Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate carcinoma after radiotherapy.

Despite improvements in treatment of localized prostate cancer, local recurrence remains a significant problem. A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospective clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gland. Persistent complications included one urethra-rectal fistula, incontinence (2), retention (3), and treatment induced erectile dysfunction (7). Using the PSA definitions for biochemical failure as PSA>or=0.3 ng/ml, the Kaplan-Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44% at 1 and 2 y, respectively. For a PSA>or=1.0, the values at 1 and 2 y were 72 and 58%.

A model for the time dependent three-dimensional thermal distribution within iceballs surrounding multiple cryoprobes.

A time dependent three-dimensional finite difference model of iceball formation about multiple cryoprobes has been developed and compared to experimental data. Realistic three-dimensional probe geometry is specified and the number of cryoprobes, the cryoprobe cooling rates, and the locations of the probes are arbitrary inputs by the user. The simulation accounts for observed longitudinal thermal gradients along the cryoprobe tips. Thermal histories for several points around commercially available cryoprobes have been predicted within experimental error for one, three, and five probe configurations. The simulation can be used to generate isotherms within the iceball at arbitrary times. Volumes enclosed by the iceball and any isotherms may also be computed to give the ablative ratio, a measure of the iceball's killing efficiency. This ratio was calculated as the volume enclosed by a critical isotherm divided by the total volume of the iceball for assumed critical temperatures of -20 and -40 degrees C. The ablative ratio for a single probe is a continuously decreasing function of time but when multiple probe configurations are used the ablative ratio increases to a maximum and then essentially plateaus. Maximum values of 0.44 and 0.55 were observed for three and five probe configurations, respectively, with an assumed critical temperature of -20 degrees C. Assuming a critical temperature of -40 degrees C, maximum ablative ratios of 0.21 and 0.3 for three and five probe configurations, respectively, were observed.

A semi-empirical treatment planning model for optimization of multiprobe cryosurgery.

A model is presented for treatment planning of multiprobe cryosurgery. In this model a thermal simulation algorithm is used to generate temperature distribution from cryoprobes, visualize isotherms in the anatomical region of interest (ROI) and provide tools to assist estimation of the amount of freezing damage to the target and surrounding normal structures. Calculations may be performed for any given freezing time for the selected set of operation parameters. The thermal simulation is based on solving the transient heat conduction equation using finite element methods for a multiprobe geometry. As an example, a semi-empirical optimization of 2D placement of six cryoprobes and their thermal protocol for the first freeze cycle is presented. The effectiveness of the optimized treatment protocol was estimated by generating temperature-volume histograms and calculating the objective function for the anatomy of interest. Two phantom experiments were performed to verify isotherm locations predicted by calculations. A comparison of the predicted 0 degrees C isotherm with the actual iceball boundary imaged by x-ray CT demonstrated a spatial agreement within +/-2 mm.

Suppression of high-density artefacts in x-ray CT images using temporal digital subtraction with application to cryotherapy.

Image guidance in cryotherapy is usually performed using ultrasound. Although not currently in routine clinical use, x-ray CT imaging is an alternative means of guidance that can display the full 3D structure of the iceball, including frozen and unfrozen regions. However, the quality of x-ray CT images is compromised by the presence of high-density streak artefacts. To suppress these artefacts we applied temporal digital subtraction (TDS). This TDS method has the added advantage of improving the grey scale contrast between frozen and unfrozen tissue in the CT images. Two sets of CT images were taken of a phantom material, cryoprobes and a urethral warmer (UW) before and during the cryoprobe freeze cycle. The high density artefacts persisted in both image sets. TDS was performed on these two image sets using the corresponding mask image of unfrozen material and the same geometrical configuration of the cryoprobes and the UW. The resultant difference image had a significantly reduced artefact content. Thus TDS can be used to significantly suppress or eliminate high-density CT streak artefacts without reducing the metallic content of the cryoprobes. In vivo study needs to be conducted to establish the utility of this TDS procedure for CT assisted prostate or liver cryotherapy. Applying TDS in x-ray CT guided cryotherapy will facilitate estimation of the number and location of all frozen and unfrozen regions, potentially making cryotherapy safer and less operator dependent.

