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3 The post-endoscopic submucosal dissection mucosal defect was observed to extend from the medial wall to the anterior wall of the second portion of the duodenum. A 50-year-old man was endoscopically diagnosed with a duodenal adenoma, which was a flat, elevated, 3-cm lesion located near the ampulla and extended from the medial wall to the anterior wall of the second portion of the duodenum (Fig. [Extracted from the article]

Computed tomography revealed a giant lipoma extending from the third portion of the duodenum to the proximal jejunum, and the ampulla and pancreas head were pulled and deviated to the third portion by the giant lipoma (Fig. The current case describes a novel and noninvasive technique involving ESD followed by laparoscopic per-jejunal tumor collection for a giant duodenal lipoma causing repeated pancreatitis. [Extracted from the article]

The current imaging modalities are not sufficient to identify inoperable tumor factors, including distant metastasis and local invasion. Hence, we conducted this study using urine samples to discover non-invasive biomarkers for the incurability of gastric cancer (GC). Urine samples from 111 GC patients were analyzed in this study. The GC cohort was categorized and analyzed according to disease stage and operability. In the discovery phase, protease protein array analysis identified 3 potential candidate proteins that were elevated in the urine of advanced GC patients compared to early GC patients. Among them, urinary kallikrein 10 (KLK10) was positively associated with tumor stage progression. Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the urine of patients with inoperable GC compared to operable GC patients (median, 118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size distinguished operability of GC with an area under the curve of 0.859, 82.4% sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical analyses also demonstrated a positive correlation between tumor stage and KLK10 expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval, 1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the inoperability and incurability of GC., Version of Record

Background. Tacrolimus (FK506) is effective for patients with ulcerative colitis (UC). However, there are few reports on tacrolimus therapy (TT) with respect to the relationship with endoscopic and clinicopathologic findings. Methods. Thirty patients with moderate/severe active UC refractory to or dependent on corticosteroid were treated with oral tacrolimus. The expression of ectopic MUC5AC in the colon was pathologically analyzed before and at 12 weeks after TT, evaluating the Mayo score and steroid-sparing effects. Results. Both mean disease and endoscopic activity index scores were reduced at levels of statistical significance in 26 UC patients receiving more than one month of TT (P < 0.0001). The dose of prednisolone was reduced by a statistically significant amount (P = 0.00022), and 14 of the 26 patients (53.8%) had steroid-free status 12 weeks after TT. The decrease in ectopic MUC5AC expression in the mucous cells of the colon was significantly associated with endoscopic improvement of inflammation in the UC patients with TT (P = 0.043). Loss of ectopic MUC5AC expression was detected in all patients who had complete response. Conclusions. Tacrolimus appears to be effective for the treatment of moderate/severe UC patients. Loss of ectopic MUC5AC expression may be important for pathologic remission in the colon of UC patients. [ABSTRACT FROM AUTHOR]

Gamma radiation is a commonly used adjuvant treatment for abdominally localized cancer. Since its therapeutic potential is limited due to gastrointestinal (GI) syndrome, elucidation of the regenerative response following radiation-induced gut injury is needed to develop a preventive treatment. Previously, we showed that Krüppel-like factor 4 (KLF4) activates certain quiescent intestinal stem cells (ISCs) marked by Bmi1-CreER to give rise to regenerating crypts following γ irradiation. In the current study, we showed that γ radiation-induced expression of p21Waf1/Cip1 in Bmi1-CreER cells is likely mitigated by MUSASHI-1 (MSI1) acting as a negative regulator of p21Waf1/Cip1 mRNA translation, which promotes exit of the Bmi1-CreER cells from a quiescent state. Additionally, Bmi1-specific Klf4 deletion resulted in decreased numbers of MSI1+ cells in regenerating crypts compared to those of control mice. We showed that KLF4 binds to the Msi1 promoter and activates its expression in vitro. Since MSI1 has been shown to be crucial for crypt regeneration, this finding elucidates a pro-proliferative role of KLF4 during the postirradiation regenerative response. Taken together, our data suggest that the interplay among p21Waf1/Cip1, MSI1 and KLF4 regulates Bmi1-CreER cell survival, exit from quiescence and regenerative potential upon γ radiation-induced injury. [ABSTRACT FROM AUTHOR]

Background and study aims Although deep vein thrombosis (DVT) and pulmonary embolism (PE) are major postoperative complications, risk of DVT/PE after endoscopic procedures remains unknown. This study aimed to identify risks of DVT/PE after colorectal endoscopic submucosal dissection (ESD) and double-balloon endoscopy (DBE). Patients and methods Patients who were scheduled to undergo DBE and colorectal ESD were prospectively enrolled in this study. Before enrollment, all patients were confirmed to have no DVT on whole-leg ultrasonography (US) or contrast-enhanced computed tomography (CECT). All patients routinely underwent whole-leg US after ESD or DBE. The primary endpoint was incidence of DVT after colorectal ESD and DBE. The preplanned sample size was 170 patients in the colorectal ESD group and 75 in the DBE group. Results Between September 2020 and June 2022, 170 patients who had colorectal ESD and 75 who had DBE were recruited for this study; however, 238 patients (ESD, n = 167; DBE, n = 71) were analyzed. Of these 238 patients, DVT occurred in only one patient after colorectal ESD and incidence of DVT was 0.4% (95% confidence interval [CI] 0-1.2) in total, including 0.6% (95% CI 0-1.8) after colorectal ESD and 0% after DBE. Conversely, no PE occurred in the entire cohort. Conclusions This prospective study demonstrated that risk of DVT/PE following highly invasive endoscopic procedures including colorectal ESD and DBE is very low., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor, expressed in villus cells of the intestinal epithelium, that promotes cellular differentiation and tissue homeostasis. Previous studies suggest that BMI1 ＋ cells represent secretory progenitors with reserve intestinal stem cell (rISC) activity. However, it has not been elucidated how KLF4 contributes to crypt regeneration originated from BMI1 ＋ rISC lineage during homeostasis. In this study, Bmi1 -Cre ER ;Rosa26 eYFP ( Bmi1 Ctrl) and Bmi1 -Cre ER ;Rosa26 eYFP ; Klf4 fl/fl ( Bmi1 ΔKlf4 ) mice were injected with tamoxifen to label BMI1 ＋ cells and their lineage and to delete Klf4 . During homeostasis, MUC2 ＋ goblet cells appeared in the BMI1 ＋ cell lineage 2, 3 and 7 days after tamoxifen administration. After Klf4 deletion in BMI1 ＋ cells, the number of KLF4 ＋ and MUC2 ＋ cells in eYFP ＋ cells decreased in Bmi1 ΔKlf4 mice compared with Bmi1 Ctrl mice. Thus, KLF4 was positively correlated with goblet cell differentiation in BMI1 ＋ cell derived lineage. In ex-vivo analysis, organoids derived from single eYFP ＋ cells of Bmi1 Ctrl mice contained MUC2-expressing cells that co-expressed KLF4. On the other hand, organoids derived from Klf4-deleted eYFP ＋ cells from Bmi1 ΔKlf4 mice showed reduced number of MUC2-expressing cells. In conclusion, these results suggest that KLF4 regulates goblet cell differentiation in BMI1 ＋ ISC-derived lineage during homeostasis.

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.