***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 AND STUDY AIM While colonoscopy screening is widely used in several European countries and the United States , there are no r and omized trials to quantify its benefits . The Nordic-European Initiative on Colorectal Cancer ( NordICC ) is a multinational , r and omized controlled trial aim ing at investigating the effect of colonoscopy screening on colorectal cancer ( CRC ) incidence and mortality . This paper describes the rationale and design of the NordICC trial . STUDY DESIGN Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and r and omly assigned to either once-only colonoscopy screening with removal of all detected lesions , or no screening ( st and ard of care in the trial regions ) . All individuals are followed for 15 years after inclusion using dedicated national registries . The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up . POWER ANALYSIS : We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance , yielding a 25 % mortality reduction among those invited to screening . For 90 % power and a two-sided alpha level of 0.05 , using a 2:1 r and omization , 45 600 individuals will be r and omized to control , and 22 800 individuals to the colonoscopy group . Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up . CONCLUSIONS The aim of the NordICC trial is to quantify the effectiveness of population -based colonoscopy screening .  This will allow development of evidence -based guidelines for CRC screening in the general population Because interleukin-6 ( IL-6 ) is considered important in the proliferation of early multiple myeloma ( MM ) , we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone ( VMP ) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM . One hundred and six patients were r and omized to receive 9 cycles of VMP or VMP plus siltuximab ( 11 mg/kg every 3 weeks ) followed by siltuximab maintenance . Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions . With a complete response ( CR ) rate of 27 % on siltuximab plus VMP ( S+VMP ) and 22 % on VMP , the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10 % . Overall response rate was 88 % on S+VMP and 80 % on VMP , and at least very good partial response rates were 71 % and 51 % ( P = .0382 ) , respectively . Median progression-free survival ( 17 months ) and 1-year overall survival ( 88 % ) were identical in the 2 arms . Grade ≥3 adverse-event incidence was 92 % on S+VMP and 81 % on VMP ( P = .09 ) , with trends toward more hematologic events and infections on S+VMP . Maintenance therapy with siltuximab was well tolerated . In conclusion , the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes . This study was registered at http:// clinical trials.gov as # NCT00911859 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 ological 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 the study results . The development of guidelines for the reporting of  tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . Similar to the successful CONSORT initiative for r and omised trials and the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned 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 Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities . We investigated the association of eight different cytokines with  venous thromboembolism ( VTE ) and prognosis in cancer patients . The Vienna Cancer and Thrombosis Study ( CATS ) , a prospect i ve study , includes patients with newly diagnosed tumour or disease progression . Patients with an overt infection are excluded . Study end‐points are VTE , death , loss to follow‐up or study completion . Interleukin ( IL ) serum levels were measured using the xMAP technology developed by Luminex .  Among 726 included patients , no associations between IL levels and VTE were found , with the exception of a trend for IL‐1β and IL‐6 in pancreatic cancer . Elevated levels of IL‐6 [ as continuous variable per double increase hazard ratio ( HR ) = 1·07 , 95 % confidence interval ( CI ) = 1·027–1·114 , P = 0·001 , IL‐8 ( HR = 1·12 , 95 % CI = 1·062–1·170 , P < 0·001 ) and IL‐11 ( HR = 1·37 , 95 % CI = 1·103–1·709 , P = 0·005 ] were associated with worse survival . In subgroup analyses based on tumour type , colon carcinoma patients , who had higher IL‐6 levels , showed a shorter survival ( HR = 2·405 , 95 % CI = 1·252–4·618 , P = 0·008 ) . A significant association of elevated IL‐10 levels with a decrease in survival ( HR = 1·824 , 95 % CI = 1·098–3·031 , P = 0·020 ) was seen among patients with lung cancer . No correlation between VTE and IL levels was found , but higher IL‐6 , IL‐8 and IL‐11 levels were associated with worse survival in cancer patients . Further , elevated IL‐6 levels might be a prognostic marker in colorectal cancer and elevated IL‐10 levels in lung cancer patients Considering that the prognosis of patients with advanced biliary tract cancer ( BTC ) remains very poor , with a median survival of less than 1 year , new therapeutic approaches need to be developed . In the present study , a phase II clinical trial of personalized peptide vaccination ( PPV ) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers . A maximum of 4 human leukocyte antigen-matched peptides , which were selected based on the pre-existing host immunity prior to vaccination , were subcutaneously administered ( weekly for 6 consecutive weeks and bi-weekly thereafter ) to 25 advanced BTC patients without severe adverse events .  