Cryosurgical Procedure Research Articles

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 anomolous 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.

Cryosurgery as a treatment for advanced stage hepatocellular carcinoma: results, complications, and alcohol ablation.

The objective of this study was to investigate the use of cryosurgery and to determine whether there is a role for combined therapy with alcohol ablation in the treatment of patients with hepatocellular carcinoma. Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound-guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation was performed on those patients who were found to have residual tumor or recurrence after the cryosurgical procedure. Of the 12 patients (9 males, 3 females) the size of the primary tumor ranged from 3-13 cm with average size of 7 cm in greatest dimension. Most patients had advanced disease according to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1 Stage II. Three patients had residual tumors after the cryosurgical procedure. The residual tumor was treated with alcohol ablation. The 1-year survival rate for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of 10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years and another patient with a 13-cm tumor was disease free for 2.5 years. Both of these patients had Stage IVA disease. The authors found cryosurgery to be promising in the treatment of this extremely aggressive form of cancer, with the ability to prolong patient survival. Follow-up treatment with alcohol ablation is an important adjunct in treating residual tumor and controlling recurrences.

Cryosurgical palliation of metastatic neuroendocrine tumors resistant to conventional therapy

Background. Hepatic cryosurgery is a well-recognized modality for hepatic colon metastases. We examined its potential use for refractory neuroendocrine tumors causing progressive symptoms. Methods. Between July 1992 and February 1997, 19 patients (with islet cell, 7; carcinoid, 8; vasoactive intestinal peptide, 1; gastrinoma, 3) underwent cryosurgery with ultrasonography. The number of lesions frozen ranged from 1 to 16 (median, 8), and their diameters ranged from 2 to 15 cm with an average of 4 cm. Patients underwent resection of the primary tumor either before (37%) or concurrent with (32%) cryosurgery, and half underwent excision of metastases with cryosurgery. Before cryosurgery, patients received chemotherapy (63%), somatostatin (47%), interferon (10%), hepatic artery ligation (5%), radiation (10%), and/or omeprazole (16%). Results. The reduction in tumor markers reached 90% (5-hydroxyindoleacetic acid), 80% (vasoactive intestinal peptide), 90% (gastrin), 90% (pancreatic polypeptide), and 80% (serotonin). At a median follow-up of 17 months, the metastases had progressed in 11 patients (two underwent a second cryosurgical procedure that eliminated symptoms) and five had died. Subsequently an additional five patients received chemotherapy and three somatostatin. Median symptom-free and overall survival were 10 months and more than 49 months, respectively. Conclusions. Cryosurgery dramatically relieved symptoms with significant reduction in tumor markers. The reduced tumor burden may explain the subsequent response to systemic therapy. Cryosurgery is a useful adjuvant in symptomatic patients with refractory hepatic neuroendocrine metastases.

Fractional Cryosurgery

Cryosurgery is an established method to treat malignant tumors of the eyelids and periorbital area. Nevertheless, it has been abandoned for tumors greater than 10 mm, because it gives irregular esthetic results and, in some cases, lagophthalmos. To devise a new method for the treatment of such tumors. Fractional cryosurgery is performed in stages: the center of the lesion is frozen, resulting in a reduction of the tumor; this procedure is repeated, as necessary, until the lesion's diameter is smaller than 10 mm; the standard cryosurgical procedure is then carried out. The treatment of the first 20 basal cell carcinomas with diameters between 10 and 24 mm is described, with excellent clinical and cosmetic results. With fractional cryosurgery, the final scar bears no relation to the size of the original tumor but, instead, corresponds to the size of the lesion preceding the final cryosurgical procedure.

Monitoring during cryosurgery of bone tumors.

