Combined Ablation and Resection (CARe) as an Effective Parenchymal Sparing Treatment for Extensive Colorectal Liver Metastases

Background

Combined intra-operative ablation and resection (CARe) is proposed to treat extensive colorectal liver metastases (CLM). This multicenter study was conducted to evaluate overall survival (OS), local recurrence-free survival (LRFS), hepatic recurrence-free survival (HRFS) and progression-free survival (PFS), to identify factors associated with survival, and to report complications.

Materials and Methods

Four centers combined retropectively their clinical experiences regarding CLM treated by CARe. CLM characteristics, pre- and post-operative chemotherapy regimens, surgical procedures, complications and survivals were analyzed.

Results

Of the 288 patients who received CARe, 210 (73%) had synchronous and 255 (88%) had bilateral CLM. Twenty-two patients (8%) had extrahepatic disease. Median follow-up was 3.17 years (95%CI 2.83–4.08). Median OS was 3.33 years (95%CI 3.08–4.17) and 5-year OS was 37% (95%CI 29–45). One- and 5-year LRFS from ablated lesions were 87.9% (95%CI 83.3–91.2) and 78.0% (95%CI 71–83), respectively. Median HRFS and PFS were 14 months (95%CI 11–18) and 9 months (95%CI 8–11), respectively. One hundred patients experienced complications: 29 grade I, 68 grade II–III–IV, and three deaths. In the multivariate models adjusted for center, the occurrence of complications was confirmed as a major independent factor associated with 3-year OS (HR 1.80; P = 0.008). Five-year OS was 25.6% (95%CI 14.9–37.6) for patients with complications and 45% (95%CI 33.3–53.4) for patients without.

Conclusions

Recent strategies facing advanced CLM include non-anatomic resections, portal-induced hypertrophy of the future remnant liver and aggressive medical preoperative treatments. CARe has the qualities of an approach that allows effective tumor clearance while maintaining good tolerance for the patient.     

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.     

Downregulated E-Cadherin Expression Indicates Worse Prognosis in Asian Patients with Colorectal Cancer: Evidence from Meta-Analysis

Background

Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.

Methodology

Eligible studies were searched from the PubMed, Embase and Web of Science databases. Correlation between E-cadherin expression and clinicopathological features and prognosis was analyzed. Subgroup analysis was also performed according to study location, number of patients, quality score of studies and cut-off value.

Principal Findings

A total of 27 studies comprising 4244 cases met the inclusion criteria. Meta-analysis suggested that downregulated E-cadherin expression had an unfavorable impact on overall survival (OS) of CRC (n = 2730 in 14 studies; HR = 2.27, 95%CI: 1.63–3.17; Z = 4.83; P = 0.000). Subgroup analysis indicated that low E-cadherin expression was significantly associated with worse OS in Asian patients (n = 1054 in 9 studies; HR = 2.86, 95%CI: 2.13–3.7, Z = 7.11; P = 0.000) but not in European patients (n = 1552 in 4 studies; HR = 1.14, 95%CI: 0.95–1.35, Z = 1.39; P = 0.165). In addition, reduced E-cadherin expression indicated an unfavorable OS only when the cut off value of low E-cadherin expression was >50% (n = 512 in 4 studies; HR = 2.08, 95%CI 1.45–2.94, Z = 4.05; P = 0.000). Downregulated E-cadherin expression was greatly related with differentiation grade, Dukes'' stages, lymphnode status and metastasis. The pooled OR was 0.36(95%CI: 0.19–0.7, Z = 3.03, P = 0.002), 0.34(95%CI: 0.21–0.55, Z = 6.61, P = 0.000), 0.49(95%CI: 0.32–0.74, Z = 3.02, P = 0.002) and 0.45(95%CI: 0.22–0.91, Z = 3.43, P = 0.001), respectively.

Conclusions

This study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC. However, downregulated E-cadherin expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients. Additionally, this meta-analysis suggested that the negative threshold of E-cadherin should be >50% when we detected its expression in the immunohistochemistry stain.     

