minimally invasive cryosurgery—technological advances

CRYOBIOLOGY 34, 373–384 (1997)ARTICLE NO. CY972017

Minimally Invasive Cryosurgery—Technological Advances1

John Baust,*,† Andrew A. Gage,†,‡ Hewu Ma,† and Chao-Min Zhang†*Center for Cryobiological Research State University of New York, Binghamton, New York 13902;

†Cryomedical Sciences Inc., Rockville, Maryland 20850; and ‡Department of Surgery,State University of New York, Buffalo, New York 14214, U.S.A.

The technological advances which have caused renewed interest in cryosurgery are the development ofintraoperative ultrasound to monitor the therapeutic process and the development of new cryosurgicalequipment designed to use supercooled liquid nitrogen. The thin, highly efficient probes, available inseveral sizes, can be placed in diseased sites via endoscopy or percutaneously in minimally invasiveprocedures. The manner of use is to place the probe in the desired location in the diseased tissue withultrasound guidance. If required by the size or location of the tumor, as many as five probes can beinserted and cooled to 01957C simultaneously. The process of freezing is monitored by ultrasound whichdisplays a hypoechoic (dark) image when the tissue if frozen. Rapid freezing, slow thawing, and repetitionof the freeze/thaw cycle are standard features of technique. Clinical applications which have becomecommon in the past 4 years include the treatment of prostatic cancer and liver tumors. The cases selectedfor cryosurgery are generally those for which no conventional treatment is possible. However, especiallyin prostatic cancer, the operative morbidity is so low and the results of therapy are sufficiently good inthe short term to merit consideration of use in earlier stages of the disease. Diverse tumors in other sites,such as the brain, bronchus, bone, pancreas, kidney, and uterus, have also been treated in small numbersby cryosurgery. Judging from this experience, further expansion in the use of cryosurgical techniquesseems certain. q 1997 Academic Press

Cryosurgery, a method of treating disease The scope of the renewed interest in cryo-surgery can best be appreciated by a brief re-by the use of tissue-freezing temperatures,view of status of cryosurgery in the 1980s.which for many years has been practicallyFollowing the development of automatedignored by surgeons, is currently enjoying acryosurgical apparatus cooled by liquid nitro-renaissance. The scope of renewed interest isgen early in the 1960s, cryosurgical tech-focused on the treatment of visceral disease,niques received clinical trial for the treatmentan area of use which was not practical untilof a wide variety of diseases, including cancer,recently. However, in the past few years, in-in the diverse specialties of medicine. Manytraoperative ultrasound imaging has permit-early reports were enthusiastic about the po-ted monitoring of the frozen tissue and cryo-tential usefulness of cryosurgery, but thesurgical apparatus has improved substantially1970s represented a period of reassessment ofin design, yielding greater therapeutic effi-its value. Some uses of cryosurgery, such ascacy and extending the range of use of cryo-the treatment of benign prostatic hypertrophy,surgery. Endoscopic and percutaneous cryo-fell into disuse. Other uses, such as the treat-surgery for visceral disease is now possible.ment of cutaneous and gynecologic diseases,This review will focus on these advances andwere accepted by physicians and achievedthe consequent new frontiers of therapy usingtextbook status. In general, however, cryosur-cryosurgery.gery remained a technique of minor surgicalimportance, useful at times to treat some can-cers which presented difficult problems in sur-gical management, perhaps especially in thoseReceived October 1, 1996; accepted February 12, 1997.patients in need of palliation of distressing1 Presented at the 33rd Annual Meeting of the Society

for Cryobiology, Indianapolis, Indiana, August 21, 1996. symptoms caused by cancers (7).

3730011-2240/97 $25.00Copyright q 1997 by Academic PressAll rights of reproduction in any form reserved.

AID CRYO 2017 / a90a$$$$$1 06-03-97 00:19:09 cryoas AP: CRYO

374 BAUST ET AL.

The several advantages of cryosurgery were standing of the nature of the cryosurgical in-jury was achieved.obvious in these early years of clinical use. In

its purest form, no tissue was excised, butMECHANISMS OF CRYODESTRUCTIONrather the diseased tissue was frozen in situ

with techniques appropriate to the nature, size, The destructive effects of cryosurgery arerelated to a host of factors, most of which areand location of the lesion. Then the devitalized

tissue was allowed to slough and the wound well known from previous studies on cryo-preservation and frostbite, but some of whichallowed to heal. Avoidance of excision greatly

reduced the need for anesthesia and practically are characteristic of the sudden severe changesproduced by freezing tissue in situ. Twoeliminated the chance of bleeding from the

tissue. The procedure, commonly performed mechanisms of injury, one immediate and theother delayed, are associated with cryosur-with surface freezing techniques, was simple,

easy, and quick. Morbidity was low, hospital- gery. The immediate mechanism of injury isthe deleterious effect of freezing on the cells.ization was short, and the cost reduced. The

wound healed slowly but favorably because As the cooling of the tissue falls to a fewdegrees below zero, ice crystals form in thethe collagen structure of the tissue remained

as a framework for repair. The preservation extracellular spaces and in the microvascula-ture, removing water from the biologic systemof tissue structure was especially advanta-

geous in bone disease. Attractive also was the and exposing the cells to progressively moredeleterious hyperosmotic conditions. Rapidpossibility of a cryoimmunologic response;

that is, the repeated local freezing of a tumor freezing produces intracellular ice crystalswhich are certainly lethal. In the warming cy-might elicit an immunologic response which

would affect tumor in distant untreated sites. cle, the recrystallization or fusion of small icecrystals to form large crystals is another po-The limitations of cryosurgery were also

obvious. Biologic tissue resisted freezing in- tential destructive feature. As tissue thaws, thesecond mechanism of injury becomes opera-jury. Large tumors, especially if irregularly

shaped, were difficult to destroy. Monitoring tive. The circulation is restored to the pre-viously frozen area for 15–30 min, but duringof the freezing process was not easy. The use

of thermocouples to measure tissue tempera- this time, the failure of the microcirculationis progressive. Endothelial cells are destroyed,ture provided valuable information, but ther-

mocouple use was limited in applicability in the blood vessel walls become porous, edemadevelops, and platelet aggregation leads tomany locations.

Treatment was provided only to accessible thrombosis and vascular occlusion (20, 27,28). With failure of the circulation, tissuelesions and surface treatment techniques dom-

inated. The lack of imaging technology ham- death is certain and the resultant injury is asharply circumscribed necrosis.pered the potential for use in visceral disease.

These limitations accounted in large part for Cryosurgery is performed in a manner thatseeks to maximize cell injury. The basic tech-the lack of acceptance in surgical practice. An

additional factor of substantial importance is nique requires fast freezing to tissue tempera-tures considered certainly lethal for cells, slowthe fact that cryosurgery did not provide a

surgical specimen for examination by the pa- thawing, and repetition of the freeze/thaw cy-cle. The freezing rate is as fast as possible.thologist. Surgical training programs did not

teach cryosurgical techniques. Finally, a mea- Therefore, the cryosurgical probe should beas cold as possible in order to facilitate heatsure of uncertainty about optimal technique

existed. Some of these limitations persist, but exchange. At the point of contact with a cryo-surgical probe, the freezing rate is rapid, com-in the years of relative disuse, before the re-

cent technologic advances, a better under- monly more than 607C/min. As time passes


375CRYOSURGERY—TECHNOLOGICAL ADVANCES

and tissue cooling continues, freezing extends mal efficiency of this type of apparatus is low(10). Cryogens which have been used in cryo-further into the tissue. The more distal from

the probe, the slower the tissue cooling rate. surgery include liquid nitrogen (01967C), ni-trous oxide (089.57C), solid carbon dioxideTherefore, the frozen area is commonly a con-

tinuum of various freezing rates, from fast to (078.57C), argon (0187.57C), and the diversefluorinated hydrocarbons which provide aslow. Fortunately, even slow freezing rates

have lethal effects. range of freezing temperatures warmer thanthe other agents just cited. However, no otherCare must be taken to achieve tissue tem-

peratures certainly lethal for cells. Cell death agent has the freezing capacity of liquid nitro-gen—only liquid nitrogen should be used inoccurs over a wide range of freezing tempera-

tures due to crystallization of water and to the treatment of invasive cancer. The lessercryogenic agents have a measure of use-progressive physicochemical changes. Cer-

tainly a substantial degree of damage occurs fulness for the treatment of inflammatory orbenign neoplastic disease, for which lesser de-in the 020 to 0307C range. However, experi-

mental and clinical reports have shown that grees of freezing will suffice. The use of thelesser cryogens should be avoided when at-temperatures in the 040 to 0507C range must

be produced to be certain of cell death, which tempting to ablate bulky tumors.Liquid nitrogen has been used in severalis of critical importance in the treatment of

cancer (9, 16). The repetition of the freeze/ ways, i.e., the cryogen has been sprayed orpoured on tissue or used to cool metal probesthaw cycle carries the cells again through the

same deleterious effects, including a longer during application to the tissue. The spray orpour techniques were applicable only to sur-hypothermic period, and adds a greater degree

of certainty to the destructive process. face disease but the probes had a greater versa-tility and were used to a limited extent for

