Hepatocellular Carcinoma

Current Trends in the Management of Hepatocellular Carcinoma (HCC)

A focused multidisciplinary team including a Liver surgeon, hepatologist, interventional radiologist and medical oncologist is important for the comprehensive management of HCC patients.

A number of treatments are available for patients with a HCC. These include:

Surgical resection through either partial or total liver resection (i.e. liver transplant);

Less invasive procedures aimed at physically or chemically destroying the tumour by Percutaneous route and

Systemic or regional chemotherapy. Patient eligibility for treatment depends on the stage of the disease and the status of liver function.

Surgical Excision

Open surgical excision is a reliable method for treating stage I HCC. The goal is to obtain a 1-cm margin of normal tissue around the tumour. Beyond that requirement, the type of excision does not impact in any way on cancer treatment outcome. The excision of surface tumours is best accomplished as a nonanatomic wedge excision, in which the tumour is simply excised with a 1-cm margin and no more. This can be performed safely for tumours up to 5 cm in diameter with minimal blood loss. Deep tumours within the hepatic parenchyma and tumours larger than 5 cm must be managed by an anatomic resection, in which the most distal portal triad to the region involved by the tumour is controlled and the segment or segments are resected. Centrally located tumours may require a lobectomy, and large tumours may require an extended hepatectomy. Preoperative portal vein occlusion can sometimes be performed to cause atrophy of the HCC-involved lobe and compensatory hypertrophy of the noninvolved liver. This allows for a safer resection. Intraoperative ultrasonography is useful for planning the surgical approach for HCC & screening the rest of the liver for small tumours.

The morbidity and mortality of a simple wedge excision should be minimal, but even slight manipulation of a cirrhotic liver may lead to liver failure and other complications, such as respiratory failure (adult respiratory distress syndrome, pneumonia), cardiovascular compromise, ascites, and infection. Cirrhotic patients are fragile with respect to the tolerance of any major surgery. Any significant postoperative complications may lead to liver failure.

The Child-Pugh classification of liver failure is still the most reliable prognosticator for tolerance of hepatic surgery. Only patients with disease classified as Child’s A should be considered for surgical resection. Patients with Child’s B and C disease with stage I HCC tumours should be referred for transplant if appropriate. Patients with ascites or a recent history of variceal bleeding should be treated with transplantation. A variety of tests have been described for quantitative assessment of hepatic reserve like indocyanine green clearance test, CT and MR volumetry. Minimal residual functional liver volume should be 30% when underlying liver is normal. This volume should be at least 40% in cirrhotics due to impaired function and reduced capacity to regenerate. A laparoscopic approach to resection of small surface liver tumours is safe and feasible.

Transplantation

Liver transplantation is obviously the most attractive therapeutic option for HCC because it removes detectable and undetectable tumour nodules together with all the pre-neoplastic lesions that are present in the cirrhotic liver. It simultaneously treats the underlying cirrhosis and prevents postoperative and distant complications associated with portal hypertension and liver failure. Most commonly used criteria to select patients with HCC for transplant, originally proposed by Bismuth et al. and then later studied prospectively by Mazzaferro et al., are 1. patients with a single lesion of 5 cm or smaller or multifocal disease limited to three or fewer nodules, each 3 cm or smaller (2) no signs of extrahepatic metastasis (3) No vascular involvement. This resulted in excellent tumour-free survival (70% or higher at 5 years).

Local Injection Therapy

Percutaneous Ethanol injection(PEI) into HCC is the most widely used therapy. The relatively soft HCC within the hard background cirrhotic liver allows injection of large volumes of ethanol into the tumour without diffusion into the hepatic parenchyma or leakage out of the liver. Ethanol causes a direct destruction of cancer cells.

Local Ablation Strategies

Radiofrequency ablation(RFA) is a technique that uses heat to thermally ablate tumours. Currently, the maximum size of the probe arrays allows for a 7-cm zone of necrosis. This would be adequate for a 5-cm tumour. The heat reliably kills cells within the zone of necrosis. The treatment can be performed percutaneously with CT or US guidance, or at the time of laparoscopy with US guidance.

Transarterial embolisation(TAE /TACE)

The rationale of treating HCC by Transarterial embolisation(TAE) is based on the fact that, in contrast with the normal parenchyma, HCC receives 100% blood supply from the hepatic artery. Embolisation causes ischemia with resultant necrosis. TAE may be combined with regional chemotherapy(TACE).

Targeted Radiotherapy

Targeted therapy with 131-iodine-lipiodol injected via hepatic artery in an adjuvant setting has shown reduced recurrence after resection. 90-Yttrium microsphere is also being evaluated for the same. 131-iodine-lipiodol has also shown disappearance of portal vein thrombosis when used as a neo-adjuvant therapy.

Systemic Chemotherapy

Systemic chemotherapy has a limited value with partial response rate of 20% and negligible complete response rate.