Resectable and borderline resectable pancreatic ductal adenocarcinoma: Role of the radiologist and oncologist in the era of precision medicine

The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer

New advances in radiomics of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are uncommon neoplasms of the gastrointestinal tract with peculiar clinical, genetic, and imaging characteristics. Preoperative knowledge of risk stratification and mutational status is crucial to guide the appropriate patients’ treatment. Predicting the clinical behavior and biological aggressiveness of GISTs based on conventional computed tomography (CT) and magnetic resonance imaging (MRI) evaluation is challenging, unless the lesions have already metastasized at the time of diagnosis. Radiomics is emerging as a promising tool for the quantification of lesion heterogeneity on radiological images, extracting additional data that cannot be assessed by visual analysis. Radiomics applications have been explored for the differential diagnosis of GISTs from other gastrointestinal neoplasms, risk stratification and prediction of prognosis after surgical resection, and evaluation of mutational status in GISTs. The published researches on GISTs radiomics have obtained excellent performance of derived radiomics models on CT and MRI. However, lack of standardization and differences in study methodology challenge the application of radiomics in clinical practice. The purpose of this review is to describe the new advances of radiomics applied to CT and MRI for the evaluation of gastrointestinal stromal tumors, discuss the potential clinical applications that may impact patients’ management, report limitations of current radiomics studies, and future directions

In Vitro Biocompatibility Evaluation of Nine Dermal Fillers on L929 Cell Line

Objective. Biomaterial research for soft tissue augmentation is an increasing topic in aesthetic medicine. Hyaluronic acid (HA) fillers are widely used for their low invasiveness and easy application to correct aesthetic defects or traumatic injuries. Some complications as acute or chronic inflammation can occur in patients following the injection. Biocompatibility assays are required for medical devices intended for human use, in order to prevent damages or injuries in the host. In this study, nine HA fillers were tested in order to evaluate their cytotoxicity and their effects on L929 cell line, according to the UNI EN ISO 10993 regulation. Methods. Extracts were prepared from nine HA fillers, and MTS viability assay was performed after 24 h, 48 h, and 72 h of exposure of cells to extracts. Cells cultured with HA filler extracts were monitored for up to 72 h, counted, and stained with haematoxylin/eosin in order to evaluate the cell proliferation rate and morphology. Results. None of the filler tested showed a cytotoxic effect. Two samples showed a higher vitality percentage and higher cell number while two samples showed a lower vitality percentage and lower cell number at 72 h. Conclusion. Data obtained suggest that although examined fillers are not cytotoxic, they show different effects on the in vitro cell proliferation rate. In vitro studies of medical devices could lead to important implications since these could aid to predict effects about their in vivo application. These easy and rapid assays could be useful to test new materials intended for human use avoiding animal tests

Analisi biomolecolare di ceppi di Canine Distemper Virus (CDV) in furetti domestici (Mustela putorius furo)

