British Journal of Radiology 75 (2002),950-958 © 2002 The British Institute of Radiology
The ability of lymphoscintigraphy to direct sentinel node biopsy in the clinically N0 neck for patients with head and neck squamous cell carcinoma
G L Ross, MRCSEd1,
D S Soutar, ChM1,
T Shoaib, FRCSEd1,
I G Camilleri, FRCS (Plast)1,
D G MacDonald, FRCPath2,
A G Robertson, PhD5,
R G Bessent, MA, Dphil, FIPEM1 and
H W Gray, FRCP4
1 Plastic Surgery Unit, Canniesburn Hospital, Switchback Road, Bearsden, Glasgow, Departments of 2 Oral Pathology, 3 Clinical Physics and 4 Nuclear Medicine, Glasgow Royal Infirmary, Glasgow, and 5 Beatson Oncology Centre, Western Infirmary, Glasgow, UK
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Abstract
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This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct sentinel node biopsy (SNB) in the identification of occult metastases in the clinically N0 neck for patients with head and neck squamous cell carcinoma (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma probe and blue dye. SNB was performed after radiocolloid and blue dye injection. Pre-operative LSG and the intra-operative use of a gamma probe identified radioactive sentinel nodes, and visualization of blue stained lymphatics identified blue sentinel nodes. 104 sentinel nodes were harvested from 43 patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested, 17 of 62 (27%) nodes identified as both radioactive and blue were positive for occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39 (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05). LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC.
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Introduction
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The advent of sentinel node biopsy (SNB) has allowed a multiteam approach in the treatment of head and neck squamous cell carcinoma (HNSCC). A combination of techniques employed by nuclear medicine, surgery and pathology has led to an improved understanding of lymphatic pathways.
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Lymphoscintigraphy
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Lymphoscintigraphy (LSG) is a simple and non-invasive functional test for demonstrating lymphatic pathways. Both the substance to be labelled and the radioactive nuclide are usually used in such small amounts that no pharmacological effect ensues upon administration to the patient. The first radiographic study of the lymphatic system using an interstitial injection of radioactive colloid gold (198Au) was performed in rabbits in 1953 [1]. Over the years almost every lymphatic basin and region has been demonstrated by LSG, employing a variety of injection techniques and tracers. Much information has been gained regarding a variety of radiopharmaceuticals.
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Radiopharmaceuticals
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An ideal radiopharmaceutical for LSG should meet the following requirements:- The radiation dose to the injection site should be as low as possible and the radiopharmaceutical should have a short physical half-life, emit only gamma rays but have a suitable energy for detection by imaging equipment.
- The compound should clear rapidly from the injection site allowing early visualization of the lymphatics and faster study times.
- There should be homogeneity in particle size of the radiopharmaceutical, allowing reproducibile results.
- The compound should have high uptake with a relatively long residence in the lymph nodes.
- The compound should be commercially available in a simple, ready-to-use kit form at a reasonable cost.
Although 198Au was first used in the 1950s [1], it had a long half-life (2.7 days) and was a beta-emitter. A lower radiation dose is associated with radiolabelled technetium (99Tcm) which is a gamma emitter, has a short half-life and can be produced at low cost. Since its first reported use in 1965 [2] there have been many radiopharmaceuticals produced using a variety of compounds labelled with 99Tcm.
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Lymphoscintigraphy as applied to head and neck cancer
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Accurate staging of malignant diseases, including lymph node involvement, is necessary for treatment planning and prediction of prognosis. The replacement of lymph nodes with disease leads to a change in lymph flow and hence a change in appearance using LSG. This concept has been utilized in HNSCC. Parell et al [3] compared differences in drainage patterns of oral cavity between neck sides after interstitial injection of 99Tcm sulphur minicolloid. Where decreased or absent uptake occurred in the side of the neck suspected of nodal disease, the neck was considered positive. Parell et al showed that LSG predicted the presence of metastases in all patients with palpable nodes. A similar study by Sri-Pathmanathan et al [4], using bilateral injections of 99Tc labelled sulphur microcolloid, compared drainage patterns of the neck; any perfusion or gap defects between neck sides was considered abnormal. There were no patients with normal LSG scans who developed subsequent disease. LSG has also been described as a means to detect abnormal drainage pathways for intra-oral tumours.
