Hepatic cysts generally are almost exclusive benign lesions. They can be solitary or multiple and often are identified incidentally on imaging for other symptoms.

Asymptomatic cysts require no treatment regardless of size. Large cysts may be symptomatic because of increased abdominal volume or compression of adjacent structures. Bleeding, infection, or bile duct obstruction can occur but are infrequent.

Symptomatic cysts can be unroofed operatively by either an open approach or, more recently, by laparoscopy (key hole).  Polycystic kidney disease (a rare genetic disorder characterized by numerous cysts in the kidneys) sometimes is accompanied by polycystic liver disease, which usually is asymptomatic. Liver function is rarely impaired by the gross displacement of parenchyma by these massive cystic cavities.

Neoplastic cystic lesions such as cystadenoma or cystadenocarcinoma rarely occur in the liver. These lesions are distinguished from simple cysts by the presence of a mass or septa. They are treated by resection or enucleation (in the case of cystadenoma) to completely remove cyst epithelium.

Hemangioma is the most common benign liver tumour, and it occurs in up to 5% of the adult population. The majority are diagnosed in middle-aged women, and there is a female-to-male ratio of 5:1. The cause of hemangiomas is poorly understood. It is a benign liver lesion formed by an abnormality in the blood vessels development.

Hemangiomas are usually less than 5 cm in diameter, but they can reach 20 cm or larger. Their blood supply is derived from the hepatic artery. Malignant degeneration (transformation of a benign lesion into a cancerous one) does not occur, and spontaneous rupture is exceedingly rare. Most hemangioma are asymptomatic and are identified incidentally during an ultrasound for abdominal pain. Large lesions (>5cm) can occasional cause vague abdominal pain. Intermittent symptoms may occur when there is necrosis, infarction, or thrombosis of the tumour. Life-threatening haemorrhage is extremely uncommon, even in large tumours, but can be precipitated by needle biopsy. Kasabach–Merritt syndrome is a rare consumptive coagulopathy resulting from sequestration of platelets and clotting factors in a giant hemangioma, and this is usually treated with urgent resection/embolization. Laboratory abnormalities are rare. Because of the possibility of severe haemorrhage from attempts at biopsy (it is like to insert a needle into a conglomerate of blood vessels- image what can happen), diagnosis relies on imaging investigations. On ultrasound, hemangiomas appear as well-defined, lobulated, hyperechoic masses. Computed tomography (CT) scans reveal a low-density area with characteristic peripheral enhancement in the early phase. Subsequently, contrast enhancement progresses toward the centre of the lesion until, in the delayed enhanced images, the tumour appears uniformly enhanced. The best imaging study is gadolinium-enhanced magnetic resonance imaging (MRI), with specificity and sensitivity approximately 90% and 95%, respectively. These tumours appear bright on T2-weighted images – a characteristic almost only seen in these type of lesions). Most hemangiomas are treated safely with observation. Indications for intervention (which are very rare) include symptoms, complications, and inability to exclude malignancy. In these select patients, the preferred treatment is surgical removal.

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor, constituting about 8% of cases and is found predominantly in women of child-bearing age, with a female-to-male ratio of 8:1. Although an association with contraceptive pills has been suggested, the correlations are much lower than are those for hepatic adenomas (see below)

Classically they are characterized by a dense, central stellate scar with septa radiating outward, thereby dividing the tumour into nodules. Clinical manifestations of FNH are rare and malignant degeneration has not been reported, but it is critical to distinguish FNH from the fibrolamellar variant of hepatocellular carcinoma (fHCC), a malignant lesion that may have a similar central scar. Although ultrasound is often the imaging study that first detects focal hepatic lesions, it does not discriminate FNH from other tumours/lesions. Diagnosis is made with a combination of CT and MRI scans in 70% to 90% of cases. When the diagnosis remains in doubt, histologic examination (doing a biopsy) is indicated.

Surgery is not indicated in asymptomatic patients when studies differentiate FNH from adenoma or malignant lesions. OCPs should be avoided. There is no contraindication to pregnancy with this lesion, but close observation for tumour growth during pregnancy and the postpartum period is prudent. This is usually done repeating an ultrasound examination periodically.

