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العنوان
Chemoembolization of hepatocellular carcinoma with drug eluting beads /
المؤلف
Adl El Baz, Ahmed El Baz El.
هيئة الاعداد
باحث / Ahmed El Baz El Adl El Baz
مشرف / Medhat Mohamed RefaatMedhat Mohamed Refaat
مشرف / Ikram Hamed Mahmoud
مشرف / --------------------------------------------------------
الموضوع
Radiology.
تاريخ النشر
2009.
عدد الصفحات
174p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
1/1/2012
مكان الإجازة
جامعة بنها - كلية طب بشري - الأشعة
الفهرس
Only 14 pages are availabe for public view

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Abstract

Hepatocellular carcinoma is the most frequent primary tumor of
the liver, the incidence of which is increasing worldwide. Cirrhosis of the
liver, regardless of etiology, is considered to be the main risk factor for
the onset of HCC. Hepatitis C and B virus are the main factor related to
the presence of cirrhosis of the liver in patients with hepatocellular
carcinoma. Trans arterial chemoembolisation (TACE) is the most widely
used treatment for hepatocellular carcinoma in non surgical patients not
suitable for radiofrequency ablation .
To best assess the prognosis of hepatocellular carcinoma patients
it is recommended that the staging system takes into account tumor stage,
liver function and physical status. Currently, the BCLC system is the only
staging system that accomplishes this aim. Patients who have
intermediate-stage hepatocellular carcinoma according to the BCLC
staging system are the optimal candidates for transcatheter arterial
chemoembolization as a palliative treatment. Palliative options should
aim to improve survival without greatly impairing the quality of life.
In conventional TACE therapy, tumor selectivity is achieved
when chemotherapeutic agents are mixed with lipidol , to induce
ischemia in tumors. In addition, there are side effects of Lipidol as it
penetrates the portal venules and hepatic sinusoids and affects the hepatic
microcirculation, also doxorubicin is lost from lipidol in a very short
period of time.
DC Bead microspheres are a new embolic material for TACE, in
which the embolization particles are made from a unique drug –eluting
bead (DEB) technology based on polyvinyl alcohol (PVA) hydrogel that
has been modified with sulphonate groups. They can be loaded with a
chemotherapeutic agent widely accepted for treatment of HCC.
The advantage of using it is sustained release of chemotherapeutic
agent over a long period of time, which contrasts with the more rapid
release of the agents from the lipidol solution in standard TACE therapy.
With a controlled gradual and local release, contact time of the drugs with
the tumor is greater and plasma levels of the drugs are lower than those
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with standard TACE therapy, also less side effects and doubling the dose
using 150 mg instead of 70 -100 mg using lipidol
Good results are generally observed when a reduced number of
not very large tumors are embolized in a selective fashion (ideally
through a distinct feeding vessel). from a mechanistic point of view,
DEB are a much more reasonable and reproducible way to perform
TACE. In fact, the two particles available are claimed to turn TACE into
a feasible and well-tolerated procedure associated with a low
complication rate and a promising tumor response rate.( Bruno Sangro
et ,2011).
Secondary endpoints, including reduction in drug-related adverse
events or increased intra tumoral necrosis (which makes the difference
between RECIST and EASL criteria), have been proven successful and
are consistent with the well-known characteristics of the beads as shown
in preclinical work. The potential advantage of DEB-TACE over
conventional TACE in the subgroup of patients with the worst prognosis
(Child-Pugh B, ECOG 1, bi lobar or recurrent disease, Okuda stage I
tumor and CLIP score _3) should be treated with caution because it
comes from the analysis of a very small group of patients and it is
generally recognized that TACE should be indicated very in this
subgroup of patients who have a poor prognosis for which a survival
advantage has not been shown after conventional TACE, The safety
profiles of the two modalities of treatment appear similar.. .( Bruno
Sangro et ,2011)
authors of a recent prospective randomized comparison
(Malagari K et al 2010 ) of chemoembolization with doxorubicineluting
beads and arterial embolization with Bead Block
(Biocompatibles, UK) for HCC concluded that although ischemia plays
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a role in the development of tumor necrosis, there is a clear additional
benefit from the addition of doxorubicin. In that study, there was a
complete response in 26.8% of patients in the drug-eluting bead group
and 14% in the arterial embolization group at 6 months.
Altogether, the results of RCTs and retrospective series suggest
that 131I-lip could achieve similar a disease control rate and overall
survival a conventional TACE and that, in fact, it could be an alternative
to TACE for patients with bi lobar disease or PVT as it is better tolerated
and less likely to induce liver dysfunction. However, 131I-lip has not
gained widespread use in the management of un resectable HCC, its
major drawbacks being the need for radioprotection due to the gamma
radiation emitted that keeps patients isolated for 7 - 10 days after therapy.
90Y-RE circumvents these drawbacks and an incremental use has
been observed in the last decade. How 90Y-RE compares with TACE in
the same patient population is a difficult question to answer due to the
lack of RCTs comparing the two techniques. A rough estimate from the
available survival data suggests that a non-inferiority trial would
probably need to recruit more than 1000 patients, which makes such a
trial quite unlikely. (Bruno Sangro et ,2011).
