survival analyses with time until discontinuation as the dependent variable and antipsychotic monotherapy as the predictor variable. The analysis was controlled for common confounders. Results 65.7% of the patients were men, mean age was 42.4 years, and 12.9% were first-episode patients. 287 were prescribed antipsychotic monotherapy. In the multivariate Cox analysis with time to all-cause discontinuation only clozapine was significant different from olanzapine, Adjusted Hazard Rate (AHR) 0.17 (0.07,0.45) (p = 0.0003), this was also the case for the prediction of time to clinician-decided discontinuation, AHR (0.20 (0.06,0.70) (p = 0.012). In the analysis with time to patient-decided discontinuation as the dependent variable also Second Generation Antipsychotic Long-Acting Injectables (LAI) (AHR 0.26 (0.09,0.77) (p = 0.015) and First Generation Antipsychotic (LAI) (AHR 0.35 (0.16,0.80) (p = 0.013) had significant lower risk for discontinuation. Conclusions Clinicians and patients discontinued clozapine at a lower rate than olanzapine, patients also discontinued LAI formulations at a lower rate than olanzapine.

BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients

Malignant pleural mesothelioma is an incurable, asbestos-associated cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis deregulation is an important feature of cancer and survivin, a member of the inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been suggested to have a role in the development and progression of several cancers. Genetic variability, in particular single nucleotide polymorphisms in the BIRC5 promoter, may affect the protein's expression levels. The aim of our study was to elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on survivin expression, patient survival and age at diagnosis in malignant pleural mesothelioma. Archival mesothelioma samples from 101 Slovenian patients were immunohistochemically analysed for survivin expression. DNA was extracted from tumour samples and genotyped for three BIRC5 promoter single nucleotide polymorphisms (-31G > C, -241C > T and -625G > C). Genotypes were associated with nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes, histological type, gender and asbestos exposure were included in univariate Cox survival analyses. Survivin expression was detected in both tumour cell nuclei and cytoplasms in all analysed samples. No association between BIRC5 promoter polymorphism genotypes or haplotypes and nuclear survivin expression was found. Polymorphism -241C > T affected patients' age at diagnosis. Survival analysis confirmed that younger age at diagnosis and epitheloid histological type improved survival, but no significant effects of nuclear survivin expression or genotype/haplotype on overall survival were observed. Our findings indicate no relationship between BIRC5 genotypes and survivin expression or overall survival in mesothelioma patients. We observed that BIRC5 -241C > T polymorphism had a significant effect on patient age at diagnosis.

Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer

Ovarian cancer is associated with high mortality due to presentation at advanced stage and high recurrence following treatment with chemotherapy. Most of the prognostic variables in ovarian cancer, including stage and residual disease, are amenable for assessment only after surgery. Currently there are no established preoperative markers including, CA-125, that can predict overall survival in patients with ovarian cancer. The aim of our study was to evaluate the prognostic significance of the preoperative haematological markers platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) in patients with ovarian cancer. Preoperative PLR and NLR were evaluated in 235 patients undergoing surgery for ovarian cancer. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. High preoperative PLR (p < 0.001) and NLR (p = 0.001) were significantly associated with poor survival using univariate Cox survival analysis. The median overall survival in patients with a PLR of < 300 was 37.4 months (95% CI 26.1-48.7) and 14.5 months (95% CI 11.7-17.2) in those with a PLR of > 300. PLR (p = 0.03) but not NLR (p = 0.575) retained its significance as a prognostic marker on multivariate Cox's regression analysis, along with stage (p < 0.001) and residual disease (p = 0.015). We have shown for the first time that PLR is a novel independent prognostic marker in patients with ovarian cancer.

Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients

High expression of KIAA0101 (p15PAF/OEATC-1) which contains a proliferating cell nuclear antigen (PCNA)-binding motif, a key factor in DNA repair and/or apoptosis and cell cycle regulation, has been observed in a variety of human malignancies. The aim of this study was to observe the expression of KIAA0101 in human non-small-cell lung cancer (NSCLC), explore its clinicopathological significance and evaluate KIAA0101 expression as a potential prognostic marker. KIAA0101 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 357 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases), and correlated with male gender (P<0.0001), tumor progression (pT status) (P=0.0008), lymph node metastasis (pN status) (P=0.0003), non-adenocarcinoma histological classification (P<0.0001), and smoking history (P<0.0001), but not with patient age or pleural invasion. Patients with tumors displaying high-level KIAA0101 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level KIAA0101 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0320). These results provide additional information for determining postoperative adjuvant treatment of NSCLC.

Expression of Adam28 as a prognostic biomarker of survival in patients with early-stage non-small cell lung cancer.