Klutmann et al [5] described a study of LSG using interstitially injected 99Tcm labelled colloid in 75 patients with biopsy proven squamous cell carcinoma of the oral cavity. In 70% of patients, drainage was seen in either one or both lymphatic basins. LSG showed an accurate correlation of lymphatic drainage to the cervical basin in comparison with the pathological neck dissection specimens. LSG alone has been shown to be unable to detect micrometastasis in HNSCC [6], presumably because of minimal changes to the lymphatic architecture and hence lymphatic flow. A combination of LSG and SNB, however, is a potential method of detecting such micrometastasis.
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Lymphoscintigraphy as applied to sentinel node biopsy
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The sentinel node concept is based on the premise that lymphatic flow from the primary tumour travels sequentially to the sentinel, or first draining lymph node, and then onto the remaining regional lymph nodes, and the pathologic status of the sentinel node accurately reflects the histology of the remaining regional lymphatics.
In order to solely identify a sentinel node without the visualization of any other nodes, the ideal pharmaceutical should selectively identify the sentinel node, reach the sentinel node and remain trapped within, therefore reducing non-sentinel node background emissions.
Lymph node uptake and retention strongly depend on the radiopharmaceutical particle size. Particles of a few nanometres diameter generally pass into the bloodstream through venous capillaries [7], while particles greater than a few hundred nanometres diameter are likely to be trapped at the site of injection. Particles with intermediate sizes are absorbed into lymphatics, but once there, particle size continues to play an important role in their accumulation in lymph nodes. The greater the number and size of particles in the lymph flowing to the sentinel node, the greater the probability that these particles will be phagocytosed and retained in the first lymph node they encounter [8–10].
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Lymphoscintigraphy and sentinel node biopsy for head and neck cancer
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Although SNB has been used in a number of cancers, the concept has been mainly applied to malignant melanoma [11] and breast cancer [12]. In these cancers, sentinel nodes free from tumour imply a regional lymph node basin free from tumour with a high degree of accuracy. In malignant melanoma it was found that the triple diagnostic technique of LSG and intra-operative use of blue dye and a gamma probe facilitated sentinel node identification and improve the accuracy of staging [13–15].
In HNSCC the first use of LSG for SNB was by Koch et al [16] using a 99Tcm unfiltered sulphur colloid radiocolloid and intra-operative gamma probe. Within the small patient cohort they did not identify nodes in two patients who were subsequently found to have cancer in the lymph nodes on histological evaluation. Shoaib et al [17] described the technique using pre-operative LSG, blue dye and radiocolloid in 40 clinically N0 patients showing a procedure sensitivity of 94% (comparing the pathology of the sentinel node and the subsequent pathology of the neck dissection). LSG for SNB has successfully been used by a number of institutions [18–26]. The sensitivity of the technique improves with experience [27] and has recently been described in our unit as a means of staging the clinically N0 neck without the need for an elective neck dissection [28].
The aim of this study was to evaluate the ability of LSG to direct SNB in the identification of occult metastases in the clinically N0 neck for patients with HNSCC, without the need for an elective neck dissection.
