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[Sequential MRI and CT monitoring in cryosurgery--an experimental study in rats].

Cryosurgery is one of treatments of cancer, such as carcinomas of the face, oral cavity, prostate, breast, rectum and liver. But the method of cryosurgery seemed to be not yet completely established. The most important problem in this procedure is to define the extent of the cryolesion. But the trial with MRI and CT has not been reported. The purpose of this study is to investigate whether the image diagnosis such as Magnetic Resonance (MR) and CT is useful for the determination of the region during and after cryosurgery. The animal experiments were performed using 13 Wistar rats with inoculated Walker 256 cancer on both sides of femoral regions subcutaneously in the concentration of 1 million cells. After 7 days, cryosurgery was done by contacting for 15 sec with the absorbent cotton ball dipped in liquid nitrogen to the surface of right femoral tumor 3 to 6 times. The left side of tumor was intact. MRI was performed with a 0.1 Tesla ASAHI MR Mark-J and CT images were obtained using GE 9800. From the freezing to thawing, LF image (Low Flip Angle gradient echo image of Tr = 100 msec, Te = 18 msec, 60 degrees of flip angle) of MR and plain CT were taken every one minute. After thawing is over, SE image of Tr = 1500 msec, Te = 90 msec, IR images of Tr = 1200 msec, Td = 400 msec, and plain and contrast enhanced CT were carried out. Two and 7 days after cryosurgery, LF, SE and IR images of MR and CT with and without contrast medium were obtained with corresponding pathological examinations. The frozen cryolesion was of no signal intensity on the LF MR image and hypodensity on plain CT. Identification of cryolesion became possible during the cryosurgery. The cryolesion immediately after thawing showed higher intensity on the SE and LF images and hypodensity on enhanced CT. Therefore, the extent of cryosurgery can be diagnosed easily by these methods during and immediately after cryosurgery. In the follow-up studies after cryosurgery, the histological changes such as necrosis or tissue reaction were well represented by MRI and enhanced CT, but insufficiently by plain CT. From these experimental results, it may be concluded that MRI and CT are useful for monitoring the process of cryosurgery during and after the procedure.

Animals

Combined chemotherapy and cryosurgery for oral cancer.

The inadequacies of traditional methods for control of advanced oral carcinomas at their sites of origin prompted evaluation of combined chemotherapy and cryosurgery in seventy-three patients treated since 1969. Our experience with thirty-nine unlikely candidates for salvage by other therapy is the subject of this report. The majority had recurrent disease after other therapy. The observed morbidity potential of combined chemotherapy and cryosurgery with earlier experience led to abbreviations and refinements of method that are described and consist mainly of the following. (1) A two day postcryosurgical infusion (intra-arterial) of 5-fluorouracil (1 gm per twenty-four hours, or less) in lieu of methotrexate, the systemic toxicity and therapeutic efficacy of which seem less predictable with cryosurgery. (2) Electrosurgical subtotal tumor resection at the time of initial cryosurgery to reduce swelling and magnitude of in situ tissue slough. (3) Use of a flexible copper mesh cryoprobe that enhances feasibility of in-depth wide field cryosurgery. (4) Systematic use of multiple marginal wound biopsies as a principal guide to repetitive cryosurgery or other therapeutic adjunct selection. A special warning that available toxicologic data for independent drug therapy may not be applicable in patients after cryosurgery is given. Current experience indicates that negative biopsy after such combined therapy may be 85 per cent reliable in foretelling lesion outcome. Among the thirty-nine patients reported, twenty remain alive from six months to six years, only two of whom have clinically evident recurrent disease. If such could be reasonably accomplished, comparative evaluation of single methods should precede attempts to combine two or more modes of therapy. Since neither chemotherapy nor cryosurgery, as known today, can eliminate nodal metastases, each must be regarded as potentially adjunctive to other methods for achieving the ultimate goal of a cancer-free patient. It is within this context that combined chemotherapy and cryosurgery have been applied to unfavorable candidates for cure with seemingly worthwhile gains. Potential applicability for patients with less formidable stages of disease cannot be extrapolated from this experience. Large scale controlled clinical trials must provide the ultimately conclusive test of efficacy for such combined forms of therapy before decisive revision of traditional standards of practice might result.

Adult

Cryosurgery for ocular and periocular lesions.

This preliminary report suggests that cryosurgery has a definite place in the management of certain external periocular and ocular problems. Cryosurgery for basal- or squamous-cell carcinoma of the lid is easily performed, gives excellent cosmetic results, and has a low recurrence rate. It is not recommended for lesions involving the fornices, nor for sclerotic or morphea-type basal-cell carcinomas. Tumor recurrences following radiation, surgery, or cryosurgery can still be retreated with cryosurgery. To date, there is no evidence that cryosurgery at temperatures above --40 degrees C causes damage to the lacrimal outflow system. Cryosurgery is of value in the management of trichiasis, reactive lymphoid hyperplasia, spider hemangioma, molluscum contagiosum, and conjunctival dysplasia. Cryotherapy for management of intraepithelial epithelioma and squamous-cell carcinoma of the conjunctiva and cornea is still under investigation. Cryosurgery will, in our opinion, become the treatment of choice for basal- and squamous-cell carcinomas of the eyelids. The 96% cure rate with one treatment for these lesions reported here is artificially high since the follow-up period is too short. However, retreatment with cryosurgery is a simple 10- min outpatient procedure which is certainly not the case with recurrences after other forms of therapy.

Animals

Cryosurgery in the treatment of cancer.

