Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma.

The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.

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Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0.01 vs. controls). Significant elevation of FoxP3 was also detected. In conclusion, ipilimumab administration results in elevations of effector lymphocytes and pro-inflammatory mediators in the gut lamina propria.

Histone deacetylases (HDACs) have been associated with human malignant tumor development and progression, and HDAC inhibitors are currently being explored as anticancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression in human malignant and benign thyroid lesions. HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 74 patients with benign and malignant thyroid lesions. Enhanced HDAC-2 and HDAC-6 expression was significantly more frequently observed in malignant, compared to benign, thyroid lesions (p = 0.0042 and p = 0.0069, respectively). Enhanced HDAC-2, HDAC-4, and HDAC-6 expression was significantly more frequently observed in cases with papillary carcinoma compared to hyperplastic nodules (p = 0.0065, p = 0.0394, and p = 0.0061, respectively). In malignant thyroid lesions, HDAC-1, HDAC-4, and HDAC-6 expression was significantly associated with tumor size (p = 0.0169, p = 0.0056, and p = 0.0234, respectively); HDAC-2 expression with lymphatic and vascular invasion (p = 0.0299 and p = 0.0391, respectively); and HDAC-4 expression with capsular invasion (p = 0.0464). The cellular pattern of HDAC-1 and HDAC-2 distribution (nuclear vs. nuclear and cytoplasmic) presented a distinct discrimination between malignant and benign thyroid lesions (p = 0.0030 and p = 0.0028, respectively) as well as between papillary carcinoma and hyperplastic nodules (p = 0.0036 and p = 0.0028, respectively). HDAC-1, HDAC-2, HDAC-4, and HDAC-6 may be associated with the malignant thyroid transformation and could be considered as useful biomarkers and possible therapeutic targets in this neoplasia.

Hepatitis B virus (HBV) poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates, especially in developed countries. The best preventive method is vaccination. Patients with chronic renal disease should ideally be vaccinated prior to dialysis, otherwise, reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis. HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA, and liver enzyme testing and by liver biopsy. When needed, one must consider treating patients with tenofovir or entecavir rather than lamivudine. Depending on the cirrhosis stage, dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication. Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBsAg(-) recipients. Moreover, in the cases of immunized HBsAg(-) potential recipients with concurrent prophylaxis, we are enabled today to safely use renal grafts from both HBsAg(+) and HBsAg(-)/anti-HBc(+) donors. In so doing, we avoid unnecessary organ discarding. Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively. One of the most important issues in HBV(+) kidney transplantation is the duration of antiviral prophylaxis. In the absence of robust data, it seems that prophylactic treatment may be discontinued in selected stable, low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered. All immunosuppressive agents in kidney transplantation can be used in HBV(+) recipients. Immunosuppression is intimately associated with increased viral replication; thus it is important to minimize the total immunosuppression burden long term.

Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the "silent" clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the "beneficial" impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of "hepatoprotective" cytokines such as interferon (IFN)-α and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking.

Focal Adhesion Kinase (FAK) and Src have been reported to regulate tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate by immunohistochemistry the clinical significance of FAK and Src expression in 108 patients with benign and malignant thyroid lesions. Total FAK expression provided a distinct discrimination between malignant and benign (p = 0.00001), as well as between papillary carcinoma and hyperplastic nodules thyroid lesions (p = 0.00005), being also associated with follicular cells' proliferative capacity (p = 0.0003). In malignant thyroid lesions, total FAK expression was associated with tumor size (p = 0.0455), and presence of capsular (p = 0.0102) and lymphatic (p = 0.0173) invasion. Total Src expression was borderline increased in cases of papillary carcinoma compared to hyperplastic nodules (p = 0.0993), being also correlated with tumor size (p = 0.0169). FAK and Src expression was ascribed to a significant extent to the phosphorylated forms of the enzymes, which provided a better discrimination between malignant and benign thyroid lesions. The current data revealed that FAK and to a lesser extent Src expression could be considered of clinical utility in thyroid neoplasia with potential use as therapeutic targets.