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Histopathological growth patterns (HGPs) of liver metastases represent a potential biomarker for prognosis after resection. They have never been studied in neuroendocrine tumor liver metastases (NETLM). This study evaluated if distinct HGPs can be observed in resected NETLM and if they have prognostic value. Sixty-three patients who underwent resection of NETLM between 01–01-2001 and 31–12-2021 were retrospectively included. HGPs were scored on Haematoxylin&Eosin slides using light microscopy, distinguishing desmoplastic- (dHGP), pushing- (pHGP) and replacement HGP (rHGP). Average HGP scores were calculated per patient. Each patient was classified according to predominant HGP. Overall and Disease-Free Survival (OS and DFS) were evaluated through Kaplan–Meier analysis and Cox regression. Eighteen patients had predominant dHGP (29%), 33 had predominant pHGP (52%) and 11 had predominant rHGP (17%). One patient had mixed HGP (2%). Five-year OS was 76% (95%CI: 66–87%) for the overall cohort. Five-year OS was 92% (95%CI: 77–100%) for dHGP, was 73% (95%CI: 59–91%) for pHGP, 50% (95%CI: 25–100%) for rHGP. Five-year DFS was 39% (95%CI: 19–83%) for dHGP, 44% (95%CI: 27–71%) for rHGP and 50% (95%CI: 23–100%) for pHGP. There was no significant association between HGP and OS or DFS in multivariable analysis. Distinct HGPs could be identified in NETLM. In patients who underwent resection of NETLM, no association was found between HGPs and postoperative survival. Half of the patients with NETLM have a predominant pushing growth pattern, which is a rare growth pattern in liver metastases from breast and colorectal cancer.

ObjectivesShwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. Its predominant manifestations include exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive and susceptibility to short stature. Average birth weight is at the 25th percentile; by the first birthday, >50% of patients drop below the third percentile for height and weight.The study aims at estimating the growth charts for patients affected by SDS in order to give a reference tool helpful for medical care and growth surveillance through the first 8 years of patient’s life.Setting and participantsThis retrospective observational study includes 106 patients (64 M) with available information from birth to 8 years, selected among the 122 patients included in the Italian National Registry of SDS and born between 1975 and 2016. Gender, birth date and auxological parameters at repeated assessment times were collected. The General Additive Model for Location Scale and Shape method was applied to build the growth charts. A set of different distributions was used, and the more appropriate were selected in accordance with the smallest Akaike information criterion.ResultsA total of 408 measurements was collected and analysed. The median number of observations per patient amounted to 3, range 1–11. In accordance with the methods described, specific SDS growth charts were built for weight, height and body mass index (BMI), separately for boys and girls.The 50th and 3rd percentiles of weight and height of the healthy population (WHO standard references) respectively correspond to the 97th and 50th percentiles of the SDS population (SDS specific growth charts), while the difference is less evident for the BMI.ConclusionsSpecific SDS growth charts obtained through our analysis enable a more appropriate classification of patients based on auxological parameters, representing a useful reference tool for evaluating their growth during childhood.

13th World Biennial Congress of the International-Hepato-Pancreato-Biliary-Association (IHPBA) -- SEP 04-07, 2018 -- Geneva, SWITZERLAND, Ardito, Francesco/0000-0003-1596-2862; PESCE, ANTONIO MD/0000-0002-7560-551X; Gallagher, Tom/0000-0002-5765-2574; Bernon, Marc/0000-0002-7967-8548; Stattner, Stefan/0000-0002-5226-7597; GIULIANTE, FELICE/0000-0003-2087-2589; Omoshoro-Jones, Jones A. O./0000-0002-1071-298X; de Rose, Agostino Maria/0000-0003-3310-8088; Abu Hilal, Mohammed/0000-0002-3162-4639; Kleeff, Jorg/0000-0003-3432-6669; Prieto, Mikel/0000-0001-6662-4252; Stromberg, Cecilia/0000-0003-0843-7920, WOS: 000500283700006, PubMed: 31151812, Background: Treatment of bile duct injuries (BDI) during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. the aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy. Methods: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0-7), intermediate (1-6 weeks) and late (6 weeks-6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality. Results: in total 913 patients from 48 centers were included in the analysis. in 401 patients (44%) the bile duct injury was diagnosed intraoperatively, and 126 patients (14%) suffered from concomitant vascular injury. in multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. the rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37-8.65; p = 0.009). Conclusion: After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable., Int Hepato Pancreato Biliary Assoc

