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Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

Immunotherapy in recent years has revolutionized the oncology practice. ICIs targeting T lymphocyte antigen–4 (CTLA–4) and programmed death–1/ligand–1 (PD–1/PD–L1) transformed treatment landscape of many different cancers. The answers occur in a substantial fraction of patients and are often durable. ICI‘s combined block (CB) (CTLA–4 + PD–1/PD–L1) seems to improve even further clinical outcomes compared to monotherapies. However, this treatment exposes patients to the risk of immune adverse events (iAE) including cardiovascular (CV) iAE, which can be potentially fatal and, in any case, compromise the continuation of oncological treatment. Here we present the case of a young woman with advanced renal cancer (Stage IV, T3b, N0, M1) in ICI combined block therapy (Nivolumab + Ipilumab) complicated early by a pericardial effusion (PE) Clinical case Oct 2021: a 48 yrs old woman with sarcomatoid and rhabdoid renal cell cancer with liver metastases underwent left radical nephrectomy and splenectomy + cavotomy for neoplastic thrombus removal. Dec 21, she started ICIs CB (Nivolumab + Ipilumab) X 4 and sequential Nivolumab. March 2022: on CT assessment for disease restaging at the end of induction therapy with nivolumab + Ipilumab a favorable response of metastases was detected but incidental finding of G2–G3 PE was identified (figure 1). Therapy with prednisone (1 mg/kg/day) and Colchicine 0.5 mg/day was promptly started with progressive reduction of the effusion in the serial cardiological checks without recurrence although maintenance immunotherapy with Nivolumab was rechallenged. ICIs was permanently discontinued in June 2022 due to gastrointestinal G4 toxicity. At MRI evaluation after 6 months ICIs discontinuation (December 2022), liver metastases were further reduced compared to previous assessments. Conclusion This case confirms that the association between iAE side effects and efficacy of ICIs is a real possibility. Vigilant surveillance and close collaboration between oncologists and cardiologists facilitate timely capture of CV iAE and appropriate management to allow effective management.

Confronto tra osteotomia laterale più gibbectomia e rimodellamento del gibbo senza osteotomia laterale: effetti sulla visione frontale.Questo articolo presenta la nostra esperienza clinica degli ultimi anni nell’approccio alla correzione del gibbo nasale mediante il confronto tra osteotomia laterale più gibbectomia e rimodellamento del gibbo senza osteotomia laterale e valutando i risultati ottenuti nel tempo in termini di modificazione della larghezza e del contorno del dorso nasale, in visione frontale. Per la realizzazione del lavoro sono state considerate due diverse coorti di pazienti sottoposte a rinoplastica primaria, rispettivamente con o senza ricorso ad osteotomie laterali. Lo studio è stato condotto nel periodo compreso tra il 1 Gennaio 2010 ed il 31 Dicembre 2013, esaminando 42 pazienti sottoposti a rinoplastica primaria e considerando le modificazioni della larghezza dorsale della piramide nasale, misurata a livello del canto mediale ed a livello del margine inferiore del bordo orbitale e della larghezza ventrale della piramide nasale, misurata a livello del canto mediale e del margine inferiore del bordo orbitale. Nel primo gruppo di soggetti è stato osservato un significativo incremento postoperatorio della larghezza dorsale e del restringimento di quella ventrale, mentre nel secondo gruppo di pazienti è stato riscontrato un restringimento significativo della larghezza dorsale postoperatoria, misurata sia a livello del canto mediale, che della giunzione anteriore delle ossa nasali. La nostra analisi ha mostrato che il ricorso ad innesti dorsali può essere utile per una correzione persistente ed armonica del profilo nasale in visione frontale e che la rimozione semplice del gibbo sia da considerare in casi selezionati, evitando così osteotomie laterali. Il nostro lavoro ha inoltre evidenziato l’importanza delle caratteristiche anatomiche dell’osso nasale nella valutazione dell’approccio chirurgico: ossa grandi, forti e curve meritano un restringimento aggressivo con osteotomie continue laterali e mediali senza elevazione periostale, tuttavia questo approccio può essere in alcuni casi insufficiente per ridurre le dimensioni della regione superiore del dorso nasale.This article reviews the personal experience and evolution of osteotomy approach in the last years of practice to obtain a natural appearance of the nasal pyramid in the frontal view. The aim is to analyse the long-term results after rhinoplasty on nasal width in two different cohorts of patients subjected to lateral osteotomy plus hump resection vs. hump re-modeling without lateral osteotomy considering the impact on frontal nasal view and how this relates to changes observed over time in the nasal width and contour. The study was carried out between January 2010 and December 2013, considering 42 patients undergoing primary rhinoplasty. Comparisons were made between the change in the dorsal width of the nasal pyramid at the level of the medial canthi, at the level of the inferior margin of the orbital rim, of ventral width of the nasal pyramid at the level of the medial canthi and at the level of the inferior margin of the orbital rim. In the first group, we found significant postoperative mean widening of the intercanthal dorsal width and narrowing of the ventral, while in the second group there was significant postoperative mean narrowing of the dorsal width both at level of the medial canthi and the anterior junction of the nasal bones. Our analysis seems to point out that dorsal grafting is useful for re-shaping the nasal profile with a persistent and harmonious correction of the dorsal frontal dimension of the nose. Simple hump removal/repositioning may be considered in selected instances to avoid lateral osteotomies. It also seems of paramount importance to tailor osteotomies according to nasal bone anatomy: large, strong and curved bones deserve aggressive narrowing by lateral and medial continuous osteotomies without periosteal elevation, although this approach may be insufficient to narrow the upper dorsal aspect of the nose.

The drooping tip deformity is both a bothersome aesthetic feature and functional impairment of the nose. Both static and dynamic factors may affect tip appearance and it seems logical to take into account these factors when planning correction of drooping tip. Many studies have examined this topic, but its treatment remains controversial. In order to make nasal tip surgery successful, it is useful to identify the keystone anatomical characteristics of the tip itself. Naso-labial angle, nostril axis, tip rotation angle according to Frankfort plane and columellar-facial angle may be measured to assess nasal tip position. The present study focuses on the authors' personal experience on the key anatomic changes of the nose that deserve correction and on the main surgical steps needed to achieve consistent results when dealing with a drooping tip. Pre- and post-operative nasal tip rotation and projection were studied. Correction of the drooping tip was accomplished by an open or closed septorhinoplasty approach according to patient's needs. The surgical techniques mostly employed for tip repositioning was septum straightening (41/41) and tongue-in-groove (36/41 cases) (87.8%). A columellar strut was used in 8/41 (19.51%) cases. LLC cephalic resection was applied in 29/41 patients (70.73%), LLC re-orienting sutures were made in 18/41 cases (43.9%) and lateral crural overlay was needed in 2/41 (4.8%). The key anatomic changes of the nose that deserve correction and the surgical steps needed to ease the often intriguing pre-operative decision-making process are reviewed.La punta cadente è una fastidiosa deformità estetica e funzionale del naso. L’aspetto della punta è influenzato da aspetti sia statici che dinamici. Per questo motivo, appare logico tenere in considerazione questi fattori nel pianificare la correzione chirurgica di questa deformità. Molti studi hanno affrontato questo argomento, ma il trattamento resta controverso. Per rendere efficace la chirurgia della punta appare indispensabile identificare le caratteristiche anatomiche fondamentali della punta stessa. Diversi angoli e misure possono essere calcolati per definire la posizione della punta tra cui: l’angolo nasolabiale, l’asse della narice, l’angolo di rotazione della punta in rapporto al piano di Francoforte, l’angolo columellare-facciale. L’obiettivo di questo studio è focalizzare l’attenzione sulla nostra esperienza personale sulle alterazioni anatomiche del naso che meritano una correzione e sulle procedure chirurgiche necessarie per ottenere risultati soddisfacenti nel trattamento della punta cadente. Nel presente studio sono stati presi in considerazione la proiezione e la rotazione della punta pre e post-operatorie. La correzione della punta cadente è stata ottenuta mediante settorinoplastica aperta o chiusa a seconda dei casi. La tecnica prevalentemente usata per riposizionare la punta è risultata essere il raddrizzamento del setto (41/41 casi) e la tecnica Tongue-in-groove (36/41 casi) (87,6%). Lo strut columellare è stato impiegato in 8/41 pazienti (19,51%). Resezioni cefaliche delle cartilagini alari sono state applicate in 29/41 pazienti (70,73%). Suture per ri-orientare le cartilagini alari sono state impiegate in 18/41 casi (43,9%). Il Lateral crural overlay è stato necessario in 2/41 casi (4,8%). Il presente articolo rivaluta le principali varianti anatomiche del naso che meritano correzione e le tecniche chirurgiche utilizzabili per semplificare il processo decisionale preoperatorio.

Children with recurrent upper-airway infections (UI) represent a social issue for their economic burden and negative impact on families. Bacteriotherapy is a new therapeutic strategy that could potentially prevent infections. The current study tested the hypothesis that recurrent UI may be prevented by bacteriotherapy.This open study was conducted in an outpatient clinic, enrolling 80 children (40 males, mean age 5.26±2.52 years) suffering from recurrent UI. Children were treated with a nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a, 2 puffs per nostril twice a day for a week; this course was repeated for 3 months. The evaluated parameters were: number of UI and number of school and work absences; these outcomes were compared with those recorded in the past year.The mean number of UI significantly diminished: from 5.98 (2.30) in the past year to 2.75 (2.43) after treatment (p0.0001). The number of school and work absences significantly diminished (from 4.50±2.81 to 2.80±3.42 and from 2.33±2.36 to 1.48±2.16 respectively; p0.0001 for both).This preliminary experiment suggests that bacteriotherapy using Streptococcus salivarius 24SMB and Streptococcus oralis89a nasal spray could prevent recurrent UI in children.

Probiotics S. salivarius 24SMBc and S. oralis 89a comprised in the nasal spray Rinogermina are known to exert inhibition of harmful pathogens and ameliorate the outcome of patients with chronic upper airways infections. In this study, for the first time, the effect of this formulation on the modulation of the microflora of healthy subjects was evaluated, with particular interest on pathobionts and pathogens present.Metagenomic identification and quantification of bacterial abundances in healthy subjects were carried out by means of Ion Torrent Personal Machine. In particular, nasal swabs were sampled one, two and four weeks after seven days of treatment with Rinogermina.The modulation of the abundance of pathobionts and pathogenic species (i.e., Corynebacterium diphtheriae, Haemophilus parainfluenzae, Moraxella catarrhalis, Prevotella denticola, Prevotella melaninogenica, Rothia dentocariosa, Staphylococcus aureus and Streptococcus pseudopneumoniae) was characterized and a significant temporary decrease in their presence was identified.The beneficial effects of S. salivarius 24SMBc and S. oralis 89a nasal intake was assessed but seemed to be restricted in specific temporal windows. Thus it would be interesting to evaluate also this positive impact of longer administration of this probiotic formulation.

Nasal tip under projection is often found in rhinoplasty cases both for congenital or post-traumatic deformity. Nasal trauma may result in alteration of the external and internal nasal structures with following aesthetic impairment and difficulties in breathing. Post-traumatic surgery is frequent, but restoration of pre-traumatic form and function remains a challenge. The present paper describes a new method to increase tip projection by a columellar strut harvested from the autologous nasal bone and cartilage of the resected hump. A total of 15 cases (11 women/4 men, mean age 32.6 ± 12.3 years) of major tip projection/misalignment abnormalities to be corrected by increased nasal tip projection were drawn, and all underwent closed or open rhinoplasty with the placement of a bony columellar strut harvested from the resected hump of the patient. Short and long-term advantages of this procedure are to be underlined. Harvesting is routinely performed during dorsal resection and preparation of the graft is easy. Differently from bone of the vomer or the inferior turbinate, this is cortical bone straight in shape and rigid in framework, and therefore ideal to gain reliable tip support overtime. No additional harvesting areas are needed. Placement of this bony strut is carried out in the standard fashion without additional dissection or further procedures. Long-term follow-up shows maintained projection over time. This graft can be combined with various grafting or suturing techniques usually applied according to each surgeon's experience and the needs of each patient.Lo strut columellare ricavato dal gibbo nasale: una tecnica affidabile per la correzione di deficit di proiezione della punta.Nasal tip under projection is often found in rhinoplasty cases both for congenital or post-traumatic deformity. Nasal trauma may result in alteration of the external and internal nasal structures with following aesthetic impairment and difficulties in breathing. Post-traumatic surgery is frequent, but restoration of pre-traumatic form and function remains a challenge. The present paper describes a new method to increase tip projection by a columellar strut harvested from the autologous nasal bone and cartilage of the resected hump. A total of 15 cases (11 women/4 men, mean age 32.6 ± 12.3 years) of major tip projection/misalignment abnormalities to be corrected by increased nasal tip projection were drawn, and all underwent closed or open rhinoplasty with the placement of a bony columellar strut harvested from the resected hump of the patient. Short and long-term advantages of this procedure are to be underlined. Harvesting is routinely performed during dorsal resection and preparation of the graft is easy. Differently from bone of the vomer or the inferior turbinate, this is cortical bone straight in shape and rigid in framework, and therefore ideal to gain reliable tip support overtime. No additional harvesting areas are needed. Placement of this bony strut is carried out in the standard fashion without additional dissection or further procedures. Long-term follow-up shows maintained projection over time. This graft can be combined with various grafting or suturing techniques usually applied according to each surgeon’s experience and the needs of each patient.

