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A closer association has been found between the microRNA-146a rs2910164 polymorphism and the risk of head and neck carcinoma in some molecular epidemiological studies. Recently two meta-analyses were performed to explore the relationship between miRNA-146a polymorphisms and the susceptibility of squamous cell carcinoma of the head and neck (SCCHN); however, they yielded conflicting results in susceptibility regarding ethnic variations. Hence, the present study was performed to explain the relationship between the miRNA-146a rs2910164 polymorphism and the risk of SCCHN development of Chinese patients. We retrieved databases and screened eligible papers up to March 10, 2017 and then we extracted the essential data. The subgroup analyses were also performed based on the tumor site, region, and genotyping means. Crude odds ratios (OR) at 95% confidence intervals (CI) were chosen to describe the strength of the association. As a result, 6 publications were included in our study which involved 8 independent case-control studies. A significant association was found between miR-146a rs2910164 polymorphisms and the risk of SCCHN in Chinese patients according to the overall data [CC+CG vs. GG: OR = 1.13; 95%CI = 1.00–1.29; CC vs. GG: OR = 1.19; 95%CI = 1.03–1.38]. According to the subgroup analysis based on tumor site, the risk of cancer was significantly increased among laryngeal cancer (dominant model: OR = 1.76, 95%CI = 1.26~2.46, P = 0.001; homozygote model: OR = 1.83, 95%CI = 1.25~2.67, P = 0.002) and nasopharyngeal carcinoma (homozygote model: OR = 1.41, 95%CI = 1.05~1.90, P = 0.022). In summary, variant alleles of miR-146a rs2910164 alleles may have an association with the increased risk of SCCHN in Chinese patients, and these associations differed based on tumor site. Further studies including a larger sample size will be necessary to clarify these results. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods: Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results: A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion: The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria. [ABSTRACT FROM AUTHOR]

Background: Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. Objectives: We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Methods: Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Results: Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79–0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76–0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. Conclusions and Implications: The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. Systematic Review Protocol Number: CRD42015014145 [ABSTRACT FROM AUTHOR]

Background: Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. Methods: Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. Results: Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64–0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53–0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73–1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). Conclusion: Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers? [ABSTRACT FROM AUTHOR]

How can we predict the occurrence of acute kidney injury (AKI) in cancer patients based on machine learning with serum creatinine data? Given irregular and heterogeneous clinical data, how can we make the most of it for accurate AKI prediction? AKI is a common and significant complication in cancer patients, and correlates with substantial morbidity and mortality. Since no effective treatment for AKI still exists, it is important to take timely preventive measures. While several approaches have been proposed for predicting AKI, their scope and applicability are limited as they either assume regular data measured over a short hospital stay, or do not fully utilize heterogeneous data. In this paper, we provide an AKI prediction model with a greater applicability, which relaxes the constraints of existing approaches, and fully utilizes irregular and heterogeneous data for learning the model. In a cohort of 21,022 cancer patients who were registered into Korea Central Cancer Registry (KCCR) in Seoul National University Hospital between January 1, 2004 and December 31, 2013, our method achieves 0.7892 precision, 0.7506 recall, and 0.7576 F-measure in predicting whether a patient will develop AKI during the next 14 days. [ABSTRACT FROM AUTHOR]

In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) protocol are well established in many surgical disciplines, leading to decrease in morbidity and length of hospital stay. These multi-modal protocols have been also introduced to oesophageal cancer surgery. This review aimed to evaluate current literature on ERAS in oesophageal cancer surgery and conduct a meta-analysis on primary and secondary outcomes. Methods: MEDLINE, Embase, Scopus and Cochrane Library were searched for eligible studies. We analyzed data up to May 2016. Eligible studies had to contain four described ERAS protocol elements. The primary outcome was overall morbidity. Secondary outcomes included length of hospital stay, specific complications, mortality and readmissions. Random effect meta-analyses were undertaken. Results: Initial search yielded 1,064 articles. Thorough evaluation resulted in 13 eligible articles which were analyzed. A total of 2,042 patients were included in the analysis (1,058 ERAS group and 984 treated with traditional protocols). Analysis of overall morbidity as well as complication rate did not show any significant reduction. Non-surgical complications and pulmonary complications were significantly lower in the ERAS group, RR = 0.71 95% CI 0.62–0.80, p < 0.00001 and RR = 0.75, 95% CI 0.60–0.94, p = 0.01, respectively. Meta-analysis on length of stay presented significant reduction Mean difference = -3.55, 95% CI -4.41 to -2.69, p for effect<0.00001. Conclusions: This systematic review with a meta-analysis on ERAS in oesophageal surgery indicates a reduction of non-surgical complications and no negative influence on overall morbidity. Moreover, a reduction in the length of hospital stay was presented. [ABSTRACT FROM AUTHOR]

Background: LncRNA CCAT1 is significantly overexpressed in various types of cancers, suggesting that it might be associated with prognosis and clinicopathological features in patients with cancer. Methods: A comprehensive search was performed in Pubmed, Web of Science, OVID and CNKI databases. We also retrieved articles from other sources, such as retrieving from the reference lists of relevant articles. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. Results: A total of 1587 patients from 11 eligible studies were included in the meta-analysis. The results showed that high expression level of CCAT1 was significantly associated with shorter overall survival in cancer patients (HR 2.335, 95% CI:1.551–3.517); in the subgroup analysis, region (China or UK), sample size (more or less than 100), type of cancer (digestive or non-digestive disease) and paper quality (score more or less than 7) did not alter the association between CCAT1 expression and cancer prognosis but preoperative treatment did. And CCAT1 expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.195, 95%CI:1.316–3.664) using Cox multivariate analyses. The clinicopathological parameters analysis further showed that increased expression level of CCAT1 was correlated with tumor size, lymph node metastasis, TNM stage, distant metastasis, microvascular invasion and capsular formation in relevant cancers. Conclusions: The meta-analysis results from present study suggested that increased expression level of CCAT1 was associated with poor prognosis and can serve as an independent biomarker. And the expression level of CCAT1 was associated with clinicopathological features in relevant cancers. [ABSTRACT FROM AUTHOR]

