HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael J. Liptay Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liptay, M. J. Search for Related Content PubMed PubMed Citation Articles by Liptay, M. J. Related Collections Lung - cancer Related Article

J Thorac Cardiovasc Surg 2002;124:428-430
© 2002 The American Association for Thoracic Surgery

Editorials

Commentary on sentinel lymph node identification with technetium-99m tin colloid in non–small cell lung cancer

From the Section of Thoracic Surgery, Evanston Northwestern Healthcare, Evanston, Ill.

Received for publication April 23, 2002. Accepted for publication May 10, 2002. Address for reprints: Michael J. Liptay, MD, Head, Section of Thoracic Surgery, Evanston Northwestern Healthcare, Burch 100, 2650 Ridge Ave, Evanston, IL 60201 (E-mail: m-liptay{at}nwu.edu).

	Introduction

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 
See related article on page 486.

Sentinel node mapping techniques have been applied to the resection and treatment of nearly all solid tumors. The principle involves the injection of a lymphophylic tracer (either blue dye or a radioisotope) followed by visual or gamma counter measurements of individual lymph node stations to assess the first site of lymphatic drainage from a tumor. This sentinel nodal station should be the first site of lymphatic involvement if metastases have occurred.

The technique has become standard of care in both breast cancer and melanoma. The primary utility in these tumors is avoidance of nontherapeutic axillary or groin lymph node dissections and their incumbent morbidities. The morbidity of a complete mediastinal node dissection for lung cancer is not excessive and the procedure may be therapeutic. ^1,2

An equally important potential role may be directing pathologic examination to specific sentinel nodes and applying more sensitive techniques on a limited amount of tissue to detect occult micrometastatic disease.

Lymph node status is the single most important prognostic factor for localized potentially resectable non-small cell lung cancer. ³ Recent studies suggest that the presence of nodal micrometastatic disease in lung cancer may garner the same poor prognosis as metastases evident by conventional techniques. ^4,5 Nonetheless, more than 40% of "histologically node negative" patients who have a complete resection have a relapse and die of their original cancers, usually within 2 years. This is at least in part due to inaccurately staged nodal disease.

Sentinel node mapping in lung cancer is in the developmental phase. Numerous questions regarding technique, patient selection, and ultimate utility still remain unanswered. Initial studies by our group and others ^6-8 have demonstrated the feasibility of intraoperative injection of both blue dye and radioisotope for sentinel node mapping.

The report by Nomori and colleagues ⁹ in this issue of the Journal examines the sentinel node procedure by preoperative tumor injection with technetium Tc 99m tin colloid. The larger technetium tin colloid molecule required at least 6 hours to migrate to a sentinel node station as demonstrated by lymphoscintigraphy. This is compared to 10 to 15 minutes with the 20-µm filtered smaller technetium 99m sulfur colloid particle used in our intraoperative studies. The larger particle appears better suited for the preoperative injection performed the day before surgery.

The current study details results in 46 patients after injection 1 day preoperatively with technetium tin colloid. Nomori and associates obtained accurate sentinel node readings in 40 of the 46 patients undergoing anatomic resection with mediastinal node dissection for NSCLC. No inaccurate sentinel nodes were found in the 14 patients with N1 or N2 disease.

	Technical factors and selection criteria

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 
We have now performed the intraoperative mapping procedure in more than 150 patients. We have noted less success of the technique in patients with large necrotic tumors as well as those with hilar and mediastinal adenopathy. The reasons for this are intuitive. Larger necrotic tumors may have altered lymphatic and vascular supply and established adenopathy may cause efferent lymphatic obstruction. Clearly, the technique holds the most promise in patients with small clinically early stage tumors. Those patients with adenopathy and bulky tumors will more than likely have multiple involved nodal stations.

Nomori and colleagues ⁹ also noted that patients with chronic obstructive pulmonary disease were less likely to have identifiable sentinel nodes with their technique. One possible explanation would be an attenuation of lymphatics along with the loss of alveoli and functional lung tissue seen with emphysema. Further study will elucidate whether these patterns continue.

	Intraoperative versus preoperative technique

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 
In Japan the use of radioisotopes is strictly limited to designated areas. The intraoperative injection technique is impractical in this environment. The benefits of preoperative tumor injection the night before include better logistical coordination with nuclear medicine and radiation safety issues and the ability to perform preoperative imaging to plan surgery. These are balanced by the patient requiring a separate procedure with the small but real risks of pneumothorax, bleeding, and tumor seeding of the needle tract. Which technique will ultimately be used is unclear, as currently available data show both to have reasonable sentinel node detection rates.

	"Skip metastases"

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 
Mediastinal lymph node involvement without concurrent spread to the intraparenchymal and hilar nodal basins has been termed "skip metastasis," The incidence of this phenomenon in patients with positive N2 mediastinal nodes has been reported to be between 20% to 30% in most series. ¹⁰ Recent studies have attempted to distinguish between patients with skip N2 metastases and those with traditional N1 and N2 positive findings by arguing that patients with the skip pattern have a prognosis similar to that of patients with stage II (N1) rather than stage III (N2) disease. ¹¹ New data suggest that the nearly 40,000 patients with stage III locoregionally advanced disease have a wide variation of prognoses within the same stage. ¹¹ The sentinel node technique may allow better understanding of common drainage patterns of different tumor locations. This may lead to improved prognostic separation of patients based on the number and degree (gross/micrometastatic) of nodes involved. The impact on overall prognosis, therapeutic decision-making, and new staging systems remains to be determined.

