Non-advanced Adenomas Research Articles

Mitotic and apoptotic activity in colorectal neoplasia

BackgroundColorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia.MethodsA total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3.ResultsIn controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity.ConclusionsSignificant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

Association of Colonoscopy Adenoma Findings With Long-term Colorectal Cancer Incidence

Individuals with adenomatous polyps are advised to undergo repeated colonoscopy surveillance to prevent subsequent colorectal cancer (CRC), but the relationship between adenomas at colonoscopy and long-term CRC incidence is unclear. To compare long-term CRC incidence by colonoscopy adenoma findings. Multicenter, prospective cohort study of participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer randomized clinical trial of flexible sigmoidoscopy (FSG) beginning in 1993 with follow-up for CRC incidence to 2013 across the United States. Participants included 154 900 men and women aged 55 to 74 years enrolled in PLCO of whom 15 935 underwent colonoscopy following their first positive FSG screening result. The final day of follow-up was December 31, 2013. Enrolled participants had been randomized to FSG or usual care. Participants who underwent FSG and had abnormal findings were referred for follow-up. Subsequent colonoscopy findings were categorized as advanced adenoma (≥1 cm, high-grade dysplasia, or tubulovillous or villous histology), nonadvanced adenoma (<1 cm without advanced histology), or no adenoma. The primary outcome was CRC incidence within 15 years of the baseline colonoscopy. The secondary outcome was CRC mortality. There were 15 935 participants who underwent colonoscopy (men, 59.7%; white, 90.7%; median age, 64 y [IQR, 61-68]). On initial colonoscopy, 2882 participants (18.1%) had an advanced adenoma, 5068 participants (31.8%) had a nonadvanced adenoma, and 7985 participants (50.1%) had no adenoma; median follow-up for CRC incidence was 12.9 years. CRC incidence rates per 10 000 person-years of observation were 20.0 (95% CI, 15.3-24.7; n = 70) for advanced adenoma, 9.1 (95% CI, 6.7-11.5; n = 55) for nonadvanced adenoma, and 7.5 (95% CI, 5.8-9.7; n = 71) for no adenoma. Participants with advanced adenoma were significantly more likely to develop CRC compared with participants with no adenoma (rate ratio [RR], 2.7 [95% CI, 1.9-3.7]; P < .001). There was no significant difference in CRC risk between participants with nonadvanced adenoma compared with no adenoma (RR, 1.2 [95% CI, 0.8-1.7]; P = .30). Compared with participants with no adenoma, those with advanced adenoma were at significantly increased risk of CRC death (RR, 2.6 [95% CI, 1.2-5.7], P = .01), but mortality risk in participants with nonadvanced adenoma was not significantly different (RR, 1.2 [95% CI, 0.5-2.7], P = .68). Over a median of 13 years of follow-up, participants with an advanced adenoma at diagnostic colonoscopy prompted by a positive flexible sigmoidoscopy result were at significantly increased risk of developing colorectal cancer compared with those with no adenoma. Identification of nonadvanced adenoma may not be associated with increased colorectal cancer risk. clinicaltrials.gov Identifier: NCT00002540.

Flexible sigmoidoscopy in colorectal cancer screening: implications of different colonoscopy referral strategies

Flexible sigmoidoscopy (FS) screening reduces colorectal cancer incidence and mortality. Its potential to detect proximal neoplasms depends on colonoscopy referral. We estimated diagnostic performance of sigmoidoscopy using 12 different referral criteria in detecting colorectal cancer and advanced adenomas. Colonoscopy results from 14,947 participants of screening colonoscopy in Germany were used to derive sensitivity of sigmoidoscopy for colorectal cancer, advanced adenomas (AAs), and any advanced neoplasms in the proximal colon. It was assumed that FS detects the same neoplasms as colonoscopy within its reach and that distal neoplasms would be followed by colonoscopy. In addition, numbers of colonoscopies needed (NCN) to detect one proximal advanced neoplasm were calculated. The most advanced findings during colonoscopy were colorectal cancer in 213 subjects (1.4%), AA in 1539 subjects (10.2%) and non-advanced adenomas in 2988 subjects (19.8%). Without colonoscopy referral, overall sensitivities for any colorectal cancer, advanced adenoma and any advanced neoplasm (proximal or distal) would be 79, 65 and 66%, respectively. These sensitivities could be increased to up to 86, 83 and 84% by the referral strategies investigated. Compared to referral due to advanced adenomas, referral due to non-advanced adenomas would substantially increase the NCN at a modest gain in sensitivity. Sensitivities were higher and NCNs were lower in men than in women for every strategy. In conclusion, colonoscopy referral can substantially increase sensitivity of sigmoidoscopy-based screening, but the gain by referral due to non-advanced adenomas substantially increases NCN compared to referral due to advanced neoplasms only. Major sex differences may call for sex-specific referral strategies.

Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.

Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population

The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population. We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50-79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenoma (NAAs), and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and NAA according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study. An increased GRS was associated with higher prevalence of advanced neoplasms, but not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence interval [CI], 0.76-1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70-1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8-27.3). In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.

Evaluation of Patients with an Apparent False Positive Stool DNA Test: The Role of Repeat Stool DNA Testing.

There is uncertainty as to the appropriate follow-up of patients who test positive on multimarker stool DNA (sDNA) testing and have a colonoscopy without neoplasia. To determine the prevalence of missed colonic or occult upper gastrointestinal neoplasia in patients with an apparent false positive sDNA. We prospectively identified 30 patients who tested positive with a commercially available sDNA followed by colonoscopy without neoplastic lesions. Patients were invited to undergo repeat sDNA at 11-29months after the initial test followed by repeat colonoscopy and upper endoscopy. We determined the presence of neoplastic lesions on repeat evaluation stratified by results of repeat sDNA. Twelve patients were restudied. Seven patients had a negative second sDNA test and a normal second colonoscopy and upper endoscopy. In contrast, 5 of 12 subjects had a persistently positive second sDNA test, and 3 had positive findings, including a 3-cm sessile transverse colon adenoma with high-grade dysplasia, a 2-cm right colon sessile serrated adenoma with dysplasia, and a nonadvanced colon adenoma (p = 0.045). These corresponded to a positive predictive value of 0.60 (95% CI 0.17-1.00) and a negative predictive value of 1.00 (95% CI 1.00-1.00) for the second sDNA test. In addition, the medical records of all 30 subjects with apparent false positive testing were reviewed and no documented cases of malignant tumors were recorded. Repeat positive sDNA testing may identify a subset of patients with missed or occult colorectal neoplasia after negative colonoscopy for an initially positive sDNA. High-quality colonoscopy with careful attention to the right colon in patients with positive sDNA is critically important and may avoid false negative colonoscopy.

Advances in Faecal DNA Testing for Colorectal Cancer Screening: A Literature Review for Primary Care Providers

Recent epidemiological data gathered by the Centers for Disease Control and Prevention (CDC) suggest that colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the USA. Clinicians currently use five types of test to screen for CRC. Two of these five types, the DNA stool test and the faecal occult blood test, are non-invasive. The DNA stool test successfully detects both advanced neoplasias and non-advanced adenomas with more sensitivity than the faecal occult blood test. However, data suggest that it also generates more false-positive results. There is only one DNA stool test that has been approved by the U.S. Food and Drug administration (FDA): the approved Cologuard® (Exact Sciences, Madison, Wisconsin, USA) test. This test screens for nine different DNA biomarkers, one haemoglobin biomarker, and one β-actin. This article is a literature review of research on faecal DNA biomarkers conducted in the past 5 years from four large databases. Key findings include the ability to reach a sensitivity as high as 98% to detect abnormalities in the colon using a multi-target stool DNA-based assay. In comparison, the Cologuard offers 92% sensitivity and 87% specificity for all stages of CRC. Testing DNA biomarkers can serve as an adequate screen for cancer and adenomas in average-risk adults. Areas for further research include implementing studies to compare long-term health consequences for patients who receive colonoscopies versus DNA stool tests, finding ways to improve both the sensitivity and specificity of screening tests, and finding ways to improve the detection of those biomarkers most associated with CRC, including microRNA detection in the marking panel.

