Perilesional Protection Prior to Cryosurgery of Advanced Cancer

Treating advanced external cancers or bulky neoplastic masses should follow three rules: efficient protection around the lesions; the use of a thick spray of liquid nitrogen, supplied by an apparatus with high pressure through a nozzle, measuring 1 mm in diameter; and accurate control of the advance of the ice front on the surface and in the interior of the mass.

Alternatively to the thick spray of liquid nitrogen some authors use multiple penetrating probes with an apparatus that has a high capability to quickly remove heat from the neoplastic tissues (56, 77). The difficulty in freezing large and bulky cancers is to obtain cancericidal temperatures in the entire tumoral mass. If a single non-penetrating cryoprobe is used, the progress of the freezing decelerates; a few minutes later, the freezing stops, having attained about 2 cm in depth; only rarely is it useful to freeze for more than 10 minutes (12).

When feasible, prior reduction of the tumoral mass – so-called “debulking” – is a good technique that considerably improves the cure rate (29, 35-37, 41-44). With really large and advanced cancers that are very irrigated, particularly if they are friable, non-solid and fungating, debulking by conventional surgery can be difficult or even impossible, due to the difficulty in controlling hemorrhage. In these cases, debulking must be done by cryosurgery.

In order to achieve cancericidal temperatures inside bulky tumors a thick spray must be applied for long periods. To prevent dripping of liquid nitrogen and freezing of skin around the target,the drops must be stopped with efficient perilesional protection.The following three methods usually are used: a) for cancers located on the head and extremities, we use many layers of common bandages (Fig. 8.6, 8.22); b) for neoplasms on the trunk, a paraffinated gauze bandage that must be folded some fifteen times, creating a smooth and flexible “plaque” that is stitched onto the edge of the target (Fig. 8.26, 8.27, 8.29, 8.47); c) for any location, the placement of a large reinforced, adherent silicone sheet (commercially available for small cancers) with a central hole cut into it, in accordance with the size of the target (Fig. 8.8).

The important consequence of the careful physical limitation is that the limits of the cryonecrosis are accurate and predictable (Fig. 8.9, 8.32, 8.48). The cryosurgeon can use liquid nitrogen spray continuously, and for as long as necessary, between 15 and 60 minutes and can thus concentrate on monitoring the progress of the ice front.

Ultrasonography is important to a previous definition of the real size of the tumor and to control the advance of the freezing, in real time.

Cryosurgery of advanced cancer of the extremities

Squamous cell carcinomas (SCC) of the extremities occur mostly on the dorsa of the hands of outdoor workers. When these tumors are left to their natural evolution they become adherent to important underlying structures, and amputation is the usual treatment. In 1980, O. Martins et al. published the cryosurgical treatment of an SCC of the dorsum of a hand, measuring three centimeters. It was successfully treated after debulking (53). Through 1995, Turjansky and Stolar treated 2480 malignant lesions of the extremities (72). They always use debulking by radio frequency and cryosurgery with liquid nitrogen spray from hand-held devices.

In 1986, one of us (JCAG) published his cryosurgical technique to deal with these dangerous cancers (17). The surgical protocol (Figs. 8.6-8.11) is as follows:

Anesthesia can be general, nerve block or caudal, depending on the tumor location and the patient’s general condition. Adherent silicone sheets (Cryosil ) (Fig. 8.8) or bandages are firmly applied around the tumor and safety margin (Fig. 8.6). The number of layers depends on the physical type of the bandage and must be sufficient to prevent the freezing of normal skin and stop the running droplets. Usually, we do not use debulking for cancers of the extremities. Thermocouples are introduced inside the cancer, under its apparent inner limit and under its borders (Fig. 8.8). An open, thick spray, obtained from an apparatus with high pressure, is used (Frigitronics CE-4). Inside the tumor the temperature attained is low, around -50°c, but at the edge of the tumor and at the underlying structures it is important to have temperatures higher than -20°c in order to spare those structures. Necrosis is completed in about 6 days and the necrotic tissue is easily removed with scissors. Any suspect site is biopsied and, if necessary, cryosurgery is repeated. The resulting ulceration is permitted to heal by second intention, which occurs within four to eight weeks. As a rule, no grafting is performed. Moreover, the cosmetic results are very good and grafting or other plastic correction is not necessary (Fig. 8.12-8.13).

