Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view.

The alcoholic liver disease (ALD) is the leading cause of death from liver failure in Italy and worldwide. Ethanol abstention, a healthy diet, and a significant improvement of life-style are the mainstay of treatment for this disease. Currently, we do not have effective therapeutic options are at our disposal to restore and maintain an improved clinical status. Silymarin is a complementary and alternative medicine often prescribed and self-prescribed; it has anti-oxidant, anti-inflammatory, anti-fibrotic, and metabolic properties. It improves the laboratoristic values and the ultrasonographic grading of liver disease in case of steatosis/steatohepatitis. S-adenosyl-L-methionine (SAMe) is the principal biological methyl donor, and it is also a precursor of glutathione (GSH), essential for the anti-oxidant pathways. SAMe is particularly important for opposing the toxicity of free radicals generated by various toxins, including alcohol. An association between Silymarin and SAMe (labelled as a dietary supplement) has been recently brought to market, and seems to be promising. It could be beneficial in such cases of alcoholic hepathopathies. New therapeutic options are needed by hepatologists to successfully overcome a constantly growing disease.

Recurrent hepatitis C and non-alcoholic fatty liver disease in transplanted patients: a review.

Non-alcoholic fatty liver disease (NAFLD) is a common occurrence after orthotopic liver transplantation (OLT). The association steatosis/HCV determines important implications for clinical practice: steatosis accelerates the progression of fibrosis and reduces the likelihood of obtaining a sustained virological response (SVR) with antiviral therapy. In post-transplant HCV patients we have evidenced a strong correlation between body mass index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis. In subjects with BMI <25 and TGC <160 ng/mL, the chance of SVR was 48 times higher than that of non response. The chances of SVR and sustained biochemical response for patients with percentage of steatosis <15 were 12 times higher than that with higher percentage of steatosis. We can conclude how the amount of steatosis be noted specifically in biopsy examination reports of patients with relapse chronic hepatitis C and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and the response to antiviral therapy.

Human carcinogenesis and alcohol in hepato-gastroenterology.

Alcohol consumption is one of the top-10 risks for worldwide burden of disease. The International Agency for Research for Cancer affirmed that there was evidence for the carcinogenicity of ethanol in animals and classified alcohol consumption as carcinogenic for humans. Alcohol consumption causes cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum, liver, pancreas and female breast. Most alcohol-induced diseases increases in a linear fashion as intake increases: oral, oesophagus and colon cancer fall into this pattern: very little is known about safe margins of alcohol consumption. Given the linear dose-response relation between alcohol intake and risk of cancer, control of heavy drinking remains the main target for cancer control. European Code Against Cancer recommends keeping daily consumption within two drinks (20 g [corrected] of alcohol/day) for man and one drink for women and US Department of Health and Human Services suggest as a low risk, a maximum of 10 g [corrected] of alcohol a day in man and half of this in women.

Gastric precancerous changes: carcinogenesis, clinical behaviour immunophenotype study and surveillance.

Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Two-thirds of the GC patients are diagnosed in advanced stages, when surgery can only be a palliative. When the diagnosis is made at an early stage, the surgical treatment results in 10 years survival rates are higher than 85%. From the critical evaluation of the literature data we can affirm that there are some obstacles to an exclusive acceptance of the idea that the relation of Helicobacter pylori (H. pylori) infection with noninvasive (formerly dysplasia) or invasive neoplastic modifications solely develop by means of chronic gastritis with its atrophic evolution and achlorhydria. Intestinal metaplasia as a precursor of GC has been overemphasized and doubts persist about the real necessity to operate histologically a subdivision into subtypes. The extent of the metaplastic process is probably more important that the metaplastic subtype. The evaluation of the clinical behaviour shows how low grade noninvasive neoplasia is associated with or progressed to GC in about 9% of cases, while high grade noninvasive neoplasia is associated with or progressed to GC in about 75% of cases, thus proving to be a real histological marker of GC. The subdivision of the cases according to the TNM classification demonstrates that, in most of the cases, early GC is present (43/45: 95.5%). An appropriate endoscopy follow-up with biopsies according to well defined criteria increases the likelihood of invasive neoplasia being detected in its early stage with a better postsurgical prognosis. Noninvasive neoplasia is characterized by severe alterations of the immunophenotype profile in association with a high proliferation index and frequent p53 mutations. The choice to address the patients to surgical intervention could be made not only on the basis of histochemical techniques, but also with the help of immunohistochemical evaluations.

Role of chronic atrophic gastritis of the body-fundus and achlorhydria in the development of epithelial dysplasia and gastric carcinoma.

BACKGROUND/AIM: Chronic atrophic gastritis of the body-fundus with hypo-achlorhydria has been long since considered the precursor of gastric cancer (GC). A study has been made about the histological pattern of the body-fundic mucosa (oxyntic area) in course of preneoplastic lesions (epithelial dysplasia), associated or progressed to gastric cancer, in order to evaluate the real association with chronic atrophic gastritis and, therefore, with a reduced acid secretion. METHODOLOGY: The study of the histological condition of the body-fundic mucosa and of the acid secretion has been effected in 120 cases of epithelial dysplasia (ED) from January 1990 to November 1997. The casuistry is composed of 70 cases of low grade dysplasia (LGD) and 50 cases of high grade dysplasia (HGD). Gastric biopsy specimens were studied for dyspepsia: for each patient, at least 8 specimens were obtained from the lesion area and in surrounding areas. Besides, at least 4 biopsies have been performed in the opposite gastric region. ED diagnosis was effected according to well defined criteria. The histological study of gastric mucosa in gastritis was effected or revised in accordance with the updated Sydney system (Houston). Stimulated acid secretion was expressed as Maximal Acid Output (MAO), which is the amount of HCl produced in one hour, following stimulation with pentagastrin (6 micro-g/kg). The clinical outcome subdivision of ED was made using the criteria of Rugge et al. (12). RESULTS: HGD significantly associates with GC in comparison with LGD. The histological evaluation of the oxyntic area shows severe chronic atrophic gastritis (SCAG) in a low percentage of cases (15/120: 12.5%): LGD 9/70: 12.85% ; HGD 6/50: 12%. Complete achlorhydria has been noted in 5 cases of LGD and in 1 case of HGD only. In case of GC (43 subjects) SCAG has been evidenced in 10 cases and complete achlorhydria in 5 cases. CONCLUSIONS: From the data of the present experience emerges that the presence of SCAG of the oxyntic area in course of ED or early GC is limited to a low percentage of cases. Such concepts induce to modify some indications related to the endoscopic surveillance and, in accordance with the American Society of Gastrointestinal Endoscopy we are stating that there are no sufficient data to support subsequent endoscopic surveillance for the subjects with atrophic gastritis.

