The Cytokinome Profile in Patients with Hepatocellular Carcinoma and Type 2 Diabetes.

Understanding the dynamics of the complex interaction network of cytokines, defined as ''cytokinome'', can be useful to follow progression and evolution of hepatocellular carcinoma (HCC) from its early stages as well as to define therapeutic strategies. Recently we have evaluated the cytokinome profile in patients with type 2 diabetes (T2D) and/or chronic hepatitis C (CHC) infection and/or cirrhosis suggesting specific markers for the different stages of the diseases. Since T2D has been identified as one of the contributory cause of HCC, in this paper we examined the serum levels of cytokines, growth factors, chemokines, as well as of other cancer and diabetes biomarkers in a discovery cohort of patients with T2D, chronic hepatitis C (CHC) and/or CHC-related HCC comparing them with a healthy control group to define a profile of proteins able to characterize these patients, and to recognize the association between diabetes and HCC. The results have evidenced that the serum levels of some proteins are significantly and differently up-regulated in all the patients but they increased still more when HCC develops on the background of T2D. Our results were verified also using a separate validation cohort. Furthermore, significant correlations between clinical and laboratory data characterizing the various stages of this complex disease, have been found. In overall, our results highlighted that a large and simple omics approach, such as that of the cytokinome analysis, supplemented by common biochemical and clinical data, can give a complete picture able to improve the prognosis of the various stages of the disease progression. We have also demonstrated by means of interactomic analysis that our experimental results correlate positively with the general metabolic picture that is emerging in the literature for this complex multifactorial disease.

Cytokinome profile evaluation in patients with hepatitis C virus infection.

The ''omics sciences'' (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group's ''omics'' work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.

Cancer biomarker profiling in patients with chronic hepatitis C virus, liver cirrhosis and hepatocellular carcinoma.

The detection and diagnosis of hepatocellular carcinoma (HCC) at an early stage may significantly affect the prognosis of HCC patients. Thus, it is necessary to always identify novel putative markers for improving diagnosis. Hepatocarcinogenesis correlates with pathological hepatic angiogenesis. However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitis C (CHC) virus, liver cirrhosis (LC) and HCC. Our results demonstrated: i) high levels of hepatocyte growth factor (HGF) and prolactin only in LC and HCC patients, ii) high levels of soluble human epidermal growth factor receptor­2 (sHER-2/neu; ErbB-2), sIL-6Ra, leptin (LEP) and platelet endothelial cell adhesion molecule­1 (PECAM-1) in CHC, LC and HCC patients and iii) that sIL-6R correlated with the fibrosis stage in CHC patients, with Child­Pugh score in those patients with LC and with tumor size in those patients with HCC, confirming that this protein may be used as a predictor of liver damage and of inflammatory process leading to fibrosis, cirrhosis, and subsequently to cancer. Moreover, an interactomic study conducted using the Ingenuity Pathway Analysis (IPA) software proved the existence of a correlation between 5 significant proteins [ErbB-2, sIL-6Ra, prolactin (PRL), HGF and LEP] which are involved in the same metabolic pathways.

[Abdominal tuberculosis in a young immigrant patient: a clinical case]. / Tubercolosi addominale in un giovane paziente extracomunitario: descrizione di un caso clinico.

In developing countries, tuberculosis (TBC) is commonly associated with inadequate socio-economic and sanitary conditions. Currently, in Western countries, TBC is often linked with HIV infection, an ageing population or trans-global migration. Approximately two out of ten TB cases worldwide are extra-pulmonary, of which abdominal tuberculosis accounts for 11%-16%. The Mycobacterium tuberculosis complex involves the abdomen as primary or secondary localization (hematogenous spread or from pulmonary foci or infected neighbouring organs). Abdominal TBC can infect the gastrointestinal tract, peritoneum, mesentery, abdominal lymph nodes, liver, spleen, and pancreas. Diagnosis of abdominal tuberculosis is difficult because of vague and non-specific clinical features and due to the differential diagnosis with other granulomatous diseases such as Crohn's Disease. It is of great importance for clinicians to pay great attention to tubercular aetiology as a possible cause of gastrointestinal symptoms. Here we describe the clinical case of a young immigrant patient with intestinal TB for whom the wrong initial diagnosis led to a delay in the correct diagnosis and a worsening of the already serious general conditions.

Cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C infection.

