1. Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma Sheung Tat FAN Department of Surgery, The University of HongKong Chair Professor The 6 th Chinese Conference on Oncology & 9 th Cross-Strait Academic Conference on Oncology

2. Hepatectomy for Hepatocellular Carcinoma Hospital mortality 5-year survival Foster （ USA ） 1977 58%- Lee （ HongKong ） 1982 20% Nagasue （ Japan ） 1993 7%26.4% Belghiti （ France ） 1994 4.7%- Sheen （ Taiwan ） 1996 6%22%

3. Improvement of prognosis after hepatectomy for hepatocellular carcinoma(1989 – 2008 ） % major hepatectomy % patients not requiring blood transfusion % hospital death percent

5. Improvement of prognosis after hepatectomy for hepatocellular carcinoma(1989 – 2008 ） % major hepatectomy % patients not requiring blood transfusion % hospital death 百分比

6. 5-year survival: 36% → 49%

7. Refinement of surgical skills Meticulous perioperative nursing care Intensive postoperative follow-up

8. Whether the efficacy of hepatetomy for hepatocellular carcinoma would be further improved?

9. Comparison of survival rates after hepatectomy for hepatocellular carcinoma preoperative data 1989–1998 (n=390) 1999–2008 (n=808) age5456* Concurrent disease 27.7%39.4%* Indocyaninc green clearance test 11.3%11.4% Serum albumin 41 g/L40 g/L* Serum bilirubin 11µmol/L12µmol/L* *P<0.05

10. Comparison of survival rates after hepatectomy for hepatocellular carcinoma data of surgery 1989–1998 (n=390) 1999–2008 (n=808) Major hepatectomy 68.7%57.5%* Anterior approach for right hepatectomy 28.6%62%* Use of ultracision harmonic scalpel 71.5%92.6%* Blood loss major hepatectomy minor hepatectomy 1.5L 1.7L 1L 0.7L* 0.92L* 0.5L* Abdominal drainage 85.4%20.9%* *P<0.05

11. Comparison of survival rates after hepatectomy for hepatocellular carcinoma pathologic data 1989–1998 (n=390) 1999–2008 (n=808) Liver cirrhosis49.5%60.4%* Chronic hepatitis36.7%27.1% Normal liver13.8%12.5% TNM staging I II IIIA IVA 5.4% 36.2% 31% 27.4% 8.7% 33.3% 24.7% margin9.7%3.7%* *P<0.05

12. Comparison of survival rates after hepatectomy for hepatocellular carcinoma postoperative data 1989 – 1998 (n=390) 1999 – 2008 (n=808) Machanical ventilation 53%17.2%* ICU duration2 days1 day* Hospital stay12 days10 days* Rates of complication39.2%24.8%* Hospital mortality cirrhosis of the liver chronic hepatitis normal liver 6.2% 7.8% 4.2% 5.6% 3.1%* 2.3% 5 Overall recurrence78.2%60.2%* *P<0.05

13. Long-term overall survival rate of patients with hepatocellular carcinoma treated by hepatetomy 1989 – 1998 (n=390) 1999 – 2008 (n=808) survival rate 1-year 3-year 5-year 74.8% 54.2% 42.1% 83.3%* 64.9%* 54.8%* *P<0.000

14. 1999-2008 (n=808) 1999-2008 (n=772) Overall survival Tumor-free survival year Cumulative survival （ % ） 1989-1998 (n=390) 1989-1998 (n=349) P<0.0001P=0.0024

15. Comparison of overall survival rates of patients with hepatocellular carcinoma treated by hepatetomy based on TNM Staging (UICC 1997) Stage I 1999-2008 (n=70) 1989-1998 (n=21) P=0.4523 Stage II 1999-2008 (n=269) 1989-1998 (n=141) P=0.0032 Stage III 1999-2008 (n=269) 1989-1998 (n=121) P=0.0106 Stage IV 1999-2008 (n=200) 1989-1998 (n=107) P=0.0069 year Cumulative survival （ % ）

