Stage IV non-small cell lung cancer among young individuals: Incidence, presentations, and survival outcomes of conventional therapies.

Background: There is a paucity of data published on the clinicopathological features and prognosis of stage IV non-small cell lung cancer (NSCLC) patients aged ≤45 years. Herein, we evaluated a large clinical series in an effort to provide a clearer picture of this population. Methods: The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to identify prognostic factors for NSCLC among individuals aged ≤45 years. The Kaplan-Meier method with log-rank test was used to compare overall survival (OS) differences between groups. Competing risk analysis with the Fine-Gray test was used to analyze cancer-specific survival (CSS) differences. Propensity score matching (PSM) was used to minimize selection bias. Results: Incidence-rate analyses, including 588,680 NSCLC cases (stage IV, 233,881; age ≤ 45 years stage IV, 5,483; and age > 45 years stage IV, 228,398) from 2004 to 2015, showed that the incidence of stage IV NSCLC among young individuals decreased over the years. In comparative analyses of clinical features and survival outcomes, a total of 48,607 eligible stage IV cases (age ≤ 45 years stage IV, 1,390; age > 45 years stage IV, 47,217) were included. The results showed that although patients in the young cohort were more likely to be diagnosed at advanced stages, they were also more likely to receive aggressive treatments. In addition, the survival rates of the young patients were superior to those of the older patients both before and after PSM. Conclusions: Stage IV NSCLC patients aged ≤45 years comprise a relatively small but special NSCLC subgroup. Although this population had better survival outcomes than older patients, these patients deserve more attention due to their young age and the significant socioeconomic implications.

Lymphovascular invasion: A non-sized T descriptor for stage IA non-small cell lung cancer.

BACKGROUND: Lymphovascular invasion (LVI) has not been included in the tumor-node-metastasis (TNM) staging manual of non-small-cell lung cancer (NSCLC). We aimed to investigate the predictive value of LVI on stage IA NSCLC and proposed a method of incorporating LVI into the T category based on the latest TNM staging manual. METHODS: The least absolute shrinkage and selection operator (LASSO)-penalized Cox multivariable regression model was performed to identify prognostic factors. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS) between groups. Propensity score matching (PSM) was used to minimize bias. RESULTS: A total of 1452 eligible stage I NSCLC cases (stage IA without LVI, 1022 cases; stage IA with LVI, 120 cases; stage IB, 310 cases) were included. LASSO-penalized multivariable Cox analysis revealed that LVI was an independent prognostic factor for both OS and DFS. Survival analysis demonstrated that the survivals of stage IA NSCLCs without LVI were better than those of stage IA with LVI and stage IB NSCLCs. In the matched cohort, the survivals of stage IA NSCLCs with LVI were comparable to those of stage IB NSCLCs. CONCLUSIONS: Stage IA NSCLCs with LVI and stage IB NSCLCs had similar survivals, and we proposed that LVI might be a non-sized T descriptor that upstaged stage IA diseases to stage IB.

Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies.

Glutathione S-transferase Omega (GSTO) plays an important role in the development of cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms on GSTO and susceptibility to cancer; however, the results remain inconclusive. We performed a meta-analysis of 20 studies, involving 4770 cases and 5701 controls to identify the strength of association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall, the pooled results revealed a significantly increased risk of susceptibility for GSTO2 polymorphism (GG vs. AA: OR = 1.20, 95%CI: 1.02-1.41, Pheterogeneity = 0.116), but no significant association was found for GSTO1 polymorphism. Subgroup analysis showed that GSTO2 polymorphism significantly increased cancer risk in Caucasian population (GG vs. AA: OR = 1.32, 95%CI 1.06-1.64, Pheterogeneity = 0.616) and GSTO2 polymorphism was significantly associated with elevated risk of breast cancer (GG vs. AA OR = 1.37, 95%CI: 1.06-1.77; Pheterogeneity = 0.281). This meta-analysis demonstrates that GSTO2 polymorphism may significantly increase cancer risk in Caucasian population and is associated with elevated risk of breast cancer; while GSTO1 polymorphism is not associated with cancer risk.

Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.

