Image guided surgery - sentinel lymph node biopsy

1. Image Guided Oncological
Surgery
Julio M. Mayol
Servicio de Cirugia , Hospital Clinico San Carlos
Madrid, Spain

2. Goals
• SLN Biopsy: the concept
– Current status in GI surgical oncology
• Colon cancer
• Gastric cancer
• Research
– Image-Guided SLN Biopsy

3. Principles of Oncologic Surgery
En-bloc excision
– Primary tumor
– Vascular pedicle
• Lymphatic nodes and vessels included

4. Principles of Oncologic Surgery
Lymphadenectomy
– Therapeutic
– Staging
• Prognosis
• Selection for adjuvant treatment

5. The Halstedian Principle
larger incisions, more aggresive approach, unnecessary procedures

6. SLN Biopsy: the concept
Riveros M, et al. Cancer. 1967;20:2026–2031.

7. Sentinel lymph node:
The first lymph node to receive lymphatic
drainage from a tumor
Cabañas RM. Cancer 1977;39:456-66

8. Intraoperative lymphatic mapping with
sentinel node biopsy
Morton D et al. Arch Surg 1992;127:392

9. SLN Biopsy: the concept
• To modify the surgical approach
• To minimize morbidity
• To improve accuracy and survival

10. SLN Biopsy: the concept
Morton - 1990 Giuliano - 1994

11. Image-Guided SLN Bx

12. Image-Guided SLN Bx
Post Ant
Lateral derecha

13. Image-Guided SLN Bx
Preoperative planning

14. Gamma camera

15. Portable gamma camera
Sentinella
FDA approval pending

16. Image-Guided SLN Bx
Intraoperative identification

17. Image-Guided SLNBx
Intraoperative monitoring

18. Does it work for GI
malignacies?

19. • SLN Biopsy: the concept
• Current status in GI surgical oncology
• Research
– Image-guided surgery

20. SLNBx Goals in GI malignancy

21. SLNBx Goals in GI malignancy

22. SLNBx Goals in GI malignancy

23. SLNBx Goals in GI malignancy
• To modify the surgical approach
• To minimize morbidity ?
• To improve accuracy and survival

24. Current applications
• Colon cancer
• Gastric cancer
• Other: rectum, esophagus, pancreas

25. SLNBx in Colon Cancer
– Stage II – recurrence 20-30%
• Understaging?
• Hematogenous route?
– Stage III
• Chemotherapy increases survival

26. SLNBx in Colon Cancer
The larger number of LNs, the better
• Better staging
• Improved survival in LN - patients
– More LN + patients receive chemotherapy
– Less false-negative LN - patients

27. SLNBx in Colon Cancer
Number of lymph nodes assessed
depends on:
“Overall, the quantitative requirement for
The patient the nodal staging of colorectal carcinomas
is to recover as many lymph nodes as
The surgeon possible”
The pathologist
Cserin G. Nodal staging of colorectal carcinomas and sentinel nodes. J Clin Pathol
2003;56:327

28. Lymphadenectomy – same morbidity
Why SLNBx in colon cancer?

29. SLNBx in Colon Cancer
Length of specimen
– Perioperative transfusions
– Diarrhea
– Dehydration
– Meteorism
Tartter PI et al. World J Surg 2005;10:516-520

30. SLNBx in Colon Cancer
Understaging
15%-20% of CRC patients
• Insufficient number of nodes
• About 70% of positive nodes <5 mm
S. Saha et al. The American Journal of Surgery 2006;191: 305–310

31. Ultrastaging
Sentinel lymph node biopsy
“.. was developed in part to identify the first few nodes most likely to harbor
metastatic disease when present in order to reduce such pathological
understaging and thereby increase the accuracy of nodal staging”
S. Saha et al. The American Journal of Surgery 2006;191: 305–310

32. SLNBx in Colon Cancer
Saha et al in 1997
Indications
• Patients without metastatic disease
• Open or laparoscopic approach

33. SLNBx in Colon Cancer
Technique
– In vivo
• Injection of dye and/or radiotracer
– Submucosal - via colonoscopy
– Subserosal - laparotomy
• Identification
– Visually
– Gamma probe

34. SLNBx in Colon Cancer
Technique
– Ex vivo
• Injection of dye
– After removal of the specimen
– Subserosal injection
• Visual identification
Wong JH, et al. Ann Surg Oncol 2004;11:772–777

35. SLNBx in Colon Cancer
Technique
– Histophathology
• Hematoxilin-eosin
• Immunohistochemistry
• RT-PCR Micrometastases
• Frozen section

36. SLNBx in Colon Cancer
Results
Saha S. et al. The American Journal of Surgery 2006;191: 305–310

37. SLNBx in Colon Cancer
Results
Cancer & Leukemia Group B
• False negative rate: 54% (13/24)
• False positive rate: 20%
• Sensitivity: 40%
SNs did not accurately predict the presence of either conventionally
defined nodal metastases or MMD
Redston M et al. JCO 2006;24:878-883

38. SLNBx in Colon Cancer
Results
– Meta-analysis; 33 CRC papers
– Patients: n = 1794 ( colon 1201; rectum 332)
• Sensitivity 70%
• Specificity 81%
“...for future studies of CRC, it
• False negative 9% will be necessary to stratify
• Failure rate 10% patients according to their T
stage.”
• DOR 10.7
Des Guetz D et al. World J Surg (2007) 31:1304–1312

39. SLNBx in Colon Cancer
Results
Technique
– Dyes = radioactive tracer
– In vivo = ex vivo
Des Guetz D et al. World J Surg (2007) 31:1304–1312

