Symposium on Surgical Techniques in Small Animal Practice
Cryosurgery Thomas P. Greiner, D.V.M.,* William D. Liska, D.V.M.,t and Stephen J. Withrow, D.V.M.t
"Be not the first by whom the new are tried, nor yet the last to lay the old aside." ALEXANDER POPE
Cryosurgery is defined as the therapeutic application of cold to freeze biological tissues, producing controlled physiologic inhibition or anatomic destruction.3 This concept is nothing new, as the beneficial effects of local cold to control hemorrhage and reduce swelling are mentioned in the writings of Hippocrates. However, James Arnott of England is credited as being the first to apply local cold as a therapeutic method for the treatment of cancer in 1845. Cryosurgery did not begin to receive widespread acceptance until the early 1960's when Cooper and Lee introduced a liquid nitrogen system whereby they were able to achieve probe temperature of -190° C. Shortly after the introduction of the system, the instrument was perfected and became commercially available. With this, its widespread usage in the fields of dermatology, neurosurgery, ophthalmology, gynecology, and proctology became available. Prior to its acceptance by the medical profession, however, its development received a major setback when some writings on "Observations on Prolonged Human Refrigeration" by Dr. Temple Fay were seized by the Nazis during World War II. In the minds of the public the Nazis' explorations of hypothermia without anesthesia in concentration camps were associated with their other atrocities and subsequently, any association with it was deplored for several years. From the Department of Surgery, The Animal Medical Center, New York, New York *Staff Surgeon tResident tResident Veterinary Clinics of North America- Vol. 5, No. 3, August 1975
565
566
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
Little has been done in the field of veterinary medicine with cryosurgery. Most reports on its usage in veterinary medicine have come from England with Borthwick, Lane, and Robins and Lane publishing reports on its usefulness in the treatment of perianal fistulas and certain neoplastic diseases. Currently in this country, several veterinary schools are investigating its efficacy. At The Animal Medical Center in New York City, its clinical applications are under investigation and so far, cryosurgery has been found to be useful in a number of naturally occurring diseases in small animals. 12
CRYOBIOLOGY
In veterinary medicine, as well as human medicine, cryosurgery is of interest .as another modality in its surgical armamentarium for the treatment of certain neoplastic and inflammatory diseases that do not respond well to or are difficult to treat with conventionaf methods. The central aim is to kill all cells in a diseased target area while simultaneously producing minimal tissue damage to normal surrounding tissue. As a surgical agent, cryosurgery is said to offer the advantages of combined anesthetic coagulant and destructive properties;. however, before discussing advantages, indications, instruments, and limitations, one should understand the changes that occur when biological systems undergo ice formation, and those changes associated with the destruction of cells. At least five basic mechanisms are involved in cellular destruction- dehydration and toxic concentration of electrolytes, crystallization and rupture of cellular membranes, denaturization of lipid protein substances within the cell structure, vascular stasis with subsequent cell death, and thermal shock. These changes occur as part of a dynamic system and may be simultaneous. To better understand the pathophysiology of the biological systems, a description of the work of Rinfret11 follows. When the refrigerant or probe of the cryogenic system is placed in the target area, heat is extracted from the tissue surrounding it. As the major component of all living cells, water is the first of the substances affected. As the temperature of the tissue is reduced, the water in both the intracellular and extracellular spaces begins to freeze, first in the area of the refrigerant and then radiating outward as the temperature of the tissue reaches the freezing point. The rate at which heat is extracted will determine where the ice crystals form. If heat is removed at a relatively slow rate, ice crystals form in the extracellular space with water being extracted from the cell as freezing progresses. With the passage of intracellular water to extracellular spaces, a higher concen-
CRYOSURGERY
567
tration of electrolytes within the cells occurs. To establish an equilibrium, the electrolytes within the cells diffuse to the extracellular spaces and become concentrated in the interstices between the ice crystals. This eventually accounts for tremendous concentrations of electrolytes between the ice crystals, and as the concentration is increased, the electrolytes become lethal to the cells. As ice formation continues and crystals grow in size, the cells become dehydrated and their membranes are compressed eventually leading to their rupture and death. The distortion of cellular shape by the growing ice crystals and changes produced by electrolyte concentration produce unfavorable changes in the subcellular elements, contributing to the lethal effect produced. The description just given explains what transpires when heat is extracted slowly. When heat is extracted rapidly at a decrease of tens to hundreds of degrees per minute, ice crystals will form within the cell because the water does not have sufficient time to pass to the extracellular spaces. Factors such as cell wall permeability and vapor pressure within the cell play a role in determining this effect which is usually as toxic as that previously described. With rapid heat extraction, tiny ice crystals form within the cell and cause disruption of the subcellular elements such as denaturization of the buffer enzyme systems which leads to death of the cell. At the same time, the arterioles and capillaries become occluded, their cells damaged, and thrombosis results on thawing. This leads to vascular stasis and ischemia of the affected tissue further augmenting cellular death. Tht;rmal shock increases cellular destruction in cryosurgery, but the mechanism is not well understood. Not all cells in a given target area will be killed in one freeze, as many variables affect the amount of cellular destruction taking place. Of primary importance is the relationship between time, velocity, and temperature. It i!> generally agreed that a "rapid freeze-slow thaw" technique produces the optimal lethal effect, provided the temperature reaches a minimum of -20° C. Some cells in the target area will survive regardless of the technique used. This phenomenon is best explained by referring back to the mechanisms of cellular destruction. When the temperature of the tissue is dropped rapidly (greater than 10° per minute), the tissue becomes supercooled prior to ice formation, more rapidly around the source of refrigerant first and then radiating outward. After the tissue is supercooled, ice crystals form in the extracellular spaces first and with it, water is drawn from the cell. As ice crystal formation proceeds, a toxic concentration of electrolytes accumulates, and ice crystals form within the cell, subjecting it to subcellular damage and breakdown of the cellular membrane. Some of the cells in a given target area and especially around the periphery will escape the lethal effects by remaining supercooled. If an extremely rapid
568
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
