Cryosurgical Lesions Research Articles

Cryosurgery with Pulsed Electric Fields

This study explores the hypothesis that combining the minimally invasive surgical techniques of cryosurgery and pulsed electric fields will eliminate some of the major disadvantages of these techniques while retaining their advantages. Cryosurgery, tissue ablation by freezing, is a well-established minimally invasive surgical technique. One disadvantage of cryosurgery concerns the mechanism of cell death; cells at high subzero temperature on the outer rim of the frozen lesion can survive. Pulsed electric fields (PEF) are another minimally invasive surgical technique in which high strength and very rapid electric pulses are delivered across cells to permeabilize the cell membrane for applications such as gene delivery, electrochemotherapy and irreversible electroporation. The very short time scale of the electric pulses is disadvantageous because it does not facilitate real time control over the procedure. We hypothesize that applying the electric pulses during the cryosurgical procedure in such a way that the electric field vector is parallel to the heat flux vector will have the effect of confining the electric fields to the frozen/cold region of tissue, thereby ablating the cells that survive freezing while facilitating controlled use of the PEF in the cold confined region. A finite element analysis of the electric field and heat conduction equations during simultaneous tissue treatment with cryosurgery and PEF (cryosurgery/PEF) was used to study the effect of tissue freezing on electric fields. The study yielded motivating results. Because of decreased electrical conductivity in the frozen/cooled tissue, it experienced temperature induced magnified electric fields in comparison to PEF delivered to the unfrozen tissue control. This suggests that freezing/cooling confines and magnifies the electric fields to those regions; a targeting capability unattainable in traditional PEF. This analysis shows how temperature induced magnified and focused PEFs could be used to ablate cells in the high subzero freezing region of a cryosurgical lesion.

Pre-conditioning cryosurgery: Cellular and molecular mechanisms and dynamics of TNF-α enhanced cryotherapy in an in vivo prostate cancer model system

Cryosurgery is increasingly being used to treat prostate cancer; however, a major limitation is local recurrence of disease within the previously frozen tissue. We have recently demonstrated that tumor necrosis factor alpha (TNF-α), given 4 h prior to cryosurgery can yield complete destruction of prostate cancer within a cryosurgical iceball. The present work continues the investigation of the cellular and molecular mechanisms and dynamics of TNF-α enhancement on cryosurgery. In vivo prostate tumor (LNCaP Pro 5) was grown in a dorsal skin fold chamber (DSFC) on a male nude mouse. Intravital imaging, thermography, and post-sacrifice histology and immunohistochemistry were used to assess iceball location and the ensuing biological effects after cryosurgery with and without TNF-α pre-treatment. Destruction was specifically measured by vascular stasis and by the size of histologic zones of injury (i.e., inflammatory infiltrate and necrosis). TNF-α induced vascular pre-conditioning events that peaked at 4 h and diminished over several days. Early events (4–24 h) include upregulation of inflammatory markers (nuclear factor-κB (NFκB) and vascular cell adhesion molecule-1 (VCAM)) and caspase activity in the tumor prior to cryosurgery. TNF-α pre-conditioning resulted in recruitment of an augmented inflammatory infiltrate at day 3 post treatment vs. cryosurgery alone. Finally, pre-conditioning yielded enhanced cryosurgical destruction up to the iceball edge at days 1 and 3 vs. cryosurgery alone. Thus, TNF-α pre-conditioning enhances cryosurgical lesions by vascular mechanisms that lead to tumor cell injury via promotion of inflammation and leukocyte (esp. neutrophil) recruitment.

27. Ultra low temperatures within cryosurgical lesions induce an early-onset programmed cell death

27. Ultra low temperatures within cryosurgical lesions induce an early-onset programmed cell death

Bone grafting of cryosurgically treated bone defects: experiments in goats.

It is hypothesized that cryosurgically treated bone defects are inappropriate host sites for cancellous bone grafting. The influence of autologous cancellous bone grafting on the healing of cryosurgically treated gap defects of long bones was investigated. A unilateral in vivo experiment was done to study bone strength and graft incorporation in the goat. The lining of a cylindrical defect of the femoral diaphysis was treated with a closed liquid nitrogen cryoprobe in 62 goats. Thirty-one animals received an impacted, morselized, cancellous bone graft harvested from the sternum. The other 31 animals served as controls. At 0, 4, 7, 10, 13, 16, and 26 weeks animals were euthanized and the femurs were evaluated for torsional strength, computed tomography, and histologic assessment. Specimens with a bone graft showed no significant increase in torsional strength with time compared to the controls. In all goats euthanized at 10 weeks or later, the graft was resorbed. The amount of bone apposition at the site of the cryosurgical lesion and the time at which the defect was bridged were similar in both groups. Autologous cancellous bone grafting does not accelerate healing of cryosurgically treated, stable, diaphyseal defects in the goat.