Background: Previous studies have revealed conflicting findings concerning the efficacy of radiotherapy (RT) and radiochemotherapy (RCT) in IE/IIE extranodal nasal-type natural killer/T cell lymphoma (ENKTL). In this study, we conducted a comprehensive meta-analysis to address this issue. Methods: We systematically searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EmBase, BISOS, Clinical Trials and some Chinese databases for relevant studies, and 2 prospective and 15 retrospective studies involving a total of 1595 patients met our inclusion criteria. Results: The meta-analysis showed no significant differences in complete remission (CR) [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.42–1.72, p = 0.65], 5-year overall survival (OS) [hazard ratio (HR) 1.11, 95% CI 0.85–1.45, p = 0.43] and 5-year progression free survival (PFS) (HR 1.07, 95% CI 0.75–1.53, p = 0.70) in patients who received RT versus RCT. Furthermore, the addition of CT decreased neither systemic failure (SL) (OR 0.75, 95% CI 0.47–1.21, p = 0.24) nor locoregional failure (LF) (OR 1.17, 95% CI 0.68–2.01, p = 0. 57). Conclusions: RCT did not have an obvious advantage over RT for treating IE/IIE ENKTL. [ABSTRACT FROM AUTHOR]

Covariate selection is a fundamental step when building sparse prediction models in order to avoid overfitting and to gain a better interpretation of the classifier without losing its predictive accuracy. In practice the LASSO regression of Tibshirani, which penalizes the likelihood of the model by the L1 norm of the regression coefficients, has become the gold-standard to reach these objectives. Recently Lee and Oh developed a novel random-effect covariate selection method called the modified unbounded penalty (MUB) regression, whose penalization function can equal minus infinity at 0 in order to produce very sparse models. We sought to compare the predictive accuracy and the number of covariates selected by these two methods in several high-dimensional datasets, consisting in genes expressions measured to predict response to chemotherapy in breast cancer patients. These comparisons were performed by building the Receiver Operating Characteristics (ROC) curves of the classifiers obtained with the selected genes and by comparing their area under the ROC curve (AUC) corrected for optimism using several variants of bootstrap internal validation and cross-validation. We found consistently in all datasets that the MUB penalization selected a remarkably smaller number of covariates than the LASSO while offering a similar—and encouraging—predictive accuracy. The models selected by the MUB were actually nested in the ones obtained with the LASSO. Similar findings were observed when comparing these results to those obtained in their first publication by other authors or when using the area under the Precision-Recall curve (AUCPR) as another measure of predictive performance. In conclusion, the MUB penalization seems therefore to be one of the best options when sparsity is required in high-dimension. Further investigation in other datasets is however required to validate these findings. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic impact of circulating tumor cells (CTC) on disease recurrence, progression and survivals in patients with head and neck squamous cell carcinoma (HNSCC) has not been adequately described. The objective of this study was to determine the impacts of the presence of CTC on loco-regional recurrence and survival of HNSCC patients by conducting a systematic review and meta-analysis. Methods: A comprehensive search for articles published between 1990 and 2016 was conducted and data from these studies were extracted, using the MEDLINE, Cochrane Library, and EMBASE databases. The main outcomes were overall survival (OS) and recurrence-free survival (RFS) of HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. The quality of the studies, heterogeneity and publication bias were assessed with the appropriate statistical methods. Results: Six eligible studies with 429 patients were identified. The presence of CTC was significantly associated shorter RFS (HR = 4.88 [95%CI: 1.93–12.35], P < 0.001). However, it could not predict patients’ OS (HR = 1.92 [95%CI: 0.93–3.96], P = 0.078). The following analyses using univariable values of each study also made the similar results (HR = 1.70 [95%CI: 0.83–3.45] for OS, HR = 3.79 [95%CI: 2.02–7.13] for RFS). Heterogeneity and publication bias were not significant, except one enrolled study. Conclusions: The presence of CTC is not a significant prognostic indicator for OS of patients with HNSCC, although it could reflect the outcomes of loco-regional disease. [ABSTRACT FROM AUTHOR]

Background: Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods: A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results: A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%. Conclusions: Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review with network meta-analysis compared the efficacy and safety of currently licensed second-line treatments in patients with late stage non-small cell lung cancer (NSCLC). Methods: Randomised controlled trials (RCTs) of participants with advanced/metastatic NSCLC receiving second/third line treatments were screened. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 to July, 2017. Two reviewers screened bibliographic records, extracted data, and assessed risk of bias of included studies. The outcomes were overall survival (OS), progression-free survival (PFS), and drug-related grade 3–5 adverse-events (AEs). We pooled study-specific hazard ratios (HR; for OS and PFS) and risk ratios (RR; for AEs) using conventional and network-meta-analyses, and ranked interventions by the surface under the cumulative ranking curve. Findings: We included 11 RCTs (7,581 participants) comparing nine drugs. All drugs except for erlotinib significantly improved OS compared to docetaxel. Nivolumab was the highest ranking drug followed by atezolizumab and pembrolizumab. There was no significant difference in OS across these three drugs (HR = 0.98, 95% CI 0.79, 1.21 for nivolumab vs atezolizumab; HR = 0.98, 95% CI 0.77, 1.25 for nivolumab vs pembrolizumab). For PFS, ramucirumab + docetaxel and nivolumab were the drugs with the highest ranking. All interventions except ramucirumab + docetaxel had a reduced risk for severe drug-related AEs vs. docetaxel. Of the drugs with the highest ranking on AEs, nivolumab was significantly safer compared to atezolizumab (RR = 0.55, 95% CI 0.38, 0.79) or pembrolizumab (RR = 0.52, 95% CI 0.34, 0.81). Implications: Nivolumab, pembrolizumab and atezolizumab exhibited superior benefit/risk balance compared to other licensed drugs used late stage NSCLC. Our results indicate that the use of immunotherapies in people diagnosed with non-specific late stage NSCLC should be promoted. The use of docetaxel may now be judged irrelevant as a comparator intervention for approval of new drugs for second line treatment of NSCLC. Study registration number: PROSPERO . [ABSTRACT FROM AUTHOR]

