Introduction: Optimizing treatment with biological agents is an ideal goal for patients with ulcerative colitis (UC). Recent data suggest that mucosal inflammation patterns and serum cytokine profiles differ between patients who respond and those who do not. Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, has shown promise, but predicting treatment response remains a challenge. We aimed to identify prognostic markers of response to ustekinumab in patients with active UC, utilizing information from their mucosal transcriptome. Methods: We performed a prospective observational study of 36 UC patients initiating treatment with ustekinumab. Colonic mucosal biopsies were obtained before treatment initiation for a gene expression analysis using a microarray panel of 84 inflammatory genes. A differential gene expression analysis (DGEA), correlation analysis, and network centrality analysis on co-expression networks were performed to identify potential biomarkers. Additionally, machine learning (ML) models were employed to predict treatment response based on gene expression data. Results: Seven genes, including BCL6, CXCL5, and FASLG, were significantly upregulated, while IL23A and IL23R were downregulated in non-responders compared to responders. The co-expression analysis revealed distinct patterns between responders and non-responders, with key genes like BCL6 and CRP highlighted in responders and CCL11 and CCL22 in non-responders. The ML algorithms demonstrated a high predictive power, emphasizing the significance of the IL23R, IL23A, and BCL6 genes. Conclusions: Our study identifies potential biomarkers associated with ustekinumab response in UC patients, shedding light on its underlying mechanisms and variability in treatment outcomes. Integrating transcriptomic approaches, including gene expression analyses and ML, offers valuable insights for personalized treatment strategies and highlights avenues for further research to enhance therapeutic outcomes for patients with UC.

Various endoscopic techniques have been described for the treatment of post-operative colonic strictures. Our aim is to report a solely EUS-guided recanalization procedure for a complete rectal stricture, without the use of fluoroscopy or stenting. A 66-year-old male was submitted to low anterior resection and protective ileostomy for rectal adenocarcinoma, complicated with complete anastomotic stricture 6 months later. The patient was treated with a modified EUS-guided rendezvous technique. A colonoscope was advanced through the ileostomy to the sigmoid colon, which was subsequently filled with water. A linear echoendoscope was advanced transanally to the distal part of the rectal anastomosis. The proximal colon was punctured with a 19G needle and a guidewire was advanced through the needle. The rectocolonic fistula tract was first dilated by graduated dilation catheters. Subsequently, progressive pneumatic dilatation was performed. There were no post-procedural complications. At 6-month follow-up the anastomosis was patent, with no significant stricture recurrence. In conclusion, a rendezvous technique for EUS-guided recanalization of complete rectal anastomotic strictures is feasible and safe in a non-radiology assisted setting. In selected cases of distal stenoses balloon dilation could effectively serve as the sole treatment, without the adjunct of stent placement.

Cancer immunotherapy is an emerging beneficial treatment for cancer that acts by activating the immune system to produce antitumour effects. In particular, immune checkpoint therapy has recently provided novel strategies for cancer treatments. Nevertheless, these new therapeutic approaches have introduced immune-related adverse events to clinical practice. In the elderly, checkpoint inhibitors might have limited efficacy because of immunosenescence. Limited literature data demonstrate a higher incidence of irAEs and an earlier discontinuation of immunotherapy in these patients. We report the case of an 89-year-old male patient with metastatic urothelial carcinoma, who presented with Grade 4 immune-related hepatitis after receiving pembrolizumab treatment.

Resident Survey of Gastroenterology Training in Greece.