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the European Association for the Study of the Liver (EASL) technique suffered from the need for multiple treatment
guidelines. Survival by stage was assessed. Univariate sessions, the uncertainty of the ablation zone, and
and multivariate analyzes were performed. Toxicities a high local progression rate of 17-38%. [42,43] Several
included fatigue (57%), pain (23%), nausea and vomiting randomized controlled trials compared PEI vs. RFA in the
(20%), and 19% exhibited grade 3/4 bilirubin toxicity. The treatment of small HCC. [44-46] These trials demonstrated
30-day mortality rate was 3%. Response rates were 42% an approximately 20% advantage for RFA vs. PEI in overall
and 57% based on WHO and EASL criteria, respectively. survival at 3-4 years, mainly as a result of a much lower
The overall time to progression was 7.9 months. Survival incidence of local tumor recurrence in the RFA group.
times differed between patients with Child-Pugh class A In addition, approximately threefold fewer treatment
and B disease (class A, 17.2 months; class B, 7.7 months; sessions were required for RFA compared to PEI. Two
P = 0.002). Patients with Child-Pugh class B disease recent meta-analyzes comparing RFA vs. PEI echoed these
who had portal venous thrombosis survived 5.6 months sentiments, declaring RFA superior to PEI in the treatment
(95% confidence interval, 4.5-6.7). Baseline age, sex, of small HCC. [47,48] PEI maintains the advantage of allowing
performance status, the presence of portal hypertension, treatment of tumors near sensitive organs and tissues
tumor distribution, levels of bilirubin, albumin, and alpha- and avoids the problem of the “heat-sink” effect adjacent
fetoprotein, and WHO/EASL response rate were important to vessels. The applicability of PEI in other situations is
predictors of survival. While Y-90 has anti-tumor activity, limited.
controlled data comparing TARE with TACE is lacking, and
its impact on survival is not well established. Percutaneous acetic acid injection
[49]
Ohnishi et al. reported percutaneous acetic acid
Intra-arterial injection of radiolabeled lipiodol injection (PAAI) in 1994. Acetic acid is a noxious chemical
Lipiodol is a mixture of iodized ethyl esters from the characterized by better tissue diffusion than ethanol.
fatty acids of poppyseed oil, containing 37% iodine by Usually, it is proposed as an alternative to ethanol, to
weight. It is selectively taken up by hepatic tumors when decrease the number of sessions. Sequential therapy
[50]
administered via the hepatic artery, and it is retained by HCC with TACE and PAAI is superior to repeated PAAI alone
for many weeks, even up to a year, while it is cleared from for patients with 3-5 cm HCC. Acetic acid has a higher
[51]
normal or cirrhotic liver within 4 weeks. When injected diffusion capacity; it is easily available and cheap. A smaller
into the hepatic artery, it travels the peribiliary plexus to volume of acetic acid and fewer treatment sessions can
the portal veins, resulting in a dual embolization. Early achieve the same degree of tumor ablation as ethanol.
[37]
[50]
in the course of exploiting lipiodol’s unique features, the In addition, PAAI, unlike PEI, helps in infiltrating the tumor
addition of a radionuclide to this substance gave a new septae and capsule. There is not much literature about the
dimension to its clinical use. So far, most clinical research efficacy of PAAI in ablating HCC. [49-51] The procedure of
has been performed with 131I-labeled lipiodol, which is PAAI is similar to PEI. This amount is injected in multiple
commercially available as Lipiocis (CIS Bio International, sessions (1-2 mL of acetic acid per tumor per session per
Gif sur Yvette, France). 131I-lipiodol has been used for the week) using a 23 G spinal/Chiba needle. The response to
[38]
palliative, adjuvant, or neoadjuvant treatment of HCC. the treatment is assessed by contrast enhanced computed
Although most studies have failed to demonstrate any
survival benefits, it seems that 131I-lipiodol is much better tomography (CECT) of the liver after 4 weeks. CECT
tolerated (fewer side effects) than chemoembolization. characterizes the liver lesion better, and the residual or
recurrent disease can be seen well. The ideal lesion for PEI
131I-lipiodol has the theoretical advantage that there is
no particle embolization at the end of the procedure and is small HCC < 3 cm in size. The local tumor recurrence
that portal venous thrombosis is thus not a relative or rate is 51% at 1 year and 74% at 3 years. The survival rate
[50]
absolute contraindication. at 1 and 3 years is 84% and 51%, respectively. PAAI is a
safe technique, with no major complications. The rare side
PERCUTANEOUS LOCAL ABLATION THERAPIES effects include transient hemoglobinuria (but without any
renal impairment), fever, right upper abdominal pain and
Chemical ablative therapies with larger doses, segmental infarction, and metabolic
Percutaneous ethanol injection acidosis can occur. [49-51] Transient hemoglobinuria can occur
One of the first methods devised to ablate liver tumors immediately after tumor ablation, even after using small
involved percutaneous ethanol injection (PEI). Several volumes (5-10 mL) of 50% acetic acid and it usually clears
non-randomized trials in the 1990s confirmed that PEI with a few urinary voids. Precautionary alkalinization
could safely achieve complete necrosis of small HCCs, [39- of urine by administering intravenous fluids containing
41] with 5-year survival rates of 32-38%. However, the bicarbonates can be helpful.

4 Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016