Background and purpose: The role of preoperative short-course radiotherapy (SCRT) in rectal cancer treatment, when compared to long-course radiochemotherapy (LCRT), is still controversial. Thus the meta-analysis with trial sequential analysis (TSA) was performed to evaluate the long-term survival of SCRT and LCRT as therapeutic regimens for locally advanced rectal cancer. Material and methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to August 2017 for eligible studies. Hazard ratios (HRs) or odds ratios (ORs) of overall survival (OS), disease free survival (DFS) and local recurrence (LR) with the corresponding 95% confidence intervals (CIs) were calculated and TSA was applied. Results: 11 studies with 1984 patients were included. There was no significant difference in OS (HR = 0.92, 95% CI: 0.75–1.13, p = 0.44), DFS (HR = 0.94, 95% CI: 0.79–1.12, p = 0.50) and LR (OR = 0.73, 95% CI: 0.49–1.08, p = 0.11) between SCRT and LCRT groups. TSA suggested firm evidence for lacking on average a -10% relative risk reduction (RRR) in 4-year OS but no statistical significance in 4-year DFS. Conclusions: Preoperative SCRT is as effective as LCRT for locally advanced colorectal cancer in long-term survival. SCRT could be preferential while facing long waiting lists or lacking medical resource. [ABSTRACT FROM AUTHOR]

Background: We evaluated the associations of handgrip strength and cognitive function in cancer survivors ≥ 60 years old using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Data in two waves of NHANES (2011–2014) were aggregated. Handgrip strength in kilogram (kg) was defined as the maximum value achieved using either hand. Two cognitive function tests were conducted among adults 60 years and older. The Animal Fluency Test (AFT) examines categorical verbal fluency (a component of executive function), and the Digital Symbol Substitution test (DSST) assesses processing speed, sustained attention, and working memory. Survey analysis procedures were used to account for the complex sampling design of the NHANES. Multiple linear regression models were used to estimate associations of handgrip strength with cognitive test scores, adjusting for confounders (age, gender, race/ethnicity, education, marital status, smoking status, depressive symptoms and leisure time physical activity). Results: Among 383 cancer survivors (58.5% women, mean age = 70.9 years, mean BMI = 29.3 kg/m2), prevalent cancer types were breast (22.9%), prostate (16.4%), colon (6.9%) and cervix (6.2%). In women, each increase in kg of handgrip strength was associated with 0.20 (95% CI: 0.08 to 0.33) higher score on AFT and 0.83 (95% CI: 0.30 to 1.35) higher score on DSST. In men, we observed an inverted U-shape association where cognitive function peaked at handgrip strength of 40–42 kg. Conclusions: Handgrip strength, a modifiable factor, appears to be associated with aspects of cognitive functions in cancer survivors. Prospective studies are needed to address their causal relationship. [ABSTRACT FROM AUTHOR]

In the traditional two-step procedure used in intensity-modulated radiation therapy, fluence map optimization (FMO) is performed first, followed by use of a leaf sequencing algorithm (LSA). By contrast, direct aperture optimization (DAO) directly optimizes aperture leaf positions and weights. However, dose calculation using the Monte Carlo (MC) method for DAO is often time-consuming. Therefore, a rapid DAO (RDAO) algorithm is proposed that uses a dose influence matrix based piecewise aperture dose model (DIM-PADM). In the proposed RDAO algorithm, dose calculation is based on the dose influence matrix instead of MC. The dose dependence of aperture leafs is modeled as a piecewise function using the DIM. The corresponding DIM-PADM-based DAO problem is solved using a simulated annealing algorithm.The proposed algorithm was validated through application to TG119, prostate, liver, and head and neck (H&N) cases from the common optimization for radiation therapy dataset. Compared with the two-step FMO–LSA procedure, the proposed algorithm resulted in more precise dose conformality in all four cases. Specifically, for the H&N dataset, the cost value for the planned target volume (PTV) was decreased by 32%, whereas the cost value for the two organs at risk (OARs) was decreased by 60% and 92%. Our study of the proposed novel DIM-PADM-based RDAO algorithm makes two main contributions: First, we validate the use of the proposed algorithm, in contrast to the FMO–LSA framework, for direct optimization of aperture leaf positions and show that this method results in more precise dose conformality. Second, we demonstrate that compared to MC, the DIM-PADM-based method significantly reduces the computational time required for DAO. [ABSTRACT FROM AUTHOR]

Silicon-diode-based detectors are commonly used for the dosimetry of small radiotherapy beams due to their relatively small volumes and high sensitivity to ionizing radiation. Nevertheless, silicon-diode-based detectors tend to over-respond in small fields because of their high density relative to water. For that reason, detector-specific beam correction factors () have been recommended not only to correct the total scatter factors but also to correct the tissue maximum and off-axis ratios. However, the application of to in-depth and off-axis locations has not been studied. The goal of this work is to address the impact of the correction factors on the calculated dose distribution in static non-conventional photon beams (specifically, in stereotactic radiosurgery with circular collimators). To achieve this goal, the total scatter factors, tissue maximum, and off-axis ratios were measured with a stereotactic field diode for 4.0-, 10.0-, and 20.0-mm circular collimators. The irradiation was performed with a Novalis® linear accelerator using a 6-MV photon beam. The detector-specific correction factors were calculated and applied to the experimental dosimetry data for in-depth and off-axis locations. The corrected and uncorrected dosimetry data were used to commission a treatment planning system for radiosurgery planning. Various plans were calculated with simulated lesions using the uncorrected and corrected dosimetry. The resulting dose calculations were compared using the gamma index test with several criteria. The results of this work presented important conclusions for the use of detector-specific beam correction factors ( in a treatment planning system. The use of for total scatter factors has an important impact on monitor unit calculation. On the contrary, the use of for tissue-maximum and off-axis ratios has not an important impact on the dose distribution calculation by the treatment planning system. This conclusion is only valid for the combination of treatment planning system, detector, and correction factors used in this work; however, this technique can be applied to other treatment planning systems, detectors, and correction factors. [ABSTRACT FROM AUTHOR]

