Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis

Objective

There is a heated debate on whether the prognostic value of SPARC is favorable or unfavorable. Thus, we carried out a meta-analysis evaluating the relationship between SPARC expression and the prognosis of patients with pancreatic cancer.

Methods

We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled hazard ratios (HRs) and corresponding 95%CI of overall survival (OS) were calculated to evaluate the prognostic value of SPARC expression in patients with pancreatic cancer. We also performed subgroup analyses.

Results

With 1623 patients pooled from 10 available studies, the incorporative HR showed an unfavorable prognosis of patients with pancreatic cancer in the multivariate analysis (HR = 1.55, 95%CI: 1.11–2.17, P = 0.01), but not in univariate analysis (HR = 1.41, 95%CI: 0.47–4.21, P = 0.54) and estimate (HR = 1.24, 95%CI: 0.72–2.13, P = 0.44). And this adverse impact could also be found in the subgroup analyses in multivariate analysis, especially in the stroma (HR = 1.53, 95%CI: 1.05–2.24, P = 0.03). However, the combined HR had the highly significant heterogeneity. No obvious publication bias was found.

Conclusions

SPARC might be an unfavorable indicator in patients with pancreatic cancer, especially in the stroma. More and further researches should be conducted to reveal the prognostic value of SPARC.     

Establishment and Validation of SSCLIP Scoring System to Estimate Survival in Hepatocellular Carcinoma Patients Who Received Curative Liver Resection

Background and Aims

There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients.

Methods

668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed.

Results

Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019–1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681–0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751–0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203–178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes.

Conclusions

A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.     

Prognostic Value,Clinicopathologic Features and Diagnostic Accuracy of Interleukin-8 in Colorectal Cancer: A Meta-Analysis

Background

The prognostic value and diagnostic accuracy of Interleukin-8 (IL-8) in colorectal cancer have been assessed with several studies, but the conclusions were inconclusive. Thus we performed a meta-analysis to evaluate the impact of IL-8 expression on colorectal cancer prognosis, clinicopathologic features and diagnostic accuracy.

Methods

Comprehensive search strategies were used to search relevant literature in the PubMed, EBSCO and the ISI Web of Science databases. The correlation between IL-8 expression and prognosis, clinicopathologic features and diagnostic accuracy was analyzed.

Results

A total of 18 articles met the inclusion criteria, including 1509 patients for clinicopathologic features or prognosis evaluation and 725 participants for diagnostic evaluation. The results suggested that overexpression of IL-8 was significantly associated with poor prognosis in colorectal cancer (HR = 1.54, 95%CI 1.03–2.32), especially in Union for International Cancer Control (UICC) stage IV patients (HR = 2.28, 95%CI 1.60–3.25). With further subgroup analysis, we found that high IL-8 level in serum was significantly correlated with poor prognosis (HR = 2.13, 95%CI 1.49–3.05). In addition, significant correlations were observed between high IL-8 expression and advanced stage (OR = 3.01, 95%CI 1.98–4.56), lymphatic metastasis (OR = 2.24, 95%CI 1.39–3.63), and liver metastasis (OR = 3.47, 95%CI 1.74–6.89). Moreover, IL-8 had high diagnostic accuracy, with pooled sensitivity 0.70(95%CI 0.66–0.74), specificity 0.91(95%CI 0.86–0.94), positive likelihood ratio (LR) 7.00(95%CI 2.48–19.73), negative LR 0.24(95%CI 0.09–0.64), diagnostic OR 24.00(95%CI 5.52–104.38).

Conclusions

This study showed that IL-8 could be a potential indicator for detecting colorectal cancer and predicting prognosis. In addition, high IL-8 level was significantly correlated with advanced stage, lymphatic metastasis, liver metastasis.     

The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I–III Breast Cancer Patients Undergoing Surgical Treatment

Background

Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors.

Methods

A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC).

Results

The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169–1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653–3.724, p< 0.001).

Conclusions

The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.     

Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

Background

Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients.

Method

A systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

A total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347–2.129, P < 0.001; HR = 1.611, 95%CI: 1.419–1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460–2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330–2.420, P < 0.001) and 1.709 (95%CI: 1.157–2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610–3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065–2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis.

Conclusions

Our findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression.     

Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

Background

The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.

Materials and Methods

A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.

Results

This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85).

Conclusion

Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer.     

Surgical Complications of Primary Rhegmatogenous Retinal Detachment: A Meta-Analysis

Background

To investigate the surgical complications of scleral buckling (SB) and pars plana vitrectomy (PPV) performed on primary rhegmatogenous retinal detachment (RRD) and to discover which surgical procedures bring fewer complications.

Methods

An electronic literature search using the PubMed database, ISI Web of Knowledge and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and observational studies comparing SB with PPV on primary RRD. Outcome measures included intra-operative complications and early and late post-operative complications.

