Evaluation of thermal therapy in a prostate cancer model using a wet electrode radiofrequency probe.

PURPOSE: To determine the temperature-time threshold of local cell death in vivo for thermal therapy in a prostate cancer animal model and to use this value as a benchmark to quantify global tissue injury. MATERIALS AND METHODS: Two studies were designed in the Dunning AT-1 rat prostate tumor hind limb model. For both studies, a wet electrode radiofrequency (RF) probe was used to deliver 40 W of energy for 18 to 62 seconds after a 30-second infusion of hypertonic saline/Hypaque through the RF antenna. Thermal history measurements were obtained in tumors from at least two Fluoroptic probes placed radially 5 mm from the axis of a RF probe and 10 mm below the surface of the tissue. In study 1, the thermal history required for irreversible cell injury was experimentally determined by comparing the predicted injury accumulation (omega) with cell viability at the fluoroptic probe locations using an in vivo-in vitro assay. The omega value was calculated from the measured thermal histories using an Arrhenius damage model. In study 2, RF energy was applied for 40 seconds in all cases. At 1, 3, and 7 days after thermal therapy, triphenyltetrazolium chloride dye (TTC) and histologic analyses were performed to assess global tissue injury within a 5-mm radius from the axis of the RF probe. RESULTS: Study 1 showed that cell survival dropped to 0 for 0.42 < omega < 0.7. This result was the basis for selection of 40 seconds of RF thermal therapy in study 2, which yielded omegaave = 0.5 in the tissue 5 mm from the probe axis. Both TTC and histology analysis showed that sham-treated tissue was not irreversibly injured. However, there was an inherent heterogeneity present in the tumor that accounted for as much as 15% necrosis in control or sham-treated tissue. In contrast, at 1, 3, and 7 days after therapy, significantly less enzyme activity was observed by TCC in thermally treated tissue compared with sham-treated tissue (35 v 85%; P < 0.001). Histologic analysis of thermally treated tissues revealed a gradual increase in the percent of coagulative necrosis (47%-70%) with a concomitant decrease in the percentage of shocked cells (53%-28%). At day 7, <3% viability was observed in treated tumors compared with 90% viability in sham-treated tissue. CONCLUSION: The threshold of cellular injury in vivo corresponded to omega > 0.7 (> or =48 degrees C for 40 seconds). Global tissue injury could be conservatively predicted on the basis of local thermal histories during therapy.

Radiofrequency ablation of rabbit kidney using liquid electrode: acute and chronic observations.

BACKGROUND AND PURPOSE: The percentage of small renal tumors being diagnosed has increased at least five-fold in the last 20 years. The question of how best to treat these lesions remains unanswered. We studied the effectiveness of "wet" radiofrequency (RF) ablation of renal tissue. MATERIALS AND METHODS: New Zealand white rabbits (N = 48) underwent a 1- or 2-minute ablation of renal parenchyma with a modified insulated spinal needle capable of infusing saline, measuring temperature and impedance, and delivering RF energy. Animals were followed and examined up to 54 days after surgery. RESULTS: All animals survived for the planned period. Intravenous urograms showed no fistula or urinoma formation and confirmed continued function of the remaining parenchyma. The 1-minute treatments consistently ablated 20% to 25% (average 7 cm) of the tissue, whereas the 2-minute treatments ablated 34% to 36% (average 10 cm). Acutely, there was coagulative necrosis and infiltration of inflammatory cells. Chronically, there were well-demarcated lesions with complete effacement of the tubular epithelium and destruction of the glomeruli. CONCLUSION: Wet radiofrequency ablation with a liquid electrode can reproducibly create large lesions safely and quickly. The technique may soon become an alternative, minimally invasive therapy for small renal tumors.

Pressure measurements during injection of corticosteroids: in vivo studies.