It is a benign liver lesion formed by a dysfunctional growth of liver cells. It is not to be confused with the term “hepatoma,” which refers to HCC (hepatocellular carcinoma or liver cancer). It is usually found in young women and has a 10:1 female-to-male ratio. There is a strong association with all synthetic estrogen and progesterone preparations (contraceptive pills). In addition, anabolic steroids an also make these lesions grow. Adenomas are usually solitary (70% to 80%), round, well-circumscribed lesions. Although they are unencapsulated, there is often a pseudo capsule formed by compression of normal surrounding tissue.

Adenoma are of clinical importance because of its tendency to spontaneous rupture and bleed. The rate of rupture has been estimated between 25% and 35% with nearly 100% of all spontaneous ruptures occurring in lesions greater than 5 cm. About one-third of patients with symptoms present with intra-abdominal bleeding, and others present with abdominal pain without rupture. Generally, these lesions present with vague symptoms such as fullness or discomfort in the right upper quadrant or are detected incidentally. Spontaneous rupture occurs more often in men, especially in steroid users. It may also occur during pregnancy due to rapid growth under the influence of estrogens.

Different from Heamangiomas and HNF, adenomas are potentially premalignant, with large or multiple tumours carrying a greater risk of malignant degeneration. Nowadays, we know that certain subtypes are more prone to bleed and others to become a cancer.

The diagnosis of adenoma is made by MRI with a special contrast (Primovist). Nowadays, size and location will dictate the management, but in some cases, biopsy will rule out the chances of been a subtype that will become a cancer. As a rule, males are more prone to have the mutation responsible to turn the benign lesion into a cancer.

Because of the risk of spontaneous rupture and malignant transformation, adenomas must be identified and treated promptly. Operative intervention after an adenoma rupture is usually mandatory. Small (<5 cm), asymptomatic lesions occasionally regress with cessation of OCPs may not need an operation at all. Although radio frequency ablation (RFA) may be an option when there are multiple adenomas, resection of HA remains the standard therapy. Indications for operative intervention include the following: 1) patients with lesions that are 5 cm or greater in diameter. 2) large tumours that do not reduce in size after discontinuation of oral contraception 3) patients who medically cannot stop oral contraception use with adenomas greater than 5 cm 4) beta catenin mutation on biopsy.

HCC is the most common liver cancer and 8 out of 10 HCC are linked to Hepatitis B and C infection. There is a 3:1 male-to-female predominance. In 2019, liver cancer was the seventh most common cause of cancer death in Australia. with 2,187 deaths. It was estimated that in 2021, there were 2,424 deaths. Overall survival has improved over the years and depends mostly on the tumour behaviour (aggressiveness) and in the background liver status (cirrhotic patients are more prone to have de novo recurrence). Across the Asia-Pacific region, there is a changing burden of liver disease, but the increase in metabolic conditions (obesity, diabetes, high cholesterol) and associated non-alcoholic fatty liver disease (NAFLD) in Australia will have a long-term negative impact on HCC incidence, diagnosis and management.

HCC is diagnosed mainly in the fifth and sixth decades and the major risk factors for cirrhosis include hepatitis B, hepatitis C, alcohol abuse, autoimmune phenomena such as primary biliary cirrhosis and autoimmune hepatitis, and hereditary metabolic disorders. From 70% to 85% of HCC arises in the setting of cirrhosis. Malignant tumours of the liver occur in 4.5% of cirrhotic patients and in up to 10% when hemochromatosis is the inciting factor.

Symptoms area vague and up to 80% of patients experience weight loss and weakness. Approximately 50% have abdominal pain that can be dull, persistent, and is usually located in the epigastrium or right upper quadrant. Acute severe abdominal pain is rare and can be due to intra-tumoral bleeding or associated with intraperitoneal haemorrhage due to rupture of a necrotic nodule.

In cirrhotic patients, HCC may be associated with abnormal liver function tests due to different degrees of hepatitis. Elevated serum α-fetoprotein (AFP) occurs in up tp 75% of affected patients and when elevated, its level can be used for follow up after treatment. AFP can be also elevated in chronic hepatitis and cirrhosis, so a slight elevation of this tumour marker can be seen in patients without any tumour. A level greater than 200 ng/mL (normal <20 ng/mL) is suggestive of HCC, even in the cirrhotic patient.

Work up of patients with HCC:

Ultrasonography can be highly accurate in the detection of HCC, especially when coupled with concomitant AFP elevations. It is the method of choice (from the populational point of view) for surveillance of HCC in cirrhotic patients.

MRI and CT scan can be useful in differentiating other small nodular masses from HCC. MRI is the most accurate imaging modality for distinguishing HCC from dysplastic or regenerative nodules in the cirrhotic patient.

When required, laparoscopic or image-guided percutaneous biopsies may be used to obtain a tissue diagnosis (a small sample of the tumour is removed and analysed by a pathologist). However, a tissue diagnosis is not required before therapeutic intervention (including surgical resection and liver transplantation) if other diagnostic modalities favour HCC as the diagnosis. Unresectable tumours likewise usually do not require biopsy to confirm the diagnosis because imaging and laboratory studies allow a definitive diagnosis in most cases.

Treatment

Surgical resection is the treatment of choice for noncirrhotic patients who have HCC and for some cirrhotic patients (depending on the background liver status). Tumour excision is the only curative treatment - either by a liver resection (hepatectomy) or by liver transplantation. A macroscopic margin of 1 cm generally is regarded as adequate. Overall 5-year survival rates for patients with HCC treated with resection is 40% to 50%, with recurrence rates of around 40% to 50%. The most important predictors of recurrence are microvascular invasion and multinodular tumours. Repeat hepatic resection for recurrence has been demonstrated to be safe and effective in selected lesions.

Orthotopic liver transplantation (OLT) is theoretically the best treatment option for HCC occurring in cirrhotic livers because it removes the tumour together with the entire diseased liver, thus eliminating the risk of de novo or recurrent disease. However, transplantation is suitable only in selected cases (Transplant Society of Australia and New Zealand). In this setting, the 4-year actuarial survival rate was 75%, with recurrence-free survival of 83%. These number can differ depending on tumour characteristics on histology and the biological behavior of the tumour. So, these survival numbers need to be taken with caution - they are a reflection of a population, not a reflection of a case.

Local thermal ablation (destruction) is the best treatment option for patients who have early-stage HCC who are not suitable for resection or transplantation. The most common modality is called Microwave ablation (MWA). It can also serve as bridges to liver transplantation for those on the transplant waiting list. Indeed, downstaging tumours (when you can shrink the tumour after the treatment is done) improve survival of HCC patients who subsequently undergo OLT. MWA is performed usually by a radiologist with expertise in interventions. A needle electrode is placed into the tumour, destroying tissue by heating it to temperatures of 60°C to 100°C. MWA may be also performed intraoperatively (during the operation).

Transarterial chemoembolization (TACE) involves selective intra-arterial administration of chemotherapeutic agents followed by embolization of the major tumour artery. HCC preferentially derives its blood supply from the hepatic artery rather than from a combination of the hepatic artery and portal vein as for normal hepatic parenchyma. TACE has a survival benefit for select patients. The procedure is rarely complicated by hepatic failure due to infarction of adjacent normal liver. For this reason, it should not be used in decompensated cirrhosis.

Systemic chemotherapy and external beam radiation have had poor results. Chemotherapy with conventional cytotoxic agents is ineffective and does not seem to modify the natural history of disease. Recent identification of signalling pathways in HCC has resulted in the development of new drugs. One of them is called Sorafenib. Sorafenib is a kinase inhibitor with antiangiogenic and antiproliferative properties that has shown modest efficacy in patients with advanced HCC.

Without treatment, HCC has a very poor prognosis, with a median length of survival of 3 to 6 months after the diagnosis.

This is a rare variant of fHCC that is not as aggressive as the standard HCC. Males and females are equally affected, commonly at a younger age (20 to 40 years old). It is uncommon for fHCC to be associated with underlying liver disease such as cirrhosis. FHCC is best treated with complete surgical resection, which is possible in 80% of patients. Compared with standard HCC, fHCC is associated with a better prognosis; patients with resectable FLHCC have a greater 5-year survival rate (>70%) than noncirrhotic patients who have resectable nonfibrolamellar HCC. Late recurrence is common (more than two thirds of cases), and repeat resection of local disease should be considered. Liver transplantation is an option for unresectable but nonmetastatic lesions.