10600 Background: The Adam (a disintegrin and metalloproteinase) family could modulate key cell signaling pathways via the shedding of membrane-associated proteins. Overexpression of Adam28 is involved in cell proliferation and progression in various carcinomas. This study was aimed to evaluate Adam28 expression to serve as prognostic marker in non-small cell lung cancer (NSCLC). Methods: 100 lung cancer tumor tissues and 53 adjacent tissues from patients with stage Ι – IIIa were obtained between 2004 and 2006 in Guangdong Lung Cancer Institute. All of them were pathologically assessed and analyzed with expression profile microarray. Then we conducted the real-time quantitative PCR (qPCR) for validation on the expression level of Adam28 in cancer tissues. Disease free survival was plotted using the Kaplan-Meier method, univariate and multivariate analyses were performed for factors affecting survival of patients. Results: Microarray data demonstrated significantly increased expression of Adam28 in cancer tissues (P<0.001), and confirned by qPCR. Mean value of qPCR was considered as the cut-off point. The expression of Adam28 is significantly correlated with T staging and histology. Patients whose tumors displayed high-level Adam28 showed a significantly shorter mean recurrence time of 39.6 vs 53.4 months (P=0.017). Similarly,N status, clinical stage and performance status (PS) were significant prognostic markers in univariate Cox survival analysis (P-value of 0.1 was adopted as the limit for entering into multivariate survival analysis).Importantly, Adam28 expression (P=0.029) together with N status (P=0.036) and PS (P=0.024) proved to be independent prognostic parameters in multivariate analysis. Conclusions: Our results suggest that Adam28 expression is significantly increased in NSCLC and provides additional prognostic information for survival of surgically treated NSCLC patients. We further hypothesize that high-level expression of Adam28 could relate to an enhanced propensity of tumor cells for survival, proliferation and migration, which calls for further investigation.

Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients

High-level expression of mitotic arrest defective protein 2 (MAD2), a central component of the spindle assembly checkpoint, has been observed in a variety of human malignancies. Aim of the present study was to observe the expression of MAD2 in human non-small-cell lung cancer (NSCLC) and explore its clinicopathologic significance and evaluate MAD2 expression as a prognostic marker. MAD2 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 358 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level MAD2 expression was observed in 26.3% (94 of 358 cases), and correlated with male sex ( P = 0.0002), tumor progression (pT status) ( P = 0.0009), visceral or parietal pleural invasion ( P = 0.0151), non-adenocarcinoma, histological classification ( P < 0.0001), and smoking history ( P = 0.0022), but not with patient age or lymph node metastasis (pN status). Patients with tumors displaying high-level MAD2 expression showed significantly shorter survival ( P < 0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level MAD2 expression was also identified as an independent prognostic factor by multivariate analysis ( P = 0.0076). These results provide additional prognostic information for surgical treatment of NSCLC.

Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio

Background The objective of this study was to investigate whether the preoperative hematologic markers, the platelet-lymphocyte ratio (PLR), or the neutrophil-lymphocyte ratio (NLR) ratio are significant prognostic indicators in resected pancreatic ductal adenocarcinoma. Methods A total of 84 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a retrospectively maintained database. Results The preoperative NLR was found to be a significant prognostic marker ( P = .023), whereas PLR had no significant relationship with survival ( P = .642) using univariate Cox survival analysis. The median overall survival in patients with an NLR of ≤3.0 (n = 55) was 13.7, 17.0 months in those with an NLR of 3.0 to 4.0 (n = 17) and 5.9 months in patients with a value of >4.0 (n = 12) (log rank, P = .016). The NLR retained its significance on multivariate analysis ( P = .039) along with resection margin status ( P = .001). Conclusion The preoperative NLR represents a significant independent prognostic indicator in patients with resected pancreatic ductal adenocarcinoma, whereas PLR does not.

Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma

Background The objective of this study was to investigate whether the preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic index in resected pancreatic ductal adenocarcinoma. Methods A total of 110 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a prospectively maintained database. Results The preoperative P/L ratio was found to be a more significant prognostic marker ( P < .001) than either the lymphocyte count ( P = .007) or platelet count ( P = .068) on univariate Cox survival analysis. The median overall survival in patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a value of greater than 300 (n = 19) (log-rank, P = .006). The preoperative P/L ratio retained significance on multivariate analysis ( P < .001), along with tumor size ( P = .010) and lymph node ratio ( P = .013). Conclusions The preoperative P/L ratio represents a significant independent prognostic index in patients of resected pancreatic adenocarcinoma.

Echocardiography in Chagas Heart Disease

Chagas heart disease is a frequent cause of morbidity and mortality in Latin America. Echocardiography provides useful diagnostic and prognostic information and is an important tool in the management of patients with Chagas disease. A search for relevant publications was obtained from MEDLINE, LILACS, and SCIELO sources. Acute Chagas myocarditis is a rare disorder in which pericardial effusion is frequent. Echocardiography may exclude pericardial tamponade in case of heart failure. Chronic Chagas cardiomyopathy evolves for several decades after the infection. Epidemiological history, positive serology, and suggestive clinical and ECG abnormalities establish the diagnosis. About three quarters of chronic Chagas cardiomyopathy subjects remain asymptomatic with normal (indeterminate form) or abnormal ECGs. Early Doppler abnormalities includes prolongation of isovolumic contraction and relaxation times. Systolic function frequently is normal, but dysfunction may be elicited by stress tests. Half or more of symptomatic patients have a left ventricular apical aneurysm and other segmental contractile abnormalities similar to those seen in coronary heart disease. The dilated nonsegmental form is indistinguishable from dilated cardiomyopathy. Results from univariate and multivariate Cox survival analyses indicate that impaired systolic function and increased ventricular dimensions have significant value in predicting cardiac morbidity and mortality. Cardiac ultrasound commonly is used in the follow-up of patients and in the assessment of various therapeutic modalities. Echocardiographic and Doppler techniques provide useful structural and functional information in the detection of early myocardial damage, risk assessment of prognosis, disease progression, and management of patients with Chagas disease.