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Methods
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48 patients have entered the study to date. Patients undergoing SNB were admitted the day prior to surgery. The triple diagnostic procedure of pre-operative LSG and intra-operative blue dye and gamma probe has previously been described [17] and will only be briefly elaborated here. Patients underwent LSG up to 1 day prior to surgery. A maximum of 40 MBq 99Tcm labelled human serum albumin (Albures or Nanocoll; Nycomed Amersham, High Wycombe, UK) was injected throughout the normal mucosa surrounding the tumour edge and the submucosa on the deep aspect of the tumour, in a volume of approximately 0.5–1.0 ml. Albures was used for floor of mouth (FOM) and anterior tongue tumours, and Nanocoll for other sites. A syringe with a permanently secured needle was used for injection to prevent inadvertent spillage of colloid into the mouth. Colloid was injected at as many points as necessary in an attempt to completely surround the tumour. Mouthwash was used immediately following injection to prevent pooling or swallowing of residual radioactivity by the patient. Static LSG was performed in two planes at 15 min, 30 min and 1 h post injection, or until the appearance of radioactive nodes. It was usual to see uptake of activity 15 min post-injection. If visible uptake in nodes was still absent 1 hour after injection, either the lymph nodes were deemed to be too close to the injection site or radiocolloid had leaked out of the injection site. Either a radiolabelled Cobalt (57Co) marker was employed to trace the patient outline or a flood source of 57Co or 99Tcm was placed behind the patient to produce a silhouette of the patient outline. A gamma camera fitted with a low energy, general purpose collimator was used to image the patient. A 20% window centred on the 140 keV photopeak was selected and the camera interfaced to a suitable computing system. The locations of radioactive lymph nodes were marked on the patients' skin; the position of a 57Co solid source pen was observed on the cameras' persistence display and the pen moved until its position overlay that of a radioactive node. This position was then marked on the skin using indelible ink. During skin marking, a lead plate of an appropriate thickness was used to shield the injection site.
Following image acquisition a software mask was applied to all images to eliminate radioactivity from the injection site. A region of interest, drawn around the image of the site of injection, was used as the basis for the mask applied.
The LSG hard copy was available for the surgeon in theatre intra-operatively. During surgery, approximately 0.5–2 ml of patent blue V dye (Laboratoire Guerbet, Aulnay-Sous-Bois, France) was injected into the same site as the radiocolloid. A suitable incision was made in the neck in such a position as to facilitate excision of the scar should a subsequent therapeutic neck dissection (TND) be necessary. Blue stained lymphatics, if seen, were followed to the first draining lymph node, which was harvested. All radioactive lymph nodes were identified with a Neoprobe 1500 hand held gamma probe (Neoprobe Corporation, Dublin, OH ) and anatomical positions confirmed with the position on the LSG scans. The hand held gamma probe was used to identify radioactive sentinel nodes, including those marked pre-operatively during LSG. To reduce detection of radiation from the injection site, a series of malleable sterilized lead plates were used to mask the injection site, thus aiding in vivo identification of radioactive nodes. Radioactive nodes were excised and radioactivity within the node was confirmed ex vivo. Sentinel nodes were labelled according to their colour, radioactivity and anatomical neck level [29]. Levels of all radioactive nodes harvested were compared with those on LSG scans by the consultant surgeon.
Sentinel nodes were fixed in 10% neutral buffered formalin and, after fixation, were bisected through their longest axis. If the thickness of the halves was more than approximately 2.5 mm, the slices were further trimmed to provide additional 2.5 mm thick blocks. One haematoxylin-eosin (H&E) stained section was prepared from each histological block and examined for possible metastasis.
The full pathological protocol was used to examine nodes that appeared negative following examination with H&E, and these nodes were step serial sectioned at 150 µm levels. One section from each level within the block was stained for H&E and examined. If the node still appeared free from tumour, immunocytochemistry for cytokeratin was undertaken. Cytokeratin positivity was compared with the adjacent H&E section to confirm that it represented viable tumour cells. If metastatic tumour was found, either on routine H&E, step sectioning or immunohistochemistry, a TND in the form of a modified radical neck dissection [29] with preservation of the accessory nerve, sternocleidomastoid muscle and the internal jugular vein was undertaken.
Patients with negative SNB findings were followed up as out-patients every 3 months and no further treatment to the neck was carried out. The mean follow-up for these patients has been 18 months (range 9–32 months).
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Results
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Sentinel nodes were harvested from 90% (43 of 48) of patients and 88% (50 of 57) of neck sides. Nine patients underwent bilateral SNB when either bilateral drainage was visible on LSG or where bilateral SNB was required to stage a midline tumour. 21% (22 of 104) of sentinel nodes harvested in 35% (15 of 43) of patients were positive for occult metastases. Of the 104 nodes harvested, 27% (17 of 62) of nodes identified as both radioactive and blue were positive, and 12% (5 of 42) of the remaining nodes were identified as either hot only or blue only (p<0.05).