Results

During the operation, significantly less subretinal hemorrhage occurred in the PPV group than in the SB group (OR = 4.71; 95%CI, 1.33–16.64; p = 0.02) and the hypotony incidence was significantly higher in the SB group (OR = 18.24; 95%CI, 2.37–140.44; p = 0.005); however, the occurrence of iatrogenic breaks was significantly lower in the SB group (OR = 0.05; 95%CI, 0.01–0.21; p<0.0001). In the early stage of post-operation, significantly higher incidence of choroidal detachment was identified in the SB group than in the PPV group (OR = 10.19; 95%CI, 2.36–44.09; p = 0.002); patients undergoing SB had significantly higher odds of residual subretinal fluid (OR = 14.71; 95%CI, 1.84–117.32; p = 0.01); the occurrence of high intraocular pressure was significantly lower in the SB group (OR = 0.46; 95%CI, 0.23–0.89; p = 0.02); and no significant difference was shown in the incidence of epithelia defect (p = 0.37) between the two groups. In the late stage of post-operation, the incidence of diplopia/extraocular muscle dysfunction was significantly higher in the SB group (OR = 4.04; 95%CI, 1.30–12.52; p = 0.02); and significantly less cataract was observed in the SB group (OR = 0.20; 95%CI, 0.14–0.30; p<0.00001); no significant difference was found in the incidences of cystoid macular edema (p = 0.65), macular pucker (p = 0.52), post-operative proliferative vitreoretinopathy (p = 0.73) and epiretinal membrane (p = 0.47) in other late post-operative complications.

Conclusions

This meta-analysis suggests that PPV could be considered as potential surgical management on primary RRD.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients

Background

There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.

Methods

We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.

Results

The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377–3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147–4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178–3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167–6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005–2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171–2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761–3.250, P = 0.222; HR = 1.432, 95%CI: 0.108–19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211–2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547–3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921–4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685–5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620–3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625–3.568, P<0.001).

Conclusions

The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.     

The Prevalence and Incidence of Atrial Fibrillation in Patients with Acute Pulmonary Embolism

Background

Symptomatic pulmonary embolism (PE) is a major cause of cardiovascular death and morbidity. Estimated prevalence and incidence of atrial fibrillation (AF) in developed countries are between 388–661 per 100,000, and 90–123 per 100,000 person-years respectively. However, the prevalence and incidence of AF in patients presenting with an acute PE and its predictors are not clear.

Methods

Individual patient clinical details were retrieved from a database containing all confirmed acute PE presentations to a tertiary institution from 2001–2012. Prevalence and incidence of AF was tracked from a population registry by systematically searching for AF during any hospital admission (2000–2013) based on International Classification of Disease (ICD-10) code.

Results

Of the 1,142 patients included in this study, 935 (81.9%) had no AF during index PE admission whilst 207 patients had documented baseline AF (prevalence rate 18,126 per 100,000; age-adjusted 4,672 per 100,000). Of the 935 patients without AF, 126 developed AF post-PE (incidence rate 2,778 per 100,000 person-years; age-adjusted 984 per 100,000 person-years). Mean time from PE to subsequent AF was 3.4 ± 2.9 years. Total mortality (mean follow-up 5.0 ± 3.7 years) was 42% (n = 478): 35% (n = 283), 59% (n = 119) and 60% (n = 76) in the no AF, baseline AF and subsequent AF cohorts respectively. Independent predictors for subsequent AF after acute PE include age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04–1.08, p<0.001), history of congestive cardiac failure (HR 1.88, 95% CI 1.12–3.16, p = 0.02), diabetes (HR 1.72, 95% CI 1.07–2.77, p = 0.02), obstructive sleep apnea (HR 4.83, 1.48–15.8, p = 0.009) and day-1 serum sodium level during index PE admission (HR 0.94, 95% CI 0.90–0.98, p = 0.002).

Conclusions

Patients presenting with acute PE have a markedly increased age-adjusted prevalence and subsequent incidence of AF. Screening for AF may be of importance post-PE.     

Elevated High-Sensitivity C-Reactive Protein Levels Predict Decreased Survival for Nasopharyngeal Carcinoma Patients in the Intensity-Modulated Radiotherapy Era

Purpose

This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era.

Patients and Methods

In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS).

Results

Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238–2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273–2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394–2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS.

Conclusion

Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.     

Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

Background

Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis.

Method

Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis.

Results

Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC.

Conclusion

This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer.     

Overhydration,Cardiac Function and Survival in Hemodialysis Patients

Background and objectives

Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered.

Design, setting, participants and measurements

A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort).

Results

In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30–3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72–4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12–3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60–4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48–7.02 for RFO >17.4%) Cox regression analysis.

Conclusions

The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.     

The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis

Background

The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.

Methods

EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.

