Joint Hospital Surgical Grand Round Radiofrequency Ablation of

Joint Hospital Surgical Grand Round Radiofrequency Ablation of Hepatic Tumor (Factors affect local recurrence rate) Dr K Y Yuen United Christian Hospital

Introduction • Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world • Global annual incidence is one million new patients • 70% in Asia and 12% in Africa

Introduction • Surgery is the only known curative option for either primary or secondary hepatic carcinoma • Resection or transplantation is the gold standard of treatment for liver tumor • Only 20% to 37% of patients is suitable for hepatectomy Fan et la, Annals of Surgery 1999

Introduction Factors limit the surgical intervention: • multiple / diffuse tumors • tumor in unresectable locations (proximity of the tumors to major • • • vascular and biliary structures) Poor co-morbidity inadequate liver reserve significant portal hypertension 5 - year survival rate for resectable HCC or liver metastasis is only 20 - 40 % Loco-regional therapies have been developed for the treatment of unresectable liver tumor

Nguyen et la, Clinical Gastroenterology 2005

Radio Frequency Ablation • First described by Rossi et al in 1993 • High-frequency (450 - 500 KHz) alternating RF current causes oscillatory movement of ions in tissue • The mechanism of tissue heating is frictional heat caused by the motion from the ionic current • Cause coagulation necrosis at temperature between 50 -80 o. C

Radio Frequency Ablation Indications: • Alterative to surgery in poor liver function patient with • • primary or secondary liver tumor Supplementary to surgery in bilobal tumors Liver transplant candidates (bridge) Some transplant surgeons are using percutaneous or laparoscopic RFA to treat HCCs detected in patients with cirrhosis on the transplant waiting list in an attempt to attain local control of tumor and prevent progression Robert Goldstein, MD, personal communication, April 2000

Radio Frequency Ablation Contraindications: – Child’C cirrhosis (gross ascites) – Excessive tumor burden – Extrahepatic diseases – Active infection – Renal insufficiency – Coagulopathy – Near major ductal confluence

Radio Frequency Ablation • Complications (0 -12%): ● ● ● ● ● Abscess formation Bleeding(delayed bleeding into the ablated area, subcutaneous/ subcapsular haematoma) Needle tract seeding (up to 12. 5%) Bile leakage Bile duct stricture hydropneumothrorax Liver failure Grounding pad burn Acute renal failure Mortality: 0 -1%

Radio Frequency Ablation • RFA may be a superior option amount the locoreginal ablation therapy: Lower complication rate Less recurrence rate Shorter hospital stay R Poon et la, Annals of Surgery 1999

Radio Frequency Ablation Question to answer • What determine the efficacy of RFA in liver tumor patient ? • Local Recurrence is one of the important aspects Local recurrence was defined as radiological (CT, MRI or contrast -enhanced ultrasound) and/or histological (tumor cells with intact mitochondrial enzyme staining) detection of residual or recurrent viable tumor at the site of the original tumor, during follow-up and after completion of all (one or more) sessions.

Pre OT Post OT 3 months Siperstein A et la, Annals of Surgical Oncology 2005 Post OT 1 week

Local Recurrence After Hepatic Radiofrequency Coagulation Multivariate Meta-Analysis and Review of Contributing Factors Stefaan Mulier, MD, Yicheng Ni, Ph. D, Jacques Jamart, MD, Theo Ruers, Ph. D, Guy Marchal, Ph. D, and Luc Michel, MD Annals of Surgery, August 2005

Local Recurrence • Local recurrence rate after RFA of liver tumors • • varies widely between 2% and 60% A local recurrence seriously jeopardizes the chances of cure Re-treatment is often impossible or has a high risk of failure From Solbiati L et al 1999, only 55% recurrent tumors were re-treated and a complete coagulation was obtained in only cases 36%. Reasons for not considering re-treatment: unfavorable geometry diffuse metastases

Local Recurrence Rate: Univariable Analysis of Contributing Factors • 9 factors: Diameter (size) Pathology Proximity of major vessel Location Approach (surgery Vs percutaneous) Intentional Margin Vascular occlusion Anaethesia Imaging Physician’s experience

Diameter (Size) • Current recommended tumor size <5 cm • Nearly all authors agree tumor size determining local recurrence /efficacy • Goletti O et al, Montorsi M et al , Livraghi T et al, • showed that complete tumor necrosis in 80% to 90% of HCCs smaller than 3 to 5 cm Livraghi T et al, complete ablation rate for larger tumors is less favorable: a study of RFA for 126 HCCs 3. 1 to 9. 5 cm (mean 5. 4 cm) reported a complete necrosis rate of 48% with the use of a clustered electrode.

