Remaining Issues for Future Clinical Applications

Laparoscopic SN mapping is still under developmentdue to several technical and material limitations [18].Currently available rigid type laparoscopic gammaprobes are fixed by entry-trocar and the freedom tosearch for SN, and to avoid a ‘‘shine through’’ effect frominjection site, is seriously restricted. At this moment,laparoscopic SN detection is feasible for cases with thelesion on the greater curvature of the middle or lower partof stomach. In cases of carcinoma at the EG junction,a flexible type of gamma probe will be required foraccurate sampling of SNs.

The clinical significance of micrometastasis and iso-lated tumor cells in regional lymph nodes with gastriccancer is still controversial. Unlike multimodal optionsfor preventing axillary lymph node recurrence in breastcancer, it is difficult to control lymph node recurrence inpatients with gastric cancer. At this moment, we must becareful to deal with micrometastasis and isolated tumorcells in SNs in patients with gastric cancer for safeclinical application of these techniques. The sensitivity ofintra-operative histological examination of SN is stillunsatisfactory [19]. In our own experience, intra-operative accurate diagnosis by H and E staining usinga frozen sample with a single section was only 74%.Although utilization of intra-operative immunohisto-chemistry using anti-pankeratin antibody (AE1/AE3)improved the sensitivity to detect micrometastasis up to92%, it is still not a perfect examination. Although theissue of a false positive study is still controversial, intra-operative utilization of real time RT-PCR to detectmolecular metastasis might well be a useful technologyfor safer clinical application of SN concept for GI cancer[20]. We must clear these unresolved issues verycarefully as we proceed.

CONCLUSIONS

Although there are still some remaining issues, SNnavigation should provide a new paradigm shift for thesurgical management of early gastric cancer. Individua-lized minimally invasive surgery based on SN distribu-tion and status should be both feasible and beneficial forpatients with early gastric cancer in near future.

REFERENCES

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2. Saha S, Nora D, Wong JH, et al.: Sentinel node mapping in colo-rectal cancer—A review. Surg Clin N Am 2000;80:1811–1819.

3. Kitagawa Y, Fujii H, Mukai M, et al.: The role of sentinel lymphnode in gastrointestinal cancer. Surg Clin N Am 2000;80:1799–1809.

4. Bilchik AJ, Saha S, Wiese D, et al.: Molecular staging of earlycolon cancer on the basis of sentinel node analysis: A multicenterphase II trial. J Clin Oncol 2001;19:1128–1136.

5. Kitagawa Y, Fujii H, Mukai M, et al.: Radio-guided sentinel nodedetection for gastric cancer. Brit J Surg 2002;89:604–608.

6. Miwa K, Kinami S, Taniguchi K, et al.: Mapping sentinel nodes inpatients with early-stage gastric carcinoma. Br J Surg 2003;90:178–182.

7. Nimura H, Narimiya N, Mitsumori N, et al.: Infrared rayelectronic endoscopy combined with indocyanine green injectedfor detection of sentinel nodes of patients with gastric cancer. BrJ Surg 2004;91:575–579.

8. Kim S, Lim YT, Soltesz EG, et al.: Near-infrared fluorescent typeII quantum dots for sentinel lymph node mapping. Nat Biotechnol2004;22:38–39.

9. Uenosono Y, Natsugoe S, Higashi H, et al.: Evaluation of colloidsize for sentinel nodes detection using radioisotope in earlygastric cancer. Cancer Lett 2003;200:19–24.

10. Ellner SJ, Mendez J, Vera DR, et al.: Sentinel lymph nodemapping of the colon and stomach using lymphoseek in a pigmodel. Ann Surg Oncol 2004;11:674–681.

11. Kitagawa Y, Ohgami M, Fujii H, et al.: Laparoscopic detectionof sentinel lymph nodes in gastrointestinal cancer: A novel andminimally invasive approach. Ann Surg Oncol 2001;8:86–89.

12. Hiratsuka M, Miyashiro I, Ishikawa O, et al.: Application ofsentinel node biopsy to gastric cancer surgery. Surgery 2001;129:335–340.

13. Ichikura T, Morita D, Uchida T, et al.: Sentinel node concept ingastric carcinoma. World J Surg 2002;26:318–322.

14. Hayashi H, Ochiai T, Mori M, et al.: Sentinel lymph node mappingfor gastric cancer using a dual procedure with dye- and gammaprobe-guided techniques. J Am Coll Surg 2003;196:68–74.

15. Isozaki H, Kimura T, Tanaka N, et al.: An assessment of thefeasibility of sentinel lymph node-guided surgery for gastriccancer. Gastric Cancer 2004;7:149–153.

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17. Bertagnolli M, Miedema B, Redston M, et al.: Sentinel nodestaging of resectable colon cancer. Results of a multicenter study.Ann Surg 2004;240:624–628.

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COMMENT

More than a decade ago, Dr. Donald Morton initiatedthe concept of studying the ‘‘sentinel’’ lymph node ina lymph node basin draining the site of a malignantmelanoma as a guide to the presence or absence of ametastatic spread from a specific lesion. After appro-

priate laboratory studies, he initiated clinical studies,and the technique has rapidly been accepted as the

DOI 10.1002/jso.20221

Published online in Wiley InterScience (www.interscience.wiley.com).

Sentinel Node Navigation for Gastric Cancer 151

� 2005 Wiley-Liss, Inc.

standard of care for the management of malignantmelanoma. His partner at the John Wayne CancerInstitute, Dr. Armand Giuliano, accomplished the samestatus for the sentinel node for axillary lymph nodeassessment in patients with breast cancer. Ongoingstudies of this technique for breast cancer will answersome remaining questions, but sentinel lymph nodebiopsy has essentially replaced axillary lymph nodedissection for many patients. In both instances, prog-nostic information is obtained and the technique servesas a guide for the therapeutic management of the re-maining lymph nodes in that basin. The potentialclinical usefulness of sentinel lymph node biopsy forgastrointestinal cancers is not as clear cut as for thesetwo disease entities, however. For example, lymphaticdrainage of gastrointestinal cancers is not as clear as it isfor the skin or the breast, and the patterns of metastasisfor gastrointestinal cancers are not quite as predictable.In spite of this, a number of investigators have pursuedthe sentinel lymph node concept for various gastro-intestinal cancers and this surgical group in Japan hasbeen the ‘‘standard bearer’’ for such studies.

In the United States, sentinel node mapping for gastro-intestinal cancer is focused on cancer of the colon due tothe high frequency of this type of cancer in the westernworld. Results from studies thus far have been conflictingfrom both the standpoint of our ability to identify the‘‘gateway’’ node in the colon mesentery as well as theprognostic significance of a negative sentinel lymphnode. These issues should settle out in time so that we candetermine the actual role of the sentinel node concept inthe surgical management of colorectal cancer. Mean-while, Dr. Kitagawa and his colleagues at Keio Universityin Tokyo have led the way in the study of sentinel nodesurgery for many gastrointestinal sites but, due to thehigher frequency of gastric cancer in Japan, they havefocused on gastric cancer where they have already made anumber of interesting observations. In this discussion,both the accomplishments and the unresolved issues arecarefully outlined, but the authors make a strong argu-ment for the role of sentinel lymph node assessment inpatients with gastric cancer.

Walter Lawrence, Jr., MD

Guest Editor

152 Kitagawa et al.