drop in temperature occurs, ice crystals form in the cellular structures at the same rate as in the extracellular spaces. It is speculated that this may have a more lethal effect than that mechanism previously described and that the two mechanisms occur simultaneously. The rate of thaw is important in the destruction of tissue. If thawing is slow, the equilibrium between the cell and extracellular spaces cannot be re-established and death occurs. However, if thawing were to be hastened, an equilibrium could be re-established and these cells may survive, especially those that are supercooled. Those cells that have been frozen extremely rapidly where crystallization of ice occurs within the cells will then be more dependent on a slow thaw for destruction. The ice that forms rapidly in the cell will usually form much smaller crystals than those of a slow freeze. If thawed too rapidly, these crystals may disappear before subcellular elements have been disrupted. On the other hand, a slow thaw will bring about the so-called recrystallization effect in the cells. In this situation, when thawing is occurring, the smaller particles form large ice particles which disrupt cellular structures and result in death. In essence, the rate of freezing as well as the subsequent rate of thawing will dictate the size and location of ice crystals both intracellularly and extracellularly. It is on this explanation that the recommendations for freezing are based. 1. Rapid freeze. 2. Slow thaw- allow 20 to 30 minutes for tissue to be free of ice. 3. Repeat freeze twice to kill those cells that may have escaped the lethal effects of the first freeze. 4. Freeze 5 mm beyond the suspect border of the mass of tissue desired to be removed. 5. Always biopsy prior to and following completion of the healing process. 3, 4, s. u, 14
TYPES OF TISSUE AFFECTED Those tissues that do not contain fluid will escape destruction by freezing. In the freezing of bone, for example, the bone-forming elements containing fluid are destroyed, but the mineral and fibrous architecture of bone remain undamaged and eventually become revascularized and repopulated with bone-forming cells. The warming effect of the blood flowing through large vessels results in their escaping destruction by freezing. Nerve tissue is destroyed, but the fibrous sheath surrounding the nerve remains intact and maintains their integrity. 2
569
CRYOSURGERY
ADVANTAGES Since cryosurgery in veterinary medicine is in its early development, some of the advantages discussed will be from reports in human medicine. Even with limited experience, however, many of these have been found applicable to veterinary medicine. Cryosurgery has been preferable to conventional cold scalpel incision of tissue in certain diseases of the oral cavity and perianal area (neoplasms, fistulas, etc.) where unwanted destruction of tissue causes undesirable side effects. In perianal fistulas, for example, fecal continence is usually unaffected for any length of time, possibly because of the preservation of the caudal rectal nerve and anal sphincter during destruction of the fistulous tissue. Prevention of hemorrhage is more easily accomplished using cryosurgery than with sharp excision. Control of hemorrhage is difficult with certain oral neoplasms where small vessels in and around the bony structures of the maxilla are usually ligated. With necrosis by cryosurgery, the small vessels are thrombosed and occluded after freezing. A wide variety of probe adapters for the cryosurgery machine offers the advantage of removing unwanted diseased tissue from inaccessible areas by the conventional method without the use of timeconsuming exposure techniques. Rectal neoplasms, posterior oral and pharyngeal neoplasms are examples. Diseased tissue can also be removed easily in areas that do not heal well following surgical excision. Joint surfaces, interdigital spaces, and other areas where presspre necrosis on motion is likely to lead to wound dehiscence are some examples. Some form of anesthesia is required in most cases of deep cryosurgery, however, smaller neoplasms such as perianal adenomas and warts may be frozen with no anesthesia. This is particularly advantageous in the geriatric patient where a general anesthesia would create a surgical risk. However a local anesthetic infiltration is advised in these patients. The time required for cryosurgery versus the conventional method of surgical excision is greatly reduced. This may be particularly advantageous in a busy small animal practice. Several other advantages have been discussed in the human literature, however, veterinary medicine's limited experience has not allowed us to confirm these. Among those which require further investigation is the matter of safety both of the operator and the patient. Cryosurgery offers fewer hazards than radiation therapy. It also offers a certain degree of reversibility whereupon once the procedure is begun it can be stopped and reversed to a degree. 3 • 12 The possible prevention of dissemination of neoplastic tissue with rapid freezing and the development of antigens to the neoplastic processes offer a considerable advantage.
570
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
DISADVANTAGES Compared to the advantages, the disadvantages are few. One of the most important, however, is the manifestation of tissue necrosis following freezing. Pain does not seem to be a severe side effect after the first four to six hours because of the distribution of the nerve endings. However the exudate and necrosing process that follow still present undesirable effects. Prior to surgery, the pet owner must be advised of the malodorous exudate from the necrosed area for up to a period of two weeks following surgery. The swelling and erythema that follow immediately after thawing may be undesirable, especially if it involves the oral cavity and pharynx where it may obstruct the patient's airway. The freezing of hair-covered cutaneous lesions may result in the regrowth of different colored hair when the area is healed. 12
EQUIPMENT AND TECHNIQUE Cryosurgery begins with the selection of a refrigerant and a method for its application. The equipment and refrigerant chosen will dictate the cryosurgical technique to be used.
Refrigerant Many gases can be converted into their liquid state to serve as a refrigerant, however, only four or five are readily available for cryosurgical equipment. These gases and their respective boiling points are: Freon 12 -29.8° C. Freon 22 -41.0° C. Carbon dioxide -78.5° C. Nitrous oxide -89.5° C. Liquid nitrogen -195.6° C. The uses of these gases are dictated by their boiling point. As was stated earlier, the temperature of the target tissue must be reduced fairly rapidly to at least -20° C. Nitrous oxide and carbon dioxide will exceed the required tissue drop, however, their use will need to be restricted to much smaller areas of tissue destruction at any one freeze than with liquid nitrogen. These two refrigerants and their commercially available units have gained widespread acceptability in the fields of dermatology and gynecology in human medicine. It has been observed at The Animal Medical Center that the nitrous oxide unit* is not as acceptable as the liquid nitrogen unitt for destruction of large neoplasms or perianal fistulas. *Ohio Model 880, Ohio Medical Products, Lodi, New Jersey. tModel SP-5, Brymill Corp., Vernon, Connecticut.
571
CRYOSURGERY
Figure I. Pyrometer with nee dle placed at base o f neoplasm while ti ssue is being frozen. The tissue at the base of the neoplasm has reached a tempe ra ture o f - 20° C. as indicated on the pyrometer.
With its extremelv low boiling point, liquid nitrogen is probably the most commonly used refrigerant for cryosurgery. It is relatively safe to work with, none xplosive, inexpensive, and readily available. The necessary precautions must be adhered to in h a ndling any of the liquid gases.5
Skin Pyrometer needle
Neoplasm Cryoprobe
Figure 2. Diagrammatic illustration of placement of p yromete r needles with cryop robe inserte d in neoplasm.
572
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 3. Brymill SP5 cryosurgical uni t with an asso rtmen t of cryoprobes a nd spray applicators. (Courtesy of Brymill Corporation, Vernon, Connecticut.)
Equipment The demand or variety of indications in one's practice will determine the type of cryosurgical unit needed. Regardless of the type of unit used, a pyrometer (a tissue temperature indicator) will need to be purchased. This piece of equipment is necessary to monitor tissue that is to be destroyed (Fig. 1). The needle(s) of the p yrometer is placed at the depth of the tissue to be destroyed and within the tissue mass to ensure that the tissue r eaches a temperature of at least -200 C (Fig. 2).
573
CRYOSURGERY
The needles may also be placed in and around vital structures to prevent their destruction. There are a wide variety of cryosurgery machines available for each of the refrigerants mentioned. These range in price from a few hundred dollars to several thousands. Currently in use at The Animal Medical Center are the Ohio Model 880 and the Brymill Model SP-5 and Kryospray Model (Fig. 3). The Kryospray is a small liquid nitrogen unit that has the advantage of being relatively inexpensive, but it is somewhat limited in its use with large tissue masses. The SP-5 allows the veterinarian to accomplish any indication he may have for its use. Application of the Refrigerant The size and location of the target tissue will determine the method of applying the refrigerant, and these will be discussed later. One of the simplest forms is the application of liquid nitrogen directly to small masses such as warts or papillomas. A cotton swab is soaked in liquid nitrogen and directly applied to the small mass until it is frozen. Direct application by pouring liquid nitrogen onto the mass or into the cavity is another method of application. This method works well for applying liquid nitrogen to bone neoplasms where holes in the tumor may be trephined prior to applying the refrigerant. Direct application by pouring liquid nitrogen onto a skin neoplasm can also be utilized. Strict precautions should be taken to protect the periphery of the lesion so that normal tissue is not destroyed. This is best accomplished by the application of a thick layer of Vaseline around the periphery which will act as an insulator to the normal tissue. A tin or styrofoam container: with both ends removed and of a diameter equal to that of the tumor may be seated over the tumor and sealed to the skin with Vaseline to prevent spillage of liquid nitrogen on normal tissueP Other methods of application will require the use of a cryosurgical unit. A wide variety of cryoprobes or heat sinks are available for specific uses. Some of the more expensive ones have self-contained heaters for rapid tissue probe release following freezing. Direct application by spray is a very effective form of rapid freezing. Most units are equipped with a spray applicator of varying sized orifices. Direct application with spray under pressure is a most effective method of freezing large masses rapidly. INDICATIONS The indications for cryosurgery in veterinary medicine are many, with new applications continuously being discovered.L 7 • 12 Cryosurgery may be used as the primary surgical procedure or it may supplement conventional surgical techniques and therapeutic measures.
574
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
In most cases general anesthesia is required for doing cryosurgery. However sedatives and local anesthetics have been used successfully in geriatric patients, high anesthetic risk patients, exotic pets, and in docile animals with superficial lesions. Licking of cryosurgical sites by the animal can be prevented with wraps or protective devices over the head if necessary and seldom presents a problem. Postoperative infections are rare.
Oral and Pharyngeal Tumors Since resection by standard surgical techniques of most oral and pharyngeal tumors, such as squamous cell carcinomas, melanomas, fibrosarcomas, adamantinomas, tonsillar carcinomas, and osteosarcomas have many associated problems, cryosurgery offers many advantages. After a biopsy is taken, the appropriate sized probe tip is placed in the center of the mass lesion. Thermocouples are placed around the periphery of the mass to monitor tissue temperature and indicate when the freeze is adequate. The mass is frozen twice to at least -20" C. The surgery site is re-biopsied two to three weeks postoperatively. In extensive tumors, repeat freezings are done until the desired results are achieved. Among the beneficial results are relief of pain, improved general appearance, decreased odor, and the ease with which the patient can eat, swallow, and breathe. Tonsillectomies for neoplastic or non-neoplastic diseases can also be done cryosurgically.
Dermatological Surgery Papillomas, sebaceous cysts, lick granulomas, basal cell tumors, squamous cell carcinom!ls, mastocytomas, melanomas, hemangiomas, interdigital cysts, eosinophilic granulomas, and proliferative lesions in the external ear canal have all been successfully removed by cryosurgical techniques. If the lesion is small, the probe tip is placed in the center of the mass after a biopsy is taken. The spray attachment is used to apply liquid nitrogen directly on large or diffuse lesions. Precautions must be taken to prevent the liquid nitrogen from freezing normal skin around the periphery of the mass being frozen. Thermocouples are placed under the mass to monitor tissue temperature.
Nasal Tumors After routine exposure and currettage of the nasal cavity and turbinates for nasal tumors, islands of neoplastic cells often still remain from which the tumor can regrow. Liquid nitrogen is sprayed or poured into the open nasal cavity to destroy the remaining neoplastic cells. The soft palate and nares should be packed off with moistened sponges to prevent unwanted tissue necrosis in those areas. Thermocouples are placed submucosally against the hard palate on the oral side, as
CRYOSURG ERY
575
freezing of the hard palate would result in postoperative necrosis. Preoperative and postoperative corticosteroids will relieve facial edema which can persist for two to four days. Analgesics should also be used. Gauze packs which can be removed through the nares in 24 to 48 hours will be necessary in those cases where hemostasis is inadequate at the time of closure. Rectal Neoplasia and Polyps Rectal neoplasia has been approached cryosurgically with favorable results (Fig. 4). The appropriate cryoprobe is inserted through an anal speculum and is placed on the mucosal surface of a neoplastic mass or at the base of a polyp . Careful placeme nt of thermocouples submucosally to monitor tissue temperature is necessary to avoid freezing and necrosis of the rectal wall. The mass is frozen twice to -20° C. This approach is most successful in those polypoid growths where no invasion of submucosal structures is present. However, even if loca1ly invasive neoplasia is prese nt and thought to be inoperable , palliative therapy (relief of te nesmus, d ysch ezia and he matoch ezia) can usually be offe red for several months. In these cases, the freeze is as extensive as possible without freezing rectal muscle wall. Biopsies are taken at two to three week intervals, and the mass is refrozen if indicated by recurrence of clinical signs.
Figu re 4. A , Oral neoplasm in a feline being frozen with cryopr obe. Note ice formatio n (white area) arou nd perip her y o f cr yoprobe. B, Oral n eoplasm 14 d ays post freezing, sh owing extensive necrosis a nd sloughing of neoplastic tissue. C, Oral neoplasm 30 days post freezing. Area of slough has almost comple tely granulated a nd healed to stage where only a small cavity exists.
576
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN ]. WITHROW
Figure 5 . A, An undifferenti ated sarcoma o n the tip of the nose of a 15 yea r old male dog. B, Vaseline packed around base of neoplasm and h eld in place with gauze. With th e rmocoupl e in place, liquid nitrogen is directed onto the mass. C, Eight weeks post freezing , nose is disfigured, but two biopsies ta ken two weeks apart were both negative for neo pl as ia .
Perianal Fistulae Perianal fistulae are a prime indication for cryosurgery (Fig. 5). A liquid nitrogen spray is necessary for this procedure. Prior to freezing, a bilateral anal sacculectomy is performed and the extent of all fistulous tracts and diseased anal mucosa are bluntly exposed and explored. When completed, a fine liquid nitrogen spray is directed to the d epth of all fistulous tracts and diseased tissue. Even though portions of the perianal area may appear grossly normal in some cases, it too should be refrozen to avoid the possibility of future fistulae arising in the area. The fistulae , diseased anal mucosa, and perianal area are frozen twice to -20° C. The entire anal sphincter is not frozen . Hemorrhage is minimal. Thermocouples monitoring tissue temperature should be placed in the rectal wall and anal sphincter. The rectal wall is not to be frozen in an y case. Recurre nce of fistulae and the incidence of postoperative incontinence is low. In some cases, especially if the disease is severe, a repeat freezing at four to eight weeks may be necessary to eliminate remaining fistulae. The perianal area heals by granulation
CRYOSURGERY
577
in about eight to ten weeks. In some cases, an anoplasty for anal stenosis is necessary to remove superficial fibrous tissue that forms as the granulation bed is re-epithelializing.
