Joint Hospital Surgical Grand Round Radiofrequency Ablation of Hepatic Tumor Factors affect local recurrence rate Dr K Y Yuen United Christian Hospital I by 9X1VW9K


									    Joint Hospital Surgical
         Grand Round
Radiofrequency Ablation of Hepatic Tumor
  (Factors affect local recurrence rate)

              Dr K Y Yuen
        United Christian Hospital

• 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
• Surgery is the only known curative option
 for either primary or secondary hepatic

• 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
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- 500KHz) 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 50-80oC
Radio Frequency Ablation
• 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

  – 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
  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, PhD, Jacques Jamart, MD,Theo
    Ruers, PhD, Guy Marchal, PhD, 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)
  Proximity of major vessel
  Approach (surgery Vs percutaneous)
  Intentional Margin
  Vascular occlusion
  Physician’s experience
Diameter (Size)
• Current recommended tumor size <5cm
• 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
                                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 1st coagulation – hyperechoeic
  microbubble cloud
                         R Poon et la, Annals of Surgery 2000
Diameter (Size)
Large tumors have irregular
 borders and present satellite
                           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
Effect of Tumor Size on
Outcome of RF Ablation

Tumors       100%              <100%               p value
             Necrosis          Necrosis
3.1-5.0 cm   49(61%)           31(39%)             .001

>5cm         11(24%)           35(76%)

               Livraghi T et al. Hepatocellular carcinoma:
               radio-frequency ablation of medium and large lesions.
               Radiology 2000; 214:761–768.
Diameter (Size)

• 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

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

• 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

• 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
• 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
                Steven A. Curley et la, Annals of Surgery 2000
Surgical (open / laparoscopic) Vs
• 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
• 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
• 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
• 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
   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
• 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
                                                        tumor        10 mm

  Intentional Margin According to Approach
                                                     Ablation zone

Approach       No. of No    0.5 cm 1 cm   p
               Cases Margin Margin Margin

Percutaneous 3046      88.4%    5.4%         6.2%        <0.001
                       (2692)   (165)        (189)

Surgical       1248    28.8%    13.6%        57.55% <0.001
                       (360)    (170)        (718)
Surgical (open / laparoscopic) Vs
• 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
                  R Poon et la, Annals of Surgery 2002
Surgical (open / laparoscopic) Vs
• 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 MRI-
    guided percutaneous procedure.
  May be performed as a day procedure
 Surgical (open / laparoscopic) Vs
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
• 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

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

• 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

• 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 >3cm
                 Vivarelli M et la, Annals of Surgery 2004
RFA – Bridge therapy
•   Retrospective study
•   14 cirrhotic patients with small HCC ( 3.5cm)
•   RFA prior to transplanatation
•   Median follow-up: 16 months
•   Histology :
    – complete necrosis: 71%
    – incomplete necrosis: 29%
    – tumour satellites < 1cm from main tumour: 57%
• No complication/ death/ recurrence

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