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Ann Thorac Surg 2004;77:426-430
© 2004 The Society of Thoracic Surgeons
a First Department of Surgery, Yamaguchi University School of Medicine, Ube Yamaguchi, Japan,
b Department of Radiology, Yamaguchi University School of Medicine, Ube Yamaguchi, Japan
Accepted for publication July 3, 2003.
* Address reprint requests to Dr Ueda, First Department of Surgery, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube Yamaguchi 755-8505, Japan.
e-mail: kaueda{at}yamaguchi-u.ac.jp
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Abstract |
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 Top Abstract IntroductionPatients and methodsReferences |
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METHODS: The subjects were 15 patients clinically diagnosed with N0 nonsmall cell lung cancer. Technetium-99m tin colloid was injected into the peritumoral area 1 day preoperatively and a time course of tracer migration was monitored by scintigraphy. A hand-held gamma probe counter was used to count the intrathoracic lymph node stations. Resected nodes were also counted to assess the accuracy of the intrathoracic counting.
RESULTS: Serial scintigraphies showed that the tracer migrated through airways and the appearance resembled hot nodes. On intrathoracic counting, 50% of the nodal stations appeared positive; however, only 23% of these apparently positive nodal stations were ultimately shown to be truly radioactive. The true positive and true negative rates of detecting intrathoracic hot nodes were 100% and 56%, respectively. Because the counts of the nodal stations could include the counts from the hot primary tumor ("shine-through") or airway radioactivity, legitimate hot nodes were identified after dissecting all the apparently positive nodal stations. Two of the 9 patients in whom hot nodes were identified had nodal metastatic disease and actually had tumor cells within the hot nodes. The only complication related to the preoperative injection of technetium-99m was a minor pneumothorax.
CONCLUSIONS: Although radioisotope intrathoracic lymph node mapping is safe, it appears to be unsuitable for sentinel node biopsy because shine-through and the airway-migrated radioactive tracer complicated the intrathoracic counting. Only serial scintigraphy could distinguish hot nodes from airway migration.
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Introduction |
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TopAbstractIntroductionPatients and methodsReferences |
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Lymph node mapping using the blue dye method [6] has some disadvantages. First, the blue dye can rapidly infiltrate the sentinel node and pass through into the distal drainage nodes, compromising the identification of a true sentinel node [7]. Second, every stained lymph node should be visually assessed by dividing the pulmonary vessels or even by incising the mediastinal pleura. Third, anthracotic black lymph nodes can be difficult to distinguish among the blue and negative nodes.
The advantages are that radiolabeled nodes can be quantitatively detected by a hand-held gamma probe even when they are not visible, allowing for a mediastinal node search without manipulation. Several investigators have attempted sentinel lymph node mapping after the intraoperative local injection of various kinds of nanocolloid particles (less than 80 nm in diameter and labeled by technetium-99m) [8–10]. In these trials, successful lymph node labeling was done, achieving a sentinel lymph node identification ratio in more than 80% of patients; however, there is still concern that such small particles could pass through into the distal drainage lymph nodes [11] and that the intraoperative lymphatic drainage could be artificial. Technetium-99m tin colloid is about 400 to 1000 nm in diameter and can slowly migrate to the sentinel lymph node and, on rare occasions, pass through into the next drainage lymph node even 1 day after the injection [11, 12]. In terms of accurate lymph node mapping under physiologic lymphatic conditions, a preoperative injection of technetium-99m tin colloid appears to be ideal. Thus, we conducted a clinical trial to determine the safety of lymph node mapping in patients with nonsmall cell lung cancer after a 1-day preoperative local injection of technetium-99m tin colloid. We also evaluated the accuracy of conducting an intrathoracic search for radiolabeled lymph nodes to determine the usefulness of this practice for selective lymph node dissection.
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Patients and methods |
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TopAbstractIntroductionPatients and methodsReferences |
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All patients had a final pathologic diagnosis of nonsmall cell lung cancer, differentiated as either adenocarcinoma in 12 patients and as squamous cell carcinoma in 3. There were 10 men and 5 women with a mean age of 65 years (range, 54 to 78). Lesions were located in the right upper lobe in 5 patients, the right middle lobe in 2, the right lower lobe in 3, the left upper lobe in 3, and the left lower lobe in 2. The mean tumor size was 2.2 cm (range, 1.2 to 3.5 cm). Postoperative pathologic examination confirmed that all patients were free of visceral pleural invasion. We performed lobectomy in 13 patients and segmentectomy in 2. The pathologic disease stages were stage IA in 9 patients, stage IB in 2, stage IIA in 1, stage IIB in 1, stage IIIA in 1, and stage IIIB in 1 (which was due to an intrapulmonary metastasis [pm1] diagnosed postoperatively).
