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Sentinel Lymph Node Mapping of the Gastrointestinal Tract by Using Invisible Light

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Abstract

Background

Because many gastrointestinal (GI) tumors spread by way of lymphatics, histological assessment of the first draining lymph nodes has both prognostic and therapeutic significance. However, sentinel lymph node mapping of the GI tract by using available techniques is limited by unpredictable drainage patterns, high background signal, and the inability to image lymphatic tracers relative to surgical anatomy in real time. Our goal was to develop a method for patient-specific intraoperative sentinel lymph node mapping of the GI tract by using invisible near-infrared light.

Methods

We developed an intraoperative near-infrared fluorescence imaging system that simultaneously displays surgical anatomy and otherwise invisible near-infrared fluorescence images of the surgical field. Near-infrared fluorescent quantum dots were injected intraparenchymally into the stomach, small bowel, and colon, and draining lymphatic channels and sentinel lymph nodes were visualized. Dissection was performed under real-time image guidance.

Results

In 10 adult pigs, we demonstrated that 200 pmol of quantum dots quickly and accurately map lymphatic drainage and sentinel lymph nodes. Injection into the mid jejunum and colon results in fluorescence of a single lymph node at the root of the bowel mesentery. Injection into the stomach resulted in identification of a retrogastric node. Histological analysis in all cases confirmed the presence of nodal tissue.

Conclusions

We report the use of invisible near-infrared light for intraoperative sentinel lymph node mapping of the GI tract. This technology overcomes the limitations of currently available methods, permits patient-specific imaging of lymphatic flow and sentinel nodes, and provides highly sensitive, real-time image-guided dissection.

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References

  1. Daneker GW Jr, Ellis LM. Colon cancer nodal metastasis: biologic significance and therapeutic considerations. Surg Oncol Clin North Am 1996;5:173–89

    Google Scholar 

  2. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127:392–9

    CAS  PubMed  Google Scholar 

  3. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977;39:456–66

    CAS  PubMed  Google Scholar 

  4. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998;227:645–51; discussion 651–3

    CAS  PubMed  Google Scholar 

  5. Saha S, Bilchik A, Wiese D, et al. Ultrastaging of colorectal cancer by sentinel lymph node mapping technique—a multicenter trial. Ann Surg Oncol 2001;8(9 Suppl):94S–98S

    CAS  PubMed  Google Scholar 

  6. Wood TF, Nora DT, Morton DL, et al. One hundred consecutive cases of sentinel lymph node mapping in early colorectal carcinoma: detection of missed micrometastases. J Gastrointest Surg 2002;6:322–9; discussion 229–30

    Article  PubMed  Google Scholar 

  7. Bilchik AJ, Giuliano A, Essner R, et al. Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms. Cancer J Sci Am 1998;4:351–8

    CAS  PubMed  Google Scholar 

  8. Alazraki NP, Eshima D, Eshima LA, et al. Lymphoscintigraphy, the sentinel node concept, and the intraoperative gamma probe in melanoma, breast cancer, and other potential cancers. Semin Nucl Med 1997;27:55–67

    CAS  PubMed  Google Scholar 

  9. Kitagawa Y, Ohgami M, Fujii H, et al. Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach. Ann Surg Oncol 2001;8(9 Suppl):86S–89S

    CAS  PubMed  Google Scholar 

  10. Kitagawa Y, Ohgami M, Fujii H, et al. Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach. Ann Surg Oncol 2001;8:86S–89S

    CAS  PubMed  Google Scholar 

  11. De Grand AM, Frangioni JV. An operational near-infrared fluorescence imaging system prototype for large animal surgery. Technol Cancer Res Treat 2003;2:553–62

    CAS  PubMed  Google Scholar 

  12. Kim S, Lim YT, Soltesz EG, et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 2004;22:93–7

    CAS  PubMed  Google Scholar 

  13. Lim YT, Kim S, Nakayama A, et al. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol Imaging 2003;2:50–64

    Article  CAS  PubMed  Google Scholar 

  14. Zaheer A, Lenkinski RE, Mahmood A, et al. In vivo near-infrared fluorescence imaging of osteoblastic activity. Nat Biotechnol 2001;19:1148–54

    Article  CAS  PubMed  Google Scholar 

  15. Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995;222:394–9; discussion 399–401

    CAS  PubMed  Google Scholar 

  16. Morton DL, Thompson JF, Essner R, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg 1999;230:453–63; discussion 463–5