Humoral and /or T cell responses specific to the vaccine antigens were substantially induced in a subset of the vaccinated patients . As shown by multivariate Cox regression analysis , lower interleukin-6 ( IL-6 ) and higher albumin levels prior to vaccination and greater numbers of selected vaccine peptides were significantly favorable factors for overall survival [ hazard ratio (HR)=1.123 , 95 % confidence interval ( CI ) 1.008 - 1.252 , P=0.035 ; HR=0.158 , 95 % CI 0.029 - 0.860 , P=0.033 ; HR=0.258 , 95 % CI 0.098 - 0.682 , P=0.006 ; respectively ] . Based on the safety profile and substantial immune responses to vaccine antigens , PPV could be a promising approach for refractory BTC , although its clinical efficacy remains to be investigated in larger-scale prospect i ve studies . The identified biomarkers are potentially useful for selecting BTC patients who would benefit from PPV Background : Inflammation contributes to the pathogenesis of colorectal cancer ( CRC ) , and cytokine levels are altered during colorectal carcinogenesis . Methods : The serum levels of 13 cytokines and their relation to clinical and pathological parameters , and systemic inflammatory response ( mGPS , CRP and neutrophil – lymphocyte ratio ) , were analysed from a prospect i ve series of 148 CRC patients and 86 healthy age- and sex-matched controls . Results : CRC patients had higher serum platelet-derived growth factor , interleukin (IL)-6 , IL-7 , and IL-8 levels and lower monocyte chemotactic protein-1 ( MCP-1 ) levels than the controls . A logistic regression model for discriminating the patients from the controls – including the five most predictive cytokines ( high IL-8 , high IL-6 , low MCP-1 , low IL-1ra , and low IP-10 ) – yielded an area under curve value of 0.890 in receiver operating characteristics analysis . Serum cytokines showed distinct correlation with other markers of systemic inflammatory response , and advanced CRCs were associated with higher levels of IL-8 , IL-1ra , and IL-6 . A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu . Conclusion : CRC is associated with extensive alterations in serum cytokine environment , highlighting the importance of study ing relative cytokine level alterations . Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed Purpose We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival . Patients and Methods In all , 559 patients with pancreatic cancer from prospect i ve biomarker studies from Denmark ( n = 448 ) and Germany ( n = 111 ) were studied .  Plasma YKL-40 and IL-6  were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay . Results Odds ratios ( ORs ) for prediction of pancreatic cancer were significant for all biomarkers , with CA 19.9 having the highest AUC ( CA 19.9 : OR = 2.28 , 95 % CI 1.97 to 2.68 , p<0.0001 , AUC = 0.94 ; YKL-40 : OR = 4.50 , 3.99 to 5.08 , p<0.0001 , AUC = 0.87 ; IL-6 : OR = 3.68 , 3.08 to 4.44 , p<0.0001 , AUC = 0.87 ) . Multivariate Cox analysis ( YKL-40 , IL-6 , CA 19.9 , age , stage , gender ) in patients operated on showed that high preoperative IL-6 and CA 19.9 ( dichotomized according to normal values ) were independently associated with short overall survival ( CA 19.9 : HR = 2.51 , 1.22–5.15 , p = 0.013 ; IL-6 : HR = 2.03 , 1.11 to 3.70 , p = 0.021 ) . Multivariate Cox analysis of non-operable patients ( Stage IIB-IV ) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival ( YKL-40 : HR = 1.30 , 1.03 to 1.64 , p = 0.029 ; IL-6 : HR = 1.71 , 1.33 to 2.20 , p<0.0001 ; CA 19.9 : HR = 1.54 , 1.06 to 2.24 , p = 0.022 ) . Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival ( p<0.005 ) compared to patients with normal levels of both biomarkers ( 45 % vs. 92 % alive after 12 months ) . Conclusions Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9 . Combination of pretreatment YKL-40 , IL-6 , and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis OBJECTIVES : Difficult diagnoses and a lack of effective therapy complicate biliary tract malignancies .  Interleukin-6 ( IL-6 ) is a human bile duct epithelium growth factor correlated with tumor burden . We evaluated the usefulness of serum IL-6 in the diagnosis of primary BDC and measured changes in serum IL-6 levels following photodynamic therapy ( PDT ) . METHODS : We prospect ively measured serum IL 
    Output:
    
Circulating IL-6 levels appear to be an independent prognostic biomarker in patients with GI cancer , with high IL-6 levels associated with short overall survival ( OS ) .
The results for colorectal cancer were too ambiguous to give conclusive results .
IL-6 seemed to be a marker for some of the clinical characteristics of GI cancer , and may have a role in the diagnostic workup in general practice .
In conclusion , high circulating IL-6 was associated with short OS in most studies in GI cancer patients .
Whether inhibition of IL-6 would decrease GI cancer symptoms and increase quality of life is unknown