BackgroundArteriovenous malformations (AVM) developed in the small intestine are rare, and it is sometimes difficult to identify and treat bleeding from small intestinal AVMs endoscopically because of their localization. We present a case of a jejunal AVM successfully treated with the combination of metallic coil embolization and laparoscopic surgery.Case presentationA 50-year-old woman with a history of repetitive gastrointestinal bleeding was admitted to the hospital. Selective angiography revealed a jejunal AVM that was treated with metallic coil embolization. However, the lesion rebled 3 months later, and it was embolized again with metallic coils. Considering the risk of rebleeding, we performed laparoscopic resection of the jejunal AVM. Under laparoscopy alone, it was impossible to detect the lesion of the AVM. We used X-ray fluoroscopy intraoperatively to detect the metallic coils at the AVM. Partial resection of the jejunum with the AVM was performed followed by functional end-to-end anastomosis. The patient was discharged from the hospital without any complications after the surgery.ConclusionsThe combination of metallic coil embolization by angiography and laparoscopic surgery with X-ray fluoroscopy can be effective for patients with repetitive bleeding from jejunal AVM.

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation.

Purpose The pathogenesis of cancers depends on the molecular background of each individual patient. Therefore, verifying as many biomarkers as possible and clarifying their relationships with each disease status would be very valuable. We performed a large‐scale targeted proteomics analysis of plasma extracellular vesicles (EVs) that may affect tumor progression and/or therapeutic resistance. Experimental design Plasma EVs from 59 were collected patients with colorectal cancer (CRC) and 59 healthy controls (HC) in cohort 1, and 150 patients with CRC in cohort 2 for the large‐scale targeted proteomics analysis of 457 proteins as candidate CRC markers. The Mann–Whitney‐Wilcoxon test and random forest model were applied in cohort 1 to select promising markers. Consensus clustering was applied to classify patients with CRC in cohort 2. The Kaplan–Meier method and Cox regression analysis were performed to identify potential molecular factors contributing to the overall survival (OS) of patients. Results In the analysis of cohort 1, 99 proteins were associated with CRC. The analysis of cohort 2 revealed two clusters showing significant differences in OS ( p = 0.017). Twelve proteins, including alpha‐1‐acid glycoprotein 1 (ORM1), were suggested to be associated with the identified CRC subtypes, and ORM1 was shown to significantly contribute to OS, suggesting that ORM1 might be one of the factors closely related to the OS. Conclusions The study identified two novel subtypes of CRC, which exhibit differences in OS, as well as important biomarker proteins that are closely related to the identified subtypes. Liquid biopsy assessment with targeted proteomics analysis was proposed to be crucial for predicting the CRC prognosis.

Background: Killian-Jamieson diverticulum is a rare pharyngoesophageal diverticulum. The risk of intraoperative injury of the recurrent laryngeal nerve (RLN) is high during surgical resection of Killian-Jamieson diverticulum because the RLN usually runs next to the base of the diverticulum. We present a case of Killian-Jamieson diverticulum that was safely resected with effective use of an intraoperative nerve monitoring (IONM) system with a handheld stimulating probe to prevent RLN injury. Case presentation: A 69-year-old man complaining of dysphagia was diagnosed with Killian-Jamieson diverticulum and underwent open transcervical diverticulectomy. Because the anterior aspect of the diverticulum was expected to be close to the RLN, the accurate location of the RLN was checked during dissection by intermittent stimulation using a handheld probe of the IONM system to avoid mechanical and thermal injury. The diverticulum was transected longitudinally using a linear stapler, and the staple line was buried using absorbable sutures from the distal end. During its closure, RLN was identified very close to the diverticulum stump by IONM, and the upper side of the stump was left unburied to avoid RLN injury. The postoperative course was uneventful and the patient was discharged on postoperative day 7. Postoperative evaluation showed no vocal cord paralysis. Conclusion: IONM may be beneficial during open surgery for Killian-Jamieson diverticulum, which usually protrudes just lateral to the RLN.

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