Search

Contrast-enhanced ultrasonography (CEUS) is increasingly being performed in Italy and Europe, particularly in the field of hepato-gastroenterology. Initially, it was mainly carried out to characterize focal hepatic lesions, but, since then, numerous studies have demonstrated its efficacy in the differential diagnosis of focal pancreatic pathologies (D’Onofrio et al. in Expert Rev Med Devices 7(2):257–273, 2010; Vidili et al. in J Ultrasound 22(1):41–51, 2019). The purpose of this paper is to provide Italian Medical Doctors with recommendations and thereby practical guidelines on the management of these patients. The present paper reports the final conclusions reached by the SIUMB guideline commission. This paper addresses particularly percutaneous ultrasound (US) examination (transabdominal US) and is drawn up specifically for publication.

The present document describes the SIUMB (Italian Society of Ultrasound in Medicine and Biology) guidelines for the use of ultrasound in the management of focal liver disease. The aim of the paper is to provide a clinical practice guideline for Italian physicians who are approaching the ultrasound study of a focal liver lesion. In particular, these guidelines provide simple indications, recommendations and general practice advices for the correct use of contrast-enhanced ultrasound (CEUS) in this scenario. They represent the SIUMB position of the ultrasound role in the diagnostic flow charts of the principal focal liver lesions, and are in agreement with other, previously published national and international guidelines.

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74–1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p

Studies show that in emergency situations, like in the aftermath of natural disasters, people tend to self-organize into so-called ephemeral organizations and transitional communities based on common problems, common places, etc. Strict interactions among victims, fundamental to strengthen such small communities, may be efficiently supported by a new generation of mobile-empowered disaster management systems based on the social networking approach, with crowd-generated and geo-referenced data. In this paper we discuss how a shift of perspective in the interaction, conceptual, logical and physical models adopted for the social network can efficiently support the dynamic bonding/de-bonding/re-bonding of communities that emerge based on alliances around shared problems and/or objectives.

Background and aims Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. Methods Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50–75 years, BMI 20–45 Kg/m 2 , on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. Conclusions TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. Registration: Clinicaltrials.gov ID NCT00700856.

Objective: It is not known whether the presence of obesity is responsible for a more severe autoimmune thyroiditis and consequently for a higher prevalence of hypothyroidism. The present study was addressed to investigate this aspect in a cohort of subjects, all affected by autoimmune thyroiditis, with a wide range of Body mass index (BMI) in euthyroidism or subclinical hypothyroidism. Design: 311 subjects were enrolled : 160 of them underwent levothyroxine treatment, since they were affected by subclinical hypothyroidism, defined as having a TSH level higher than 4.0 µU/ml (Group 1); 151 subjects were affected by autoimmune thyroiditis, but they were euthyroid (TSH: 0.7- 3.0 µU/ml) (Group 2). Methods: Family and medical history were carefully evaluated in all patients and, in particular, metabolic and cardiovascular diseases were investigated. Serum concentrations of FT4, FT3, TSH, antithyroglobulin (Tg-Ab) and antithyroperoxidase antibodies (TPOAb) were measured in all patients. BMI was calculated and thyroid morphology was evaluated using a high-resolution 7.5-MHz linear transducer. Results: Obesity (BMI > 30.0) was present in 44.4% of patients (71/160) in Group 1, and only in 22.3% (29/151) of patients in group 2 (p

