Hepatocellular Carcinoma
Generally, most authors agree that surgical resection is mainly suitable for cirrhotic patients with Child–Pugh class A or early B with minimal or no portal hypertension and an FLR of more than 50%.20
The principles
of liver resection in cirrhotic patients are: parenchymal preservation, minimal blood loss, and negative resection margin of at least 1cm. Contraindications to surgical resection of HCC are the presence of extra-hepatic metastases, diffuse bilobar disease, and an underlying severe liver dysfunction. Invasion of the biliary confluence or tumor thrombus in the main portal vein, major hepatic veins, or inferior vena cava are relative contradictions.20
Careful patient selection and
improved surgical techniques have reduced the operative mortality from more than 10% in the last three decades to less than 5%.21,22
One of the largest published series is from a Japanese nationwide database of HCC patients who underwent liver resection, which showed a reported survival at three and five years of 67 and 50%, respectively.25
The overall long-term results after resection are favorable. In patients with favorable prognostic features (solitary tumor, Child–Pugh class A, absence of portal hypertension, no vascular invasion, and a negative surgical margin), five-year survival rates of 50–70% have been reported.23,24
Despite curative surgical resection, 60–80% of patients develop recurrent HCC within five years because of latent intra-hepatic metastasis from the primary tumor or metachronous multicentric carcinogenesis due to the underlying liver disease.26–28
The risk for
recurrence is influenced by several variables including micro- and macro-vascular invasion, multi-nodularity (severity of the underlying liver disease), tumor size and number, the pathologic features of the tumor, and width of the tumor-free resection margin.25,29,30
In selected
patients, repeat resection provides good long-term benefits; however, these patients are better served with a liver transplant (which deals with the underlying liver cirrhosis).
Bridge to Hepatic Transplantation and Palliative Care In patients who are candidates for liver transplantation, a combination of various locoregional therapies helps to keep a check on the tumor volume and minimize disease progression while they await a transplant. Furthermore, patients deemed ineligible for a liver transplant can have their disease downstaged to become eligible for a transplant.
In patients with non-resectable disease, the main aim of treatment is symptom control, prolonged survival, and improved quality of life. A number of image-guided therapies are available to palliate patients with advanced or unresectable disease, including transcatheter arterial chemoembolization (TACE), ablation (thermal or chemical), and radioembolization using 90Y.
Transcatheter Arterial Chemoembolization— Principle, Indication, and Treatment
Treatment of HCC with TACE results in a survival advantage when compared with conservative treatment and is currently the mainstay of treatment in 10% of HCC patients.31
Unlike the normal liver, which has
dual blood supply, HCC is solely supplied by the hepatic artery. As a result of this, the tumors can be precisely targeted for delivery of chemotherapy. In combination with embolizing particles they bring about varying degrees of ischemia in the tumor and limit the rapid wash-out of chemotherapeutic agents from the tumor. This results
46
Gel foam is frequently used as an embolic agent since it usually results in transient occlusion with recanalization of the artery in two to four weeks.18
Embolization of the hepatic artery can be performed using various embolic agents such as gel foam, polyvinyl alcohol (PVA), embospheres, and coils. The aim is to minimize the efflux of chemotherapy agents from the tumor and to embolize the distal smaller vessels without blocking the main artery, so as to preserve arterial access for subsequent sessions.37
The PVA particles used range from 50 to 300
microns in size and cause permanent occlusion of the distal vessels. Embospheres (100–700 microns), owing to their ability to deform, lack of aggregation, and smooth hydrophilic surface, are able to embolize to more distal vessels than the PVA particles of similar size.38
The role of TACE in neoadjuvant therapy is not entirely clear. There may be a possible survival advantage in patients treated with TACE prior to resection as opposed to resection alone.39
TACE is also used as a bridging
therapy prior to liver transplantation. It helps control growth of the tumor while the patient awaits an organ and also causes significant necrosis of the tumor, which may minimize tumor dissemination during surgery. The reported survival rates post TACE range from 34 to 88% at one year, 33 to 64% at two years, and 18 to 51% at three years.40
Drug-eluting Beads
Drug-eluting beads (DEBs) are the most recent innovation in arterial liver-directed therapy. They are a polyvinyl alcohol hydrogel, and are biocompatible, hydrophilic, and non-resorbable. The primary advantage of DEBs is the sustained release of chemotherapy over long periods of time, in contrast to standard TACE therapy:41
DEBs are able to adsorb
doxorubicin onto their surface and to release it slowly. They range from 100 to 1,200 microns in size. Initial results at follow-up imaging show a positive response, as evidenced by the lack of enhancement in the tumor, indicative of necrosis. Initial data comparing DEBs with standard
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
in increased availability and concentration of chemotherapeutic drug to the tumor—100 times greater than that achieved with systemic chemotherapy.32,33
TACE is reserved for such patients with advanced HCC and is effective in palliation and improves patient survival.34
The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of Liver (EASL)35
have
recommended TACE as first-line non-curative treatment for patients unfit for surgery due to large or multifocal disease without vascular invasion or extra-hepatic spread. Contraindications to treatment are advanced liver disease (Child–Pugh C), vascular invasion or portal vein occlusion by tumor, refractory ascites, hepatic encephalopathy, active gastrointestinal hemorrhage, portosystemic shunt, hepatofugal blood flow, extra-hepatic metastases, and World Health Organization (WHO) performance status 3 or 4. The outcome is poor in patients with significantly impaired baseline liver function and large tumors.
A number of anticancer agents are used, including doxorubicin, cisplatin, carboplatin, epirubicin, mitoxantrone, and mitomycin C.36
These agents
are used in combination with lipiodol, an oily contrast agent, which is avidly taken up by the tumor cells and is therefore used to deliver and concentrate the chemotherapy into the tumor. This mixture is selectively injected into the appropriate subsegmental branches of the hepatic artery.
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76