Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers.

The assessment of complexity in internal medicine patients. The FADOI Medicomplex Study.

BACKGROUND: Although the number of elderly people is progressively increasing in the world, old and very old patients have been under-represented and understudied in trials evaluating the efficacy of chronic illness management models. The usual hospital indicators and practice guidelines do not consider the effects of complexity - co-morbidity, social support, functional and cognitive status, patient adherence to therapy, risk of adverse drug reactions - in these subjects. The aim of this observational, multi-centric cohort study was to carefully assess factors contributing to the complexity of care for patients admitted to internal medicine wards. This was done by evaluating the severity of disease and degree of stability at admission, co-morbidity, age-related impairments, and the need for discharge planning plus post-discharge support. METHODS: A total of 386 patients from 11 internal medicine wards in Emilia-Romagna and Marche, Italy, enrolled in a given week were evaluated. At admission, the following variables were recorded: demographic characteristics, medical history, global clinical-social prognostic evaluation, co-morbidity, severity of illness, presence of shock or hemodynamic instability, coma, and frequencies and causes of unscheduled hospital re-admission. RESULTS: Cancer, congestive heart failure, pneumonia, stroke, and chronic obstructive pulmonary disease were the most frequent primary diagnoses. The complexity of our case study was characterized by several concomitant diseases. Over 50% of the patients were considered severe or more than severe, and over 20% extremely severe, with very high co-morbidity indices and illness severity scores. Some 55% of our patients were in need of partial or total care; 10% had some speech impairment, and 63% needed in-home health care after hospital discharge. CONCLUSIONS: The increasing numbers of elderly patients admitted to internal medicine departments suggests the need for a chronic illness management model, integrating gerontological and geriatric care to improve outcomes. For effective care, future protocols need to take a multi-dimensional, interdisciplinary approach to these patients and to develop a coordinated, integrated plan for treatment and long-term follow-up.