Cystic Fibrosis (CF) is an autosomal recessive genetic disease. Two models for screening CF are normally used: newborn screening and population-based CF carrier screening. In turn, there are three main models of population-based CF carrier screening: prenatal carrier screening, preconception carrier screening, and carrier screening outside clinical settings.To evaluate, in the light of the personalist view, the use of carrier screenings for CF outside the clinic, i.e. in non-clinical settings, such as school and workplaces.Analysis has been carried out according to the "Personalist approach" (also called "Triangular model"), an ethical method for performing ethical analysis within HTA process. It includes factual, anthropological and ethical data in a ''triangular'' normative reflection process.Implementing carrier screening for cystic fibrosis outside the clinical settings allows acquisition of knowledge for informing reproductive choices, that can be considered as valuable; benefit-risk ratio seems to be not much favorable; autonomous and responsible decisions can be taken only under certain conditions; economic advantage is difficult to determine; therefore, from a personalist view, implementing carrier screenings outside the clinic seems not to be ethically justified.In accordance with the personalist perspective, public health programs providing carrier screenings outside the clinic should not be implemented.

Background This study was designed to evaluate Streptococcus pneumoniae ( S . pneumoniae ) carriage rates in patients with cystic fibrosis (CF). Methods An oropharyngeal swab was obtained from 212 CF children and adolescents enrolled during routine clinical visits. DNA from swabs was analyzed by real-time polymerase chain reaction. Results A total of 42 (19.8%) CF patients (mean age±standard deviation [SD], 12.0±3.3years) were colonized by S. pneumoniae . Carriage was more common in younger patients and tended to decline with age. Administration of systemic and/or inhaled antibiotics in the last 3months significantly correlated with a reduced carrier state [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07–0.69, and OR 0.26, 95% CI 0.08–0.77, respectively]. Vitamin D serum levels ≥30ng/mL were less common in carriers than that in non-carriers (OR 0.35; 95% CI 0.08–1.49). In both the vaccinated and unvaccinated subjects, serotypes 19F, 5, 4, and 9V were the most commonly carried serotypes. Conclusions S. pneumoniae carrier state of school-age children and adolescents with CF is more prevalent than previously thought, and pneumococcal conjugate vaccination administered in the first year of life does not reduce the risk of re-colonization in later childhood and adolescence.

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107-1114 2016 AASLD

In cystic fibrosis (CF) patients the normal community of commensal bacteria in the gut can be affected by intestinal exocrine alfunction, antibiotic usage and swallowing of infected respiratory mucus. However, CFrelated gut dysbiosis has only recently been subjected to detailed investigation. Herein we report on the integrated metaproteomic, metagenomic and metabolomic workflow for monitoring gut microbiota composition. Twenty-four faecal samples were collected from cystic fibrosis young patients (age range 0-6 years) and 6 faecal samples from healthy children. All samples were processed for peptide, DNA and metabolite analysis. Protein content was analyzed with a shotgun metaproteomic approach by a nano-scale LC-MS2 set-up (Bruker amaZon-ETD) and filtered for operational taxon units (OTUs) assignment. OTUs were corroborated by hybridization of the small subunit ribosomal RNA (SSU rRNA) gene variable regions against the human intestinal tract microarray platform HITChip. In order to evaluate the volatile metabolites a gas-chromatographic (GC)–mass spectrometer (MS)/solid-phase microextraction (SPME) analysis was performed. 1H-NMR spectra were acquired on a Varian 400 MHz Mercury-plus NMR. Pre-analytical steps of the metaproteomics workflow were devised to improve hit coverage, while the OTUs repository was guaranteed by metagenomics entries. 1H-NMR and GC-MS/SPME were used to identify and quantify fecal metabolites. The application of integrated meta-omics-based approaches to the characterization of the membership and dynamics of the polymicrobial communities colonizing the gut is expected to have important predictive potential in translational medicine, specially in CF-related gut dysbiosis.