Genetic Variant rs7758229 in 6q26–q27 Is Not Associated with Colorectal Cancer Risk in a Chinese Population

Background

A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.

Methods

We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations.

Results

No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI  = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR  = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR  = 0.96, 95%CI  = 0.82–1.13, P = 0.621 for rectum cancer).

Conclusions

Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population.     

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.     

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.     

Association of Thymidylate Synthase Polymorphisms with Acute Pancreatitis and/or Peripheral Neuropathy in HIV-Infected Patients on Stavudine-Based Therapy

Background

Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy.

Methods

We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student’s t test, Pearson’s correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done.

Results

Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10–5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33–6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23–7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; OR_A+B = 0.34 [95%CI: 0.08 to 1.44], OR_B+A = 3.38 [95%CI: 1.33 to 8.57], OR_B+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm³ (OR = 0.38; 95%CI: 0.17–0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18–0.85, P = 0.018).

Conclusions

Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients.     

Association of Three Common Single Nucleotide Polymorphisms of ATP Binding Cassette G8 Gene with Gallstone Disease: A Meta-Analysis

Background

In this study, we evaluated the association between these polymorphisms and gallstone disease using meta-analysis and compared the hepatic ABCG5/G8 mRNA expression and biliary lipids composition in patients with different genotypes of T400K and Y54C.

Methods

Data were analyzed using the Stata/SE 11.0 software and a random- effects model was applied irrespective of between-study heterogeneity. Hepatic mRNA expression of ABCG5/G8 genes in 182 patients with gallstone disease and 35 gallstone-free patients who underwent cholecystectomy were determined using real-time PCR. Genotypes of Y54C and T400K in the ABCG8 gene were determined by allelic discrimination using either genomic DNA or hepatic cDNA as template by Taqman assays. Biliary compostion in gallbladder bile was assayed in these patients as well.

Results

Ten papers including 13 cohorts were included for the final analysis. In the genotype model, the overall association between genotype with gallstone was significant for D19H (OR = 2.43, 95%CI: 2.23–2.64, P<0.001), and for Y54C (OR = 1.36, 95%CI: 1.01–1.83, P = 0.044), or T400K (OR = 1.17, 95%CI: 0.96–1.43. P = 0.110). In allele model, minor alleles of D19H polymorphism (allele D: OR = 2.25, 95%CI: 2.10–2.42, P<0.001) and of T400K polymorphism (allele K: OR = 1.18, 95%CI: 1.06–1.31, P<0.001) were related with an increased risk of gallstone disease. However, minor allele of Y54C polymorphism (allele Y, OR = 1.08, 95%CI: 0.96–1.21, P = 0.146) was not related with gallstone disease. I ² statistics indicated no significant between-study heterogeneity for all genetic models for any of the three polymorphisms. Funnel plot and Egger’s test suggested the absence of publication bias as well. However, no association of T400K and Y54C polymorphism with hepatic ABCG8/G5 mRNA expression or biliary lipids composition was found.

Conclusions

Our study showed strong association of D19H polymorphism with gallstone disease. T400K and Y54C polymorphism, though to a less extent, may also relate with gallstone disease.     

Investigation of Variants in UCP2 in Chinese Type 2 Diabetes and Diabetic Retinopathy

Purpose

The aim of this study was to investigate variants in UCP2 genes in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population.

Materials and Methods

We conducted a single nucleotide polymorphism-based and haplotype-based case-control study between the variants of UCP2 and DM and between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and 479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected as genetic markers.

