Evaluating tumour margins when preparing to treat cancer: part 2
Kathryn Pratschke, in the second part of a two-part article, discusses preoperative tumour staging, sentinel node evaluation and tumour margins in oncology surgery.
Kathryn Pratschke
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Figure 4. Full thickness thoracic wall resection (in this case, a four-rib portion of thoracic wall incorporating two lung lobectomies due to tumour adhesions) is an example of radical resection.
In the first part of this article (VT46.07) the importance of preoperative patient assessment and planning, including the role of surgical oncology in obtaining tissue diagnosis and treatment, was discussed.
In this article, the importance of preoperative tumour staging and the concept of sentinel node evaluation is reviewed, and surgical principles and appropriate selection of tumour margins are discussed.
Tumour staging prior to surgery
Figure 1. The surgeon should avoid handling ulcerated or open areas on the tumour during surgery. If possible, a tumour with ulcerated, open or bleeding areas should be wrapped or covered with a sterile drape or swab to reduce the risk of contamination during resection.
Staging describes the process of classifying the extent of malignant disease present. Understanding the biologic behaviour patterns for different tumour types means a veterinary surgeon can prioritise staging tests appropriately. The tumour node metastasis (TNM) system, as described by the World Health Organization, is probably the most commonly used for categorisation of neoplastic disease involvement in veterinary medicine, although formal staging is not as developed in veterinary oncology as in human medicine.
Tumours exist where the optimum staging process has not been clarified, and what comprises staging protocols varies between individuals. The minimal staging before surgery for masses likely to be malignant should include:
definitive identification of the primary lesion(s)
thoracic imaging for a “met check”, either inflated chest radiographs (three views) or advanced imaging (CT scan)
evaluation of regional lymph nodes
abdominal imaging, ultrasound or advanced imaging – depending on tumour type and location
Sentinel lymph nodes
Regional lymph node metastasis is an important risk factor for recurrence or persistence of disease in patients with completely resected tumours, both in humans and animals (Krick et al, 2009; Saltman et al, 2010; Huynh and Bilchik, 2015).
The concept of sentinel nodes has gained a lot of attention. The sentinel node hypothesis states the histopathological status of the first node on the lymphatic drainage pathway from a primary tumour reflects the tumour status of the entire lymphatic drainage basin. Underlying this hypothesis is the assumption the surgeon can correctly and consistently identify which node is the sentinel node (Hsueh et al, 2001).
The anatomical definition of the sentinel node as the lymph node closest to the primary lesion does not take into consideration the physiology of lymph drainage – the node closest to the primary tumour is the first one to be involved only when it receives direct drainage from the site (Krick et al, 2009; Tuohy et al, 2009). In some cases, this will not be the “logical” node; for example, an oral tumour may have a mandibular node as its sentinel node, but it could equally be retropharyngeal or zygomatic.
Considerations for tumour removal
Figure 2. If an incomplete resection is achieved from an initial surgery then revision surgery must treat the surgical scar as potentially contaminated with tumour cells. The area of regrowth at one end of the scar is identified with a circle, but the planned area for resection includes lateral margins around the associated scar, as well as those around the regrowth.
Adhering to certain key surgical principles will increase the chance of success and reduce the risk of recurrence, as well as minimising the risk of local/distant seeding of tumour cells:
The tumour should be draped off from the rest of the surgical field and the surgeon should avoid handling any ulcerated or open areas of the tumour (Figure 1).
Minimising manipulation of the tumour may help reduce the risk of shedding cells from tumour types that readily exfoliate, such as carcinoma or mast cell tumour.
It has been suggested sharp dissection should be used, if possible, as blunt dissection can increase the risk of straying from a predetermined margin and leaving neoplastic cells in the patient (Ehrhart and Culp, 2012); however, definitive evidence is lacking.
All biopsy tracts must be removed en bloc with the tumour – if the biopsy tract is placed outside the palpable tumour diameter, the “tumour diameter” must be redrawn to incorporate the biopsy tract. Similarly, any adhesions should be resected with the tumour.
When considering whether to use a drain at the tumour resection site, remember if residual tumour cells are in the surgical site, they may seed along the drain. This means anywhere the drain has been must subsequently be considered contaminated with tumour cells for revision surgery or adjunctive radiation.
If performing revision surgery in response to a report of dirty margins, or because regrowth has been noted, the entire surgical scar must be considered a “tumour”, as the surgical site will have been potentially contaminated with tumour cells. Margins should be drawn using the scar plus any local regrowth as a guideline (Figure 2).
Try to avoid cutting, opening or breaking open the tumour or pseudocapsule,
as this increases the risk of tumour dissemination.
Careful attention to haemostasis will reduce the incidence of postoperative haematomas and/or seromas. These can allow tumour cells to gain access to areas they would not otherwise reach as the seroma/haematoma fluid disperses subcutaneously and along fascial planes during movement.
If a tumour is malignant then, following resection, the surgeon should change gloves, use a clean set of instruments and consider redraping the patient before reconstruction.
The same principle applies if more than one tumour is being removed from the same animal: different gloves, instruments and drapes should be used to ensure cells from one site are not transposed to another, such as from a mast cell tumour to a lipoma wound bed.
Surgical margins for tumour removal
Figure 3. A soft tissue sarcoma on the limb of a 10-year-old Labrador retriever. Curative intent surgery is not possible without amputation, but a good alternative option is a planned, or deliberate, marginal resection that keeps sufficient skin for primary wound closure with a view to radiation therapy post-surgery. If this approach is being considered, a radiation oncologist should always be consulted first to discuss the case, so the entire treatment is planned in advance.