PREFAZIONE: La Diagnostica per Immagini è oggi al primo posto fra le indagini strumentali indispensabili a supporto della prima diagnosi clinica ed è il filo conduttore del monitoraggio del decorso clinico di diverse patologie. Nei dieci anni intercorsi dalla prima edizione, l’imaging ha subito tumultuose evoluzioni tecnologiche in termini di digitalizzazione delle immagini, con straordinari risultati applicativi, tanto da introdurre nuove metodiche e ridurne l’indicazione o farne scomparire altre. L’acquisizione delle immagini in TC ed RM è divenuta più veloce e i pixel delle immagini digitali più piccoli. Ciò ha consentito nuove applicazioni cliniche quali la cardio-TC, l’entero-TC e la colonscopia virtuale, l’angio-TC di tutti gli apparati fino a livello dei piccoli vasi: quest’ultima ha completamente sostituito l’angiografia convenzionale. I sistemi CAD (Computed Aided Detection) stanno sempre più affiancando la diagnosi radiologica come strumento di seconda lettura in settori quale il torace, la mammografia e la colonscopia virtuale, specie negli esami di screening. Inoltre, la digitalizzazione delle immagini insieme alla diffusione dei sistemi RIS-PACS ha radicalmente mutato l’attività del radiologo, che oggi si svolge su workstation capaci di visualizzare velocemente migliaia di immagini, facilitandone così la lettura, e di eseguire su queste ricostruzioni tridimensionali in tempo reale; per di più essa può essere svolta in sedi distanti. Contemporaneamente, negli ultimi anni si è osservato in tutto il mondo uno smisurato incremento di richieste delle indagini radiologiche, che ha indotto la necessità di strumenti per promuovere l’appropriatezza e l’efficacia degli interventi ed un uso più razionale delle risorse: da qui la nascita di numerose linee guida per le indicazioni alle varie metodiche di imaging e di algoritmi decisionali condivisi dalle varie società scientifiche per le diverse patologie, che devono essere conosciuti. I radiologi in formazione, come anche gli specialisti di altre discipline, debbono dunque rendersi edotti delle numerose problematiche di ordine tecnico-metodologico e interpretativo che emergono nelle applicazioni cliniche delle tante e complesse apparecchiature, con l’imperativo del più razionale e accurato utilizzo di esse. Essi sentono profondamente questo loro dovere ed è infatti molto frequente da parte loro la richiesta di testi che forniscano chiare e complete informazioni sull’ottimale impiego delle varie tecniche d’indagine, specie se trattano nel loro insieme e con criterio d’integrazione tutte le tecniche di diagnostica per immagini. Con questo nostro lavoro abbiamo dunque inteso concorrere a soddisfare tale domanda, proponendoci di fornire ai radiologi un testo di approfondimento ed una guida ragionata nella scelta della tecnica di elezione e di quelle complementari nello studio morfologico e funzionale delle patologie dei diversi apparati e di illustrarne i principali reperti morfologici. Abbiamo cercato di redigere questo testo con modalità e terminologia tali da poterlo rendere anche un manuale di facile consultazione per tutti i medici operanti nel campo della medicina generale e nelle branche specialistiche, che vogliano orientarsi nel complesso settore della diagnostica per immagini, vogliano acquisire le informazioni necessarie per valutare in ciascuna patologia l’utilità delle varie tecniche, desiderino conoscerne le potenzialità e anche i limiti e vogliano rendersi edotti dei risultati che si possono ottenere mediante l’integrazione delle diverse tecniche. Negli ultimi dieci anni si sono inoltre sviluppate la genomica e la proteomica e, per lo studio di questi fenomeni, si sono sviluppate le nanotecnologie (quali i sistemi meccanici di microelettronica, o MEMS), in grado di identificare a livello molecolare le variazioni della composizione dei costituenti del corpo umano e l’imaging molecolare (la micro-PET o tomografia ad emissione di positroni, la micro-SPECT o tomografia ad emissione di un singolo fotone, la micro-TC, la micro-RM, la micro-ecografia e l’optical imaging), alcune delle quali vengono applicate solamente in campo pre-clinico su modelli animali da laboratorio (come l’optical imaging), altre già trovano analoga e routinaria applicazione sia preclinica che clinica. Tali argomenti, che probabilmente troveranno applicazione umana negli anni a venire, sono anch’essi stati oggetto di trattazione. L’opera si compone di due volumi ed è organizzata in cinque parti. La Parte Prima (capitoli 1-3) tratta dei principi fisici delle metodiche computerizzate (TC ed RM) e dei relativi mezzi di contrasto. La Parte Seconda (capitoli 4-26) è dedicata a tutti i settori di applicazione delle metodiche TC ed RM nei diversi distretti anatomici, passando in rassegna tutte le principali patologie d’organo; è la più ampia in quanto in essa è contenuta la maggior parte delle informazioni (dati epidemiologici e anatomopatologici, classificazioni nosologiche, algoritmi diagnostici, classificazioni in stadi della patologia neoplastica, ecc.) che servono anche come riferimento nell’esporre le applicazioni cliniche delle altre tecniche. La Parte Terza (capitoli 27-29) presenta tre metodiche innovative (spettroscopia RM, RM funzionale, ed imaging molecolare). La Parte Quarta (II volume) esamina le applicazioni dell’US nei diversi distretti anatomici. La Parte Quinta (II volume) è dedicata alle applicazioni della Medicina Nucleare. ... ANTONINO LENTINI, RITA GOLFIERI

