Veterinary Surgical Oncology. Группа авторов

Figure 4.9 Radical excision of a feline injection‐site‐associated sarcoma. (a) Five cm margins are measured and marked with sterile marker on the skin. (b) The radical excision required abdominal body wall excision and excision of facias in the pelvic limb and over the epaxial muscles, en bloc with the tumor. (c) It was possible to close the skin defect primarily, without the use of reconstructive techniques, which is often the case in cats after radical excision.

      It is important to consider that the margin size will alter directly after removal of the specimen. Significant decreases in surgical margin length in FISASs specimens occur immediately following excision (prior to formalin fixation). Median tumor volume decreases significantly between in vivo and ex vivo assessments regardless whether measurements are obtained from 2‐D or 3‐D CT images. Subgross evaluation of tumor‐free margins from on‐slide grossly normal surgical margins to pathologist‐reported histologic tumor‐free margin overestimates the actual (histologic) tumor‐free margins (Terry et al. 2016, 2017).

      Radical surgery is easier with the guidance of advanced imaging in the form of CT or MRI compared to manual palpation. Preoperatively the skin is marked as required for sufficient margins. Available amount of skin for closure has to be assessed preoperatively. If insufficient, a skin flap can be used (Montinaro et al. 2015), or skin stretcher can help to recruit extra skin in two to three days. Changes in the muscular form according to the forelimb positioning must be appreciated. It is important to have an in‐depth anatomical knowledge of the interscapular region of the feline patient to approach the study of any pathology located there and, in particular, to set up an appropriate therapy for the FISASs (Longo et al. 2015).

Adjuvant radiation therapy can improve outcomes. Median DFIs after complete resection combined with radiation therapy were 405–1110 days. Survival times after complete resection combined with radiation therapy were 476–1290 days. DFIs after resection with contaminated margins combined with radiation therapy were 112–600 days. Median survival times for contaminated margins combined with radiotherapy were 502–900 days (Cohen et al. 2001; Cronin et al. 1998; Eckstein et al. 2009). According to Eckstein et al. (2009), radiation therapy of residual microscopic tumor improves median DFI and survival time (20 and 30 months, respectively) compared to residual macroscopic tumor (4 and 7 months, respectively). However, even with neoadjuvant radiation therapy and complete margins after surgical excision, local recurrence has been reported to be 42% (Kobayashi et al. 2002).

      In a study of 76 cats with vaccine‐associated sarcomas, 26 cats were treated with chemotherapy in addition to surgery and radiotherapy. Neither recurrence rates, rate of metastasis, nor survival times were improved in the chemotherapy group (Cohen et al. 2001). Neoadjuvant and adjuvant chemotherapy with epirubicin (25 mg/m²) combined with anatomical resection of FISAS resulted in local tumor recurrence in 3 cats (14%) at days 264, 664, and 1573 after surgery (Bray and Polton 2016), according to the authors these results demonstrate superior rates of tumor‐free survival and disease‐free interval when compared to historical controls.

      Of 11 cats treated by stereotactic radiation for FISAS, 8 responded. The median DFI was 242 days, and an MST of 301 days (Nolan et al. 2013).

      No significant effect of chemotherapy only in the treatment of FISAS in clinical settings has been reported yet, although the high metastatic rate is an indication for systemic treatment (Bregazzi et al. 2001; Cohen et al. 2001). Possibly the tyrosine kinase inhibitor, imatinib, will have an effect on FISAS. It inhibited the growth of FISAS in a murine xenograft model (Katayama et al. 2004) and could affect FISAS due to the presence of platelet derived growth factor receptor which is a receptor tyrosine kinase. In one phase 1 clinical trial of imatinib, 4/9 cases trialed had FISAS. In these four cases, a response to treatment was noted and consisted predominantly of short‐term tumor stabilization (Lachowicz et al. 2005).

      In vitro doxorubicin and etoposide alone and in combination differentially alter FISAS cell viability and cycle (Hill et al. 2014).

      Although masitinib did not directly enhance FISAS cell radiosensitivity under normal in vitro conditions (Turek et al. 2014), combined chemo/radiation therapy has been reported to result in a significant reduction in tumor growth compared to the respective mono‐therapies with either doxorubicin or radiation. These results support the use of the concomitant chemo/radiation therapy for adjuvant treatment of FISS, particularly in advanced or recurrent disease where surgery alone is no longer feasible (Petznek et al. 2014).

      Immunotherapy has been reported successful in xenogeneic cells secreting human interleukin‐2 (IL‐2). Totally, 16 cats with FISAS were treated, two of which had local recurrence and three had metastatic disease. MST was 16 months in IL‐2 treated cats vs. 8 months for nontreated cats (Quintin‐Colonna et al. 1996).

      A second study conducted with human and feline IL‐2 resulted in a lower tumor recurrence rate compared to control cats not receiving immunotherapy after surgery and iridium‐based radiotherapy (39% and 28% vs. 61% for the controls) (Jourdier et al. 2003).

      Despite the recommendation for vaccine administration to be on the distal aspect of a limb to facilitate the attainment of clean surgical margins via limb amputation, a high proportion of tumors still developed in the interscapular region in a recent study evaluating the demographics of VAS. For prevention, administration of any irritating substance should be avoided. Vaccination should be performed as often as necessary, but as infrequently as possible. Nonadjuvanted, modified‐live, or recombinant vaccines should be selected in preference to adjuvanted vaccines. Injections should be given at sites at which surgery would likely lead to a complete cure; the interscapular region should generally be avoided. Postvaccination monitoring should be performed (Hartmann et al. 2015; Shaw et al. 2009). However, these current feline vaccine site recommendations may not be appropriate for cat owners as was concluded by Carwardine et al. (2014) based on an anonymous internet‐based cross‐sectional study in the UK wherein cat owning respondents would not allow amputation of their cats’ forelimb (20%), hindlimb (15%), or tail (15%).

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