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Ulcerative colitis (UC) is a condition at increased risk for colorectal carcinoma (CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors (extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogen receptors (ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anti-carcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.

Background and Aims: Both inflammation and fibrosis may be detected in Crohn's disease (CD). The molecular pattern of Basic Fibroblastic Growth Factor (bFGF) and Syndecan-1 (SD1) expression is altered in stenosing CD, but we do not know what the behaviour of this teamwork factor is in CD in deep remission under treatment with anti-TNFα antibodies. Our aim was to compare the expression of bFGF, SD1 and TNF-α in patients with CD in deep remission under treatment with Infliximab (IFX) or Adalimumab (ADA) and a control group of patients with active CD., Methods: We assessed the expression of bFGF, SD1 and TNF-α in 10 patients with active CD and in 28 patients with CD in sustained deep remission for at least 6 months. All patients underwent surveillance colonoscopy with biopsies, while receiving maintenance therapy with IFX or ADA. Analysis was conducted by real-time reverse transcriptase PCR (RT-PCR) in biopsy samples., Results: We found that bFGF, SD1 and TNF-α were significantly reduced under treatment with anti-TNFα versus controls (p=0.000). bFGF and SD1 expression were similar between IFX and ADA patients (p=0.335 and p=0.289, respectively), while TNF-α was significantly under-expressed in ADA patients (p=0.008)., Conclusions: bFGF, SD1 and TNF-α are significantly reduced in CD patients in deep remission under treatment with anti-TNFα, likely as an expression of optimal control of inflammation. The significance of the TNF-α under-expression in patients under treatment with ADA with respect to those under treatment with IFX should be elucidated in further studies.

Background: Visual perception deficits are a recurrent manifestation in Parkinson's disease (PD). Recently, structural abnormalities of fronto-parietal areas and subcortical regions, implicated in visual stimuli analysis, have been observed in PD patients with cognitive decline and visual hallucinations. The aim of the present study was to investigate the salient aspects of visual perception in cognitively unimpaired PD patients., Methods: Eleven right-handed non-demented right-sided onset PD patients without visuospatial impairment or hallucinations and 11 healthy controls were studied with functional magnetic resonance imaging while performing a specific visuoperceptual/visuospatial paradigm that allowed to highlight the specific process underlying visuospatial judgment., Results: Significant changes in both cortical areas and subcortical regions involved in visual stimuli processing were observed. In particular, PD patients showed a reduced activation for the right insula, left putamen, bilateral caudate, and right hippocampus, as well as an over-activation of the right dorso-lateral prefrontal and of the posterior parietal cortices, particularly in the right hemisphere., Conclusions: We found that both loss of efficiency and compensatory mechanisms occur in PD patients, providing further insight into the pathophysiological role of the functional alterations of basal ganglia and limbic structures in the impairment of visuoperceptual and visuospatial functions observed in PD.

Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT) occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT), it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice.

Intestinal microbiota is composed by a community of microorganisms, which regulate intestinal functions and affect the global health. It is presumable that the well-known intestinal damages induced by Non Steroidal Antiinflammatory Drugs (NSAIDs) mirror on the homeostasis of microbiota, as confirmed by studies investigating this aspect. This review reports the evolving knowledge in this field taking into account both intestinal damage and microbiota involvement. In addition, we analyze a recent study reporting how NSAIDs change intestinal bacterial composition and, on this basis, hypothesize further possible interactions. Indeed, NSAIDs are responsible for a marked reduction of Lactobacilli, which act in the maintenance of luminal pH, mucosal permeability, enterocyte adhesion, mucus production, and immune system modulation. Moreover, Bifidobacteria are involved in the modulation of intestinal motility and local immunity and the demonstrated dangerous effect of NSAIDs could operate through an interference with these functions. A participation of microbiota in mesalazine and salycilate prevention of intestinal cancer may be supposed through their ability to stimulate bacterial production of molecules interfering with cell cycle on the basis of scanty available data. Finally, a supplementation with probiotics in chronic users of NSAIDs may help microbiota remodeling in a damaged intestine, but the poor current knowledge does not allow setting a clear indication for their use despite few evidences of a beneficial effect. In conclusion, it is presumable that the multiple effects of NSAIDs on the lower gastro-intestinal tract may involve microbiota alterations and this consideration suggests further investigations.

Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the "ideal therapy", paradoxically, appears to be a "utopia", despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter., (© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.)

Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenesis may be considered as a "two-faced" process when related to chronic intestinal inflammation. Many types of cells may be converted into the fibrogenic phenotype at different levels of the intestinal wall. A complex interaction of cytokines, adhesion molecules and growth factors is involved in the process. We report an overview of recent advances in molecular mechanisms of stricturizing Crohn's disease (CD) including the potential role of trasforming growth factor beta, protein kinase C and Ras, Raf and ERK proteins. Fibrotic growth factors such as vascular endothelial growth factor and platelet-derived growth factor, as well as the Endothelial-to-Mesenchymal Transition induced by transforming growth factor-β, are considered. Finally, our experience, focused on tumor necrosis factor α (the main cytokine of inflammatory bowel diseases) and the link between syndecan 1 (a heparan sulphate adhesion molecule) and basic fibroblast growth factor (a strong stimulator of collagen synthesis) is described. We hypothesize a possible molecular pattern for mucosal healing as well as how its deregulation could be involved in fibrotic complications of CD. A final clinical point is the importance of performing an accurate evaluation of the presence of fibrotic strictures before starting anti-tumor necrosis α treatment, which could worsen the lesions.

Background: Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated., Objective: We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects., Methods: Forty-nine patients (mean age 41±16 years), 25 with CD and 23 with UC, and forty controls (mean age 45±15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate., Results: FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function., Conclusions: Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Conventional triple therapies for Helicobacter pylori (H. pylori) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatric population we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. Clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PCR). In a recent comparative study we found a 71.2% agreement between the two methods. Culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PCR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G, A2142G and A2142C, are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142C, significantly lowered the H. pylori eradication rate. Treatment failure has considerable cost/benefit implications because of "waste" of National Health System and patient resources, in terms of drugs, further diagnostic tests and medical examination expenses. Therefore, in future it would be very useful to be able to test for clarithromycin resistance before starting conventional triple therapy. Hopefully, fast, effective non-invasive tests may soon be devised to determine this condition.

Aim: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures., Methods: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry., Results: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-Neumann-Keuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e., basolateral area of the crypts and TNF-α very poorly expressed., Conclusion: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by post-transcriptional regulation.

Aim: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas., Methods: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples., Results: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07)., Conclusion: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction.

Background: Gastroparesis is a disorder characterized by delayed gastric emptying of a meal in the absence of a mechanical gastric outlet obstruction. Idiopathic gastroparesis is at least as common as diabetic gastroparesis in most case series, and the true prevalence of gastroparesis is unknown., Results: We report here an interesting case of idiopathic gastroparesis characterized by sudden onset in a female patient. The diagnosis was confirmed by ultrasonographic study of gastric emptying and electrogastrography, by gastric endoscopy/histology, and finally by allergy tests. The disorder was found to be due to a rare cause, namely an allergic predisposition. In fact, our patient, who demonstrated an allergy to gold salts, had drunk a glass of a liqueur containing gold flakes and developed an eosinophilic aggregation in the gastric mucosa observed at gastric endoscopy/histology. The symptoms disappeared after steroid administration., Conclusion: Our experience suggests that gastric histology and close enquiry into any history of allergy may be useful diagnostic tools in cases of idiopathic gastroparesis.

Unlabelled: Bacterial intestinal overgrowth syndrome (SIBO) treatment is based on antibiotics. Probiotics have been shown to give similar results, whilst no study is available about prebiotics. This study evaluated the addition of probiotics or prebiotics to antibiotics on SIBO symptoms in a 6-month follow-up. We enrolled 40 patients (14 males and 26 females) reporting abdominal compliant without gastrointestinal diseases/alarm symptoms. SIBO was diagnosed by the agreement of lactulose and glucose breath tests. Patients were randomly divided into two groups homogeneous for sex and age: group 1 received Rifaximin 400 mg/day for 7 days/month followed by Lactobacillus casei for 7 days more and group 2 antibiotic followed by short chain fructo-oligosaccharides. All patients recorded a questionnaire for subjective symptom evaluation according to Rome III criteria and Bristol scale for stool characters before the study and after 6 months., Statistics: Student's t and Fisher's exact tests. In group 1, a significant improvement was obtained in 5 out of 6 symptoms, whilst in group 2 in 4 out of 6 symptoms (nausea and number of bowel movements failed to improve). Despite we observed a trend of probiotics to be more effective than prebiotics, the difference in the percentage of improved symptoms was not significant (83,3% vs 66.6%; p= 0.57). Our preliminary data show a good outcome with sequential antibioticprobiotic/ prebiotic administration in patients with SIBO.

