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From the Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Correspondence: Address correspondence and reprint requests to: Masaki Kitajima, MD, Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan; Fax: 81-3-3355-4707; E-mail: kitajima{at}sc.itc.keio.ac.jp
ABSTRACT
The sentinel node (SN) concept was originally proposed by several pioneers in the middle of the last century. After Donald Morton and his colleagues demonstrated the clinical significance of the SN concept in melanoma, it attracted vast attention in surgical oncology. At recent international conferences, a number of new approaches in this field for various solid tumors have been reported. Now, there are several possible applications with different technological aspects, such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. This article provides an overview of the future potential of SN technology.
Key Words: Individualization • Sentinel node • Solid tumor • Minimally invasive surgery
The first draining node from the primary lesion is the first site of micrometastasis.1 This concept itself is very simple and attractive for surgeons. Some pioneers had already attempted to utilize this concept in the middle of the 20th century for specific organs.2,3 Although these brave challenges were extremely innovative, the procedures were not initially widely accepted as feasible and reproducible clinical practice. As we now know, the hypothesis is basically sound and generally acceptable.
A number of advanced technologies and clinical circumstances played various roles in the realization of the significance of this concept. For example, a gamma probe with high collimation enabled accurate detection of sentinel nodes (SNs), in addition to the traditional dye-guided method. Now we must try to detect the micrometastasis by molecular biological techniques. SN mapping is essential for intensive examinations to detect molecular metastasis. The increasing prominence of endoscopic surgery has changed surgical thinking since the 1990s. Even in the field of surgical oncology, surgeons tend to pay attention not only to radicality but also to minimal invasiveness and enhanced quality of life after surgery. Furthermore, the number of early-stage cancers treated surgically is increasing because of developments in diagnostic technologies. These clinical circumstances have contributed to the huge amount of attention paid to the SN concept in recent years.
SN CONCEPT IN VARIOUS SOLID TUMORS
Safe and curative standard surgical procedures for various solid tumors were developed during the last century. To secure the curativity of these procedures, it was essential to perform a sufficient extent of lymph node dissection and ensure a safe surgical margin. However, we have already learned that the uniform application of extended surgery can be deleterious for postoperative quality of life. The emergence of the SN concept has contributed greatly to surgical management of breast cancer and melanoma. To date, the validity of this concept has been investigated in various types of human solid tumors, as shown in Table 1. However, the clinical significance of the SN concept differs in each type of solid tumor because of the anatomical situation and biological behavior of cancer cells. In the management of melanoma and breast cancer, the general validity of the concept has already been confirmed by clinical trials, and the main focus of attention now is how to identify micrometastasis limited to SNs. In these cases, sentinel lymph node dissection (SLND) itself would be a curative procedure. For gastrointestinal cancers, there are several promising reports to support the feasibility of sentinel node navigation surgery (SNNS).4–6 Now, we must pay attention to organ-specific lymphatic systems and accumulate evidence supporting the optimal procedure. It seems natural that the general concept of SN is applicable for various solid tumors rather than being a specific phenomenon related to malignancies with lymphatic involvement limited to superficial areas.
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A good example of the clinical applications was already clearly demonstrated in breast cancer surgery. An axillary lymph node dissection can be avoided in cases with negative sentinel node status. SN biopsy for breast cancer is minimally invasive and a relatively simple clinical procedure. On the other hand, SN biopsy for esophageal cancer is neither so simple nor less invasive for patients because of the complicated anatomical situation and widespread distribution of multiple SNs. For gastric cancer, laparoscopic SN biopsy is feasible, and laparoscopic local resection would be applicable for SN-negative cases. There are great advantages in this novel approach in comparison with conventional gastrectomy with extensive lymph node dissection in terms of both invasiveness and organ preservation (Fig. 1).7 Even if the SN concept is universally acceptable for various solid tumors, we have to consider the benefit of an individualized approach based on the concept in each organ.
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Amazingly effective transportation of nonspecific colloid particles encourages us to develop novel SN-targeted treatments. Now we have a number of technologies and much information for various tracer particles in SN mapping. An innovative local chemotherapy targeted to micrometastasis in SN could be effective for a certain type of neoplasm, e.g., superficial esophageal cancer. Although the primary lesion of superficial esophageal cancer can be resected by endoscopic mucosal resection, extensive lymph node dissection is required to control clinically undetectable micrometastasis in regional lymph nodes. An injection of anticancer reagent with a particular particle oriented to SNs could be a reasonable tool to control micrometastasis in SNs. Immunological modification to stimulate anticancer immunity in SNs would be another possible approach for micrometastasis in SNs.
CROSS-TALK BETWEEN BASIC SCIENCE AND CLINICAL PRACTICE
Recently, several reports have demonstrated the downmodulation of immune functions in SNs. Cochran et al. reported that the frequency of paracortical interdigitating dendritic cells (IDCs) was dramatically reduced in SNs from melanoma patients, and most IDCs lacked the complex dendrites associated with active antigen presentation.8 This immunosuppressive reaction might be attributed to the release of factors from primary melanoma and the mechanism of formation of micrometastasis. SNs are the second important battlefield for malignant cells against the host immune system, after the primary site. It is essential to investigate the process of the formation of micrometastasis in SNs to gain insight into the mechanism of cancer metastasis. These insights might provide valuable suggestions for novel biological approaches using cytokine modification or immunomodulation. Cross-talk between basic science and clinical approaches could be provided by actual SNs from various organs and may introduce breakthroughs for clinical oncology.
ACKNOWLEDGMENTS
The authors are indebted to Prof. J. Patrick Barron, of the International Medical Communications Center of Tokyo Medical University, for his review of the manuscript.
The acknowledgments are available online in the fulltext version at www.annalssurgicaloncology.org. They are not available in the PDF version.
FOOTNOTES
There are several possible applications of the sentinel node concept, with different technological aspects, such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. This article provides an overview of the potential of SN technology.
Received for publication October 23, 2003. Accepted for publication November 19, 2003.
REFERENCES
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