BACKGROUND AND OBJECTIVE: Evidence has shown that matrix metalloproteinases-3 (MMP3) is important for cancer progression. Recent studies about the association between the -1171(5A>6A) polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A) polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A) polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR=0.74, 95%CI: 0.60-0.91; I(2)=1.9%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.77, 95%CI: 0.64-0.94; I(2)=29.0%). Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR=0.68, 95%CI: 0.52-0.90; I(2)=26.7%), heterozygote comparison (6A/5A vs. 5A/5A: OR=0.75, 95%CI: 0.58-0.98; I(2)=0.0%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.69, 95%CI: 0.54-0.88; I(2)=0.5%). It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR=1.92, 95%CI: 1.25-2.96; I(2)=72.7%). CONCLUSION: This meta-analysis suggests that the -1171(5A>6A) polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.

A comparison of remifentanil parturient-controlled intravenous analgesia with epidural analgesia: a meta-analysis of randomized controlled trials.

BACKGROUND: Epidural analgesia is generally accepted as the most effective form of pain relief during labor. Remifentanil patient-controlled IV analgesia (PCIA), which is less invasive than epidural analgesia, may be an attractive alternative. In this meta-analysis, we compared the efficacy and safety of the 2 analgesic techniques for labor pain. METHODS: Databases of PubMed, EMBASE, and Cochrane Library were searched independently by 2 reviewers to retrieve eligible randomized controlled clinical trials. The primary end points were pain scores at 1 and 2 hours, and the secondary end points were nausea, vomiting, pruritus, and umbilical artery pH values. Mean difference (MD) or risk ratio with 95% confidence intervals (CIs) were calculated for each end point. GRADE profiler was applied to assess the quality of evidence. RESULTS: Five eligible trials were retrieved and analyzed. We found that parturients with remifentanil PCIA had higher visual analog scale (10-cm scale) pain scores than those who received epidural analgesia at 1 hour (MD = 1.9 cm; 95% CI, 0.5-3.3; I = 94%) and 2 hours (MD = 3.0 cm; 95% CI, 0.7-5.2; I = 89%) after initiation of analgesia. There was no statistical difference between epidural analgesia and remifentanil PCIA in the incidence of nausea, vomiting, pruritus, or umbilical artery pH values. However, the CIs are quite wide and contain clinically significant differences. According to GRADE profiler, most end points had moderate quality except that pain scores at 1 hour were of low quality. CONCLUSIONS: This meta-analysis suggests that remifentanil PCIA is not superior to epidural analgesia in analgesic efficacy during labor. Given the wide CIs of the pooled results for secondary maternal and neonatal outcomes, definite conclusions cannot be drawn for those outcomes. Further studies are still warranted to validate these conclusions.

Lack of association of three common polymorphisms in toll-like receptors (TLRs), TLR2+597T>C, +1350C>T and Arg753Gln with cancer risk: a meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) occurring in Toll-like receptors (TLRs) may contribute to cancer risk. Many polymorphisms of TLR2 have been studied for associations, but the findings are conflicting. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 14 studies to confirm the association between TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms and cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of associations. There was no significant association between TLR2+597T>C and cancer risk in the codominant models (CC vs. TT: OR = 1.01, 95%CI = 0.86-1.17, Pheterogeneity = 0.148; CT vs. TT: OR = 0.92, 95%CI = 0.69-1.23, Pheterogeneity < 0.001), the recessive model (CC vs. CT+TT: OR = 0.86, 95%CI = 0.67-1.10, Pheterogeneity = 0.007) , the dominant model (CC+CT vs. TT: OR = 0.93, 95%CI = 0.76-1.15, Pheterogeneity = 0.001) and the allele model (C vs. T: OR = 0.93, 95%CI = 0.81-1.08, Pheterogeneity = 0.019). Similarly, no significant associations between TLR2+1350C>T, Arg753Gln polymorphisms and cancer risk were found. However, in the sub-group analysis of ethnicities, the trend of pooled ORs in Asians was opposite to Caucasians. CONCLUSIONS: The present meta-analysis suggests that TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms are not associated with cancer risk.

FASL rs763110 polymorphism contributes to cancer risk: an updated meta-analysis involving 43,295 subjects.