p53 and Ki-67 expression in epithelial gastric dysplasia and in gastric cancer.

BACKGROUND: The aim of this study was to examine p53 and Ki-67 expression in relation to high grade dysplasia (HGD) clinical behaviour. METHODS: A retrospective, cross sectional study was conducted on mucosal biopsies from the stomach of 38 consecutive cases of HGD (25 males, average age: 57.5). The studied samples are represented by gastric biopsies obtained in course of gastroscopy for dyspepsia (at least 8 biopsies). HGD diagnosis was done by experienced pathologists (MC, DG) according to Goldstein's criteria. There were 12 non-dysplastic controls (7 males, average age: 49.4). The immunohistochemical study has been led with the utilization of a p53-antibody. For the cell proliferation assay, the sections were incubated with the MM1 monoclonal antibody. The clinical outcome subdivision of HGD was effected using the criteria of Rugge et al. For the classification of gastric cancer (GC): UICC TNM. RESULTS: p53 positivity has been evidenced in 65.5% of cases, while hyperproliferation in 100% of cases. That independently of the clinical behaviour. CONCLUSIONS: p53 positivity has been found only in part of the HGD cases and moreover a number of HGD with low or absent p53 scores has been found associated with high proliferation indices independently of the clinical evolution. This dissociation of cell kinetics and p53 expression suggests that other genetic events contributing to unregulate cell proliferation may occur in these lesions.

[Helicobacter pylori and gastric carcinogenesis]. / Helycobacter pylori e carcinogenesi gastrica.

Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis Helicobacter pylori (Hp) induced in most cases. There are some obstacles to an exclusive acceptance of the idea that the relation of Hp with the preneoplastic/neoplastic changes solely develops by means of the chronic gastritis with its atrophic evolution and achlorydria. Hp may be considered a trigger by means of alteration of cellular synetics without any direct influence on genetic alterations. Under the push of an intense proliferation, the expression of typical antigens of the organ is progressively lost, with acquisition of antigens from other organs. Cellular dedifferentiation displayed, with the progressive increase of immature elements that progress to the more or less total disappearance of differentiated gastric cells or differentiating ones, with the formation of metaplastic/dysplastic clones or even neoplastic ones. The bacteria, together with other environmental factors and individual genetic susceptibility, determine the final risk for the development of gastric cancer. Considering that 1-2% of the Hp positive subjects are estimated to develop gastric cancer and that Hp is considered the cause of 75% of gastric cancer, the eradication of the infection, not only in the initial phases but even in those with preneoplastic changes, involves an advantage for the prevention of gastric cancer. For the prevention among the general population testing Hp-positive subjects for serum antibodies against CagA protein might represent an effective way of identifying patients in whom Hp eradication is advisable also in term of gastric cancer prevention.

[Endoscopic surveillance of precancerous changes in the stomach]. / Sorveglianza endoscopica delle modificazioni precancerose dello stomaco.

Undoubtedly, one of the most important achievements of gastroenterology is the demonstration that, for many pathological conditions with future neoplastic degeneration risk, a periodical endoscopic surveillance is a determining element for the restraining of possible evolutive complications. Nonetheless, it is to be considered how, during the last years, the prevention and follow-up procedures for the stomach disease have been sometimes emphasized. In fact, various recent evidences originated from precise scientific evaluations have contained same prevention strategic attitudes so as to reach the best cost-benefit ratio. In this survey the various gastric preneoplastic modifications, subdivided in precancerous conditions and lesions are examined and guidelines are proposed in order to offer quick and easily applicable solutions.

Collagenous colitis in symptomatic subjects without endoscopic morphologic evidence: case report.

Collagenous colitis (CC) is a rare pathology and, even though various etiopathogenetic hypotheses have been put forward, the etiology and pathology are still not well defined. We report the case of a female patient suffering from chronic watery diarrhoea, positive for guaiac-based fecal occult blood test and morphologically negative to endoscopic investigation, but histologically classifiable as CC. This case report suggests that the clinical history must lead towards the execution of a colonoscopy with bioptic samples done even on apparently normal mucosa. Furthermore, the clinic should always signal a suspect CC to the anatomopathologist in order to have a correct diagnosis.

[Gastric epithelial dysplasia]. / La displasia epiteliale gastrica.

Gastric epithelial dysplasia represents the only true histological marker of gastric cancer. In this bringing up to date, such subject is reproposed in consideration of taking into account the most recent acquisitions, subdividing gastric dysplasia into two degrees only: moderate and severe. For the first time an immunophenotypic study is made by means of the evaluation of gastric-entero-pancreatic antigens, which better identify the evolutive potential of the two degrees of gastric dysplasia and, furthermore, the clinical development is evaluated, thus showing the necessity of a strict endoscopic surveillance of such lesion.