Perianal Adenomas Removal of perianal adenomas is greatly simplified by cryosurgery (Fig. 6). A biopsy is taken from the center of the tumor. The appropriate
Figure 6 . A , Large infiltrating p erianal adenoma involving ventral half of perianal area. Neoplastic tissue invaded perianal tissue close to anal orifice. Size of neop lasm apparently .'i x 5 x 5 em. B, Three weeks post freezing using cryoprobe. Neoplastic tissue h as necrosed, and cavity has filled with granulation tissue. Area involved is approximately 2 em in diameter.
578
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 7. A, Ulcerated h ypertrophied caudal e nd organ of tail two weeks post freezing with cryoprobe using liquid nitrogen. Ulcerated hypertrophied tiss ue has sloughed and good granulation bed is present. Ep ithelialization is beginning. B, Lesions five weeks post freezing show tha t healing has ta ken place with epithelialization complete.
sized probe tip is the n inserted into the mass through the skin incision at the biopsy site. Each tumor is then frozen entirely in the routine manner. The mass that was frozen will necrose in 7 to 14 days, at which time a healthy granulation bed is present at the surgery site. Complete healing will be present in two to four weeks. Licking is minimal and infection h as not been a problem in over 75 cases done . Routine castration is done in conjunction with cryosurgery for the perianal adenomas. Caudal Tail Organs Hypertrophied and neoplastic caudal tail organs may be removed cryosurgically. If the mass is small, probe tips may be used . However in most cases the liquid nitrogen spray applied directly on the mass is preferred. Vaseline should be packed around the periphery of the mass to act as an insulator, thereby avoiding freezing n ormal skin on the lateral and ventral tail. Thermocou pies are also placed at the base of the mass. Th.e freeze must not include the vessels under the mass which run distally to the rest of the tail (Fig. 7) . Extremity Lesions When large extremity lesions such as locally invasive, nonmetastatic, soft tissue tumors are to be excised, difficulty is often e ncounte red when
579
CRYOSURGERY
primary skin closure is attempted because an inadequate amount of skin remains. These are excellent candidates for cryosurgery. Either liquid nitrogen spray or probe tips may be used depending primarily on the size of the mass. Vaseline is used to pack off and prevent freezing healthy skin around the periphery of the mass if the liquid nitrogen spray is used. Postoperative management is similar to any granulating wound. Healing takes three weeks to three months depending on the size of the mass. Refreezing at two to three week intervals is sometimes necessary (Fig. 8).
Ophthalmology Cryosurgery may be used by the veterinary ophthalmologist on patients with glaucoma. 9 • 10 The cryoprobe is placed on the sclera, 1 mm from the limbus, with one to three freezes made in each quadrant at temperatures of less than -20° C. for 15 to 60 seconds. The freeze is primarily over the sclera, but the periphery of the cornea will also be frozen. The effect of the freeze is to cause atrophy of the ciliary body. This then decreases the production of aqueous humor by the ciliary body, located just interior to the corneal scleral junction, and thereby reduces anterior chamber pressures. At this time the technique is reserved for patients unresponsive to medical management. More precise determination of the most effective duration and temperature of the freeze as well as critical evaluation of long-term follow-up is needed. Luxated lens may be removed with small disposable cryosurgical units. The tip of the cryoprobe is placed on the luxated lens. Cryoadhesions occur as the lens freezes to the probe tip, resulting in a very firm attachment. The lens is then extracted while cryoadhesion is being maintained. · If the lens is luxated anteriorly, preoperative miotics are used to trap the lens in the anterior chamber to facilitate removal. Caution should be exercised to prevent rupture of the hyaloid membrane and to avoid freezing the iris which will result in its atrophy. Use of the cryoprobe to remove posteriorly located lens is also recommended because of the hazards and difficulties associated with manipulation and surgical removal of a lens that has dropped into the vitreous. The lens is extracted using cryoadhesion in a similar manner to the anteriorly luxated lens. 6
Bone Tumors A possible future application of cryosurgery will include early detected bone tumors. Of particular interest are the nonaggressive, well circumscribed tumors or singular metastatic neoplasms. ACKNOWLEDGMENT
The authors gratefully acknowledge the editorial assistance of Miss Cynthia Fazzini in the preparation of this manuscript.
580
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 8. A . Large infi ltrating cutaneous n eoplasm involving lateral and ventral palmar surface of carpal joint. Neoplasm h as been frozen to estimated depth of tumor. Pyrometer needle is visible to monitor the temperature at base of tumor. B, Neop lastic tissue has slough ed and biopsy revealed no n eopla stic tissue present at biopsy site, 2112 weeks p ost freeze. Skin is beginning to close over surface from per ipherv. C, Gra nulation and epithelialization of wound surface almost complete at 4 weeks post freezing.
c
581
CRYOSURGERY
REFERENCES 1. Borthwick, R.: Cryosurgery in veterinary practice. A preliminary report. Vet. Rec., 86:683, 1970. 2. Borthwick, R.: Cryosurgery and its role in the treatment of malignant neoplasms. J. Small Anim. Pract., 13:369, 1972. 3. Cooper, I. S.: Cryogenic surgery: A new method of destruction or extirpation of benign or malignant tissue. New Engl.]. Med., 268:743, 1963. 4. Gonder, J., Jonas, W. A., and Smith, V.: Experimental prostate cryosurgery. Invest. Urol., 1:610, 1964. 5. Hall, F. A.: Advantages and limitations of liquid nitrogen in the therapy of skin lesions. Arch. Dermatol., 82:63/9, 1960. 6. Jensen, H. E.: Stereoscopic Atlas of Clinical Ophthalmology of Domestic Animals. St. Louis, C. V. Mosby Co., 1971. 7. Lane,]. G.: Practical Surgery: An introduction for small animal clinicians. J. Small Anim. Pract., 15:715, 1974. 8. Mazur, P.: Physical chemical factors underlying all injury in cryosurgical freezing. In Rand, R. W. (ed.): Cryosurgery. Springfield, Charles C Thomas, 1968. 9. McClean, ]. M., and Lincoff, H. A.: Cryosurgery of the ciliary body. Trans. Am. Ophthal. Soc., 62:385, 1964. 10. Polack, F. M., and Roetth, A.: Effect of freezing on the ciliary body (cyclocryotherapy). Invest. Ophthal., 3:164, 1964. 11. Rinfret, A. P.: Cryobiology: Some fundamentals in surgical context. In Rand, R. W. (ed.): Cryosurgery. Springfield, Charles C Thomas, I 968. 12. Withrow, S. .J., Greiner, T. P., and Liska, W. D.: Cryosurgery: Veterinary considerations. J. Am. Anim. Hosp. Assoc., 11: I 975. 13. Zacarian, S. A.: Cryosurgery for cutaneous carcinoma. Dermatol. Dig., 'i:49, 1970. 14. Zacarian, S. A.: Cancer of the eyelid: a cryosurgical approach. Ann. Ophthal., 4:473, 1972.
Department of Surgery The Animal Medical Center 510 East 62nd Street New York, New York 10021.