Sickle cell anemia (SCA) and β -thalassemia major are well-recognized beta-globin gene disorders of red blood cells associated to mortality and morbidity included bone morbidities due to ineffective erythropoiesis and bone marrow expansion, which affect every part of the skeleton. While there are an abundance of described disease manifestations of the head and neck, the manner of paranasal sinuses involvement and its relations to β-thalassemia and SCA process was not studied yet. Therefore, the aim of this study was to investigate a possible increased risk of rhinosinusitis and the real pathogenetic mechanism of it, comparing these two hematological diseases using msCT, gold standard for paranasal sinuses evaluation.A retrospective analysis of 90 patients affected by β-thalassemia major or SCA (respectively 59 and 31) underwent allogeneic bone marrow transplantation (BMT), and 44 control subjects was performed. Both patient categories and control group have been subjected to hematological and radiological evaluation using 64-multidetector-row CT scanner without contrast injection.Statistical analysis reveals that patients of the two study groups exhibit a significantly increased risk of sinusitis in comparison with the normal controls (RR: 3.55 for β-thalassemic pediatric subjects; RR: 3.35 for SCA pediatric subjects). A significant difference (p 0,5) was found between the β -thalassemic patients on the one side, and SCA and control group on the other side, with regard to the evaluation of the typical anatomic alteration of maxillary sinus: β-thalassemic children had significant increase in the bone thickness of anterior and lateral sinus walls and significant reduction in volume and density compared to SCA patients and control group, with normal conditions of these parameters.In these hematological patients, there is an increased incidence of sinonasal infections due their therapy-induced immunosuppression post transplantation. In β-thalassemic patients, furthermore, the specific anatomical variants play an important confounding factor in radiological interpretation of CT images. Therefore, a cranio-facial CT scan evaluation could be a useful tool in the management of upper airway infections after BMT and should be a routinely exams in order to avoid useless surgical or antibiotic approaches.

Introduction Beta thalassemia is a blood dyscrasia that caused a marked expansion of active marrow spaces and extramedullary haematopoiesis results. In these patients various alterations and abnormalities affects different body areas, including increased risk of sinusitis. The marrow expansion in the facial bones results in delay in pneumatisation of the sinuses, overgrowth of the maxillae, and forward displacement of the upper incisors with skeletal deformities. In current literature, maxillary sinuses are not deeply evaluated by CT scan studies in these kind of patients. The aim of our study was to investigate the presence of maxillary sinuses abnormalities by the use of CT in patients with beta-thalassemia major and to compare these findings with a control group free from this disease. Materials and methods A retrospective analysis of 22 paediatric patients with beta-thalassemia major and 22 control subjects without sinonasal diseases was performed. CT was done using a 64-multidetector-row CT scanner without contrast injection, obtained in axial plane using thin-slice technique. Evaluated parameters were: bone thickness of the lateral and anterior wall, density and volume of the maxillary sinuses. Results Significant difference was found between the study group and control group in the evaluation of all the parameters examined. The maxillary sinus of β thalassemic patients was smaller respect of controls, the bone was more dense and thick in the side and anterior wall. Beta-thalassemic patients have a relative risk of 2.87 to develop a maxillary sinusitis. Discussion In these patients there is an increased incidence of sinonasal infections due to the abnormal development of cranio facial skeleton. These bone alterations might confuse the physicians and lead to an increased rate of sinusitis diagnoses.

Background: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant inherited disorder clinically characterized by variable systemic manifestations. Among clinical features of the disease, ‘precocious presbyacusis’ has been previously reported. The underlying mechanism of this auditory impairment remains still poorly understood. Hearing is an active process located in the cochlea, where the outer hair cells (OHCs) play an important role in sound perception through a ‘contractile’ like movement resembling skeletal muscle fibers dynamics. OHCs status has not yet been investigated in DM1 patients. OHCs integrity can be assessed by measuring transient-evoked otoacoustic emissions (TEOAE), a non-invasive, repeatable, and objective quantitative tool. Methods: We recruited 25 patients with a genetically confirmed diagnosis of DM1, and 28 age-matched control subjects. All of them underwent a routine audiological evaluation and TEOAE recordings. Results: We detected a high prevalence of sensorineural high-frequency hearing loss (HFHL) in DM1 patients, significantly different if compared to control subjects. Interestingly, the accurate analysis of DM1 recorded data showed a marked impairment of TEOAE both in HFHL+ and unexpectedly in HFHL− group. Cochlear dysfunction was restricted to frequencies above 2000 Hz in the HFHL− group, but it extended to 1000 Hz in HFHL+ DM1 patients. Conclusions: Our study indicates that cochlear impairment in DM1 is present, even in patients without evidence of hearing loss at a standard audiometric analysis. Hence, in the current clinical practice, an assessment of cochlear function by TEOAE recording may be useful in DM1 patients to identify precocious signs of cochlear dysfunction.

Background: Recent literature on recovery describes the process as deeply personal and unique to each individual. While there are aspects of recovery that are unique to each individual, this article argues that focusing solely on these overlooks the fact that recovery unfolds within a social and interpersonal context.Materials: Drawing from qualitative data, this article describes aspects of recovery that involve the contributions of others, the social environment and society.Discussion: These aspects of recovery include relationships, adequate material conditions and responsive services and supports.Conclusion: The authors consider the implications of these social factors for transforming psychiatric research and theory as well as for recovery-orientated practice.