We treated 30 SCCs of the extremities of 23 patients (23). All cancers were so advanced that amputation had been proposed.Eighteen patients had a single cancer and five had multiple lesions. Twenty-five patients had lesions on the upper limbs and five on the lower limbs. Nineteen carcinomas were on the dorsa of the hands. One was at the rool of the fourth and fifth fingers and the proposed surgery had been amputation of both fingers. Three were on the leg and two on the foot. The time of evolution was between 1 and 6 years. The tumors were primary in 21 patients, and recurrent after conventional surgery in two. Their major axes were between 25 mm and 130 mm in length. In all patients with a single tumor, it was invasive and adherent to the underlying planes; in the patients with multiple lesions, at least one was invasive. A skin graft was carried out only in one patient who had a cancer on the heel. Debulking was performed in one of our first patients who had a large cancer on the tenar region, by cryosurgery. One week later, another cryosurgical procedure was performed with definitive eradication of the cancer.

Eighteen patients had their malignancies cured and physical function was maintained, in follow-ups between 1 and 8 years. In a few cases the extensor tendons of the dorsum of the hand were exposed after removal of the cryonecrosed tumor.They were slowly covered by granulation tissue and, after healing, their function was maintained without any impairment. Two carcinomas persisted after cryosurgery and produced metastases, and the patients eventually died. In two others, cryosurgery was unable to cure the cancers and the patients were treated by another technique – chemosurgery with zinc chloride paste (20). These patients suffered amputation of two fingers by this method, but the remaining fingers permitted a functional hand.

Besides the advanced cancers that had been proposed for amputation, 21 SCCs of the extremities, measuring between 20 mm and 50 mm were also treated by cryosurgery.18 patients were without evidence of disease – between six months and nine years after cryosurgery – and 3 had recurrences soon after.

It is extremely important to carefully control the advance of freezing when it approaches the edge of the tumor, in order to prevent irreparable damage to the underlying structures. Less attentive practice may result in amputation, the prevention of which is the very aim of this method.

The overall results and prevention of amputation in 18/ 23 patients supports the position that cryosurgery is the best treatment for advanced cancer of the extremities.

Cryosurgery of advanced carcinoma arising in pilonidal sinus

Among the complications of a long-standing sinus pilonidalis, malignant degeneration of the cyst wall or of the sinus tract is rare around 0.1% (1). The resulting cancer is usually a squamous cell carcinoma (SCC).

We treated by cryosurgery five men aged between 50 and 75 years (mean 59.6 years). All patients had suffered from a long-standing sinus pilonidalis with multiple episodes of infection and suppuration. The precise length of time during which their cysts were present before malignant transformation was in all cases longer than 25 years. The histological diagnosis was SCC in all patients, two being classified as well differentiated. One carcinoma was primary: all the others had recurred after conventional surgery and radiotherapy (21, 25, 32).

All cancers were submitted to two freeze/thaw cycles with thick spray from a high-pressure apparatus (Frigitronics CE-4) down o -70°C. In one patient a single cryosurgical procedure (with two freeze/thaw cycles) was performed. In the others, the tumors were too bulky and the first cryosurgical procedure was intended as massive debulking. The necrotic tissue was removed over the two or three weeks following cryosurgery. Approximately one month later, another cryosurgical procedure was performed to eradicate the remaining cancer. The resulted were: three patients had no more evidence of disease for between seven or fourteen years; one had a recurrence 8 year later and was again submitted to an aggressive cryosurgery and subsequent plastics surgery and is well at four years after the last intervention; the fifth patient, who had a enormous tumor, measuring 150mm × tastasic disease 10 months after the cryosurgical treatment.

Complete removal of these cancers by conventional surgery is difficult, because the tumor soon becomes adherent to the sacrum and coccyx, originating arduous or impossible eradication. Cryosurgery offers the possibility or carrying out real tissue sterilization, without destroying bone. The local eradication achieved in all patients demonstrates the value of cryosurgery in such advanced cancers.