Although studies from pediatric cancers (largely acute lymphoblastic leukemia) have shown that patients undergoing systemic chemotherapy may experience decreased growth velocity during the treatment phase, no such data exist for retinoblastoma patients treated with systemic chemotherapy or ophthalmic artery chemosurgery (OAC). The purpose of this study is to report growth patterns of our retinoblastoma (Rb) population who were treated with OAC in a retrospective, single center (Memorial Sloan Kettering Cancer Center) review of 341 patients treated between 2006 and 2016. Children who only received OAC were classified as naive; those who were treated initially with systemic chemotherapy and subsequently presented to our center for OAC were termed secondary; and a small group of patients who received single-agent systemic chemotherapy prior to OAC were labeled bridge. For all patients, height and weight were recorded at monthly intervals during OAC (short-term) and then annually during a follow-up period (long-term) up to 3 years after treatment. Excluded from this study were children who received external radiation therapy and those with genetic syndromes, which are independently associated with growth derangements. During OAC, there was no significant difference in growth velocity between the naïve and secondary groups. In either group, number of treatments also did not affect growth rate. Three years after the end of OAC, naïve patients were in the 68th percentile by height (95% CI 61.30, 74.63) compared to secondary patients in the 61st percentile (95% CI 51.1, 71.47). Both groups were in the same weight percentiles during the first two years of follow-up but at the three-year follow-up period, naïve patients were in the 63rd percentile (95% CI 57.4, 69.4) and secondary patients were in the 60th percentile (95% CI 50.4, 69.7). OAC for retinoblastoma does not appear to impact short-term growth velocity, weight gain during the treatment period or after three years. [ABSTRACT FROM AUTHOR]

Background: mTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. The effect of mTOR-Is on the overall incidence of tumors irrespective of their origin is not entirely clear. Furthermore, conflicting data have been shown on mortality under mTOR-Is. Methods: The current literature was searched for prospective randomized controlled renal transplantation trials. There were 1415 trials screened of which 13 could be included (pts. = 5924). A minimum follow-up of 24 months was mandatory for inclusion. Incidence of malignancies and patient survival was assessed in meta-analyses. Results: The average follow-up of all trials was 40.6 months. Malignancy was significantly reduced under mTOR-Is compared to CNIs (RR 0.70, CI 0.49–0.99, p = 0.046). This effect remained stable when combined with CNIs (RR 0.58, CI 0.34–1.00, p = 0.05). When NMSCs were excluded the risk for malignancy remained significantly reduced under mTOR-I therapy (mono and combi) (RR 0.43, CI 0.24–0.77, p = 0.0046). Graft survival was minimally decreased under mTOR-Is (RR 0.99, CI 0.98–1.00, p = 0.054). This effect was abrogated when mTOR-Is were combined with CNIs (RR 0.99, CI 0.97–1.02, p = 0.50). Patient survival was not different (RR 1.00, CI 0.99–1.01, p = 0.54). Conclusions: Posttransplant patients have a lower incidence of malignancy when treated with an mTOR-I no matter if it is used in combination with CNIs or not. This beneficial effect remains significant even when NMSCs are excluded. With currently used mTOR-I-based regimen patient and graft survival is not different compared to CNI therapies. [ABSTRACT FROM AUTHOR]

Background: This study assessed the prognostic value of HE4 marker measurements at various stages of first-line chemotherapy for ovarian cancer. Methods: The study consisted of 90 ovarian cancer patients, including 48 women undergoing primary surgical treatment and 42 patients qualified for neoadjuvant chemotherapy. Each patient underwent HE4 and CA 125 level measurements at the time of diagnosis and subsequently as follows: after surgical treatment, after the third course of adjuvant chemotherapy, before interval cytoreductive surgery and after chemotherapy. The HE4 value was assessed based on the PSF, OS, DFS, surgical outcome, two-year survival and platinum sensitivity. Results: Preoperative HE4 levels were a predictor of platinum sensitivity (AUC– 0.644; p = 0.035) and DFS (AUC = 0.637; p = 0.0492). A univariate logistic regression analysis showed that serum HE4 significantly correlated with PFS (baseline results over median HR = 2.96, p = 0.0009; baseline over 75 percentile HR = 2.44, p = 0.0062; normalization after treatment HR = 0.46, p = 0.0125; 50% reduction before IDS HR = 0.64, p = 0.0017). In the multivariate analysis, normalization after treatment and 50% reduction before IDS significantly influenced the PFS (HR = 0.29, p = 0.00008; HR = 0.23, p = 0.0024). The HE4 levels also correlated with the OS as follows: values below the median (HR = 1.88, p = 0.0087), normalization after chemotherapy (HR = 0.08, p = 0.0003), and 50% reduction before IDS (HR = 0.39, p = 0.0496). Conclusions: The significant effect of the normalization of the HE4 marker after therapy and 50% reduction of HE4 levels before interval cytoreductive surgery on PFS and OS confirmed that HE4 might be an independent prognostic factor of treatment response. HE4 measurements performed during first-line treatment of ovarian cancer may have prognostic significance. [ABSTRACT FROM AUTHOR]