CRYOSURGICAL INSTRUMENTS the freezing of some deeply located lesions.Nevertheless, after the original apparatus andModern cryosurgical apparatus, cooled by

liquid nitrogen (01967C), used with vacuum- probes were designed in the 1960s, few designchanges were made in the succeeding 25insulated probes, was introduced into clinical

practice by Cooper early in the 1960s (5). years. The equipment was engineered to pro-vide probe tip temperatures of 01607C as aThis stimulated the development of a wide

range of devices using diverse cryogens and result of change of phase (liquid to gas) in theprobe tip. Probes of small diameter (5 mm),methods of refrigeration. In addition to Coo-

per’s apparatus, in which probe cooling was providing a tip temperature of about 01257C,had even less freezing capacity. Clearly, in-produced by a change in phase of liquid nitro-

gen, i.e., liquid to gaseous state, other appara- creased tissue freezing capability was needed.tus featured probe cooling by the expansion

ADVANCED CRYOSURGICAL TECHNOLOGYof a compressed gas after passage through arestricting orifice (Joule–Thomson effect) or The significant advance in cryosurgical

equipment technology came with the develop-by thermoelectric cooling (Peltier effect). Inthe Joule–Thomson apparatus, refrigerants ment of a technique to use liquid nitrogen

supercooled to about 02097C in newly de-such as nitrous oxide, carbon dioxide, andargon can be used. Though this type of appa- signed equipment (3). The supercooling was

achieved by passing pressurized liquid nitro-ratus has some attractive features, such asquick response time, its freezing capacity is gen though a heat exchanger immersed in a

liquid nitrogen chamber (02097C) held un-limited. The thermoelectric method cools bypassing a direct current through dissimilar der vacuum. The supercold liquid nitrogen

was circulated through the probes. With newmetal junctions, i.e., thermocouples. The ther-


376 BAUST ET AL.

FIG. 1. Flow diagram of the major components of the CMS AccuProbe System. The subcooling heat-exchange system provides liquid nitrogen flow to disposable cryoprobes. Liquid nitrogen is retrieved afterdelivery.

improved probe designs, the liquid nitrogen desired size and shape, as is required in pros-tatic cryoablation (Fig. 4).remained liquid in the probe and was largely

recovered on its return to the console (Figs. 1 The new apparatus features the use of dis-posable probes, a choice of design which in-and 2). The temperature of the surface of the

probe commonly ranged between 0165 and sures consistent, high quality probe perfor-mance. In contrast, reusable probes are subject01957C, depending on the diameter of the

probe, in clinical use of this apparatus. This to sporadic performance and slow deteriora-tion of freezing capability as time passes.means that the gradient in temperature be-

tween tissue and probe was greater than ever Probes are available in diameters, lengths, andshapes to suit their use in diverse locationsprovided by any cryosurgical apparatus. The

steeper the temperature gradient, the more ef- (Fig. 5). This diversity includes probes suit-able for endoscopic and laparoscopic use andficient is the freezing capability. Frozen vol-

umes of about 180 cc, 7 cm in diameter, can for percutaneous placement. In general, thelarger the probe, the greater the capability tobe produced by a single 8-mm probe in about

20 min with this apparatus (Fig. 3). This is freeze a volume of tissue in certain time. How-ever, the performance of a 3.4-mm probe issubstantially greater freezing capacity than

provided by any other technology. As many almost as good as that of the 8-mm probe ifboth are used at the same temperature andas five probes can be cooled simultaneously

in this apparatus. The use of multiple probes under same heat load (Fig. 6). Even the newlydeveloped 2-mm diameter probes have excel-permits the overlapping of frozen areas in the

treatment of large cancers and provides a lent freezing capability.In clinical practice, the manner of use is tomethod of sculpting the frozen tissue to the



vation was possible. Knowing the performancecharacteristics of various probes permittedtreatment with reasonable accuracy in manysites, especially on body surfaces. Neverthe-less clinical judgment was subject to errors,especially since the temperature of frozen tis-sue cannot be determined from its appearance.Therefore clinical judgment must be confirmedor supplemented by monitoring the freezingprocess.