Intralesional injection of corticosteroids is an effective treatment for capillary hemangiomas. Complications include embolisation of corticosteroid particles into the ocular circulation resulting in permanent loss of vision. This research is aimed at developing an injection cannula and monitoring system to prevent such inadvertent embolisation. A cannula has been designed to simultaneously estimate the pressure at its tip and the flow rate during injection. The estimation technique has previously been validated using an in vitro model. In this study, the cannula was tested in vivo with canine liver at injection flow rates of 2.5 to 21 ml min-1. The pressure generated in the tissue during injection was calculated using the technique developed. This was compared with direct in situ pressure measurements made with a coaxial outer cannula. The mean calculated pressure was seen to be linearly related to the mean measured pressure with a slope of 0.97, correlation coefficient of 0.99 and standard error of 2.74 mmHg. Similar trends were observed between the maximum calculated and maximum measured injection pressure: slope = 1.0, r = 0.99 and standard error = 5.54 mmHg. The estimation of the mean and maximum pressure from the cannula and monitoring system was accurate in canine liver. High pressures close to 250 mmHg were generated in tissues during injection.

Transurethral prostate ablation using saline-liquid electrode introduced via flexible cystoscope.

An interstitial saline-electrode has been developed to couple radiofrequency (RF) energy to prostate tissue in order to produce large lesions quickly and controllably. In this study, we attempted to produce similar results using a flexible catheter introduced transurethrally via a flexible cystoscope. An insulated 4F catheter with an extendable needle electrode (26-gauge, 5-mm exposed metal tip) was introduced through a port of a flexible cystoscope into the urethra of 10 dogs via a small perineal incision (required for the canine U-shaped urethra). Under visual endoscopic guidance, the electrode was placed in the center of the prostate and the needle electrode extended at an angle into the prostate, one lobe at a time. Hypertonic saline (14.6% NaCl) was infused at 2 mL/min through the needle electrode into the tissue for 30 seconds before and during RF application. The energy (50 W, 475 kHz) was delivered for 30, 45, 60, or 90 seconds (RFT System; U.S. Surgical Corporation). Prostate and urethral temperatures were monitored using thermocouples mounted on the catheter. There was an automatic high-temperature shut-off if the urethra reached >42 degrees C or if impedance reached >300 omega during RF energy application. Prostate sizes ranged from 1.4 x 2.0 x 1.4 cm to 5.0 x 4.5 x 4.2 cm. In this group, there were no automatic shut-offs at any of the energy durations, and the lesions produced ranged from 1.3 x 1.3 x 1.1 cm (0.99 cm3) to 1.6 x 2.7 x 2.2 cm (5.03 cm3). The average ablation volumes produced were 1.76 cm3 at 30 seconds' RF application, 2.42 cm3 at 45 seconds, 3.96 cm3 at 60 seconds, and 5.03 cm3 at 90 seconds. Histologic examination revealed typical coagulation necrosis in the treatment zone without tissue desiccation. Introduction of the saline-electrode through a flexible cystoscope provides a minimally invasive procedure that quickly and controllably produces large lesions that may provide effective treatment for benign prostatic hyperplasia with less patient discomfort.

Pressure measurements during injection of corticosteroids.

Corticosteroid injection into the orbit, eyelid and larynx is a common treatment for inflammation and neoplasm. Complications include embolisation into the ocular circulation resulting in permanent loss of vision. The overall aim of the reported research is to develop an injection cannula and monitoring system which can prevent inadvertent embolisation into the ocular circulation during injection of corticosteroids. To that end, a special cannula was designed that allows simultaneous estimation of pressure at the tip of the cannula and flow rate during injection. The cannula was tested with backpressures corresponding to physiological ranges of 0 to 125 mmHg and injection flow rates of 3 to 11 cm3 min-1. The estimated pressure at the tip of the cannula during injection of corticosteroids was compared with direct pressure measurements. The results show that the mean estimated pressure is linearly related to the mean measured pressure with a slope of 0.99 and correlation coefficient of 0.99. Statistical analyses show that with standard error of estimate (SEE) of 2.14 mmHg, the estimated pressure is well within the 95% prediction interval limits of the measured values. The estimation of pressure from the cannula and monitoring system was accurate and warrants further testing in animal models.

