[Colorectal cancer: prevention and screening]. / Il cancro del colon-retto: prevenzione e screening.

At present, colorectal carcinoma is one of the few types of cancer for which it is possible to carry out both primary and secondary prevention. Primary prevention involves following a correct diet and maintaining a healthy lifestyle. Secondary prevention includes carrying out appropriate diagnostic examinations on subjects at risk for this type of cancer. Randomized trials, cohort and case-control studies have demonstrated that mortality due to colorectal carcinoma decreases significantly when these screening tests are done. They include testing for fecal occult blood (if annual mortality reduction ranges from 25 to 33%), sigmoidoscopy (case-control studies have shown that this technique can reduce mortality by 60-80%), colonoscopy, and the double-contrast barium enema. Total effectiveness increases when these tests are used in combination. This review synthetically illustrates current knowledge of risk factors and the molecular genetics of colorectal cancer. It offers indications for primary prevention, investigates the effectiveness of each screening test used in secondary prevention, and presents the most highly accredited guidelines for surveillance of the at-risk population.

[Drugs inhibiting the hepatic fibrogenesis]. / Farmaci che inibiscono la fibrogenesi epatica.

The treatment of chronic liver disease represents still now an open problem in medicine. The first objective of therapy has to be the causal agent removal; however, there are many cases (viral infections, autoimmunity, genetic disease) in which it is not possible to reach this issue; in these situations the secondary objective of the therapy is to inhibit the hepatic fibrogenesis, in attempt of easing or blocking the transformation of chronic liver disease in cirrhosis. The aim of this work is to review the various compounds which showed an antifibrotic activity, using a simple classification model, allowing a fast setting of different compounds. These last, on the basis of their main action, can be divided into two main groups: drugs with direct action, which interfere with collagen metabolism (for instance interferons, glucocorticoids, prolyl 4-hydroxylase inhibitors, cyclosporin A, colchicine, D-penicillamine, phosphatidylcholine and so on) and drugs with indirect action, that decrease the inflammatory stimuli, capable of stirring up the fibrogenetic hepatic process (S-adenosylmethionine, malotilate, ursodeoxycholic acid, ribavirin and so on). There are drugs that have both mechanisms of action, without the prevalence of one or other mechanism (prostaglandins).

[Serum markers of liver fibrogenesis and fibrosis]. / Marker sierici di fibrogenesi e fibrosi epatica.

Serum levels of some extracellular matrix components increased in different liver diseases are studied. Hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PNIIIP) have been the most extensively studied serum components. In particular, serum levels of PNIIIP seem to be mainly correlated with histological activity in chronic hepatitis. Considering the close pathophysiological relationship between histological activity and fibrogenesis, it is possible to consider PNIIIP as a marker of fibrogenesis. Thus, serum PNIIIP could be a useful tool for monitoring the therapeutic response in patients with chronic hepatitis in treatment with antifibrogenetic and antifibrotic agents. Like PNIIIP, serum HA concentrations increase in patients with liver fibrosis. There is evidence that serum levels of HA are more strongly correlated with histological grades of liver fibrosis than serum PNIIIP. This suggests that serum HA may be preferable for discriminating patients with cirrhosis from those without cirrhosis. There are other extracellular matrix components and a combination of several serum markers could increase their diagnostic value, but further studies are needed to confirm this.

[The physiopathological mechanism of hepatic fibrosis]. / La fibrosi epatica ed il suo meccanismo fisiopatologico.

Liver fibrosis is the end result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. The extracellular matrix of the liver is complex. It comprises multiple components of three major types of macromolecules: proteins, glycoproteins and proteoglycans. The normal liver contains limited amounts of extracellular matrix composed of elastin, fibronectin, collagen, proteoglycans and other macromolecules. These molecules have specific structure-function properties. In the liver they provide a structural framework and modulate tissue repair. The fibrogenesis is a reaction to liver injury, it leads to marked impairment of hepatic sinusoidal blood flow and ultimately to cirrhosis associated with portal hypertension and hepatocyte dysfunction. The process of fibrosis is the result from complex interactions between extracellular matrix macromolecules, hepatic cells, cytokines and growth factors, that activate the stellate cells of the liver to induce the synthesis of extracellular matrix components that deposit into the local extracellular matrix and to produce the inhibitor of metalloproteinase. The end result of these activities is an imbalance in the synthesis/degradation homeostasis of the liver, that is, liver fibrosis.