Prognostic Value of Survivin in Patients with Gastric Cancer: A Systematic Review with Meta-Analysis

Objective

The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator.

Methods

Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients’ ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I²=74%, p=0.009).

Conclusions

This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients’ overall survival.     

Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis

Purpose

The potential prognostic value of survivin in resected non-small cell lung carcinoma (NSCLC) is variably reported. The objective of this study was to conduct a systematic review of literatures evaluating survivin expression in resected NSCLC as a prognostic indicator.

Methods

Relevant literatures were identified using PubMed, EMBASE and Chinese Biomedicine Databases. We present the results of a meta-analysis of the association between survivin expression and overall survival (OS) in NSCLC patients. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses and publication bias were also conducted.

Results

We performed a final analysis of 2703 patients from 28 evaluable studies. Combined HRs suggested that survivin overexpression had an unfavorable impact on NSCLC patients'' survival with no evidence of any significant publication bias (HR = 2.03, 95%CI: 1.78–2.33, Egger''s test, P = 0.24) and no severe heterogeneity between studies (I² = 26.9%). Its effect also appeared significant when stratified according to the studies categorized by histological type, HR estimate, patient race, cutoff point (5%, 10%), detection methods and literature written language except for disease stage. Survivin was identified as a prognostic marker of advanced-stage NSCLC (HR = 1.93, 95%CI: 1.49-2.51), but not early-stage NSCLC (HR = 1.97, 95%CI: 0.76-5.14), in spite of the combined data being relatively small.

Conclusion

This study shows that survivin expression appears to be a pejorative prognostic factor in terms of overall survival in surgically treated NSCLC. Large prospective studies are now needed to confirm the clinical utility of survivin as an independent prognostic marker.     

Prognostic Value of Human Equilibrative NucleosideTransporter1 in Pancreatic Cancer Receiving Gemcitabin-Based Chemotherapy: A Meta-Analysis

Background

The potential prognostic value of human equilibrative nucleoside transporter1 in pancreatic cancer receiving gemcitabine-based chemotherapy is variably reported.

Objective

The objective of this study was to conduct a systematic review of literature evaluating human equilibrative nucleoside transporter1 expression as a prognostic factor in pancreatic cancer receiving gemcitabine-based chemotherapy and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods

Related studies were identified and evaluated for quality through multiple search strategies. Only studies analyzing pancreatic cancer receiving gemcitabine-based chemotherapy were eligible for inclusion. Data were collected from studies comparing overall, disease-free and progression-free survival (OS, DFS and PFS) in patients with low human equilibrative nucleoside transporter1 levels and those having high levels. The hazard ratio (HR) and its 95% confidence interval (95%CI) were used to assess the strength of associations. Hazard ratios greater than 1 reflect adverse survival associated with low human equilibrative nucleoside transporter1 levels.

Results

A total of 12 studies (n = 875) were involved in this meta-analysis (12 for OS, 5 for DFS, 3 for PFS). For overall and disease-free survival, the pooled HRs of human equilibrative nucleoside transporter1 were significant at 2.93 (95% confidence interval [95% CI], 2.37–3.64) and 2.67 (95% CI, 1.87–3.81), respectively. For progression-free survival, the pooled HR in higher human equilibrative nucleoside transporter1 expression in pancreatic cancer receiving gemcitabine-based chemotherapy was 2.76 (95% CI, 1.76–4.34). No evidence of significant heterogeneity or publication bias was seen in any of these studies.

Conclusion

These results support the case for a low human equilibrative nucleoside transporter1 level representing a significant and reproducible marker of adverse prognosis in pancreatic cancer receiving gemcitabine-based chemotherapy.     

Prognostic Role of Survivin in Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose

The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on bladder cancer prognosis.

Materials and Methods

We carefully searched online Pubmed, Cochrane Library and SCOPUS database from August 1997 to May 2013.

Results

A total of 14 articles met the eligibility criteria for this systematic review. The eligible studies included a total of 2,165 patients with a median number of 155 patients per study (range: 17–726). Of the 14 studies, nine evaluated immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. In non-muscle invasive bladder tumor, the pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.81; 95% confidence interval [CI], 1.30–2.52), progression-free survival (pooled HR, 2.12; 95% CI, 1.60–2.82), cancer-specific survival (pooled HR, 2.01; 95% CI, 1.32–3.06), and overall survival (pooled HR, 1.53; 95% CI, 1.02–2.29). The overall HRs by survivin status were robust across advanced stages. When only adjusted survival data were included, statistically significant differences were identified for all survival subgroup analyses. There was no between-study heterogeneity in the effect of survivin status on the majority of meta-analyses. There was no clear evidence of publication bias in this meta-analysis.

Conclusions

Survivin expression indicates worse prognosis in patients with bladder cancer but the results should be interpreted with caution. It is necessary that better-designed studies with standardized assays need to provide a better conclusion about the relationship between survivin expression and the outcome of patients with bladder cancer.     

Prognostic Role of Pre-Treatment Serum AFP-L3% in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Background

Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.

Methods

Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.

Results

Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).

Conclusion

The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.     

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

Background

The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.

Methods

Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.