Objectives: To compare clinical outcomes of concurrent chemoradiotherapy (CCRT) with those of radiotherapy alone for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy (IMRT) era. Materials and methods: We comprehensively searched PubMed, Embase, and the Cochrane Library to identify eligible studies. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRRFS) with hazard ratios (HRs), and toxicities with odd ratios (ORs) were analyzed. Results: A total of seven studies met the criteria, with 1302 patients who were treated with IMRT alone or IMRT plus concurrent chemotherapy. No significant survival benefit was shown by CCRT regardless of OS (HR = 1.17, 95% CI 0.73–1.89, P = 0.508), PFS (HR = 0.76, 95% CI 0.38–1.50, P = 0.430), DMFS (HR = 0.89, 95% CI 0.33–2.41, P = 0.816), or LRRFS (HR = 1.03, 95% CI 0.95–1.12, P = 0.498). Additionally, CCRT notably increased the risk of acute grade 3–4 leukopenia (OR = 4.432, 95% CI 2.195–8.952, P < 0.001), compared to IMRT alone. Conclusion: Adding concurrent chemotherapy to IMRT led to no survival benefit and increased acute toxicity reactions for stage II nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. Methods: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). Results: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. Conclusion: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient’s HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients’ information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer. Methods: We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration’s Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS. Results: A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25–0.98; p = 0.04), 0.34 (95% CI, 0.21–0.55; p<0.0001) and 0.44 (95% CI, 0.30–0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS, respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25–0.72; p = 0.002). Conclusion: Patients with resectable gastric or GEJ cancer who achieved pCR after neoadjuvant chemotherapy can gain a better outcome than patients without pCR. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials. Using data on 9,651 patients who underwent first allogeneic HLA-identical sibling or unrelated donor HCT between 01/1999-12/2011 for treatment of a hematologic malignancy, we developed and evaluated a suite of risk prediction tools for: (i) acute GVHD within 100 days post-transplant and (ii) a composite endpoint of acute GVHD or death within 100 days post-transplant. We considered two sets of inputs: (i) clinical factors that are typically readily-available, included as main effects; and, (ii) main effects combined with a selection of a priori specified two-way interactions. To build the prediction tools we used the super learner, a recently developed ensemble learning statistical framework that combines results from multiple other algorithms/methods to construct a single, optimal prediction tool. Across the final super learner prediction tools, the area-under-the curve (AUC) ranged from 0.613–0.640. Improving the performance of risk prediction tools will likely require extension beyond clinical factors to include biological variables such as genetic and proteomic biomarkers, although the measurement of these factors may currently not be practical in standard clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: To describe the proportion of colorectal cancer (CRC) survivors who perceive a need for dietary support; to examine which socio-demographic, cancer-related, and health-related characteristics are associated with this need; to explore reasons for (not) needing support; and to explore CRC survivors’ specific needs and preferences with regard to lifestyle (i.e., dietary, exercise, and/or weight management) support. Methods: This mixed-methods study comprised a cross-sectional survey among 1774 Dutch CRC survivors and three focus groups (n = 16). To examine associations, logistic regression analyses were conducted. Focus groups were audio-taped, transcribed verbatim, and analyzed using a thematic approach. Results: Of 1458 respondents (82%), 1198 (67.5%) were included for analyses. 17.5% reported a need for dietary support. Characteristics associated with this need were: being younger, living without a partner, having a stoma, having diabetes, and being overweight or obese. The main reason for needing support was being unable to initiate and maintain lifestyle changes without support. CRC survivors preferred receiving information soon after diagnosis to make an autonomous, informed decision on improving their lifestyle. They preferred to receive individually-tailored lifestyle support in an autonomy-supportive environment, preferably with involvement of their family and fellow-sufferers. Conclusions: This study has provided knowledge on appropriate support for CRC survivors in need for dietary support to improve health outcomes by promoting adherence to lifestyle and body weight recommendations. Findings can be used to better identify CRC survivors in need for dietary support, and to tailor lifestyle support to their needs and preferences in order to promote uptake, adherence, and effectiveness. [ABSTRACT FROM AUTHOR]

Background: Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities. Methods: The biological data gained during these experiments were fed into our previously developed computer model “Cancer and Treatment Simulation Tool” (CaTSiT) to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model. Results: According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels’ geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor’s therapeutic susceptibility and its metastatic spreading behavior. Conclusion: Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor. [ABSTRACT FROM AUTHOR]

Background/Purpose: Radiation treatment (RT) stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA) to analyze cytokines in non-small cell lung cancer (NSCLC) patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT) and conventionally fractionated RT (CFRT) without or with chemotherapy. Methods: The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16), CFRT (n = 18), or CFRT (n = 107) with concurrent chemotherapy (ChRT). Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point. Results: Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l. Conclusions: PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA. [ABSTRACT FROM AUTHOR]

Background: Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. Methodology & findings: Systematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH) assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year’s treatment and then decreased over time to zero. Conclusion: With all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was preferred after 24 months. [ABSTRACT FROM AUTHOR]

Background: Selective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals. Methods: We searched PubMed for randomized controlled trials from Jan 1, 2010 –Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined. Results: 180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results. Conclusion: Across trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes. [ABSTRACT FROM AUTHOR]

Background: In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods: We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results: Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions: Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value. [ABSTRACT FROM AUTHOR]

