Sentinel Lymphadenectomy: Expanding Indications
Sentinel Lymphadenectomy: Expanding Indications
abstract & commentary
Synopsis: Sentinel lymphadenectomy is evaluated for gastrointestinal neoplasms. The tumor status of the sentinel node accurately predicted the tumor status of the locoregional lymph nodes in 95% of cases. In 8% of the cases, findings changed the planned operative management. The technique did not seem as reliable in rectal cancer or advanced tumors.
Source: Tsioulias G, et al. Arch Surg 2000;135: 926-932.
Although the use of sentinel lymphadenectomy has gained widespread acceptance in breast cancer and melanoma, its use in other solid-organ malignancies has not been fully explored. Therefore, Tsioulias and colleagues from the John Wayne Cancer Institute in California have studied 65 patients with gastrointestinal neoplasms by performing lymphatic mapping with en bloc resection of the primary neoplasm and locoregional lymph nodes. Most of the patients had colorectal cancer (42 colon, 8 rectal cancer), with the remaining cases consisting of stomach cancer (6), small bowel cancer (3 adenocarcinomas and 2 carcinoid tumors) and pancreatic cancer (4).
The surgical technique involved the circumferential injection of isosulfan blue dye followed by visual inspection to identify the sentinel lymph nodes. This resulted in an extra 10 minutes of surgical time and no complications. An en bloc resection of the primary site and the associated regional lymph nodes was then performed. Preoperative lymphoscintigraphy, as frequently used in melanoma, would not be helpful because of the internal location of these gastrointestinal cancers. In addition, Tsioulias et al have not found the intraoperative use of radioisotopes with the hand-held gamma counter to be very useful in this setting.
The pathologic handling of the sentinel lymph nodes included hematoxylin and eosin (H&E) stains of both standard sections and additional "multisections" as well as immunohistochemical stains for the presence of cytokeratin. Stains for chromogranin and serotonin were included for cases of carcinoid tumor.
The identification of a sentinel node was successful in 95% of the cases. Two of the three cases in which a sentinel node could not be identified involved a rectal cancer.
Nodal skip metastases were seen in four cases. One of these four cases, just mentioned above, involved a rectal cancer in which the sentinel node was never located. The other three node-positive cases with negative sentinel nodes all had T3/T4 disease, including two additional cases of rectal cancer.
Significant upstaging occurred with the intensive analysis of the sentinel nodes. Of the 15 cases with metastatic deposits confined to the sentinel nodes, only four were identified by standard pathologic procedures. The other cases were upstaged by preparing multisections for H&E staining (2 cases) or by immunohistochemical analysis (9 cases).
Of further interest was the relationship between the T stage and the likelihood of being upstaged. Obviously, the chance of being node-positive will increase as the T stage increases. Conversely however, the chance of having a positive sentinel node as the only involved node decreases with increasing T stage, as was seen in this study. Therefore, upstaging by finding micrometastases only was far more common with low T-stage than with high T-stage disease. For example, lymph node metastases in T1 disease were invariably micrometastatic.
The power of the sentinel node technique to identify the appropriate nodal region was easily seen as 8% of tumors drained to unexpected, anatomically aberrant locations. Dramatic examples of altered surgical procedures are provided by Tsioulias et al.
COMMENT by Kenneth W. Kotz, MD
With the ability to accurately locate and intensively evaluate the sentinel lymph node, it is likely that this procedure will be used with greater frequency in cancer patients with solid malignancies. For example, recent articles have reported results of sentinel lymph node dissection in thyroid cancer,1 vulvar cancer2 and other gynecologic malignancies,3 head and neck cancer,4 and Merkel cell carcinoma.5 In the report by Tsioulias et al, the use of lymphatic mapping and "focused analysis" of sentinel lymph nodes was evaluated in patients with gastrointestinal neoplasms.
One of the important messages from this study is the presence of an unexpected lymphatic drainage pattern in 8% of cases. In these cases, the extent or location of the surgical resection was altered. Examples are provided by Tsioulias et al, such as a patient with a right-sided colon cancer whose sentinel node was located on the left of the middle colic artery.
Another key finding in the study was that sentinel node mapping may not be as useful in patients with rectal cancer. For these patients, there seemed to be an increased chance of two problems. First, a sentinel node could not be identified in two cases of rectal cancer. Second, two other cases of rectal cancer had "skip" metastases to non-sentinel lymph nodes. Tsioulias et al hypothesize that this might be due to the extensive dissection required to mobilize the neoplasm during which time the dye has passed beyond the sentinel node. As a result, they have developed an ex vivo mapping technique that identifies the sentinel node in rectal cancer after the specimen has been resected.
A third point to emphasize was the relationship between the T stage and the results of lymphatic mapping. First, with increasing T stage, it becomes much less likely that the sentinel node would be the only positive node, as has also been demonstrated in breast cancer.6 Second, upstaging caused by multiple sectioning or immunohistochemistry was inversely related to the T stage. These results suggest that sentinel mapping and intensive pathologic evaluation of the sentinel node may be more productive in early T-stage disease and less beneficial in big, bulky, obstructing or advanced T-stage disease, a conclusion reached by others.7
Other reports on the successful use of lymphatic mapping in gastrointestinal carcinomas have been published.8,9 For example, the preoperative use of an endoscopic, submucosal injection of radioactive tracer followed by intra-operative localization with a gamma probe was reported to be an accurate and minimally invasive technique in gastrointestinal neoplasms.9 On the other hand, other studies have concluded that the concept of lymphatic mapping in colorectal cancer was "not valid."10 The ongoing work at the John Wayne Cancer Institute will move us closer toward determining the appropriate role of lymphatic mapping in oncology.
References
1. Haigh P, et al. Recent Results Cancer Res 2000;157: 201-205.
2. de Hullu J, et al. J Clin Oncol 2000;18:2811-2816.
3. Levenback C. Recent Results Cancer Res 2000;157: 150-158.
4. Nieuwenhuis E, et al. Recent Results Cancer Res 2000;157:206-217.
5. Wasserberg N, et al. Dermatol Surg 2000;26:138-141.
6. Giuliano A, et al. Ann Surg 1995;222:394-399.
7. Cserni G, et al. Pathol Oncol Res 1999;5:291-296.
8. Saha S, et al. Ann Surg Oncol 2000;7:120-124.
9. Kitagawa Y, et al. Nippon Geka Gakkai Zasshi 2000;101:315-319.
10. Joosten J, et al. Br J Surg 1999;86:482-486.
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