Introduction: gabexate mesylate (gm), a protease inhibitor, has been shown to exert a significant antitumoral activity in pancreatic cancer (PC) cells. Aim: To evaluate whether pre-treatment with gm could improve PC cells response toward gemcitabine (gem). Methods: Studies have been performed on PanC-1, SW1990 PC cells and ea.hy926 endothelial cells. Treatment consisted of gm 50 µg/ml for 24 hrs, followed by 24 hrs of treatment with gem 6 µg/ml; 24 hrs of gm 50 µg/ml followed by 24 hrs in culture medium; 24 hrs of gem 6 µg/ml followed by 24 hrs in culture medium. aspects studied included: cell viability (mTT assay), cell invasiveness and migration (Boyden chambers chemoinvasion and chemotaxis assay), angiogenesis (endothelial tube formation assay), nf-kB activation (nf-kB luciferase assay, Western Blotting,), vegf and il-8 levels (eliSa), mmP-2 and mmP-9 activity (gelatin zymography), Ras signalling (Western Blotting). results: gm significantly enhanced gem anti-invasive and anti-angiogenic efficacy by inhibition of gem-induced nf-kB activation (P< 0.001). This phenomenon occurred by the block of ikBalpha degradation that, in turn, prevented Rela/p65 nuclear translocation (P

299 Background: Biliary tract cancer is a rare malignancy with poor prognosis. Surgery is the only potential curative approach, but even if surgical intervention is performed correctly the relapse risk remains very high. In adjuvant setting only few randomized trials using no standard treatments and producing controversial data are reported in literature. Methods: This is a retrospective analysis on 144 consecutive biliary tract cancer patients (pts), undergone potentially curative resection in our institution (109 pts with R0 surgery and 31 pts with R1 surgery). The series included 57 intrahepatic cholangiocarcinomas (ICC), 68 extrahepatic cholangiocarcinomas (ECC), 19 gallbladder cancers (GBC) (Table). Median age was 63, 80 pts were males and 64 pts were females. 80 (60 R0 and 20 R1) out of 144 pts received adjuvant chemotherapy and the remaining 64 pts (49 R0 and 15 R1) started a follow-up program. Adjuvant chemotherapy schedule was gemcitabine 1000 mg/m2 at day 1, 8, 15 every 28, for six months. Results: Median time to relapse (TTR) in the treatment group and in the follow-up group were 18 months and 11 months respectively (p=0.038). No grade 3-4 chemotherapy-related adverse events were observed and only grade 1-2 thrombocytopenia occurred. This hematologic toxicity did not affect treatment dose intensity. Conclusions: Our preliminary retrospective analysis suggests a significant advantage of adjuvant treatment on TTR in radically resected biliary tract cancer patients, although further placebo-controlled double blind trials are required. [Table: see text] No significant financial relationships to disclose.

Background: Mutations of KRAS and BRAF genes have been associated with resistance to treatments targeted at EGFR pathway in advanced colorectal cancer and other solid tumors. Cetuximab is currently being tested in advanced biliary tract cancer, with encouraging preliminary results although definitive evidence of activity is still lacking. It is reasonable that cetuximab efficacy be restricted to tumors bearing wild-type KRAS and BRAF. Our study is aimed at determining KRAS and BRAF mutational status to evaluate the proportion of patients affected by biliary tract cancer who could benefit from EGFR-cascade targeted therapies. Methods: This is a retrospective analysis on 24 consecutive cases of cholangiocarcinoma undergone potentially curative resection in our institution. The mutational analyses have been conducted on the surgical specimen. After microdissection of the neoplastic area, DNA was extracted from enriched pathologic material with QIAmp DNA FFPE Tissue Kit (Qiagen S. p. A., Milan, Italy). Extracted DNA have been quantified after real-time PCR (Quantifiler Human DNA Quantification Kit, Applied Biosystems, Foster City, CA, USA) with ABI PRISM 7000 Sequence Detection System (Applied Biosystems). KRAS and BRAF mutations were detected in real-time PCR using specific commercially available kits (DxS Diagnostic, Manchester, UK) and confirmed with direct genomic sequencing of the same DNA specimen (Applied Biosystems 3730xl DNA Analyzer, Applied Biosystems). Results: Among patients included, 16 were extrahepatic cholangiocarcinomas and 8 intrahepatic; 14 pts showed lymph nodes involvement at surgery. 7 mutations of KRAS (all in exon 2, codon 12) and 2 of BRAF (1 in exon 11, 1 in exon 15) were identified, occurring respectively in 29% and 8% of patients. There were no double-mutated patients. 63% of study population (15 patients) was wild-type for both KRAS and BRAF. No relationship between mutational status and time to relapse has been found in this population (p 0.7). Conclusions: These preliminary data show that the majority of biliary tract cancer patients could benefit from anti-EGFR targeted therapies. Expansion of the number of patients and correlation with clinical data are ongoing.

Background: Asbestos exposure is a well recognized risk factor in mesothelioma and lung cancer development but the association with other tumors, such as gastrointestinal and bile ducts cancers (BTC), is uncertain and has not been univocally demonstrated. Asbestos fibers can cross the alveolar barrier after inhalation and penetrate the gastrointestinal mucosa by ingestion. Than they can reach the interstitial environment, the circulatory system and are finally delivered to all tissues, including liver and bile ducts. This work aims at evaluating the potential correlation between previous asbestos exposure and BTC occurrence. Methods: Over the previous year, we carefully interviewed 70 consecutive BTC patients using a standardized questionnaire asking about their exposure to asbestos and other known risk factors linked to bile duct carcinogenesis. Results: In addition to the association with known risk factors for the onset of BTC, we observed occupational or household exposure to asbes-tos in 25 patients (36%), 11 of whom were intrahepatic (ICC), 8 extrahepatic (ECC) and 6 patients had gallbladder cancer (GBC). 11 patients did not have other certain risk factors. The remaining 14 patients presented HCV chronic infection, exposure to proven or suspected carcinogenic compounds, or primary sclerosing cholangitis. Occupational exposure occurred in 5/11 ICC and 4/8 ECC; household exposure was noticed in 7/11 ICC, 4/8 ECC and 6/6 GBC. Only one ICC patient had both exposure type. Conclusions: A substantial proportion of BTC patients had an history of asbestos exposure. Further studies could clarify this putative relation and perhaps explain the increasing incidence of ICC in Western countries observed during the last decades.

