Proximal Aberrant Crypt Foci Associate with Synchronous Neoplasia and Are Primed for Neoplastic Progression.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas.Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy.Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR.

Low Serum Vitamin D: A Surrogate Marker for Advanced Colon Adenoma?

AIMS: To examine the association between low 25-OH Vitamin D levels and prevalence of advanced adenomas (AAs) in screening/surveillance colonoscopy patients. RATIONALE: Low serum 25-OH Vitamin D has been associated with an increased risk for colon cancer. In the Adenoma-Carcinoma pathway, a subset of colon polyps (AA) have been regarded as high-risk precursor lesions. We used a retrospective case-control design to examine the association between Vitamin D deficiency and the prevalence of AA in a high-risk population. MATERIALS AND METHODS: We examined a total of 354 patients who presented for initial screening or surveillance colonoscopy at our Colon Cancer Prevention Program. Our main exposure variable was serum Vitamin D levels and the outcome was AAs defined as those adenomas that were large (≥1 cm) or had advanced pathology (>25% villous components or high-grade dysplasia). Known risk factors were also collected from the patients' charts including gender, age, smoking, and family history. Bivariate and multivariate analyses were performed to examine the relationship between serum 25-OH Vitamin D levels and AAs. A total of 354 patients [(males, 188; females, 166); average age, 61 y] charts were reviewed. Vitamin D levels ranged between 4 and 70 ng/mL, with a mean of 25 ng/mL (clinical laboratory normal>30 ng/mL). There was no significant association between serum levels and time of the year of blood draw. Risk for tubular adenoma and AA increased as Vitamin D levels decreased to <30 ng/mL (P=0.002). In total, 80% of AAs were detected in patients whose levels were below this value (odds ratio, 3.36; 95% confidence interval, 1.40-8.03; P=0.007). Bivariate analysis also showed a positive association between smokers with AA as well as those with a family history of colon cancer (P=0.011) and low Vitamin D levels (P=0.001). A multivariate analysis using quintiles of Vitamin D levels demonstrated an increased risk of AAs for patients with levels in the second quintile (33 ng/mL) (odds ratio, 4.3; P=0.01) MAIN CONCLUSIONS:: Most patients presenting in our Colon Cancer Prevention Program have low levels of serum 25-OH Vitamin D. Analysis of the results of both screening and surveillance colonoscopies demonstrated an inverse relation between serum 25-OH Vitamin D level and AAs.

Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy.

OBJECTIVE: To estimate the risk for colorectal neoplasia detected on repeat colonoscopy in relation to aberrant crypt foci (ACF) frequency reported during the previous baseline examination. METHODS: From July 2003 until December 2008, patients had a colonoscopy with an ACF study using a magnifying colonoscope. The distal 20 cm section of colon was sprayed with Methylene Blue to ascertain the ACF frequency, the independent variable. Patients were categorized into low and high ACF count using the median as the cut point. Data collected from consenting patients included age, gender, height, weight, ethnicity, smoking history, family history of colorectal cancer (CRC), and personal history of colorectal neoplasia. A follow-up colonoscopy was performed at an interval as dictated by clinical surveillance guidelines. The main outcome was surveillance detected advanced colorectal neoplasia (SDAN) detected on repeat colonoscopy. Logistic Regression was used to calculate risk of SDAN on repeat colonoscopy in relation to baseline ACF count. RESULTS: 74 patients had a baseline ACF exam and a repeat surveillance colonoscopy. The median ACF was six and thus a high ACF count was >6 ACF and a low ACF count was ≤6 ACF. Patients diagnosed with SDAN were more likely to have had a high ACF number at baseline compared to patients without these lesions at follow-up (adjusted odds ratio = 12.27; 95% confidence interval: 2.00-75.25) controlling for age, sex, smoking, history of prior adenoma, family history of colon cancer, obesity, and time interval to surveillance exam. A sub analysis of our results demonstrated that this relationship was observed in 48 patients who were undergoing a surveillance colonoscopy for a previous adenoma and not those receiving surveillance for a family history of neoplasia. CONCLUSIONS: Increased number of ACF in the distal colorectum was independently associated with substantial risk for future advanced neoplasia. This relationship was observed in patients undergoing surveillance for previous adenomas. Thus, ACF may serve as potential biomarkers in patients with adenomas to help identify patients who may need additional surveillance.