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Background: Nonalcoholic fatty liver disease (NAFLD) is strictly associated with the epidemic of obesity and is becoming the most prevalent liver disease worldwide. In severe obesity, bariatric surgery (BS) is the most effective treatment not only for obesity but also for the associated metabolic co-morbidities, NAFLD, among others. To date, noninvasive diagnostic/prognostic methods cannot evaluate hepatic improvements following surgery. Objectives: We aimed to measure plasma level of insulin-growth factor-2 protein (IGF2) and epithermal growth factor receptor (EGFR), and to assess their relationship with clinical and biochemical parameters during the 12 months follow-up. Methods: Demographic, clinical–biochemical data, and plasma IGF2 and EGFR were measured in 69 patients preoperatively (T0) and 6 and 12 months (T6M and T12M, respectively) after BS. Liver biopsy was performed at T0. Relationships between IGF2, EGFR, and several biochemical parameters were performed using Pearson or Spearman correlation analysis. Results: IGF2 plasma level increases during follow-up, passing from 2.5 (1.8–15.5) at baseline to 13.3 (8.6–19.1) at T12M, p < 0.001. Conversely, EGFR showed a not significant reduction. At T12M, the plasma level of both markers was comparable to those of lean subjects. The clinical–biochemical parameters (BMI, glycated hemoglobin, HOMA-IR) also return to the normal range at T12M. Correlation analysis demonstrated that IGF2 was significantly associated with total bilirubin, direct bilirubin, and albumin at T0 while with blood glucose, ALT, GGT, and AST/ALT ratio at T6M and T12M. Conclusions: IGF2 plasma levels increase after bariatric surgery, and these changes are associated with the modification of hepatic biochemical parameters, even if other clinic or metabolic improvements cannot be excluded.

Background & Aims: In the next 20 years, non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of liver transplantation. Fibrosis is the most important prognostic factor for liver-related outcomes and mortality, but the need for liver biopsy limits diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis. FCN-2 candidate was selected by an in silico discovery strategy. Methods: We enrolled 235 morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n=44; F1, n=134; F2, n=46; F3/F4, n=11) and 40 cirrhotic patients as positive controls. The cohort was subdivided into discovery (n=76) and validation groups (n=159). The plasma level of FCN-2 and other biomarkers was determined by enzyme-linked immunoabsorbent assay. Results: Plasma level of FCN-2 correlated inversely with the stage of liver fibrosis (ρ = -0.49, pConclusion: FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs . moderate/advanced). Its inclusion in the diagnostic workup significantly improves the fibrosis diagnostic algorithms.

Item does not contain fulltext Breast computed tomography (BCT) is an emerging application of X-ray tomography in radiological practice. A few clinical prototypes are under evaluation in hospitals and new systems are under development aiming at improving spatial and contrast resolution and reducing delivered dose. At the same time, synchrotron-radiation phase-contrast mammography has been demonstrated to offer substantial advantages when compared with conventional mammography. At Elettra, the Italian synchrotron radiation facility, a clinical program of phase-contrast BCT based on the free-space propagation approach is under development. In this paper, full-volume breast samples imaged with a beam energy of 32 keV delivering a mean glandular dose of 5 mGy are presented. The whole acquisition setup mimics a clinical study in order to evaluate its feasibility in terms of acquisition time and image quality. Acquisitions are performed using a high-resolution CdTe photon-counting detector and the projection data are processed via a phase-retrieval algorithm. Tomographic reconstructions are compared with conventional mammographic images acquired prior to surgery and with histologic examinations. Results indicate that BCT with monochromatic beam and free-space propagation phase-contrast imaging provide relevant three-dimensional insights of breast morphology at clinically acceptable doses and scan times.

Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.

Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients&rsquo, tumors. They can be propagated in culture maintaining several features of the tumor of origin, including cellular and genetic heterogeneity, thus representing a promising tool for precision cancer medicine. Here, we established patient-derived tumor organoids (PDOs) from different breast cancer subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative). The established model systems showed histological and genomic concordance with parental tumors. However, in PDOs, the ratio of diverse cell populations was frequently different from that originally observed in parental tumors. We showed that tumor organoids represent a valuable system to test the efficacy of standard therapeutic treatments and to identify drug resistant populations within tumors. We also report that inhibitors of mechanosignaling and of Yes-associated protein 1 (YAP) activation can restore chemosensitivity in drug resistant tumor organoids.

