Summary
Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1+ cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in a muscarinic acetylcholine receptor-3 (M3R)-dependent manner, in part through suppression of Yes-Associated Protein (YAP) function. This feed-forward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.
Colonic diverticulosis and diverticular bleeding are prevalent and increasing in Japan. Given the significant association of age with this trend, both diseases can be expected to increase for decades to come.
We developed and validated a scoring system for risk of severe LGIB based on 8 factors (NOBLADS score). The system also determined the risk for blood transfusion, longer hospital stay, and intervention. It might be used in decision making regarding intervention and management.
BACKGROUND & AIMS: We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). METHODS: We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24-96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. RESULTS: SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective
ObjectiveTo compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.DesignUsing the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.ResultsIn the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.ConclusionThe risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.
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