Results

The risk allele C at UCP2 rs660339 was closely associated with DM in Chinese population. There was significant difference in rs660339 between DM and controls (P = 0.0016; OR [95%CI]  = 1.37 (1.14–1.65)). Subjects who were homozygous of the C allele were more likely to develop DM. The frequency of C allele was higher in DM (58%) than in control (51%). But this locus didn''t have a definite effect on the onset of non-proliferative diabetic retinopathy (NPDR) (P = 0.44; OR [95%CI]  = 0.80 (0.56–1.14)) and proliferative diabetic retinopathy (PDR) (P = 1.00; OR [95%CI]  = 0.99 (0.74–1.34)) comparing to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2 rs659366 polymorphism showed no significant difference between DM and control (P = 0.66; OR [95%CI]  = 1.10 (0.91–1.32)). However, there was a significant difference between PDR and DWR (P = 0.016; OR [95%CI]  = 0.66 (0.49–0.90)), but there was no difference between NPDR and DWR (P = 1.00; OR [95%CI]  = 0.96 (0.67–1.37)). Participants who carried the G allele at rs659366 were more likely to develop PDR. For the haplotype, C-A was present more frequently in DM than in control (16% vs 7%), indicating that it was risky, and T-A was present less in DM than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no significant difference (P = 0.068).

Conclusion

It was indicated that UCP2 may be implicated in the pathogenesis of type 2 DM and DR in Chinese population.     

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.     

Is Hepatitis B Immunoglobulin Necessary in Prophylaxis of Hepatitis B Recurrence after Liver Transplantation? A Meta-Analysis

Background & Aims

Application of nucleoside analogues and hepatitis B immunoglobulin (HBIG) has reduced hepatitis B virus (HBV) recurrence rate after liver transplantation (LT) dramatically. Recent data suggests therapy without HBIG is also effective. We sought to evaluate the necessity of HBIG in prophylaxis of HBV recurrence after LT.

Methods

A meta-analysis was performed. PubMed/MEDLINE, Web of Knowledge and other databases were searched for eligible literatures. The major end points were recurrence rate, patient survival, and YMDD mutant. Risk difference (RD) or risk ratio (RR) was calculated to synthesize the results.

Results

Nineteen studies with a total of 1484 patients were included in this analysis. Application of HBIG was helpful to reduce HBV recurrence [P<0.001; RD = 0.16; 95% confidence interval (CI)(0.12, 0.20)] and virus mutants [P<0.001; RR = 3.13; 95%CI (1.86–5.26)], it also improved patients'' 1-year [P = 0.03; RD = 0.08; 95%CI (0.01, 0.15)] and 3-year survival rates [P = 0.005; RD = 0.17; 95%CI(0.05, 0.28)]. No significant difference was found for patients'' 5-year survival [P = 0.46; RD = −0.06; 95%CI (−0.21, 0.10)]. Sub-group analysis showed that in patients with positive pre-operative HBV DNA status, HBIG was necessary to reduce HBV recurrence rate (P<0.001; RD = 0.42; 95%CI (0.32, 0.52)). In patients with negative HBV DNA, combined therapy gained no significant advantages (P = 0.18; RD = 0.06; 95%CI (−0.03, 0.14)). Non-Lamivudine (non-LAM) antiviral drugs performed as well as combination therapy in prophylaxis of HBV recurrence after LT (P = 0.37; RD = 0.06; 95%CI (−0.02, 0.14)).

Conclusions

HBIG with nucleoside analogues is helpful to reduce HBV recurrence and virus mutants. The necessity of HBIG in prophylaxis of HBV recurrence after LT when using new potent nucleoside analogues, especially for patients with negative pre-transplant HBV DNA status remains to be evaluated.     

Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis

Background

Tumor necrosis factor- alpha (TNF-α) is an inflammatory cytokine which may play important role on the immune response may control the progression of cervical lesions. There is a possible association between TNF-α rs1800629 G/A polymorphism and cervical lesions, but previous studies report conflicting results. We performed a meta-analysis to comprehensively assess the association between TNF-α rs1800629 polymorphism and cervical lesions risk.

Methods

Literature searches of Pubmed, Embase, Web of Science, and Wanfang databases were performed for all publications on the association between TNF-α rs1800629 polymorphism and cervical lesions through December 15, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the strength of the association.