Background: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. Methods: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. Results: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P

The Silent Sinus Syndrome (SSS) is a quite rare idiopathic clinical condition characterized by atelectasis/hypoplasia of the maxillary sinus which outlines a subclinical chronic maxillary sinusitis. This framework therefore causes some ipsilateral eyepieces alterations, such as silent and progressive enophtalmos and hypoglobus that may be associated with visual changes; in all cases the medical history is negative for previous facial trauma and sinonasal or maxillofacial surgery. Montgomery (1964), Wilkins and Kulwin (1981) described some cases of spontaneous and monolateral enophtalmos and hypoglobus with diplopia and ptosis caused by pauci or asymptomatic maxillary sinus disease. The term Silent Sinus Syndrome was used for the first time 30 years later by Soparkar and co. in the ophthalmic literature. Rose and co. use instead the term “imploding antrum syndrome” to emphasize the concept that a chronic sinus condition may lead in a relatively brief period to ocular signs. This study refers the case of an 11-year old boy affected by SSS.

Sixteen patients affected by benign paroxysmal positional vertigo of the horizontal semicircular canal (BPPV-HSC) were investigated by means of dynamic posturography (DP) and during bithermal caloric stimulation. Data were compared to data from 40 patients with benign paroxysmal positional vertigo of the posterior semicircular canal (BPPV-PSC) and 20 healthy controls. No postural deficit was observed before or after a liberative Lempert's manoeuvre when patients were compared to control subjects. BPPV-PSC postural scores were significantly impaired compared to scores from the BPPV-HSC group. A residual significant postural impairment was also observed after a successful liberative manoeuvre in the BPPV-PSC group. Electronystagmographic recordings before recovery revealed significant hypoexcitability of the affected ear in 8/16 patients of the BPPV-HSC group. After the liberative manoeuvre, a symmetric bilateral response to caloric stimulation was recorded in all patients. Three main conclusions can be drawn from the present data. First, disorders of the horizontal semicircular canal do not change postural control. Second, dynamic posturography can detect the postural imbalance due to posterior semicircular canal dysfunction even after resolution of paroxysmal vertigo attacks. Third, utricular dysfunction can be ruled out as a cause of the residual postural deficit observed in BPPV-PSC patients. Therefore the recovery delay observed even 1 month after the liberative manoeuvre in the BPPV-PSC-group might be due to the persistence of small amounts of residual debris in the canal, to paralysis of ampullar receptors, or to the time needed for central vestibular re-adaptation.

Few articles on neuroimaging techniques in the study of central and peripheral olfactory pathways are present in the literature. By Single Photon Emission Computed Tomography (SPECT), cortical perfusion increment after sensorial stimulation can be evaluated objectively. In the present research, 10 healthy adults underwent SPECT by CER.TO.96 cerebral tomograph, before and after olfactory stimulation with lavender-water. A variable degree of cortical activation was detected in all patients. Cyrus rectus (+24.5%), orbito-frontal cortex (right +26.6%, left +25.6%), and superior temporal (right +9.9%, left +5.5%) cortical areas were always activated. A slight perfusion increase was present in middle temporal (right +3.2%, left +2.1%) and parieto-occipital (right +0.4%, left +2%) regions. Five patients affected by posttraumatic anosmia were also investigated: they showed a perfusion increment markedly inferior to 0.5% in every olfactory area. SPECT is a rather diffused, easily performed technique which yields objective semi-quantitative information on brain perfusion. Hence, it can be regarded as a promising contribution in the fields of smell neurophysiology, clinical olfactometry, and medicolegal queries.

In the framework of the Global Navigation Satellite System, European industries are identifying and studying new satellite constellations able to cope with required navigation performance for terrestrial, maritime, air, and space users. Alenia Aerospazio has identie ed many new satellite constellations. (Some of them are constituted by low Earth orbits or intermediate circular orbits for global coverage; others consider satellites in high elliptical orbits or geosynchronous orbits for regional coverage. ) All of them have been compared in terms of navigation performance, e.g., accuracy, availability, continuity, and integrity. The best one is a constellation of 27 satellites located in intermediate circular orbits at a common altitude of 10,389 km and a common inclination of 57 deg. This constellation has been identie ed by the Walker method to e nd a space system able to guarantee a global and continuous coverage with low positioning dilution of precision values (always less than 4 )and with a coverage level equal to 6, i.e., from each point of the Earth surface it is always possible to see at least six of the satellites. After both thepayload design and thebudget have been identie ed and analyzed,thesatellite platform hasbeen designed, obtaining, in this way, mass, power, and propellant budgets. The launch strategy and the orbit acquisition phase have been dee ned.

Thirty-two patients affected by idiopathic benign paroxysmal positional vertigo (BPPV) of the posterior semicircular canal were studied before, 3 days and I month after a resolutive Semont manoeuvre by means of dynamic posturography. The overall postural control in BPPV patients was shown to be impaired, as demonstrated by the pathological equilibrium scores. Data obtained before treatment showed a specific pattern of vestibular involvement and a pathological composite score. After the liberatory manoeuvre the Sensory Organization Test indicated a significant improvement in the pathological composite and vestibular scores. However, significant differences from controls were still detected 3 days and 1 month after clinical recovery from BPPV. The results clearly show that, in BPPV patients, there is an impairment of the vestibular system, which seems unable to maintain a normal postural balance. This deficit can be particularly detected when dynamic posturography evaluates the vestibular cues. After the liberatory manoeuvre a consistent improvement in the overall postural control has been observed but the residual differences from controls seem to suggest that damage to the otoconial maculae influences postural control, even when there is significant improvement in the clinical signs.

The paper describes the characteristics of new satellite constellations identified and studied by Alenia Spazio for future Global Navigation Satellite Systems (GNSS2) services. The optimization work makes use of advanced software tools, developed in house, based on iterative and exhaustive variations of the orbital parameters and using mission specific performance objectives as driving criteria. More in particular, the following methods have been used: 1. a) Walker method: to find constellations of satellites in circular orbits (LEO, ICO) 2. b) GRACE (Generalized Rules for Advanced Constellations Evaluation) method: to find constellations of satellites in High Elliptical Orbits (HEO). Two different service areas have been considered: 1. a) regional coverage: which can include all Europe+Africa, or America, or Asia+Australia 2. b) global coverage: which includes all the Earth surface. The driving criteria to compare the constellations are expressed in terms of availability, continuity, integrity and accuracy at system level.

