Colon Sparing Endoscopic Full-Thickness Resection for Advanced Colorectal Lesions: Is It Time for Global Adoption?

The majority of colon lesions are <10 mm in size and are easily resected by endoscopists with appropriate basic training. Lesions ≥10 mm in size are difficult to remove technically and are associated with higher rates of incomplete resection. Currently, the main endoscopic approaches include endoscopic mucosal resection (EMR) for lesions without submucosal invasion, and endoscopic submucosal dissection (ESD) for relatively larger lesions involving the superficial submucosal layer. Both of these approaches have limitations, EMR cannot reliably ensure complete resection for larger tumors and recurrence is a key limitation. ESD reliably provides complete resection and an accurate pathological diagnosis but is associated with risk such as perforation or bleeding. In addition, both EMR and ESD may be ineffective in treating subepithelial lesions that extend beyond the submucosa. Endoscopic full-thickness resection (EFTR) is an emerging innovative endoscopic therapy which was developed to overcome the limitations of EMR and ESD. Advantages include enabling a transmural resection, complete resection of complex colorectal lesions involving the mucosa to the muscularis propria. Recent studies comparing EFTR with current resection techniques and radical surgery for relatively complicated and larger lesion have provided promising results. If the current trajectory of research and development is maintained, EFTR will likely to become a strong contender as an alternative standard of care for advanced colonic lesions. In the current study we aimed to address this need, and highlighted the areas of future research, while stressing the need for multinational collaboration provide the steppingstone(s) needed to bring EFTR to the mainstream.

DNMT3a-Mediated Enterocyte Barrier Dysfunction Contributes to Ulcerative Colitis via Facilitating the Interaction of Enterocytes and B Cells.

Objective: Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method: Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result: DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-ß), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro results revealed that DNMT3a silencing or TNFSF13 overexpression in IECs partly abolished the result of LPS-induced epithelial barrier dysfunction, as well as abrogated the effect of IEC-regulated B cell differentiation, while si-TACI transfection reversed these effects. Moreover, DNMT3a silencing decreased TNFSF13 methylation level and induced CD1d+ B cell differentiation, and the si-TNFSF13 transfection reversed the trend of B cell differentiation but did not affect TNFSF13 methylation level. Conclusion: Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.

Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2-STAT3 pathway.

Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of L-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)-signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2-STAT3 signalling.