Appropriateness and yield of surveillance colonoscopy in first-degree relatives of colorectal cancer patients: A 5-year follow-up population-based study

Background and aimsThere are few prospective data about the use of surveillance colonoscopy and the risk of recurrent neoplasia in first degree relatives (FDRs) of colorectal cancer (CRC) patients. We examined the use and yield of surveillance colonoscopy in a population-based screening program (Trentino, Italy) Methods1252 FDRs have been included in this study. We calculated compliance (percentage of FDRs who underwent surveillance colonoscopy among those eligible), appropriateness of colonoscopy (appropriate if performed within 6 months of the guidelines recommended interval) and diagnostic yield for neoplasia. We compared these data with those of 765 individuals without a family history (FH) of CRC who underwent screening colonoscopy in the same period (controls). ResultsCompliance and appropriateness were higher in FDRs than in controls (93.0% vs. 48.0%; p < 0.001; 59.6% vs. 18.8%; p < 0.0001, respectively). Younger age, female sex, FH of CRC and both non-advanced adenomas (nAA) and advanced adenomas (AA) at screening colonoscopy were predictors of appropriate surveillance. The cumulative incidence of nAA and AA was similar in FDRs and controls (31.7% and 4.9% in FDRs, including three invasive cancers; 32.4% and 5.8% in controls, respectively). ConclusionFH does not increase the risk of AA in a 5-year follow-up; appropriate surveillance practices in FDRs could be highly expected in an organized screening program.

Three-year colonoscopy surveillance after polypectomy in Korea: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter prospective study.

Background/AimsColonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy.MethodsA total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics.ResultsAmong 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence.ConclusionsA colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study.

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Case-control study. Colonoscopy-controlled referral population from several centers. 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P= 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

Adenoma detection rate influences the risk of metachronous advanced colorectal neoplasia in low-risk patients

In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas. We identified 7171 participants with no or 1 to 2 nonadvanced adenomas at first-time screening colonoscopy. The risk of metachronous AN was investigated at surveillance colonoscopy, according to clinical characteristics and the ADR. In multivariate analysis the risk for metachronous AN was strongly associated with increasing age, male sex, increasing number of adenomas, and the ADR of the endoscopist. With the ADR modeled as a continuous variable, each 1.0% increase in the rate of ADR predicted a 3.0% decrease in the risk of metachronous AN (adjusted odds ratio [OR], .97; 95% confidence interval [CI], .95-.99). With the ADR modeled using a binary cut-off (32%), the risk of metachronous AN was reduced in patients of endoscopists with an ADR≥32% (adjusted OR, .53; 95% CI, .35-.83). Moreover, the risk of metachronous AN was reduced (adjusted OR, .66; 95% CI, .46-.95) in patients of endoscopists with an ADR in the highest tertile, compared with patients of endoscopists with ADRs in the lowest tertile. The impact of ADR on metachronous AN was significant for patients with low-risk adenomas rather than patients with no adenoma. In patients with low-risk adenomas, the ADR of the endoscopist was inversely associated with the risk of metachronous AN.

Risk of advanced colorectal neoplasm by the proposed combined United States and United Kingdom risk stratification guidelines

The U.K. guidelines for risk stratification after colon polypectomy differ from the U.S. guidelines in 2 ways: the U.K. guidelines consider≥5 adenomas as high risk and do not consider histology (villous or high-grade dysplasia) in the assessment. Thus, we aimed to investigate the risk of advanced colorectal neoplasm (CRN) by categorized risk groups, considering both≥5 adenomas and histology. A total of 2570 patients with≥1 adenoma at index colonoscopy were included. The patients were divided into 6 groups: group 1, 1 to 2 non-advanced adenomas (non-AAs)≥10mm or high-grade dysplasia or villous adenoma; group 1A, 1 to 2 adenomas with≥1 advanced adenoma (AA); group 2, 3 to 4 non-AAs; group 2A, 3 to 4 adenomas with≥1 AA; group 3,≥5 non-AAs; and group 3A,≥5 adenomas with≥1 AA. The risk of advanced CRN at 3 years was compared among the 6 groups. Group 3A showed a higher risk of advanced CRN (9.6%) than group 3 (4.5%; P= .03) and group 1A (4.6%; P< .001). The risk of advanced CRN in group 3 (4.5%) showed no difference compared with group 1A (4.6%; P= .91) or group 2A (6.8%; P= .25). There was no difference between group 1 and group 2 in the risk of advanced CRN (1.7% vs 2.2%; P= .22). More than 1 AA at index colonoscopy was an independent risk factor for advanced CRN. More-intensive surveillance than the 3-year interval for patients with≥5 adenomas with≥1 AA and less-intensive surveillance than the 3-year and 1-year intervals for those with 3 to 4 non-AAs and≥5 non-AAs, respectively, might be suggested.