BACKGROUND: Published studies investigating the association between genetic polymorphism -884C/T (rs763110) of the FAS ligand (FASL) promoter and cancer risk reported inconclusive results. To derive a more precise estimation of the relationship, we performed an updated meta-analysis of all eligible studies. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a meta-analysis, including 47 studies with 19,810 cases and 23,485 controls, to confirm a more conclusive association between the FASL rs763110 polymorphism and cancer susceptibility. Overall, significantly reduced cancer risk was associated with the variant -884T when all studies were pooled (TC vs. CC: OR = 0.83, 95%CI = 0.75-0.92; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.85, 95%CI = 0.77-0.94; P(heterogeneity)<0.001). Stratified analysis revealed that there was a statistically reduced cancer risk in Asians (TC vs. CC: OR = 0.76, 95%CI = 0.67-0.87; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.79, 95%CI = 0.70-0.90; P(heterogeneity)<0.001) and in patients with cancers of head and neck (TC vs. CC: OR = 0.87, 95%CI = 0.77-0.99; P(heterogeneity) = 0.118; TT+TC vs. CC: OR = 0.88, 95%CI = 0.78-0.99; P(heterogeneity) = 0.168) and ovarian cancer (TC vs. CC: OR = 0.67, 95%CI = 0.49-0.90; P(heterogeneity) = 0.187; TT+TC vs. CC: OR = 0.64, 95%CI = 0.48-0.86; P(heterogeneity) = 0.199). Meta-regression showed that ethnicity (p = 0.029) and genotyping method (p = 0.043) but not cancer types (p = 0.772), sample size (p = 0.518), or source of controls (p = 0.826) were the source of heterogeneity in heterozygote comparison. CONCLUSION: Our results suggest that the FASL polymorphism rs763110 is associated with a significantly reduced risk of cancer, especially in Asian populations.

Lack of association between hsa-miR-149 rs2292832 polymorphism and cancer risk: a meta-analysis of 12 studies.

BACKGROUND: MicroRNAs (miRNAs) participate in various cellular processes such as cell growth, differentiation, cell death and play an important role in a variety of diseases, especially in cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms (SNPs) on the hsa-miR-149 rs2292832 and susceptibility to cancer; however, the results remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a meta-analysis of 12 studies including 5937 cases and 6081 controls from PubMed to assess the association between the hsa-miR-149 rs2292832 and cancer risk by pooled odds ratios (ORs) and 95% confidence intervals (CIs). However, our results showed that genotype distribution of the hsa-miR-149 rs2292832 was not associated with cancer risk in all genetic models. Subgroup analysis by cancer type, ethnicity or study design showed no significant association either. CONCLUSION: Results of this meta-analysis suggest that the hsa-miR-149 rs2292832 polymorphism is not associated with cancer risk in spite of the potentially protective role of C allele in hepatocellular carcinoma and male gastric cancer.

Association of interleukin-18 gene promoter -607 C>A and -137G>C polymorphisms with cancer risk: a meta-analysis of 26 studies.

BACKGROUND: Evidence suggest that IL-18 gene polymorphisms may be risk factors for several cancers. Increasing studies investigating the association between IL-18 gene promoter polymorphisms (-607 C>A and -137G>C) and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 26 studies including 4096 cases and 5222 controls. We assessed the strength of the association of IL-18 gene promoter -607 C>A and -137G>C polymorphisms with cancer risk and performed sub-group analyses by cancer types, ethnicities, source of controls and sample size. The pooled results revealed a significant increased risk of cancer susceptibility for -607 C>A (CA vs. CC: OR = 1.19, 95%CI: 1.04, 1.37, Pheterogeneity = 0.033; CA/AA vs. CC: OR = 1.17, 95% CI: 1.01, 1.34, Pheterogeneity = 0.007), but no significant association for -137 G>C was observed with overall cancer risk. Sub-group analyses revealed that an increased risk of nasopharyngeal carcinoma was both found for -607 C>A (CA/AA vs. CC: OR = 1.32, 95% CI: 1.04, 1.69, Pheterogeneity = 0.823) and -137G>C (GC/CC vs. GG: OR = 1.57, 95%CI: 1.26, 1.96, Pheterogeneity = 0.373). Consistent with the results of the genotyping analyses, the -607A/-137C and -607C/-137C haplotypes were associated with a significantly increased risk of nasopharyngeal carcinoma as compared with the -607C/-137G haplotype (-607A/-137C vs. -607C/-137G: OR = 1.26, 95%CI: 1.13, 1.40; Pheterogeneity = 0.569; -607C/-137C vs. -607C/-137G: OR = 1.14, 95%CI: 1.03, 1.27; Pheterogeneity = 0.775). As for gastrointestinal cancer, we also found that -607 C>A polymorphism was significantly associated with increased cancer risk (CA/AA vs. CC: OR = 1.25, 95% CI: 1.05, 1.50, Pheterogeneity = 0.458). Further sub-group analysis revealed that -137G>C polymorphism contributed to cancer risk in Asians but not in Caucasians (GC/CC vs. GG: OR = 1.31, 95%CI: 1.05, 1.64, Pheterogeneity<0.001). CONCLUSIONS: The meta-analysis results suggest that IL-18 gene promoter -607 C>A polymorphism is significantly associated with overall cancer risk, especially in nasopharyngeal carcinoma and gastrointestinal cancer; and the -137 G>C polymorphism is associated with increased overall cancer risk in Asian populations and also significantly increases the risk of nasopharyngeal carcinoma.