Dalla Prefazione: La Diagnostica per Immagini è oggi al primo posto fra le indagini strumentali indispensabili a supporto della prima diagnosi clinica ed è il filo conduttore del monitoraggio del decorso clinico di diverse patologie. Nei dieci anni intercorsi dalla prima edizione, l’imaging ha subito tumultuose evoluzioni tecnologiche in termini di digitalizzazione delle immagini, con straordinari risultati applicativi, tanto da introdurre nuove metodiche e ridurne l’indicazione o farne scomparire altre. L’acquisizione delle immagini in TC ed RM è divenuta più veloce e i pixel delle immagini digitali più piccoli. Ciò ha consentito nuove applicazioni cliniche quali la cardio-TC, l’entero-TC e la colonscopia virtuale, l’angio-TC di tutti gli apparati fino a livello dei piccoli vasi: quest’ultima ha completamente sostituito l’angiografia convenzionale. I sistemi CAD (Computed Aided Detection) stanno sempre più affiancando la diagnosi radiologica come strumento di seconda lettura in settori quale il torace, la mammografia e la colonscopia virtuale, specie negli esami di screening. Inoltre, la digitalizzazione delle immagini insieme alla diffusione dei sistemi RIS-PACS ha radicalmente mutato l’attività del radiologo, che oggi si svolge su workstation capaci di visualizzare velocemente migliaia di immagini, facilitandone così la lettura, e di eseguire su queste ricostruzioni tridimensionali in tempo reale; per di più essa può essere svolta in sedi distanti. Contemporaneamente, negli ultimi anni si è osservato in tutto il mondo uno smisurato incremento di richieste delle indagini radiologiche, che ha indotto la necessità di strumenti per promuovere l’appropriatezza e l’efficacia degli interventi ed un uso più razionale delle risorse: da qui la nascita di numerose linee guida per le indicazioni alle varie metodiche di imaging e di algoritmi decisionali condivisi dalle varie società scientifiche per le diverse patologie, che devono essere conosciuti. I radiologi in formazione, come anche gli specialisti di altre discipline, debbono dunque rendersi edotti delle numerose problematiche di ordine tecnico- metodologico e interpretativo che emergono nelle applicazioni cliniche delle tante e complesse apparecchiature, con l’imperativo del più razionale e accurato utilizzo di esse. Essi sentono profondamente questo loro dovere ed è infatti molto frequente da parte loro la richiesta di testi che forniscano chiare e complete informazioni sull’ottimale impiego delle varie tecniche d’indagine, specie se trattano nel loro insieme e con criterio d’integrazione tutte le tecniche di diagnostica per immagini. Con questo nostro lavoro abbiamo dunque inteso concorrere a soddisfare tale domanda, proponendoci di fornire ai radiologi un testo di approfondimento ed una guida ragionata nella scelta della tecnica di elezione e di quelle complementari nello studio morfologico e funzionale delle patologie dei diversi apparati e di illustrarne i principali reperti morfologici. Abbiamo cercato di redigere questo testo con modalità e terminologia tali da poterlo rendere anche un manuale di facile consultazione per tutti i medici operanti nel campo della medicina generale e nelle branche specialistiche, che vogliano orientarsi nel complesso settore della diagnostica per immagini, vogliano acquisire le informazioni necessarie per valutare in ciascuna patologia l’utilità delle varie tecniche, desiderino conoscerne le potenzialità e anche i limiti e vogliano rendersi edotti dei risultati che si possono ottenere mediante l’integrazione delle diverse tecniche. Negli ultimi dieci anni si sono inoltre sviluppate la genomica e la proteomica e, per lo studio di questi fenomeni, si sono sviluppate le nanotecnologie (quali i sistemi meccanici di microelettronica, o MEMS), in grado di identificare a livello molecolare le variazioni della composizione dei costituenti del corpo umano e l’imaging molecolare (la micro-PET o tomografia ad emissione di positroni, la micro-SPECT o tomografia ad emissione di un singolo fotone, la micro-TC, la micro-RM, la micro-ecografia e l’optical imaging), alcune delle quali vengono applicate solamente in campo pre-clinico su modelli animali da laboratorio (come l’optical imaging), altre già trovano analoga e routinaria applicazione sia preclinica che clinica. Tali argomenti, che probabilmente troveranno applicazione umana negli anni a venire, sono anch’essi stati oggetto di trattazione. L’opera si compone di due volumi ed è organizzata in cinque parti. La Parte Prima (capitoli 1-3) tratta dei principi fisici delle metodiche computerizzate (TC ed RM) e dei relativi mezzi di contrasto. La Parte Seconda (capitoli 4-26) è dedicata a tutti i settori di applicazione delle metodiche TC ed RM nei diversi distretti anatomici, passando in rassegna tutte le principali patologie d’organo; è la più ampia in quanto in essa è contenuta la maggior parte delle informazioni (dati epidemiologici e anatomopatologici, classificazioni nosologiche, algoritmi diagnostici, classificazioni in stadi della patologia neoplastica, ecc.) che servono anche come riferimento nell’esporre le applicazioni cliniche delle altre tecniche. La Parte Terza (capitoli 27-29) presenta tre metodiche innovative (spettroscopia RM, RM funzionale, ed imaging molecolare). La Parte Quarta (II volume) esamina le applicazioni dell’US nei diversi distretti anatomici. La Parte Quinta (II volume) è dedicata alle applicazioni della Medicina Nucleare. ANTONINO LENTINI, RITA GOLFIERI

