Liver Cancer (HCC) Advances in Surgery and Transplantation

Dr Tan Yu-Meng FRCS (Edin), FAMS (Gen Surg) Deputy Head and Senior Consultant, Department of Surgical Oncology, National Cancer Centre Singapore Surgical Director, Liver Transplant Program, Singapore General Hospital Senior Consultant, Department of Surgery, Singapore General Hospital

Hepatocellular cancer (HCC) presents a major health problem and is the leading cause of abdominal cancer death in Singapore. Our population has a high prevalence of cirrhosis and hepatitis B virus (HBV). This remains the main underlying risk factor for HCC development. As such, patients with, or at risk for hepatocellular carcinoma present a special challenge to the clinician. The primary care physician plays an important role in providing screening and prevention for HCC. However, clinical care once HCC is suspected or diagnosed is a specialized task. A multidisciplinary team of ‘liver specialists’ including a liver/transplant surgeon, hepatologist, oncologist, and liver/interventional radiologist is essential. Surgical resection and liver transplantation are today, the only potential curative treatment for HCC. Recent advances in surgical assessment and technique have expanded the criteria for surgical options and this short review will highlight the current surgical approach in the management of HCC.

Diagnosis of HCC and the role of liver biopsy

Fig 1. CT of a typical hepatoma (arterial phase)

This is one of the most controversial questions in the management of HCC. Traditionally in cancer diagnosis, cytological or histological diagnosis is the gold standard. However, there is widespread acceptance amongst liver specialists for a noninvasive radiological diagnosis of HCC in the background of cirrhosis and raised alphafetoprotein (AFP). Hepatomas (HCC) are perfused preferentially by the hepatic artery rather than portal vein. Hence, diagnosis relies on dynamic and rapid sequence imaging that demonstrates this specific hepatic vascularization property (Fig 1). Triphasic computed tomography (CT) or magnetic resonance imaging (MRI) of the liver provides excellent diagnostic accuracy with reported sensitivity and specificity of over 95%. In addition, they also give information on liver volumes and surgical resectability.

The role of liver biopsy is controversial and is not necessary to make a diagnosis in HCC prior to surgery or liver transplantation. The process Advances in Surgery and Transplantation for Liver Cancer (HCC) of liver biopsy is fraught with problems. Patients with liver cirrhosis may have coagulopathy and thrombocytopenia that increase the risk of bleeding. Small lesions may be difficult to target even with image guidance. There is a risk of tumour seeding along the needle tract.

Moreover, small lesions are suspect to sampling error or inadequate sampling. Finally, diagnostic criteria differentiating regenerative or dysplastic nodules from malignant lesions are ambiguous. Hence, a negative biopsy may not rule out a HCC. The author recommends performing a biopsy only if diagnostic doubt persists after thorough review of all non-invasive data (preferably with a second opinion from a liver specialist team) and if the result of the biopsy changes the management plan for the patient.

Surgical Assessment for Surgery and Transplant

The results for liver resection and transplantation for HCC have improved dramatically over the last decade. In our experience, both procedures carry low major morbidity rates of less than 10% and almost zero mortality rates. In liver resection, blood transfusion and the use of intensive care facilities are required in only a minority of patients. This is attributed to better patient selection and assessment using image-guided liver volumetry and liver functional reserve studies in addition to traditional Child-Pugh grading.

With such improvements, the important question once HCC is diagnosed, is whether the patient is amenable for curative treatment by surgical resection or transplantation?

Fig 2. Resected left lobe of liver containing hepatoma	Fig 3a. Liver Transplantation for treatment - Cirrhotic liver with multiple HCC	Fig 3b. Liver Transplantation for treatment - New Donor liver implanted

 
This is dependent on 2 factors: (1) tumour load and location, (2) underlying liver function and reserve. There is an overlap in terms of indication for surgical treatment options and decisions are best managed by a multidisciplinary specialist team including a liver surgeon, hepatologist and medical oncologist for the best results. Ideally, the specialist should be part of a liver transplant program or have good access to one so that all options are discussed and tailored for each patient.

Role of Liver Resection

This is the treatment of choice for non-cirrhotic patients and cirrhotic patients with good liver functional reserve (Child’s A). HCC lesions resected with a clear margin in carefully selected patient groups give outcomes of up to 70% 5-year survivals. The best results are obtained for small tumors < 5cm, single lesions that lack microvascular invasion and in non-cirrhotic patients. However, tumour recurrence complicates up to 70% of patients within 5 years as most patients continue to have risk-prone livers from their underlying liver cirrhosis. These patients require close surveillance after liver resection.

The role of surgery in large tumors (> 8cm), multifocal tumors (2 or more lesions), and tumors with portal vein invasion (Fig 2) can also be carried out safely albeit with poorer results. The 5-year survival in these groups are between 20-40% and the recurrence rates are understandably high because of aggressive tumor biology. However, the role of surgery remains a cornerstone of treatment, as results for patients amenable to surgery are still much better than other nonsurgical options where 5-year survivals are almost negligible. The role of surgical resection is set to increase with the introduction of neoadjuvant and downstaging techniques.

Role of Liver Transplantation

This is the ideal treatment option. It provides the widest surgical margin with no possibility of early local recurrence and it also removes the underlying liver disease without the high risk of liver failure in cirrhotic patients with portal hypertension (Child’s B and C). In doing so, all possible oncogenic foci are removed and risks of late recurrences within the liver are low. The best candidates should satisfy the ‘Milan’ criteria (1 lesion less than 5cm or 3 lesions each less than 3cm in size). These patients should also not have evidence of macrovascular invasion or extrahepatic metastases. With this selection criteria, 10-year survival exceed 70% and the recurrence at 5-years is less than 15%. These results have been duplicated worldwide and are far better than with surgical resection or local ablation therapies.

Such excellent results have prompted an expansion in the criteria for liver transplantation beyond the ‘Milan’ limits. In Singapore, the acceptable criteria have been expanded to include single HCC lesions up to 6.5cm or 3 lesions not more than 4.5 cm (up to a total diameter of 8cm). This results from comparable results from this criteria as with the conventional ‘Milan’ criteria.

However, the local problem with liver transplantation is the shortage deceased donor livers for transplant, resulting in a prolonged waiting time. Progression of HCC may occur and lead to death on the waiting list. Bridging therapies like local therapies and chemoembolization are used for disease control during this waiting period. Living donor liver transplantations (Fig 3) have recently been introduced for patients with HCC to circumvent the waiting time. Results from live donor transplants are comparable to those for cadeveric liver transplant if similar criteria for transplantation are chosen.

Currently, it is the minority of patients with HCC that are assessed for transplantation and even fewer receive this option. It has been adopted as a salvage treatment after liver resection recurrence or failure of multiple local therapies. Liver transplant should form the cornerstone of curative HCC treatment rather than just as a salvage procedure. All cirrhotic patients who are diagnosed with HCC should be evaluated for liver transplantation.