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SUPPLEMENT |
From the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California.
Correspondence: Address correspondence and reprint requests to: Donald L. Morton, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404; Fax: 310-582-7185; E-mail: mortond{at}jwci.org
I am honored to serve with Dr. Masaki Kitajima and Dr. John Thompson as a guest editor for this supplement to the Annals of Surgical Oncology. The supplement contains high-profile papers delivered at the Third International Sentinel Node Congress in Yokohama, Japan, in November 2002 ("SN2002"). This meeting, hosted by Dr. Kitajima and his colleagues from the Department of Surgery at Keio University, was the largest gathering of sentinel node (SN) investigators thus far. During the 3-day conference, investigators from around the world participated in presentations and symposia covering basic and clinical studies related to lymphatic mapping and sentinel lymphadenectomy (LM/SL). The hospitality and arrangements by Dr. Kitajima and his team were superb and unsurpassed by any meeting I have ever attended. The resounding success of SN2002 set a standard of excellence that we hope will be met by the upcoming Fourth International Sentinel Node Congress, to be hosted by the John Wayne Cancer Institute (JWCI) on December 3–6, 2004, in Santa Monica, California.
The 30 SN2002 papers in this supplement are authored by top-ranked investigators, and their range of topics underscores the multidisciplinary nature of SN technology (Table 1). Clearly the SN concept has generated exceptional interest and enthusiasm among a wide variety of investigators, from basic scientists studying the biology of early cancer metastasis, to pathologists and nuclear medicine physicians, to dermatologists and general and thoracic surgeons treating epithelial neoplasms of skin and visceral organs.
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Diagnostic Issues
The diagnostic utility of SN technology has been validated by studies at JWCI and other centers for melanoma,1–3 breast cancer,4 colon cancer,5 and virtually all solid neoplasms that spread to lymph nodes.6 These studies have confirmed a metastatic progression from the primary site through the lymphatics to one or two regional SNs; thus, the tumor status of the SN is representative of the presence or absence of metastasis in the regional nodal basin. Direct hematogenous metastasis occurs occasionally but appears to be much less frequent.
How then do we explain the regional and distant recurrence of tumor when regional SNs are apparently tumor free? The answer may lie in the lack of sensitivity for techniques used to sample and analyze the SN. Our lymphatic mapping studies in melanoma have revealed that tumor-draining regional nodes receive afferent drainage in a compartmentalized fashion,2 with a particular area of the skin draining not only to a specific lymph node but also to a specific area of that node. Because the intranodal distribution of tumor cells is localized rather than random, tumor foci can easily be missed by immunohistochemical staining (IHC) of sections that represent 1–2% of the total nodal volume. We recently reported that the use of carbon dye as a mapping adjunct can confirm the identity of the SN and permanently mark the portion of this node most likely to contain tumor cells (Fig. 1).2,7 In every node that contained melanoma metastases, tumor cells were found at the site of the carbon particles. Because carbon remains in the node long after the blue dye has dissipated, it can label a node as sentinel and identify for the pathologist the intranodal drainage site most likely to receive tumor cells.
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100% - [(the proportion of patients without SN micrometastases) +
(the proportion of patients with SN metastases and systemic metastases at the time of LM/SL) +
(the proportion of patients whose occult nodal metastases will never colonize distant sites and therefore can be salvaged by observation and delayed therapeutic lymphadenectomy)].
Since only 20% of patients with primary melanoma have SN metastases, the overall therapeutic benefit from LM/SL is probably no more than 4% to 7%, depending upon the thickness of the primary melanoma.2 Therapeutic trials of LM/SL must be quite large to detect such a small benefit.
The incubator hypothesis of metastasis (Fig. 4), upon which the therapeutic utility of LM/SL is based, is probably correct but fails to convey the complexity of immune interactions that affect the metastatic cascade. Although the patient’s endogenous immune response to the primary tumor is probably the most important determinant of regional and systemic metastasis in melanoma, other factors such as the extent of genetic changes in the primary tumor (activation of various growth-factor oncogenes) and the patient’s immune defenses are clearly involved.2 These factors would explain why a clinically palpable (2–3 cm diameter) nodal metastasis containing up to 32 x 109 melanoma cells can exist without any evidence of additional nodal or systemic involvement and why 32% of melanoma patients with at least one palpable nodal metastasis will survive at least 15 years. We assume that in these cases the metastases are confined to the regional nodes by immune defenses that inhibit the implantation and growth of blood-borne circulating tumor cells or by genetic characteristics of the metastatic clone which make tumor cells unable to adhere to the vascular endothelium and grow at distant sites. Further studies are necessary to clarify the relationship between antitumor immunity, SN tumor status, and surgical outcome. The results of these studies should indicate the type and indications for appropriate postoperative adjuvant tumor-specific therapy.
