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Image guided surgery - sentinel lymph node biopsy
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Image Guided Oncological Surgery
Julio M. MayolServicio de Cirugia , Hospital Clinico San Carlos
Madrid, Spain
• SLN Biopsy: the concept– Current status in GI surgical oncology
• Colon cancer• Gastric cancer
• Research– Image-Guided SLN Biopsy
Goals
Principles of Oncologic Surgery
En-bloc excision
– Primary tumor
– Vascular pedicle• Lymphatic nodes and vessels included
Principles of Oncologic Surgery
Lymphadenectomy
– Therapeutic
– Staging• Prognosis• Selection for adjuvant treatment
The Halstedian Principle
larger incisions, more aggresive approach, unnecessary procedures
SLN Biopsy: the concept
Riveros M, et al. Cancer. 1967;20:2026–2031.
Sentinel lymph node:
The first lymph node to receive lymphatic drainage from a tumor
Cabañas RM. Cancer 1977;39:456-66
Intraoperative lymphatic mapping with sentinel node biopsy
Morton D et al. Arch Surg 1992;127:392
SLN Biopsy: the concept
• To modify the surgical approach
• To minimize morbidity
• To improve accuracy and survival
SLN Biopsy: the concept
Morton - 1990 Giuliano - 1994
Image-Guided SLN Bx
Lateral derecha
AntPost
Image-Guided SLN Bx
Image-Guided SLN Bx
Preoperative planning
Gamma camera
Portable gamma camera
FDA approval pending
Sentinella
Image-Guided SLN Bx
Intraoperative identification
Image-Guided SLNBx
Intraoperative monitoring
Does it work for GI malignacies?
• SLN Biopsy: the concept
• Current status in GI surgical oncology
• Research – Image-guided surgery
SLNBx Goals in GI malignancy
SLNBx Goals in GI malignancy
SLNBx Goals in GI malignancy
SLNBx Goals in GI malignancy
• To modify the surgical approach
• To minimize morbidity
• To improve accuracy and survival
?
Current applications
• Colon cancer
• Gastric cancer
• Other: rectum, esophagus, pancreas
SLNBx in Colon Cancer
– Stage II – recurrence 20-30%• Understaging?• Hematogenous route?
– Stage III • Chemotherapy increases survival
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
SLNBx in Colon Cancer
Number of lymph nodes assessed depends on:
The patient
The surgeon
The pathologist
Cserin G. Nodal staging of colorectal carcinomas and sentinel nodes. J Clin Pathol 2003;56:327
“Overall, the quantitative requirement for the nodal staging of colorectal carcinomas is to recover as many lymph nodes as possible”
Lymphadenectomy – same morbidity
Why SLNBx in colon cancer?
SLNBx in Colon Cancer
Length of specimen
– Perioperative transfusions
– Diarrhea– Dehydration– Meteorism
Tartter PI et al. World J Surg 2005;10:516-520
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
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
Ultrastaging
Saha et al in 1997
Indications
• Patients without metastatic disease• Open or laparoscopic approach
SLNBx in Colon Cancer
Technique
– In vivo• Injection of dye and/or radiotracer
– Submucosal - via colonoscopy– Subserosal - laparotomy
• Identification– Visually– Gamma probe
SLNBx in Colon Cancer
Technique
– Ex vivo• Injection of dye
– After removal of the specimen– Subserosal injection
• Visual identification
SLNBx in Colon Cancer
Wong JH, et al. Ann Surg Oncol 2004;11:772–777
SLNBx in Colon Cancer
Technique
– Histophathology
• Hematoxilin-eosin• Immunohistochemistry• RT-PCR
• Frozen section
Micrometastases
Results
SLNBx in Colon Cancer
Saha S. et al. The American Journal of Surgery 2006;191: 305–310
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
Results
– Meta-analysis; 33 CRC papers– Patients: n = 1794 ( colon 1201; rectum 332)
• Sensitivity 70%• Specificity 81%• False negative 9%• Failure rate 10%• DOR 10.7
SLNBx in Colon Cancer
Des Guetz D et al. World J Surg (2007) 31:1304–1312
“...for future studies of CRC, it will be necessary to stratify patients according to their T stage.”
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
SLNBx in Colon Cancer
Results
Histopathology
– H&E – ICH (Cytokeratin +/- CEA)
Des Guetz D et al. World J Surg (2007) 31:1304–1312
Upstaging
0-38%
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
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
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
Current use
• Colon cancer
• Gastric cancer
• Other: rectum, esophagus, pancreas…
SLN Biopsy in Gastric Cancer
Gastrectomy
D2 lymphadenectomy
– T1-T2 lesions = 10-15% LN MTX
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
SLN Biopsy in Gastric Cancer
Proof-of-concept studies in 2000
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
SLN Biopsy in Gastric Cancer
Technique
– Dyes
– Radioguided biopsy
- Endoscopic injection
- Subserosal injection
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
SLN Biopsy in Gastric Cancer
Rabin I, et al. IMAJ. 2006;8:40-43
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
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
SLNBx in Gastric Cancer
Summary
SLN Biopsy in patients with gastric cancer may improve staging
Tangoku A. J Med Invest 2007;54:1-18
Role of SLN Biopsy in GI malignancies?
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
SLN Bx Issues in GI malignancy
False negative results
– Unpredictible drainage patterns
– High background signal
– Absence of real-time imaging
SLN Bx Issues in GI malignancy
• Improvements in the technique
• Intraoperative diagnosis
Role of SLN Bx in GI malignancy
• Based on SLN biopsy results, the surgical approach be can NOT be modified
Role of SLN Bx in GI malignancy
• Procedure-related morbidity is NOT reduced
Role of SLN Bx in GI malignancy
• SLN biopsy MAY increase staging accuracy
• SLN Biopsy: the concept
• Current applications in surgical oncology
• Research
Does Image-Guided SLNBx improve the results of the
traditional technique?
Research
Colorectal & gastric cancer protocols
– Inclusion criteria– Exclusion criteria
– Technique• In vivo• Ex vivo
Research
Technique
Injection
• 99mTc- colloid• Four injections
– 2.0 ml
– 0.5 mCi
Research
Technique
Dynamic intraoperative lymphoscintigraphy
Research
Technique
Identification of the SLN
• Gamma camera• Gamma probe
Probe
SLN
Research
Technique
Ex vivo
• Difficult locations• Rectal tumors• Failure with in vivo
tech.
Image-guided mapping and SLN biopsy
To improve accuracy ?
To increase survivalTo individualize the surgical technique
To decrease morbidity
Acknowledgements
Servicio de Cirugía I
Rocio Anula
María J. Peña-Soria
Ana Arbeo-Escolar
Iris Sanchez-Egido
Jesús A. Fdez-Represa
Nuclear Medicine Dpt.
Roberto Delgado-Bolton
Jose L. Carreras