Thermocouples

Early in the development of cryosurgery,tissue temperature was measured by theplacement of needle-mounted thermocouplesin appropriate places, i.e., at the border of alesion. The thermosensor was placed in posi-tion which was critical to evaluation of theextent of freezing, especially in the normaltissue at an appropriate distance from the bor-der of the tumor. For example, in a liver tu-FIG. 2. Flow schematic of a small-diameter cryoprobe

capable of circulating LN2 within the tip’s boiling mor, this position was 1 cm from the edge ofchamber. the tumor because that distance was the usu-

ally recommended margin for surgical exci-sion. Then, in freezing, care was taken to

insert one or more probes into the target tissue, achieve lethal temperatures at that site. Thecool each probe in sequence while multiple accurate positioning of the thermosensor wasprobes are placed in position, and then apply of obvious great importance. A 1-mm varia-maximum cooling power so that tissue freez- tion in thermocouple placement in the tissueing occurs as fast as possible. The freezing is represented about 10 to 157C difference inallowed to continue until all of the diseased

the temperature recorded in the usual cryosur-tissue is enclosed in the volume of frozen tis-

gical freeze/thaw cycles (8). A thermocouplesue. In the treatment of cancer, the freezing

measured the temperature only in the site inis allowed to extend into the normal tissue inwhich it was placed, so that inferences wereorder to increase the chance of cure. The vol-made about the temperature elsewhere. How-ume of tissue frozen to lethal temperaturesever, knowing the temperature of the probemust be equal to that volume which wouldtip and the temperature wherever measuredhave been removed if excisional surgery hadin the frozen tissue permitted an estimationbeen the treatment. After thawing, the processof the temperature elsewhere in the area, sinceof freezing is repeated.the growth of the frozen volume of tissue

MONITORING CRYOSURGERY was symmetrical (altered, of course, by theproximity of large blood vessels). The use ofUntil recent years, the principal guidance inmultiple thermocouples increased the infor-cryosurgical procedure was clinical judge-mation available and enhanced the control ofment. In general, most cryosurgery was per-

formed in accessible areas where direct obser- the freezing process.


378 BAUST ET AL.

FIG. 3. Temperature profiles at indicated distances from probe surface, isotherms, produced by an 8-mmprobe cooled to 01957C in 30 min.

UltrasoundA major technological advance in cryosur-

gical technique and in the breadth of its appli-cability to the treatment of disease was madepossible by the use of ultrasound imaging. Thechanging ultrasonic image during freezing ofthe liver and prostate and its application tocryosurgery were described in the 1980s (17,18). The frozen tissue was hypoechoic, so theultrasonic image was black (Fig. 7). The edgeof the frozen tissue was hyperechoic and ap-peared as a bright line. As freezing continuedand the volume of frozen tissue increased, thehyperechoic rim moved away from the probeleaving the dark zone behind it. Therefore theprocess of tissue freezing was observed duringthe cryosurgical procedure by a real-time im-age of the frozen volume of tissue. Since ultra-sound provided a more global view of the fro-zen tissue than did thermosensors, the imagingtechnique has come into wide use for monitor-ing the freeze/thaw cycle and has stimulatedthe renewal of interest in visceral cryosurgeryFIG. 4. The CMS Accuprobe System Model 450, a five-

probe device. in the 1990s.



FIG. 5. Two of the various sizes and shapes of CMS cryoprobes used in endoscopic or laparoscopicsurgery.

Experience with ultrasound monitoring in logic studies of the prostate of the dog, ob-served the ultrasonic image during freezinghepatic and prostatic cryosurgery is now sub-

stantial. Littrup and his co-workers, in histo- and described irreversible tissue damage as


380 BAUST ET AL.

FIG. 6. Performances of the 3.4- and 8-mm probes at the same temperature.

occurring ‘‘immediately behind the echogenic ing of the prostate in relation to the rectal wallwas accurate. However ultrasound has someleading edge of the iceball rim’’ (11). In their

canine model of prostatic cryotherapy, ultra- shortcomings. Much of the frozen volume isobscured by distortions and reflections of thesonic monitoring of the progression of freez-



FIG. 7. Real-time image of frozen tissue during prostate cryosurgery.

