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10.1245/ASO.2004.12.914
Annals of Surgical Oncology 11:242S-244 (2004)
© 2004 Society of Surgical Oncology
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SUPPLEMENT

Current Status and Future Prospects of Sentinel Node Navigational Surgery for Gastrointestinal Cancers

Yuko Kitagawa, MD, Hirofumi Fujii, MD, Makio Mukai, MD, Atsushi Kubo, MD and Masaki Kitajima, MD, FACS

From the Departments of Surgery (YK, MK), Radiology (HF, AK), and Pathology (MM), Keio University School of Medicine, Tokyo, Japan.

Correspondence: Address correspondence and reprint requests to: Yuko Kitagawa, MD, Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan; Fax: 81-3-3355-4707; E-mail: kitagawa{at}sc.itc.keio.ac.jp

ABSTRACT

Until the late 1990s, the application of the sentinel node (SN) concept to gastrointestinal (GI) malignancies was not recognized because of the multidirectional and complicated lymphatic flow from the GI tract. However, several studies supporting the validity of the SN concept for GI cancers have been reported in the past 5 years. Because of its anatomical location, gastric cancer is one of the most suitable targets for minimally invasive surgery based on SN status. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Although SNs in esophageal cancer are multiple and are distributed widely from the cervical to the abdominal area, selective and modified lymphadenectomy for clinically N0-stage esophageal cancer is likely to become feasible and clinically viable. Total mesorectal excision (TME) is accepted as a standard surgical procedure for rectal cancer. However, there is a risk of aberrant distribution of SNs beyond the extent of TME; for example, SNs may be lateral to the lower rectum. SN mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and accurate staging without extensive lymph node dissection. There are several practical issues to be overcome. The techniques and feasibility of laparoscopic SN sampling are still under investigation. Large-scale multicenter prospective validation studies for SN mapping in GI cancer are essential. If these remaining issues can be solved, SN mapping for GI cancer will have great clinical impact.

Key Words: Sentinel node • Esophageal cancer • Gastric cancer • Colorectal cancer • Minimally invasive surgery • Micrometastasis

Although the results of ongoing multicenter, prospective randomized controlled trials are necessary to confirm whether sentinel node (SN) biopsy can constitute the standard care in the 21st century, less invasive modified surgical approaches based on the SN concept have already been put into practice in breast cancer and melanoma.1 Universal applications of the SN concept have been a focus of attention in the past few years, and the validity of this concept is being tested with regard to various solid tumors. Until the late 1990s, the application of the SN concept for gastrointestinal (GI) malignancies was not accepted because of the multidirectional and complicated lymphatic flow from the gastrointestinal (GI) tract. However, several studies supporting the validity of the SN concept for GI cancers have been reported in the past 5 years. The most attractive clinical application of the SN concept in GI surgery is less-invasive surgery for SN-negative cases. Here we review the current status of SN mapping in various GI cancers and present practical issues related to future clinical applications.

GASTRIC CANCER

Gastric cancer is a very suitable target of SN navigational surgery. Acceptable rates of SN detection as well as sensitivity in detecting micrometastasis based on SN status were noted with use of the dye-guided method and the radio-guided method.2–4 Despite the multidirectional and complicated lymphatic flow from gastric mucosa, the anatomical location of the stomach is relatively suitable for SN mapping in comparison with organs embedded in closed spaces such as the esophagus and rectum. In Japan, the standard care for clinically T1N0-stage gastric cancer is still gastrectomy with lymph node dissection because of the potential risk of micrometastasis. SN biopsy would change the standard care for these patients, allowing less-invasive surgery based on SN status. Data reported in the literature show that micrometastases tend to be limited within the sentinel basins in cT1N0 gastric cancer. Sentinel basins are therefore good targets of selective lymphadenectomy for cT1N0 gastric cancer with potential risk of micrometastasis. Furthermore, laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer.5 In Japan, clinical application of this novel minimally invasive approach could have a great impact on patient care for gastric cancer because 60% to 80% of gastric cancer cases in major institutes belong to this stage.

However, there are several practical issues to be overcome. Intraoperative pathological evaluation of SNs is not completely reliable.6,7 The techniques and feasibility of laparoscopic SN sampling are still under investigation. Laparoscopic SN sampling is more difficult in the lesser curvature than in the greater curvature. No large-scale multicenter prospective validation study has been performed in gastric cancer. We hope that these issues will be resolved and that SN mapping for gastric cancer will be recognized to have great clinical significance.

