***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: Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers . The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test ( FOBT ) for early detection of colorectal cancer ( CRC ) is needed . A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening . Design Exhaled breath and watery stool sample s were obtained from patients with CRC and from healthy controls prior to colonoscopy .  Each test group consisted of one sample from a patient with CRC and four control sample s from volunteers without cancer . These five sample s were r and omly and separately placed into five boxes . A Labrador retriever specially trained in scent detection of cancer and a h and ler cooperated in the tests . The dog first smelled a st and ard breath sample from a patient with CRC , then smelled each sample station and sat down in front of the station in which a cancer scent was detected . Results 33 and 37 groups of breath and watery stool sample s , respectively , were tested . Among patients with CRC and controls , the sensitivity of canine scent detection of breath sample s compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99 . The sensitivity of canine scent detection of stool sample s was 0.97 and the specificity was 0.99 . The accuracy of canine scent detection  was high even for early cancer .  Canine scent detection  was not confounded by current smoking , benign colorectal disease or inflammatory disease . Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body . These odour material s may become effective tools in CRC screening . In the future , studies design ed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC BACKGROUND Sensitive , specific blood-based tests are difficult to develop unless steps are taken to maximize performance characteristics at every stage of marker discovery and development . We describe a sieving strategy for identifying high-performing marker assays that detect colorectal cancer (CRC)-specific methylated DNA in plasma . METHODS We first used restriction enzyme-based discovery methods to identify marker c and i date s with obviously different methylation patterns in CRC tissue and nonpathologic tissue . We then used a selection process incorporating microarrays and /or real-time PCR analysis of tissue sample s to further test marker c and i date s for maximum methylation in CRC tissue and minimum amplification in tissues from both healthy individuals and patients with other diseases . Real-time assays of 3 selected markers were vali date d with plasma sample s from 133 CRC patients and 179 healthy control individuals in the same age range . RESULTS Restriction enzyme-based testing identified 56 c and i date markers . This group was reduced to 6 with microarray and real-time PCR testing . Three markers , TMEFF2 , NGFR , and SEPT9 , were tested with plasma sample s. TMEFF2 methylation was detected in 65 % [ 95 % confidence interval , 56%-73 % ] of plasma sample s from CRC patients and not detected in 69 % ( 62%-76 % ) of the controls . The corresponding results for NGFR were 51 % ( 42%-60 % ) and 84 % ( 77%-89 % ) ; for SEPT9 , the values were 69 % ( 60%-77 % ) and 86 % ( 80%-91 % ) . CONCLUSIONS The stringent criteria applied at all steps of the selection and validation process enabled successful identification and ranking of blood-based marker c and i date Background About half of Americans 50 to 75 years old do not follow recommended colorectal cancer ( CRC ) screening guidelines , leaving 40 million individuals unscreened . A simple blood test would increase screening compliance , promoting early detection and better patient outcomes . The objective of this study is to demonstrate the performance of an improved sensitivity blood-based Septin 9 ( SEPT9 ) methylated DNA test for colorectal cancer . Study variables include clinical stage , tumor location and histologic grade . Methods Plasma sample s were collected from 50 untreated CRC patients at 3 institutions ; 94 control sample s were collected at 4 US institutions ; sample s were collected from 300 colonoscopy patients at 1 US clinic prior to endoscopy .  SEPT9 methylated DNA concentration  was tested in analytical specimens , plasma of known CRC cases , healthy control subjects , and plasma collected from colonoscopy patients . Results The improved SEPT9 methylated DNA test was more sensitive than previously described methods ; the test had an overall sensitivity for CRC of 90 % ( 95 % CI , 77.4 % to 96.3 % ) and specificity of 88 % ( 95 % CI , 79.6 % to 93.7 % ) , detecting CRC in patients of all stages . For early stage cancer ( I and II ) the test was 87 % ( 95 % CI , 71.1 % to 95.1 % ) sensitive . The test identified CRC from all regions , including proximal colon ( for example , the cecum ) and had a 12 % false-positive rate . In a small prospect i ve study , the SEPT9 test detected 12 % of adenomas with a false-positive rate of 3 % . Conclusions A sensitive blood-based CRC screening test using the SEPT9 biomarker specifically detects a majority of CRCs of all stages and colorectal locations . The test could be offered to individuals of average risk for CRC who are unwilling or unable to undergo colonscopy OBJECTIVES : The immunological fecal occult blood test ( IFOBT ) has established itself as a more precise marker for colorectal cancer ( CRC ) screening than traditional guaiac-based FOBT . The simpler , cheaper , and more convenient newer office-based IFOBTs have been vali date d for diagnosing CRC . Dimeric isoenzyme of pyruvate kinase , M2-PK , expressed by tumor cells , has as well been proposed as a screening tool for CRC . This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy . METHODS : Six hundred forty consecutive subjects ( symptomatic , as well as for CRC screening ) referred for colonoscopy for various indications across five centers in Germany provided the stool sample s for performing M2-PK and an immunochemical FOB strip test . The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin . For M2-PK , a commercially available s and wich enzyme-linked immunosorbent