Background: Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose: As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic meta-analysis. Data sources: Pubmed, EMBASE and Web of Science were searched from their first record to September 23th 2014. Study selection: Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis: Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when ≥5 studies per test were included. Data synthesis: We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95%CI 72–92) and specificity of 82% (71–89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74–96) and specificity of 86% (69–94). Limitations: Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions: The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis compared laparoscopic surgery (LAP) and open resection (OPEN) for the treatment of gastric gastrointestinal stromal tumors (GISTs) with regard to feasibility and safety. Methods: We searched PubMed, Embase, and Web of Science for studies published before March 2016 comparing the LAP and OPEN procedures for GISTs. RevMan 5.1 software was used for the meta-analysis. Results: In total, 28 studies met the inclusion criteria for the meta-analysis. The mean tumor sizes in the OPEN and LAP groups were 4.54 and 5.67 cm. Compared with the OPEN patients, the LAP patients experienced shorter surgical times (P = 0.05), less blood loss (P<0.01), earlier time to flatus (P<0.01) and an oral diet (P<0.01), and shorter hospital stays (P<0.01). The LAP patients also exhibited a decrease in overall complications (P<0.01). In addition, regarding the subgroup of larger GISTs (>5 cm), the present study did not report significant differences in operation time (P = 0.93), postoperative complications (P = 0.30), or recurrence rate (P = 0.61) between the two groups, though LAP was associated with favorable results regarding blood loss (P = 0.03) and hospital stay (P<0.01). Conclusions: Compared with the OPEN procedure, the LAP procedure is associated with preferable short-term postoperative outcomes and does not compromise long-term oncological outcomes. For gastric GISTs >5 cm, no significant difference was detected between LAP and OPEN if patient selection and intraoperative decisions were carefully considered. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was designed to assess the efficacy of the male sling and artificial urinary sphincter on treating post-prostatectomy incontinence by evaluating daily pad use, cure rate, frequency of improvement in incontinence, and quality of life. Methods: Medline, Cochrane, Google Scholar, and ClinicalTrials.gov were searched (until March 31, 2014) for studies that investigated the effectiveness of artificial urinary sphincter or sling surgical treatments for prostate cancer. The primary outcome was daily pad use before and after surgery and secondary outcomes were quality of life before and after surgery, and frequency of cures (no need to use of a pad for at least 1 day) and improvements (decreased pad usage) in incontinence after surgery. Results: We found that that both the sling and artificial urinary sphincter significantly decreased the number of pads used per day by about 3 (P-values <0.001) and increased the quality of life compared with before intervention (P-values < 0.001). In addition, the cure rate and was around 60%. Intervention resulted in improvement in incontinence by about 25% (P < 0.001). Conclusion: Our findings indicate that both sling and artificial urinary sphincter interventions are effective in reducing incontinence and improving the patient’s quality of life. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to prove that facial surface electromyography (sEMG) conveys sufficient information to predict 3D lip shapes. High sEMG predictive accuracy implies we could train a neural control model for activation of biomechanical models by simultaneously recording sEMG signals and their associated motions. Materials and methods: With a stereo camera set-up, we recorded 3D lip shapes and simultaneously performed sEMG measurements of the facial muscles, applying principal component analysis (PCA) and a modified general regression neural network (GRNN) to link the sEMG measurements to 3D lip shapes. To test reproducibility, we conducted our experiment on five volunteers, evaluating several sEMG features and window lengths in unipolar and bipolar configurations in search of the optimal settings for facial sEMG. Conclusions: The errors of the two methods were comparable. We managed to predict 3D lip shapes with a mean accuracy of 2.76 mm when using the PCA method and 2.78 mm when using modified GRNN. Whereas performance improved with shorter window lengths, feature type and configuration had little influence. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has demonstrated that cyclooxygenase-2 (COX-2) is involved in head and neck cancers, especially in nasopharyngeal carcinoma (NPC). However, the association between COX-2 expression and lymph node metastasis in NPC remains uncertain. This systematic review and meta-analysis meta-analysis investigated the relationship between COX-2 expression and lymph node metastasis and other signs of disease progression in NPC. Methods: Previously published studies assessing COX-2 expression and lymph node metastasis in NPC were identified in four English databases and three Chinese ones (Pubmed, Embase, Cochrane Database of Systematic Reviews, Web of Science, China National Knowledge Infrastructure, Wanfang, Vip Journal Integration Platform) up to November 2016. Quality of all eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Pooled odds ratios (OR) and their 95% confidence intervals (95%CI) were calculated with fixed-effects or random-effects model to evaluate the effects of COX-2 expression on lymph node metastasis. Results: A total of 27 studies with 1797 NPC patients met the inclusion criteria. The expression of COX-2 was significantly higher in patients with nasopharyngeal carcinoma than those without the carcinoma, with a combined OR of 21.17 (95%CI = 15.02–29.85, I2 = 35.1%, Pheterogeneity = 0.070). A statistically significant association between COX-2 expression and lymph node metastasis in NPC patients, with an OR of 4.44 (95%CI = 3.46–5.70, I2 = 38.3%, Pheterogeneity = 0.024), and with other indicators of disease progression. Subgroup analyses based on COX-2 assay and staging criteria of TNM showed no significant heterogeneity. Conclusions: The results suggest that expression of COX-2 is associated with lymph node metastasis and disease progression in NPC, indicating a potential role in evaluation of prognosis and in treatment decisions. COX-2 inhibitors have potential in the treatment of NPC that should be further investigated. [ABSTRACT FROM AUTHOR]

Purpose: The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC). Method: Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model. Results: This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4–41.5) and 55.6% (95% CI 49.2–61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3–64.9), 70.3% (95% CI 62.6–76.9), and 40.0% (95% CI 30.6–50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1–39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070). Conclusions: Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Methods and findings: Network meta-analysis (NMA) was used to examine which trials’ data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks’ trastuzumab is cost-saving and leads to more QALYs than 12 months’, i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. Conclusions: Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks’ with 14 months’ trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials’ data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results. [ABSTRACT FROM AUTHOR]

Background: Vesicovaginal fistulas (VVF) are the most commonly acquired fistulas of the urinary tract, but we lack a standardized algorithm for their management. Surgery is the most commonly preferred approach to treat women with primary VVF following benign gynaecologic surgery. Objective: To carry out a systematic review and meta-analysis on the effectiveness of operative techniques or conservative treatment for patients with postsurgical VVF. Our secondary objective was to define the surgical time and determine the types of study designs. Methods: PubMed, Old Medline, Embase and Cochrane Central Register of Controlled Trials were used as data sources. This systematic review was modelled on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, including a registration number (CRD42012002097). Results: We reviewed 282 full text articles to identify 124 studies for inclusion. In all, 1379/1430 (96.4%) patients were treated surgically. Overall, the transvaginal approach was performed in the majority of patients (39%), followed by a transabdominal/transvesical route (36%), a laparoscopic/robotic approach (15%) and a combined transabdominal-transvaginal approach in 3% of cases. Success rate of conservative treatment was 92.86% (95%CI: 79.54–99.89), 97.98% in surgical cases (95% CI: 96.13–99.29) and 91.63% (95% CI: 87.68–97.03) in patients with prolonged catheter drainage followed by surgery. 79/124 studies (63.7%) provided information for the length of follow-up, but showed a poor reporting standard regarding prognosis. Complications were studied only selectively. Due to the inconsistency of these data it was impossible to analyse them collectively. Conclusions: Although the literature is imprecise and inconsistent, existing studies indicate that operation, mainly through a transvaginal approach, is the most commonly preferred treatment strategy in females with postsurgical VVF. Our data showed no clear odds-on favorite regarding disease management as well as surgical approach and current evidence on the surgical management of VVF does not allow any accurate estimation of success and complication rates. Standardisation of the terminology is required so that VVF can be managed with a proper surgical treatment algorithm based on characteristics of the fistula. [ABSTRACT FROM AUTHOR]

