Veterinary Surgical Oncology. Группа авторов
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than the quantity. Tissue barriers such as muscle, fascia, joint capsule, cartilage, and bone are inherently resistant to tumor penetration. Most solid tumors expand within their tissue of origin initially and grow along lines of least resistance. Surgical oncologists understand that including a tissue barrier beyond where the tumor is attached will trump a larger tissue margin in the absence of that barrier in terms of the likelihood of obtaining complete margins. However, fascia, often favored as a good tissue barrier and easily identifiable to the surgeon, is frequently difficult to discern as a distinct structure on histological sections. This creates difficulty in margin interpretation especially when minimum distances between the fascial plane used as a surgical margin and the nearest tumor cell exist. Is the patient at higher risk for recurrence with a 2‐cm histologic margin of normal fat or a 2‐mm histologic margin of normal tissue that includes a defined fascial layer (per surgeon reporting)?
Human medical evidence has suggested that qualifying the peripheral growth pattern of sarcomas as either “pushing” (no infiltration into surrounding tissue beyond the pseudocapsule) or “infiltrative” (tumor pseudocapsule poorly defined or satellite nodules present) was predictive of local recurrence (Engellau et al. 2005, 2007). The “pushing” contour was seen most commonly in low‐grade sarcomas, but a significant percentage of high‐grade sarcomas also displayed this characteristic (Engellau et al. 2007). High‐grade tumors with a “pushing” growth pattern had significantly fewer local recurrences than high‐grade tumors with “infiltrative” growth patterns (Engellau et al. 2007; Lintz et al. 2012). It is therefore possible that in even high‐grade sarcomas, a pushing pattern of peripheral growth may allow a narrower resection than a tumor with an infiltrative contour. These features (pushing or infiltrative) can be seen on MRI (Iwata et al. 2014; Nakamura et al. 2017), making it conceptually possible to plan resection margins preoperatively based on tumor contour features; however, this approach has not been studied extensively in human medicine or at all in veterinary medicine.
Compartmental tumor excision has been proposed by Enneking and others as a means to diminish the risk of local recurrence in musculoskeletal sarcomas. In compartmental excision, an entire compartment of tissue is removed, for example, an entire muscle or muscle group, as opposed to circumferentially resecting en bloc. Proponents argue that wide local excision, involving an arbitrary measure of a normal tissue “cuff,” risks leaving satellite nodules beyond the resected plane, especially in high‐grade, infiltrative tumors. Indeed, compartmental tumor excision has been shown to reduce recurrences in some tumor types and may be worth considering adopting in veterinary surgical oncology.
Currently, the best‐known predictors for local recurrence of solid tumors are histologic grade and completeness of excision. These features are typically assessed after resection, although grade may be determined prior to resection if the tumor is biopsied and sufficient tissue can be evaluated. Newer technologies such as genome sequencing and proteome analysis are designed to probe deeper into the biological aggressiveness of an individual tumor. Utilization of these methods may provide more specific information, can be acquired prior to surgery, and will provide information from both the tumor and the surrounding microenvironment. The microenvironment/tumor stroma is becoming a featured player in the understanding of tumor biology, as scientists begin to understand the importance of a permissive microenvironment and its role in invasion and metastasis. These datasets may ultimately provide the most accurate assessment of biologic behavior and subsequently assist the surgeon in personalized surgical planning. These analyses may prove to be far more predictive of both local recurrence and metastatic potential than histologic grade.
Given the myriad factors that influence assessment and reporting of surgical margins, it stands to reason that surgical oncologists need to collaborate with pathologists to standardize margin reporting and continue to assess the most predictive prognostic factors within each specific tumor type. It may be that the distance method is better for predicting recurrence in one type or grade of tumor, whereas in a different tumor type, the qualitative method may be most predictive. It is imperative that surgeons understand the limits and advantages of various methods of tissue sectioning and margin interpretation, and continue to develop new means of assessing biological aggressiveness. A one‐size‐fits‐all approach is no longer the best medicine.
Palliative and Cytoreductive Surgery
The decision to perform a palliative or cytoreductive surgery is often a difficult one, and the surgeon needs to educate the client and referring veterinarian about the risks and benefits of such surgery. Piecemeal removal (debulking) of a mass should generally only be performed when the mass is physically causing obstruction or function issues. There is little advantage to debulking otherwise unless the removal results in only microscopic amounts of disease left behind. Palliation of symptoms caused by obstructive masses by removing most of or portions of large masses can temporarily improve quality of life in some cases. This should be performed only when necessary as excessive bleeding can often occur and dehiscence is very common.
Postoperative Considerations
Tissue Marking
As discussed above, following an excisional biopsy, the surgical margins of the mass should be clearly indicated in some way so that the histopathologist can accurately evaluate the mass for complete excision. Several methods have been proposed to do this including specialized sectioning techniques, suture markers, inking, and the submission of adjacent tissue as a separate sample (Rochat et al. 1992; Mann and Pace 1993; Seitz et al. 1995). Inappropriate sectioning can result in neoplastic cells being noted at the cut margin and a false positive result can occur. Sutures can be used to mark a particular area of interest or for tumor orientation, but sutures need to be removed before sectioning to prevent microscopic artifact (Mann and Pace 1993). A sample of tissue surrounding the surgical wound can also be submitted for evaluation. However, this increases the size of the wound bed and added expense may be seen due to the submission of extra biopsy samples.
In general, the marking of tumor margins with inks or dyes is recommended. Several types of inks and dyes have been evaluated including merbromin, laundry bluing, India ink, alcian blue, typists’ correction fluid, commercial acrylic pigments, and artists’ pigment in acetone (Rochat et al. 1992; Mann and Pace 1993; Seitz et al. 1995; Chiam et al. 2003). Alcian blue has been shown to be the best marking material; however, India ink and commercial kits (Davidson Marking System, IMEB Inc., San Diego, CA) are reasonable alternatives (Seitz et al. 1995). One of the benefits of the commercial kits is that multiple colors are provided. When using these kits, all the margins can be marked in different colors, but at a minimum, the lateral margin can be marked in one color and the deep margin in a different color. Yellow, black, and blue colors are considered the best to use while red, violet, and green are less ideal (Seitz et al. 1995; Milovancev et al. 2013).
Guidelines for Fixation of Surgical Tissue Specimens
Small biopsy samples should be placed in fixative immediately to prevent drying of the sample. Early fixation will initiate changes in the sample that will prevent autolysis and bacterial alteration of the sample (Stevens et al. 1974). In large biopsy submissions, the sample should be sliced evenly to allow for more complete fixation (Dernell and Withrow 1998; Ehrhart and Powers 2007). However, when slicing a large specimen, care should be taken not to slice through the surgical margins but rather leave those untouched. Therefore, the slicing is done through the skin into the tumor for cutaneous or subcutaneous tumors. Many fixatives including formalin, Bouin’s fluid, chilled isopentane, Zenker’s fluid, and glutaraldehyde have been described in veterinary medicine (Osborne 1974; Stevens et al. 1974), but in general, 10% buffered formalin is sufficient for almost all biopsies. A biopsy sample should be fixed in formalin in a 1:10 solution of tissue to formalin (Ehrhart and Withrow 2007).
Frozen Sections
The use of frozen sections is common in human medicine (Kaufman et al. 1986; Lessells and Simpson 1976). Frozen sections generate an accurate diagnosis in greater than 97% of human biopsy samples (Lessells and Simpson 1976; Kaufman et al. 1986). The process requires highly trained personnel and equipment specific