Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma: A Meta-Analysis

Backgrounds

Hepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.

Methods

A systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).

Results

Total 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37–0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28–0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25–0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54–1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52–0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48–0.90, Z = 2.64, P = 0.008). And what’s more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16–0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59–0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21–0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38–0.98, Z = 2.05, P = 0.04).

Conclusions

Reduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.     

CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

Objective

CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.

Methods

A comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software.

Results

We found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54–0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52–0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01–1.23, P = 0.03), 1.31 (95%CI 1.06–1.63, P = 0.01) and 1.24 (95%CI 1.08–1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters.

Conclusion

Our meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients.     

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.     

Socio-Demographic and Geographical Factors in Esophageal and Gastric Cancer Mortality in Sweden

Background

Socio-demographic factors and area of residence might influence the development of esophageal and gastric cancer. Large-scale population-based research can determine the role of such factors.

Methods

This population-based cohort study included all Swedish residents aged 30–84 years in 1990–2007. Educational level, marital status, place of birth, and place of residence were evaluated with regard to mortality from esophageal or gastric cancer. Cox regression yielded hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounding.

Results

Among 84 920 565 person-years, 5125 and 12 230 deaths occurred from esophageal cancer and gastric cancer, respectively. Higher educational level decreased the HR of esophageal cancer (HR = 0.61, 95%CI 0.42–0.90 in women, HR = 0.71, 95%CI 0.60–0.84 in men) and gastric cancer (HR = 0.80, 95%CI 0.63–1.03 in women, HR = 0.73, 95%CI 0.64–0.83 in men). Being unmarried increased HR of esophageal cancer (HR = 1.64, 95%CI 1.35–1.99 in women, HR = 1.64, 95%CI 1.50–1.80 in men), but not of gastric cancer. Being born in low density populated areas increased HR of gastric cancer (HR = 1.23, 95%CI 1.10–1.38 in women, HR = 1.37, 95%CI 1.25–1.50 in men), while no strong association was found with esophageal cancer. Living in densely populated areas increased HR of esophageal cancer (HR = 1.31, 95%CI 1.14–1.50 in women, HR = 1.40, 95%CI 1.29–1.51 in men), but not of gastric cancer.

Conclusion

These socio-demographic inequalities in cancer mortality warrant efforts to investigate possible preventable mechanisms and to promote and support healthier lifestyles among deprived groups.     

Presence of CHD1L Over-Expression Is Associated with Aggressive Tumor Biology and Is a Novel Prognostic Biomarker for Patient Survival in Human Breast Cancer

Background

The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.

Material and Methods

In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines.

Results

Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line.

Conclusions

Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer.     

Whole Brain Radiotherapy Plus Concurrent Chemotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: A Meta-Analysis

Objective

The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST) and toxicity in patients with brain metastases (BM) originating from non-small cell lung cancer (NSCLC) and who were treated using either whole brain radiotherapy (WBRT) plus concurrent chemotherapy or WBRT alone.

Methods

PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.

Results

In total, six randomized controlled trials (RCT) involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019) than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST) (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233) or time of neurological progression (CNS-TTP) (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543), and increased adverse events (Grade≥3) (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000). There were no significant differences in Grade 3–5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92).

Conclusion

The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.     

No Survival Benefit from Adding Cetuximab or Panitumumab to Oxaliplatin-Based Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer in KRAS Wild Type Patients: A Meta-Analysis

Background

The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MAbs) remains controversial in colorectal cancer (CRC). The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC) through meta-analysis.

Methods

Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab) in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. Hazard ratios (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals.

Results

This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn’t result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95) or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13). The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75) or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36). Patients who received combined therapy didn’t have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]). Toxicities slightly increased in anti-EGFR drugs group.

Conclusions

The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in survival benefit and response rate. More RCTs are warranted to evaluate the combination of chemotherapy and targeted therapy.     

Meta-Analysis of the Association between COX-2 Polymorphisms and Risk of Colorectal Cancer Based on Case–Control Studies

Objective

Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association.

Methods

All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).

Results

Ten studies with 6,774 cases and 9,772 controls were included for −1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for −765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to −765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113–1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295–3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297–3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to −1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses.

Conclusions

The present meta-analysis suggests that the COX-2 −765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association.     

Androgen Deprivation Therapy for Prostate Cancer Is Associated with Cardiovascular Morbidity and Mortality: A Meta-Analysis of Population-Based Observational Studies

Background

There is no consensus regarding whether androgen deprivation therapy (ADT) is associated with cardiovascular disease (CVD) and cardiovascular mortality (CVM). The objective of this study was to determine the role of ADT for prostate cancer (PCa) in development of cardiovascular events (CVD and CVM).

