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Intravasation of adipose tissue or bone marrow can lead to acute blockage of pulmonary microcirculation, with increased resistance in the arterial pulmonary capillaries and a secondary increase of pressure in the pulmonary artery and the right atrium [22]. This causes the pCO2 to rise and oxygen saturation to decrease, with tachycardia resulting from left ventricular volume deficiency. To date, no comparable trials on large animals have been done examining cryoablation in bone tissue with modern cryoprobes. Kerschbaumer et al. [23] found no lung embolisms in rabbits after cryosurgery. On the other hand, Oeseburg also used rabbits and observed a large number of bone marrow embolisms in the extraosseous veins immediately after cryoablation [21].
One of the aims of this study was the detection of larger, clinically significant lung embolisms, we restricted ourselves to venously measurable hemodynamic parameters so as not to cause additional, iatrogenic complications. Likewise, we decided against a transesophageal ultrasound probe for detecting microemboli [24,25] since the animals already were administered a large transesophageal tube to aspirate gastric juices during the operation, thus leaving no room for an ultrasound probe.
None of the animals showed histological evidence of lung embolisms, nor were any embolism-specific hemodynamic phenomena or blood gas changes observed. The rise in pCO2 seen in all animals at the end of the operation is likely to be due to the impaired pulmonary gas exchange and decreased venous flow resulting from the increased intraabdominal pressure, which in turn can probably be attributed to the distended rumen during while the animals were lying on their right side. The rise in pCO2 explains the slight acidosis which the animals showed towards the end of the operation, and is therefore not to be seen as pathological.
In our opinion, the absence of significant embolisms is due to the small diameter of the probe, which prevents the intramedullar pressure from rising when the probe is introduced. A further reason could be the controlled expansion of the ice front in the bone, which prevents intramedullar pressure from peaking, and hence bone marrow or adipose tissue from being pressed out of the marrow cavity.
As expected, we did not observe any decrease in body temperature after cryosurgery as was reported for small animals such as mice and rats [26]. The minimal reduction in body temperature which we did see towards the end of the operation can be explained by the normal cooling of the body despite a heating pad. We believe that the more pronounced decrease in body temperature in small animals is due to their smaller body volume, next to which the cryoprobe is comparatively much larger. Hence, the results of our trials with large animals can be extrapolated more readily to human patients than can results from similar trials with small animals, and a significant decrease in body temperature is not to be expected in human patients.
Except for hemoglobin, all blood chemistry values remained essentially unchanged during the operation. The drop in hemoglobin by on the average 0.5 g/dl is not clinically significant.
Clinical follow-up revealed one serious wound infection, which underscores the tendency these wounds have for infection [20]. Even so, it would seem to us that the risk of infection can be controlled with perioperative administration of antibiotics, as is also evident from the histology of the treated bone sections, none of which developed acute inflammation. Nevertheless, it must be admitted that the tissue treated here was healthy bone in animals with an intact immune system, and a higher infection rate must be expected when applying this method to patients with advanced malignancy.
Convalescence after cryosurgery is associated with changes in bone stability, a topic which few studies have addressed so far. Gage et al. (1967) reported 11 spontaneous fractures in 20 dogs, where the entire cross-section of the femur was frozen over a length of 4.5–7 cm [9]. Further studies report a maximum reduction in bone stability some 8 weeks after cryosurgery [27,20]. The absence of fractures in our trial shows that limiting bone necrosis by controlled freezing and minimum tissue loss when introducing the cryoprobe helps minimise the reduction in bone stability, and hence prevent fractures. To be sure, the size of a tumour dictates the extent of the freezing zone, so that stabilising measures may be necessary.
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