In veterinary patients, intrathoracic surgical staging of lymph nodes is most commonly done as part of diagnosis and treatment of primary lung tumors. Assessment of the tracheobronchial lymph nodes for metastatic disease is known to be an important predictor of outcome in canine patients with primary bronchioalveolar carcinoma.^9,10,11 Median survival times have been described for dogs with primary lung tumors with evidence of metastatic disease (26–58 days) to the tracheobronchial lymph nodes compared with those without evidence of tracheobronchial lymph node metastasis (186–452 days) at the time of surgical resection of the primary tumor.^9,10 However, existing data do not differentiate between patients with microscopic metastatic disease and gross metastatic disease. Intrathoracic lymph nodes are very challenging to access for percutaneous FNA or biopsy because of their location in the mediastinum, many of which are intimately associated with major neurovascular structures. Because of this, it is currently recommended that when lung tumor excision is performed, that as part of the surgical procedure, the tracheobronchial lymph nodes should be palpated and biopsied if enlarged.¹⁰ The VATS lymphadenectomy procedure precludes direct digital palpation of the pulmonary hilus. Although techniques, parameters, and outcomes for VATS lung lobectomy have been described for veterinary lung cancer patients and very good success has been obtained in removal of the primary tumor, the approach to the tracheobronchial lymph nodes and histologic information on lymph node status has been limited in these case series.^12-14 A VATS surgical approach to the tracheobronchial lymph nodes has been described in normal dogs.¹⁵

In humans, VATS is commonly used for diagnosis and treatment of early stage non–small cell lung cancer and the evaluation of regional lymph nodes.^3,16 Pathologic node status is the single most significant prognostic factor in human lung cancer; therefore, unless there is clear evidence of metastatic disease on preoperative imaging, removal of regional lymph nodes for pathologic staging is considered an intrinsically important part of primary lung tumor resection in humans. Standardized procedures for lymph node description and resection are reported for humans.¹⁷ The overall oncologic outcome for patients with lung tumors undergoing VATS resection is identical to those obtained by open thoracotomy.^3,16,18-21 Despite this, there is some controversy in the human medical literature regarding the adequacy of lymph node evaluation achieved by thoracoscopic resections compared with open dissection.²³ However, recent studies have demonstrated that mediastinal lymph node dissection can be performed as effectively by the video-assisted approach as by the open thoracotomy approach and that furthermore, the video-assisted approach allows a better visualization of different lymph node zones.^21,24 Pan et al.²² demonstrated that VATS lobectomy and lymphadenectomy in humans were associated with fewer complications, recurrence, and shorter length of stay, with no differences in blood loss or number of lymph node dissections compared with open lobectomy. Regardless, the importance of lymphatic staging for lung cancer is clear in the human medical literature, and the choice of a VATS approach should not compromise appropriate lymphatic staging and other oncologic principles.

Ideally, surgical staging would not be necessary, and minimally invasive clinical staging modalities (imaging, cytology) should result in a clinical TNM (tumor, node, metastasis) stage that is highly predictive of the final pathologic TNM stage. Although noninvasive staging modalities have improved their sensitivity and specificity, stage migration occurs when clinical T stage, N stage, or M stages differ from ultimate pathology-confirmed stages, which is seen in up to 53% of human lung cancer resections.^25-27 Pathologic micrometastasis has been reported in 27% to 45% of patients and is associated with considerably poorer outcome.²⁸ Because of these limitations, current evidence-based guidelines recommend that human patients with any mediastinal lymphadenopathy by CT or positron emission tomography (PET) scan undergo surgical lymph node sampling to ensure accurate staging.²⁹ In fact, it is recommended that lymph node sampling should be the first invasive diagnostic procedure in patients with suspected lung cancer with mediastinal lymphadenopathy without distant metastases because the procedure can be used for both diagnosis and staging.²⁹ This is unlikely to be logistically feasible in veterinary patients, but it does highlight the importance of lymph node staging on prognosis and therapeutic decisions.

Variation in long-term survival outcomes after curative intent resection in human lung tumor patients, even in patients with ostensibly similar stages of disease, is partly due to variability in the quality of lymph node evaluation.^30-32 Missed lymph node metastasis can impair survival because of misclassification of risk. Patients with missed metastatic disease are deemed to have stage I disease and do not receive adjuvant therapy, which likely contributes to recurrent disease and reduced survival rates.^26,33 Even when careful surgical staging is performed, micrometastases that can affect survival may still be missed on histopathologic evaluation. At this time, a standardized methodology for pathologic evaluation of low-­volume tumor metastasis in lymph nodes has not yet been defined in veterinary patients. In a recent study of human lung cancer, occult nodal metastasis was detected by cytokeratin immunohistochemistry in 22% of patients with tracheobronchial and mediastinal lymph nodes that were initially diagnosed as N0 on standard hematoxylin and eosin staining of the same lymph nodes, and this occult nodal metastasis was associated with decreased disease-free and overall survival times.³⁴ On the basis of their results, Rusch et al.³⁴ recommended that immunohistochemical evaluation of N0 lymph nodes should be performed to identify patients that may benefit from combined modality treatment. There is much that we do not currently know about the prognostic significance and impacts of adjuvant therapy on dogs with lung tumor micrometastasis, but it is conceivable that earlier identification of low-volume metastatic disease in the tracheobronchial lymph nodes (TBLNs) of dogs with lung cancer could alter treatment recommendations and prognosis in our patients as well.

On the flip side of the coin, there has been growing interest in limiting the extent of mediastinal lymph node dissection in human lung cancer patients, and as a result, growing interest in the application of sentinel lymph node (SLN) mapping techniques to this tumor or location. The most common methods of intraoperative SLN mapping include the use of lymphoscintigraphy; intraoperative vital blue dyes; and more recently, the use of intraoperative near-infrared fluorescent imaging.^26,35-42 Near-infrared fluorescence imaging is an emerging modality that in early studies appears to have similar sensitivity and specificity to the combined use of scintigraphy and vital blue dyes and offers the benefit of avoiding patient and surgeon exposure to ionizing radiation.^26,42 The main downsides for near-infrared imaging are the need for specialized imaging systems that are not yet widely available and that the most commonly used near-infrared tracer, indocyanine green, is nonspecific and passes very quickly through the lymphatic system, making it prone to highlight second- and third-tier nodes if close attention to timing is not given. A small volume of the chosen tracer is injected peritumorally within the lung parenchyma. Assessment for tracer uptake in the locoregional lymph nodes is then performed, and dissection is directed to the identified nodes.

In a recent meta-analysis of SLN biopsy in human non–small cell lung carcinoma, the rate of detection of SLNs by SLN mapping ranged from 77% to 84%.²⁸ Lower detection rates were identified when using dye alone than when combined with a radiotracer, which may be related to preexisting black discoloration of the lymph nodes in many patients.²⁸ Studies have demonstrated evidence of “skipped” lymphatic drainage patterns (in which the anatomically closest node was not the sentinel node) in 20% to 30% of patients, but these “skipped” lymph nodes were identified with a high sensitivity by SLN mapping.^26,28 A VATS approach does not limit the ability to perform SLN mapping for lung cancer.^28,42 Chapter 26 provides a more complete discussion of SLN mapping.

Although species differences, especially anatomic differences, exist between veterinary and human lung cancer patients, similar to the case in humans, the regional lymph node status of veterinary patients has been shown to be a very important prognostic indicator of outcome.^9,10 As a result, it is logical to infer that although the exact role of many of these techniques in veterinary species have yet to be determined, well-considered staging is likely to also benefit our patients, and VATS approaches to staging have the potential to improve owner acceptance and patient care.