Cryosurgical of advanced basal cell carcinoma invading orbital structures

When a basal cell carcinoma (BCC) originating in the eyelids or the canthi invades the orbit, it become a serious with high mortality. In such cases, the usual surgical treatment is exenteration of the orbit. The only reference we found in the literature was that of Cahan who successfully treated by cryosurgery a huge SCC that deeply invaded the orbit. Plastic reconstruction was performed one year later (7). Stolar and Turjansky also successfully treated one BCC invading the orbital structures (Figs. 8.18-8.20).
One of us (JCAG) treated six patients with long-standing, terebrant basal cell carcinomas, deeply invading the orbital structures, with loss of sight of the invaded eye. One was primary cancer and five were recurrences after multiple surgical and radiation procedures.

The cryosurgical protocol (Figs.8.21-8.23) was:

In the first five patients neither debulking nor enucleation were performed. In the sixth, only the exophytic part of the tumor was removed by electrocuting. After the anesthesia was induced, several thermocouples were inserted into the tumor (Figs 8.22). The extremities of two other thermocouple were placed against the orbital plate. The freezing was carried out with a continuous spray of liquid nitrogen from a apparatus with high pressure (Frigitronics CE-4). Freezing of the external neoplastic tissue was done as quickly as possible, but the advances of the ice front inside the orbit was carried out more slowly while always monitoring the temperatures, particularly those of the two thermocouples applied against the orbital plate. These should not be excessively cooled in order to prevent possible damages to the brain. Two freeze-thaw cycles were carried out. The temperature achieved in the neoplastic tissues were between -50 and -60°C (Figs.8.21-8.25).

In the day thereafter, the edema was considerable. The necrotic tissues was slowly removed over about six weeks. The healing was by second intention. No plastic reconstruction was done by any patient.

The results of cryosurgery were:a)in all patients, the pain ceases with the operation; b) two patients were cured and followed up for 13 years, without recurred; c) in two patients, the cancer persisted but with acceptable palliative result, with survival of 2 and 3 years, respectively; d) two patients died of non-cancerous reason shortly after cryosurgery.

Cryovulvectomy for advanced cancer

In the past, some author tried palliative cryosurgical treatment of advanced vulvar cancer, using cryoprobes, with reduced benefit (9,45,70). This is because that the cryoprobe cannot freeze the tumors deeply enough. Sommer et altreated 146 cases of advanced vulvar cancer by cryosurgery, between 1971 and 1986 (57). The cure rate was 38.4%. In 1982, A. Favard et al. treated four advanced vulvar cancers by cryosurgery, succeeding in clinically curing two patients and obtaining a good palliative result in the other two (11). Stolar and collaborators treated seven cases of vulvar carcinoma in situ with three freeze/thaw cycles with liquid nitrogen spray obtained from a hand-held device (CRY-AC,Brymill Corporation) without recurrence.

In 1974, a controlled and predictable cryovulvectomy began to use for advanced vulvar cancers (19, 22, 24, 30).

Cryovulvectomy is indicated for advanced cancer which is not possible to be excised by conventional surgery and /or if the metastases cannot be removed.

Surgical protocol: At first, protection of the tissues surrounding the cancer and its safety margin is done with a paraffinated gauze bandage, folded fifteen times, which yields a smooth and flexible “plaque” (Fig. 8.26). Three such plaques measuring about 17cm and one measuring 10-12 cm are prepared (Fig. 8.27). The plaques are applied against the skin, on the contour of the area to the frozen and their inner limit is stitches to the skin (Fig. 8.29). The larger plaques are applied as follows: one across the middle of the pubis; two generally in the size and limits of the cancer; the smaller plaque is applied transversely near the posterior vulvar commissure. The inner edges of the plaques are stitches o the skin, leaving exposed the target - the cancer and its safety margin. This provides a predictable and accurate limit of the freezing. Tissues temperature is monitored by 8-12 thermocouples, whose location is important (Fig. 8.30). They must be strategically placed, one against the pubic symphysis to prevent excessive local destruction. The others are places inside the tumor. The extremities of the thermocouple must be inserted between 3 cm and 4 cm below the surface of the tumor. The aim is to create condition to check the freezing progress, control the low temperatures inside the cancer ad prevent excessive destruction. Freezing is achieved with a continuous open thick spray of liquid nitrogen from a high-pressure apparatus (Frigitronics CE-4). When beginning the freezing, one pointed of the neoplasm is selected and the spray is persistently applied thereon, until an ice ball forms and its inner temperature falls to -60°C to -80°C. The contour of the ice ball then slowly and progressively widened to encompass the entire vulvar region and the lower half of the pubis. The tumoral mass must attain temperatures between -50°C and -80°C, but the temperature of the thermocouple adjoining the pubic bone must not go below -15°C to prevent is exposure after removal of the necrotic tissue. To complete the freezing, 30 to 45 minutes are necessary. The region is permitted slow natural thawing, after which a second freeze-thaw cycle is carried out. To begin the second freezing, another point is chosen to prevent the repetition of ay strategic mistake that may have been made in the course of the first freezing. After the second thawing, lymphadenectomy is performed, during the same surgical procedure, if feasible. On the following day, the whole area is dark violet and on the contour there are second-degree burn blisters, which should be punctured. In a few more days the regions will turn black. About three weeks later, the skin is mummified and there will be a sulcus in the contour, demarcating the necrotic tissues from the normal looking ones. The necrotic tissues are removed around three weeks later and the wound is allowed to heal by second intention. Complete local healing occurs between 9 and 12 weeks. The resulting scar is smooth, painless and without hypertrophy (Figs. 8.26 -8.34).
115 such patients were treated. The criterion to accept them for cryovulvectomy was the difficulty or impossibility of operating with conventional surgery. The time of evolution of the tumors was between some and more than six years. Eighty cancers were primary and 35 were recurrent.

