Colorectal Precancerous Lesions Research Articles

Results and cost-effectiveness of colorectal cancer screening program among urban residents in Zhejiang province, 2013-2018

Objective: To analyze the results and cost-effectiveness of colorectal cancer (CRC) screening program among Zhejiang urban residents so as to provide evidence for further optimization of CRC screening strategies. Methods: Based on the Cancer Screening Program in Urban China which was conducted in Zhejiang province from 2013-2018, data related to the rates on compliance and detection through the CRC screening program among the 40-74 year-old residents were analyzed. Chi-square tests were used to compare the differences among groups, and multivariate logistic regression models were applied to explore the potential risk factors. Cost-effectiveness ratio (CER) was calculated by using the cost per lesion detected as the indicator. Results: Among all the 166 285 participants who completed the risk assessment questionnaire, 21 975 (13.2%) were recognized as under the high risk of CRC and 4 389 (20.0%) of them received the colonoscopy. The detection rates of CRC, advanced adenoma, and non-advance adenoma were 0.3% (11 cases), 2.7% (119 cases), and 5.2% (229 cases), respectively. Results from the multivariate logistic regression analyses showed that factors as age, gender, education level, smoking, drinking alcohol, previous fecal occult blood test (FOBT), polyp history, and family history of CRC were significantly associated with the compliance rate of colonoscopy while age, smoking and polyp history were significantly associated with the detection rate of advanced neoplasms (CRC and advanced adenoma). The costs were ￥22 355.74 Yuan for every CER advanced neoplasm detection and ￥264 204.18 Yuan per CRC detection, respectively. The CER decreased along with ageing. Sensitivity analysis showed that CERs were expected to decrease when the compliance rate of colonoscopy was increasing. Conclusions: The current screening program seems effective in detecting the precancerous colorectal lesions, but the relatively low compliance rate of colonoscopy restricting both the diagnostic yields and economic benefits. It is necessary to improve the awareness and acceptance of colonoscopy among the high-risk CRC population.

Preliminary results of a multidisciplinary Italian study adopting a Psycho-Neuro-Endocrine-Immunological (PNEI) approach to the study of colorectal adenomas.

Background and aim of the work:Colorectal mucosal precancerous lesions, metabolic syndrome (MetS) and psychiatric disorders may share a common low-grade local and systemic inflammation. Aim is to report on preliminary data concerning a research adopting a psycho-neuro-endocrine-immune (PNEI) approach to study outpatients undergoing colonoscopy.Methods:A sample of patients undergoing colonoscopy was cross-sectionally investigated. Data on colorectal adenomas, MetS, early atherosclerosis, anxious-depressive symptoms, personality traits, and inflammatory markers were statistically analyzed.Results:Sixty-two patients were recruited (female 50%, mean age: 60.8±9.4 years). The prevalence of adenomas and MetS was respectively of 45.2% and 41.9%. Anxiety and depressive symptoms were detected in 16 (32.7%) and 9 (18.4%) subjects, respectively. The presence of adenomas positively correlated with male sex (p=0.01), age (p<0.01), IL-6 (p=0.03), hsCRP (p=0.04), and MetS (p=0.03); it was also associated with hsCRP concentration (aOR=3.81, p=0.03).Conclusions:Proinflammatory atherogenic status, psychological traits, increased mucosal inflammation, and metabolic parameters may share a common a pathogenic mechanism, worth studying.

Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.

Expression Profile and Prognostic Significance of EPHB3 in Colorectal Cancer.

The protein tyrosine kinase Ephrin type-B receptor 3 (EPHB3) is expressed in cells at the base of intestinal crypts, acting as a cellular guide in the maintenance of intestinal crypt architecture. We aimed to investigate the expression profile of EPHB3 in colorectal precancerous lesions and colorectal cancers (CRCs), and assess its prognostic value. EPHB3 expression was higher in CRCs than in normal mucosa and was associated with the intestinal stem cell markers EPHB2, OLFM4, LRIG1, and a proposed cancer stem cell marker, CD44. Enhanced EPHB3 expression significantly declined during the transformation from adenoma to carcinoma and as the tumor invaded into deeper tissue layers. Namely, a substantial reduction of EPHB3 expression was observed in the budding cancer cells at the invasive tumor fronts, which was more extensive than E-cadherin downregulation. In an azoxymethane/dextran sulfate sodium-induced, colitis-associated, CRC model, EPHB3 expression increased along with tumor development. In a large cohort of CRC patients, EPHB3 positivity was observed in 24% of 610 CRCs and was negatively correlated with tumor differentiation, lympho-vascular invasion, and tumor, node, and metastasis stages. EPHB3 was positively associated with microsatellite instability but was associated with neither CpG island methylation, nor with KRAS and BRAF mutations. Notably, EPHB3 positivity was associated with better clinical outcomes, although it was not an independent prognostic marker. Overexpression of EPHB3 in the colon cancer cell line, DLD1, led to decreased cell growth and migration and reduced mitogen-activated protein kinase signaling. Taken together, our data demonstrate the suppressive role of EPHB3 in CRC progression.