Advanced surveillance and communications are the main functions needed for an efficient Air Traffic Control/Management (ATC/ATM). In order to perform them over the entire Earth, a novel architecture is described and evaluated. It supplies the surveillance and data link capabilities of advanced Secondary Surveillance Radar (SSR) Mode S world-wide by means of a constellation of medium orbit satellites carrying SSR Mode S interrogators with phased-array antennas; no new equipment is required on-board aircraft, because the standard transponders are used. The rationale for the study, the system geometry, the link budget computation, the accuracy requirements as well as the subsequent design of the payload and of the optimized constellations needed for global coverage with high location accuracy are described. Moreover, details are given about the design of the spacecraft and of the main units of the space segment. The encouraging results of this overall system study pave the way to a demonstration based on simulators and ground prototypes of the critical parts.

Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an "RNA gain of function" hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis.

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant inherited disorder clinically characterized by variable systemic manifestations. Among clinical features of the disease, 'precocious presbyacusis' has been previously reported. The underlying mechanism of this auditory impairment remains still poorly understood. Hearing is an active process located in the cochlea, where the outer hair cells (OHCs) play an important role in sound perception through a 'contractile' like movement resembling skeletal muscle fibers dynamics. OHCs status has not yet been investigated in DM1 patients. OHCs integrity can be assessed by measuring transient-evoked otoacoustic emissions (TEOAE), a non-invasive, repeatable, and objective quantitative tool.We recruited 25 patients with a genetically confirmed diagnosis of DM1, and 28 age-matched control subjects. All of them underwent a routine audiological evaluation and TEOAE recordings.We detected a high prevalence of sensorineural high-frequency hearing loss (HFHL) in DM1 patients, significantly different if compared to control subjects. Interestingly, the accurate analysis of DM1 recorded data showed a marked impairment of TEOAE both in HFHL+ and unexpectedly in HFHL- group. Cochlear dysfunction was restricted to frequencies above 2000 Hz in the HFHL- group, but it extended to 1000 Hz in HFHL+ DM1 patients. Our study indicates that cochlear impairment in DM1 is present, even in patients without evidence of hearing loss at a standard audiometric analysis. Hence, in the current clinical practice, an assessment of cochlear function by TEOAE recording may be useful in DM1 patients to identify precocious signs of cochlear dysfunction.

The Galileo Test User Segment (TUS) will be an active part in the validation of the future European Galileo Navigation System. In particular the Test User receiver for the Safety of Life (SoL) GALILEO service is the most demanding due to the safety critical needs required by aeronautics, maritime or rail applications. To cope with these demanding requirements, the design of the receiver takes into account different improvements with respect to a nominal navigation receiver like interference and multipath suppression, integrity algorithms and minimization of environment errors sources impacting both hardware and software part of the receiver. This paper focuses the performances of this type of terminal mainly from the User Equivalent Range Error, positioning accuracy, availability as well as integrity aspects point of view. A Galileo (TUS) Service Volume Simulator (SVS) has been developed in order to assess the performance without considering real input signals.

We propose a novel multiplexing system for sensing of dynamic strains in which several multimode optical fibers are used as sensitive elements. In the proposed configuration several object beams emerged from different multimode fibers are mixed in one crystal altogether with a common reference beam, which is directed from the opposite face of the sample. The geometry of the light-beam interaction inside the crystal assures low cross-talk between the measuring channels in spite of the fact that all the object beams are mutually coherent since they originate from one and the same laser. We have found that the crosstalk is much smaller than the noise level of any channel, which relates to instability of the polarization state of the speckle field emerged from the fibers.

After the successful launch of the first experimental Galileo satellite, i.e. GIOVE-A, and after the signature of the Galileo-IOV-CDE1 contract, the constituted European enterprise consortium is working hard in order to achieve the Galileo In-Orbit-Validation by 2009. During this IOV phase, the first four operational satellites will be launched and the ground segment will be set up and validated, including the development of the first test user receivers. After an introduction on the Galileo overall system, this paper will describe the Galileo receivers under development in the frame of the IOV contract, focusing on the impacts of the Galileo system requirements towards the receivers design. 1 Galileo System High Level Overview Figure 1 outlines the Galileo Overall Architecture, including the following segments: ● the Galileo Space Segment including a constellation of 30 satellites placed at an altitude of in Medium Earth Orbit (MEO) altitude km ● the Ground Mission Segment (GMS) providing the determination and uplink of the navigation data messages and integrity data messages needed for the provision of navigation services and UTC time transfer service. The GMS includes a worldwide network of Galileo Sensor Stations (GSS network) providing the collection of the input observable data, which are subsequently processed at Galileo Control Center (GCC) to determination the Galileo navigation data messages and integrity data messages. ● the Ground Control Segment (GCS) providing the telemetry, telecommand and control function for the whole Galileo satellite constellation. ● the Test User Segment (TUS) including a number of Test User Receiver (TUR) Configurations. Figure 1 highlights the two different types of receivers are under development in the frame of the Galileo IOV contract, namely: ● The Test User Receiver (TUR): used to perform Galileo IOV system tests and hence demonstrating the capability of the Galileo System to meet the Galileo performance requirements. ● The Galileo Reference Chain (GRC) installed in each GSS. The GRC provides code phase and carrier measurements of the Galileo L-band navigation signals, as 260 Satellite Communications and Navigation Systems required to derive the navigation data and integrity data broadcast to user through the Galileo signals. 2 System Design Drivers The design of the navigation satellite systems (including Galileo) is usually done taking into account a lot of system requirements. Among them, a subset could heavily impact the design and performance of the system: they are usually called “design drivers”. Tables 1–3 summarise the main ones for Galileo. Three main groups can be identified: ● The frequency bands ● The services ● The navigation performance requirements Table 1. Galileo frequencies. Navigation signal in space Design aspect Value Carrier Frequency/Bandwidth E5: 1191.795MHz / 92.07MHz E6: 1278.750MHz / 40.92MHz L1: 1575.420MHz / 40.92MHz Min Receiver Power Level −152.2 dBW (at 10° elev. angle) Fig. 1. Simplified Galileo system overview.

