In equine medicine, cryosurgery was widespread in the 1980s and the technique was not only used for the treatment of tumors but also for cryoneurectomy and pain alleviation in a variety of orthopaedic diseases such as bone spavin, proximal suspensory desmitis and splint bone fractures [1, 2].
Nowadays, cryosurgery in horses is almost exclusively used for oncological applications, more specifically for the treatment of equine sarcoids and squamous cell carcinomas [3–7]. Non‐oncological applications include the destruction of the hair follicle in distichiasis [8] and the management of patent urachus [9].
Cryosurgery can either be used as the sole treatment for tumors, or as an adjunctive to surgical resection [4, 5]. Tissue injury arises from direct damage to the cell wall by intracellular ice‐crystal formation during fast freezing followed by recrystallization during the slow thawing phase [10], from microcirculation failure after the thawing phase, [11] and from post‐thaw cell stress resulting in apoptosis [12]. Maximal tissue destruction with freezing is obtained when 2 or 3 freeze–thaw cycles are performed [10].
The final result is coagulation necrosis which is characterized by the formation of a necrotic eschar that gradually detaches from the underlying granulation tissue starting from 7–10 days after cryosurgery. Complete sloughing takes approximately 2–4 weeks, but can also last up to 8 weeks [13, 14]. The resulting wound heals by second intention. The final skin scar is often depigmented and partially hairless due to destruction of hair follicles and the highly cold‐sensitive melanocytes [4, 15, 16].
The number of complications associated with cryosurgery is rather limited as long as good cryosurgical equipment is available, the technique is applied correctly, and an appropriate selection is made of lesions to which cryosurgery can be applied [15] (Table 11.1).
List of Complications Associated with Cryosurgery
Intraoperative complications
Inadequate choice of cryosurgical equipment and technique
“Run‐off” of cryogen
Early postoperative complications
Bleeding after cryosurgery
Excessive local edema and pain
Excessive tissue necrosis
Late postoperative complications
Tumor recurrence
Table 11.1 Complications related to cryosurgery
| Intraoperative | Early postoperative | Late postoperative |
|---|---|---|
| Inadequate choice of cryosurgical equipment and technique | Bleeding | Recurrence of the lesion |
| Run‐off of cryogen | Excessive edema | |
| Excessive tissue necrosis |
Intraoperative Complications
Inadequate Choice of Cryosurgical Equipment and Technique
Definition
Choice of a cryosurgical equipment and/or technique that do not allow sufficiently fast freezing of the tumoral mass and may result in:
incomplete tumor destruction with local recurrence as a late postoperative complication
excessive prolongation of the procedure for horses treated under general anesthesia
Risk factors
Thick tumors
Tumors with a large base
Pathogenesis
Maximal tissue destruction is obtained by fast freezing and slow thawing. To ensure destruction of all tumoral cells, the obtained tissue temperature should be low enough. The larger and thicker the tumoral mass is, the longer it takes to obtain sufficiently low temperatures in the entire lesion to ensure destruction. Although initial experimental data suggested that a tissue temperature of –20°C for ≥1 minute is adequate for tissue destruction [17], other studies have shown that lower temperatures are often required to destroy tumor cells [18]. Biological susceptibility to cryoablation varies according to the tumor type and moreover, not all cells within the tumor will be subjected to the same cooling and thawing temperatures and rates [19]. When a cold probe is applied to the tissue, a steep temperature gradient develops in the tissue. Whereas the tissue close to the probe freezes very fast to very low temperatures, the tissue in the peripheral lesion cools slowly and to a higher temperature, with a less destructive effect. Therefore, the application of lower temperatures is advised. Recent studies in human medicine suggest that exposure of cancer cells to low temperatures of –30°C to –40°C for ≥1 minute using a double freeze‐thaw protocol yields complete cell destruction [12, 18].
Although cryosurgery of superficial skin lesions can be performed under local analgesia in the standing sedated animal [13, 14], some locations (e.g. ventral abdomen, inguinal region, ocular tumors, etc.), or tumor or patient characteristics require general anaesthesia. When the cryoablation is seriously prolonged, there is a higher risk of anesthesia‐related intra‐ and postoperative complications (hypoxia, myositis, nerve paralysis, etc.).
Diagnosis and monitoring
Exact determination of the correct speed of freezing and thawing is not possible and the surgeon should rely on achieving an “as fast as possible” freezing and a “slow spontaneous” thawing. Tissue temperatures of –30 to –40°C should be reached to ensure tissue destruction and this should be monitored using thermocouple needles (see Prevention below).
Prevention
The choice of cryogen and cryosurgical equipment should be adequate for the size of lesion to ensure that the tumor can be frozen fast and sufficiently deep:
Liquid nitrogen is the most powerfull cryogen (–196°C) and is most commonly used in cryosurgery in horses.
Hand‐held instruments for gas‐cooling with N2O are also only suited to treat smaller lesions, even though the size of the tip can be adapted to the size of the lesion to be frozen.
Copper probes or cotton tips immersed in liquid nitrogen quickly warm up in contact with living tissue and do not allow deep freezing [13]. Their use is restricted to small and superficial lesions.
Liquid nitrogen circulation probes should be large enough to cover the entire lesion to assure a more or less equal temperature distribution. In case the tumor base exceeds the size of the largest probe, cryosurgery should be performed at multiple locations with an overlap of a few millimeters. A contact gel assures good contact between the probe and lesion and the probe should stick to the lesions once the freezing starts [13]. Air bubbles between probe and tissue must be avoided as these have an insulating effect.
Spraying liquid nitrogen directly onto the tissue results in much faster freezing compared to the use of probes held in contact with the tissue [13].
Very fast freezing of larger lesions can also be obtained by pouring the liquid nitrogen directly onto the lesion.