Quantitative immunochemical fecal occult blood test in health check-up population

Objective To assess the application of quantitative immunochemical fecal occult blood test (qFIT) in screening of gastrointestinal diseases for health check-up population. Methods Total 19 633 health check-up subjects, who received qFIT in AiKang Guobin Physical Examination Center from January 2018 to June 2019 qFIT, were enroll in the study. The positive rate of subjects who received qFIT were analyzed. Gastrointestinal endoscopy were used to diagnose gastrointestinal lesions. The application of qFIT in screening gastrointestinal diseases, especially colorectal cancer and precancerous lesions was evaluated. Results Total 718 (3.66%) subjects were positive for qFIT, among whom 103 (42.3%) underwent gastrointestinal endoscopic examinations. Finally, 33 (42.3%) cases of colon adenoma, 9 (11.5%) cases of peptic ulcer, and 4 (3.1%) cases of colorectal cancer were detected; and other conditions including gastroenteritis and hemorrhoids were were also diagnosed. There were 87 cases whose qFIT were negative performed colon endoscopy, 5 (5.7%) cases of colon adenoma, no colorectal cancer were detected. The mean value of qFIT for colon cancer was higher than that for polyps (3 569±1 085)μg/L vs. (823±106) μg/L, P=0.01]. The detection rate of colon polyps in qFIT positive subjects was higher than that in qFIT negative subjects [32%(33/103) vs.5.7% (5/87)], and the detective rate of colon cancer in qFIT positive subjects was higher than that in qFIT negative subjects [3.9%(4/103) vs.0(0/87)]. Conclusion Quantitative immunochemical fecal occult blood test can improve the detection rate of colorectal cancer and precancerous lesions in screening of gastrointestinal diseases. Key words: Occult blood; Feces; Colonic neoplasms; Healthy examination

Enterotoxigenic Bacteroides fragilis: A Possible Etiological Candidate for Bacterially-Induced Colorectal Precancerous and Cancerous Lesions.

Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models, ETBF has been shown to contribute to colon carcinogenesis. The present study was conducted to investigate mucosal colonization of ETBF in the colon to find a possible association between the presence of ETBF and precancerous and cancerous lesions. The mucosal biopsies of involved sites were obtained from 68 patients with precancerous and cancerous lesions and 52 healthy controls (HC). The samples were cultured on Bacteroides Bile Esculin agar. Then, specific primers were designed to detect B. fragilis and bft gene using quantitative real-time PCR, and the possible links of ETBF with clinicopathological characteristics was evaluated. Also real-time PCR was performed to detect the bft gene subtypes. Bacteroides fragilis was detected in 51% of the patients and 48% of HCs cultures. The 16SrRNA gene was found to be present in 63 and 81% of the patients and HCs' samples, respectively. Moreover, the bft gene was detected in 47 and 3.8% of the patients and HCs, respectively. Also, B. fragilis was significantly more abundant in the patients' samples compared to those of HCs. In the patient group, higher odds ratio (OR) of ETBF was significantly associated with serrated lesions and adenoma with low-grade dysplasia. The bft1 gene was the most prevalent subtype of bft gene, followed by the bft2 gene. This was the first study in Iran to demonstrate increased positivity of ETBF in patients with precancerous and cancerous lesions. In this study, the bft gene was found to be associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions. Moreover, the results suggest that mucosal BFT exposure is common and could be a risk factor and a screening marker for developing CRC.

微卫星不稳定性与结直肠癌及癌前病变相关性研究进展

微卫星不稳定性与结直肠癌及癌前病变相关性研究进展

The chemopreventive effects of Huangqin-tea against AOM-induced preneoplastic colonic aberrant crypt foci in rats and omics analysis.

