Joint Hospital Surgical Grand Round 16th Jan 2010 Dr James Fung Department of Surgery United...
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Transcript of Joint Hospital Surgical Grand Round 16th Jan 2010 Dr James Fung Department of Surgery United...
Joint Hospital Surgical Grand Round16th Jan 2010
Dr James FungDepartment of SurgeryUnited Christian Hospital
Surgery Liver resection Liver transplantation
Local ablation Physical (RFA, microwave, cryothreapy) Chemical (ethanol, acetic acid)
Regional therapy TACE (Transarterial chemoembolization) IAI (Intraarterial radiotherapy)
Limited by liver reserve
Disease recurrence1,2
Intrahepatic recurrences (IHR)▪ Intrahepatic metastasis▪ De novo hepatoma
Extrahepatic recurrences (HER) 1-yr, 3-yr and 5yr recurrence ~ 20%,
50% and 60%1. Poon RT et al. Long-Term Survival and Pattern of Recurrence After Resection of Small Hepatocellular
Carcinoma in Patients With preserved Liver Function: Implications for a Strategy of Salvage Transplantation. Ann Surg 2002(3): 373-82.
2. Yamamoto J et al. Recurrence of hepatocellular carcinoma after surgery. BJS 83(9): 1219-22
Aggressive treatment of IHR improves survival1
Treatment strategy2: Surgical re-resection▪ Feasible in 10% of recurrent disease
Locoregional treatment (TACE, RFA, IAI)▪ As primary treatment in ~70% of recurrent
disease Systemic chemotherapy / Conservative
1. Lai ECS et al. Hepatic resection for hepatocellular carcinoma: an audit of 343 patients. Ann Surg 1995; 221:291-298.
2. Poon RT et al. Intrahepatic Recurrence After Curative Resection of Hepatocellular Carcinoma: Long-Term Results of Treatment and Prognostic Factors. Ann Surg 1999; 216-22.
Efficacy:▪ For palliation of primarily unresectable
HCC: 3YOS 26%1
▪ For palliation of unresectable IHR: 3YOS 38.2%2
1. Lo CM et al. Randomized Controlled Trial of Transarterial Lipiodol Chemoembolization for Unresectable Hepatocellular Carcinoma. Hepatology 2002; 35:1164-71
2. Poon RT et al. Intrahepatic Recurrence After Curative Resection of Hepatocellular Carcinoma: Long-Term Results of Treatment and Prognostic Factors. Ann Surg 1999; 216-22.
Potential benefits: Treats microscopic
tumours foci inside liver decrease post-op recurrence
?Increase resectability
?Prevent tumour dissemination during surgery
Concerns: Liver failure Renal failure Liver abscess
Delay surgical resection
Can it improve survival?Who can benefit?
Hepatology 1994; 20:295-301 The first clinical trial on adjuvant TAC(E) Patients and treatment:
Hepatectomy + TAC(E) vs Hepatectomy = 23 : 27 All stage HCC No detail on pre- / post-treatment liver function
Results: No difference in overall survival 3YDFS: 32% vs 12% (p = 0.0237)
Complication: Biloma, hepatic failure
Author Journal Year
Design Result
Takenaka K et al
Am J Surg 1995
Case series Improved DFS (from historical record)
Kohno H et al Arch Surg 1996
Retrospective case-control
No benefit
Shimoda M et al
Hepatogastroenterology
2001
Retrospective case-control
Borderline survival benefit
Cheng et al World J Gastroenterology
2005
Retrospective case-control
Borderline survival benefit
World J Gastroenterol 2004; 10(19): 2791-4 Retrospective case-control study Patients and treatment:
Hepatectomy vs Hepatectomy + TAC(E) = 360: 185 Indication for adjuvant TAC(E) not clear Stratification according to risk factor of recurrent tumour▪ Tumour > 5cm, multiple tumours, vascular invasion
Results: No survival benefit for pt without risk factor of recurrence Small benefit for pt with risk factor of recurrence▪ 3YOS: 70.4% vs 75.9% (p = 0.0216)
Control arm: hepatectomy alone (HA) (estimated 5YOS 15%)
Treatment arm: hepatectomy + post-op TACE (HT) (estimated 5YOS 35%) Post-op TACE performed 4-6 wks post-op if▪ TBili < 34, Cr 135, PT <3s prolong, Plt >50,
performance status 0/1 Sample size: 118 patient (56 in each arm)
One-sided, power 80%, alpha error 0.05 Attitude of anaylsis: intention-to-treat
Overall recurrence: No significant
difference Solitary recurrence:
Borderline difference favouring HT
Potentially treatable recurrence: Favouring HT
Survival
Hepatectomy + TACE
Hepatectomy alone
p-value
3YDFS 9.3% 3.5% 0.004
3YOS 33.3% 19.4% 0.048
Borderline survival benefit after resection
Adjuvant TAC(E) may be beneficial to patient with high risk of disease recurrence after surgery
Can it improve survival?Can it improve resectability?
Annals of Surgery 1996; 224(1): 4-9 Case-control study
Neoadjuvant TACE + hepatectomy vs hepatectomy = 105 : 35 (no limit on T stage)
Results: 3YOS 77.9% vs 67.8% (p = ns) 3YDFS 37.6% vs 33.7% (p = ns) 61% had tumour reduction after
neoadjuvant TACE
Author Journal Year Design Result
Majno et al Ann Surg 1997 Retrospective case-control
Improved DFS
Zhang et al Cancer 2000 Retrospective case-control
Improved DFS
Choi et al World J Surg 2007 Retrospective case-control
No benefit
Control arm: hepatectomy Treatment arm: preoperative TACE
+hepatectomy
Pre-op TACE Stop TACE and proceed for hepatectomy if no
evidence of tumour shrinkage Hepatectomy
Performed within 2 weeks from randomization or within 8 weeks from last TACE
Sample size estimation: 100 (50 in each arm)
5 patients in pre-op TACE group could not proceed to hepatectomy Tumour progression = 4 Liver failure = 1
Tumour volume Pre-op TACE vs control = 276cm3 vs 299cm3 (p =
0.832)
Cirrhosis (by pathology) Significantly worse in pre-op TACE group
No significant difference in terms of recurrence pattern
Survival
TACE + Hepatectomy
Hepatectomy alone
p-value
3YDFS 25.5% 21.4% 0.372
3YOS 40.4% 32.1% 0.679
No added value to hepatectomy alone Does not decrease disease recurrence Cannot improve survival Cannot guarantee tumour shrinkage
Current evidence is insufficient to conclude on the issue of (neo)adjuvant TACE
Adjuvant TACE may offer borderline survival benefit to suitable patient
Neoadjuvant TACE does not offer additional benefit for resectable HCC