The range of application of cryosurgical techniques to the treatment of cancer is widely diversified and slowly increasing in scope. From these, one may reach the general conclusion that cryosurgical techniques are a standard method of treatment, competitive with other methods of therapy, in cancer located in some sites. For cancers located in other sites, cryosurgery is only useful as an end resort in selected patients. In some areas, especially in the viscera, cryosurgical techniques are only in developmental stages. Cryosurgery is most useful in easily accessible areas of the body. The results of the treatment of most carcinomas of the skin with cryosurgical techniques are as good as any other method of therapy. In carcinoma involving skin, cryosurgery has a special advantage in those situations when malignant tissue overlies bone. Cryosurgery is also useful in the management of dysplastic disease or carcinoma in situ, principally in the oral cavity and the uterine cervix. These applications are sufficiently valuable to be included in the textbooks concerned with those areas. Invasive cancer in other accessible sites, such as the oral cavity or the rectum, can be cured by cryosurgery, but the reports in the medical literature have not led to general use of the technique or descriptions of the technique in textbooks, except for occasional brief mention. Nevertheless, patients who are at high risk for surgical treatment because of coagulopathy or severe cardiopulmonary disease are appropriate candidates for the use of cryosurgical techniques. In the oral cavity, the possibility of preserving the bony structure is an attractive feature that maintains interest in cryosurgery. Unfortunately, there are no control studies to assist in the judgment of merit and in many cited reports, it is not easy to determine the survival rate or compare results with conventional therapy. In these sites, freezing techniques are more often used to achieve palliation of distressing symptoms by tumor bulk reduction, especially when little else can be done, and under these conditions, chemotherapy and radiotherapy are also commonly used. In less accessible sites, which generally require endoscopic or surgical exposure, cryosurgery is not often used. The treatment of carcinoma of the prostate gland by cryosurgery remains viable because of continued interest in the potentiation of immunologic defenses against carcinoma. This possible benefit is most evident in experimental tumors, but clinical evidence of benefit is not as clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Cryosurgery

The role of cryosurgery in external ocular and periocular disease.

This preliminary report suggests that cryosurgery has a definite place in the management of certain external periocular and ocular problems. Cryosurgery for basal or squamous cell carcinoma of the lid is easily performed, gives excellent cosmetic results, and has a low recurrence rate. It is not recommended for lesions involving the fornices, or sclerotic and morphea-type basal cell carcinomas. Tumor recurrences following radiation, surgery, or cryosurgery can still be retreated with cryosurgery. To date, there is no evidence that cryosurgery at temperatures above -40 C causes damage to the lacrimal outflow system. Cryosurgery is of value in the management of trichiasis, reactive lymphoid hyperplasia, spider hemangioma, molluscum contagiosum, and conjunctival dysplasia. Cryotherapy for management of intraepithelial epithelioma and squamous cell carcinoma of the conjunctiva and cornea is still under investigation. Cryosurgery will, in our opinion, become the treatment of choice for basal and squamous cell carcinomas of the eyelids. The 96% cure rate with one treatment for these lesions reported here is artificially high since the follow-up period is too short. However, retreatment with cryosurgery is a simple ten-minute outpatient procedure which is certainly not the case with recurrences after other forms of therapy.

Basal Cell Carcinoma

Characterisation of suppressor cells generated following cryosurgery of an HSV-2-induced fibrosarcoma.

Cryosurgery of a primary HSV-2-induced hamster fibrosarcoma resulted in the generation of a population of suppressor cells. These cells were detectable in the spleen 1-10 days post-cryosurgery by their ability to suppress the proliferation of immunocompetent splenic T-lymphocytes following exposure to concanavalin A (Con A). The spleens of tumour-bearing (t.b.) animals which received cryosurgery 3 days previously displayed gross splenomegaly due to the generation of large numbers of highly proliferative erythroblasts. The erythroblast cells were unlikely to be the source of suppression since time course studies have demonstrated the presence of suppressor cells before and after their appearance in the spleen. The erythroblasts therefore probably reflected a response by the host to regenerate the erythrocytes lost during surgery and their presence was independent of the appearance of suppressor cells. Characterisation of the suppressor cell has revealed it to be non-adherent and esterase negative making it unlikely to be of macrophage (MO) lineage. This was confirmed by the ability of splenic MOs from day 3 t.b. cryosurgery-treated animals to completely restore Con A-dependent T-lymphocyte proliferation following MO depletion. As nylonwool column-eluted cells are able to suppress Con A-dependent T-lymphocyte proliferation, it seemed unlikely that B-lymphocytes play a role in cryosurgery-induced immunosuppression. These findings suggest that cryosurgery of a t.b. animal results in the generation of a population of T-lymphocytes capable of suppressing Con A-dependent T-lymphocyte proliferation, and infers that these cells contribute to the inferior prognosis following cryosurgery as compared to excision of a metastatic tumour.

Animals

Current progress in cryosurgery.

The 4-day sessions of the Eighth Annual Meeting of the American College of Cryosurgery in New Orleans, February 18-21, 1988, provided an intense overview of the position of cryosurgery in modern day medical practice. The variety of speakers demonstrated that interest in the therapeutic technique of cryosurgery remains high and that usage is greater, more diversified, and more selective than in past years. Emphasis at the meeting was placed on the selective use of cryosurgery, that is, defining the terms under which the physician would choose between diverse methods of local therapy, such as excision, electrosurgery, laser surgery, and cryosurgery. Most of the presentations were oriented clinically with emphasis on the results of cryosurgery. This brief report is intended to mention the important new developments in cryosurgery and to focus on some of the issues and needs that affect the future of the technique.

Cryosurgery