Issues Critical to the Successful Application of Cryosurgical Ablation of the Prostate

Abstract

The techniques of present-day cryosurgery performed with multiprobe freezing apparatus and advanced imaging techniques yield predictable and encouraging results in the treatment of prostatic and renal cancers. Nevertheless, and not unique to cryosurgical treatment, the rates of persistent disease demonstrate the need for improvement in technique and emphasize the need for proper management of the therapeutic margin. The causes of persistent disease often relate to a range of factors including selection of patients, understanding of the extent of the tumor, limitations of the imaging techniques, and failure to freeze the tumor periphery in an efficacious manner. Of these diverse factors, the one most readily managed, but subject to therapeutic error, is the technique of freezing the tumor and appropriate margin to a lethal temperature [Baust, J. G., Gage, A. A. The Molecular Basis of Cryosurgery. BJU Int 95, 1187-1191 (2005)]. This article describes the recent experiments that examine the molecular basis of cryosurgery, clarifies the actions of the components of the freeze-thaw cycle, and defines the resultant effect on the cryogenic lesion from a clinical perspective. Further, this review addresses the important issue of management of the margin of the tumor through adjunctive therapy. Accordingly, a goal of this review is to identify the technical and future adjunctive therapeutic practices that should improve the efficacy of cryoablative techniques for the treatment of malignant lesions.

Effect of thermal dose on heat shock protein expression after radio-frequency ablation with and without adjuvant nanoparticle chemotherapies

“…At pathology, tissue changes from high-temperature ablation have been grossly divided into a central ‘white’ zone of immediately coagulated tissue and a periablational ‘red zone’ of reactive inflammation [28]. Currently, all ablation application algorithms have largely prioritized obtaining the most completely uniform ‘white zone’ in a clinically efficient manner (i.e., ablating the desired target volume in the shortest amount of time) or achieving a specific ablation geometry (i.e., spherical ablation volume) [29,30,31]. However, there is now greater appreciation of the various secondary reactions that occur in the periablational rim exposed to non-lethal hyperthermic injury, with increases in protective heat shock protein expression, microvascular permeability, growth factor production, and reactive oxygen species, reported [32].…”

Cryosurgery with Pulsed Electric Fields

“…The results were compared to a control case in which the electric field was calculated for a constant physiological temperature, 310.15 K. The initial temperature was assumed to be the physiological temperature, 310.15 K. At the onset of freezing, a temperature of 268.15 K was imposed on one surface (the left hand side outer surface in the slab like configuration, Figure 1a, and the central cryoprobe in the cylindrical configuration, Figure 1b). The right hand side of the slab and the outer edge of the cylinder were kept at physiological body temperature, 310.15 K. A temperature of 268.15 K (−5°C) was implemented because in very conservative estimates cell survival occurs at temperatures above 258.15 K in cryosurgery [2], [3], [9], [10]. Therefore, this thermal condition represents the outer margin of a frozen cryosurgical lesion where cells survive freezing [2], [3]; which is a range of temperatures where phenomena related to the Cryo/PEF concept occur.…”

“…These limitations are related to the mechanism of cell death by freezing and the incomplete cell death in certain ranges of subfreezing temperatures [2], [3], [8], [9], [10]. A recent review [3] points out that: “The tissue temperature is a key factor in causing injury… As a guide for the treatment of neoplasms, the many experiments suggesting that about −20°C is adequate for tissue destruction should be viewed with caution.…”

“…Indeed the same review [3] suggests that: “The greatest opportunity for improved efficacy (of cryosurgery) is in the management of the periphery of the cryogenic lesion where cell destruction is partial. Therapy adjunctive to cryosurgery, such as chemical agents, cytotoxic drugs, or irradiation should prove helpful in completing destruction of cells in the periphery of the frozen volume.” Cryoadjunctive strategies to enhance cancer cell sensitivity to freezing is the subject of several investigations [3], [8], [9], [11], [12], [13]. The goal of this study is to explore, with a mathematical model, the feasibility of using pulsed electric fields delivered through the cryosurgical probe during cryosurgery as a cryoadjunctive modality to ablate cells in the temperature range in which they survive freezing.…”

Methods for Characterizing Convective Cryoprobe Heat Transfer in Ultrasound Gel Phantoms

“…135 / 021002-1 Copyright V C 2013 by ASME temperatures. Estimates of these threshold temperatures can range from À20C to À40 C [10,11] and new preconditioning techniques utilizing adjuvants have demonstrated the potential to raise this limit up to as high as 0 C [12,13]. While biological freeze destruction is an important area of research, there are multiple mechanisms at the cellular, vascular, and even immunological level that contribute, putting this topic beyond the scope of this current work.…”