Background and Purpose: Interest in the possibility that diet might help to reduce the risk of colorectal cancer dates back to 1970 based on both the large variation in rates of specific cancers in different countries and the impressive changes observed in the incidence of cancer in migrants from low- to high-risk areas. Here, we report the state of art of literature data about this topic., Methods: Three sections have been separately considered: chemoprevention of first tumor onset, chemoprevention of recurrence after surgery, and chemoprevention of polyp recurrence in the course of the follow-up of subjects with elevated risk. A particular attention has been pointed to dietary factors and survival, whose relevance is showing a growing interest., Results: The relationship between diet and colorectal cancer has been extensively studied about the onset, sometimes with controversial results. Its influence on recurrence and survival has been examined in only few studies., Conclusions: Literature data are convincing for a protective role on the onset of preneoplastic and neoplastic lesions for some foods such as fibers, vitamin A and D, folic acid, calcium, antioxidants, and promising perspectives for some substances such as phyto-estrogens. Less evidence-based data are available on the possibility to avoid the recurrence of the disease or to affect its mortality with dietary habits. Future perspectives will be directed be not only to identify new dietary style able to prevent the onset of neoplastic lesion of the colon but also to realize an effective chemoprevention.

Coronary Arteriovenous Fistula (CAF) is a rare defect that occurs in 0.1-0.2% of patients undergoing coronary angiography; Coronary Artery Aneurism (CAA) also occurs in approximately 15-19% of patients with CAF. It is usually congenital, but in rare occasions it occurs after chest trauma, cardiac surgery, or coronary interventions. The case described is that of a 72-year-old woman, without previous history of cardiovascular disease, who presented a huge cardiac mass. A multimodal approach was necessary to diagnose a giant CAA with CAF responsible for compression and displacement of cardiac structures. Due to likely congenitally origin of the lesion and the absence of symptoms correlated to the CAA and to the CAF we decided to avoid invasive interventions and to treat the patient with medical therapy.

Purpose: To assess the outcome of reirradiation with stereotactic radiosurgery (SRS) of brain metastases (BM) recurring after whole brain radiotherapy (WBRT)., Methods and Materials: Between September 2001 and October 2008, 69 patients who recurred after WBRT were re-irradiated with SRS using a linear accelerator. The dose prescription was generally chosen according to maximum diameter of the tumor as suggested by Radiation Therapy Oncology Group (RTOG) 90-05 protocol. Patients were stratified by Karnofsky Performance Status (KPS), Neurologic Functional Score (NFS), RTOG Recursive Partitioning Analysis (RPA), Score Index for Radiosurgery (SIR), primary disease, dimension and number of BM, and time to first brain recurrence after WBRT. Response, survival, and toxicity were analyzed., Results: At time of this retrospective analysis all patients had died. The 69 patients reirradiated with SRS had 150 metastases. Median interval between prior WBRT and SRS was 11 months and median SRS prescribed dose was 20 Gy. Response was obtained in 91% of lesions with 1-year local control rate of 74±4%. Significantly longer duration of response was associated with higher doses (≥23 Gy) and response achieved after SRS (complete and partial response better than stable disease). Cause of death was brain failure only in 36 (52%) patients. Median overall survival after reirradiation was 10 months. Variables which significantly conditioned survival were KPS and NFS. Four (6%) patients had asymptomatic radionecrosis that developed prevalently when lesion diameters were larger and cumulative doses exceeded the values recommended by RTOG 90-05 protocol. About three-fourth of the patients had a good KPS and NFS after reirradiation., Conclusions: Reirradiation of BM with SRS resulted feasible and effective. A correct patient selection and an accurate evaluation of the cumulative irradiation dose were suggested., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte-monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered., (Copyright © 2011 Wiley Periodicals, Inc.)

