Botulinum toxin infusion into the mesenteric artery has selective action on peristalsis in a rat model: experimental research.

OBJECTIVE: Botulinum toxin type A (BoNT/A) reversibly blocks neurotransmission at voluntary and autonomic cholinergic nerve terminals, inducing paralysis. The aim of this study was to block panenteric peristalsis in rats through BoNT/A administration into the superior mesenteric artery (SMA) and to understand whether the toxin's action is selectively restricted to the perfused territory. MATERIALS AND METHODS: Rats were infused through a 0.25-mm surgically inserted SMA catheter with different doses of BoNT/A (10 U, 20 U, 40 U BOTOX®, Allergan Inc.) or with saline for 24 h. Animals were free to move on an unrestricted diet. As a sign of bowel peristalsis impairment, body weight and oral/water intake were collected for 15 days. Statistical analysis was conducted with nonlinear mixed effects models to study the variation over time of the response variables. In three 40 U-treated rats, the selectivity of the intra-arterial delivered toxin action was studied by examining bowel and voluntary muscle samples and checking the presence of BoNT/A-cleaved SNAP-25 (the smoking gun of the toxin action) using the Immunofluorescence (IF) method through a specific antibody recognition. RESULTS: While control rats exhibited an increasing body weight, treated rats showed an initial dose-dependent weight reduction (p<0.001 control vs. treated) with recovery after Day 11 for 10 and 20 U-treated rats. Food and water intake over time showed significantly different half-saturation constants with rats treated with higher doses who reached half of the maximum achievable in a greater number of days (p<0.0001 control vs. treated rats). BoNT/A-cleaved SNAP-25 was identified in bowel wall NMJs and not in voluntary muscles, demonstrating the remarkable selectivity of arterially infused BoNT/A. CONCLUSIONS: Blockade of intestinal peristalsis, can be induced in rats by slow infusion of BoNT/A into the SMA. The effect is long-lasting, dose-dependent and selective. BoNT/A delivery into the SMA through a percutaneous catheter could prove clinically useful in the treatment of entero-atmospheric fistula by temporarily reducing fistula output.

Risk factors and outcomes of restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Retrospective study of 75 single center cases.

OBJECTIVE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical gold standard in patients with ulcerative colitis (UC). Results are generally satisfactory but there is a significant rate of patients who experience postoperative complications. The aims of our study were to identify the pre- and intraoperative risk factors and their correlation with the reported outcomes. PATIENTS AND METHODS: A retrospective study was conducted on the medical records of all consecutive patients undergoing restorative proctocolectomy with IPAA for UC in our center from 2010 to 2021. Pre- and intraoperative factors were examined and correlated with pouchitis, endoscopic pouchitis, pouch failure, anastomotic leak, postoperative complications classified according to Clavien-Dindo score and stoma outlet obstruction. A univariate and multivariate statistical analysis was performed. RESULTS: Out of 75 patients undergoing 3- or 2-stage IPAA surgery, the coexistence of extraintestinal clinical manifestations and preoperative topical rectal stump therapy for active proctitis were significantly associated with the occurrence of pouchitis (OR=4.4, p=0.03 and OR=7.6, p=0.01). Endoscopic pouchitis was found to be related to preoperative topical rectal therapy (OR=10.2, p=0.007), but not to extraintestinal manifestations of disease. Anastomotic leak was found to be significantly related to pouch failure (OR=22.7, p=0.007). Surgical indication for malignancy increased the risk for early complications (Clavien-Dindo >2) (OR=16.0, p=0.04). Young age was associated with the occurrence of outlet stoma obstruction in patients with recent IPAA surgery (OR=0.97, p=0.05). CONCLUSIONS: Based on observed results, an appropriate preoperative patient assessment aimed at detecting specific risk factors is crucial to identify early or prevent worse outcomes in patients undergoing IPAA surgery.