Although residential facilities (RFs) have largely replaced mental hospitals (MHs) in most developed countries for the long-term residential care of severely impaired patients, the process of care in RFs has not been well studied. The aim of this paper is to investigate the process of care in 265 RFs, representing 19.3% of all RFs in Italy, and to devise a classification of RFs based on process characteristics. Structured interviews were conducted with the manager and staff of each RF. Residents were evaluated using standardized rating instruments. Most RFs had specific admission criteria, with one third having a waiting list that averaged about 3 months. There was no formal limitation to the length of stay in three quarters of RFs, and turnover rates were very low. Although a homelike atmosphere was found in many RFs, most facilities had restrictive rules on patients’ daily lives and behaviours. RFs carried out several external activities targeted at integrating patients within the local community. Standardized assessment instruments and written treatment plans were rarely used. A cluster analysis based on the levels of restrictiveness and the standardization of the process of care classified RFs into five groups that differed with respect to daily staff coverage, size, geographical distribution and proportion of former MH residents. No significant intercluster differences were associated with the current clinical and psychosocial characteristics of residents, or with several other outcome variables. This study provides naturalistic evidence of the heterogeneity of the process of residential care on a large scale. Future efforts should focus on developing an empirical classification of RFs, as well as on national and international standards of care and staffing to address patients’ needs.

The occurrence of spontaneous, positional and paroxysmal positional nystagmus was studied in patients with end-organ lesions, and in subjects with drug-induced central vestibular nystagmus. Repeated vestibular examination using electronystagmography for assessment of spontaneous and positional nystagmus in the standard head positions was carried out. The findings indicate that the paroxysmal positional nystagmus is the most frequently seen nystagmus prior to its disappearance in end-organ induced nystagmus and also the most frequently seen in drug-induced nystagmus. The direction changing type of nystagmus was very frequently encountered in end-organ lesions. These findings indicate that the type of horizontal vestibular nystagmus by itself is of no diagnostic value in localizing the site of the lesion and that the various types reflect different degrees of vestibular compensation that occur prior to their disappearance. The value of various classifications of positional nystagmus lies mainly in that they help describe the nystagmus clinically.

Computer-supported collaborative inquiry-based learning (CSCIL) represents a form of active learning in which students jointly pose questions and investigate them in technology-enhanced settings. Scaffolds can enhance CSCIL processes so that students can complete more challenging problems than they could without scaffolds. Scaffolding CSCIL, however, would optimally adapt to the needs of a specific context, group, and stage of the group's learning process. In CSCIL, the stage of the learning process can be characterized by the inquiry-based learning (IBL) phase (orientation, conceptualization, investigation, conclusion, and discussion). In this presentation, we illustrate the potential of automatic content analysis to find the different IBL phases from authentic groups' face-to-face CSCIL processes to advance the adaptive scaffolding. We obtain vector representations from words using a well-known feature engineering technique called Word Embedding. Subsequently, the classification task is done by a neural network that incorporates an attention layer. The results presented in this work show that the proposed best performing model adds interpretability and achieves a 58.92{\%} accuracy, which represents a 6{\%} improvement compared to our previous work, which was based on topic-models. peerReviewed

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes. © 2016 Springer-Verlag Berlin Heidelberg

PURPOSE: Advanced hepatocellular carcinoma (HCC) not eligible for local therapies has limited chances of cure. Sorafenib is a multikinase inhibitor with proven activity in advanced HCC. Octreotide is used in this setting with conflicting results. Treatment with sorafenib and long-acting octreotide was tested in advanced HCC to evaluate safety and activity. METHODS: Fifty patients with advanced HCC, Child-Pugh A or B, received sorafenib at a dosage of 800 mg/day for 28 days with a following week of rest and long-acting octreotide at a dose of 40 mg, administered every 28 days. RESULTS: All patients were assessable for safety and efficacy. Sixteen patients out of 50 (34%) were naïve from other therapies, while all the others were previously treated with local and/or systemic treatments. We achieved 5 partial responses (10%), 33 stable diseases (66%) and 12 progressions of disease (24%). Median time to progression was 7.0 months (95% CI, 3.0-10.9 months), and median overall survival was 12 months (95% CI, 6.3-17.4 months). Treatment was well tolerated. Diarrhoea (6%) and hypertension (4%) were the most frequent grade 3 toxicities. CONCLUSIONS: Our data suggest that the combination between sorafenib and long-acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population.

OBJECTIVE. The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. MATERIALS AND METHODS. One hundred twenty-five patients (88 women, 37 men; age range, 17–76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2–90 mL; mean, 10.3 mL) were treated with PEI. There were 1–11 PEI sessions per patient (average, 3.9) performed, with injection of 1–14 mL of ethanol per session (total injected ethanol per patient, 3–108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9–144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. RESULTS. Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients—115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules ≤ 10 mL, 63 (94.0%) of 67; nodules > 10 to ≤ 30 mL, 32 (91.4%) of 35; nodules > 30 to ≤ 60 mL, 17 (89.5%) of 19; nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months’ follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up. CONCLUSION. PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Many women in the world are still undergoing female genital mutilations (FGMs) even if in almost all the countries, the practice of FGM is illegal. The increase of immigration, particularly from African Countries, to Europe, and Italy too, led to consider this phenomenon with particular attention and skill. All the operators in health services need to know the different types of FGMs and the related complications and the psychological and sexual sequels. Urological complications, in particular, are not rare and the changing anatomy of the external genital apparatus can also make the catheter insertion sometimes difficult. This review analyzes the epidemiology of FGMs, the reasons why the practice is still made, the complications, the ethical, and the principal legal aspects of this practise that must be hopefully early banned.

Background: We assessed the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant portal vein thrombosis in patients who had cirrhosis with hepatocellular carcinoma (HCC). Methods: Fifty-four consecutive patients who had cirrhosis, biopsy-proved HCC, and thrombosis of the main portal vein and/or left/right portal vein on US were prospectively studied with color Doppler US (CDUS) and CEUS. CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent (SonoVue, Bracco, Milan, Italy). Presence or absence of CDUS signals or thrombus enhancement on CEUS were considered diagnostic for malignant or benign portal vein thrombosis. Twentyeight patients also underwent percutaneous portal vein fine-needle biopsy (FNB) under US guidance. All patients were followed-up bimonthly by CDUS. Shrinkage of the thrombus and/or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered consistent with malignancy. CDUS, CEUS, and FNB results were compared with those at follow-up. Results: Follow-up (4 to 21 months) showed signs of malignant thrombosis in 34 of 54 patients. FNB produced a true-positive result for malignancy in 19 of 25 patients, a false-negative result in six of 25 patients, and a true-negative result in three of three patients. CDUS was positive in seven of 54 patients. CEUS showed enhancement of the thrombus in 30 of 54 patients. No false-positive result was observed at CDUS, CEUS, and FNB. Sensitivities of CDUS, CEUS, and FNB in detecting malignant thrombi were 20%, 88%, and 76% respectively. Three patients showed negative CDUS and CEUS and positive FNB results; follow-up confirmed malignant thrombosis in these patients. One patient showed negative CDUS, CEUS, and FNB findings. Howewer, follow-up of the thrombus showed US signs of malignancy. Another FNB confirmed HCC infiltration of the portal vein. Conclusion: CEUS seems to be the most sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis. Key words: Hepatocellular carcinoma, cirrhosis; —Ultrasound, contrast media—Color-Doppler-US—Fine needle Biopsy

Objective: Percutaneous ethanol injection (PEI) under general anesthesia (One-shot PEI) is a therapy for large and multiple hepatocellular carcinoma (HCC) by the injection of a large amount of ethanol into the tumor. We report our results with 5-year survival rates in patients with HCC on cirrhosis treated with One-shot PEI. Patients and methods: From October 1992 to March 1998, 268 cirrhotic patients (age 42–82 years; 191 males; 95 Child-Pugh's A class, 150 B and 23 C class of cirrhosis) with 515 HCC nodules underwent One-shot PEI. Diameter of HCC nodules ranged from 0.6 to 14 cm (mean 5.02±2.2 cm; median: 4 cm). One hundred and thirty-eight patients had a single nodule (range 3.2–14 cm; mean 5.6±2.1 cm), 130 had multiple nodules, up to six nodules (mean 2.9 nodules) (range 0.6–11 cm; mean 4.8±2.1 cm) Results: CT showed complete necrosis in 357/506 nodules (70%). Five patients (1.8%) with nine nodules died as a result of the procedure (variceal bleeding in three cases, liver failure in one and hemoperitoneum in one). The overall survival rates were 93, 83, 74, 65 and 59% at 1, 2, 3, 4 and 5 years, respectively. Survival rates were 90, 84, 82 and 82% at 12, 24, 36 and 48 months, respectively, in patients with a single nodule ≤5 cm, and 97, 71, 59, 59 and 59% at 12, 24, 36, 48 and 60 months, respectively, in patients with single nodule >5 cm. Patients with multiple nodules had survival rates of 97, 89, 75, 60 and 60% at 12, 24, 36, 48 and 60 months, respectively. Conclusion: PEI of large and multiple HCC showed survivals similar to conventional PEI for patients with smaller tumors.

Objectives: Our aim was to describe the hemodynamic patterns and assess the prevalence of reversal of flow (RF) in intrahepatic portal vessels (IPV) in patients with chronic active hepatitis (CAH) and patients with cirrhosis. Patients : 100 consecutive patients with CAH, and 178 consecutive cirrhotic patients (48 Child A, 114 Child B and 38 Child C class) underwent Echo-Color-Doppler for evaluation of flow direction in segmental IPV, right and left portal vein (RPV, LPV), in main portal vein (MPV), splenic vein (SV), superior mesenteric vein (SMV) and porto-systemic shunts (paraumbilical, spleno-renal, left gastric vein). The patients were followed-up clinically for 3-15 months. Results: Patients with CAH showed RF in SV in 1/100 and hepatopetal flow in MPV, SMV, SV, IPV in 99/100 patients. Eleven of 178 (6.2%) cirrhotic patients showed RF only in the SV, 3/178 (1.7%) showed alternating ('back and forth') flow only in IPV, RPV and LPV with continuous hepatopetal flow in PV and 10/178 (5.6%) showed completely RF in IPV. Four of ten patients of this last group showed hepatopetal flow in MPV. The other six patients showed RF in MPV associated with hepatofugal flow through a large left gastric vein in three cases and through the SV in three cases. The other cirrhotic patients (154/178=86.5%) showed hepatopetal flow in IPV, MPV, SMV and SV. In no case RF in SMV was observed. Prevalence of RF in IPV was significantly higher in Child C patients (8/31=25.8%) than Child B patients (5/104=4.7%) and than in Child A patients (0%) (p0.01). Prevalence of Child C class was significantly higher in patients with RF in IPV (8/13=61.5%) than in patients with RF only in extraepatic portal vessels (2/11=18.2%) and patients without RF (21/154=13.6%) (p0.001). No patient with RF in IPV was in Child A class. Incidence of death was significantly higher in patients with RF in IPV than in patients without RF and patients with RF only in SV. Conclusions: RF in IPV is not a rare event (9% in our series) that mainly occurs in cirrhosis with advanced liver function impairment. Copyright 1997 Elsevier Science Ireland Ltd.

Objective The inflammatory myopathies (IMs) are a group of disorders characterised by weakness and inflammation of the skeletal muscles. Muscle biopsy is the most crucial test to confirm the clinical diagnosis, but also the most common cause of misdiagnosis. There are currently no markers specific or sensitive enough to distinguish IMs from other diseases with similar clinical and morphological features, and an international multidisciplinary effort is under way to develop new classification criteria for IMs. Methods Standards for Reporting of Diagnostic Accuracy recommendations to validate a diagnostic test based on the quantification of internal major histocompatibility complex class I (MHC-I) positive fibres were adopted. MHC-I immunostained specimens from 64 patients were scored by two independent blinded investigators, and the percentage of positive fibres was determined. Agreement between investigators was evaluated with the k-weighted statistic. The receiver operating characteristic curve, area under the curve, sensitivity, specificity, and positive and negative predictive values of each percentage range of positive fibres versus the diagnosis of IM were calculated. Results The main difference between IM and non-inflammatory samples was the number of internal MHC-I positive fibres. The k-weighted value was 0.89 for a percentage of MHC-I positive fibres above 50%; the positive predictive value was 100%, and the negative predictive value was 94%. Conclusions This is the first study on the validity of a quantitative analysis of internal MHC-I positive fibres for an IM diagnosis performed according to Standards for Reporting of Diagnostic Accuracy recommendations. The interobserver agreement was almost perfect, thus making the method reproducible. Applying an MHC-I cut-off above 50% is an optimal marker for polymyositis (PM) and dermatomyositis (DM) diagnosis.

Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV). Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase. The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients. The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC.

Local therapies such as radiofrequency ablation (RFA) represent a valuable choice in limited hepatocellular carcinoma (HCC) and are increasingly used also in advanced tumors. Medical treatments generally gave frustrating results in advanced HCC especially if comorbidities exist. Several biologic non-chemotherapeutic drugs are currently tested in HCC and, among them, octreotide was evaluated in single series of HCC patients reporting conflicting results. We have treated a series of 35 patients affected by advanced HCC (26 M and 9 F; age range: 55-85 years, median: 73 years) with RFA followed by octreotide to primarily evaluate the safety of combined treatment and to give preliminary evaluation on its activity. We have also evaluated serum VEGF changes during the study. Child A and Child B represented 60% and about 34% of the cases, respectively. Only two patients with Child C compensated cirrhosis were included in this study. All patients have multiple liver HCC nodules and one had bone metastases. Two complete responses, 3 partial responses and 23 disease stabilization for at least three months were obtained (overall response rate, 14,2%; clinical benefit, 80%). Mean overall survival was 31.4 months. The combined treatment was well tolerated. Statistically significant correlation was found between serum VEGF and tumor progression. In conclusion, the combination of RFA and octreotide was active in advanced HCC, however, confirmation in a larger series is required.

BACKGROUND: We describe the clinical and color Doppler ultrasound findings in a series of cases of seeding from hepatocellular carcinoma (HCC) observed in patients treated with percutaneous ablation therapy (PAT) over a 15-year period. METHODS: We reviewed the clinical and imaging records of 12 patients with cirrhosis (nine men and three women, age range 51-82 years, mean age 63 years) that showed neoplastic seeding from HCC occurring after one or more PAT procedures. Five of 12 cases of seeding were observed as a complication of 1080 PAT procedures (0.46%) performed in 545 patients (0.96%) by two of the authors (L.T., G.F.) over a long period (15 years) at different institutions. The other seven patients had been treated with PAT procedures at other institutions and had come to our attention during post-treatment follow-up. RESULTS: The 12 patients who had seeding nodules had undergone the following PAT procedures: multisession conventional percutaneous ethanol injection (PEI) without anesthesia (four patients), single-session PEI with general anesthesia (three patients), single-session PEI with general anesthesia plus multisession conventional PEI (four patients), and single-session PEI plus radiofrequency ablation (one patient). Seeding nodules ranged from 0.9 to 6.0 cm (mean 1.7 cm). Eleven of 12 seeding nodules appeared as hypervascular hypoechoic nodules with smooth and regular margins and multiple intralesional vascular signals. CONCLUSIONS: Clinical and imaging findings of seeding from HCC should be recognized by physicians who perform follow-up ultrasound examinations of patients who are treated with PAT. Early diagnosis of seeding can be reliably made by scanning the abdominal wall with small probes in the area where the previous PAT has been performed. Hypoechoic hypervascular pattern of the seeding nodule allows definitive diagnosis.

OBJECTIVE. We sought to investigate the efficacy of contrast-enhanced sonography using a second-generation contrast agent for the evaluation of hepatocellular carcinoma in patients with cirrhosis by comparing the results to those obtained with contrast-enhanced helical CT. SUBJECTS AND METHODS. Between October 2002 and March 2003, 74 patients with cirrhosis (60 men and 14 women; age range, 47–80 years; mean age, 67 years) who had a single nodule of hepatocellular carcinoma were selected to be studied from a cohort of 437 patients with cirrhosis. The size range of the 74 nodules was 9–65 mm (mean, 28.2 mm). Twenty-eight (38%) were 20 mm smaller (range, 9–20 mm; mean, 16.6 mm), and 46 (62%) were larger than 20 mm (range, 21–65 mm; mean, 35.2 mm). Contrast-enhanced sonography was performed at a low mechanical index after IV administration of the contrast agent Sono- Vue. CT scans were obtained in all patients. The enhancement pattern related to tumor hypervascularity was analyzed. The chi-square test was used for statistical analysis. RESULTS. For the 28 hepatocellular carcinomas 20 mm or smaller, contrast-enhanced sonography showed 15 (53.6%) as hypervascular and 10 (35.7%) as avascular; three (10.7%) carcinomas were missed. On CT, 12 (42.9%) of the 28 hepatocellular carcinomas appeared hypervascular, 13 (46.4%) appeared hypovascular, and three (10.7%) were missed. For the 46 hepatocellular carcinomas larger than 20 mm, contrast-enhanced sonography showed 42 (91.3%) as hypervascular and four (8.7%) as avascular. On CT, 35 (76.1%) hepatocellular carcinomas appeared hypervascular, eight (17.4%) appeared hypovascular, and three (6.5%) were missed. Differences between CT appearance of hepatocellular carcinomas and contrastenhanced sonographic appearance of the carcinomas were not statistically significant. Concordance between contrast-enhanced sonographic and CT appearances was observed in 61 (82.4%) of 74 cases. CONCLUSION. Contrast-enhanced sonography is similar to CT for detecting hepatocellular carcinoma hypervascularity. It could be complementary to conventional unenhanced sonography for evaluation of liver nodules.

Objective: To evaluate the efficacy and complications of interstitial laser photocoagulation (ILP) under ultrasound (US) guidance as a technique for focal ablation of liver tumors in patients with normal and impaired hepatic function. Patients and Methods: A total of 104 patients, 77 with 85 nodules of hepatocellular carcinoma on cirrhosis (29 in Child-Pugh A class, 43 in B e 5 in C class) and 27 patients with hepatic metastases (25 from colon, two from lung carcinoma) underwent ILP under US guidance. Depending on tumor size up to four needles were inserted in the tumor and multiple laser illuminations were performed in one or multiple sessions. Necrosis of the nodules was evaluated with triphasic contrast-enhanced CT. Results: Ninety-four patients underwent a single ILP session and nine patients two sessions. CT showed complete necrosis in 70 out of 85 HCC nodules in 65 treated patients and in 24 out of 31 patients with metastases. Three Child C class patients dropped out the control of efficacy by CT because of severe liver failure associated in one case with transient paralytic ileum. One of these patients died 2 months after treatment. Two patients with metastasis dropped the completion of the treatment because of complication occurred after the ILP session (one paralytic ileum, one gastric haemorrage). Conclusions: ILP under US guidance is effective in inducing complete necrosis in small and large liver tumors. Nevertheless, ILP can cause severe derangement of liver function in patients with advanced cirrhosis.

This paper examines user behavior during multimodal human-computer interaction (HCI). It discusses how pointing, natural language, and graphical layout should be integrated to enhance the usability of multimodal systems. Two experiments were run to study simulated systems capable of understanding written natural language and mouse-supported pointing gestures. Results allowed to: (a) develop a taxonomy of communication acts aimed at identifying targets; (b) determine the conditions under which specific referent identification strategies are likely to be produced; (c) suggest guidelines for designing effective multimodal interfaces; (d) show that performance is strongly influenced by interface graphical layout and by user expertise. Our study confirms the value of simulation as a tool for building HCI models and supports the basic idea that linguistic, visual, and motor cues can be integrated to favor effective multimodal communication.

Objective: percutaneous ethanol injection (PEI) under general anesthesia (One Shot PEI) is a new therapy for large and multiple hepatocellular carcinoma (HCC) by the injection of large amount of ethanol in the tumor. We report our results with 3 years survival rates in patients with HCC on cirrhosis treated with One Shot PEI. Patients and methods: between October 1992 and July 1996, 112 cirrhotic patients (79 males; age: 45–80; mean: 64 years) with 215 HCC nodules (diameter 0.6–14 cm; mean 4.1 cm) underwent One Shot PEI. Fifty-three patients had a single nodule (diameter=3–14 cm; mean=4.5 cm), 59 had two or more (two to five) nodules (diameter=0.6–13 cm; mean=4.9). Ethanol injected ranged between 16 and 120 ml per session. Survival rates were calculated according to Kaplan-Meier method and Wilcoxon test was used for statistical analysis. Results: five patients died within 7 h–10 days after the treatment for rupture of oesophageal varices in three cases, rupture of subcapsular HCC in one case and liver failure in one case. In the remaining 107 patients, dynamic CT or spiral CT, performed 72 h–1 month after the treatment, showed complete necrosis in 76 cases (71%) and incomplete necrosis (although always >50%) in 31. Survival rates at 1, 2, 3 years in all 107 patients were 88, 76, and 76% respectively. Survival rates in Child A Class patients were 100, 92, 92% and in Class B patients were 84, 72, and 72% at 1, 2, 3 years respectively; in Class C were 70 and 40% at 1 and 2 years respectively (P=0.01). Survival rates in patients with single nodule were 95, 82 and 82% at 1, 2 and 3 years, while in patients with multiple nodules were 80, 68 and 58% at 1, 2 and 3 years respectively (P=n.s.). During the follow-up (6–46 months) 48 patients showed intrahepatic recurrences; 41 out of them were retreated with new sessions of One Shot PEI or traditional PEI. Conclusions: PEI One Shot is more aggressive than traditional PEI. Survival rates of PEI One Shot seems similar to those obtainable by conventional PEI and even better than surgery.

To verify the efficacy of ultrasound (US)-guided injection of large amounts of ethanol into large or multiple liver lesions, in a single session under general anesthesia (one-shot PEI) for percutaneous ablation of hepatic tumors. Twenty-nine patients (27 with 51 hepatocellular carcinoma (HCC) nodules on cirrhosis, diameter range 1.0–9.0 cm; two patients with a single metastasis from the gastroenteric tract, 5.0 and 9.0 cm, respectively, in diameter) were treated with one-shot PEI. The total volume of alcohol delivered per patient ranged from 16 to 210 ml. Mean ethanol volume in all patients was 49 ml. Dynamic computed tomography (CT) examination showed complete necrosis in 41 of 50 lesions. Two patients died of hypovolemic shock due to massive upper gastrointestinal bleeding, 3 and 7 days, respectively, after the interventional procedure. All the remaining patients are live (follow-up 5–14 months) except one who died of liver failure 5 months after. New HCC nodules occurred in six patients within 6 months and one intralesional relapse was recorded. In this preliminary experience, one-shot PEI is as effective in inducing liver tumor necrosis as traditional PEI; its advantages are shorter treatment time and the capability of treating larger and multiple liver lesions.

Malignant melanoma appears in typical sites where melanocytes can usually be found (skin, eyes, meninges, and anal region ).1 In the gastrointestinal (GI) tract, melanoma can be also found in the rectum and sigmoid colon by the local migration of primordial skin melanocytes.2 Some other rare sites of primary melanomas in the GI tract were described as the gall-bladder, stomach, small and large intestine, mouth, tongue, and esophagus.2–8 Generally, most GI melanomas are metastases from a skin tumor.9,10 We report the case of a patient with a first presentation of small-bowel melanoma, which was considered a primary site because of the absence of concurrent lesions and no history of removal of a melanoma or atypical melanocytic lesion from the skin or other organs.11