Aims and Background: Few clinical data exist concerning normal brain tissue tolerance to re-irradiation. The present study evaluated long-term outcome of 22 recurrent glioblastoma patients re-irradiated with radiosurgery or fractionated stereotactic radiotherapy., Methods: Twenty-two patients were treated with radiosurgery (13, 59%) or fractionated stereotactic radiotherapy (9, 41%) for 24 lesions of recurrent glioblastoma. The male/female ratio was 14:8, median age 55 years (range, 27-81), and median Karnofsky performance status 90 (range, 70-100). The majority of the cases (77%) was in recursive partitioning analysis classes III or IV Radiosurgery or fractionated stereotactic radiotherapy was chosen according to lesion size and location., Results: Median time between primary radiotherapy and re-irradiation was 9 months. Median doses were 17 Gy and 30 Gy, whereas median cumulative normalized total dose was 141 Gy and 98 Gy for radiosurgery and fractionated stereotactic radiotherapy, respectively. All patients submitted to radiosurgery had a cumulative normalized total dose of more than 100 Gy, whereas only a few (44%) of fractionated stereotactic radiotherapy patients had a cumulative normalized total dose exceeding 100 Gy. Median follow-up from re-irradiation was 54 months. At the time of analysis, all patients had died. After re-irradiation, 1 (4%) lesion was in partial remission, 16 (67%) lesions were stable, and the remaining 7 (29%) were in progression. Median duration of response was 6 months, and median survival from re-irradiation 11 months. Three of 13 (23%) patients submitted to radiosurgery developed asymptomatic brain radionecrosis. The cumulative normalized total dose for the 3 patients was 122 Gy, 124 Gy, and 141 Gy, respectively. In one case, the volume of the lesion was large (14 cc), and in the other 2 the interval between the first and second cycle of radiotherapy was short (5 months)., Conclusions: Re-irradiation with radiosurgery and fractionated stereotactic radiotherapy is feasible and effective in recurrent glioblastoma patients. Apart from the importance of an accurate patient selection, cumulative radiotherapy dose and a correct indication for radiosurgery or fractionated stereotactic radiotherapy must be taken into account to avoid brain toxicity.

Background: To evaluate the safety, reproducibility and pitfalls of an aortic valve re-implantation (AVRei) technique., Methods: From June 2005 to December 2008, 30 patients underwent aortic valve-sparing re-implantation with Gelweave Valsalva prosthesis. Mean age was 66 +/- 7 years (range 47-81). Mean aortic root diameter was 49 +/- 6 mm (range 37-70) and 12 patients had an aortic insufficiency more than 2+. All the patients were elective, except three who underwent surgery for type A aortic dissection. Two patients had Marfan syndrome and one had a bicuspid aortic valve. Isolated aortic root replacement was performed in 26 patients, whereas hemiarch extension was required in four. All the survivors underwent serial echocardiographic assessment for functional results and multi-detector computed tomography (MDCT) for aortic root morphology evaluation., Results: There was one early death and one re-exploration for bleeding. Two patients suffered from a perioperative stroke and four required a pacemaker implantation because of a complete atrio-ventricular block. Mean follow-up was 12 +/- 10 months (range 1-42) with no late deaths, whereas freedom from reoperation was 100% and freedom from aortic insufficiency 2+ or more was 96.5%. MDCT aortic root reconstruction showed a pseudo-normalization of the neo-sinuses of Valsalva mimicking the human normal aortic root morphology., Conclusion: AVRei with Valsalva conduit is a well-tolerated procedure both in elective and emergency situations. In well-selected patients, good functional and clinical results can be achieved, regardless of the cause of the aortic root disease. Application of simple surgical manoeuvres allows durable clinical efficacy to be obtained without the risk of major complications.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal complications are rare, especially during childhood. In adults, only two cases of peptic ulcer have been reported in neurofibromatosis, both due to Zollinger-Ellison syndrome. Peptic ulcer disease (PUD) may be primary or secondary in nature and it may be life threatening in the acute phase due to the risk of perforation. A case of recurrent gastrointestinal hemorrhage in a child with systemic neurofibromatosis and primary ciliary dyskinesia (PCD) is presented. The upper gastrointestinal endoscopy revealed the presence of multiple gastric ulcers. The ulcers scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after the suspension. Laboratory and imaging studies excluded Zollinger-Ellison syndrome and other known causes of PUD, suggesting a potential role of neurofibromatosis itself and primary ciliary dyskinesia in developing of recurrent PUD. As early diagnosis of PUD is vital for patient survival, this case report highlights the possible association of neurofibromatosis and PCD with this condition, responsive to PPI therapy and the potential need of gastric protection before complications arise.

