A Triple-Stage Autologous Immunotherapy Protocol for Advanced Gallbladder Cancer: A Paradigm Shift from Physical Resection to Physiological Synergy

Background Advanced gallbladder cancer (GBC) with hepatic infiltration and peritoneal seeding presents a clinical impasse. Traditional radical resection offers limited efficacy against micro-metastasis while severely compromising the patient's quality of life (QoL). I propose LPBE-GVC (Gallbladder Vaccine Cradle), a non-resectional triple-stage protocol designed to utilize the gallbladder as an in-situ bioreactor to induce systemic immune self-healing. Methods The protocol comprises three strategic phases: (1) Phase I: In-situ Antigen Priming – Establishing a sequestered environment via cystic duct clipping, followed by mechanical fragmentation and a 42°C normobaric hyperthermic bath to transform the tumor into high-quality autologous antigens. (2) Phase II: Lymphatic Navigation (LPBE Mobilization) – Within 24 hours, diluted NAFs (Antigen Fragments) are administered via Pressure-Balanced Entry (LPBE) into targeted regional lymph nodes to trigger systemic immune scanning. (3) Phase III: Hyperthermic Global Clearance – Continuous abdominal heating at 40°C for seven days to lower Interstitial Fluid Pressure (IFP), facilitating T-cell infiltration into metastatic sites. Expected Outcomes The LPBE-GVC protocol is projected to achieve significant immune-mediated cavitation of peritoneal nodules and absorption of ascites, theoretically demonstrating a "Biochemical Margin" that exceeds traditional physical boundaries. By shifting the surgical objective, we anticipate a reduction in operative time from 10 hours to 60 minutes, with a correlated improvement in EORTC QLQ-C30 scores through the preservation of full metabolic integrity. Interpretation The LPBE-GVC protocol demonstrates that "non-resection" is not merely a humanitarian Boon but a scientifically superior choice. By precisely modulating physical parameters, We enable the conversion of localized lesions into a systemic vaccine. This innovative logic aligns with established immunological principles, offering a transformative path for clinicians to overcome the current dilemmas in HPB oncology. Original publication on SSRN: https://doi.org/10.2139/ssrn.6541707