Prospective clinical study using expressed sequencing variants on stool-derived eukaryotic RNA transcripts (seRNA) for colorectal cancer screening.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 516-516
Author(s):  
Erica Kay Barnell ◽  
Yiming Kang ◽  
Katie Marie Campbell ◽  
Andrew Ross Barnell ◽  
Kimberly Ray Kruse ◽  
...  

516 Background: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. The high mortality rate is largely attributable to the high frequency of late-stage diagnoses, caused by low patient compliance with screening guidelines. A reliable and noninvasive screening alternative is needed for the 40 million noncompliant patients. The development of a novel nucleic acid extraction method to isolate stool-derived eukaryotic RNA (seRNA) permits reliable and noninvasive evaluation of biomarkers derived from the gastrointestinal (GI) epithelium. This method enables sequencing-based tools for the detection of patients with CRC and adenomas. Methods: Stool samples were obtained from 96 individuals prior to undergoing a screening colonoscopy. Fecal immunochemical tests (FITs) were obtained for each sample. RNA isolates underwent custom library preparation, next-generation sequencing, and somatic variant identification. An seRNA assay assessed the probability of CRC risk using results from the FIT, mutational burden of transcripts implicated in precancerous change (APC), and mutational burden of transcripts associated with malignant transformation (KRAS / TP53). Results: When compared to results from a colonoscopy and subsequent biopsy, the seRNA risk assessment attained a 100% sensitivity for CRC, a 71.4% sensitivity for advanced adenomas, and an 88.5% specificity for no neoplastic findings. Conclusions: A single-center, IRB-approved, prospective and blinded clinical study is being conducted in 450 patients to further develop this seRNA assay. Supplemental data will include expression from 408 seRNA transcripts. Preliminary analysis described herein indicates this assay could be the most sensitive noninvasive screening test for the detection of CRC and adenomas. [Table: see text]

2021 ◽  
Vol 3 (2) ◽  
pp. 84-95
Author(s):  
Fabio Ingravalle ◽  
Giovanni Casella ◽  
Adriana Ingravalle ◽  
Claudio Monti ◽  
Federica De Salvatore ◽  
...  

Cystic Fibrosis (CF) is the commonest inherited genetic disorder in Caucasians due to a mutation in the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), and it should be considered as an Inherited Colorectal Cancer (CRC) Syndrome. In the United States, physicians of CF Foundation established the “Developing Innovative Gastroenterology Speciality Training Program” to increase the research on CF in gastrointestinal and hepatobiliary diseases. The risk to develop a CRC is 5–10 times higher in CF patients than in the general population and even greater in CF patients receiving immunosuppressive therapy due to organ transplantation (30-fold increased risk relative to the general population). Colonoscopy should be considered the best screening for CRC in CF patients. The screening colonoscopy should be started at the age of 40 in CF patients and, if negative, a new colonoscopy should be performed every 5 years and every 3 years if adenomas are detected. For transplanted CF patients, the screening colonoscopy could be started at the age of 35, in transplanted patients at the age of 30 and, if before, at the age of 30. CF transplanted patients, between the age of 35 and 55, must repeat colonoscopy every 3 years. Our review draws attention towards the clinically relevant development of CRC in CF patients, and it may pave the way for further screenings and studies.


2005 ◽  
Vol 12 (4_suppl) ◽  
pp. 58-69 ◽  
Author(s):  
Janice V. Bowie ◽  
Barbara A. Curbow ◽  
Mary A. Garza ◽  
Erin K. Dreyling ◽  
Lisa A. Benz Scott ◽  
...  

Although cancer-screening guidelines recommend periodic testing for women 50 years of age and older, these tests are underused. A search of databases identified 156 community-based breast, cervical, and colorectal cancer screening intervention studies published before April 2003. Most were conducted in the United States. More than half used randomization procedures or pre-post measures, and one third used both. Most reported significant intervention effects. Cervical and combined cervical and breast studies had higher rates of pre-post designs, and breast studies had the highest percentage using randomization. Although effective community-based breast and cervical interventions have been conducted, there is an urgent need for amplification of colorectal cancer screening.


2010 ◽  
Vol 11 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Rebecca Bernstein ◽  
Daniel Dejoseph ◽  
Edward M. Buchanan

Because age alone is not an indicator of health, there is no clear consensus among the various cancer screening guidelines on when to stop cancer screening. For breast, cervical, and colorectal cancer, there are recommended screening tests, while, for other gynecologic cancers, there are not. When discussing with older women patients when to stop cancer screening, we encourage practitioners to review the goals of the screening test, assess the health and functional status of the patient, and discuss her values and health goals. To facilitate this discussion, we review proposed frameworks for determining when to screen older patients for cancer. We also review the concepts of “well” and “frail” older adults. Finally, we review the current screening recommendations for breast, gynecological, and colorectal cancers, and the reasoning behind them, from the United States Preventative Screening Task Force, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the American Geriatric Society.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 431-431 ◽  
Author(s):  
Sowjanya Kanna ◽  
Asif Ali ◽  
Kiran Anna ◽  
Thimmaiah Theethira Ganapathi ◽  
Raja Shekhar Reddy Sappati Biyyani ◽  
...  

