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Updates in the diagnosis of hepatocellular carcinoma - Marilena Stoian

Updates in the diagnosis of hepatocellular carcinoma - Marilena Stoian

Name: Updates in the diagnosis of hepatocellular carcinoma - Marilena Stoian
Brand: Editura Universitară
SKU: 9786062816278
Price: 51.8 RON
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Publisher: Editura Universitară

Author: Marilena Stoian

Edition: I

Pages: 198

Publisher year: 2023

ISBN: 978-606-28-1627-8

DOI: https://doi.org/10.5682/9786062816278

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Hepatocellular carcinoma (HCC) is usually diagnosed late for two reasons: the absence of symptoms in patients with early disease and the reluctance of some clinicians to provide follow-up for patients at high risk of developing HCC. Here's why debates about the benefits of surveillance among high-risk people are needed. It is estimated that, in Western countries, less than one third of patients with cirrhosis are subject to active follow-up for the detection of HCC. This explains why many patients, at the time of hepatocarcinoma diagnosis, are in an advanced evolutionary stage. Another aspect of the causes of the severity of this form of carcinoma is the diagnosis of HCC, which can be difficult, often requiring the use of one or more imaging modalities. The goal of early, potentially curable diagnosis is to detect tumors when they are ≤2 cm in size, so that the full range of treatment options is available. The five-year survival rate for patients whose tumors are detected at an early stage and who receive treatment exceeds 70%. The late diagnosis of hepatocellular carcinoma during the evolution of primary liver diseases is responsible for a low survival rate: only 6 to 20 months, which gives it increased severity, with increased risk of mortality.

Updates in the diagnosis of hepatocellular carcinoma
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MARILENA STOIAN
Head of works - "Carol Davila" University of Medicine and Pharmacy, Faculty of Medicine, Bucharest
Primary internal medicine physician - Clinical Hospital "Dr. Ion Cantacuzino", Bucharest
Nephrology specialist doctor - Clinical Hospital "Dr. Ion Cantacuzino", Bucharest
Doctor of medicine
Internal medicine scientific research assistant - Academy of Medical Sciences, Romania
Master in Sociology - Management of Social and Health Services - University of Bucharest, Faculty of Sociology, Bucharest
Complementary studies / Competence in digestive endoscopy
Complementary studies/Competence in general ultrasound

INTRODUCTION / 9

CHAPTER I. DEFINITION AND EPIDEMIOLOGY / 13
I.1. Definition / 13
I.2. The clinical context of the appearance/development of hepatocellular carcinoma / 17
I.3. Epidemiology / 18
I.3.1. Incidence and mortality / 18
I.3.2. Geographical distribution / 20
I.3.3. Gender / 22
I.3.4. Year of birth / 23
I.3.5. Risk factors / 24
Bibliography / 43

CHAPTER II. CLINICAL AND PARACLINICAL DIAGNOSIS / 60
II.1. Introduction / 60
II.2. Clinical manifestations / 61
II.2.1. Non-specific symptoms and signs / 62
II.2.2. Clinical manifestations of cirrhosis / 62
II.2.3. Hepatomegaly / 62
II.2.4. Abdominal pain / 63
II.2.5. Digestive hemorrhage / 64
II.2.6. Jaundice / 64
II.2.7. Fever / 65
II.2.8. Invasion of the inferior vena cava / 65
II.3. Paraneoplastic syndromes / 66
II.4. Metastases / 69
II.5. Paraclinical diagnosis / 70
II.5.1. Laboratory analyzes / 70
II.5.2. Embryonic antigens / 70
II.5.3. Protein antigens / 73
II.5.4. Enzymes and isozymes / 76
II.5.5. Cytokines / 81
II.5.6. Genetic biomarkers / 82
II.5.7. Conclusions / 86
II.6. Histopathological diagnosis / 88
II.6.1. Liver biopsy: present and future / 88
II.6.2. Histopathological evaluation of HCC / 90
II.6.3. Histopathological variants of HCC / 91
II.7. Immunohistochemical diagnosis / 96
II.8. Molecular diagnosis / 101
II.9. The usefulness of histopathological, immunohistochemical and molecular diagnostic methods in the differential diagnosis of HCC / 102
II.9.1. Well-differentiated hepatocellular carcinoma versus hepatocellular adenoma / 102
II.9.2. Well-differentiated hepatocellular carcinoma versus focal nodular hyperplasia / 104
II.9.3. Well-differentiated hepatocellular carcinoma versus high-grade dysplastic cirrhotic nodule / 105
II.9.4. Hepatocellular carcinoma versus metastasis / 107
II.10. Diagnostic algorithm of hepatocellular carcinoma / 110
Bibliography / 111

CHAPTER III. IMAGING DIAGNOSIS / 135
III.1. The importance of diagnostic imaging / 135
III.2. Methods of imaging diagnosis / 139
III.3. Ultrasonography / 140
III.4. Computed tomography (CT) / 146
III.5. Nuclear magnetic resonance (NMR) / 150
III.6. Imaging diagnostic algorithm / 152
Bibliography / 155

CHAPTER IV. STAGING, PROGNOSIS AND SURVIVAL / 159
IV.1. CLIP score (Cancer of the Liver Italian Program) / 161
IV.2. BCLC classification (Barcelona Clinic Liver Cancer) / 161
IV.2.1. Albumin-bilirubin score (ALBI) / 162
IV.2.2. The choice of the staging system / 163
IV.3. Other factors influencing survival / 163
IV.3.1. Incident / 163
IV.3.2. Tumor histology / 164
IV.3.3. The serum level of alpha-fetoprotein / 164
IV.3.4. Hepatitis B and C / 164
IV.4. Antiviral therapy for HBV/165-related hepatocellular carcinoma
IV.4.1. Diabetes mellitus / 165
Bibliography / 166

CHAPTER V. SCREENING OF HEPATOCELLULAR CARCINOMA / 168
V.1. General information / 168
V.2. The surveillance intervals proposed by the screening programs / 171
V.3. Types of screening tests / 171
V.4. Practical aspects of screening tests / 174
V.5. Characteristics of screening tests / 176
V.6. Hepatocellular carcinoma screening candidates / 176
V.8. Guideline recommendations in hepatocellular carcinoma screening / 183
V.8.1. Screening recommendations for cirrhotic adults / 183
V.8.2. Screening recommendations for non-cirrhotic adults / 186
V.9. Conclusions / 189
V.10. Recommendations / 191
Bibliography / 192

Liver cancer is a major contributor to the burden of cancer worldwide. The incidence rate of this disease has increased in many countries in recent decades. Being the main histopathological type of liver cancer, hepatocellular carcinoma (HCC) represents the vast majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, currently, the most important worldwide risk factors for HCC, but their importance will probably decrease in the coming years. The effect of hepatitis B vaccination in newborns, already observed in young adults in some countries, will be more relevant as the vaccinated subjects get older. In addition, effective treatments for chronic infections with both hepatitis B virus (HBV) and hepatitis C virus (HCV) should contribute to decreasing HCC rates associated with viral infections. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may together become the major cause of HCC globally. Excessive alcohol consumption also remains an intractable risk factor, as does aflatoxin contamination of food in some parts of the world. While significant efforts in early diagnosis and effective treatment are certainly necessary for HCC, primary prevention efforts aimed at decreasing the prevalence of obesity and diabetes, but also controlling the growth of mycotoxins are equally necessary.
Medical practice brings hepatocellular carcinoma to the attention of gastroenterologists, hepatologists and oncologists both through its increased incidence, but especially through its aggressiveness and increased risk of mortality. The data published by Globocan 2020 showed that 905,700 people were diagnosed with liver cancer and 830,200 people died globally in 2020; liver cancer was among the top three causes of cancer death in 46 countries, while the number of new cases and deaths from liver cancer could increase by >55% by 2040. Furthermore, liver cancer was the second most common cause of premature death from cancer in 2020, after lung cancer, with over 530,000 deaths among people aged between 30 and 69 years. Hepatic tumors occupy the 6th place in the world in the classification of oncological pathologies. In Europe, it affects approximately 10/1000 men and 2/1000 women. In the United States of America, it is estimated that around 25,000 men and 11,000 women get sick with liver cancer every year. Deaths caused by liver tumors are approximately 19,000 and 9,000 people/year respectively. The high frequency of liver cancer cases is mainly caused by the high incidence of hepatitis B and C virus infections, the average age of liver tumor diagnosis being between 40 and 50 years. The late diagnosis of hepatocellular carcinoma during the evolution of primary diseases is responsible for a low survival rate: only 6 to 20 months, which gives it increased severity, with increased risk of mortality.
Awareness of the risk factors of HCC is useful both in diagnosis and in order to institute surveillance. The etiopathogenic ensemble of hepatocellular carcinoma is represented by a great diversity of risk factors. Among these, we must specify: individual factors, which include genetic factors, which determine the individual genetic predisposition for the development of hepatocarcinoma, and advanced age; environmental factors, the category of factors that include hepatitis B (HBV) and C (HCV), aflatoxins generated by infectious pathogens, such as Aspergillus flavus, Aspergillus parasiticus and Aspergillus nomius, chronic consumption of alcoholic beverages, smoking (chronic smoking ); particular pathological conditions (liver diseases, metabolic and systemic diseases), such as non-alcoholic fatty liver disease (NAFLD – non-alcoholic fatty liver disease) and non-alcoholic steatohepatitis (NASH – non-alcoholic steatohepatitis), liver cirrhosis, primitive biliary cirrhosis, autoimmune hepatitis, hemochromatosis, type II diabetes and obesity. Liver cirrhosis is the main risk factor, surveillance of these patients from the point of view of carcinogenic risk is indicated in these patients. A tumor identified in the cirrhotic liver is more likely to be HCC than metastases or liver adenoma. However, the differential diagnosis must also include dysplastic cirrhotic nodular lesion
The non-invasive radiological approach is the gold standard in the diagnosis of HCC, in contrast to most other malignant tumors that require confirmation by performing a biopsy. Biopsy is indicated only in radiologically controversial cases or to prove HCC in non-cirrhotic liver. Ultrasonography is used for surveillance and the initial stage of diagnosis. For the surveillance of the cirrhotic patient, ultrasound is performed once every 6 months. If a suspicious focus is revealed, the subsequent approach is based on size. Either CT or MRI is indicated for mass lesions larger than 20 mm, while both methods are recommended for a nodule measuring between 10 and 20 mm. Nodules that are smaller than 1 cm are followed by US once every 4 months. Hypervascularity is a characteristic feature of HCC in CT and MRI. PET and CEUS may have an additional role in the diagnosis of HCC.
Advances in technology, such as mass spectrometry and next-generation sequencing, hold great promise for identifying new early diagnostic biomarkers for HCC. Circulating miRNAs are particularly interesting as a completely new class of biomarkers and may outperform traditional serum protein markers. Additional advantages are that some changes in miRNAs are detected early and in body fluids, so they can be easily monitored. However, even if any of the markers discussed work well as biomarkers, the therapeutic efficacy remains weak, especially in the absence of imaging. Therefore, new treatment options and new imaging modalities are desperately needed. Ultimately, new biomarkers may provide important clues to our understanding of oncogenesis and ultimately lead to better treatment strategies. Simultaneous progress in these many medical disciplines will hopefully initiate a change in the reserved prognosis of HCC patients.

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