Results

A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98–1.12; TTP: HR = 0.94, 95%CI = 0.89–1.00; ORR: RR = 1.07, 95%CI = 0.98–1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83–1.46; PFS: HR = 0.86, 95% CI = 0.67–1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10–1.79) and rash (RR = 7.43, 95% CI = 4.56–12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25–35.93) and fatigue (RR = 9.60, 95% CI = 2.28–40.86) compared with EGFR TKI monotherapy.

Conclusions

The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.     

Prognostic Value of 18F-FDG PET/CT in Surgical Non-Small Cell Lung Cancer: A Meta-Analysis

Background

The identification of surgical non-small cell lung cancer (NSCLC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. This meta-analysis explored the prognostic value of maximal standardized uptake value (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients.

Materials and Methods

MEDLINE, EMBASE and Cochrane Libraries were systematically searched until August 1, 2015. Prospective or retrospective studies that evaluated the prognostic roles of preoperative 18F-FDG PET/CT with complete DFS and OS data in surgical NSCLC patients were included. The impact of SUV_max, MTV or TLG on survival was measured using hazard ratios (HR). Sub-group analyses were performed based on disease stage, pathological classification, surgery only and cut-off values.

Results

Thirty-six studies comprised of 5807 patients were included. The combined HRs for DFS were 2.74 (95%CI 2.33–3.24, unadjusted) and 2.43 (95%CI: 1.76–3.36, adjusted) for SUV_max, 2.27 (95%CI 1.77–2.90, unadjusted) and 2.49 (95%CI 1.23–5.04, adjusted) for MTV, and 2.46 (95%CI 1.91–3.17, unadjusted) and 2.97 (95%CI 1.68–5.28, adjusted) for TLG. The pooled HRs for OS were 2.54 (95%CI 1.86–3.49, unadjusted) and 1.52 (95%CI 1.16–2.00, adjusted) for SUV_max, 2.07 (95%CI 1.16–3.69, unadjusted) and 1.91 (95%CI 1.13–3.22, adjusted) for MTV, and 2.47 (95%CI 1.38–4.43, unadjusted) and 1.94 (95%CI 1.12–3.33, adjusted) for TLG. Begg’s test detected publication bias, the trim and fill procedure was performed, and similar HRs were obtained. The prognostic role of SUV_max, MTV and TLG remained similar in the sub-group analyses.

Conclusions

High values of SUV_max, MTV and TLG predicted a higher risk of recurrence or death in patients with surgical NSCLC. We suggest the use of FDG PET/CT to select patients who are at high risk of disease recurrence or death and may benefit from aggressive treatments.     

Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

Purpose

To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy.

Methods and Materials

Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS.

Results

Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043).

Conclusion

We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.     

BTNL2 Gene Polymorphism and Sarcoidosis Susceptibility: A Meta-Analysis

Background

Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed.

Methods

PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis. Combined data indicated that BTNL2 rs2076530 polymorphism was associated with sarcoidosis susceptibility in allelic model (A vs. G, OR = 1.59, 95%CI: 1.47–1.72), dominant model (AA + AG vs. GG, OR = 2.10, 95%CI: 1.67–2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49–2.50).

Conclusions

This meta-analysis indicates that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis.     

Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

Objective

Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1) in colorectal cancer (CRC) patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features.

Methods

Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS), disease-free survival (DFS) and clinicopathological features.

Results

9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26–0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24–0.59, P < 0.0001, respectively). High ALDH1 expression was highly correlated with the tumor (T) stage (T3 + T4 vs. T1 + T2; OR = 2.16, 95%CI: 1.09–4.28, P = 0.03), lymph node (N) stage (N1 + N2 vs. N0; OR = 1.8; 95%CI: 1.17–2.79, P = 0.008), and tumor differentiation (G3 vs. G1 + G2; OR = 1.88; 95%CI: 1.07–3.30, P = 0.03). However, high ALDH1 expression was not significantly correlated with the patient age (>60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63–1.94, P = 0.72).

Conclusions

High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age.     

Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis

Objective

This study aimed to examine the prognostic value of overexpressed p16^INK4a in vulvar cancer. Although the tumor suppressor p16^INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear.

Methods

All publications in English language on the association between p16^INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios(ORs) or risk ratios(RRs) with 95% confidence intervals(CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger’s regression test.

Results

A total of 17 studies with 2309 patients were included. The p16^INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage(I+II vs III+IV; OR = 0.60,95%CI:0.41–0.86,P = 0.006),negative lymph node metastasis(negative vs positive; OR = 0.61,95%CI:0.39–0.95,P = 0.029),patient’s age<55(OR = 0.54,95%CI:0.31–0.96,P = 0.034),human papillomavirus–positive status(OR = 0.01,95%CI:0.00–0.11,P<0.001),and higher overall survival(RR = 0.53,95%CI = 0.35–0.80,P = 0.003).

Conclusion

The p16^INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.     

High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer

Purpose

Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.

Methods

Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.

Results

There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956–8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160–0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).

Conclusions

Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC.