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Page 2 of 11                                       Silvestri et al. Mini-invasive Surg 2019;3:5  I  http://dx.doi.org/10.20517/2574-1225.2018.67


               longer-term outcomes for these techniques have become available [1-5] . They can be performed either
               laparoscopically or percutaneously with good results in spite of higher reported recurrence and retreatment
                                                          [6,7]
               rates when compared to partial nephrectomy (PN) .
               Historically laparoscopic cryoablation (LCA) has been the most popular approach for performing renal
                  [8,9]
               CA . Conversely, laparoscopic techniques for RFA have been used less in favor of percutaneous RFA,
                                                                    [10]
               successfully performed under ultrasound, CT, or MRI guidance .
               Anyway, over the years, also LCA have seen gradual decrease in utilization as image-guided techniques
               have improved greatly and currently American Urological Association (AUA) guidelines recommend also
               percutaneous cryoablation (PCA) as the best possible choice [11,12] .

               In this review, we focused on LCA in relation to its major diffusion and availability worldwide, particularly
               with SRMs with diameter > 3 cm in comparison to RFA ablation.



               CRYOBIOLOGY AND AVAILABLE SYSTEMS
               The principles of cryotherapy, including the mechanism of cell injury and cell death, have been well
               studied [13-15] . The main mechanism of cryo-toxicity is the induction of coagulative necrosis in targeted areas.
               The key factors involved in freezing injury include direct mechanical shock, osmotic shock, and cellular
               hypoxia. Mechanism of action includes protein denaturation via dehydration, transfer of water from the
               intracellular space to the extracellular space, rupture of cell membranes from ice crystal expansion, a toxic
               concentration of cellular constituents, thermal shock from rapid super-cooling, slow thawing, vascular
               stasis, and increased apoptosis. The delayed or indirect destructive effects of cryotherapy continue primarily
                                                                                       [16]
               because of vasculature disruption, resulting in tissue hypoxia and vascular thrombosis .

               Stephenson started the first cases of LCA in a canine model and the transition to the second and the third
               generation of cryoprobes have permitted the use of ultra-thin probes, leading to rapid diffusion of the
                       [17]
               technique .

               Currently, the available cryogenic systems, that use pressurized argon gas as the source of freezing, are:
                                                                                                 TM
               the SeedNet® System, the Visual-ICE® System (Galil Medical Inc., BTG, UK) and the CRYOcare  System
               (Endocare Inc., USA). These systems are used to create a conformal freezing pattern up to 25-17 gauge
               (2.4-1.47 mm) cryoprobe.


               ADVANTAGES AND DISADVANTAGES OF LCA
               Currently, considerations such as tumor location and complexity as well as patient morbidity must be made
               when selecting a modality and approach. With initial experience, LCA was utilized primarily for anteriorly
                                                                                      [18]
               and laterally located tumors, and PCA was the method of choice for posterior tumors .
                                            [19]
               The main advantages of LCA are : (1) placement of probes under direct visualization; (2) real-time US-
               guided placement of probes and monitoring of procedure (freezing and tissue viability); (3) easier treatment
               of anterior or hilar tumors; (4) major ability to displace colon or other organs or nearby structures whenever
               necessary for a safer ablation.

               However, increasing experience during the last two decades has demonstrated that although technically
               challenging, also anterior tumors can be successfully treated via the percutaneous route, often with
                                             [20]
               adjunctive displacement maneuvers .
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