image. Sonography does not provide an image The correlation between tissue temperatureand the ultrasound image is of considerablebeyond the near edge of the ice. There is com-

plete posterior acoustic shadowing which importance because a decision must be madeon the appropriate tissue temperature goal andleaves the physician ‘‘blind to anything be-

yond the near ice surface’’ (24). Some com- some knowledge of the distribution of the iso-therms in the ultrasonic image is necessary.pensation for this limitation can be obtained

by viewing the frozen volume from another The advancing edge of the freezing tissue,which appears on the ultrasonic image as aangle. In addition, one cannot determine the

temperature of frozen tissue from its ultra- hyperechoic border, is about 07C. The inneredge of the rim, which is 3–4 mm inside ofsonic appearance. The tissue temperature must

be estimated from knowledge of probe tem- the leading edge, has been stated to be about0207C (24). The location of the 0407C iso-perature, knowledge of the performance of the

cryoprobe in terms of growth of ice formation therm is critical for effective therapy. Obser-vations on gradients of temperature in frozenaround it in relation to time, and the fact that

the hyperechoic rim is at about 07C. The tem- volume of test solutions or histologic materi-als are relevant. In extensive tests in the past,perature gradient between the probe surface

and the border of the frozen zone is steep. using an 8-mm probe (model PR-5; Frigitron-


382 BAUST ET AL.

ics, Shelton, CT) at 01607C in 5- and 10- Prostate Cancermin freezing cycles, the 0407C isotherm was

The new experience with cryosurgery forcommonly about 60% of the distance from the prostatic cancer is only about 4 years old. Theprobe surface or about 8 mm inside of the ice technique features the placement of five thinboundary 2 cm from the probe (1, 6). The cryosurgical probes percutaneously throughlocation of this isotherm varied somewhat the perineum into separate areas of the pros-with the rate of cooling the tissue. A rapid tate under ultrasound guidance. Then the pros-cooling rate moved the isotherm toward the tate is frozen while the process monitoredperiphery. Our recent tests with high-effi- by ultrasound. After thawing, the punctureciency modern probes cooled to 01957C has wounds are closed and the patient is releasedplaced the critically important 0407C iso- in 1 or 2 days (2, 4). All stages of the prostatictherm 5–6 mm inside of the border of the cancer have been treated by cryosurgery, butfrozen zone in frozen volumes 6–7 cm in di- the procedure is best suited for those patientsameter. In clinical treatment, this means that whose disease is confined to the gland. Cryo-the frozen border as seen on the ultrasound surgery may be offered to those patients whoimage must be well outside the apparent bor- are not medically fit for the operative risksder of the tumor. The physician should move associated with radical prostatectomy. Cryo-in the direction of aggressive freezing tech- surgery is also practical in those patientsnique whenever possible in the treatment of whose disease was not cured by irradiation.cancer. The results of prostatic cryoablation have

To further improve the control of cryosur- been excellent. Morbidity has been low andgery by real time imaging, several new direc- prostatic biopsies are negative for residual dis-tions are being taken. Three-dimensional ease in about 95% of patients 1 year after

therapy. Almost every current study has dem-transrectal ultrasound use in cryosurgery isonstrated satisfactory short-term results offeasible (19). Computerized tomography hascryoablation for prostatic cancer and has sug-been used to monitor cryosurgery, althoughgested that long-term results will be competi-images at frequent intervals are required. How-tive with alternative, well-established methodsever, computerized tomography can show theof therapy (2, 4).entire cross section of the frozen area (23).

Magnetic resonance imaging is also in devel-Liver Tumorsopment as a monitoring method (22). The limi-

tations of these techniques in providing ther- Surgeons have used cryosurgery to treat pri-mal information during cryosurgery have led mary and metastatic tumors of the liver. Mostsome physicians to endorse the combined use experience has been with metastatic cancer ofof thermosensors and ultrasonography. the liver, originating in the colon. The cases

selected for cryosurgery are those deemed un-resectable by conventional excisional therapy,NEW CLINICAL APPLICATIONSwhether because of multiple lesions, location

The technologic advances, featuring the use near major blood vessels, or severe associatedof supercooled liquid nitrogen to cool high- disease. The technique requires the placementefficiency, small-diameter probes well suited of one or more probes into the lesion underto endoscopic or percutaneous placement, ultrasound guidance. The tissue is cooled untilcoupled with ultrasound imaging of the freez- the entire tumor and an adjacent margin ofing process, has opened or reopened new areas apparently normal tissue is enclosed in frozenof application of cryosurgery, especially in the volume. Then the tissue is thawed and frozen

again. Short-term results with the treatment oftreatment of tumors.