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Since my introduction of the modern concept of an individual-specific SN at the Society of Surgical Oncology’s 1990 annual meeting in Washington, DC, the technique of intraoperative LM/SL has been adopted by multiple specialties and applied to multiple solid neoplasms. One indicator of its widespread acceptance is the series of international meetings devoted to this topic. At the first SN Congress in Amsterdam in 1998, and the second in Santa Monica in 2000, there was a consensus that real benefit could be gained from the establishment of a society to serve and coordinate the needs of the diverse community of physicians and scientists who study the SN. Such individuals, coming from very different viewpoints, are committed to further development of the SN concept, optimization of SN approaches, extension of these approaches to the management of other appropriate tumors, and study of the biology of the SN in an effort to understand how early nodal metastases are established. At the Santa Monica meeting, it was agreed to take steps to democratically establish an international SN society at the 2002 Yokohama meeting. Such a society would oversee the conduct of periodic international meetings, foster interdisciplinary interchange of knowledge and information, promote education on "best practices" for the approaches, and encourage and facilitate the organization and conduct of cooperative trials across the full range of suitable neoplasms.
The International Sentinel Node Society (ISNS) is now officially established. The purpose of ISNS is to serve and coordinate the needs of the diverse community of physicians and scientists who study the SN. The aims of the ISNS are:
ISNS is a nonprofit corporation. Active membership in ISNS is limited to surgeons, pathologists, nuclear medicine physicians, dermatologists, oncologists, radiotherapists, and basic scientists who have shown evidence of continuing commitment to SN research and practice as demonstrated by such activities as oncologic teaching or research and involvement in a national or an international oncology research society. There are five types of active members: founding, full, associate, honorary, and sustaining:
1. Founding Members, listed below, participated in the organization and formation of the ISNS and have signed its Declaration of Bylaws. Founding members are the original group of active members and have all rights, privileges, responsibilities, and obligations of full members.
Founding members:
Donald Morton
Umberto Veronesi
John Thompson
Alistair Cochran
Sybren Meijer
Charles Balch
Omgo Nieweg
Armando Giuliano
Robert Mansel
Masaki Kitajima
Yuko Kitagawa
Stanley Leong
Nicola Mozzillo
Bernd-Rudiger Balda
Hans Starz
Stanley McCarthy
Roger Uren
Peter Ell
Dave Hoon
David Krag
Alfredo Barros
Patrick Borgen
John Buscombe
Ignacio Carrio
Krishna Clough
Heinz Hoefler
Jean Maublant
Giovanni Paganelli
Emiel Th Rutgers
Kerstin Sandelin
Gordon Schwartz
Giuseppe Viale
Stefano Zurrida
2. Full members have demonstrated an interest in or have made significant contributions to sentinel node research, clinical applications, or teaching. Full members pay an annual membership fee of $100, as established by the Executive Council. Full members have the right to vote at a General Assembly and may be elected to the Executive Council.
3. Associate members are advanced graduate students and postdoctoral fellows (up to three years after receiving doctorates). Their annual membership fee is $50 as established by the Board of Directors. Associate members have the right to vote at a General Assembly.
4. Honorary members are persons who in the opinion of the Executive Council by virtue of special attainment merit membership in ISNS. Honorary members pay no membership fee but have the right to vote at a General Assembly.
5. Sustaining members are individuals, corporations or organizations who have made substantial contributions in support of the aims and activities of ISNS. Sustaining members cannot vote at a General Assembly and may not serve on the Executive Council.
New Member Applications
We invite those individuals that have interest in SN technology to apply for membership in ISNS; as noted above, the annual dues are $100. Membership applications can be obtained from Alistair Cochran, MD, Secretary, International Sentinel Node Society, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404 (Bluenode@jwci.org). Applications for active membership will be considered by the membership committee and ratified by the Executive Council.