Purpose: While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. Methods: Seven electronic databases were searched (1990–2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. Results: Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. Conclusions: The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs. [ABSTRACT FROM AUTHOR]

Background and objective: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its impact on postoperative outcomes and long-term survival after cancer resection remains controversial. A meta-analysis of published studies was conducted to address this issue. Methods: An extensive electronic search of four databases was performed for relevant articles. Data were processed for meta-analysis using Review Manager version 5.1. Results: Seventeen observational studies involving 5407 patients were subjected to the analysis. Overall morbidity or any type of complications and mortality were comparable between diabetic and non-diabetic subjects. Overall DM has a significant negative impact on survival (risk ratio [RR], 1.24, 95% confidence interval [CI], 1.05–1.45; P = 0.01). Stratification by the type of DM revealed that new-onset DM (<2 years duration, RR, 1.54, 95% CI, 1.24–1.91; P <0.001) but not long-standing DM (≥2 years duration, RR, 1.74, 95% CI, 0.86–3.52; P = 0.12) was associated with reduced survival. Conclusions: Diabetes mellitus does not affect perioperative outcomes in patients undergoing surgery for pancreatic cancer. However, new-onset DM confers a negative impact on survival of pancreatic cancer in patients undergoing surgical resection. [ABSTRACT FROM AUTHOR]

Objective: Phosphorylated mammalian target of rapamycin (p-mTOR) is a promising prognostic marker in many types of cancer. However, its survival benefit in patients with breast carcinoma remains unknown. The aim of the present study was to assess the relationship between p-mTOR expression and prognosis in breast carcinoma based on a systematic review and meta-analysis. Materials and Methods: Electronic databases (including Pubmed, Embase, ISI web of science, and Cochrane Library) were searched up to November 24, 2015. The outcome measures were hazard ratios (HRs) with 95% confidence interval (CI) for the association between the prognosis of breast carcinoma patients and p-mTOR expression. Primary end points were disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS). Statistical analysis was performed with STATA 12.0. Results: Nine cohort studies including 3051 patients met full eligibility criteria. The pooled HRs (95% CI) for OS, DFS, and RFS were 0.84 (0.27–2.63), 0.71 (0.40–1.23), and 0.48 (0.20–1.18), respectively. Conclusions: Our findings suggested that p-mTOR overexpression was not significantly related to prognosis in breast carcinoma regarding OS and disease recurrence. Prospective studies are warranted to examine the association between p-mTOR expression and survival outcomes in breast carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: miRNAs are stable and can be extracted from tissues, blood and other body fluid without degradation. miRNAs are abnormally expressed in the presence of a pathological status, including cancer. Therefore, miRNAs are ideal biomarkers for cancer diagnosis and prognosis. Patients with triple negative breast cancer (TNBC) suffer the worst prognosis, although great efforts have been made. Many studies have investigated the role of miRNAs in predicting the outcomes of TNBC patients for better adjustment of treatment. However, results were inconsistent. Thus, we performed a meta-analysis to summarize the published studies for conclusive results. Methods: Eligible studies from different database were retrieved from the online databases, and we used STSTA 12.0 to analysis the prognostic role of miRNAs in triple negative breast cancer. Results: Overall high miRNA expression indicated a worse survival with HR value of 1.78 (95% CI: 0.97–3.25). However, subtotal HRs of oncogenic miRNAs and tumor suppressive miRNAs were 2.73 (95% CI: 2.08–3.57; P<0.001) and 0.44 (95% CI: 0.21–0.90; P = 0.024), respectively, and no heterogeneity was observed within the subgroups. Conclusions: The miRNAs showed a slightly stronger prognostic value for disease-free survival, relapse-free survival and distant metastasis-free survival compared to the overall survival of TNBC patients. Circulating miRNAs could serve as potential biomarkers for the prognosis of TNBC patients and need further investigation. [ABSTRACT FROM AUTHOR]

Background: Benign biliary stricture is a rare condition and the majority of the cases are caused by operative trauma or chronic inflammation based on various etiology. Although the initial results of endoscopic, percutaneous and surgical treatment are impressive, no comparison about long term stricture resolution is available. Aims: The goal of this study was to compare the long term disease free survival in benign biliary strictures with various etiology after surgery, percutaneous transhepatic—and endoscopic treatment. Methods: PubMed, Embase, and Cochrane Library were searched by computer and manually for published studies. The investigators selected the publications according to the inclusion and exclusion criteria, processed the data and assessed the quality of the selected studies. Meta-analysis of data of 24 publications was performed to compare long term disease free survival of different treatment groups. Results: Compared the subgroups surgery resulted in the highest long term stricture resolution rate, followed by the percutaneous transhepatic treatment, the multiple plastic stent insertion and covered self-expanding metal stents (SEMS), however the difference was not significant. All compared methods are significantly superior to the single plastic stent placement. Long term stricture resolution rate irrespectively of any therapy is still not more than 84%. Conclusions: In summary, the use of single plastic stent is not recommended. Further randomized studies and innovative technical development are required for improving the treatment of benign biliary strictures. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate the prognostic role of the duration of adjuvant chemotherapy in patients with epithelial ovarian, fallopian tube and primary peritoneal cancer (EOC). Materials and Methods: Within the present study we retrospectively evaluated the data of 165 consecutive patients with EOC treated with primary surgery followed by six completed cycles of platinum-taxan based intravenous adjuvant chemotherapy. Medians of total duration of chemotherapy were compared with clinical-pathological parameters. Patients were stratified into four risk groups according to the delay in days of total duration of chemotherapy, and univariate and multivariable survival analyses were performed. Results: The median duration of six completed cycles of chemotherapy comprised 113 days (IQR 107–124 days). Uni- and multivariable survival analyses revealed a delay of total duration of chemotherapy of at least 9 days to be associated with progression-free (PFS), cancer-specific (CSS) and overall survival (OS). Hazard ratios (HR), confidence intervals (95% CI) and p-values for PFS, CSS and OS due to delay of chemo-duration were 2.9 (1.6–5.4; p = 0.001), 2.9 (1.3–6.2; p = 0.008) and 2.6 (1.3–5.4; p = 0.008), respectively. Prolonged total chemo-duration was associated with the amount of postoperative residual disease (p = 0.001) and the patients’ age (p = 0.03). Conclusion: The present study suggests a prolonged duration of adjuvant chemotherapy after primary surgery to adversely affect PFS, CSS and OS in patients with EOC. Yet larger studies are required to validate our results. [ABSTRACT FROM AUTHOR]