Background: Gadoxetic acid (Gd-EOB-DTPA) is a “hepatocyte-specific” contrast agent for magnetic resonance (MR), taken up by hepatocytes, and thus producing both vascular and hepatocyte-specific MR patterns. Aim: To assess the diagnostic contribution of Gd-EOB-DTPA MR, including the added value of hepatocyte-specific phase images, in the recall diagnostic strategy of small liver nodules emerged during surveillance program of cirrhotic patients. Methods: Forthy-one consecutive small (10-30 mm) liver nodules detected at ultrasonography in 26 patients with cirrhosis were prospectively submitted to contrast-enhanced ultrasound, helical-computed tomography, and Gd-EOBDTPA MR. The diagnosis of HCC was made according to AASLD 2005 criteria. Results: Among the 41 nodules, 30 (73%) received a final diagnosis of HCC. Overall, Gd-EOB-DTPA MR was the most sensitive technique for detecting the typical vascular pattern (arterial hypervascularity followed by venous wash-out) which was observed in 25/30 (RMN vs CT: 80% vs 63%, p=0.2; RMN vs CEUS: 80% vs 43%, p=0.007; CT vs CEUS: 63% vs 43%, p=0.19, Fisher’s exact test). HCC (leading to 5 “hypovascular” HCC). Thirty-four nodules were hypointense during hepatocyte-specific phase: all of the 30 HCC nodules (100%) and 4 non-malignant nodules at biopsy, 2 of which receiving however a diagnosis of HCC during the follow-up. All of the 5 “hypovascular” HCC nodules appeared hypointense both in the venous and hepatocyte-specific phase of Gd-EOB-DTPA MR. Conclusions: Gd-EOB-DTPA MR may increase the diagnostic potential of non-invasive techniques, especially for HCC lacking a typical vascular pattern. Double hypointensity at Gd-EOB-DTPA MR, on venous and hepatocyte-specific phases, could be considered as a new radiological pattern highly suggestive for early HCC.