Background: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. Materials and Methods: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs

The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients&rsquo, responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells&rsquo, phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients&rsquo, responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients.

A Phase-Contrast breast CT facility based on a high-resolution CdTe photon-counting detector is under development at Elettra, the Italian Synchrotron Radiation (SR) facility in Trieste. The CT system exploits propagation-based phasecontrast imaging and phase-retrieval algorithm. The voxel size is 57×57×50 μm3 and the delivered MGDs, about 5 mGy, are comparable with clinical breast CT systems. In the present contribution, the comparisons between histological breast cancers and full breast CT images are presented from samples of breast mastectomy. The high resolution of the breast CT images and low noise due to the phase contrast allow a very fine matching between X-ray CT and histology at acceptable delivered doses.

Introduction and Objectives. Analysis of cancer biomarkers is an important tool in developing targeted-therapy and in modulating chemoresistance. Here, we analyze the relevance of CD90, a marker of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) and its correlation with autophagy. Materials and Methods. For in vivo study, 86 specimens were collected from 43 patients undergoing liver resections. In each patient, HCC nodule (HCC) and surrounding non-tumor (SNT) were collected. For in vitro study, HCC cells JHH6 subpopulations expressing CD90+ and CD90- were isolated using magnetic-sorter and confirmed by flow-cytometry. Upon doxorubicin treatment, autophagy turn-over was analyzed by RTqPCR for mRNA expression, Western blot for protein expression, and autophagosome staining for autophagy-flux. Cytotoxicity test was performed by MTT assay. Gene and protein analysis were performed in clinical samples together with immunohistostaining. Results. CD90 mRNA expression was higher in HCC than in SNT for 8-fold (p

Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We analyzed 52 and 43 selected HCC patients undergoing hepatectomy in Ho Chi Minh City (Vietnam) and Trieste (Italy). Each patient sample consisted of HCC, peri-HCC, and non-tumoral (distal) tissue. Demographic data were recorded together with clinical findings. The protocol for the collection of tissue samples and RNA was standardized in both laboratories and gene expression analysis was performed in a single laboratory with identical PCR conditions. Baseline data showed comparable laboratory findings between the two cohorts. mRNA distribution showed a comparable pattern of all CSC markers analyzed with the expression of CD90 progressively increasing from distal and peri-HCC to be highest in HCC (p &lt, 0.001), confirmed by immunofluorescence data. CD90 mRNA distribution was related to HBV-related HCC and a tumor diameter less than 5 cm. Patients with high tumoral CD90 mRNA had a shorter time (p &lt, 0.05) to tumor recurrence compared to patients with lower CD90. This comparative study showed that CD90 mRNA expressions are comparable between Eastern and Western HCC cases.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disorder progressing from an initial benign accumulation of fat (NAFL) towards steatohepatitis (NASH), a degenerative form that can lead to liver cirrhosis and cancer. The development of non-invasive, rapid and accurate method to diagnose NASH is of high clinical relevance. Surface-enhanced Raman spectroscopy (SERS) of plasma was tested as a method to distinguish NAFL from NASH. SERS spectra from plasma of female patients diagnosed with NAFL (n = 32) and NASH (n = 35) were obtained in few seconds, using a portable Raman spectrometer. The sample consisted of 5 μL of biofluid deposited on paper coated with Ag nanoparticles. The spectra show consistent differences between the NAFL and NASH patients, with the uric acid/hypoxanthine band area ratio statistically different (p-value

Background & aims Obesity is associated with non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with chronic liver disease of different aetiologies (eg HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery. Methods Two-hundred and twenty-six subjects (160 females; mean age 42.9 years ±10.8 SD) without evidence of any further cause of liver disease consecutively underwent bariatric surgery in two Italian liver centers. During surgery, all patients underwent liver biopsy for histological evaluation and molecular studies. Liver DNA extracts were tested for PNPLA3, TM6SF2, MBOAT7, IRGM polymorphisms and for OBI. Univariate and multivariate analyses were used to identify predictors of NASH. Results Histology showed NASH in 115 (50.9%) and NAFL in 111 cases (49.1%). Twenty-nine/226 (12.8%) cases had OBI, 24 (82.8%) of whom had NASH and 5 (17.2%) NAFL, whereas among the 197 OBI-negative cases, 91 (46.2%) had NASH and 106 (53.8%) NAFL (P = .0002). Multivariate analysis showed that older age (P = .03, OR 1.034), alanine aminotransferase values (P = .005, OR 1.023), insulin resistance/diabetes (P = .02, OR 2.257), TM6SF2 polymorphism (P = .04, OR 3.168) and OBI (P = .004, OR 5.503) were independent predictors of NASH. Conclusion NASH is highly prevalent in obese individuals undergoing bariatric surgery. OBI is one of the strongest risk factors of NASH in these patients.