L\u2019agente eziologico del cimurro (CDV) appartiene alla famiglia Paramyxoviridae, genere Morbillivirus ed \ue8 causa di una patologia infettiva e contagiosa in canidi, mustelidi e procionidi. Gli Autori, descrivono un caso clinico di cimurro in due furetti domestici vaccinati con un ceppo Onderstepoort avianizzato. e la caratterizzazione biomolecolare del CDV isolato. I furetti presentavano un quadro clinico caratterizzato da dermatite pruriginosa e squamo-purulenta, alla regione del mento, peri-labiale, peri-vulvare ed al condotto uditivo esterno. I soggetti venivano a morte tre settimane dopo l\u2019esordio dei sintomi. I campioni di croste prelevati sono stati sottoposti ad estrazione degli acidi nucleici ed analizzati mediante RT-PCR per CDV. E\u2019 stata effettuata l\u2019analisi con enzimi di restrizione (RFLP-PCR) di conferma, per discriminare i ceppi vaccinali dai ceppi di campo. I prodotti di amplificazione sono stati purificati e sottoposti a sequenziamento. Le sequenze di 1823 nt del gene H del CDV sono state comparate mediante Clustal X con analoghe sequenze di ceppi di campo e ceppi vaccinali disponibili su GeneBank. Sulla base dei dati ottenuti le sequenze sono risultate appartenenti al lineage Europa, ben segregato dal lineage America-1, che raccoglie i principali ceppi vaccinali avianizzati, e differente dal cluster dei ceppi Rockborn-like. Il sequenziamento ha confermato il risultato ottenuto con la RFLP-PCR e la mancanza di relazione con il ceppo vaccinale inoculato. Le due sequenze ottenute, presentando un\u2019omologia nucleotidica elevata per ceppi isolati da cani in Italia, sono risultate differenti dal lineage Wildlife. Nel furetto l\u2019infezione da cimurro ha un esito fatale quasi nel 100% dei casi e viene controllata attraverso l\u2019uso di vaccini. Questo lavoro rappresenta un contributo alla esigua disponibilit\ue0 bibliografica in merito alle infezioni da CDV nei mustelidi ed implementa i dati disponibili sui ceppi virali circolanti. Il metodo diagnostico descritto rappresenta un sistema rapido e sensibile per la diagnosi dell\u2019infezione da cimurro

Evidenza di un caso di epatite infettiva del cane in Sicilia

L’Adenovirus Canino di tipo 1 (CAV-1), appartenente al genere Mastadenovirus, famiglia Adenoviridae, è l’agente causale dell’epatite infettiva del cane (ICH). Il virus replica negli endoteli vascolari e negli epatociti, causando epatite necrotico emorragica acuta. I sintomi neurologici sono rari e sono causati da una vasculite del SNC. Negli ultimi anni, la diffusa vaccinazione ha ridotto la circolazione di CAV-1 ed i casi clinici segnalati sono diventati rari ed isolati. In questo lavoro, gli Autori descrivono un caso clinico in un cucciolo di 2 mesi, non vaccinato, con febbre, prostrazione, convulsioni, vomito, diarrea ed esito infausto in una settimana. A seguito dell’esame autoptico, sono stati prelevati campioni di vari organi (cuore, milza, polmone, rene, encefalo, fegato, intestino). Questi sono stati analizzati mediante PCR ed isolamento su colture cellulari sensibili, per la ricerca dei principali agenti virali causa di malattia nel cane: parvovirus, cimurro, CAV-1 e CAV-2, coronavirus, rotavirus. Tutti gli organi esaminati sono risultati positivi sia in PCR che all’isolamento su MDCK solo per CAV-1. Il genoma estratto è stato amplificato secondo la metodica descritta da Hu et al. (2001), in grado di discriminare CAV-1 da CAV-2. L’isolamento su MDCK ha prodotto effetto citopatico al secondo passaggio ed il virus isolato è stato identificato mediante immunofluorescenza diretta e PCR. Il presente lavoro costituisce un contributo alla esigua disponibilità bibliografica sulle infezioni da CAV-1. La vaccinazione sistematica condotta nell’ultimo decennio ha sensibilmente ridotto i casi di malattia. Infatti, gli ultimi casi risalgono al 2001 in Basilicata e Puglia dove sono stati descritti rispettivamente un caso di CAV-1 con sintomatologia classica ed un altro caratterizzato anche da sintomi neurologici. La presente indagine dimostra l’attuale circolazione di CAV-1 e la sporadica comparsa di casi clinici. La vaccinazione sistematica con CAV-2 rimane il mezzo più efficace di protezione della popolazione canina e costituisce l’unico metodo di controllo della malattia

Evaluation of posttreatment response of hepatocellular carcinoma: comparison of ultrasonography with second-generation ultrasound contrast agent and multidetector CT