Transurethral prostate ablation with saline electrode allows controlled production of larger lesions than conventional methods.

A novel technique for prostate ablation using radiofrequency (RF) energy coupled to tissue with interstitial perfusion of saline solutions from a screw-tip catheter has been developed. The electrolyte spreads the current density away from the metal electrode and increases the effective electrode surface area, allowing more RF power input. This prevents tissue desiccation and impedance rise, resulting in controlled production of large lesions. In this study, we attempted to produce similar results using a straight needle and the saline electrode with a transurethral approach and compared the results with those of the same technique without electrolyte perfusion (conventional RF method). For this study, we designed an insulated 22-gauge needle with thermocouples embedded along its length and a 1-cm exposed tip with a retractable intraluminal thermocouple. This needle was inserted into the urethra of 10 dogs through a small perineal incision. Under transrectal ultrasound guidance, the exposed tip of the needle was placed in the center of each lobe. The intraluminal thermocouple was moved from the exposed tip up to the prostate capsule to monitor temperature. The highest power that could be applied in conventional RF methods without immediate desiccation was determined from preliminary experiments as 10 W. Subsequently, 10 W of RF power (475 kHZ) was delivered in one lobe until either the capsule temperature reached 48 degrees C or high impedance (> 400 omega) occurred. In the other lobe, 50 W of RF energy (475 kHz) and electrolyte perfusion (14.6% NaCl, 1 mL/min) were delivered until the capsule temperature reached 48 degrees C or high impedance occurred. Prostate lobe sizes ranged from 3.93 cm3 to 44.47 cm3 (mean 15.07 cm3). At 10 W without saline perfusion, high impedance from tissue desiccation occurred at 45 +/- 27 seconds, with lesions ranging from 0.06 cm3 to 0.93 cm3 (mean 0.34 cm3). At 50 W with saline perfusion, there was no tissue desiccation or impedance rise. The RF application time averaged 181 +/- 115 seconds until the capsule reached 48 degrees C, resulting in lesions ranging from 2.53 cm3 to 22.88 cm3 (mean 8.54 cm3). This study demonstrates that transurethral ablation of the prostate with a saline electrode allows controlled production of larger lesions than conventional RF methods. This may permit a single RF application in each lobe to produce lesions effective for the treatment of benign prostatic hyperplasia even in large glands.

Ex vivo experiment on radiofrequency liver ablation with saline infusion through a screw-tip cannulated electrode.

PURPOSE: To investigate whether radiofrequency (RF) therapy with hypertonic saline infusion through a hollow screw-tip electrode can cause a lesion size suitable for liver tumor ablation. MATERIALS AND METHODS: RF tissue ablation of 180 sites was performed by using a hollow screw-tip electrode in 40 freshly excised swine livers. Under both power and temperature control modes, the ablation effects with and without various regimes of 5% hypertonic saline (1 ml/min) prior to and/or during the procedure were compared by measuring the size of lesions at dissection and confirmed by T1 and T2 weighted magnetic resonance (MR) imaging. RESULTS: The maximal lesion diameter of 5.5 cm was reached at 30 W with saline infusion 1 min prior to and during 12 min of ablation. The smaller sizes (P < 0.01) between 0.3 and 2.5 cm in diameter were met with noninfusion or preinfusion-only groups. The RF ablation lesions appeared as hyper- and hypointense areas on T1 and T2 MR images, respectively. CONCLUSIONS: RF ablation in combination with present hollow screw-tip electrode and saline infusion allows for necrotic development of suitable size for liver tumor ablation. Such ablated lesions can be visualized with MR imaging.

Enhanced radiofrequency ablation of canine prostate utilizing a liquid conductor: the virtual electrode.