Association of vitamin D receptor BsmI gene polymorphism with risk of tuberculosis: a meta-analysis of 15 studies.

BACKGROUND: Genetic variations in vitamin D receptor (VDR) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a comprehensive meta-analysis of 15 publications with a total of 2309 cases and 3568 controls. We assessed the strength of the association between VDR BsmI gene polymorphism and TB risk and performed sub-group analyses by ethnicity, sample size and Hardy-Weinberg equilibrium (HWE). We found a statistically significant correlation between VDR BsmI gene polymorphism and decreased TB risk in four comparison models: allele model (b vs. B: OR = 0.78, 95% CI = 0.67, 0.89; Pheterogeneity = 0.004), homozygote model (bb vs. BB: OR = 0.61, 95% CI = 0.43, 0.87; Pheterogeneity = 0.001), recessive model (bb vs. Bb+BB: OR = 0.70, 95% CI = 0.56, 0.88; Pheterogeneity = 0.005) and dominant model (bb+Bb vs. BB: OR = 0.77, 95% CI = 0.61, 0.97; Pheterogeneity = 0.010), especially in studies based on Asian population. Sub-group analyses also revealed that there was a statistically decreased TB risk in "small" studies (<500 participants) and studies with PHWE>0.5. Meta-regression and stratification analysis both showed that the ethnicity and sample size contributed to heterogeneity. CONCLUSIONS: This meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.

GSTT1 null genotype contributes to lung cancer risk in asian populations: a meta-analysis of 23 studies.

BACKGROUND: Genetic variation in glutathione S-transferases (GSTs) may contribute to lung cancer risk. Many studies have investigated the correlation between the Glutathione S-transferase T1 (GSTT1) null genotype and lung cancer risk in Asian population but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 23 studies including 4065 cases and 5390 controls. We assessed the strength of the association of GSTT1 with lung cancer risk and performed sub-group analyses by source of controls, smoking status, histological types, and sample size. A statistically significant correlation between GSTT1 null genotype and lung cancer in Asian population was observed (OR = 1.28, 95% CI = 1.10, 1.49; Pheterogeneity<0.001 and I(2) = 62.0%). Sub-group analysis revealed there was a statistically increased lung cancer risk in ever-smokers who carried the GSTT1 null genotype (OR = 1.94, 95% CI = 1.27, 2.96; P heterogeneity = 0.02 and I(2) = 58.1%). It was also indicated that GSTT1 null genotype could increase lung cancer risk among population-based studies (OR = 1.25, 95% CI = 1.04, 1.50; Pheterogeneity = 0.003 and I(2) = 56.8%). The positive association was also found in studies of sample size (≤500 participants) (OR = 1.34, 95% CI = 1.10, 1.62; Pheterogeneity<0.001 and I(2) = 65.4%). CONCLUSIONS: These meta-analysis results suggest that GSTT1 null genotype is associated with a significantly increased risk of lung cancer in Asian population.

miR-221/222: promising biomarkers for breast cancer.

MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nt that can regulate gene expression at a posttranscriptional level. Increasing evidence indicates that miRNAs participate in almost every step of cellular processes and are often aberrantly expressed in human cancer. miR-221 and miR-222 are two highly homologous miRNAs that always act as a gene cluster (miR-221/222) in cellular regulation and have extensively been studied in cancer network. Here, we review the role of miR-221/222 in breast cancer (BCa) development and progression: regulating proliferative signaling pathways, altering telomere and telomerase activity, avoiding cell death from tumor suppressors, autophagy and apoptosis, monitoring angiogenesis, supporting epithelial-mesenchymal transition, and even controlling cell-specific function within microenvironment. We consider that miR-221/222 act as promising biomarkers for BCa and they would offer a new way in molecular targeting cancer treatment.

Long noncoding RNA: an emerging paradigm of cancer research.

Recent studies have demonstrated the importance of non-protein coding part of human genome in carcinogenesis and metastasis. Among numerous kinds of non-protein coding RNAs, long noncoding RNAs (lncRNAs) play a key regulatory role in cancer biology. LncRNAs are dysregulated in different kinds of cancer and the expression levels of certain lncRNAs are associated with recurrence, metastasis, and prognosis of cancer. It is also proved that overexpression of certain lncRNAs, behaving like oncogenes, can promote matrix invasion of cancer cells and tumor growth. In this review, we focus our attention on lncRNAs those have been validated in human cancer tissues to suggest reasonable strategies for future research. We introduce an update view of lncRNA, extract cancer-related lncRNAs from literature, and describe the known functions and possible underlying molecular mechanisms of some well investigated lncRNAs (MALAT1, HOX antisense intergenic RNA, and highly upregulated in hepatocellular cancer), as well as their current and potential future application in cancer diagnosis (PCA3) and treatment (H19).

Hsa-miR-499 rs3746444 polymorphism contributes to cancer risk: a meta-analysis of 12 studies.

BACKGROUND: Single nucleotide polymorphisms (SNPs) occurred in pre-microRNAs or targets of microRNAs (miRs) may contribute to cancer risks. Since 2007, many studies have investigated the association between common SNPs located on hsa-miR-499 (rs3746444) and cancer risks; however, the results were inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 12 studies that included 5765 cases and 7076 controls to identify the strength of association. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant AG (OR = 1.215, 95% CI: 1.027, 1.437; P(heterogeneity)<0.01) and AG/GG (OR = 1.227, 95% CI: 1.046, 1.439; P(heterogeneity)<0.01) genotypes were associated with a significantly increased risk of cancer than those with wild AA genotype. Sub-group analysis revealed that the variant AG (OR = 1.411, 95% CI: 1.142, 1.745; P(heterogeneity) = 0.01) and AG/GG (OR = 1.413, 95% CI: 1.163, 1.717, P(heterogeneity) = 0.01) genotypes still showed an increased risk of cancer in Asians; however, a trend of reduced risk of cancer was observed in Caucasians (AG vs. AA: OR = 0.948, 955 CI: 0.851, 1.057, P(heterogeneity) = 0.12; AG/GG vs. AA: OR = 0.959, 95% CI: 0.865, 1.064; P(heterogeneity) = 0.19). Meta-regression showed that ethnicity (p = 0.048) and sample size (p = 0.02) but not cancer types (p = 0.89) or source of control (p = 0.97) were the sources of heterogeneity. CONCLUSIONS: These meta-analysis results suggest that hsa-miR-499 polymorphism rs3746444 is associated with a significantly increased risk of cancer, especially in Asian populations.

Fixed-dose rate infusion and standard rate infusion of gemcitabine in patients with advanced non-small-cell lung cancer: a meta-analysis of six trials.

