Although colorectal cancer (CRC) is considered one of the most preventable cancers, no non-invasive, accurate diagnostic tool to screen CRC exists. We explored the potential of urine nuclear magnetic resonance (NMR) metabolomics as a diagnostic tool for early detection of CRC, focusing on advanced adenoma and stage 0 CRC. Urine metabolomics profiles from patients with colorectal neoplasia (CRN; 36 advanced adenomas and 56 CRCs at various stages, n = 92) and healthy controls (normal, n = 156) were analyzed by NMR spectroscopy. Healthy and CRN groups were statistically discriminated using orthogonal projections to latent structure discriminant analysis (OPLS-DA). The class prediction model was validated by three-fold cross-validation. The advanced adenoma and stage 0 CRC were grouped together as pre-invasive CRN. The OPLS-DA score plot showed statistically significant discrimination between pre-invasive CRN as well as advanced CRC and healthy controls with a Q2 value of 0.746. In the prediction validation study, the sensitivity and specificity for diagnosing pre-invasive CRN were 96.2% and 95%, respectively. The grades predicted by the OPLS-DA model showed that the areas under the curve were 0.823 for taurine, 0.783 for alanine, and 0.842 for 3-aminoisobutyrate. In multiple receiver operating characteristics curve analyses, taurine, alanine, and 3-aminoisobutyrate were good discriminators for CRC patients. NMR-based urine metabolomics profiles significantly and accurately discriminate patients with pre-invasive CRN as well as advanced CRC from healthy individuals. Urine-NMR metabolomics has potential as a screening tool for accurate diagnosis of pre-invasive CRN.

Background and Aims: Although recent studies have reported that inflammatory bowel disease [IBD] is associated with the development of neurodegenerative diseases via chronic intestinal inflammation and the gut-brain axis, there is insufficient evidence supporting this notion. The aim of this study was to determine the risk of neurodegenerative diseases including Parkinson’s disease [PD] and Alzheimer’s disease [AD] in patients with IBD.Methods: Using the National Health Insurance Service data for the entire Korean population, we identified patients with IBD and controls from 2009 to 2011 and followed them up until 2017. We selected the controls in a 1:4 ratio based on age and sex for comparison with cases.Results: Of 24 830 IBD patients and 99 320 non-IBD controls, 98 IBD patients and 256 controls developed PD, and 644 IBD patients and 2303 controls developed AD. The overall neurodegenerative disease risk was higher in IBD patients (PD: adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.24-1.97; AD: adjusted HR, 1.14; 95% CI, 1.05-1.25). Younger IBD patients aged 40-65 years had a higher risk of PD compared with controls [adjusted HR, 2.34; 1.63-3.35]. In contrast, patients aged ≥65 years had an increased risk of AD compared with controls [adjusted HR, 1.14; 1.04-1.25]. In a nested case-control study of the IBD cohort, patients aged ≥65 years and the female sex were risk factors for AD, whereas living in an urban area was protective against AD.Conclusions: The risk of neurodegenerative diseases was higher in IBD patients than in the non-IBD population.

The prognosis of early-onset sporadic colorectal cancer (CRC) patients remains controversial. The objective of this study was to assess the long-term outcome and prognostic factors of sporadic CRC in young patients. From 2006 to 2011, 8207 patients underwent curative or palliative surgery for CRCs in our institution. A total of 693 patients who were ≤45 years old with sporadic CRC were enrolled as the young group. A total of 1823 patients aged between 56 and 65 years were identified as middle-aged control group for this study. Survival outcome and prognostic factors were compared between the two groups. Young patients had higher recurrence rate than older patients in stages I and II (8.8% vs 2.7%, P <0.001). There was no significant difference of recurrence rate in stage III and IV cancers (27.5% vs 27.9%, P = 0.325). Metachronous cancers were developed more frequently in young patients (1.4% vs 0.6%, P = 0.038). Advanced stage CRC was diagnosed significantly more common in the young group (55.6% vs 47.9%, P = 0.001). High microsatellite instability (MSI) tumors are less likely to have advanced stage cancers (odds ratio (OR) 0.23, 95% confidence interval (CI) = 0.07–0.70) or cancer recurrence (OR 0.11, 95% CI = 0.01–0.85) in young patients. Cancer-specific survival was worse in young patients than that in older patients (81.2% vs 87.8%, P <0.001). However, there was no significant difference in cancer-specific survival for each stage between the two groups. Independent prognostic factors for survival in young patients were undifferentiated cancer (hazard ratio (HR) 2.30, 95% CI = 1.23–4.31) and 3 months or longer duration of symptom (HR 2.57, 95% CI = 1.34–4.94). Young women had better survival compared with young men (HR 0.55, 95% CI = 0.33–0.90). Prognosis of sporadic CRC in young patients is poorer than older patients, because of poorer histologic differentiation and delay in diagnosis. Early detection of CRC confers survival benefit to young patients. Because of higher recurrence rate and metachronous cancer risk, post-operative surveillance is also important in young patients.

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn’s disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.