Effect of Cotinine-Verified Change in Smoking Status on Risk of Metachronous Colorectal Neoplasia After Polypectomy.

BACKGROUND & AIMS: Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure. METHODS: We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017. RESULTS: Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20). CONCLUSIONS: In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer.

Clinical validation of a novel urine-based metabolomic test for the detection of colonic polyps on Chinese population.

PURPOSE: Colorectal cancer is the fifth leading cause of cancer-related deaths in China. When detected early, with the removal of adenomatous polyps, precursors of colorectal cancer, it is preventable. The aim of this study was to evaluate a novel urine-based metabolomic diagnostic test for the detection of adenomatous polyps, PolypDx™, that was originally developed and validated using 1000 samples from Canadian Cohort, on Chinese population. METHODS: Prospective urine samples were collected from 1000 participants undergoing colonoscopy examination, from March 2013 to July 2014 at Minhang District, Shanghai Centre for Disease Control and Prevention. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to determine the concentrations of three key metabolites used in PolypDx™. The predicted results were then compared to the gold standard for colorectal cancer diagnostic, colonoscopy. Area under curve (AUC) was calculated specifically for the Chinese population and compared with the Canadian dataset. Sensitivity and specificity of this urine-based metabolomic diagnostic test were also compared with three commercially available fecal-based tests. RESULTS: An AUC of 0.717 for PolypDx™ was calculated on Chinese dataset which is slightly lower than the AUC on the Canadian dataset. A sensitivity of 82.6% and a specificity of 42.4% were achieved on Chinese dataset. CONCLUSIONS: Here, we validated a novel urine-based metabolomic diagnostic test for the detection of adenomatous polyps, PolypDx™, on Chinese population through a sample size of 1000 participants with a greater level of sensitivity than fecal-based tests.

A machine-learned predictor of colonic polyps based on urinary metabolomics.

We report an automated diagnostic test that uses the NMR spectrum of a single spot urine sample to accurately distinguish patients who require a colonoscopy from those who do not. Moreover, our approach can be adjusted to tradeoff between sensitivity and specificity. We developed our system using a group of 988 patients (633 normal and 355 who required colonoscopy) who were all at average or above-average risk for developing colorectal cancer. We obtained a metabolic profile of each subject, based on the urine samples collected from these subjects, analyzed via (1)H-NMR and quantified using targeted profiling. Each subject then underwent a colonoscopy, the gold standard to determine whether he/she actually had an adenomatous polyp, a precursor to colorectal cancer. The metabolic profiles, colonoscopy outcomes, and medical histories were then analysed using machine learning to create a classifier that could predict whether a future patient requires a colonoscopy. Our empirical studies show that this classifier has a sensitivity of 64% and a specificity of 65% and, unlike the current fecal tests, allows the administrators of the test to adjust the tradeoff between the two.

Matrix metalloproteinases in the urine and tissue of patients with juvenile polyps: potential biomarkers for the presence of polyps.

BACKGROUND AND AIMS: Juvenile polyps are the most common type of pediatric gastrointestinal polyp and are typically characterized as hamartomatous overgrowths. Juvenile polyps are highly vascularized tissues and display a markedly increased mucosal microcirculation. Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that play an essential role in the physiological degradation of the extracellular matrix in normal development, tumor invasion, and metastasis, as well as angiogenesis. We hypothesized that the presence of these enzymes in urine may serve as clinical biomarkers of juvenile polyps. PATIENTS AND METHODS: In this preliminary study, we analyzed 32 urine samples collected prospectively from 16 subjects with known or suspected juvenile polyps who presented to the endoscopy unit for colonoscopic evaluation and 16 age- and sex-matched controls. Urinary MMPs were analyzed by zymography and their localized tissue expression was assayed via immunohistochemistry of tissue sections. RESULTS: MMPs were detected in the urine of patients with juvenile polyps with significantly higher frequency when compared with urine of control subjects. In addition, immunohistochemistry demonstrated that high levels of MMPs were localized in the epithelium and lamina propria of polyp tissue when compared with colonic tissue collected from healthy control subjects. CONCLUSIONS: These data are the first to demonstrate that MMPs are present in the urine and tissue of patients with juvenile polyps, and these enzymes have the potential to serve as surrogate markers for the presence of polyps.

[Effect of jinfu kang to experimental precancerous colon lesions and urinary metabolites in rat].

OBJECTIVE: : To profile urinary metabolite variations from 1, 2-dimethylhydrazine (DMH)-induced precancerous colon rats, Jinfu Kang treated rats and healthy controls. METHOD: We used ethyl chloroformate derivatization and gas chromatography-mass spectrometry (GC-MS) based metabonomic method to analyze rat urines. RESULT: The time-dependent variations of metabolite profile showed a progressive deviation of the metabolism in the model group from the initial pattern over time and a systemic recovery of the metabolism in the treatment group, which is consistent with the histological results. The in-depth analysis indicated that the disorder of tricarboxylic acid cycle (TCA), tryptophan metabolism, polyamine metabolism and gut flora structure were associated with DMH intervention. CONCLUSION: Metabolic study revealed that Jinfu Kang can effectively reverse metabolic departures in DMH-induced precancerous colon rat, which is consistent with pathological results.