Disseminated intravascular coagulation (DIC) is a high mortality coagulopathy that leads to simultaneous thrombotic and bleeding problems. It occurs as a complication in different disease as malignancies, obstetrical catastrophes, bacterial sepsis and traumas. We report on an extremely rare case of acute DIC in a patient with misdiagnosed adenomyosis and massive methrorragia which led to acute kidney failure. The patient was successfully treated with hysterectomy and blood product transfusions; however, a slight reduction of renal function persisted. We were able to confirm the cause-consequence link between adenomyosis and consumptive DIC since we saw the thrombi in the adenomyotic uterus from early hysterectomy specimen. Moreover, this is the first case, for the best of our knowledge, in which systemic consequences persist in an adenomyosis patient who developed a DIC. Early diagnose and treatment of acute DIC is essential for patient's survival and to prevent severe complications: adenomyosis should be kept in mind as a possible cause of DIC when a patient shows up with massive bleeding.

The contribution of the complement system in the pathophysiology of brain cancers has been recently considered in light of its well-known involvement in carcinogenesis. Complement system represents an important component of the inflammatory response, which acts as a functional bridge between the innate and adaptive immune response. C1q, the first recognition subcomponent of the complement classical pathway, has recently been shown to be involved in a range of pathophysiological functions that are not dependent on complement activation. C1q is expressed in the microenvironment of various types of human tumors, including melanoma, prostate, mesothelioma, and ovarian cancers, where it can exert a protective or a harmful effect on cancer progression. Despite local synthesis of C1q in the central nervous system, the involvement of C1q in glioma pathogenesis has been poorly investigated. We, therefore, performed a bioinformatics analysis, using Oncomine dataset and UALCAN database in order to assess whether the expression of the genes encoding for the three chains of C1q (C1qA, C1qB, and C1qC) could serve as a potential prognostic marker for gliomas. The obtained results were then validated using an independent glioma cohort from the Chinese Glioma Genome Atlas datasets. Our bioinformatics analysis, coupled with immunohistochemistry and fluorescence microscopy, appears to suggest a positive correlation between higher levels of C1q expression and unfavorable prognosis in a diverse grade of gliomas.

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BackgroundWe investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.MethodsIntratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).ResultsTwenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.DiscussionTumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.

A program devoted to performing the first in vivo synchrotron radiation (SR) breast computed tomography (BCT) is ongoing at the Elettra facility. Using the high spatial coherence of SR, phase-contrast (PhC) imaging techniques can be used. The latest high-resolution BCT acquisitions of breast specimens, obtained with the propagation-based PhC approach, are herein presented as part of the SYRMA-3D collaboration effort toward the clinical exam. Images are acquired with a [Formula: see text] dead-time-free single-photon-counting CdTe detector. The samples are imaged at 32 and 38 keV in a continuous rotating mode, delivering 5 to 20 mGy of mean glandular dose. Contrast-to-noise ratio (CNR) and spatial resolution performances are evaluated for both PhC and phase-retrieved images, showing that by applying the phase-retrieval algorithm a five-time CNR increase can be obtained with a minor loss in spatial resolution across soft tissue interfaces. It is shown that, despite having a poorer CNR, PhC images can provide a sharper visualization of microcalcifications, thus being complementary to phase-retrieved images. Furthermore, the first full-volume scan of a mastectomy sample ([Formula: see text]) is reported. This investigation into surgical specimens indicates that SR BCT in terms of CNR, spatial resolution, scan duration, and scan volume is feasible.