us cell carcinomas, two adenocarcinomas, one Paget’s disease and one nodular and invasive melanoma. Thirty-seven patients (32.2%) presented in stage IV and for these only palliative treatments was performed, which was successful as such. Only 9 patients (7.8%) were in Stage П, and were admitted o cryosurgery, because the tumors were near either urethral meatus or the anus and it was not possible to surgically remove them with an adequate safety margin. The majority of patients -69(60%) - had stage Ш disease or were in an equivalent “phase” if recurrent.
When devising he cryovulvectomy technique, successive modification had to be made, in order to prevent complications as they arose. Over time, performance improved considerably and better results were obtained. In the first year of these treatments, 24% of the patients had two, rarely more, cryosurgical procedures. This was reduced when more experiences was acquired. There were complications in 22 patients, some of which were due to early lack of experience but contributed to the construction of an improved surgical protocol: exposure of the pubic bone in two cases with necrosis in one, when the thermocouple was not applied against the pubic symphysis; destruction of the perianal region with definitive incontinence; deep burning of the skin of the catheter; and one case of lethal embolism.
This last-mentioned case is here described in detail to alert fellow cryosurgeons to such accidents. A palliative cryovulvectomy was carried out in a patient with a T3N3M1a, stage IV, but in good general health. After removal of the necrotic tissues a persistent tumor 3 cm in diameter was observed in the middle of the cryosurgical ulceration. In a Stage Ш case, a second thorough cryosurgery would have be done, but, in this hopeless case, it was decided to carried out only a tumorectomy to limit surgical aggression. The technique chosen was freezing seemed uneventful but, at the beginning of the second, the patient suddenly died. Necropsy showed that death was due to embolism. The conclusion we drew is that Torre cones are good for short freezing of skin tumors with integral skin, but should not be used in long cryosurgical procedures on ulcerated and undermined tumors. It is also preferable not to use them with high-pressure apparatuses. In two cases, the necrotic tissues were removed by electrocuting, intending to hasten their elimination. This proved to have serious consequences. Instead of the usual thin, pliable and painless skin, a hard, irregular and painful scar resulted.
Other complication were unavoidable and can occur again: profuse hemorrhage I cases; rectovaginal fistula in two patients where the cancer invaded the posterior aspect of the vagina; fecal incontinence in two cases where was deep invasion of the anus; urinary incontinence in 2 cases where there was extensive invasion of the urethra; transient urinary incontinence in 3 cases; abscess in one case; prolapse of the bladder in one; and one case of lethal sepsis. Besides the mentioned deaths, there were two more intra-operative deaths due to cardiac failure in elderly patients. Cryovulvecomy was well tolerated in the remaining patients. A common consequences of cryovulvectomy was cicatricial stenosis of the introitus. Only two patients accepted the suggested plastic correction, which was successful. The advanced age of the patients accounts for the easy acceptance of this occurrence.
None of the patients complained of pain after the operation, but most referred to a tolerable burning sensation during the three postoperative hours, which was easily controlled with mild analgesics. The preoperative pain and discomfort completely ceased after cryovulvectomy, even in patients that were treated palliatively. The complete removal of the necrotic tissues- between 3 and 4 weeks later – depended on their individualization and demarcation. This also applies to the time required for healing – between 9 and 12 weeks. Patients with good hygienic conditions at home can leave the hospital during the fourth or fifth week postoperatively. During the first few weeks after the operation the exudates is enormous. We tried many types of dressing. Experience showed that the best one was a diaper indicated for incontinent people.
Clinical cure was obtained in 47.4% of cancers in stage П and Ш but in 66% in combination with local irradiation. The difference in percentage was due to metastases. The mortality rate was 1.66%, while with radiotherapy, chemotherapy ad surgery it is 7% (30), and many patients suffer continuous pain due to radiodermatitis after radiation. Patients in stage IV received palliative treatment. All pain and discomfort disappeared but, survival was short (mean of 4 months; range 1-15 months) (Figs. 8.35-8.40).
JCAG’s formal training is not that of a general surgeon and, during the first years of the deve- lopment of his cryovulvectomy technique, most lymphadenectomies of his patients were performed by one of the two departments of surgery of the Portuguese Institute of Oncology. It is not unusual for therapeutic teams involving different specialities to have some difficulties in their personal and work relationships. In those first years, he had considerable difficulty in obtaining early Iymphadenectomies from one of the departments. In 44/69 of those early patients, Iymphadenectomy was performed between 2 and 4 months after cryovulvectomy, and in 6 cases the interval was even between 5 and 14 months. Only in 25 cases was it carried out within one month. With a better collaboration from one of the surgical departments the results would have been much better. Only in the last 17 years has he succeeded in obtaining prompt collaboration from the surgeons, and cryovulvectomy and Iymphadenectomy – when feasible have been carried out at the same time, with obvious therapeutic advantage. In 19 patients with stages II and III disease, where Iymphadenectomy was delayed, II were clinically cured (57.9%), in eight patients who had simultaneous Iymphadenectomy five had no evidence of disease (62.5%). The difference is not statistically significant, but we consider that timely Iymphadenectomy is fundamental in the treatment of vulvar cancer. Many patients have lost their lives due to delayed Iymphadenectomy or, in a few cases, to their own refusal to submit to the procedure (22, 30). It is interesting to note that, in the last few years, the number of cryovulvectomies has diminished considerably, because patients present in earlier stages of the disease.
One frequent error in conventional surgery is removing advanced cancers with insufficient safety margins, which should be at least 2cm outside the apparent limit. In cases where this safety margin cannot be implemented, cryovulvectomy gives better results.