Results

Twenty individual case-control studies from 19 publications with a total of 4,146 cases and 4,731 controls were finally included into the meta-analysis. Overall, TNF-α rs1800629 polymorphism was significantly associated with increased risk of cervical lesions under two main genetic comparison models (For A versus G: OR 1.22, 95%CI 1.04–1.44, P = 0.017; for AA versus GG: OR 1.32, 95%CI 1.02–1.71, P = 0.034). Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical lesions in Caucasians but not in Asians. Subgroup analysis by the types of cervical lesions showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical cancer (For A versus G: OR 1.24, 95%CI 1.05–1.47, P = 0.011; for AA versus GG: OR 1.31, 95%CI 1.01–1.70, P = 0.043; for AA/GA versus GG: OR 1.25, 95%CI 1.01–1.54, P = 0.039).

Conclusion

The meta-analysis suggests that TNF-α rs1800629 polymorphism is associated with increased risk of cervical lesions, especially in Caucasians.     

Laparoscopic Hepatectomy for Hepatic Colorectal Metastases – A Retrospective Comparative Cohort Analysis and Literature Review

Background

Laparoscopic hepatectomy (LH) for management of hepatic colorectal metastases (HCRM) is commonly being performed; however, there are limited reports comparing LH outcomes with those of open hepatectomy (OH) procedure. The aim of the present study was to compare perioperative outcomes between the LH and OH procedures performed at a single medical center.

Methods

From Jan 2008 to May 2012, 30 patients with pathologically confirmed HCRM underwent LH, and 140 patients underwent OH at our hospital. Patients'' demographics, perioperative outcomes were retrospectively analyzed.

Results

2 patients (6.7%) in the LH group underwent laparotomies for intraoperative hemorrhage. The LH group had an increased surgical duration (235 min vs. 365 min, (P<0.001), shorter hospital stay (7.5 days vs. 11.5 days, P<0.001), and fewer complications (26.2% vs. 55%, P<0.001) than the OH group. However, in a matched cohort comparison of 30 LH cases and 30 OH cases, no significant variations were observed in the following parameters: surgical duration (235 min vs. 255 min, P = 0.23), positive margin rates (6.7% vs. 0.0%, P = 0.27), or postoperative hematological changes. LH patients had less estimated blood loss (215 ml vs. 385 ml, P<0.001), less morbidity (26.2% vs. 50%, P = 0.02), shorter hospital stay (7.5 days vs. 11.5 days, P<0.001), and lower analgesic requests than with those in the OH group.

Conclusions

LH for metastatic colorectal cancer is a safe and feasible treatment, even in patients who underwent prior laparotomy surgeries and provides significantly less morbidity and shorter hospital stay than OH, without compromising curability or increasing morbidity.     

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.     

Cemented versus Uncemented Hemiarthroplasty for Femoral Neck Fractures in Elderly Patients: A Meta-Analysis

Objective

Controversy still exists regarding using cemented or uncemented hemiarthroplasty for femoral neck fractures in elderly patients. The aim of this study is to compare the effectiveness and safety of the two surgical techniques in femoral neck fracture patients over 70 years old.

Methods

We searched PUBMED, EMBASE, Cochrane Library, CNKI and VIP Database from inception to December 2012 for relevant randomized controlled trials (RCTs). Outcomes of interest include postoperative hip function, residue pain, complication rates, mortality, reoperation rate, operation time and intraoperative blood loss. Odds ratios (OR) and weighted mean differences (WMD) from each trial were pooled using random-effects model or fixed-effects model given on the heterogeneity of the included studies.

Results

7 RCTs involving 1,125 patients (1,125 hips) were eligible for meta-analysis. Our results demonstrate that cemented hemiarthroplasty is associated with better postoperative hip function (OR = 0.48, 95% CI, 0.31–0.76; P = 0.002), lower residual pain (OR = 0.43, 95%CI, 0.29–0.64; P<0.0001), less implant-related complications (OR = 0.15, 95%CI, 0.09–0.26; P<0.00001) and longer operation time (WMD = 7.43 min, 95% CI, 5.37–9.49 min; P<0.00001). No significant difference was observed between the two groups in mortality, cardiovascular and cerebrovascular complications, local complications, general complications, reoperation rate and intraoperative blood loss.

Conclusions

Compared with uncemented hemiarthroplasty, the existing evidence indicates that cemented hemiarthroplasty can achieve better hip function, lower residual pain and less implant-related complications with no increased risk of mortality, cardiovascular and cerebrovascular complications, general complications, local complications and reoperation rate in treating elderly patients with femoral neck fractures.     

