- Email: [email protected]
Efficacy and Safety of Colonoscopy in the UK NHS Bowel Cancer Screening Programme
Su1141
AGA Abstracts
Efficacy and Safety of Colonoscopy in the UK NHS Bowel Cancer Screening Programme Tom J. Lee, Roger G. Blanks, Matthew D. Rutter, Sue Moss, Andrew F. Goddard, Andrew Chilton, Claire Nickerson, Richard J. McNally, Julietta Patnick, Colin Rees BACKGROUND Colonoscopy is a central investigation in all colorectal cancer (CRC) screening strategies. Success of CRC screening is dependent on the quality of colonoscopy. The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing to adults aged 60 -74 years. Colonoscopy is offered to individuals with a positive faecal occult blood (FOB) test. All colonoscopists practicing within the screening programme are required to meet predefined standards through summative assessment and are subject to ongoing quality assurance. In this study we examine the quality of colonoscopy in the NHS BCSP and describe the measures taken by the BCSP to achieve high quality colonoscopy. Comparison of current quality indicators with existing quality standards and evidence from the UK pilot study of FOB screening will be undertaken. METHODS The NHS BCSP national database prospectively collects detailed data on all screening colonoscopies. Data from the first 3 years of the programme (August 2006 to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection rate, polyp detection rate, colonoscopy withdrawal time, caecal intubation rate, rectal retroversion rate, polyp retrieval rate, mean sedation doses, patient comfort scores, bowel preparation quality and adverse event incidence) were calculated for this period. All screening centres were contacted directly to verify adverse event data. RESULTS In the study period, 2,269,983 individuals returned FOB tests and 36,460 colonoscopies were performed. Mean caecal intubation rate was 95.2% and mean withdrawal time for normal procedures was 9.2 minutes. The mean adenoma detection rate (ADR) per colonoscopist was 46.5%. ADR did not differ between prevalent and incident rounds (p=0.90). Patient comfort scores were high and adverse event rates low. CONCLUSIONS The NHS Bowel Cancer Screening Programme provides high quality colonoscopy as demonstrated by high caecal intubation rate, adenoma detection rate and comfort scores and low adverse event rate. This quality is achieved by ensuring that BCSP colonoscopists are trained to a high standard and that these standards are maintained through ongoing quality assurance measures.
Su1139 Can an Individual Risk Profile for CRC Be Used as Triage Test in CRC Screening Inge Stegeman, Thomas R. de Wijkerslooth, Esther M. Stoop, Monique van Leerdam, Evelien Dekker, Ernst J. Kuipers, Paul Fockens, Roderik A. Kraaijenhagen, Patrick M. Bossuyt Background Colorectal cancer (CRC) is one of the leading causes of cancer related death. Detecting cancer or one of its precursors at an early stage can prevent premature death and may reduce cancer morbidity. Due to its non-invasive character, triaging for colonoscopy with FOBT is an attractive method. However, FOBT has a less than perfect specificity and sensitivity. Risk stratification, based on established risk factors for advanced neoplasia, could increase the sensitivity of FOBT-based screening. This way, the diagnostic yield from screening could be increased with a similar number of colonoscopies. We explored the use of a risk prediction model in CRC screening. Methods We collected data in the Colonoscopy or Colonography for Scree¬ning (COCOS) study, a multicenter screening trial conducted in Amsterdam and Rotterdam, The Netherlands between June 2009 and October 2010. For this study 5,924 randomly selected, asymptomatic men and women between 50 and 75 years of age were invited to undergo colonoscopy. After colonoscopy, participants were identified with one or more advanced neoplasia (carcinomas and advanced adenomas). Screening participants were asked for one sample FIT (OC-sensor) and to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire data, we developed a multivariable risk model with the following factors: total calcium intake, family history, age and FIT result. We evaluated goodness-of-fit, calibration and discrimination, and compared it to a model based on primary screening with FIT. Calibration refers to the agreement between calculated risk and observed outcomes. Discrimination expresses how well the risk model distinguishes between cases and non-cases. Results 1,236 invitees participated in the study, of which 1,022 (83%) completed the questionnaire. FIT results and colonoscopy outcome were known for 787 (77%)of the participants who completed the questionnaires, of which 67 had advanced neoplasia (8.5%); 5 (7.5%) had CRC and 62 (92.5%) advanced adenoma. The risk based model significantly increased the goodness-of-fit compared to the primary FIT screening model (p=0.0006). Discrimination improved with the risk-based model (AUC: from 0.630 to 0.745), but the gain was not statistically significant (p=0.06). Calibration was good (Hosmer-Lemershow test; p=0.90). With a FIT strategy and using a cut off of 50 ng/ml, 74 of the 787 (9.4%) participants would have been referred for colonoscopy, including 22 persons with advanced neoplasia (29%). If, hypothetically, the 74 participants with the highest calculated risk had been referred for colonoscopy, this group would have included 21 (27%) persons with advanced neoplasia. Conclusion Risk based stratification can increase the accuracy of FOBT in triage for colonoscopy in CRC screening, but the actual gains in the yield of screening are probably modest.