Purpose: Cellular immunotherapy has appeared to be a promising modality for the treatment of malignant tumor. The objective of this study was to evaluate the efficacy of cellular immunotherapy combined with minimally invasive therapy. Methods: We searched PubMed, Web of Science and The Cochrane Library through March 2016 for relevant studies. Short-term efficacy (the disease control rate, the control rate of quality life and the AFP descent rate) and long-term efficacy (overall survival (OS) and progression-free survival (PFS) rate) were compared as the major outcome measures. The meta-analysis was performed using Review Manager 5.3. Results: A total of 1174 references in 3 databases were found of which 19 individual studies with 1774 HCC patients enrolled in this meta-analysis. Meta-analysis results showed that cellular immunotherapy combined with minimally-invasive treatment significantly improved the measures of short-term response (the disease control rate (OR = 5.91, P = 0.007), the control rate of quality lift (OR = 3.38, P = 0.003) and the AFP descent rate (OR = 4.48, P = 0.02)). Also higher 6-month PFS (OR = 2.78, P = 0.05), ≥12-month PFS (OR = 3.56, P<0.00001) rate and 6-month OS (OR = 2.81, P = 0.0009), 12-month OS (OR = 3.05, P<0.00001) and 24-month OS (OR = 3.52, P<0.0001) rate were observed in patients undergoing cellular immunotherapy. Conclusions: This meta-analysis suggested that cellular immunotherapy is a feasible adjuvant treatment that could be beneficial for the improvement of the clinical outcomes for hepatocellular carcinoma (HCC) patients after minimally invasive treatment, including short-term response and long-term survival. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. Methodology/Principal Findings: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included. We found that the median progression-free survival (PFS) was higher in the BV group than in the standard therapy (ST) group (pooled hazard ratio, 0.73; 95%CI, 0.62–0.86; P = 0.0001). Compared with ST, BV improved the PFS rate at 6 months (OR 3.33, 95% CI 2.73–4.06, p<0.00001) and 12 months (OR 2.10, 95% CI 1.74–2.54, p<0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR, 1.01; 95%CI, 0.83–1.23; P = 0.95). The BV group had higher survival rates at 6 months (OR, 1.41; 95% CI, 1.09–1.84; P = 0.01) and 12 months (OR, 1.23; 95% CI, 1.02–1.48; P = 0.03), but a low survival rate at the 36-month follow-up (OR, 0.57; 95% CI, 0.32–0.98; P = 0.04). For the incidence of adverse events, three adverse outcomes were found to be significantly different between BV and ST groups, including hypertension (8.37% vs. 1.62%, p<0.000001), proteinuria (7.65% vs. 0%, p<0.001), and fatigue (14.54% vs. 9.01%, p = 0.05). Conclusions/Significance: Our study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS, maintaining the quality of life and functional status. However, the long-term use of BV is associated with a higher incidence of adverse events and mortality. Study Registration: This research was registered at PROSPERO. (Registration Number: CRD42016038247). [ABSTRACT FROM AUTHOR]

Background: Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications. Methods: An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM. Results: A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61–0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98–2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52–0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60–4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42–121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71–1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43–2.50, p = 0.93). Conclusions: BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM. [ABSTRACT FROM AUTHOR]

Background: The evidence to support dressing standards for breast surgery wounds is empiric and scarce. Objective: This two-arm randomized clinical trial was designed to assess the effect of dressing wear time on surgical site infection (SSI) rates, skin colonization and patient perceptions. Methods: A total of 200 breast cancer patients undergoing breast reconstruction were prospectively enrolled. Patients were randomly allocated to group I (dressing removed on the first postoperative day, n = 100) or group II (dressing removed on the sixth postoperative day, n = 100). SSIs were defined and classified according to criteria from the Centers for Disease Control and Prevention. Samples collected before placing the dressing and after 1 day (group I) and 6 days (both groups) were cultured for skin colonization assessments. Patients preferences and perceptions with regard to safety, comfort and convenience were recorded and analyzed. Results: A total of 186 patients completed the follow-up. The global SSI rate was 4.5%. Six patients in group I and three in group II had SSI (p = 0.497). Before dressing, the groups were similar with regard to skin colonization. At the sixth day, there was a higher colonization by coagulase-negative staphylococci in group I (p<0.0001). Patients preferred to keep dressing for six days (p<0.0001), and considered this a safer choice (p<0.05). Conclusions: Despite group I had a higher skin colonization by coagulase-negative staphylococci on the sixth postoperative day, there was no difference in SSI rates. Patients preferred keeping dressing for six days and considered it a safer choice. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background/Objective: Vascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis. Methods: A systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers. Results: We identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08). Conclusions: Anti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis. [ABSTRACT FROM AUTHOR]

Background: Using serum carbohydrate antigen 19–9 (CA 19–9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19–9 in predicting malignant pancreatic cystic lesions. Methods: Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. Results: A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35–0.59), and 0.88(95% CI: 0.86–0.91), respectively, and the AUC was 0.87(95% CI, 0.84–0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. Conclusions: Serum CA 19–9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods. [ABSTRACT FROM AUTHOR]