Background The relationship between breast cancer (BC) and thyroid disease (TD) is still controversial. The aim of the study was to investigate the possible coexistence of TD in patients with newly diagnosed BC and its correlation with BC clinical presentation with regard to menopausal status and stage of disease. Methods This is a retrospective cohort study of all patients treated for primary BC between 2014 and 2016 at the Breast Unit of Trieste University Hospital. Clinical charts and reports were reviewed for coexisting thyroid disorders (i.e. hyperthyroidism, hypothyroidism, benign TD, thyroid cancer, thyroid autoimmunity) and menopausal status at the time of BC diagnosis. Biomolecular profile, stage, and grading of BC were also evaluated. Results A total of 786 women and 7 men were included in the study. Co-presence of TD was found in 161(20.3%) cases: of these, 151(19.4%) patients presented benign TD and 10(1.3%) patients presented thyroid carcinoma. Thyroid autoimmunity was found in 51(32%) patients. Regarding thyroid function, 88(55%) patients had hypothyroidism, 19(12%) hyperthyroidism, and 54(33%) normal thyroid function. No statistically significant correlation was found between age and TD (p = 0.16), although TD was more common in women aged ≥60 years. Women with BC diagnosed at pre-menopausal age were more likely to have thyroid autoimmune diseases (45% vs. 29%, p = 0.05). No association was detected among BC molecular profiles with either thyroid autoimmunity (p = 0.26) or altered thyroid function (p = 0.63). High-grade BC was more frequent in women with hyperthyroidism (52.9%, p = 0.04), but the grading was independent from the presence of thyroid autoimmune disease (p = 0.87). BC stage was related to both thyroid autoimmunity (p = 0.04) and thyroid function (p Conclusions According our study results, patients with primary BC present a greater incidence of autoimmunity disorders, especially when diagnosed in the pre-menopausal setting. However, further prospective studies are required to definitively prove causality.

A quantitative characterization of the soft tissues composing the human breast is achieved by means of a monochromatic CT phase-contrast imaging system, through accurate measurements of their attenuation coefficients within the energy range of interest for breast CT clinical examinations. Quantitative measurements of linear attenuation coefficients are performed on tomographic reconstructions of surgical samples, using monochromatic x-ray beams from a synchrotron source and a free space propagation setup. An online calibration is performed on the obtained reconstructions, in order to reassess the validity of the standard calibration procedure of the CT scanner. Three types of healthy tissues (adipose, glandular, and skin) and malignant tumors, when present, are considered from each sample. The measured attenuation coefficients are in very good agreement with the outcomes of similar studies available in the literature, although they span an energy range that was mostly neglected in the previous studies. No globally significant differences are observed between healthy and malignant dense tissues, although the number of considered samples does not appear sufficient to address the issue of a quantitative differentiation of tumors. The study assesses the viability of the proposed methodology for the measurement of linear attenuation coefficients, and provides a denser sampling of attenuation data in the energy range useful to breast CT.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: “0” or absent (between 0 and 5%), “1” or low (between 6 and 25%), “2” or moderate (between 26 and 50%) and “3” or high (between 51 and 75%). OS was then correlated with different TILs’ expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92–3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80–3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors’ efficacy warrants future investigation.

Background Thyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt’s lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy. Case presentation Here we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt’s lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence. Conclusions Clinicians should be aware that thyroid Burkitt’s lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma.

Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis. Methods: Seventy-one morbidly obese (MO) subjects with biopsy-proven NAFLD were enrolled, and the cohort was subdivided according to minimal (F0/F1) or moderate (F2/F3) fibrosis. The plasmatic level of CD44 antigen (CD44), secreted protein acidic and rich in cysteine (SPARC), epidermal growth factor receptor (EGFR) and insulin-like growth factor 2 (IGF2) were determined by ELISA. Significant associations between plasmatic levels and histological fibrosis were determined by correlation analysis and the diagnostic accuracy by the area under receiver operating characteristic curves (AUROC). Results: Eighty-two percentage of the subjects had F0/F1 and 18% with F2/F3 fibrosis. Plasmatic levels of IGF2, EGFR and their ratio (EGFR/IGF2) were associated with liver fibrosis, correlating inversely for IGF2 (P < .006) and directly (P < .018; P < .0001) for EGFR and EGFR/IGF2 respectively. The IGF2 marker had the best diagnostic accuracy for moderate fibrosis (AUROC 0.83), followed by EGFR/IGF2 ratio (AUROC 0.79) and EGFR (AUROC 0.71). Conclusions: Our study supports the potential utility of IGF2 and EGFR as non-invasive diagnostic biomarkers for liver fibrosis in morbidly obese subjects., Facultad de Ciencias Exactas