Tracer injection and time course study
Technetium-99m tin colloid was used for the radioactive tracer, which was injected 1 day preoperatively. Before injection, the location and depth of the tumor was identified by computed tomography (CT) and the puncture site was determined in relation to the position of the tumor. After the local anesthesia with a total of 5 mL of 1% lidocaine hydrochloride, one (n = 2) or two (n = 13) injections of technetium-99m tin colloid, a dose of 2 mCi (74 MBq) suspended in 1.5 mL per injection, was given into each peritumoral area using a 23-gauge needle attached to a 2.5-mL syringe. Immediately after the injection, scintigraphy was done to confirm that there was no pleural seeding of the tracer. Chest CT scanning was also done to check for pneumothorax or hemothorax and to confirm whether the injection had been successful. In the first 10 patients, the time-course of tracer migration from the injected site was monitored by serial lymphoscintigraphies 5 minutes after and then 1, 2, 4, and 19 hours after the injection.
Intraoperative counting for tracer migration
Counting was done routinely using the hand-held gamma probe counter (Navigator; Auto Suture Japan, Tokyo, Japan) for each ipsilateral nodal station: stations 1 to 4 and 7 to 9 (N2 stations) and stations 10 to 13 (N1 stations) for right-sided tumors; and stations 4 to 9 (N2 stations) and 10 to 13 (N1 stations) for left-sided tumors. Anatomic landmarks for each lymph node station were determined according to the definition adopted in 1997 by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [13]. The counts per 5 seconds for tumor tissue, nodal stations, trachea, and intrathoracic background were recorded before and after anatomical pulmonary resection. When counting each nodal station adjacent to the airway, a gamma probe was carefully directed tangential to the airway to avoid counting the airway radioactivity. Positive radioactivity for a nodal station was defined if the counts for that nodal station were more than three times the intrathoracic background values. We then performed systematic lymph node dissection for each ipsilateral nodal station, namely stations 1 to 4 and 7 to 9 for right-sided tumors and stations 4 to 9 for left-sided tumors. After the specimens were resected from the operative field, counting for the resected specimens was also done separately to assess the accuracy of the intrathoracic search for radioactive lymph nodes. Because intrathoracic counts for nodal stations could include counts from hot primary tumors or airway radioactivity, significant lymph node radiolabeling (hot nodes) was confirmed if the counts for the resected node were more than three times the intrathoracic background value or greater than the counts for resected mediastinal fatty tissue surrounding these lymph nodes.
Pathologic nodal assessment
The dissected lymph nodes were examined histologically using formalin-fixed and paraffin-embedded sections with hematoxylin and eosin staining.
Results
The only complication related to the preoperative tracer injection was a pneumothorax requiring transient tube drainage in 1 patient, although minimal free air space was detected by routine chest CT scanning in 2 other patients who were asymptomatic (Fig 1).
There were no other respiratory or systemic adverse reactions throughout the examination. Radioisotope injections were accurately delivered in all patients (Fig 1). Scintigraphy was used to confirm that no radioisotope seeding into the pleural cavity had occurred. The average duration of tracer injection and thoracotomy was 20 hours (range, 19 to 20.5).