Cryosurgery is used in orthopaedic oncology as adjuvant treatment after intralesional excision of bone tumors to induce cell death at and beyond the surgical margin. Monitoring freeze/thaw cycles during cryosurgery is beneficial in controlling a cryosurgical procedure and in preventing an unwarranted local extent of the freeze. We conducted a study of 15 cryosurgical procedures with the use of a protocolized temperature measuring system wit peroperative graphic visualization. Using a liquid nitrogen spray, intralesional temperatures of -150 degrees C were achieved, which are, according to the literature, associated with cell death. Extralesional temperature measurements showed no sub-zero temperatures of surrounding important tissues. Temperature recordings in and outside the lesion during cryosurgery in orthopaedic oncology are of importance to monitor the freeze/thaw cycles and are helpful in facilitating an effective cryosurgical procedure and in controlling the extent of the freeze, avoiding local complications.

Infectious complications of hepatic cryosurgery.

Hepatic cryosurgery is a novel procedure for patients with metastatic liver disease. To date, no reviews of the infectious complications of this procedure have been published. One hundred and fifty patients underwent 158 hepatic cryosurgical procedures at Allegheny General Hospital (Pittsburgh) from November 1987 through July 1995. Gastrointestinal malignancies accounted for 93% of the underlying diagnoses. The following 12 infections were directly related to the cryosurgical procedure: hepatic abscess (six), intraperitoneal abscess (three), ascending cholangitis (two), and an intrahepatic device (Infusaid; Strato/Infusoid, Norwood, MA) infection (one). Enterococcus was the most commonly isolated organism. Seven of the 12 infections were polymicrobial. The patients who developed infections had longer hospital stays (26 days vs. 13 days) and had more days of fever (6.5 days vs. 2.3 days). than those who did not develop infections. If perioperative manipulation of the biliary tree is avoided, the infection rate in patients who undergo hepatic cryosurgery may be decreased even further. Overall, cryoablation of the liver is not related to an increased risk of infection.

Cryosurgery as a treatment for prostate carcinoma

There has been a resurgence of interest in cryosurgical ablation of the prostate for the treatment of carcinoma. This is due to recent advances in cryosurgical technology, which have resulted in relatively lower morbidity. The objective of this study was to evaluate the effectiveness of ultrasound-guided cryosurgical ablation of prostate carcinoma. Eighty-three patients who had biopsy-proven prostate carcinoma underwent cryosurgical ablation of their entire prostate gland. The initial group of 12 patients had their procedures performed under ultrasound guidance only. The other 71 patients had cryosurgery performed with temperature monitoring in combination with ultrasound guidance. Twelve patients who had positive biopsies underwent a second cryosurgical procedure. All patients had prostate specific antigen (PSA) levels measured at 3, 6, 12, 18, 24, and 30 months after cryosurgery. Ultrasound-guided sextant biopsies were performed at 3-6, 12-18, and 24 months. The median PSA dropped by 95%, from a preoperative value of 4.3 ng/mL to 0.2 ng/mL 30 months after cryosurgery. The authors experienced a high failure rate (positive biopsies) of 83% for the initial group of 12 patients who did not have temperature monitoring during the cryosurgical procedure. This was in contrast to a success rate of 90% (negative biopsies) for the next 71 patients, who did have temperature monitoring (P < 0.05, chi-square test). Twelve patients underwent a second cryosurgery, and the success rate for this group was 91% (11 of 12 patients). The combined success rate for both the first cryosurgery and the second was 94% (62 of 77 patients). Complications included urethral sloughing, urinary incontinence, impotence, bladder neck contracture, and bladder contracture. The majority of patients recovered rapidly from their cryosurgical procedures and were able to resume normal activities 3-4 weeks afterward. These preliminary results demonstrate that cryosurgical ablation of the prostate is a viable treatment option for prostate carcinoma. In the authors' experience, ultrasound alone may not be adequate for monitoring the entire cryosurgical procedure. The authors found that temperature monitoring shortened their learning curve, enabled them to freeze prostate tissue more aggressively, and may have contributed to their overall success.

