1. Joint Hospital Surgical Grand Round 25 July 2009 Dr. David KW Leung Tseung Kwan O Hospital

2. Outline Introduction Lymphadenectomy Principle Definition and extent Literature review Conclusion

3. Introduction One of the most common cancers in the world Highest incidences in Eastern Asia (Japan and Korea) (70 per 100,000), Southern & Central America, Eastern Europe (40 per 100,000)

4. Incidence of Gastric Cancer in HK HK Cancer Registry

5. Treatment - Surgery Adequate surgical resection offers best chance of cure or long term survival Principles Resection with adequate tumor-free margin (~5cm) Subtotal/ total gastrectomy Regional lymph node clearance corresponding to the location of the primary tumor Safe and well-functioning anastomosis

6. Lymphadenectomy - principles Lymph node metastasis is the commonest mode of spread Gastric cancer with regional LN involvement considered as localized disease in the absence of haematogenous spread Adequate lymphadenectomy can be curative

7. Lymphadenectomy – Definition and extent The Japanese introduced the concept of tiers of regional lymphadenectomy Regional LNs groups into 3 tiers N1:perigastric nodes closest to the primary lesion N2:distant perigastric nodes and the nodes along the main arteries supplying the stomach N3:Nodes outside the normal lymphatic pathways of the stomach Japanese Classification of Gastric Carcinoma – 2 nd English Ed. Japanese Gastric Cancer Association

9. Lymphadenectomy - Nomenclature D1:Limited lymphadenectomy All N1 nodes removed en bloc with the stomach D2:Systematic lymphadenectomy All N1 and N2 nodes are removed en bloc with the stomach D3:Extended lymphadenectomy All three tiers nodes are removed en bloc

10. Lymphadenectomy - Japan The conventional treatment is D2 systematic lymphadenectomy in Japan Suggests a lower recurrence rate and increased survival rates Based on retrospective reports It forms the basis of two large multicentre randomized controlled trials in Europe in 1990s Noguchi et al. Radical Surgery for gastric cancer: A review of the Japanese Experience. Cancer 1989;64:2053-62. Maruyama et al. Progress in Gastric Cancer Surgery in Japan and its Limits of Radicality. World J Surg 1987;6:215-25.

11. MRC/ Dutch trial MRC trial Medical Research Council (MRC) Gastric Cancer Surgical Trial (ST01) Cuschieri et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. Lancet 1996;347:995-99. Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30 Dutch trial Bonenkamp et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745-48. Bonenkamp et al. Extended lymph-node dissection for gastric cancer. NEJM 1999;340:908-14.

12. MRC/ Dutch trial Multicenter randomized controlled trials 400 (MRC) and 711 (Dutch) patients were studied Comparing D1 and D2 lymphadenectomy Dutch trial Definition according to Japanese Research Society for the Study of Gastric Cancer (JRSGC) D1: removal of perigastric nodes D2: additional removal of LN in N2 tier

13. MRC/ Dutch trial MRC trial D1: removal of LN within 3.0cm of the tumor (N1 in old TNM staging) D2: additional removal of omental bursa, hepatoduodenal and retroduodenal LN, splenic artery/ splenic hilar and retropancreatic LN For proximal tumor, resection of spleen and distal pancreas were done for clearance of N2 lymph nodes

14. Morbidity and mortality Bonenkamp et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745-48. Cuschieri et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. Lancet 1996;347:995-99.

15. 5-year survival Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30 Bonenkamp et al. Extended lymph-node dissection for gastric cancer. NEJM 1999;340:908-14. D1: 35% D2: 33% D1: 45% D2: 47%

16. MRC/ Dutch trials - critics Inadequate pre-trial training Failure to deliver the intended treatment Contamination and non-compliance Associated morbidity and mortality in pancreatico- splenectomy McCulloch et al. Extended versus limited lymph node dissection technique for adenocarcinoma of the stomach (review). Cochrane Database of Systematic Reviews 2003, Issue 4.

17. Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30 “the possibility that D2 resection without pancreatico- splenectomy may be better than standard D1 resection cannot be dismissed”

18. Newer evidence D2 total gastrectomy without splenectomy Csendes et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002;131:401-7. Yu et al. Randomized clinical trials of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg 2006;93:559-563. D1 gastrectomy vs. D2 gastrectomy without pancreatico-splenectomy Degiuli et al. Morbidity and mortality after D1 and D2 gastrectomy for cancer: Interim analysis of the Italian Gastric cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Onco 2004;30:303-8.

19. D2 total gastrectomy without splenectomy Randomised controlled trials Total 187 (Csendes et al.) and 207 (Yu et al.) patients are included Csendes et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002;131:401-7. Yu et al. Randomized clinical trials of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg 2006;93:559-563.

20. D2 total gastrectomy without splenectomy Compare D2 total gastrectomy with or without splenectomy in proximal gastric cancers In spleen preservation group, the lymph nodes along the splenic artery (station 11) and at the hilum of spleen (station 10) are dissected without sacrificing the spleen and splenic vessels In splenectomy group, distal pancreas are not resected

21. Mortality With splenectomy Without splenectomy P values Csendes et al. 2002 4/90 (4.4%)3/97 (3.1%)> 0.7 Yu et al. 20062/104 (1.9%)1/103 (1%)1.000

22. Morbidity Yu et al. Br J Surg 2006;93:559-563. Csendes et al. Surgery 2002;131:401-7. TG: total gastrectomy TGS: total gastrectomy with spelenectomy

23. 5-year survival With splenectomy Without splenectomy P values Csendes et al. 2002 42%36%> 0.5 Yu et al. 200659/104 (56.7%)52/103 (50.4%)0.503

24. D1 vs. D2 gastrectomy without pancreatico-splenectomy – IGCSG trial Prospective randomised trial Comparing D1 with D2 gastrectomy according to the JRSGC rules D2: during total gastrectomy Pancreas was removed only when it is suspected to be involved by the tumor Splenectomy was performed with pancreas preservation technique when required (T>1 on the greater curvature of the proximal/ middle thirds of stomach) Degiuli et al. Morbidity and mortality after D1 and D2 gastrectomy for cancer: Interim analysis of the Italian Gastric cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Onco 2004;30:303-8.

25. D1 vs. D2 gastrectomy without pancreatico-splenectomy – IGCSG trial Quality control Restricted to 5 centers at which more than 25 D2 dissections had been performed during earlier studies A minimum number of 25 retrieved nodes were required 162 patients (76 in D1) and (86 in D2) are included Splenectomy performed in 16 patients Distal pancreatectomy was done in 4 patients

26. Results Long term results (5-year survival) is pending P<0.29

27. Conclusion Evidence from RCT that D1 and D2 resection confers no difference in survival Distal pancreatectomy and splenectomy is associated with higher morbidity and mortality but offers no survival benefit D2 gastrectomy should be performed by surgeons with experience of this type of radical surgery