ISNS Officers and Council Members
Elected Officers
President: Donald Morton
President-elect: Umberto Veronesi
Vice-President: John Thompson
Secretary: Alistair Cochran
Treasurer: Sybren Meijer
Executive Council
Skin: Charles Balch, Omgo Nieweg
Breast: Armando Giuliano, Robert Mansel
GI: Masaki Kitajima, Yuko Kitagawa
Other: Stanley Leong, Nicola Mozzillo, Bernd-Rudiger Balda
Pathology: Hans Starz, Stanley McCarthy
Nuclear Medicine: Roger Uren, Peter Ell
Basic Science: Dave Hoon, David Krag
Address Roster
Charles M. Balch, MD, American Society of Clinical Oncology, 1900 Duke St., Suite 200, Alexandria, VA 22314, balchc@asco.org
Bernd-Rudiger Balda, MD, Klinikum Augsburg, Department of Dermatology and Allergology, Stenglinstr. 2, Augsburg D86156 Germany, balda.dermallerg@klinikum-augsburg.de
Alistair J. Cochran, MD, FRCP (Glasg.), FRCPath (Lond.), UCLA School of Medicine, Department of Pathology, Box 951713, Los Angeles, CA 90095–1713, acochran@mednet.ucla.edu
Peter J. Ell, MD, MSc, PD, FRCR, FRCP, Royal Free University College Medical School, University College of London, Mortimer Street, London, United Kingdom, p.ell@nucmed.ucl.ac.uk
Armando E. Giuliano, MD, FACS, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404, giulianoa@jwci.org
Dave S. B. Hoon, MSc, PhD, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404, hoond@jwci.org
Yuko Kitagawa, MD, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan, kitagawa@sc.itc.keio.ac.jp
Masaki Kitajima, MD, FACS, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan, snns@sc.itc.keio.ac.jp
David Krag, MD, University of Vermont, Department of Surgery, Given Bldg., Surg E309, Burlington, VT 05405, David.krag@uvm.edu
Stanley P. L. Leong, MD, FACS, UCSF Medical Center at Mt. Zion, 1600 Divisadero St., San Francisco, CA 94143, leongs@surgery.ucsf.edu
Robert E. Mansel, MS, FRCS (Eng & Edin), University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom, manselre@cf.ac.uk
Stanley McCarthy, MD, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW, Sydney, Australia, stan.mccarthy@email.cs.nsw.gov.au
Sybren Meijer, MD, PhD, The University Hospital, Vrije Universiteit, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands, s.meijer@vumc.nl
Donald L. Morton, MD, FACS, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404, mortond@jwci.org
Nicola Mozzillo, MD, National Cancer Institute, Division of Surgical Oncology B, Via M. Semmola, Naples 80132 Italy, nimozzi@tin.it
Omgo E. Nieweg, MD, PhD, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, The Netherlands, o.nieweg@nki.nl
Hans Starz, MD, Klinikum Augsburg, Department of Dermatology and Allergology, Stenglinstr. 2, Augsburg D86156 Germany, hstarz@web.de
John F. Thompson, MD, FRACS, FACS, Royal Prince Alfred Hospital GH3, Camperdown, Sydney, NSW 2050 Australia, thompson@smu.org.au
Roger F. Uren, MD, FRACP, Royal Prince Alfred Hospital, Nuclear Medicine & Diagnostic Ultrasound, Suite 206, Level Two, 100 Carillon Avenue, Newtown, NSW, 2042, Australia, ruren@mail.usyd.edu.au
Umberto Veronesi, MD, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy, umberto.veronesi@ieo.it
ACKNOWLEDGMENTS
Supported by grant CA29605 from the National Cancer Institute and by funding from the Amyx Foundation, Inc. (Boise, ID), Mrs. Alice Johnson McKinney, and Nancy and Carroll O’Connor (Los Angeles, CA).
Received for publication January 7, 2004. Accepted for publication January 16, 2004.
REFERENCES
This article has been cited by other articles:
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  I. Satzger, B. Volker, A. Meier, A. Kapp, and R. Gutzmer Criteria in Sentinel Lymph Nodes of Melanoma Patients that Predict Involvement of Nonsentinel Lymph Nodes Ann. Surg. Oncol., June 1, 2008; 15(6): 1723 - 1732. [Abstract] [Full Text] [PDF]
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