Methods and Findings

We performed a meta-analysis from population-based observational studies comparing ADT vs control aimed at treating PCa in patients with PCa, reporting either CVD or CVM as outcome. Publications were searched using Medline, Embase, Cochrane Library Central Register of observational studies database up to May 31th 2014, and supplementary searches in publications from potentially relevant journals. 6 studies were identified with a total of 129,802 ADT users and 165,605 controls investigating the relationship between ADT and CVD. The incidence of CVD was 10% higher in ADT groups, although no significant association was observed (HR = 1.10, 95%CIs: 1.00–1.21; P = 0.06). For different types of ADT, CVD was related with gonadotropin-releasing hormone (GnRH) (HR = 1.19, 95%CIs: 1.04–1.36; P<0.001) and GnRH plus oral antiandrogen (AA) (HR = 1.46, 95%CIs: 1.03–2.08; P = 0.04), but not with AA alone or orchiectomy. For CVM, 119,625 ADT users and 150,974 controls from 6 eligible studies were included, pooled results suggested that ADT was associated with CVM (HR = 1.17, 95%CIs: 1.04–1.32; P = 0.01). Significantly increased CVM was also detected in GnRH and GnRH plus AA groups. When patients received other treatments (e.g. prostatectomy and radiotherapy) were ruled out of consideration, more increased CVD (HR = 1.19, 95%CIs: 1.08–1.30; P<0.001) and CVM (HR = 1.30, 95%CIs: 1.13–1.50; P<0.001) were found in men treated with ADT monotherapy.

Conclusions

ADT is associated with both CVD and CVM. Particularly, GnRH alone and GnRH plus AA can significantly increase the incidence of cardiovascular events in patients with PCa.     

Impact of Risk Factors on Different Interval Cancer Subtypes in a Population-Based Breast Cancer Screening Programme

Background

Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers.

Methods

We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000–2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women''s characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes.

Results

A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28–3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24–12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59–3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60–2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23–2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58–9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18–2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00–2.49).

Conclusion

The role of women''s characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.     

Memory Concerns,Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment

Background

Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).

Methods

We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.

Results

Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.

Conclusions

Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.     

Smoking Modifies the Associated Increased Risk of Future Cardiovascular Disease by Genetic Variation on Chromosome 9p21

Aims

Genetic predisposition for cardiovascular disease (CVD) is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors.

Methods and results

A total of 24944 middle-aged subjects (62% females) from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309), ischemic stroke (N = 1253) and CVD-mortality (N = 1156). Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035) and CVD-mortality (P = 0.012). The hazard ratios (HR) per risk allele of rs4977574 were highest in never smokers (N = 9642) for CAD (HR = 1.26; 95% CI 1.13–1.40; P<0.001) and for CVD-mortality (HR = 1.40; 95% CI 1.20–1.63; P<0.001), whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000) for both CAD (HR = 1.05; 95%CI 0.95–1.16; P = 0.326) and CVD-mortality (HR = 1.08; 95%CI 0.94–1.23; P = 0.270). A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574.

Conclusion

Smoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.     

Early Hemoperfusion May Improve Survival of Severely Paraquat-Poisoned Patients

Background

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2−4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown.

Methods

We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed.

Results

The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16–0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39–0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05–0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24–0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables.

Conclusion

The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.     

Immediate Postmastectomy Breast Reconstruction Showed Limited Advantage in Patient Survival after Stratifying by Family Income

Background

Postmastectomy breast reconstruction is widely used in breast cancer patients for its aesthetic effect. Although several studies have casted suspicion upon the oncological safety of immediate breast reconstruction after mastectomy, the potential impact of different reconstruction methods on patient survival remains unclear.

Patients and Methods

We identified 35,126 female patients diagnosed with breast cancer from January 1, 1998 to December 31, 2002 in the Surveillance, Epidemiology, and End Results database. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients who underwent mastectomy with or without immediate breast reconstruction (autologous reconstruction or implant reconstruction) using Cox proportional hazard regression models.

Results

In multivariate analysis unadjusted for family income, patients undergoing immediate postmastectomy reconstruction exhibited improved BCSS [pooled reconstruction (any types of reconstruction): hazard ratio (HR)  =  0.87, 95% confidence interval (CI) 0.80–0.95, P = 0.001] and OS (pooled reconstruction: HR = 0.70, 95% CI 0.65–0.75, P<0.001) compared to patients who underwent mastectomy alone. However, after stratifying by family income, patients receiving reconstruction showed limited advantage in BCSS and OS compared with those undergoing mastectomy alone. When comparing between the two reconstruction methods, no significant differences were observed in either BCSS (implant versus autologous reconstruction: HR = 1.11, 95%CI 0.90–1.35, P = 0.330) or OS (implant versus autologous reconstruction: HR = 1.07, 95% 0.90–1.28, P = 0.424).

Conclusions

Compared to mastectomy alone, immediate postmastectomy reconstruction had limited advantage in survival after adjusting for confounding factor of family income. Our findings, if validated in other large databases, may help to illustrate the actual effect of immediate postmastectomy reconstruction on patient survival.     

Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer

Background

Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.

Material and Methods

IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.

Results

160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).

Conclusion

Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer.     

Benefits of Therapeutic Drug Monitoring of Vancomycin: A Systematic Review and Meta-Analysis

Background and Objective

The necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections.

Methods

Medline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively.