Cryosurgery Thomas P. Greiner, D.V.M.,* William D. Liska, D.V.M.,t and Stephen J. Withrow, D.V.M.t
"Be not the first by whom the new are tried, nor yet the last to lay the old aside." ALEXANDER POPE
Cryosurgery is defined as the therapeutic application of cold to freeze biological tissues, producing controlled physiologic inhibition or anatomic destruction.3 This concept is nothing new, as the beneficial effects of local cold to control hemorrhage and reduce swelling are mentioned in the writings of Hippocrates. However, James Arnott of England is credited as being the first to apply local cold as a therapeutic method for the treatment of cancer in 1845. Cryosurgery did not begin to receive widespread acceptance until the early 1960's when Cooper and Lee introduced a liquid nitrogen system whereby they were able to achieve probe temperature of -190° C. Shortly after the introduction of the system, the instrument was perfected and became commercially available. With this, its widespread usage in the fields of dermatology, neurosurgery, ophthalmology, gynecology, and proctology became available. Prior to its acceptance by the medical profession, however, its development received a major setback when some writings on "Observations on Prolonged Human Refrigeration" by Dr. Temple Fay were seized by the Nazis during World War II. In the minds of the public the Nazis' explorations of hypothermia without anesthesia in concentration camps were associated with their other atrocities and subsequently, any association with it was deplored for several years. From the Department of Surgery, The Animal Medical Center, New York, New York *Staff Surgeon tResident tResident Veterinary Clinics of North America- Vol. 5, No. 3, August 1975
565
566
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
Little has been done in the field of veterinary medicine with cryosurgery. Most reports on its usage in veterinary medicine have come from England with Borthwick, Lane, and Robins and Lane publishing reports on its usefulness in the treatment of perianal fistulas and certain neoplastic diseases. Currently in this country, several veterinary schools are investigating its efficacy. At The Animal Medical Center in New York City, its clinical applications are under investigation and so far, cryosurgery has been found to be useful in a number of naturally occurring diseases in small animals. 12
CRYOBIOLOGY
In veterinary medicine, as well as human medicine, cryosurgery is of interest .as another modality in its surgical armamentarium for the treatment of certain neoplastic and inflammatory diseases that do not respond well to or are difficult to treat with conventionaf methods. The central aim is to kill all cells in a diseased target area while simultaneously producing minimal tissue damage to normal surrounding tissue. As a surgical agent, cryosurgery is said to offer the advantages of combined anesthetic coagulant and destructive properties;. however, before discussing advantages, indications, instruments, and limitations, one should understand the changes that occur when biological systems undergo ice formation, and those changes associated with the destruction of cells. At least five basic mechanisms are involved in cellular destruction- dehydration and toxic concentration of electrolytes, crystallization and rupture of cellular membranes, denaturization of lipid protein substances within the cell structure, vascular stasis with subsequent cell death, and thermal shock. These changes occur as part of a dynamic system and may be simultaneous. To better understand the pathophysiology of the biological systems, a description of the work of Rinfret11 follows. When the refrigerant or probe of the cryogenic system is placed in the target area, heat is extracted from the tissue surrounding it. As the major component of all living cells, water is the first of the substances affected. As the temperature of the tissue is reduced, the water in both the intracellular and extracellular spaces begins to freeze, first in the area of the refrigerant and then radiating outward as the temperature of the tissue reaches the freezing point. The rate at which heat is extracted will determine where the ice crystals form. If heat is removed at a relatively slow rate, ice crystals form in the extracellular space with water being extracted from the cell as freezing progresses. With the passage of intracellular water to extracellular spaces, a higher concen-
CRYOSURGERY
567
tration of electrolytes within the cells occurs. To establish an equilibrium, the electrolytes within the cells diffuse to the extracellular spaces and become concentrated in the interstices between the ice crystals. This eventually accounts for tremendous concentrations of electrolytes between the ice crystals, and as the concentration is increased, the electrolytes become lethal to the cells. As ice formation continues and crystals grow in size, the cells become dehydrated and their membranes are compressed eventually leading to their rupture and death. The distortion of cellular shape by the growing ice crystals and changes produced by electrolyte concentration produce unfavorable changes in the subcellular elements, contributing to the lethal effect produced. The description just given explains what transpires when heat is extracted slowly. When heat is extracted rapidly at a decrease of tens to hundreds of degrees per minute, ice crystals will form within the cell because the water does not have sufficient time to pass to the extracellular spaces. Factors such as cell wall permeability and vapor pressure within the cell play a role in determining this effect which is usually as toxic as that previously described. With rapid heat extraction, tiny ice crystals form within the cell and cause disruption of the subcellular elements such as denaturization of the buffer enzyme systems which leads to death of the cell. At the same time, the arterioles and capillaries become occluded, their cells damaged, and thrombosis results on thawing. This leads to vascular stasis and ischemia of the affected tissue further augmenting cellular death. Tht;rmal shock increases cellular destruction in cryosurgery, but the mechanism is not well understood. Not all cells in a given target area will be killed in one freeze, as many variables affect the amount of cellular destruction taking place. Of primary importance is the relationship between time, velocity, and temperature. It i!> generally agreed that a "rapid freeze-slow thaw" technique produces the optimal lethal effect, provided the temperature reaches a minimum of -20° C. Some cells in the target area will survive regardless of the technique used. This phenomenon is best explained by referring back to the mechanisms of cellular destruction. When the temperature of the tissue is dropped rapidly (greater than 10° per minute), the tissue becomes supercooled prior to ice formation, more rapidly around the source of refrigerant first and then radiating outward. After the tissue is supercooled, ice crystals form in the extracellular spaces first and with it, water is drawn from the cell. As ice crystal formation proceeds, a toxic concentration of electrolytes accumulates, and ice crystals form within the cell, subjecting it to subcellular damage and breakdown of the cellular membrane. Some of the cells in a given target area and especially around the periphery will escape the lethal effects by remaining supercooled. If an extremely rapid
568
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
drop in temperature occurs, ice crystals form in the cellular structures at the same rate as in the extracellular spaces. It is speculated that this may have a more lethal effect than that mechanism previously described and that the two mechanisms occur simultaneously. The rate of thaw is important in the destruction of tissue. If thawing is slow, the equilibrium between the cell and extracellular spaces cannot be re-established and death occurs. However, if thawing were to be hastened, an equilibrium could be re-established and these cells may survive, especially those that are supercooled. Those cells that have been frozen extremely rapidly where crystallization of ice occurs within the cells will then be more dependent on a slow thaw for destruction. The ice that forms rapidly in the cell will usually form much smaller crystals than those of a slow freeze. If thawed too rapidly, these crystals may disappear before subcellular elements have been disrupted. On the other hand, a slow thaw will bring about the so-called recrystallization effect in the cells. In this situation, when thawing is occurring, the smaller particles form large ice particles which disrupt cellular structures and result in death. In essence, the rate of freezing as well as the subsequent rate of thawing will dictate the size and location of ice crystals both intracellularly and extracellularly. It is on this explanation that the recommendations for freezing are based. 1. Rapid freeze. 2. Slow thaw- allow 20 to 30 minutes for tissue to be free of ice. 3. Repeat freeze twice to kill those cells that may have escaped the lethal effects of the first freeze. 4. Freeze 5 mm beyond the suspect border of the mass of tissue desired to be removed. 5. Always biopsy prior to and following completion of the healing process. 3, 4, s. u, 14
TYPES OF TISSUE AFFECTED Those tissues that do not contain fluid will escape destruction by freezing. In the freezing of bone, for example, the bone-forming elements containing fluid are destroyed, but the mineral and fibrous architecture of bone remain undamaged and eventually become revascularized and repopulated with bone-forming cells. The warming effect of the blood flowing through large vessels results in their escaping destruction by freezing. Nerve tissue is destroyed, but the fibrous sheath surrounding the nerve remains intact and maintains their integrity. 2
569
CRYOSURGERY
ADVANTAGES Since cryosurgery in veterinary medicine is in its early development, some of the advantages discussed will be from reports in human medicine. Even with limited experience, however, many of these have been found applicable to veterinary medicine. Cryosurgery has been preferable to conventional cold scalpel incision of tissue in certain diseases of the oral cavity and perianal area (neoplasms, fistulas, etc.) where unwanted destruction of tissue causes undesirable side effects. In perianal fistulas, for example, fecal continence is usually unaffected for any length of time, possibly because of the preservation of the caudal rectal nerve and anal sphincter during destruction of the fistulous tissue. Prevention of hemorrhage is more easily accomplished using cryosurgery than with sharp excision. Control of hemorrhage is difficult with certain oral neoplasms where small vessels in and around the bony structures of the maxilla are usually ligated. With necrosis by cryosurgery, the small vessels are thrombosed and occluded after freezing. A wide variety of probe adapters for the cryosurgery machine offers the advantage of removing unwanted diseased tissue from inaccessible areas by the conventional method without the use of timeconsuming exposure techniques. Rectal neoplasms, posterior oral and pharyngeal neoplasms are examples. Diseased tissue can also be removed easily in areas that do not heal well following surgical excision. Joint surfaces, interdigital spaces, and other areas where presspre necrosis on motion is likely to lead to wound dehiscence are some examples. Some form of anesthesia is required in most cases of deep cryosurgery, however, smaller neoplasms such as perianal adenomas and warts may be frozen with no anesthesia. This is particularly advantageous in the geriatric patient where a general anesthesia would create a surgical risk. However a local anesthetic infiltration is advised in these patients. The time required for cryosurgery versus the conventional method of surgical excision is greatly reduced. This may be particularly advantageous in a busy small animal practice. Several other advantages have been discussed in the human literature, however, veterinary medicine's limited experience has not allowed us to confirm these. Among those which require further investigation is the matter of safety both of the operator and the patient. Cryosurgery offers fewer hazards than radiation therapy. It also offers a certain degree of reversibility whereupon once the procedure is begun it can be stopped and reversed to a degree. 3 • 12 The possible prevention of dissemination of neoplastic tissue with rapid freezing and the development of antigens to the neoplastic processes offer a considerable advantage.
570
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
DISADVANTAGES Compared to the advantages, the disadvantages are few. One of the most important, however, is the manifestation of tissue necrosis following freezing. Pain does not seem to be a severe side effect after the first four to six hours because of the distribution of the nerve endings. However the exudate and necrosing process that follow still present undesirable effects. Prior to surgery, the pet owner must be advised of the malodorous exudate from the necrosed area for up to a period of two weeks following surgery. The swelling and erythema that follow immediately after thawing may be undesirable, especially if it involves the oral cavity and pharynx where it may obstruct the patient's airway. The freezing of hair-covered cutaneous lesions may result in the regrowth of different colored hair when the area is healed. 12
EQUIPMENT AND TECHNIQUE Cryosurgery begins with the selection of a refrigerant and a method for its application. The equipment and refrigerant chosen will dictate the cryosurgical technique to be used.
Refrigerant Many gases can be converted into their liquid state to serve as a refrigerant, however, only four or five are readily available for cryosurgical equipment. These gases and their respective boiling points are: Freon 12 -29.8° C. Freon 22 -41.0° C. Carbon dioxide -78.5° C. Nitrous oxide -89.5° C. Liquid nitrogen -195.6° C. The uses of these gases are dictated by their boiling point. As was stated earlier, the temperature of the target tissue must be reduced fairly rapidly to at least -20° C. Nitrous oxide and carbon dioxide will exceed the required tissue drop, however, their use will need to be restricted to much smaller areas of tissue destruction at any one freeze than with liquid nitrogen. These two refrigerants and their commercially available units have gained widespread acceptability in the fields of dermatology and gynecology in human medicine. It has been observed at The Animal Medical Center that the nitrous oxide unit* is not as acceptable as the liquid nitrogen unitt for destruction of large neoplasms or perianal fistulas. *Ohio Model 880, Ohio Medical Products, Lodi, New Jersey. tModel SP-5, Brymill Corp., Vernon, Connecticut.
571
CRYOSURGERY
Figure I. Pyrometer with nee dle placed at base o f neoplasm while ti ssue is being frozen. The tissue at the base of the neoplasm has reached a tempe ra ture o f - 20° C. as indicated on the pyrometer.
With its extremelv low boiling point, liquid nitrogen is probably the most commonly used refrigerant for cryosurgery. It is relatively safe to work with, none xplosive, inexpensive, and readily available. The necessary precautions must be adhered to in h a ndling any of the liquid gases.5
Skin Pyrometer needle
Neoplasm Cryoprobe
Figure 2. Diagrammatic illustration of placement of p yromete r needles with cryop robe inserte d in neoplasm.
572
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 3. Brymill SP5 cryosurgical uni t with an asso rtmen t of cryoprobes a nd spray applicators. (Courtesy of Brymill Corporation, Vernon, Connecticut.)
Equipment The demand or variety of indications in one's practice will determine the type of cryosurgical unit needed. Regardless of the type of unit used, a pyrometer (a tissue temperature indicator) will need to be purchased. This piece of equipment is necessary to monitor tissue that is to be destroyed (Fig. 1). The needle(s) of the p yrometer is placed at the depth of the tissue to be destroyed and within the tissue mass to ensure that the tissue r eaches a temperature of at least -200 C (Fig. 2).