OBJECTIVE: To prospectively assess the additional value of the hepatobiliary (HB) phase of Gd-EOB-DTPA-MRI in identifying and characterising small (≤ 2 cm) hepatocellular carcinomas (HCCs) undetermined in dynamic phases alone because of their atypical features, according to the AASLD criteria. METHODS: 127 cirrhotic patients were evaluated with Gd-EOB-DTPA-MRI in two sets: unenhanced and dynamic phases; unenhanced, dynamic and HB phases. Sixty-two out of 215 nodules (29%) were atypical in 42 patients (33%). RESULTS: 62 atypical nodules were reported at histology: high-grade dysplastic nodules (HGDN)/early HCC (n = 20), low-grade DN (LGDN) (n = 21), regenerative nodules (n = 17) and nodular regenerative hyperplasia (n = 4). The sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were increased by the addition of the HB phase: 88.4-99.4%, 88-95%, 88-98.5%, 97-99%, and 65-97.5%, respectively. Twenty atypical nodules were malignant (32%), 19 of which were characterised only during the HB phase. CONCLUSIONS: The HB phase is 11% more sensitive in the classification of HGDN/early HCC than dynamic MRI, with an added value of 32.5% in the NPV. The high incidence (33%) of atypical nodules and their frequent malignancy (32%) suggest the widespread employment of Gd-EOB-DTPA-MRI in the follow-up of small nodules (≤ 2 cm) in cirrhosis.

Background: Patients undergoing liver transplantation for hepatocellular carcinoma within the Milan criteria (single tumour ≤5 cm in size or ≤3 tumours each ≤3 cm in size, and no macrovascular invasion) have an excellent outcome. However, survival for patients with cancers that exceed these criteria remains unpredictable and access to transplantation is a balance of maximising patients' chances of cure and organ availability. The aim of this study was to explore the survival of patients with tumours that exceed the Milan criteria, to assess whether the criteria could be less restrictive, enabling more patients to qualify as transplant candidates, and to derive a prognostic model based on objective tumour characteristics, to see whether the Milan criteria could be expanded. Methods: Data on patients who underwent transplantation for hepatocellular carcinoma despite exceeding Milan criteria at different centres were recorded via a web-based survey completed by specialists from each centre. The survival of these patients was correlated retrospectively with the size of the largest tumour nodule, number of nodules, and presence or absence of microvascular invasion detected at pathology. Contoured multivariable regression Cox models produced survival estimates by means of different combinations of the covariates. The primary aim of this study was to derive a prognostic model of overall survival based on tumour characteristics, according to the main parameters used in the Tumour Node Metastasis classification. The secondary aim was the identification of a subgroup of patients with hepatocellular carcinoma exceeding the Milan criteria, who achieved a 5-year overall survival of at least 70%-ie, similar to the outcome expected for patients who meet the Milan criteria. Findings: Over a 10-month period, between June 25, 2006, and April 3, 2007, data for 1556 patients who underwent transplantation for hepatocellular carcinoma were entered on the database by 36 centres. 1112 patients had hepatocellular carcinoma exceeding Milan criteria and 444 patients had hepatocellular carcinoma shown not to exceed Milan criteria at post-transplant pathology review. In the group of patients with hepatocellular carcinomas exceeding the criteria, the median size of the largest nodule was 40 mm (range 4-200) and the median number of nodules was four (1-20). 454 of 1112 patients (41%) had microvascular invasion and, for those transplanted outside the Milan criteria, 5-year overall survival was 53·6% (95% CI 50·1-57·0), compared with 73·3% (68·2-77·7) for those that met the criteria. Hazard ratios (HR) associated with increasing values of size and number were 1·34 (1·25-1·44) and 1·51 (1·21-1·88), respectively. The effect was linear for size, whereas for number of tumours, the effect tended to plateau above three tumours. The effect of tumour size and number on survival was mediated by recurrence (b=0·08, SE=0·12, p=0·476). The presence of microvascular invasion doubled HRs in all scenarios. The 283 patients without microvascular invasion, but who fell within the Up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumour [in cm] and the number of tumours) achieved a 5-year overall survival of 71·2% (64·3-77·0). Interpretation: More patients with hepatocellular carcinoma could be candidates for transplantation if the current dual (yes/no) approach to candidacy, based on the strict Milan criteria, were replaced with a more precise estimation of survival contouring individual tumour characteristics and use of the up-to-seven criteria. Funding: Specific funding was not used to do this study. © 2009 Elsevier Ltd. All rights reserved

Scopo: Valutare l'accuratezza diagnostica della Colonscopia Virtuale (CV) mediante utilizzo di sistema CAD in un gruppo di pazienti (pz) con sangue occulto positivo (FOBT).