Sentinel nodes were identified in 81% (39 of 48) of patients on LSG (Figure 1
). Nine patients had bilateral nodes visible on LSG. Sentinel nodes were identified in 82% (47 of 57) of neck sides. Of 39 patients in whom sentinel nodes were identified using LSG, 95% (37 of 39) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 44% (4 of 9) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05).
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Figure 1. Identification rates of nodes on lymphoscintigraphy and harvested radioactive sentinel nodes following injection of radiocolloid. SCC, squamous cell carcinoma; SNB, sentinel node biopsy.
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We compared T classification (Table 1) and site of tumour (Table 2) to determine if these factors had any influence on whether a sentinel node would be visible on LSG. There were no statistically significant differences.
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Table 1. T stage, its effect on lymphoscintigraphy (LSG) identification rates and its effect on the ability to harvest radioactive nodes intra-operatively
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There were three FOM, four anterior tongue, one posterior tongue and one retromolar tumour(s) in which no nodes were identified on LSG. Subsequent harvesting of sentinel nodes found no radioactive nodes in four FOM, two posterior and one anterior tongue tumour(s). In three of four anterior tongue tumours, absence of sentinel nodes on LSG did not prevent radioactive sentinel nodes being harvested.
There were 78 sentinel nodes visible on LSG and 87 sentinel nodes subsequently harvested as radioactive. (Table 3).
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Table 3. Number of harvested and positive radioactive sentinel nodes for patients with nodes visible on lymphoscintigraphy (LSG) images (number of radioactive nodes that were also blue shown in parentheses)
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The distribution of harvested positive radioactive sentinel nodes by cervical level was similar to that of harvested negative radioactive sentinel nodes. There were no positive radioactive sentinel nodes in level 4 and there were no sentinel nodes harvested in level 5. 26% (15 of 57) of nodes identified on LSG were subsequently harvested as both hot and blue compared with 13% (4 of 30) that were harvested as hot only. This was not statistically significant (Table 4).
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Table 4. Distribution of harvested radioactive sentinel nodes if nodes visible on lymphoscintigraphy (number of radioactive nodes that were also blue shown in parentheses)
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Two radioactive sentinel nodes harvested as positive, after no nodes being visible on LSG, were both from level 1 (Table 5). The distribution of all radioactive nodes is shown in Table 6.
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Table 5. Distribution of radioactive sentinel nodes if nodes not visible on lymphoscintigraphy (number of radioactive nodes that were also blue shown in parentheses)
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Table 6. Distribution of all radioactive nodes (number of radioactive nodes that were also blue shown in parentheses)
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There were only two patients in whom sentinel nodes were identified using blue dye only. In both cases one node was harvested from level 2. In both cases no nodes were initially visible on LSG or detected intra-operatively as radioactive with the gamma detector. In one case the sentinel node was positive.
After a follow-up of 18 months (range 9–32 months), one patient staged as sentinel node negative has developed disease. Therefore the sensitivity of the technique is at present 94% (15 of 16) [28].
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Discussion
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The importance of pre-operative LSG for SNB to stage the clinically N0 neck without neck dissection in HNSCC has not been previously reported. We have shown that the presence of sentinel nodes on LSG is a significant predictor of whether a radioactive sentinel node will subsequently be harvested during surgery. SNB for tumours in the midline has proved a revelation to our practice, the use of LSG determining which neck side the tumour will drain. Tumours with bilateral drainage can thus be targeted before surgery and a bilateral SNB performed.
There was one case of a lateralized tongue tumour where drainage was bilateral. By performing LSG, abnormal drainage patterns such as these can be determined pre-operatively (Figure 2) [5]. The images in Figure 2 also highlight other important aspects of LSG. Both anteroposterior (AP) and lateral views, and software masking are recommended. Figure 2 shows clearly, in the AP view after software masking, bilateral asymmetrical drainage. Use of non-software masked images in both views may have missed the bilateral drainage.
