Presented by: Franz Schmidlin MD
Urology Center Clinic Hirslanden Grangettes

Introduction

A major sideeffect of focal prostate cryosurgery is injury to the neurovascular bundle (NVB). Cryoinjury halts conduction of action potential (APs) in the nerve that may lead to erectile dysfunction and hence diminish the patients quality of life. The objective of this study was to analyze the feasibility of using a gel containing cryoprotective agents (CPA) that is applied directly to the regions of the nerves exposed to the cold to minimize non-recovery loss of APs conduction thereby preserving the neuronal function.

Materials

We modeled cryosurgical procedures based on data taken during clinical cases by measuring temperature profiles at specific locations of the NVB during cryosurgical procedures.The same temperature profiles were applied ex-vivo to porcine phrenic nerves and rat sciatic nerves in a controlled experimental setting (cryostage). The APs were measured before and after the CPA exposure alone and in combination with a gel during 3 hours of recovery. Threshold for nerve injury was considered loss of 70% or more of AP amplitude. To determine the temperature profiles of the NVB 3D temperature distribution was calculated by numerical modeling for different clinical tumor locations.

Results

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The modeling of the coldest temperature (-10 ⁰ C) on the NVB for most (anterior and lateral) tumor locations is consistent with clinical measurements. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO +7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of respective AP, respectively). Good nerve protection was also achieved with CPA-containing gel (2% hydroxyethyl cellulose). Diffusion modeling showed more than 50% CPA penetration in the nerve after 45 min. No AP recovery was observed in nerves not protected by CPA compositions.

Conclusion

This work demonstrates the feasibility of a nerve-sparing approach to employ cryoprotective agents embedded in a gel to prevent cryoinjury around the NVB during prostate cryoablation and hence reduce ereftile dysfunction. This method appears to be effective and easy to implement clinically as the gel may be injected by a perineal approach under ultrasound guidance similar to saline injections we perform presently to increase the space between the prostate and the rectum. Preoperative 3D cryosurgery modeling may also become a helpful tool to predict and hence prevent possible cryosurgical side-effects in the future.

 

Funding

Research Fund Medical Immersion Technology

Co-Authors

Pegah Ranjbartehrani, PHD
Department of Mechanical Engineering University of Minnesota

Qi Shao, PHD
Department of Mechanical Engineering University of Minnesota

Michael Etheridge,
Department of Mechanical Engineering University of Minnesota

David Ramirez,
Department of Surgery University of Minnesota

Paul Iaizzo, PHD
Department of Surgery University of Minnesota

John Bischof, PHD
Department of Mechanical Engineering University of Minnesota