Irreversible electroporation (IRE) is a new tissue ablation technique in which micro to millisecond electrical pulses are delivered to undesirable tissue to produce cell necrosis through irreversible cell membrane permeabilization. IRE affects only the cell membrane and no other structure in the tissue. The goal of the study is to test our IRE tissue ablation methodology in the pig liver, provide first experience results on long term histopathology of IRE ablated tissue, and discuss the clinical implications of the findings. The study consists of: a) designing an IRE ablation protocol through a mathematical analysis of the electrical field during electroporation; b) using ultrasound to position the electroporation electrodes in the predetermined locations and subsequently to monitor the process; c) applying the predetermined electrotroporation pulses; d) performing histolopathology on the treated samples for up to two weeks after the procedure; and e) correlating the mathematical analysis, ultrasound data, and histology. We observed that electroporation affects tissue in a way that can be imaged in real time with ultrasound, which should facilitate real time control of electroporation during clinical applications. We observed cell ablation to the margin of the treated lesion with several cells thickness resolution. There appears to be complete ablation to the margin of blood vessels without compromising the functionality of the blood vessels, which suggests that IRE is a promising method for treatment of tumors near blood vessels (a significant challenge with current ablation methods). Consistent with the mechanism of action of IRE on the cell membrane only, we show that the structure of bile ducts, blood vessels, and connective tissues remains intact with IRE. We report extremely rapid resolution of lesions, within two weeks, which is consistent with retention of vasculature. We also document tentative evidence for an immunological response to the ablated tissue. Last, we show that mathematical predictions with the Laplace equation can be used in treatment planning.The IRE tissue ablation technique, as characterized in this report, may become an important new tool in the surgeon armamentarium.

Percutaneous prostate cryo-ablation has become an accepted treatment for primary prostate cancer. Thermal tissue ablation based on cold, however, does have some distinct limitations. These include, variable damage at the cryo lesions margin, injury to adjacent structures such as rectum, urethra and NVB (neurovascular bundle), and long procedure time due to the need for multiple freeze thaw cycles, that have limited the acceptance of this modality. Irreversible electroporation IRE, is a new non-thermal ablation modality that uses short pulses of DC electric current to create irreversible pore in the cell membrane, thus, causing cell death. This method theoretically should have significant advantages in ablating prostate tissue. Six males dogs had their prostates treated using IRE. Pulses were applied using a DC generator that delivered pulses in the microsecond range of duration, with a variable pulse interval and voltage range. IRE probes were placed percutaneously or trans-rectally using trans-rectal ultrasound guidance. In one of the dogs, the lesions were made purposely to include the rectum, urethra, and neurovascular bundle (NVB). Subjects were followed for 1 to 14 days before sacrifice. IRE lesions in the prostate had unique characteristics compared to thermal lesions. The margins of the IRE lesions was very distinct with a narrow zone of transition from normal to complete necrosis, there was complete destruction within the IRE lesion, and rapid resolution of the lesions with marked shrinkage within two weeks. Structures such as urethra, vessels, nerves, and rectum were unaffected by the IRE application. IRE lesions have characteristics that are distinctly different than thermal lesions. The differences could be very advantageous in a clinical setting, improving the results and acceptance of prostate ablation.

Background. The two major treatments for prostate cancer, radical prostatectomy and radiation therapy, are associated with considerable morbidity and variable results. This article presents the preliminary results using percutaneous radical cryosurgical ablation under ultrasound guidance to treat prostate cancer. Methods. The patient group consisted of all patients with localized prostate cancer who underwent cryosurgery between June 1, 1990 and May 1, 1992. Patients in Group 1 were treated by freezing of the tumor with two cryoprobes placed multiple times. Group 2 patients were treated by freezing of the tumor with five cryoprobes placed simultaneously. Cryoprobes (3 mm in diameter) were placed percutaneously with a transperineal approach. Cryoprobe placement and freezing were monitored using the transrectal ultrasound. Results. Of the 55 patients (68 procedures) undergoing treatment, 23 have 3 months of follow‐up with associated biopsy (Group 1, 8 patients; Group 2, 15 patients). In Group 1, three (37.5%) patients had residual disease. In Group 2, one (6.7%) patient had residual disease, whereas 14 (93.3%) patients did not. Combining both groups, 19 (82.6%) patients had no residual disease, whereas 4 (17.4%) patients had positive results on postoperative biopsy. Complications included rectal freezing, urethrorectal fistula, sloughing urethral tissue, impotence, perineal ecchymosis, penile edema, and ileus. Conclusions. Preliminary results indicate that percutaneous transperineal ultrasound‐guided prostate cryo‐surgery may be an effective treatment for prostate cancer with minimal associated morbidity.

Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a possible treatment for unresectable hepatic tumors. Its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection, allowing treatment of multiple lobes. Because cryosurgery does not affect large vessels, tumors in difficult locations, such as adjacent to the inferior vena cava (IVC), can be treated. With the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process, 18 patients with unresectable metastatic colon carcinoma confined to the liver were treated. Of the 18 patients treated, 4 (22%) are in complete remission as determined by computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at the time of cryosurgery. The number of lesions frozen in each patient ranged from 1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive. Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable (including patients with bilobar and multiple lesions). These preliminary results indicate that the procedure warrants further study.

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