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Figure 2. (a) Lymphoscintigraphy (LSG) scan before application of software masking in the anteroposterior (AP) view. (b) LSG scan before application of software masking in the lateral view. (c) LSG scan after application of software masking in the AP view. (d) LSG scan after application of software masking in the lateral view.
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Using LSG, sentinel nodes were present but not harvested in only two patients, one with a FOM tumour and one with a posterior tongue tumour. This was owing to technical difficulties during surgery.
In patients with nodes on LSG, the harvested radioactive nodes corresponded to those on the scan. There were nine harvested radioactive nodes that were not apparently visible on the pre-operative scan. We do not currently perform late imaging and one possible explanation is that as the surgery was performed the day after the LSG scan, there may have been further drainage of colloid into additional second echelon nodes. It is our current protocol to remove all radioactive nodes that are detected intra-operatively. Another explanation is that it is likely that radioactive sentinel nodes in close proximity to each other may result in only one node being visible on the LSG image owing to an amalgamation shine through affect. During surgery where a sentinel node was found in addition to those on LSG, it was always in close proximity to a sentinel node visible on the LSG image.
We have looked at a number of variables to determine why sentinel nodes may not be visible on LSG or harvested. One factor affecting injection techniques and subsequent LSG/harvesting is the closeness of the primary site to the cervical draining basin and the potential spilling of colloid following injection. All tumours may be affected by spillage of colloid; both swallowing and pooling of colloid around the primary site should be avoided. Asking the patient to rinse his/her mouth out repeatedly following injection and withdrawing on the syringe as the needle is removed, help prevent these problems occurring. This is more common in ulcerated lesions and in larger posterior tumours where visualization of the tumour is impaired. We have found that posterior tumours, such as posterior tongue and retromolar tumours, are more difficult to inject. Injection of all posterior tumours requires the use of an assistant to provide adequate access and lighting. For posterior tongue tumours we use a gauze swab to provide sufficient grip on the tongue and prevent the retraction of the tongue following injection. By palpating the tumour with the hand, while holding the gauze swab, the lesion can be targeted. The lesion can then be surrounded by radiocolloid injection.
T classification and site of tumour have shown no statistical significance in determining whether sentinel nodes are visible on LSG. However, in three of four anterior tongue tumours, absence of sentinel nodes on LSG did not prevent radioactive sentinel nodes being harvested. This may be owing to the improved access for anterior tongue tumours during surgery. With the patient anaesthetized, a tongue stitch is placed in such a way as to allow manipulation of the tongue away from the drainage nodal basin. Shine-through of the primary site is therefore less if the tongue is manipulated in such a way. Although projection of the tongue by the patient during LSG undoubtedly aids in location of sentinel nodes, projection is much less useful than the use of a tongue stitch during surgery.
Techniques employed during the LSG procedure to enable identification of sentinel nodes close to the primary involve the use of lead plates (Figure 3) to mask the primary and the use of software masking (Figure 2
). These techniques hide the primary source of radioactivity and allow more accurate imaging of the neck. Lead shields may be manipulated in the oral cavity to prevent shine through (Figure 3). This is easiest for palatal tumours (Figure 3b middle) but virtually impossible for FOM tumours. For FOM tumours, manipulating the lead plates under the superior platysmal flap may be more useful (Figure 3c bottom).
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Figure 3. (a) Malleable lead plates. (b) The use of lead plates to prevent shine-through of radioactivity from the palatal tumour into the neck. (c) Manipulation of lead plate under superior subplatysmal flap.
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We have found that the chance of detecting a positive node is higher if the node is detected as both hot and blue rather than if the node is either hot or blue only. 67% (62 of 92) of all radioactive nodes harvested were blue. Blue dye is therefore an important adjunct to the identification of sentinel nodes aiding the surgeon in the identification of sentinel nodes. There was only one positive sentinel node that was identified as blue that was not radioactive. This was a posterior tongue tumour in which there was difficulty injecting the radioactive tracer pre-operatively. There were no nodes visible on LSG. Blue dye injection was performed more easily intra-operatively, with the patient anaesthetized and with better access. Intra-operative injection of radiocolloid has been previously used in HNSCC [17, 26]. Although intra-operative injection has not been performed on any patients within this study, as the problem has only been encountered in one patient, it should be considered where the pre-operative injection of radiocolloid is not considered satisfactory.