THE FUTUREliver tumors have been excellent, that is, acomplete response in 25% of patients may be The improvement in imaging technologyexpected (21, 26, 29). Considering that these and further development of cryosurgical appa-patients were considered surgically unresect- ratus, both of which are already close to appli-able, this salvage rate is impressive. cation to clinical practice, will further broaden

the usefulness of cryosurgical techniques. TheBone Tumors impact on surgical practice will be comple-

Benign bone tumors, such as giant cell tu- mentary as the cryosurgical techniques findmors and ameloblastoma, which are locally use in situations in which conventional exci-aggressive and prone to recurrence after curet- sional surgery cannot be used, including thosetage, have been successfully treated by cryo- patients who have severe associated disease.surgery. Aneurysmal bone cysts and other be- However, the advantageous features of cryo-nign bone lesions have been treated success- surgery may make the techniques competitivefully also. The technique is to curette the with excisional surgery in many situations.tumor and then freeze the lining of the resul- The costs associated with cryosurgical proce-tant cavity. In this way, cryosurgery extends dures are usually much less than the costs ofthe curative potential of the conventional cu- excisional surgery. Cryosurgery is well suitedrettage. Depending on the size and location of to ambulatory surgical settings.the tumor, the bone cavity is reinforced with Cryosurgery should be regarded as one ofbone grafts or acrylic cement. The healing pe- the tools that a physician may choose to treatriod is long but avoidance of unnecessary bone a variety of neoplastic and nonneoplastic dis-removal is a substantial benefit (13, 14, 25). eases. As with any tool, it requires a physician

skilled in its use and with the judgment toBronchial Tumors choose the right tool for the task at hand.

Interest in the cryosurgical treatment of tra- When used in the correct way for the appro-cheobronchial obstruction due to benign and priate indications, the techniques may helpmalignant tumors has been evident since the solve some difficult problems in therapy.mid 1980s. Nitrous oxide-cooled probes are

REFERENCESmost useful in this location. Most commonly,

1. Augustinowicz, S., and Gage, A. Temperature andthe treatment is palliative and intended to re- cooling rate variations during cryosurgical probelieve obstruction to the airway, which is testing. Int. J. Refrig. 8, 198–208 (1985).

2. Bahn, D., Lee, F., Solomon, H., Gontina, H., Klion-achieved in the majority of patients (12, 15).sky, E., and Lee, F., Jr. Prostate cancer: US guidedThe technique is considered safe, relativelypercutaneous cryoablation. Radiology 194, 551–easy to perform, and has few complications.556 (1995).

3. Baust, J., and Chang, Z. Underlying mechanisms ofTumors in Other Sitesdamage and new concepts in cryosurgical instru-mentation. In ‘‘Cryosurgery. Mechanism and Ap-Tumors of the kidney, the pancreas, theplications,’’ pp. 21–36. International Inst. Re-breast, and other organs are being treated byfrigeration, Paris, France, 1995.cryosurgery at the present time, but this expe-

4. Cohen, J., Miller, R., Rooker, G., and Shuman, B.rience is just beginning as surgeons continue Cryosurgical ablation of the prostate: two yearto develop techniques for diverse sites. Cryo- prostate specific antigen and biopsy results. Urol-

ogy 47, 395–401 (1996).surgical techniques are also under develop-5. Cooper, I. Cryogenic surgery: A new method of de-ment for benign tumors, such as leiomyomas

struction or extirpation of benign or malignant tis-of the uterus, and for nonneoplastic disease,sue. N. Engl. J. Med. 268, 743–749 (1963).

such as endometrial dysfunction. From these 6. Gage, A. Correlation of electrical impedance andearly trials, it is clear that the scope of cryosur- temperature in tissue during freezing. Cryobiology

16, 56–62 (1979).gery will continue to expand.


384 BAUST ET AL.

7. Gage, A. Cryosurgery in the treatment of cancer. terfield, B. US characteristics of frozen prostate.Radiology 168, 629–631 (1988).Surg. Gynecol. Obstet. 174, 73–92 (1992).

