How to get more nodes in laparoscopic colon surgery

John Marks MD

Chief Division of Colorectal SurgeryLankenau Hospital and Institute of Medical Research

What factors impact lymph node harvest?

1. Number of lymph nodes in patient

2. Surgical technique – Acquiring the lymph nodes

3. Pathologists technique – Detecting lymph nodes in specimen

Pathologist Technique

Fat-Clearing Technique

• Specimen submitted in formalin

•Mesenteric fat dehydrated over 24 hours in Carnoy’s solution

• 6 parts ethyl alcohol• 3 parts chloroform• 1 part glacial acetic acid

•Manual dissection and lymph node harvest of entire specimen

•In cases with few nodes, additional mesenteric fat is submitted

N = 103Results

• Colon and rectal specimens fix overnight

•The next day, traditional histological blocks taken, LNs counted

• Half of each node remains in specimen for reference

•The same specimen is then placed in alcohol/xylene for 3-4 weeks

•Fully cleared specimen examined, additional lymph nodes recovered are counted

Site of primary tumors and numbers of LNs identified by both techniques

Tumor SiteNumber of Cases

Number of lymph nodes identified*

Traditional dissection

Fat clearance Total

Right colon 15 9.6 (8.8) 11.3 (7.1) 20.9 (13.4)

Transverse colon 3 4.3 (1.5) 6.3 (9.3) 10.9 (9.3)

Left colon 8 4.5 (2.2) 13.4 (7.3) 17.9 (9.1)

Sigmoid colon 26 5.2 (4.5) 13.2 (8.4) 18.5 (10.2)

Rectosigmoid 10 5.4 (3.1) 11.4 (7.2) 16.7 (8.5)

Rectum 41 6.1 (4.3) 12.7 (8.1) 18.9 (10.9)

TOTAL 103 6.2 (5.1) 12.4 (7.9) 18.5 (10.7)

*Mean (s.d.)

# Nodes - Manual vs. Fat-Clearing

• Fat-clearance yielded increases LNs compared to traditional dissection

Mean nodes recovered

Fat-Clearing 18.5

Traditional 6.2

200%

Greater Yield

Surgical Technique

Lymph node harvest: Lap vs. Open

• N=729 (243 lap, 486 open)• All colorectal cancer resections• Mean # LNs per case: 24.8 ± 20.6• No difference in mean LN with lap vs. open (p=0.4)

Laparoscopic resection of colorectal cancer can achieve lymph node retrieval similar to the open approach

IMA/IMV

Middle Colic

Ileocolic

Benefit of Increasing Nodes

J Clin Oncol, 2006; 24(22):3570-5

• Improved survival reported with node-negative colon cancer and # of LNs assessed

• Relationship between survival with stage III colon cancer and # LNs is unclear

• Prognostic effect of increasing number of positive nodes is a confounding factor

Background

J Clin Oncol, 2006; 24(22):3570-5

• Identified patients with stage III colon cancer surgery between January 1988 and December 1997– SEER cancer registry

• Disease-specific survival examined by substage based on no. of negative nodes

• Proportional hazards model determined effect of negative nodes on survival

Methods

J Clin Oncol, 2006; 24(22):3570-5

Results

J Clin Oncol, 2006; 24(22):3570-5

N = 20,702• Right sided cancers found

in 50% of patients

• 74% had well or moderately differentiated tumors

• Median no. positive LN = 7• IIIC > IIIB > IIIA

• Median no. negative LN = 2

Stage IIICn=6,476

Stage IIIBn=12,504

Stage IIIAn=1,722

• Median follow up 5 yrs

• For stage IIIB and IIIC, significant decrease in disease-specific mortality as nodes increased (both p<0.001)

• No association between no. of negative nodes and survival for stage IIIA (p=0.90)

Results

J Clin Oncol, 2006; 24(22):3570-5

Stage IIIB Cancer

5-year mortality

≥ 13 negative nodes 27%

≤ 3 negative nodes 45%

J Clin Oncol, 2006; 24(22):3570-5

Relative Reduction of 40%

in deaths

Stage IIIC Cancer

5-year mortality

≥ 13 negative nodes 42%

≤ 3 negative nodes 65%

J Clin Oncol, 2006; 24(22):3570-5

Relative Reduction of 35%

in deaths

Disease-Specific survival for Stage III Colon Cancer

No. of Negative

Lymph Nodes

Cumulative 5-Year Survival (%)

Stage IIIA Stage IIIB Stage IIIC

≤ 3 85.5 54.7 35.5

4-7 83.2 63.3 46.5

8-12 86.0 65.8 52.6

≥ 13 86.0 72.6 58.1

J Clin Oncol, 2006; 24(22):3570-5

• Higher number of negative nodes is independently associated with improved disease-specific survival

Conclusion

J Clin Oncol, 2006; 24(22):3570-5

Rectal Cancer LN #s

• Effect of radiation on LN count after TME

LN presentation

Elsa and the crew

Less than 12 lymph nodes can be expected in surgical specimen after high dose chemoradiation for rectal

cancer

Marks J H, Valsdottir E B,, Yarandi S, Newman D A, Newze I, DeNittis A, Marks G

Lankenau Hospital and Institute of Medical Research

Purpose

• To determine if harvesting >12 lymph nodes is a useful quality indicator for rectal cancer surgery after neoadjuvant XRT

• Selected patients who underwent TME after neoadjuvant XRT from database

– January 1997 – August 2007

• Compared <12 LN to ≥12 LNs relative to multiple patient and treatment factors

Methods

Results

• Mean LN harvest = 10.1 (1-38)

• No significant difference in LN harvest relative to radiation dose, age, tumor response, or type of surgery

• No correlation between LN harvested and # positive nodes

N=176

#LN harvested

≥ 6 to < 12 Nodes40%

≥ 12 Nodes28%

N=176

Conclusion

• With standardized surgical technique and pathological evaluation, # LN present after neoadjuvant chemoradiation and TME for rectal cancer varies greatly

• Increased number of nodes does not increase yield of + nodes

• Further study necessary to determine if number of nodes correlate with outcome

• Due to the high variability of number of lymph nodes after the sterilizing effect of radiation, a target number of nodes that correlates to surgical adequacy is likely unobtainable

Conclusion

Conclusion

• Lymph Nodes: More is better

• Surgical Technique Optimization

• Pathologic Technique Optimization

• Variable in rectal cancer after irradiaiton