Results

There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.

Conclusion

The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.     

Clinicopathological and Prognostic Significance of Survivin Over-Expression in Patients with Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Background

The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis.

Methodology

Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed.

Principal Findings

Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients'' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45–2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96–5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14–0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC.

Conclusions

This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC.     

HIF1-Alpha Expression Predicts Survival of Patients with Squamous Cell Carcinoma of the Oral Cavity

Background

Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood.

Patients and Methods

In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth.

Results

Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse.

Conclusion

These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient.     

Prognostic Value of Ezrin in Solid Tumors: A Meta-Analysis of the Literature

Purpose

Ezrin is a cytoskeletal protein involved in tumor growth and invasion. However its prognostic value for survival in patients with solid tumor remains controversial.

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results

Twenty-seven eligible trials involving 4693 patients were ultimately identified. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive Ezrin expression had an impact on overall survival (OS) [1.95, 95% confidence interval (CI) 1.60–2.39; P<0.001] in all eligible studies and progress free survival (PFS): (2.30 95% CI 1.0–3.61; P = 0.001). Similar results were also observed in subgroup analysis, according to tumor types, regions, patients'' number and publication year.

Conclusions

Our findings suggested that Ezrin protein expression might be a factor for a poor prognosis in patients with solid tumor. So large well-designed prospective studies are now needed to confirm the clinical utility of Ezrin as an independent prognostic marker.     

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective

The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients.

Methods

The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival.

Results

Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001).

Conclusion

Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.     

LAPTM4B allele *2 is a marker of poor prognosis following hepatic tumor resection for hepatocellular carcinoma

Background

Lysosomal protein transmembrane 4 beta (LAPTM4B) is a gene related to hepatocellular carcinoma that has two alleles designated LAPTM4B*1 and LAPTM4B*2. This study aimed to investigate the correlation of LAPTM4B genotype with prognosis and clinicopathologic features in patients who have undergone resection for hepatocellular carcinoma (HCC).

Methodology/Principal Findings

The LAPTM4B genotype was analyzed by PCR in 68 patients who had undergone curative hepatic resection for hepatocellular carcinoma. The correlation of LAPTM4B genotype with clinicopathologic parameters was assessed with the Chi-squared test. Differences in patient survival were determined by the Kaplan–Meier method. Multivariate analysis of prognostic factors was carried out with Cox regression analysis. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both P<0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both P<0.001).

Conclusions/Significance

Allele *2 of LAPTM4B is a risk factor associated with poor prognosis in patients with resected HCC. LAPTM4B status may be useful preoperatively as an adjunct in evaluation of the operability of HCC.     

Circulating Tumor Cells in Patients with Recurrent or Metastatic Head and Neck Carcinoma: Prognostic and Predictive Significance

Introduction

We investigated the frequency of detection and the prognostic and predictive significance of circulating tumor cells (CTCs) in patients with recurrent/metastatic (R/M) head and neck carcinoma (HNC) before starting systemic therapy.

Patients and methods

Using the CellSearch technology, CTCs were assessed prospectively in peripheral blood of 53 R/M-HNC patients. We performed spiking experiments to test the diagnostic performance of the CellSearch platform in identifying squamous carcinoma cells.

Results

CTCs were identified in 14 (26%) and 22 (41%) patients at baseline and at any time point, respectively. In univariate analysis ≥2 CTCs had a poorer prognostic role than 0–1 CTC. In multivariate analysis, the presence of one CTC or more was associated with a poor prognosis both in terms of progression-free survival (PFS) [Hazard Ratio (HR): 3.068, 95% confidence interval (CI): 1.53–6.13, p 0.002] and overall survival (OS) [HR: 3.0, 95% CI: 1.48–6.0, p 0.002]. A disease control after systemic therapy was obtained in 8% of CTC-positive patients as opposed to 45% in CTC-negative ones (p 0.03). The epidermal growth factor receptor (EGFR) expression was identified in 45% of CTC-positive patients.

Discussion

In conclusion, CTCs are detected in one out of three patients with RM-HNC. CTC detection is a strong prognostic parameter and may be predictive of treatment efficacy. The frequency of EGFR expression in CTCs seems to be lower than that expected in the primary tumor.     

Prognostic Significance of EBV Latent Membrane Protein 1 Expression in Lymphomas: Evidence from 15 Studies

Background

Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma.

Methods

The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival.

Results

Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92–1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR  = 1.84, 95% CI: 1.02–3.34), but not with survival of patients with Hodgkin disease (HD) (HR  =  1.03, 95% CI: 0.74–1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value.

Conclusions

This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression.     

The Prognostic Value of SOX2 Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.

Methods

Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.

Results

A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).

Conclusions

SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.     

Prognostic Value of FGFR Gene Amplification in Patients with Different Types of Cancer: A Systematic Review and Meta-Analysis

Background

Fibroblast growth factor receptor (FGFR) gene amplification has been reported in different types of cancer. We performed an up-to-date meta-analysis to further characterize the prognostic value of FGFR gene amplification in patients with cancer.