Several reports have indicated that fecal elastase-1 (EL-1) determination is a new, sensitive, and specific noninvasive pancreatic function test; however, very few patients with malabsorption due to small intestine diseases have been included in the previous studies. The aim of the study was to compare the diagnostic accuracy of fecal EL-1 and fecal chymotrypsin (FCT) in distinguishing between pancreatic maldigestion and intestinal malabsorption. Three groups of subjects were studied: group A included 49 patients with known cystic fibrosis (25 males, median age 5 years); group B included 43 subjects with various small intestine diseases (17 males, median age 6 years); and group C included 45 children without any history of gastrointestinal disease (22 males, median age 5 years). In all patients, stools were collected for 72 h on a standard diet and fecal EL-1, FCT, and steatocrit tests were performed. Both EL-1 and FCT were below normal limits in all CF patients with pancreatic maldigestion not treated with pancreatic enzyme (100% sensitivity for both assays); El-1, but not FCT, was also below normal in all the CF patients with pancreatic maldigestion treated with pancreatic extracts. Both EL-1 and FCT values in the CF group were significantly lower than in subjects with various small intestinal diseases and in children without any history of gastrointestinal disease (P < 0.0001). FCT, but not EL-1, values showed an inverse statistically significant correlation with steatocrit values in the whole CF group (P < 0.001); FCT was below normal in three of four CF patients with steatorrhea on pancreatic enzyme therapy. Both EL-1 and FCT had 100% specificity when calculated in children without any history of gastrointestinal disease; in contrast, specificity was 86% for EL-1 and 76% for FCT if we considered the control group with small intestinal diseases: low EL-1 was observed in two cases of intestinal giardiasis, two cases of short bowel syndrome, one case of celiac disease, and one case of intestinal pseudobstruction; FCT was abnormal in four cases of intestinal giardiasis, three cases of celiac disease, one case of short bowel syndrome, one case of Crohn's disease, and one case of intestinal pseudobstruction. Diagnostic accuracy was 92% for fecal EL-1 and 82% for FCT. Steatocrit values were over the normal limit in 11 patients with small intestine diseases; in 7/11 of these patients at least one of the pancreatic test results was below the normal limit. In conclusions, in patients with CF, fecal EL-1 determination is not more sensitive than FCT in identifying pancreatic maldigestion; however, fecal EL-1 assay is more specific than FCT determination in distinguishing pancreatic maldigestion from intestinal malabsorption.

Cystic fibrosis is a lethal autosomal recessive condition caused by a defect of the transmembrane conductance regulator gene that has a key role in cell homeostasis. A dysfunctional cystic fibrosis transmembrane conductance regulator impairs the efflux of cell anions such as chloride and bicarbonate, and also that of other solutes such as reduced glutathione. This defect produces an increased viscosity of secretions together with other metabolic defects of epithelia that ultimately promote the obstruction and fibrosis of organs. Recurrent pulmonary infections and respiratory dysfunction are main clinical consequences of these pathogenetic events, followed by pancreatic and liver insufficiency, diabetes, protein-energy malnutrition, etc. This complex comorbidity is associated with the extensive injury of different biomolecular targets by reactive oxygen species, which is the biochemical hallmark of oxidative stress. These biological lesions are particularly pronounced in the lung, in which the extent of oxidative markers parallels that of inflammatory markers between chronic events and acute exacerbations along the progression of the disease. Herein, an abnormal flux of reactive oxygen species is present by the sustained activation of neutrophils and other cystic fibrosis-derived defects in the homeostatic processes of pulmonary epithelia and lining fluids. A sub-optimal antioxidant protection is believed to represent a main contributor to oxidative stress and to the poor control of immuno-inflammatory pathways in these patients. Observed defects include an impaired reduced glutathione metabolism and lowered intake and absorption of fat-soluble antioxidants (vitamin E, carotenoids, coenzyme Q-10, some polyunsaturated fatty acids, etc.) and oligoelements (such as Se, Cu and Zn) that are involved in reactive oxygen species detoxification by means of enzymatic defenses. Oral supplements and aerosolized formulations of thiols have been used in the antioxidant therapy of this inherited disease with the main aim of reducing the extent of oxidative lesions and the rate of lung deterioration. Despite positive effects on laboratory end points, poor evidence was obtained on the side of clinical outcome so far. These aspects examined in this critical review of the literature clearly suggest that further and more rigorous trials are needed together with new generations of pharmacological tools to a more effective antioxidant and anti-inflammatory therapy of cystic fibrosis patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