Topiramate (TPM) is a new antiepileptic drug approved for the prevention of migraine headache. However its use is limited by treatment-emergent adverse events; in particular, therapy can exert profound impact on language function. In this investigation, we used functional magnetic resonance imaging (fMRI) to study the anatomofunctional correlates of language disturbances in TPM patients experiencing subjective cognitive impairment. Ten right-handed individuals receiving therapy (five with and five without language disfluency) and five matched healthy control subjects took part in this study. During fMRI subjects alternately rested and performed a word-generating task. The task comprised the silent generation of words beginning with a different input letter visually presented. The activation paradigm consisted of six activation blocks alternating with six baseline rest blocks. The main fMRI measure was the pattern activation of the prefrontal regions (Brodmann's areas 44, 45, and 46) in both left and right hemispheres. Patients receiving TPM (50-100 mg/day) significantly reduced mean monthly migraine frequency. However several differences in fMRI activation were evident in the subject group comparison. Notably, changes in brain activity were observed during the phonemic task in patients with language disturbances. It is likely that TPM therapy is associated with a "remapping" of the language cerebral network.

Background: A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions., Aim: In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue., Patients/methods: Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated., Results: In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs. 44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by confocal microscopy evaluation., Conclusions: Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.

Tumor necrosis factor alpha (TNFalpha) in intestinal mucosa plays a key role in the inflammation characterizing Crohn's disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFalpha and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFalpha and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFalpha and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFalpha in CD. In conclusion, TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.

The authors report two cases of nodular calcium pyrophosphate dihydrate (CPPD) crystal deposition close to the thoracic neural foramen, which caused chronic radiculopathy. Preoperatively, the lesions were interpreted as calcified disc herniations. Both patients underwent surgery in which an extended transfacet pedicle-sparing approach was used. Incision of the posterior longitudinal ligament released soft degenerated material. In both cases, histological examination showed abundant degenerative debris along with CPPD crystals. Spinal CPPD deposition is a comparatively rare disease that almost invariably involves the posterior aspect of the spinal canal, typically the ligamentum flavum. The exceptional foraminal location of the lesions reported here, combined with the surgical findings, indicated that the CPPD crystals were deposited on a laterally herniated disc fragment. A distinctive feature in both cases was the soft consistency of the resected tissue. The consistency of the disc material and the location of the lesion in the axial plane (that is, median compared with lateral) are key factors in determining the optimal surgical approach to thoracic disc herniations. In describing consistency, terms such as "calcified" and "hard" have been used interchangeably in the literature. In the cases reported here, what appeared on computerized tomography and magnetic resonance imaging studies to be densely calcified lesions were shown intraoperatively to be soft herniations. The authors' experience underscores that not all densely calcified herniated discs are hard. Although detection of this discrepancy would have left surgical planning for the lateral disc herniations unchanged, it could have altered planning for centrally or centrolaterally located disc herniations.

We assessed possible advantages of the use of fluid-attenuated inversion-recovery (FLAIR) sequences with magnetisation-transfer contrast (MTC) over conventional FLAIR images. We carried out cranial MRI at 1 tesla on 50 patients with both sequences. In nine patients with multiple sclerosis (MS) we performed a quantitative comparison of the two sequences, looking at the contrast-to-noise ratio between lesions and normal white matter and counting the number of lesions shown using each method. A qualitative comparison on all patients consisted of the analysis of the appearance of the normal parenchyma, of any lesions, and of artefacts, with particular reference to cerebrospinal fluid (CSF) motion artefacts. The quantitative analysis showed no meaningful difference between the two sequences. The cerebral parenchyma and lesions appeared substantially the same with both techniques. With FLAIR MTC there was a clear, and consistent reduction in CSF motion artefacts. FLAIR MTC sequences can usefully be used in place of the conventional sequence at 1 tesla.