Results

One randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34–5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13–0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34–6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34–6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = −0.40, 95%CI −2.83–2.02 P = 0.74) or length of stay (WMD = −1.01, 95%CI −7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported mortality rates.

Conclusions

Studies to date show that TDM significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin.     

Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

Objective

The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.

Methods

A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.

Results

A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.

Conclusion

CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.     

Association between Common Allergic Symptoms and Cancer in the NHANES III Female Cohort

Background

Previous epidemiological studies have investigated the association between allergic symptoms and cancer occurrence. However, the role of allergy in cancer has been elusive, especially for the female population.

Methods

We examined the relationship between cancer prevalence and common allergic symptoms of rhinoconjunctivitis (RC) and wheezing (WZ) among NHANES III female participants.

Results

Among 4600 people, 36.3% (n = 1669) did not have any allergic symptoms (NO), while 47.6% (n = 2188) reported RC, and 16.2% (n = 743), WZ. The proportion of cancer among NO groups was 5.43% (91/1669), among RC group, 7.63% (167/2188), and among WZ group, 11.23% (83/743) (RC group- OR 1.44 with 95% CI 1.00–2.08; p = 0.05 while for WZ group- OR 2.20 with 95%CI 1.27–3.80; p = 0.01). After adjusting for all the possible confounding variables including age, smoking, or COPD, having symptoms of RC (AOR 1.49 with 95%CI 1.12–2.36; p = 0.01) or WC (AOR 2.08 with 95%CI 1.11–3.89; p = 0.02) demonstrated consistent strong association with cancer. Among nonsmokers (n = 2505, 54.5%) only symptoms of RC showed association with cancer (AOR 1.51 with 95%CI 1.00–2.28; p = 0.05). Among former or current smokers (n = 2094, 45.5%), only symptoms of WZ demonstrated association with cancer (AOR 2.38 with 95%CI 1.16–4.87; p = 0.02). Among different types of cancers, odds of having breast cancer among participants with symptoms of RC or WZ were approximately twice the odds of having breast cancer among participants without any of these symptoms. AOR for RC group was 1.89 with 95%CI 1.04–3.42 and p = 0.04 while AOR for WC group was 2.08 with 95%CI 0.90–4.78 and p = 0.08.

Conclusions

In summary, we found associations between common allergic symptoms like rhinitis/conjunctivitis and wheezing and prevalence of cancer, specifically between rhinitis/conjunctivitis and breast cancer that were not found in previous studies. Larger prospective studies are required to validate our findings.     

Prognostic Significance of Tumor-Associated Macrophages in Solid Tumor: A Meta-Analysis of the Literature

Purpose

Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial.

Experimental Design

We conducted a meta-analysis of 55 studies (n = 8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS). The impact of M1 and M2 type TAM (n = 5) on survival was also examined.

Results

High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR)  = 1.20 (95% confidence interval (CI), 1.14–1.28)] and bladder cancer [RR = 3.30 (95%CI, 1.56–6.96)] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35–0.77)]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24–2.16)], breast cancer [RR = 8.62 (95%CI, 3.10–23.95)], bladder cancer [RR = 5.00 (95%CI, 1.98–12.63)], ovarian cancer [RR = 2.55 (95%CI, 1.60–4.06)], oral cancer [RR = 2.03 (95%CI, 1.47–2.80)] and thyroid cancer [RR = 2.72 (95%CI, 1.26–5.86)],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43–0.96)]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival.

Conclusions

Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.     

Prognostic Role of MicroRNA-221 in Various Human Malignant Neoplasms: A Meta-Analysis of 20 Related Studies

Background

MicroRNA-221 (miR-221) has been shown to play an important role in cancer prognosis. In order to evaluate the predictive value of miR-221, we compiled the evidence from 20 eligible studies to perform a meta-analysis.

Design

All of relevant studies were identified by searching PubMed, Embase, and Web of Science, and were assessed by further quality evaluation. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and stratified analyses, for overall survival (OS) and recurrence-free survival (RFS), were calculated to investigate the association between high miR-221 expression and cancer prognosis.

Results

We found that high miR-221 expression can predict a poor OS in malignant tumors (pooled HR = 1.55, P = 0.017) but has no significant association with RFS (pooled HR = 1.02, P = 0.942). Further in stratified analyses, high miR-221 expression was significantly associated with a poor OS in Asians (pooled HR = 2.04, P = 0.010) or serum/ plasma subgroup (pooled HR = 2.28, P<0.001), and even showed significantly poor OS (pooled HR = 1.80, P<0.001) and RFS (pooled HR = 2.43, P = 0.010) in hepatocellular carcinoma (HCC) subgroup, but was correlated to a favorable RFS in prostate cancer subgroup (pooled HR = 0.51, P = 0.004).

Conclusions

Our findings demonstrate that miR-221 is more suitable to predict cancer prognosis in Asians, and it is a promising prognostic biomarker for HCC. The detection of miR-221 in serum or plasma samples may make it become an effective method for monitoring patients'' prognosis and assessing therapeutic efficacy in the future.