ICC is the second most common primary hepatic tumour and arises from the malignant transformation of the cells that line the bile ducts within the liver. Primary sclerosing cholangitis (PSC) is the main risk factor in Western countries, and there also appears to be an association between iCC and cirrhosis. There are at least types of iCC described by its features: mass-forming, periductal infiltrating-type, and intraductal growth-type. Patients with mass-forming do worse than patients with periductal infiltrating or intraductal type following resection. This may be in part due to a propensity for the mass forming on having vascular invasion and lymph node metastasis. It has also the ability to extend along the biliary tree in some patients, translating into significantly shorter survival.

Surgical resection offers the only chance for cure, with 5-year survival rates of 13% to 44%. Clinicopathologic factors that adversely affect survival are large tumours, vascular invasion, nodal involvement, bile duct involvement, multiple nodules, and margin status. Although lymph node involvement is common in iCC, the extent of lymphadenectomy during resection has not been proven to affect survival. Even though, some centres advise for it.

Colorectal cancer metastatic to the liver is only treated by partial hepatectomy. Approximately 50% of all patients with colorectal cancer develop metastases, and of these, about one-third have disease limited to the liver. Without treatment, hepatic metastasis has a dismal prognosis, with a median survival of 6 to 12 months. In contrast, numerous studies have shown that resection of hepatic metastases is associated with 60-70% 5-year survival rate. As a result, operative resection has been established as the most effective therapy for patients with isolated colorectal liver metastases.

The most common images used to evaluate and stage colorectal liver metastases are CT and MRI scans. Also the use of whole-body positron emission tomography (PET) after administration of 18F-fluorodeoxyglucose (FDG) is valuable for the detection of occult metastases, both inside and outside the liver.

The main objective in the resection of colorectal metastasis is removal of all disease with gross negative margins. Factors predictive of poor outcomes after resection of hepatic colorectal metastases include node positivity of the primary tumour, multiple metastases, and size of the largest metastasis greater than 5 cm.

Postoperative follow-up consists of serial physical examination, serum CEA level, and abdominal/pelvic CT or MRI scans every 3 to 4 months for the first 2 years, then every 6 months for the subsequent 3 years. Unfortunately, disease recurrence is common, but when cancer is isolated to the liver, repeat resection can provide additional survival benefit.

Local ablation with MWA should be considered in patients unfit for operative resection or who have unresectable disease. In those patients with multiple lesions in both sides of the liver, a combined approach of resection of the larger tumours with RFA of the remaining lesions may be feasible.

The treatment of colorectal liver metastases is challenging and has progressed a lot in the last 10 years. New chemotherapy drugs have been discovered and new surgical techniques have turned unresectable patients into resectable. The possibility of multiple liver resections (two stage operation), the addition of intra operative ablation techniques and the advances in peri-operative care have allowed surgeons to offer operations and options that were not possible few years ago. Dr Perini has a special interest in colorectal liver metastases and is the head of the Liver Research Group at the Department of Surgery at the University of Melbourne, a group focused in discovering new strategies for the treatment of colorectal liver metastases.

Liver resection for other metastatic tumours is limited and the most common ones are: neuroendocrine, breast and some types of melanoma.

There are several reasons supporting resection of neuroendocrine hepatic metastases. These include their relatively long tumour doubling time, lack of effective chemotherapy, and the ability of metastasectomy to provide symptom palliation and long-term survival.

There is limited experience with liver resection for noncolorectal and nonneuroendocrine metastasis. The presence of liver metastasis from melanoma or cancer of the breast or stomach should be viewed as a marker of disseminated disease, and liver resection in these contexts is usually not recommended. In exceptional cases it can be done.

Any liver lesion found on ultrasound or CT scan while something else was investigated (usually an abdominal pain) is termed incidental liver nodule or lesion. Most of the incidental liver nodules are benign and woman at young age to most common once to have these lesions. They can be solid or cystic (filled with water). All incidental liver nodule should be investigated mainly to exclude a primary or metastatic liver tumour.