573
CRYOSURGERY
The needles may also be placed in and around vital structures to prevent their destruction. There are a wide variety of cryosurgery machines available for each of the refrigerants mentioned. These range in price from a few hundred dollars to several thousands. Currently in use at The Animal Medical Center are the Ohio Model 880 and the Brymill Model SP-5 and Kryospray Model (Fig. 3). The Kryospray is a small liquid nitrogen unit that has the advantage of being relatively inexpensive, but it is somewhat limited in its use with large tissue masses. The SP-5 allows the veterinarian to accomplish any indication he may have for its use. Application of the Refrigerant The size and location of the target tissue will determine the method of applying the refrigerant, and these will be discussed later. One of the simplest forms is the application of liquid nitrogen directly to small masses such as warts or papillomas. A cotton swab is soaked in liquid nitrogen and directly applied to the small mass until it is frozen. Direct application by pouring liquid nitrogen onto the mass or into the cavity is another method of application. This method works well for applying liquid nitrogen to bone neoplasms where holes in the tumor may be trephined prior to applying the refrigerant. Direct application by pouring liquid nitrogen onto a skin neoplasm can also be utilized. Strict precautions should be taken to protect the periphery of the lesion so that normal tissue is not destroyed. This is best accomplished by the application of a thick layer of Vaseline around the periphery which will act as an insulator to the normal tissue. A tin or styrofoam container: with both ends removed and of a diameter equal to that of the tumor may be seated over the tumor and sealed to the skin with Vaseline to prevent spillage of liquid nitrogen on normal tissueP Other methods of application will require the use of a cryosurgical unit. A wide variety of cryoprobes or heat sinks are available for specific uses. Some of the more expensive ones have self-contained heaters for rapid tissue probe release following freezing. Direct application by spray is a very effective form of rapid freezing. Most units are equipped with a spray applicator of varying sized orifices. Direct application with spray under pressure is a most effective method of freezing large masses rapidly. INDICATIONS The indications for cryosurgery in veterinary medicine are many, with new applications continuously being discovered.L 7 • 12 Cryosurgery may be used as the primary surgical procedure or it may supplement conventional surgical techniques and therapeutic measures.
574
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
J.
WITHROW
In most cases general anesthesia is required for doing cryosurgery. However sedatives and local anesthetics have been used successfully in geriatric patients, high anesthetic risk patients, exotic pets, and in docile animals with superficial lesions. Licking of cryosurgical sites by the animal can be prevented with wraps or protective devices over the head if necessary and seldom presents a problem. Postoperative infections are rare.
Oral and Pharyngeal Tumors Since resection by standard surgical techniques of most oral and pharyngeal tumors, such as squamous cell carcinomas, melanomas, fibrosarcomas, adamantinomas, tonsillar carcinomas, and osteosarcomas have many associated problems, cryosurgery offers many advantages. After a biopsy is taken, the appropriate sized probe tip is placed in the center of the mass lesion. Thermocouples are placed around the periphery of the mass to monitor tissue temperature and indicate when the freeze is adequate. The mass is frozen twice to at least -20" C. The surgery site is re-biopsied two to three weeks postoperatively. In extensive tumors, repeat freezings are done until the desired results are achieved. Among the beneficial results are relief of pain, improved general appearance, decreased odor, and the ease with which the patient can eat, swallow, and breathe. Tonsillectomies for neoplastic or non-neoplastic diseases can also be done cryosurgically.
Dermatological Surgery Papillomas, sebaceous cysts, lick granulomas, basal cell tumors, squamous cell carcinom!ls, mastocytomas, melanomas, hemangiomas, interdigital cysts, eosinophilic granulomas, and proliferative lesions in the external ear canal have all been successfully removed by cryosurgical techniques. If the lesion is small, the probe tip is placed in the center of the mass after a biopsy is taken. The spray attachment is used to apply liquid nitrogen directly on large or diffuse lesions. Precautions must be taken to prevent the liquid nitrogen from freezing normal skin around the periphery of the mass being frozen. Thermocouples are placed under the mass to monitor tissue temperature.
Nasal Tumors After routine exposure and currettage of the nasal cavity and turbinates for nasal tumors, islands of neoplastic cells often still remain from which the tumor can regrow. Liquid nitrogen is sprayed or poured into the open nasal cavity to destroy the remaining neoplastic cells. The soft palate and nares should be packed off with moistened sponges to prevent unwanted tissue necrosis in those areas. Thermocouples are placed submucosally against the hard palate on the oral side, as
CRYOSURG ERY
575
freezing of the hard palate would result in postoperative necrosis. Preoperative and postoperative corticosteroids will relieve facial edema which can persist for two to four days. Analgesics should also be used. Gauze packs which can be removed through the nares in 24 to 48 hours will be necessary in those cases where hemostasis is inadequate at the time of closure. Rectal Neoplasia and Polyps Rectal neoplasia has been approached cryosurgically with favorable results (Fig. 4). The appropriate cryoprobe is inserted through an anal speculum and is placed on the mucosal surface of a neoplastic mass or at the base of a polyp . Careful placeme nt of thermocouples submucosally to monitor tissue temperature is necessary to avoid freezing and necrosis of the rectal wall. The mass is frozen twice to -20° C. This approach is most successful in those polypoid growths where no invasion of submucosal structures is present. However, even if loca1ly invasive neoplasia is prese nt and thought to be inoperable , palliative therapy (relief of te nesmus, d ysch ezia and he matoch ezia) can usually be offe red for several months. In these cases, the freeze is as extensive as possible without freezing rectal muscle wall. Biopsies are taken at two to three week intervals, and the mass is refrozen if indicated by recurrence of clinical signs.
Figu re 4. A , Oral neoplasm in a feline being frozen with cryopr obe. Note ice formatio n (white area) arou nd perip her y o f cr yoprobe. B, Oral n eoplasm 14 d ays post freezing, sh owing extensive necrosis a nd sloughing of neoplastic tissue. C, Oral neoplasm 30 days post freezing. Area of slough has almost comple tely granulated a nd healed to stage where only a small cavity exists.
576
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN ]. WITHROW
Figure 5 . A, An undifferenti ated sarcoma o n the tip of the nose of a 15 yea r old male dog. B, Vaseline packed around base of neoplasm and h eld in place with gauze. With th e rmocoupl e in place, liquid nitrogen is directed onto the mass. C, Eight weeks post freezing , nose is disfigured, but two biopsies ta ken two weeks apart were both negative for neo pl as ia .
Perianal Fistulae Perianal fistulae are a prime indication for cryosurgery (Fig. 5). A liquid nitrogen spray is necessary for this procedure. Prior to freezing, a bilateral anal sacculectomy is performed and the extent of all fistulous tracts and diseased anal mucosa are bluntly exposed and explored. When completed, a fine liquid nitrogen spray is directed to the d epth of all fistulous tracts and diseased tissue. Even though portions of the perianal area may appear grossly normal in some cases, it too should be refrozen to avoid the possibility of future fistulae arising in the area. The fistulae , diseased anal mucosa, and perianal area are frozen twice to -20° C. The entire anal sphincter is not frozen . Hemorrhage is minimal. Thermocouples monitoring tissue temperature should be placed in the rectal wall and anal sphincter. The rectal wall is not to be frozen in an y case. Recurre nce of fistulae and the incidence of postoperative incontinence is low. In some cases, especially if the disease is severe, a repeat freezing at four to eight weeks may be necessary to eliminate remaining fistulae. The perianal area heals by granulation
CRYOSURGERY
577
in about eight to ten weeks. In some cases, an anoplasty for anal stenosis is necessary to remove superficial fibrous tissue that forms as the granulation bed is re-epithelializing.