Clinical and pathological features of upper gastrointestinal serrated lesions

Objective To analyze the clinical and pathological features of upper gastrointestinal serrated lesions. Methods A total of 21 patients with upper gastrointestinal serrated lesions in Tianjin Medical University General Hospital between January 2011 and December 2015 were retrospective analyzed. Data of the patients including demographics, clinical and pathological features were collected. Among the 21 patients, 18 patients, who underwent colonoscopy simultaneously or within six months, were selected as the study group, each patient was compared to 4 randomly selected controls without serrated lesions, who also underwent colonoscopy within the same time period. Differences of colorectal neoplasia detection were analyzed between the cases and controls. Results The mean age of 21 patients was 55.3±17.2 years, and 11 cases were male. Involving the locations of serrated lesions, 17 cases were found in the stomach (including 3 in the cardia, 9 in the corpus, and 5 in the antrum), and followed by 3 in the duodenum and 1 in lower esophagus. The mucosa pathological morphology showed that 6 cases were serrated hyperplasia, 8 cases were hyperplastic polyps, 6 cases were serrated adenomas with low grade dysplasia and 1 case was in the duodenum intramucosal carcinoma. Seven (38.9%) colorectal adenomas were found in the study group, including 3 (16.7%) non-advanced colorectal adenomas and 4 (22.2%) advanced colorectal adenomas. Eight (11.1%) colorectal adenomas were found in the control group, including 5 (6.9%) non-advanced colorectal adenomas and 3 (4.2%) advanced colorectal adenomas. The rate of colorectal adenoma detection in the study group was significantly higher than that in the control group (38.9% VS 11.1%, P=0.010, OR=5.091, 95%CI: 1.534-16.890). Conclusion Upper gastrointestinal serrated lesions can be found in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is likely to be recommended to detect concurrent colorectal adenoma for these patients. Key words: Endoscopy; Upper gastrointestinal tract; Serrated lesions; Colorectal adenoma

Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study

Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development.

Serology of Streptococcus gallolyticus subspecies gallolyticus and its association with colorectal cancer and precursors.

Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case-control study measured antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 and identified significant associations with a small fraction of CRC cases. We aimed at replicating and expanding these findings in an independent study including additional SGG antigens and explored the association with precancerous lesions. We applied multiplex serology to measure antibodies to eleven SGG proteins in serum samples of a screening colonoscopy trial (BliTz study) including participants diagnosed with either non-advanced adenoma (NAA, n = 30), advanced adenoma (AA, n = 100), CRC (n = 50) or controls (n = 228). In addition, we analyzed CRC samples (n = 318) from patients recruited in a clinical setting (DACHSplus study). The association of antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 with CRC was replicated with 4% positive DACHSplus cases compared to 0% positive BliTz controls. Positivity to two or more proteins of a newly defined panel of six SGG markers was significantly associated with CRC in the DACHSplus study (OR: 1.81, 95% CI: 1.07-3.06). Odds for CRC, AA and NAA in the BliTz study were also increased with antibody responses to SGG, and the association was significant for NAA (OR: 2.98, 95% CI: 1.18-7.57). Antibody responses to SGG are associated with CRC and its precursors. The newly identified SGG six-marker panel and associations found with precancerous lesions should be further explored.