19. Onik, G., Donnelly, D., and Fenster, A. Three-dimen-8. Gage, A., Caruana, J., and Garamy, G. A comparisonsional monitored cryosurgery in a prostate phan-of instrument methods of monitoring freezing intom. J. Ultrasound Med. 16, 267–270 (1996).cryosurgery. J. Dermatol. Surg. Oncol. 9, 209–

20. Rabb, J., Renaud, M., Brandt, P., and Witt, C. Effect214 (1983).of freezing and thawing on the microcirculation9. Gage, A., Caruana, J., and Montes, M. Critical tem-and capillary endothelium of the hamster cheek

perature for skin necrosis in experimental cryosur-pouch. Cryobiology 11, 508–518 (1974).

gery. Cryobiology 19, 273–282 (1982).21. Ravikumar, T., Buenaventura, A., Salem, R., and

10. Garamy, G. Engineering aspects of cryosurgery. In Dandrea, B. Intraoperative ultrasonography of‘‘Cryosurgery’’ (R. Rand, A. Rinfret, and H. von liver—Detection of occult liver tumors and treat-Leden, Eds.), pp. 92–132. Thomas, Springfield, ment by cryosurgery. Cancer Detect. Prevent. 18,IL, 1968. 131–138 (1994).

11. Littrup, P., Monti, J., Mody, A., et al. Prostatic cryo- 22. Rubinsky, B., Gilbert, J., Onik, G., Roos, M., Wong,S., and Brennan, K. Monitoring cryosurgery intherapy: Ultrasonic and pathologic correlation inthe brain and in the prostate with proton NMR.the canine model. Urology 44, 175–184 (1994).Cryobiology 30: 191–199 (1993).12. Maiwand, M., and Homasson, J. Cryotherapy for tra-

23. Saliken, J., McKinnon, J., and Gray, R. CT for moni-cheobronchial disorders. Int. Pulmonol. 16, 427–toring cryosurgery. Am. J. Roentgenol. 166, 853–443 (1995).855 (1996).

13. Malawer, M., and Dunham, W. Cryosurgery and24. Saliken, J., Cohen, J., Miller, R., and Rothert, M.

acrylic cementation as surgical adjuncts in theLaboratory evaluation of ice formation around a 3

treatment of aggressive (benign) bone tumors: mm Accuprobe. Cryobiology 32, 285–295 (1995).Analysis of 25 patients below the age of 21. Clin. 25. Salmassy, D., and Pogrel, A. Liquid nitrogen cryosur-Orthop. 262, 42–57 (1991). gery and immediate bone grafting in the manage-

14. Marcove, R., Sheth, D., Brien, E., Hovos, A., and ment of aggressive primary jaw lesions. J. Oral.Healy, J. Conservative surgery for giant cell tu- Maxillofac. Surg. 53: 784–790 (1995).mors of the sacrum. Cancer 74, 1253–1260 26. Weaver, M., Atkinson, D., and Zemel, R. Hepatic(1994). cryosurgery in treating colorectal metastases. Can-

cer 76, 210–214 (1995).15. Mathur, P., Wolf, K., Busk, M., Briete, M., and Datz-27. Whittaker, D. Vascular responses in the oral mucosaman. Fiberoptic bronchoscopic cryosurgery in the

following cryosurgery. J. Periodont. Res. 1, 55–management of tracheobronchial obstruction.63 (1977).Chest 110, 718–723 (1996).

28. Zacarian, B., Stone, D., and Clater, M. Effects of16. Neel, H., Ketcham, A., and Hammond, W. Requisitescryogenic temperatures on the microcirculation in

for successful cryogenic surgery of cancer. Arch.the Golden hamster cheek pouch. Cryobiology 7,

Surg. 102, 45–48 (1971). 27–39 (1970).17. Onik, G., Gilbert, J., Hoddick, W., Filly, R., Callen, 29. Zhou, X. D., Tang, Zy., Yu, Y-Q., Weng, J-M., Ma,

P., Rubinsky, B., and Farrel, L. Sonographic moni- Z-C., Zhang, B-H., and Zheng, Y-X. The role oftoring of hepatic cryosurgery in an experimental cryosurgery in the treatment of hepatic cancer: aanimal model. AJR 144, 1043–1047 (1985). report of 113 cases. J. Cancer Res. Clin. Oncol.

120, 100–102 (1993).18. Onik, G., Cobb, C., Cohen, J., Zabkar, J., and Por-


minimally invasive cryosurgery—technological advances

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