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Since a fecal occult blood test for colorectal cancer (CRC) does not offer sufficient diagnostic power for CRC, novel non-invasive biomarkers are hopeful for CRC screening. We conducted the current study to discover non-invasive urinary biomarkers for diagnosing CRC. Among urine samples from 258 patients (CRC, n = 148; healthy controls, n = 110), a cohort of 176 patients composed of 88 patients with GC and 88 healthy controls was selected after age- and sex-matching using propensity score. This cohort was then randomly divided into 2 groups: 53 pairs (106 patients) in the training cohort, and 35 pairs (70 patients) in the validation cohort. No significant differences were found for baseline characteristics between the CRC and healthy control groups in both training and validation cohorts. On multivariate analysis in the training cohort, urinary levels of cysteine-rich protein 61 (uCyr61) and trefoil factor 3 (uTFF3) were identified as independent significant diagnostic markers for CRC. Moreover, uCyr61 alone and the combination of uCyr61 and uTFF3 allowed significant differentiation between healthy controls and CRC groups in the training set (uCyr61: area under the curve (AUC) = 0.745 [95% CI, 0.653–0.838]; uCyr61 + uTFF3: AUC = 0.753 [95% CI, 0.659–0.847]). In the validation cohort, uCyr61 and uTFF3 were significantly higher in the CRC group than in the healthy control group, and they also allowed significant differentiation between healthy control and CRC groups (uCyr61: AUC = 0.696 [95% CI, 0.571–0.822]; uTFF3: AUC = 0.639 [95% CI, 0.508–0.770]; uCyr61 + uTFF3: AUC = 0.720 [95% CI, 0.599–0.841]), as in the training cohort. A panel combining uCyr61 and uTFF3 offers a promising non-invasive biomarker for diagnosing CRC.

Background/Aims: Adalimumab dose escalation is one of the most important options in refractory Crohn’s disease patients with loss of response to adalimumab. The goal of this study was to evaluate the effectiveness of adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab, since there are few reports of adalimumab dose escalation, especially in East Asia. Methods: The clinical response to adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab was evaluated retrospectively, using the Crohn’s disease activity index score, serum C-reactive protein levels, and endoscopic analyses. Results: Of the 203 Crohn’s disease patients treated with anti-tumor necrosis factor, 14 refractory Crohn’s disease patients with loss of response to adalimumab received adalimumab dose-escalation therapy. The C-reactive protein level was significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in the whole group, although there were no significant reductions of Crohn’s disease activity index scores. Both Crohn’s disease activity index scores and C-reactive protein levels were significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in patients without previous infliximab treatment, although C-reactive protein levels were positive in all cases with previous infliximab exposure at weeks 12 and 52. Endoscopic mucosal healing was achieved with adalimumab dose escalation in 2 cases without previous infliximab treatment. Conclusions: Adalimumab dose-escalation therapy is effective in refractory Crohn’s disease patients with loss of response to adalimumab, especially in cases without previous infliximab treatment.

Colonic diverticular bleeding (CDB) is the most frequent cause of acute lower gastrointestinal bleeding. The aim of this study was to evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for CDB as first-line treatment with extravasation on contrast-enhanced computed tomography (CECT), compared with endoscopic hemostasis. Three Japanese institutions participated in this retrospective cohort study. Data from consecutive patients admitted with a diagnosis of CDB with extravasation on CECT were reviewed. One hospital performed TAE and the others conducted urgent colonoscopy (CS) as the first-line treatment for CDB with extravasation on CECT. The primary outcome was rebleeding rate within 30 days after first-line treatment. In total, 165 CDB cases with extravasation on CECT (TAE group, n = 39; CS group, n = 126) were analyzed in this study. The rebleeding rate within 30 days was significantly lower in the TAE group (7.69%) than in the CS group (23.02%; P= .038). The bleeding point detection rate was significantly higher in the TAE group (89.74%, 35/39) than in the CS group (37.30%, 47/126; P< .0001). Even in those cases in which a bleeding point was detected, the rebleeding rate was significantly lower in the TAE group (0%) than in the endoscopic hemostasis-success group (23.91%; P= .005). No severe complications of Grade 3 or more were seen with TAE. We showed that TAE is an effective, safe hemostatic method, and a useful alternative to endoscopic hemostasis for first-line treatment of CDB.

Stem cells are influenced by a microenvironmental niche that includes mesenchymal cells. We established a novel long-term method for primary mouse glandular stomach culture with mesenchymal myofibroblasts to investigate gastric epithelial-mesenchymal interactions. A gastric mesenchymal myofibroblast (GMF) cell line was established from mouse glandular stomach. Glandular stomach cells from neonatal mice and GMF cells were co-cultured in a collagen gel. Cultured stomach cells yielded expanding sphere-like structures. In the GMF co-culture system, the number and size of gastrospheres were increased compared with control cultures (P = 0.009 and 0.008, respectively). Immunohistochemistry showed cells positive for human gastric mucin, HIK1083, and chromogranin A, indicating differentiation into surface mucous cells, mucous neck cells, and enteroendocrine cells, respectively. RNA in situhybridization for Lgr5 showed Lgr5+stem cells in the cultured gastrospheres. Lgr5+cells were observed persistently in the epithelium of gastrospheres in the GMF co-culture system for 2 months. GMFs allowed the cultured gastric epithelium to maintain active proliferation similar to that seen in vivo. Real-time quantitative RT-PCR showed that Gas1 expression was higher in GMFs (P = 0.0445), and Hoxc8, Notch1, and Sox10 expressions were higher in intestinal mesenchymal myofibroblasts (P = 0.0003, 0.0143, and 0.0488, respectively). We show the potential role of GMFs in sustaining Lgr5+stem cell activity and affecting normal gastric epithelial differentiation and proliferation.

A 64-year-old man with Crohn’s disease (CD) was admitted to our hospital due to moderate risk of pneumonia while receiving scheduled adalimumab maintenance therapy. Symptoms remained virtually unchanged following administration of antibiotics. A final diagnosis of organizing pneumonia (OP) was made based on findings of intra-alveolar buds of granulation tissue and fibrous thickening of the alveolar walls on pathological examination and patchy consolidations and ground glass opacities on computed tomography. Immediate administration of prednisolone provided rapid, sustained improvement. Although a rare complication, OP is a pulmonary manifestation that requires attention in CD patients.