X-ray CT monitoring of iceball growth and thermal distribution during cryosurgery.

X-ray CT is able to image the internal architecture of frozen tissue. Phantoms of distilled water, a saline-gelatin mixture, lard and a calf liver-gelatin suspension cooled by a plastic tube acting as a long liquid nitrogen cryoprobe were used to study the relationship between Hounsfield unit (HU) values and temperature. There is a signature change in HU value from unfrozen to completely frozen tissue. No discernible relation exists between temperature in a completely frozen tissue and its HU value for the temperature range achieved with commercial cryoprobes. However, such a relation does exist in the typically narrow region of phase change and it is this change in HU value that is the parameter of concern for quantitative monitoring of the freezing process. Calibration of temperature against change in HU value allows a limited set of isotherms to be generated in the phase change region for direct monitoring of iceball growth. The phase change temperature range, mid-phase change temperature and the absolute value of HU change from completely frozen to unfrozen tissue are shown to be sensitive to the medium. Modelling of the temperature distribution within the region of completely frozen phantom using the infinite cylinder solution to the Fourier heat equation allows the temperature history of the phantom to be predicted. A set of isotherms, generated using a combination of thermal modelling and calibrated HU values demonstrates the feasibility of routine x-ray CT assisted cryotherapy. Isotherm overlay will be a major aid to the cryosurgeon who adopts a fixed target temperature as the temperature below which there is a certainty of ablation of the diseased tissue.

A model for the time-dependent thermal distribution within an iceball surrounding a cryoprobe.

The optimal cooling parameters to maximize cell necrosis in different types of tissue have yet to be determined. However, a critical isotherm is commonly adopted by cryosurgeons as a boundary of lethality for tissue. Locating this isotherm within an iceball is problematic due to the limitations of MRI, ultrasound and CT imaging modalities. This paper describes a time-dependent two-dimensional axisymmetric model of iceball formation about a single cryoprobe and extensively compares it with experimental data. Thermal histories for several points around a CRYOprobe are predicted to high accuracy (5 degrees C maximum discrepancy). A realistic three-dimensional probe geometry is specified and cryoprobe temperature may be arbitrarily set as a function of time in the model. Three-dimensional temperature distributions within the iceball, predicted by the model at different times, are presented. Isotherm locations, as calculated with the infinite cylinder approximation, are compared with those of the model in the most appropriate region of the iceball. Infinite cylinder approximations are shown to be inaccurate when applied to this commercial probe. Adopting the infinite cylinder approximation to locate the critical isotherm is shown to lead the user to an overestimate of the volume of target tissue enclosed by this isotherm which may lead to incomplete tumour ablation.

Histological findings in the prostate two years following cryosurgical ablation.

We examined the pathological findings from prostatic whole mounts obtained at post-mortem, 2 years following cryosurgical ablation of the prostate (CSAP), to evaluate the presence or absence of residual benign or malignant tissue. Whole prostates were obtained from two patients at post-mortem, in which the cause of death was not related to prostate cancer. The patients had received CSAP 24 and 30 months earlier, as the primary treatment for prostate cancer. Complete ablation of the gland was demonstrated in one case, with some residual viable benign glands in the transitional zone in the second case. These results suggest that localized prostate cancer can be successfully eradicated by CSAP.

Use of a moratorium to achieve consistent liquid nitrogen cryoprobe performance.

