Shirin Demma

Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

Background Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

Chronic hepatitis C: This and the new era of treatment

Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

The Immune System in Hepatocellular Carcinoma and Potential New Immunotherapeutic Strategies

Background Hepatocellular carcinoma is a major health problem worldwide and the third most common cause of cancer-related death. HCC treatment decisions are complex and dependent upon tumor staging. Several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Despite of only modest objective response rates according to the Response Evaluation Criteria in Solid Tumors, several studies showed encouraging results in terms of prolongation of the time to progression, disease stabilization, and survival. Cellular immunotherapy would improve the immune state and has potential in enhancing the therapeutic outcome for HCC patients. Materials and Methods A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” “molecular immunological targets,” “tumour-associated antigens,” “Tregs,” “MDSCs,” “immunotherapy.” Discussion and Conclusion. Treatment strategies combining blockade of immunoregulatory cell types such as Tregs and MDSCs and of inhibitory receptors, with vaccine-induced activation of TAA-specific T cells, may be necessary to achieve the most effective therapeutic antitumour activity in HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

“Dangerous Relationships”: Asthma and Substance Abuse

Commonly abused drug are cocaine, marijuana, cigarettes, heroin, and alcohol. The review emphasizes the importance for clinicians to be alert to the possibility of this substance as a precipitating factor for acute asthma. Substance use disorders to characterize illnesses associated with drug use. The use of drugs of abuse increases risk of developing more severe symptoms, higher frequency of exacerbations and having and significant effect on care resources due to clinicians visits and frequent hospital admissions. Abused drug has been shown to accelerate the decline in lung function and to increase numbers of life-threatening asthma attacks, and greater asthma mortality.

Management of Hepatocellular Carcinoma: An Update at the Start of 2014

Background: Over the past 15 years, the incidence of hepatocellular carcinoma [HCC] has more than doubled. Materials and methods: A search of the literature was made using cancer literature and the PubMed, Scopus, and Web of Science [WOS] database for the following keywords: “hepatocellular carcinoma”, “molecular hepatocarcinogenesis”, “RFA”, “TACE”, “TABE”, “OLTx”, “targeted therapy”, “sorafenib”, “sunitinib”, “tivantinib”, “antiangiogenic” “drugs”, “immunotherapy”. Discussion and conclusion: For a correct and effective treatment strategy in patients with cirrhosis, it is necessary to perform a liver ultrasound twice a year. With the recent dramatic advances in diagnostic modalities, the diagnosis of HCC is primarily based on imaging. Ultrasound plays a crucial role in HCC surveillance, dynamic multiphasic multidetector-row CT [MDCT] and magnetic resonance imaging [MRI] are the standard diagnostic methods for the noninvasive diagnosis of HCC. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension and the underlying degree of liver dysfunction, as well as local expertise, as indicated by the NCCN, APASL, AASLD, BCLC,EASL. Unfortunately, HCC is diagnosed at an advanced stage. In this case the therapeutic option is the systemic therapy. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways. Thus, it will be necessary in the future to classify HCCs into subgroups according to their genomic and proteomic profiling. The identification of the key molecules/receptors/signaling pathways and the assessment of their relevance as potential targets will be the main future challenge. Defining molecular targeted agentseffecttive for a specific subgroup will hopefully lead to personalized therapy.

Disabling inflammatory pathways with biologics and resulting clinical outcomes in severe asthma

Introduction: Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent hospital admissions and requirement for intensive and expensive medications. There is a compelling need for more effective and safer therapies to help severe asthma sufferers to achieve adequate control of their disease. Areas covered: Expanding knowledge of innate and adaptive immune responses has led to development of new biologic approaches for severe asthma. Here, the authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma. Their specific role in distinctively targeted subpopulations of severe asthmatics will be also discussed. Expert opinion: Defining and phenotyping severe asthma patients will become increasingly important as some patients who were previously classified as having severe asthma may become well-controlled with a targeted phenotype-specific treatment. However, pharmacoeconomic concerns should also be taken into account given the elevated acquisition costs of recombinant human monoclonals and of the diagnostic screening procedures for the identification of potential responders.

Rare Benign Tumors of the Liver: Still Rare?

BackgroundBenign liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk. In fact, in most cases, benign liver tumors are not diagnosed because patients are asymptomatic. When they are detected, it’s usually because the person has had medical imaging tests, such as an ultrasound (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI), for another condition.Materials and methodsA search of the literature was made using cancer literature and the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatic benign tumors”, “hepatic cystic tumors”, “polycystic liver disease”, “liver macroregenerative nodules”, “hepatic mesenchymal hamartoma”, “hepatic angiomyolipoma”, “biliary cystadenoma”, and “nodular regenerative hyperplasia”.Discussion and conclusionHepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide. Approximately 750,000 new cases are reported per year. More than 75 % of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. The incidence of HCC is increasing in the USA and Europe because of the increased incidence of hepatitis C virus (HCV) infection. Unlike the liver HCC, benign tumors are less frequent. However, they represent a chapter always more interesting of liver disease. In fact, a careful differential diagnosis with the forms of malignant tumor is often required in such a way so as to direct the patient to the correct therapy. In conclusion, many of these tumors present with typical features in various imaging studies. On occasions, biopsies are required, and/or surgical removal is needed. In the majority of cases of benign hepatic tumors, no treatment is indicated. The main indication for treatment is the presence of significant clinical symptoms or suspicion of malignancy or fear of malignant transformation.

Emerging hepatic syndromes: pathophysiology, diagnosis and treatment

Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions.

An uncommon cause of syncope

The authors present a case of a man with recurrent syncopal episodes. The patient had been hospitalized twice before reaching a correct diagnosis. The syncope was originally ascribed to a sick sinus syndrome, which led to pacemaker implantation. Nonetheless, the patient relapsed with no evidence of pacemaker dysfunction, and was readmitted to the hospital where the likely cause for his symptoms was identified: an adenocarcinoma of the lung infiltrating the vagus and recurrent laryngeal nerves. No further syncopal episodes occurred after thoracic surgery. This syncope led to an early diagnosis of lung cancer leading to appropriate and life extending treatment.

Expansion of Access to HBV Treatment

Chronic hepatitis B is a substantial burden on health care systems. It will remain a cause of substantial morbidity and mortality for several decades, despite effective vaccination programs. Barriers to expanding therapy for hepatitis B in resource-limited settings include a limited understanding of the prevalence of the disease and its distribution, limited data on treatment efficacy in low income countries, and limited infrastructural resources to perform appropriate diagnostic and monitoring assays. Surveillance for hepatitis B virus (HBV) varies widely in its methods and completeness. Antiviral treatments for hepatitis B have reduced in costs and have become affordable through generic production and subsidies. Antiviral therapy can be targeted to the active phases of CHB when the risk of disease progression is higher. Effective treatments for hepatitis B exist, but a delivery gap exits. As with HIV—AIDS, partners are required to assist countries to implement operational plans to define their hepatitis B treatment programs. There has to be a fundamental acceptance that viral hepatitis, which can be treated, leads to high numbers of deaths annually—despite the advent of HBV vaccination and effective treatments.