ESOPHAGEAL CANCER

Esophageal cancer is a particularly aggressive GI malignancy because of the high incidence and widespread distribution of lymph node metastasis. However, the SN concept seems to be applicable according to recent reports.8,9 There are several specific features of SN mapping in esophageal cancer. A dye-guided method is not applicable for esophageal cancer because of its anatomical situation. It is impossible to trace the flow of blue dye without destruction of the lymphatic network. SNs in esophageal cancer are multiple and distributed widely from the cervical to the abdominal area. Therefore, the lymphoscintigram is essential to identify the SNs in esophageal cancer (Fig. 1). Recently, chemoradiotherapy (CRT) has attracted attention as a multidisciplinary curative treatment for cT1N0 esophageal cancer. In this approach, control of micrometastasis is essential. Lymphoscintigrams revealing the distribution of SNs in each individual case are useful to design the field of irradiation.



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  		FIG. 1. Lymphoscintigram for a patient with thoracic esophageal cancer. Sentinel lymph nodes (SNs) are indicated by black arrows. The distribution of SNs was widespread from the cervical area to the abdominal area.

 
A complete sampling of multiple and widespread SNs in esophageal cancer is not a minimally invasive procedure, unlike in breast cancer. At present local resection of a primary esophageal cancer with negative SNs is not practical. However, selective and modified lymphadenectomy for clinically N0-stage esophageal cancer should become feasible and clinically useful. Although three-field lymph node dissection is recognized as an extensive and curative procedure for thoracic esophageal cancer, its prognostic significance is still controversial. Uniform application of this highly invasive procedure may increase the morbidity and reduce quality of life after surgery. Individualized selective lymphadenectomy for clinically N0-stage esophageal cancer based on SN status would be a reasonable surgical approach.10 If mediastinal SNs are all negative and no hot spot is detected in the cervical area by preoperative scintigraphy, cervical lymph node dissection would not be necessary. Approaches for lower thoracic and abdominal esophageal cancer, including Barrett’s adenocarcinoma, could be individualized by SN status. If abdominal SNs are all negative and no hot spot is detected in the mediastinal area by preoperative scintigraphy, transthoracic extensive lymph node dissection is not required.

COLORECTAL CANCER

The usefulness of dye-guided SN detection in colon cancer has already been established.11 Because of their simple distribution, SNs in colon cancer are relatively easy to identify by intraoperative subserosal injection of blue dye. Accurate staging by intensive examination is as useful for colon cancer as for other neoplasms.12 The unexpected distribution of paracolic SNs distant from the primary lesion can change the extent of resection.13

For rectal cancer, introduction of a radio-guided method is essential because the anatomical situation is the same as esophageal cancer.14 Preoperative scintigraphy is also essential for mapping in rectal cancer. In particular, 10% of the cases with lower rectal cancer showed SNs in the lateral area. Although total mesorectal excision (TME) is accepted as a standard surgical procedure for rectal cancer, there is a risk of aberrant distribution of SNs beyond the extent of TME. SN mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and for accurate staging without extensive lymph node dissection.

HEPATOBILIARY TRACT AND PANCREATIC CANCER

There are only a few studies investigating the SN concept in this field.15 In hepatocellular carcinoma (HCC), lymph node metastasis is a relatively rare and late event in progression. It is unlikely that the SN concept would contribute to patient care for HCC. Although lymph node metastasis is a significant prognostic factor in intrahepatic cholangiocarcinoma, there is no study on SN mapping in this entity. For pancreatic cancer, Ohta et al.15 reported an innovative study concerning individualized surgical approaches based on SN status. Using the dye-guided method, they demonstrated that most SNs from pancreatic head cancer are located in the posterior pancreatic duodenal area, and the pathological status of these SNs is useful to predict the status of para-aortic lymph nodes. They proposed selective para-aortic lymph node dissection for pancreatic cancer based on this technique. Further accumulation of data for SN mapping would be required to evaluate the clinical significance of the SN concept in this field.

REMAINING ISSUES AND FUTURE PROSPECTS

SN navigational surgery has great potential to alter the management of early-stage GI cancer. Establishment of standard procedures and further evidence to support the validity of the SN concept based on the results from multicenter prospective validation studies are required. To make a contribution as a minimally invasive approach, SN navigational surgery should be combined with endoscopic (laparoscopic or thoracoscopic) surgery. Modified surgery for cT1N0 gastric cancer may be the most practical clinical application initially. To avoid unnecessary lymph node dissection for the cases with negative SNs, establishment of a sensitive and rapid intraoperative system to detect micrometastasis is essential. It would then be possible to introduce selective lymphadenectomy instead of uniform extended lymph node dissection for cN0 GI cancer.

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 are available online in the fulltext version at www.annalssurgicaloncology.org. They are not available in the PDF version.

FOOTNOTES

Sentinel node (SN) mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and accurate staging without extensive lymph node dissection. The techniques and feasibility of laparoscopic SN sampling are still under investigation. Large-scale multicenter prospective validation studies must be performed, but SN mapping for GI cancer may have great clinical impact in the future.

Received for publication November 20, 2003. Accepted for publication December 16, 2003.

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