Hepatocellular carcinoma is one of the cancers with the highest mortality rate, being the third leading cause of cancer-related death.

Symptoms

In early stages, the disease is asymptomatic, meaning there are no clinical manifestations. In advanced stages, some of the following symptoms may appear:

• Abdominal pain or tenderness
• Abdominal enlargement (ascites)
• Yellowing of the skin or eyes (jaundice)
• Tendency to bleed or form bruises
• Unexplained weight loss

Who does the disease affect?

In more than 80% of cases, hepatocellular carcinoma occurs in patients with underlying liver disease, especially liver cirrhosis.

Diagnosis

Screening is important for diagnosing the disease at early stages, which is the ideal time to apply curative-intent treatment.

The diagnostic tests and procedures used depend on the patient profile:

• Patients at risk with known liver disease: Screening should be performed every six months using ultrasound. If a nodule is detected, contrast imaging tests such as CT scan or contrast-enhanced MRI are performed to confirm the diagnosis. In some cases, a liver biopsy is required, which involves extracting tumor tissue.
• Patients with unknown predisposing factors and not in a screening program: Usually diagnosed after the appearance of initial symptoms, using the following diagnostic tests:
  • Imaging tests such as CT scans and MRI
  • Tumor biopsy to extract liver tissue for histopathological examination

Usual treatment

Treatment for hepatocellular carcinoma varies for each patient, depending on tumor burden, liver function, and overall health status.

The most commonly used treatments are:

• Surgical: Resection surgery and liver transplantation, applicable in early stages
• Locoregional: Aimed at destroying tumor cells through direct ablation (radiofrequency ablation, microwave ablation, cryoablation, etc.) or via endovascular methods (transarterial chemoembolization or radioembolization)
• Systemic: Used mainly in advanced stages, currently including immunotherapy drugs and tyrosine kinase inhibitors

Survival in advanced stages has improved significantly thanks to the successful results of treatment combinations that include immunotherapy. Many patients have benefited and continue to benefit from these treatments before their official approval and commercialization through participation in clinical trials.

Most common tests

The most common diagnostic tests for this condition are ultrasound, CT scan, contrast-enhanced MRI, and biopsy. Blood tests are also used both for diagnosis and follow-up in daily clinical practice.

Prevention

The best way to prevent hepatocellular carcinoma is to avoid risk factors, such as alcohol consumption and smoking, control diabetes (a key component of metabolic syndrome associated with fatty liver disease), and prevent or treat hepatitis B and C infections.

There are several types of tumour, which dictates prognosis and treatment. Malignant tumours, hepatoblastoma and hepatocarcinoma are the most frequent, accounting for 2/3 of all liver tumours. Benign tumours include haemangiomas, hamartomas and focal hyperplasia. In the case of benign tumours, especially those of a vascular nature (haemangiomas), vascular and interventionist radiology plays a decisive role, being able to avoid unnecessary surgical procedures, improving the prognosis and avoiding liver transplants.

Surgical treatment is an essential part of the cure of most malignant cases, and liver transplants can be the only possibility for curing some patients. Interventional radiology techniques also play an important role. Vall d’Hebron Hospital has gained considerable experience in treating these tumours and is involved in the first global study to treat hepatic malignant tumours for children (PHITT), being one of the reference centres for this pathology in Spain within the European ERN networks.

Symptoms

Patients usually present with abdominal distension, a palpable abdominal mass, or both. Weight loss, non-focus fever and loss of appetite are also common. Sometimes they can also be discovered incidentally when performing an ultrasound for another reason. If there is any accompanying liver disease or the bile duct is compressed, a yellowish colouration of the skin and mucous membranes (jaundice) may appear. Some patients may present with abdominal pain.

Who is affected by the condition?

It can affect children of any age, even newborns. Tumour types are different at the different stages of life (newborns, young children and adolescents). Haemangiomas (benign tumours) are more frequent in premature children. Some malignant tumours are associated with liver and metabolism diseases, as well as genetic and hereditary syndromes or with vascular anomalies.

Diagnosis

The tumour is generally detected by the primary care paediatrician, who will refer the patient for evaluation. Diagnoses can sometimes be established in a prenatal ultrasound or shortly after birth. Lastly, it can be detected in routine clinical controls in children with illnesses related to the development of these tumours. When the patient presents a malignant tumour, it will be important to complete the study of possible syndromes and related diseases.

Typical treatment

It depends on the type of tumour. In benign cases, it may consist of image controls, include pharmacological treatments or interventional radiology, and reserving surgery for very specific cases. In malignant tumours, surgery is essential for curing the patient and will be accompanied in general by chemotherapy treatment, which is administered before or after the intervention. In very advanced cases, liver transplants will be necessary.

Typical tests

Blood tests with tumour markers, an abdominal ultrasound and a magnetic resonance imaging scan are normally carried out. In order to plan surgery, it is usually necessary to carry out a CT scan. When there is a suspicion of malignancy, a chest CT will also be done and a small sample of tissue will be taken to know the exact tumour type.

Prevention

Unfortunately, there are no preventive measures. Unlike liver tumours in adults, closely related to the consumption of alcohol and viral infections (hepatitis), in children they are generally isolated cases. Only a small percentage of cases appear in children with illnesses and syndromes that predispose to their appearance, such as bile ducts atresia or some metabolic diseases, in which it is essential to monitor them so that, if they appear, they can be detected early.

Cutaneous melanoma is a cancer that originates in cells known as melanocytes. These cells produce melanin, which is why the tumours are usually coffee coloured or black, but they can also be pink, pale coloured or white. Overall, cutaneous melanomas represent approximately 1% of all tumours in both sexes, and every year 15 out of every 100,000 people are diagnosed, a figure that is increasing in nearly all European countries.

Cutaneous melanomas can develop on any part of the skin, but they are more frequent on the chest and back in men and the legs in women. The neck and face are other common sites. Having skin with a dark pigmentation reduces the risk of melanoma in these more common locations.

Melanomas are much less frequent than other types of skin cancer, but they are more dangerous, because they grow more quickly and they are very likely to spread to other parts of the body if they are not discovered and treated in time.

Symptoms

The first signs of a melanoma are as follows:

• A change in an existing freckle.
• The formation of a new lump on the skin that is pigmented or of unusual appearance.

Melanomas do not always start with a freckle: they can also appear on normal-looking skin and can form on any part of the body. They very often appear on parts of the body that have been exposed to the sun, such as a person’s back, legs, arms or face. They can also occur on parts that have little exposure to sunlight, such as the soles of the feet, the palms of the hands and in the nail beds. These hidden melanomas are more frequent in people who have darker skin.

Who is affected by the condition?

In Spain, the condition especially affects women, with an average initial-diagnosis age of 55, and men at an average age of 57. For white individuals, the incidence of cutaneous melanoma is increasing at an alarming rate, in all Cancer Registries. In Europe, it is the ninth most frequent cancer, with around 200,000 cases diagnosed every year. Although it only represents between 1.5 and 1.7% of skin cancers, it is responsible for 65% of deaths from skin cancer. This figure is stable in spite of the increased incidence, probably because of early diagnosis, which is the most important factor, and improvements in treatment.

The reason why melanoma occurs is unclear, although some risk factors have been identified, which should be taken into account:

• Exposure to ultraviolet light: Sunlight increases the risk of melanoma, especially if sunburn occurs, and still further during childhood. Tanning booths should also be avoided.
• Freckles: Someone who has a lot of freckles is more likely to suffer melanoma.
• Type of skin: People with fair skin are at a higher risk.
• Family history of melanoma: The risk of suffering a melanoma is greater if one or various first-degree relatives have had one. Approximately 10% of all people with melanoma have a family history of this illness.
• Personal history of melanoma or other skin cancers: Someone who has already suffered a melanoma has a higher risk of suffering it again.
• Weakened immune system: People with a weakened immune system, due to certain illnesses or medical treatments, are more likely to suffer from the illness.
• Advanced age: Melanoma is more likely to be present in people of more advanced age, due to accumulated sun damage.

Diagnosis

It is usually diagnosed after observing a suspect freckle that presents alterations known as (1,2,3,4):

1. Asymmetrical shape.
2. Irregular or poorly-defined edges
3. Changeable colour that varies according to the areas.
4. Its evolutionary dynamics, such as itching, bleeding, etc.

For this reason, if a new, unusual freckle is found, or a change is noted in an existing one, it should always be examined by a dermatologist, as early diagnosis is vital in this illness. The tests and procedures used to diagnose cutaneous melanoma include the following:

• Physical examination: The doctor will ask you questions about your medical history and examine your skin to search for signs that may indicate the presence of a melanoma.
• Extraction of a tissue sample for analysis (biopsy): In order to determine whether a suspect cutaneous lesion is a melanoma, the doctor may recommend the extraction of a skin sample for analysis. The sample is sent to a laboratory for examination.

Typical treatment

The recommendations for treatment depend on many factors, such as the thickness of the primary melanoma, the possibility that the cancer has spread or the presence of specific genetic changes in the melanoma cells, among others.

However, surgery is the main treatment against local and regional melanoma. It may also be an option for combating metastatic melanoma. If surgery is not an option, the melanoma can be called “unresectable”. In order to recommend a specific treatment plan, the doctors will take into account the state of the illness and the risk of relapse in each person. Subsequently, in accordance with the state, a systematic treatment can be indicated for a period of one year. In recent years, the treatment of melanomas that have spread extensively through the body has changed, as the newest forms of immunotherapy and targeted drugs have proven to be more effective than chemotherapy.

Typical tests

A complete physical examination must be conducted, including a general examination of the skin. The purpose of these tests is to identify risk factors and signs or symptoms that may indicate that the melanoma has spread beyond the original site. For most low-risk melanomas, less than 1 mm thick, it is generally unnecessary to carry out an additional search for metastasis or spreading.

In the case of people with high-risk melanoma, more exhaustive tests may be considered, including the following:

• Ultrasound: Creating an image of the internal organs.
• Exploration using computed tomography (CT): Creating images of the internal body using X-rays, taken from different angles. If the melanoma has spread, it can be used to measure the size of the tumour.
• Magnetic resonance (MRI) This uses magnetic fields instead of X-rays, in order to produce detailed images of the body, and it can be used to measure the size of the tumour.
• Exploration via positron emission tomography (PET) or PET-CT: This is a way of creating images of the organs and internal tissues. A small quantity of a radioactive sugar is injected into the patient's body. This is absorbed by the cells which use the highest amount of energy. Subsequently, a scan detects this substance in order to generate images of the internal body.

Prevention for reducing the risk of melanoma appearing

- Limiting exposure to ultraviolet rays.

• Seek out shade and avoid direct exposure to sunlight between 11 am and 6 pm.
• Use hats, caps, shirts or tee-shirts with solar filters.
• Use sunglasses.
• Use sun protection, several times, every day of the year, even on cloudy days.

- Avoid tanning booths.

- Protect children from the sun, to avoid sunburn.

- Pay attention to unusual freckles when examining your skin. If in doubt, it is always a good idea to make an appointment with a dermatologist, for a thorough check up.

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