assay ( ELISA ) was used . The M2-PK test needs 6 h , while the office-based test can be read in just 10 min and is five times cheaper . RESULTS : Office-based IFOBT had sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and positive and negative likelihood ratios ( LR ) of 64.5 , 96.3 , 72.0 , 94.9 , 17.5 , and 0.4 for diagnosing colorectal neoplasia ( CRN ) , while the above performance characteristics for M2-PK at a cutoff value of 4U/mL were 72.4 , 73.8 , 29.0 , 94.8 , 2.8 , and 0.8 respectively . CONCLUSIONS : This office-based IFOBT was found to have significantly higher specificity , PPV , and positive LR as compared with M2-PK . IFOBT proved to be a convenient , noncumbersome , quick , and cheap tool in patients with above-average risk for detection of CRN Purpose Neoplasia cells exfoliated from colorectal epithelium have dysfunctional apoptotic mechanisms , thus it is possible to identify high-molecular weight DNA fragments in feces . This prospect i ve single-center study was performed to evaluate the sensitivity and specificity of fecal-based DNA integrity versus immunological fecal occult blood test ( iFOBT ) and calprotectin for colorectal cancer ( CRC ) and adenoma detection . Methods Feces were collected from 204 subjects and DNA integrity was quantified by quantitative-denaturing high performance liquid chromatography ( QdHPLC ) . Calprotectin and iFOBT  were assessed using commercial kits . The diagnostic performance was calculated by receiver operating characteristic ( ROC ) curves analysis . Results A total of 192 fecal specimens were analyzed and 12 sample s were excluded due to DNA degradation . We found long DNA ( L-DNA ) occurrence in feces with a sensitivity of 86 % ( n = 24/28 ) and a specificity of 81 % for CRC detection . To minimize false-positive cases of the developed test , area under the curve of ROC was evaluated such that the specificity was increased to 92 % with decreased sensitivity to 79 % , p = 0.0001 for CRC detection . iFOBT was positive in 51 % ( n = 14/27 ) while calprotectin was positive in 75 % ( n = 18/27 ) . The combination of iFOBT and L-DNA identified a greater number of CRC cases with a sensitivity of 89 % and a specificity of 95 % , p < 0.001 . The combination also improved the sensitivity of polyps , particularly high- grade dysplasia and advanced adenoma ( 33 % , p = 0.0015 ) as opposed to a single evaluation assay ( 17–21 % ) . Conclusions This study illustrates the usefulness of fecal DNA integrity assay by QdHPLC as a non-invasive , easy-to-perform , and reproducible method with a high level of sensitivity in detecting individuals with colorectal neoplasia . Combination of iFOBT and L-DNA improves the sensitivity for CRC and adenoma detection BACKGROUND & AIMS Screening colonoscopy examinations for colorectal cancer are offered in the United States and some European countries . Data on results and adverse effects of screening colonoscopy are limited . In autumn 2002 , colonoscopy was introduced as part of a nationwide cancer screening program in Germany ; it was offered to the general population for individuals 55 years of age or older . We collected and analyzed data from this program . METHODS We performed a prospect i ve cross-sectional study , collecting results from 2,821,392 screening colonoscopies performed at more than 2100 practice s by highly qualified endoscopists in Germany from January 2003 to December 2008 . Data on participation , colorectal adenoma and cancer detection , and complications were collected using st and ardized documentation forms . The data generated were central ly processed and evaluated . RESULTS The cumulative participation rate was 17.2 % of eligible women and 15.5 % of eligible men 55 - 74 years old . The adenoma detection rate ( ADR ) was 19.4 % , with a higher rate in men ( 25.8 % vs 16.7 % in women ) . Advanced adenomas were found in 6.4 % of patients . Carcinomas were detected in 25,893 subjects ( 0.9 % ) ; most were of an early UICC stage ( I , 47.3 % ; II , 22.3 % ; III , 20.7 % ; IV , 9.6 % ) . The ADRs for gastroenterologists and nongastroenterologists were 25.1 % and 22.3 % , respectively ( adjusted odds ratio , 1.18 ; 95 % confidence interval , 1.16 - 1.21 ) . The overall complication rate was 2.8/1000 colonoscopies , and the rate of serious complications was 0.58/1000 colonoscopies . CONCLUSIONS A nationwide colonoscopy screening program that uses highly qualified endoscopists can detect a significant number of adenomas and early-stage carcinomas . The ADR for gastroenterologists was higher than for nongastroenterologists Proliferating cells , particularly the tumor cells , express a dimeric isoenzyme of pyruvate kinase , termed M2‐PK . It 's a direct target of several oncoproteins ; the determination of fecal tumor pyruvate kinase type M2 ( M2‐PK ) might be another promising tool for colorectal cancer ( CRC ) screening . In this study , we have evaluated fecal M2‐PK as a screening biomarker for colorectal neoplasia . It was compared against  fecal occult blood ( FOB )  and  colonoscopy .  Three hundred and seventeen consecutive subjects from 4 different centers were included .  Stool specimens were collected before purgation , processed appropriately and were tested for FOB and quantitatively analyzed for M2‐PK . Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results . At cutoff value of 4 U/ml , fecal M2‐PK assay had a sensitivity , specificity , PPV and NPV of 81.1 , 86.7 , 71.1 and 61.9 % respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5 % , specificity of 92.2 % , PPV of 72.9 % and NPV of 71.5 % for CRC . Such low specificity of fecal M2‐PK will lead to unacceptably high number of false positives if it is used for mass CRC screening , leading to unindicated colonoscopies with its associated inconveniences , risks and costs . CRC screening test must have high specificity ; 
    Output:
    
Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection .
Combinations of fecal and serum biomarkers produce higher sensitivities , specificities , and PPVs for early detection of colorectal cancer and adenomas .