P-279 - Metabolomics-based test accurately detects and differentiates adenomatous polyps from human sera

Introduction: Most colorectal cancers are believed to originate from adenomatous polyps that acquire distinct mutations and accumulate other molecular alterations that allow them to progress through distinct histopathologic stages before becoming invasive carcinomas. Adenomatous polyp detection and removal is the ultimate goal of colon cancer screening programs. However not all adenomas have the same potential to progress into carcinomas and thus a test that could detect more advanced adenomas with high sensitivity but could also separate advanced and non-advanced adenomas could be useful for screening purposes. The aim of our study was to show that metabolomic technology can be successfully used to distinguish persons with advanced adenomatous polyps from those without adenomas and the use of the technology could be further used for separation of patients with advanced adenomas from patients with non-advanced adenomas with potential to sub-categorization patients according to their pathological severity. Methods: Prospective serum samples were collected from 131 participants undergoing colonoscopy examination in a colon cancer screening program, from April 2016 to December 2016 at the Hospital Clínic de Barcelona. Colonoscopy reference standard identified 35 participants with no colonic polyps, 12 patients with hyperplastic polyps, 45 patients with non-advanced adenomas and 38 patients with advanced colonic adenomatous polyps. Mass-spectrometry based metabolite and lipid profiles were analysed to define a predictive metabolomic profile for advanced colonic adenomas and confirm if advanced adenoma patients could be separated from non-advanced adenoma patients. Serum metabolomic diagnostic test accuracy was defined for advanced colonic adenomatous polyps using Monte-Carlo 50-fold cross-validation with 70% samples used in a training and 30% of the samples in the validation set. Results: Using random forest algorithm on the metabolomic profile we could identify patients with colonic advanced adenomatous polyps from control patients with 87% sensitivity and 73% specificity. Additionally we could achieve identification of advanced adenoma patients from extended control set that included also patients with hyperplastic polyps and non-advanced adenomas with sensitivity of 81% and specificity of 70%. Additionally we could see clear distinction between advanced and non-advanced adenomas with sensitivity of 80% and specificity of 80%. Classification improvements could be observed even further when classifying adenomas into sub-groups according to severity of the pathology. Conclusion: We describe a proof-of-concept for serum-based metabolomic test that identifies patients with advanced adenomatous polyps with good level of sensitivity (87%) and allows distinction between advanced and non-advanced adenomas with sensitivity of 80% and allows further classification of different adenoma sub-groups according to their pathological severity.

Clinical, endoscopic and pathological characteristics of colorectal polyps in elderly patients: Single-center experience.

Increasing age is a risk factor for the development of colorectal adenomas and advanced adenomas. However, few studies have been published on the features of colorectal polyps in the elderly. The present study aimed to investigate the clinical, enteroscopic and pathological characteristics of colorectal polyps in Chinese elderly patients in a single center (The Central Hospital of Wuhan, Hubei, China). The endoscopic and pathological reports of colonoscopies performed in our center were retrospectively analyzed. A total of 7,795 consecutive patients referred for colonoscopy were evaluated between January 2013 and December 2014. Of the 297 who met the inclusion criteria, 279 polyps were observed in men and 230 in women. Of all the polyps, 263 were non-adenomatous polyps, 104 were non-advanced adenomas and 142 were advanced adenomas. 336 polyps were left-sided and 173 were right-sided. Polyps ≥10 mm were more likely to exhibit an adenomatous component and advanced features, and these findings continued to hold true when the size cut-off was set at 5 mm. The data shown in the present study have revealed that a significant number of polyps lie proximal to the splenic flexure. Thus, evaluation of the whole bowel is particularly important in elderly patients who are undergoing colonoscopy. In addition, the polyp size was associated with the presence of adenoma, and advanced component, diminutive and small polyps should not be ignored in elderly patients.

