microwave ablation versus hepatic resection in managment of hcc by dr mohammed hussien

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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.

Microwave Ablation

MW

RF

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

Hepatocellular Carcinoma before and after Microwave Ablation

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.

Publications

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*