Angiogenesis is a common characteristic of tumours, and it is reasonable to assume that it has an influence on tumour growth, depending on the grade of malignancy. We therefore studied angiogenesis in 25 patients: 14 with glioblastoma multiforme and 11 with grade I meningioma. Our aim was to assess how angiogenesis conditions growth and necrosis. The patients underwent MRI with standard and perfusion sequences. We calculated the volume of each tumour; for the glioblastomas the solid portion was taken as the difference between the overall volume and the volume of any necrotic portion. In the glioblastomas, we found an inverse relationship between blood volume and the size of the tumour, whereas in the meningiomas there was of a direct relationship. These correlations confirm in vivo the knowledge about necrosis in glioblastomas and its relationship to their inadequate vascular network. On the contrary, grade 1 meningiomas show an equilibrium between their microcirculation and the cellular component.

Present knowledge suggests that in glioblastoma multiforme the value of the apparent diffusion coefficient (ADC) is elevated in the solid part and hyperintense in T1, in spite of the elevated cellularity, and also in areas where peritumoral vasogenic edema is present. The purpose of our study has been to verify in vivo if the ADC increases in areas of solid tumor because of an increased presence of edema, like it happens in areas surrounding the tumor. Sixteen patients with histologically verified glioblastoma multiforme underwent a magnetic resonance (MR) examination with sequences: T1-weighted pre and post contrast, diffusion-weighted at b = 0 and b = 1000 s/mm(2), perfusion-weighted. One hundred sixty-five regions of interest (ROI) have been obtained for all set of patients. In each ROI we have estimated 4 parameters: ADC, intensity of T2-signal normalised to the white matter (SI(T2W)(n)), regional cerebral blood volume (rCBV), T1-signal enhancement (E%). With the SI(T2W)(n) the presence of edema was estimated. For each pair of measured parameters a statistical test of linear regression on the set of all ROI was made. A directed linear correlation between: ADC and SI(T2W)(n) (p

Purpose: Perfusion and diffusion Magnetic Resonance Imaging (MRI) studies allow us to quantitatively evaluate the vascularisation and anaplastic grade of glioblastomas based on the regional cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) values. The aim of our study was to compare these values and enhancement % in order to determine whether enhancement of glioblastomas depends mainly on their vascularisation or anaplastic grade., Materials and Methods: Seventeen patients with brain glioblastomas were studied with perfusion, diffusion and T1-weighted Spin-Echo MR sequences, with and without contrast medium. The quantitative evaluations were made on solid tumour tissue regions of interest (ROI), and the high vascularisation (high rCBV) and low anaplastic grade (high ADC) ROI group was separated from the low vascularisation (low rCBV) and high anaplastic grade (low ADC) group. The mean enhancement % values of the two groups were compared by using statistical METHODS., Results: In 14 patients there were no statistically significant differences between the two groups. In one patient, the enhancement of high anaplastic grade and low vascularisation ROIs was significantly higher, whereas in two patients, the enhancement of high vascularisation and low anaplastic ROIs clearly prevailed., Conclusions: Given that the anaplastic grade is proportional to blood-brain barrier (BBB) impairment, our results show that, in most cases, enhancement of glioblastomas is equally dependent on vascularisation and BBB impairment.

Aim: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids., Methods: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate., Results: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery., Conclusions: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials.

Background and Aim: Even if different Helicobacter species can colonise animal livers and induce hepatitis, there is no evidence that Helicobacter pylori can damage this organ and only a potential capacity of cytotoxic strains to increase transaminases in humans has been suggested. We have, therefore, carried out an immunohistochemical study on vacuolating cytotoxin in the hepatocytes of subjects with isolated hypertransaminasaemia., Patients, Methods and Results: Five male patients with isolated hypertransaminasaemia without signs of known causes of liver diseases were studied. Endoscopy demonstrated diffuse mucosal hyperaemia in 3 patients and duodenal ulcer in one. Histology revealed active chronic pangastritis in all. Helicobacter pylori was assessed by histology and culture and its cytotoxity, demonstrated by positive immunoblotting for both anti-CagA and VacA. Percutaneous liver biopsy showed minimal changes. Hepatic and gastric sections were tested either with autologous serum and rabbit antibody to VacA toxin. Immune reaction was revealed by immunoperoxidase. Both autologous sera and anti-VacA toxin antibody showed a reaction with a similar pattern which involved 60% of hepatocytes. Anti-VacA toxin showed a reaction to gastric epithelial cells and autologous sera to parietal cells in 4/5 patients. All patients received triple therapy and eradication of Helicobacter pylori was assessed by urea breath test. Serum transaminase levels 3 months after eradication, are still abnormal., Conclusions: Our immunohistochemical findings suggest that vacuolating cytotoxin could reach the hepatocytes of patients suffering from both isolated hypertransaminasaemia and infection by cytotoxic strains of Helicobacter pylori. Nevertheless, a clear relationship between these two condition remains uncertain.

Shiga toxin-producing Escherichia coli (STEC) has been associated with pathogenesis of hemolytic uremic syndrome (HUS) worldwide. The aim of the present study was to characterize the HUS cases reported in Mendoza and to determine their association with STEC infection. From July 1994 through June 1996 thirty-six patients with HUS were admitted to Hospital Pediátrico "Dr. HJ Notti" (Mean age 22.8 +/- 14.9 months, 44% females). The children developed HUS following an acute diarrheal illness in 94.4% of the cases. Bloody diarrhea was observed in 83.3% of them. Antimicrobial therapy had been administered to 69.4% of the patients. Most of the patients were well-nourished (88.9%), belong to middle-low socioeconomical condition (91.7%), from urban areas (72.2%) and they were mostly assisted during summer and the beginning of autumn. The acute stage of the disease occurred with presentation of pallor (100%), edema (25%), anuria (38.9%), oliguria (41.7%), hemolytic anemia (97.2%), thrombocytopenia (86.1%) and neurological involvement (41.7%). Twenty-five of them presented the full clinical syndrome. Peritoneal dialysis were performed in 50% and packed blood cell transfusion in 88.9%. The mean days of hospitalization was 15.1 +/- 9.2 [range 1-32]. A 91.7% of the patients recovered renal function, two developed chronic renal failure and one died. Cumulative evidence of STEC infection was found in 19 (86.4%) of 22 HUS patients. STEC O157:H7, biotype C was found in 8 (36.4%). The prevalent Stx type was Stx2 in STEC, free fecal Stx (STMF) and Stx-neutralizing antibodies (a-Stx). In Mendoza, as in the rest of Argentina E. coli O157:H7, biotype C, Stx2 producer is the most frequently detected pathogen in HUS cases.

Background: Impaired changes in gastric epithelium proliferation have been described in Helicobacter pylori infection, and a progressive increase of proliferating cells has been shown with the progression of mucosal lesions., Aims: Purpose of this investigation was to study the effect of eradication on bacterium-induced proliferative changes, evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein p21, involved in early events of gastric carcinogenesis., Patients and Methods: This retrospective study was performed, before and after therapy, in five different groups of patients with progressive stages of Helicobacter pylori damage (N: normality; HG: histological gastritis with normal endoscopy; EHG: histological gastritis with endoscopic chronic erosions; CIM: complete intestinal metaplasia; IIM: incomplete intestinal metaplasia)., Results: Six months after eradication, a normalization of PCNA LI was observed in the areas of gastritis, but not in those of intestinal metaplasia, which showed on unchanged type. Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only associated to intestinal metaplasia. The protein was also expressed in the cytoplasm in 3 patients with incomplete type., Conclusions: These results suggest that the development of intestinal metaplasia may be associated with an alteration in the control of gastric epithelium proliferation and could represent an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes are necessary for a complete progression to neoplastic disease. A long-term follow-up on extension, type, proliferative situation and oncoprotein expression in areas of intestinal metaplasia may be helpful to explain whether the present data provide new information on the mechanism of Helicobacter pylori induced gastric carcinogenesis.