Cryosurgery of invasive Penile Cancer

The most frequent treatment for invasive carcinoma involving the glans penis-generally a squamous cell carcinoma-is radical or partial amputation (2, 55). Among the therapeutic modalities of conservative treatment for this cancer is cryosurgery. To our knowledge, the first such treatment was performed by P.S.H Hughes who in 1979 treated two cases of verrucous carcinoma of the penis, with debulking by electrocuting followed by cryosurgery with liquid nitrogen spray and thermocouple monitoring. Both patients were well one year after cryosurgery. One of them was young and the sexual function was preserved (39). In 1982, G. Madej and J. Meyza treated 15 patients with either superficial invasion of the subcutaneous tissues or invasion of the glans penis-corpus spongiosum, measuring between 2cm and 5cm. They used contact with a cryoprobe covering the whole surface of the lesion and freeze twice for three minutes. All patients were cured, with urinary and sexual functions maintained (52). In the two following years, B.P.Matveev and collabprators published papers in Russian, to which we have no access. They sometimes combined cryosurgery and chemotherapy (54). G. Castro-Ron in 1989 presented in a cryosurgical workshop at Durham five cases successfully treated with the cryoprobe technique. Three tumors were small, one was medium-sized and was large. Considerable ederma developed, but no catheterization was needed. Turjansky and Stolar used a quite different protocol. They excised the cancer with radiofrequency and carried out three freeze/thaw cycles with close spray of liquid nitrogen inside Torre’s cones, between 120 and 180 seconds. They treated 12 patients with four recurrences (72).
One of us (JCAG) treated 13 cases of invasive squamous cell carcinoma of the penis, between 1993 and 2000, but at the time of writing only 10 have acceptable long follow-up. Cryosurgery with curative purpose is indicated when the cancer invades the glans penis but not the corpus cavernosum (Fig. 8.40). Therefore, accurate staging of the primary tumor is important and the clinical examination must now be supported by ultrasonography and magnetic resonance imaging.
The surgical protocol (Figs. 8.41-8.44) is as follows: Anesthesia is general or regional. The former is used when Iymphadenectomy is carried out at the same time. The shape and size of the prepuce is clinically assessed. If the risk of phimosis is foreseeable, due to the edema after cryosurgery, prior circumcision is performed. Catheterization is usually done, which is indispensable when the meatus is to be frozen. When the tumor is too thick debulking can be done. The cryoprobe technique is used. One probe of adequate size is chosen and a hydrophilic gel (K-YJelly , Johnson and Johnson) is applied between the tumor and the probe. If possible, the progression of freezing should be controlled by ultrasound. A safety margin of at least one centimeter is advisable. The criterion for Iymphadenectomy is that accepted in urologic oncology (2, 55). On the following day, considerable edema develops (Figs. 8.43 and see Atlas of Cryosurgery, 2001). Ten uncircumcised patients with penile cancer treated cryosurgically are analyzed herein. Nine cancers were primary and one was recurrent. The age of the patients ranged between 44 and 83 years (mean 64.7 years). The time of evolution of the disease was between five months and six years (mean 19 months). Major axes varied between 10mm and 41mm (mean 26.4mm). The histological diagnosis was: nine SCCs-five of which accompanied by lichen sclerosus-and one verrucous carcinoma (tumor of Buschke-Lowenstein). Eight patients were submitted to a single cryosurgical procedure, one patient underwent two and the remaining patient underwent three. Only one cancer was debulked. In five patients, Iymphadenectomy was carried out at the same time. Five patients were cured and had no evidence of disease for between two and five years. One had three small local recurrences, always treated by cryosurgery. At the timewriting, he is well, two years after the last cryosurgical procedure. One patient who suffered from an SCC, measuring 30mm x 20mm, after cicatrisation had a small persistence of the tumor at the posterior limit of the glans penis. It was removed by conventional surgery and there is no evidence of disease after three years. One patient who also suffered from lichen sclerosus had either a new local cancer or a recurrent one after five years of apparent cure. In fact, we could not decide between the two, because after this period it could be a new cancer originating from the persistent lichen sclerous. He underwent another cryosurgical procedure and there is no evidence of disease at the time of writing, after three years of follow-up. One patient abandoned the outpatient clinic and only returned two years later, with a large local recurrence that required amputation. One patient abandoned our department, had successive recurrence and was treated elsewhere, and eventually died nine years post cryosurgery.

In summary: eight patients apparently cured with maintained physiological function, one underwent amputation and one died.
The treatment of superficial penile neoplasms is analogous to similar skin situations and is not referred to in this chapter (2, 55, 58, 71).
The usual treatment of invading SCC of the penis - total or partial amputation - causes considerable psychological suffering and despair. Amputation can be prevented by cryosurgery in many cases, with maintained functional performance. Nevertheless, this is an aggressive and dangerous cancer with a high mortality rate. Staging is essential and the established criteria for cryosurgery must be strictly observed.