The discovery of active mechanisms in the cochlea and the efferent auditory pathways from the brain to the cochlea demonstrated the existence of a modulation of the auditory input in the central nervous system (CNS). Otoacoustic emissions (OAEs) are weak signals that can be recorded in the ear canal and are considered a byproduct of an active process from the outer hair cells (OHCs) to the basilar membrane. The efferent auditory system plays an inhibitory role on the activity of OHCs; its stimulation reduces auditory nerve response, basilar membrane motility and OAEs amplitude. Indirect stimulation by contralateral sound is also inhibitory; a reduction of OAEs amplitude can be recorded and such an effect disappears after olivocochlear bundle section. The efferent system seems to play a role in detection of signals in noise, protection in noise-induced cochlear damage, development of hearing and processing of complex auditory signals. With respect to clinical application, OAEs suppression after contralateral auditory stimulation seems to be the only objective and non-invasive method for evaluation of the functional integrity of the medial efferent system, and, therefore, for evaluation of the structures lying along its course, at least up to the level of inferior colliculi.

The auditory implant provides a new mechanism for hearing when a hearing aid is not enough. It is the only medical technology able to functionally restore a human sense i.e. hearing. The auditory implant is very different from a hearing aid. Hearing aids amplify sound. Auditory implants compensate for damaged or non-working parts of the inner ear because they can directly stimulate the acoustic nerve. There are two principal types of auditory implant: the cochlear implant and the auditory brainstem implant. They have common basic characteristics, but different applications. A cochlear implant attempts to replace a function lost by the cochlea, usually due to an absence of functioning hair cells; the auditory brainstem implant (ABI) is a modification of the cochlear implant, in which the electrode array is placed directly into the brain when the acoustic nerve is not anymore able to carry the auditory signal. Different types of deaf or severely hearing-impaired patients choose auditory implants. Both children and adults can be candidates for implants. The best age for implantation is still being debated, but most children who receive implants are between 2 and 6 years old. Earlier implantation seems to perform better thanks to neural plasticity. The decision to receive an implant should involve a discussion with many medical specialists and an experienced surgeon.

The auditory implant provides a new mechanism for hearing when a hearing aid is not enough. It is the only medical technology able to functionally restore a human sense i.e. hearing. The auditory implant is very different from a hearing aid. Hearing aids amplify sound. Auditory implants compensate for damaged or non-working parts of the inner ear because they can directly stimulate the acoustic nerve. There are two principal types of auditory implant: the cochlear implant and the auditory brainstem implant. They have common basic characteristics, but different applications. A cochlear implant attempts to replace a function lost by the cochlea, usually due to an absence of functioning hair cells; the auditory brainstem implant (ABI) is a modification of the cochlear implant, in which the electrode array is placed directly into the brain when the acoustic nerve is not anymore able to carry the auditory signal. Different types of deaf or severely hearing-impaired patients choose auditory implants. Both children and adults can be candidates for implants. The best age for implantation is still being debated, but most children who receive implants are between 2 and 6 years old. Earlier implantation seems to perform better thanks to neural plasticity. The decision to receive an implant should involve a discussion with many medical specialists and an experienced surgeon.

This work presents an adaptive fiber-optic interferometer which is based on multimode optical fiber (MOF) as a sensor and diffusion holograms recorded in semiconductor PR crystal CdTe:V without any electric field as adaptive phase demodulators. Vectorial mixing of light waves (lambda = 1064 nm) with different polarization states (linear and elliptical) in the geometry of anisotropic diffraction makes possible to avoid applying electric field to the crystal for realization of linear phase-to-intensity transformation. At the same time recording of the hologram at high spatial frequencies (Lambda ap 0.19 mum) in the reflection geometry with appropriate concentration of PR centers allows to increase both hologram efficiency and, as a sequence, interferometer's sensitivity without applying external electric field to the crystal.

Systemic sclerosis (SSc) is a multi-systemic disease of unknown etiology characterized by damage to the small arteries, arterioles and capillaries. The documented occurrence of various neuropathies in SSs patients led us to hypothesize that there is a potential for postural control impairments in such disease. This study was aimed at evaluating the orthostatic postural control of SSc patients who do not manifest balance or hearing symptoms.Postural stability was assessed in 36 female SSc patients by means of a static computerized posturography technique. Their immunological and microvascular condition were evaluated by means of blood tests and microcapillaroscopy of the digital vessels. Posturography and microcapillaroscopy were performed before and after treating the patients with Iloprost. In order to compare results, posturography was also carried out on a control group composed of 10 healthy women of similar age. Both groups were studied in two different sensory conditions, i.e. with eyes opened and with eyes closed.Posturography results showed relevant differences in body sway between patients and control subjects. Fourier spectral analysis of body sway showed that, independently from visual control, SSc patients exhibit a higher level of low/middle frequency oscillations (both on the lateral and the anteroposterior axis). No relationship was established between disease stage and postural performance.This study seems to indicate a subtle neurophysiological dysfunction in the orthostatic postural control of female SSc patients. Further tests on the somatosensory neurological function of SSc patients may help support the above mentioned findings.

Background: Surgery of laryngeal cancer used to profoundly alter the anatomy of the cervical region. Accurate anatomo-embryologic studies and repeated surgical trials allowed recognition of the cricoarytenoid complex as the smallest anatomofunctional unit able to maintain all the laryngeal functions. Objectives: The aim of this study was to determine whether significant variations of neck anatomical parameters exist after partial laryngectomy, and to analyze whether some of these parameters are associated with a positive functional outcome. Methods: Out of 48 patients treated with a surgical technique according to Mayer-Piquet (cricohyoidoepiglottopexy, CHEP) over a 6-year period, 18 patients were enrolled in the study. Patients were all males with a mean age of 60 years. Cervical structures and their relationships were measured by computed tomography, and the measurements before and after surgery were compared. Results: Our data showed that hyoid bone is modified, both in morphology and position during CHEP. More specifically the relation of the hyoid bone to other neck structures (identified by the α-angle) is modified. The neolarynx and trachea undergo a caudocranial shift. All diameters of the cricoid cartilage remain unchanged after surgery. The position of the epiglottis after CHEP, in particular its relation with the arytenoid cartilage, is closely related to swallowing function outcome and recovery time. Conclusions: Our study showed that these structures, and more specifically the relations among them, undergo significant variations after CHEP. Our results identify some parameters, i.e. the α-angle, width of the hyoid bone and position of the epiglottis, that may predispose to a positive functional outcome after surgery.