MR imaging assisted temperature calculations during cryosurgery

MRI has the potential of becoming an important imaging modality for monitoring the extent of the frozen region during cryosurgery. However, while the temperature history inside the frozen region is of utmost importance in determining the likely outcome of a cryosurgical procedure, it cannot be accessed directly through MRI because of the extremely low signal produced by the frozen region. We have developed a new MRI-assisted numerical technique that can calculate and display the temperature distribution in the frozen region on a standard MR image. The technique combines MR imaging data with a finite difference formulation of the energy equation. Here, the technique is described and experimental results that verify the technique are shown.

Surgery for atrioventricular node reentry tachycardia

Surgical treatment options for interruption of atrioventricular node reentrant tachycardia include (1) skeletonization of the atrioventricular node by dissecting it from most of its atrial inputs and (2) discrete cryosurgery of the perinodal tissues by applying a series of sequential cryolesions to the atrial tissues immediately adjacent to the atrioventricular node. Both these techniques attempt to interrupt one of the dual atrioventricular node conduction pathways while preserving the other. This report describes 17 consecutive patients who underwent surgical treatment, 10 patients with skeletonization of the atrioventricular node and seven patients with discrete perinodal cryosurgery. There were 10 female and seven male patients and their ages ranged from 28 to 56 years (mean 38). Two of the 17 patients had Wolff-Parkinson-White syndrome and their accessory pathways were interrupted before the atrioventricular nodal reentrant tachycardia was ablated. All the procedures were performed in a normothermic beating heart while atrioventricular conduction was monitored closely. In the skeletonization technique, the right atrial septum was mobilized and the atrioventricular node exposed anterior to the tendon of the Todaro. The perinodal cryosurgical procedure was also performed through a right atriotomy and a series of sequential 3 mm cryolesions were placed around the borders of the triangle of Koch on the inferior right atrial septum. There were no operative deaths. Two patients who underwent the skeletonization operation had heart block necessitating pacemaker therapy. At postoperative electrophysiologic study, no echoes or atrioventricular nodal reentrant tachycardia were inducible in any of the 17 patients. All patients have remained free of arrhythmia recurrence and have required no antiarrhythmic therapy after a follow-up of 5 to 28 months (mean 14). In conclusion, both atrioventricular node skeletonization and perinodal cryosurgery successfully ablate atrioventricular nodal reentrant tachycardia; however, perinodal cryosurgery appears to be safer in avoiding heart block, is more easily performed, and is our procedure of choice for the management of medically refractory atrioventricular nodal reentrant tachycardia.

Controlled Freezing of Nonideal Solutions With Application to Cryosurgical Processes

Success of a cryosurgical procedure, i.e., maximal cell destruction, requires that the cooling rate be controlled during the freezing process. Standard cryosurgical devices are not usually designed to perform the required controlled process. In this study, a new cryosurgical device was developed which facilitates the achievement of a specified cooling rate during freezing by accurately controlling the probe temperature variation with time. The new device has been experimentally tested by applying it to an aqueous solution of mashed potatoes. The temperature field in the freezing medium, whose thermal properties are similar to those of biological tissue, was measured. The cryoprobe temperature was controlled according to a desired time varying profile which was assumed to maximize necrosis. The tracking accuracy and the stability of the closed loop control system were investigated. It was found that for most of the time the tracking accuracy was excellent and the error between the measured probe temperature and the desired set point is within +/- 0.4 degrees C. However, noticeable deviations from the set point occurred due to the supercooling phenomenon or due to the instability of the liquid nitrogen boiling regime in the cryoprobe. The experimental results were compared to those obtained by a finite elements program and very good agreement was obtained. The deviation between the two data sets seems to be mainly due to errors in positioning of the thermocouple junctions in the medium.

