1. RFA Experience In Nicosia General Hospital (CLM) P. Hadjicostas,,M.Dietis, C. Antreou / Surgical Department

2. Liver Tumors (primary or metastatic) Resection: is the gold standard of treatment. BUT in only 9 – 27% in patients with HCC & 20% inpatients with Liver CRM’s.  The 2 nd cause of death  If untreated (6-18 months live)  70% recurence after Resection  50% recurence within the liver  The worsen development in a cancer patient

3. History:Thermal Cancer Therapy Hot oil treatment of tumors described in 5000 y.o Egyptian papyrus Tumor´´ cautery´´ used for numerous cancer types over past 400 years Electrocautery destruction of superficial and endothelial malignancies over past 120 years More recently, cryoablation, laser photocoagulation, radiofrequency ablation and microwave coagulation

4. Local Ablative therapy (unresectable Liver tumors) A. Percutaneous injection 1. Chemicals - Alcohol (P.E.I.T) - Acetic acid 2. Radio active isotopes 3. Hyperthermic agents - Saline - Water 4. Chemotherapeutic agents - Chemoembolization B. Percutaneous application of an energy source 1. Thermal ablation - Radiofrequency - Microwave (P.M.C.T) - Interstitial laser photocagulation 2. Cryoablation

5. “ A good local ablative method should be locally effective to the cancer, non-toxic to nontumorous liver, and easy and safe to administer”. “The endpoint of local ablation is complete tumor necrosis with a margin of tissue” Lau et al 2002

6. RFA is a new promising treatment for Liver tumors. “to heat and thereby kill tumor cells and normal surrounding parenchyma” Strasberg et al 2003 “thermal tissue destruction” Curley et al 2000 “…… What is not cured by knife is cured by fire” Heppocrates

7. The Cool-Tip™RF System Slide 7Ε

8. Useful Tips 2. Always place the end of the Cool Tip needle to the distant end of Lesion. Slide 5Δ

9. Cool-tip ™ Radio Frequency Ablation

10. Tissue response to Heat 100° C 50° C Collagen denatures Thermal injury starts 60° C 70° C 80° C 90° C RF Ablation Technology Cool Tip Minimum Target Temp

11. RFA By Surgeon and in the OR Friendly environment Anesthesiologist is present Continuous monitoring (BP, Pulse, ECG, Sat O 2 ) Arrhythmia Hyperthermia/Sweating/ Discomfort More analgesia Maybe gen. anesthesia Higher safety

12. Indications RFA

13. RFA should be reserved for pts. Unresected metastases/ Downsizing Unable to tolerate lapatatomy for resection BUT could challenged hepatectomy New hepatic metastasis following liver resection( Elias 2002, Joosten 2007) Limited central disease/hemihepatectomy( Evrard 2006,Abitabile 2007,Bremers 2007) Small metastasis (Evrard 2007,Wagman 2007) Solidary metastasis ( Oshowo 2003)

14. RFA - percutaneously (65-75%) -Open Surgery -Laparoscopic (Treatment approach individualized in any given patient)

20. If not resectable is ablated.

21. Post – RFA

22. Early Studies: Local Recurrence Mean (F/U) (months) TumorTypeLocal Recurrence Rossi, 199622HCCPerc4.8% Solbiati, 199718MetsPerc33% Curley, 199915HCC/MetsPerc/Open1.8% Siperstein, 200014HCC/MetsLap12% Da Baere, 200014MetsPerc/Open9% Bowles, 200115HCC/MetsPerc/Lap/Open9% Solbiati, 200128MetsPerc39% Bleicher, 200313MetsPerc/lap/Open12% Abdalla, 200421MetsOpen9% Berber, 200529MetsLap46%

23. Cost-effectiveness of RFA vs Hepatic Resection TreatmentFU testing and treatment (mo) #Mets treatedCost/pt RFA12624,800 Resection12661,000 Gazelle et al: radiology;2004:729 State Transition Decision Model – Disease Extent, Post Treatment Imaging

24. Morbitity of RFA Vs Resection NoNo Morbidity % RFAResectionRFAResection Lu, 20065154811 Chen, 20067190455 Lupo, 200660421017 Guglielmi, 2008109911036 Huang, 2010115 428 Randomized Control Trials 7%30%

25. Surgical Resection vs RFA (PCT) 180 Patients (HCC < 5cm) Annals of Surgery:Chen MS 243:March, 2006 71 (RFA)69 (Resection) DFSOSDFSOS 1 year86%96%86%93% 2 year69%82%77%82% 3 year64%71%69%73% 4 year46%68%51%64% No Difference

26. Ablation Vs Resection

27. Tension: Resection VS Ablation Open Resection Ablation Long Term Risk of Recurrence Short Term Risk of QOL impairment