431 Background: Colorectal cancer (CRC) is the second most common cancer with an estimated incidence of 72,090 men and 70,480 women and a cause specific mortality of 51,370 in 2010. Despite promotion of CRC screening by various professional societies ACG /AGA and USPSTF, there seems to be an under utilization of screening colonoscopy for unclear reasons. We aimed to study the awareness of physicians towards CRC screening across various levels of training in different specialities. Methods: A survey questionnaire of 16 questions, assessing awareness of CRC screening guidelines was provided to 100 physicians in our academic medical center who are at various levels of training in Primary Care Group (PCG comprising residents, attending physicians in Internal Medicine and Family Medicine) and Specialty Group (SG comprising fellows, attending physicians in Gastroenterology). Results: Out of 100 questionnaires, we received 59 responses (50 PCG and 9 SG) which are included in the results. About 54% of the study group followed CRC guidelines (32% USPSTF CRC screening guidelines compared to 22 % ACG/AGA guidelines) and 46% did not. All the physicians who did not follow the guidelines belonged to the PCG. Most common screening modality chosen was colonoscopy alone (46% PCG and 100% SG), followed by colonoscopy with FOBT (36% PCG), FOBT (12% PCG) and 3% PCG answered barium enema along with FOBT/ sigmoidoscopy. A 100% response from both SG and PCG was obtained for commencing screening colonoscopy at 50 years of age but only 27% of the PCG compared to 80% SG were aware of the screening cessation guidelines. Interestingly a vast majority of the study group (88%) text messaging as a better way of reminder to improve compliance compared to phone calls and postal letters. About 72% of the respondents themselves would want colonoscopy as screening modality compared to 17% for FOBT and 7% for sigmoidoscopy. An overwhelming majority of the study group (80% of both PCG and SG) felt the need for continued education in regards to guidelines for screening in didactic sessions. Conclusions: Despite clear guidelines for screening colonoscopy, we found a significant lack of awareness amongst PCG compared to SG, and our study emphasizes the need for continued education.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Wen-Sy Tsai ◽  
Ashish Nimgaonkar ◽  
Oscar Segurado ◽  
Ying Chang ◽  
Ben Hsieh ◽  
...  

556 Background: Colorectal cancer (CRC) is among the most preventable cancers when precancerous lesions are detected at an early stage. Current screening methods for CRC require bowel prep or stool-based testing that are inconvenient, resulting in low compliance. Stool based tests have limited sensitivity for the detection of precancerous lesions. We have conducted a prospective clinical study over a period of > 3 years to assess a novel assay to detect and enumerate circulating tumor cells (CTCs) in a blood sample for early CRC detection. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted in 620 subjects including 438 with adenoma, polyps or stage I-IV CRC and 182 healthy controls. For each subject, 2mL peripheral whole blood collected through a routine blood draw was processed using the CellMax biomimetic platform (CMx). The CMx test is a proprietary microfluidic biochip that minimizes non-specific binding and accurately enumerates CTCs. A multivariate analysis was performed to assess the clinical performance characteristics of the CMx test. Results: Disease status was evaluated by a standard clinical protocol which included colonoscopy and biopsy results. Probability of CRC risk was assessed by an age-adjusted regression model which correlated CTCs to clinical status. The CMx test’s overall accuracy was 88% for all stages of colorectal illness, including precancerous lesions. Conclusions: The study has demonstrated high accuracy for the detection of CRC using a novel CTC assay. It is the first study to show high sensitivity in the detection of precancerous colorectal lesions. The simple blood draw required can be easily integrated into a patient’s routine physical, increasing test compliance.[Table: see text]


2011 ◽  
Vol 6 (3) ◽  
pp. 196-203 ◽  
Author(s):  
Joseph A. Diaz ◽  
Teresa Slomka

Although colorectal cancer is the third leading cause of cancer-related deaths in the United States, the burden of this disease could be dramatically reduced by increased utilization of screening. Evidence-based recommendations and guidelines from national societies recommend screening all average risk adults starting at age 50 years. However, the myriad screening options and slight differences in screening recommendations between guidelines may lead to confusion among patients and their primary care providers. In addition, varied colorectal cancer incidence and screening rates among different racial/ethnic groups, inconsistent screening recommendations based on family history and/or age, and increasing awareness of the role of nonadenomatous and nonpolypoid lesions also pose potential challenges to primary care providers when counseling patients. The goal of this review, therefore, is to briefly summarize the colorectal cancer screening guidelines issued by 3 major organizations, compare their recommendations, and address emerging issues in colorectal cancer screening.


2017 ◽  
Vol 9 (4) ◽  
pp. 295-299 ◽  
Author(s):  
David J Gibson ◽  
Blathnaid Nolan ◽  
Joanna Rea ◽  
Maire Buckley ◽  
Gareth Horgan ◽  
...  

Introduction52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT.AimsDetermine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up.MethodsA single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4–6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention.Results112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3–11.9, P=0.04)).ConclusionFIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 561
Author(s):  
Vanessa Erben ◽  
Gernot Poschet ◽  
Petra Schrotz-King ◽  
Hermann Brenner

Analysis of metabolomics has been suggested as a promising approach for early detection of colorectal cancer and advanced adenomas. We investigated and compared the metabolomics profile in blood, stool, and urine samples of screening colonoscopy participants and aimed to evaluate differences in metabolite concentrations between people with advanced colorectal neoplasms and those without neoplasms. Various types of bio-samples (plasma, feces, and urine) from 400 participants of screening colonoscopy were investigated using the MxP® Quant 500 kit (Biocrates, Innsbruck, Austria). We detected a broad range of metabolites in blood, stool, and urine samples (504, 331, and 131, respectively). Significant correlations were found between concentrations in blood and stool, blood and urine, and stool and urine for 93, 154, and 102 metabolites, of which 68 (73%), 126 (82%), and 39 (38%) were positive correlations. We found significant differences between participants with and without advanced colorectal neoplasms for concentrations of 123, 49, and 28 metabolites in blood, stool and urine samples, respectively. We detected mostly positive correlations between metabolite concentrations in blood samples and urine or stool samples, and mostly negative correlations between urine and stool samples. Differences between subjects with and without advanced colorectal neoplasms were found for metabolite concentrations in each of the three bio-fluids.


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