Читать книгу Veterinary Surgical Oncology - Группа авторов - Страница 142

Surgical resection is the treatment of choice for most STS. Careful preoperative planning and a wide first excision, accomplishing 2–3 cm surgical margins around the tumor and one fascial plane deep to the tumor, are considered for surgery with curative intent.

If the tumor is attached to a muscle or fascial plane, the entire anatomical layer must be removed. Fat and loose connective tissues do not function as good tumor barriers, necessitating wide margins. If 3 cm tissue is not available in depth, at least a fascial plane underneath the tumor should be obtained. Tumors should not be shelled out of their pseudocapsule due to the high risk of regrowth of tumor cells remaining in and beyond the capsule. In general, wide surgical excision is the preferred therapy for all STS to achieve complete excision. For skin and subcutaneous tumors, this implies either surgical margins of 2–3 cm in all directions or 2–3 cm lateral to the tumor and at least one additional, non‐involved tissue plane beneath the tumor. An important rule is that the first surgery offers the best chance for cure (“the first cut is the deepest”) (Connery and Bellenger 2002; Dernell et al. 1998; Liptak and Forrest 2013). If the initial surgical excision was incomplete, curative‐intent re‐excision, if possible at all, will always imply wider margins and therefore higher morbidity than would have been the case if the initial surgery had been wide enough.

Recently, the importance of wide margins has been debated as wide margins were not associated with increased disease‐free interval or overall survival (Bray et al. 2014; Chase et al. 2009; McSporran 2009; Stefanello et al. 2008). But in view of patient selection with predominant low‐grade STS in primary care practices vs. high‐grade STS in referral practices, and current absence of available diagnostic tests to predict required margins for a certain STS, wide surgical margins continue to be the surgeon’s goal in patients treated by surgery only.

Incomplete resections increase patient morbidity, treatment costs, risk of further recurrence, and ultimately decreases survival time (Dernell et al. 1998; Kuntz et al. 1997; McKnight et al. 2000). Risk of incomplete excision is increased when the tumor is excised by a surgical resident compared to a board‐certified surgeon (Monteiro et al. 2011). More experienced oncologic surgeons achieve a significantly better outcome, most likely due to a superior ability to use aggressive surgical removal techniques (Rohrborn and Roher 1998). Extensive resections are complicated and may be impossible to close primarily depending on the extent, location, and quality of the surrounding tissue (Prpich et al. 2014). Adequate margins are often not achievable with larger STS located on extremities. Amputation (radical resection) may be an alternative in the absence of major orthopedic or neurological problems, but clearly often meets resistance from the owner. As recurrences after marginal excision of low‐grade STS may be less common than expected in high‐grade STS (McSporran 2009; Stefanello et al. 2008) smaller margins might be of choice in individual cases. Marginal resection of STS on extremities, either as sole therapy or combined with radiation therapy, may result in a long‐term outcome with lower morbidity compared to amputation. Only 11% of marginally excised low‐grade STS from extremities of 35 dogs resulted in recurrence, and median disease‐free interval and median survival time were not reached after a mean follow‐up of more than 1000 days (Stefanello et al. 2008). Another study reported a grade‐dependent recurrence after marginal excision of 3 of 41 (7%) grade I tumors, 14 of 41 (34%) grade II tumors, and 3 of 4 grade III tumors. The median time to recurrence was 12 months. In contrast, no recurrences were observed in the 30 tumors treated with complete excision. Thus, histologic grade is a strong predictor for recurrence for marginally excised subcutaneous STS, and clean margins predict nonrecurrence. However, tumor recurrence did not significantly reduce survival time, since no significant differences in survival time were found between grades treated with marginal excision, between marginal excision and wide excision, or between dogs that died from STS and dogs that died from other causes. This may be explained by the old age of affected dogs and the relatively slow growth of soft tissue sarcomas. Because high‐grade STS were not present in adequate numbers, conclusions about grade III tumors in this study could not be made (McSporran 2009).

Bacon et al. (2007) reported a recurrence rate of 15% (6/39) after re‐excision with margins of 0.5–3.5 cm, with a median follow‐up of 816 days. Residual tumor was identified in 9 of 41 (22%) resected scars. It was concluded that after incomplete resection of STS, resection of local tissue should be performed, even if excisable tissue margins appear narrow. A long‐term favorable prognosis was achievable without radiation therapy or amputation. According to the data in this study, the presence of residual tumor in resected scar tissue should not be used to predict local recurrence (Bacon et al. 2007).

Based on these studies therefore marginal excision of low‐ and intermediate grade‐STS may not influence survival time compared to wide or radical resection. This is most likely caused by the relatively old age (median age of 10 years) of affected dogs and relatively slow growth of low‐grade STS. Reported percentages of dogs that died of known STS‐related causes after treatment is between 10 and 33% (Baker‐Gabb et al. 2003; Ettinger et al. 2006; Kuntz et al. 1997; McSporran 2009; Simon et al. 2007), and many dogs will die of other age‐related causes. Radical resection of extremity STS may therefore be considered a last resort treatment for recurrent and high‐grade tumors (McSporran 2009; Stefanello et al. 2008).

All removed tumors should be submitted for histologic examination. Marking the surgical margins or specific areas of questionable margin status with ink or suture material will guide the pathologist in evaluating the completeness of excision, given the fact that standard histological margin assessment does not evaluate the complete cut edge of the excised tissue specimen but relies on a limited amount of sections through the margin. There are additional methods with the intention to increase reliability of histological margin evaluation, such as intraoperative frozen sections evaluation, and intra‐ or postoperative margin imprint cytology. By taking a superficial section of tissue from the wound bed after tumor excision, a so‐called shaved margin is obtained that can be assessed by the pathologist for remaining tumor cells. It remains to be proven if any of these techniques results in superior surgical margin assessment for specific tumor types in dogs and cats (Harris et al. 2014; Milovancev et al. 2017).

Using technology for intraoperative real‐time assessment of surgical margins is promising to improve the complete excision of canine soft tissue sarcomas. Using a fluorescent‐based imaging technique, sensitivity and specificity of the imaging system for identification of cancer (soft tissue sarcomas and mast cell tumors) in biopsies have been reported to be 92% for both (Bartholf DeWitt et al. 2016). Using optical coherence tomography, it is possible to differentiate soft tissue sarcoma, muscle, and adipose tissue from one another (Mesa et al. 2017; Selmic et al. 2019). The sensitivity and specificity of using optical coherence tomography to detect soft tissue sarcoma at the margins in one study were 88.2 and 92.8%, respectively, for within the surgical wound bed (in vivo) and 82.5 and 93.3%, respectively, for the excised tumor specimens (ex vivo). The accurate classification for all specimens was 91.4% in vivo and 89.5% ex vivo (Dornbusch et al. 2021).