Su1142 Soluble Transferrin Receptor Level in Patients With Gastrointestinal Neoplasm: Is It Useful for Improving Screening Efficacy? Seyed Amir Mirbagheri, Behtash Saeidi, Alireza Momeni, Behtash G. Nezami, Kaveh Hajifathalian BACKGROUND AND OBJECTIVES: soluble transferrin receptor (sTfR) is a marker of Iron Deficiency (ID), and could be used to detect gastrointestinal cancers through ID, even before development of anemia. We evaluated the usefulness of sTfR as a possible diagnostic tool for detection of gastrointestinal (GI) malignant and pre malignant lesions. METHODS: we studied non-anemic patients referred for gastrointestinal endoscopy. sTfR was evaluated in those with gastrointestinal cancers or polyps ≥ 10mm (case group, 97 patients). 95 age and sex matched patients with normal upper and lower endoscopy were enrolled as the control group. Additionally, serum ferritin concentrations and a guaiac-based fecal occult blood test (FOBT) were obtained for each individual. RESULTS: 63 patients had a high sTfR level in case group (64.9%) compared to only 6 (6.3%) in controls (P=0.000). In this study, Patients with GI lesions were 27.5 times more likely than controls for having a high sTFR level (OR: 27.5, 95% CI: 10.9 - 69.4). ROC curve of sTfR as a diagnostic test for GI cancers had an area under the curve (AUC) of 0.922 (95% CI: 0.885 - 0.959). Using a cut off value of 8.3 mg/l, sTfR had a sensitivity of 64.9% and specificity of 93.7% for detecting patients with premalignant or malignant gastrointestinal lesions, with a positive predictive value (PPV) of 91.3% and a negative predictive value (NPV) of 72.3%. FOBT was positive in 10 (10.5%) healthy controls and only 28 (28.9%) cases; However this difference remained to be significant (p = 0.005). Ferritin levels did not show any significant difference between cases and controls (p = 0.392). CONCLUSIONS: We suggest that measuring serum sTfR level could be a useful adjunct to regular fecal occult blood testing in detection of both upper and lower GI cancers, especially at early stages of disease, by identifying the cases that remain undetected by FOBT. Moreover, negative sTfR result together with negative FOBT may help clinicians rule out GI neoplasm with better confidence.
Su1140 Predominance of Left-Sided Colorectal Cancer Among Asians Chanda K. Ho, Hal F. Yee, Ma Somsouk Background: Previous literature has suggested that there are racial/ethnic differences in the anatomical distribution of colorectal cancer (CRC) lesions. Specifically, some studies have shown that Asian patients may have a higher likelihood of developing distal or left-sided cancers. These results potentially support a role for flexible sigmoidoscopy as an effective screening modality for this patient population that has historically been difficult to screen. Research to date, however, does not indicate whether the relative decrease in the proportion of left-sided lesions among non-Asians is attributable to exposure to CRC screening. Aims: 1) To compare the anatomic location of colorectal cancer stratified by race/ethnicity 2) To examine the level of exposure to CRC screening tests on the proportion of left-sided lesions. Methods: We undertook a retrospective cohort study of all new colorectal cancer diagnoses from 1997-2009 at San Francisco General Hospital (SFGH). Diagnoses of CRC were determined by ICD-9 code in the electronic medical record and confirmed by pathology. Lesions located at or distal to the descending colon were categorized as left-sided after review of the medical records. We analyzed the proportion of left-sided CRC lesions stratified by race and duration of utilization of our health care system. For those patients in the system greater than 1 year prior to their diagnosis of a left-sided CRC, we measured what proportion had any previous exposure to CRC screening. Results: From 1997-2009 there were 342 new diagnoses of CRC at SFGH, of which 58% were men. There were 134 Asians, 69 Caucasians, 68 African-Americans, 61 Latino patients, and 10 patients classified as “Other.” There were 218 (64 %) left-sided cancers and 115 right-sided cancers. Asians had a statistically higher proportion (73%, p<0.007) of left-sided CRC compared to all other racial groups -Caucasians 52%, African-Americans 54%, Latinos 65.5%. Of the 342 patients, 204 (60%) had been in the SFGH system for at least a year. Of these patients, any previous CRC screening was evident in 13% of Asians, 21% of African-Americans, and 13% of Latinos. Conclusions: Asians have a higher likelihood of developing left-sided CRC. There are likely biological factors driving the increased prevalence of left-sided lesions among Asians since exposure to CRC screening did not significantly affect the proportion of left-sided lesions. Therefore, among Asians, a CRC screening strategy using flexible sigmoidoscopy may be very costeffective in detecting and preventing CRC. The low rate of exposure to CRC screening across all racial groups highlights an important gap in prevention services underutilized by the urban poor.
AGA Abstracts
Su1143 Fecal Beta2-Microglobulin and Creatine Kinase B mRNA Assays as a Marker for Colorectal Cancer Screening Shigeru Kanaoka, Yasushi Hamaya, Shigeru Kuriyama, Mutsuhiro Ikuma, Hiroaki MIyajima Background and Aims: We reported that fecal COX-2 plus MMP-7 mRNA assays is useful for colorectal cancer (CRC) screening. Since approximately 20% CRC subjects with negative results of fecal COX-2 plus MMP-7 mRNA assays exist, improving sensitivity is one of challenging for this assay. We reported that the number of exfoliated cells is more abundant in CRC subjects than healthy subjects (Br J Cancer 2010). Therefore, fecal beta2-microglobulin (B2M) mRNA assay would be a marker for detection of CRC. Additionally, we identified creatine kinase B (CKB) as a candidate marker through microarray analysis comparing gene expression between fecal RNA of a CRC subject with negative result of fecal COX-2 mRNA assay and fecal RNA of a healthy subject. In this study, we performed a study of whether fecal multi-markers RNA panel (COX-2, MMP-7, B2M and CKB) is useful or not for detection of CRC and advanced adenoma. Methods: Stool samples from 111 subjects with CRC, from 24 subjects with colorectal advanced adenoma (AA; at least 10mm in diameter), 113 healthy subjects were obtained. Standard histological techniques were used to classify malignancy at 0 to IV stage according to TNM classification, yielding stage 0 (n = 11), I (n = 24), II (n = 37), III or IV (n = 39). We purified RNA from routinely collected stool samples and analyzed mRNA expressions of COX-2, MMP-7, B2M, and CKB by quantitative real-time RT-PCR with standard plasmid DNA, compared the results with those of a single fecal
S-414
AGA Abstracts
Efficacy and Safety of Colonoscopy in the UK NHS Bowel Cancer Screening Programme Tom J. Lee, Roger G. Blanks, Matthew D. Rutter, Sue Moss, Andrew F. Goddard, Andrew Chilton, Claire Nickerson, Richard J. McNally, Julietta Patnick, Colin Rees BACKGROUND Colonoscopy is a central investigation in all colorectal cancer (CRC) screening strategies. Success of CRC screening is dependent on the quality of colonoscopy. The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing to adults aged 60 -74 years. Colonoscopy is offered to individuals with a positive faecal occult blood (FOB) test. All colonoscopists practicing within the screening programme are required to meet predefined standards through summative assessment and are subject to ongoing quality assurance. In this study we examine the quality of colonoscopy in the NHS BCSP and describe the measures taken by the BCSP to achieve high quality colonoscopy. Comparison of current quality indicators with existing quality standards and evidence from the UK pilot study of FOB screening will be undertaken. METHODS The NHS BCSP national database prospectively collects detailed data on all screening colonoscopies. Data from the first 3 years of the programme (August 2006 to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection rate, polyp detection rate, colonoscopy withdrawal time, caecal intubation rate, rectal retroversion rate, polyp retrieval rate, mean sedation doses, patient comfort scores, bowel preparation quality and adverse event incidence) were calculated for this period. All screening centres were contacted directly to verify adverse event data. RESULTS In the study period, 2,269,983 individuals returned FOB tests and 36,460 colonoscopies were performed. Mean caecal intubation rate was 95.2% and mean withdrawal time for normal procedures was 9.2 minutes. The mean adenoma detection rate (ADR) per colonoscopist was 46.5%. ADR did not differ between prevalent and incident rounds (p=0.90). Patient comfort scores were high and adverse event rates low. CONCLUSIONS The NHS Bowel Cancer Screening Programme provides high quality colonoscopy as demonstrated by high caecal intubation rate, adenoma detection rate and comfort scores and low adverse event rate. This quality is achieved by ensuring that BCSP colonoscopists are trained to a high standard and that these standards are maintained through ongoing quality assurance measures.
Su1139 Can an Individual Risk Profile for CRC Be Used as Triage Test in CRC Screening Inge Stegeman, Thomas R. de Wijkerslooth, Esther M. Stoop, Monique van Leerdam, Evelien Dekker, Ernst J. Kuipers, Paul Fockens, Roderik A. Kraaijenhagen, Patrick M. Bossuyt Background Colorectal cancer (CRC) is one of the leading causes of cancer related death. Detecting cancer or one of its precursors at an early stage can prevent premature death and may reduce cancer morbidity. Due to its non-invasive character, triaging for colonoscopy with FOBT is an attractive method. However, FOBT has a less than perfect specificity and sensitivity. Risk stratification, based on established risk factors for advanced neoplasia, could increase the sensitivity of FOBT-based screening. This way, the diagnostic yield from screening could be increased with a similar number of colonoscopies. We explored the use of a risk prediction model in CRC screening. Methods We collected data in the Colonoscopy or Colonography for Scree¬ning (COCOS) study, a multicenter screening trial conducted in Amsterdam and Rotterdam, The Netherlands between June 2009 and October 2010. For this study 5,924 randomly selected, asymptomatic men and women between 50 and 75 years of age were invited to undergo colonoscopy. After colonoscopy, participants were identified with one or more advanced neoplasia (carcinomas and advanced adenomas). Screening participants were asked for one sample FIT (OC-sensor) and to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire data, we developed a multivariable risk model with the following factors: total calcium intake, family history, age and FIT result. We evaluated goodness-of-fit, calibration and discrimination, and compared it to a model based on primary screening with FIT. Calibration refers to the agreement between calculated risk and observed outcomes. Discrimination expresses how well the risk model distinguishes between cases and non-cases. Results 1,236 invitees participated in the study, of which 1,022 (83%) completed the questionnaire. FIT results and colonoscopy outcome were known for 787 (77%)of the participants who completed the questionnaires, of which 67 had advanced neoplasia (8.5%); 5 (7.5%) had CRC and 62 (92.5%) advanced adenoma. The risk based model significantly increased the goodness-of-fit compared to the primary FIT screening model (p=0.0006). Discrimination improved with the risk-based model (AUC: from 0.630 to 0.745), but the gain was not statistically significant (p=0.06). Calibration was good (Hosmer-Lemershow test; p=0.90). With a FIT strategy and using a cut off of 50 ng/ml, 74 of the 787 (9.4%) participants would have been referred for colonoscopy, including 22 persons with advanced neoplasia (29%). If, hypothetically, the 74 participants with the highest calculated risk had been referred for colonoscopy, this group would have included 21 (27%) persons with advanced neoplasia. Conclusion Risk based stratification can increase the accuracy of FOBT in triage for colonoscopy in CRC screening, but the actual gains in the yield of screening are probably modest.
Su1142 Soluble Transferrin Receptor Level in Patients With Gastrointestinal Neoplasm: Is It Useful for Improving Screening Efficacy? Seyed Amir Mirbagheri, Behtash Saeidi, Alireza Momeni, Behtash G. Nezami, Kaveh Hajifathalian BACKGROUND AND OBJECTIVES: soluble transferrin receptor (sTfR) is a marker of Iron Deficiency (ID), and could be used to detect gastrointestinal cancers through ID, even before development of anemia. We evaluated the usefulness of sTfR as a possible diagnostic tool for detection of gastrointestinal (GI) malignant and pre malignant lesions. METHODS: we studied non-anemic patients referred for gastrointestinal endoscopy. sTfR was evaluated in those with gastrointestinal cancers or polyps ≥ 10mm (case group, 97 patients). 95 age and sex matched patients with normal upper and lower endoscopy were enrolled as the control group. Additionally, serum ferritin concentrations and a guaiac-based fecal occult blood test (FOBT) were obtained for each individual. RESULTS: 63 patients had a high sTfR level in case group (64.9%) compared to only 6 (6.3%) in controls (P=0.000). In this study, Patients with GI lesions were 27.5 times more likely than controls for having a high sTFR level (OR: 27.5, 95% CI: 10.9 - 69.4). ROC curve of sTfR as a diagnostic test for GI cancers had an area under the curve (AUC) of 0.922 (95% CI: 0.885 - 0.959). Using a cut off value of 8.3 mg/l, sTfR had a sensitivity of 64.9% and specificity of 93.7% for detecting patients with premalignant or malignant gastrointestinal lesions, with a positive predictive value (PPV) of 91.3% and a negative predictive value (NPV) of 72.3%. FOBT was positive in 10 (10.5%) healthy controls and only 28 (28.9%) cases; However this difference remained to be significant (p = 0.005). Ferritin levels did not show any significant difference between cases and controls (p = 0.392). CONCLUSIONS: We suggest that measuring serum sTfR level could be a useful adjunct to regular fecal occult blood testing in detection of both upper and lower GI cancers, especially at early stages of disease, by identifying the cases that remain undetected by FOBT. Moreover, negative sTfR result together with negative FOBT may help clinicians rule out GI neoplasm with better confidence.
Su1140 Predominance of Left-Sided Colorectal Cancer Among Asians Chanda K. Ho, Hal F. Yee, Ma Somsouk Background: Previous literature has suggested that there are racial/ethnic differences in the anatomical distribution of colorectal cancer (CRC) lesions. Specifically, some studies have shown that Asian patients may have a higher likelihood of developing distal or left-sided cancers. These results potentially support a role for flexible sigmoidoscopy as an effective screening modality for this patient population that has historically been difficult to screen. Research to date, however, does not indicate whether the relative decrease in the proportion of left-sided lesions among non-Asians is attributable to exposure to CRC screening. Aims: 1) To compare the anatomic location of colorectal cancer stratified by race/ethnicity 2) To examine the level of exposure to CRC screening tests on the proportion of left-sided lesions. Methods: We undertook a retrospective cohort study of all new colorectal cancer diagnoses from 1997-2009 at San Francisco General Hospital (SFGH). Diagnoses of CRC were determined by ICD-9 code in the electronic medical record and confirmed by pathology. Lesions located at or distal to the descending colon were categorized as left-sided after review of the medical records. We analyzed the proportion of left-sided CRC lesions stratified by race and duration of utilization of our health care system. For those patients in the system greater than 1 year prior to their diagnosis of a left-sided CRC, we measured what proportion had any previous exposure to CRC screening. Results: From 1997-2009 there were 342 new diagnoses of CRC at SFGH, of which 58% were men. There were 134 Asians, 69 Caucasians, 68 African-Americans, 61 Latino patients, and 10 patients classified as “Other.” There were 218 (64 %) left-sided cancers and 115 right-sided cancers. Asians had a statistically higher proportion (73%, p<0.007) of left-sided CRC compared to all other racial groups -Caucasians 52%, African-Americans 54%, Latinos 65.5%. Of the 342 patients, 204 (60%) had been in the SFGH system for at least a year. Of these patients, any previous CRC screening was evident in 13% of Asians, 21% of African-Americans, and 13% of Latinos. Conclusions: Asians have a higher likelihood of developing left-sided CRC. There are likely biological factors driving the increased prevalence of left-sided lesions among Asians since exposure to CRC screening did not significantly affect the proportion of left-sided lesions. Therefore, among Asians, a CRC screening strategy using flexible sigmoidoscopy may be very costeffective in detecting and preventing CRC. The low rate of exposure to CRC screening across all racial groups highlights an important gap in prevention services underutilized by the urban poor.
AGA Abstracts
Su1143 Fecal Beta2-Microglobulin and Creatine Kinase B mRNA Assays as a Marker for Colorectal Cancer Screening Shigeru Kanaoka, Yasushi Hamaya, Shigeru Kuriyama, Mutsuhiro Ikuma, Hiroaki MIyajima Background and Aims: We reported that fecal COX-2 plus MMP-7 mRNA assays is useful for colorectal cancer (CRC) screening. Since approximately 20% CRC subjects with negative results of fecal COX-2 plus MMP-7 mRNA assays exist, improving sensitivity is one of challenging for this assay. We reported that the number of exfoliated cells is more abundant in CRC subjects than healthy subjects (Br J Cancer 2010). Therefore, fecal beta2-microglobulin (B2M) mRNA assay would be a marker for detection of CRC. Additionally, we identified creatine kinase B (CKB) as a candidate marker through microarray analysis comparing gene expression between fecal RNA of a CRC subject with negative result of fecal COX-2 mRNA assay and fecal RNA of a healthy subject. In this study, we performed a study of whether fecal multi-markers RNA panel (COX-2, MMP-7, B2M and CKB) is useful or not for detection of CRC and advanced adenoma. Methods: Stool samples from 111 subjects with CRC, from 24 subjects with colorectal advanced adenoma (AA; at least 10mm in diameter), 113 healthy subjects were obtained. Standard histological techniques were used to classify malignancy at 0 to IV stage according to TNM classification, yielding stage 0 (n = 11), I (n = 24), II (n = 37), III or IV (n = 39). We purified RNA from routinely collected stool samples and analyzed mRNA expressions of COX-2, MMP-7, B2M, and CKB by quantitative real-time RT-PCR with standard plasmid DNA, compared the results with those of a single fecal
S-414