***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Multiple clinical , biologic , and pathologic factors are known to correlate with outcome in patients with invasive breast cancer . The utility of lymphovascular invasion as an additional useful prognostic indicator has been heretofore ill defined . The purpose of the current study was to determine whether the presence or absence of peritumoral lymphovascular invasion ( LVI ) contribute further significant information in assessing survival . METHODS Using a prospect i ve data base of 1,258 patients with invasive breast cancer followed up for as long as 12 years , eight factors were evaluated for their impact on patient survival : lymph node status , LVI , age at diagnosis , tumor size , tumor palpability , estrogen and progesterone receptor status , and nuclear grade . RESULTS Multivariate analysis revealed that both lymph node status and the presence or absence of LVI were highly significant independent predictors of outcome . CONCLUSIONS Knowledge of both lymph node status and the presence or absence of LVI can be used to predict which subset of patients will do extremely well ( node negative + LVI absent ) or extremely poorly ( node positive + LVI present ) . The combination of the two factors is most meaningful in patients with 1 to 3 positive nodes PURPOSE To prospect ively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis ( CS I NSGCT ) . PATIENTS AND METHODS From September 1996 to May 2002 , 200 patients with CS I NSGCT were prospect ively assigned to retroperitoneal lymph node dissection ( RPLND ) , and risk factor assessment was performed within a multicenter protocol . One hundred sixty-five patients had an adequate minimum follow-up of 12 months ( mean , 34.5 months ) or had pathologic stage II . RESULTS Pathologic stage II disease was found in 27.9 % of patients . Only 0.6 % of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease . With reference pathology , vascular invasion ( VI ) was most predictive of stage in multifactorial analysis ( accuracy , 65.1 % ) . However , the positive predictive value ( PPV ) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7 % . With absent VI , low-risk patients had a negative predictive value ( NPV ) of 76.9 % . With a combination of several risk factors , the PPV increased to 63.6 % and the negative predictive value increased to 86.5 % . CONCLUSION Even with an optimal combination of prognostic factors and reference pathology , more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and , therefore , would be overtreated with adjuvant therapy . However , patients at low risk may be predicted at an 86.5 % level , and thus , surveillance in highly compliant patients would be a valuable option . For high-risk patients , further reduction of adjuvant treatment is necessary BACKGROUND Retrospective studies demonstrated that cell cycle-related and proliferation biomarkers add information to st and ard pathologic tumor features after radical cystectomy ( RC ) . There are no prospect i ve studies validating the clinical utility of markers in bladder cancer . OBJECTIVE To prospect ively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder ( UCB ) who were likely to experience disease recurrence or mortality . DESIGN , SETTING , AND PARTICIPANTS Between January 2007 and January 2012 , every patient with high- grade bladder cancer , including 216 patients treated with RC and lymphadenectomy  , underwent immunohistochemical staining for tumor protein p53 ( Tp53 ) ; cyclin-dependent kinase inhibitor 1A ( p21 , Cip1 ) ( CDKN1A ) ; cyclin-dependent kinase inhibitor 1B ( p27 , Kip1 ) ; antigen identified by monoclonal antibody Ki-67 ( MKI67 ) ; and cyclin E1 . INTERVENTION Every patient underwent RC and lymphadenectomy , and marker staining . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality ( CSM ) . RESULTS AND LIMITATIONS Pathologic stage among the study population was pT0 ( 5 % ) , pT1 ( 35 % ) , pT2 ( 19 % ) , pT3 ( 29 % ) , and pT4 ( 13 % ) ; lymphovascular invasion ( LVI ) was seen in 34 % . The median number of removed lymph nodes was 23 , and 60 patients had lymph node involvement ( LNI ) . Median follow-up was 20 mo . Expression of p53 , p21 , p27 , cyclin E1 , and Ki-67 were altered in 54 % , 26 % , 46 % , 15 % , and 75 % patients , respectively . In univariable analyses , pT stage , LNI , LVI , perioperative chemotherapy ( CTx ) , margin status , and number of altered biomarkers predicted disease recurrence . In a multivariable model adjusting for pathologic stage , margins , LNI , and adjuvant CTx , only LVI and number of altered biomarkers were independent predictors of recurrence and CSM . The concordance index of a baseline model predicting CSM ( including pathologic stage , margins , LVI , LNI , and adjuvant CTx ) was 80 % and improved to 83 % with addition of the number of altered markers . CONCLUSIONS Molecular markers improve the prediction of recurrence and CSM after RC . They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline .  Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Despite years of research and hundreds of reports on tumour markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ologic problems have been cited to explain these discrepancies . Unfortunately , many tumour marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of study results . The development of guidelines for the reporting of  tumour marker studies  was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omised trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , pre-planned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply 
    Output:
    
LVI was associated with higher pathological T stage and tumor grade , as well as lymph node metastasis .
This meta- analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy .