microwave ablation versus hepatic resection in managment of hcc by dr mohammed hussien
TRANSCRIPT
Microwave Ablation versus Hepatic Resection in
Management of Hepatocellular Carcinoma
(Short Term Evaluation).
Thesis submitted for fulfillment of MD Degree in Tropical Medicine and Gastroenterology
Submitted By
Mohammed Hussien Ahmed Assistant Lecturer of Hepatogastroentology and infectious disease
department
Faculty of Medicine -Kafrelsheikh University
Supervised by
Prof. Osman Abdel -Hameed OsmanProfessor of Tropical medicine and Gastroenterology Assiut University
Prof. Ehab Fawzy Abdou MoustafaProfessor of Tropical medicine and Gastroenterology Assiut University
Ass.Prof Mohamed Mahmoud EL –KassasAssistant professor of Tropical Medicine, Faculty of Medicine Helwan University
DR. Ahmed Mohammed AliAssistant professor of General Surgery, Faculty of Medicine Assiut University.
Faculty of Medicine
2017
AACCKKNNOOWWLLEEDDGGEEMMEENNTT
Special thanks to Ass. Prof. Sahar Hassany for her
generous support, who happily gave me her time, effort and
experience to finish this thesis and was patient with me
throughout this work.
Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the
liver with a significant cause of morbidity and mortality and carries an
unfavorable prognosis with aggressive behavior and a high recurrence rate
(Goldman et al., 2016).
Egypt is confronted with a huge HCV infection that distinguishes it from the
rest of North Africa. It has the highest prevalence of HCV in the world and up to
90% of HCC cases in the Egyptian population were due to HCV. So, HCC
represents an important public health problem in Egypt and is the third among
male cancers (Daw et al., 2016).
Hepatic resection is the treatment of choice for early HCC in
noncirrhotic patients and offers the best curative rate with a 5-year
survival of 41%–74%. The resectability of the tumor is dependent on the
tumor size, location, underlying liver function, and whether or not the
remaining liver volume will allow for resection without increasing post
resection morbidity and mortality. However, unfortunately this option is
feasible in only 5% of the cases in Western countries (Balogh et al.,
2016).
Microwave Ablation :- is one of ablation techniques that can destroy tumors
and soft tissue by using microwave energy to create thermal coagulation and
localized tissue necrosis (Brace, 2010).
Advantage of microwave over other ablative therapy ( PEI, RFA and laser
ablation) is greater tissue penetration and larger zones of coagulative necrosis
also the heating process is active, which produces higher temperatures than the
passive heating of RFA and should allow for more complete thermal ablation in
a shorter period of time.
The higher temperatures reached with MWA (over 100° C) can overcome the
“heat sink” effect in which tissue cooling occurs from nearby blood flow in
large vessels.
To evaluate and compare microwave ablation versus
hepatic resection in the management of hepatocellular
carcinoma (HCC) by assessment of the patients pre-
intervention and post intervention in a short term follow
up (4 weeks after the procedure).
Aim of The Study
Patients and methods
This study is a prospective study performed between December 2014
to August 2016.
The study included 40 cases who were enrolled to and assigned
to undergo either Hepatic resection or MWA
Patients who were candidates for hepatic resection were recruited from
Assuit University Hospital while those who underwent microwave
ablation were recruited from National Hepatology and Tropical Medicine
Research Institute in Cairo .
Patients with Liver cirrhosis and Hepatocellular Carcinoma that fulfilled the inclusion criteria
(n=46 )
Follow up was done for 40 cases (n=40)
Group I
Hepatic resection (n=20) .
Male(n=18) Female(n=2)
Group II
Microwave ablation (n=20)
Male(n=13)Female(n=7)
Patients not enrolled in follow up and statistical
analysis
(n=6)
4 cases missed on follow up
(were planned to undergo
Microwave ablation)
2 cases refuse to continue in the
study.
(were planned to undergo Hepatic
Resection)
Inclusion criteria: was predefined as follows:
1- Radiology proven cases of HCC.
2-Patients with HCC ≤ 5 cm and amenable for microwave
ablation or surgical resection.
3- The child score (A) and early (B) (not more than score 7).
Patient selection for microwave or hepatic resection carried out by a
multidisciplinary team included hepatobiliary surgeon.
Exclusion Criteria:
1-Patients with advanced HCC or with focal lesion not amenable for resection or
microwave ablation.
2-Patients who refused follow up and evaluation.
3- Patients with INR > 2.0 or platelet count ≤ 50 × 109/L.
4-Failure to obtain the consent.
5-Pregnant patients to avoid potential risks to the patient and/or fetus.
6-Patients with implanted electronic devices such as implantable pacemakers
that may be adversely affected by microwave power output
All individuals participated in this study were subjected to the following (before and after
intervention).
Full medical history:
Clinical examination:
Laboratory studies:
Blood samples were tested for complete blood count, liver function tests, renal
profile and international normalization ratio (INR) level.
Hepatitis Markers (HBs Ag - HCV Ab).
Serum alpha-fetoprotein.
Imaging studies:
Abdominal ultrasound
Triphasic CT examination of the abdomen. Patients with lesions, which were
showed an enhancement in the arterial phase and a washout in the venous
phase, were be included in this study. Appropriate candidates were subjected
to either microwave or hepatic resection or dynamic MRI.
Study procedures:
Microwave Ablation Technique (MWA)
Patients were treated under sedation with intravenous administration of fentanyl
and/or propofol, with oxygen mask support.
The technique in which the use of microwave energy induces an ultra-high speed,
915 MHz or 2.450 MHz (2.45 GHz), alternating electric field, which causes water
molecule rotation and the creation of heat. This results in thermal coagulation and
localized tissue necrosis.
In MWA, we use a single microwave antenna connected to a generator are
inserted directly into the tumor or tissue to be ablated; energy from the antennas
generates friction and heat.
The size and the shape of the hyperechoic zone caused by gas microbubbles
appearing in the ablated zone during MWA procedure were monitored by US to
assess the completeness of therapy.
Treatment was stopped when the entire target was completely hyperechoic and
the determined time and power according to the size of the lesion reached.
Hepatic resection
Hepatic resection was done on the basis of the segmental anatomy of
the liver, which can be delineated using intraoperative ultrasound during
operation. The delineation of a proper transaction plane is important not
only for adequate tumor-free margin in resection of liver tumors but also
to avoid inadvertent injuries to major intrahepatic vessels or bile duct
pedicles.
Follow up after the intervention:
1-immediate follow up after the procedure---Hemodynamics of patients.
2- 4 weeks after the initiation of therapy---for Evolution of HCC and child score.
Reassessment of the patient include
1-Complete clinical examination.
2-Laboratory: A- complete blood count, liver function tests, renal profile,
international normalization ratio (INR).
B -Serum alpha-fetoprotein level.
3-Radiological evaluation: abdominal ultrasound and triphasic CT examination of
the abdomen to evaluate HCC eradication.
First, the number of participants is relatively small.
Second, the follow-up duration was short.
Third, we didn't include the survival benefit of both interventions.
Limitations:-
Strength
First, few studies have recently started to evaluate the microwave ablation as method of HCC
eradication in cirrhotic patient and compare it with other ablative methods But, its first study
in Egypt to compere Microwave ablation by hepatic resection.
Second, the Complete evaluation was done to patients with HCC before and after both
Procedure.
Third, Patient Selection was according to Multidysplinary team Following the same scoring
systems ( WHO performance status, child score, BCLC classification).
Table 1: Demographic data of the studied patients
Microwave (n=20) Hepatic resection (n=20) P. value
No. % No. %
Age
Mean+SD 58.1+7.7 57.8+4.3 0.880
24 - 34 years 1 5.0 0 0.0 0.323
46 - 65 years 16 80.0 19 95.0
66 - 85 years 3 15.0 1 5.0
Sex
Male 13 65.0 18 90.0 0.058
Female 7 35.0 2 10.0
Hepatitis markers
HBs Ag 1 5.0 1 5.0 1.000
HCV ab 19 95.0 19 95.0
Table 2: Child Scoring Before and After Both Microwave Abaltion and Hepatic
resection
Child before Child after P. value
Microwave (n=20)
Mean+SD 6.1+0.7 6.1+1.0
No. % No. %
5 4 20.0 6 30.0
0.7896 10 50.0 8 40.0
7 6 30.0 3 15.0
8 0 0.00 3 15.0
Hepatic resection
(n=20)
Mean+SD 5.5+0.6 7.2+1.4
5 11 55.0 3 15.0
6 8 40.0 3 15.0 0.000*
7 1 5.0 6 30.0
8 0 0.0 4 20.0
9 0 0.0 3 15.0
10 0 0.0 1 5.0
Table 3: Description of Hepatocellular Carcinoma.