BACKGROUND AND OBJECTIVES: During liver cryosurgical procedures, the authors observed seriously inconsistent rates of iceball growth implying inconsistent probe cooling rates. This inconsistency can lead to several problems, most importantly, loss of precision and reliability in freezing the chosen volume of tissue. The observation led to investigation of the performance of the cryosurgery machine. METHODS: The performance of the Cryotech LCS 3000 with different moratorium periods was investigated. Freezing was performed in a gelatin phantom with thermocouple monitoring at the probe tip. RESULTS: It was determined that a moratorium period between unit filling and clinical use essentially eliminates the uncertainty in probe performance. The need for this arises from the design of the system. A full liquid nitrogen tank does not have the necessary pressure required to induce effective freezing. A partially filled tank increases vapor pressure in the storage dewar driving more liquid nitrogen through the probes, thus allowing a more reliable and faster freeze. CONCLUSION: The simple measure of introducing a moratorium period between filling the dewar with liquid nitrogen and its use in surgery allows partial evaporation of the nitrogen and enhances cryoprobe performance. This protocol modification may reduce the chance of inconsistent probe performance thus making liver cryosurgery more reliable.

Considerations during clinical operation of two commercially available cryomachines.

BACKGROUND AND OBJECTIVES: Advances in the technology of cryomachines in the last 10 years have led to the development of both liquid nitrogen and argon-based Joule-Thompson cryomachines. Theoretical and practical evaluation of the CMS Accuprobe and the ENDOcare CRYOcare was performed as respective examples of these technologies. METHODS: Thermal gradients were calculated about both probes for the best case scenario of probe surface temperature equaling that of the cryogen used. Also, experimental evaluation in gelatin phantoms was performed with five probe arrays. RESULTS: Theoretically, a liquid nitrogen-cooled probe provides only a slight advantage over one cooled with liquid argon. However, the experimental performance evaluation demonstrated that the CRYOcare system creates an iceball faster with steeper internal temperature gradients than the Accuprobe. Further, temperature outputs from the Accuprobe were shown to be in error, likely due to the position of the thermocouple within the probe. CONCLUSIONS: Cryomachine performance is determined more by technological innovations than by cryogen temperature. Thermocouple monitoring is urged for users of the Accuprobe.

Flounder antifreeze peptides increase the efficacy of cryosurgery.

Type I antifreeze protein (AFP) from the winter flounder (Pseudopleuronectes americanus) was used as an adjuvant to cryosurgery of subcutaneous tumors of Dunning AT-1 rat prostate cells grown in Copenhagen rats. The cryosurgical procedure was performed with a commercially available cryosurgery device (CRYO-HIT, Galil Medical) with clinically relevant single- and double-freeze protocols. Injury was assessed with the alamar blue indicator of metabolic activity. The assay gave anomalous results when used to assess the extent of injury immediately following the procedure, underestimating the extent of injury. However, a double-freeze procedure with antifreeze protein present was found to give significantly better ablation than a double-freeze without AFP or a single-freeze with or without AFP.

Prospective trial of cryosurgical ablation of the prostate: five-year results.

OBJECTIVES: To determine in a prospective pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma. METHODS: A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998. All patients had histologically proved adenocarcinoma of the prostate, with prostate-specific antigen (PSA) readings of less than 30 ng/mL. Clinical evaluations, PSA determinations, and patient self-reported quality-of-life questionnaires (functional assessment of cancer treatment-prostate; FACT-P) were used to determine biochemical and clinical disease-free status and complications. Patients had a mean follow-up of 50 months (minimum 36). RESULTS: Follow-up biopsies were performed in 73 patients, and 72 were negative for malignancy after one or more treatments. Ten patients required two treatments and 1 patient required three treatments. The 5-year overall and cancer-specific survival rate was 89% (95% confidence interval, 83% to 97%) and 98.6% (95% confidence interval, 96% to 100%), respectively. The undetectable PSA rate (less than 0.3 ng/mL) for low-risk patients (n = 13) was 60% at 5 years; for moderate-risk patients (n = 23), it was 77%, and for high-risk patients (n = 40), 48%. The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75%, 89%, and 76%. Sloughing occurred in 3 patients (3.9%), incontinence in 1 (1.3%), and testicular abscess in 1 (1.3%). At 3 years, 18 (47%) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse, 5 spontaneously and 13 with sildenafil or prostaglandin. CONCLUSIONS: The results of this prospective evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer.