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Since the mid '90s, the concept of evidence-based medicine has grown exponentially, contributing to the advancement of personalized medicine, which considers the "female gender" as an extremely important area of customization, but orphan of targeted research. Strong evidence do exists demonstrating gender differences in bleeding risk associated with antithrombotic treatment, mostly related to lower values of body mass, organ size and renal function in women than men. Across clinical studies, the search for the specific risk of bleeding in the female vs male gender has gained attention only recently; therefore, data from different studies and relatively limited meta-analyses should be assessed carefully. As for antiplatelet therapy for primary prevention, the risk of major bleeding events, such as cerebral hemorrhage, is lower for women than for men. Conversely, in acute situations in which antithrombotic drugs are given in association, the risk of bleeding is greater for women, in particular for combination therapies with heparin or low molecular weight heparin or thrombolytic agents. Numerous studies in the literature evaluated the incidence of minor and major bleeding during oral anticoagulant therapy in relation to gender, but the results are not entirely consistent and appear to vary over the years. In summary, there are some aspects of guidance in the complex spectrum of the bleeding risk related to antithrombotic treatment, with indications of a lower bleeding risk in women than men related to long-term preventive single antithrombotic drug treatments. In addition, hormonal effects and use of outprescribed drugs may also play a significant role in modulating hemostasis.

Between 1991 and 1998, 45 cirrhotic patients with hepatocellular carcinoma (1 or 2 lesions smaller than 5 cm) were treated either with percutaneous ethanol injection (26 patients) or with trans arterial chemoembolization (19 patients) in our Department. Percutaneous ethanol injection was performed on 37 nodules: mean diameter of 3.1 +/- 0.8 cm. Transarterial chemoembolization was performed on 27 nodules: mean diameter of 2.8 +/- 0.7 cm. Therapeutic success at first treatment was obtained in 81.5% of percutaneous ethanol injection treated lesions and in 60.0% of trans arterial chemoembolization treated lesions. Local recurrence after first treatment occurred in 7 of 22 percutaneous ethanol injection patients (31.8%) and 8 of 15 transarterial chemoembolization patients (53.3%). Distant hepatic recurrence after first treatment occurred in 16 of 26 (61.5%) alcolization treated patients and in 14 of 25 (56.0%) chemoembolization treated. Multivariate analysis selected therapeutic success and modality of treatment as the best predictor of better survival probability in all treated patients. Survival probability at 12/24/36/48 months was 96.1/80.8/61.6/42.3% in percutaneous ethanol injection group and 89.5/68.4/36.8/15.8% in transarterial chemoembolization group (p < 0.05 Log rank). Few data are available comparing the efficacy of percutaneous ethanol injection and transarterial chemoembolization in patients with hepatocellular carcinoma. Our data confirm that percutaneous ethanol injection is better than trans arterial chemoembolization in the treatment of patients with one or two lesions of hepatocellular carcinoma.

Hypoxic-ischaemic encephalopathy, the clinical neurological syndrome that follows birth asphyxia, is one of the main causes of neurological sequelae in term newborns. Despite the advent of new imaging and neurophysiological techniques in the last two decades, the value of the neurological assessment of the newborn has not been reduced. The possibility to perform easily serial neurological evaluations allows a detailed and non-invasive follow up of the early developmental processes, providing reliable prognostic information. In this paper we report our experience and a more general review of the literature on the prognostic value of the neurological assessment in term newborns with hypoxic-ischaemic encephalopathy.

The present study, performed in the Department of Internal Medicine and Gastroenterology of Policlinico of Modena, shows the results of the treatment with percutaneous ethanol injection of cirrhotic patients with hepatocellular carcinoma. In the period between June 1991-May 1998, 37 nodules of hepatocellular carcinoma, in 26 cirrhotic patients, were treated with ethanol injection under the ecographic guidance; the total number of sessions was 179. Ten lesions were recurrences (local or distant) in patients already treated. These patients were excluded from surgical treatment because of the high age, the high surgical risk or patient's choice. "Therapeutic success", defined as radiologic (TC or RM) demonstration of complete necrosis at the end of the first cycle of treatment, was achieved in 22/27 nodules after the first treatment (81.5%). Therapeutic success of the recurrence (second treatment) was achieved in 7/10 nodules (70%). In treated patients, survival probability (obtained with Kaplan Meier method) was 84.5%, 73.0%, 50.0%, 38.5%, 26.9%, respectively at 1st, 2nd, 3rd, 4th and 5th year. After a total number of 179 sessions, there were no relevant complications. The results obtained in our experience prove the efficacy and safety of this therapeutic technique in patients with cirrhosis and hepatocellular carcinoma.

211 patients were submitted to percutaneous ultrasound-guided liver biopsy: 184 patients (87.2%) had only one focal lesion, the other 27 had two or more lesions. In 9 patients (4.27%) the material drawn out from the liver was not adequate for microscopic examination (Retrieval Rate 95.7%). Histological evaluation revealed: absence of neoplasm in 67 patients (31.75%), benign lesion in 29 patients (13.74%), primitive malignant lesion in 70 patients (33.18%) and metastatic malignant lesion in 36 patients (17.06%). Combining the histological data with disease manifestation, biopsy showed a sensitivity of 95.1%, specificity of 100%, positive predictive value of 100%, negative predictive value of 89.4% and a diagnostic accuracy of 92.4%. None of the most important complications described in literature was observed. Our study confirms that ultrasound guided biopsy is a procedure of high diagnostic value in patients with nodular liver lesions, advantageous for its simplicity, low cost and safety.

Spontaneous bacterial perionitis (SBP) is a relatively frequent complication of liver cirrhosis and is associated with a high mortality if not early recognized and immediately treated. The text-books of Medicine available in Italy suggest the use of traditional laboratory tests (gravity, total protein concentration, Rivalta's test) to whom add white blood cell count for the assessment of the nature transudative (not infected) or exudative (infected) of ascitic fluid; nevertheless, in every day clinical practice, the association between total protein concentration and type of ascitic fluid may be misleading with respect to the diagnosis of SPB. The aim of this retrospective study, undertaken on 86 patients with liver cirrhosis consecutively admitted and separated in two groups, one without and the other with PSB (white blood cell count > 500/mm3), was to identify criteria for diagnosis of PSB. The traditional laboratory tests were significantly different in the two groups but Rivalta's test. Yet, none of them showed a diagnostic measurement sufficient for the use in the diagnosis of PSB (positive predittive value: gravity 41%, Rivalta's test 36%, total protein concentration 40%). The results of this work show the traditional laboratory tests unable to define the nature of the ascitic fluid. For the diagnosis of PSB the only reliable parameter is the white blood cell count.

In about 50% of patients with liver cirrhosis, upper digestive bleeding is not due to oesaphageal varices rupture, but to a group of peculiar mucosal lesions usually referred as "congestive gastropathy" and "hepatogenic ulcer". The pathogenesis of such mucosal damage is still unclear: an important causative role is commonly thought to be played by portal hypertension, but the role of peptical pathway and of the mucosal barrier impairment must not be underscored as well. Aim of this study was to evaluate the effect of roxatidine in the long-term treatment of mucosal damage in 19 patients with liver cirrhosis. Patients showed a good tolerance and no side effects. The improvement of endoscopic pattern after a three months period of roxatidine therapy was statistically significant; moreover there was no occurrence of digestive bleeding. In conclusion, H2 antagonist may be considered as the drug of choice for the treatment of mucosal damage in patients with liver cirrhosis, for both its safety and effectiveness.

The cases of two patients with liver cirrhosis HCV-related, admitted in our Department in consequence of the development of ascites, anemia and clinical deterioration, are reported. Both patients had all major risk factors for hepatocellular carcinoma and anamnestic and physical findings suggesting this diagnosis; nevertheless, the alpha-1-fetoprotein serum levels and the ultrasonographic findings were not diagnostic for primary hepatic neoplasm. Explorative paracentesis was diagnostic, demonstrating the presence of hemoperitoneum (the hematocrit ratio in the ascitic fluid was 12 and 10, respectively). Magnetic resonance revealed extensive diffuse hepatocellular carcinoma on both cases. Hemoperitoneum, in patients with liver cirrhosis, in face of non diagnostic levels of alpha-1-fetoprotein and ultrasonographic findings, can be indicative of the spontaneous rupture of a diffuse type of hepatocellular carcinoma.

Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro-duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal pain and diarrhea and stopped treatment. Three months later, a new endoscopy was performed in the 11 patients that completed the study (3 patients were lost at follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6 patients (55%), with complete absence of mucosal lesions in 2 patients (P = 0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had digestive bleeding during treatment. Digestive bleeding is a common complication of liver cirrhosis, originating in about 50% of cases from gastro-duodenal mucosal damage. Misoprostol suggests itself as a possible alternative therapy to the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but individual intolerance is frequent and must be preliminary excluded.

Diagnostic techniques as a whole and periodic ultrasonography (US) in particular frequently allows tumors < 3 cm (small hepatocellular carcinomas) to be detected in patients suffering from liver cirrhosis. Multifocal diseases are a major limitation to surgery. Recently, MR imaging has shown its capabilities in the diagnosis of small hepatocellular carcinomas. In our study the diagnostic value of MR imaging was compared with that of US, of pre- and post-contrast CT, of digital angiography and of CT after lipiodol injection (Lipiodol CT). The morphologic and signal intensity MR features of small hepatocellular carcinomas were investigated. Fifteen cirrhotic patients with 31 nodules of hepatocellular carcinoma < 3 cm were examined. All patients were studied with US, MR imaging, angiography and Lipiodol CT; 12/15 patients underwent CT. Histologic confirmation was obtained in 12 nodules (2 at surgery and 10 by means of percutaneous biopsy); in the extant 19 cases the diagnosis was made by combining US, CT, MR, angiographic and lipiodol-CT findings; in 9 tumors < 1 cm Lipiodol retention one month after angiography was considered as diagnostic. MR imaging detected 21/31 nodules (63%), US 22/31 (66.6%), CT 12/24 (50%), angiography 24/31 (74%), lipiodol CT 29/31 (92.5%). Mc Nemar test showed no difference in sensitivity between MR imaging and CT, MR and angiography, MR and US, lipiodol CT and angiography; however, the differences between the detection rates of MR imaging and Lipiodol CT and CT and lipiodol CT and US were statistically significant (p < 0.05). The difference in sensitivity between the detection rates of lipiodol CT and US was just above the threshold value which is usually considered significant (p = 0.065). One false positive was observed on US and none with MR, CT, angiography and lipiodol CT. On Se T1-weighted images 18 nodules were hyperintense, 2 isointense and 2 hypointense; on proton-density images 14 nodules were hyperintense, 7 isointense and none hypointense. On SE T2-weighted images 18 nodules were hyperintense, 3 isointense and none hypointense. A pseudocapsule was seen in 10/17 nodules (58%), especially on T1-weighted images. Accuracy and limitations of each technique and morphologic and signal intensity MR findings of small hepatocellular carcinoma are discussed. We believe that US is still the best diagnostic technique for the screening of hepatocellular carcinomas in cirrhotic livers.(ABSTRACT TRUNCATED AT 400 WORDS)

Two liver cirrhosis (LC) patients with all major risk factors for hepatocellular carcinoma (HCC) had, at presentation, serum alfa-fetoprotein levels (AFP) higher than 500 ng/ml, usually considered diagnostic for HCC. They had elevated serum ALT levels too. No neoplastic liver lesions were detected by imaging techniques in both cases. During the following three months we noted a progressive improvement of clinical conditions with contextual normalization of AFP and ALT values. Therefore we suggest, when AFP is strongly elevated in LC patients but no hepatic lesion is detectable, a check for AFP and ALT time-course, before diagnosis HCC.

Immunoglobulin (Ig) serum levels have been assayed in 729 patients with liver cirrhosis of different etiologies, in order to evaluate their prognostic value. Serum levels of three classes of Ig resulted mainly elevated in the three etiological groups (post-hepatitic, post-alcoholic, cryptogenetic) and they were significantly related to the severity of the liver disease, evaluated according to the Child-Turcotte score. The computerized analysis of the survival curves of patients with IgG, IgM, IgA values normal or elevated demonstrated an adverse prognostic rate in those with elevated Ig values. The difference among the survival curves, compared by the Lee-Desu method, was statistically significant (p less than 0.001). Our data suggest that the Ig levels can be considered as a prognostic index in liver cirrhosis patients.