In our practice, 19% of patients had no visible sentinel nodes on LSG, of which only 4 of 9 patients had radioactive sentinel nodes harvested. The two nodes harvested as positive were both from level 1. The shine-through effect of the primary tumour undoubtedly prevented nodes being visible on LSG. Performing the procedure in patients in whom a sentinel node is not visible on LSG should be with heightened caution and should involve a detailed search of levels 1 and 2.
After follow-up of 18 months, only one patient staged sentinel node negative has developed subsequent disease. During the initial SNB procedure a hot blue sentinel node was harvested from level 3 following pre-operative LSG scan showing a node in level 3. The subsequent neck dissection found disease in both levels 1 and 2. It is likely that in this case the sentinel node harvested was in fact a second echelon node and the true first echelon/sentinel node was not harvested. This patient had a FOM tumour and, as previously described, the closeness of the primary site may have been the reason why the incorrect node was initially harvested. It may also be the reason why the node was not visible on the LSG scan.
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Conclusion
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LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC. Targeting T1/2 lesions only may improve identification rates, although results of multicentre trials are required before the clinical benefits of SNB are known. The protocol for our current multicentre trial is available at www.canniesburn.org.
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Acknowledgments
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We thank Joyce Hope for the pathological preparation of sentinel nodes.
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Footnotes
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Funded by the Scottish Office and the White Lily trust. 
Received for publication July 30, 2001.
Revision received August 21, 2002.
Accepted for publication September 11, 2002.
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References
|
|---|
- Sherman A, Ter-Pogossian M. Lymph node concentration of radioactive colloid gold following interstitial injection. Cancer 1953;6:1238–40.
- Garzom OL, Palcos MC, Radicella R. Technetium-99m labelled colloid. Int J AppI Radiat Isotopes 1965;16:613.
- Parell GJ, Becker GD, Simpson GT. Prediction of lymph node metastases by LSG of the neck after peri-cancer injection of a radiocolloid. Otolaryngol Head Neck Surg 1981;89:67–8.[Medline]
- Sri-Pathmanathan R, Railton R. Lymphoscintigraphy in the detection of cervical metastases from oral carcinoma: a pilot study. Ann R Coll Surg Engl 1989;71:281–4.[Medline]
- Klutmann S, Bohuslavizki KH, Brenner W, Hoft S, Kroger S, Werner JA, et al. LSG in tumors of the head and neck using double tracer technique. J Nucl Med 1999;40:776–82.[Abstract/Free Full Text]
- Hildmann H, Kosberg RD, Tiedjen KU. Lymphoscintigraphic studies of regional lymph vessels in patients with head and neck tumors. HNO 1987;35:31–3.[Medline]
- Bergqvist L, Strand S-E, Persson BRR. Particle sizing and biokinetics of intersticial lymphoscintigraphic agents. Sem Nucl Med 1983;13:9–19.[Medline]
- Glass E, Essner R, Guiliano E. Sentinel node localization in breast cancer. Semin Nucl Med XXIX:57–68.
- Nathanson SD, Anaya P, Karvelis KC, Eck L, Havstad S. Sentinel lymph node uptake of two different technetium-labeled radiocolloids. Ann Surg Oncol 1997;4:104–10.[Abstract]
- Strand S-E, Persson BRR. Quantitative LSG: basic concepts for optimal uptake of radiocolloids in the parastemal lymph nodes of rabbits. Nucl Med 1979;20:1038–46.
- Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127:392–9.[Abstract]
- Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 1993;2:335–9.[Medline]
- Gershenwald JE, Tseng CH, Thompson W, Mansfield PF, Lee JE, Bouvet M, et al. Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabelled colloid. Surgery 1998;124:203–10.[Medline]
- Albertini JJ, Cruse CW, Rapaport D, Wells K, Ross M, DeConti R, et al. Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surg 1996;223:217–24.[Medline]
- Ross G, Shoaib T, Scott J, Soutar D, Gray H, Mackie R. The learning curve of sentinel node biopsy in malignant melanoma. Br J Plast Surg 2002;55:298–301.[Medline]
- Koch WM, Choti MA, Civelek AC, Eisele DW, Saunders JR. Gamma probe-directed biopsy of the sentinel node in oral squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1998;124:455–9.[Abstract/Free Full Text]
- Shoaib T, Soutar DS, MacDonald DG, Camilleri IG, Dunaway DJ, Gray HW, et al. The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck. Cancer 2001;91:2077–83.[Medline]
- Werner JA, Dunne AA, Brandt D, Ramaswamy A, Kulkens C, Lippert BM, et al. Studies on significance of sentinel lymphadenectomy in pharyngeal and laryngeal carcinoma. Laryngorhinootologie 1999;78:663–70.[Medline]
- Bilchik AJ, Giuliano A, Essner R, Bostick P, Kelemen P, Foshag LJ, et al. Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms. Cancer J Sci Am 1998;4:351–8.[Medline]
- Chiesa F, Mauri S, Grana C, Tradati N, Calabrese L, Ansarin M, et al. Is there a role for sentinel node biopsy in early N0 tongue tumors? Surgery 2000;128:16–21.[Medline]
- Alex JC, Sasaki CT, Krag DN, Wenig B, Pyle PB. Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma. Laryngoscope 2000;110:198–203.[Medline]
- Taylor RJ, Wahl RL, Sharma PK, Bradford CR, Terrell JE, Teknos TN, et al. Sentinel node localization in oral cavity and oropharynx squamous cell cancer. Arch Otolaryngol Head Neck Surg. 2001;127:970–4.[Abstract/Free Full Text]
- Zitsch RP, Todd DW, Renner GJ, Singh A. Intraoperative radiolymphoscintigraphy for detection of occult nodal metastasis in patients with head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2000;122:662–6.[Medline]
- Stoeckli SJ, Steinert H, Pfaltz M, Schmid S. Sentinel lymph node evaluation in squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 2001;125:221–6.[Medline]
- Mozzillo N, Chiesa F, Botti G, Caraco C, Lastoria S, Giugliano G, et al. Sentinel node biopsy in head and neck cancer. Ann Surg Oncol 2001;8(Suppl.9):103S–105S.
- Dunne AA, Kulkens C, Ramaswamy A, Folz BJ, Brandt D, Lippert BM, et al. Value of sentinel lymphonodectomy in head and neck cancer patients without evidence of lymphogenic metastatic disease. Auris Nasus Larynx 2001;28:339–44.[Medline]
- Ross GL, Shoaib T, Soutar DS, MacDonald DG, Camilleri IG, Bessent RG, et al. The First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer and adoption of a multicentre trial protocol. Ann Surg Oncol 2002;9:406–10.[Abstract/Free Full Text]
- Ross G, Shoaib T, Soutar DS, Camilleri IG, Gray HW, Bessent RG, et al. The use of sentinel node biopsy to upstage the clinically N0 neck in head and neck cancer. Arch Otolaryngol Head Neck Surg 2002;128:1287–91.[Abstract/Free Full Text]
- Robbins KT. Classification of neck dissection: current concepts and future considerations. Otolaryngol Clin North Am 1998;31:639–55
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J. A. Werner, A. A. Dunne, B. J. Folz, R. Moll, and T. Behr
Value of Sentinel Lymphadenectomy in Head and Neck Cancer
Ann. Surg. Oncol.,
March 1, 2004;
11(3_suppl):
267S - 270S.
[Abstract]
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G.L. Ross, D.S. Soutar, D.G. MacDonald, T. Shoaib, I.G. Camilleri, and A.G. Robertson
Improved Staging of Cervical Metastases in Clinically Node-Negative Patients With Head and Neck Squamous Cell Carcinoma
Ann. Surg. Oncol.,
February 1, 2004;
11(2):
213 - 218.
[Abstract]
[Full Text]
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Abstract
Introduction