Diameter (Size) Size of individual RFA is limited • Single coagulation cannot cover a large lesion i. e. < 100% necrosis – higher risk of local recurrence Adam R et la, Arch Surg 2002 • For large tumors, overlapping coagulations is necessary, however, technically difficulty – Ultrasonogram is difficult to visualize the tumor after 1 st coagulation – hyperechoeic microbubble cloud R Poon et la, Annals of Surgery 2000

Diameter (Size) Large tumors have irregular borders and present satellite lesions Livraghi T et la, Radiology 2000 • If the coagulation is restricted to the main tumor without safety margin, spiky irregular extensions and satellites will be left untreated.

Effect of Tumor Size on Outcome of RF Ablation Tumors 3. 1 -5. 0 cm 100% Necrosis 49(61%) <100% Necrosis 31(39%) >5 cm 11(24%) 35(76%) p value. 001 Livraghi T et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000; 214: 761– 768.

Diameter (Size) Conclusion • There is no consensus for the optimal size for RFA • Smaller tumor size ( < 3 cm diameter ), the better the outcome, the lesser the local recurrance rate • Due the advancing technology, future electrode may tackle with larger tumor

Approach • Surgical (open / laparoscopic) Vs Percutaneous • Absence of RCT • No consensus

Surgical (open / laparoscopic) Vs Percutaneous • From Steven A. Curley et la, complete ablations in the 65 HCCs treated during laparotomy or laparoscopy, however, 7. 1% (6/84) incidence of incomplete RFA in the HCCs treated percutaneously. • From Rhim H et al, incomplete tumor destruction has been reported in up to 18% of liver cancers treated percutaneously with RFA

Surgical (open / laparoscopic) Vs Percutaneous • One disadvantage to RFA is the difficulty in determine accurately the exact area that has been coagulated • Intraoperative or laparoscopic ultrasonography provides better resolution of the tumor and RFA treatment compared with transabdominal ultrasonography for percutaneous treatment Steven A. Curley et la, Annals of Surgery 2000

Surgical (open / laparoscopic) Vs Percutaneous • Better tumor visualization compared with external ultrasound especially of tumors located in the superior right lobe of the liver • ~30% increase in tumor detection rate by intraoperative ultrasound during laparoscopy or laparotomy compared with preoperative imaging Siperstein T et la, Annals of Surgical Oncology 2002 • Accurate tumor staging K K-C Ng et la, Journal of Gastro-Hepatology 2003

Surgical (open / laparoscopic) Vs Percutaneous • Easy access to tumors located in the superior right lobe of the liver • Improved visibility will lead to a more correct insertion of the electrodes and an increased chance of complete covering of the tumor, including its irregular margins, satellites, and a 1 cm safety margin • Mobilization of the liver allows larger degree of freedom for inserting the electrodes under an optimal angle Rossi S et la, AJR AM J Roent-genol. 1996

Surgical (open / laparoscopic) Vs Percutaneous • Laparoscopic approach, pneumoperitoneum and the upward movement of the diaphragm, liver movement is minimal, facilitating precise electrode placement. Siperstein A et la, Surgical Endoscopy 2002 • Surgical route, allows multiple parallel reinsertions of the electrode when overlapping coagulations are necessary Rossi S et la, AJR AM J Roent-genol. 1996

Surgical (open / laparoscopic) Vs Percutaneous • Intraoperative RFA allows the use of Pringle maneuver to minimize the “heat sink” effect of the hepatic vessels Mulier S et la, Eur J Surgical Oncology 2003 • During laparoscopy, a 12 -mm Hg pneumoperitoneum by itself causes a 40% decrease of portal vein flow Smith MK et la, Surgical Endoscopy 2004