Perianal Adenomas Removal of perianal adenomas is greatly simplified by cryosurgery (Fig. 6). A biopsy is taken from the center of the tumor. The appropriate
Figure 6 . A , Large infiltrating p erianal adenoma involving ventral half of perianal area. Neoplastic tissue invaded perianal tissue close to anal orifice. Size of neop lasm apparently .'i x 5 x 5 em. B, Three weeks post freezing using cryoprobe. Neoplastic tissue h as necrosed, and cavity has filled with granulation tissue. Area involved is approximately 2 em in diameter.
578
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 7. A, Ulcerated h ypertrophied caudal e nd organ of tail two weeks post freezing with cryoprobe using liquid nitrogen. Ulcerated hypertrophied tiss ue has sloughed and good granulation bed is present. Ep ithelialization is beginning. B, Lesions five weeks post freezing show tha t healing has ta ken place with epithelialization complete.
sized probe tip is the n inserted into the mass through the skin incision at the biopsy site. Each tumor is then frozen entirely in the routine manner. The mass that was frozen will necrose in 7 to 14 days, at which time a healthy granulation bed is present at the surgery site. Complete healing will be present in two to four weeks. Licking is minimal and infection h as not been a problem in over 75 cases done . Routine castration is done in conjunction with cryosurgery for the perianal adenomas. Caudal Tail Organs Hypertrophied and neoplastic caudal tail organs may be removed cryosurgically. If the mass is small, probe tips may be used . However in most cases the liquid nitrogen spray applied directly on the mass is preferred. Vaseline should be packed around the periphery of the mass to act as an insulator, thereby avoiding freezing n ormal skin on the lateral and ventral tail. Thermocou pies are also placed at the base of the mass. Th.e freeze must not include the vessels under the mass which run distally to the rest of the tail (Fig. 7) . Extremity Lesions When large extremity lesions such as locally invasive, nonmetastatic, soft tissue tumors are to be excised, difficulty is often e ncounte red when
579
CRYOSURGERY
primary skin closure is attempted because an inadequate amount of skin remains. These are excellent candidates for cryosurgery. Either liquid nitrogen spray or probe tips may be used depending primarily on the size of the mass. Vaseline is used to pack off and prevent freezing healthy skin around the periphery of the mass if the liquid nitrogen spray is used. Postoperative management is similar to any granulating wound. Healing takes three weeks to three months depending on the size of the mass. Refreezing at two to three week intervals is sometimes necessary (Fig. 8).
Ophthalmology Cryosurgery may be used by the veterinary ophthalmologist on patients with glaucoma. 9 • 10 The cryoprobe is placed on the sclera, 1 mm from the limbus, with one to three freezes made in each quadrant at temperatures of less than -20° C. for 15 to 60 seconds. The freeze is primarily over the sclera, but the periphery of the cornea will also be frozen. The effect of the freeze is to cause atrophy of the ciliary body. This then decreases the production of aqueous humor by the ciliary body, located just interior to the corneal scleral junction, and thereby reduces anterior chamber pressures. At this time the technique is reserved for patients unresponsive to medical management. More precise determination of the most effective duration and temperature of the freeze as well as critical evaluation of long-term follow-up is needed. Luxated lens may be removed with small disposable cryosurgical units. The tip of the cryoprobe is placed on the luxated lens. Cryoadhesions occur as the lens freezes to the probe tip, resulting in a very firm attachment. The lens is then extracted while cryoadhesion is being maintained. · If the lens is luxated anteriorly, preoperative miotics are used to trap the lens in the anterior chamber to facilitate removal. Caution should be exercised to prevent rupture of the hyaloid membrane and to avoid freezing the iris which will result in its atrophy. Use of the cryoprobe to remove posteriorly located lens is also recommended because of the hazards and difficulties associated with manipulation and surgical removal of a lens that has dropped into the vitreous. The lens is extracted using cryoadhesion in a similar manner to the anteriorly luxated lens. 6
Bone Tumors A possible future application of cryosurgery will include early detected bone tumors. Of particular interest are the nonaggressive, well circumscribed tumors or singular metastatic neoplasms. ACKNOWLEDGMENT
The authors gratefully acknowledge the editorial assistance of Miss Cynthia Fazzini in the preparation of this manuscript.
580
THOMAS
P.
GREINER, WILLIAM
D.
LISKA, AND STEPHEN
j.
WITHROW
Figure 8. A . Large infi ltrating cutaneous n eoplasm involving lateral and ventral palmar surface of carpal joint. Neoplasm h as been frozen to estimated depth of tumor. Pyrometer needle is visible to monitor the temperature at base of tumor. B, Neop lastic tissue has slough ed and biopsy revealed no n eopla stic tissue present at biopsy site, 2112 weeks p ost freeze. Skin is beginning to close over surface from per ipherv. C, Gra nulation and epithelialization of wound surface almost complete at 4 weeks post freezing.
c
581
CRYOSURGERY
REFERENCES 1. Borthwick, R.: Cryosurgery in veterinary practice. A preliminary report. Vet. Rec., 86:683, 1970. 2. Borthwick, R.: Cryosurgery and its role in the treatment of malignant neoplasms. J. Small Anim. Pract., 13:369, 1972. 3. Cooper, I. S.: Cryogenic surgery: A new method of destruction or extirpation of benign or malignant tissue. New Engl.]. Med., 268:743, 1963. 4. Gonder, J., Jonas, W. A., and Smith, V.: Experimental prostate cryosurgery. Invest. Urol., 1:610, 1964. 5. Hall, F. A.: Advantages and limitations of liquid nitrogen in the therapy of skin lesions. Arch. Dermatol., 82:63/9, 1960. 6. Jensen, H. E.: Stereoscopic Atlas of Clinical Ophthalmology of Domestic Animals. St. Louis, C. V. Mosby Co., 1971. 7. Lane,]. G.: Practical Surgery: An introduction for small animal clinicians. J. Small Anim. Pract., 15:715, 1974. 8. Mazur, P.: Physical chemical factors underlying all injury in cryosurgical freezing. In Rand, R. W. (ed.): Cryosurgery. Springfield, Charles C Thomas, 1968. 9. McClean, ]. M., and Lincoff, H. A.: Cryosurgery of the ciliary body. Trans. Am. Ophthal. Soc., 62:385, 1964. 10. Polack, F. M., and Roetth, A.: Effect of freezing on the ciliary body (cyclocryotherapy). Invest. Ophthal., 3:164, 1964. 11. Rinfret, A. P.: Cryobiology: Some fundamentals in surgical context. In Rand, R. W. (ed.): Cryosurgery. Springfield, Charles C Thomas, I 968. 12. Withrow, S. .J., Greiner, T. P., and Liska, W. D.: Cryosurgery: Veterinary considerations. J. Am. Anim. Hosp. Assoc., 11: I 975. 13. Zacarian, S. A.: Cryosurgery for cutaneous carcinoma. Dermatol. Dig., 'i:49, 1970. 14. Zacarian, S. A.: Cancer of the eyelid: a cryosurgical approach. Ann. Ophthal., 4:473, 1972.
Department of Surgery The Animal Medical Center 510 East 62nd Street New York, New York 10021.
