This document discusses various minimally invasive interventions for liver tumors. It describes procedures such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation, cryoablation, ethanol ablation, and drug-eluting bead chemoembolization. For each procedure, it covers the mechanism of action, patient selection criteria, technical details, imaging guidance and follow up. It emphasizes that these minimally invasive therapies can be used to treat primary and secondary liver malignancies when surgery is not possible or as an adjunct to other treatments, with the aim of improving patient prognosis.

1. Interventions In
Liver Tumors
Dr Apurv Raj

2. • Liver malignanciesis the fifth most frequently found
primary malignant tumor in the world.
• Hepatic surgery and liver transplantation are considered
optimal for the curative treatment of HCC.
• However, less than 20% of malignancies can be treated
surgically because of multifocal diseases, proximity of the
tumor to key vascular or biliary strictures precluding a
margin-negative resection and inadequate functional
hepatic reserve with cirrhosis.

3. Criteria for surgery
1. Usually, patients with single small HCC (≤ 5 cm)
2. Up to three lesions ≤ 3 cm are indicated for surgery.
• Even when surgery is precluded, interventional treatments can
be used to improve the prognosis of the patients.
• Such therapies, which rely on imaging guidance for tumor
targeting and response assessment, include various catheter-
based and percutaneous ablative techniques.
• These minimally invasive therapies have been used mainly for
palliation but have also increasingly been used with curative
intent.

4. BCLC staging-
• Barcelona clinic liver cancer (BCLC) staging uses a set of
criteria to guide the management of patients
with hepatocellular carcinoma (HCC).
• The classification takes the following variables into account 1,2:
• performance status (PS)
• Child-Pugh score
• radiologic tumor extent
• tumor size
• multiple tumors
• vascular invasion
• nodal spread and extrahepatic metastases

5. Performance Status-
• Grade 0: fully active, able to carry on all pre-disease
performance without restriction
• Grade 1: restricted in physically strenuous activity otherwise
normal.
• Grade 2: ambulatory and capable of all self-care but unable to
carry out any work activities
• Grade 3: capable of only limited self-care, confined to bed or
chair more than 50% of waking hours
• Grade 4: completely disabled, cannot carry on any self-care,
totally confined to bed or chair
• Grade 5: dead

8. Intra-arterial catheter-based
therapies
• 1. Embolotherapy/chemotherapy-based therapies (TACE)-
• Embolization agents, like gelatin, may be administered
together with selective intra-arterial chemotherapy mixed
with lipiodol (iodized oil). Doxorubicin, mitomycin, and
cisplatin are commonly used anti-tumor drugs.
• Cytotoxic drugs achieve higher intra-tumoral concentrations
when injected in the hepatic artery and are liberated
progressively inside the tumor.
• Lipiodol, which destroys capillary beds and induces extensive
necrosis.

9. • Complications related to aberrant arterial embolization,
such as stenosis of the biliary tract, acute ischaemic
cholecystitis , or gastroduodenal ulcerations have also
been reported

10. Indications for TACE-
• Hepatocellular carcinoma
• Metastatic lesions eg-colorectal carcinoma
• Cholangiocarcinoma
• As palliative treatment for unresectable carcinomas
• Sometimes may be performed prior to radiofrequency
ablation.

11. Contraindications for TACE-
• Extensive hepatic involvement
• Extra-hepatic metastasis
• Uncorrectable coagulopathy
• Significant arterio-venous shunting through the liver lesions.
• Hepatic or renal failure

12. Procedure-
• Catherization is done through trans-femoral route.
• Selective cannulization of hepatic artery branch supplying the
tumor is identified and catheter is passed into it.
• Catheter tip is placed as close as possible to the tumor.
• Chemoembolization agents are passed through this catheter.
• The amount of emulsion to be injected is decided during the
procedure. When the lesion shows complete coverage with
the lipidol or there is reflux of emulsion through normal
branches further injection is stopped.
• Intra-arterial lidocaine is also given to reduce the pain.

