Conventional Gastrectomy for Gastric Cancer Franklin Wright UCHSC Department of Surgery Grand Rounds January 14, 2008
Overview Gastric Adenocarcinoma Conventional vs Radical Lymphadenectomy Non-randomized studies RCTs Recent studies Survival Differences Conclusion
Gastric Carcinoma Second leading cause of cancer deaths in men world-wide (2007 ACS) 1 13th cause of male death in US 2:1 M:F Fresh fruit/vegetables Smoked/salted/pickled foods, H. Pylori, atrophic gastritis
Gastric Carcinoma Not homogenous disease Intestinal vs diffuse type Proximal vs distal location Dramatic differences between nations
Incidence in men (per 100,000) UK/German Japan U.S. y 52.6 6.3 16-20
Gastric Carcinoma Subtotal vs Total gastrectomy - based on location of tumor Survival U.S. - 24% Europe - 20-25% Japan - 60-70%
Lymphadenectomy 2
Lympadenectomy Japanese - D2 lymphadenectomies 1960 s Radical D3 considered Radical in Japan Western - D1 lymphadenectomies
Stage Migration More extensive lympadenectomy = more accurate staging Upstaging Improves stage-specific survival in D2 or D3 resections D2-20% D3-43% 3
Non-Randomized Siewert (Germany) Studies 1998 - Annals of Surgery 4 n=1654 Prospective, non-randomized Defined extent of lympadenectomy by # of LNs in specimen Planned for all D2, retrospectively called inadequate resections D1
Non-Randomized Studies D2 D1
Non-Randomized Studies Roukos (German) 1998 - Surgery 5 n=125 D2 patients only Prospective Showed 31 patients with N2 nodes resected with intent to cure 17% 5-yr survival
RCTs - British Cuschieri: 1996/1999 - Lancet/Br J Cancer 6,7 n=400 Intra-operatively randomized Median F/U 6.5 years 90% followed to death or 5 years
Disease-Specific Survival - No benefit
Increased post-operative complications and death in D2 group (p < 0.05)
RCTs - Dutch Bonenkamp: 1995/1999 - Lancet / NEJM 8,9 n=711 Pre-operatively randomized Median F/U 6 years
Overall Survival - No benefit
D1 (n=380) D2 (n=331) p-value Post-op Death 15 (4%) 32 (10%) 0.004 Complications 94 (25%) 142 (43%) < 0.001 Increased post-operative complications and death in D2 group (p < 0.05)
RCTs No stage-specific survival seen in either study Despite 30% D2 stage migration in Dutch study 10
RCTs - Flaws Distal pancreatectomy/splenectomy British - 56% vs 4% (both) Dutch - 30% vs 3% (distal pancreatectomy) Distal pancreatectomy did not alter M&M Protocol non-compliance / contamination (Dutch) 6% of D1 dissections showed extra LNs 51% of D2 dissections showed missing LNs
RCTs - Flaws Surgeon training Video & pamphlet (British) 6 month training by Japanese surgeon & 11 regional supervisors thereafter (Dutch) 25-50 case learning curve for D2 Dutch trial showed surgeon experience not an independent predictor of outcome
Recent Studies Sasagawa (Costa Rica): 2008, Am J Surg 11 n=199 (CR), n=497 (Japanese Cohort) All received D2 resection F/U not specified Japanese surgeon assisted with all operations
Recent Studies Overall 5 yr survival 72.5% Costa Rica 69.7% Japan Morbidity / Mortality 39% / 5% - Costa Rica (p < 0.05) 27% / 0.8% - Japan (p < 0.05)
Recent Studies Japanese radiologists, endoscopists, pathologists, surgeons, and nurses came to Costa Rica to train Costa Ricans Improvement in survival may be multifactorial No proof of D2 effect on survival Different population, unable to directly compare to European RCTs
Why are Japanese survival rates higher? Surgical Technique? Different Disease? Technical Differences? NO!
Different Disease Tumor biology Incidence of intestinal type higher in high prevalance areas - better prognosis Different tumor markers Japanese - higher nm23 British - higher c-erbb-2 and PCNA 12 Japanese-American s survival 13
Technical Differences Understaging of Western tumors D2 stage migration effect More early (low stage) tumors Better screening Chemotherapy
Technical Differences Pathologic staging different Japanese pathologists look at nuclear and structural atypia over invasion Cases called high or even low grade dysplasia by Western pathologists were called carcinoma by Japanese pathologists 14
Technical Differences Japanese surgeons dissect LNs themselves on the fresh specimen Significantly higher LN yield 15 Patient population Less obesity Younger age (8 yrs compared to Dutch) Less cardiovascular disease 15
Conclusion Improved Japanese survival likely multifactorial, unrelated to extent of LN dissection Even if D2 resection can be safely performed in Western patients, there is still no solid evidence that it should be done Lessons from Halstead s radical mastectomy
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