Conventional radiofrequency (RF) ablative techniques have shown promise for the treatment of symptomatic benign prostatic hyperplasia (BPH); however, present RF technology is limited by the small lesion size, necessitating several probe placements and heating cycles to achieve sizable lesions. This limitation is attributable primarily to a rapid increase in electrical impedance secondary to tissue desiccation and charring at the electrode tip. We devised a hollow screw-tip needle electrode that permits fixation to tissue, recording of temperature and impedance, infusion of fluid, and delivery of RF energy. Infusion of electrolyte solution (i.e., saline) into tissue prevents impedance rise by conducting RF energy away from the metal electrode and permits the creation of large lesions. By varying the conductivity of the perfusate (concentration and temperature), lesions of large diameter can be created in a controlled manner. To determine the long-term tissue effects, we applied this new modified RF technique to the prostates of five mongrel dogs in a chronic (0.5 to 8-week) study. The screw-tip electrode was serially embedded into each lobe of the perineally exposed glands with 1-minute infusion of 0.9% saline (2 mL/min) followed by application of RF energy (500 KHz, 50 W, 2-18 minutes) along with continuous saline infusion. Thermocouples were embedded 5 mm below and at the gland capsule, and RF application was discontinued when the temperature reached 50 degrees C at the periphery. Postoperatively, the animals were examined daily for clinical status and weekly for glandular changes using transrectal ultrasonography. At predetermined intervals, the animals were sacrificed and the prostates excised, measured, sectioned, and examined for histologic changes. Ablative tissue temperatures of 50 to 100 degrees C were produced while impedance remained stable. Four animals required a single catheterization for relief of urinary retention between days 2 and 3; otherwise, all animals demonstrated a quick and uneventful recovery with no edema detectable on day 7 ultrasound examination. The outside dimensions of the gland remained relatively constant throughout the study (+ or - 0.39 cm L + W + H). Histologic examination revealed coagulation necrosis (ablation) in both lobes of all prostates (69.94% + or - 16.62% of the gland) with tissueless cavities forming from the ablation area (28.71% + or - 8.24% of the gland) contained within the capsule surrounded by healthy tissue at the periphery. Intraprostatic lesions were obtained without any gross damage to surrounding tissue, including the bladder and rectal wall. Utilizing a liquid conductor in prostate tissue allows a single electrode-placement heating cycle for controlled ablation for the potential treatment of BPH. This new technique produces more extensive and uniform lesions than conventional RF procedures, and lesion size is limited only by the duration of RF energy application.

Suppression of ventricular fibrillation and positive inotropic action of bethanidine sulfate, a chemical analog of bretylium tosylate that is well absorbed orally.

Bethanidine sulfate is a closely related chemical analog of bretylium that has virtually identical pharmacologic and antifibrillatory actions on the ventricle. Unlike bretylium, which is very poorly absorbed from the gut, bethanidine is rapidly and effectively absorbed after oral administration. Bethanidine increased ventricular fibrillation threshold in the normal dog heart from an average control value of 28.5 mA to an average peak value of 66.5 mA, an increase of 150 percent. In the infarcted heart, bethanidine increased ventricular fibrillation threshold from an average postinfarction level of 14.4 mA to an average peak value of 55.3 mA, an increase of 327 percent. Like bretylium, the antifibrillatory action of bethanidine was manifested by the appearance of nonsustained ventricular fibrillation when superthreshold shocks induced episodes of ventricular fibrillation lasting from 2 to 120 seconds and converting spontaneously to sinus rhythm. In contrast, the untreated dog heart must always be defibrillated electrically. The onset of antifibrillatory action began as early as 2 minutes after intravenous administration and 15 to 30 minutes after oral administration; peak action occurred in approximately 60 minutes. Bethanidine had prolonged positive inotropic action in the isolated heart as reflected by an increase in cardiac output and blood pressure lasting up to 60 minutes. Bethanidine lowered coronary vascular resistance and increased coronary blood flow. The oral efficacy and rapid onset of action gives bethanidine a potential role in the prevention of out-of-hospital ventricular fibrillation.