Both type 2 diabetes (T2D) and chronic hepatitis C (CHC) infection are associated with increased risk of developing hepatocellular carcinoma (HCC). Cytokines are known to play an important role not only in the mechanisms of insulin resistance and glucose disposal defects but also in the pathological processes occurring in the liver during viral infection. We evaluated the serum levels of many cytokines, chemokines, adipokines and growth factors in patients with type 2 diabetes, CHC, CHC-related cirrhosis, CHC and type 2 diabetes and CHC-related cirrhosis and type 2 diabetes by BioPlex assay. The obtained data evidenced that the serum levels of some proteins are significantly up-regulated in all the patients or in those with only one disease and are often higher, even if in different amounts, when both diseases are associated. In particular, our results can be useful for the clinical monitoring of patients because they give specific information in regard to the progression from CHC to LC and CHD to LCD. Moreover, some molecules have shown significant correlations with clinical/biochemical data, suggesting the possibility to define mini-panels that can be used as specific markers for the different disease staging. However, our observations demonstrate that an integrated approach is much more powerful than isolated measurements to evaluate specific stages of these two complex pathologies (type 2 diabetes and chronic CHC hepatitis) alone or when they are concomitant in a patient. In fact it has emerged as an accurate, simple, specific, noninvasive, reproducible and less expensive method that, in future, could be included in routine clinical practice to monitor the association of type 2 diabetes and/or CHC to liver cirrhosis and, possibly, to cancer, and to improve the prognosis of these diseases.

Serum cytokine levels as putative prognostic markers in the progression of chronic HCV hepatitis to cirrhosis.

Hepatitis C virus (HCV) infection can present as an acute manifestation, and can lead to severe complications such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). It represents a global health problem because there is no vaccine currently available. Cytokines play an important role in viral clearance, infection control, inflammation, regeneration and fibrosis, and also are implicated in the pathological processes occurring in the liver during viral infection. Immunological markers of chronic HCV hepatitis progression as compared to cirrhosis and HCC would be extremely useful, particularly for distinguishing between the molecules produced during HCV-induced chronic inflammation and those secreted during cirrhosis and HCC. In this work, we evaluated the serum levels of several cytokines, chemokines and growth factors in 30 patients affected by chronic HCV (HC), 30 patients affected by HCV-related cirrhosis (LC) and 20 healthy, control subjects. We used a multiplex biometric ELISA-based immunoassay in order to identify molecules that might be useful for monitoring the progression of HCV to liver cirrhosis and, possibly, to cancer. Our results show that some pro-inflammatory molecules are significantly up-regulated, and play a role as immunological markers in the intermediate steps towards liver cancer, and that hepatocyte growth factor (HGF) is a specific marker of liver cirrhosis. Finally, these data will be used to define a cytokinome profile, which might prove useful for studies involving the transition of chronic inflammation to neoplastic processes.

Infected atrial myxoma: case report and literature review.

Myxoma is the most common type of cardiac tumour in all age groups. It may simulate infective endocarditis but is rarely infected. We describe one case of infected left atrial myxoma caused by Enterococcus faecalis. Combined therapy, consisting of surgical management and antimicrobial therapy, was used. Histological examination of the excised tumour revealed a typical myxoma with infiltrates of neutrophils. Few cases of infected atrial myxomas have been reported in the literature.

[Pathways for surgical antibiotic prophylaxis]. / Percorsi in antibiotico-profilassi chirurgica.

Surgical site infections (SSIs) are a notable cause of hospital morbidity and mortality. Antibiotic prophylaxis has demonstrated a significant reduction in infection rate in clean-contaminated surgery and in clean surgery to a limited extent. To make antibiotic prophylaxis effective it is necessary to choose the right antibiotic, to administer it preoperatively and maintain sufficient serum and tissue levels through the operation. Open issues remain: antibiotic prophylaxis duration in prosthetic surgery, its use in hernia repair, breast surgery and mini-invasive surgery.

[Multicentre survey of post-surgical infections in Campania (Italy)]. / Multicentre survey of post-surgical infections in Campania (Italy).

The aim of the study was to evaluate the incidence of post-surgical infections and to assess the way of managing antibiotic surgical prophylaxis. The survey was carried out by means of a questionnaire in order to obtain diverse information such as demographics, length of pre- and post-operative hospitalization, type of surgery, intervention duration, possible antibiotic prophylaxis and onset of post-surgical infections also monitored by post-discharge ambulatory controls. Four General Surgery and five Obstetrics and Gynaecology Departments in Campania (southern Italy) participated in the study, which was carried out in the period December 2001-January 2002. Overall, 410 questionnaires were collected referring to as many patients; antibiotic prophylaxis was performed in 385 (93.9%) patients. Antibiotic prophylaxis was generally managed not according to the general principles suggested by the international guidelines either for timing or for its duration or for the route of administration. Substantial differences were also noted in patient selection and antibiotic choice. Surgical site infections were recorded in 0.6% of patients undergoing clean surgery, in 5.3% of patients undergoing clean-contaminated surgery and in 3.2% of those undergoing contaminated surgery. Distant infections occurred in 1.8% and 6.5% in clean-contaminated and contaminated surgery, respectively. The results of the present study suggest the need of a continuous and accurate monitoring of post-surgical infections and the need to adopt appropriate guidelines to improve the management of surgical prophylaxis.