Clinico-instrumental criteria to reliably detect simulated vertigo remain to be defined. Computed dynamic posturography (Equitest) has been used to identify additional factors to distinguish simulated, from real vertigo. The present study population comprised 23 normal subjects and 16 patients with documented vestibular impairment. Normal subjects were also studied during a state of simulated vertigo. In malingerers, the Equilibrium Score and the Composite Equilibrium Score showed a statistically significant reduction in all test conditions as compared to normal subjects, patients and "non-malingerers". Upon Sensory Analysis, statistically significant differences were found for the somatosensory component between malingerers and "non-malingerers". In 20/23 cases, Strategy Score values recorded in malingerers were 2 Standard Deviations lower than the mean obtained in "non-malingerers" in at least one of the six test conditions. By combining the latter observation with Goebel's 1st criterion it was possible to differentiate malingerers from non-malingerers with 86.9% sensitivity and 89.7% specificity. The Equitest, therefore, in combination with conventional methods, provides the clinician with an important tool, in the identification of a state of simulated vertigo.

Background: The antiangiogenic drug sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC) not suitable for surgical or loco-regional therapies in patients with preserved liver function. Many second-line drugs are currently under investigation, but none has proven effective so far. Metronomic chemotherapy is characterized by antiangiogenic activity as well and good tolerability. Therefore we started a phase II clinical study to assess efficacy of metronomic capecitabine in advanced HCC patients. Methods: This phase II trial allowed inclusion of 90 HCC patients (pts) in two sub-studies: first-line systemic treatment (60 pts) and second-line after sorafenib (30 pts.) Main inclusion criteria were Child-Pugh liver function class A and progressive disease not candidate for surgery or loco-regional treatments. Treatment schedule was capecitabine 500 mg bid after meals continuously. In case of severe toxicity up to two weeks off-therapy were permitted for recovery; no dose adjustment was allowed. Primary endpoint is three-months progression-free survival rate (PFS3mo), assessed by RECIST 1.1. This preliminary analysis aims at evaluating efficacy and toxicity of metronomic capecitabine after progression on sorafenib treatment. Results: Patients’ accrual ended in December 2010. A total of 30 pts pre-treated with sorafenib have been included; of these, 12 had relapsed after surgery and 24 had been previously managed with percutaneous ablations or chemoembolizations. 23 pts are currently assessable for efficacy. We observed no objective responses, 9 stable disease and 14 progressive disease, for a PFS3mo of 39%. Overall and progression-free survival will be evaluated in a further analysis with longer follow-up. All patients are assessable for toxicity. The most common adverse events were asthenia, nausea, diarrhoea and pruritus, generally mild and tolerable. Conclusions: Metronomic capecitabine is well tolerated and can be active in HCC patients after progression under sorafenib treatment. The extent of clinical benefit will be determined in the final analysis.

Background: Biliary tract cancers are rare malignancies with a very poor prognosis. Several studies comparing chemotherapy and supportive care showed significant survival prolongation and improvement in life quality with chemotherapy. The association of gemcitabine and a platinum compound is considered the standard first-line treatment but there are no adequate data supporting any second-line therapy. Our retrospective study aims at evaluating retrospectively the impact of second-line chemotherapy in this setting. Methods: We reviewed medical records of patients (pts) affected by histologically confirmed biliary tract cancer, treated in our institution from 2005 to 2010 with a second line chemotherapy after first-line treatment progression. Results: We identified 121 pts progressing after first-line chemotherapy. 56 (46%) of these were considered fit for a second-line treatment and 49 (40%) were effectively treated. Of these 49, 34 had relapsed after radical surgery and 15 were unresectable at diagnosis. The primary site was intrahepatic in 25 pts, extrahepatic in 18 and gallbladder in 6. The first-line schedules were mainly gemcitabine plus a platinum compound (n=35) or gemcitabine plus capecitabine (n=8). As second line, gemcitabine plus a platinum compound and gemcitabine plus capecitabine were delivered respectively in 15 and 14 pts. The remaining 20 were treated with other regimens (6 gemcitabine plus irinotecan, 14 monochemotherapy). Median time to progression was 3.5 months (IC95% 2.0-5.0) and median overall survival, calculated since second-line treatment start, was 8.1 months (IC95% 4.3-11.9). Median overall survival calculated since first-line start was 18.7 months (IC95% 13.9-23.5). Conclusions: Many patients affected by biliary tract cancer have still a good performance status after first-line chemotherapy and could be treated in second-line with potential survival benefit. The optimal regimen has not yet been identified.

The aim of this study was to investigate the pattern of nasal mucosal involvement in patients with Systemic Lupus Erythematosus (SLE). The authors selected patients affected by SLE with a symptomatology based on bad nasal breathing, in absence of anatomical deformities of the nose. Specimens representing eighteen histological sections of nasal mucosa were examined under the light microscope to establish a set of histopathologic and immunopathologic features. A number of significant alterations were identified. The authors indicate the possible physiopathogenetic relationship between nasal mucosal involvement and systemic disease.

Advanced surveillance, communications and navigation are the main functions needed for an efficient air traffic management. In order to perform them over the entire Earth, including areas (such as oceans and desert regions) not covered by ground stations, it is possible to exploit the potential advantage of satellite technology. A novel architecture based on low-elevation orbit satellites is described and evaluated. The constellation is designed in order to supply the surveillance and data link capabilities of advanced secondary surveillance radar (SSR) Mode S, as well as to allow satellite communication and (by means of a GPS-compatible system) navigation functions.

Auditory cortex activation following multifrequency acoustic stimulation has been evaluated by means of single photon emission tomography (SPET) in one patient before and after an auditory brainstem implant (ABI). No activation could be observed after acoustic stimulation before ABI. After ABI stimulation in the coronal and axial slices, the activation within the temporal cortex contralateral to the stimulated ear was twice (43.76%) that of normal controls (23.94 +/- 2.74%). This marked difference was not present in other selected cortical auditory areas (homolateral temporal, homolateral and contralateral parietal cortices). The temporal cortex was also examined with six consecutive sagittal slices from 18.75 mm up to 56.25 mm lateral to the midline. A very strong activation (51.20%) compared with that of normal controls (9.94 +/- 7.45%) was detected in the 25.26-mm sagittal slice of the temporal cortex contralateral to the stimulated side. The remaining sagittal slices showed an almost normal post-stimulatory activation. As the 25.26-mm sagittal slice corresponds to the medial part of the auditory temporal cortex, its activation suggests that electrode stimulation is concentrated on the region of the cochlear nucleus in which the neurons that transduce high frequencies are located. SPET can be considered useful, in combination with electric auditory-evoked potentials, to obtain information on ABI placement and function, effectiveness of acoustic stimulation, degree of cortical stimulation and tonotopic spatial distribution of auditory cortex activation.