    Article  CAS  PubMed  Google Scholar 

  17. Bertagnolli M, Miedema B, Redston M, et al. Sentinel node staging of resectable colon cancer: results of a multicenter study. Ann Surg 2004;240:624–8; discussion 628–30

    PubMed  Google Scholar 

  18. Maruyama K, Sasako M, Kinoshita T, et al. Can sentinel node biopsy indicate rational extent of lymphadenectomy in gastric cancer surgery? Fundamental and new information on lymph-node dissection. Langenbecks Arch Surg 1999;384:149–57

    Article  CAS  PubMed  Google Scholar 

  19. Siewert JR, Sendler A. Potential and futility of sentinel node detection for gastric cancer. Recent Results Cancer Res 2000;157:259–69

    CAS  PubMed  Google Scholar 

  20. Mori M, Mimori K, Inoue H, et al. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res 1995;55:3417–20

    CAS  PubMed  Google Scholar 

  21. Wood TF, Nora DT, Morton DL, et al. One hundred consecutive cases of sentinel lymph node mapping in early colorectal carcinoma: detection of missed micrometastases. J Gastrointest Surg 2002;6:322–9; discussion 229–30

    Article  PubMed  Google Scholar 

  22. Adell G, Boeryd B, Franlund B, et al. Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes’ B colorectal carcinoma: an immunohistochemical study. Eur J Surg 1996;162:637–42

    CAS  PubMed  Google Scholar 

  23. Ferris RL, Xi L, Raja S, et al. Molecular staging of cervical lymph nodes in squamous cell carcinoma of the head and neck. Cancer Res 2005;65:2147–56

    Article  CAS  PubMed  Google Scholar 

  24. Bigio IJ, Bown SG, Briggs G, et al. Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results. J Biomed Opt 2000;5:221–8

    Article  CAS  PubMed  Google Scholar 

  25. Johnson KS, Chicken DW, Pickard DC, et al. Elastic scattering spectroscopy for intraoperative determination of sentinel lymph node status in the breast. J Biomed Opt 2004;9:1122–8

    Article  PubMed  Google Scholar 

  26. Sanidas EE, de Bree E, Tsiftsis DD. How many cases are enough for accreditation in sentinel lymph node biopsy in breast cancer? Am J Surg 2003;185:202–10

    Article  PubMed  Google Scholar 

  27. Kitagawa Y, Fujii H, Mukai M, et al. Radio-guided sentinel node detection for gastric cancer. Br J Surg 2002;89:604–8

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by National Institutes of Health (NIH) National Research Service Award F32-HL-071464-02 (E.G.S), the National Science Foundation-Materials Research Science and Engineering Center Program under grant DMR-9808941 (M.G.B.), the Office of Naval Research (M.G.B.), the Department of Energy (Office of Biological and Environmental Research) grant DE-FG02-01ER63188 (J.V.F.), an Application Development Award (J.V.F.) from the Center for Integration of Medicine and Innovative Technology, and NIH grant R33-EB-000673 (J.V.F. and M.G.B.).

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Authors and Affiliations

  1. Department of Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts, 02115

    Edward G. Soltesz MD, MPH, Rita G. Laurence BS, Cherie P. Parungo MD & Lawrence H. Cohn MD

  2. Department of Chemistry, Massachusetts Institute of Technology, Building 6-221, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139

    Sungjee Kim PhD & Sang-Wook Kim PhD

  3. Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, Massachusetts, 02215

    Alec M. De Grand BS & John V. Frangioni MD, PhD

  4. Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, Massachusetts, 02215

    Moungi G. Bawendi PhD & John V. Frangioni MD, PhD

Authors
  1. Edward G. Soltesz MD, MPH
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  2. Sungjee Kim PhD
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  3. Sang-Wook Kim PhD
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  4. Rita G. Laurence BS
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  5. Alec M. De Grand BS
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  6. Cherie P. Parungo MD
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  7. Lawrence H. Cohn MD
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  8. Moungi G. Bawendi PhD
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  9. John V. Frangioni MD, PhD
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Corresponding author

Correspondence to John V. Frangioni MD, PhD.

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Soltesz, E.G., Kim, S., Kim, SW. et al. Sentinel Lymph Node Mapping of the Gastrointestinal Tract by Using Invisible Light. Ann Surg Oncol 13, 386–396 (2006). https://doi.org/10.1245/ASO.2006.04.025

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  • DOI: https://doi.org/10.1245/ASO.2006.04.025

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