Despite that colorectal cancer (CRC) is a severe global health problem, effective chemopreventive strategies against CRC are still lacking. Huang-qin tea (HQT), a healthy herbal tea, is prepared from the aerial parts of Scutellaria baicalensis Georgi and has been consumed in China for thousands of years. HQT contains abundant flavonoids, which display potent anticancer effects, but no research studies have investigated the cancer-preventive effects of HQT on CRC in vivo. Here, we found that HQT inhibits azoxymethane-induced aberrant crypt foci (ACF) formation in a preneoplastic colonic ACF rat model. The essential role of the gut microbiota in the chemopreventive effect of HQT on CRC in a pseudo-germ-free rat model was confirmed. Besides, HQT modulates inflammatory cytokine expression by significantly decreasing IL-1β, IL-6, IL-10, and TNF-α expression, and elevating IFN-γ production. 16S rDNA sequencing analysis indicated that HQT regulated the gut microbiota by increasing the abundance of beneficial bacteria (Lachnoclostridium, Alistipes, Roseburia, and Lactococcus) and reducing the levels of Bacteroides, Parasutterella, and unidentified_Clostridiales. Fecal metabolomics showed that HQT modulated the AOM-induced metabolomic disorder, and these altered metabolites were almost involved in the lipid metabolic pathways. The Spearman correlation analysis revealed a correlation between the gut microbiota and fecal metabolites. Collectively, these results suggested that HQT exerted beneficial effects on host health by inhibiting inflammation, and by regulating the gut microbiota profile and certain metabolic pathways. In conclusion, HQT inhibits AOM-induced ACF formation by modulating the gut microbiota composition and improving metabolomic disorders, indicating the potential of HQT as a functional beverage candidate for the prevention and treatment of CRC.

175 Clinical Usefulness of SMOC1 as a Diagnostic Marker for Colorectal Serrated Lesions and Colorectal Precancerous Lesions

INTRODUCTION: Colorectal serrated lesions (SLs) include hyperplastic polyp (HP), traditional serrated adenoma (TSA) and sessile serrated adenoma/polyp (SSA/P). SSA/Ps are well known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability (MSI). However, clinical and molecular characteristics of TSAs are not fully understood. We have reported that epigenetic silencing of SMOC1 is associated with development of traditional serrated adenomas (TSAs) and that SMOC1 may play a role in neoplastic pathways in TSAs and conventional adenomas. 1 We aimed to clarify the clinical usefulness of SMOC1 in colorectal tumors. METHODS: Expression of SMOC1 was analyzed in a series of 127 colorectal tumors and adjacent normal colonic mucosa by immunohistochemistry (IHC). The staining intensity of SMOC1 was assessed as strong (3), moderate (2), weak (1) or negative (0). The proportions of positively stained tumor cells were assessed as 0 to 10 for each staining intensity. Because neoplasm heterogeneity caused varying degrees of immunoreactivity in respective specimens, we used the sum of each intensity × proportion as an IHC score (e.g., intensity × proportion = (3) × 5 + (2) × 3 + (1) × 1 + (0) × 1 = IHC score 22, scale of 0 to 30). RESULTS: Our IHC analysis revealed that SMOC1 is abundantly expressed in normal colon, HPs and SSA/Ps, while it was significantly downregulated in TSAs, high-grade adenomas and CRCs. Among serrated lesions, SMOC1 is expressed in HPs, SSA/Ps and SSA/Ps with CRC, while it was significantly downregulated in TSAs and TSAs with CRC. Notably, in TSAs which consisted of flat and protruding subcomponents, SMOC1 expression levels were lower in the protruding portions than those in the flat portions (P &lt; 0.001). CONCLUSION: These results suggest that downregulated expression of SMOC1 could be a hallmark of TSAs and conventional adenomas at high risk of developing CRC.

Dietary Polyacetylenic Oxylipins Falcarinol and Falcarindiol Prevent Inflammation and Colorectal Neoplastic Transformation: A Mechanistic and Dose-Response Study in A Rat Model

Falcarinol (FaOH) and falcarindiol (FaDOH) are cytotoxic and anti-inflammatory polyacetylenic oxylipins, which are commonly found in the carrot family (Apiaceae). FaOH and FaDOH have previously demonstrated a chemopreventive effect on precursor lesions of colorectal cancer (CRC) in azoxymethane (AOM)-induced rats. The purpose of the present study was to elucidate possible mechanisms of action for the preventive effect of FaOH and FaDOH on colorectal precancerous lesions and to determine how this effect was dependent on dose. Gene expression studies performed by RT-qPCR of selected cancer biomarkers in tissue from biopsies of neoplastic tissue revealed that FaOH and FaDOH downregulated NF-κβ and its downstream inflammatory markers TNFα, IL-6, and COX-2. The dose-dependent anti-neoplastic effect of FaOH and FaDOH in AOM-induced rats was investigated in groups of 20 rats receiving a standard rat diet (SRD) supplemented with 0.16, 0.48, 1.4, 7 or 35 µg FaOH and FaDOH g−1 feed in the ratio 1:1 and 20 rats were controls receiving only SRD. Analysis of aberrant crypt foci (ACF) showed that the average number of small ACF (<7 crypts) and large ACF (>7 crypts) decreased with increasing dose of FaOH and FaDOH and that this inhibitory effect on early neoplastic formation of ACF was dose-dependent, which was also the case for the total number of macroscopic neoplasms. The CRC protective effects of apiaceous vegetables are mainly due to the inhibitory effect of FaOH and FaDOH on NF-κB and its downstream inflammatory markers, especially COX-2.