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.     

Elevated 12-Month and Lifetime Prevalence and Comorbidity Rates of Mood,Anxiety, and Alcohol Use Disorders in Chinese Men Who Have Sex with Men

Background

This study aimed to assess whether Chinese men who have sex with men (MSM) had a significantly elevated prevalence of psychiatric disorders compared to urban males in China.

Methods

807 MSM were recruited using a respondent-driven sampling (RDS) method in urban area of northeast China. Psychiatric disorders were assessed employing the Composite International Diagnostic Interview (CIDI. Version 1.0) according to the criteria of the DSM-III-R.

Results

Chinese MSM had a significantly elevated standardized prevalence ratios (SPR) for lifetime prevalence of any disorder (SPR = 2.8; 95%CI: 2.5–3.2), mood disorder (SPR = 3.0; 95%CI: 2.3–3.7), anxiety disorder (SPR = 5.5; 95% CI: 4.6–6.5), alcohol use disorder (SPR = 2.4, 95%CI: 2.0–2.8), and combination of disorders (SPR = 4.2; 95%CI: 3.4–5.1).

Conclusions

Chinese MSM had significantly elevated prevalence and comorbidity of psychiatric disorders. RDS is a suitable sampling method for psychiatric epidemiological survey in MSM population.     

Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients

Purpose

To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS).

Methods

Three-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method.

Results

HALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53–3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/10⁶ cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): ‘A+A’; OR for ‘A+B’ vs. ref.: 1.39 [0.69–2.80]; OR for ‘B+A’ vs. ref.: 2.16 [1.22–3.83]; OR for ‘B+B’ vs. ref.: 3.13, 95%CI: 1.54–6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56–4.14, P = 0.001), (c) use of EFV (1.10 [1.00–1.21], P = 0.008, per year of use).

Conclusion

HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine.     

The Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor Gamma-2 Gene (PPARγ2) Is Associated with Increased Risk of Coronary Artery Disease: A Meta-Analysis

Background

Contradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARγ2 and coronary artery disease (CAD). We sought to estimate the inconsistent results by performing a comprehensive meta-analysis.

Methods

Studies in English or Chinese publications were identified by screening MEDLINE, Embase, CNKI, Wanfang and CBM. 22 studies including 8948 cases and 14427 controls were selected. A random-effects model was applied to combine the divergent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias.

Results

The Pro12Ala polymorphism of control population followed Hardy-Weinberg equilibrium for all studies (P>0.05). Overall, a marginal increased risk of CAD under the recessive genetic model (AlaAla vs ProAla+ProPro: P = 0.04, OR = 1.31, 95%CI 1.01–1.69, P_{heterogeneity} = 0.67, I² = 0%) and the homozygote comparison (AlaAla vs ProPro: P = 0.04,OR = 1.30, 95%CI 1.01–1.68, P_{heterogeneity} = 0.68, I² = 0%) was observed. In the subgroup analysis by ethnicity, carriers of AlaAla homozygotes had a significant increased risk for CAD among Caucasians (AlaAla vs ProAla+ProPro: P = 0.01, OR = 1.45, 95%CI 1.08–1.96, P_{heterogeneity} = 0.48, I² = 0%; AlaAla vs ProPro: P = 0.02,OR = 1.44, 95%CI 1.07–1.93, P_{heterogeneity} = 0.46, I² = 0%). After dividing into population source, the CAD risk magnitude of hospital-based studies was distinctly strengthened under the recessive model (P = 0.03,OR = 1.85,95%CI 1.07–3.19, P_{heterogeneity} = 0.87,I² = 0%) and the homozygote comparison (P = 0.03,OR = 1.83, 95%CI 1.06–3.16, P_{heterogeneity} = 0.88, I² = 0%). There was no observable publication bias as reflected by funnel plot and Egger’s linear regression test (t = -0.12, P = 0.91).

Conclusion:

Our results demonstrated that the PPARγ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians.     

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.