16. Survival rates of patients treated by major hepatectomy VS. minor hepatectomy 1999-2008 (n=465) 1999-2008 (n=343) Cumulative survival （ % ） Cumulative surviva （ % ） year Major hepatectomy Minor hepatectomy Overall survival 1989-1998 (n=268) 1989-1998 (n=122) P=0.0054P=0.0002

17. Overall survival rates based on potential liver status A 1999-2008 (n=488) 1989-1998 (n=193) 1999-2008 (n=219) 1989-1998 (n=143) 1999-2008 (n=101) 1989-1998 (n=54) cirrhosis Chronic hepatitis Normal liver Cumulative survival(% ） year P<0.0001 P=0.4566 P=0.0200 B C

18. Continuous improvement of survival rates Overall survival Cumulative survival （ % ） year 2004-2008 (n=426) 1999-2003 (n=382) 1994-1998 (n=241) 1989-1993 (n=149) P<0.0001

19. Factors affecting survival rates Symptoms Blood loss > 2L Postopertive complications Number of tumor nodules Microvessel invasion Margin of resection TNM staging

20. Contributions of surgons to the improvement of survival rate Reduce blood loss Avoid postoperative complications Acquire R0 resection

22. Distribution of 15 min ICG retention rate for patients treated by hepatectomy Liver function Child-Pugh A grade (n=1074) Hospital death 4% Liver function Child-Pugh B grade (n=46) Hospital death 8.7% P < 0.0001 Median=11.1 Median=17.4 Preoperative 15 min ICG retention rate Fan ST, J Hepatobiliary Pancreat Surg, 2009

23. 範上達, Mastery of Surgery, 2007, P. 1090 Liver congestion Liver failure Mortaluty SIRS Hyperdynamic injury to small liver remnant Liver ischemiaMassive bleeding Sepsis

24. Smaller segment II/III Invaded right hepatic vein & middle hepatic vein Anterior approach for right hepatectomy, resection of proximal middle hepatic vein &segment IVb hepatic vein

26. Overall survival rates of liver cancer patients with tumor status meeting Milan Criteria after hepatectomy 1999-2008 (n=343) Cumulative survival （ % ） year 72.5% 1989-1998 (n=110) P=0.0237

27. Predicting survival after liver transplantation for patients with liver cancer 5-year survival Meeting Milan criteria (n=444)73.3% Beyond Milan criteria (n=1112)53.6% Mazzaferro V et al, Lancet Oncology, 2009

28. Comparison of survival after partial hepatectomy single tumor  5cm vs. tumor number 2 – 3, each  3cm Single tumor  5cm (n=385) tumor number 2-3, each  3cm (n=25) P=0.0306 Cumulative survival （ % ） year 70.2%

29. Major hepatectomy R0 resection No postoperative complications No microvessel invasions Associated factors with the survival of patients meeting Milan Criteria after hepatectomy Multivariate analysis

30. Comparison of survival between patients treated by major hepatectomy (single tumor  5cm, negtive margin) and patients receiving living donor liver transplantation living donor liver transplantation (n=36) Partial hepatectomy (n=116) P=0.2684 Cumulative survival （ % ）

31. Long-term survival after partial hepatectomy （ 1989 – 2000.5 ） Patients survive more than 10 years (n=127) 26.4% Patients survive less than 10 years (n=354) P<0.0001 Cumulative survival （ % ） year

32. Cumulative survival rate of tumor-free patients vs. Patients with recurrence in 10 years after hepatectomy for cancer (1989 – May 2000) Tumor-free survive more than 10 years (n=74) 17% Tumor-free survive less than 10 years (n=360) P<0.0001 Cumulative survival （ % ） year

33. Death reasons for patients survived more than 10 years without recurrence ReasonsNumber of patients Time after surgery Lung recurrence110.8 Bleeding of duodenal ulcer 113.2 MODS112.5 Lung cancer217.8 11.6

34. Summary 5 -year TNM StagingI81.7% II 77.2% IIIA 44% IVA28.2% For the patients with high TNM staging, the efficacy of patients comlicated with cirrhosis receiving major hepatectomy improves continuously. The efficacy of hepatectomy with tumor status meeting Milan Criteria is similar to liver transplantation. For patients with resectable liver cancer, hapetectomy still remains the first choice in areas short of corpse organs.