Role of sln biopsy 12-12-12

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