Cryosurgical ablation of fetal atrioventricular node: New model to treat fetal malignant tachyarrhythmias

Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

Role of cryosurgery and MRI for Parkinson's disease.

Three basic principles underlie the techniques of stereotactic cryosurgery for Parkinson's disease: (1) high-resolution MRI of the surgical target using thin sequential coronal, axial and sagittal views: (2) clinical-physiological verification of localization of the surgical target by reversible inhibition test, and (3) production of the cryosurgical freezing lesion in a conscious, cooperative patient. The cryosurgical lesion is created in the ventrolateral nucleus of the thalamus for control of tremor and rigidity, or in the posterior ventral area of the pallidum for control of rigidity and bradykinesia. An initially reversible inhibition is produced by cooling the probe tip to -10 degrees C. This cools the brain tissue within 3 mm of the probe to 2-15 degrees C. If parkinsonian symptoms are suppressed, the cryoprobe tip temperature is then lowered incrementally, resulting in a gradually enlarging lesion surrounded by a reversible buffer zone. The final temperature is that in which parkinsonian symptoms are abolished and/or side effects appear. After performing and evaluating over 1,000 cryothalamotomies and cryopallidotomies on patients for whom medical treatments had failed, the author concludes that cryosurgical techniques are safer and produce lesions that are better controlled for size and location than other techniques, resulting in lasting, successful therapeutic results.

Comparison of left ventricular cryolesions created by liquid nitrogen and nitrous oxide

Objectives. This study was designed to compare the cryosurgical lesions produced by liquid nitrogen (−196 °C) and nitrous oxide (−76 °C).Background. Cryosurgical ablation is a useful method of arrhythmia surgery, but information on the dimensions of cardiac lesions produced by modifying cryoprobe temperature is limited.Methods. We compared the dimensions, volumes and electrophysiologic effects of cryolesions created by a liquid nitrogen cryoprobe (Group I) and a nitrous oxide cryoprobe (Group II) on the left ventricular myocardium in the beating canine heart. Exposure time was compared at 1, 2, 3 and 4 min. In each of 18 dogs, two to four lesions were created on the left ventricle and analyzed: 35 lesions created with use of the nitrous oxide cryoprobe and 30 lesions created with the liquid nitrogen cryoprobe. Lesions were measured at the time of induced death 6 weeks postoperatively and assessed by tissue staining with the masson trichrome technique.Results. The volumes (mm3) of the cryolesions created by the liquid nitrogen cryoprobe were significantly larger (p < 0.05) than those of lesions created by nitrous oxide: 826 ± 163 versus 493 ± 197 at 1 min; 1,101 ± 327 versus 666 ± 185 at 2 min; 1,356 ± 318 versus 787 ± 258 at 3 min and 1,735 ± 534 versus 923 ± 376 at 4 min.Conclusions. Decreasing the temperature of the cryoprobe by using liquid nitrogen increases the volume of the lesions. Programmed electrical stimulation before and 6 weeks after cryoablation indicated no arrhythmogenicity.

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 the atrioventricular node: A closed heart approach in the dog

Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be an alternative to His bundle ablation in patients with refractory supraventricular arrhythmias. It was postulated that a cryosurgical lesion at the posterior interatrial septum in the closed heart could achieve this. An electrophysiologic study was performed in anesthetized dogs. The AV fat pad was mobilized to expose the posteroseptal region. A cryoprobe cooled to 0 to -10 degrees C was moved in the exposed region until reversible AV block indicated proximity of the AV node. The probe was then cooled to -70 degrees C for 30 seconds. Four weeks later, five dogs had a favorable result with a mean prolongation of Wenckebach cycle length of 45 +/- 7% (p less than 0.05). Two dogs had complete heart block. Decreased (one dog) or increased (one dog) duration of freezing resulted in no change and complete heart block, respectively. Histologic examination verified partial damage to the AV node with preservation of the His bundle. Thus, controlled cryoinjury to modify AV node function is feasible in the closed heart; preservation of AV conduction provides an advantage over His bundle ablation.