Gallbladder Polyps Are Associated with Proximal Colon Polyps.

Background The association between gallbladder (GB) disease and colorectal precancerous lesions remains elusive. This study sought to explore the association between GB disease and colorectal neoplasms at different locations. Methods Patients who received general health checkup from January to December 2008 were included and subgrouped into three groups by polyp location: proximal, distal, and whole colon. GB disease and other known risk factors for colon cancer were compared and analyzed. Different types of polyps at different locations were further investigated. Results Of a total of 3136 patients (1776 men and 1360 women; mean age, 49.3 years) who had colon polyps, 212 (6.8%) had GB stone and 512 (16.3%) had GB polyps. Patients in the proximal colon polyp group had higher rates of GB polyps and stones. GB polyps were independently associated with proximal colon polyps, including both hyperplastic polyps (odds ratio, 1.523; P = 0.034) and adenomatous polyps (odds ratio, 1.351; P = 0.048). No relationship between GB polyps and distal or any colon polyps was observed. Irrespective of the polyp location (i.e., proximal, distal, or any part of the colon), GB stone did not show any association with colon polyp. Conclusions We suggested that GB polyps are associated with proximal colon polyps. Colonoscopy may be a more effective strategy for screening proximal precancerous lesions among patients with GB polyps. The association between GB disease and colon polyps demands further prospective investigation.

Therapeutic value of endoscopic submucosal dissection for early colorectal cancers and precancerous colorectal lesions of different diameters

Objective To study the differences of endoscopic submucosal dissection (ESD) for colorectal tumors of different diameters. Methods Data of 210 cases which were treated with ESD for colorectal tumors at the Endoscopy Center, the Seventh Medical Center of PLA General Hospital from October 2012 to December 2015 were retrospectively analyzed. The lesions were divided into two groups according to different diameters (≥4.0 cm group and <4.0 cm group) for comparative analysis of related factors. Results The mean procedure time of ESD for 210 colorectal tumor cases was 50.3±42.7 min and the mean size of lesions was 7.98±10.84 cm2 . En bloc resection rate was 91.4%, R0 resection rate was 90.5%, and the curative resection rate was 88.6%. Perforation rate was 5.2% (11/210), and the late hemorrhage rate was 0.5% (1/210). Compared with lesions < 4.0 cm, those ≥ 4.0 cm required longer resection time (79.63±53.91 min VS 35.28±24.99 min, P<0.001); and the lesions were mainly located in the rectum (61.97%). LSTs were mainly mixed granular/nongranular type (54.93%); en bloc resection rate, complete resection rate and curative resection rate of the tumors ≥ 4.0 cm were all lower than those of tumors < 4.0 cm. The difference in complete resection rate was statistically significant (85.92% VS 94.24%; P=0.041). The perforation rate (7.04%) was higher in ≥ 4.0 cm group, but the difference was not statistically significant. Conclusions ESD of colorectal tumors of diameters ≥ 4.0 cm requires longer time with higher operation risk. Additionally, physicians should be more careful with non-rectal lesions. Key words: Colorectal cancer; Endoscopic submucosal dissection; Tumor diameter; Difference

Cost-utility analysis of screening for colorectal precancerous lesions and cancer in Beijing: A case-control study.

To provide an objective cost-utility evaluation of a colorectal cancer screening program in a hypothetical general population. A cost-utility analysis was conducted comparing screened individuals with the general population. Patients were evaluated as part of the screening program which conducted colorectal cancer risk assessments and performed colonoscopies from October 2012 to May 2013. Data were compared to a hypothetical group of the same size, consisting of the general population in which no cancer screening had been conducted. The cost and utility data have been published previously. The average cost per quality-adjusted life year (QALY) of colorectal cancer screening population was 84,092 CNY, while the average cost per QALY of the general population was 122,530 CNY. The colorectal cancer screening program saved 43,530 CNY per additional QALY. The colorectal cancer screening program could improve health-related quality of life and reduce medical expenditure.