The decision to submit a patient for 90Y-RE should then be taken
individually. The rate of complete necrosis seems to favor the use of
90Y-RE over TACE in those patients with early tumors that cannot be
treated radically because of age, poor liver function, comorbidity, or
lack of per cutaneous accessibility. Either procedure can be used as a
bridge to liver transplantation or with the intention to downstage tumor
at intermediate stage for radical therapies. TACE is certainly the
standard of care for those patients with small to medium-sized tumors
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that can be treated selectively, and it can be provided in most centers.(
Bruno Sangro et al ,2011).
90Y-RE could be then be an alternative to repeated TACE for
patients who fail to respond to initial TACE, and a first option in those
who are poor candidates for TACE, mainly because of bulky disease and
PVT, but who still have good liver function. Although, in this group of
patients who are poor candidates for TACE, 90Y-RE may have a role as
an alternative to sorafenib, more reasonably both therapies should be
combined to extend disease control and suppress the development of new
lesions.
Preliminary results from this combination are encouraging and a
large clinical trial is underway to provide an answer to this relevant
question. After years of indiscriminate use in unresectable HCC
patients, the availability of alternative therapies with documented
(sorafenib) or highly suspected (radioembolization) activity is
progressively restricting the indications for TACE. In the coming years,
much attention is likely to be paid to the combination of targeted agents
with antiangiogenic activity and locoregional therapies. .( Bruno
Sangro et ,2011).
The results of ongoing clinical trials will establish the best way of
combining sorafenib and other targeted therapies with trans arterial
procedures including TACE and 90Y-RE. Until they are reported, it is
important to bear in mind that in those patients who are not good
candidates for TACE (mainly because of a high tumor burden or the
presence of vascular invasion) and in those who progress to the first
sessions of TACE, a treatment switch to either 90Y-RE or sorafenib has
to be seriously considered. Finally, there is the need to develop
calibrated particles with an intermediate size (in the range of 50 -- 100
microns -- larger that those used in radio embolization but smaller than
Summary and conclusion
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those currently used in TACE) that could load anticancer agents
(isotopes, chemicals, or biologicals).( Bruno Sangro et ,2011)
(Carr BI et al,2010) found therapeutic equivalence in
survival when comparing radioembolization and chemoembolization in
a two-cohort study of patients with unresectable HCC. In 2009,
Lewandowski et al compared the downstaging effectiveness of
chemoembolization versus radioembolization in 86 patients with
unresectable HCC.
Disease in 58% of patients who underwent radioembolization
was downstaged to stage T2, while that in 31% of those who underwent
chemoembolized was downstaged ( P = .02). Radioembolization was
shown to be a better tool than chemoembolization for downstaging the
disease from a size outside transplant criteria to a size within the Milan
criteria for transplantation.
Recently, Salem et al 2011 demonstrated similar survival
times for patients with unresectable HCC treated with transarterial
chemoembolization or radioembolization. In that comparative
effectiveness analysis, radioembolization resulted in longer time to
progression and less toxicity than did chemoembolization ( P , .05).
CEUS is a feasible and safe method for rapid, onsite
assessment of the effect of TAE/TACE. Similar to CEUS performed days
or weeks after TACE intraprocedural CEUS easily differentiated necrotic
(nonenhancing) from viable (enhancing) tumor components sonography
can detect parenchymal and perfusional changes that occur hyperacutely
within minutes after the injection of embolic material into liver tumor
vessels. Although most of the relevant unenhanced sonographic findings
correlate poorly with the efficacy of the treatment, CEUS may readily
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and reliably demonstrate decreased tumor enhancement caused by
TAE/TACE.With increasing experience and refinements in the
technique, intraprocedural CEUS could serve as a monitoring tool in
selected cases of embolotherapy of liver tumors. (Malagari K et al
2010 )
The future of transcatheter therapies is promising. Ongoing
research in this field incorporates advances in the knowledge of liver
cancer biology, new concepts in targeting liver cancer, development of
new drugs, improvement of intra arterial drug delivery techniques, and
technological advances in imaging systems . (Liapi E et al, 2011).
It is anticipated that delivered agents will become more potent,
translating into higher efficacy and survival benefit. Furthermore, new
therapies will be developed that may be more tumor specific or potent.
These therapies may involve the delivery of genetic information. Recent
research has investigated the targeted delivery of gene therapy to the liver
by means of isolated hepatic perfusion or via the portal vein (Liapi E et
al, 2011).
The delivery of gene therapies and other future therapies will
likely use nanotechnology. Nanocomposites could also be tagged to be
tumor specific, tumor avid, visible at time of delivery, and carry a
specific therapy (Liapi E et al, 2011).
Finally, new classes of drugs delivered intra arterially could lead
to markedly more potent tumor kill than conventional chemotherapeutic
agents. For example, a new class of anticancer drugs, such as 3-
bromopyruvate, specifically targeting tumor metabolism could be infused
locally by means of transcatheter delivery for increased potency, By
disrupting the ability of the cancer cell to generate energy, but leaving
normal cells intact, this new approach is extremely promising.