28. Score Sheet Short term QOL SafetyAccess / Anatomy PrognosticRecurrenceSurvival Ablation Resection

29. N.G.H. RFA Experience FROM SEPTEMBER 2003 UNTIL TODAY RFARFA Number of Patients 74 HCC Liver Metastasis Pelvic Tumor Pancreas Ca Liver Trauma CLRBreast Ca Gastric Ca SarcRenal Ca Neuro endoc 1036242112151

30. Age (mean) GenderMethod No Tumors Tumor Size ComplicationLROS MFOP 68.1y241211251 – 61– 9cm5.6%8.3%32.2m median N.G.H. RFA CLM Table RFA performed36 patients Metastatic lesions77 Metastatic lesion / patient1 – 5 Metastatic lesion size1 – 9cm

31. Patient pre-operative evaluation 1.Patient pre-operative evaluation from specialized team. (General surgeon, Oncologist, Pathologist, Radiologist) 2.Unresectional patients. Fits ablation criteria. 3.CT scan, occasional MRI. 4.Technical planning. (individualized) 5.Patient briefing, concept form.

32. Technical Method 1.Patient re-evaluation. 2.Operation theatre. 3.Presence of anesthesiologist, radiologist. 4.US guidance. 5.Single probe, triple probe, overlapping technique.

33. Follow up 1.Patient follow up evaluation from specialized team. 2.Ablation CT scan re-evaluation. (1-6 months)

34. Complication of RFAPatients Hemorrhage Abscess Biliary Leakage / Stricture Pleural Effusion Damage to vascular Systems Pneumothorax Liver Failure Ascites Fever 2 Colon Perforation Myocardial Infraction TOTAL 2 ( 5.6%) RFA Complications

35. Age (mean) GenderMethod No Tumors Tumor Size ComplicationLROS MFOP 68.1y241211251 – 61– 9cm5.6%8.3%32.2m median N.G.H. RFA CLM Table Minor Complications2 / 36 (5.6%) Local Recurrence3 / 36 (8.3%) Survival (months)1 – 72m (32m)

36. AgeGenderMethodNo TumorsTumor Size ≤ 68y> 68yMFOP=1>1≤3cm>3cm Patient19172412112521151719 LR1221032112 OS (Mean) p= 35m29.3m33.4m30.2m35.1m29m37.6m25m38m27m 0.2810.5610.2790.010.05 N.G.H. RFA CLM Table

37. 92% / 12m 55% / 24m 39% / 36m RFA N.G.H. RFA Survival Chart

38. 93% / 12m 59% / 24m 42% / 36m 92% / 12m 55% / 24m 39% / 36m Abdalla et al, Annals of Surgery 2004

39. N.G.H. RFA Survival Chart Solitary tumor >1 tumor 52% / 36m 20% / 36m p=0.01

40. 68% / 36m 43% / 36m 52% / 36m 20% / 36m Abdalla et al, Annals of Surgery 2004

41. ≤3cm >3cm 65% / 36m 16% / 36m N.G.H. RFA Survival Chart p=0.05

42. Berber et al, Journal of Clinical Oncology 2005 50% / 36m 65% / 36m ≤3cm 3 – 5cm <5cm

43. ArticleYearMethodNo PatientsNo Tumors Tumor Size LROS Jakobs2006P682.72.3cmNR3y, 68% Chen2005P96NR4.1cm10.5%3y, 25.1% Gillams2004P1674.13.9cm14%3y, 40% Oshowo2003P25NR3cmNR3y, 43% Schindera2006P14NR1.8cm14.8%3y, 60% White2004P3013cm16%22m median Basdanis2004O18NR5.6cm11%NR Chow2006O,L,P2912.4cm20.5%6m median Chhabra2006O,P14NR3.1cm7%16m median Marchi2006O,L,P1003.53cm6.7%3y, 42% Abitabile2007O,L,P473.12cm1.6%3y, 57% Recurrence and Survival review table

44. Marginal Recurrence S/P-Hepatic Resection Not zero but 1.2- 10.4% ( Mulier 2008)

45. GroupMethodNo PatientsNo Tumors Tumor Size LROS MD Anderson Texas O5712.5cm9%3y, 37% John Wayne O,L,P743.33.6cm31% >3cm 35.5% Cleveland Clinic L1353.23.8cm46%3y, 30% Gustav Roussy P,L6321.3cm7.1%3y, 46% Italian Group P1171.52.8cm39%3y, 46% NGHO,P361.94cm8.3%32m median Recurrence and Survival review table

46. Conclusion 1.Minimally invasive method. Low complications. 2.Well tolerated. 3.Low cost effective. 4.Easily repeatable. 5.Local recurrence?