Meat intake and risk of colorectal polyps: results from a large population-based screening study in Germany ,

Background: Red and processed meats have been shown to be associated with colorectal adenomas in many, but not all, studies, and the association according to the type of colorectal adenoma or the location in the colorectum is unclear.Objectives: We investigated the association of meat intake in relation to colorectal polyps and further investigated the association according to histologic subtypes and subsites in a large population-based screening study in Germany.Design: In this cross-sectional study, 15,950 participants aged ≥55 y underwent a screening colonoscopy. We calculated prevalence ratios (PRs) and 95% CIs for associations between meat intake and the most-advanced findings from a colonoscopy with the use of log binomial regression.Results: Overall, 3340 participants (20.4%) had nonadvanced adenomas, 1643 participants (10.0%) had advanced adenomas, and 189 participants (1.2%) had colorectal cancer. We observed no statistically significant association between red or processed meat consumption and the prevalence of any adenomas or advanced adenomas [highest compared with lowest: red meat, PR: 1.07 (95% CI: 0.83, 1.37); processed meat, PR: 1.11 (95% CI: 0.91, 1.36)]. In site-specific analyses, although no dose-response relation was observed, processed meat was positively associated with the prevalence of advanced adenomas in the rectum only (multiple times per day compared with <1 time/wk, PR: 1.87; 95% CI: 1.19, 2.95). Poultry intake was not associated with any outcome.Conclusions: On the basis of this large colonoscopy-based study, there are no significant associations between red or processed meat intake and the prevalence of any adenomas or advanced adenomas. However, processed meat may be positively associated with the prevalence of advanced adenomas in the rectum, but prospective cohort studies are needed to further clarify this association. There is no association between poultry consumption and the prevalence of colorectal polyps in this study.

The Association between Distal Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta-Analysis.

Whether screening participants with distal hyperplastic polyps (HPs) detected by flexible sigmoidoscopy (FS) should be followed by subsequent colonoscopy is controversial. We evaluated the association between distal HPs and proximal neoplasia (PN)/advanced proximal neoplasia (APN) in asymptomatic, average-risk patients. We searched Ovid Medline, EMBASE, and the Cochrane Library from inception to 30 June 2016 and included all screening studies that examined the relationship between different distal findings and PN/APN. Data were independently extracted by two reviewers with disagreements resolved by a third reviewer. We pooled absolute risks and odds ratios (ORs) with a random effects meta-analysis. Seven subgroup analyses were performed according to study characteristics. Heterogeneity was characterized with the I2 statistics. We analyzed 28 studies (104,961 subjects). When compared with normal distal findings, distal HP was not associated with PN (OR=1.16, 95% confidence interval (CI)=0.89-1.51, P=0.14, I2=40%) or APN (OR=1.09, 95% CI=0.87-1.36, P=0.39, I2=5%), while subjects with distal non-advanced or advanced adenoma had higher odds of PN/APN. Higher odds of PN/APN were observed for more severe distal lesions. Weaker association between distal and proximal findings was noticed in studies with higher quality, larger sample size, population-based design, and more stringent endoscopy quality-control measures. The Egger's regression tests showed all P>0.05. Distal HP is not associated with PN/APN in asymptomatic screening population when compared with normal distal findings. Hence, the presence of distal HP alone detected by FS does not automatically indicate colonoscopy referral for all screening participants, as other risk factors of PN/APN should be considered.

Surveillance after positive colonoscopy based on adenoma characteristics

BackgroundPatients with adenomatous polyps are at increased risk for developing colorectal cancer based on the characteristics and number of polyps, but less is known about the individual and combined contribution of these factors. This study aimed to better characterize the risk of advanced adenoma and cancer in patients with positive baseline colonoscopy. MethodsPatients who had polyps at baseline colonoscopy were included in this retrospective cohort study (N=1165) and were categorized into 6 groups: (1) 1–2 non-advanced adenomas (NAA’s), (2) ≥3 NAA’s, (3) advanced tubular adenoma, (4) small tubulovillous adenoma (TVA), (5) large TVA and (6) multiple advanced adenomas (MAA’s). Findings at surveillance colonoscopy were documented in each group. ResultsThe combined incidence of advanced adenoma, ≥3 NAA’s, and colorectal cancer at surveillance colonoscopy was significantly higher in the baseline large TVA (29.2%) than small TVA groups (13.5%, P<0.001), as well as in the MAA’s group (44.1%) compared with large TVA group (P=0.02). The incidence of colorectal cancer, however, was not significantly different between the groups. ConclusionsThe size of the polyp and the number of advanced lesions are more important than its histology for predicting the risk of high-risk metachronous lesions at follow-up.