We evaluated the ability of one-month follow-up contrast- enhanced ultrasound (CEUS) with second-generation contrast agent in monitoring radio frequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) treatments of hepatocellular carcinoma (HCC). One-hundred forty-eight HCCs were studied using CEUS: 110 nodules were treated with RFA [41/110 RFA were performed using a pretreatment and an immediate postablation evaluation using CEUS (group 1); 69/110 using only US guidance (group 2)] and 38 nodules treated with TACE. For statistical analysis, McNemar test was used. Overall complete response was observed in 107/148 nodules (92/110 treated with RFA and 15/38 with TACE). A better rate of complete response was found in group 1 compared to group 2 (92.7% vs. 78.3%). In RFA treatment, CEUS showed a sensitivity of 83.3% and a specificity of 100% (diagnostic accuracy of 97%) using MDCT as reference standard with no statistical difference (p > 0.05). CEUS detected all cases of incomplete response in HCC treated with TACE using angiography as reference standard (diagnostic accuracy 100%).We recommend assessing residual intratumoral flow on CEUS during RFA procedure to determine the necessity of immediate additional treatment. In case of positive CEUS results, HCC treated with TACE should be considered still viable

Analisi filogenetica condotta su ceppi di Bovine Diarrhea Virus (BVDV) isolati in Sicilia

La Diarrea Virale del Bovino-Malattia delle Mucose, è una malattia infettiva che colpisce i bovini, ampiamente diffusa a livello mondiale. L’agente infettivo responsabile è un virus provvisto di envelope e con un genoma ad RNA a singolo filamento e a polarità positiva, appartenente al genere Pestivirus, famiglia Flaviviridae. A causa dell’elevata capacità di andare in contro a mutazioni genetiche, esistono numerose varianti di BVDV con diverso assetto antigenico e differente patogenicità. Ad oggi sono noti due genotipi: il BVDV-I e il BVDV-II. Il BVDV-I comprende almeno 13 sottotipi, mentre ne sono stati descritti solo 2 per il BVDV-II. Quest’ultimo, poco diffuso nel nostro territorio, è responsabile di una sindrome emorragica altamente letale. In Italia è stato isolato da bovini che erano stati trattati con vaccini anti-IBR contaminati. Recentemente è stata anche ipotizzata la presenza in Italia di una terza variante, il BVDV-III. L’infezione da BVDV spesso è associata con disordini a livello riproduttivo e nelle bovine gravide può esitare in aborto, malformazioni fetali o nascita di vitelli persistentemente infetti (PI). Scopo del presente lavoro è stato quello di genotipizzare i ceppi di BVDV isolati, al fine di approfondire la conoscenza circa la diffusione delle diverse varianti virali in Sicilia. Sono stati sequenziati ed analizzati filogeneticamente 18 ceppi, isolati su linee cellulari MDBK, da campioni di animali che erano risultati positivi in RT-PCR specifica per una porzione della regione 5’ UTR e in ELISA per la ricerca dell’antigene virale. Per il sequenziamento, i ceppi virali sono stati sottoposti ad estrazione dell’RNA ed amplificazione di una porzione della regione 5’ UTR, secondo quanto descritto da Vilcek et al. (1994). Le sequenze ottenute sono state successivamente allineate e comparate con altre sequenze di riferimento disponibili in GeneBank. L’analisi filogenetica condotta attraverso il metodo Neighbour-Joining, ha permesso di evidenziare la presenza di due sottotipi virali appartenenti al genotipo BVDV-I: BVDV-Ib e BVDV-Ie. Nessun ceppo virale è risultato appartenere al genotipo BVDV-II. Una successiva analisi di restrizione condotta sugli amplificati utilizzando l’enzima di restrizione AvaI, ha confermato infine l’origine bovina di ciascun isolato. L’analisi filogenetica dei ceppi virali isolati in un determinato territorio, rappresenta un valido strumento per il monitoraggio di una malattia infettiva, permettendo l’evidenziazione di nuove eventuali varianti causa di emergenze sanitarie, la realizzazione di test diagnostici specifici e la realizzazione di una profilassi vaccinale mirata

Advanced magnetic resonance imaging of cortical laminar necrosis in patients with stroke

