1. How to get more nodes in laparoscopic colon surgery John Marks MD Chief Division of Colorectal Surgery Lankenau Hospital and Institute of Medical Research

2. 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

3. Pathologist Technique

5. 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

6. N = 103 Results 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

7. Site of primary tumors and numbers of LNs identified by both techniques Tumor Site Number of Cases Number of lymph nodes identified* Traditional dissection Fat clearanceTotal Right colon159.6 (8.8)11.3 (7.1)20.9 (13.4) Transverse colon34.3 (1.5)6.3 (9.3)10.9 (9.3) Left colon84.5 (2.2)13.4 (7.3)17.9 (9.1) Sigmoid colon265.2 (4.5)13.2 (8.4)18.5 (10.2) Rectosigmoid105.4 (3.1)11.4 (7.2)16.7 (8.5) Rectum416.1 (4.3)12.7 (8.1)18.9 (10.9) TOTAL1036.2 (5.1)12.4 (7.9)18.5 (10.7) *Mean (s.d.)

8. # 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

9. Surgical Technique

11. 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

12. IMA/IMV

13. Middle Colic

14. Ileocolic

15. Benefit of Increasing Nodes

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

17. 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

18. 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

19. 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 IIIC n=6,476 Stage IIIB n=12,504 Stage IIIA n=1,722

20. 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

21. 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

22. 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

23. Disease-Specific survival for Stage III Colon Cancer No. of Negative Lymph Nodes Cumulative 5-Year Survival (%) Stage IIIAStage IIIBStage IIIC ≤ 385.554.735.5 4-783.263.346.5 8-1286.065.852.6 ≥ 1386.072.658.1 J Clin Oncol, 2006; 24(22):3570-5

24. Higher number of negative nodes is independently associated with improved disease-specific survival Conclusion J Clin Oncol, 2006; 24(22):3570-5

25. Rectal Cancer LN #s Effect of radiation on LN count after TME

26. 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

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

28. 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

29. 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

30. #LN harvested ≥ 6 to < 12 Nodes 40% ≥ 12 Nodes 28% N=176

31. 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

32. 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

33. Lymph Nodes: More is better Surgical Technique Optimization Pathologic Technique Optimization Variable in rectal cancer after irradiaiton