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.

HBV- and HCV-related infections and risk of pancreatic cancer.

Pancreatic carcinoma is one of the most lethal cancers in humans. The poor prognosis of this malignancy depends on several factors, such as: lack of early symptoms, advanced stage at detection, early metastatic spread and no effective systemic treatment. To date, only few risk factors for this malignancy are known; therefore, considerable efforts are required to identify additional causative agents involved in the process of pancreatic carcinogenesis. In the last years, a large series of epidemiological investigations have suggested that both bacteria and viruses may play a important role in the initiation and progression of several animal and human cancers. In particular, some studies have showed that hepatitis B (HBV) and hepatitis C (HCV) viruses, two hepatotropic pathogens with well-known oncogenic properties for liver, may be detected also in extra-hepatic tissues, such as pancreas. The aim of this paper is to briefly report the results of available studies, assessing the possible association between HBV/HCV and pancreatic cancer development as well as to discuss the limiting factors of these researches.

Vitamins in the treatment of chronic viral hepatitis.

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic infections represent a major health problem worldwide. Although the efficacy of HBV and HCV treatment has improved, several important problems remain. Current recommended antiviral treatments are associated with considerable expense, adverse effects and poor efficacy in some patients. Thus, several alternative approaches have been attempted. To review the clinical experiences investigating the use of lipid- and water-soluble vitamins in the treatment of HBV- and HCV-related chronic infections, PubMed, the Cochrane Library, MEDLINE and EMBASE were searched for clinical studies on the use of vitamins in the treatment of HBV- and HCV-related hepatitis, alone or in combination with other antiviral options. Different randomised clinical trials and small case series have evaluated the potential virological and/or biochemical effects of several vitamins. The heterogeneous study designs and populations, the small number of patients enrolled, the weakness of endpoints and the different treatment schedules and follow-up periods make the results largely inconclusive. Only well-designed randomised controlled trials with well-selected endpoints will ascertain whether vitamins have any role in chronic viral hepatitis. Until such time, the use of vitamins cannot be recommended as a therapy for patients with chronic hepatitis B or C.

[Obesity and metabolic syndrome: clinical and therapeutic review]. / Obesità e Sindrome Metabolica: considerazioni cliniche e terapeutiche.

The recent ATP III classification defines metabolic syndrome as including > or = 3 of the following characteristics: abdominal adiposity, atherogenic dyslipidemia, high blood pressure, and insulin resistance. In these patients the visceral fat may produce inflammatory cytokines that may account for an enhanced cardiovascular risk. The treatment of obese patients is complex and often ineffective: patients may initially reduce weight but subsequently regain or even increase it, according to the so-called "yo-yo syndrome". Given the difficulties of treatment of patients with increased BMI, visceral adiposity, or metabolic syndrome, a multidisciplinary approach to these patients may yield more frequent positive results. The different strategies that may be applied, in varying mix targeted to the individual patient, include diet, drugs, educational and psychological support and, in few selected cases, surgery.

Laparoscopic adjustable esophagogastric banding: preliminary results.

BACKGROUND: Laparoscopic gastric banding is effective in surgical treatment of morbid obesity, but has had the drawback of specific complications, like slippage and gastric erosion. To prevent such complications, modifications have been used, including high retrogastric positioning above the bursa omentalis, complete anterior fixation by gastro-gastric stitches over the band, and reduction of the pouch volume to < or = 15 ml. These technical variants may induce dysphagia. METHODS: We adopted a different technique, consisting of placement of the band (9.75 cm BioEnterics Lap-Band) around the esophagus just above the cardia, to induce an amplification of the dysphagic mechanism. No fixation stitches were used. RESULTS: From January 1999 to March 2001, 80 consecutive patients (16 males, 64 females, mean age 41 years, average BMI 45) were operated this way. All operations were completed laparoscopically. However, in 1 patient the procedure had to be interrupted for bleeding from a large fatty liver injury by the retractor. Complications included 2 cases of slippage: an early one after 24 h, requiring surgical removal, and a late one after 9 months, treated by laparoscopic repositioning. The third complication, a reactive esophageal stenosis, occurred in a transsexual male on estrogen treatment, that needed replacement with a wider Swedish band. Band adjustment was required in 28 patients, one time in 22 cases and twice in the other 6. Mean BMI decreased from 45 to 38 after 6 months, remaining at 37 after 24 months, while excess weight was reduced by 50% at 24 months. CONCLUSIONS: The technique has a re-educational function, in that patients are induced to chew thoroughly, to introduce small morsels of food and to prolong the mastication time, in order to avoid dysphagia. Laparoscopic adjustable esophagogastric banding gave no problem if well positioned, and promoted new alimentary habits through a dysphagic mechanisms, inducing significant excess weight loss.