A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.

Specimen processing and pathological evaluation of 113 samples of early colorectal cancer and precancerous lesion after endoscopic submucosal dissection

Objective To study the pathology and its significance of early colorectal cancer and precancerous lesions treated by endoscopic submucosal dissection (ESD). Methods A total of consecutive 113 cases were collected at the endoscopy center from August 2012 to June 2016, which were diagnosed as early colorectal cancer and precancerous lesions and undergone ESD. According to Japanese colorectal cancer treatment guidelines, specimens were processed and pathologically evaluated for histological type, tumor diameter, depth of invasion, budding grading, vessel invasion, and horizontal and vertical margin, as well as curative resection. Results There were 63 cases of adenoma (55.75%), including 29(25.66%) tubular adenoma, 2(1.77%) villous adenoma, and 32(28.32%) villioustublar adenoma. Thirty-four cases of serrated lesion were found, which included 19(16.81%) traditional serrated adenoma, 11(9.73%) sessile serrated adenoma, and 4(3.54%) hyperplasic polyp. There were also 16(14.16%) cases of early colorectal cancer with 7 cases of well-differentiated adenocarcinoma, 7 cases of moderately-differentiated adenocarcinoma, 1 case of poorly-differentiated adenocarcinoma, and 1 case of mucinous adenocarcinoma. Vessel invasion were observed in 2 of 16 cases of early colorectal cancer which were both moderately-differentiated adenocarcinoma in sigmoid colon. The vertical margins were negative in 108(95.58%) of 113 cases. Positive vertical margin were found in only 1 case (moderately-differentiated adenocarcinoma, pT1b2) and another case was suspected as positive. The rest 3 cases could not be precisely diagnosed. The horizontal margins were negative in 80(70.80%) of 113 cases and positive horizontal margin were found in 20(17.7%) cases (19 adenoma and 1 moderately-differentiated adenocarcinoma). Thirteen cases cannot be precisely diagnosed. Histologically, complete resection rate was 82.30%. The complete resection rate of invasive adenocarcinoma was 93.75%. Among 16 cases of invasive adenocarcinoma, 5 cases (curative rate: 31.25%) were judged as curative resection whereas 11 cases were considered as non-curative resection. Seven non-curative resection cases were treated with further surgery and did not relapse after the follow-up. Conclusion The standardized processing and precise histopathological evaluation are key factors for colorectal ESD technique, which play an important role in the success of endoscopic therapy. Key words: Colorectal neoplasms; Early diagnosis; Pathology, clinical; Endoscopic submucosal dissection

Next-generation sequencing for miRNA profiling of stool and plasma samples of patients with colorectal cancer or precancerous lesions

Next-generation sequencing for miRNA profiling of stool and plasma samples of patients with colorectal cancer or precancerous lesions

Second-harmonic imaging microscopy for identifying colorectal intraepithelial neoplasia.

In this study, second-harmonic imaging microscopy was used to monitor precancerous colorectal lesions at different stages. It was found that the morphology of glands and lamina propria in mucosa changes with the progression of colorectal diseases from normal to low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and this microscopy has the ability of direct visualization of these warning symptoms. Furthermore, two morphologic variables were quantified to determine the changes of glands and collagen in lamina propria during the development of colorectal intraepithelial neoplasia. These results suggest that second-harmonic imaging microscopy has the potential in label-freely and effectively distinguishing between normal and precancerous colorectal tissues, and will be helpful for early diagnosis and treatment of colorectal diseases.

Prospective clinical study of circulating tumor cells for colorectal cancer screening.

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 &gt; 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]

Chemopreventive effects of Ku-jin tea against AOM-induced precancerous colorectal lesions in rats and metabolomic analysis

Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.

Tumor-associated DNA mutation detection in individuals undergoing colonoscopy.

The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. Two hundred patients without a history of nonskin cancer had blood drawn before a colonoscopy. Plasma ctDNA was measured with a 96 mutation panel for nine cancer driver genes. The ctDNA results were correlated with the findings at colonoscopy. Of the 200 patients, 176 (88%) had wild‐type DNA, 12 (6%) had mutations detected, and 12 (6%) had indeterminate results. Colonoscopy was normal in 80% of the patients and 20% were found to have polyps. No CRC was found in this study, precluding a determination of true‐positive rate for CRC detection. Our ctDNA panel was positive in 13.2% of patients with colonic polyps found at colonoscopy, while 4.7% of patients with normal colonoscopy also had ctDNA detected, which may represent ctDNA released from a benign process, an occult tumor, or an acquired somatic mutation from clonal hematopoiesis.