Surgical ablation of posterior septal accessory pathways in the Wolff-Parkinson-White syndrome by a closed heart technique

The conventional technique for surgical ablation of posterior septal accessory pathways in the Wolff-Parkinson-White syndrome has been associated with a significant incidence of inadvertent permanent atrioventricular block. We report our experience with the ablation of posterior septal accessory pathways by a closed heart technique that combines mobilization of the posterior septal atrioventricular fat pad and exposure and cryoablation of the atrioventricular junction. The operation is performed on the normothermic beating heart. Consequently, atrioventricular node-His bundle conduction and accessory pathway conduction can be continuously monitored to avoid inadvertent injury to the atrioventricular node-His bundle system. This technique for ablation of posterior septal accessory pathways was used in 13 patients (four female and nine male patients, aged 14 to 59 years). The heart was exposed via a median sternotomy. Epicardial mapping was used to determine the insertion of the accessory pathway either to the left ventricular process or the immediately adjacent right or left ventricular free wall. Normothermic cardiopulmonary bypass was used in nine patients and omitted in four. Accessory pathway conduction disappeared in the course of dissecting the fat pad from the atrial wall and atrioventricular sulcus in all patients. Cryosurgical lesions were then applied to the atrioventricular sulcus in the area of interest (while monitoring atrioventricular conduction) to ensure transmural fibrosis of the atrioventricular ring. All patients tolerated the procedure well. There were no complications and, specifically, not a single instance of atrioventricular block. All patients remain arrhythmia free after a follow-up period of 10 months. This closed heart approach allows the ablation of posterior septal accessory pathways while the electrocardiogram is being monitored. It obviates the need for aortic cross-clamping and minimize the risk of inadvertent heart block.

The electrophysiologic effects of discrete cryosurgery for the treatment of supraventricular tachycardia due to AV nodal reentry.

The electrophysiologic effects of multiple cryosurgical lesions along the circumference of Koch's triangle were evaluated as a treatment of AV nodal reentrant tachycardia in 31 dogs. These animals were divided into a control group (n = 8) and a cryosurgical group (n = 23), and were studied using incremental atrial pacing and programmed atrial premature stimulation. In the cryosurgical group, significant prolongation of AV nodal conduction time, initiation of Wenckebach periodicity at a slower atrial pacing rate, and an increase in the functional refractory period of the AV node were documented postoperatively. In contrast, there were no significant differences between preoperative and postoperative AV node conduction characteristics in the control group. Four dogs in which the effective refractory period of the AV node could be measured showed an increase of 28-104 msec following cryosurgery. In 2 dogs, discontinuous conduction curves (i.e., dual AV nodal pathways) were demonstrated preoperatively. Postoperatively, a uniform conduction curve was demonstrated. In conclusion, these results strongly suggest that this new cyrosurgical method is an effective surgical procedure for the interruption of the reentrant circuit responsible for AV nodal reentry while preserving AV conduction.

Recovery of function after cryosurgical lesions of peripheral nerves in rats

Unilateral lesions were made in rat sciatic nerves with a cryoprobe at about −65°C. Three months later, recovery of motor and sensory function of the hindlimb had occurred. The compound action potential from the dorsal root indicated that myelinated and unmyelinated fibre groups had regenerated. Cryosurgery may be useful in the long-term blockade of sensory nerves for pain relief.

Experimental cryosurgical lesion of the optic nerve.

The right optic nerves of three cynomolgus monkeys were frozen under direct visualization after a modified Kröhnlein operation. Left optic nerves were subjected to an identical procedure without freezing. Postoperatively, visual evoked responses (VERs) could not be obtained by stimulating right eyes, while electroretinograms from both eyes and VERs obtained by stimulating left eyes were normal. Extensive lesions which were found in the right optic nerves of all animals were histologically similar to those obtained by freezing in the brain.

Tissue reparation of the liver after thermo- and cryosurgical lesions: Comparative cell analytical investigation

Histological and cell kinetic studies were performed on the liver of rats after local thermocoagulation. The dynamics of the wound healing were compared with those after in situ freezing (cryonecrosis) of the liver. The postoperative time ranged from 12 hr to 30 days. In the histological slides the morphological changes and the percentages of cells in the granulation tissue as well as in the autoradiograms were determined. The morphologic consequences of cryolesions in the liver are characterized by a shorter duration of the leukocytic reaction, stronger activities of macrophages, and a relatively prominent fibroblast-fibrocyte involvement. The dynamic process of the wound healing after cryonecrosis leads to a small fibrous scar 3–4 weeks postoperatively. After thermonecrosis, the leukocytic reaction is prolonged, the resorptive activity of the granulation tissue is lower but still visible 4 weeks after the injury, and the thermonecrotic carbonized material is not yet resorbed. Therefore, it can be stated that thermosurgically induced tissue lesions exhibit a delayed wound healing in comparison to other physical injuries, especially cryosurgical processes.