PURPOSE: To compare the response, survival, hematological and non-hematological toxicities of gemcitabine administrated at fixed-dose rate infusion (10 mg/m(2)/min, FDR) and standard 30 min infusion in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Electronic databases of MEDLINE, EMBASE and Cochrane Library were searched using key words of "gemcitabine," "fixed-dose rate," "non-small-cell lung cancer" and their alternative spellings. An expanded search of references of relative articles was also performed. The last search was performed on September 10, 2012. Primary endpoints were overall survival rate (ORR) and 1-year survival rate (1-year SR); hematological and non-hematological toxicities were secondary endpoints. RESULTS: Six randomized controlled trials, involving 867 patients, met our inclusion criteria and were analyzed. Pooled results showed that FDR infusion of gemcitabine had an equal ORR (RR = 0.91, 95 % CI: 0.74-1.13; heterogeneity p = 0.39) and 1-year SR (RR = 1.09, 95 % CI: 0.93-1.29; heterogeneity p = 0.75) compared with standard infusion. Subgroup analysis found that chemotherapy drug combinations do not affect the results of ORR or 1-year SR. Patients received FDR infusion, however, experienced more grade 3/4 hematological (neutropenia, leukopenia and anemia) and non-hematological (diarrhea and fatigue) toxicities. CONCLUSION: This meta-analysis found that FDR infusion of gemcitabine had equal ORR and 1-year SR with standard infusion in patients with advanced NSCLC, while FDR infusion was associated with more grade 3/4 hematological and non-hematological toxicities.

Ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean section: an updated meta-analysis.

AIMS: A systematic literature review comparing the efficacy of ephedrine and phenylephrine for the management of spinal anesthesia-induced hypotension during Cesarean sections (C-sections) was published in 2002. A number of well-designed trials with controversial results have been published afterward. Therefore, an updated meta-analysis was necessary. METHODS: The MEDLINE, EMBASE, and the Cochrane Library databases were searched (last search performed on September 26, 2011). Pooled risk ratio (RR) or standard mean difference (SMD) and their 95% confidence intervals (95% CI) were calculated for the incidence of intra-operative hypotension or umbilical blood pH values. RESULTS: A total number of 15 trials and 742 parturients under elective C-sections were analyzed. When used to prevent hypotension, patients receiving ephedrine and phenylephrine did not differ significantly in the incidence of hypotension (RR = 1.22; 95% CI, 0.83-1.80), umbilical arterial pH values (SMD = -0.38; 95% CI, -1.67 to 0.92) or venous pH values (SMD = -0.18; 95% CI, -0.44 to 0.07). And administration routes did not affect the incidence of hypotension and umbilical blood pH values. When used to treat hypotension, patients given ephedrine and phenylephrine had comparable incidence of intra-operative hypotension (RR = 0.79; 95% CI, 0.40-1.56), while parturients receiving phenylephrine had neonates with higher umbilical arterial pH values (SMD = -1.32; 95% CI, -2.35 to -0.30) and venous pH values (SMD = -0.79; 95% CI, -1.09 to -0.49) than those given ephedrine. CONCLUSION: Prophylactic use of ephedrine and phenylephrine were both effective in preventing maternal hypotension during C-section under spinal anesthesia; phenylephrine was superior to ephedrine in treating hypotension, evidenced by higher umbilical blood pH values.

Combination of low-dose bupivacaine and opioids provides satisfactory analgesia with less intraoperative hypotension for spinal anesthesia in cesarean section.

AIMS: This meta-analysis was undertaken to compare the three most common drug regimens of bupivacaine in spinal anesthesia for cesarean section: high-dose bupivacaine (≥10 mg, HB), low-dose bupivacaine (<10 mg, LB) and combination of low-dose bupivacaine and opioids (LBO). METHODS: Databases of MEDLINE, EMBASE, and Cochrane Library were searched (updated on October 30, 2011). Primary endpoints were the incidence of intraoperative hypotension and analgesia efficacy. Pooled risk ratio (RR) or standard mean difference and their 95% confidence intervals (95% CI) were calculated. A RR <1 indicates that LB or LBO regimen is associated with less intraoperative complications and better anesthesia or analgesia efficacy. RESULTS: A total of 11 randomized controlled trials including 605 parturients were analyzed. Results of this meta-analysis showed that compared with HB regimen, LB regimen decreased the incidence of intraoperative hypotension (RR = 0.64, 95% CI: 0.42-0.96) with less satisfactory analgesia (fixed model, RR = 1.50, 95% CI: 1.14-1.98). LBO regimen significantly reduced the incidence of intraoperative hypotension (RR = 0.52, 95% CI: 0.33-0.82) with reliable analgesia efficacy (RR = 2.56, 95% CI: 0.77-8.48). CONCLUSION: Compared with conventional HB regimen and LB regimen, LBO regimen not only reduced intraoperative hypotension but also provided reliable analgesia. Therefore, LBO regimen should be considered as the preferred drug combination for spinal anesthesia in cesarean section.