13. Follow Up-
• Ct is the preferential modality for follow up (after 5 to 16
weeks).
• The enhancement pattern of mass and accumulation product
of iodized oil are observed to evaluate the response.
• Residual tumor appears as enhancing mass.
• Four types of respoinse-

14. Four patterns of Response-
• 1) Complete
• 2) Residual
• 3) Recurrence
• 4) Fresh Lesions

15. Chemoembolization of hepatic tumor. (a) Right hepatic arteriogram, obtained after a microcatheter has
been advanced into the right hepatic artery through a 5.5-F diagnostic catheter parked in the celiac
artery, demonstrates a hypervascular tumor in the posterior segment.
(b) CT scan obtained before chemoembolization shows a low-attenuation hepatoma (arrow) occupying
most of the posterior segment of the right hepatic lobe.
(c) Postchemoembolization CT scan demonstrates a 65% reduction in tumor volume (arrow) with dense,
persistent uptake and retention of the iodized oil. Oil retention correlates positively with tumor necrosis
and helps predict longer survival.

16. ImageshowingcompleteresponsefollowingTACE.
A)Showslargeenhancingtumor inliver.
B)Scantaken6monthafterTACEshowingaccumulationof lipidol.
Howevercontrastenhancementwasnoted.

17. C)CTscan Imageafter1year of TACE
d)Imageafter3yearsofTACE.

18. Drug-eluting bead
chemoembolization
• Drug-eluting bead (DEB)-TACE is a drug delivery system that
combines the local embolization of vasculature with the
release of chemotherapy into adjacent tissue.
• Beads are composed of biocompatible polymers such as
polyvinyl alcohol (PVA) hydrogel that have been sulfonated to
enable the binding of chemotherapy. The beads occlude
vasculature, causing embolization, and the chemotherapy is
delivered locally.

19. • DEB-TACE may also use as an adjunctive therapy for liver
resection or as a bridge to liver transplantation, as well
as before or after radiofrequency ablation (RFA).
• Like conventional TACE, DEB-TACE is considered a
palliative option for unresectable HCC.
• The current results show that DEB-TACE produces
beneficial tumor response and has exceptionally low
complication rates. Most common complication is liver
abscess.

20. Radiotherapy-based therapies
• Transarterial radioembolization (TARE) with
intra-arterial injection of yttrium-90
microspheres (Y-90).
• These spheres can safely deliver up to 150 Gy of
β radiation to induce tumor necrosis by
radiation and microscopic embolization once
they obstruct the tumor capillary bed. This
limits radiation exposure to adjacent healthy
tissue, given its half-life of 62 h and radius of
action of up to 1 cm.

21. • Patient selection requires pretreatment procedures,
including an angiogram to perform prophylactic
embolization in which variant anatomy is identified to
avoid non-target delivery of Y-90.
• Potential complications caused by non-target delivery of
Y-90 include gastrointestinal ulcerations, pancreatitis,
pneumonitis, and cholecystitis.

22. Minimal Invasive Therapy
Six existing minimally invasive techniques for the
treatment of primary and secondary malignant
hepatic tumors—
1. Radio-frequency ablation
2. Microwave ablation
3. Laser ablation
4. Cryoablation
5. Ethanol ablation
6. Chemoembolization

23. Radio-frequency Ablation:
Perspectives
• Mechanism-
• Alternating electric current operated in the range of
radiofrequency can produce a focal thermal injury in
living tissue.
• The tip of the shielded needle electrode conducts the
current, which causes local ionic agitation and
subsequent frictional heat Temperatures in excess of
100°C produce coagulative necrosis.
• A 2– 5-cm spherical thermal injury can be produced with
each ablation.

24. Patient Selection and Technique
• Most investigators are limiting treatment with radio-frequency ablation to
patients with four or fewer, 5-cm or smaller, primary or secondary
malignant hepatic tumors and no extrahepatic tumor.
• Ideal tumors are smaller than 3 cm in diameter, completely surrounded by
hepatic parenchyma, 1 cm or more deep to the liver capsule, and 2 cm or
more away from large hepatic or portal veins.
• Subcapsular liver tumors can be ablated, but their treatment is usually
associated with greater procedural and post-procedural pain.
• Tumors adjacent to large blood vessels are more difficult to ablate
completely because the blood flow in the vessels cools the adjacent
tumor, thus limiting the extent of the ablation.

25. • Any of the radio-frequency devices can be used
percutaneously or intraoperatively. Percutaneous
ablation can be performed on an outpatient basis with
use of conscious sedation alone.
• Ultrasonography (US) is the primary modality for guiding
the procedure, although both computed tomography
(CT) and magnetic resonance (MR) imaging can be used.