Five levels of surgical margin (often referred to as the surgical “dose”) exist to classify the extent of surgical tumour resection (Dernell and Withrow, 1998; Withrow, 2001):
Intralesional or intracapsular resection implies dissection that happens within the confines of the tumour dimensions and residual disease will always remain (Soderstrom and Gilson, 1995). It is rarely an appropriate treatment for neoplastic diseases as this technique may leave a significant tumour cell burden that negates the possibility of a positive outcome, even with adjunctive treatments such as radiation and chemotherapy (McChesney et al, 1989).
Marginal excision is defined as removing the tumour with a 1cm or less cuff of “normal” tissue. While adequate for lipomas and other benign masses, such as cysts, this approach tends to fail with malignant neoplasms unless it is part of a planned overall treatment protocol. For example, planned marginal resection can be combined with adjuvant radiation for soft tissue sarcoma or mast cell tumour of the distal limb as a way of circumventing the problem of how to reconstruct a large deficit in an area with very limited skin (Demetriou et al, 2012; Figure 3). Excisional biopsy of a malignant tumour, without prior knowledge of tumour type, is basically an unplanned marginal resection and is not recommended, although it remains commonplace in veterinary practice (Chase et al 2009; Bray et al, 2014).
Wide resection implies tumour removal with margins between 1cm to 3cm of normal tissue in all directions, including the deep margin. To satisfy the definition of wide resection, the mass must be removed en bloc, and the pseudocapsule and the reactive zone should be completely contained within an envelope of normal tissue.
Radical resection implies removal of a tumour with margins greater than 3cm in all directions; or contained within an entire tissue compartment, such as limb amputation and body wall resection (Figure 4).
Extra-compartmental resection is defined by a plane of resection beyond a defined anatomic compartment considered to have a cancer-resistant tissue barrier (Soderstrom and Gilson, 1995), such as hemipelvectomy.
In some cases, taking the appropriate surgical margins may result in a procedure too disfiguring, painful or expensive for an owner to consider, minimally advantageous in terms of survival benefit, or incompatible with life (Farese et al, 2012). Therefore, when considering a radical resection for definitive treatment, it is essential to take quality of life into account and have a full and frank discussion with the client.
Figure 4. Full thickness thoracic wall resection (in this case, a four-rib portion of thoracic wall incorporating two lung lobectomies due to tumour adhesions) is an example of radical resection.
The most common mistake in cancer surgery is to pick too small a margin, usually due to concerns about whether the resulting defect can be closed if wider margins are taken.
Surgical margin should always be selected based on what is most appropriate for the tumour type, unless, after discussion with an owner, they decide they want to pursue palliative treatment only. Once the appropriate margins are decided, it is possible to estimate the size of the resulting defect.
If an individual is not confident to deal with a defect that will result from taking curative intent margins then, in the patient’s best interest, a referral offer to a more experienced surgeon should be made.
Deep margin
The deep margin is often a source of confusion. It is easy to visualise and understand what is meant by a 3cm lateral margin, but much harder to do so for the deep margin. The critical issue with deep margins is whether a fascial plane clear of all tumour involvement has been removed and, if so, what it comprised.
Connective tissues, including muscle fascia, cartilage and bone, are fairly resistant to neoplastic invasion, providing a natural “tissue barrier” while subcutaneous fat, muscle and parenchymal organs are not (Eisenstein et al, 1973).
Unfortunately, there is still no clear, uniform definition for the term “fascial plane” in the context of cancer surgery. Some authors consider fatty tissue to be a fascial plane while others do not (Fasel et al, 2007), although there are reports from more than 100 years ago documenting ready invasion of fatty tissue with malignant tumours (Halsted, 1894).
The definition of fascia is considered to be “sheaths, sheets, or other dissectible connective tissue aggregations visible to the unaided eye” (Wendell-Smith, 1997) and/or “gross structures enveloping and/or supporting other formations” (Fasel et al, 2007).
Fixation of surgical tissue specimens
Figure 5. Tissue ink is a useful way of marking the margins of resection after tumour removal. It allows the pathologist to accurately recognise the true margin, regardless of how the tissue is orientated on the slide. Image: Fui Yap.
Once a tumour has been removed, it is important to make sure you get the best histopathology report possible, which means handling and submitting tissue specimens appropriately:
Small tissue samples should be placed in formalin as soon as possible to prevent desiccation that may cause artifactual changes.
Large tissue samples should be sliced evenly to allow more complete fixation (Dernell and Withrow, 1998; Ehrhart and Withrow, 2007).
Biopsy samples should be fixed in formalin in a 1:10 solution of tissue to formalin.
Give consideration to marking the tumour margins, with either tissue ink (Figure 5) or suture tags.
This should ideally be accompanied by a sketch, or a good written description explaining to the pathologist where the tumour came from and how the markers relate to tumour orientation, such as the yellow ink identifies the dorsal margin, the blue ink identifies the caudal margin, the red ink identifies the deep margin and so on.
Pertinent information regarding patient signalment and history should also be included to give the pathologist context for the tumour they are examining.
Summary
For veterinary surgeons in practice, surgery remains a key tool for treating cancer. Pursuit of better treatment options, the increasing availability of a wider range of treatment options and ready availability of this information to the general public will require veterinary surgeons dealing with cancer to remain up to date with their thinking and be able to adapt to change.
Adhering to certain basic principles of good practice in surgical management of tumours ensures the patient genuinely receives the best care possible and the best outcome. A key part of this involves understanding how to select tumour margins appropriately and the implications of compromising on appropriate margins.