40. SLNBx in Colon Cancer
Results
Histopathology
Upstaging
0-38%
– H&E
– ICH (Cytokeratin +/- CEA)
Des Guetz D et al. World J Surg (2007) 31:1304–1312

41. SLNBx in Colon Cancer
• Micrometastases in N0 - Meta-analysis
– Eleven studies
– ICH: 566 patients
– RT-PCR: 173 patients
– Disease free and overall survival
– Upstaging
– ICH: 32%
– RT-PCR: 37%
– 3 year-OS: RT-PCR positive < RT-PCR negative
Iddigins D et al. Ann Surg Oncol 2006; 13:1386–1392

42. SLNBx in Colon Cancer
“Based on the results of our meta-analysis, future studies on the use
of SLNM in CRC patients should:
1. Use blue dye for reasons of simplicity,
2. Be performed by experienced surgeons and pathologists,
3. Be prospective,
4. Include more than 40 consecutive patients.
Des Guetz D et al. World J Surg (2007) 31:1304–1312

43. SLNBx in Colon Cancer
Summary
SLN Biopsy in patients with colon cancer
may improve staging
Saha S. et al. The American Journal of Surgery 2006;191: 305–310

44. Current use
• Colon cancer
• Gastric cancer
• Other: rectum, esophagus, pancreas…

45. SLN Biopsy in Gastric Cancer
Gastrectomy
D2 lymphadenectomy
– T1-T2 lesions = 10-15% LN MTX

46. SLN Biopsy in Gastric Cancer
Lymphadenectomy in LN positive patients
prolongs survival
Lymphadenectomy in LN negative patients does
not increase survival
Extended lymphadenectomy increases morbidity

47. SLN Biopsy in Gastric Cancer
Proof-of-concept studies in 2000

48. SLN Biopsy in Gastric Cancer
…the feasibility of sentinel node mapping in gastrointestinal cancers and
its diagnostic reliability remains unclear because of the complicated
lymphatic drainage of the GI tract and the high frequency of skip
metastasis.
Zulfikaroglu et al. Surgery 2005;138:899-904

49. SLN Biopsy in Gastric Cancer
Technique
– Dyes
– Radioguided biopsy
- Endoscopic injection
- Subserosal injection

50. SLN Biopsy in Gastric Cancer
Detection rates
– Dye: 90%
– Radioguided biopsy: 90%
– Dual method: 100%
Hayashi H et al. J Am Coll Surg 2003;196:68-74

51. SLN Biopsy in Gastric Cancer
Rabin I, et al. IMAJ. 2006;8:40-43

52. SLN Biopsy in Gastric Cancer
Sensitivity for a positive LN
– Dye: 66%
– Radioguided biopsy: 92%
– Dual method: 92%
SLN negative patients may be selected for limited surgical
procedure
Gretschel S, et al. Ann Surg Oncol. 2007;14:2028-35

53. SLN Biopsy in Gastric Cancer
Results
– Number of SLN: 2-7
– Sensitivity 85%-100%
– Specificity 90-95%
– Failure rate 0-6%
– False negative (skip mtx): 0-20%
Hayashi H et al. J Am Coll Surg 2003;196:68-74
Zulfikaroglu et al. Surgery 2005;138:899-904
Gretschel S, et al. Ann Surg Oncol. 2007;14:2028-35

54. SLNBx in Gastric Cancer
Summary
SLN Biopsy in patients with gastric cancer
may improve staging
Tangoku A. J Med Invest 2007;54:1-18

55. Role of SLN Biopsy in GI
malignancies?

56. SLN Bx Issues in GI malignancy
• Technical issues
• Complex lymphatic drainage
• Intraoperative identification
• Imaging methods
• Histopathological study
• Impact on morbidity and mortality
• Distant Mtx in the absence of LN mtx
• Micrometastases
• Adjuvant therapy available

57. SLN Bx Issues in GI malignancy
False negative results
– Unpredictible drainage patterns
– High background signal
– Absence of real-time imaging

58. SLN Bx Issues in GI malignancy
• Improvements in the technique
• Intraoperative diagnosis

59. Role of SLN Bx in GI malignancy
• Based on SLN biopsy results, the surgical
approach be can NOT be modified

60. Role of SLN Bx in GI malignancy
• Procedure-related morbidity is NOT
reduced

61. Role of SLN Bx in GI malignancy
• SLN biopsy MAY increase staging
accuracy

62. • SLN Biopsy: the concept
• Current applications in surgical oncology
• Research

63. Does Image-Guided SLNBx
improve the results of the
traditional technique?

64. Research
Colorectal & gastric cancer protocols
– Inclusion criteria
– Exclusion criteria
– Technique
• In vivo
• Ex vivo

65. Research
Technique
Injection
• 99mTc- colloid
• Four injections
– 2.0 ml
– 0.5 mCi

66. Research
Technique
Dynamic
intraoperative
lymphoscintigraphy

67. Research
Technique
Identification of the SLN
• Gamma camera
• Gamma probe
Probe
SLN

68. Research
Technique
Ex vivo
• Difficult locations
• Rectal tumors
• Failure with in vivo tech.

69. Image-guided mapping and
SLN biopsy
To improve accuracy ?
To increase survival
To individualize the surgical technique
To decrease morbidity

70. Acknowledgements
Servicio de Cirugía I Nuclear Medicine Dpt.
Rocio Anula Roberto Delgado-Bolton
María J. Peña-Soria Jose L. Carreras
Ana Arbeo-Escolar
Iris Sanchez-Egido
Jesús A. Fdez-Represa