X-ray phase imaging has the potential to dramatically improve soft tissue contrast sensitivity, which is a crucial requirement in many diagnostic applications such as breast imaging. In this context, a program devoted to perform in vivo phase-contrast synchrotron radiation breast computed tomography is ongoing at the Elettra facility (Trieste, Italy). The used phase-contrast technique is the propagation-based configuration, which requires a spatially coherent source and a sufficient object-to-detector distance. In this work the effect of this distance on image quality is quantitatively investigated scanning a large breast surgical specimen at three object-to-detector distances (1.6, 3, 9 m) and comparing the images both before and after applying the phase-retrieval procedure. The sample is imaged at 30 keV with a [Formula: see text] pixel pitch CdTe single-photon-counting detector, positioned at a fixed distance of 31.6 m from the source. The detector fluence is kept constant for all acquisitions. The study shows that, at the largest distance, a 20-fold SNR increase can be obtained by applying the phase-retrieval procedure. Moreover, it is shown that, for phase-retrieved images, changing the object-to-detector distance does not affect spatial resolution while boosting SNR (four-fold increase going from the shortest to the largest distance). The experimental results are supported by a theoretical model proposed by other authors, whose salient results are presented in this paper.

A program devoted to perform the first in-vivo monochromatic breast computed tomography (BCT) is ongoing at the Elettra Synchrotron Facility. Since the synchrotron radiation provides high energy resolution and spatial coherence, phase-contrast (PhC) imaging techniques can be used. The latest high resolution BCT acquisitions of breast specimens, obtained with the propagation-based PhC approach, are herein presented as part of a wider framework, devoted to the optimization of acquisition and reconstruction parameters towards the clinical exam. Images are acquired with a state-of-the-art dead-time-free single-photon-counting CdTe detector with a 60 µm pixel size. The samples are imaged at 32 and 38 keV in continuous rotating mode, delivering 5-20 mGy of mean glandular dose (MGD). Contrast-to-noise ratio (CNR) and spatial resolution performances are evaluated for both absorption and phase-retrieved images considering tumor/adipose tissue interfaces. We discuss two different phase-retrieval approaches, showing that a remarkable CNR increase (from 0.5 to 3.6) can be obtained without a significant loss in spatial resolution. It is shown that, even if the non-phase-retrieved image has a poorer CNR, it is useful for evaluating the spiculation of a microcalcification: in this context, absorption and phase-retrieved images have to be regarded as complementary information. Furthermore, the first full volume acquisition of a mastectomy, with a 9 cm diameter and 3 cm height, is reported. This investigation on surgical specimens indicates that monochromatic BCT with synchrotron radiation in terms of CNR, spatial resolution, scan duration and scan volume is feasible.

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.

Background: One of the strongest prognostic factor for breast cancer is the regional lymph node status, which can be evaluated intraoperatively by sentinel lymph node biopsy. Many methods (e.g. frozen section, touch imprint cytology (TIC) and one-step nucleic-acid amplification) are available to detect metastatic cells in axillary lymph nodes. The aim of this study is to evaluate the feasibility of using TIC to detect metastatic cells in sentinel lymph nodes. Methods: This is a retrospective single center cohort analysis conducted on prospectively recorded data. The study included all patients admitted to the Department of General Surgery of Trieste University Hospital for invasive clinically node-negative breast cancer who underwent sentinel lymph node assessment by means of TIC. Results: Between January 2015 and December 2016, 343 patients (338 females and 5 males) underwent breast surgery and sentinel lymph node TIC. Patient’s median age was 66 (33-92) years. The sensitivity of TIC was 54% (95% C.I. 39% to 69%), whereas its specificity and accuracy were 99% (95% C.I. 98% to 100%) and 90%, respectively. The median time required to obtain the result was 20 (15-45) min. The overall cost per each TIC analysis was about 20.50€. Conclusion: Touch imprint cytology appears to be a fast, cost-effective and reliable technique to intraoperatively detect breast cancer lymph node metastasis.