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Comment
In 2000, Liptay and coworkers reported successful intraoperative radioisotope lymph node mapping [8], since when several validation studies of this practice have been conducted [9, 10, 14, 15]. However, the best methods of radioactive tracing remain controversial. We believe that injecting Technetium-99m tin colloid 1 day preoperatively could be ideal for intraoperative radioisotope lymph node mapping for the following reasons: preoperative injection methods may be more reflective of the physiologic lymphatic state than intraoperative methods; as shown by the present serial scintigraphies, the tracer migrates initially through the airways rather than through the lymphatics when injected into the lung tissue, thereby complicating an accurate lymph node count, whereas airway tracers would be cleared time-dependently; and tin colloid may slowly migrate into the first drainage lymph node but it will rarely pass through into the following nodes because the colloid consists of relatively large particles (about 400 to 1000 nm in diameter). According to a time-course study of breast lymphoscintigraphy, hot sentinel nodes persisted for up to 1 day after the injection of tin colloid without passing through to the following nodes [12]. Therefore, previous investigators defined a sentinel node as any hot node identified using tin colloid and found an average 1.7 to 2.0 sentinel nodes per patient [14, 15], which is comparable with our results. On the contrary, some nanocolloid particles will rapidly migrate to a sentinel lymph node, then pass through and be distributed widely to the following lymph nodes [11]. These colloid particles have mainly been used in the intraoperative migration method to find the sentinel node just as the tracer reaches the node [8–10]. However, concern remains that sentinel nodes might be incorrectly identified even with the intraoperative use of these nanocolloid particles. The true sentinel node can be missed during anatomical resection because it may be hidden by a hot primary tumor or airway radioactivity until the nodes are resected.
Our study confirmed the safety of preoperative radioisotope injections. Scintigraphy showed successful radioisotope injection into lung parenchyma without radioisotope seeding into the pleural cavity and CT showed that the injection site was indeed a peritumor lesion located within the same subsegment as the tumor (Fig 1). Furthermore, in our series, the incidence of complications resulting from preoperative tracer injections was well within acceptable limits.
We found hot nodes in 60% of the patients, which seemed a relatively low percentage compared with those of previous studies using tin colloid for the identification of breast [16] or gastric [17] sentinel lymph nodes. In our series, 5 of the 6 patients in whom hot nodes were not identified had moderate to severe anthracotic lymph node silicosis and pulmonary emphysema due to heavy smoking. Nomori and colleagues found that patients without lymph node radiolabeling had complications associated with obstructive respiratory dysfunction [13]. Either attenuated density of lymphatics at the injection site or lymphatic dysfunction may have existed in these patients and ours due to degenerative pulmonary diseases such as emphysema.
We clarified the accuracy of the intrathoracic detection of hot nodes to determine whether this practice is appropriate for so-called sentinel node biopsy. As a result, we identified all the hot nodes without overlooking any, although overestimation frequently occurred. In fact, 44% of nonhot nodes were overestimated to be hot because the hot primary tumor and airway radioactivity complicated the search for true hot nodes. Although the hot primary tumor and airway radioactivity seem to be a common and specific pitfall in sentinel node assessment of the respiratory tract, few reports address this issue. Nomori and associates studied the correlation between the intrathoracic and extrathoracic detection of hot nodes [14]. They overlooked only one hot node by intrathoracic detection in their series, but found greater discrepancy between the intrathoracic and extrathoracic detection of hot nodes when counting N1 stations rather than N2 stations, probably because the hot primary tumor and airway radioactivity resulted in false intrathoracic counting. Although these results would appear to be similar to ours, they are not comparable because they did not show the accuracy of intrathoracic detection in terms of the overall frequency of overestimated lymph node stations. This seems to be important for assessing whether this practice is useful for sentinel node biopsy because in the present series, all the overestimated nodal stations had to be dissected before the true hot node was able to be identified.
The high incidence of airway radioactivity in our study may not be directly related to the size of the tracer. Regardless of molecular size, some parts of the intraalveolarly administered tracer are assumed to inherently migrate into the tracheobronchus due to coughing or respiratory lung motion even when it is properly injected into the peritumoral area under CT guidance. However, one might speculate that even the airway-migrating tracer could contribute to incorrect lymph node radiolabeling or that airway migration may leave insufficient tracer in the injected site, resulting in inaccurate lymph node radiolabeling. To dispel these concerns, we analyzed the linear dependence of the tracheal radioactivity and the highest lymph node radioactivity by linear regression analysis, and found no significant correlation between these two values (n = 15, Y = 11.99 to 0.243X, r = 0.004, p = 0.826; Fig 3). Furthermore we believe that the tracer migrated correctly to the hot node through the lymphatic route because none of the background tissues surrounding the hot nodes showed significant radioactivity.
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In conclusion, although radioisotope intrathoracic lymph node mapping was found to be safe, it appears to be unsuitable for sentinel node biopsy because shine-through and the airway-migrating radioactive tracer complicated the intrathoracic counting. Only serial scintigraphy can truly distinguish hot nodes from airway migration.
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References |
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TopAbstractIntroductionPatients and methodsReferences |
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