Work

Chemical pancreatectomy alleviates tumor burden in a novel inducible mouse model of intraductal papillary mucinous neoplasm

Year: 2026

Type: article

Abstract: Background Intraductal papillary mucinous neoplasm (IPMN) represents a field genetic defect with significant recurrence risk after resection. Chemical pancreatectomy selectively ablates pancreatic ducts and acinar tissue while preserving islets. We aim to develop an inducible IPMN mouse model and evaluate chemical pancreatectomy efficacy in tumor prevention. Methods Pancreas-specific Cas9-expressing mice underwent pancreatic tail injection with adeno-associated virus serotype 6 (AAV6) containing single guide RNAs targeting Kras (G12D) and Lkb1 mutations at 14 weeks of age. Mice received either intraductal saline (control, n=4) or 1% acetic acid (experimental, n=4) infusion and were sacrificed at 8 weeks postoperatively. IPMN phenotype was confirmed by MRI, histology, and immunostaining. Tumor burden, acinar ablation, islet preservation, and survival were assessed. Results AAV6 injection induced cystic tumors with IPMN characteristics including mucin production (alcian blue and MUC5AC positive), ductal identity (CK19 positive), and mutant Kras (G12D) expression. Chemical pancreatectomy significantly reduced mean tumor volume (2.48mm³ vs. 13.5mm³, p=0.016) and achieved 89.3% acinar ablation (p<0.0001) while preserving functional islets and glucose homeostasis. No significant differences in survival or pancreatitis rates were observed between groups. Conclusion We established an inducible IPMN mouse model using AAV6-CRISPR-Cas9 technology. Chemical pancreatectomy effectively reduced tumor burden while maintaining islet function, supporting its potential as a prophylactic strategy for high-risk patients.

Source: Journal of Gastrointestinal Surgery Open

DOI: 10.1016/j.jogsop.2026.100013