26. • The goal of radio-frequency thermal ablation is to kill the
target tumor as well as a 5–10-mm circumferential cuff
of adjacent normal hepatic parenchyma.
• Each ablation requires exact placement of the electrode
tip in the tumor. A single ablation takes 8–20 minutes,
raises local tissue temperatures to 100 C, and produces
an approximate 2–5-cm spherical thermal injury.
• The size of each ablation is delineated sonographically by
echogenic microbubbles that are produced during the
ablation.

27. Computer-generatedimagedepictstheessential
elementsofUS-guidedpercutaneousablationof
livertumorsaswellasrepresentativepre-and
postablationCTscans.

28. Mechanism of radio-frequency ablation. (a) Schematic depicts a four-prong needle electrode in which
an alternating electric current at 460 KHz has caused ionic agitation around the electrode tip. (b)
Schematic illustrates the ionic agitation, which causes frictional heat immediately around the needle.
(c) Schematic shows how the heat caused by the agitation expands by conduction into the
surrounding tissues to form a roughly spherical thermal injury

29. CT evaluation of radio-frequency thermal ablation. (a) CT scan obtained before ablation
shows a hypervascular hepatocellular carcinoma (arrow). (b) CT scan obtained after ablation
shows that the tumor has become avascular. Note the prominent peritumoral hyperemia
around the treated tumor (arrowheads) that is caused by the ablation process.

30. Microwave Ablation
• In microwave coagulation therapy or ablation, molecular
dipoles are vibrated and rotated, resulting in thermal
coagulation of the target tissue. The basic mechanism of
heat generation in living tissue consists of rotation of
water molecules.
• The rotation follows the alternating electric field
component of the ultra-high-speed (2,450- MHz)
microwaves.
• Microwaves emitted from the distal segment of a
percutaneous probe cause the thermal coagulation of
the adjacent tissues.

31. Patient Selection and Technique
• Potential candidates for microwave ablation include
patients with inoperable tumors that cannot be
chemoembolized due to severe liver dysfunction or
hypovascularity and patients with tumors that failed
chemoembolization or alcohol ablation.
• Generally, the therapy is limited to patients with four or
fewer tumors that are each less than 5 cm in diameter.

33. • (8) Microwave ablation of swine liver. Photograph of the cut surface of
the liver shows an elliptical ablation (yellow arrowheads) around the
distal shaft (arrow) of the monopolar electrode. Note the tip of the
electrode (asterisk). (9) CT evaluation of microwave ablation performed
in a 68- year-old man with hepatocellular carcinoma who had previously
been treated with arterial chemoembolization with iodized oil. (a)
Enhanced CT scan obtained before embolization shows a hypervascular
tumor nodule (arrowheads). (b) Unenhanced CT scan obtained 7 days
after embolization shows incomplete accumulation of iodized oil in the
tumor (arrow). (c) Sonogram obtained before microwave ablation (left)
shows a 35-mm hypoechoic nodule in the anterior segment of the right
hepatic lobe (arrows). Sonogram obtained immediately after treatment
(two emissions) (right) shows a markedly echogenic region of
coagulation (arrow) that has replaced the tumor. (d) Enhanced CT scan
obtained 4 days after microwave ablation shows ablated tissue as
unenhanced areas within and around the tumor (arrows). (e) Dynamic
CT scan obtained 9 months after treatment shows that the lesion
(arrow) has decreased in size, without evidence of new tumor growth.

34. Laser Ablation-
• A reproducible thermal injury can be produced with
neodymium yttrium aluminum garnet (Nd YAG) laser.
• From a single, bare 400-mm laser fiber, light at optical or
near-infrared wavelengths will scatter within tissue and be
converted into heat. Light energy of 2.0–2.5 W will produce a
spherical volume of coagulative necrosis.

35. Patient Selection and Technique
• The indications and contraindications for laser ablation are the
same as those for radio-frequency and microwave ablation.