Perinodal cryosurgery for atrioventricular node reentry tachycardia in 23 patients

Atrioventricular node reentry tachycardia is the most common cause of paroxysmal supraventricular tachycardia. Available nonpharmacologic therapies include (1) catheter ablation or cryosurgical ablation of the His bundle and insertion of a permanent pacemaker and (2) surgical dissection around the atrioventricular node or discrete cryosurgery of the perinodal tissues, in an attempt to divide or ablate only one of the dual atrioventricular node conduction pathways responsible for the tachycardia while leaving the other intact. This report describes 23 consecutive patients who underwent the discrete cryosurgical procedure between August 13, 1982, and March 16, 1989. The first patient in this series, a 38-year-old woman, is the first patient in whom refractory atrioventricular node reentry tachycardia was cured surgically by a procedure designed to treat this arrhythmia. The ages of the 13 female and 10 male patients ranged from 12 to 56 years with an average age of 29 years. Fourteen of the 23 patients (61%) had the Wolff-Parkinson-White syndrome. Other associated arrhythmias included atrial flutter/fibrillation (n = 2), right atrial reentrant tachycardia (n = 1), junctional tachycardia (n = 1), and a Mahaim fiber (n = 1). Associated anatomic abnormalities included Ebstein's anomaly in two patients and a large right atrial aneurysm in one patient. The perinodal cryosurgical procedure was performed through a right atriotomy in the normothermic beating heart. Multiple 3 mm diameter cryolesions were placed around the borders of the triangle of Koch on the lower right atrial septum to alter the input pathways of the atrioventricular node. There were no operative deaths in this series of patients. Postoperatively, all 23 patients had normal atrioventricular conduction, and no heart block has occurred in any patients during the follow-up period. All patients have remained free of atrioventricular node reentry tachycardia (and of the Wolff-Parkinson-White syndrome) and none has required postoperative antiarrhythmic drugs for either of these arrhythmias. We consider this simple, safe, easily performed, and uniformly successful operation to be the procedure of choice for the treatment of medically refractory atrioventricular node reentry tachycardia.

Effects of Nd-YAG laser and cryosurgery on the oral mucosa in rabbits

In 32 rabbits, lesions of comparable depths were created in the oral mucosa using a Nd-YAG laser (Medilas II, 1.06 μm, MBB Co., Munich) and a cryosurgery unit (Kryo-S, Erbe Co., Hannover). Histologic specimens were examined between 1 h and up to 8 weeks following operation. The laser lesion was restricted horizontally to the laser-exposed area; the full extent of the lesion could already be seen after 1 day. Cryosurgical lesions showed their maximum extent 3 days following treatment. Wound healing processes following laser application, were accelerated compared to cryosurgical procedure.

Cryosurgical modification of retrograde atrioventricular conduction: Implications for the surgical treatment of atrioventricular nodal reentry tachycardia

Paroxysmal supraventricular tachycardia resulting from atrioventricular nodal reentry is a common arrhythmia that usually responds to medical therapy. When atrioventricular nodal reentry tachycardia is refractory to medical therapy, cryoablation or endocardial catheter ablation of the His bundle has been employed to protect the ventricles from the tachycardia. However, these techniques necessitate implantation of a permanent ventricular pacemaker. A cryosurgical procedure that ablates the anatomic-electrophysiologic substrate for atrioventricular nodal reentry tachycardia while preserving antegrade atrioventricular conduction has been described. The purpose of the present study was to determine the effects of this procedure on retrograde atrioventricular conduction and on the ventricular echo phenomenon in particular. Thirty adult mongrel dogs underwent either the cryosurgical procedure (n = 20) or a sham operation (n = 10). The animals were studied either immediately postoperatively (acute cryosurgery group and control group, n = 10 for each group) or 14 weeks postoperatively (chronic cryosurgery group, n = 10). Decremental ventricular pacing and programmed premature ventricular pacing protocols were used to determine the retrograde atrioventricular nodal conduction time, Wenckebach point, atrioventricular nodal refractory periods, and ventricular echo reflection time. No electrophysiologic alterations were noted in the sham-operated group. In the acute cryosurgery group, the retrograde Wenckebach point, atrioventricular nodal conduction time, functional refractory period of the atrioventricular node, effective refractory period of the atrioventricular node, and ventricular echo reflection time were all significantly prolonged. In the chronic cryosurgery group, no significant change in ventriculoatrial conduction was noted, but the ventricular echo phenomenon was eliminated in all but one animal. These data further document that this cryosurgical procedure is capable of ablating the anatomic-electrophysiologic substrate necessary for atrioventricular nodal reentry tachycardia while preserving atrioventricular conduction.