In Italy the incidence of hepatocellular-carcinoma (HCC) in patients with liver cirrhosis is estimated approximately 5% per year. The new imaging technologies make it possible to perform screening programs for the early detection of HCC in these patients; early diagnosis of HCC is recommended as the best strategy in order to enable surgical approach, which seems to be the only effective therapy: screening programs must consider the cost-benefit ratio in the choice of patients and standards of investigation. In the Japanese authors' opinion all patients with liver cirrhosis must be screened every three months with an ultrasonographic liver examination (US) and a measurement of serum alpha-1-fetoprotein level (AFP) and every nine months with a computed tomography (CT) of the liver: at a 5% annual incidence of HCC the cost of a single diagnosis is estimated about 8000 +. In our opinion the cirrhotic patients in Child's C class (approximately 20%) can be excluded from the screening programs, since the survival expectation of these patients is always poor, whether HCC is present or not. Furthermore, considering the acknowledged reliability of the US in the detection of space occupying lesions of the liver, periodical CT examination seems to be unproductive. AFP has a low sensibility as a marker of HCC; nevertheless a progressive increase of its levels can be considered an index of possible blastomatous transformation of cirrhotic liver. In comparison with the Japanese screening programs, the proposed changes might obtain a 55% reduction of the cost of a single diagnosis of HCC, without significant diagnostic loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Unlabelled: Serum levels of gammaglobulins were evaluated in a population of 1334 patients with liver cirrhosis (mean age +/- SD 54.8 +/- 10.9; 898 males). Hypergammaglobulinemia was not as frequently observed as described in the literature 278 patients (20.8%) had gammaglobulin levels lower than 1.5 g/dl (first group) and the other 1056 had more than 1.5 g/dl of gammaglobulins (second group). At analysis of survival curves the first group had a median survival time of over 60 months, significantly higher than the 37.6 months of the other patients, when compared with the Lee-Desu statistic (p less than 0.01). Moreover, the patients of the first group had a lower incidence of ascites as compared to the second group (28% versus 45%; p less than 0.001), hepatic encephalopathy (7% versus 14%; p less than 0.01) and hepatocellular carcinoma (5.7% versus 8.4%; n.s.). The presence and the degree of oesophageal varices were significantly lower in the patients of the first group than in the others (p less than 0.001); a number of laboratory tests for the evaluation of liver cell function and the Child class distribution were more favourable in the first group than in that of hypergammaglobulinemic patients., In Conclusion: normal blood gamma globulin level is not uncommon in liver cirrhosis and it may be considered a positive prognostic factor, which identifies a group of patients with a better quality of life, a lower incidence of decompensation symptoms and a longer survival time.

The matter examined regards the possible prosthetic therapies in temporary emergency situations following paradontopathic tooth extractions, of which comparisons are made between the positive and negative aspects of realizable therapeutic processes. Considering the advantages of the type of prosthetic therapy chosen, the Author describes the entire therapeutic process, both clinical and technical, emphasizing its methodology and the equipment and materials required, which make it possible for the doctor himself to put it immediately into practice in his office.

Laboratory diagnosis of disseminated intravascular coagulation (DIC) in liver cirrhosis (LC) could be complicated by the presence of the usual decrement of the hemocoagulative parameters and of an increase of the fibrinogen/fibrin degradation products (FDP). The D-dimer test, more sensible than the one for FDP and specific for the cross-linked fibrin degradation products is now available. A significant difference between the two tests, assayed simultaneously has been demonstrated in 217 LC patients, without any recent or present hemorrhagic signs. The D-dimer was increased in only 60 of the 108 patients with high values of FDP; therefore this test has a screening value higher than FDP. If only the D-dimer is elevated, the FDP assay is indicated: if FDP are normal a thrombosis may be present and, finally, if the FDP are also increased with a concomitant decrement of fibrinogenemia, the laboratory diagnosis of DIC is reasonably certain.

The recent development of the duplex-Doppler technique, which combined real-time US with pulsed Doppler flowmetry, has allowed the flowmetric hemodynamic study of large abdominal vessels. As yet, however, both accuracy and possible applications of this method in the study of portal hypertension have not been fully investigated. This study was aimed at assessing whether or not the combined use of Doppler flowmetry and bidimensional US is able to detect portal hypertension in patients with liver cirrhosis (LC), and could therefore represent a valid alternative to endoscopic, angiographic, and direct pressure measurement techniques. Twenty-six patients with LC and 25 control patients were studied with a strictly standardized method; portal hypertension was detected in the patients with LC by EGDS and laparoscopy. The results demonstrated pulsed duplex-Doppler US to be able to detect portal hypertension in 92.4% of LC patients, with 2 false negatives only (7.6%). The difference in the flowmetric data of normal and LC patients was highly significant (p less than 0.001 Student's t test). In conclusion, duplex-Doppler US can be considered as a valid technique to detect portal hypertension in LC patients, and can thus be used as an alternative to more invasive techniques of general use in clinics.

107 (8.2%) of 1297 patients with liver cirrhosis admitted to our Clinic between 1980 and 1987 had hepatocellular carcinoma (HCC). This disorder was more frequent in patients with liver cirrhosis of dual etiology, alcoholic and post-hepatitic (9.9%), than in those with liver cirrhosis of unknown (7.82%), alcoholic (9.35%) or post-hepatitic (5.16%) etiology. The mean age of the patients with HCC of dual etiology (51.2 years) was significantly lower than that of the other three groups (61.0, 62.0 and 64.5 years, respectively; p less than 0.001). The conclusion is that in patients with liver cirrhosis of dual etiology the onset of HCC is frequent and precocious. This fact must be considered in epidemiological studies, in the prognosis and in the clinical management of the patient since early diagnosis is of importance in deciding therapy.