Purpose: The aim of this study was to assess the novel advanced magnetic resonance imaging findings of acute stage cortical laminar necrosis developing after complicated cardiovascular or abdominal surgery. Materials and methods: This institutional review board-approved study included patients with postoperative stroke due to cortical laminar necrosis imaged with magnetic resonance in the acute stage. Brain magnetic resonance imaging examinations were obtained on a 3T magnetic resonance scanner within 48 hours of the neurological symptoms, including diffusion-weighted images (b value, 1000 s/mm2) and arterial spin labelling using a pseudo-continuous arterial spin labelling method in four patients. Conventional and advanced magnetic resonance images were analysed to assess the imaging features in acute stage cortical laminar necrosis. Results: The final population consisted of 14 patients (seven men and seven women, mean age 61 years, range 32–79 years) diagnosed with stroke and acute phase cortical laminar necrosis. All the patients presented with cortical lesions showing restricted diffusion on diffusion-weighted images and hypointensity on the apparent diffusion coefficient map. Cortical hyperintensity on T2-weighted or fluid-attenuated inversion recovery images was found in three (21%) and six (43%) patients, respectively. Reduced perfusion was noted in three out of four patients imaged with arterial spin labelling, while in one case no corresponding perfusion abnormality was noted on the arterial spin labelling maps. Arterial spin labelling abnormalities were much more extensive than diffusion restriction in two patients, and they were associated with a poor outcome. Conclusion: Cortical hyperintense abnormalities on diffusion-weighted imaging may be the only sign of developing cortical laminar necrosis injury. The acquisition of arterial spin labelling helps to identify perfusion alterations and the extension of the ischaemic injury

Resting-State Functional Connectome in Patients with Brain Tumors Before and After Surgical Resection

Purpose: High-grade glioma surgery has evolved around the principal belief that a safe maximal tumor resection improves symptoms, quality of life, and survival. Mapping brain function has been recently improved by resting-state functional magnetic resonance imaging (rest-fMRI), a novel imaging technique that explores networks connectivity at “rest.” Methods: This prospective study analyzed 10 patients with high-grade glioma in whom rest-fMRI connectivity was assessed both in single-subject and in group analysis before and after surgery. Seed-based functional connectivity analysis was performed with CONN toolbox. Network identification focused on 8 major functional connectivity networks. A voxel-wise region of interest (ROI) to ROI correlation map to assess functional connectivity throughout the whole brain was computed from a priori seeds ROI in specific resting-state networks before and after surgical resection in each patient. Results: Reliable topography of all 8 resting-state networks was successfully identified in each participant before surgical resection. Single-subject functional connectivity analysis showed functional disconnection for dorsal attention and salience networks, whereas the language network demonstrated functional connection either in the case of left temporal glioblastoma. Functional connectivity in group analysis showed wide variations of functional connectivity in the default mode, salience, and sensorimotor networks. However, salience and language networks, salience and default mode networks, and salience and sensorimotor networks showed a significant correlation (P uncorrected <0.0025; P false discovery rate <0.077) in comparison before and after surgery confirming non-disconnection of these networks. Conclusions: Resting-state fMRI can reliably detect common functional connectivity networks in patients with glioma and has the potential to anticipate network alterations after surgical resection

Hepatocellular carcinoma with macrovascular invasion: Multimodality imaging features for the diagnosis

Hepatocellular carcinoma (HCC) is frequently associated with macrovascular invasion of the portal vein or hepatic veins in advanced stages. The accurate diagnosis of macrovascular invasion and the differentiation from bland non-tumoral thrombus has significant clinical and management implications, since it narrows the therapeutic options and it represents a mandatory con-traindication for liver resection or transplantation. The imaging diagnosis remains particularly challenging since the imaging features of HCC with macrovascular invasion may be subtle, espe-cially in lesions showing infiltrative appearance. However, each radiologic imaging modality may provide findings suggesting the presence of tumor thrombus rather than bland thrombus. The purpose of this paper is to review the current guidelines and imaging appearance of HCC with macrovascular invasion. Knowledge of the most common imaging features of HCC with macro-vascular invasion may improve the diagnostic confidence of tumor thrombus in clinical practice and help to guide patients’ management