Nomori and colleagues ⁹ reported 14 of 40 sentinel nodes as mediastinal. Their ability to identify these in vivo was highly accurate (88%). Although the sentinel node technique may not ever be used to stratify those requiring a full mediastinal node dissection from a sampling or no dissection, the information gained from detailing the actual nodal drainage of each tumor will continue to blur the lines between N1 and N2 disease, calling for a reconsideration of the staging of single site skip pattern metastases.

	Micrometastases/ultrastaging

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 
Nomori's group ⁹ found no micrometastases in the 26 sentinel nodes classified as negative by standard histologic evaluation. The authors report performing additional 3-step sections and immunohistochemistry with cytokeratin antibodies. This is in contrast to our recent report ⁷ detailing results in our first 100 patients in which 7 patients were upstaged with the identification of micrometastatic disease in the sentinel nodes. We performed serial sections at 30-µm intervals (average 10 per slide) as well as cytokeratin antibody staining.

With the increasing availability of real time reverse transcriptase-polymerase chain reaction analysis and other even more sensitive techniques to identify single cell nodal metastases, the future role of sentinel node identification in directing these examinations to the most likely site for metastases remains promising. Likewise molecular staging techniques may become more prognostically important as more specific markers and patterns are identified. ¹² The partnering of more precise sentinel node identification with more sensitive and informative ultrastaging molecular techniques will likely revolutionize the way we stage lung cancer and decide on appropriate postoperative treatment plans.

Currently, conflicting data exist to support the administration of chemotherapy for localized completely resected lung cancer, although clinical trials continue to investigate this intervention. If improvements in systemic therapy are forthcoming, more accurate or "ultrastaging" techniques may assist in selecting patients at highest risk for recurrence and perhaps most likely to benefit from additional therapies.

The current study by Nomori and colleagues ⁹ is a welcome addition to the growing experience of the sentinel node mapping technique. Their results confirm the promise of this staging tool to assist in giving patients the most precise information about their disease and aid in the identification of those most likely to benefit from future adjuvant therapies. These findings await broader application in resectable lung cancer to refine the sentinel node mapping technique and patient selection criteria.

	Reference

Top Introduction Technical factors and selection... Intraoperative versus... "Skip metastases" Micrometastases/ultrastaging Reference

 

1. Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg. 2000;70:358-65.[Abstract/Free Full Text]
   
2. Bollen EC, van Duin CJ, Theunissen PH, vt Hof-Grootenboer BE, Blijham GH. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg. 1993;55:961-6.[Abstract]
   
3. Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. 1978;76:832-39.[Abstract]
   
4. Kubuschock B, Passlick B, Izbicki JR, Thetter O, Pantel K. Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small cell lung cancer. J Clin Oncol. 1999;17:19-24.[Abstract/Free Full Text]
   
5. Perez-Cardona JH, Ordonez NG, Fossella FV. Lymph node micrometastases in non-small cell lung cancer: clinical applications. Clin Lung Cancer. 2000;2:116-20.[Medline]
   
6. Liptay MJ, Masters GA, Winchester DJ, Edelman BL, Garrido BJ, Hirschtritt TR, et al. Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer. Ann Thorac Surg. 2000;70:384-9.[Abstract/Free Full Text]
   
7. Liptay MJ, Grondin SC, Pozdol C, Carson D, Knop C, Masters GA, et al. Detection of micrometastases with intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer. Proc Am Soc Clin Oncol. 2001;20:313A.
   
8. Little AG, DeHoyos A, Kirgan DM, Arcomano TR, Murray KD. Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique. J Thorac Cardiovasc Surg. 1999;117:220-34.[Abstract/Free Full Text]
   
9. Nomori H, Horio H, Naruke T, Suemasu K, Orikasa H, Yamazaki K. Use of technetium TC 99m tin colloid for sentinel lymph node identification in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2002;124:486-92.[Abstract/Free Full Text]
   
10. Yoshino I, Yokoyama H, Yano T, Ueda T, Takai E, Mizutani K, et al. Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer. Ann Thorac Surg. 1996;62:1021-5.[Abstract/Free Full Text]
    
11. Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000;18:2981-9.[Abstract/Free Full Text]
    
12. D'Amico TA, Aloia TA, Moore MB, Herndon JE, Brooks KR, Lau CL, et al. Molecular biologic substaging of stage I lung cancer according to gender and histology. Ann Thorac Surg. 2000;69:882-6.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				K. Sugi, S. Kobayashi, R. Yagi, and T. Matsuoka Usefulness of sentinel lymph node biopsy for the detection of lymph node micrometastasis in early lung cancer Interactive CardioVascular and Thoracic Surgery, October 1, 2008; 7(5): 913 - 915. [Abstract] [Full Text] [PDF]

				K. Sugi, Y. Kaneda, M. Sudoh, H. Sakano, and K. Hamano Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 568 - 573. [Abstract] [Full Text] [PDF]

				D. Lardinois, T. Brack, A. Gaspert, T. Spahr, D. Schneiter, H.C. Steinert, and W. Weder Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer Eur. J. Cardiothorac. Surg., May 1, 2003; 23(5): 824 - 827. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael J. Liptay Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liptay, M. J. Search for Related Content PubMed PubMed Citation Articles by Liptay, M. J. Related Collections Lung - cancer Related Article