A 5 -cm hepatocellular carcinoma at the dome of the liver (A, arrow) treated by intraoperative radiofrequency ablation using a clustered probe (B). R Poon et la, Annals of Surgery 2002

Intraoperative ultrasound provides guidance to positioning of the probe (C, arrow shows the tip of the probe) in the tumor before starting radiofrequency ablation, but the exact margin of ablation is obscured by hyperechoic shadow resulting from thermal changes in the tissue after starting the ablation (D, arrows). R Poon et la, Annals of Surgery 2002

Surgical (open / laparoscopic) Vs Percutaneous • Intended safety margin of 1 cm, was used much less in the percutaneous approach than in the surgical approach • Subcapsular tumors are often undertreated by a percutaneous approach because of fear of burning adjacent organs, diaphragm, or the abdominal wall R Poon et la, Annals of Surgery 2002

Surgical (open / laparoscopic) Vs Percutaneous tumor Intentional Margin According to Approach 10 mm Ablation zone No. of No 0. 5 cm 1 cm p Cases Margin Percutaneous 3046 88. 4% (2692) 5. 4% (165) 6. 2% (189) Surgical 28. 8% (360) 13. 6% (170) 57. 55% <0. 001 (718) 1248 <0. 001

Surgical (open / laparoscopic) Vs Percutaneous Conclusion • Laparoscopic or open approach is recommended in patients with a high risk of bleeding from severe coagulopathy, large HCCs (5 cm), superficial nodules adjacent to other visceral organs at risk of thermal injury, or deeply located lesions not accessible to percutaneous puncture R Poon et la, Annals of Surgery 2002

Surgical (open / laparoscopic) Vs Percutaneous • The percutaneous route remains valuable for certain indications: For patients that are too fragile to undergo laparoscopy or laparotomy. Tumors that are invisible on ultrasound imaging can be treated by a CT- or MRIguided percutaneous procedure. May be performed as a day procedure

Surgical (open / laparoscopic) Vs Percutaneous Local Recurrence Rate According to Size and Approach Percuteneous (%) Laparoscopy/ Laparotomy (%) <3 cm 16. 0 3. 6 3 -5 cm 25. 9 21. 7 >5 cm 60. 0 50. 0

Conclusion • Surgery remain the gold standard of treating liver tumor • RFA is superior option in treating unresectable primary and secondary • Surgical approach have less local recurrance rate and better outcome when compared with percutaneous route • Small size tumor have better outcome, however, advance technology may overcome this problem in future

RFA Vs Cryoablation • Local recurrence rate: • 2. 2% Vs 13. 6% • Treatment mortality: • 0% Vs 2% • Complication rate: • 3. 3% Vs 40% Pearson AS et al. Am. J. Surg. 1999

RFA Vs Microwave Coagulation Therapy • Complete ablation: • 91% Vs 85% • Local recurrence • 4%Vs 17% Lencioni et al. Radiology 1999

RFA Vs PEI • Complete necrosis : • RFA Vs PEI – 90% Vs 80% • Treatment section: • Mean 1. 2 Vs 4. 8 sessions • Complication rate: • 12% Vs 0% Livraghi T et al. Radiology 1999

RFA Vs TACE • Complete control of tumor growth: • 50% Vs 30% • Mortality: • 0% Vs 4% Livraghi et al. Radiology 2002

RFA Vs Resection • Recurrence • 53% Vs 30% • Resection recurrence – distant recurrence • RFA recurrence – local recurrence Montorsi M et la, The Society for Surgery of the Alimentary Tract 2005 • Resection is more effective, in terms of overall and disease-free survival, in Child’s A patient with a single tumour >3 cm Vivarelli M et la, Annals of Surgery 2004

RFA – Bridge therapy • • • Retrospective study 14 cirrhotic patients with small HCC ( 3. 5 cm) RFA prior to transplanatation Median follow-up: 16 months Histology : – complete necrosis: 71% – incomplete necrosis: 29% – tumour satellites < 1 cm from main tumour: 57% • No complication/ death/ recurrence