Methods

A search of several databases, including MEDLINE (PubMed), EMBASE, Web of Science, and China National Knowledge Infrastructure, was conducted to identify studies examining the association between FGFR gene amplification and cancer. A total of 24 studies met the inclusion criteria, and overall incidence rates, hazard risk (HR), overall survival, disease-free survival, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included studies.

Results

In the meta-analysis of 24 studies, the prevalence of FGFR gene amplification was FGFR1: 0.11 (95% CI: 0.08–0.13) and FGFR2: 0.04 (95% CI: 0.02–0.06). Overall survival was significantly worse among patients with FGFR gene amplification: FGFR1 [HR 1.57 (95% CI: 1.23–1.99); p = 0.0002] and FGFR2 [HR 2.27 (95% CI: 1.73–3.00); p<0.00001].

Conclusions

Current evidence supports the conclusion that the outcomes of patients with FGFR gene amplified cancers is worse than for those with non-FGFR gene amplified cancers.     

High Weight Loss during Radiation Treatment Changes the Prognosis in Under-/Normal Weight Nasopharyngeal Carcinoma Patients for the Worse: A Retrospective Analysis of 2433 Cases

Background

Although weight loss is common in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, the prognostic influence of weight loss and its impact modified by body mass index (BMI) are still unclear.

Methods

2433 NPC patients receiving radical radiotherapy at Sun Yat-sen University Cancer Center from November, 2000 to December, 2004 were enrolled. Weight change during radiation treatment was categorized into high weight loss (HWL) and low weight loss (LWL). The associations of HWL with overall survival (OS) and disease-specific survival (DSS) were analyzed by Cox regression.

Results

Among underweight patients, HWL was independently associated with poor OS (hazard ratio [HR], 2.06; 95% CI 1.36–3.11) and DSS (HR, 2.27; 95% CI 1.38–3.73), as compared with LWL, after adjusting for covariates. In normal weight patients, the impact of HWL on OS (HR, 1.47; 95% CI 1.19–1.80) and DSS (HR, 1.59; 95% CI 1.24–2.03) was moderate. Among overweight/obese patients, no significant association between HWL and OS (HR, 1.22; 95% CI 0.95–1.55), or DSS (HR, 1.23; 95% CI 0.93–1.64) was found.

Conclusion

Except for overweight/obese patients, high weight loss during radiation treatment was independently associated with poor survival in NPC. This impact was more prominent in the underweight patient group.     

Prognostic Significance of COX-2 Immunohistochemical Expression in Colorectal Cancer: A Meta-Analysis of the Literature

Background

Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial.

Methods

Electronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed.

Results

We performed a meta-analysis of 23 studies (n  =  4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio]  =  1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR  =  1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer.

Conclusions

Cox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified.     

Analysis of FoxP3+ T-Regulatory Cells and CD8+T-Cells in Ovarian Carcinoma: Location and Tumor Infiltration Patterns Are Key Prognostic Markers

Purpose

Tumor infiltrating CD4+CD25+FoxP3+ regulatory immune cells (Treg) have been associated with impaired anti- tumor immune response and unfavorable prognosis for patients affected by ovarian carcinoma, whereas CD8+ T-cells have been found to positively influence survival rates in a large panel of solid tumors. Recently, density, location and tumor infiltration patterns of the respective immune cell subtypes have been identified as key prognostic factors for different types of tumors.

Patients and Methods

We stained 210 human ovarian carcinoma samples immunhistochemically for FoxP3 and CD8 to identify the impact different immune cell patterns have on generally accepted prognostic variables as well as on overall survival.

Results

We found that FoxP3+ cells located within lymphoid aggregates surrounding the tumor were strongly associated with reduced survival time (P = 0.007). Central accumulation of CD8+ effector cells within the tumor bed shows a positive effect on survival (P = 0,001).

Conclusion

The distribution pattern of immune cells within the tumor environment strongly influences prognosis and overall survival time of patients with ovarian carcinoma.     

Nucleot(s)ide Analogues for Hepatitis B Virus-Related Hepatocellular Carcinoma after Curative Treatment: A Systematic Review and Meta-Analysis

Aim

The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment has been widely debated due to the relatively weak evidence. The objective of this systematic review was to evaluate the effect of NA on recurrence and survival after curative treatment of HBV-HCC.

Methods

A systematic electronic search was performed. All controlled trials comparing NA versus placebo or no treatment were considered for inclusion. Results were expressed as Hazard Ratio for recurrence and survival with 95% confidence intervals using RevMan 5.2.

Results

We included 13 trials with 6350 patients. There were significant improvements for recurrence-free survival (HR 0.66, 95% CI 0.54–0.80; p<0.0001) and overall survival (HR 0.56, 95% CI 0.43–0.73; p<0.0001) in the adjuvant NA group compared with the control group. Sensitivity analyses confirmed the robustness of the results. There were no serious adverse effects being reported. Lamivudine resistance was from 28.6% to 37.5% but could be rescued by other types of NA or combination therapy.

Conclusion

Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving clinical and viral parameters besides HCC, further studies should be focused on broadening the indications for NA therapy after curative treatment of HBV-HCC.     

Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer

Background

To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum).

Patients and methods

This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints.

Results

Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007).

Conclusions

This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.