The splenic reaction to cryosurgical lesions on parenchymal organs.

The splenic reaction to cryosurgical lesions on parenchymal organs.

Cryosurgery of the Retina

In 1931, J. Gonin presented his original concept that retinal detachment is caused by a retinal break and reattachment could be achieved by inducing inflammation around the break with diathermy and by simultaneous draining of subretinal fluid. The primary advantage of cryosurgery is the ability to penetrate the sclera and to create a retinal adhesion without causing scleral necrosis. The early ophthalmoscopic appearance of a cryosurgical lesion is a function of retinal transparency. The reluctance to employ cryosurgery was the uncertainty of the strength of the cryopexy-induced adhesion. Cryosurgery allows retinal coagulation through full-thickness sclera without scleral damage and thus allows a minimal extraocular procedure for retinal detachment that employs an elastic explant to buckle the area limited to the retinal break. The pattern of the healed retinal cryosurgical lesion depends on the depth of thermal necrosis created by the cryopexy application and the extent of the basement membrane interruption.

Standardization of cryosurgical lesions

In order to establish treatment standards for tumours of various types and sizes, one must have full control over the cryosurgical operation. The requirements for such controlled cryotherapy are discussed, and it is argued that it should be possible to keep the freezing rate between 30–50°C per minute irrespective of tumour size, and that the tissue must be thawed as quickly as possible once the desired minimum temperature has been reached. For controlled cryotherapy one has to rely on freezing damage as damage caused during thawing is difficult to predict. Freezing probes of different designs and sizes must be available to meet the demands mentioned for heat exchange and a pressure gauge must be at hand to record the force with which the freezing probe rests against the tissue. Finally a reliable flowmeter must be found with which to measure the number of calories drained away from the tissue.

Cryomarcation Line and Pigment Migration After Retinal Cryosurgery

Some degree of pigment migration invariably follows cryosurgery of the retina. Immediately upon thawing, pigment granules lysed from the pigment epithelium of the choroid may migrate through the retinal tear and into the vitreous. Pigment migration may also occur through the subretinal fluid to form a deposit behind the macula, or a pigmented line representing the farthest advance of the retinal separation. Pigment deposited in the foveal area may impair macular function. The important difference between cryopexy and diathermy applications to the choroid is the apparent absence of coagulation of the tissue proteins in the cryosurgical lesion. The complications of pigment migration are perhaps the most serious observed with the cryosurgical method.

L-dopa in the treatment of Parkinsonism; a preliminary appraisal.

HE treatment of parkinsonism from the time of its first clear description by Parkinson 1~ to the modern era has been less than satisfactory. Neurosurgical procedures directed at the pyramidal tracts ranged from the premotor cortex through the cerebral peduncles and into the spinal cord. The goal was to relieve unilaterally a single troublesome symptom, namely, tremor, leaving the problems of bradykinesia, gait, balance, posture, voice, speech, swallowing, and others untouched. Some success was obtained, usually at the price of significant weakness in the limbs involved. When the weakness diminished, as it often did following surgery, the tremor tended to recur. Neurosurgical procedures directed at the basal ganglia ushered in a whole new phase of treatment, chiefly because relief of tremor, rigidity, and poor alternating movements could be obtained without producing any weakness whatsoever. This divorced the tremor and rigidity from what had previously been thought to be their intrinsic dependence upon the great voluntary motor pathway, the pyramidal tract. Reports from neurosurgical centers throughout the world concurred on this point. Our own experiences have been extensively reported and show that alleviation of tremor and rigidity can be obtained in 85% to 90% of properly selected patients with cryosurgical lesions directed at the ventrolateral and posteroventrolateral nuclei of the contralateral thalamus. ~ Acceptable mortality and morbidity figures were also reported from our clinic in a series of nearly 3000 eases. 11 The mortality in that series of consecutive operations done for parkinsonism

The control and predictability of a cryolesion

Summary An attempt has been made to analyze some of the physical factors which influence the quantitative effect of freezing as used in cryosurgical procedures. The predictability of a cryosurgical lesion has been considered and certain factors in the use of thermocouples to provide control are emphasized.