Real time ultrasonic monitoring of hepatic cryosurgery

Cryosurgery has a number of advantages that make it particularly appealing in the treatment of liver cancer. However, a major problem in the clinical application of hepatic cryosurgery is the lack of a precise means of monitoring the freezing process in situ. Preliminary investigations on simulated tissue have shown that standard ultrasonography is capable of accurately determining the amount of frozen material during a cryosurgical procedure. To extend these results to living tissue, cryosurgery was performed, in vivo, on the livers of four mongrel dogs. An ultrasound imaging device using a new intraoperative ultrasound transducer monitored the entire process in real time. The results indicate that the entire freezing and thawing cycle can be monitored easily using real time ultrasound. During freezing, the solidification interface can be seen to move through the tissue allowing clear imaging of the cryolesion. After complete thawing, the cryolesion became less echogenic than before freezing and was therefore distinguishable under ultrasound. Postsurgical pathologic examination showed excellent correlation between the lesion size and its ultrasonic image.

Alteration of antegrade atrioventricular conduction by cryoablation of peri-atrioventricular nodal tissue: Implications for the surgical treatment of atrioventricular nodal reentry tachycardia

Paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry is a common arrhythmia that usually responds to medical therapy. When atrioventricular nodal reentry tachycardia is refractory to medical therapy, surgical cryoablation or endocardial catheter ablation of the His bundle has been employed to protect the ventricles from the tachycardia. However, these techniques necessitate implantation of a permanent ventricular pacemaker. The purpose of the present study was to develop a cryosurgical procedure capable of ablating the anatomic-electrophysiological substrate of atrioventricular nodal reentry by modifying, rather than ablating, atrioventricular conduction. Thirty-three adult mongrel dogs underwent either the cryosurgical procedure (n = 23) or a sham operation (n = 10). All animals were restudied immediately postoperatively (acute cryosurgery group [n = 12) and sham group [n = 10]), and 11 animals (chronic cryosurgery group) subjected to cryosurgery were studied 14 weeks postoperatively. Decremental atrial pacing and programmed premature atrial stimulation protocols were utilized to determine atrioventricular nodal conduction time, atrioventricular nodal refractory period, and the Wenckebach point before and after operation in all animals. No electrophysiological alterations were noted in the sham-operated group. In the cryosurgery groups, atrioventricular nodal conduction time, functional refractory period of the atrioventricular node, and the Wenckebach point were all significantly prolonged in the immediate postoperative period, but only atrioventricular nodal conduction time remained prolonged 14 weeks postoperatively. The potential application of the new cryosurgical procedure for the treatment of atrioventricular nodal reentry tachycardia was demonstrated in three animals that exhibited dual atrioventricular nodal conduction preoperatively but had monophasic atrioventricular conduction curves postoperatively. The results in these animals documented that the cryosurgical procedure is capable of ablating the anatomic-electrophysiological substrate necessary for atrioventricular nodal reentry tachycardia.

Thermal Aspects of Cryosurgery

Tissue reactions to cryosurgical procedures depend on temperature variations and on rates of temperature variations induced by freezing probes. In this paper thermal responses of biological systems undergoing freezing are obtained through the application of the finite element method to the solution of the nonlinear bio-equation. This model allows realistic predictions of isotherm fields and of rates of freezing in practically any cryosurgical procedure.

Cryosurgery in the Treatment of Perianal Fistulae

The advantages of cryosurgery over resection techniques in treating perianal fistulae include low recurrence rate, low incidence of incontinence, ease of performance, the relatively short amount of time required for the procedure, and minimal blood loss. If the disease is diagnosed and treated early in its course, complete resolution may be expected after one cryosurgical procedure. However several months and more than one surgical procedure are sometimes required in severe cases. The prognosis is good to excellent, depending on the stage and severity of the disease.