Microwave Hepatic resectionP. value
No. % No. %
Size 3.15+1.15 3.82+0.84 0.043*
Site
Rt. lobe 15 75.0 16 80.00.705
Lt.lobe 5 25.0 4 20.0
Segment
II 1 5.0 0 0.0
0.705
III 3 15.0 3 15.0
IV 0 0.0 4 20.0
Ivb 1 5.0 1 5.0
V 3 15.0 4 20.0
VI 5 25.0 4 20.0
VII 3 15.0 2 10.0
VIII 4 20.0 2 10.0
C.T Criteria of HCC
Atypical 3 15.0 5 25.00.526
Typical 17 85.0 15 75.0
Table 4: Comparison between Blood picture Values in the studied patient underwent both microwave and Hepatic resection.
Microwave Hepatic resection
Before AfterP. value
Before After
P. value
WBC
4.88+1.56 5.16+1.51
0.147
6.63+2.91 12.71+9.03
0.005**
RBC
4.09+0.59 4.35+0.45
0.271
5.29+1.99 4.98+4.34
0.003**
HB
11.67+1.89 12.44+1.4
0.058
14.31+1.21 11.81+1.72
0.000**
MCV84.41+9.31 85+7.84
0.43389.05+9.16 91.35+6.94
0.126
PLT118.8+28.79 125.05+44.46
0.136158.75+71.9 159.1+67.32
0.779
Table 5: Comparison between Liver Function Values in the Studied Patient underwent both Microwave and Hepatic resection.
Microwave Hepatic resection
Before After P. value Before After P. value
Total BIL1.29+0.56
mg/dl
1.13+0.48
mg/dl0.110
1.1+0.7
mg/dl
2.05+3.25
mg/dl0.131
Direct BIL 0.57+0.41
mg/dl
0.52+0.37
mg/dl0.437
0.5+0.32
mg/dl
1.41+2.96
mg/dl0.014*
Total Protein 67.33+4.41
gm/l
57.13+26.67
gm/l
0.896 70.75+11.98
gm/l
58.48+15.25
gm/l
0.030*
Albumin3.33+0.49
gm/dl
3.34+0.63
gm/dl0.837
3.68+0.41
gm/dl
2.83+0.75
gm/dl0.033*
SGPT45.59+23.16
IU/L
63.74+34.87
IU/L0.073
57.58+33.44
IU/L
169.81+303.69
IU/L0.191
SGOT50.7+29.86
IU/L
70.9+37.07
IU/L0.042*
68.67+58.42
IU/L
116.01+162.99
IU/L0.422
GGT85.5+91.22
IU/L
121+124.45
IU/L0.180
225.33+138.01
IU/L
133.36+86.05
IU/L0.182
ALP 138.8+53.2
265.6+129.4
3 0.017* 103.08+40.41 112.82+62.29 0.754
Table 6 : Complication Post Microwave Ablation and Hepatic Resection.
Microwave Hepatic resectionP. value
No. % No. %
Complications
Recurrence 0 0.0 1 5.0
0.057
Residual activity 2 10.0 0 0.0
Appearance of new lesion 5 25.0 1 5.0
Hepatic encephalopathy 0 0.0 2 10.0
Pleural effusion 3 15.0 2 10.0
Ascites 4 20.0 10 50.0
Skin laceration 1 5.0 0 0.0
Figure 1 : Variation in level of Albumin after Both Microwave and Hepatic Resection in Comparison to Pre intervention level.
afterbefore
Serum Albumin
3.3413.329
2.828
3.6765
Microwave
Hepatic resection
Figure 2 : Changes in Prothrombin Concentration after Both Microwave and Hepatic Resection in Comparison to Pre intervention level.
Microwave
Hepatic resection
58.0
60.0
62.0
64.0
66.0
68.0
70.0
72.0
74.0
76.0
Prothrombine Concentration before
Prothrombine Concentration After
Microwave
Hepatic resection
Fig 3: Changes in the level of alpha fetoprotinebefore and after intervention
Microwave
Hepatic resection
0
50
100
150
200
250
afterbefore
Serum alpha fetoprotine
130.8405
217.5545
10.9458
172.7347
Hepatic resection
Conclusions:
Hepatic resection is superior to microwave ablation in hepatocellular
carcinoma eradication as no residual activity but, residual activity about
10% in patient underwent microwave ablation.