In this study we describe and discuss the way we daily act in remote telematic tracking of CF outpatients, a procedure which has been improved through our daily experience in telehomecare.Currently, there are almost 30 patients involved in our telehomecare project. We describe and discuss intervention parameters and the way we manage a register of performances in spreadsheet format. We also describe the training program for the patients and their and the procedures through which we maintain contacts with patients and Vivisol assistance and the periodical satisfaction surveys.(from 15 of february 2010 to 24 of may 2011). Total transmissions 882, Spirometry 1317, SaO2 291, Compliance (transmissions/patient days) 8,91%, Hospital controls 19, Total contacts 722, Phone calls 494.We analyze the 2010 - 2011 data. We discuss the compliance of patients toward Telehomecare, the efficacy of cell phone in establishing contact with patients and the relevancy of symptoms' rescue in diagnosing the pulmonary relapse episodes. We discuss medico-legal aspects of telemedicine activity, in the light of standards and legislation, including issues related to the processing of privacy and security data. We discuss the professional team needs and requirements, dedicated to the activities of telemedicine and procedures related to clinical risk management. We conclude by underlying how telemedicine represents a promising new tool for patients and health professionals, and that under certain conditions it can improve the assistance, working conditions and also to reduce costs. However, its usage has to be followed by precise studies about its efficacy, and also by paying particular attention to the partly new issues that derive from it.

Three-dimensional reconstruction techniques have been used since the development of computed tomography. In skeletal radiology they have been used to better visualize fractures and spatial relationships between fragments in maxillo-facial surgery. Aim of this paper is to illustrate the most important reconstruction techniques and their application in skeletal radiology. Images can be obtained by means of a Spiral CT scanner with the following parameters: collimation/pitch/reconstruction interval 2/1/1. Acquired images are sent to a workstation with a software running on a Window NT platform Vitrea 2.01 (Vital Images, USA) equipped with Volume Rendering algorithm. SSD as well as MPR and curved reformatted reconstruction algorithms is available at the CT console. Three-dimensional reconstruction have been shown to be useful for the diagnosis and for a preoperative planning. Other applications of three-dimensional reconstruction techniques are prosthesis engineering and biomechanic research. 3D images help the communication between radiologist and surgeons. Technical advances in acquisition methods and in reconstruction algorithms are needed to improve image quality and use in skeletal radiology.

Earlier analysis of the Italian population showed patterns of genetic differentiation that were interpreted as being the result of population settlements going back to pre-Roman times. DNA disease mutations may be a powerful tool in further testing this hypothesis since the analysis of diseased individuals can detect variants too rare to be resolved in normal individuals. We present data on the relative frequencies of 60 cystic fibrosis (CF) mutations in Italy and the geographical distribution of the 12 most frequent CF mutations screened in 3492 CF chromosomes originating in 13 Italian regions. The 12 most frequent mutations characterize about 73% of the Italian CF chromosomes. The most common mutation, delta F508, has an average frequency of 51%, followed by N1303K and G542X, both with average frequencies around 5%. Multivariate analyses show that the relative frequencies of CF mutations are heterogeneous among Italian regions, and that this heterogeneity is weakly correlated with the geographical pattern of non-DNA 'classical' genetic markers. The northern regions are well differentiated from the central-southern regions and within the former group the western and eastern regions are remarkably distinct. Moreover, Sardinia shows the presence of mutation T338I, which seems absent in any other European CF chromosome. The north-western regions of Italy, characterized by the mutation 1717-1G--A, were under Celtic influence, while the north-east regions, characterized by the mutations R1162X, 2183AA--G and 711 + 5G--A, were under the influence of the Venetic culture.