36. Cryoablation
• Cryoablation is a method of in situ tumor ablation in
which subfreezing temperatures are delivered through
penetrating or surface cryo-probes in which a cryogen is
circulated.
• Thermally conductive material allows cooling at the
probe tip while the shaft and delivery hoses are insulated
. Irreversible tissue destruction occurs at temperatures
below -20°C to -30°C.
• Cell death is caused by direct freezing, denaturation of
cellular proteins, cell membrane rupture, cell
dehydration, and ischemic hypoxia.
• Cryolesions as large as 6–8 cm in diameter can be
created safely.

37. US guidance of hepatic cryoablation. (a) Sonogram shows an echogenic 5-mm
cryoprobe (arrow) placed centrally within a relatively isoechoic colon metastasis
(arrowheads). (b) Sonogram obtained at the partial freeze stage (ie, at 3 minutes)
demonstrates that the ice ball (arrow) has extended to the lateral margin of the
tumor, but the anterior margin (arrowheads) is still visible. (c) Sonogram obtained at
the complete freeze stage (ie, at 8 minutes) shows the ice ball (arrow), which now
completely encompasses and extends beyond the anterior margin of the tumor,
indicating a successful ablation

38. Patient Selection and Technique
• At present, cryoablation is primarily an open surgical
technique with fewer than 10% of patients treated
laparoscopically.
• US is the most predominantly used method of guiding
the procedure. Depending on tumor size, one or two
probes are placed centrally within the lesion with the tips
of the probes touching the deep edge of the tumor.
• The cryogenic material (-196°C) is circulated through the
probes. The ice ball is visualized as an echogenic,
expanding, hemispherical rim .
• Freezing is continued until the cryolesion extends
through the tumor and into the adjacent normal tissue,
with the goal of achieving a 5–10-mm ablation margin.

39. CT evaluation of hepatic cryoablation. (a) Pretreatment CT scan shows a colorectal
metastasis (arrow) in the dome of the liver that measures 3.5 cm. (b) CT scan obtained
4 days after cryoablation shows a low-attenuation cryolesion (arrow) measuring 5 ´ 6
cm completely encompassing the tumor site. Small gas bubbles are also seen, a finding
indicative of necrosis. (c) Follow-up CT scan obtained 8 months after cryoablation
shows the residual cryolesion (arrow) markedly decreased in size as a result of healing
and fibrosis

40. Ethanol Ablation
• Within neoplastic cells, ethanol causes dehydration of
the cytoplasm and subsequent coagulation necrosis,
followed by fibrous reaction. Within neoplastic vessels,
ethanol induces necrosis of endothelial cells and platelet
aggregation, thus causing thrombosis and tissue
ischemia.

41. Photograph shows ethanol ablation equipment, which consists of a syringe, sterile 95% ethanol,
and a 20-cm-long, 21-gauge needle with a closed conical tip and three terminal holes (Hakko)

42. US guidance of ethanol ablation. (a) Pretreatment sonogram shows a 3.2-cm
hepatocellular carcinoma with the tip of the treatment needle (arrow)
visible in the tumor. (b) Sonogram obtained after injection of ethanol shows
diffuse increase in echogenicity of the tumor (arrow).

43. Patient Selection and Technique
• Ethanol ablation is generally performed in cirrhotic patients
with hepatocellular carcinoma. The treatment is ineffective for
liver metastases, and since 1995 radio-frequency ablation has
replaced ethanol ablation for treating metastatic lesions .
• Candidates for ethanol ablation must have tumors whose
volume is less than 30% of the total volume of the liver.
Contraindications include extrahepatic disease, thrombosis of
the portal vein, Child C class, prothrombin time less than 40%,
and a platelet count of less than 40,000/mm3 .

44. • Ethanol ablation is generally performed in cirrhotic
patients with hepatocellular carcinoma.
• Candidates for ethanol ablation must have tumors whose
volume is less than 30% of the total volume of the liver.
Contraindications include extrahepatic disease,
thrombosis of the portal vein, Child C class, prothrombin
time less than 40%, and a platelet count of less than
40,000/mm3 .

45. CT evaluation of ethanol ablation of hepatocellular carcinoma. (a) CT scan obtained before
ablation shows an encapsulated 7-cm hepatocellular carcinoma (arrow). (b) CT scan obtained 3
years after ethanol ablation shows that the tumor (arrow) has decreased markedly in size and
shows no contrast enhancement. The tumor was treated by a single-session injection of 60 mL of
ethanol