Appearance of new hepatocellular carcinoma in follow up is more
common in microwave ablation (25%) than with hepatic resection (5%).
Conclusions: cont
Child score was more affected in patient who underwent hepatic resection than
those who underwent microwave ablation.
Microwave had a shorter intervention time, less blood loss, and a shorter hospital
stay than hepatic resection so, should be considered as the first choice for the
treatment for very early HCCs in cirrhotic patients as it presents an efficacious and
economic option.
Hepatic Encephalopathy and Ascites are usually common complication post hepatic
resection due to decompensation which may affect the survival.
Recommendations
• - Multidisciplinary team is highly required for patient with HCC for
appropriate choice of treatment with measurement of risk benefit ratio for
every case.
• Patient counseling before any intervention with detailed description of the
maneuver and its benefit and risks is highly recommended.
• Microwave ablation as Locoregional treatment for HCC has good ablation
Power and could be considered as effective as hepatic resection especially
in patient with small HCC.
Recommendation cont.
• -Hepatic resection usually followed by postoperative hepatic
decompensation so, good selection of patient should be considered before
hepatic resection.
• -Microwave Ablation is considered as a simple and rapid ablative measure
with less post intervention complication in comparison to hepatic
resection.
• Hepatic resection considered superior to microwave ablation in HCC
eradication with less possibility for residual activity or appearance of new
lesion.
• Post hepatic resection care in intensive care unit highly recommended to
decrease possibility of post resection complications.
• Post microwave ablation and hepatic resection follow up after one
month is recommended to assure complete eradication of HCC.
• Long term follow up is highly recommended to evaluate the efficacy and survival
of both techniques.
Recommendation cont.
Table 4: Laboratory investigation before both microwave ablation and hepatic Resection.
. Before
Microwave Hepatic resection P. value
WBC 4.88+1.56 6.63+2.91 0.007**
RBC 4.09+0.59 5.25+1.95 0.000**
HB 11.67+1.89 14.31+1.21 0.000**
MCV 84.95+9.38 89.05+9.16 0.134
PLT 118.8+28.79 158.75+71.9 0.068
Total BIL 1.29+0.56 1.1+0.7 0.134
Direct BIL 0.57+0.41 0.5+0.32 0.820
Total Protein 67.33+4.41 70.75+11.98 0.076
Albumin 3.33+0.49 3.68+0.41 0.030*
SGPT 45.59+23.16 57.58+33.44 0.265
SGOT 50.7+29.86 68.67+58.42 0.327
GGT85.5+66.62 182.86+122.28 0.042*
ALP 143.33+52.72 108.89+41.9 0.016*
Time 17.91+14.97 14.27+2.26 0.221
Concentration 73.55+14.88 72.84+17.85 0.862
INR 1.27+0.16 1.22+0.19 0.201
Urea 3+0.71 4.49+1.43 0.001**
Creatinine .87+.23 .97+.30 0.371
Serum FP 217.55+450.79 172.73+261.92 0.602
Table 5: Laboratory investigation after both microwave ablation and hepatic resection.
After
Microwave Hepatic resection P. value
WBC 5.16+1.51 12.71+9.03 0.000**
RBC 4.35+0.45 4.98+4.34 0.113
HB 12.44+1.4 11.81+1.72 0.253
MCV 85+7.84 91.35+6.94 0.016*
PLT 125.05+44.46 159.1+67.32 0.157
Total BIL 1.13+0.48 2.05+3.25 1.000
Direct BIL 0.52+0.37 1.41+2.96 0.134
Total Protein 57.13+26.67 58.48+15.25 0.314
Albumin 3.34+0.63 2.83+0.75 0.033*
SGPT 63.74+34.87 169.81+303.69 0.904
SGOT 70.9+37.07 116.01+162.99 0.640
GGT 121+124.45 133.36+86.05 0.923
ALP 265.6+129.43 112.82+62.29 0.000**
Time 14.49+2.48 15.68+4.06 0.414
concentration 74.79+16.15 63.7+16.47 0.056
INR 1.25+0.23 1.35+0.34 0.192
Urea 3.28+1.42 4.33+2.12 0.030*
Creatinine 0.91+ 0.25 1.06+0.63 0.892
Serum FP 130.84+268.84 10.95+6.73 0.035*